question,context,answer,category
does radioiodine therapy change the atherosclerotic burden of the carotid arteries?,"atherosclerosis evolves or accelerates when arteries are exposed to ionizing radiation, both early and late after exposure. radioiodine therapy of benign thyroid disease exposes the carotid arteries to 4-50 gy, and may thereby increase the risk of atherosclerosis. increased risk of cerebrovascular events has been reported after radioiodine therapy. this study aimed to examine whether atherosclerosis develops early or late after radioiodine therapy of benign thyroid disease. patients treated for benign thyroid disorders (nontoxic goiter, adenoma, and hyperthyroidism) were examined with ultrasound for the main outcome, carotid intima media thickness (cimt), and for plaque presence (plaque presence only in late damage). signs of early damage from radioiodine were studied in 39 radioiodine-treated patients, who were examined before treatment and at 1, 3, 6, and 12 months after treatment. late changes were studied in a cross-sectional case-control design, with radioiodine-treated patients as cases (n 193) and patients treated with surgery as controls (n 95). data were analyzed with repeated measurement for longitudinal data, and with multivariate regression for cross-sectional data. results were adjusted for age, sex, cholesterol, smoking status, known atherosclerotic disease, and body mass index. no changes in cimt were found in the patients followed prospectively for one year after treatment with radioactive iodine for benign thyroid disease (p 0.58). in the study on late effects, there was no difference in cimt (p 0.25) or presence of plaques (p 0.70) between those treated with radioactive iodine and those treated with surgery (9.8 and 5.6 years since treatment, respectively). furthermore, the level of thyrotropin (tsh) did not influence these atherosclerosis markers.",no early changes in cimt were detected in patients treated with radioactive iodine for benign thyroid disease. no signs of late effects of radioactive iodine on cimt or plaque presence were found after 10 years of follow-up. the radiation to the carotid arteries by radioactive iodine therapy for benign thyroid disease may therefore have no or low effect on atherosclerotic burden of the carotid arteries in general.,Treatment
do interleukin-15 gene therapy and the mammalian target of rapamycin inhibitor everolimus inhibit the growth of metastatic breast cancer?,"novel methods to control and treat metastatic breast cancer are needed. interleukin (il)-15 is a promising cytokine for cancer immunotherapy, and everolimus is an orally administered mammalian target of rapamycin (mtor) inhibitor, which is already approved for cancer treatment. in the present study, we investigated the efficacy of il-15 gene therapy and explored the possibility of combining il-15 therapy with everolimus to treat metastatic breast cancer. a plasmid encoding il-15 and everolimus were given to mice inoculated with 4 t1 mouse breast cancer cells. tumor size and metastasis were monitored to assess the effect of different treatment regimens. immunohistochemistry was used to detect cd4, cd8 and nkg2d cells and also the expression of ki-67 in tumor tissue; these analyses helped establish the immunization status and tumor proliferation rate of different treatment groups. terminal deoxynucleotidyl transferase dutp nick end labeling assays were performed to assess cellular apoptosis in tumor tissues. both il-15 and everolimus significantly decreased tumor size. il-15 gene therapy increased the proportion of cd4 t and natural killer (nk) cells but had no effect on cd8 t cells. by contrast, everolimus decreased the number of cd8 t cells but had no effect on cd4 t and nk cells compared to the control group. both il-15 and everolimus decreased expression of ki-67 and increased rates of apoptosis. although effective on their own, no synergistic effect was observed with a combined treatment of everolimus and il-15 gene therapy.",il-15 gene therapy was potentially useful for the treatment of metastatic breast cancer. the possibility of combining immunotherapy with everolimus requires further study.,Medication
are implantable loop recorders cost-effective when used to investigate transient loss of consciousness which is either suspected to be arrhythmic or remains unexplained?,"to assess the cost-effectiveness of implantable loop recorders (ilrs) in people with transient loss of consciousness (tloc), which, after initial assessment and specialist cardiovascular assessment, is either suspected to be arrhythmic in origin or remains unexplained. this analysis was conducted to inform clinical guideline recommendations made by the national institute for health and clinical excellence (nice) on the management of tloc. decision analytic modelling was used to estimate the costs and benefits of using ilrs compared with a strategy of no further diagnostic testing. diagnostic outcomes were estimated from a systematic review and used to populate a decision tree model. to capture the main consequences of diagnosis, the costs and benefits of treatment for several clinically significant arrhythmias were estimated within the model. we used a cost-utility approach, in which benefits are measured using quality adjusted life years (qalys), and took a uk national health service (nhs) and personal social services perspective. the cost per qaly was 17,400 in patients with unexplained syncope and 16,400 in patients with suspected arrhythmic syncope. sensitivity analysis found that the cost-effectiveness estimates are fairly robust despite the areas of uncertainty identified in the evidence and assumptions used to inform the model.",implantable loop recorder monitoring is likely to be a cost-effective strategy in people presenting to the uk nhs who are experiencing infrequent episodes of tloc which either remain unexplained or are suspected to be arrhythmic after initial assessment and specialist cardiovascular assessment. implantable loop recorder monitoring has been recommended by nice for these populations.,Treatment
do courses of change in knee adduction moment and lateral thrust differ up to 1 year after tka?,"in total knee arthroplasty (tka), dynamic knee loading may loosen the artificial joint and bone or cause polyethylene wear after prolonged use. tka decreases knee adduction moment at 6 months, but this effect is lost by 1 year post-operatively. however, lateral thrust after tka has not been clarified. we hypothesized that like knee adduction moment, lateral thrust would return to baseline levels by 1 year post-operatively. participants were 15 patients who underwent tka for medial knee oa. japanese orthopaedic association (joa) score, numeric rating scale, and gait analysis (measurement of peak knee adduction moment, knee varus angle at peak knee adduction moment, lateral thrust, and gait speed) were performed preoperatively (baseline) and 3 weeks, 3 and 6 months, and 1 year post-operatively. joa score improved from 55 9.8 to 78 12.1 at 1 year post-operatively, and pain decreased significantly from baseline at each follow-up (p 0.001). significant increases in gait speed were observed at 6 months and 1 year (p 0.001). peak knee adduction moment during stance phase was significantly lower at 3 weeks, 3 months, and 6 months compared to baseline (p 0.05), but no significant changes were seen at 1 year. knee varus at peak knee adduction moment did not differ significantly between any measurement points, while lateral thrust was decreased at 6 months and 1 year compared to baseline (p 0.05).","temporal courses of changes up to 1 year after tka differed between knee adduction moment and lateral thrust, so our hypothesis was rejected.",Treatment
do expression of aurora-b and foxm1 predict poor survival in patients with nasopharyngeal carcinoma?,"the purpose of this work was to investigate the relationship between aurora-b, foxm1, and clinical outcomes in patients with nasopharyngeal carcinoma (npc) who were treated with a combination of induction chemotherapy and radiotherapy. the expression of aurora-b and foxm1 were investigated by immunohistochemistry using a tissue microarray (tma) containing samples from 166 npc patients who were treated with cisplatin (ddp) fluorouracil (5-fu) induction chemotherapy and radiotherapy between 1999 and 2005. the relationship of aurora-b, foxm1, and survival of these npc patients was analyzed. informative tma results were obtained in 91 tumor cases for aurora-b and 93 tumor cases for foxm1. the 8-year failure-free survival rate (ffs) for the aurora-b-negative and aurora-b-positive group was 65.6 and 37.3, respectively (p 0.024), and the 8-year distant ffs (d-ffs) rate was 65.6 and 41.5, respectively (p 0.047). the 8-year overall survival (os) in the foxm1-negative group was moderately higher than in the foxm1-positive group (58.4 vs 39.1, p 0.081). cox regression analysis revealed that for ffs, aurora-b expression was a significant prognostic factor (p 0.025), while for d-ffs, aurora-b expression was a marginally significant prognostic factor (p 0.056). when foxm1 expression was analyzed, the cox regression analyses showed that foxm1 expression was a marginally significant prognostic factor (p 0.056) for os. correlation analysis showed that aurora-b and foxm1 expression had no significant correlation.","aurora-b and foxm1 were both adverse prognostic markers for npc patients treated with chemoradiotherapy. however, the two markers had no significant correlation.",Medication
are breastfeeding rates increasing in scotland?,"to measure the change in prevalence of breastfeeding between 1990/1991 and 1997/1998 in scotland, using information collected on guthrie cards when newborn infants are about seven days old. analysis, by geographic postcode area, health board and maternity unit, for babies born in 1990/1991 and 1997/1998. for 1997, maternity unit and health board breastfeeding rates were also compared after standardisation for maternal age, deprivation and age of infant. scotland. 131,759 babies born in 1990/1991 and 118,055 in 1997/1998. in 1990/1991, 46,949 (35.6) were breastfed as were 49,615 (42.0) in 1997/1998, an increase of 6.4 (95 ci 6.0, 6.8) over eight years. a 3.8 increase remained after adjustment for change in maternal age. maternity units with the baby friendly award improved 8.1 (95 ci 7.0, 9.2) compared with those with a certificate of commitment 6.1 (95 ci 5.2, 7.0). other units improved 2.2 (95 c1 1.6, 2.8) no more than estimates due to increase in maternal age. standardised rates were higher on the east coast of scotland 111 (109, 112) than the west or central regions 97 (96, 99).",breastfeeding has increased over eight years in scotland. less than half can be explained by demographic change in maternal age. however present breastfeeding targets are unlikely to be met. maternity units should be urged to participate fully in the unicef u.k. baby friendly initiative. effective interventions prior to pregnancy are required so that more young men and women want their babies to be breastfed.,Prevention
is immediate cea for symptomatic carotid disease preferably performed under local anaesthesia safe?,"previous general reservations against carotid endarterectomy (cea) early after stroke, which were primarily based on concerns of postoperative intracerebral hemorrhage, are resolved. moreover, a delay of surgery is proofed to be associated with a risk of recurrent cerebral ischemia. however, the complication rate of cea seems to increase with less time interval to the onset of symptoms. the main purpose of this study was to assess the safety of very early cea. patients having a symptomatic high-grade ( 70) internal carotid artery (ica) stenosis were referred by neurologists for cea within different timeframes, so that they were later differentiated depending on whether surgery was performed within 2 days (immediate cea icea) or 2 weeks (urgent cea ucea) after neurological deficits have occurred primarily. the perioperative complication rate in these groups was than evaluated and compared. from january 2000 until august 2006 130 consecutive patients (median age 68 years, range: 42-90; 66 male, 34female)presenting with an ipsilateral tia (n 80), stroke (n 50) underwent icea (n 40) or ucea (n 90). demographic and clinical characteristics were equally distributed between treatment groups. mostly (121/130), cea was performed under local anaesthesia with selective shunt use which became necessary in 26. besides postoperative hemorrhage (n 4), cardiac complications (n 2) and temporary cranial nerve lesions (n 2), new perioperative neurological deficits occurred in total in 8 patients of which 6 were temporary. the other 2 patients developed strokes of which one patient died. therefore, the combined stroke- and mortality rate was 1.5 (2/130) for the whole study population. with regard to the timing of surgery, a single incident was observed after icea (1/40) which also was the only intracerebral hemorrhage.",it seems that patients with a symptomatic high-grade ica stenosis can undergo cea particularly under local anaesthesia as soon as possible without anticipating an increased complication rate.,Medication
are waist circumference and waist-to-hip ratio related to gestational glucose tolerance?,"to evaluate the relationship of central fat distribution with gestational glucose tolerance during the usual time for screening gestational diabetes. this cross-sectional study investigated 1,113 consecutive women, or 20 years old, pregnant for approximately 21 to 28 weeks, without history of previous diabetes outside pregnancy, who attended two general prenatal care units in porto alegre, brazil, from 1991 to 1993. weight, height, waist and hip circumferences, and skinfolds were measured, and a 2-h, 75-g glucose tolerance test was performed. data were analyzed using multiple linear regression models. waist-to-hip ratio (whr) and waist circumference were independently associated with higher 2-h glycemia. glycemic level was 0.11 and 0.13 mmol/l greater for each standard deviation increase in whr (0.06) and waist circumference (8.0 cm), respectively (p 0.02). restricting analyses to the subset of women with uterine height or 26 cm improved the association (0.13 and 0.19 mmol/l, respectively, p 0.02); differences of 0.22 and 0.19 mmol/l were observed for 1 sd changes in the sum of skinfold thicknesses (24.7 mm) and in age (5.5 years), respectively.","central fat distribution measured in pregnancy is an independent predictor of gestational glucose intolerance. this finding supports the concept that niddm and gestational diabetes are parts of the same disease, differing basically in their moment of detection. the usefulness of these anthropometric measurements in identifying pregnant women at high risk of having gestational glucose intolerance merits further investigation.",Diagnosis
does hyperglycemia impair isoflurane-induced adenosine triphosphate-sensitive potassium channel activation in vascular smooth muscle cells?,"isoflurane activates vascular adenosine triphosphate sensitive potassium (k(atp)) channels, and may induce vasodilation. in the present study, we investigated whether hyperglycemia modifies isoflurane activation of vascular k(atp) channel. we used a cell-attached patch-clamp configuration to test the effects of isoflurane on k(atp) channel activity in vascular smooth muscle cells (vsmcs) after incubation for 24 h in medium containing normal glucose (ng, 5.5 mm d-glucose), l-glucose (lg, 5.5 mm d-glucose plus 17.5 mm l-glucose), or high glucose (hg, 23 mm d-glucose). superoxide levels in aortas were measured by the lucigenin-enhanced chemiluminescence technique. isoflurane-induced open probabilities were significantly reduced in vsmcs from arteries incubated in hg (0.06 /- 0.01) compared with ng (0.17 /- 0.02; p 0.05) and lg (0.15 /- 0.02; p 0.05). pretreatment of vsmcs with protein kinase c (pkc) inhibitors, calphostin c and pkc inhibitor 20-28, greatly reduced hg inhibition of isoflurane-induced k(atp) channel activity. in addition, a pkc activator, pma, mimicked the effects of hg. superoxide release was significantly increased in arteries incubated in hg (18.3 /- 11.5 relative light units (rlu) x s(-1) x mg(-1); p 0.05 versus ng). coincubated with polyethylene glycol-superoxide dismutase (250 u/ml), a cell-permeable superoxide scavenger, greatly reduced the hg-induced increase of superoxide, but failed to reduce hg inhibition of isoflurane-induced k(atp) channel activity.","our results suggest that the metabolic stress of hyperglycemia can impair isoflurane-induced vascular k(atp) channel activity mediated by excessive activation of pkc. this could impede the coronary vasodilation response to isoflurane, causing ischemia or hypoxia in patients with perioperative hyperglycemia.",Medication
is postoperative atrial fibrillation associated with an increase risk of stroke or the type and number of grafts : a single-center retrospective analysis?,"atrial fibrillation (af) and atrial flutter are the 2 most common types of dysrhythmia in patients undergoing coronary artery bypass graft (cabg) surgery and are associated with increased morbidity and mortality. we sought to explore the association between the type and quantity of bypass grafts and cardiovascular outcomes in patients with postoperative af (poaf). the type and quantity of bypass grafts is associated with poaf. we queried the society of thoracic surgery national database for cabg operations, both with and without valve procedures, performed at baystate medical center between january 2002 and july 2007. we used multivariable logistic regression modeling to identify predictors of poaf and to explore the impact of af on major adverse cardiac outcomes in this post-cabg population. a total of 3068 patients received cabg surgery, 187 (6.1) of whom received concurrent valve replacement or repair. the incidence of poaf was 38.3. poaf was significantly associated with readmission within 30 days (p 0.009), increased length of stay (p 0.0001), and a strong trend toward increased 30 day mortality (p 0.058). there was no association between poaf and postoperative stroke (p 0.92), graft type (p nonsignificant) or number of grafts (p nonsignificant).","patients with poaf experienced increased morbidity and mortality as demonstrated by previous studies. neither the number of grafts nor type of grafts was associated with poaf. furthermore, the rate of stroke was not associated with poaf.",Treatment
are emergency departments ( eds ) in the united kingdom ( uk ) prepared for emerging biological threats and bioterrorism?,"to assess the preparedness of emergency departments (eds) in the united kingdom (uk) for the management of potential biological incidents. we telephoned all hospitals in the uk listed as having a major ed. we surveyed their ed facilities and procedures for managing patients with infectious diseases. we determined how many of the eds had an isolation room available and, if present, whether this had an independent ventilation system and separate access from outside the ed. in addition, we determined how many of the eds would isolate patients with suspected cases of chickenpox, tuberculosis (tb), severe acute respiratory syndrome (sars) and other suspicious infections. we obtained complete data from 203 (79) of the 257 hospitals approached. only 49 (24) of these hospitals had isolation facilities available in the ed. of these 49 eds, 30 (61) reported an independent ventilation system and 18 (37) reported a separate access from outside the ed. the majority of eds would isolate patients with potential infectious diseases, however, 47 (23) would not isolate patients with suspected chickenpox, 37 (18) eds would not isolate patients with suspected tb, 12 (6) eds would not isolate patients with suspected sars and 55 (27) eds would not isolate patients with other suspicious infections.",eds in the uk are not prepared for emerging biological threats and bioterrorism. with current facilities and procedures it is highly likely that an infectious agent will spread to staff and other patients in any future biological incident.,Treatment
does initial conservative management of severe hemispheric stroke reduce decompressive craniectomy rates?,"pooled european trial results of early decompressive craniectomy (dc) for severe hemispheric stroke did not require radiographic mass effect as an inclusion criterion. early surgery for supratentorial cerebral hemorrhage does not improve functional status or survival compared to initial conservative medical management. early versus delayed dc for hemispheric stroke has not been investigated. a prospective inpatient neurosurgical database from october 2007 to march 2015 was queried for neurocritical care admissions for hemispheric ischemic stroke in patients aged 18-60 under irb approval. a retrospective chart review was conducted using a structured questionnaire and the electronic medical record. we identified 30 patients who met the inclusion criteria for the pooled european early dc stroke trial. the mean age was 46, and the median nih stroke score was 19. all hemispheric stroke patients were monitored in the neurocritical care unit with hourly neurochecks and daily ct scans for a minimum of 3 days. eighteen patients (60 ) were managed with medical treatment only (mto) with an average maximal septal shift of 5.2 mm and a pineal shift of 3.1 mm. twelve patients (40 ) underwent dc with an average maximal septal shift of 6.8 mm and a pineal shift of 4.1 mm. modified rankin (mr) outcomes at 3 months for the overall group, mto, and dc were as follows: mr 0-3 60 versus 67 versus 50 ; mr 4-5 27 versus 17 versus 42 ; and death 13 versus 17 versus 8 , respectively. four patients in the mto group declined dc; 3 died and one survived with an mr of 4. no patients developed brainstem herniation prior to referral for dc. surgical complications occurred in 4/12 (33 ) patients.","delayed dc for hemispheric stroke patients managed under protocol in the neurocritical care unit is a safe alternative to early, prophylactic dc for adults with severe hemispheric stroke. this strategy reduced dc rates by 60 without an excess of death or survival with severe disabilities.",Treatment
does high-dose external beam irradiation inhibit neointima formation in stented pig coronary arteries?,"to evaluate high-dose external beam irradiation (ebrt) in a pig coronary stent preparation because low and intermediate-dose ebrt failed to show inhibition of neointima formation in stented animal models. thirty-five stents were implanted in the coronary arteries of 17 pigs. seven pigs were exposed to a single dose of 21 gy ebrt immediately after stenting. ten stented, nonirradiated pigs served as controls. after 4 weeks, the study arteries and myocardium were examined by light and scanning electron microscopy. compared with controls, 21 gy ebrt resulted in a larger lumen area (7.57 /- 1.67 mm2 vs. 4.00 /- 1.63 mm2, p 0.001), a smaller neointima area (0.47 /- 0.43 mm2 vs. 3.36 /- 2.26 mm2, p 0.001) and a smaller maximal intimal thickness (0.16 /- 0.09 mm vs. 0.68 /- 0.31 mm, p 0.001). unresorbed intramural hemorrhages and adherent mural thrombi were present in the irradiated vessels, which also showed incomplete re-endothelialization. the irradiated hearts demonstrated diffuse interstitial and perivascular inflammation and fibrosis.","ebrt at 21 gy to the entire heart significantly inhibited neointima formation in stented pig coronary arteries but also resulted in incomplete re-endothelialization, myocardial inflammation, and fibrosis. improvements in localization and delivery techniques are required to allow clinical implementation of this technique.",Medication
does inhibition of notch signaling promote the adipogenic differentiation of mesenchymal stem cells through autophagy activation and pten-pi3k/akt/mtor pathway?,"the notch signaling pathway is implicated in a broad range of developmental processes, including cell fate decisions. this study was designed to determine the role of notch signaling in adipogenic differentiation of human bone marrow derived mscs (bm-mscs). the notch signaling was inhibited by the -secretase inhibitor n-n-(3,5-difluor- ophenacetyl-l-alanyl)-s-phenylglycine t-butylester (dapt). the markers involving adipogenic differentiation of mscs, the relative pathway pten-pi3k/akt/mtor and autophagy activation were then analyzed. furthermore, the autophagy inhibitor chloroquine (cq) and 3-methyladenine (3-ma) were used to study the role of autophagy in the dapt-induced the adipogenic differentiation of mscs. we first confirmed the down -regulation of notch gene expression during mscs adipocyte differentiation, and showed that the inhibition of notch signaling significantly enhanced adipogenic differentiation of mscs. furthermore, notch inhibitor dapt induced early autophagy by acting on pten-pi3k/akt/mtor pathway. the autophagy inhibitor cq and 3-ma dramatically abolished the effects of dapt-induced autophagy and adipogenic differentiation of mscs.",our results indicate that inhibition of notch signaling could promote mscs adipogenesis mediated by autophagy involving pten-pi3k/akt/mtor pathway. notch signaling could be a novel target for regulating the adipogenic differentiation of mscs.,Medication
does ant species identity mediate reproductive traits and allocation in an ant-garden bromeliad?,"determining the sources of variation in floral morphology is crucial to understanding the mechanisms underlying angiosperm evolution. the selection of floral and reproductive traits is influenced by the plant's abiotic environment, florivores and pollinators. however, evidence that variations in floral traits result from mutualistic interactions with insects other than pollinators is lacking in the published literature and has rarely been investigated. we aimed to determine whether the association with either camponotus femoratus or pachycondyla goeldii (both involved in seed dispersal and plant protection) mediates the reproductive traits and allocation of aechmea mertensii, an obligatory ant-garden tank-bromeliad, differently. floral and reproductive traits were compared between the two a. mertensii ant-gardens. the nitrogen flux from the ants to the bromeliads was investigated through experimental enrichments with stable isotopes ((15)n). camponotus femoratus-associated bromeliads produced inflorescences up to four times longer than did p. goeldii-associated bromeliads. also, the numbers of flowers and fruits were close to four times higher, and the number of seeds and their mass per fruit were close to 15 times higher in c. femoratus than in p. goeldii-associated bromeliads. furthermore, the (15)n-enrichment experiment showed that c. femoratus-associated bromeliads received more nitrogen from ants than did p. goeldii-associated bromeliads, with subsequent positive repercussions on floral development. greater benefits were conferred to a. mertensii by the association with c. femoratus compared with p. goeldii ants.","we show for the first time that mutualistic associations with ants can result in an enhanced reproductive allocation for the bromeliad a. mertensii. nevertheless, the strength and direction of the selection of floral and fruit traits change based on the ant species and were not related to light exposure. the different activities and ecological preferences of the ants may play a contrasting role in shaping plant evolution and speciation.",General
does early exposure to genistein exert long-lasting effects on the endocrine and immune systems in rats?,"although the immunologic effects of endogenous and synthetic estrogens are well studied, few studies have examined the hormonal effects of phytoestrogens (i.e., plant-derived estrogens) on the immune system. the primary goal of this study was to compare the effects of perinatal exposure with life-long exposure to genistein, an estrogenic compound in soy, on the endocrine and immune system in adulthood. pregnant female rats were exposed to no, low (5 mg/kg diet), or high (300 mg/kg diet) genistein diets throughout gestation and lactation. at weaning, male offspring exposed to genistein perinatally were either switched to the genistein-free diet or remained on the genistein-dosed diets. at 70 days of age, immune organ masses, lymphocyte subpopulations, cytokine concentrations, and testosterone concentrations were assessed in male offspring. data were analyzed based on the diets that males were exposed to during gestation and lactation because life-long exposure to genistein had no additional effect on any of the dependent measures. relative thymus masses were greater among males exposed to the high genistein diet than among males exposed to no genistein. although the proportions of splenic and thymic cd4 t cells were not altered by genistein, the percentages of cd4cd8 thymocytes, cd8 splenocytes, and total t cells in the spleen were higher and the percentages of cd4-cd8- thymocytes were lower among males exposed to genistein than among males not exposed to genistein. synthesis of interferon-gamma (ifn-gamma) was marginally higher and testosterone concentrations were lower among genistein-exposed than genistein-free males.","these data illustrate that exposure to genistein during pregnancy and lactation exerts long-lasting effects on the endocrine and immune systems in adulthood. whether exposure to phytoestrogens during early development affects responses to infectious or autoimmune diseases, as well as cancers, later in life requires investigation.",Medication
are increased high mobility group box-1 protein levels associated with impaired cardiopulmonary and echocardiographic findings after acute myocardial infarction?,"several markers of systemic inflammation seem to play an active role in the pathophysiology of acute coronary syndrome and its evolution. high mobility group box-1 (hmgb-1), a ubiquitous nuclear protein constitutively expressed in quiescent cells, was recently recognized as a newer critical mediator of inflammatory diseases. the present study aimed to evaluate the possible association between hmgb-1 levels and structural and functional indices of cardiovascular performance such as cardiopulmonary and doppler-echocardiography indices in patients after acute myocardial infarction (mi). fifty-four consecutive patients (mean age 58.3 years, 83 males) recovering from acute mi were included in the study protocol. all patients underwent doppler-echocardiography, cardiopulmonary exercise, and hmgb-1 assay. hmgb-1 levels in acute mi patients were significantly higher compared with age- and body mass index-matched controls (14.8 /- 6.8 vs. 2.3 /- 1.0 ng/ml, p .0001, respectively). postinfarction patients showed oxygen consumption at peak exercise (vo(2 peak)) 14.4 /- 4.2 ml x kg x min and a slope of increase in ventilation over carbon dioxide output (ve/vco(2 slope)) 32.1 /- 6.2, whereas doppler-echocardiography values were: left ventricular end-diastolic volume (lvedv) 53.4 /- 8.2 ml/m(2); left ventricular ejection fraction (lvef) 41.7 /- 7.0. multiple linear regression analysis (stepwise method) showed that vo(2 peak) (beta -0.276, p .012), ve/vco(2 slope) (beta 0.244, p .005), lvedv (beta 0.267, p .018), peak creatine kinase-mb (beta 0.339, p .004), peak troponin i (beta 0.244, p .002), and lvef (beta -0.312, p .021) were significantly associated with hmgb-1 levels.","the present study demonstrated that in postinfarction patients, hmgb-1 levels were significantly higher compared with controls, and significantly correlated with cardiopulmonary and doppler-echocardiography parameters.",Prevention
is the chemokine receptor ccr4 expressed and associated with a poor prognosis in patients with gastric cancer?,"there is increasing evidence that chemokines and chemokine receptors are causally involved in the metastasis of cancer. little is known about the possible role of chemokine receptors in the metastasis of gastric cancer. the aim of this study was to investigate the expression of chemokine receptors and their prognostic role in patients with gastric cancer. we screened the expression of ccr and cxcr chemokine receptors in 12 gastric cancer cell lines using the semi-quantitative rt-pcr. the expression of ccr4, one of the most commonly expressed chemokines, was confirmed using western blot and flow cytometry analysis of 8 gastric cancer cell lines. the function of ccr4 was examined using migration and proliferation assays. then the migratory response of ccr4 was blocked using blocking antibodies. finally, the clinical significance of the chemokine receptors was explored using tissue microarray methods and immunohistochemical staining of specimens from 753 gastric cancer patients. we found that 6 out of 8 (75.0) gastric carcinoma cell lines expressed a functional ccr4 for its ligand, chemokine ccl17, as demonstrated by the migration assays, and the migration was inhibited by anti-ccr4 antibodies. the clinical samples evaluated by immunohistochemical assay of tissue microarrays showed that ccr4-positive carcinoma cells were detected in 128 of 753 (17.0) cases. in addition, there was a significant difference in recurrences between the ccr4-positive and -negative cases (p 0.009). the patients with ccr4-positive tumors had significantly poorer prognosis than did those with ccr4-negative tumors (5-year survival rate; 71.6 versus 82.5, respectively, p 0.008).",these results suggest that ccr4 and its ligands were associated with increased tumor recurrence and impaired overall survival in patients with gastric cancer.,Diagnosis
does gh replacement improve quality of life and metabolic parameters in cured acromegalic patients with growth hormone deficiency?,"effects of gh replacement in patients with gh deficiency (ghd) after a cure for acromegaly so far have been poorly studied, although its prevalence among acromegalic patients may reach the 60. the aim of the study was to evaluate whether metabolic parameters and quality of life are improved by gh replacement in patients with prior acromegaly and severe ghd. this was a prospective study on 42 ghd subjects 22 men, mean age (sd): 48 10: 10 acromegalics treated with recombinant human gh (group a), 12 acromegalics who refused treatment (group b), and 20 subjects operated for nonfunctioning pituitary adenoma on recombinant human gh (group c). serum igf-i levels, lipid profile, glucose levels (fasting and after an oral glucose tolerance test), glycosylated hemoglobin, insulin resistance (homeostasis model assessment insulin resistance index), anthropometric parameters (body mass index, waist circumference, body composition), and quality of life (questions on life satisfaction-hypopituitarism z-scores) were evaluated at baseline and after 12 and 36 months. at baseline, group b showed higher igf sd score than group a and c, as well as better quality of life and higher post-oral glucose tolerance test glucose levels than group a. after 12-months, similarly in group a and c, the igf-i sd score significantly increased, and body composition and lipid profile improved, without deterioration of glucose tolerance. quality of life significantly improved too, and the baseline difference between group a and b disappeared. results were confirmed after 36 months.","in ghd acromegalic patients, gh therapy improved body composition, lipid profile, and quality of life as in patients with ghd due to nonfunctioning pituitary adenoma, without negative effects on glucose metabolism. gh replacement therapy should be considered in these patients, as in patients with ghd from other causes.",Treatment
does maltose-binding protein isolated from escherichia coli induce toll-like receptor 2-mediated viability in u937 cells?,"stimulation of toll-like receptors (tlrs) by microbial products has been utilised to potentiate immune responses against haematologic malignancies. the maltose-binding protein (mbp) of escherichia coli could induce the activation of immune cells via tlr4. the aim of the present study was to investigate whether tlrs mediated the biological effects of mbp on u937 and jurkat cells in vitro. methods we observed the effect of mbp on u937 and jurkat cells by using the wst, cell cycle analysis and morphological observation. further, cells were stimulated with mbp for indicated times and doses, and detected by rt-pcr, western blotting, immunohistochemistry and immunofluorescence staining to investigate the mechanisms involved in cell viability. mbp enhanced the viability of u937 and jurkat cells, and the effects were blocked by anti-tlr2, but not anti-tlr4 in u937 cells. further studies confirmed that mbp was able to directly bind to u937 and jurkat cells and modulate tlr expression. the effects of mbp depended on the activation of nf-b and map kinase in u937 and jurkat cells.",our results demonstrated that mbp could directly promote u937 cell viability via tlr2. it suggested that mbp may be used as an adjuvant for participating in the immunotherapy of haematologic malignancies.,Medication
does mir-30c mediate upregulation of cdc42 and pak1 in diabetic cardiomyopathy?,"cardiac hypertrophy and myocardial fibrosis significantly contribute to the pathogenesis of diabetic cardiomyopathy (dcm). altered expression of several genes and their regulation by micrornas has been reported in hypertrophied failing hearts. this study aims to examine the role of cdc42, pak1, and mir-30c in the pathogenesis of cardiac hypertrophy in dcm. dcm was induced in wistar rats by low-dose streptozotocin-high-fat diet for 12 weeks. cardiac expression of cdc42, pak1 and mir-30c, and hypertrophy markers (anp and -mhc) was studied in dcm vs control rats and in high-glucose (hg)-treated h9c2 cardiomyocytes. diabetic rats showed cardiomyocyte hypertrophy, increased heart-to-body weight ratio, and an increased expression of anp and -mhc. cardiac expression of cdc42 and pak1 genes was increased in diabetic hearts and in hg-treated cardiomyocytes. mir-30c was identified to target cdc42 and pak1 genes, and cardiac mir-30c expression was found to be decreased in dcm rats, patients with dcm, and in hg-treated cardiomyocytes. mir-30c overexpression decreased cdc42 and pak1 genes and attenuated hg-induced cardiomyocyte hypertrophy, whereas mir-30c inhibition increased cdc42 and pak1 gene expression and myocyte hypertrophy in hg-treated cardiomyocytes.",downregulation of mir-30c mediates prohypertrophic effects of hyperglycemia in dcm by upregulation of cdc42 and pak1 genes.,Medication
does acute portal hypertension increase ileal vulnerability to platelet-activating factor in rats?,"patients with portal hypertension can easily develop sepsis of enteric origin after suffering severe trauma and hemorrhagic shock. platelet-activating factor (paf) is one of the key mediators of such stress. the aim of this study was to investigate whether portal hypertension increases the vulnerability of the ileum to paf. seven days after surgery, paf (1.5 microg/kg) was intravenously injected into portal stenosis (ps) rats and sham-operated rats. the levels of tumor necrosis factor-alpha (tnf-alpha), cytokine-induced neutrophil chemoattractant (cinc), and endotoxin in portal plasma were determined. the levels of paf receptor (pafr), tnf-alpha, and cinc mrna in the ileum were also investigated. after paf administration, ps rats showed (1) significantly higher portal plasma levels of tnf-alpha, cinc, and endotoxin; (2) higher histological damage scores in the ileum; (3) more infiltrating neutrophils in the ileum; and (4) a significantly higher mortality rate than sham-operated rats (p 0.01). however, pafr mrna levels were similar in the two groups. the cinc mrna level in the ileum of ps rats was increased from 1 to 4 h after paf administration, while that of the sham-operated rats was transiently increased at 1 h.",portal hypertension increases the vulnerability of the ileum to paf. these findings suggest that conditions which causes paf production may be dangerous in patients with portal hypertension.,Medication
is fibrillization of human tau accelerated by exposure to lead via interaction with his-330 and his-362?,"neurofibrillary tangles, mainly consisted of bundles of filaments formed by the microtubule-associated protein tau, are a hallmark of alzheimer disease. lead is a potent neurotoxin for human being especially for the developing children, and pb(2) at high concentrations is found in the brains of patients with alzheimer disease. however, it has not been reported so far whether pb(2) plays a role in the pathology of alzheimer disease through interaction with human tau protein and thereby mediates tau filament formation. in this study, we have investigated the effect of pb(2) on fibril formation of recombinant human tau fragment tau(244-372) and its mutants at physiological ph. as revealed by thioflavin t and 8-anilino-1-naphthalene sulfonic acid fluorescence, the addition of 5-40 m pb(2) significantly accelerates the exposure of hydrophobic region and filament formation of wild-type tau(244-372) on the investigated time scale. as evidenced by circular dichroism and fourier transform infrared spectroscopy, fibrils formed by wild-type tau(244-372) in the presence of 5-40 m pb(2) contain more -sheet structure than the same amount of fibrils formed by the protein in the absence of pb(2). however, unlike wild-type tau(244-372), the presence of 5-40 m pb(2) has no obvious effects on fibrillization kinetics of single mutants h330a and h362a and double mutant h330a/h362a, and fibrils formed by such mutants in the absence and in the presence of pb(2) contain similar amounts of -sheet structure. the results from isothermal titration calorimetry show that one pb(2) binds to one tau monomer via interaction with his-330 and his-362, with sub-micromolar affinity.",we demonstrate for the first time that the fibrillization of human tau protein is accelerated by exposure to lead via interaction with his-330 and his-362. our results suggest the possible involvement of pb(2) in the pathogenesis of alzheimer disease and provide critical insights into the mechanism of lead toxicity.,General
does berberine acutely inhibit the digestion of maltose in the intestine?,"the chinese goldthread rhizome has been used in the traditional chinese medicine as an important ingredient of many formulas for the treatment of diabetes mellitus. berberine, the main effective composition of chinese goldthread rhizome, is also effective in treating diabetes in today's clinical practice of traditional chinese medicine. to evaluate the hypoglycemic activity of berberine which treats acutely on the postprandial blood glucose, and to explore the mechanism of this activity. 1. one-dose preprandial intragastric administrations of berberine were given to normal animals (dogs and rats), and the postprandial blood glucose concentration curves were measured. serum insulin enzyme linked immunosorbent assay (elisa) was only performed in rats. 2. the euglycemic clamp test was performed to evaluate the effect of one-dose berberine intragastric administration on the blood glucose transformation and utilization rate in rats. 3. in the caco-2 cell monolayer test, the changes of glucose concentration on the apical and basolateral sides were measured when the maltose solution containing berberine was added to the apical side. 4. the inhibition ratio of berberine against -glucosidase was measured in vitro. 5. the effect of berberine on the fluorescence emission spectrums of -glucosidase was studied. one-dose preprandial intragastric administration of berberine delayed the rise of post-maltose blood glucose, did not affect postprandial blood glucose after glucose meal, and did not affect the insulin level in normal rats; reduced post-maltose blood glucose in normal dogs. 2. the result of euglycemic clamp test showed that one-dose intragastric administration of berberine had no effect on the blood glucose transformation and utilization rate in rats. 3. berberine added to the maltose solution on the apical side of caco-2 cell monolayer reduced the glucose concentration on the apical side. glucose in basolateral side of all groups cannot be detected. 4. berberine inhibited the activity of -glucosidase in vitro. 5. berberine significantly and concentration dependently quenched the fluorescence emission spectrum of -glucosidase.","our findings suggest an additional mechanism of the hypoglycemic activity of berberine by demonstrating its ability to acutely inhibit the -glucosidase, and support the traditional use of berberine and chinese goldthread rhizome for the treatment of diabetes mellitus.",Medication
is coronary heart disease and stroke attributable to major risk factors similar in argentina and the united states : the coronary heart disease policy model?,"cardiovascular disease is the leading cause of death in argentina and the u.s. argentina is 92 urban, with cardiovascular disease risk factor levels approximating the u.s. the coronary heart disease (chd) policy model is a national-scale computer model of chd and stroke. risk factor data were obtained from the cardiovascular risk factor multiple evaluation in latin america study (2003-04), argentina national risk factor survey (2005) and u.s. national surveys. proportions of cardiovascular events over 2005-2015 attributable to risk factors were simulated by setting risk factors to optimal exposure levels systolic blood pressure (sbp) 115 mm hg, low-density lipoprotein cholesterol (ldl) 2.00 mmol/l (78 mg/dl), high-density lipoprotein cholesterol (hdl) 1.03 mmol/l (60 mg/dl), absence of diabetes, and smoking. cardiovascular disease attributable to body mass index (bmi) 21 kg/m was assumed mediated through sbp, ldl, hdl, and diabetes. cardiovascular disease attributable to major risk factors was similar between argentina and the u.s., except for elevated sbp in men (chd 8 points higher in argentine men, 6 higher for stroke). chd attributable to bmi 21 kg/m was substantially higher in the u.s. (men 10-11 points higher; women chd 13-14 higher).","projected cardiovascular disease attributable to major risk factors appeared similar in argentina and the u.s., though elevated bmi may be responsible for more of u.s. cardiovascular disease. a highly urbanized middle-income nation can have cardiovascular disease rates and risk factor levels comparable to a high income nation, but fewer resources for fighting the epidemic.",Prevention
does overexpression of factor vii ameliorate bleeding diathesis of factor viii-deficient mice with inhibitors?,"factor viii (fviii) treatment for hemophilia a has difficulties in correcting bleeding diathesis in the presence of inhibitors. an adeno-associated virus type 8 (aav8) vector containing the factor vii (fvii) gene or the activated factor vii (fviia) gene was used to investigate the therapeutic effect of fvii or fviia overexpression in fviii-deficient mice with inhibitors. following repeated human fviii injection, fviii-deficient mice developed anti-human fviii antibodies that cross-reacted with mouse fviii. high transgene expression of murine fvii or murine fviia was achieved using the aav8 vector and resulted in increased blood fvii activity greater than 800 of normal murine fvii levels in vector-injected fviii-deficient mice. thromboelastography analysis showed significant improvements in clotting time, clot formation time, angle, and mean clot firmness in aav8 vector-injected fviii-deficient mice with inhibitors. overexpression of fviia ameliorated the bleeding phenotype of fviii-deficient mice with inhibitors and significantly increased the survival rate after tail clipping. in addition, overexpression of fvii increased the survival rate of fviii-deficient mice with inhibitors after tail clipping though it was not as efficient as fviia overexpression.",these data suggest that fvii overexpression is an alternative strategy for the treatment of hemophilia a with inhibitors.,Medication
does arecoline induce ha22t/vgh hepatoma cells to undergo anoikis - involvement of stat3 and rhoa activation?,"our previous study showed that, in basal cell carcinoma cells, arecoline reduces levels of the tumor cell survival factor interleukin-6 (il-6), increases levels of tumor suppressor factor p53, and elicits cell cycle arrest, followed by apoptosis. in preliminarily studies, we observed that arecoline induces detachment of the human-derived hepatoma cell line ha22t/vgh from the extracellular matrix. in the present study, we explored the fate of the detached ha22t/vgh cells and investigated the underlying mechanism. ha22t/vgh cells or primary cultured rat hepatocytes were treated with arecoline, then changes in morphology, viability, apoptosis, and the expression of surface beta1-integrin, apoptosis-related proteins, and il-6 were examined. furthermore, activation of the signal transducer and activator of transcription 3 (stat3) pathway and the rhoa/rock signaling pathway, including p190rhogap and src homology-2 domain-containing phosphatase shp2, was examined. a low concentration of arecoline (or 100 microg/ml) caused cytoskeletal changes in ha22t/vgh cells, but not hepatocytes, and this was accompanied by decreased beta1-integrin expression and followed by apoptosis, indicating that ha22t/vgh cells undergo anoikis after arecoline treatment. il-6 expression and phosphorylation of stat3, which provides protection against anoikis, were inhibited and levels of downstream signaling proteins, including bcl-xl and bcl-2, were decreased, while bax expression, mitochondrial cytochrome c release, and caspase-3 activity were increased. in addition, phosphorylation/activation of p190rhogap, a rhoa inhibitor, and of its upstream regulator, shp2, was inhibited by arecoline treatment, while rho/rock activation was increased. addition of the rhoa inhibitor attenuated the effects of arecoline.",this study demonstrated that arecoline induces anoikis of ha22t/vgh cells involving inhibition of stat3 and increased rhoa/rock activation and that the stat3 and rhoa/rock signaling pathways are connected.,Medication
does immunization with pre-erythrocytic antigen celtos from plasmodium falciparum elicit cross-species protection against heterologous challenge with plasmodium berghei?,"the plasmodium protein cell-traversal protein for ookinetes and sporozoites (celtos) plays an important role in cell traversal of host cells in both, mosquito and vertebrates, and is required for successful malaria infections. celtos is highly conserved among the plasmodium species, suggesting an important functional role across all species. therefore, targeting the immune response to this highly conserved protein and thus potentially interfering with its biological function may result in protection against infection even by heterologous species of plasmodium. to test this hypothesis, we developed a recombinant codon-harmonized p. falciparum celtos protein that can be produced to high yields in the e. coli expression system. inbred balb/c and outbred cd-1 mice were immunized with various doses of the recombinant protein adjuvanted with montanide isa 720 and characterized using in vitro and in vivo analyses.",immunization with pfceltos resulted in potent humoral and cellular immune responses and most importantly induced sterile protection against a heterologous challenge with p. berghei sporozoites in a proportion of both inbred and outbred mice. the biological activity of celtos-specific antibodies against the malaria parasite is likely linked to the impairment of sporozoite motility and hepatocyte infectivity. the results underscore the potential of this antigen as a pre-erythrocytic vaccine candidate and demonstrate for the first time a malaria vaccine that is cross-protective between species.,Medication
does mir-195 affect cell migration and cell proliferation by down-regulating diexf in hirschsprung 's disease?,"hirschsprung's disease (hscr) is the most common congenital gut motility disorder. we aimed to investigate the roles of mir-195 in the pathogenesis of hscr. in this study, we measured the expression levels of mirna, mrna, and protein in colon tissues from 78 patients with hscr and 66 controls without hscr. transwell, cell counting kit-8 (cck-8) and flow cytometry assay were employed to detect the function role of mir-195 in vitro. our results showed that expression levels of mir-195 from patients with hscr were significantly higher than control group; along with aberrant lower expression levels of digestive-organ expansion factor (diexf) were tested. increased level of mir-195 could suppress the level of diexf in cell, which induced the impairment of cell migration and proliferation.",aberrant expression of mir-195 may involved in the pathogenesis of hscr by down-regulated the level of diexf.,General
does exercise training reduce the frequency of menopausal hot flushes by improving thermoregulatory control?,"postmenopausal hot flushes occur due to a reduction in estrogen production causing thermoregulatory and vascular dysfunction. exercise training enhances thermoregulatory control of sweating, skin and brain blood flow. we aimed to determine if improving thermoregulatory control and vascular function with exercise training alleviated hot flushes. twenty-one symptomatic women completed a 7-day hot flush questionnaire and underwent brachial artery flow-mediated dilation and a cardiorespiratory fitness test. sweat rate and skin blood flow temperature thresholds and sensitivities, and middle cerebral artery velocity (mcav) were measured during passive heating. women performed 16 weeks of supervised exercise training or control, and measurements were repeated. there was a greater improvement in cardiorespiratory fitness (4.45 ml/kg/min 95 ci: 1.87, 8.16; p 0.04) and reduced hot flush frequency (48 hot flushes/wk 39, 56; p 0.001) after exercise compared with control. exercise reduced basal core temperature (0.14c 0.01, 0.27; p 0.03) and increased basal mcav (2.8 cm/s 1.0, 5.2; p 0.04) compared with control. sweat rate and skin blood flow thresholds occurred approximately 0.19c and 0.17c earlier, alongside improved sweating sensitivity with exercise. mcav decreased during heating (p 0.005), but was maintained 4.5 cm/s (3.6, 5.5; p 0.005) higher during heating after exercise compared with control (0.6 cm/s -0.4, 1.4).",exercise training that improves cardiorespiratory fitness reduces self-reported hot flushes. improvements are likely mediated through greater thermoregulatory control in response to increases in core temperature and enhanced vascular function in the cutaneous and cerebral circulations.,Prevention
does ginsenoside rh1 induce mouse osteoblast growth and differentiation through the bone morphogenetic protein 2/runt-related gene 2 signalling pathway?,"this study aimed to investigate the stimulative and pharmacological effects of ginsenoside rh1 (hereinafter referred to as: rh1) on differentiation and mineralization of osteoblast and its possible mechanism of action on the expression of bone morphogenetic protein 2 (bmp-2)/runt-related gene 2 (runx2) signalling pathways using mouse preosteoblastic mc3t3-e1 cell line as in-vitro model. an in-vitro stimulative activity of rh1 was assessed by analyzing alkaline phosphatase activity (alp), type-i collagen (coll-i) synthesis, mineralization and glutathione content. its antioxidant activity was measured by evaluating the reactive oxygen species (ros) production in the presence of antimycin a (ama), one of the mitochondrial dysfunction factors. the level of bmp-2/runx2 signal-regulated osteoblast-specific proteins such as osteocalcin (ocn), coll-i and alp were detected using western blot analysis. rh1 was capable to stimulate cell growth, alp activity, coll-i synthesis, mineralization and glutathione content in the mc3t3-e1 cells. bmp-2 and runx2 expression were also increased by rh1 concentration dependently. additionally, rh1 also showed inhibitory action on the level of ros production enhanced by ama in mc3t3-e1 cells. rh1 could increase the expression level of bmp-2/runx2 signal-regulated osteogenic markers such as alp, coll-i and ocn.","rh1, a protopanaxatriol type's active ingredients of panax ginseng meyer, possesses osteoblast differentiation, osteogenic stimulatory and anti-oxidative activity.",Medication
does experimental heart failure cause depression-like behavior together with differential regulation of inflammatory and structural genes in the brain?,"depression and anxiety are common and independent outcome predictors in patients with chronic heart failure (chf). however, it is unclear whether chf causes depression. thus, we investigated whether mice develop anxiety- and depression-like behavior after induction of ischemic chf by myocardial infarction (mi). in order to assess depression-like behavior, anhedonia was investigated by repeatedly testing sucrose preference for 8 weeks after coronary artery ligation or sham operation. mice with large mi and increased left ventricular dimensions on echocardiography (termed chf mice) showed reduced preference for sucrose, indicating depression-like behavior. 6 weeks after mi, mice were tested for exploratory activity, anxiety-like behavior and cognitive function using the elevated plus maze (epm), light-dark box (ldb), open field (of), and object recognition (or) tests. in the epm and of, chf mice exhibited diminished exploratory behavior and motivation despite similar movement capability. in the or, chf mice had reduced preference for novelty and impaired short-term memory. on histology, chf mice had unaltered overall cerebral morphology. however, analysis of gene expression by rna-sequencing in prefrontal cortical, hippocampal, and left ventricular tissue revealed changes in genes related to inflammation and cofactors of neuronal signal transduction in chf mice, with nr4a1 being dysregulated both in prefrontal cortex and myocardium after mi.","after induction of ischemic chf, mice exhibited anhedonic behavior, decreased exploratory activity and interest in novelty, and cognitive impairment. thus, ischemic chf leads to distinct behavioral changes in mice analogous to symptoms observed in humans with chf and comorbid depression.",Diagnosis
are plasma adiponectin levels associated with fat oxidation in humans?,"to test the hypothesis that low adiponectin is associated with low fat oxidation in humans. we measured plasma adiponectin concentrations in 75 healthy, nondiabetic pima indians (age, 28 /- 7 years; 55 men and 20 women; body fat, 29.7 /- 7.5) and 18 whites (age, 33 /- 8 years; 14 men and 4 women; body fat, 28.2 /- 10.8 (means /- sd) whose body composition was measured by dxa and 24-hour energy expenditure (24-hour ee) by a respiratory chamber. respiratory quotient (an estimate of whole-body carbohydrate/lipid oxidation rate) was calculated over 24 hours (24-hour rq). before correlational analyses, waist-to-thigh ratio (wtr) and percentage of body fat (pfat) were adjusted for age, sex, and race; 24-hour ee was adjusted for fat mass and fat-free mass, and 24-hour rq were adjusted for energy balance. plasma adiponectin concentrations were negatively correlated with wtr (r -0.42, p 0.0001) and pfat (r -0.46, p 0.0001). there was no correlation between plasma adiponectin concentrations and 24-hour rq, (r 0.09, p 0.36) before or after adjustment for pfat (r 0.001, p 0.99, respectively, partial correlation), and no correlation was found between plasma adiponectin concentrations and 24-hour ee (r -0.12, p 0.27).",our cross-sectional data do not suggest physiological concentrations of fasting plasma adiponectin play a role in the regulation of whole-body fat oxidation or energy expenditure in resting conditions. whether administration of adiponectin to individuals with low levels of this hormone will increase their fat oxidation rates/energy expenditure remains to be established.,General
does andrographolide ameliorate diabetic retinopathy by inhibiting retinal angiogenesis and inflammation?,"andrographolide (andro) is the main compound distributed in medicinal herb andrographis paniculata. this study aims to observe the amelioration of andro on streptozotocin (stz)-induced diabetic retinopathy (dr) in mice. stz-induced non-proliferative dr (npdr) for 2 months and proliferative dr (pdr) for 5 month in c57bl/6 mice were used in this study, respectively. retinal vessels were observed by immunofluorescence staining for cluster of differentiation 31 (cd31). evans blue permeation assay was used to detect the breakdown of blood-retinal barrier (brb). real-time pcr and immune-blot were used to detect mrna and protein expression. enzyme-linked immunosorbent assay (elisa) was used to detect serum tumor necrosis factor- (tnf-), interleukin (il)-6, and il-1. retinal immunofluorescence staining with cd31 showed that andro reduced the increased retinal vessels in stz-induced pdr mice. evans blue permeation results demonstrated that andro attenuated the breakdown of brb in stz-induced npdr mice. in stz-induced pdr mice, andro decreased the increased vascular endothelial growth factor (vegf) in serum and vitreous cavity, and reduced the increased retinal mrna expression of vegf and its receptors. in stz-induced npdr mice, andro abrogated the nuclear translocation of nuclear factor b (nf-b) p65 and early growth response-1 (egr-1), and reduced the increased phospho-nf-bp65, -inhibitor of kappa b (ib), and -ib kinase (ikk). andro also decreased the increased serum and retinal mrna expression of tnf-, il-6, il-1, serpine1, and tissue factor (tf).","andro ameliorates dr via attenuating retinal angiogenesis and inflammation, and vegf, nf-b, and egr1 signaling pathways all play important roles in this process.",Medication
does nerve growth factor selectively regulate expression of transcripts encoding ribosomal proteins?,"ngf exerts a variety of actions including promotion of neuronal differentiation and survival. the pc12 rat pheochromocytoma cell line has proved valuable for studying how ngf works and has revealed that the ngf mechanism includes regulation of gene expression. accordingly, we used sage (serial analysis of gene expression) to compare levels of specific transcripts in pc12 cells before and after long-term ngf exposure. of the approximately 22,000 transcripts detected and quantified, 4 are ngf-regulated by 6-fold or more. here, we used database information to identify transcripts in our sage libraries that encode ribosomal proteins and have compared the effect of ngf on their relative levels of expression. among the transcripts detected in our sage analysis, 74 were identified as encoding ribosomal proteins. ribosomal protein transcripts were among the most abundantly expressed and, for naive and ngf-treated pc12 cells, represented 5.2 and 3.5, respectively, of total transcripts analyzed. surprisingly, nearly half of ribosomal protein transcripts underwent statistically significant ngf-promoted alterations in relative abundance, with changes of up to 5-fold. of the changes, approximately 2/3 represented decreases. a time course revealed that the relative abundance of transcripts encoding rpl9 increases within 1 hr of ngf treatment and is maximally elevated by 8 hr.",these data establish that ngf selectively changes expression of ribosomal protein transcripts. these findings raise potential roles for regulation of ribosomal protein transcripts in ngf-promoted withdrawal from the cell cycle and neuronal differentiation and indicate that regulation of individual ribosomal protein transcripts is cell- and stimulus-specific.,Treatment
do eccentric gaze direction in patients with central field loss?,"this study describes the binocular eccentric gaze direction (egd) of 434 patients with binocular central field loss and presents a comparison with other studies on eccentric gaze behavior. we reviewed the records of 434 patients with bilateral central scotomas. eligible patients had not received eccentric viewing training and demonstrated a spontaneously developed eccentric gaze behavior. data were collected on monocular and binocular egd, visual acuity, and underlying ocular pathology. findings concerning the egd were compared with other studies that evaluated gaze behavior in patients with central field loss. in the group of 434 patients, age-related macular disease was the most frequent pathology (77). the majority of these patients demonstrated a binocular egd (begd) to the right (50). in 25 of the patients, a superior begd was found. less often, a begd to the left (14) and to inferior (11) were encountered. review of the literature indicates that the majority of patients developed a monocular egd in the superior direction.",this is a study on begd behavior in a large population of patients with bilateral central scotomas. the begd was guided by the gaze of the better-seeing eye. the preference for a begd to the right differs from findings of previous studies. review of the literature suggests that not only the ocular pathology but also the method of investigation is most likely to influence the observed egd. most studies evaluated the location of the preferred retinal locus using a monocular technique; this may not reflect an individual's actual binocular behavior as it relates to activities of daily living.,General
does parenteral vitamin b12 reduce hyperhomocysteinemia in end-stage renal disease?,"the authors found considerably lower plasma total homocysteine (thcy) concentrations in patients with end-stage renal disease (esrd) on maintenance hemodialysis, who routinely received high-dose parenteral vitamin b12, than in comparable patients receiving much higher doses of folic acid but only replacement-dose oral vitamin b12. they therefore sought prospective evidence that high-dose parenterally administered vitamin b12 may partially ameliorate renal failure-associated hyperhomocysteinemia. open phase 2 clinical trial. outpatient hemodialysis unit. fourteen clinically stable patients on maintenance hemodialysis with normal baseline serum vitamin b12 concentrations. three parenteral injections of 1 mg vitamin b12 given at 4-week intervals. plasma thcy and serum vitamin b12 concentrations were measured before, during and 7 months after the termination of vitamin b12 therapy. the mean (and standard error) baseline plasma thcy was 26.5 (1.8) micromol/l. the plasma thcy value fell successively after each vitamin injection to reach a value of 23.6 (1.6) micromol/l 1 month after the final injection (p 0.05), while the serum vitamin b12 concentration increased from 471 (42) pmol/l to 890 (74) pmol/l (p 0.05). seven months after the final injection, the serum b12 concentration had fallen and thcy had risen to near their original values.",three monthly vitamin b12 injections modestly but distinctly reduced thcy concentrations in hemodialysis patients whose prior vitamin b12 status was normal. randomized placebo-controlled clinical trials of longer duration and using larger or more frequent parenteral doses are indicated to determine whether administration of this safe and inexpensive vitamin can improve hyperhomocysteinemia in esrd.,Medication
does alveolar plasminogen activator inhibitor-1 predict ards in aspiration pneumonitis?,to test the hypothesis that alveolar plasminogen activator inhibitor-1 (pai-1) can identify patients with witnessed aspiration at risk for progression to acute respiratory distress syndrome (ards). prospective observational study. medical intensive care unit in a tertiary care center. fifty-one patients with witnessed aspiration who had a pao2/fio21518 ng/ml was found to be 82.4 (56.6-96.0) sensitive and 97.1 (84.6-99.5) specific in predicting progression to ards. there was also a significant inverse relationship between elevation of pai-1 antigen levels and the degree of lung injury as assessed by the days of unassisted ventilation (r20.37; p0.001).,elevation of alveolar pai-1 antigen levels postaspiration is the consequence of local rather than systemic activation of the fibrinolytic system. measurement of alveolar pai-1 antigen levels can be a useful clinical marker in predicting progression to ards after gastric aspiration.,Medication
does csf cytology have limited value in the evaluation of patients with ependymoma who have mri evidence of metastasis?,"to investigate the usefulness of cerebrospinal fluid (csf) cytology in pediatric patients with ependymoma who relapsed after focal irradiation. eighty-eight patients with ependymoma received conformal radiotherapy (crt) from july 1997 through january 2003 on an irb approved prospective treatment protocol. csf cytology results from evaluations performed prior to crt and at the time of failure were reviewed for patients who progressed after crt as documented by magnetic resonance imaging (mri). twenty-two patients had mri documented evidence of progression after crt. ten patients developed distant failure without local failure, four had combined local and distant failure and eight had local failure without distant failure. the median time from the start of crt to progression was 19 months (range: 6-73). csf cytology at diagnosis was negative for the presence of malignant cells in all patients. at the time of progression, csf cytology was performed in 16 of 22 patients including all 10 patients with distant failure without local recurrence. malignant cells were not found in any of the evaluated csf specimens including those with distant failure documented by mri.",csf cytology does not add valuable information when evaluating patients with ependymoma who have evidence of distant failure documented by mri. the usefulness of csf cytology in the general follow-up evaluation of pediatric patients with ependymoma remains uncertain.,Diagnosis
does elevated tissue factor expression contribute to exacerbated diabetic nephropathy in mice lacking enos fed a high fat diet?,"human enos (nos3) polymorphisms that lower its expression are associated with advanced diabetic nephropathy (dn), and the lack of enos accelerates dn in diabetic mice. diabetes is associated with fibrin deposition. lack of nitric oxide and fatty acids stimulates the nf-kb pathway, which increases tissue factor (tf). to test the hypothesis that tf contributes to the severity of dn in the diabetic enos(-/-) mice fed a high-fat diet (hf). we made enos(-/-) and wild-type mice diabetic with streptozotocin. half of them were placed on hf. blood glucose levels were not affected by either the diet or enos genotype. lack of enos in the diabetic mice increased urinary albumin excretion, glomerulosclerosis, interstitial fibrosis, and glomerular basement membrane thickness. hf by itself did not affect dn in the wild-type mice, but significantly enhanced dn in enos(-/-) mice. more than half of diabetic enos(-/-) mice on hf died prematurely with signs of thrombotic complications. diabetic kidneys contained fibrin and tf, and their levels were increased by the lack of enos and by hf in an additive fashion. the hf diet increased the kidney expression of inflammatory genes. the increase in tf preceded dn, and administration of an anti-mouse tf antibody to diabetic mice reduced the expression of inflammatory genes.","together, these data indicate a causal link between tf and the exacerbation of dn in enos(-/-) mice. the condition is significantly worsened by enhanced inflammatory responses to an hf diet via tf.",Prevention
does the variable number of tandem repeats element in dat1 regulate in vitro dopamine transporter density?,"a 40-bp variable number of tandem repeats (vntr) polymorphism exists in the 15th exon of dat1, the gene encoding the human dopamine transporter (dat). though the vntr resides in a region encoding the 3' untranslated region (utr) and does not alter the protein's amino acid sequence, the prevalent 10-repeat variant has shown both linkage and association to attention deficit hyperactivity disorder (adhd). in this study, we examined the effects of the dat1 vntr on measures of in vitro dat expression and pharmacology. a series of four dat1 constructs, each containing the dat1 coding region, but varying with respect to the downstream presence or content of the 3'utr, were engineered and stably transfected into an hek-293 variant using flp-in integration, an enzyme-mediated, site-specific recombination technology. 3h win 35,428 saturation binding assays and dat immunoblots revealed statistically significant differences in dat expression attributable to dat1 genotype. cells harboring the 10-repeat dat1 variant were characterized by a bmax approximately 50 greater than cells with the 9-repeat vntr; those containing only the dat1 coding region or the coding region flanked by a truncated 3' utr resulted in greater dat density than either of the naturalistic 9- and 10-repeat variants. competition binding assays showed no statistically significant dat1 genotype effects on the dat affinity for methylphenidate, a finding consistent with the positional location of the vntr.",this study identified the dat1 vntr as a functional polymorphism and provides an interpretive framework for its association with behavioral phenotypes.,Medication
is warfarin-associated intracerebral hemorrhage inadequately treated at community emergency departments?,"the purpose of this study was to investigate time delays, adherence to guidelines, and their impact on outcomes in patients with warfarin-associated intracerebral hemorrhage transferred from community emergency departments to a comprehensive stroke center. we collected demographic, clinical, transfer time, treatment, and outcome data for patients transferred to our institution with warfarin-associated intracerebral hemorrhage from community emergency departments. among 928 patients with intracerebral hemorrhage, 56 (6) with warfarin-associated intracerebral hemorrhage (median international normalized ratio, 2.55) were transferred to the comprehensive stroke center. twenty patients received no acute reversal therapy before transfer, only 4 of whom had international normalized ratios 1.4 in the community emergency department. median time of emergency department stay was 3.66 hours and median time to initiation of acute reversal therapy was 4.48 hours. those who received 3 u of fresh-frozen plasma or recombinant activated factor viia (11 patients) before transfer had lower repeat international normalized ratios and better discharge dispositions than those treated less aggressively.",treatment of warfarin-associated intracerebral hemorrhage in community emergency departments is often suboptimal and does not adhere to published guidelines. treating coagulopathy aggressively before interhospital transfer may improve outcomes and warrants further investigation.,Treatment
does genetic variation in four maturity genes affect photoperiod insensitivity and phya-regulated post-flowering responses of soybean?,"absence of or low sensitivity to photoperiod is necessary for short-day crops, such as rice and soybean, to adapt to high latitudes. photoperiod insensitivity in soybeans is controlled by two genetic systems and involves three important maturity genes: e1, a repressor for two soybean orthologs of arabidopsis flowering locus t (gmft2a and gmft5a), and e3 and e4, which are phytochrome a genes. to elucidate the diverse mechanisms underlying photoperiod insensitivity in soybean, we assessed the genotypes of four maturity genes (e1 through e4) in early-flowering photoperiod-insensitive cultivars and their association with post-flowering responses. we found two novel dysfunctional alleles in accessions originally considered to have a dominant e3 allele according to known dna markers. the e3 locus, together with e1 and e4, contained multiple dysfunctional alleles. we identified 15 multi-locus genotypes, which we subdivided into 6 genotypic groups by classifying their alleles by function. of these, the e1-as/e3/e4 genotypic group required an additional novel gene (different from e1, e3, and e4) to condition photoperiod insensitivity. despite their common pre-flowering photoperiod insensitivity, accessions with different multi-locus genotypes responded differently to the post-flowering photoperiod. cultivars carrying e3 or e4 were sensitive to photoperiod for post-flowering characteristics, such as reproductive period and stem growth after flowering. the phytochrome a-regulated expression of the determinate growth habit gene dt1, an ortholog of arabidopsis terminal flower1, was involved in the persistence of the vegetative activity at the stem apical meristem of flower-induced plants under long-day conditions.","diverse genetic mechanisms underlie photoperiod insensitivity in soybean. at least three multi-locus genotypes consisting of various allelic combinations at e1, e3, and e4 conferred pre-flowering photoperiod insensitivity to soybean cultivars but led to different responses to photoperiod during post-flowering vegetative and reproductive development. the phya genes e3 and e4 are major controllers underlying not only pre-flowering but also post-flowering photoperiod responses. the current findings improve our understanding of genetic diversity in pre-flowering photoperiod insensitivity and mechanisms of post-flowering photoperiod responses in soybean.",Diagnosis
are both glut-1 and glut-14 independent prognostic factors in gastric adenocarcinoma?,"the role of glucose transporter 14 (glut-14/slc2a14) in tumor biology is entirely unknown, and the significance of hypoxia inducible factor 1-alpha (hif1-) for gastric adenocarcinoma is controversial. the impact of glut-1/slc2a1 has never been confirmed in a caucasian cohort. between 1996 and 2007, 124 patients underwent gastrectomy for gastric adenocarcinoma. tumor sections were incubated with glut-1, glut-14, and hif1- antibodies. expression was analyzed for correlations with histopathology, marker coexpression, and patient survival by uni- and multivariate analyses. expressions of glut-1, glut-14, and hif1- were detectable in 50, 77.4, and 27.1 , respectively. expression of glut-1 was associated with pt-category (p 0.019), pn-category (p 0.019), tubular (who, p 0.008), and intestinal (lauren classification; p 0.002) histologic subtypes. expression of glut-14 was correlated with pt category (p 0.043), whereas hif1- did not show any correlation with histopathology or survival. the median survival period was 14 months (95 confidence interval ci 9.2-18.8 months) for glut-1-positive patients and 55 months (95 ci 25.8-84.2; p 0.01) for glut-1-negative patients. an inferior prognosis also was seen for glut-14-positive cases compared with glut-14-negative cases (p 0.004). thus, worst survival was seen with both glut-1- and glut-14-positive expression followed by single-positive and then double-negative cases (p 0.004). in multivariate analysis including international union against cancer (uicc) stages, r category, lauren classification, surgery alone versus neoadjuvant/perioperative chemotherapy, and marker expression as covariates, glut-1 (p 0.011) and glut-14 (p 0.025) kept their prognostic independence.","the study findings suggest that detection of glut-1 and glut-14 is of high prognostic value. it gives additional information to uicc stages and identifies patients with inferior prognosis. if confirmed in prospective studies, these markers need to be considered for future classification systems.",Diagnosis
does trpa1 mediate the effects of hypothermia on the monocyte inflammatory response?,"hypothermia is a well-known risk factor for postoperative complications because it prolongs the monocyte inflammatory response. the purpose of this study was to investigate whether temperature-activated ion channels (transient receptor protein channels trp a1 and v1) mediate the effects of temperature on monocytes. primary human monocytes were isolated and stimulated with lipopolysaccharide at 32c or 39c. rna was isolated for analysis of microrna (mir)-155 expression, and cytokines in the supernatant were measured with an enzyme-linked immunosorbent assay. specific inhibitors of trpa1 (hc- 030031) and a specific activator of trpv1 (capsaicin) were used to block or activate trpa1 and trpv1, respectively. statistical analysis was performed using the wilcoxon signed-rank test. trpm8 mrna was not expressed in primary human monocytes, whereas trpa1 and trpv1 were expressed. trpv1 mrna expression was suppressed at 32c but not at 39c. trpa1 was induced strongly at 32c and 39c. immunofluorescence microscopy confirmed that monocytes express trpa1 and trpv1 on their cell surface. interleukin-10 secretion was increased by blocking trpa1 (77.8 3 2.8 pg/ml) and activating trpa1 (79.4 16.1 pg/ml) after 24 hours at 32c (control 37.4 17.1 pg/ml, p .05). at 36 hours, tumor necrosis factor secretion was decreased after trpa1 blockade (2,321 439 pg/ml) and trpv1 activation (2,137 411 pg/ml) compared with control (2,567 495 pg/ml, p .05). furthermore, mir-155 expression also was suppressed at 24 hours by trpa1 blockade and trpv1 activation (both p .05). silencing of trpa1 normalized monocyte il-10 secretion at 32c.",these results demonstrate that hypothermia mediates its effects on monocytes through trpa1. blockade of trpa1 or activation of trpv1 may be used to modify the effects of hypothermia on the monocyte inflammatory response.,Medication
are the ankle-brachial pressure index and a standardized questionnaire easy and useful tools to detect peripheral arterial disease in non-claudicating patients at high risk?,"this observational study (survey of peripheral arterial disease epidemiology, spade) evaluated the prevalence of asymptomatic peripheral arterial disease (pad) in general practice. pad was determined as an ankle-brachial pressure index (abi) 0.9 measured with doppler ultrasound. included patients had a history of ischemic events and/or risk factors for pad, but no spontaneous complaints of intermittent claudication. patients with an abi 0.9 filled in a standardized questionnaire and their drug use was registered. a total of 4 536 patients was included. the prevalence of pad was 18.7 for the total population, 26.5 for those with a history of ischemic events and 15.2 for those without such history. the prevalence increased with age, but was independent of gender. a standard questionnaire revealed leg pain when walking uphill or when hurrying in 2/3 of patients with an abi 0.9 and in 45 criteria for claudication were met.",abi detects pad in a considerable number of asymptomatic patients at increased risk and followed in general practice. when properly questioned almost half of these patients appear to have intermittent claudication.,Prevention
does infrequent delivery of a long-acting pth-fc fusion protein have potent anabolic effects on cortical and cancellous bone?,"skeletal anabolism with pth is achieved through daily injections that result in brief exposure to the peptide. we hypothesized that similar anabolic effects could be achieved with less frequent but more sustained exposures to pth. a pth-fc fusion protein with a longer half-life than pth(1-34) increased cortical and cancellous bmd and bone strength with once- or twice-weekly injections. the anabolic effects of pth are currently achieved with, and thought to require, daily injections that result in brief exposure to the peptide. we hypothesized that less frequent but more sustained exposures to pth could also be anabolic for bone, provided that serum levels of pth were not constant. pth(1-34) was fused to the fc fragment of human igg1 to increase the half-life of pth. skeletal anabolism was examined in mice and rats treated once or twice per week with this pth-fc fusion protein. pth-fc and pth(1-34) had similar effects on pth/pthrp receptor activation, internalization, and signaling in vitro. however, pth-fc had a 33-fold longer mean residence time in the circulation of rats compared with that of pth(1-34). subcutaneous injection of pth-fc once or twice per week resulted in significant increases in bone volume, density, and strength in osteopenic ovariectomized mice and rats. these anabolic effects occurred in association with hypercalcemia and were significantly greater than those achievable with high concentrations of daily pth(1-34). pth-fc also significantly improved cortical bone volume and density under conditions where daily pth(1-34) did not. antiresorptive co-therapy with estrogen further enhanced the ability of pth-fc to increase bone mass and strength in ovariectomized rats.",these results challenge the notion that brief daily exposure to pth is essential for its anabolic effects on cortical and cancellous bone. pth-derived molecules with a sustained circulating half-life may represent a powerful and previously undefined anabolic regimen for cortical and cancellous bone.,Medication
does tgf signaling play a critical role in promoting alternative macrophage activation?,"upon stimulation with different cytokines, macrophages can undergo classical or alternative activation to become m1 or m2 macrophages. alternatively activated (or m2) macrophages are defined by their expression of specific gene products and play an important role in containing inflammation, removing apoptotic cells and repairing tissue damage. whereas it is well-established that il-4 can drive alternative activation, if lack of tgf signaling at physiological levels affects m2 polarization has not been addressed. vav1-cre x triifx/fx mice, lacking trii function in hematopoietic cells, exhibited uncontrolled pulmonary inflammation and developed a lethal autoimmune syndrome at young age. this was accompanied by significantly increased numbers of splenic neutrophils and t cells as well as elevated hepatic macrophage infiltration and bone marrow monocyte counts. trii-/- cd4 and cd8 t-cells in the lymph nodes and spleen expressed increased cell surface cd44, and cd69 was also higher on cd4 lymph node t-cells. loss of trii in bone marrow-derived macrophages (bmdms) did not affect the ability of these cells to perform efferocytosis. however, these cells were defective in basal and il-4-induced arg1 mrna and arginase-1 protein production. moreover, the transcription of genes that are typically upregulated in m2-polarized macrophages, such as ym1, mcr2 and mgl2, was also decreased in peritoneal macrophages and il-4-stimulated trii-/- bmdms. we found that cell surface and mrna expression of galectin-3, which also regulates m2 macrophage polarization, was lower in trii-/- bmdms. very interestingly, the impaired ability of these null mutant bmdms to differentiate into il-4 polarized macrophages was stat6- and smad3-independent, but correlated with reduced levels of phospho-akt and -catenin.","our results establish a novel biological role for tgf signaling in controlling expression of genes characteristic for alternatively activated macrophages. we speculate that lack of trii signaling reduces the anti-inflammatory m2 phenotype of macrophages because of reduced expression of these products. this would cause defects in the ability of the m2 macrophages to negatively regulate other immune cells such as t-cells in the lung, possibly explaining the systemic inflammation observed in vav1-cre x triifx/fx mice.",Treatment
is kras mutation associated with lung metastasis in patients with curatively resected colorectal cancer?,"oncogene mutations contribute to colorectal cancer development. we searched for differences in oncogene mutation profiles between colorectal cancer metastases from different sites and evaluated these as markers for site of relapse. one hundred colorectal cancer metastases were screened for mutations in 19 oncogenes, and further 61 metastases and 87 matched primary cancers were analyzed for genes with identified mutations. mutation prevalence was compared between (a) metastases from liver (n 65), lung (n 50), and brain (n 46), (b) metastases and matched primary cancers, and (c) metastases and an independent cohort of primary cancers (n 604). mutations differing between metastasis sites were evaluated as markers for site of relapse in 859 patients from the victor trial. in colorectal cancer metastases, mutations were detected in 4 of 19 oncogenes: braf (3.1), kras (48.4), nras (6.2), and pik3ca (16.1). kras mutation prevalence was significantly higher in lung (62.0) and brain (56.5) than in liver metastases (32.3; p 0.003). mutation status was highly concordant between primary cancer and metastasis from the same individual. compared with independent primary cancers, kras mutations were more common in lung and brain metastases (p 0.005), but similar in liver metastases. correspondingly, kras mutation was associated with lung relapse (hr 2.1; 95 ci, 1.2 to 3.5, p 0.007) but not liver relapse in patients from the victor trial.","kras mutation seems to be associated with metastasis in specific sites, lung and brain, in colorectal cancer patients. our data highlight the potential of somatic mutations for informing surveillance strategies.",Treatment
does complement c3 contribute to ethanol-induced liver steatosis in mice?,"it is becoming increasingly clear that liver steatosis, a typical early consequence of alcohol exposure, sensitizes the liver to more severe inflammatory and fibrotic changes. on the other hand, activation of the key complement component c3, a central player in causing inflammation and tissue damage, is also known to be involved in the regulation of lipid metabolism. this prompted us to study the development of alcoholic liver steatosis in mice lacking c3 (c3-/-). both c3-/- and normal c3/ mice were fed a steatosis-promoting high-fat diet with or without ethanol for 6 weeks. the diet without ethanol caused moderate liver steatosis in c3-/- but not in c3/ mice. as expected, ethanol-containing diet caused marked macrovesicular steatosis and increased the liver triglyceride content in c3/ mice. in contrast, ethanol diet tended to reduce steatosis and had no further effect on liver triglycerides in c3-/- mice. furthermore, while in normal mice ethanol significantly increased the liver/body weight ratio, liver malondialdehyde level and serum alanine aminotransferase (alt) activity, these effects were absent or small in c3-/- mice. a separate experiment with mice on chow diet confirmed the aberrant steatotic effect of ethanol in c3-/-mice: 4 hours after acute dosing of ethanol the liver triglyceride level had increased by 138 in c3/ mice (p0.001), but only by 64 in c3-/- mice (n.s.).",in c3-/- mice alcohol-induced liver steatosis is absent or strongly reduced after chronic or acute alcohol exposure. this suggests that the complement system and its component c3 contribute to the development of alcohol-induced fatty liver and its consequences.,Prevention
does prometastatic nedd9 regulate individual cell migration via caveolin-1-dependent trafficking of integrins?,"the dissemination of tumor cells relies on efficient cell adhesion and migration, which in turn depends upon endocytic trafficking of integrins. in the current work, it was found that depletion of the prometastatic protein, nedd9, in breast cancer cells results in a significant decrease in individual cell migration due to impaired trafficking of ligand-bound integrins. nedd9 deficiency does not affect the expression or internalization of integrins but heightens caveolae-dependent trafficking of ligand-bound integrins to early endosomes. increase in mobility of ligand-bound integrins is concomitant with an increase in tyrosine phosphorylation of caveolin-1 (cav1) and volume of cav1-vesicles. nedd9 directly binds to cav1 and colocalizes within cav1 vesicles. in the absence of nedd9, the trafficking of ligand-bound integrins from early to late endosomes is impaired, resulting in a significant decrease in degradation of ligand-integrin complexes and an increase in recycling of ligand-bound integrins from early endosomes back to the plasma membrane without ligand disengagement, thus leading to low adhesion and migration. reexpression of nedd9 or decrease in the amount of active, tyrosine 14 phosphorylated (tyr14) cav1 in nedd9-depleted cells rescues the integrin trafficking deficiency and restores cellular adhesion and migration capacity. collectively, these findings indicate that nedd9 orchestrates trafficking of ligand-bound integrins through the attenuation of cav1 activity.",this study provides valuable new insight into the potential therapeutic benefit of nedd9 depletion to reduce dissemination of tumor cells and discovers a new regulatory role of nedd9 in promoting migration through modulation of cav1-dependent trafficking of integrins.,General
does intrathecal dexmedetomidine attenuate hypercapnic but not hypoxic cerebral vasodilation in anesthetized rabbits?,"systemic dexmedetomidine (dxm) attenuates the cerebral vasodilation induced by hypercapnia and decreases the cerebral blood flow response to hypoxia. we determined whether lumbar intrathecal dxm affected the cerebrovascular reactivity to hypercapnia and hypoxia. rabbits (n 55) anesthetized with pentobarbital were prepared for measurement of pial vessel diameters using a closed cranial window preparation. the first study evaluated the response to hypercapnia after intrathecal administration of dxm (2 microg/kg; n 7) or normal saline (n 8). the second evaluated the response to hypercapnia after intrathecal dxm in the presence of yohimbine (20 microg/kg followed by dxm 2 microg/kg; n 7). the third evaluated the response to mild or moderate hypoxia after intrathecal dxm (2 microg/kg; n 7) or normal saline (n 7). the hypercapnic responses were also examined in the presence of systemic dxm (2, 10 microg/kg; n 6), topical dxm (10-8 m, 10-6 m; n 6) and of intrathecal clonidine (2 microg/kg; n 7). the pial arteriolar dilator response to hypercapnia was significantly attenuated after intrathecal administration of dxm. pretreatment with yohimbine completely blocked the decreased reactivity to hypercapnia. intrathecal clonidine, although less than dxm, also attenuate the hypercapnic response. intrathecal dxm did not affect the vasodilation of pial arterioles induced by mild or moderate hypoxia. the systemic dxm 10 microg/kg and topical dxm 10-6 m, but not systemic 2 microg/kg and topical 10-8 m, attenuated hypercapnic vasodilation of pial arterioles.","the presence of alpha2-adrenoceptor agonist administered intrathecally into the lumbar spinal region attenuates hypercapnic but not hypoxic cerebral vasodilation, probably via a stimulation of central alpha2-adrenergic receptors of the central nervous system.",Medication
do variant rs1421085 in the fto gene contribute childhood obesity in chinese children aged 3-6 years?,"childhood obesity has become a public health crisis worldwide due to an alarming increase in its prevalence. numerous studies have demonstrated that the common variants (rs1421085 and rs17817449) of the fat mass and obesity associated (fto) gene are associated with the obesity in adult and children in european. however, these two variants of fto gene in childhood obesity have not been established in chinese populations. in this population-based case-control study, 158 obese preschooler and 397 normal population controls aged 3-6 years were recruited between june 2007 and april 2008 from 6 kindergartens of huai-an city in jiangsu province, china. all the children were conducted the body examinations and provided blood sample to detect the serum lipid levels and fto rs1421085 tc and rs17817449 tg genetic variances. in the association analysis between the fto gene variant and risk of childhood obesity, compared with the rs1421085tt wide-type genotype, rs1421085 cc and ct/cc genotypes were associated with 59 and 71 increased risks of childhood obesity (adjusted or 1.59, 95ci 1.00-2.53 for cc; adjusted or 1.71, 95ci 1.10-2.65 for ct/cc), while the rs17817449 t g variant was not associated with the significantly increased risk of childhood obesity. in addition, the higher level of serum tg (0.64 mmol/l) was associated with 93 increased risk of childhood obesity (adjusted or 1.93, 95ci 1.30-2.87), and the higher serum hdl-c level (1.14 mmol/l) was associated with 45 decreased risk of childhood obesity (adjusted or 0.55, 95ci 0.37-0.81). but the quantitative phenotypes analysis regarding the levels of tc, tg, hdl-c, and ldl-c were not found to be significantly associated with the variants of rs1421085 and rs17817449 both in the cases and controls.",the fto rs1421085 tc polymorphism may modulate the magnitude of dyslipidemia in chinese early-onset obesity.,Prevention
is the triglyceride content in skeletal muscle associated with hepatic but not peripheral insulin resistance in elderly twins?,"total muscle triglyceride (mt) content has been associated with insulin resistance. we investigated the predictors and impact of mt on relevant metabolic parameters including peripheral and hepatic insulin resistance in elderly twins. seventy-four elderly same-sex twins underwent hyperinsulinemic euglycemic clamps preceded by an iv glucose tolerance test. aerobic capacity (vo2max) and body composition (dual-energy x-ray absorptiometry scan) were determined in all twins. a biopsy from the vastus lateralis muscle was excised in the fasting state. the muscle triacylglycerol content was analyzed by biochemical extraction from these biopsies. the percentage of total body fat was the only independent predictor of mt content. after adjustment for trunk fat percentages and sex, mt level was significantly associated to fasting plasma levels of glucose and insulin as well as hepatic insulin resistance. however, the association was weakened after adjustment for total fat percentages. a 1 sd (34.5 mmol/kg dry weight) increase in mt content was associated with a 24 increase of hepatic insulin resistance. no association between mt content and peripheral insulin sensitivity was observed.","mt content is associated with hepatic but not peripheral insulin resistance in elderly twins. we speculate that mt content may reflect the general ectopic accumulation of triglycerides, including fat in the liver.",Medication
is previous pregnancy a favourable prognostic factor in women with localised cutaneous melanoma?,"the influence of pregnancy on survival in melanoma has been a controversial issue. in this retrospective study we investigated whether pregnancy (overall or temporally melanoma-related) has any effect on melanoma progression or patient outcome. patient data were collected from turku university hospital records concerning all women in fertile age (15-45 years) and diagnosed with melanoma between january 1, 1990 and december 31, 2009. we collected data on melanoma characteristics, treatment, pregnancies and patient outcomes. of the 334 patients, 248 (74) had been pregnant in some point during their life while 55 (17) were nulliparous. the history of pregnancies could not be verified in 31 women (9). progression of melanoma to advanced stage was found in 58 (17) of these women. altogether, 35 women (14) with at least one pregnancy had disease progression in contrast to 14 women (26) with no pregnancies (p 0.049). women with at least one pregnancy had a 94 probability to survive from melanoma compared to nulliparous women of whom only 83 survived (p 0.041). in multivariate (cox) analysis pregnancy was a favourable factor for disease-specific survival (dss) (hr 3.75; 95 ci 1.24-11.34; p 0.019) when adjusted for age (hr 1.064; 95 ci 1.00-1.13; p 0.50), localisation and stage (p 0.040), and breslow (hr 1.32; 95 ci 1.10-1.58; p 0.002). however, when ulceration of the primary tumour was included in the multivariate model, breslow remained as the only independent predictor of dss (hr 1.58; 95 ci 1.34-1.86; p 0.0001) and pregnancy was dropped from the stepwise backward model in the step preceding the last one (p 0.081).","pregnancy is not a risk factor for disease recurrence or progression in melanoma patients, but instead can exert some favourable influence on prognosis.",Diagnosis
are increases in electroencephalogram and electromyogram variability associated with an increased incidence of intraoperative somatic response?,"sbis, the variability of the bispectral index (bis), semg, the variability of facial electromyogram power (emg), and the composite variability index (cvi) are 3 new measures of electroencephalogram and emg variability. cvi is a single measure of the combined variability in bis and emg. we investigated whether increases in these variables are associated with intraoperative somatic responses. this multicenter study included 120 patients undergoing elective, noncardiac surgery from 4 different sites. general anesthesia was maintained using propofol and remifentanil at 2 of the sites and sevoflurane and remifentanil at the 2 other sites. propofol or sevoflurane was adjusted to maintain bis between 45 and 60. clinicians were blinded to cvi (v2.0) at all times, and remifentanil infusions were adjusted at the discretion of the clinician. the times of all intraoperative somatic events, defined as movement, grimacing, or eye opening, were recorded. offline, the maintenance phase of each case was divided into consecutive, nonoverlapping, 10-minute segments. segments were identified as containing a somatic event or containing no events. for each segment, mean sbis, semg, and cvi and the heart rate (hr) range and mean arterial blood pressure range were calculated. to quantify how effectively each variable discriminated between somatic event segments and nonevent segments, we computed the area under the receiver operating characteristic (roc) curve for each variable. finally, we observed the time course of sbis, semg, cvi, and the hr range before each somatic event and characterized the earliest time before the somatic event at which each variable was able to discriminate between the somatic events and a specified set of nonevents. the analysis included 33 somatic event segments and 829 nonevent segments from 105 surgical cases. the areas under the roc curve (se) for sbis, semg, and cvi were 0.83 0.04, 0.92 0.02, and 0.89 0.03, respectively. the areas under the roc curve for hr range and mean arterial blood pressure range were 0.77 0.03 and 0.68 0.05, respectively. cvi, sbis, and semg all demonstrated higher average values before upcoming somatic events when compared with nonevents. hr range only showed a difference within a few seconds before the somatic event.","sbis, semg, and cvi, measures of electroencephalogram and emg variability, increased when intraoperative somatic events occurred. sbis, semg, and cvi discriminated between 10-minute segments that contained a somatic event and those segments that did not contain an event better than changes in hr and mean arterial blood pressure. furthermore, cvi increases before somatic events began earlier than hr changes and may provide caregivers with an early warning of potentially inadequate antinociception.",Medication
are t2 relaxation times increased in skeletal muscle of dmd but not bmd patients?,"exon-skipping drugs in duchenne muscular dystrophy (dmd) aim to restore truncated dystrophin expression, which is present in the milder becker muscular dystrophy (bmd). mri skeletal muscle t2 relaxation times as a representation of edema/inflammation could be quantitative outcome parameters for such trials. we studied t2 relaxation times, adjusted for muscle fat fraction using dixon mri, in lower leg muscles of dmd and bmd patients and healthy controls. t2 relaxation times correlated significantly with fat fractions in patients only (p 0.001). after adjusting for muscle fat, t2 relaxation times were significantly increased in 6 muscles of dmd patients (p 0.01), except for the extensor digitorum longus. in bmd, t2 relaxation times were unchanged.",t2 relaxation times could be a useful outcome parameter in exon-skipping trials in dmd but are influenced by fat despite fat suppression. this should be accounted for when using quantitative t2 mapping to investigate edema/inflammation.,Medication
are increased levels of stress and burnout related to decreased physician experience and to interventional gastroenterology career choice : findings from a us survey of endoscopists?,"physician stress and burnout can decrease job satisfaction, increase medical errors, and reduce quality of life. gastrointestinal endoscopic practice is increasing in complexity, with an associated increase in complications. these factors may result in more stress and burnout in younger gastroenterologists (ges) and interventional ges (iges) who perform more complex endoscopic procedures. we aimed to create a valid measure of ge endoscopic practice stress and to evaluate stress and burnout related to endoscopist experience and ige versus non-ige practice. we used both a qualitative and a cross-sectional correlation design. semistructured interviews were conducted and thematically coded to create a measure of stressors in ge practice, the gastroenterologist stress inventory (gesi). gastroenterology fellows and attending physicians were approached to participate. four ges were interviewed, and 489 completed the online survey. endoscopists completed the maslach burnout inventory, the gesi, and demographic, training, and practice data. the gesi met reliability standards. junior iges and junior non-iges reported more stress related to endoscopic practice than senior attendings. all ges reported moderate levels of burnout; decreased physician experience was a predictor of burnout for iges.","ges report moderate levels of stress and burnout. iges and those who have experienced an endoscopic complication report significantly more stress. less experience is related to more stress and burnout, with junior iges reporting the highest levels.",Treatment
is systemic ketoconazole an effective treatment of atopic dermatitis with ige-mediated hypersensitivity to yeasts?,"ige-mediated hypersensitivity to yeasts is often seen in atopic dermatitis (ad) patients, especially when dermatitis is located in the head, neck, and shoulder regions. two studies have shown the efficacy of ketoconazole in the treatment of this type of ad, in contrast to results of topical treatment. the objective was to assess the clinical efficacy of antifungal treatment in ad in a randomized, double-blind, placebo-controlled study with oral ketoconazole and yeast-specific ige levels and saprophytic yeast growth monitored simultaneously. eighty patients with ad and positive p. ovale and/or c. albicans rast/skin prick test results were randomized to receive ketoconazole or placebo for 30 days. the yeast growth of skin and pharynx; p. ovale, c. albicans, ands. cerevisiae rast; serum total ige; and the severity of the eczema (scorad) were assessed at day 0 and thereafter at 1 and 3 months. a significant improvement was seen in the scorad scale in the ketoconazole group at the second visit in comparison to the first visit (p0.0005; n36), but not in the placebo group (n39). of the individual determinants of the scorad, itching (p0.005), the extent of dermatitis (area percentage), excoriation, lichenification (p0.01), erythema, papulation, and dryness (p0.05) improved significantly in the ketoconazole group. in the placebo group, only the extent of dermatitis (area percentage) decreased significantly (p0.05). in the ketoconazole group, the number of positive p. ovale cultures decreased from 60 to 31 (n35) compared to the placebo group (64 to 56; n39). the clinical response was most significant in female patients with positive yeast cultures.","saprophytic yeasts may be a source of allergens in ad. thus, patients with ad, yeast growth, and elevated ige levels to yeasts should be offered antifungal treatment.",Treatment
"is self-efficacy for managing pain associated with disability , depression , and pain coping among retirement community residents with chronic pain?","little is known about cognitive and behavioral factors that influence older adults' adjustment to chronic pain. the objective of this study was to investigate the relationship of self-efficacy for managing pain to reports of pain intensity, pain-related disability, depressive symptoms, and pain coping strategy use among 140 retirement community residents (88 female; age mean 81.7, range 66-99 years) with chronic pain. the 8-item arthritis self-efficacy scale, modified to specify pain rather than arthritis, demonstrated good psychometric characteristics (cronbach alpha .89, minimal floor and ceiling effects, and validity) in this sample. controlling for age, gender, and pain intensity, self-efficacy was associated significantly and negatively with pain-related disability and depressive symptoms (p values .001), and positively with use of pain coping strategies previously found to be associated with better outcomes (task persistence, exercise/stretch, coping self-statements, activity pacing; p values .05). self-efficacy for managing pain appears to be important in the adjustment of older adults with pain. research is needed to determine whether interventions designed to increase self-efficacy improve quality of life and prevent functional declines in this population.","among retirement community residents (mean age of 82 years) with chronic pain, higher self-efficacy for managing pain is associated with less disability and depression and with the use of pain coping strategies related to better adjustment. this suggests the potential value of interventions to increase self-efficacy in this population.",Symptoms
"are cerebral hemodynamics and systemic endothelial function already impaired in well-controlled type 2 diabetic patients , with short-term disease?","impaired cerebral vasomotor reactivity (vmr) and flow-mediated dilation (fmd) were found in selected subgroups of type 2 diabetes mellitus (t2dm) patients with long-term disease. our study aimed to evaluate cerebral hemodynamics, systemic endothelial function and sympatho-vagal balance in a selected population of well-controlled t2dm patients with short-term disease and without cardiac autonomic neuropathy (can). twenty-six t2dm patients with short-term (4.404.80 years) and well-controlled (hba1c 6.711.29) disease, without any complications, treated with diet and/or metformin, were consecutively recruited. eighteen controls, comparable by sex and age, were enrolled also. fmd and shear rate fmd were found to be reduced in t2dm subjects with short-term disease (8.5 sd 3.5 and 2.5 sd 1.3, respectively) compared to controls (15.4 sd 4.1 and 3.5 sd 1.4; p.05).",in well-controlled t2dm patients with short-term disease cerebral hemodynamics and systemic endothelial function are altered while autonomic balance appeared to be preserved.,Medication
is time now : venous thromboembolism prophylaxis in blunt splenic injury?,the safety and timing of venous thromboembolism (vte) prophylaxis in patients with blunt splenic injuries is not well known. we hypothesized that early initiation of vte prophylaxis does not increase failure of nonoperative management or transfusion requirements in these patients. a retrospective review of trauma patients with blunt splenic injury was performed. patients were compared based on initiation and timing of vte prophylaxis (72 hours). patients who received vte prophylaxis were matched with those who did not. primary outcomes included were operation or angioembolization. a total of 497 patients (256 received vte prophylaxis and 241 did not) were included. there was no difference in the number of interventions based on presence of or time to vte prophylaxis initiation.,"early initiation (48 hours) of vte prophylaxis is safe in patients with blunt splenic injuries treated nonoperatively, and may be safe as early as 24 hours.",Prevention
does endogenous interleukin-10 regulate th1 responses that induce crescentic glomerulonephritis?,"interleukin (il)-10 plays a pivotal role in regulating the th1/th2 predominance of immune responses. exogenously administered il-10 suppresses nephritogenic th1 responses, inhibits macrophage function, and attenuates crescentic glomerulonephritis (gn). to determine the role of endogenous il-10, the development of the nephritogenic immune response and crescentic gn was compared in il-10-deficient (il-10-/-) and normal (il-10/) c57bl/6 mice. gn was initiated in sensitized mice by the intravenous administration of sheep antimouse glomerular basement membrane globulin. renal injury was evaluated 21 days later. following the administration of anti-glomerular basement membrane globulin, normal (il-10/) c57bl/6 mice developed proliferative gn with occasional crescents, glomerular cd4 t-cell and macrophage accumulation, and fibrin deposition. using an identical induction protocol, il-10-/-mice developed more severe gn. crescent formation (il-10-/-, 23 /- 2 of glomeruli; il-10/, 5 /- 2), glomerular cd4 t cells il-10-/-, 1. 0 /- 0.2 cells per glomerular cross-section (c/gcs); il-10 /, 0.3 /- 0.05 c/gcs, glomerular macrophages (il-10-/-, 4.8 /- 0.3 c/gcs; il-10 /, 1.7 /- 0.2 c/gcs), fibrin deposition fibrin score (range 0 to 3); il-10-/-, 1.10 /- 0.04; il-10/, 0.6 /- 0. 07, and serum creatinine (il-10-/-, 30 /- 2 micromol/l; il-10 /, 23 /- 1 micromol/l) were all significantly increased in il-10-/- mice (p 0.05). circulating antibody (il-10-/-, 1.05 /- 0.16 od units; il-10/, 0.63 /- 0.08 od units) and cutaneous delayed-type hypersensitivity (skin swelling; il-10-/-, 0.21 /- 0.03 mm; il-10/, 0.12 /- 0.02 mm) to the nephritogenic antigen (sheep globulin) were also increased (both p 0.05). interferon-gamma production by cultured splenocytes was increased (il-10-/- 7.9 /- 2. 5 ng/4 x 106 cells, il-10/ 0.28 /- 0.09 ng/4 x 106 cells, p 0. 05), but il-4 production was unchanged.",endogenous il-10 counter-regulates nephritogenic th1 responses and attenuates crescentic gn.,Medication
do the kidneys play an important role in the clearance of rfviia in rats?,"previous distribution and histological studies have indicated that the kidneys and renal proximal tubular cells play a role in clearance of rfviia. however, the relative importance of the kidneys in clearance of rfviia has not previously been addressed. the objective of the present study was to evaluate the importance of the kidneys in the clearance process of rfviia after iv administration to rats using a nephrectomy model. a nephrectomized rat model was established and validated using inulin, a compound primarily cleared by the kidneys, as a test substance and several physiological parameters were monitored to ensure viability and robustness of the model. the model was then used for pharmacokinetic evaluation of renal clearance of rfviia. the pharmacokinetic parameters for rfviia were evaluated both by use of standard non-compartmental methods and by use of mixed effects methods, where a pharmacokinetic model was used to simultaneously model all data from healthy, sham operated, and nephrectomized rats. nephrectomized animals showed stable rectal temperature, spo2 and pulse and as expected, clearance of inulin was essentially abolished compared to control animals (p0.001). for rfviia, nephrectomy resulted in a clearance and terminal half-life of 34ml/h/kg and 2.8h compared to 68ml/h/kg and1.9h in rats exposed to sham surgery (p0.0001 for both parameters).",the present data show that about 50 of the total clearance of rfviia from circulation in rats under isoflurane anaesthesia is due to renal clearance.,Treatment
"are serum her2 extra-cellular domain , s100 and ca 15-3 levels independent prognostic factors in metastatic breast cancer patients?","metastatic breast cancer (mbc) prognosis is highly variable, depending on various factors such as the biological subtype, the performance status, disease extension. a better evaluation of a patient's prognostic factors could allow for a more accurate choice of treatments. the role of serum tumor markers remains, however, unclear in this population. considering the recent interest in phenotypic changes and tumor heterogeneity during breast cancer progression, additional tumor markers could be interesting in this setting. two hundred fifty mbc patients treated at the montpellier cancer institute (2008-2015) were retrospectively selected, based on the availability of frozen serum samples. the usual mbc clinical and pathological variables were collected, altogether with cancer antigen 15-3 (ca15-3), carcinoembryonic antigen (cea), her2 extra-cellular domain (ecd), neuron specific enolase (nse), s100 protein and matrix metalloproteinase 9 (mmp-9) serum levels in order to determine their prognostic value. with a median follow-up of 40.8 months, median overall survival was 16.2 months (95 ci 12.4-20.6). in multivariate analysis, the performance status, brain or subcutaneous metastases, the number of previous metastatic chemotherapy lines and the tumor biological subtype were independent prognostic factors. elevated ca 15-3 (hr 1.95, ic 95 1.31-2.93, p 0.001), her2 ecd (regardless of tumor her2 status, hr 2.51, ic 95 1.53-4.12, p 0.001) and s100 (hr 1.93, ic 95 1.05-3.54, p 0.033) serum levels were independently associated with a poor outcome.","serum ca 15-3, her2 ecd and s100 could represent useful independent prognostic factors in mbc. of particular interest is the independent value of serum her2 ecd levels, regardless of the tumor her2 status, possibly linked to metastatic tumor heterogeneity.",Diagnosis
does octreotide increase the proportions of arachidonic acid-rich phospholipids in gall-bladder bile?,"octreotide treatment of acromegalic patients induces cholesterol gallstone formation, in part by impairing cholecystokinin release and gall-bladder contraction. however, there are few data on the effect of octreotide on biliary arachidonic acid-rich phospholipids or mucin glycoprotein, factors which also influence cholesterol gallstone formation. in acromegalic patients studied before and during 3 months of octreotide treatment, we measured mucin glycoprotein concentrations and the molecular species of phosphatidylcholine, and related the results to the cholesterol saturation and percentage of deoxycholic acid in gall-bladder bile. the relative proportions of the major arachidonic acid-rich phosphatidylcholine species, pc 16:0-20:4 and pc 18:0-20:4, increased significantly during octreotide treatment. these changes were associated with a rise in the cholesterol saturation index and a non-significant twofold increase in mucin glycoprotein concentration. there were significant correlations between pc 16:0-20:4 and the cholesterol saturation index, percentage of vesicular cholesterol and percentage of deoxycholic acid in gall-bladder bile.","in acromegalic patients, octreotide increases the proportions of arachidonic acid-rich phospholipids, with associated rises in: (a) the cholesterol saturation index and percentage of vesicular cholesterol, and (b) the percentage of deoxycholic acid in gall-bladder bile-changes similar to those found in patients with cholesterol-rich gall-bladder stones.",Treatment
does fak inhibition abrogate the malignant phenotype in aggressive pediatric renal tumors?,"despite the tremendous advances in the treatment of childhood kidney tumors, there remain subsets of pediatric renal tumors that continue to pose a therapeutic challenge, mainly malignant rhabdoid kidney tumors and nonosseous renal ewing sarcoma. children with advanced, metastatic, or relapsed disease have a poor disease-free survival rate. focal adhesion kinase (fak) is a nonreceptor tyrosine kinase that is important in many facets of tumor development and progression. fak has been found in other pediatric solid tumors and in adult renal cellular carcinoma, leading to the hypothesis that fak contributes to pediatric kidney tumors and would affect cellular survival. in the current study, fak was present and phosphorylated in pediatric kidney tumor specimens. moreover, the effects of fak inhibition upon g401 and sk-nep-1 cell lines were examined using a number of parallel approaches to block fak, including rna interference and small-molecule fak inhibitors. fak inhibition resulted in decreased cellular survival, invasion and migration, and increased apoptosis. furthermore, small-molecule inhibition of fak led to decreased sk-nep-1 xenograft growth in vivo. these data deepen the knowledge of the tumorigenic process in pediatric renal tumors, and provide desperately needed therapeutic strategies and targets for these rare, but difficult to treat, malignancies.","this study provides a fundamental understanding of tumorigenesis in difficult to treat renal tumors and provides an impetus for new avenues of research and potential for novel, targeted therapies.",Treatment
do mitochondria-derived reactive intermediate species mediate asbestos-induced genotoxicity and oxidative stress-responsive signaling pathways?,"the incidence of asbestos-induced human cancers is increasing worldwide, and considerable evidence suggests that reactive oxygen species (ros) are important mediators of these diseases. our previous studies suggested that mitochondria might be involved in the initiation of oxidative stress in asbestos-exposed mammalian cells. we investigated whether mitochondria are a potential cytoplasmic target of asbestos using a mitochondrial dna-depleted ((0)) human small airway epithelial (sae) cell model: (0) sae cells lack the capacity to produce mitochondrial ros. we examined nuclear dna damage, micronuclei (mn), intracellular ros production, and the expression of inflammation-related nuclear genes in both parental and (0) sae cells in response to asbestos treatment. asbestos induced a dose-dependent increase in nuclear dna oxidative damage and mn in sae cells. furthermore, there was a significant increase in intracellular oxidant production and activation of genes involved in nuclear factor b and proinflammatory signaling pathways in sae cells. in contrast, the effects of asbestos were minimal in (0) sae cells.","mitochondria are a major cytoplasmic target of asbestos. asbestos may initiate mitochondria-associated ros, which mediate asbestos-induced nuclear mutagenic events and inflammatory signaling pathways in exposed cells. these data provide new insights into the molecular mechanisms of asbestos-induced genotoxicity.",Medication
do adjustment of gut hormones release pattern following a fixed mealtime change in human?,"gut hormones secretion is related to habitual mealtimes. however, how fast gut hormones adjust to that change when people change their fixed mealtime remains unknown. seven healthy male volunteers were asked to eat a test breakfast at 0700 am for 2 weeks before the start of the study. then, their fixed mealtime was intentionally changed from 0700 am to 0900 am for next 2 weeks. blood samples were drawn every half hour from 0500 am until next 3h after breakfast for determining gut hormone levels every week. after a change in fixed mealtime, the release pattern of acylated ghrelin was first adjusted identically according to the change and then total ghrelin was made. the meal-related fluctuations of acylated ghrelin were delayed by 120 min from week 1 after the change, while those of total ghrelin were delayed by 60 min at week 1, by 120 min at week 2. two weeks was not enough time to adjust completely for pyy(3-36) to the change.","two weeks is enough time until the pattern release of ghrelin, but not pyy(3-36) , is adjusted fully after a fixed mealtime change in human.",General
does mitokatp channel activation suppress gap junction permeability in the ischemic myocardium by an erk-dependent mechanism?,"ischemic preconditioning accelerates suppression of gap junction (gj) permeability during myocardial ischemia, and gj blockers reduce infarct size. we hypothesized that the mitochondrial atp-sensitive k (mitokatp) channel is one of the mechanisms regulating gj permeability through the mitogen-activated protein kinase erk, leading to cardioprotection. in isolated rabbit hearts, tissues were sampled before and after infusion of diazoxide, a selective mitokatp channel opener, and their intercalated disc-rich fractions were obtained for immunoblotting of mitogen-activated protein kinases. gj permeability in the myocardium was assessed by using lucifer yellow as a tracer of gj communication. infarction was induced by 30-min global ischemia/2 h reperfusion, and infarct size was expressed as a percent of area-at-risk (is/ar). diazoxide (100 microm) induced phosphorylation of erk1/2 and 279ser/282ser of connexin-43, a gj subunit protein, and phospho-erk1/2 was co-immunoprecipitated with connexin-43 in the diazoxide-treated myocardium. this erk1/2 phosphorylation by diazoxide was inhibited by n-2-mercaptopropionyl-glycine, a free radical scavenger. diazoxide at 10 and 100 microm reduced intercellular transport of lucifer yellow during ischemia by 44 and 69, respectively, and this effect of diazoxide on gj communication was abolished by pd98059, an erk inhibitor. pretreatment with 10 microm and 100 microm diazoxide reduced is/ar from 57.1/-3.7 to 21.5/-10.5 and 5.0/-1.3, respectively. pd98059 abolished cardioprotection by 10 microm diazoxide but not that by 100 microm diazoxide.",opening of the mitokatp channel activates erk1/2 via free radicals and induces erk-mediated suppression of gj permeability. this suppression of gj permeability may partly contribute to cardioprotection afforded by mitokatp channel activation.,Medication
is perineural invasion a prognostic factor in intrahepatic cholangiocarcinoma?,"perineural invasion is commonly observed in biliary tract cancer and is an independent prognostic factor. since intrahepatic cholangiocarcinoma (icc) develops from biliary epithelia in the liver, icc may share the same characteristics in terms of the prognostic implications of perineural invasion. the aim of this study was to evaluate the clinical significance of perineural invasion in icc. a total of 59 patients with icc who underwent hepatectomy were retrospectively reviewed. the numbers of nerves with and without tumor involvement were counted. the perineural invasion index (pni) was calculated as the number of involved nerves divided by the total number of nerves examined. predictors for perineural invasion and prognostic factors were analyzed. perineural invasion was observed in 47 of 59 (80) patients, and the median pni was 0.082. the macroscopic tumor appearance and tumor location were significantly associated with perineural invasion (p 0.013 and 0.032, respectively). univariate and multivariate analyses (excluding seven in-hospital deaths) revealed that histologic grade, the presence of perineural invasion, nodal metastasis, and intrahepatic metastasis were independent prognostic factors. the survival rate of the patients with (n 42) or without (n 10) perineural invasion was 17 and 80 at 3 years; and 17 and 70 at 5 years, respectively (p 0.001).","perineural invasion is frequently found in patients with icc and is an independent prognostic factor. icc is an aggressive tumor similar to other biliary tract cancers. because perineural invasion is a histologic marker of aggressiveness, it potentially has a role as a determinant of patient selection for adjuvant therapy.",Diagnosis
does deletion polymorphism of the angiotensin converting enzyme gene predict persistent proteinuria in henoch-schnlein purpura nephritis?,"to study the influence of deletion/insertion polymorphism in the 16th intron of the angiotensin converting enzyme (ace) gene on clinical manifestations of henoch-schnlein purpura nephritis. cross sectional study. ace gene polymorphism was determined in patients (4-15 years old at onset) with henoch-schnlein purpura nephritis (n 40) and compared with that in patients with iga nephropathy (n 79). ace genotypes, systemic blood pressures, urine protein excretion rate, haematuria, creatinine clearance, serum ace activities. the initial clinical manifestations of both henoch-schnlein purpura nephritis and iga nephropathy were no different among homozygotes for insertion (ii) and deletion (dd), and heterozygotes (id) for the ace gene. in patients with henoch-schnlein purpura nephritis, the incidence of moderate to heavy proteinuria at four and eight years after onset was more than five times higher in the dd genotype than in the ii or id genotypes. no such trend was seen in patients with iga nephropathy. the number of patients with henoch-schnlein purpura nephritis in whom proteinuria resolved at four and eight years after onset was significantly lower in the dd genotype compared with the ii genotype, whereas no differences were detected among the three different genotypes in patients with iga nephropathy. plasma ace activities in patients with the dd genotype were significantly higher than in those with non-dd genotypes.",the ace dd genotype predicts persistent proteinuria in henoch-schnlein purpura nephritis. the proteinuria might be related to a defective angiotensin system which is genetically determined by the d/i polymorphism.,Symptoms
does basic fibroblast growth factor autocrine loop control human osteosarcoma phenotyping and differentiation?,"we focused on the phenotype of non-mineralizing mg 63 and mineralizing te 85 human osteosarcoma cells and investigated the role of bfgf in modulating their differentiative responses. basic fgf expression and bfgf effects on osteocalcin, runt-related transcription factor-2 (runx2), matrix molecular production and bfgf receptors, were evaluated. osteocalcin and runx2 gene expression were studied by rt-pcr analysis. we evaluated cell proliferation by dna content and performed differentiation studies on glycosaminoglican (gag), collagen and proteoglican (pg) synthesis by using radiolabelled precursors and northern blotting. bfgf receptors were quantified by bfgf receptor binding assay. osteocalcin is expressed in mg63 and te65. runx2 rna is differentially spliced in the two cell lines. bfgf elicits the effects of differentially splicing runx2. proliferation, gag synthesis, bfgf and proteoglycan mrna expression, high and low affinity bfgf receptors, were more marked in mg 63 and differently affected by bfgf. procollagen expression and alkaline phosphatase activity were significantly reduced. bfgf increased te 85 cell proliferation and reduced te 85 procollagen and osteocalcin production.",the different splice variants in runx2 gene in the two cell lines might be related to their different phenotypes. the less differentiated stage of mg63 could also be related to bfgf over-production and more bfgf receptors. the consequent increase in bfgf-bfgf receptor binding could explain the bfgf differentiative effects on mg 63. we suggest an autocrine role of bfgf endogenous release in controlling the different osteosarcoma phenotypes.,Medication
does hepatocyte growth factor stimulate dna synthesis in rat preneoplastic hepatocytes but not in liver carcinoma cells?,"it is not well clarified whether hepatocyte growth factor (hgf) stimulates the growth of preneoplastic hepatocytes and liver carcinoma cells in vivo. the effect of hgf on in vivo dna synthesis in these cells and also its effect on tyrosine phosphorylation of the hgf receptor protein (c-met) in liver carcinoma were examined. lesions were induced in rats using 3'-methyl-4-dimethylaminoazobenzene (3'-me-dab). the rats were given intravenous recombinant human hgf or vehicle, and dna synthesis was assessed by the 5-bromo-2'-deoxyuridine labeling index. tyrosine phosphorylation of c-met by hgf was analyzed by western blot. the labeling indices were significantly higher in the hgf group than in the vehicle control group in altered foci and hyperplastic nodules (preneoplastic hepatic lesions). no significant differences in the labeling indices were observed between the two groups with carcinoma. tyrosine phosphorylation of c-met in carcinoma cells was unaffected by hgf administration.",hgf promotes the growth of preneoplastic hepatocytes but does not affect the growth of liver carcinoma cells in 3'-me-dab-treated rats.,Medication
does strength exercise improve muscle mass and hepatic insulin sensitivity in obese youth?,"data on the metabolic effects of resistance exercise (strength training) in adolescents are limited. the objective of this study was to determine whether a controlled resistance exercise program without dietary intervention or weight loss reduces body fat accumulation, increases lean body mass, and improves insulin sensitivity and glucose metabolism in sedentary obese hispanic adolescents. twelve obese adolescents (age 15.5 0.5 yr, body mass index 35.3 0.8 kgm; 40.8 1.5 body fat) completed a 12-wk resistance exercise program (two times 1 hwk, exercising all major muscle groups). at baseline and on completion of the program, body composition was measured by dual-energy x-ray absorptiometry, abdominal fat distribution was measured by magnetic resonance imaging, hepatic and intramyocellular fat was measured by magnetic resonance spectroscopy, peripheral insulin sensitivity was measured by the stable-label intravenous glucose tolerance test, and hepatic insulin sensitivity was measured by the hepatic insulin sensitivity index 1000/(gpr fasting insulin). glucose production rate (gpr), gluconeogenesis, and glycogenolysis were quantified using stable isotope gas chromatography/mass spectrometry techniques. all participants were normoglycemic. the exercise program resulted in significant strength gain in both upper and lower body muscle groups. body weight increased from 97.0 3.8 to 99.6 4.2 kg (p 0.01). the major part (80) was accounted for by increased lean body mass (55.7 2.8 to 57.9 3.0 kg, p 0.01). total, visceral, hepatic, and intramyocellular fat contents remained unchanged. hepatic insulin sensitivity increased by 24 9 (p 0.05), whereas peripheral insulin sensitivity did not change significantly. gpr decreased by 8 1 (p 0.01) because of a 12 5 decrease in glycogenolysis (p 0.05).","we conclude that a controlled resistance exercise program without weight loss increases strength and lean body mass, improves hepatic insulin sensitivity, and decreases gpr without affecting total fat mass or visceral, hepatic, and intramyocellular fat contents.",Prevention
does vascular endothelial growth factor c promote lymph node metastasis in a rectal cancer orthotopic model?,"vascular endothelial growth factor c (vegf-c), a novel member of the vascular endothelial growth factor family, is a relatively specific lymphangiogenic growth factor. it has been suggested that increased expression of vegf-c in primary tumors is correlated with lymph node metastasis. we conducted this study to determine whether vegf-c directly affects lymphangiogenesis and lymph node metastasis in colorectal cancer. for an accurate analysis and clear visualization of metastases, the rectal cancer cell line, dld1, was engineered to stably express green fluorescent protein (gfp) (dld1/gfp). we implanted dld1/gfp cells overexpressing vegf-c orthotopically into the rectal walls of nude mice. lymph node metastasis was confirmed in all (100) of the mice bearing dld1/gfp-vegf-c tumors, but in only 25 of the mice bearing control tumors. there were more lymph node metastases per mouse in the mice bearing dld1/gfp-vegf-c tumors than in the mice bearing control tumors. there were no differences in cell growth and motility in vitro or in the resulting tumor volume from the implanted cells between the two groups. immunohistochemical staining revealed that vegf-c induced the growth of lymphatic vessels, which were enlarged in the tumor periphery and contained tumor cell emboli.",these results suggest that vegf-c-induced lymphangiogenesis mediates tumor spread and the formation of lymph node metastasis.,General
is anaesthesia for awake craniotomy safe and well-tolerated?,"awake craniotomy for tumour resection has been performed at glostrup hospital since 2004. we describe and discuss the various anaesthetic approaches for such surgery and retrospectively analyse the 44 planned awake craniotomies performed at glostrup hospital. the surgery falls into four phases: craniotomy, mapping, tumour resection and closing. three methods are being used: monitored anaesthetic care, asleep-awake-asleep and asleep-awake (aa). anaesthesia is induced and maintained with propofol and remifentanil. a laryngeal mask (lm) is used as an airway during the craniotomy phase. in the aa method, patients are mapped and the tumour is resected while the patient is awake. a total of 41 of 44 planned aa craniotomies were performed. three had to be converted into general anaesthesia (ga) due to tight brain, leaking lm and tumour haemorrhage, respectively. the following complications were observed: bradycardia 10, leaking lm 5, nausea 10, vomiting 5, focal seizures 28, generalized seizures 10, hypoxia 2, hypotension 5 and hypertension 2.","our results comply well with the international literature in terms of complications related to haemodynamics, respiration, seizures, vomiting and nausea and in terms of patient satisfaction. awake craniotomy is a well-tolerated procedure with potential benefits. more prospective randomized studies are required.",Medication
do how social desirability and acquiescence affect the age-personality relationship?,"recent studies have suggested that the age-personality relationship may be partially explained by age-related changes in social desirability. in the present study, we analyze how age affects social desirability and acquiescence, and how they affect the age-personality relationship. we used a specially designed personality test, which provides response bias and personality dimension scores independently of each other. we applied this test to a sample of 3773 individuals aged between 13 and 97 years old (49.69 female) and analyzed the effects of age, sex, and their interactions on response bias and personality dimensions. age affects social desirability and acquiescence, both of which increase with age, and this increase affects the age-personality relationship, especially for dimensions such as agreeableness or conscientiousness.","the age-related differences found in self-reported personality measures might be partly attributable to age-related increases in response bias. furthermore, the high scores of elderly people on response bias measures implies that the results of self-reports that do not incorporate any correction for response bias should be viewed with caution, especially when they are obtained in samples of people over 50 years old.",General
does cerebral blood flow during treadmill exercise be a marker of physiological postconcussion syndrome in female athletes?,"some patients with postconcussion syndrome (pcs) have reduced exercise capacity that may reflect altered central cardiorespiratory control. the purpose of this study was to evaluate control of cerebral blood flow (cbf) during exercise in females with pcs. university concussion clinic. nine female division 1 collegiate team athletes with pcs (23 6 years) and a reference group of 13 healthy female recreational aerobic athletes (21 3 years). a prospective experimental study. all pcs athletes were compared with the reference group at the beginning of the study. six of the pcs athletes were subsequently measured before and after a subsymptom threshold aerobic exercise treatment program. exercise treadmill test during which blood pressure (bp), minute ventilation ((equation is included in full-text article.)e), end-tidal co2 (petco2), and cbf velocity (cbfv, by transcranial doppler) were measured. participants with pcs had significantly lower (equation is included in full-text article.)e (by 18) and greater petco2 (5) and cbfv (14) versus the reference group at similar workloads in association with appearance of symptoms and premature exercise cessation. subthreshold exercise normalized (equation is included in full-text article.)e, petco2, cbfv and exercise tolerance. before treatment, pcs had low co2 sensitivity that blunted their exercise ventilation. co2 sensitivity and ventilation improved after exercise treatment.",some pcs patients have exercise intolerance due to abnormal cbf regulation that may be the result of concussion-induced altered sensitivity to co2. return of normal cbf control and exercise tolerance may be physiological markers of recovery from concussion.,Prevention
does coniferyl aldehyde reduce radiation damage through increased protein stability of heat shock transcriptional factor 1 by phosphorylation?,"we previously screened natural compounds and found that coniferyl aldehyde (ca) was identified as an inducer of hsf1. in this study, we further examined the protective effects of ca against ionizing radiation (ir) in normal cell system. western blotting and reverse transcription-polymerase chain reaction tests were performed to evaluate expression of hsf1, hsp27, and hsp70 in response to ca. cell death and cleavage of parp and caspase-3 were analyzed to determine the protective effects of ca in the presence of ir or taxol. the protective effects of ca were also evaluated using animal models. ca increased stability of the hsf1 protein by phosphorylation at ser326, which was accompanied by increased expression of hsp27 and hsp70. hsf1 phosphorylation at ser326 by ca was mediated by ekr1/2 activation. cotreatment of ca with ir or taxol in normal cells induced protective effects with phosphorylation- dependent patterns at ser326 of hsf1. the decrease in bone marrow (bm) cellularity and increase of terminal deoxynucleotidyl transferase dutp nick end labeling-positive bm cells by ir were also significantly inhibited by ca in mice (30.6 and 56.0, respectively). a549 lung orthotopic lung tumor model indicated that ca did not affect the ir-mediated reduction of lung tumor nodules, whereas ca protected normal lung tissues from the therapeutic irradiation.",these results suggest that ca may be useful for inducing hsf1 to protect against normal cell damage after ir or chemotherapeutic agents.,Treatment
are increased il-6 levels related to nf-b or hif-1 transcription factors activity in the vitreous of proliferative diabetic retinopathy?,"the purpose was to assess the activity of nuclear factor (nf)-b and hypoxia inducible factor (hif)-1 transcription factors and the expression levels of inflammation markers interleukin (il)-6 and il-8 in the vitreous of patients suffering from proliferative diabetic retinopathy (pdr) scheduled for elective vitreous surgery in a single academic-based retina practice in a prospective clinical study. twenty-seven patients with pdr were enrolled in the study. the severity of retinopathy was classified (0, 1, 2, 3, 4) and the activity of neovascularization was graded (0, 1, 2, 3, 4) by the surgeon intraoperatively. samples of the vitreous were collected during surgery, and the activity of nf-b and hif-1 transcription factors and the expression levels of il-6 and il-8 were measured. the majority of samples fell into the retinopathy class 3 (n 12) or 4 (n 13). the level of il-6 increased from 68.9 46.8 pg/ml to 102.7 94.1 pg/ml, and il-8 increased from 165.1 136.0 pg/ml to 521.0 870.9 pg/ml (mean s.d., nonsignificant change: normality test followed with mann-whitney rank sum test). according to the neovascularization activity, the samples fell into grade 1 (n 7), 2 (n 12) or 3 (n 7). in il-6, there was a statistically significant increase (p .05) from grade 2 to 3: 58.6 40.3 pg/ml and 158.4 102.5 pg/ml, respectively (kruskal-wallis one-way analysis of variance on ranks followed with dunn's method). the level of il-8 was as follows: in grade 1: 118.0 62.4 pg/ml, in grade 2: 192.3 127.1 pg/ml and in grade 3: 884.3 1161.0 pg/ml (statistically nonsignificant change). there was a statistically significant linear regression between il-6 and il-8 (p .001): il-6 51.88 pg/ml (0.092il-8), r 0.772. increased activity of the nf-b and hif-1 transcription factors was not observed.",interleukin-6 is a candidate to indicate activity of neovascularization process in pdr. it might be a new molecular therapeutic target to regulate innate immunity response in vitreous.,Treatment
is higher anthocyanin intake associated with lower arterial stiffness and central blood pressure in women?,"although a high intake of some flavonoid subclasses may reduce cardiovascular disease mortality, data regarding the in vivo mechanisms of action are limited. we examined associations between habitual flavonoid intakes and direct measures of arterial stiffness, central blood pressure, and atherosclerosis. in a cross-sectional study of 1898 women aged 18-75 y from the twinsuk registry, intakes of total flavonoids and their subclasses (flavanones, anthocyanins, flavan-3-ols, polymers, flavonols, and flavones) were calculated from validated food-frequency questionnaires by using an updated and extended usda database. direct measures of arterial stiffness and atherosclerosis included central systolic blood pressure (csbp), central diastolic blood pressure, mean arterial pressure (map), augmentation index, pulse wave velocity (pwv), and intima-media thickness. in multivariate analyses, a higher anthocyanin intake was associated with significantly lower csbp (mean se: -3.0 1.4 mm hg for quintile 5 compared with quintile 1; p-trend 0.02), map (-2.3 1.2 mm hg for quintile 5 compared with quintile 1; p-trend 0.04), and pwv (-0.4 0.2 m/s for quintile 5 compared with quintile 1; p-trend 0.04), whereas a higher flavone intake was associated with a lower pwv (-0.4 0.2 m/s for quintile 5 compared with quintile 1; p-trend 0.04). although a higher wine and berry intake was associated with a lower pwv, no associations were observed for total and other flavonoid subclasses.","these data, which include direct measures of arterial stiffness and thickness, suggest that higher intake of anthocyanins and flavones are inversely associated with lower arterial stiffness. the intakes of anthocyanins associated with these findings could be incorporated into the diet by the consumption of 1-2 portions of berries daily and are, therefore, relevant for public health strategies to reduce cardiovascular disease risk.",General
does infliximab treatment maintain employability in patients with early rheumatoid arthritis?,"to evaluate the impact of infliximab therapy on the employment status of patients with early rheumatoid arthritis (ra). methotrexate (mtx)-naive patients with active early ra were randomly allocated to receive mtx plus placebo or mtx plus infliximab (3 mg/kg or 6 mg/kg) at weeks 0, 2, and 6 and then every 8 weeks through week 46. data for patients younger than age 65 years were included in the analyses. a patient was categorized as employable if he or she was employed or felt well enough to work if a job were available. the change in actual employment was not significantly different between patients receiving mtx plus infliximab and those receiving mtx plus placebo (0.5 versus 1.3; p 0.5). however, the proportion of patients whose status changed from employable at baseline to unemployable at week 54 was smaller in the group receiving mtx plus infliximab compared with that in the group receiving mtx alone (8 versus 14; p 0.05). patients who were treated with infliximab plus mtx had a significantly greater likelihood of improvement rather than deterioration in employability (odds ratio 2.4; p 0.001); this likelihood was not significantly greater in patients receiving mtx alone. the proportion of employed patients who lost workdays during the trial was smaller in the mtx plus infliximab group than in the mtx-alone group (p 0.010).","the actual employment rates among patients in the 2 treatment groups were not different. however, patients with early ra who were treated with mtx plus infliximab had a higher probability of maintaining their employability compared with those who were treated with mtx alone.",Treatment
does bradykinin stimulate eotaxin production by a human lung fibroblast cell line?,"bradykinin, a potent inflammatory peptide, is increased in the airways of allergic patients. accompanying the elevated bradykinin levels are increases in both eosinophils and fibroblasts. eotaxin, a potent eosinophil-specific chemotactic factor, is released by fibroblasts and increased in the lower respiratory tract of allergic patients. we sought to test the hypothesis that lung fibro-blasts release eotaxin in response to bradykinin. the potential of bradykinin to induce the release of eotaxin from the human lung fibroblast cell line hfl-1 was tested by cell culture and evaluation of the culture supernatant fluids and rna for immunoreactive eotaxin and eotaxin messenger rna. hfl-1 cells released eotaxin constitutively without stimulation, but bradykinin stimulated eotaxin release in a dose- and time-dependent manner and resulted in augmented expression of eotaxin messenger rna. the release of eotaxin was sensitive to the action of glucocorticoids. eosinophil chemotactic activity by hfl-1 supernatant fluids was inhibited by anti-human eotaxin-neutralizing antibody. consistent with these results, inhibitors of bradykinin b2 receptors, but not bradykinin b1 receptors, inhibited bradykinin-induced eotaxin release.",these data demonstrate that bradykinin may stimulate lung fibroblasts to release eotaxin and suggest the potential for this mechanism to be important in modulation of lung inflammation.,Medication
does pathogenesis and progression of oesophageal adenocarcinoma vary by prior diagnosis of barrett 's oesophagus?,"the absolute risk of oesophageal adenocarcinoma (ea) among individuals with barrett's oesophagus (be) is low and a majority of ea cases are diagnosed among individuals with no prior be diagnosis. to ensure that insights from ea case-control studies are transferable to clinical management of be populations, we conducted a case-case study to compare the clinical presentation, medical history and survival of ea cases with and without a prior be diagnosis in the surveillance, epidemiology and end results medicare database. eligible ea cases were diagnosed at age 68 years during 1994-2009. there were 5271 ea cases in this study, 87 of which did not have a prior diagnosis of be (ea-no prior be). multivariable case-case comparisons evidenced adverse associations of gerd, ever cigarette smoking, hypertension, dyslipidemia, weight loss, peptic ulcer and irritable bowel disease each in ea-prior be compared with ea-no prior be. obesity, metabolic syndrome, impaired fasting glucose and diabetes did not differ between groups. ea-prior be cases were diagnosed with less advanced disease, were more likely to undergo surgery and less likely to receive chemotherapy and radiotherapy, and had better overall mean survival (2.5 vs 1.4 years). this survival advantage persisted in the multivariable cox model (hr0.69, 95ci: 0.60, 0.78), despite adjustment for many factors including stage, grade and clinical interventions.","this study provides evidence that ea cases occurring among individuals previously diagnosed with be are different from the large majority of ea cases that occur without a prior be diagnosis. regardless of whether these differences emanate from aetiology, biology and/or selection biases, they underscore the importance of a prudent approach in using knowledge from eac case-control studies in the management of be populations.",Diagnosis
does brain histamine be crucial for selective serotonin reuptake inhibitors ' behavioral and neurochemical effects?,"the neurobiological changes underlying depression resistant to treatments remain poorly understood, and failure to respond to selective serotonin reuptake inhibitors may result from abnormalities of neurotransmitter systems that excite serotonergic neurons, such as histamine. using behavioral (tail suspension test) and neurochemical (in vivo microdialysis, western-blot analysis) approaches, here we report that antidepressant responses to selective serotonin reuptake inhibitors (citalopram or paroxetine) are abolished in mice unable to synthesize histamine due to either targeted disruption of histidine decarboxylase gene (hdc(-/-)) or injection of alpha-fluoromethylhistidine, a suicide inhibitor of this enzyme. in the tail suspension test, all classes of antidepressants tested reduced the immobility time of controls. systemic reboxetine or imipramine reduced the immobility time of histamine-deprived mice as well, whereas selective serotonin reuptake inhibitors did not even though their serotonergic system is functional. in in vivo microdialysis experiments, citalopram significantly increased histamine extraneuronal levels in the cortex of freely moving mice, and methysergide, a serotonin 5-ht1/5-ht2 receptor antagonist, abolished this effect, thus suggesting the involvement of endogenous serotonin. creb phosphorylation, which is implicated in the molecular mechanisms of antidepressant treatment, was abolished in histamine-deficient mice treated with citalopram. the creb pathway is not impaired in hdc(-/-) mice, as administration of 8-bromoadenosine 3', 5'-cyclic monophosphate increased creb phosphorylation, and in the tail suspension test it significantly reduced the time spent immobile by mice of both genotypes.",our results demonstrate that selective serotonin reuptake inhibitors selectively require the integrity of the brain histamine system to exert their preclinical responses.,Medication
does passive leg raising predict fluid responsiveness in the critically ill?,"passive leg raising (plr) represents a ""self-volume challenge"" that could predict fluid response and might be useful when the respiratory variation of stroke volume cannot be used for that purpose. we hypothesized that the hemodynamic response to plr predicts fluid responsiveness in mechanically ventilated patients. prospective study. medical intensive care unit of a university hospital. we investigated 71 mechanically ventilated patients considered for volume expansion. thirty-one patients had spontaneous breathing activity and/or arrhythmias. we assessed hemodynamic status at baseline, after plr, and after volume expansion (500 ml nacl 0.9 infusion over 10 mins). we recorded aortic blood flow using esophageal doppler and arterial pulse pressure. we calculated the respiratory variation of pulse pressure in patients without arrhythmias. in 37 patients (responders), aortic blood flow increased by or 15 after fluid infusion. a plr increase of aortic blood flow or 10 predicted fluid responsiveness with a sensitivity of 97 and a specificity of 94. a plr increase of pulse pressure or 12 predicted volume responsiveness with significantly lower sensitivity (60) and specificity (85). in 30 patients without arrhythmias or spontaneous breathing, a respiratory variation in pulse pressure or 12 was of similar predictive value as was plr increases in aortic blood flow (sensitivity of 88 and specificity of 93). in patients with spontaneous breathing activity, the specificity of respiratory variations in pulse pressure was poor (46).","the changes in aortic blood flow induced by plr predict preload responsiveness in ventilated patients, whereas with arrhythmias and spontaneous breathing activity, respiratory variations of arterial pulse pressure poorly predict preload responsiveness.",Diagnosis
does localized irradiation of cell membrane by auger electrons be cytotoxic through oxidative stress-mediated nontargeted effects?,"we investigated whether radiation-induced nontargeted effects are involved in the cytotoxic effects of anticell surface monoclonal antibodies labeled with auger electron emitters, such as iodine 125 (monoclonal antibodies labeled with (125)i (125)i-mabs). we showed that the cytotoxicity of (125)i-mabs targeting the cell membrane of p53(/) hct116 colon cancer cells is mainly due to nontargeted effects. targeted and nontargeted cytotoxicities were inhibited in vitro following lipid raft disruption with methyl--cyclodextrin (mbcd) or filipin or use of radical oxygen species scavengers. (125)i-mab efficacy was associated with acid sphingomyelinase activation and modulated through activation of the akt, extracellular signal-related kinase (erk1/2), p38 kinase, c-jun n-terminal kinase (jnk) signaling pathways, and also of phospholipase c- (plc-), proline-rich tyrosine kinase 2 (pyk-2), and paxillin, involved in ca(2) fluxes. moreover, the nontargeted response induced by directing 5-(125)iiodo-2'-deoxyuridine to the nucleus was comparable to that of (125)i-mab against cell surface receptors. in vivo, we found that the statistical significance of tumor growth delay induced by (125)i-mab was removed after mbcd treatment and observed oxidative dna damage beyond the expected auger electron range. these results suggest the involvement of nontargeted effects in vivo also. low-energy auger electrons, such as those emitted by (125)i, have a short tissue range and are usually targeted to the nucleus to maximize their cytotoxicity. in this study, we show that targeting the cancer cell surface with (125)i-mabs produces a lipid raft-mediated nontargeted response that compensates for the inferior efficacy of non-nuclear targeting.","our findings describe the mechanisms involved in the efficacy of (125)i-mabs targeting the cancer cell surface. antioxid. redox signal. 25, 467-484.",Treatment
do patterns of joint involvement at onset differentiate oligoarticular juvenile psoriatic arthritis from pauciarticular juvenile rheumatoid arthritis?,"to compare the patterns of joint involvement of patients with oligoarticular onset juvenile psoriatic arthritis (oligo-jpsa) and pauciarticular onset juvenile rheumatoid arthritis (pauci-jra) in order to estimate the predictive performance of specific patterns for the diagnosis of oligo-jpsa. twenty-three children who fulfilled the diagnostic criteria for jpsa (vancouver criteria) and who had fewer than 5 joints involved in the first 6 months of disease (oligo-jpsa), and 64 children with pauci-jra (acr criteria) were enrolled. patients were also classified with respect to the ilar criteria for juvenile idiopathic arthritis (jia). patient characteristics and clinical features at onset and during followup were determined. patterns of joint involvement at onset of disease and their ability to differentiate between oligo-jpsa and pauci-jra/oligo-jia were evaluated. small joint disease (defined as involvement of any of the metatarsophalangeal or proximal or distal interphalangeal joints of the foot, or metacarpophalangeal or proximal or distal interphalangeal joints of the hand) was significantly more frequent in oligo-jpsa than in pauci-jra at disease onset. the odds of patients with oligo-jpsa having small joint disease or wrist disease within 6 months of disease onset were much higher than those with pauci-jra or oligo-jia (p 0.05 or 0.001).",small joint disease and wrist disease are suggestive of oligo-jpsa. the use of a criterion consisting of small joint disease and/or wrist disease and/or dactylitis instead of dactylitis alone may increase the ability to differentiate oligo-jpsa from pauci-jra or oligo-jia.,Diagnosis
do the effects of high-frequency jet ventilation ( hfjv ) on pneumoperitoneum-induced cardiovascular changes during laparoscopic surgery?,"standard mechanical ventilation may cause adverse cardiovascular effects in addition to those already related to positive-pressure pneumoperitoneum (pp) during laparoscopic surgery. high-frequency jet ventilation (hfjv) is associated with much less airway pressure, with potentially less influence on venous return, thus potentially it may reduce those effects. the aim of this study was to evaluate the benefits of hfjv to reduce the adverse cardiovascular effects during laparoscopic cholecystectomy. we conducted a randomized prospective trial, comparing 12 patients undergoing elective laparoscopic cholecystectomy under conventional mechanical ventilation (control) with 13 similar subjects under hfjv (study). both groups were categorized as asa i-ii and underwent total intravenous anesthesia. cardiac functionality was continuously evaluated by analysis of arterial pressure wave changes (edwards flo-trac sensor and vigileo monitor). there was no significant difference between both groups regarding age, gender, bmi, and general medical condition, as well as hemodynamic stability and blood gases throughout surgery. a significant reduction in cardiac output was noted in the control group under pp during the initiation of anti-trendelenburg position (from 5.6 to 5.0 l/min, p 0.049). a reciprocal change was observed regarding stroke volume. such changes were not noticed under hfjv. total peripheral resistance was significantly increased during pp, and heart rate was not significantly affected throughout surgery in both groups. unexpectedly, we did not observe marked adverse hemodynamic changes in the control group during pp without position adjustment.",the use of hfjv in upper laparoscopic surgery can impede the adverse cardiovascular changes that usually occur during induction of pp. we also suggest that the use of total intravenous anesthesia (as used in our study) may also lessen the cardiovascular impairment during pp.,Treatment
does a new algorithm for integrated analysis of mirna-mrna interactions based on individual classification reveal insights into bladder cancer?,"micrornas (mirnas) are small non-coding rnas that regulate gene expression. it has been proposed that mirnas play an important role in cancer development and progression. their ability to affect multiple gene pathways by targeting various mrnas makes them an interesting class of regulators. we have developed an algorithm, classification based analysis of paired expression data of rna (cape rna), which is capable of identifying altered mirna-mrna regulation between tissues samples that assigns interaction states to each sample without preexisting stratification of groups. the distribution of the assigned interaction states compared to given experimental groups is used to assess the quality of a predicted interaction. we demonstrate the applicability of our approach by analyzing urothelial carcinoma and normal bladder tissue samples derived from 24 patients. using our approach, normal and tumor tissue samples as well as different stages of tumor progression were successfully stratified. also, our results suggest interesting differentially regulated mirna-mrna interactions associated with bladder tumor progression.","the need for tools that allow an integrative analysis of microrna and mrna expression data has been addressed. with this study, we provide an algorithm that emphasizes on the distribution of samples to rank differentially regulated mirna-mrna interactions. this is a new point of view compared to current approaches. from bootstrapping analysis, our ranking yields features that build strong classifiers. further analysis reveals genes identified as differentially regulated by mirnas to be enriched in cancer pathways, thus suggesting biologically interesting interactions.",Diagnosis
do age and sex predict pao2/fio2 ratio in brain-dead donor lungs?,"to define the prevalence of various ranges of the ratio of partial arterial oxygen tension to fraction of inspired oxygen (pao(2)/fio(2)) and to determine correlative and predictive variables of donor lung pao(2)/fio(2). from the brain death database of masih daneshvari hospital organ procurement center, we extracted demographic data, cause of injury, patient clinical condition, and laboratory findings as independent data. donor lung suitability was determined with an oxygen challenge test, with results of 400 mm hg considered ideal; 300 to 399 mm hg, good; 200 to 299 mm hg, borderline; and less than 200 mm hg, not acceptable. using the pao(2)/fio(2) cutoff points, 6.7 of donor lungs were considered ideal; 26.7, good; 40, borderline; and 26.7, unacceptable. mean (sd; range) pao(2)/fio(2) was 266.6 (85.6; 110-460). the pao(2)/fio(2) was significantly correlated with age (r -0.35; p .02). after entering the study variables into a linear regression model, age (-2.3; p .008) and sex (51.5; p .04) were significant predictors of donor lung suitability (r(2) 0.95; p .001).",results of oxygen challenge tests demonstrated better suitability of lungs from male and younger brain-dead donors. this finding is independent of other variables including cause of brain death and clinical and paraclinical data.,General
does a three generations nation-wide population study of family load estimate in bipolar disorder with different age at onset?,"this nation-wide register-based study investigates how often bipolar disorder (bd) occurs in affected families compared to control families by estimating the family load as a random effect; this effect measures the degree of dependence among family members in relation to bd. furthermore, the study addresses the impact of certain risk factors, namely, sex, age at onset of bd, degree of urbanization, year of birth, month of birth, and maternal and paternal age at birth. a total of n1204 children and adolescent psychiatric cases born between 1950 and 1997 and registered in the danish central psychiatric register (dpcr) developed bd before the age of 58 years. n3553 controls without any psychiatric diagnosis were matched for age, gender, and region of residence. psychiatric diagnoses were also obtained on the relatives, e.g. parents, siblings, and offspring as a part of the danish three generation study (3gs). a family component was obtained by using different regression models. familial factors accounted for 20 of the variation in disease outcome when controlling for year and month of birth, sex, and degree of urbanization. only female sex was associated with an increased hazard ratio of bd. also having a mother, father or a sibling with the disorder was proven to be a significant risk factor. furthermore, case relatives did not develop bd earlier than control relatives.",these findings based on a very large and representative dataset provide further and very solid evidence for the high family aggregation of bd.,Prevention
is brg1 expression increased in human cutaneous melanoma?,"the swi/snf chromatin remodelling complex plays important roles in cellular processes including cell differentiation, cell cycle control and dna repair. aberrant expression of swi/snf subunits is involved in cancer development. the core subunit of the swi/snf complex, snf5, has been shown to be inactivated in malignant rhabdoid tumours and has been defined as a tumour suppressor. however, the role of the catalytic subunit, brg1, is not well defined in cancer. to investigate the role of brg1 in melanoma development, we examined the expression of brg1 in melanocytic lesions at different stages and analysed the correlation between brg1 expression and clinicopathological variables and patient survival. using tissue microarray and immunohistochemistry, we evaluated brg1 staining in 48 dysplastic naevi, 90 primary melanomas and 47 metastatic melanomas. we studied melanoma cell proliferative ability with reduced brg1 expression by small interfering rna using cell proliferation assay and cell cycle analysis. we found that brg1 expression was increased in primary melanoma and metastatic melanoma compared with dysplastic naevi (p00001). we did not find any correlation between brg1 expression and melanoma patient survival. in addition, we demonstrated that knockdown of brg1 in melanoma cell lines resulted in significantly reduced cell proliferative ability. this reduced cell proliferation is due to g(1) phase arrest as cyclin d(1) is downregulated upon brg1 knockdown.",our data indicate that brg1 is significantly increased in human melanoma and is involved in melanoma initiation.,Treatment
does acid suppression increase rates of barrett 's esophagus and esophageal injury in the presence of duodenal reflux?,"the contribution of gastric acid to the toxicity of alkaline duodenal refluxate on the esophageal mucosa is unclear. this study compared the effect of duodenal refluxate when acid was present, decreased by proton pump inhibitors (ppi), or absent. we randomized 136 sprague-dawley rats into 4 groups: group 1 (n 33) were controls; group 2 (n 34) underwent esophagoduodenostomy promoting ""combined reflux""; group 3 (n 34) underwent esophagoduodenostomy and ppi treatment to decrease acid reflux; and group 4, the 'gastrectomy' group (n 35) underwent esophagoduodenostomy and total gastrectomy to eliminate acid in the refluxate. esophaguses were examined for inflammatory, barrett's, and other histologic changes, and expression of proliferative markers ki-67, proliferating cell nuclear antigen (pcna), and epidermal growth factor receptor (egfr). in all reflux groups, the incidence of barrett's mucosa was greater when acid was suppressed (group c, 62; group d, 71) than when not suppressed (group b, 27; p 0.004 and p .001). erosions were more frequent in the ppi and gastrectomy groups than in the combined reflux group. edema (wet weight) and ulceration was more frequent in the gastrectomy than in the combined reflux group. acute inflammatory changes were infrequent in the ppi group (8) compared with the combined reflux (94) or gastrectomy (100) groups, but chronic inflammation persisted in 100 of the ppi group. egfr levels were greater in the ppi compared with the combined reflux group (p .04). ki-67, pcna, and combined marker scores were greater in the gastrectomy compared with the combined reflux group (p .006, p .14, and p .001).","gastric acid suppression in the presence of duodenal refluxate caused increased rates of inflammatory changes, intestinal metaplasia, and molecular proliferative activity. ppis suppressed acute inflammatory changes only, whereas chronic inflammatory changes persisted.",Medication
is a novel polymorphism of the cyp19 gene associated with essential hypertension in china?,"aromatase which is encoded by the cyp19 gene is a key enzyme in the conversion of androgen to estrogen and plays an important role in the balance of the gender hormone levels. the gender hormone has a causal role in the development of cardiovascular disease. the goal of this study was to investigate the interaction between the snps in cyp19 gene and essential hypertension. the case-control study including han population (410 eh patients and 410 control subjects) and uygur population (371 eh patients and 463 control subjects). individual testing was conducted to identify the association of three snps in cyp19 with eh by using chi2 test or fisher's exact test. differences in lipids and the parameters of echocardiography among individuals with different genotypes were assessed by using one way analysis of variance (anova). for women in han, the distribution of rs2289105 in cyp19 gene showed a significant difference between eh and controls (p 0.049) and the dominant model (cc vs. cttt) has a significantly lower risk than the homozygous wild-type cc (p 0.014). the dominant model of rs12050772 (gg vs. gttt) has a significantly lower risk in eh patients (p 0.021). for men in uygur, the recessive model of rs4774585 (aa vs. aggg) has a significantly higher risk in eh patients (p 0.021). anova indicated the left ventricular end-diastolic dimension is significantly higher in the homozygous wild-type (respectively, p 0.001 and p 0.015).",the t allele of rs2289105 in cyp19 gene might be a protective genetic marker of eh for women in han population.,General
does national patterns and correlate of mentholated cigarette use in the united states?,"to examine the patterns and correlates of mentholated cigarette smoking among adult smokers in the united states. cross-sectional data on adult current smokers (n 63,193) were pooled from the 2003 and 2006/07 tobacco use supplements to the current population survey. the associations between socio-demographic and smoking variables were examined with gender- and race/ethnicity-stratified multivariate logistic regression models predicting current use of mentholated cigarettes. multivariate logistic regression analyses demonstrated that black smokers were 10-11 times more likely to smoke mentholated cigarettes than white smokers men: odds ratio (or): 11.59, 99 confidence interval (ci): 9.79-13.72; women: or: 10.12, 99 ci: 8.45-12.11). with the exception of american indian/aleut/eskimo smokers, non-white smokers were significantly more likely to smoke mentholated cigarettes than were white smokers. additional significant factors associated with mentholated cigarette smoking included being unmarried (never married: or: 1.21, 99 ci: 1.09-1.34; divorced/separated: or: 1.13, 99 ci: 1.03-1.23), being born in a us territory (or: 2.01, 99 ci: 1.35-3.01), living in a non-metropolitan area (or: 0.87, 99 ci: 0.80-0.96), being unemployed (or: 1.24, 99 ci: 1.06-1.44) and lower levels of education. race/ethnicity-stratified analyses showed that women were more likely than men to smoke mentholated cigarettes. among black smokers, young adults (aged 18-24 years) were four times more likely to smoke mentholated cigarettes compared with individuals aged 65.","race/ethnicity, gender and age are significant correlates of mentholated cigarette smoking among current smokers. given the importance of menthol in the cigarette market and the potential untoward health effects of this additive, continued surveillance of the prevalence and correlates of mentholated cigarette use among diverse socio-demographic groups is warranted to inform appropriate interventions.",Medication
is airflow limitation in smokers associated with arterial stiffness : the nagahama study?,"pathophysiological mechanisms of associations between airflow limitation (al) and arterial stiffness remain unclear. one factor that might affect both al and arterial stiffness is habitual smoking. the aim of this study is to investigate a possible interaction of smoking on the association between al and arterial stiffness. study subjects consisted of 8790 apparently healthy community residents. airflow limitation was defined as a ratio of forced expiratory volume in 1 s (fev1) to forced vital capacity of less than 70. brachial-to-ankle pulse wave velocity (bapwv) was used as an index of arterial stiffness. smoking habit was investigated using a structured questionnaire. subjects with al had significantly higher bapwv (al 1381 334, control 1261 227 cm/s, p 0.001). in a separate analysis by smoking habit, advanced arterial stiffness in al was observed only in smokers (non-smokers: al 1300 220, control 1260 218; smokers: al 1436 384, control 1264 243 cm/s). other clinical features of subjects with al were older age; increased plasma hscrp levels; and a high prevalence of male sex, hypertension, and smoking experience. multiple linear regression analysis adjusted for these covariates identified the smoking al interaction as an independent determinant of bapwv ( 0.066, p 0.001). conversely, bapwv was an independent determinant of al in current and past smokers, but not in never smokers.","al arising from cigarette smoking, but not al in non-smokers, was associated with arterial stiffness in a general population independently of established risk factors. measurement of subclinical arterial change in smokers may be useful in identifying persons at risk for al.",General
do activity and similarity on safe sex workshops led by peer educators?,"sexually transmitted disease is a growing problem for college students. to address this problem, health professionals on many campuses have turned to peer led prevention workshops. the research evaluated the effectiveness of four types of such workshops. the workshops followed either an information based format or an activity based format. in addition, the peer leaders were portrayed as similar to their audience or as dissimilar. results indicate that the activity workshop was more effective than the information workshop at encouraging condom use in the month following the workshop. also, the similarity of the peer leaders influenced behavioral intentions to use a condom with new sex partners.",the discussion focuses on self-persuasion and changes in social norms as possible theoretical mechanisms underlying these effects.,Prevention
are pharmacogenetic and metabolite measurements associated with clinical status in patients with rheumatoid arthritis treated with methotrexate : results of a multicentred cross sectional observational study?,"to investigate the contribution of red blood cell (rbc) methotrexate polyglutamates (mtx pgs), rbc folate polyglutamates (folate pgs), and a pharmacogenetic index to the clinical status of patients with rheumatoid arthritis treated with mtx. 226 adult patients treated with weekly mtx for more than 3 months were enrolled at three sites in a multicentred cross sectional observational study. clinical status was assessed by the number of joint counts, physician's global assessment of disease activity, and a modified health assessment questionnaire (mhaq). rbc mtx pg and folate pg metabolite levels were measured by high performance liquid chromatography fluorometry and radioassay, respectively. a composite pharmacogenetic index comprising low penetrance genetic polymorphisms in reduced folate carrier (rfc-1 g80a), aicar transformylase (atic c347g), and thymidylate synthase (tser2/3) was calculated. statistical analyses were by multivariate linear regression with clinical measures as dependent variables and metabolite levels and the pharmacogenetic index as independent variables after adjustment for other covariates. multivariate analysis showed that lower rbc mtx pg levels (median 40 nmol/l) and a lower pharmacogenetic index (median 2) were associated with a higher number of joint counts, higher disease activity, and higher mhaq (p0.09). multivariate analysis also established that higher rbc folate pg levels (median 1062 nmol/l) were associated with a higher number of tender and swollen joints after adjustment for rbc mtx pg levels and the pharmacogenetic index (p0.05).",pharmacogenetic and metabolite measurements may be useful in optimising mtx treatment. prospective studies are warranted to investigate the predictive value of these markers for mtx efficacy.,Treatment
do lower urinary tract symptoms affect one-third of men in a prostate cancer screening population?,"lower urinary tract symptoms (luts) are common in elderly men. radical prostatectomy may relieve obstructive symptoms, whereas radiation therapy may exacerbate obstructive or irritative symptoms. baseline luts rates are unknown in populations screened for prostate cancer (pca). thus, it is difficult to determine the changes in luts that can be attributed to pca treatment. therefore, we assessed baseline rates of luts in a pca screening cohort and assessed which of the international prostate symptom score (ipss) symptoms had the most detrimental effect on quality of life (qol). the ipss was completed by 1273 men without clinical evidence of pca who participated in an annual pca screening event. presence of irritative or obstructive symptoms was considered when they were reported at least two of five times. using linear regression analyses, we evaluated the effect of each questionnaire symptom on the ipss qol domain. mean age was 57.6 years (range 40-89 years). of all in the cohort, 40 (n 472) reported moderate to severe luts (ipss score or 8), and 21 (n 255) were mostly dissatisfied with this condition. irritative symptoms were reported by 39 (n 495) and obstructive symptoms by 37. of all ipss symptoms, urinary straining was associated with the least favorable qol, followed by urinary frequency.","more than one-third of persons at risk of pca are affected by either irritative or obstructive symptoms, and one in five of these men is bothered by luts. because pca treatment may exacerbate luts, the severity and impact on qol should be considered carefully before diagnosis and/or treatment.",Diagnosis
is gut microbiome composition associated with temperament during early childhood?,"understanding the dynamics of the gut-brain axis has clinical implications for physical and mental health conditions, including obesity and anxiety. as such disorders have early life antecedents, it is of value to determine if associations between the gut microbiome and behavior are present in early life in humans. we used next generation pyrosequencing to examine associations between the community structure of the gut microbiome and maternal ratings of child temperament in 77 children at 18-27months of age. it was hypothesized that children would differ in their gut microbial structure, as indicated by measures of alpha and beta diversity, based on their temperamental characteristics. among both boys and girls, greater surgency/extraversion was associated greater phylogenetic diversity. in addition, among boys only, subscales loading on this composite scale were associated with differences in phylogenetic diversity, the shannon diversity index (sdi), beta diversity, and differences in abundances of dialister, rikenellaceae, ruminococcaceae, and parabacteroides. in girls only, higher effortful control was associated with a lower sdi score and differences in both beta diversity and rikenellaceae were observed in relation to fear. some differences in dietary patterns were observed in relation to temperament, but these did not account for the observed differences in the microbiome.","differences in gut microbiome composition, including alpha diversity, beta diversity, and abundances of specific bacterial species, were observed in association with temperament in toddlers. this study was cross-sectional and observational and, therefore, does not permit determination of the causal direction of effects. however, if bidirectional brain-gut relationships are present in humans in early life, this may represent an opportunity for intervention relevant to physical as well as mental health disorders.",Prevention
does the apolipoprotein e ( apoe ) gene appear functionally monomorphic in chimpanzees ( pan troglodytes )?,"the human apolipoprotein e (apoe) gene is polymorphic, with three primary alleles (e2, e3, e4) that differ at two key non-synonymous sites. these alleles are functionally different in how they bind to lipoproteins, and this genetic variation is associated with phenotypic variation for several medical traits, including cholesterol levels, cardiovascular health, alzheimer's disease risk, and longevity. the relative frequencies of these alleles vary across human populations, and the evolution and maintenance of this diversity is much debated. previous studies comparing human and chimpanzee apoe sequences found that the chimpanzee sequence is most similar to the human e4 allele, although the resulting chimpanzee protein might function like the protein coded for by the human e3 allele. however, these studies have used sequence data from a single chimpanzee and do not consider whether chimpanzees, like humans, show intra-specific and subspecific variation at this locus. to examine potential intraspecific variation, we sequenced the apoe gene of 32 chimpanzees. this sample included 20 captive individuals representing the western subspecies (p. troglodytes verus) and 12 wild individuals representing the eastern subspecies (p. t. schweinfurthii). variation in our resulting sequences was limited to one non-coding, intronic snp, which showed fixed differences between the two subspecies. we also compared apoe sequences for all available ape genera and fossil hominins. the bonobo apoe protein is identical to that of the chimpanzee, and the denisovan apoe exhibits all four human-specific, non-synonymous changes and appears functionally similar to the human e4 allele.","we found no coding variation within and between chimpanzee populations, suggesting that the maintenance of functionally diverse apoe polymorphisms is a unique feature of human evolution.",General
is functional p53 required for effective execution of telomerase inhibition in bcr-abl-positive cml cells?,"in chronic myeloid leukemia (cml), increased cellular turnover of hematopoietic cells driven by the oncogene bcr-abl leads to accelerated telomere shortening despite increased telomerase activity. it has been postulated that shortened telomeres, particularly in the context of increased telomerase activity, might facilitate accumulation of genetic aberrations and, consequently, disease progression from chronic phase to accelerated phase and blast crisis. therefore, inhibition of telomerase might be a promising approach in cml therapy. to investigate the therapeutic potential of telomerase inhibition in this model disorder, we used a small molecule telomerase inhibitor, bibr1532 as well as expression of a dominant-negative mutant of htert (dnhtert-ires-gfp) in the p53-negative cml blast crisis cell line k562 and characterized the effects in long-term culture. furthermore, we expressed an inducible p53 construct (vector pbabe-p53er(tam)) via retroviral transduction in cells with critically short telomeres and in cells with a normal telomere length to explain the role of the tumor suppressor in response to critical telomere shortening in bcr-abl-positive cells. bibr1532-treated bulk cultures did not show altered growth kinetics despite significant telomere shortening to a critical length of approximately 5 kb. in comparison, dnhtert-expressing clones either lost telomere length, leading to a significant but transient slow down in proliferation but eventually all escaped senescence/crisis (group i) or, alternatively, remained virtually unaffected despite measurable telomerase inhibition (group ii). further analyses of group i clones revealed impaired dna damage response and an accumulation of dicentric chromosomes. however, upon restoration of p53 in telomerase-negative k562 clones with critically short telomeres, immediate reinduction of apoptosis and complete eradication of cells was observed, whereas vector control cells continued to escape from crisis.",these results suggest that the success of strategies aimed at telomerase inhibition in cml is highly dependent on the presence of functional p53 and should be explored preferentially in chronic phase cml.,Treatment
are strain-dependent variations in stress coping behavior mediated by a 5-ht/gaba interaction within the prefrontal corticolimbic system?,"serotonin and -aminobutyric acid (gaba) transmission is crucial in coping strategies. here, using mice from 2 inbred strains widely exploited in behavioral neurochemistry, we investigated whether serotonin transmission in medial prefrontal cortex and gaba in basolateral amygdala determine strain-dependent liability to stress response and differences in coping. c57bl/6j mice displayed greater immobility in the forced swimming test, higher serotonin outflow in medial prefrontal cortex, higher gaba outflow in basolateral amygdala induced by stress, and higher serotonin 1a receptor levels in medial prefrontal cortex accompanied by lower gabab receptor levels in basolateral amygdala than dba/2j mice. in assessing whether serotonin in medial prefrontal cortex determines gaba functioning in response to stress and passive coping behavior in c57bl/6j and dba/2j mice, we observed that selective prefrontal serotonin depletion in c57bl/6j and dba/2j reduced stress-induced gaba outflow in basolateral amygdala and immobility in the forced swimming test.",these results show that strain-dependent prefrontal corticolimbic serotonin/gaba regulation determines the strain differences in stress-coping behavior in the forced swimming test and point to a role of a specific neuronal system in genetic susceptibility to stress that opens up new prospects for innovative therapies for stress disorders.,Medication
do laboratory colonisation and genetic bottlenecks in the tsetse fly glossina pallidipes?,"the iaea colony is the only one available for mass rearing of glossina pallidipes, a vector of human and animal african trypanosomiasis in eastern africa. this colony is the source for sterile insect technique (sit) programs in east africa. the source population of this colony is unclear and its genetic diversity has not previously been evaluated and compared to field populations. we examined the genetic variation within and between the iaea colony and its potential source populations in north zimbabwe and the kenya/uganda border at 9 microsatellites loci to retrace the demographic history of the iaea colony. we performed classical population genetics analyses and also combined historical and genetic data in a quantitative analysis using approximate bayesian computation (abc). there is no evidence of introgression from the north zimbabwean population into the iaea colony. moreover, the abc analyses revealed that the foundation and establishment of the colony was associated with a genetic bottleneck that has resulted in a loss of 35.7 of alleles and 54 of expected heterozygosity compared to its source population. also, we show that tsetse control carried out in the 1990's is likely reduced the effective population size of the kenya/uganda border population.","all the analyses indicate that the area of origin of the iaea colony is the kenya/uganda border and that a genetic bottleneck was associated with the foundation and establishment of the colony. genetic diversity associated with traits that are important for sit may potentially have been lost during this genetic bottleneck which could lead to a suboptimal competitiveness of the colony males in the field. the genetic diversity of the colony is lower than that of field populations and so, studies using colony flies should be interpreted with caution when drawing general conclusions about g. pallidipes biology.",General
do potassium channel openers and prostacyclin play a crucial role in mediating the vasorelaxant activity of gynura procumbens?,"previous studies of gynura procumbens (g. procumbens) have shown that partially purified fractions of the leaves are capable of lowering the blood pressure of rats by inhibiting angiotensin-converting enzymic activity and causing vasodilatation. the objectives of this study were therefore to further purify the active compounds that exhibited selective effects on blood vessels, determine the mechanism of actions, and to qualitatively analyse the putative compounds present. the butanolic fraction (bu) of the crude ethanolic extract was purified using column chromatography to obtain several sub-fractions of different polarities. the in vitro effects of bu and the sub-fractions on vascular tension were subsequently determined using isolated rat thoracic aortic rings. the most potent sub-fraction (f1) alone was then investigated for its mechanisms of the vasorelaxant activity. in another experiment, thin-layer chromatography was used to qualitatively analyse the active compounds found in f1. the bu and the sub-fractions ranging from 10-7 to 10-2 g/ml significantly (p 0.05) inhibited the sustained tonic contractions induced by phenylephrine and potassium chloride in a concentration-dependent manner with various degree of potency. the most potent sub-fraction (f1) antagonised the calcium-induced vasocontractions (1 x 10-4 - 1 x 10-2 m) in calcium-free with high concentration of potassium as well as in calcium- and potassium-free krebs-henseleit solutions. contractions induced by noradrenaline and caffeine were not affected by f1. the vasorelaxing effect caused by f1 was significantly attenuated with preincubation of potassium channel blockers (glibenclamide and 4-aminopyridine) and prostacyclin inhibitor (indomethacin) while it was not affected by preincubation with tetraethylammonium, l-nitro-arginine methyl esther, propanolol, atropine, oxadiazolo quinoxalin one and methylene blue. the qualitative phytochemical analysis of f1 indicated the presence of flavonoids.","these results confirm previous findings that g. procumbens causes vasodilatory effects by blocking calcium channels. in addition, the present study further demonstrates that the vasodilatory effect of g. procumbens may also be due to the opening of potassium channels and the stimulation of prostacyclin production. the putative compounds are probably flavonoids in nature.",Medication
is serum interleukin-10 but not interleukin-6 related to clinical outcome in patients with resectable hepatocellular carcinoma?,"to evaluate the clinical significance of preoperative serum levels of interleukin-10 (il-10) and interleukin-6 (il-6) in patients with resectable hepatocellular carcinoma (hcc). il-10 is an immunosuppressive factor and il-6 is a multifunctional cytokine that plays a role in host defense mechanisms. both have been reported to be related to the disease prognosis in some human solid tumors. their role in human hcc has not been investigated. preoperative serum samples of 67 patients with hcc who underwent potentially curative resection and 27 normal healthy donors were assayed. levels of il-10 and il-6 were determined by enzyme-linked immunosorbent assay. the clinical significance of serum il-10 and il-6 was evaluated and compared with conventional clinicopathologic factors. levels of il-10 and il-6 were significantly higher in patients with hcc than in healthy subjects. there was no correlation between il-10 and il-6 levels. tumor resection resulted in a decrease in il-10 and il-6 levels. on univariate analysis, patients with high il-10 levels had a worse disease-free survival, but il-6 levels had no correlation with the disease-free survival. multivariate analysis identified il-10 levels as a predictor of postresectional outcome, in addition to the well-established clinical risk factors.","in patients with hcc, the preoperative serum il-10 level is related to the clinical outcome. il-10 may play an important role in the progression of hcc.",Treatment
is hyperinsulinemia and insulin resistance associated with low t/t ratio in pre diabetic euthyroid pakistani subjects?,"to investigate the relationship of thyroid hormones in glucose homeostasis in impaired glucose-tolerant subjects with normal thyroid functions. cross-sectional analysis was carried out in (n260) impaired glucose-tolerant (igt) and normal glucose-tolerant (ngt) subjects. thyrotropin (tsh), total triiodothyronine (tt), total thyroxin (tt) free t (ft), free t (ft), and insulin were assessed by enzyme-linked immunoassays (elisa). fasting plasma glucose (fpg) and hba1c were measured by glucose oxidase and low-pressure cation exchange chromatography. homeostasis model of assessment (homa-ir) was employed to assess the level of insulin resistance; ft/ft ratio was calculated. anthropometric measurement and habits were recorded. marked hyperinsulinemia and insulin resistance were observed in igt subjects. serum tt and ft levels were significantly low in the igt as compared to normal glucose-tolerant (ngt) controls. tt and tsh were higher in igt subjects as compared to control subjects. there was a significant positive correlation of tsh with bmi only in the control group (r0.351; p0.05). correlation of insulin with tt, ft,and tsh was significant (p0.05) in igt subjects. a significant low ft/ft ratio was observed in igt subjects as compared to ngt subjects (p0.01). in multiple regression analysis, tsh, tt and ft contributed significantly to the variance of fasting insulin and insulin resistance in igt subjects.",hyperinsulinemia and insulin resistance are associated with low t/t ratio in pre-diabetic euthyroid pakistani subjects.,Medication
does deficit of rack1 contribute to the spatial memory impairment via upregulating beclin1 to induce autophagy?,"deficiency of activated c kinase1 (rack1) in the brain of aging animal and alzheimer's disease was characterized by cognitive dementia and spatial memory impairment. however, the correlation between the rack1 and spatial memory impairment and the mechanism involved in it remains unknown. spatial memory impairment was performed in mice by lateral ventricle injection of a25-35 (n16, 10l) and intraperitoneal injection of scopolamine (n16, 10ml/kg). after the morris water maze (mwm) which was performed to determine the ability of learning and memory in mice, expression of rack1 was tested and the damage of hippocampus was confirmed by histopathology test. shrack1 was then used to decrease the level of rack1 in hippocampus to test the ability of learning and memory and histopathology changes in hippocampus. to look into the mechanism of rack1 on spatial memory impairment, we further measured the expression of autophagy proteins beclin1 and lc3-ii/i in hippocampus of all mice. both the a25-35, scopolamine impaired the spatial memory in mice (for escape latency, p0.0004, p0.0001) and severely damaged hippocampal dg neurons (p0.012, p0.014). the expression of rack1 was significantly decreased which was concomitant with elevated beclin1 and lc3-ii/i (p0.001). suppression of rack1 by shrack1 plasmid (shgnb2l1) significantly impaired the spatial memory in mice, damaged hippocampal dg neurons (p0.013), and increased the proteins of beclin1 and lc3-ii/i (p0.005).",it demonstrated that the deficit of rack1 in hippocampus impairs the ability of learning and memory in mice via up regulating autophagy.,Medication
are orexin neurons necessary for the circadian control of rem sleep?,"the orexin-producing neurons are hypothesized to be essential for the circadian control of sleep/wake behavior, but it remains unknown whether these rhythms are mediated by the orexin peptides or by other signaling molecules released by these neurons such as glutamate or dynorphin. to determine the roles of these neurotransmitters, we examined the circadian rhythms of sleep/wake behavior in mice lacking the orexin neurons (ataxin-3 atx mice) and mice lacking just the orexin neuropeptides (orexin knockout ko mice). we instrumented mice for recordings of sleep-wake behavior, locomotor activity (lma), and body temperature (tb) and recorded behavior after 6 days in constant darkness. the amplitude of the rapid eye movement (rem) sleep rhythm was substantially reduced in atx mice but preserved in orexin ko mice. this blunted rhythm in atx mice was caused by an increase in the amount of rem sleep during the subjective night (active period) due to more transitions into rem sleep and longer rem sleep episodes. in contrast, the circadian variations of tb, lma, wake, non-rem sleep, and cataplexy were normal, suggesting that the circadian timekeeping system and other output pathways are intact in both atx and ko mice.",these results indicate that the orexin neurons are necessary for the circadian suppression of rem sleep. blunting of the rem sleep rhythm in atx mice but not in orexin ko mice suggests that other signaling molecules such as dynorphin or glutamate may act in concert with orexins to suppress rem sleep during the active period.,General
do pneumoconiosis in affiliated workers have irreversible sequelae ?,"to analyze the frequency and importance of pneumoconiosis in affiliated workers to instituto mexicano del seguro social. it was carried out a transverse, observational and comparative study; the behavior of the qualified pneumoconiosis was revised 1994-2004. the analyzed variables were sex, age, occupation, permanent disability and economic activity. it was carried out the analysis of absolute frequencies and rates. it was registered 14,827 cases; the rate for 10,000 workers oscillated from 0.48 to 2.39. the 99 were presented in males, with 14,262 cases with permanent disability (rate: 96.89 per 100 cases of pneumoconiosis); employments with more frequency were miners, quarry workers and bricklayers. the average of permanent disability for pneumoconiosis in the period was of 11.09 to 15 . states with a higher number of cases were coahuila, zacatecas and hidalgo. economic activities with a greater incidence were the extraction and benefit of mineral coal, graphite and metallic and non-metallic minerals.","cases of pneumoconiosis have been decreasing, but even the determination of diagnosis is delayed, and due to this most workers have irreversible sequelae.",General
does bone morphogenetic protein signaling regulate gastric epithelial cell development and proliferation in mice?,"we investigated the role of bone morphogenetic protein (bmp) signaling in the regulation of gastric epithelial cell growth and differentiation by generating transgenic mice that express the bmp inhibitor noggin in the stomach. the promoter of the mouse h/k-atpase -subunit gene, which is specifically expressed in parietal cells, was used to regulate expression of noggin in the gastric epithelium of mice. the transgenic mice were analyzed for noggin expression, tissue morphology, cellular composition of the gastric mucosa, gastric acid content, and plasma levels of gastrin. tissues were analyzed by immunohistochemical, quantitative real-time polymerase chain reaction, immunoblot, microtitration, and radioimmunoassay analyses. in the stomachs of the transgenic mice, phosphorylation of smad 1, 5, and 8 decreased, indicating inhibition of bmp signaling. mucosa were of increased height, with dilated glands, cystic structures, reduced numbers of parietal cells, and increased numbers of cells that coexpressed intrinsic factor, trefoil factor 2, and griffonia (bandeiraea) simplicifolia lectin ii, compared with wild-type mice. in the transgenic mice, levels of the h/k-atpase -subunit protein and messenger rna were reduced, whereas those of intrinsic factor increased. the transgenic mice were hypochloridric and had an increased number of ki67- and proliferating cell nuclear antigen-positive cells; increased levels of plasma gastrin; increased expression of transforming growth factor-, amphiregulin, and gastrin; and activation of extracellular signal-regulated kinase 2.","inhibiting bmp signaling in the stomachs of mice by expression of noggin causes loss of parietal cells, development of transitional cells that express markers of mucus neck and zymogenic lineages, and activation of proliferation. bmps are therefore important regulators of gastric epithelial cell homeostasis.",Medication
is anti-angiogenic effect of metformin in mouse oxygen-induced retinopathy mediated by reducing levels of the vascular endothelial growth factor receptor flk-1?,"to evaluate the effect of metformin on vascular changes in oxygen-induced retinopathy (oir) in mouse, and to elucidate the possible underlying mechanism. oir mice were treated with metformin by intraperitoneal injection from postnatal day 12 (p12) to p17 or p21. at p17 and p21, vessel formation and avascular areas were assessed using retinal flat mounts. levels of vascular endothelial growth factor (vegf) were measured by enzyme-linked immunosorbent assays, and the effects of metformin on vegf-induced proliferation of human umbilical vein endothelial cells (huvecs) were assessed. the effects of metformin on the levels of flk1 (vegf receptor-2) and phosphorylated flk1 (pflk1) were measured by western blotting (huvecs) and immunohistochemistry (retinal tissue). retinal morphologic changes were analyzed between two groups (saline-treated oir; metformin-treated oir). metformin treatment did not change the extent of avascular areas at p17. however, at p21, when oir pathology was markedly improved in the saline-treated group, oir pathology still remained in the metformin-treated oir group. vegf expression levels did not differ between metformin- and saline-treated oir groups at p17 and p21, but flk1 levels were significantly reduced in the metformin group compared with saline-treated oir group. moreover, metformin inhibited vegf-induced cell proliferation and decreased levels of flk1 and pflk1, consistent with the interpretation that metformin inhibits vascular growth by reducing flk1 levels.","metformin exerts anti-angiogenesis effects and delays the normal vessel formation in the recovery phase of oir in mice, likely by suppressing the levels of flk1.",Medication
does prostaglandin ep2 receptor signalling inhibit the expression of matrix metalloproteinase 13 in human osteoarthritic chondrocytes?,"matrix metalloproteinase (mmp) 13 is a pathogenic collagenase that causes cartilage destruction and plays a leading role in causing osteoarthritis. this study focused on 114 genes that are differentially expressed between intact and damaged osteoarthritis cartilage, in order to determine which molecules are involved in suppressing mmp-13 expression. mmp-13 concentrations were measured in the supernatant of human osteoarthritis chondrocyte cultures transfected with small interfering rna (sirna) against the 114 genes. mmp-13 levels changed most dramatically in response to sirna against prostaglandin ep2 receptor. the authors performed further measurements of mmp-13 production in osteoarthritis chondrocytes stimulated by the ep2 agonist butaprost in the presence or absence of interleukin-1 (il-1) and/or cyclooxygenase-2 (cox-2) inhibitor. they also assessed the effect of butaprost on chondrocyte viability, and investigated the involvement of the camp-protein kinase a (pka) pathway on ep2 signalling using inhibitors. cartilage-related gene expression was examined in chondrocytes treated with butaprost. the authors also investigated which e series of prostaglandin (ep) receptors are expressed in osteoarthritis cartilage. mmp-13 messenger rna expression was significantly affected by two molecules, ep2 receptor and slc14a1, a urea transporter. in il-1-treated osteoarthritis chondrocytes, butaprost suppressed mmp-13 production, which was further decreased by cox-2 inhibitor. ep2 signalling downregulated mmp-13 mrna expression via the camp-pka pathway without affecting cell viability. although ep2 signalling enhanced il-6 expression, the expressions of several catabolic factors (mmp-1, mmp-3, mmp-13, adamts5, il-1 and tumour necrosis factor alpha) were inhibited. ep2 receptor was the major ep receptor in osteoarthritis cartilage.",the results suggest that ep2 signalling has 'anti-catabolic' effects in osteoarthritis chondrocytes.,Medication
is deletion of lce3clce3b associated with rheumatoid arthritis and systemic lupus erythematosus in the chinese han population?,"the deletion of lce3clce3b confers susceptibility to psoriasis and rheumatoid arthritis (ra) in caucasians. the aim of this study was to investigate the variant involvement in ra in the chinese han population and to further explore its potential role in the susceptibility to systemic lupus erythematosus (sle). lce3clce3b-del was genotyped in 898 patients with ra and 681 healthy controls. two single nucleotide polymorphisms (snps, rs4112788 and rs4085613) in strong linkage disequilibrium with lce3clce3b-del were then genotyped in patients with ra (n1222), sle (n870) and healthy controls (n1031). the deletion of lce3clce3b and snps rs4112788 and rs4085613 showed an association with ra (allele analysis: p7.7210(-4), or 1.28, 95 ci 1.11 to 1.47; p6.3910(-4), or 1.23, 95 ci 1.09 to 1.38; and p5.3810(-4), or 1.23, 95 ci 1.10 to 1.39, respectively). the two snps were also signicantly associated with sle (allele analysis: p7.6810(-3), or 1.19, 95 ci 1.05 to 1.36 and p5.3010(-3), or 1.20, 95 ci 1.06 to 1.37).","this study provides evidence for an association between lce3clce3b-del and ra in non-caucasian populations, and snps rs4112788 and rs4085613 tagging lce3clce3b-del were novel susceptibility factors for sle.",General
is simple exercise recovery index for sympathetic overactivity linked to insulin resistance?,"exercise hr recovery (hrr) has proven an effective clinical means to assess parasympathetic dysfunction linked to all-cause mortality, but an analogous functional assessment for sympathetic dysfunction has not been developed. we investigated whether exercise recovery provides additional cardiorespiratory information, beyond the initial hrr period, to index sympathetic overactivity associated with insulin resistance. young people (n 20) with diverse percent body fat (9-52) were studied using fasting, oral glucose tolerance test (ogtt), and high-carbohydrate meal measurements. participants also completed a graded fitness test (oxygen consumption peak test on cycle ergometer) after which hr and oxygen consumption (v x o2) measurements were continued for 3 min into recovery. the first, rapid phase of exercise recovery was used as the clinical measurement for parasympathetic control (hrr hr2 min - hrmax). the second, initial plateau phase of exercise recovery was used to calculate a novel functional index for sympathetic overactivity (the plateau value for the ratio of hr normalized for v x o2 (hr/v x o2 plat)). as expected, parasympathetic function (hrr) was within the normal range in these young people (-58 /- 2 bpm). the index for sympathetic overactivity varied over a wide range from 9 to 34 bpm/(ml x kg x min(-1)), with obese adolescents having values in the highest 25th percentile. we found that this simple index was correlated to both the ogtt-derived whole-body insulin sensitivity index (r -0.74, p 0.001) and homeostasis assessment model for insulin resistance (r 0.76, p 0.001), independent of percent body fat and parasympathetic function. meal-induced thermogenesis was also associated with hr/v x o2 plat (r -0.64, p 0.01) but not with hrr.","in young individuals, recovery from intense exercise may provide a simple means to quantify both parasympathetic and sympathetic function. the exercise recovery index for sympathetic overactivity was linked to insulin resistance.",Medication
is shorter sleep duration associated with decreased insulin sensitivity in healthy white men?,"short sleep has been linked to increased risk for type 2 diabetes and incident cardiovascular disease and acute sleep restriction impairs insulin-mediated glucose disposal. here, we examined whether indices of glucose metabolism vary with naturally occurring differences in sleep duration. subjects were midlife, nondiabetic community volunteers (n 224; mean age 44.5 6.6 y range: 30-54; 52 female; 89 white). laboratory measures of insulin sensitivity (si) and acute secretion (airg), glucose effectiveness (sg), and disposition index (di) were obtained from a 180-min, intravenous glucose tolerance test. shorter self-reported sleep duration (in hours) was associated with lower si (p 0.043), although an interaction of sleep duration with participant race ( -0.81, p 0.002) showed this association significant only in whites. moreover, sex-stratified analyses revealed that shorter sleep duration predicted lower si in white men ( 0.29, p 0.003) but not in white women (p 0.22). findings were similar for airg. the relationship between sleep duration and airg was moderated by race as well as sex, such that shorter sleep duration associated with greater insulin release only in white men ( -0.28, p 0.004). sleep duration was unrelated to sg and di (p's 0.05).","our findings suggest that shorter sleep duration may impair insulin sensitivity and beta-cell function in nondiabetic white men, possibly contributing to later type 2 diabetes and cardiovascular disease.",Medication
is dna aneuploidy by flow cytometry an independent prognostic factor in squamous cell carcinoma of the oral cavity?,"the clinical significance of flow cytometric dna content in head and neck squamous cell carcinoma is still controversial. we prospectively investigated the prognostic importance of tumor size (t), lymph node involvement at presentation (n), degree of histologic differentiation (g) and dna ploidy (dna) in 429 surgically treated patients with primary oral squamous cell carcinoma using multivariate statistics. t, g and dna were independent predictors of metastasis to the neck. n and dna were independent prognostic factors of loco-regional recurrence development. n and t were prognostic of overall survival. n and dna were predictive of recurrence-free survival. for the neck negative group, dna remained as the only predictor of overall and relapse-free survival.",dna flow cytometry adds significant prognostic information beyond that provided by established prognostic factors.,Diagnosis
does virus-mediated epor76e gene therapy preserve vision in a glaucoma model by modulating neuroinflammation and decreasing oxidative stress?,"glaucoma is a complex neurodegeneration and a leading cause of blindness worldwide. current therapeutic strategies, which are all directed towards lowering the intraocular pressure (iop), do not stop progression of the disease. we have demonstrated that recombinant adeno-associated virus (raav) gene delivery of a form of erythropoietin with attenuated erythropoietic activity (epor76e) can preserve retinal ganglion cells, their axons, and vision without decreasing iop. the goal of this study was to determine if modulation of neuroinflammation or oxidative stress played a role in the neuroprotective activity of epo.r76e. five-month-old dba/2j mice were treated with either raav.epor76e or a control vector and collected at 8 months of age. neuroprotection was assessed by quantification of axon transport and visual evoked potentials. microglia number and morphology and cytokine and chemokine levels were quantified. message levels of oxidative stress-related proteins were assessed. axon transport and visual evoked potentials were preserved in raav.epor76e-treated mice. the number of microglia was decreased in retinas from 8-month-old raav.epor76e-treated mice, but proliferation was unaffected. the blood-retina barrier was also unaffected by treatment. levels of some pro-inflammatory cytokines were decreased in retinas from raav.epor76e-treated mice including il-1, il-12, il-13, il-17, ccl4, and ccl5. tnf messenger rna (mrna) was increased in retinas from 8-month-old mice compared to 3-month-old controls regardless of treatment. expression of several antioxidant proteins was increased in retinas of raav.epor76e-treated 8-month-old mice.","treatment with raav.epor76e preserves vision in the dba/2j model of glaucoma at least in part by decreasing infiltration of peripheral immune cells, modulating microglial reactivity, and decreasing oxidative stress.",Treatment
is hepatic steatosis associated with higher incidence of liver metastasis in patients with metastatic breast cancer ; an observational clinical study?,"to investigate the relationship between hepatic steatosis (hs) (at the time of diagnosis) and hepatic metastasis (at the time of diagnosis and follow-up) in metastatic breast cancer (bc) patients by using computed tomography (ct). a total of 107 metastatic bc patients who had an abdominal ct were retrospectively enrolled in this study. patients without hs (n79) were regarded as the control group and those with hs constituted the hs study group (n-28). hepatic metastases at diagnosis and during follow-up were more common in patients with hs (p0.018 and p0.041, respectively) and in the premenopausal group (p0.001 and p0.004, respectively), whereas they were similar in patients with and without hs in the postmenopausal group (p0.655 and p0.656, respectively). overall survival rates were similar in patients with and without hs (p0.606).","hepatic metastases at diagnosis and during follow-up were more frequent in patients with hs, especially in premenopausal patients. survival was similar in both groups.",Diagnosis
does association mapping by pooled sequencing identify toll 11 as a protective factor against plasmodium falciparum in anopheles gambiae?,"the genome-wide association study (gwas) techniques that have been used for genetic mapping in other organisms have not been successfully applied to mosquitoes, which have genetic characteristics of high nucleotide diversity, low linkage disequilibrium, and complex population stratification that render population-based gwas essentially unfeasible at realistic sample size and marker density. we designed a novel mapping strategy for the mosquito system that combines the power of linkage mapping with the resolution afforded by genetic association. we established founder colonies from west africa, controlled for diversity, linkage disequilibrium and population stratification. colonies were challenged by feeding on the infectious stage of the human malaria parasite, plasmodium falciparum, mosquitoes were phenotyped for parasite load, and dna pools for phenotypically similar mosquitoes were illumina sequenced. phenotype-genotype mapping was carried out in two stages, coarse and fine. in the first mapping stage, pooled sequences were analysed genome-wide for intervals displaying relativereduction in diversity between phenotype pools, and candidate genomic loci were identified for influence upon parasite infection levels. in the second mapping stage, focused genotyping of snps from the first mapping stage was carried out in unpooled individual mosquitoes and replicates. the second stage confirmed significant snps in a locus encoding two toll-family proteins. rnai-mediated gene silencing and infection challenge revealed that toll 11 protects mosquitoes against p. falciparum infection.","we present an efficient and cost-effective method for genetic mapping using natural variation segregating in defined recent anopheles founder colonies, and demonstrate its applicability for mapping in a complex non-model genome. this approach is a practical and preferred alternative to population-based gwas for first-pass mapping of phenotypes in anopheles. this design should facilitate mapping of other traits involved in physiology, epidemiology, and behaviour.",Diagnosis
do patients with uncomplicated coronary artery disease have reduced heart rate variability mainly affecting vagal tone?,"to investigate whether uncomplicated chronic coronary artery disease causes changes in heart rate variability and if so, whether the heart rate variability pattern is different from that described in patients with acute myocardial infarction. heart rate variability was studied in 65 patients with angina who had no previous myocardial infarcts, no other diseases, and were on no drug that could influence the sinus node. results were compared with 33 age matched healthy subjects. the diagnosis of coronary artery disease in angina patients was established by coronary angiography in 58, by thallium scintigraphy in six, and by exercise test only in one. patients and controls were holter monitored 24 hours outside hospital, and heart rate variability was calculated in the frequency domain as global power (gp: 0.01-1.00 hz), low frequency peak (lf: 0. 04-0.15 hz), high frequency peak (hf: 0.15-0.40 hz), lf/hf in ms(2), and in the time domain as sdnn (sd of normal rr intervals), sdann (sd of all five minute mean normal rr intervals), sd (mean of all five minute sds of mean rr intervals), rmssd (root mean square of differences of successive normal rr intervals) (all in ms), and pnn50 (proportion of adjacent normal rr intervals differing more than 50 ms from the preceding rr interval) as per cent. the mean age in patients and controls was 60.4 (range 32-81) and 59.1 (32-77) years, respectively (ns), the male/female ratio, 57/65 and 24/33 (ns), and the mean time of holter monitoring, 23.0 (18-24) and 22.8 (18-24) hours (ns). mortality in angina patients was 0 (0/65) at one year, 0 (0/56) at two years, and 3 (1/33) at three years. compared with healthy subjects angina patients showed a reduction in gp (p 0.007), hf (p 0.02), lf (p 0.02), sd (p 0.02), rmssd (p 0.01), and pnn50 (p 0.01). no significant difference was found in rr, lf/hf, sdnn, or sdann.","uncomplicated coronary artery disease without previous acute myocardial infarction was associated with reduced high and low frequency heart rate variability, including vagal tone. sdann and sdnn, expressing ultra low and very low frequencies which are known to reflect prognosis after acute myocardial infarction, were less affected. this is in agreement with the good prognosis in uncomplicated angina in this study.",Medication
do the value of serum mean platelet volume in ischaemic stroke patient?,"to investigate the value of serum mean platelet volume in acute ischaemic stroke patients. the retrospective case-control study was conducted at ankara numune training and research hospital in turkey and comprised record of patients of acute ischaemic stroke admitted to the emergency department between june 2010 and january 2012. the two groups were statistically compared using spss 18.0. overall, there were 482 stroke patients (group 1) and 315 subjects as controls (group 2). the median value in group 1 was 9.0 (2.1) (fl), while in group 2 it was 8.80 (2.4) (fl).the difference was statistically significant (z -2.80; p 005).",mean platelet volume increased in the stroke patients.,General
do mice deficient in telomerase activity develop hypertension because of an excess of endothelin production?,"telomere shortening has been related to vascular dysfunction and hypertension. in the present study, we analyzed the influence of telomerase deficiency and telomere shortening on arterial pressure (ap). ap was evaluated in 6-month-old mice lacking the rna component of the telomerase (terc-/-) at the first generation and third generation (g3). first generation and g3 mice showed higher ap than wild-type (wt) mice. to analyze the mechanisms involved, mean ap and vascular resistance in response to vasoactive substances were measured in g3 and wt mice. these mice showed similar responses to acetylcholine, n(g)-nitro-l-arginine methyl ester, angiotensin ii, and losartan administration. mean ap did not increase after endothelin-1 (et-1) administration in g3 mice, but it did in wt animals. bosentan treatment decreased mean ap only in g3 mice. serum and urine concentrations of et-1 were higher in terc-/- than in wt mice. endothelin-converting enzyme (ece-1) mrna expression was higher in terc-/- animals than in the wt group. fr901533, an ece antagonist, decreased blood pressure in conscious g3 mice. studies in mouse embryonic fibroblasts from g3 mice suggest that ece-1 overexpression could be mediated by reactive oxygen species in an ap-1-dependent mechanism, in which some kinases such as pi3-kinase, akt, erk1/2, and jun kinase could be involved. an increased activity of nicotinamide adenine dinucleotide phosphate oxidase seems to be the main source of reactive oxygen species.","mice lacking telomerase activity show hypertension as a result of an increase in plasma et-1 levels, which is a consequence of ece-1 overexpression. a direct link between telomerase activity and hypertension is reported.",Medication
does radial artery pressure monitoring underestimate central arterial pressure during vasopressor therapy in critically ill surgical patients?,"radial artery pressure is known to differ from central arterial pressure in normal patients (distal pulse amplification) and in the early postcardiopulmonary bypass period. the adequacy of the radial artery as a site for blood pressure monitoring in critically ill patients receiving high-dose vasopressors has not been carefully examined. prospective observational study comparing simultaneous intra-arterial measurements of radial (peripheral) and femoral artery (central) pressures. clinical investigation in a university-based surgical intensive care unit. fourteen critically ill patients with presumed sepsis who received norepinephrine infusions at a rate of or 5 microg/min. all patients were managed in accordance with our standard practice for presumed sepsis, which consisted of intravascular volume repletion followed by vasopressor administration titrated to a mean arterial pressure of or 60 mm hg. systolic and mean arterial pressures were significantly higher when measured from the femoral vs. radial site (p .005). the higher mean arterial pressures enabled an immediate reduction in norepinephrine infusions in 11 of the 14 patients. no change in cardiac output or pulmonary artery occlusion pressure was noted after dose reduction. in the two patients in whom simultaneous recordings were made after discontinuation of norepinephrine infusions, equalization of mean arterial pressures was observed.","radial artery pressure underestimates central pressure in hypotensive septic patients receiving high-dose vasopressor therapy. clinical management, based on radial pressures, may lead to excessive vasopressor administration. awareness of this phenomena may help minimize adverse effects of these potent agents by enabling dosage reduction.",Treatment
does prior radiation and/or chemotherapy have no effect on the outcome of metal stent placement for oesophagogastric carcinoma?,"it is still unclear whether prior radiation and/or chemotherapy (rtct) increases the risk of complications after the placement of self-expanding metal stents in patients with inoperable oesophagogastric carcinoma. we evaluated the influence of prior rtct on the outcome of stent placement in a large group of patients. from october 1994 to december 2000, 200 patients underwent placement of self-expanding metal stents for malignant dysphagia, and were followed prospectively. forty-nine of these patients had received prior rtct (chemotherapy n 35, radiation therapy n 8, or both n 6). at 4 weeks after stenting, the dysphagia score had improved similarly in patients with or without prior rtct, from a median of 3 to 0 (p 0.001). the occurrence of major complications (bleeding, perforation, fistula formation, fever and severe pain) was not different between patients with or without prior rtct (29 vs 21; relative risk (rr) 1.15 (95 ci 0.54-2.46; p 0.72)), as was the occurrence of recurrent dysphagia due to tumour overgrowth, stent migration, or impaction of a food bolus (35 vs 27; rr 1.49 (95 ci 0.71-3.13; p 0.29)). median survival of both patient groups after stent placement was similar (110 vs 93 days; rr 0.90 (95 ci 0.60-1.34; p 0.60) for prior rtct versus no prior treatment). only minor complications (mainly mild retrosternal pain) occurred more frequently in patients with prior rtct (41 vs 15; rr 2.12 (95 ci 1.06-4.25; p 0.035)).","both the incidence of life-threatening complications and survival after placement of self-expanding metal stents for oesophagogastric carcinoma are not affected by prior rtct, but retrosternal pain occurs more frequently in patients who had previously undergone rtct.",Medication
does palmitate enhance toll-like receptor 4 expression and signaling in porcine vascular endothelial cells ?,"to study the effect of palmitate on toll-like receptor 4 (tlr4) expression and signaling in vascular endothelial cells. pig iliac endothelial cells (piecs) were incubated with palmitate. tlr4 gene expression levels were measured by quantitative real-time pcr, and tlr4 and ib protein expressions by western blotting. the expression levels of tlr4 protein on the surface of piecs were quantified using flow cytometry. elisa was employed to detect tumor necrosis factor- (tnf-) and interleukin-6 (il-6) concentrations in the cell medium. palmitate treatment significantly increased tlr4 mrna and protein expression levels in piecs compared with those in the control cells (4.730.61 vs 1.250.90, p0.05; 5.790.05 vs 4.070.31, p0.05). the expression levels of tlr4 on the cell surface significantly increased (38.0703.907 vs 29.3901.072, p0.05), while ib protein level was significantly lowered in piecs after palmitate treatment as compared with those in the control cells (2.040.22 vs 3.980.18, p0.05). palmitate treatment significantly elevated tnf- (2.520.30 vs 1.380.26, p0.05) and il-6 (il-6: 3.280.32 vs 1.440.28, p0.05) concentrations in the cell culture medium.",palmitate can enhance tlr4 expression and signaling in porcine vascular endothelial cells.,Medication
are the plant-associated bacillus amyloliquefaciens strains mep2 18 and arp2 3 capable of producing the cyclic lipopeptides iturin or surfactin and fengycin effective in biocontrol of sclerotinia stem rot disease?,"this work was conducted to identify the antifungal compounds produced by two previously isolated bacillus sp. strains: arp(2) 3 and mep(2) 18. both strains were subjected to further analysis to determine their taxonomic position and to identify the compounds responsible for their antifungal activity as well as to evaluate the efficiency of these strains to control sclerotinia stem rot in soybean. the antifungal compounds were isolated by acid precipitation of cell-free supernatants, purified by rp-hplc and then tested for antagonistic activity against sclerotinia sclerotiorum. mass spectra from rp-hplc eluted fractions showed the presence of surfactin c(15) , fengycins a (c(16) -c(17)) and b (c(16)) isoforms in supernatants from strain arp(2) 3 cultures, whereas the major lipopeptide produced by strain mep(2) 18 was iturin a c(15) . alterations in mycelial morphology and sclerotial germination were observed in the presence of lipopeptides-containing supernatants from bacillus strains cultures. foliar application of bacillus amyloliquefaciens strains on soybean plants prior to s. sclerotiorum infection resulted in significant protection against sclerotinia stem rot compared with noninoculated plants or plants inoculated with a nonlipopeptide-producing b. subtilis strain.","both strains, renamed as b. amyloliquefaciens arp(2) 3 and mep(2) 18, were able to produce antifungal compounds belonging to the cyclic lipopeptide family. our data suggest that the foliar application of lipopeptide-producing b. amyloliquefaciens strains could be a promising strategy for the management of sclerotinia stem rot in soybean.",Medication
does xiaojin wan inhibit the expression of cox-2 in prostate tissues of prostatitis pain rats ?,"to study the effect of xiaojin wan on the expression of cox-2 in the prostate tissues of rats with prostatitis pain, and the action mechanism of the drug alleviating the prostatitis pain. sixty male wistar rats were randomized into two groups, 10 as blank controls, injected with aqua pro injection into the ventral part of prostate, and the other 50 as prostatitis pain models, given complete freund's adjuvant (cfa). three days later, the pain model rats were again equally divided into 5 subgroups: model control, celecoxib capsules, high-, median- and low-dose xiaojin wan, receiving intragastric administration of distilled water, celecoxib capsules and different doses of xiaojin wan respectively for 4 weeks. then they were killed, the harvested tissues fixed with 10 paraformaldehyde and the changes of the cox-2 expression in the prostate detected with the immunohistochemical technique and graphics video analysis system. the expression of cox-2 was strong in the model group, significantly lower in the high- and median-dose and the celecoxib capsules groups than in the model control (p 0.01) as well as in the high-dose than in the median- and low-dose groups (p 0.01).",xiaojin wan may alleviate prostatitis pain by inhibiting the expression of cox-2 in prostate tissues.,Medication
do variants in the netrin-1 receptor unc5c prevent apoptosis and increase risk of familial colorectal cancer?,"expression of the netrin-1 dependence receptor unc5c is reduced in many colorectal tumors; mice with the unc5c mutations have increased progression of intestinal tumors. we investigated whether specific variants in unc5c increase risk of colorectal cancer (crc). we analyzed the sequence of unc5c in blood samples from 1801 patients with crc and 4152 controls from 3 cohorts (france, united states, and finland). almost all cases from france and the united states had familial crc; of the finnish cases, 92 of 984 were familial. we analyzed whether crc segregates with the unc5c variant a628k in 3 families with histories of crc. we also performed haplotype analysis to determine the origin of this variant. of 817 patients with familial crc, 14 had 1 of 4 different, unreported missense variants in unc5c. the variants p.asp353asn (encodes d353n), p.arg603cys (encodes r603c), and p.gln630glu (encodes q630e) did not occur significantly more often in cases than controls. the variant p.ala628lys (a628k) was detected in 3 families in the french cohort (odds ratio, 8.8; wald's 95 confidence interval, 1.47-52.93; p .03) and in 2 families in the us cohort (odds ratio, 1.9; p .6) but was not detected in the finnish cohort; unc5c a628k segregated with crc in families. three families with a628k had a 109-kilobase identical haplotype that spanned most of unc5c, indicating recent origin of this variant in white subjects (14 generations; 95 confidence interval, 6-36 generations). transfection of hek293t cells with unc5c-a628k significantly reduced apoptosis compared with wild-type unc5c, measured in an assay of active caspase-3.",inherited mutations in unc5c prevent apoptosis and increase risk of crc.,Prevention
is serum level of interleukin-21 elevated in chronic rhinosinusitis?,"chronic rhinosinusitis (crs) is an inflammatory disease of the sinuses and mucosa with unclear pathogenesis. interleukin (il)-21 is mainly expressed in activated cluster of differentiation (cd)4() t cells and has potent regulatory effects on the immune system. this study is to determine whether il-21 in the blood is correlated with crs. the blood samples from crs patients and normal controls were analyzed in correlation with clinical features. the eosinophil percentage was counted, and serum levels of total immunoglobulin e (ige) and il-21 were analyzed by enzyme-linked immunosorbent assay (elisa). in addition, il-21 and interferon (ifn)- secreted from stimulated peripheral blood mononuclear cells (pbmcs) were measured by elisa, and their mrna expression levels were analyzed by real-time quantitative polymerase chain reaction (rt-qpcr). disease severity was scored based on computed tomography (ct) scan, nasal endoscopy, and global osteitis scoring scale (goss). a total of 55 crs and 37 healthy subjects were recruited. the average levels of serum total ige were 20 ku/l in normal group, 290 ku/l in crs with nasal polys (crswnp), and 187 ku/l in crs without nasal polys (crssnp). il-21 levels were 28 pg/ml in normal group, 54 pg/ml in crswnp, and 71 pg/ml in crssnp. both ige and il-21 were significantly elevated in both crs patient subgroups. however, no significant difference was found between these two patient subgroups. the serum il-21 levels correlated well with the disease severity in the patients. in addition, the secreted il-21 was enhanced significantly in the patient's pbmcs stimulated by phytohemagglutin (pha).",il-21 could be a target for diagnosis and treatment of crs.,Medication
does treatment of chronic bacterial prostatitis with levofloxacin and ciprofloxacin lower serum prostate specific antigen?,"we compared baseline and post-therapy prostate specific antigen (psa) in patients with chronic bacterial prostatitis who were treated with levofloxacin or ciprofloxacin. subset analysis was done using a randomized, multicenter, double-blind, active control trial of 500 mg levofloxacin daily for 28 days vs 500 mg ciprofloxacin twice daily in 28 days in men with chronic bacterial prostatitis. of the 377 men in the intent to treat population, including 197 treated with levofloxacin and 180 treated with ciprofloxacin, 35 on levofloxacin and 37 on ciprofloxacin with baseline psa greater than 4 ng/ml were included in this analysis. excluded from analysis were 2 levofloxacin treated patients with extremely high psa at baseline (62 and 103 ng/ml, respectively). mean baseline psa /- sd in the patients analyzed was 8.33 /- 4.46 ng/ml, which decreased to 5.36 /- 3.82 ng/ml after therapy. there was no significant difference in the mean change in psa between the levofloxacin and ciprofloxacin groups. approximately 42 of patients with increased baseline psa had a post-therapy psa of 4 ng/ml or less. of patients who were microbiologically evaluable and had normalized psa after therapy levofloxacin eradicated the pathogen in 90.9 (10 of 11). however, of patients in whom post-therapy psa remained increased the microbiological eradication rate was 69.2 (9 of 13). similarly 93.3 of the ciprofloxacin group (14 of 15 patients) with normalized post-therapy psa experienced microbiological eradication compared with 61.5 (8 of 13) with continued increased psa after therapy.",approximately 20 of patients diagnosed with chronic bacterial prostatitis had increased psa. a significant decrease in psa was observed in these patients after treatment with levofloxacin or ciprofloxacin. an association was observed between bacterial persistence and the likelihood that psa would return to normal.,Treatment
does perioperative use of tirofiban hydrochloride ( aggrastat ) increase surgical bleeding after emergency or urgent coronary artery bypass grafting?,"the platelet glycoprotein iib/iiia inhibitor tirofiban hydrochloride improves outcome in patients with acute coronary syndrome. nevertheless, a considerable number of patients require emergency or urgent coronary artery bypass grafting and may be at increased risk of postoperative bleeding after treatment with this molecule. the aim of this study is to evaluate the incidence of bleeding complications among patients undergoing bypass grafting after treatment with tirofiban. we investigated the influence of the molecule on postoperative bleeding after cardiac surgery, comparing 2 groups of patients undergoing emergency or urgent coronary artery bypass grafting: group a (n 20) received tirofiban, and group b (n 68) received conventional therapy with intravenous heparin up until the operation. a total of 88 patients underwent coronary artery bypass surgery within 2 hours of ceasing the hemodynamic study. clinical outcome, chest tube outputs, bleeding complications, transfusion requirements, platelet and hemoglobin counts, and clinical complications were examined. bleeding differences were noted between the 2 groups at 8, 16, and 24 hours postoperatively. the incidence of blood, platelet, and fresh frozen plasma transfusions was higher in the control group. postoperative thrombocytopenia was preserved in group a (199.5 /- 70.4 vs 150.6 /- 33.4 10(3)/ml, p .01). no significant differences were noted between the 2 groups in the incidence of perioperative myocardial infarction, but significant differences were noted in enzyme levels, length of stay in the intensive care unit, and length of stay in the hospital. no deaths were observed. hospital morbidity was increased in group b because of factors that were not apparently linked with tirofiban infusion.","patients may safely undergo coronary artery bypass surgery after treatment with tirofiban hydrochloride. this molecule, administered in the immediate preoperative period, has no adverse clinical effects and does not seem to negatively influence the incidence of perioperative myocardial infarction. although extracorporeal circulation can modify platelet numbers and function, our ongoing data could show significant reduction in the loss of platelets induced by cardiopulmonary bypass, minor postoperative bleeding, and a minor transfusion requirement in general.",Treatment
do kinematics and kinetics of 2 styles of partial forward lunge?,"to evaluate the anterior shift of the body's center of gravity (cg) and the associated inertial forces produced by 2 styles of a partial forward lunge. gait-analysis laboratory of a research institution. 10 healthy volunteers. 3 trials of each lunge. kinematic data were collected, and inertial reaction forces were resolved into net compressive and shear forces using an inverse dynamic model. significantly (p .001) greater anterior translation of the cg was found with an arms-in-front v arms-across-chest lunge style. no significant differences were found between the average peak inertial compressive and shear forces of the 2 styles (427 /- 184 n v 426 /- 187 n, -536 /- 113 n v -538 /- 127 n).","anterior translation of the cg was larger with the arms-forward partial-lunge position, creating increased balance demands. both styles produced clinically safe (posteriorly directed) inertial shear forces, with greater anterior cg shift with the arms-forward style.",General
does hiv rev used a conserved cellular protein export pathway for the nucleocytoplasmic transport of viral rnas?,"the structural proteins of human immunodeficiency virus type 1 (hiv-1) are encoded by intron-containing mrnas that normally are retained in the nucleus. a viral regulatory protein, rev, specifically induces the accumulation of these transcripts in the cytoplasm. rev is an rna-binding protein that also contains an 'effector' domain. the rev effector domain has recently been shown to function as an autonomous nuclear export signal (nes) that, when fused to a foreign protein, will cause its rapid nuclear export. we and others have recently reported the cloning of a human protein (hrip/rab), that specifically interacts with the effector domain of rev. here we show that the ness contained within two cellular proteins, pki and i kappa b, which are not involved in rna metabolism, also interact with hrip. fusion of these cellular sequences to the rev rna-binding domain reconstitutes a functional rev protein. in addition to hrip, these ness also bind to several nuclear pore complex (npc). we show that this protein export pathway is highly conserved by demonstrating that mammalian ness also function in yeast.","our results indicate that the hiv-1 rev protein evolved to take advantage of a cellular protein export pathway in order to allow the nucleocytoplasmic transport of unspliced viral rna. our data suggest a model in which the export substrate is translocated through the npc by sequential interactions with different nucleoporins. finally, our experiment suggests a mechanism by which i kappa b can downregulate nuclear nf kappa b activity by causing its rapid export from the nucleus.",General
"is isolated vitamin d deficiency associated with nonthyroidal illness syndrome , but with thyroid autoimmunity?","this study aimed to compare thyroid functions, thyroid autoantibodies, and the existence of nonthyroidal illness syndrome (ntis) according to vitamin d level. the study included age- and bmi-matched healthy volunteers with and without vitamin d deficiency. in addition, the nonthyroidal illness syndrome status was evaluated. anti-tpo positivity was significantly more common in those with severe and moderate vitamin d deficiency, as compared to those with a normal 25(oh)d level. furthermore, tsh levels were significantly lower in those with severe and moderate vitamin d deficiency than in those with a normal 25(oh)d level. in addition, there was a significant weak inverse correlation between anti-tpo positivity and the 25(oh)d level and a positive correlation between the tsh level and 25(oh)d level. only 1 thyroid function test result was compatible with ntis among the participants with moderate vitamin d deficiency; therefore the difference was not significant.",the prevalence of thyroid autoantibody positivity was higher in those with severe and moderate vitamin d deficiency than in those with a normal 25(oh)d level. additional large-scale studies must be conducted to determine if vitamin d deficiency plays a causal role in the pathogenesis of hashimoto's thyroiditis and ntis.,General
does fibre tract analysis using diffusion tensor imaging reveal aberrant connectivity in a rat model of depression?,"abnormal brain connectivity has been described in depressive disorder. however, these studies are correlational or cross-sectional and their design does not examine causal relationships. we aimed to investigate structural connectivity in a genetic rat model of depression. using diffusion tensor imaging (dti), we reconstructed white matter tracts and analysed fractional anisotropy (fa) and diffusivity indices (mean, axial and radial) to investigate structural connectivity in fibre tracts implicated in major depression: the corpus callosum, fornix, cingulum and anterior commissures. tractography-based analysis revealed that, compared to wistar control rats, the wistar-kyoto strain (wky) rat model of depression exhibited decreased connectivity, manifested by decreased fa in the corpus callosum, right and left anterior commissures. a statistical trend of decreased fa was observed in both the right and left cingulum. increased diffusivity (mean diffusion) was detected in both the corpus callosum and the fornix of wky rats compared to controls. voxel-based analysis confirmed differences between wky and controls in the regions investigated.",decreased connectivity in a genetic rat model of depression corroborates the findings in patients suffering from major depression suggesting that the vulnerability for developing depression is mainly polygenic and less likely to be due to childhood adversity per se.,Diagnosis
are socioeconomic differences in outpatient healthcare utilisation mainly seen for musculoskeletal problems in groups with poor self-rated health?,"to assess whether there are socioeconomic (ses) differences in outpatient visits within groups of comparable morbidity (medical disease and self-rated health) and whether psychosocial factors can explain these differences. baseline data for ses, presence of disease, self-rated health (srh), and psychosocial factors were collected during 2003-04 from 923 men and women aged 45-69 years in southeast sweden. outcome data were all registered outpatient healthcare visits to physicians during 2004-08. cumulative incidences and standardised rate ratios (ssr) were calculated for strata of comparable morbidity for all visits, for visits due to cardiovascular disorders (cvd)/diabetes and for musculoskeletal problems. low ses was associated with more outpatient visits due to musculoskeletal problems (srr for education 1.52, 95 ci 1.35-1.73; for occupation 1.40, 95 ci 1.26-1.56) and accentuated in groups with poor srh. the ses effect was significant for visits to primary care and to hospitals, for men and women, and independent of present disease, srh, and psychosocial factors. low ses was significantly associated with more total outpatient visits at primary healthcare centres. in contrast, for outpatient visits due to cvd/diabetes, high ses was related to more visits to hospitals among people with good srh at baseline.",we found a consistent pattern for outpatient visits related to musculoskeletal problems where people with low ses counted more visits and this was most prominent in groups of poor srh. the results demonstrate the need to apply different morbidity measures when studying inequalities in healthcare utilisation.,General
do -opioid receptors in the central nucleus of the amygdala modulate sucrose solution intake in rats ?,"to explore the role of -opioid receptors (mor) in the central nucleus of the amygdala (cea) in modulating sucrose solution intake in rats. sprague-dawley rats received intra-cea injection of mor agonist damgo or saline, and then underwent two bottle choice test between sucrose solution and distilled water. after intake of sucrose solution or distilled water, activated neurons in the cea were labeled and identified with mor/fos-double labeling immunohistochemistry. compared with saline injection, intra-cea injection of damgo significantly increased sucrose solution intake in rats over a 3-h period. sucrose solution intake induced significantly more c-fos and mor/fos double-labeled neurons in the cea than distilled water intake.","the cea participates in modulation of sucrose intake in rats, and mor may partly mediate this mechanism.",Medication
are why birds with deferred sexual maturity sedentary on islands : a systematic review?,"island faunas have played central roles in the development of evolutionary biology and ecology. birds are among the most studied organisms on islands, in part because of their dispersal powers linked to migration. even so, we lack of information about differences in the movement ecology of island versus mainland populations of birds. here we present a new general pattern indicating that large birds with deferred sexual maturity are sedentary on islands, and that they become so even when they are migratory on the mainland. density-dependent variation in the age at first breeding affects the survivorship of insular populations and this, in turn, affects the movement ecology of large birds. because density-dependent variation in the age of first breeding is critical to the long-term survival of small isolated populations of long-lived species, migratory forms can successfully colonize islands only if they become sedentary once there. analyses of the movement ecology of continental and insular populations of 314 species of raptors, 113 species of ciconiiformes and 136 species of passerines, along with individual-based population simulations confirm this prediction.","this finding has several consequences for speciation, colonization and survival of small isolated population of species with deferred sexual maturity.",General
does clobenpropit enhance anti-tumor effect of gemcitabine in pancreatic cancer?,"to evaluate the anti-tumor effect of clobenpropit, which is a specific h3 antagonist and h4 agonist, in combination with gemcitabine in a pancreatic cancer cell line. three kinds of human pancreatic cancer cell lines (panc-1, miapaca-2, and aspc-1) were used in this study. expression of h3 and h4 receptors in pancreatic cancer cells was identified with western blotting. effects of clobenpropit on cell proliferation, migration and apoptosis were evaluated. alteration of epithelial and mesenchymal markers after administration of clobenpropit was analyzed. an in vivo study with a panc-1 xenograft mouse model was also performed. h4 receptors were present as 2 subunits in human pancreatic cancer cells, while there was no expression of h3 receptor. clobenpropit inhibited cell migration and increased apoptosis of pancreatic cancer cells in combination with gemcitabine. clobenpropit up-regulated e-cadherin, but down-regulated vimentin and matrix metalloproteinase 9 in real-time polymerase chain reaction. also, clobenpropit inhibited tumor growth (gemcitabine 294 46 mg vs combination 154 54 mg, p 0.02) and enhanced apoptosis in combination with gemcitabine (control 2.5, gemcitabine 25.8, clobenpropit 9.7 and combination 40.9, p 0.001) by up-regulation of e-cadherin and down-regulation of zeb1 in panc-1 xenograft mouse.",clobenpropit enhanced the anti-tumor effect of gemcitabine in pancreatic cancer cells through inhibition of the epithelial-mesenchymal transition process.,Medication
are single nucleotide polymorphisms ( snps ) highly conserved in rhesus ( macaca mulatta ) and cynomolgus ( macaca fascicularis ) macaques?,"macaca fascicularis (cynomolgus or longtail macaques) is the most commonly used non-human primate in biomedical research. little is known about the genomic variation in cynomolgus macaques or how the sequence variants compare to those of the well-studied related species, macaca mulatta (rhesus macaque). previously we identified single nucleotide polymorphisms (snps) in portions of 94 rhesus macaque genes and reported that indian and chinese rhesus had largely different snps. here we identify snps from some of the same genomic regions of cynomolgus macaques (from indochina, indonesia, mauritius and the philippines) and compare them to the snps found in rhesus. we sequenced a portion of 10 genes in 20 cynomolgus macaques. we identified 69 snps in these regions, compared with 71 snps found in the same genomic regions of 20 indian and chinese rhesus macaques. thirty six (52) of the m. fascicularis snps were overlapping in both species. the majority (70) of the snps found in both chinese and indian rhesus macaque populations were also present in m. fascicularis. of the snps previously found in a single rhesus population, 38 (indian) and 44 (chinese) were also identified in cynomolgus macaques. in an alternative approach, we genotyped 100 cynomolgus dnas using a rhesus macaque snp array representing 53 genes and found that 51 (29/57) of the rhesus snps were present in m. fascicularis. comparisons of snp profiles from cynomolgus macaques imported from breeding centers in china (where m. fascicularis are not native) showed they were similar to those from indochina.","this study demonstrates a surprisingly high conservation of snps between m. fascicularis and m. mulatta, suggesting that the relationship of these two species is closer than that suggested by morphological and mitochondrial dna analysis alone. these findings indicate that snp discovery efforts in either species will generate useful resources for both macaque species. identification of snps that are unique to regional populations of cynomolgus macaques indicates that location-specific snps could be used to distinguish monkeys of uncertain origin. as an example, cynomolgus macaques obtained from 2 different breeding centers in china were shown to have indochinese ancestry.",General
does wnt-11 signalling control ventricular myocardium development by patterning n-cadherin and beta-catenin expression?,"the stage-dependent organization of the cardiomyocytes during formation of the different layers of the developing ventricular wall is critical for the establishment of a functional heart, but the instructive signals involved are still poorly known. we have addressed the potential role of wnt-11 in the control of early ventricular myocardium assembly. we demonstrate by means of expression analysis and a mouse model in which wnt-11 function has been inactivated that wnt-11 is expressed by the embryonic ventricular cardiomyocytes and serves as one important signal for ventricular wall development. in the absence of wnt-11, the coordinated organization, intercellular contacts, co-localized expression of the cell adhesion components n-cadherin and beta-catenin, and the cytoskeleton of the differentiating ventricular cardiomyocytes are all disturbed. moreover, the ventricular wall lacking wnt-11 signalling is thinner and the expression of the gata-4, nkx2.5, mef2c, anp, and bnp genes is down-regulated relative to controls. these defects lie behind disturbed embryonic cardiac functional development, marked by an increase in the ventricular relaxation time during the early diastole.","we conclude that wnt-11 signalling serves as a critical cell adhesion cue for the organization of the cardiomyocytes in the developing ventricular wall, which is essential for the establishment of a functional heart.",General
is arterial stiffness associated with carotid atherosclerosis in hypertensive patients ( the campania salute network )?,"pulse pressure/stroke volume indexed to height(2.04) (pp/svi) is a validated measure of arterial stiffness, but its relation to carotid atherosclerosis is unknown. clinical, echocardiographic, and carotid ultrasound data from 6,209 hypertensive patients without prevalent cardiovascular (cv) disease in the campania salute network were analyzed. the population was grouped into tertiles of pp/svi. from carotid ultrasound, peak and mean intima-media thickness (imt) and presence of carotid plaques in the common and internal carotid arteries were reported. increasing pp/svi tertile was associated with a parallel increase in age, blood pressure, total serum cholesterol and the number of antihypertensive drugs used (all p 0.01). higher pp/svi was also associated with greater peak and mean imt (all p 0.01), also when adjusting for age, gender, blood pressure, lipid profile, and diabetes mellitus (all p 0.01). similarly, compared to the lower pp/svi tertile, the multiple adjusted prevalence ratio of carotid plaque was 7 (95 confidence interval (ci) 1-13, p 0.03) in the middle tertile and 21 (95 ci 15-28, p 0.0001) in the upper tertile, independently of confounders.","in treated hypertensive patients participating in the campania salute network, higher pp/svi is associated with carotid atherosclerosis independent of well-known clinical confounders.",Medication
does uso1 promote tumor progression via activating erk pathway in multiple myeloma cells?,"this study aimed to explore the influence of uso1 on multiple myeloma (mm) cell proliferation and apoptosis and the related molecular mechanism. the expression of uso1 and mif in mm tissues and cells, normal bone marrow tissues and cells were determined by qrt-pcr and western blot assay. the cell proliferation and apoptosis of mm cells before and after knockdown of uso1 were determined by mtt assay and flow cytometry, respectively. before and after knockdown of uso1, the expression of the proliferation-related genes cyclin d1, mcm2 and pcna in mm cells was determined by qrt-pcr and western blot assay. the protein level of p-erk1/2 and mif was determined by western blot assay and elisa, respectively. the expression levels of uso1 and mif in mm tissues and cells were much higher than those in normal bone marrow tissues and cells. knockdown of uso1 resulted in the inhibited ability of cell proliferation and induced cell apoptosis. the expression of cyclin d1, mcm2, pcna and p-erk1/2 decreased significantly after knockdown of uso1 as well as the decreased mif secretion.",uso1 gene may be a promising target for the therapy of human mm and its diagnosis marker.,General
does ligation of the fas antigen stimulate chemokine secretion in pancreatic cancer cell line panc-1?,"the role of chemokines in the process of immune cell infiltration into pancreatic cancer tissue has been reported. in this study, we investigated the induction of chemokines (interleukin (il)-8 and monocyte chemoattractant protein (mcp)-1) by fas antigen (ag)-stimulation in a human pancreatic cancer cell line, panc-1. the chemokine secretion was evaluated by using an elisa and a northern blot, and the activation of nuclear factor-kappa b (nf-kappa b) was assessed by using an electrophoretic gel mobility shift assay (emsa). the fas antigen (ag) stimulation clearly induced an increase in il-8 and mcp-1 secretion in panc-1 cells. this effect was also observed at the mrna level. the induction of chemokine secretion by fas ag stimulation required de novo gene expression and protein synthesis. the pretreatment with interferon (ifn)-gamma markedly enhanced the effects of fas ag stimulation; ifn-gamma pretreatment and fas ag stimulation synergistically induced not only apoptosis but also il-8 and mcp-1 secretion. flow cytometric analysis demonstrated that ifn-gamma significantly enhanced fas ag expression. in addition, fas ag stimulation actually evoked nf-kappa b activation in this cell line.","our results indicate that fas ag stimulation can induce chemokine secretion in panc-1 cells, suggesting the contribution of fas stimulation to the accumulation of immune cells in pancreatic cancer tissue.",General
are mutations in aldh6a1 encoding methylmalonate semialdehyde dehydrogenase associated with dysmyelination and transient methylmalonic aciduria?,"methylmalonate semialdehyde dehydrogenase (mmsdh) deficiency is a rare autosomal recessive disorder with varied metabolite abnormalities, including accumulation of 3-hydroxyisobutyric, 3-hydroxypropionic, 3-aminoisobutyric and methylmalonic acids, as well as -alanine. existing reports describe a highly variable clinical and biochemical phenotype, which can make diagnosis a challenge. to date, only three reported cases have been confirmed at the molecular level, through identification of homozygous mutations in aldh6a1, the gene encoding mmsdh. confirmation by enzyme assay has until now not been possible, due to the extreme instability of the enzyme substrate. we report a child with severe developmental delays, abnormal myelination on brain mri, and transient/variable elevations in lactate, methylmalonic acid, 3-hydroxyisobutyric and 3-aminoisobutyric acids. compound heterozygous mutations were identified by exome sequencing and confirmed by sanger sequencing within exon 6 (c.514 t c; p. tyr172his) and exon 12 (c.1603c t; p. arg535cys) of aldh6a1. the resulting amino acid changes, both occurring in residues conserved among mammals, are predicted to be damaging at the protein level. subsequent mmsdh enzyme assay demonstrated reduced activity in patient fibroblasts, measuring 2.5 standard deviations below the mean.","we present the fourth reported case of mmsdh deficiency with confirmation at the molecular level, and expand on what is already an extremely variable clinical and biochemical phenotype. furthermore, this is the first report to demonstrate a corresponding reduction in mmsdh enzyme activity. this report illustrates the emerging utilization of whole exome sequencing and variant data filtering using clinical data as an early tool in the diagnosis of rare and variable conditions.",Diagnosis
do prior sternotomy and ventricular assist device implantation adversely impact survival or allograft function after heart transplantation?,"orthotopic heart transplantation (oht) remains the gold standard for end-stage heart failure. however, donor availability is severely limited. with a median wait time of 6.6 months and more than 12 of patients waiting 5 or more years, the decision is often made to implant a left ventricular assist device (lvad) as a bridge to transplantation for medical stabilization. furthermore, the number of patients who have had at least one prior sternotomy while awaiting transplantation is increasing. previous studies have indicated reoperative sternotomy as a risk factor for compromised survival. concerns are specifically focused on perioperative, short-term, and long-term outcomes after lvad explantation or redo sternotomy before oht because of increasing operative complexity. we hypothesize that despite the greater technical difficulty caused by lvad explantation or redo sternotomy, outcomes would not be compromised. we retrospectively analyzed patients who underwent oht at the university of pennsylvania during a 5-year period (2008-2013; n 253). all patients who underwent a bridge to transplantation lvad (n 72) or prior sternotomy (n 65) were compared with those undergoing oht with a virgin chest (n 116). preoperative, intraoperative, and postoperative variables were analyzed. short- and long-term survival were studied (minimum follow-up, 6 months). comorbidities were similar among the groups. there was no difference in donor allograft ischemic time (p 0.6). however, cardiopulmonary bypass time was longer in both bridge to transplantation and prior sternotomy cohorts (p 0.00001). the blood transfusion requirement was higher in bridge to transplantation (12.5 13.7 units; p 0.0007) and prior sternotomy groups (11.7 12.9 units; p 0.02) as compared with the virgin chest cohort (7.1 10.7 units). for bridge to transplantation, both time to extubation (1.0 1.6 versus 0.9 1.0 days; p 0.03) and intensive care unit length of stay (7.0 7.0 versus 6.0 7.0 days; p 0.06) were longer compared with the virgin chest cohort. the same was true for prior sternotomy (extubation time, 1.9 4.4 days; p 0.005; intensive care unit length of stay, 8.0 12.0 days; p 0.06). there was no difference in hospital length of stay (p 0.2). overall, there was no difference in short- or long-term survival.","implantation of an lvad as a bridge to transplantation or prior sternotomy does not adversely impact allograft function, hospital length of stay, or long-term outcomes after oht. the decision to manage a patient medically while awaiting transplantation versus an lvad bridge strategy should not be limited by concerns of subsequent poor outcomes after transplantation.",Treatment
does mir-506 inhibit cell proliferation and invasion by targeting tet family in colorectal cancer?,"ten-eleven translocation (tet) family members have been shown to be involved in the development of many tumors. however, the biological role of the tet family and its mechanism of action in colorectal carcinogenesis and progression remain poorly understood. we measured the expression levels of tet family members in colorectal cancer (crc) specimens, in the corresponding normal tissues and in cell lines using quantitative real-time pcr (qrt-pcr) and in situ hybridization (ish). both the protein function and the protein-independent role of tets were investigated by cell viability assays and cell invasion assays using in vitro and in vivo models. we found that all three tet genes were strongly up-regulated at the transcript level in crc samples compared to matched normal tissues. the same results were observed in colorectal cancer cell lines. knockdown of tets by shtet1/2/3 showed that tet family members inhibited crc growth and metastasis. we showed that tet family member degradation by mir-506 inhibits cell proliferation and invasion in colorectal cancer.","through this study, we advance our understanding of the expression levels tets and mir-506 in crc and further clarify the internal regulatory mechanism of mir-506 by targeting tet during crc processes. these findings may contribute to a novel avenue for researching and developing targeted therapies for crc.",General
do subjective perceptions associated with the ascending and descending slopes of breath alcohol exposure vary with recent drinking history?,"the differentiator model predicts that individuals with a positive family history of alcoholism (fha) or heavy alcohol consumers will feel more sensitive to the effects of alcohol on the ascending phase of the blood alcohol content while feeling less sedated on the descending phase. this study tested whether subjective perceptions are sensitive to the slope of breath alcohol concentration (brac) and whether that sensitivity is associated with an fha and/or recent drinking history (rdh). family-history-positive (fhp, n 27) and family-history-negative (fhn, n 27) young adult nondependent drinkers were infused intravenously with alcohol in 2 sessions separated by 1 week. after 20 minutes, one session had an ascending brac (3.0 mg/min), while the other session had a descending brac (-1 mg/min). the brac for both sessions at this point was approximately 60 mg, referred to as the crossover point. subjective perceptions of intoxication, high, stimulated, and sedation were sampled frequently and then interpolated to the crossover point. within-subject differences between ascending and descending responses were examined for associations with fha and/or rdh. recent moderate drinkers reported increased perceptions of feeling intoxicated (p 0.023) and high (p 0.023) on the ascending slope compared with the descending slope. in contrast, recent light drinkers felt more intoxicated and high on the descending slope.","subjective perceptions in young adult social drinkers depend on the slope of the brac when examined in association with rdh. these results support the differentiator model hypothesis concerning the ascending slope and suggest that moderate alcohol consumers could be at risk for increased alcohol consumption because they feel more intoxicated and high on the ascending slope. subjects did not feel less sedated on the descending slope, contrary to the differentiator model but replicating several previous studies.",Medication
does left ventricular hypertrophy influence cardiac prognosis in patients undergoing dobutamine cardiac stress testing?,"this study was performed to determine the utility of dobutamine stress test results for predicting myocardial infarction (mi) and cardiac death in patients with chest pain and left ventricular hypertrophy (lvh). three hundred fifty-three participants with a mean/-sd age of 64/-12 years (54men) underwent dobutamine cardiovascular magnetic resonance stress testing and then were followed up for 6/-2 years (mean/-sd; range, 0.5-11.5) to assess the post-dobutamine cardiovascular magnetic resonance stress test occurrence of mi or cardiac death. lv mass and the presence or absence of ischemia were determined; lvh was defined as an lv mass index 96 g/m(2) in men and 77 g/m(2) in women. lvh was present in 62 participants (18 of the men and 17 of the women, p0.90). seventy-one (20) participants experienced an mi or cardiac death during follow-up. the mi and cardiac death rate was more frequent in those with versus without lvh (32 vs 17, p0.009). in multivariable analysis that accounted for the presence of preexisting coronary artery disease, hypertension, diabetes, stress-induced ischemia, and reduced lv ejection fraction, lvh was an independent predictor of mi and cardiac death (hazard ratio1.99; 95 ci, 1.13-3.50; p0.02).","lvh is predictive of future mi and cardiac death in patients with or without inducible ischemia during dobutamine cardiac stress testing. as a result, lvh should be reported in those referred for dobutamine cardiac stress tests, particularly in those without inducible ischemia, in whom one would otherwise assume a favorable cardiac prognosis.",Diagnosis
does inhibition of c-jun nh2-terminal kinase or extracellular signal-regulated kinase improve lung injury?,"although in vitro studies have determined that the activation of mitogen-activated protein (map) kinases is crucial to the activation of transcription factors and regulation of the production of proinflammatory mediators, the roles of c-jun nh2-terminal kinase (jnk) and extracellular signal-regulated kinase (erk) in acute lung injury have not been elucidated. saline or lipopolysaccharide (lps, 6 mg/kg of body weight) was administered intratracheally with a 1-hour pretreatment with sp600125 (a jnk inhibitor; 30 mg/kg, io), or pd98059 (an mek/erk inhibitor; 30 mg/kg, io). rats were sacrificed 4 hours after lps treatment. sp600125 or pd98059 inhibited lps-induced phosphorylation of jnk and erk, total protein and ldh activity in bal fluid, and neutrophil influx into the lungs. in addition, these map kinase inhibitors substantially reduced lps-induced production of inflammatory mediators, such as cinc, mmp-9, and nitric oxide. inhibition of jnk correlated with suppression of nf-kappab activation through downregulation of phosphorylation and degradation of ikappab-alpha, while erk inhibition only slightly influenced the nf-kappab pathway.","jnk and erk play pivotal roles in lps-induced acute lung injury. therefore, inhibition of jnk or erk activity has potential as an effective therapeutic strategy in interventions of inflammatory cascade-associated lung injury.",Medication
is carotid imt more associated with stroke than risk calculators?,"it is unclear whether a natural marker of atherosclerosis (carotid intima-media thickness: cimt) or calculated risk score is more associated with stroke. we therefore comparatively examined the relationship between cimt as well as two cardiovascular risk calculators (omnibus risk score -ors and framingham risk score- frs) and the occurrence of stroke among hypertensive african patients. cimt was measured in 555 consecutive consenting hypertensive adults (377 stroke patients and 178 stroke-free subjects). the 10-year cardiovascular risk was calculated for each participant with the frs and ors. the strengths of association between frs, ors, cimt, and stroke occurrence were examined using logistic regression. the discriminative capacity of frs, ors, and cimt for stroke occurrence was assessed with c-statistics. higher average cimt (or 11.71; 95 ci 1.65-83.07; p 0.01) was strongly associated with stroke after adjusting for age, sex, blood pressure, serum cholesterol, and blood sugar. neither the frs (or: 1.03; ci: 0.89-1.19, p 0.68) nor the ors (or: 1.08; ci: 0.90-1.30; p 0.41) was significantly associated with stroke. cimt had a higher c-statistic for differentiating stroke patients from hypertensive controls (right: c 0.63, p 0.001; left: c 0.67, p 0.001; average: c 0.66, p 0.001) than some conventional risk factors. neither frs (p 0.39) nor ors (p 0.55) was able to independently differentiate between stroke and hypertensive patients.","cimt, but neither frs nor ors, is independently associated with stroke among nigerian african hypertensive patients. cimt may be a better tool for estimating the overall risk of stroke than frs or ors in this population.",Prevention
is allergen sensitization associated with increased dna methylation in older men?,"variation in epigenetic modifications, arising from either environmental exposures or internal physiological changes, can influence gene expression and may ultimately contribute to complex diseases such as asthma and allergies. we examined the association of asthma and allergic phenotypes with dna methylation levels of retrotransposon-derived elements. we used data from 704 men (mean age 73 years) in the longitudinal normative aging study to assess the relationship between asthma, allergic phenotypes and dna methylation levels of the retrotransposon-derived elements alu and long interspersed nuclear element (line)-1. retrotransposons represent a large fraction of the genome (30) and are heavily methylated to prevent expression. percent methylation of alu and line-1 elements in peripheral white blood cells was quantified using pcr pyrosequencing. data on sensitization to common allergens from skin prick testing, asthma and methacholine responsiveness were gathered approximately 8 years prior to dna methylation analysis. prior allergen sensitization was associated with increased methylation of alu ( 0.32 for sensitized vs. nonsensitized patients; p 0.003) in models adjusted for pack-years of smoking, body mass index, current smoking, air pollutants, percentage of eosinophils, white blood cell count and age. of the men interviewed, 5 of subjects reported a diagnosis of asthma. neither alu nor line-1 methylation was associated with asthma.",these data suggest that increased dna methylation of repetitive elements may be associated with allergen sensitization but does not appear to be associated with asthma. future work is needed to identify potential underlying mechanisms for these relationships.,Prevention
does calcitonin pump improve nerve regeneration after transection injury and repair?,"after nerve injury, excessive calcium impedes nerve regeneration. we previously showed that calcitonin improved nerve regeneration in crush injury. we aimed to validate the direct effect of calcitonin on transected and repaired nerve. two rat groups (n 8) underwent sciatic nerve transection followed by direct repair. in the calcitonin group, a calcitonin-filled mini-osmotic pump was implanted subcutaneously, with a catheter parallel to the repaired nerve. the control group underwent repair only, without a pump. evaluation and comparison between the groups included: (1) compound muscle action potential recording of the extensor digitorum longus (edl) muscle; (2) tetanic muscle force test of edl; (3) nerve calcium concentration; and (4) nerve fiber count and calcified spot count. the calcitonin pump group showed superior recovery.",calcitonin affects injured and repaired peripheral nerve directly. the calcitonin-filled mini-osmotic pump improved nerve functional recovery by accelerating calcium absorption from the repaired nerve. this finding has potential clinical applications.,Treatment
is poor response to ovulation induction a stronger predictor of early menopause than elevated basal fsh : a life table analysis?,"during the course of assisted reproduction treatment, a number of women exhibit a ""poor response"" to ovulation induction, or demonstrate an elevated basal fsh level ( or 10 iu/l) at a young age. we sought to determine whether these women are at increased risk of early menopause and poor reproductive performance. a retrospective cohort study included 118 ""poor responders"" with normal basal fsh level ( or 10 iu/l), and 265 controls, who underwent assisted reproduction treatment between 1987 and 1998. all women were 40 years of age at the time of treatment and had normal menstrual cycles. participants were sent a postal questionnaire in 2000-2001, seeking information on ovarian function and reproductive performance following cessation of treatment. after adjusting for age and smoking habits, women with poor response and raised basal fsh levels were more likely to experience symptoms of the peri-menopause hazard ratios 2.4, 95 confidence interval (ci) 1.52-3.78, and 2.76, 95 ci 1.78-4.29 respectively, p 0.0001. poor responders were six times and 23 times more likely to experience the menopause within 10 years of treatment than those with raised basal fsh levels and controls respectively (hazard ratio 5.97 and 23.9, p 0.015 and 0.002 respectively). poor responders and those with raised basal fsh levels have half the chance of spontaneous conception after discontinuation of treatment compared with controls (p 0.007).",both poor response to ovarian stimulation and raised basal fsh are markers of reduced ovarian reserve and predict an increased risk of early menopause.,Treatment
does inhibition of membrane-bound carbonic anhydrase decrease subretinal ph and volume?,"the lipophilic carbonic anhydrase (ca) inhibitor acetazolamide has been shown to enhance subretinal fluid resorption, reduce subretinal ph, and can improve cystoid macular edema, but its clinical use is limited by systemic side effects. while these are most likely a result of inhibiting intracellular ca isoenzymes, retinal pigment epithelial (rpe) transport is thought to be modulated via membrane-bound ca. this study investigates whether benzolamide, a hydrophilic ca inhibitor that does not readily penetrate cell membranes, is sufficient to modulate subretinal volume and ph. volume and ph were assessed in the subretinal space (srs) of the perfused chick retina-rpe-choroid preparation by calculating these variables from data obtained with two different double-barreled, ion-selective electrodes (h for ph and the extracellular space marker tetramethylammonium (tma) for srs volume). light induced variations and changes in baseline measurements were recorded before and after addition of 10(-4) m acetazolamide or benzolamide to the basal perfusion. basal perfusion with either drug induced both an acidification of the srs by 0.02-0.04 ph units, which occurred within 60 s, as well as an increase in the amplitude of the light-induced alkalinisation of the srs. tma concentration in the srs increased steadily over a period of several minutes after basal perfusion with either of the ca inhibitors, and the calculated srs volume was reduced by 40 within 8-10 min.",the observation that benzolamide had effects equal to acetazolamide suggests that inhibition of membrane-bound ca at the basolateral membrane of the rpe is sufficient to decrease subretinal ph and volume. this may represent a clinically important mechanism for the resorption of sub- and intraretinal fluid.,Medication
does high anterior release of the levator fascia improve sexual function following open radical retropubic prostatectomy?,"recent anatomical studies have shown that branches of the cavernous nerves running adjacent to the prostate at the apex travel more anteriorly than previously recognized. outcomes of robot assisted radical prostatectomy suggest improved postoperative sexual outcomes following high anterior release of the levator fascia. we prospectively evaluated the effect of high anterior release on oncological and sexual function outcomes following open radical retropubic prostatectomy. a total of 167 patients with clinically localized prostate cancer with a preoperative sexual health inventory for men score of greater than 21 underwent radical retropubic prostatectomy with bilateral nerve sparing and selective high anterior release, as performed by a single surgeon. data on postoperative sexual function were collected by an independent third party. sexual function outcomes at 12 months were defined as 1) a sexual health inventory for men score of 16 or greater and/or a satisfaction score of 4 or greater and 2) a sexual health inventory for men score of 22 or greater. because unilateral high anterior release was equivalent to bilateral high anterior release for both definitions (p 0.3), they were combined into 1 group for analyses. patients undergoing high anterior release were more likely to achieve a sexual health inventory for men score of 16 or greater and/or a satisfaction score of 4 (93 vs 77, p 0.007), and a sexual health inventory for men score of 22 or greater (70 vs 54, p 0.07) at 1 year. return to baseline (a sexual health inventory for men score of 22 or greater) was even higher among patients receiving high anterior release who were more sexually active (greater than 1 attempt per week) preoperatively (78 vs 52, p 0.05). the improved outcomes in potency achieved with high anterior release did not increase the likelihood of a positive surgical margin.",unilateral or bilateral high anterior release of the levator fascia in open radical retropubic prostatectomy provides excellent oncological results and is associated with improved postoperative sexual function.,Treatment
is nuclear localization of survivin a positive prognostic factor for survival in advanced non-small-cell lung cancer?,"expression of survivin, a member of the inhibitor of apoptosis protein family, is commonly detected in cancers but not in normal differentiated tissues. survivin is usually localized in the cytoplasm of cancer cells, but nuclear localization has also been described, and we recently reported that survivin is a nuclear-cytoplasmic shuttling protein. fifty-three tumor specimens from patients with inoperable non-small-cell lung cancer (nsclc) (55 stage iiia, 17 stage iiib and 28 stage iv) who underwent chemotherapy treatment were evaluated with immunohistochemistry for survivin expression and localization. these two sets of data were processed and tested for correlation with major patient characteristics, response to chemotherapy, and overall and relapse-free survival. survivin was present only in malignant tissues, and 47/53 (89) of the specimens were positive. the overall median expression of tumor cells was 40, and this value was used as a cut-off point for statistical analysis. by dichotomizing the specimens as expressing low or high levels of survivin, a significant association was seen between the expression of survivin and the histology of the tumors (p0.020), squamous cell carcinoma being the histotype with lower levels of survivin expression. three patterns of localization were observed: 42 of cases (22/53) showed reactivity confined to the nucleus, 17 (nine of 53) only in the cytoplasm and 30 (16/53) in both the nucleus and the cytoplasm. interestingly, nuclear survivin levels predicted longer overall and relapse-free survival, in univariate and multivariate analyses. expression and localization of survivin did not correlate with response to chemotherapy.",our results indicate that differential localization of survivin may be a prognostic factor for nsclc. further studies are warranted.,Medication
does copper-induced apical trafficking of atp7b in polarized hepatoma cells provide a mechanism for biliary copper excretion?,"mutations in the atp7b gene, encoding a copper-transporting p-type adenosine triphosphatase, lead to excessive hepatic copper accumulation because of impaired biliary copper excretion in wilson's disease. in human liver, atp7b is predominantly localized to the trans-golgi network, which appears incompatible with a role of atp7b in biliary copper excretion. the aim of this study was to elucidate this discrepancy. immunofluorescence and electron-microscopic methods were used to study the effects of excess copper on atp7b localization in polarized hepg2 hepatoma cells. atp7b is localized to the trans-golgi network only when extracellular copper concentration is low (1 micromol/l). at increased copper levels, atp7b redistributes to vesicular structures and to apical vacuoles reminiscent of bile canaliculi. after copper depletion, atp7b returns to the trans-golgi network. brefeldin a and nocodazole impair copper-induced apical trafficking of atp7b and cause accumulation of apically retrieved transporters in a subapical compartment, suggesting continuous recycling of atp7b between this vesicular compartment and the apical membrane when copper is increased.","copper induces trafficking of its own transporter from the trans-golgi network to the apical membrane, where it may facilitate biliary copper excretion. this system of ligand-induced apical sorting provides a novel mechanism to control copper homeostasis in hepatic cells.",General
do transcriptional double-autorepression feedforward circuits act for multicellularity and nervous system development?,"the transcriptional regulatory network is considered to be built from a set of circuit patterns called network motifs. experimental studies have provided instances where a feedforward circuit (ffc) appears with modification of autoregulation, but little is known systematically about such autoregulation-integrated ffcs. therefore, we aimed to examine whether the autoregulation-integrated ffc is a network motif relevant to describing the human transcriptional regulatory systems, and explored the relationship of such network motifs with biological functions. based on human-mouse evolutionarily conserved transcription factor binding sites (tfbss) in 76600 conserved blocks for 5169 genes, we compiled the human transcriptional connections into a matrix, and examined the number of ffc appearances in comparison with randomized networks. the results revealed that the configuration of autoregulation integrated in the ffc critically affects the abundance or avoidance of ffc appearances. in particular, an ffc comprising two repressors that are both autoregulated was revealed as a significant network motif, which we termed the double-autoregulation ffc (dar-ffc). interestingly, this network motif preferentially constitutes effecter transcriptional circuits with functions in cell-cell signaling and multicellular organization, and is particularly related to nervous system development.","we have revealed that the configuration of autoregulation integrated in the ffcs is a critical factor for abundance or avoidance of the appearance of the ffcs. in particular, we have identified the dar-ffc as a distinctive integrated network motif endowed with properties that are indispensable for forming the transcriptional regulatory circuits involved in multicellular organization and nervous system development. this is the first report showing that the dar-ffc is a significant network motif.",Prevention
are aortic root dynamics asymmetric?,"the presence of conformational changes in the aortic root during the cardiac cycle is well known, but precise information on time-related changes at each level of the root is lacking. high-resolution, 3d sonomicrometry (200 hz) was applied in an acute sheep model. twelve crystals were implanted in eight sheep at each base (n 3), commissure (n 3), sinotubular junction (n 3) and ascending aorta (n 3). under stable hemodynamic conditions, geometric changes of the perimeter of each sinus of valsalva, sinus height, and twist and root tilt angles were time-related to left ventricluar (lv) and aortic pressures. expansion of the perimeter of the three sinuses of valsalva was homogeneous, but in significantly different proportions (p 0.001): the right sinus expanded (32.4 /- 2.4) more than the left (29.3 /- 3.2), and more than the non-coronary (nc) sinus (25.8 /- 1.7). a similar pattern was found for aortic root height: right greater than left, and left greater than nc sinus (p 0.001). this asymmetry resulted in changes of the root's twist and tilt angles. although the twist deformation was consistent for each sheep, no general pattern was found. the aortic root tilt angle (between the basal plane and the commissural plane) was 16.3 /- 1.5 degrees at end-diastole (angle oriented posteriorly and to the left). during systole, it was reduced by 6.6 /- 0.5 degrees, aligning the lv outflow tract with the ascending aorta. this tilt angle returned to its original value after valve closure.","aortic root expansion is asymmetric, generating precise changes in its tilt angle. during systole, tilt angle reduction resulted in a straight cylinder that probably facilitates ejection; during diastole, the tilt angle increased, probably reducing leaflet stress. these findings should impact upon surgical procedures and the design of new prostheses.",General
do protein expression changes in a cell system of beta-cell maturation reflect an acquired sensitivity to il-1beta?,"type 1 diabetes mellitus (t1dm) is caused by specific destruction of the pancreatic beta cells in the islets of langerhans. increased sensitivity to cytokines, in particular to interleukin-1beta (il-1beta) seems to be an acquired trait during beta-cell maturation. in response to cytokines both protective and deleterious mechanisms are induced in beta cells, and when the deleterious prevail, t1dm develops. the aims of this study were to identify perturbation in protein patterns (pipp) associated with beta-cell maturation, and compare these changes to previous analyses of il-1beta exposed rat islets. for this purpose, proteome analyses were carried out using a cell-line, which matures from a glucagon-producing pre-beta-cell phenotype (nhi-glu) to an insulin-producing beta-cell phenotype (nhi-ins). we have previously shown that this maturation is accompanied by acquired sensitivity to the toxic effects of il-1beta. 2d-gel electrophoresis was used to separate the proteins and maldi-ms and database searches were performed to identify the proteins. during beta-cell maturation 135 protein spots out of 2239 detectable changed expression levels. of these, 74 were down-regulated, 44 up-regulated, 16 were suppressed and 1 was expressed de novo. using maldi-ms, positive identification was obtained for 93 out of the 135 protein-spots revealing 97 different proteins. of these, 22 proteins were in common with changes identified in previous proteome analysis of perturbation in protein pattern in il-1beta exposed rat islets. several of the proteins were present in more than one spot suggesting post-translational modification.","several proteins and protein modifications were identified that could be critically involved in beta-cell maturation, insulin-gene expression and the acquired il-1beta sensitivity.",Diagnosis
does whole exome sequencing reveal gucy2d as a major gene associated with cone and cone-rod dystrophy in israel?,"the israeli population has a unique genetic make-up, with a high prevalence of consanguineous marriages and autosomal recessive diseases. in rod-dominated phenotypes, disease-causing genes and mutations that differ from those identified in other populations often are incurred. we used whole exome sequencing (wes) to identify genetic defects in israeli families with cone-dominated retinal phenotypes. clinical analysis included family history, detailed ocular examination, visual function testing, and retinal imaging. whole exome sequencing, followed by segregation analysis, was performed in 6 cone-dominated retinopathy families in which prior mutation analysis did not reveal the causative gene. based on the wes findings, we screened 106 additional families with cone-dominated phenotypes. the wes analysis revealed mutations in known retinopathy genes in five of the six families: two pathogenic mutations in the gucy2d gene in three families, and one each in cdhr1 and c8orf37. targeted screening of additional cone-dominated families led to identification of gucy2d mutations in four other families, which included two highly probable novel disease-causing variants.","our study suggested that gucy2d is a major cause of autosomal dominant cone and cone-rod dystrophies in israel; this is similar to other caucasian populations and is in contrast with retinitis pigmentosa (primary rod disease), where the genetic make-up of the israeli population is distinct from other ethnic groups. we also conclude that wes permits more comprehensive and rapid analyses that can be followed by targeted screens of larger samples to delineate the genetic structure of retinal disease in unique population cohorts.",Diagnosis
is anticholinergic medication use associated with globus pharyngeus?,"globus pharyngeus has been linked to salivary hypofunction. we hypothesise that a considerable portion of the globus experienced by patients is due to a drying effect secondary to anticholinergic medication use; this study aimed to determine their association. a cross-sectional study was conducted of 270 patients who presented to a laryngology practice over 6 months. participants rated globus sensation on a 5-point severity scale, with those scoring 0 considered as controls (non-globus). participants were excluded if they had a likely cause of globus. scores were compared with participants' medication lists, co-morbidities, age and gender, and evaluated using multivariate analysis, with significance set at p 0.05. any participant taking at least 2 anticholinergic medications had a 3.52 increased odds (p 0.02) of experiencing globus. a previous diagnosis of gastroesophageal reflux disease was also significantly associated with globus (p 0.004), with an odds ratio of 3.75.",a substantial portion of idiopathic globus may be due to anticholinergic use or reflux. the findings implicate medication use as a risk factor for globus. an awareness of these associations is invaluable for identifying cause and treating globus.,Medication
is serum indoxyl sulfate a useful predictor for progression of chronic kidney disease ?,"indoxyl sulfate, an endogenous metabolite of tryptophan is normally excreted into urine. in patients with chronic kidney disease (ckd), however, the reduced indoxyl sulfate renal clearance leads to elevated indoxyl sulfate serum level. in this study we determined whether the serum levels of indoxyl sulfate are related to the progression rate of ckd stage in ckd patient. the association between indoxyl sulfate and progression of ckd stage was studied in 47 ckd patients (19 male, 28 female). serum levels of is were measured by using high performance liquid chromatography and the measured values of the study cohort were divided into quintiles. the mean serum amount indoxyl sulfate in the healthy subject was 0.06 /- 0.04 mg/dl (mean /- sd). those with indoxyl sulfate serum levels of or 0.3 mg/dl had a significantly progression of ckd than with 0.3 mg/dl. especially, those patients with indoxyl sulfate serum levels of 0.47 mg/dl had the highest ckd progression.","high serum levels of indoxyl sulfate are related with a progression of ckd stage in ckd patients. thus, serum indoxyl sulfate is one of the clinical factors that affect ckd progression.",Medication
"is food insecurity associated with hiv , sexually transmitted infections and drug use among men in the united states?","to examine the population-level association between food insecurity, hiv risk factors, and hiv serostatus among men, the group representing the majority of hiv diagnoses in the united states. cross-sectional secondary data analysis using the national health and nutrition examination survey 1999-2012, a nationally representative survey of the civilian noninstitutionalized us population. logistic regression with design weights and complex survey commands was used to estimate nationally representative associations between food insecurity and hiv serostatus (primary outcome), herpes simplex virus 2, self-reported sexually transmitted infections (stis), and past-year illicit drug use among men, adjusting for potential confounders. food security was measured using the 18-item household food security survey. we analyzed data for 9150 men representing 61 million individuals in the united states. unadjusted hiv prevalence was 1.5 among food insecure men, compared with 0.4 among food secure men (p 0.001). in adjusted models, food insecure men had over two times higher odds of hiv seropositivity compared with food secure men adjusted odds ratio (aor) 2.10; 95 confidence interval (ci) 1.01-4.37; p 0.05. food insecurity was associated with higher odds of herpes simplex virus 2 seropositivity (aor 1.28; 95 ci 1.04-1.57; p 0.05), self-reported stis (aor 1.54; 95 ci 1.08-2.20; p 0.05), and illicit drug use (aor 1.57; 95 ci 1.14-2.15; p 0.01). results were robust to sensitivity analyses restricted to lower incomes.","food insecurity is associated with prevalent hiv, stis, and illicit drug use among men in the united states. further research is needed to establish whether and through what mechanisms improved food security may help prevent new hiv infections.",Medication
is the mir-184 binding-site rs8126 t c polymorphism in tnfaip2 associated with risk of gastric cancer?,"tnfaip2 is a crucial gene involved in apoptosis. single nucleotide polymorphisms (snps) in its mirna binding sites could modulate functions of the mirna-target genes and thus risk of cancers. in this study, we investigated associations between potentially functional snps in the mirna binding sites of the 3'utr of tnfaip2 and gastric cancer risk in a us population. we conducted a case-control study of 301 gastric cancer patients and 313 cancer-free controls frequency-matched by age, sex and ethnicity. we genotyped four selected tnfaip2 snps (rs8126 tc, rs710100 ga, rs1052912 ga and rs1052823 gt) and used the logistic regression analysis to assess associations of these snps with cancer risk. the rs8126 cc genotype was associated with a significantly elevated risk of gastric cancer (adjusted or 2.00, 95 ci 1.09-3.64 and p 0.024), compared with the combined rs8126 tttc genotypes, particularly in current drinkers. however, none of other tnfaip2 snps was associated with risk of gastric cancer.","our data suggested that the tnfaip2 mirna binding site rs8126 tc snp may be a marker for susceptibility to gastric cancer, and this finding requires further validation by larger studies.",General
does 2-microglobulin deficiency cause a complex immunodeficiency of the innate and adaptive immune system?,"most patients with mhc class i (mhc-i) deficiency carry genetic defects in transporter associated with antigen processing 1 (tap1) or tap2. the clinical presentation can vary, and about half of the patients have severe skin disease. previously, one report described 2-microglobulin (2m) deficiency as another monogenetic cause of mhc-i deficiency, but no further immunologic evaluation was performed. we sought to describe the molecular and immunologic features of 2m deficiency in 2 turkish siblings with new diagnoses. based on clinical and serologic findings, the genetic defect was detected by means of candidate gene analysis. the immunologic characterization comprises flow cytometry, elisa, functional assays, and immunohistochemistry. here we provide the first extensive clinical and immunologic description of 2m deficiency in 2 siblings. the sister had recurrent respiratory tract infections and severe skin disease, whereas the brother was fairly asymptomatic but had bronchiectasis. not only polymorphic mhc-i but also the related cd1a, cd1b, cd1c, and neonatal fc receptor molecules were absent from the surfaces of 2m-deficient cells. absent neonatal fc receptor surface expression led to low serum igg and albumin levels in both siblings, whereas the heterozygous parents had normal results for all tested parameters except 2m mrna (b2m) expression. similar to tap deficiency in the absence of a regular cd8 t-cell compartment, cd8() t cells were strongly expanded. natural killer cells were normal in number but not ""licensed to kill.""","the clinical presentation of patients with 2m deficiency resembles that of patients with other forms of mhc-i deficiency, but because of the missing stabilizing effect of 2m on other members of the mhc-i family, the immunologic defect is more extensive than in patients with tap deficiency.",Medication
does hypoxia inducible factor-1 protect against nitrate tolerance and stunning in rabbit cardiac myocytes?,"we tested whether upregulation of hypoxia inducible factor-1 (hif-1) would restore the blunted effects of natriuretic peptides and nitric oxide caused by chronic nitrate exposure and stunning in cardiac myocytes. hif-1alpha was increased with deferoxamine (150 mg/kg for 2 days). nitrate tolerance was induced by a chronic nitroglycerin patch (0.3 mg/h for 5 days). we used freshly isolated rabbit ventricular myocytes. half the myocytes were subjected to simulated ischemia 15 min 95 n(2)-5 co(2) and reperfusion reoxygenation to produce stunning. cell function was measured utilizing a video-edge detector. shortening was examined at baseline and after brain natriuretic peptide (bnp, 10(-8), 10(-7) m) or s-nitroso-n-acetyl-penicillamine (snap, 10(-6), 10(-5) m) followed by kt5823 (cyclic gmp protein kinase inhibitor, 10(-6) m). we also measured cyclic gmp protein kinase protein levels and kinase activity. in control, bnp (-29) reduced percent shortening, while kt5823 partially restored function. deferoxamine treated control myocytes responded similarly. in patched nonstunned myocytes, bnp (-12) reduced shortening less and kt5823 did not increase function. however, deferoxamine restored the blunted effects of bnp (-21) and kt5823. in stunned myocytes, bnp (-11) reduced shortening less and kt5823 did not affect function. deferoxamine increased the effects of bnp (-27) and kt5823 in stunning. patch combined with stunning also similarly blunted the effects of bnp (-12) and kt5823. deferoxamine improved the effects of bnp (-22) and kt5823. similar results were observed after snap. stunning reduced cyclic gmp protein kinase activity and deferoxamine restored activity. deferoxamine had no effect on kinase activity in nitrate tolerance.",we found that upregulation of hif-1 could protect isolated cardiac myocytes against nitrate tolerance through a cyclic gmp protein kinase-independent mechanism and through a kinase-dependent mechanism in stunning.,Medication
do very mild stroke patients benefit from intravenous tissue plasminogen activator without increase of intracranial hemorrhage?,"intravenous recombinant tissue plasminogen activator (iv rt-pa) is an effective medication currently used to treat acute ischemic stroke within three hours of symptom onset in patients with an identifiable clinical deficit measured using the national institute of health stroke scale (nihss). we compared the outcomes of 27 identified patients with an nihss of 6 or less who received iv rt-pa for acute ischemic stroke treatment within three hours of symptom onset in our center with 24 historic controls from the nationally available national institute of neurological disorders and stroke (ninds) study database. the mean initial nihss was not significantly different in patients and control groups (mean /- sd: 4.52 /- 1.25 and 4.71 /- 1.4) (p 0.45). the mean modified rankin score (mrs) at the time of discharge in patients and control group were 0.78 /- 1.19 and 1.75 /- 1.75, respectively. the mrs at discharge demonstrated a statistically significant (p 0.03) improved clinical outcome for iv rt-pa treated group. the rate of intracranial hemorrhage (ich) in the iv rt-pa group and control group was not significantly different (p 1, odds ratio: 0.88, ci: 0.05-14.09).",this retrospective study demonstrates that administering intravenous rt-pa to patients with a very mild stroke (nihss of 6 or less) can lead to improved clinical outcome when compared to patients with similar nihss who have not received similar treatment.,Medication
does perimuscular connective tissue contain more and larger lymphatic vessels than the shallower layers in human gallbladders?,"to clarify whether perimuscular connective tissue contains more lymphatic vessels than the shallower layers in human gallbladders. lymphatic vessels were stained immunohistochemically with monoclonal antibody d2-40, which is a specific marker of lymphatic endothelium, in representative sections of 12 normal human gallbladders obtained at the time of resection for colorectal carcinoma liver metastases. in individual gallbladder specimens, nine high-power (x 200) fields with the highest lymphatic vessel density (lvd), termed ""hot spots"", were identified for each layer (mucosa, muscle layer, and perimuscular connective tissue). in individual hot spots, the lvd and relative lymphatic vessel area (lva) were measured microscopically using a computer-aided image analysis system. the mean lvd and lva values for the nine hot spots in each layer were used for statistical analyses. in the mucosa, muscle layer, and perimuscular connective tissue, the lvd was 16.1 /- 9.2, 35.4 /- 15.7, and 65.5 /- 12.2, respectively, and the lva was 0.4 /- 0.4, 2.1 /- 1.1, and 9.4 /- 2.6, respectively. thus, both the lvd and lva differed significantly (p 0.001 and p 0.001, respectively; kruskal-wallis test) among the individual layers of the wall of the gallbladder, with the highest lvd and lva values in the perimuscular connective tissue. most (98 of 108) of the hot spots within the perimuscular connective tissue were located within 500 mum of the lower border of the muscle layer.",the perimuscular connective tissue contains more and larger lymphatic vessels than the shallower layers in the human gallbladder. this observation partly explains why the incidence of lymph node metastasis is high in t2 (tumor invading the perimuscular connective tissue) or more advanced gallbladder carcinoma.,Treatment
does the mds-updrs track motor and non-motor improvement due to subthalamic nucleus deep brain stimulation in parkinson disease?,"the movement disorders society revision of the unified parkinson disease rating scale (mds-updrs) improves upon the original updrs by adding more non-motor items, making it a more robust tool to evaluate the severity of motor and non-motor symptoms of parkinson disease. previous studies on deep brain stimulation have not used the mds-updrs. to determine if the mds-updrs could detect improvement in both motor and non-motor symptoms after bilateral subthalamic nucleus deep brain stimulation for parkinson disease. we compared scores on the entire mds-updrs prior to surgery (baseline) and approximately six months following the initial programming visit in twenty subjects (12m/8f) with parkinson disease undergoing bilateral subthalamic nucleus deep brain stimulation. stn dbs significantly improved the scores for every section of the mds-updrs at the 6 month follow-up. part i improved by 3.1 points (22), part ii by 5.3 points (29), part iii by 13.1 points (29) with stimulation alone, and part iv by 7.1 points (74). individual non-motor items in part i that improved significantly were constipation, light-headedness, and fatigue.","both motor and non-motor symptoms, as assessed by the mds-updrs, improve with bilateral subthalamic nucleus stimulation six months after the stimulator is turned on. we recommend that the mds-updrs be utilized in future deep brain stimulation studies because of the advantage of detecting change in non-motor symptoms.",Symptoms
does longitudinal ultrasound curriculum improve long-term retention among internal medicine residents?,"point-of-care ultrasound is a rapidly evolving component of internal medicine (im) residency training. the optimal approach for teaching this skill remains unclear. we sought to determine whether the addition of a longitudinal ultrasound curriculum to a stand-alone workshop for ultrasound training improved knowledge retention in im residents. we conducted an observational cohort study from july to december 2013. all postgraduate year (pgy)-1 im residents attended an ultrasound workshop during orientation. ability to identify static images of ascites, kidney, thyroid, pleural fluid, inferior vena cava, and internal jugular vein was assessed immediately after the workshop. an ultrasound curriculum, including morning report and ultrasound rounds, was initiated during the inpatient medicine rotation. pgy-1 residents were randomly assigned to participate in the longitudinal curriculum. six months later, we conducted a follow-up survey with all pgy-1 residents. forty-eight pgy-1 residents (67) completed the postworkshop test and the 6-month follow-up test. of these, 50 (24 of 48) had participated in the ultrasound curriculum. residents not exposed to the curriculum showed a decline in the identification of ascites, pleural effusion, and internal jugular vein at 6 months (p .05), whereas those who participated in the curriculum maintained their performance (p .05).","six months after exposure to a longitudinal ultrasound curriculum, residents were more likely to correctly identify ultrasound images of ascites, kidney, and pleural effusion. the addition of a longitudinal ultrasound curriculum may result in improved knowledge retention in im residents.",Diagnosis
are aphasias for verbal and sign languages due to lesions of nearly localised but not identical brain regions of the left hemisphere ?,"to study the characteristics of verbal and sign language aphasia in a patient fluent in both languages, who had had a recent left hemisphere stroke as well as to localise the site responsible for spanish sign language aphasia. 56 years old male, with risk factors for stroke, who presented an episode of sudden onset aphasia and right hemiplegia that partially recovered in a few hours. the residual deficit of language was explored with a detailed protocol that included comprehension, denomination, oral and phonetic praxis, propositional and automatic spontaneous language, reading and writing tasks. the examination of verbal and sign language was video-recorded. the lesion was localised by magnetic resonance imaging 24 days after the stroke. the patient, whose infarction involved the superior temporal gyrus and sylvian operculum, presented similar abnormalities for comprehension of complex sentences, many phonemic paraphasias and no trouble to repeat single words. oral language was not fluent, but sign language was quite fluent with a rich vocabulary, but with semantic paraphasias, agrammatism and without self-criticism for his own mistakes.","the pattern of oral and sign language alterations is partially different, more for expressive than perceptive discourse, although both types of aphasias are caused by lesions of the left hemisphere. the regions responsible for these abnormalities of both symbolic languages are localised close to each other, but not in the same place.",Prevention
does stigmatization of a person visiting psychiatrist depend on observer 's gender ?,"the two types of stigmatization are social stigma, which includes discrimination, underestimation and distance in various social circumstances and personal stigma, which includes private relation i.e. a contact in person with stigmatized subject. majority of recent publications has shown gender asymmetry in stigmatization (mostly indicating male predominance in stigmatizing processes), whereas the opposite data can be also found in some publications. the present study was aimed at exploring the relation of students' gender with their tendency to stigmatize subjects visiting a psychiatrist and at analyzing whether the gender influences the process of stigmatization. the survey included 523 students (227 on the second and 296 on the sixth year of school of medicine, university of belgrade). the instrument consisted of a vignette with questionnaire (14 items). four versions of vignette were distributed: with/without ""label"" and male/female subject in the vignette. a more personal stigmatization was evident in the female students (p 0.05). the stigmatization positively correlated with the intimacy of student's relation with the subject going to a psychiatrist. a higher rate of stigmatization was evident if the vignette was showing a person of the opposite gender.","this is a unique study which analyzes separately the gender of a stigmatizing subject versus the subject being stigmatized and types of stigmatization. the data obtained should contribute to recognizing, understanding and controlling the widespread problem of stigma.",General
does hyaluronic acid-based nanogels produced by microfluidics-facilitated self-assembly improve the safety profile of the cationic host defense peptide novicidin?,"cationic host defence peptides constitute a promising class of therapeutic drug leads with a wide range of therapeutic applications, including anticancer therapy, immunomodulation, and antimicrobial activity. although potent and efficacious, systemic toxicity and low chemical stability have hampered their commercial development. to overcome these challenges a novel nanogel-based drug delivery system was designed. the peptide novicidin was self-assembled with an octenyl succinic anhydride-modified analogue of hyaluronic acid, and this formulation was optimized using a microfluidics-based quality-by-design approach. by applying design-of-experiment it was demonstrated that the encapsulation efficiency of novicidin (15 to 71) and the zeta potential (-24 to -57 mv) of the nanogels could be tailored by changing the preparation process parameters, with a maximum peptide loading of 36 4. the nanogels exhibited good colloidal stability under different ionic strength conditions and allowed complete release of the peptide over 14 days. furthermore, self-assembly of novicidin with hyaluronic acid into nanogels significantly improved the safety profile at least five-fold and six-fold when tested in huvecs and nih 3t3 cells, respectively, whilst showing no loss of antimicrobial activity against escherichia coli and staphylococcus aureus.",formulation in nanogels could be a viable approach to improve the safety profile of host defence peptides.,Medication
does off-pump coronary artery bypass grafting decrease the incidence of atrial fibrillation?,"postoperative atrial fibrillation remains a significant source of morbidity after coronary artery bypass grafting. we reviewed the data on 2,569 patients to determine if the absence of cardiopulmonary bypass resulted in a lower incidence of atrial fibrillation. all patients undergoing coronary artery bypass grafting without cardiopulmonary bypass from january 1, 1997 through june 30, 2001 were evaluated for postoperative atrial fibrillation. the data of 252 patients with no cardiopulmonary bypass (group 1) were reviewed and compared with three other patient groups. group 2 consisted of 1,470 patients using cardiopulmonary bypass during the same study period. group 3 consisted of 841 patients with a similar number of grafts as the study group but using cardiopulmonary bypass. group 4 consisted of historical data for 847 patients operated on using cardiopulmonary bypass collected from january 1995 through december 1996. prophylactic beta-blockade was instituted in january 1997. groups 1 to 3 received this treatment, but group 4 did not. group 1 had an incidence of atrial fibrillation of 8.8. groups 2, 3, and 4 had incidences of atrial fibrillation of 11.6, 9.4, and 28.0, respectively. when compared with group 1, the incidence of atrial fibrillation in group 4 was statistically different (p . 0001).",avoiding cardiopulmonary bypass did not aid the reduction of atrial fibrillation at our institution.,Treatment
does specific suppression of interleukin 2 biosynthesis by synthetic antisense oligodeoxynucleotides influence allograft rejection?,"interleukin (il)-2 supplementation can reverse both blood transfusion-induced tolerance to kidney allografts and spontaneous tolerance to liver allografts in rats. moreover, il-2 expression is frequently suppressed in models of allograft tolerance. the failure of il-2 biosynthesis might therefore play a critical role in tolerance induction. three antisense oligodeoxynucleotides (as-1, as-2, as-3) to rat il-2, and a control oligo (c-1) consisting of a scrambled version of as-1, were evaluated for gene-specific suppression of il-2 biosynthesis in vitro and in vivo, and for their effects on kidney allograft survival. reverse transcriptase-polymerase chain reaction and il-2 protein assays were used to assay concanavalin a-driven il-2 biosynthesis by lymph node lymphocytes in vitro. pvg recipients of dark agouti kidney allografts were treated with the oligos. graft survival and il-2 biosynthesis by reverse transcriptase-polymerase chain reaction in spleen and graft biopsy specimens were assessed. the as-1 oligo, but not the as-2, as-3 or c-1 oligos, suppressed concanavalin a-driven il-2 biosynthesis for the 4 days of culture. this effect was dependent on delivery of the as-1 oligo with lipofectamine. supplementation with exogenous il-2 reversed the suppression of lymphocyte proliferation in as-1-treated cultures. administration of as-1 intravenously at 10 mg/kg/day to pvg recipients of dark agouti kidney allografts suppressed il-2 (but not il-6, interferon-gamma, or tumor necrosis factor-alpha) synthesis in the grafts of seven of nine rats, as measured in biopsy specimens taken at days 2-7. by contrast, all nine control grafts strongly expressed il-2. however, neither graft histopathology nor graft survival was affected.","antisense oligonucleotides can powerfully suppress il-2 biosynthesis in vitro and in allograft recipients in vivo, but this does not affect kidney allograft rejection.",Medication
do aberrant cell and basement membrane architecture contribute to sidestream smoke-induced choroidal endothelial dysfunction?,"environmental tobacco smoke (ets) is widely regarded as a major modifiable risk factor for age-related macular degeneration (amd). yet, precisely how it exerts its pathologic effects is poorly understood. since early-stage amd is characterized by choroidal capillary loss, this study examined the effect of sidestream smoke (ss), the major component of ets, on the viability of choroidal endothelial cells (ec), with an emphasis on the role of aberrant cell and basement membrane (bm) architecture in mediating ss-induced response. chorioretinal ecs (rf/6a) were treated with ss, and cell viability and architecture were analyzed by colorimetric assay and actin cytoskeletal organization, respectively. the structure of rf/6a ec-secreted bm was examined by immunofluorescence for collagen iv and immunoblotting for lysyl oxidase (lox), a collagen-crosslinking enzyme. finally, fresh rf/6a ecs were cultured on decellularized ss-treated bm to evaluate its active role in ec dysfunction. the rf/6a ec viability decreased progressively with increasing ss dose, which correlated strongly with a significant decline in actin cytoskeleton-dependent ec spreading. sidestream smoke also caused marked disruption of the rf/6a ec-secreted bm that was accompanied by suppression of lox expression. further, fresh, non-ss-treated rf/6a ecs exhibited a significant loss in viability and actin cytoskeletal organization when cultured on ss-treated corrupt bm.",these findings indicate that aberrant physical cues in the form of ec and bm architecture likely have an important role in choriocapillaris dysfunction seen in ss-associated early amd and implicate choroidal bm as a potential target for amd management strategies.,Symptoms
is epidural analgesia for labor pain associated with a decreased frequency of uterine activity?,to evaluate the effect of epidural and pethidine analgesia on the frequency of uterine contractions during the first stage of labor. retrospective study. delivery ward of a public hospital. forty consecutive parturients. the mean number of contractions in the 30 min before administration of pethidine analgesia was 8.2/-1.7 as compared to 8.7/-1.3 after administration of the analgesia. the mean number of contractions in the 30 min before administration of epidural analgesia was 8.0/-1.4 as compared to 8.8/-1.9 after administration of the analgesia. the differences between the two groups and between the number of contractions before and after the administration of both types of analgesia were not statistically significant.,properly and timely administered epidural analgesia during the first stage of labor has no effect on frequency of uterine activity.,Medication
do schizophrenia-related rgs4 gene variations specifically disrupt prefrontal control of saccadic eye movements?,"the gene encoding the regulator of g-protein signaling subtype 4 (rgs4), located on chromosome 1q23-3, has been proposed as a possible susceptibility gene for schizophrenia and has been specifically linked to prefrontal cortical structural and functional integrity. the effects of four core single nucleotide polymorphisms (snps) within the rgs4 gene on oculomotor parameters in a battery of oculomotor tasks (saccade, antisaccade, smooth eye pursuit, fixation) were investigated in a sample of 2243 young male military conscripts. the risk allele of rgs4snp18 was found to be associated with two variables of antisaccade performance, increased error rate and variation in the correct antisaccade latency. by contrast, the same allele and also the risk allele of rgs4snp4 led to an improvement in smooth eye pursuit performance (increased gain). structural equation modeling confirmed that the combined gene variation of rgs4snp4 and rgs4snp18 was a significant predictor of antisaccade but not smooth eye pursuit performance.","these results provide evidence for a specific effect of schizophrenia-related rgs4 genotype variations to prefrontal dysfunction measured by oculomotor indices of performance in normal individuals, further validating the hypothesis that rgs4 is related to prefrontal dysfunction in schizophrenia.",General
are key adhesion molecules present on long podia extended by hematopoietic cells?,"we recently reported that cd34() hematopoietic cells and the kg1a cell line extend long, thin podia. these podia can dynamically extend and retract, often adhere to the substrate, and appear to connect cells up to 300 microm apart. the surface receptors found on these podia have not been described. by using time-lapse fluorescent microscoscopy and immunostaining techniques, we describe a method for detecting surface receptors on these podia. this includes an in situ antibody staining procedure without fixing cells. we demonstrate, using cd34 selected mobilized peripheral blood cells and kg1a cells, that adhesion molecules known to play important roles in blood-cell migration and adhesion are present on these podia. these include: cd11a, cd18, cd29, cd34, cd45, cd49d, cd49e, and cd62l. additionally, cd54 and cd44 were present on the podia extended by kg1a cells, but were not detectable on the primary cd34() cells. the integrin cd49d localized at the base of these podia in a time-dependent manner in kg1a cells. the frequency and morphology of these long podia on three myeloid leukemia-cell lines (kg1a, mv4-11, and aml-193) and a cd34-negative t-cell line (cem) are also compared. kg1a and cem cell lines extend long, dynamic podia that are similar to the podia on primary cd34() cells in morphology and adhesion molecule expression. the aml-193 and mv4-11 cell lines, however, did not extend these long podia.",we describe a technique that provides a method of detecting surface receptors on thin cell membrane projections. these results support the likely role of these podia in cell migration and cell-cell communication.,Medication
does bortezomib induce apoptosis and autophagy in osteosarcoma cells through mitogen-activated protein kinase pathway in vitro?,"to investigate the effects of bortezomib on human osteosarcoma cells from the hos cell line, and the underlying associated mechanisms. viability of hos cells treated with bortezomib (5-20 nm) for different time periods was measured and changes in the cell cycle were assessed. apoptosis and autophagy in hos cells treated with bortezomib were analysed using annexin v-fluorescein isothiocyanate assay, transmission electron microscopy and western blotting. surges in mitogen-activated protein kinase (mapk) pathways including mapk/extracellular signal-regulated kinase (erk) kinase (mek1/2), erk1/2, c-jun n-terminal kinase (jnk) and p38 mapk were analysed using western blotting. bortezomib induced growth inhibition in a time- and dose-dependent manner, and autophagy and apoptosis in a dose-dependent manner, in hos cells. hos cell autophagy and apoptosis in response to bortezomib, corresponded with changing levels of intracellular mapk signalling molecules.","this study provided new insights into the mechanisms underlying bortezomib-induced apoptosis in human osteosarcoma hos cells, and suggests that bortezomib could be a potent chemotherapeutic agent in the treatment of osteosarcoma.",Medication
does reduced lymph node yield in rectal carcinoma specimen after neoadjuvant radiochemotherapy have no prognostic relevance?,"in colorectal surgery uicc/ajcc criteria require a yield of 12 or more locoregional lymph nodes for adequate staging. neoadjuvant radiochemotherapy for rectal carcinoma reduces the number of lymph nodes in the resection specimen; the prognostic impact of this reduced lymph node yield has not been determined. one hundred two patients with ut3 rectal carcinoma who were receiving neoadjuvant radiochemotherapy were compared with 114 patients with ut3 rectal carcinoma who were receiving primary surgery followed by adjuvant radiochemotherapy. total lymph node yield and number of tumor-positive lymph nodes were determined and correlated with survival. after neoadjuvant radiochemotherapy both total lymph node yield (12.9 vs. 21.4, p 0.0001) and number of tumor-positive lymph nodes (1.0 vs. 2.3, p 0.014) were significantly lower than after primary surgery plus adjuvant radiochemotherapy. reduced total lymph node yield in neoadjuvantly treated patients had no prognostic impact, with overall survival of patients with 12 or more lymph nodes the same as that of patients with less than 12 lymph nodes. overall survival of neoadjuvantly treated patients was significantly influenced by the number of tumor-positive lymph nodes with 5-year-survival rates of 88, 63, and 39 for 0, 1-3, and more than 3 positive lymph nodes (p 0.0001).",the uicc/ajcc criterion of a total lymph node yield of 12 or more should be revised for rectal carcinoma patients.,Diagnosis
does collaborative working empower staff to cut the number of cardiac arrests?,"at salford royal foundation trust, 179 patients suffered a cardiac arrest between march 2007 and april 2008. maine measures for mprovement: our primary outcome measure was the number of cardiac arrests per 1,000 admissions. eleven wards were invited to participate in a breakthrough series collaborative from april 2008 to january 2009. it is a short term (6-15 months) learning system thatbrings together several teams to s eekimprovement, focusing on one topic. frontline teams worked to develop changes in their clinical areas with the aim of reducing cardiac arrests by 50 in one year. april-december 2008 saw a reduction of 32 in the cardiac arrest rate, resulting in an average arrest rate of 0.79 per 1,000 admissions. since the project began to upscale its work in january 2009, a further reduction has been noted. however,another 4 months' data is required to assess whether this equates to a sustained change.","preliminary data suggests that a breakthrough series collaborative is an effective method of engaging frontline staff in developing and implementing change, with improvements in patient care.",General
does response to transarterial chemoembolization in candidates with hepatocellular carcinoma within milan criteria predict post-transplant disease-free survival?,"few groups have studied the impact of pretransplant transarterial chemoembolization (tace) in the outcomes of liver transplant recipients with hepatocellular carcinoma (hcc). we verified whether response to tace in hcc candidates impacts post-transplant disease-free survival. this a single center retrospective study of patients who underwent liver transplantation from 2006-2013. included were those transplanted due to hcc within the milan criteria who were treated with tace in the pre-transplant period. response to tace followed the modified recist (mrecist) criteria. disease free-survival was the main endpoint of the study. we included 187 patients in this study. the population had an average age of 57.5 years, predominantly formed by men (82.5), with an average imc of 26.7, meld of 13, with viral hepatitis as main cause of liver disease. average waiting time was 253 days and follow-up was 27.3 months. based on response to tace, 3-year disease-free survival was 84.1 for those with complete response to tace, 84.1 for those with partial response to tace, 85.7 for those with stable disease and 100 for patients with progressive disease. multivariate analysis did not identify response to tace as a predictor of disease-free post-transplant survival.",response to tace in candidates with hcc within milan criteria does not predict post-transplant disease-free survival.,Treatment
do appraisal of maternity management and family planning guidelines using the agree ii instrument in india?,"guideline development gathered pace in india after the inception of national rural health mission (nrhm) in 2005. however, there is a lack of adequate information about guideline development process, review, and update. this paper reports on the systematic appraisal of indian guidelines related to maternity management (mm) and family planning (fp) using the appraisal of guidelines for research and evaluation ii (agree ii) instrument, which was one of the components of a pilot research in 2012-13. forty-four selected guidelines about mm and fp, identified through a consensus building workshop, were independently appraised by two appraisers with agree instrument having six different domains. mean item scores, domain scores, and standardized scores were calculated by averaging the scores across the two appraisers. most guidelines scored high in scope and purpose and clarity of presentation. however, they had little documentation about the development group member details, incorporation of patient views, evidence search method, method chosen for formulating recommendations, tools for application, potential barriers, cost implications, and information about the funding body. nonclinical guidelines scored higher than clinical guidelines (p 0.01) for mm in the domain applicability. clinical fp guidelines scored higher than nonclinical guidelines in the domain of rigor of development (0.01).","despite being clinically sound, indian guidelines score poorly due to weak documentation about their development process. it is recommended that the guideline development process be improved with systematic documentation for achieving standardization.",Treatment
is survival transcriptome in the coenzyme q10 deficiency syndrome acquired by epigenetic modifications : a modelling study for human coenzyme q10 deficiencies?,"coenzyme q10 (coq10) deficiency syndrome is a rare condition that causes mitochondrial dysfunction and includes a variety of clinical presentations as encephalomyopathy, ataxia and renal failure. first, we sought to set up what all have in common, and then investigate why coq10 supplementation reverses the bioenergetics alterations in cultured cells but not all the cellular phenotypes. design modelling study: this work models the transcriptome of human coq10 deficiency syndrome in primary fibroblast from patients and study the genetic response to coq10 treatment in these cells. four hospitals and medical centres from spain, italy and the usa, and two research laboratories from spain and the usa. primary cells were collected from patients in the above centres. we characterised by microarray analysis the expression profile of fibroblasts from seven coq10-deficient patients (three had primary deficiency and four had a secondary form) and aged-matched controls, before and after coq10 supplementation. results were validated by q-rt-pcr. the profile of dna (cpg) methylation was evaluated for a subset of gene with displayed altered expression. coq10-deficient fibroblasts (independently from the aetiology) showed a common transcriptomic profile that promotes cell survival by activating cell cycle and growth, cell stress responses and inhibiting cell death and immune responses. energy production was supported mainly by glycolysis while coq10 supplementation restored oxidative phosphorylation. expression of genes involved in cell death pathways was partially restored by treatment, while genes involved in differentiation, cell cycle and growth were not affected. stably demethylated genes were unaffected by treatment whereas we observed restored gene expression in either non-methylated genes or those with an unchanged methylation pattern.","coq10 deficiency induces a specific transcriptomic profile that promotes cell survival, which is only partially rescued by coq10 supplementation.",Medication
does leucocyte count indicate carotid plaque instability in stroke patients?,"increasing evidence points to the inflammatory character of atherosclerosis and several parameters of inflammation have been proposed as cerebrovascular risk markers. the objective of the research was to examine the connection of serum inflammatory parameters and ultrasound (us) characteristics of the structure and size of carotid plaque. we assumed that the number of leukocytes (le) was an indicator of carotid plaque instability and an increased risk of stroke. serum inflammatory parameters: erythrocyte sedimentation rate in the first (esr i) and second hour (esr ii), the number of le, high sensitivity c-reactive protein (hscrp) and fibrinogen were measured by standard methods. all the subjects (n 75) were divided into 3 groups (symptomatic, asymptomatic and control). us evaluation of extracranial carotid arteries was performed in a duplex system. plaques were classified into categories according to stenosis percentage ( 50, 50) and pursuant to echomorphological characteristics (gray-weale classification). in the subjects with stroke an ischemic lesion was confirmed by computed tomography. the average values of biochemical parameters in the symptomatic group were: esr i 29.57 29.87 cm, esr ii 51.60 36.87 cm, the number of le 10.10 3.20 x 10 u/l, hscrp 8.15 5.50 mg/l and fibrinogen 4.03 0.70 g/l. the average values of all testing biochemical parameters in symptomatic patients were significantly higher than in the asymptomatic ones and the control group: for esr i (p 0.05) and esr ii (p 0.05); for the number of le (p 0.001); for hscrp (p 0.001) and fibrinogen (p 0.001). category i of echomorphological characteristics in the symptomatic group was present in 66.7 of the cases and it was significantly higher than in the asymptomatic (40.0; p 0.05) and the control group (20.0; p 0.01). univariate logistic regression analysis confirmed that all testing biochemical parameters are indicators of stroke risk. multivariate logistic regression analysis confirmed a statistically significant correlation of the number of le and stroke risk, while the increase in the value by a unit of measurement was associated with the growth of risk by 3.22 times (from 1.67 to 6.22).",the number of le is associated with the phenomenon of carotid plaque instability and may be a useful additional marker of increased risk for developing acute cerebral infarction.,Diagnosis
"are autoantibodies , metalloproteinases and bone markers in rheumatoid arthritis patients unable to predict their responses to infliximab?","to identify biochemical, immunological and bone markers as predictors of rheumatoid arthritis (ra) patients' responses to infliximab. a total of 76 patients with active ra (american college of rheumatology criteria), refractory to disease-modifying anti-rheumatic drugs, including methotrexate, received infliximab (3 mg/kg) infusions at weeks 0, 2, 6, and then every 8 weeks in combination with methotrexate or leflunomide. at week 14, infliximab efficacy was evaluated using disease activity score (das)28. a serum sample, collected just before starting infliximab, was tested by elisa (unless stated otherwise) for the following immunological markers: rheumatoid factor by agglutination and elisa (iga, igg and igm isotypes); anti-cyclic citrullinated protein; autoantibodies recognizing calpastatin domain i and its 27 c-terminal fragment, glucose-6-phosphate isomerase, alpha-enolase; anti-keratin and anti-perinuclear factor antibodies (immunofluorescence); biochemical markers: c-reactive protein (nephelometry), metalloproteinase-1 and -3, tissue inhibitors of metalloproteinases-1 and -2, antioxidants (vitamins a and e; selenium); bone resorption markers: pyridinoline, deoxypyridinoline, osteoprotegerin, soluble receptor activator of nuclear factor-kappab ligand, cartilage oligomeric matrix protein. each parameter's predictive value of the response to infliximab was analysed using fisher's exact, mann-whitney and chi-square tests. hierarchical clustering was performed with the institute for genomic research (tigr) multiple experiment viewer software. good, moderate and non-responder rates were 6.5, 61.8 and 31.5, respectively. no significant difference was observed between responders and non-responders, regardless of the serum parameters considered. analysis of dichotomous or continuous variables failed to identify markers predictive of a good or poor response to infliximab.","the search for soluble markers in ra patients' sera likely to predict response to infliximab because of their involvement in ra pathogenesis seems disappointing. however, because of the limited power to detect smaller differences in biomarkers, the present study is a preliminary exploratory analysis.",Medication
does polypeptide n-acetylgalactosaminyltransferase-6 expression independently predict poor overall survival in patients with lung adenocarcinoma after curative resection?,"polypeptide n-acetylgalactosaminyltransferases (galnac-ts) are important glycosyltransferases in cancer, but the clinical role of its individual isoforms is unclear. we investigated the clinical significance and survival relevance of one isoform, galnac-t6 in lung adenocarcinoma after curative resection. galnac-t6 was identified in 27.8 (55/198) of patients, and statistically indicated advanced tnm stage (p 0.069). multivariate analysis showed galnac-t6 to be an independent predictor for reduced overall survival of patients (p 0.027), and the result was confirmed with bootstraping techniques, and on line ""kaplan-meier plotter"" and ""survexpress"" database analysis, respectively. moreover, roc curve demonstrated that galnac-t6 expression significantly improved the accuracy of survival prediction. with 198 paraffin-embedded tumor samples from lung adenocarcinoma patients, galnac-t6 expression was immunohistochemically assessed for the association with clinicopathological parameters. the prognostic significance was evaluated by cox proportional hazards regression analysis with 1000 bootstraping. ""kaplan-meier plotter"", ""survexpress"" database analysis, and receiver-operating characteristic (roc) curve were performed to provide further validation.","galnac-t6 expression correlated significantly with advanced tnm stage, and independently predicted worse os for lung adenocarcinoma.",Treatment
does subunit interaction determine iks participation in cardiac repolarization and repolarization reserve?,"the role of iks, the slow delayed rectifier k current, in cardiac ventricular repolarization has been a subject of debate. we develop a detailed markov model of iks and its alpha-subunit kcnq1 and examine their kinetic properties during the cardiac ventricular action potential at different rates. we observe that interaction between kcnq1 and kcne1 (the beta-subunit) confers kinetic properties on iks that make it suitable for participation in action potential repolarization and its adaptation to rate changes; in particular, the channel develops an available reserve of closed states near the open state that can open rapidly on demand.","because of its ability to form an available reserve, iks can function as a repolarization reserve when ikr, the rapid delayed rectifier, is reduced by disease or drug and can prevent excessive action potential prolongation and development of arrhythmogenic early afterdepolarizations.",General
is energy expenditure at rest and during sleep in children with prader-willi syndrome explained by body composition?,"obesity in prader-willi syndrome (pws) seems to be related to a low basal metabolic rate (bmr). in addition, abnormal sleep patterns reported in pws might affect sleeping metabolic rate (smr). our objective was to assess bmr and smr adjusted for fat-free mass in young pws patients. subjects were 17 pws patients (10 females and 7 males aged 7.5-19.8 y) and 17 obese control subjects matched for sex and bone age. smr was measured in a respiratory chamber, bmr with a ventilated-hood system, and body composition by deuterium dilution. bmr and smr were significantly lower in the pws group than in the control group (5.36 /- 1.18 and 4.62 /- 1.08 mj/d compared with 6.38 /- 1.55 and 5.60 /- 1.52 mj/d, respectively; p 0.05). when fat-free mass was included in the analysis, multiple regression showed no differences in bmr and smr between groups. when weight was included in the analysis instead of fat-free mass, smr was lower in the pws group. fat-free mass was lower in the pws group both as an absolute value and when adjusted for height.",bmr and smr are low in young patients with pws because of a low fat-free mass.,Prevention
do advanced glycation end products upregulate the endoplasmic reticulum stress in human periodontal ligament cells?,"the accumulation of advanced glycation end products (ages) appears to be the main factor responsible for modulating periodontal inflammation in diabetes. the aim of this study is to examine the effects of ages on inflammation in human periodontal ligament cells and to investigate the mechanism with a specific emphasis on the role of endoplasmic reticulum (er) stress-induced nuclear factor-kappa b (nf-b) pathway. cytotoxicity was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (mtt) assay. the protein expressions of er markers and nf-b were examined by western blot analysis. the translocation of nf-b was observed by immunofluorescence assay. proinflammatory chemokine production was determined by enzyme-linked immunosorbent assay. treatment with ages reduced cell viability in a concentration- and time-dependent manner. ages induced er stress, as evidenced by survival molecules, such as glucose-regulated protein 78 (grp78), double-stranded rna-activated protein kinase-like er kinase (perk), and activating transcription factor 6 (atf-6), and apoptotic molecules, such as ccaat/enhancer binding protein homologous protein (chop) and caspase 12. ages upregulated the nucleoprotein expression of nf-b, enhanced translocation of nf-b from the cytoplasm to the nucleus, and increased the production of proinflammatory chemokines interleukin-6 and interleukin-8.",ages mediate inflammation of human periodontal ligament cells via the er stress-induced nf-b pathway.,Treatment
is migraine with aura associated with an incomplete circle of willis : results of a prospective observational study?,"to compare the prevalence of an incomplete circle of willis in patients with migraine with aura, migraine without aura, and control subjects, and correlate circle of willis variations with alterations in cerebral perfusion. migraine with aura, migraine without aura, and control subjects were prospectively enrolled in a 111 ratio. magnetic resonance angiography was performed to examine circle of willis anatomy and arterial spin labeled perfusion magnetic resonance imaging to measure cerebral blood flow. a standardized template rating system was used to categorize circle of willis variants. the primary pre-specified outcome measure was the frequency of an incomplete circle of willis. the association between circle of willis variations and cerebral blood flow was also analyzed. 170 subjects were enrolled (56 migraine with aura, 61 migraine without aura, 53 controls). an incomplete circle of willis was significantly more common in the migraine with aura compared to control group (73 vs. 51, p 0.02), with a similar trend for the migraine without aura group (67 vs. 51, p 0.08). using a quantitative score of the burden of circle of willis variants, migraine with aura subjects had a higher burden of variants than controls (p 0.02). compared to those with a complete circle, subjects with an incomplete circle had greater asymmetry in hemispheric cerebral blood flow (p 0.05). specific posterior cerebral artery variants were associated with greater asymmetries of blood flow in the posterior cerebral artery territory.","an incomplete circle of willis is more common in migraine with aura subjects than controls, and is associated with alterations in cerebral blood flow.",Diagnosis
do increases in spinal cerebrospinal fluid potassium concentration increase isoflurane minimum alveolar concentration in rats?,"previous studies demonstrated that mac for isoflurane directly correlates with the concentration of na() in cerebrospinal fluid surrounding the spinal cord, the primary site for mediation of the immobility produced by inhaled anesthetics. if this correlation resulted from increased irritability of the cord, then infusion of increased concentrations of potassium (k()) might be predicted to act similarly. however, an absence of effect of k() might be interpreted to indicate that k() channels do not mediate the immobility produced by inhaled anesthetics whereas na() channels remain as potential mediators. accordingly, in the present study, we examined the effect of altering intrathecal concentrations of k() on mac. in rats prepared with chronic indwelling intrathecal catheters, we infused solutions deficient in k() and with an excess of k() into the lumbar space and measured mac for isoflurane 24 h before, during, and 24 h after infusion. rats similarly prepared were tested for the effect of altered osmolarity on mac (accomplished by infusion of mannitol) and for the penetration of na() into the cord. mac of isoflurane never significantly increased with increasing concentrations of k() infused intrathecally. at infused concentrations exceeding 12 times the normal concentration of kcl, i.e., 29 meq/l, rats moved spontaneously at isoflurane concentrations just below, and sometimes at mac, but the average mac in these rats did not exceed their control mac. at the largest infused concentration (58.1 meq/l), mac significantly decreased and did not subsequently return to normal (i.e., such large concentrations produced injury). infusions of lower concentrations of k() had no effect on mac. infusion of osmotically equivalent solutions of mannitol did not affect mac. na() infused intrathecally measurably penetrated the spinal cord.",the results do not support a mediation or modulation of mac by k() channels.,Medication
does microbiological and clinical profile of uropathogenic escherichia coli isolate in kathmandu university hospital?,"treatment of patients infected by multidrug resistant bacteria is a major challenge. immunocompromised status, prolonged hospital stay, malignancy, diabetes are some of the risk factors for emergence of multidrug resistance. our study focused on microbiological and clinical profile of multidrug resistant uropathogenic escherichia coli. this was a cross-sectional study conducted between june 2014-may 2015 in kathmandu university hospital. urine sample from outpatients and inpatients from which escherichia coli isolated was included. specimen collection, culture, identification tests were done following guidelines given by american society for microbiology. total number of urine samples received during the study were 3,554. escherichia coli isolates were 645(18.14) and 245(37.98) were extended spectrum beta-lactamase producer. extended spectrum beta-lactamase producers were found more among inpatients 148(60.41) p0.001, patients with underlying urological abnormalities 38 (15.51) p0.0039, pregnant ladies 46(18.77) p0.0028, diabetic patients 27 (11.02) p0.0084, patients who received prior antibiotic therapy 155 (63.26) p0.0043 than extended spectrum beta-lactamase non-producer. malignancy was seen more among extended spectrum beta-lactamase producer having patients 5 (2.04) p0.031 and all these isolates were more resistant to fluoroquinolones 168(68.57), trimethoprim-sulfamethoxazole 239 (97.55) p0.0633, aminoglycosides p0.0001 but only 2(0.80) were resistant to carbapenems.","diabetes, pregnancy, malignancy, prior antibiotic therapy, underlying urological abnormalities were found associated with emergence of extended spectrum beta-lactamase producer in urine samples. proper antibiotic usage may help to overcome the problem of emergence of antibiotic resistance.",Treatment
is early hyperglycemia associated with poor gross motor outcome in asphyxiated term newborns?,"hyperglycemia after ischemic stroke in adults and after near-drowning in children is associated with a poor neurological outcome. anaerobic metabolism of glucose leads to buildup of lactic acid, free radical production, mitochondrial failure, and ultimately an increase in neurological injury. in asphyxiated infants, high lactate peaks are seen in the basal ganglia with magnetic resonance spectroscopy. because motor disability in asphyxiated full-term newborns often relates to injury in the basal ganglia, we hypothesized that hyperglycemia and associated buildup of lactic acid may lead to worse gross motor outcome. glucose, blood gas values, and demographic data were abstracted from the medical records of 41 term infants with asphyxia and without confounding diagnoses. their gross motor function classification system scores were determined from the medical record or by structured telephone interviews. the outcomes of 14 infants were considered poor on the basis of death within the first 6 months or moderate-to-severe cerebral palsy (gross motor function classification system score 1-5). the other 27 infants had no gross motor disability (gross motor function classification system score 0). the highest recorded blood glucose correlated with poor outcome (p 0.046 by logistic regression). infants with hyperglycemia (blood glucose 150 mg/dl) were more likely to have poor outcome (p 0.017; odds ratio: 5.9; 95 confidence interval: 1.4-24.7).",high blood glucose in the first 12 hours is associated with poor gross motor outcome in this cohort of asphyxiated term infants. clinicians should avoid hyperglycemia in managing term infants with asphyxia.,Diagnosis
do fat and vitamin intakes during pregnancy have stronger relations with a pro-inflammatory maternal microbiota than does carbohydrate intake?,"although diet is known to have a major modulatory influence on gut microbiota, knowledge of the specific roles of particular vitamins, minerals, and other nutrients is limited. modulation of the composition of the microbiota in pregnant women is especially important as maternal microbes are transferred during delivery and initiate the colonization process in the infant. we studied the associations between intake of specific dietary nutrients during pregnancy and gut microbiota composition. utilizing the norwegian nomic cohort, we examined the relations between intakes of 28 dietary macro- and micronutrients during pregnancy, derived from food frequency questionnaires administered to 60 women in the second trimester, and observed taxonomic differences in their gut microbiota four days after delivery (assessed through illumina 16s rrna amplicon analysis). higher dietary intakes of fat-soluble vitamins, especially vitamin d, were associated with reduced microbial alpha diversity (p value 0.001). furthermore, using recently developed statistical methodology, we discovered that the variations in fat-soluble vitamins, saturated and mono-unsaturated fat, and cholesterol intake, were associated with changes in phyla composition. specifically, vitamin d, mono-unsaturated fat, cholesterol, and retinol were associated with relative increases in proteobacteria, which is a phylum known to encompass multiple pathogens and to have pro-inflammatory properties. in contrast, saturated fat, vitamin e, and protein were associated with relative decreases in proteobacteria.",the results in this article indicate that fats and fat-soluble vitamins are among the most potent dietary modulators of gut microbiota in mothers. the shifts in microbiota due to diet need to be further studied alongside gut microbiota changes during pregnancy to better understand the impact on infant gut microbiota.,Medication
"are patients over 65 years assigned lower ecog ps scores than younger patients , although objectively measured physical activity is no different?","the eastern cooperative group performance status (ecog ps) is a widely used standard functional classification in oncology practice, the verbal descriptors of which refer to physical activity (pa). little is known about the cut-off points of this scale and measured pa levels. this research investigated the relationship between ps assigned, objectively measured pa, and patient age. one hundred ambulatory patients with treatment-naive cancer wore an accelerometer (rt3) for a mean (sd) of 5.6 (1.1) days before initial oncology evaluation and ecog ps assignment. seventy five participants (75) were 65 years and 25 were 65 years. eighty nine (89) were assigned an ecog ps of 0 or 1 and 11 a ps of 2 or 3. a weak but significant inverse association was found between objectively measured pa and ps (rho -0.26, p 0.01). seventy one participants (80) with a ps of 0 or 1 spent more than 50 of waking hours resting. participants assigned a ps of 2-3 spent significantly more time resting than those assigned a ps of 0 (p 0.01). age 65 years was significantly related to ps assigned (p 0.04), although the older cohort were no less sedentary than younger patients.","pa levels were low, but ps scoring reflected relative pa levels and differentiated between patients of ps 0 and 2-3. chronological age was not predictive of activity levels, but older patients were assigned lower ps scores. incorporation of objective pa measures may merit further investigation especially in the geriatric oncology setting.",Prevention
does two-stage portal vein ligation facilitate liver regeneration in rats?,"recent reports have demonstrated that some patients are unable to undergo scheduled liver resection after preoperative portal vein embolization due to insufficient hypertrophy of the future remnant liver. the present study examined whether two-stage portal vein ligation (pvl) increases hypertrophy of the future remnant liver compared to conventional pvl in rats. rats were divided into 3 groups: group a, ligation of left primary branch; group b, ligation of right and left primary branches; group c, ligation of the left primary branch, followed by 2-stage pvl 7 days postoperatively. to evaluate liver regeneration, the proliferating cell nuclear antigen labeling index (li), mitotic index (mi) in the caudate lobe and weight ratio of caudate lobe to body weight were measured. the weight ratio of caudate lobe to body weight was significantly higher in group c than in groups a or b 14 days postoperatively. in groups a and b, li and mi in the caudate lobe peaked 2 days postoperatively, then decreased to preoperative levels by 7-8 days postoperatively, but remained significantly elevated until 10-14 days postoperatively in group c.",two-stage pvl increases hypertrophy of the future remnant liver compared to conventional pvl in rats.,Treatment
are rural-to-urban migrants at high risk of sexually transmitted and viral hepatitis infections in china : a systematic review and meta-analysis?,"rapid economic development in urban china has led to a mass migration of surplus rural residents into urban areas for better employment opportunities. this study aims to identify prevalence levels and risks of sexually transmitted infections (stis) and hepatitis among the rural-to-urban migrant population in china. chinese and english literature databases were searched for studies reporting prevalence of hiv, stis and viral hepatitis among rural-to-urban migrants in china between 1990 and 2013. the estimates were summarised through a systematic review and meta-analysis. the risks of infection were compared between migrants and the general chinese population. we identified a total of 411 eligible studies. the prevalence of hiv, syphilis, gonorrhea, genital warts and hcv among migrants were 0.23 (0.20-0.27), 0.69 (0.57-0.84), 2.18 (1.30-3.64), 1.54 (0.70-3.36) and 0.45 (0.31-3.65), representing 4.0 (3.1-5.2), 1.9 (1.1-3.0), 13.6 (5.8-32.1), 38.5 (15.7-94.5) and 3.8 (1.9-7.3) higher odds of infection than among the general population. construction workers, long-distance truck drivers and migrant women through marriage were migrant subgroups that were highly susceptible to stis and hepatitis. hiv prevalence among migrant pregnant women (0.10, 0.02-0.49) was significantly higher than that of pregnant women in the general chinese population (or 7.7, 3.4-17.4). however, no significant differences were observed in stis and hepatitis between overall female sex workers (fsws), men who have sex with men (msm) and drug users (dus), and the corresponding subgroups with a migratory background.","rural-to-urban migrants have a higher risk of stis and hepatitis than the general chinese population, but a migratory background does not increase the infection risks of stis and hepatitis in fsws, msm and dus.",Medication
is mucosal-associated invariant t cell a potential marker to distinguish fibromyalgia syndrome from arthritis?,"fibromyalgia (fm) is defined as a widely distributed pain. while many rheumatologists and pain physicians have considered it to be a pain disorder, psychiatry, psychology, and general medicine have deemed it to be a syndrome (fms) or psychosomatic disorder. the lack of concrete structural and/or pathological evidence has made patients suffer prejudice that fms is a medically unexplained symptom, implying inauthenticity. furthermore, fms often exhibits comorbidity with rheumatoid arthritis (ra) or spondyloarthritis (spa), both of which show similar indications. in this study, disease specific biomarkers were sought in blood samples from patients to facilitate objective diagnoses of fms, and distinguish it from ra and spa. peripheral blood mononuclear cells (pbmcs) from patients and healthy donors (hd) were subjected to multicolor flow cytometric analysis. the percentage of mucosal-associated invariant t (mait) cells in pbmcs and the mean fluorescent intensity (mfi) of cell surface antigen expression in mait cells were analyzed. there was a decrease in the mait cell population in fms, ra, and spa compared with hd. among the cell surface antigens in mait cells, three chemokine receptors, ccr4, ccr7, and cxcr1, a natural killer (nk) receptor, nkp80, a signaling lymphocyte associated molecule (slam) family, cd150, a degrunulation marker, cd107a, and a coreceptor, cd8 emerged as potential biomarkers for fms to distinguish from hd. additionally, a memory marker, cd44 and an inflammatory chemokine receptor, cxcr1 appeared possible markers for ra, while a homeostatic chemokine receptor, cxcr4 deserved for spa to differentiate from fms. furthermore, the drug treatment interruption resulted in alternation of the expression of ccr4, ccr5, cxcr4, cd27, cd28, inducible costimulatory molecule (icos), cd127 (il-7 receptor ), cd94, nkp80, an activation marker, cd69, an integrin family member, cd49d, and a dipeptidase, cd26, in fms.","combined with the currently available diagnostic procedures and criteria, analysis of mait cells offers a more objective standard for the diagnosis of fms, ra, and spa, which exhibit multifaceted and confusingly similar clinical manifestations.",Diagnosis
does recombinant human growth hormone improve the fat redistribution syndrome ( lipodystrophy ) in patients with hiv?,"to determine the efficacy of recombinant human growth hormone (rhgh) in the treatment of the fat redistribution syndrome (frs) in patients with hiv. a prospective, open-label study. an urban, university-affiliated infectious disease clinic. ten hiv-infected patients (seven men, three women) with frs. treatment with 6 mg of rhgh a day, subcutaneously for 12 weeks. body mass index (bmi), body composition by bioelectrical impedance analysis (bia), body composition by anthropometrics (including waist/hip ratio), buffalo hump. the mean age was 41.7 years, the cd4 cell count was 247, and the hiv rna was 95 735 copies/ml; 50 had undetectable viral rna. the bmi was significantly increased from baseline to the end of treatment with growth hormone (25.3-26.9 kg/m2; p 0.04); the waist/hip ratio significantly decreased from baseline levels, after treatment with growth hormone (1.03-0.9; p 0.04); mid-thigh circumference increased significantly when baseline was compared with measures after treatment (49.1-51.8 cm; p 0.03). one patient had to discontinue therapy because of hyperglycemia.",short-term treatment with rhgh improved the alterations in body shape that occur with frs in hiv-infected patients. waist/hip ratios and mid-thigh circumference are useful measures to follow alterations in body shape in frs.,Treatment
does rosuvastatin intensify the beneficial effects of rho-kinase inhibitor in reversal of monocrotaline-induced pulmonary hypertension?,"it remains controversial whether statins have a beneficial effect on pulmonary arterial hypertension (pah). this study is intended to evaluate whether statin, co-administered with rho-kinase inhibitor, could enhance its efficacy. although rho-kinase inhibitors, including fasudil, have been reported to improve pulmonary hypertension in experimental and clinical studies, the combination of these agents has not been tested in the treatment of pulmonary hypertension (ph). the effects of such a regimen on hemodynamics, right ventricle hypertrophy, and rho-associated protein kinase (rock) activity in experimental monocrotaline (mct)-induced pulmonary hypertension were examined. fourteen days after monocrotaline injection (60 mg/kg), male rats were treated orally for another 14 days with fasudil (15 mg/kg per day), or with a combination of fasudil rosuvastatin (10 mg/kg per day). the drug combination reversed the mct-induced increase in right ventricle pressure (rvp) and reduced right ventricular hypertrophy (rv/lv s ratio) more than rho kinase inhibitor alone. the simultaneous administration of fasudil and rosuvastatin caused a further decrease of rhoa kinase activity in isolated lung tissues as compared to fasudil alone.",the results indicate that rosuvastatin intensifies the beneficial effects of rho-kinase inhibitor on the rho/rho-kinase pathway and such a combination may represent an option for the treatment of pulmonary arterial hypertension.,Medication
is sirolimus based immunosuppression associated with need for early repeat therapeutic ercp in liver transplant patients with anastomotic biliary stricture?,"sirolimus has inhibitory effects on epithelial healing and cholangiocyte regeneration. in liver transplantation (lt) patients, these effects may be greatest at the biliary anastomosis. we therefore investigated whether sirolimus use is associated with need for early or emergent repeat therapeutic endoscopic retrograde cholangiography (erc) in lt patients with anastomotic biliary stricture (abs). medical records of patients who underwent lt from 1998-2009 at johns hopkins were reviewed and patients with abs identified. primary outcome was early repeat erc, defined as need for unscheduled (i.e. unplanned) or emergent repeat therapeutic erc. univariate and multivariate logistic regression analyses (adjusting for age, sex, lt to erc time, and stent number) were performed to assess association between sirolimus and early repeat erc. 45 patients developed abs and underwent 156 ercs total. early (median 26 days) repeat erc occurred in 14/56 (25) and 6/100 (6) ercs performed with and without concomitant sirolimus-based immunosuppression, respectively (or 1.22; 95 ci 1.02-1.45; p 0.03). in multivariate analysis, sirolimus use was associated with early repeat erc (or 1.24; 95 ci 1.04-1.47; p 0.015); this association remained significant when sirolimus dose was modeled as a continuous variable (or 1.04 for each mg of sirolimus per day; 95 ci 1.02-1.08; p 0.038).","sirolimus-based immunosuppression appears to be associated with a modest but significantly increased, dose-dependent risk of early repeat erc in lt patients with abs. prospective studies are needed to further investigate these findings and determine if sirolimus use or dose should potentially be reconsidered once abs is diagnosed.",Treatment
"does selective blockade of cholecystokinin type b receptors with l-365,260 impair gallbladder contraction in normal humans?","to evaluate the effect of selective blockade of type b cholecystokinin receptors on gall bladder contraction in normal humans and to compare methods for quantitative analysis of gall bladder contraction. l-365,260, a novel, nonpeptide cholecystokinin antagonist shown to be selective for type b cholecystokinin receptors, was administered every 6 h over a 5-7 day period. plasma levels of l-365,260 were determined by high pressure liquid chromatography. gallbladder contraction after a standardized fatty meal was measured by ultrasonography, and results were calculated by ellipsoid or sum of cylinders methods. l-365,260 levels were comparable to levels in earlier studies demonstrating inhibition of pentagastrin-stimulated acid secretion in normal subjects and blockade of anxiogenic effects of cholecystokinin injections in patients with panic disorder. regardless of the method used for estimating gallbladder size, none of the l-365,260 doses studied inhibited gallbladder contraction. gallbladder size was most consistently estimated by the ellipsoid method using measurements normalized to individual values for minimum and maximum gallbladder dimensions.","multiple oral doses of l-365,260 do not alter ultrasonographically assessed gallbladder contraction at doses shown to be clinically effective in earlier studies. despite being more difficult to implement, the sum of cylinders method for estimating gall bladder size offers no advantage over the ellipsoid method.",Medication
are intracellular cytokine production in anca-associated vasculitis : low levels of interleukin-10 in remission associated with a higher relapse rate in the long-term follow-up?,"dysregulation of cell-mediated immune response likely plays a role in the pathogenesis of anti-neutrophil cytoplasmic autoantibody (anca)-associated vasculitis (aav), but it has not yet been fully established. the aim of this study was to assess the intracellular cytokine production in patients with aav at different stages of the disease, in particular, in relation to the long-term prognosis. we included 69 patients with aav and 24 healthy controls. using flow cytometry, the following intracellular cytokines (ic) were measured in all patients: interferon-gamma (ifn-gamma), tumor necrosis factor alpha (tnf-alpha), interleukin-2 and interleukin-4 in cd3t cells and interleukin-10 (il-10) and interleukin 12 (il-12) in monocytes. patients were then prospectively followed for a median of 43 months and cytokine production was related to the long-term prognosis. when compared to healthy controls, increased il-12 production was observed in aav patients, both active (p0.01) and in remission (p0.05). in remission, increased ifn-gamma production was also found (p0.01). il-10 production was higher in active patients than in patients in remission (p0.05) but did not differ from controls. patients in remission who developed a relapse during follow-up had significantly lower il-10 production than those without relapse (p0.01). results of this prospective study of ic production in aav confirm findings of previous studies measuring circulating cytokine levels.","activation of the immune system in aav patients is noticeable even in remission. patients with aav display increased il-12 production, which seems to be counterbalanced by il-10. low il-10 levels in remission are associated with a higher relapse rate in the long-term follow-up.",Diagnosis
does piceatannol facilitate conduction block and ventricular fibrillation induction in ischemia-reperfused rabbit hearts with pacing-induced heart failure?,"piceatannol, a hydroxystilbene natural product, has been reported to exert antiarrhythmic action via ina inhibition and slow ina inactivation in ischemia-reperfused (ir) rat hearts. the present study aimed to clarify the proarrhythmic property of piceatannol during regional ir injury in failing rabbit hearts. heart failure (hf) was induced by rapid right ventricular pacing for 4 weeks. the ir model was created by coronary artery ligation for 30 min, followed by reperfusion for 15 min in vivo. simultaneous voltage and intracellular ca(2) (cai) optical mapping was then performed in isolated langendorff-perfused hearts (n11 in each hf and control group). action potential duration (apd) restitution, arrhythmogenic alternans and vf inducibility were evaluated by a dynamic pacing protocol. conduction velocity was measured along lines across the ir and non-ir zones during pacing. piceatannol (10 m) was administered after baseline studies. in the hf group, piceatannol decreased conduction velocity, induced rate-dependent regional inhomogeneity of conduction delay and wavelength shortening, slowed cai decay, and facilitated arrhythmogenic alternans instead of apd prolongation to increase vf inducibility. in the control group, the proarrhythmic effects of piceatannol on apd restitution, arrhythmogenic alternans and conduction delay were offset by its antiarrhythmic effects (apd and wavelength prolongation), resulting in a neutral effect on vf inducibility.",piceatannol (10 m) is proarrhythmic in failing rabbit hearts with regional ir injury. the increased vf inducibility by piceatannol in hf suggests that its undesirable effects are more pronounced than its benefits in failing hearts.,Medication
is amygdala reactivity to masked negative faces associated with automatic judgmental bias in major depression : a 3 t fmri study?,"in a previous study, we demonstrated that amygdala reactivity to masked negative facial emotions predicts negative judgmental bias in healthy subjects. in the present study, we extended the paradigm to a sample of 35 inpatients suffering from depression to investigate the effect of amygdala reactivity on automatic negative judgmental bias and clinical characteristics in depression. amygdala activity was recorded in response to masked displays of angry, sad and happy facial expressions by means of functional magnetic resonance imaging at 3 t. in a subsequent experiment, the patients performed an affective priming task that characterizes automatic emotion processing by investigating the biasing effect of subliminally presented emotional faces on evaluative ratings to subsequently presented neutral stimuli. significant associations between (right) amygdala reactivity and automatic negative judgmental bias were replicated in our patient sample (r-0.59, p0.001). further, negatively biased evaluative processing was associated with severity and longer course of illness (r-0.57, p0.001).",amygdala hyperactivity is a neural substrate of negatively biased automatic emotion processing that could be a determinant for a more severe disease course.,Diagnosis
does nicorandil reduce the incidence of minor cardiac marker elevation after coronary stenting?,"minor cardiac marker elevation after percutaneous coronary intervention has long-term prognostic significance. we examined whether nicorandil, a nicotinamide-nitrate ester, reduces the incidence of minor cardiac marker elevation after coronary stenting. patients (n192) undergoing coronary stenting were randomly assigned to receive nicorandil (nicorandil group, n91) or vehicle (control group, n101). nicorandil (2 mug/kg/min, intravenously) was administered immediately after the patients were transferred into the catheterization laboratory and continued for 6 h. we measured the serum concentrations of creatine kinase isoenzyme mb (ck-mb) before, immediately after, and 6, 12, and 24 h after the procedure, and those of cardiac troponin t (ctnt) 24 h after the procedure. there was no significant difference in clinical background between the 2 groups. the nicorandil group showed a significantly lower incidence of ck-mb elevation (1x upper limit of control range, 20 iu/l) than the control group (8.8 vs 21.8, p1x (0.1 ng/ml) or 2x (0.2 ng/ml) upper limit of control range than the control group (14.3 vs 26.7, p0.05, or 7.7 vs 17.8, p0.05). serum ctnt levels were also significantly lower in the nicorandil group than in the control group (0.05/-0.10 vs 0.15/-0.36 ng/ml, p0.05).",the results demonstrated that nicorandil reduces minor cardiac marker elevation after coronary stenting.,Diagnosis
"does hormone replacement therapy affect plasma homocysteine in postmenopausal women with coronary artery disease . free tissue factor pathway inhibitor antigen , a circulating anticoagulant , is related to plasma homocysteine?","the objective was to evaluate the effect of hormone replacement therapy (hrt) on plasma homocysteine levels in postmenopausal women with coronary artery disease (cad) and to investigate associations of homocysteine to other cardiovascular risk factors. the women in this single-center, controlled, and randomized study were examined at baseline, and after 3 and 12 months, after they had been recruited consecutively from patients referred for investigational coronary angiography. all analyses were performed examiner blind. they were randomized to hrt consisting of transdermal application of continuous 17beta-estradiol with cyclic medroxyprogesterone acetate (mpa) tablets for 14 days every 3rd month, or to a control group. after 3 months of unopposed 17beta-estradiol, no significant effect on homocysteine was observed compared to the control group. the absolute decrease of 5 in median plasma homocysteine levels after 12-month hrt did not reach statistical significance. plasma homocysteine seemed slightly higher in women with three- or four-vessel disease, but the difference was not significant. with increasing homocysteine levels, free tissue factor pathway inhibitor (tfpi) antigen increased, whereas e-selectin decreased. in women with diabetes or elevated blood glucose 6.0 mmol/l, plasma homocysteine was correlated to body mass index, c-peptide and insulin as well as age.","transdermal application of 17beta-estradiol and sequential mpa do not affect plasma homocysteine in women with established cad. plasma homocysteine is stable in women with cad over time, and unless special intervention is undertaken, repetitive measurements are not necessary in this particular group of high-risk individuals. the circulating anticoagulant tepi is related to plasma homocysteine.",Medication
does a pyruvate-buffered dialysis fluid induce less peritoneal angiogenesis and fibrosis than a conventional solution?,"conventional lactate-buffered peritoneal dialysis (pd) fluids containing glucose and glucose degradation products are believed to contribute to the development of fibrosis and angiogenesis in the dialyzed peritoneum. to reduce potential negative effects of lactate, pyruvate was substituted as a buffer and its effects on peritoneal pathological alterations were studied in a chronic peritoneal exposure model in the rat. 20 wistar rats were infused intraperitoneally with pyruvate-buffered (n 9) or lactate-buffered pd fluid. after 20 weeks of daily infusion, peritoneal function was assessed. in omental peritoneal tissue, the number of blood vessels was analyzed following alpha-smooth muscle actin staining. the degree of fibrosis was quantitated in picro sirius red-stained sections and by assessment of the hydroxyproline content. plasma lactate/pyruvate and betahydroxybutyrate/acetoacetate (bba/aa) ratios were determined. plasma and dialysate vascular endothelial growth factor (vegf) levels were quantitated by elisa. the mass transfer area coefficient of creatinine was higher and the dialysate-to-plasma ratio of sodium was lower in pyruvate-treated animals compared to the lactate-treated group (0.11 vs 0.05 ml/min, p 0.05, and 78 vs 89, p 0.05). the bba/aa ratio tended to be lower in the pyruvate animals (p 0.07). the number of blood vessels was lower in pyruvate-treated animals (16 vs 37 per field, p 0.001). total surface area, luminal area, and wall/total area of the vessels were larger in the pyruvate group. the degree of fibrosis was lower in intersegmental and perivascular areas of pyruvate-exposed animals. effluent vegf was higher in the pyruvate group.","replacement of lactate by pyruvate resulted in changes in peritoneal solute transport, accompanied by a reduction in both peritoneal membrane angiogenesis and fibrosis, suggesting potentially novel mechanisms to reduce glucose-driven alterations to the peritoneal membrane in pd patients.",Treatment
does incident depression increase medical utilization in medicaid patients with hypertension?,"hypertension is an important risk factor for cardiovascular disease and occurs disproportionately among patients with depression. few studies have rigorously examined outcomes specifically among hypertensive patients with newly diagnosed comorbid depression. we hypothesized that incident depression would exacerbate hypertensive disease and that this would be evident through greater utilization of medical services than would otherwise occur in the absence of depression. claims data for hypertensive patients enrolled in maryland medicaid (2005-2010) were used to estimate the change in annualized utilization following incident depression, compared to a matched cohort of hypertensive patients never diagnosed with depression. multivariate regression was used to adjust for changes in antihypertensive medications, adherence and comorbidity that followed depression onset. while medical utilization increased after incident depression, additional encounters tended to be for nonacute medical care and there was no significant increase in encounters specifically for cardiovascular or hypertension-related conditions.",the results contribute to the discussion on the relationship between depression and cardiovascular disease and will inform future studies that aim to look at longer term outcomes in patients with hypertension.,Medication
does the novel tlr-9 agonist qbg10 show clinical efficacy in persistent allergic asthma?,"allergen-specific th2 responses contribute to the development of allergic asthma. their increase may be due to a reduced early exposure to environmental pathogens, which induces a th1 response, and thereby suppresses the allergic th2 response. qbg10 (bacteriophage qbeta-derived virus-like particle with cpg-motif g10 inside), a novel toll-like receptor 9 agonist packaged into virus-like particles, was designed to stimulate the immune system toward a th1-mediated protective response. we examined clinical efficacy, safety, and tolerability of qbg10 with patient-reported and objective clinical outcome parameters in patients with mild-to-moderate persistent allergic asthma. in this proof-of-concept parallel-group, double-blind, randomized trial, 63 asthmatic patients followed conversion to a standardized inhaled steroid and were treated with 7 injections of either qbg10 or placebo. incorporating a controlled steroid withdrawal, the effects on patient-reported (day- and nighttime asthma symptoms, salbutamol usage, and 7-item-asthma control questionnaire scores) and objective clinical outcome measures (fev1, fraction of exhaled nitric oxide, and blood eosinophils) were assessed over 12 weeks (clinicaltrials.gov number, nct00890734). all patient-reported parameters improved overall between week 0 and 12 in qbg10-treated patients (n 33) despite steroid withdrawal, compared with deteriorations observed under placebo (n 30, p .05). at week 12, two thirds of the qbg10-treated patients had their asthma ""well controlled"" (asthma control questionnaire score 0.75) compared with one third under placebo. fev1 had worsened to a clinically significant extent in patients on placebo, while it remained stable in qbg10 patients. adverse events were mostly injection site reactions occurring after qbg10 administration.",treatment with qbg10 may contribute to continued asthma control during steroid reduction in patients on moderate or high-dose inhaled steroids.,Medication
does doxycycline improve wound strength after intestinal anastomosis in the rat?,"the strength of intestinal anastomoses is relatively low in the first days after operation, possibly as a result of localized degradation of the supporting matrix by enzymes from the matrix metalloproteinase (mmp) family. the aim of this study was to examine whether doxycycline, a drug known to inhibit mmp activity, could enhance anastomotic strength. male wistar rats received anastomoses in both ileum and colon. from the day before operation onwards, animals were treated daily with doxycycline (orally or subcutaneously) in a dose of 10 mg/day or with saline only. rats were killed 1, 3, or 5 days after operation, and anastomotic bursting pressure and breaking strength were measured. at day 3, anastomotic hydroxyproline levels were measured, mmp (gelatinase) activity was analyzed by gelatin zymography, and anastomotic histology was examined. doxycycline enhanced wound strength, but only at day 3, when it was at its lowest. subcutaneous administration of 10 mg/day increased median colonic and ileal breaking strength by 27 (p .0019) and 104 (p .0376), respectively. colonic bursting pressure was increased by 93 (p .0002). wound histology was similar in experimental and control groups.",administration of doxycycline enhances anastomotic strength and should be investigated further as a means to preserve anastomotic integrity.,Medication
does combination of angiotensin ii receptor blockers promote proton pump inhibitor-based healing of reflux esophagitis?,"several studies have described factors associated with the failure of proton pump inhibitors (ppis) to effect endoscopic healing of reflux esophagitis (re), but few studies have addressed factors promoting ppi-based endoscopic healing. we performed post hoc analysis of a multicenter prospective cohort of re patients to identify factors encouraging endoscopic healing of this disorder. patients with re received 10 or 20 mg rabeprazole for 8 weeks, and endoscopic findings before and after treatment were studied. to evaluate the effects of patient background factors on endoscopic healing, we performed multiple logistic regression analysis and determined the respective odds ratios (ors) and 95 confidence intervals (cis). a total of 454 patients who underwent endoscopy at baseline and again at week 8 were included in the analysis. after 8 weeks of treatment, improvement in endoscopic findings was observed in 94.1 (427/454) of patients, and endoscopic healing was seen in 76.7 (348/454). multiple logistic regression analysis revealed that a combination of angiotensin ii receptor blockers (arbs) had a significant positive impact on endoscopic healing (or 3.9, 95 ci 1.411-10.903), but no significant positive relationship was seen for other concomitant drugs such as nonsteroidal anti-inflammatory drugs and calcium channel blockers. severe re at baseline (or 0.365, 95 ci 0.281-0.475) and ppi therapy prior to enrollment (or 0.154, 95 ci 0.052-0.453) were found to have significant negative effects on endoscopic healing.",concomitant use of arbs may promote endoscopic healing of re treated with ppis.,Medication
does oct reveal regional differences in macular thickness with age?,"to assist identification of macular thickness abnormalities by optical coherence tomography (oct), we use techniques that improve spatial localization across the retina to establish any age-related retinal thickness changes in healthy eyes. retinal thickness was measured in 30 eyes of 30 healthy subjects aged 13 to 69 years. using stratus oct 3, 12 radial scans centered at the foveola were acquired and points between scans were interpolated to create a topographic map of the central 20 degrees . the thickness map was divided into 37 hexagonal regions. a mean retinal thickness for each hexagon was computed. retinal thickness vs. age was evaluated for the entire scanned area, five anatomical regions, and within individual hexagons. the retinal nerve fiber layer (rnfl) contribution to total retinal thinning was analyzed in the papillomacular region. there was a small but significant thinning of the overall macular area with increasing age (2.7 mum/decade; p 0.027). comparing the 10 youngest subjects (age 13 to 27 years) with the 10 oldest (age 51 to 68 years), retinal thicknesses in the temporal, superior, inferior, and foveal regions were not significantly different. however, the two age groups differed significantly in retinal thickness in the nasal region (p 0.008). across all subjects, retinal thickness in this region was linearly correlated with age, decreasing by 4.1 mum/decade (p 0.002). approximately 43 of the retinal thinning in the nasal region was attributed to rnfl loss.","the method of oct acquisition and analysis used in this study allows for greater spatial localization of change in retinal thickness associated with aging or pathological processes. based on the results of this study, the macula thins with increasing age but does so nonuniformly. the greatest amount of thinning occurs nasal to the fovea. rnfl loss accounts for much, but not all the thinning in this area.",General
does cognitive processing speed have minimal influence on the construct validity of multiple sclerosis walking scale-12 scores?,"the multiple sclerosis walking scale-12 (msws-12) has been a commonly used patient reported outcome for measuring walking impairment in research involving multiple sclerosis (ms). we examined the possibility that cognitive processing speed (cps) influences the association between msws-12 scores and other measures of ambulation (i.e., construct validity). 96 ms patients completed the msws-12, underwent a neurological examination for generating an expanded disability status scale (edss) score, and completed the symbol digit modalities test (sdmt), timed 25-foot walk (t25fw), 4 trials on the gaitrite for generating the functional ambulatory profile (fap) score, and six-minute walk (6mw). the sdmt was significantly correlated with msws-12 scores (r-.428) and t25fw (r-.459), 6mw (r.512), fap (r.275), and edss (r-.404) scores. there were statistically significant correlations between msws-12 and t25fw (r.568), 6mw (r-.680), fap (r-.595), and edss (r.737) scores. lastly, four separate hierarchical linear regression analyses indicated that, after controlling for age, gender, disease duration, and clinical course, t25fw, 6mw, fap, and edss scores individually were significant correlates of msws-12 scores, and the associations (i.e., standardized beta-coefficients) were still statistically significant with minimal attenuation when controlling for sdmt scores.",there was minimal evidence that cps influenced the construct validity of msws-12 scores.,General
does skin gene expression correlate of severity of interstitial lung disease in systemic sclerosis?,"we undertook this hypothesis-generating study to identify skin transcripts correlating with severity of interstitial lung disease (ild) in systemic sclerosis (ssc). skin biopsy samples from 59 patients enrolled in the genetics versus environment in scleroderma outcome study (genisos) cohort or an open-label imatinib study (baseline visit) were examined by global gene expression analysis using illumina ht-12 arrays. skin transcripts correlating with concomitantly obtained forced vital capacity (fvc) values and the modified rodnan skin thickness score (mrss) were identified by quantitative trait analysis. also, immunofluorescence staining for selected transcripts was performed in affected skin and lung tissue. plasma levels of ccl2, soluble selp, and soluble p-selectin glycoprotein ligand 1 (spsgl-1) were examined in all patients enrolled in the genisos cohort (n 266). eighty-two skin transcripts correlated significantly with fvc. this gene list distinguished patients with more severe ild (fvc 70 predicted) in unsupervised hierarchical clustering analysis (p 0.001). these genes included selp, ccl2, and matrix metalloproteinase 3, which are involved in extravasation and adhesion of inflammatory cells. among the fvc correlates, 8 genes (ccl2, hapln3, gpr4, adcyap1, wars, cdc25b, plp1, and stxbp6) also correlated with the mrss. immunofluorescence staining revealed that selp and ccl2 were also overexpressed in affected skin and lung tissue from ssc patients compared to those from controls. plasma levels of ccl2 and spsgl-1 correlated with concomitantly obtained fvc values (r -0.22, p 0.001 and r 0.17, p 0.015, respectively). this relationship was independent of potential confounders (age, sex, ethnicity, smoking status, anti-topoisomerase i positivity, treatment with immunosuppressive agents, mrss, disease type, and disease duration).",a limited number of skin transcripts including genes involved in extravasation and adhesion of inflammatory cells correlate with severity of ild.,Medication
is crispr an optimal target for the design of specific pcr assays for salmonella enterica serotypes typhi and paratyphi a?,"serotype-specific pcr assays targeting salmonella enterica serotypes typhi and paratyphi a, the causal agents of typhoid and paratyphoid fevers, are required to accelerate formal diagnosis and to overcome the lack of typing sera and, in some situations, the need for culture. however, the sensitivity and specificity of such assays must be demonstrated on large collections of strains representative of the targeted serotypes and all other bacterial populations producing similar clinical symptoms. using a new family of repeated dna sequences, crispr (clustered regularly interspaced short palindromic repeats), as a serotype-specific target, we developed a conventional multiplex pcr assay for the detection and differentiation of serotypes typhi and paratyphi a from cultured isolates. we also developed evagreen-based real-time singleplex pcr assays with the same two sets of primers. we achieved 100 sensitivity and specificity for each protocol after validation of the assays on 188 serotype typhi and 74 serotype paratyphi a strains from diverse genetic groups, geographic origins and time periods and on 70 strains of bacteria frequently encountered in bloodstream infections, including 29 other salmonella serotypes and 42 strains from 38 other bacterial species.","the performance and convenience of our serotype-specific pcr assays should facilitate the rapid and accurate identification of these two major serotypes in a large range of clinical and public health laboratories with access to pcr technology. these assays were developed for use with dna from cultured isolates, but with modifications to the assay, the crispr targets could be used in the development of assays for use with clinical and other samples.",Symptoms
is growth in the first 5 years of life unaffected in children with perinatally-acquired hepatitis c infection?,"to identify the effect of vertical hepatitis c virus (hcv) infection or exposure on growth in childhood. children (n1203) born to hcv-infected mothers were followed up from birth prospectively in centers of the european paediatric hepatitis c virus network. z-scores compared height- and weight-for-age in hcv-infected and -uninfected children, adjusting for other factors using linear regression. we also quantified the effect of maternal chronic infection with hcv on childhood growth. there was no significant effect of vertical hcv infection on growth (height p.223, weight p.095) nor a significant effect of maternal chronic infection with hcv (height p.733, weight p.274). prematurity and maternal injecting drug use were associated with a significant reduction in height (p .001) and weight (p .001) in all hcv-exposed children.","this population of hcv exposed infants has higher rates of maternal injecting drug use and prematurity than standard populations and so there are implications for growth of these children, but this is not a direct result of hcv infection or exposure to chronic maternal hcv infection.",Medication
does inhibition of monoacylglycerol lipase ( magl ) enhance cue-induced reinstatement of nicotine-seeking behavior in mice?,"tobacco smoking is still a major population health issue. the endocannabinoid system has been shown to control drug-seeking behaviors. there are two main endocannabinoids: anandamide degraded by fatty acid amide hydrolase (faah) and 2-arachidonoylglycerol (2-ag) degraded by monoacylglycerol lipase (magl). the role of magl has only been explored recently, and so far, no study have been performed to evaluate the effects of magl inhibitor on nicotine reinforcing properties and cue-induced reinstatement of nicotine seeking. here, we investigated the effects of the magl inhibitor jzl184 on nicotine self-administration under fixed and progressive-ratio schedules of reinforcement and on cue-induced reinstatement of nicotine seeking in mice. we also evaluated the effects of jzl184 on food self-administration for possible non-specific effects. jzl184 (0, 8, and 16 mg/kg) did not affect food taking, nicotine taking, or motivation for nicotine. magl inhibition by jzl184 (16 mg/kg) increased reinstatement of previously extinguished nicotine seeking induced by presentation of nicotine-associated cues, but did not produce reinstatement on its own.",this study implicates involvement of 2-ag in nicotine-seeking behaviors.,Medication
does urinary peptide profiling identify a panel of putative biomarkers for diagnosing and staging endometriosis?,"to identify a potential diagnostic endometriosis marker using matrix-enhanced laser desorption/ionization time-of-flight mass spectrometry (maldi-tof-ms)-based urinary proteomics. prospective randomized pilot study. university hospital, tertiary referral center for endometriosis. 53 women undergoing laparoscopic surgery for pain and/or infertility comprising 30 women without endometriosis and 23 with endometriosis. laparoscopy and urine specimens. urinary peptide profiles. we observed distinct patterns of peptide profiles in the urine samples of women presenting with typical clinical symptoms of endometriosis. six statistically significant putative peptide markers were identified (four during the periovulatory phase and two during the luteal phase) by comparing controls with moderate/severe endometriosis patients. the periovulatory peptide mass of 1,767.1 da and the luteal peptide mass of 1,824.3 da both showed a sensitivity of 75 and a specificity of 85 and 71, respectively. also detected were seven peptide markers (two during the periovulatory phase and five during the luteal phase) by comparing the urinary peptide profiles of patients with minimal/mild to moderate/severe endometriosis. the periovulatory peptide mass of 3,280.9 da and the luteal peptide mass of 1,933.8 da showed a sensitivity of 82 and 75 and a specificity of 88 and 75, respectively.",urinary proteomic analysis may provide a novel method of diagnosing and staging endometriosis.,Diagnosis
do standard biocompatibility studies predict all effects of pva/cmc anti-adhesive gel in vivo?,"pva/cmc (polyvinyl alcohol/carboxymethyl cellulose) hydrogel fulfills various physiochemical properties required for an adhesion barrier and has shown good anti-adhesion properties in previous in vivo studies. in this investigation, we assessed the in vitro and in vivo biocompatibility of pva/cmc gel and compared this to the functionality and promotion of wound healing for two surgical indications. standardized iso10993 in vitro and in vivo biocompatibility studies, comprising cytotoxicity, genotoxicity, acute systemic toxicity, delayed contact and maximization sensitization test, intracutaneous reactivity and local muscle implantation, were performed on pva/cmc gel. in the functional studies, pva/cmc gel was applied - on the one hand - to a rabbit abdominal wall model enforced with a polypropylene mesh for testing the anti-adhesion properties and - on the other hand - to an end- to-end anastomosis model that was selected for surveying potential influences of different dosages of pva/cmc gel on anastomotic wound healing. the iso10993 methods indicated generally good biocompatibility properties, such as the absence of cytotoxic and mutagenic effects as well as no signs of systemic toxicity and sensitization potentials. no irritation effects were observed after the intracutaneous injection of lipophilic pva/cmc sesame oil extract. however, the injection of hydrophilic pva/cmc physiologic saline extract induced slight irritation. following rabbit muscle implantation of the pva membrane for 2, 4, 12, 26 and 52 weeks, a slight irritant effect was observed at 12 weeks due to the peak of phagocytosis. in the functionality tests, pva/cmc gel showed good anti-adhesive effects in the abdominal wall model enforced with the mesh, with significantly lower and less tense adhesions compared to the untreated control. however, moderate signs of inflammation, especially in the spleen were observed after the intra-abdominal implantation of 3.3 ml pva/cmc gel per kg body weight. in the end-to-end anastomosis model, pva/cmc gel had no influence on wound healing. for dosages of 1-6 ml gel per treatment, no signs of intestinal leaks were detected, and tensile strength was equal to that of the untreated control, but again more moderate signs of inflammation in the spleen were observed at a dosage 3 ml.","comparing the standardized iso10993 methods, anti-adhesive pva/cmc gel displays good biocompatibility. however, those methods do not seem to be sensitive enough because the rabbit abdominal wall and the end-to-end anastomosis models display more effects with respect to the dosage and routes of the intra-abdominal resorption of pva/cmc gel - with the recommended 2 ml pva/cmc gel per kg body weight as a secure dosage.",Medication
does resolvin e1 regulate adenosine diphosphate activation of human platelets?,"to investigate the ability of resolvin e1 (rve1) to regulate adenosine diphosphate (adp) activation of platelets via specific receptors because rve1 reduces platelet aggregation with certain agonists, including adp. rve1 is an eicosapentaenoic acid-derived specialized proresolving mediator generated during the resolution of acute inflammation. rve1 exhibits potent organ-protective actions in vivo and acts on specific cell types, including platelets. rve1, 0.1 to 100 nmol/l, incubated with platelets gave reduced adp-stimulated p-selectin mobilization (ic(50), approximately 1.610(-12) mol/l) and polymerized actin content compared with control platelets. rve1, 1 to 100 nmol/l, did not stimulate or block intracellular ca(2) mobilization. by using a new p2y(12)--arrestin-coupled cell system, adp-activated p2y(12) with an ec(50) of 510(-6) mol/l and rve1 did not directly stimulate p2y(12) or block the adp-p2y(12) signals. in this system, another eicosanoid, leukotriene e(4) (lte(4)) (ec(50), 1.310(-11) mol/l), dose dependently activated p2y(12). when recombinant p2y(12)-expressing cells were transiently transfected with an rve1 receptor, human chemr23 (present on human platelets), with the addition of rve1 (0.1-10.0 nmol/l), blocked adp signals (ic(50), approximately 1.610(-11) mol/l) in p2y(12)-chemr23-expressing cells compared with mock transfections.","rve1's regulatory actions (ie, reducing adp-stimulated p-selectin mobilization and actin polymerization) are human (h)chemr23-dependent. moreover, specific platelet actions of rve1 selectively engaged with adp-activated platelets that illuminate a new cellular mechanism and affect -3 eicosapentaenoic acid, which may contribute to both resolution of vascular inflammation and adp-dependent platelet activation relevant in pathological cardiovascular events.",Medication
'm i afraid of those ones just 'cause they 've been prescribed '' : perceptions of risk among illicit users of pharmaceutical opioids?,"there has been a rise in the illicit use of pharmaceutical opioids (""pain pills"") in the united states. conducted with young adult non-medical users of pharmaceutical opioids, this study uses qualitative methods and cultural consensus analysis to describe risk perceptions associated with pharmaceutical opioids and to determine patterns of cultural sharing and intra-cultural variation of these views. the qualitative sub-sample (n47) was selected from a larger sample of 396 young adults (18-23 years old), who were participating in a natural history study of illicit pharmaceutical opioid use. qualitative life history interviews, drug ranking task, and cultural consensus analysis were used to elicit participant views about risks and harms associated with pain pills and other drugs, as well as alcohol and tobacco. cultural consensus analysis revealed that the participants shared a single cultural model of drug risks, but the level of agreement decreased with the increasing range of drugs ever used. further, those with more extensive drug use histories differed from less ""experienced"" users in their views about oxycontin and some other drugs. overall, pain pills were viewed as addicting and potentially deadly substances, but these properties were linked to the patterns and methods of use, as well as characteristics of an individual user. further, risks associated with pharmaceutical opioids were further curtailed because they ""came from the doctor,"" and thus had a legitimate aspect to their use.",this study highlights potential problems with universal approaches to substance use prevention and intervention among young people since such approaches ignore the fact that substance use education messages may be experienced differently depending on an individual's drug use history and his/her perceptions of drug risks. findings reported here may be useful in the development of prevention and intervention programs aimed at reducing the harm associated with illicit use of pain pills.,Medication
does continuous subcutaneous insulin infusion preserve axonal function in type 1 diabetes mellitus?,"diabetic peripheral neuropathy is a common and debilitating complication of diabetes mellitus. although strict glycaemic control may reduce the risk of developing diabetic peripheral neuropathy, the neurological benefits of different insulin regimens remain relatively unknown. in the present study, 55 consecutive patients with type 1 diabetes mellitus underwent clinical neurological assessment. subsequently, 41 non-neuropathic patients, 24 of whom were receiving multiple daily insulin injections (mdii) and 17 receiving continuous subcutaneous insulin infusion (csii), underwent nerve excitability testing, a technique that assesses axonal ion channel function and membrane potential in human nerves. treatment groups were matched for glycaemic control, body mass index, disease duration and gender. neurophysiological parameters were compared between treatment groups and those taken from age and sex-matched normal controls. prominent differences in axonal function were noted between mdii-treated and csii-treated patients. specifically, mdii patients manifested prominent abnormalities when compared with normal controls in threshold electrotonus (te) parameters including depolarizing te(10-20ms), undershoot and hyperpolarizing te (90-100 ms) (p 0.05). additionally, recovery cycle parameters superexcitability and subexcitability were also abnormal (p 0.05). in contrast, axonal function in csii-treated patients was within normal limits when compared with age-matched controls. the differences between the groups were noted in cross-sectional analysis and remained at longitudinal follow-up.",axonal function in type 1 diabetes is maintained within normal limits in patients treated with continuous subcutaneous insulin infusion and not with multiple daily insulin injections. this raises the possibility that csii therapy may have neuroprotective potential in patients with type 1 diabetes.,Medication
is routine 24-hour computed tomography brain scan useful in stable patients post intravenous tissue plasminogen activator?,"obtaining a routine computed tomography (ct) brain scan 24 hours after treatment with intravenous tissue plasminogen activator (iv-tpa) is included in the american heart association/american stroke association acute stroke guidelines. the usefulness of the test in stable patients is not known. we hypothesized that the results of routine, 24-hour post-treatment neuroimaging (ct or magnetic resonance imaging mri brain scans) would not alter the management of clinically stable patients. patients treated with iv-tpa between january 2011 and december 2013 were identified from a single hospital's stroke registry. all patients were closely monitored for changes in stroke severity. demographics, changes in neurological status, neuroimaging results, and changes in therapy were abstracted from the patients' medical records. patients having a neuroimaging study because of neurological deterioration were excluded. of 136 patients treated with iv-tpa, 131 met criteria for inclusion. of these, 86.7 had moderate to severe neurological deficits (i.e., initial national institutes of health stroke scale score 5 points; median 8 points). all patients had routine imaging 24 hours after treatment (ct brain 62.6, mri brain 12.4, both ct and mri brain 25). asymptomatic hemorrhagic transformation occurred in 6.7 and potentially changed management in a single patient (target systolic blood pressure was lowered from 185 to 180 mmhg).","over a 3-year period, routine neuroimaging 24-hours after iv-tpa in clinically stable patients was associated with a change in therapy in only 1 (.95) patient. if confirmed in other cohorts, these results suggest that routine neuroimaging after iv-tpa may be safely avoided in clinically stable patients, eliminating unnecessary radiation exposure in those having ct brain and reducing costs.",Medication
do fecal eosinophil granule-derived proteins reflect disease activity in inflammatory bowel disease?,"the aims of this study were: 1) to examine whether the fecal levels of eosinophil granule-derived proteins reflect disease activity in inflammatory bowel disease (ibd); and 2) to examine the extracellular release of these proteins from eosinophils and their stability in feces by an in vitro study. we investigated 42 patients with ulcerative colitis (uc), 37 patients with crohn's disease (cd), and 29 control subjects. the stool samples were collected at 4 degrees c over 48 h and were homogenized. the fecal levels of eosinophil cationic protein (ecp) and eosinophil protein x (epx) were measured by radioimmunoassay. fecal hb (hb), alpha1-antitrypsin (at), and lactoferrin (lf) were also measured by elisa. fecal ecp and epx concentrations were significantly increased in both active uc and active cd compared to inactive uc and inactive cd, respectively. fecal epx concentration correlated with the fecal hb, at, and lf concentrations more closely than fecal ecp concentration. even in the inactive stage, cd patients who relapsed within the following 3 months showed higher fecal ecp and epx concentrations compared to the patients who did not. epx was released extracellularly more efficiently than ecp (18.6 vs 6.3, after incubation for 15 min at 25 degrees c). epx was more stable in the feces than ecp.",the measurement of eosinophil granule-derived proteins in feces is useful for evaluating disease activity and predicting relapse in patients with ibd. epx may be more suitable than ecp as a fecal eosinophil marker.,General
does serotonin protect mouse liver from cholestatic injury by decreasing bile salt pool after bile duct ligation?,"obstructive cholestasis induces liver injury, postoperative complications, and mortality after surgery. adaptive control of cholestasis, including bile salt homeostasis, is necessary for recovery and survival. peripheral serotonin is a cytoprotective neurotransmitter also associated with liver regeneration. the effect of serotonin on cholestatic liver injury is not known. therefore, we tested whether serotonin affects the severity of cholestatic liver injury. we induced cholestasis by ligation of the bile duct (bdl) in either wild-type (wt) mice or mice lacking peripheral serotonin (tph1(-/-) and immune thrombocytopenic itp mice). liver injury was assessed by the levels of plasma aspartate aminotransferase (ast), alanine aminotransferase (alt) and tissue necrosis. bile salt-regulating genes were measured by quantitative polymerase chain reaction and confirmed by western blotting and immunohistochemistry. tph1(-/-) mice displayed higher levels of plasma ast, alt, bile salts, and hepatic necrosis after 3 days of bdl than wt mice. likewise, liver injury was disproportional in itp mice. moreover, severe cholestatic complications and mortality after prolonged bdl were increased in tph1(-/-) mice. despite the elevation in toxic bile salts, expression of genes involved in bile salt homeostasis and detoxification were not affected in tph1(-/-) livers. in contrast, the bile salt reabsorption transporters ost and ost were up-regulated in the kidneys of tph1(-/-) mice, along with a decrease in urinary bile salt excretion. serotonin reloading of tph1(-/-) mice reversed this phenotype, resulting in a reduction of circulating bile salts and liver injury.",we propose a physiological function of serotonin is to ameliorate liver injury and stabilize the bile salt pool through adaptation of renal transporters in cholestasis.,Treatment
is plasma high-sensitivity c-reactive protein level associated with impaired estimated glomerular filtration rate in hypertensives?,"both inflammation and chronic kidney disease (ckd) are related to cardiovascular disease. whether inflammatory biomarkers are associated with impaired glomerular filtration rate (gfr) is unclear in hypertensives. we recruited hypertension patients from the cardiovascular clinic of a tertiary medical center in taiwan. gfr was calculated using the 7-item modification of diet in renal disease (mdrd) study equation and impaired gfr (igfr) was defined as gfr less than 60 ml/min/1.73 m(2). high-sensitivity c-reactive protein (hscrp) kits were used for the measurement of the crp levels. in our study, 572 consecutive hypertensive patients were enrolled. the range of patient age was 26-91 years (mean 60.5 11.7), and hscrp and gfr ranged from 0.01 to 9.99 mg/l and 16.6 to 239.6 ml/min//1.73 m(2), respectively. hscrp levels were correlated with gfr (p 0.01) and the presence of igfr (p 0.009). multivariate regression analysis showed hscrp (p 0.03), age (p 0.001) and urinary albumin-to-creatinine ratio (uacr) (p 0.002) are independent factors associated with gfr. furthermore, hscrp levels odds ratio (or) 1.16, 95 ci 1.03-1.31, p 0.02, age (or 1.09, 95 ci 1.07-1.12, p 0.001), and uacr (or 1.02, 95 ci 1.01-1.04, p 0.001) independently predicted the presence of igfr using binary logistic regression analysis.",information obtained from our study showed that hscrp is associated with igfr in hypertensives.,Diagnosis
are men more likely than women to slow in the marathon?,"studies on nonelite distance runners suggest that men are more likely than women to slow their pace in a marathon. this study determined the reliability of the sex difference in pacing across many marathons and after adjusting women's performances by 12 to address men's greater maximal oxygen uptake and also incorporating information on racing experience. data were acquired from 14 us marathons in 2011 and encompassed 91,929 performances. for 2929 runners, we obtained experience data from a race-aggregating web site. we operationalized pace maintenance as the percentage change in pace observed in the second half of the marathon relative to the first half. pace maintenance was analyzed as a continuous variable and as two categorical variables, as follows: ""maintain the pace,"" defined as slowing 10, and ""marked slowing,"" defined as slowing 30. the mean change in pace was 15.6 and 11.7 for men and women, respectively (p 0.0001). this sex difference was significant for all 14 marathons. the odds for women were 1.46 (95 confidence interval, 1.41-1.50; p 0.0001) times higher than men to maintain the pace and 0.36 (95 confidence interval, 0.34-0.38; p 0.0001) times that of men to exhibit marked slowing. slower finishing times were associated with greater slowing, especially in men (interaction, p 0.0001). however, the sex difference in pacing occurred across age and finishing time groups. making the 12 adjustment to women's performances lessened the magnitude of the sex difference in pacing but not its occurrence. although greater experience was associated with less slowing, controlling for the experience variables did not eliminate the sex difference in pacing.","the sex difference in pacing is robust. it may reflect sex differences in physiology, decision making, or both.",Treatment
does analysis of weekly mortality as a tool for the early detection of alert in public health ?,"there is a growing interest in public health in monitoring indicators in real time that permit immediate action to be taken. the aim of this study is to evaluate the utility of the analysis of weekly mortality for the early detection of alerts in public health. we analysed the early reception of mortality (erm) from five computerised civil registers in navarre and gathered 70 of total mortality (tm) for the 2003-2007 period. we identified the weeks when mortality exceeded the threshold calculated on the basis of the five previous years. we analysed the correspondence of these excesses in mortality with flu levels of incidence and with high atmospheric temperatures. the was moderate concordance between the alerts detected from the information proceeding from the erm and tm sources (kappa index 0.59; ci 95 0.42-0.76). both sources behaved analogously in the detection of excesses of mortality when these occurred in weeks of severe flu, with 13 and 12 alerts respectively. in relation to high temperatures, tm only generated alerts in the years when heat waves were declared, while erm also generated them in other weeks which were hot but did not reach the heat wave threshold.","the early availability of results, the acceptable concordance between sources and the high percentage of excesses of mortality attributable to identified public health problems, show the potential utility of monitoring weekly mortality in epidemiological surveillance.",Prevention
do changes in gloss after simulated generalized wear of composite resins?,"generalized wear of composite resins in the noncontact area may result in changes of gloss, which can influence esthetics of restorations. the purpose of this study was to determine the changes in gloss of composite resins after generalized wear simulation. surface roughness and amount of wear were measured for comparison. generalized wear simulation was performed with a wear tester for 400,000 cycles with 6 composite resins (estelite sigma, esthet x improved, filtek supreme, heliomolar, renamel microfill, and tetric-ceram). composite resin was placed into a mold (8 mm in diameter, 3 mm in depth) in an acrylic resin block, and 8 specimens were prepared per group. a flat-planed stylus made with polyacetal was loaded perpendicularly. gloss was measured after every 100,000 cycles with a glossmeter in gloss units (gu). average surface roughness (r(a)) of each specimen before and after 400,000 cycles of wear was determined. the amount of wear was measured with a 3-dimensional profilometer. changes in gloss were analyzed by repeated-measures analysis of variance, and mean values were compared by fisher's plsd interval (alpha.05). gloss was influenced by the number of wear cycles and the composite resin, and there was a significant interaction (p.000) between the number of wear cycles and the brand of composite resin. there were no significant correlations between the wear depth and the gloss or changes in gloss after 400,000 cycles.","generalized wear simulation for approximately 3 years of clinical use resulted in gloss changes of 36 to 64 gu, and maximum wear depth was in the range of 35 to 75 mum. change in gloss varied among the composite resins, but average surface roughness was not influenced by the various composite resins.",General
is valvular heart disease associated with nonfocal neuropsychiatric systemic lupus erythematosus?,"central nonfocal neuropsychiatric systemic lupus erythematosus (npsle) manifests as cognitive dysfunction, acute confusional state, seizures, and psychosis. valvular heart disease (vhd) is currently not a causal consideration of nonfocal npsle. the objective of this study was to determine whether vhd is associated with nonfocal npsle. twenty-eight patients with sle underwent: 1) clinical and laboratory evaluations; 2) neuropsychiatric evaluation; 3) brain magnetic resonance imaging (mri); and 4) transesophageal echocardiography (tee). their findings were compared with those of 28 age- and-sex matched healthy volunteers. eighteen patients (64) had nonfocal npsle. cerebral infarcts on mri were more common in patients with than without npsle (50 vs 10, p0.048) and antiphospholipid antibodies (apl) were associated with old cerebral infarcts (p0.03). valvular heart disease was detected in 20 patients (71) of whom 20 (71) had valve thickening, 17 (61) had valve regurgitation, and 15 (53) had valve vegetations (12 on the mitral valve). mitral valve vegetations were more common in patients with than without nonfocal npsle and in those with old cerebral infarcts (61 vs 10 and 75 vs 30, respectively, por0.02 for both). the nonneurologic activity of sle and mitral valve vegetations were the only independent predictors of npsle (odds ratio or, 1.27 per unit value; confidence interval ci, 1.1-1.6; p0.03; and or, 16.5; ci, 1.26-217; p0.03, respectively). among controls, none had neuropsychiatric syndromes, 4 (15) had mri abnormalities, and 3 (11) had vhd (all por0.001 vs patients).","nonfocal npsle, cerebral infarcts, and vhd were highly associated and mitral valve vegetations were independent predictors of npsle. thus, vhd exacerbated by hypercoagulability may cause thromboembolic ischemic brain injury and nonfocal npsle.",Diagnosis
does short-course of ranolazine prevent postoperative atrial fibrillation following coronary artery bypass grafting and valve surgeries?,"postoperative atrial fibrillation (poaf) is a common complication arising after coronary artery bypass grafting (cabg) and valve replacement or repair surgeries. poaf has been associated with increased mortality, morbidity and cost. the study was conducted to evaluate the incidence of poaf following cabg, valve or combination surgeries when perioperative ranolazine (1,000 mg preoperatively, then 1,000 mg twice daily for 7 days or until discharge) was or was not added to standard therapy. a total of 205 patients were evaluated for poaf after cabg, valve or combination surgeries. poaf occurred less frequently in the ranolazine group compared with the non-ranolazine group in unmatched analysis (10.1 vs. 41.9 , p 0.0001). after adjusting for potential sources of bias through propensity-score matched-pair analysis and conditional logistic regression, ranolazine was an independent predictor of preventing poaf (p 0.0001). there were no differences in bradycardia, new renal failure or neurological events between the two groups. early, symptomatic hypotension occurred more frequently in the ranolazine group (p 0.0004) although this difference did not persist after 72 h. no significant difference was found in the length of stay in the intensive care unit following cardiac surgery. while a significant difference was found in the hospital readmission rate for a cardiac cause within 30 days in the unmatched analysis (p 0.046), this difference was nonexistent after matching (p 0.39). no difference was found in 30-day cardiovascular mortality.","adding ranolazine to standard therapy was independently associated with a significant decrease in poaf development after cabg, valve or combination surgeries.",Treatment
does adrenal androgen production capacity remain high up to menopause in women with polycystic ovary syndrome?,"hyperandrogenism is one of the main features of polycystic ovary syndrome (pcos). of circulating androgens, 50 of androstenedione and testosterone are of ovarian and adrenal origin, whereas dehydroepiandrosterone (dhea) and dhea sulfate are almost uniquely of adrenal origin. our previous studies have indicated that ovarian androgen production capacity is enhanced in women with pcos, and it remains high until late reproductive age. to study whether this also applies to adrenal androgen production, acth tests were performed in healthy women and in women with pcos. sixty-nine healthy women (aged 19-62 yr; body mass index 19.2-35.0 kg/m2) and 58 women with previously diagnosed pcos (aged 18-59 yr; body mass index 19.0-42.9 kg/m2) participated in the study. the subjects underwent acth stimulation tests, and serum cortisol, 17-hydroxyprogesterone, androstenedione, testosterone, dhea, and dhea sulfate levels were analyzed at 0, 30, and 60 min. basal and acth-stimulated levels of most adrenal androgens decreased in healthy women with age, whereas in women with pcos, only the concentrations of basal serum 17-hydroxyprogesterone decreased, and all areas under the curve (aucs) remained unchanged and significantly higher (except for dhea) than those in control women. likewise, at the menopausal transition, pre- and postmenopausal women with pcos exhibited mainly unchanged and higher basal androgen and auc levels.","similarly to ovarian endocrine function, serum adrenal steroid levels and adrenal steroid production capacity remain enhanced at least up to menopause in women with pcos.",Diagnosis
does neutralization of vascular endothelial growth factor slow progression of retinal nonperfusion in patients with diabetic macular edema?,"to determine the effect of suppression of vascular endothelial growth factor (vegf) by monthly injection of ranibizumab on posterior retinal nonperfusion (rnp) in patients with diabetic macular edema (dme). unplanned retrospective analysis of prospectively collected data from 2 randomized, sham injection-controlled, double-masked, multicenter clinical trials. six hundred sixty-six patients with dme. an independent reading center measured the area of rnp on fluorescein angiograms obtained in the phase 3 rise and ride trials. the percentage of patients with no posterior rnp. the percentage of patients with no posterior rnp decreased in the sham group between baseline and month 24, but remained relatively stable in the 2 ranibizumab groups. after month 24, the sham group crossed over to receive monthly injections of ranibizumab 0.5 mg, and the differences between the sham and ranibizumab groups were reduced. the percentage of patients who showed an increase in posterior rnp from baseline increased over time in all 3 groups, but at a faster rate in the sham group, resulting in statistically significant differences at every time point between months 3 (9.6 vs. 18.5; p 0.016) and 24 (16.1 vs. 37.6; p0.0001) for ranibizumab 0.5 mg versus sham and from months 6 (12.3 vs. 23.0; p 0.013) through 24 (15.0 vs. 37.6; p0.0001) for ranibizumab 0.3 mg. initiation of ranibizumab in the sham group at month 24 was followed by reduction in the percentage of patients with an increase in posterior rnp from baseline at months 30 and 36, whereas the 2 ranibizumab groups continued their gradual rise.","just as high vegf levels contribute to progression of retinal nonperfusion in retinal vein occlusion, the same is true in patients with dme, suggesting that regardless of the underlying disease process, high levels of vegf can cause closure of retinal vessels. however, our data also suggest that vegf-induced worsening of retinal perfusion in dme is superimposed on another cause of more gradually worsening perfusion, possibly glucotoxicity. thus, monthly injections of ranibizumab can slow, but not completely prevent, retinal capillary closure in patients with dme.",Medication
does adiponectin provide additional information to conventional cardiovascular risk factors for assessing the risk of atherosclerosis in both genders?,"this study evaluated the relation between adiponectin and atherosclerosis in both genders, and investigated whether adiponectin provides useful additional information for assessing the risk of atherosclerosis. we measured serum adiponectin levels and other cardiovascular risk factors in 1033 subjects (454 men, 579 women) from the korean genomic rural cohort study. carotid intima-media-thickness (cimt) was used as measure of atherosclerosis. odds ratios (ors) with 95 confidence intervals (95 ci) were calculated using multiple logistic regression, and receiver operating characteristic curves (roc), the category-free net reclassification improvement (nri) and integrated discrimination improvement (idi) were calculated. after adjustment for conventional cardiovascular risk factors, such as age, waist circumference, smoking history, low-density and high-density lipoprotein cholesterol, triglycerides, systolic blood pressure and insulin resistance, the ors (95ci) of the third tertile adiponectin group were 0.42 (0.25-0.72) in men and 0.47 (0.29-0.75) in women. the area under the curve (auc) on the roc analysis increased significantly by 0.025 in men and 0.022 in women when adiponectin was added to the logistic model of conventional cardiovascular risk factors (auc in men: 0.655 to 0.680, p 0.038; auc in women: 0.654 to 0.676, p 0.041). the nri was 0.32 (95ci: 0.13-0.50, p0.001), and the idi was 0.03 (95ci: 0.01-0.04, p0.001) for men. for women, the category-free nri was 0.18 (95ci: 0.02-0.34, p 0.031) and the idi was 0.003 (95ci: -0.002-0.008, p 0.189).","adiponectin and atherosclerosis were significantly related in both genders, and these relationships were independent of conventional cardiovascular risk factors. furthermore, adiponectin provided additional information to conventional cardiovascular risk factors regarding the risk of atherosclerosis.",Prevention
does rapamycin enhance docetaxel-induced cytotoxicity in a androgen-independent prostate cancer xenograft model by survivin downregulation?,"docetaxel is a first-line treatment choice in castration-resistant prostate cancer (crpc). however, the management of crpc remains an important challenge in oncology. there have been many reports on the effects of rapamycin, which is an inhibitor of the mammalian target of rapamycin (mtor), in the treatment of carcinogenesis. we assessed the cytotoxic effects of the combination treatment of docetaxel and rapamycin in prostate cancer cells. furthermore, we examined the relationship between these treatments and survivin, which is a member of the inhibitory apoptosis family. prostate cancer cells were cultured and treated with docetaxel and rapamycin. the effects on proliferation were evaluated with the mts assay. in addition, we evaluated the effect on proliferation of the combination treatment induced knockdown of survivin expression by small interfering rna transfection and docetaxel. protein expression levels were assayed using western blotting. pc3 cells and xenograft growth in nude mice were used to evaluate the in vivo efficacy of docetaxel and its combination with rapamycin. in vitro and in vivo, the combination of rapamycin with docetaxel resulted in a greater inhibition of proliferation than treatment with rapamycin or docetaxel alone. in addition, in vitro and in vivo, rapamycin decreased basal surviving levels, and cotreatment with docetaxel further decreased these levels. transfection sirna against survivin enhanced the cytotoxicity of docetaxel in pc3 cells.",the rapamycin-dependent enhancement of the cytotoxic effects of docetaxel was associated with the downregulation of survivin expression. our results suggest that the combination of docetaxel and rapamycin is a candidate for the improved treatment of advanced prostate cancer.,Treatment
does new approach to diagnosis and classification of axial and peripheral spondyloarthritis?,"ankylosing spondylitis (as) is characterized by inflammatory back pain, impaired spinal mobility, and sacroiliitis on radiographs. the diagnostic delay in as of several years is mainly attributable to the late appearance of definite sacroiliitis on radiographs. efforts have been made in recent years to improve and standardize making an early diagnosis. mri can visualize sacroiliitis in patients with typical symptoms of as, that is inflammatory back pain, but yet normal radiographs of the sacroiliac joints, and has evolved as the most important diagnostic imaging tool in early disease, also referred to as nonradiographic axial spondyloarthritis (spa). both human leukocyte antigen-b27 and sacroiliitis on mri play a major role in the recently proposed diagnostic algorithm which is meant to be applied in individual patients as well as in the new assessment of spondyloarthritis international society (asas) classification criteria for axial spa. most recently, asas has also developed new criteria for peripheral spa.","the new asas criteria for axial spa will facilitate the conduct of clinical trials and other studies in early axial spa and will help establishing a diagnosis. yet, they should not be misused as diagnostic criteria. the new criteria for peripheral spa may better reflect the current view on peripheral spa.",Diagnosis
does interleukin 6 g-174c polymorphism influence outcome following coronary revascularization surgery?,"levels of the proinflammatory cytokine interleukin 6 (il-6) increase after surgery. the functional polymorphism in the il-6 promoter region, g-174c, is associated with an increased risk of coronary heart disease. we investigated the genetic predisposition in il-6 response to coronary revascularization and studied the association between the g-174c polymorphism, il-6 levels, and clinical outcomes of surgery. dna was obtained from 96 consecutive patients who underwent elective coronary revascularization. patients were genotyped for the il-6 g-174c polymorphism by means of sequence-specific primer-polymerase chain reaction analysis. il-6 levels were measured with an enzyme-linked immunosorbent assay on serum samples taken 3 hours postoperatively. il-6 levels and genotypes (cc, cg, and gg) were correlated with perioperative clinical data. the prevalences of the cc, cg, and gg il-6 -174 genotypes were 8, 54, and 38, respectively. patients homozygous for the c allele had higher circulating levels of il-6 postoperatively than the patients with the cg and gg genotypes (p .09). patients homozygous for the g allele had a significantly lower incidence of postoperative atrial fibrillation (p .032) and a shorter hospital stay (p .005). this result remained statistically significant following risk stratification. the severity of coronary artery disease and a higher number of bypass grafts were associated with a significant increase in il-6 level postoperatively (p .028, and p .005, respectively). higher levels of il-6 were associated with increased blood loss postoperatively (p .016).",the c allele is associated with higher postoperative il-6 levels and a less favorable clinical outcome. the g-174c polymorphism is related to the outcome after coronary revascularization.,Treatment
"is obesity in young age a risk factor for preeclampsia : a facility based case-control study , northwest ethiopia?","preeclampsia is one of the most commonly encountered hypertensive disorders of pregnancy. for many years, obesity has been suggested to play a role in preeclampsia. however, the hypotheses have been diverse and often revealed inconsistent results. this study has aimed to estimate the effect of obesity and dietary habits on preeclampsia in bahir dar city, north-western ethiopia. a facility-based unmatched case-control study was conducted on 453 (151 cases and 302 controls) pregnant women, attending antenatal care or skilled delivery at bahir dar city. data were collected through face to face interviews and measurements of mid-upper-arm circumference (muac) at the time of the interviews. data were cleaned and entered into ibm spss version 20 and later analyzed using stata version 12. univariate and multivariate logistic regression analyses were employed to estimate the effect of independent variables on preeclampsia. stratified analysis was conducted to check for presence of confounding and/or effect modification between covariates. the odds of preeclampsia were higher among obese (muac 25 cm) women than their leaner counterparts (aor 3.33, 95 ci: 1.87, 5.79). obesity was also found to have a similar magnitude of risk for late onset preeclampsia (aor 3.63, 95 ci: 1.89, 6.97). when stratified by age, the effect of obesity on overall and late onset preeclampsia was significant among young (age 35 years) women (cor 1.81, 95 ci: 1.11, 2.99) and (cor 2.09, 95 ci: 1.16, 3.86), respectively. as the age groups became more homogenous through adjusted stratification, obesity showed a particularly significant effect in women age 24 and 25-29 years; (aor 2.31, 95 ci: 1.06, 5.12) and (aor 3.66, 95 ci: 1.37, 10.87) respectively. similarly, the effect of obesity on late onset preeclampsia was evident among younger women age 24 and 25-29 years; (aor 3.16, 95 ci: 1.21, 8.24) and (aor 1.98, 95 ci: 1.16, 3.40) respectively. however, obesity has no significant effect on early onset of preeclampsia (aor 1.98, 95 ci: 0.79, 4.94). on the other hand, compliance to folate supplementation during pregnancy and fruit consumption were associated with reduced risk of preeclampsia.","obesity in young age was found to be a risk factor for preeclampsia while compliance to folate supplement and adequate fruit consumption were found to be protective against preeclampsia. promoting healthy life style, including body weight control, consumption of fruits and vegetables, and folate supplementation should be promoted to reduce the risk of preeclampsia.",Prevention
is rna interference induced in the glassy winged sharpshooter homalodisca vitripennis by actin dsrna?,"the glassy winged sharpshooter, homalodisca vitripennis, is an unusually robust and efficient leafhopper vector of xylella fastidiosa. x. fastidiosa is the causative agent of pierce's disease, almond scorch, citrus variegated chlorosis and other serious plant diseases. the present study was conducted to establish whether rna interference (rnai) was induced in nymphal h. vitripennis that were injected with actin dsrnas and other dsrnas. a dramatic reduction in target h. vitripennis actin mrnas and the formation of small interfering rnas (sirnas), hallmarks of rnai, were found following the injection of actin dsrnas. quantitative reverse transcription pcr indicated an 80 reduction in actin mrna levels by 5 days post-injection. western blot analysis showed a dramatic drop in actin protein levels by 3 days post-injection. biological effects such as incomplete nymphal-adult ecdysis and 95 mortality were also found following the injection of fifth-instar nymphs with actin dsrna. dramatic reductions in target mrna levels were also found following the injection of other dsrnas into fifth-instar h. vitripennis.",the findings indicate that rnai is induced in post-embryonic leafhoppers by dsrna. the present system can be used to screen potential gene-silencing targets that can be used for reducing the vector competence of h. vitripennis and other leafhoppers.,Medication
does lysine-derived urethane surgical adhesive prevent seroma formation in a canine abdominoplasty model?,"seroma formation is a common postoperative complication following many surgical procedures, including abdominoplasty. several approaches have been investigated to prevent seroma formation by draining fluid or attempting to eliminate dead space, but these approaches have limited effectiveness. a canine model of abdominoplasty was developed that reliably produced seroma formation. bilateral subcutaneous pockets were created in the ventrolateral abdominal wall and additional tissue damage was inflicted using electrocautery. on one side, the tissue layers were treated with a lysine-derived urethane adhesive before closure, whereas the control side received no treatment before standard closure of the incision. seroma formation (60 /- 45 ml) was observed on the control side, whereas the treated side had adherence between the tissue layers and minimal if any fluid accumulation (1.7 /- 1.4 ml) (p 0.01) (n 7). the adhesive invoked little or no cellular response, based on histologic examination of the tissue.",the urethane surgical adhesive was effective in preventing the formation of seroma in this canine abdominoplasty model.,Prevention
does sodium nitroprusside iontophoresis on the finger pad consistently increase skin blood flow in healthy controls and patients with systemic sclerosis?,"sodium nitroprusside (snp) iontophoresis is a commonly used technique to assess non endothelium-dependent skin microvascular function in the forearm. however, the lack of data on the finger pad is a limitation when studying diseases affecting the digits (e.g. systemic sclerosis, ssc). we thus aimed to validate this technique in the finger pad compared to the forearm in ssc patients and healthy controls. six ssc patients and six controls were recruited. snp and nacl iontophoresis were performed on the finger pad and the forearm, with and without lidocaine/prilocaine. cutaneous blood flow was simultaneously monitored using laser doppler flowmetry. in all subjects, iontophoresis of snp induced hyperemia in the forearm, which was not affected by pretreatment with lidocaine/prilocaine. in contrast, no increase in cutaneous vascular conductance was observed in the finger pad in any subject (apart from one patient with ssc).","the iontophoresis of snp leads to a consistent, non axon reflex-dependent, increase in cutaneous vascular conductance in the forearm, both in patients with ssc and in healthy controls. on the finger pad however, such hyperemia was not consistent. as a consequence, other tools should be considered to assess non endothelium-dependent skin microvascular function in the finger pad.",General
is radiotherapy associated with improved survival in adjuvant and palliative treatment of extrahepatic cholangiocarcinomas?,"extrahepatic cholangiocarcinomas (ehc) are rare tumors of the biliary tree because of their low incidence, large randomized studies examining radiotherapy (rt) for ehc have not been performed. the purpose of this study was to examine the role of adjuvant and palliative rt in the treatment of ehc in a large patient population. this was a retrospective analysis of 4,758 patients with ehc collected from the surveillance, epidemiology, and end results database. the primary endpoint was overall survival. patients underwent surgery (28.8), rt (10.0), surgery and rt (14.7), or no rt or surgery (46.4). the median age of the patient population was 73 years (range, 23-104), 52.5 were men, and 80.7 were white. the median overall survival time was 16 months (95 confidence interval ci 15-17), 9 months (95 ci 9-11), 9 months (95 ci 9-10), and 4 months (95 ci 3-4) for surgery and rt, surgery, rt, and no rt or surgery, respectively. the overall survival was significantly different between the surgery and surgery and rt groups (p .0001) and rt and no rt or surgery groups (p .0001) on the log-rank test. the propensity score-adjusted analyses of surgery and rt vs. surgery (hazard ratio, 0.94; 95 ci, 0.84-1.05) were not significantly different, but that for rt vs. no rt or surgery (hazard ratio, 0.61; 95 ci, 0.54-0.70) was significantly different.",these results suggest that palliative rt prolongs survival in patients with ehc. the benefit associated with surgery and rt was significant on univariate analysis but not after controlling for potential confounders using the propensity score. future studies should evaluate the addition of chemotherapy and biologic agents for the treatment of ehc.,Treatment
do application of ultrafast papanicolaou stain to body fluid cytology?,"to investigate the applicability of the ultrafast papanicolaou stain to the cytology of fluids and to compare it with other methods. over a 30-month period, 528 unfixed fluids (462 serous effusions, 48 pelvic washings, 16 cyst fluids and 2 bile duct drain fluids) were mixed thoroughly and centrifuged. two swedish-style air-dried smears were made and stained with diff-quik (mercedes medical, inc., sarasota, florida, u.s.a.) and ultrafast papanicolaou stain (richard allan scientific, kalamazoo, michigan, u.s.a.), and the remaining sediment was fixed in cytorich red (tripath imaging, inc., burlington, north carolina, u.s.a.), centrifuged onto a 17.5-mm circle with a hettich cytocentrifuge and stained by the papanicolaou method. for the 115 malignant fluids, ultrafast papanicolaou stain was the preferred method in the 94 non-hematopoietic malignant fluids, diff-quik was the preferred method in the 9 hematopoietic malignancies, and cytorich red was the preferred preparation in 8 bloody effusions containing rare cancer cells and 4 malignant pelvic washings. the diagnostic turnaround time of smears stained by ultrafast papanicolaou stain was 15 minutes, fast enough for intraoperative consultations.","it seems that ultrafast papanicolaou stain improves the resolution of cytoplasmic and nuclear details of nonhematopoietic cells in body fluids. however, to detect cancer in all types of fluids, diff-quik and cytorich preparations are also required. we now examine three slides per fluid sample, one slide by each of the three techniques.",Diagnosis
is overexpression of hexokinase-2 in giant cell tumor of bone associated with false positive in bone tumor on fdg-pet/ct?,"the aim of the current study was to evaluate the usefulness of maximum standardized uptake value (suv(max)) in 2-deoxy-2-f(18)-fluoro-d-glucose positron emission tomography combined with computed tomography (18f-fdg-pet/ct) for preoperative differential diagnosis between benign and malignant bone tumors. seventy-nine patients with bone tumors were examined by fdg-pet prior to histopathological diagnosis. the suv(max) was calculated and compared between benign and malignant lesions, and among different histopathological subgroups, to identify false-positive histological subtypes. there was a statistically significant difference in the suv(max) of benign (3.7 3.3; n 17) and malignant (5.3 3.3; n 62) bone tumors. however, receiver operating characteristic curve analysis revealed the poor accuracy of this distinction. the cut-off value was determined to be 2.6, while the value of sensitivity and specificity was calculated to be 74.2 and 64.7 , respectively. giant cell tumor of bone (9.0 2.0; n 5) displayed a higher suv(max) than osteosarcoma (4.2 2.3; n 18). immunohistochemical analysis demonstrated that markers of these cancers, hexokinase-2 (hk-2) and glucose transporter type 1 (glut-1), supported our findings.","the poor accuracy of suv(max) in 18f-fdg-pet/ct in distinguishing malignant from benign bone tumors was confirmed; some benign bone tumors showed high fdg uptake. giant cell tumor of bone was a major false-positive histopathological subtype of bone tumors, showing high fdg accumulation. hk-2 contributed significantly to fdg uptake, whereas glut-1 appeared to play no role in fdg uptake in giant cell tumor of bone.",Diagnosis
does quercetin ameliorate hypobaric hypoxia-induced memory impairment through mitochondrial and neuron function adaptation via the pgc-1 pathway?,"acute hypobaric hypoxia (hh) causes persistent cognitive impairment, affecting memory function specifically. mitochondrial dysfunction and synaptic morphological change were the prominent pathological features of hh exposure on brain. quercetin, a flavonoid found in fruits, vegetables, leaves and grains, is reported to prevent ischemia induced by neuronal injury. this study investigated the efficacy of quercetin to ameliorate hh-induced memory deficit. rats were exposed to hh equivalent to 5000 m for 7 days in a decompression chamber and received quercetin daily (50, 75 or 100 mg/kgbw) via gavage during the period of exposure. cognitive performance was assessed by the morris water maze test. in vitro, the effect of quercetin was tested in hippocampus tissue. quercetin, especially at 100 mg/kgbw, significantly reduced hh-induced memory decline. meanwhile, hh-induced hippocampus mitochondrial and synaptic lesions were ameliorated by quercetin. furthermore, quercetin regulated the expression of sirtuin 1(sirt1), pgc-1, and the proteins related with mitochondrial biogenesis and dynamics. moreover, quercetin increased expression of fibronectin type iii domain-containing protein 5 (fndc5) and brain-derived neurotrophic factor (bdnf), showing the pgc-1/fndc5/bndf pathways might be involved in neuronal adaptation.","the results suggest quercetin has prophylactic potential for amelioration of hh-induced memory impairment, which is associated with the mitochondrial and neuronal adaptation in hippocampus.",Prevention
is sagittal abdominal diameter an independent predictor of all-cause and cardiovascular mortality in incident peritoneal dialysis patients?,"visceral fat has a crucial role in the development and progression of cardiovascular disease, the major cause of death in end-stage renal disease (esrd). although sagittal abdominal diameter (sad), as an index of visceral fat, significantly correlated with mortality in the general population, the impact of sad on clinical outcomes has never been explored in esrd patients. therefore, we sought to elucidate the prognostic value of sad in incident peritoneal dialysis (pd) patients. we prospectively determined sad by lateral abdominal x-ray at pd initiation, and evaluated the association of sad with all-cause and cardiovascular mortality in 418 incident pd patients. the mean sad was 24.5 4.3 cm, and during a mean follow-up of 39.4 months, 97 patients (23.2) died, and 49.4 of them died due to cardiovascular disease. sad was a significant independent predictor of all-cause 3rd versus 1st tertile, hr (hazard ratio): 3.333, 95 ci (confidence interval): 1.514-7.388, p 0.01; per 1 cm increase, hr: 1.071, 95 ci: 1.005-1.141, p 0.03 and cardiovascular mortality (3rd versus 1st tertile, hr: 8.021, 95 ci: 1.994-32.273, p 0.01; per 1 cm increase, hr: 1.106, 95 ci: 1.007-1.214, p 0.03). multivariate fractional polynomial analysis also showed that all-cause and cardiovascular mortality risk increased steadily with higher sad values. in addition, sad provided higher predictive value for all-cause (auc: 0.691 vs. 0.547, p0.001) and cardiovascular mortality (auc: 0.644 vs. 0.483, p0.001) than body mass index (bmi). subgroup analysis revealed higher sad ( 24.2 cm) was significantly associated with all-cause mortality in men, women, younger patients (65 years), and patients with lower bmi (22.3 kg/m(2)).",sad determined by lateral abdominal x-ray at pd initiation was a significant independent predictor of all-cause and cardiovascular mortality in incident pd patients. estimating visceral fat by sad could be useful to stratify mortality risk in these patients.,Treatment
is fluticasone propionate aqueous nasal spray safe and effective for children with seasonal allergic rhinitis?,"fluticasone propionate aqueous nasal spray, a new topical corticosteroid preparation, is effective when given as 200 micrograms once daily in patients ( 12 years of age) with seasonal allergic rhinitis. to evaluate the efficacy and safety of fluticasone proprionate aqueous nasal spray in children aged 4 to 11 years with seasonal allergic rhinitis. multicenter, randomized, double-blind, placebo-controlled, parallel-group. two hundred fifty children aged 4 to 11 years with moderate-to-severe nasal symptoms, a positive skin test reaction to a late-summer or autumn allergen, a history of seasonal allergic rhinitis, and documentation of an unsatisfactory response to conventional treatment. children were randomly assigned to receive fluticasone propionate, either 100 micrograms or 200 micrograms, or placebo, given by intranasal spray once daily in the morning for 14 days. severity of nasal symptoms (obstruction, rhinorrhea, itching, and sneezing) was recorded on visual analog scales by investigators at weekly visits and by patients (or adult guardian) daily in the evening. according to investigator and patient ratings, both fluticasone propionate 100 micrograms/d and 200 micrograms/d lowered total nasal symptom scores when compared with placebo. both dosages of fluticasone propionate were more effective than placebo on the basis of investigator-rated overall clinical evaluation of efficacy at the end of treatment, with significant improvement (as opposed to moderate or mild improvement, no change or worsening) noted in 21 to 29 of the active-treatment groups vs 9 in the placebo group. there were no significant differences between the two fluticasone propionate dosages in any efficacy measurement. morning plasma cortisol concentrations and frequency of drug-related adverse events were similar in the fluticasone propionate and placebo groups.","in children as young as 4 years, 100 micrograms of fluticasone propionate aqueous nasal spray given once daily is as effective as 200 micrograms given once daily, the usual adult dose for the treatment of seasonal allergic rhinitis. both fluticasone propionate dosages were well tolerated and neither dosage appears to interfere with the hypothalamic-pituitary-adrenal axis in children.",Medication
does teriparatide increase bone formation and bone mineral density in adult women with anorexia nervosa?,"anorexia nervosa (an), a prevalent psychiatric disorder predominantly affecting women, is characterized by self-induced starvation and low body weight. increased clinical fractures are common, and most women have low bone mineral density (bmd). previously investigated treatments have led to no or modest increases in bmd in an. our objective was to investigate the effect of teriparatide (tpt; human pth1-34), an anabolic agent, on low bone mass in women with an. this randomized, placebo-controlled trial at a clinical research center included 21 women with an: 10 (mean age sem, 47 2.7 years) treated with tpt and 11 (47.1 2.3 years) treated with placebo. tpt (20 g s.c.) or placebo was administered for 6 months. our primary outcome measure was change in bmd of the spine and hip by dual-energy x-ray absorptiometry. secondary outcome measures included changes in serum n-terminal propeptide of type 1 procollagen (p1np), c-terminal collagen cross-links, sclerostin, and igf-1 levels. at 6 months, spine bmd increased significantly more with tpt (posteroanterior spine, 6.0 1.4; lateral spine, 10.5 2.5) compared with placebo (posteroanterior spine, 0.2 0.7, p .01; lateral spine, -0.6 1.0; p .01). the results remained significant after controlling for baseline body mass index, p1np, and igf-1. changes in femoral neck (p .4) and total hip (p 0.8) bmd were comparable in both groups, as were changes in weight. serum p1np levels increased after 3 months of tpt treatment and remained at this higher level at 6 months, whereas p1np levels were unchanged in the placebo group (p .02). tpt was well-tolerated by all subjects.",this study demonstrates that tpt administration increases spine bmd substantially after only 6 months of therapy in women with an.,Medication
are blood urea level and diabetes duration independently associated with ankle-brachial index in type 2 diabetic patients?,"the purpose of the study was to determine factors of ankle-brachial index (abi) in a population of patients with type 2 diabetes and coronary artery disease. 370 patients (mean age 60.3 8.3 years and diabetes duration 8.6 6.2 years) with type 2 diabetes and coronary artery disease were enrolled in a cross sectional study during 2006-2007. multivariable linear regression analysis was conducted to determine the factors of abi, considering systolic and diastolic blood pressure, weight, body mass index, waist circumference, glycemia, urea, creatinin, triglycerides, total cholesterol, ldl- and hdl-cholesterol. peripheral arterial disease was detected in 82.35 (280 pts). mean abi value of 0.97 0.33, and its minimal value of 0.95 0.38 was detected in this study population. regression analysis demonstrated that mean and minimal values of abi were independently associated with diabetes duration ( 0.120, 95 ci -0.014, -0.001) and blood urea level ( -0.126, 95 ci -0.020, -0.002).",results might have clinical implications for patients with type 2 diabetes and coronary artery disease in defining those with a long diabetes duration and a higher blood urea level to have greater probability of detecting pathological ankle-brachial index.,General
does transplantation of center for disease control high-risk '' donor hearts adversely impact long-term outcomes in adults?,"the ""high-risk donor"" (hrd) label was applied to donors who met the centers for disease control and prevention criteria for high-risk behavior in 2004. the number of potential recipients who die awaiting orthotopic heart transplantation (oht) has increased. despite organ shortages, hrd grafts are often declined given infectious concerns. we hypothesized that recipients would have equivalent outcomes. we retrospectively analyzed the united network of organ sharing adult heart transplant data from june 2004 to december 2013. oht recipients were divided into 2 cohorts by donor status. during the study period, 37,408 ohts were performed and 3196 (8.5) patients received hrd grafts. recipients of hrd were significantly older (p .0001) and had a higher body mass index (p .0001) compared with standard-risk donor recipients. no significant difference in waitlist time (p .69) or blood type (p .07) was noted. a higher number of hrd recipients were on mechanical circulatory support (35.6) compared with standard-risk donor (33.3, p .009). both grafts manifested similar, low rates of rejection before discharge (p .88). one1 (84.3 vs 83) and 5-year (71.2 vs 65.5) survival was similar in the cohorts (log-rank p .7571).",hrd status does not significantly affect recipient outcomes after oht. increased use of hrd grafts could augment donor pool and decrease the mortality associated with long waitlist times.,Treatment
is bone marrow iron depletion common in patients with coronary artery disease?,"iron deficiency (id) may be an important, treatable co-morbidity complicating cardiovascular diseases, but considerable uncertainty exists about the diagnostic accuracy of blood tests. accordingly, we investigated the relationship between blood tests for id and iron stores in bone marrow aspirates, the diagnostic gold-standard for id, in patients with stable coronary artery disease (cad). bone marrow aspirates were obtained from 65 patients with stable cad undergoing cardiac surgery and 10 healthy controls. id was defined as depleted extracellular iron stores (0-1 grade according to gale scale) accompanied by 10 of erythroblasts containing iron. bone marrow id was found in 31 (48) patients with cad but in none of the controls (p0.01). amongst patients with cad, id was present in 10 of 16 (63) with and 21 of 49 (43) without anaemia (p0.17). the clinical profiles of patients with and without id were similar. of circulating biomarkers of id, serum soluble transferrin receptor had the strongest association with bone marrow id (area under curve: 0.8760.048, 95 confidence interval: 0.762-0.948, for cut-off of 1.32mg/l-sensitivity: 67, specificity: 97).",almost half of patients with stable cad have profound bone marrow iron depletion that can be accurately assessed non-invasively using serum soluble transferrin receptor.,Diagnosis
does background correction using dinucleotide affinities improve the performance of gcrma?,"high-density short oligonucleotide microarrays are a primary research tool for assessing global gene expression. background noise on microarrays comprises a significant portion of the measured raw data, which can have serious implications for the interpretation of the generated data if not estimated correctly. we introduce an approach to calculate probe affinity based on sequence composition, incorporating nearest-neighbor (nn) information. our model uses position-specific dinucleotide information, instead of the original single nucleotide approach, and adds up to 10 to the total variance explained (r2) when compared to the previously published model. we demonstrate that correcting for background noise using this approach enhances the performance of the gcrma preprocessing algorithm when applied to control datasets, especially for detecting low intensity targets.","modifying the previously published position-dependent affinity model to incorporate dinucleotide information significantly improves the performance of the model. the dinucleotide affinity model enhances the detection of differentially expressed genes when implemented as a background correction procedure in genechip preprocessing algorithms. this is conceptually consistent with physical models of binding affinity, which depend on the nearest-neighbor stacking interactions in addition to base-pairing.",General
do selective activation of atf6 and perk endoplasmic reticulum stress signaling pathways prevent mutant rhodopsin accumulation?,"many rhodopsin mutations that cause retinitis pigmentosa produce misfolded rhodopsin proteins that are retained within the endoplasmic reticulum (er) and cause photoreceptor cell death. activating transcription factor 6 (atf6) and protein kinase rna-like endoplasmic reticulum kinase (perk) control intracellular signaling pathways that maintain er homeostasis. the aim of this study was to investigate how atf6 and perk signaling affected misfolded rhodopsin in cells, which could identify new molecular therapies to treat retinal diseases associated with er protein misfolding. to examine the effect of atf6 on rhodopsin, wild-type (wt) or mutant rhodopsins were expressed in cells expressing inducible human atf6f, the transcriptional activator domain of atf6. induction of atf6f synthesis rapidly activated downstream genes. to examine perk's effect on rhodopsin, wt or mutant rhodopsins were expressed in cells expressing a genetically altered perk protein, fv2e-perk. addition of the dimerizing molecule (ap20187) rapidly activated fv2e-perk and downstream genes. by use of these strategies, it was examined how selective atf6 or perk signaling affected the fate of wt and mutant rhodopsins. atf6 significantly reduced t17m, p23h, y178c, c185r, d190g, k296e, and s334ter rhodopsin protein levels in the cells with minimal effects on monomeric wt rhodopsin protein levels. by contrast, the perk pathway reduced both levels of wt, mutant rhodopsins, and many other proteins in the cell.",this study indicates that selectively activating atf6 or perk prevents mutant rhodopsin from accumulating in cells. atf6 signaling may be especially useful in treating retinal degenerative diseases arising from rhodopsin misfolding by preferentially clearing mutant rhodopsin and abnormal rhodopsin aggregates.,Prevention
do comparative transcriptomic analyses of atopic dermatitis and psoriasis reveal shared neutrophilic inflammation?,"atopic dermatitis (ad) and psoriasis are common inflammatory diseases canonically described as involving distinct t(h) polarization and granulocytic infiltration. acute ad lesions are associated with t(h)2 and eosinophilic inflammation, whereas psoriatic lesions are associated with t(h)1/t(h)17 and neutrophilic inflammation. despite intensive investigation, these pathways remain incompletely understood in vivo in human subjects. using ad and psoriatic lesional skin as exemplar t(h)2 and t(h)1/t(h)17 diseased tissue, we sought to clarify common and unique molecular and pathophysiologic features in inflamed skin with different types of inflammatory polarization. we conducted gene expression microarray analyses to identify distinct and commonly dysregulated expression in ad (based on hanifin and rajka criteria) and psoriatic lesions. we defined gene sets (gss) as comprising genes encoding cytokines, chemokines, and growth factors that were uniquely or jointly dysregulated in patients with ad and those with psoriasis and calculated aggregate gs expression scores for lesional skin of patients with these dermatoses and healthy control skin. the atopic dermatitis gene set (ad-gs) score correlated with systemic and local measures of allergic inflammation, including serum ige levels, blood eosinophil counts, and tissue eosinophil counts. unexpectedly, genes encoding neutrophil chemoattractants among the common gs were highly expressed in ad lesional skin. hematoxylin and eosin and immunohistochemical analyses showed the numbers of neutrophils in ad lesional skin were comparable with those in psoriatic lesional skin, and both were correlated with the extent of expression of neutrophil chemoattractant genes.",these data are evidence that neutrophilic inflammation is a feature of lesional ad pathology comorbid with allergic inflammation.,General
does tgf- stimulation in human and murine cells reveal commonly affected biological processes and pathways at transcription level?,"the tgf- signaling pathway is a fundamental pathway in the living cell, which plays a key role in many central cellular processes. the complex and sometimes contradicting mechanisms by which tgf- yields phenotypic effects are not yet completely understood. in this study we investigated and compared the transcriptional response profile of tgf-1 stimulation in different cell types. for this purpose, extensive experiments are performed and time-course microarray data are generated in human and mouse parenchymal liver cells, human mesenchymal stromal cells and mouse hematopoietic progenitor cells at different time points. we applied a panel of bioinformatics methods on our data to uncover common patterns in the dynamic gene expression response in respective cells. our analysis revealed a quite variable and multifaceted transcriptional response profile of tgf-1 stimulation, which goes far beyond the well-characterized classical tgf-1 signaling pathway. nonetheless, we could identify several commonly affected processes and signaling pathways across cell types and species. in addition our analysis suggested an important role of the transcription factor egr1, which appeared to have a conserved influence across cell-types and species. validation via an independent dataset on a549 lung adenocarcinoma cells largely confirmed our findings. network analysis suggested explanations, how tgf-1 stimulation could lead to the observed effects.","the analysis of dynamical transcriptional response to tgf- treatment experiments in different human and murine cell systems revealed commonly affected biological processes and pathways, which could be linked to tgf-1 via network analysis. this helps to gain insights about tgf- pathway activities in these cell systems and its conserved interactions between the species and tissue types.",General
does lumbar plexus block reduce pain and blood loss associated with total hip arthroplasty?,"the usefulness of peripheral nerve blockade in the anesthetic management of hip surgery has not been clearly established. because sensory afferents from the hip include several branches of the lumbar plexus, the authors hypothesized that a lumbar plexus block could reduce pain from a major hip procedure. in a double-blind prospective trial, 60 patients undergoing total hip arthroplasty were randomized to receive general anesthesia with (plexus group, n 30) or without (control group, n 30) a posterior lumbar plexus block. the block was performed after induction using a nerve stimulator, and 0.4 ml/kg bupivacaine, 0.5, with epinephrine was injected. general anesthesia was standardized, and supplemental fentanyl was administered per hemodynamic guidelines. postoperative pain and patient-controlled intravenous morphine use were serially assessed for 48 h. the proportion of patients receiving supplemental fentanyl intraoperatively was more than 3 times greater in the control group (20 of 30 vs. 6 of 29, p 0.001). in the postanesthesia care unit, a greater than fourfold reduction in pain scores was observed in the plexus group (visual analogue scale vas pain score at arrival 1.3 /- 2 vs. 5.6 /- 3, p 3) were administered 10 times less frequently (in 2 of 28 vs. in 22 of 29 patients, p 0.0001). pain scores and morphine consumption remained significantly lower in the plexus group until 6 h after randomization (vas at 6 h, 1.4 /- 1.3 vs. 2.4 /- 1.4, p 0.007; cumulative morphine at 6 h, 5.6 /- 4.7 vs. 12.6 /- 7.5 mg, p 0.0001). operative and postoperative (48 h) blood loss was modestly decreased in the treated group. epidural-like distribution of anesthesia occurred in 3 of 28 plexus group patients, but no other side-effects were noted.","posterior lumbar plexus block provides effective analgesia for total hip arthroplasty, reducing intra- and postoperative opioid requirements. moreover, blood loss during and after the procedure is diminished. epidural anesthetic distribution should be anticipated in a minority of cases.",Treatment
is the lateral radiograph useful in predicting shortening in 31a2 pertrochanteric hip fractures?,"we sought to determine if angulation or translation measured on the lateral preoperative injury radiographs of patients with 31a2 pertrochanteric fractures is related to excessive postoperative shortening when treated with a sliding hip screw. we retrospectively reviewed the radiographs of consecutive patients with hip fractures treated at a level i university trauma centre between 2003 and 2008. patients with 31a2 pertrochanteric fractures treated with a sliding hip screw were identified through a search of medical records. the study variables were angulation and translation on the preoperative injury lateral radiograph. the outcome measure was radiographic evidence of fracture shortening, measured as the change in length of sliding hip screw visible outside the barrel between the time of fixation and final follow up. of the 131 patients treated, 23 met our inclusion criteria and had sufficient follow-up (mean 6.4 mo). the average shortening for 31a2 fractures with angulation on the injury lateral radiograph was 1.83 (95 confidence interval ci 1.18-2.47) cm, compared with 0.93 (95 ci 0.49-1.36) cm for fractures with no angulation (p 0.019). there was no statistical difference in quality of reduction, tip-apex distance, orthopedic trauma association (ao/ota) classification or incidence of lateral wall fracture across groups based on the presence of angulation.","angulation on the lateral preoperative injury radiograph may be useful in predicting excessive shortening in 31a2 pertrochanteric fractures. further investigation is warranted to confirm this result and to identify the role of other predictors, such as fracture comminution.",Diagnosis
is apoptosis of ejaculated human sperm induced by co-incubation with chlamydia trachomatis lipopolysaccharide?,"previous work has shown that co-incubation of human sperm with chlamydia trachomatis serovars e and lgv leads to premature sperm death and that this is due primarily to chlamydial lipopolysaccharide (lps). here, we investigated the possible involvement of apoptosis in this premature sperm death. highly motile preparations of sperm from normozoospermic patients were co-incubated for 6 h with extracted lps from c. trachomatis serovars e and lgv. three different methods were used to determine if lps-treated sperm underwent apoptosis, including: (i) flow cytometry; (ii) measurement of adp:atp ratios; and (iii) measurement of mono- and oligonucleosomal dna fragments. caspase activity was also investigated by fluorimetry and by use of a pan-caspase inhibitor and caspase-3 inhibitor. all three methods used for detection indicated that c. trachomatis lps induced some apoptosis in sperm after 6 h when compared with a staurosporine (apoptosis-positive) control. moreover, a greater degree of apoptosis was seen with c. trachomatis serovar e than with serovar lgv. it was also shown that c. trachomatis lps-induced apoptosis of sperm could be blocked with a pan-caspase inhibitor and a caspase-3 inhibitor. moreover, by using a fluorogenic substrate, apoptosis was shown to be caspase-mediated.","in general it is believed that apoptosis does not occur in c. trachomatis-infected host cells. however, using three different methods, our findings clearly indicate that co-incubation of sperm with c. trachomatis lps results in cellular death which is in part due to apoptosis and is caspase-mediated. these findings provide an explanation as to how c. trachomatis can mediate premature death in human sperm.",Medication
are sex differences in exercise-induced physiological myocardial hypertrophy modulated by oestrogen receptor beta?,"oestrogen receptor alpha (er) and beta (er) are involved in the regulation of pathological myocardial hypertrophy (mh). we hypothesize that both er are also involved in physiological mh. therefore, we investigated the role of er in exercise-induced physiological mh in loss-of-function models and studied potential mechanisms of action. we performed 1 and 8 weeks of voluntary cage wheel running (vcr) with male and female c57bl/6j wild-type (wt), er- and er-deleted mice. in line with other studies, female wt mice ran more than males (p 0.001). after 8 weeks of vcr, both sexes showed an increase in left ventricular mass (females: p 0.01 and males: p 0.05) with more pronounced mh in females (p 0.05). as previously shown, female er-deleted mice run less than female wt mice (p 0.001). er-deleted mice showed similar running performance as wt mice (females vs. male: p 0.001), but did not develop mh. only female wt mice showed an increase in phosphorylation of serine/threonine kinase (akt), erk1/2, p38-mitogen-activated protein kinase (mapk), and ribosomal protein s6, as well as an increase in the expression of key regulators of mitochondrial function and mitochondrial respiratory chain proteins (complexes i, iii, and v) after vcr. however, er deletion abolished all observed sex differences. mitochondrial remodelling occurred in female wt-vcr mice, but not in female er-deleted mice.","the sex-specific response of the heart to exercise is modulated by er. the greater increase in physiological mh in females is mediated by induction of akt signalling, mapk pathways, protein synthesis, and mitochondrial adaptation via er.",Medication
is early growth response-1 a regulator of dr5-induced apoptosis in colon cancer cells?,"tumour necrosis factor-related apoptosis-inducing ligand (trail) induces tumour cell apoptosis by binding to death receptor 4 (dr4) and dr5. dr4 and dr5 activation however can also induce inflammatory and pro-survival signalling. it is not known how these different cellular responses are regulated and what the individual role of dr4 vs dr5 is in these processes. dna microarray study was carried out to identify genes differentially expressed after dr4 and dr5 activation. rt-pcr and western blotting was used to examine the expression of early growth response gene-1 (egr-1) and the proteins of the trail signalling pathway. the function of egr-1 was studied by sirna-mediated knockdown and overexpression of a dominant-negative version of egr-1. we show that the immediate early gene, egr-1, regulates trail sensitivity. egr-1 is constitutively expressed in colon cancer cells and further induced upon activation of dr4 or dr5. our results also show that dr4 mediates a type ii, mitochondrion-dependent apoptotic pathway, whereas dr5 induces a mitochondrion-independent, type i apoptosis in hct15 colon carcinoma cells. egr-1 drives c-flip expression and the short splice variant of c-flip (c-flip(s)) specifically inhibits dr5 activation.","selective knockdown of c-flip(s) sensitises cells to dr5-induced but not dr4-induced apoptosis and egr-1 exerts an effect as an inhibitor of the dr5-induced apoptotic pathway, possibly by regulating the expression of c-flip(s).",Diagnosis
is patient compliance critical for equivalent clinical outcomes for breast cancer treated by breast-conservation therapy?,"to determine the compliance with a standard breast-conservation therapy (bct) program in a predominantly indigent, minority population of patients with early breast cancer (stage i and ii) served by a rural state institution in the south; to compare the clinical outcomes of this group with those reported in clinical trials; and to examine the socioeconomic factors that may have contributed to the rate of compliance. disease-free survival and overall survival in early breast cancer treated by bct versus modified radical mastectomy are reported to be equivalent in prospective randomized trials. however, patients enrolled in clinical trials may not be representative of patients living in the various diverse communities that make up the united states. the authors' hypothesis is that patients enrolled in clinical trials at the national level may not be representative of indigent patients in the rural south and that clinical trial results may not be directly applicable. a retrospective review of 55 women with early-stage breast cancer treated from 1990 to 1995 was performed. clinical data, compliance with treatment and clinical follow-up, and recurrence rates were examined. statistical analysis performed include the fisher exact test, kaplan-meier survival analysis, and log-rank test. full compliance (defined as completion of the entire course of radiation therapy and clinical follow-up) with the bct program was observed in only 36 of patients. fifteen of the 35 noncompliant patients did not complete radiation therapy. a significantly higher local failure rate was observed: 8 of these 15 patients (53) have had local failure. in contrast, patients who were either in full compliance with the bct program or were deficient only in that they missed part of their clinical follow-up had local failure rates of 5 (1/20) and 10 (2/20), respectively. age, race, stage of cancer, economic status (measured by availability of medical insurance), distance of patient's residence from the hospital, and education level were evaluated as potential predictors of compliance. none predicted patient compliance, although a trend toward higher compliance was noted in patients with a higher education level, as determined by literacy testing.","compliance with the bct protocol at the authors' institution was worse than reported in clinical trials, and noncompliance translated into a significant increase in the local failure rate. factors examined suggest that literacy may play a role in predicting compliance. although bct should be discussed with all breast cancer patients, the judicious application of clinical trial data to an institution's local population is warranted.",Treatment
does oestradiol stimulate prolactin secretion in women through oestrogen receptors?,"to examine the effects of clomiphene and raloxifene on basal and gnrh-induced prolactin (prl) secretion in postmenopausal women. postmenopausal women participated in two experimental procedures a month apart. in one experiment they received raloxifene (180 mg/day) (r-exp) and in the other clomiphene (150 mg/day) (cl-exp). in group 1, the women (n 8) received raloxifene or clomiphene for 30 days plus oestradiol via skin patches (100 microg/24 h) for the last 10 days. in group 2, the women (n 8) received oestradiol for 30 days plus raloxifene (r-exp) or clomiphene (cl-exp) for the last 10 days. the pituitary response to gnrh (100 microg i.v.) was investigated in all women on days 0, 10, 20 and 30 of each experiment. the study included 16 healthy postmenopausal volunteer women aged 56-60 years. basal levels of prl and the area under the curve (auc) of deltaprl response to gnrh were calculated. in group 1, basal levels of prl and the area under the curve (auc) of prl response to gnrh did not change significantly in both experiments. in group 2, during both experiments basal levels of prl and the auc of prl increased significantly on days 10 (p 0.05) and 20 (p 0.05) as compared to day 0 and then they decreased significantly on day 30 as compared to day 20 (p 0.05).",our study demonstrates for the first time that raloxifene and clomiphene affect the secretion of prl in postmenopausal women in a similar manner. it is suggested that oestradiol stimulates the secretion of prl in women by acting through oestrogen receptors.,Medication
"is anhedonia , but not irritability , associated with illness severity outcomes in adolescent major depression?","unlike adult major depressive disorder (mdd) which requires anhedonia or depressed mood for diagnosis, adolescent mdd can be sufficiently diagnosed with irritability in the absence of the former symptoms. in addition, the current diagnostic and statistical manual of mental disorders (dsm) schema does not account for the interindividual variability of symptom severity among depressed adolescents. this practice has contributed to the high heterogeneity and diagnostic complexity of adolescent mdd. here, we sought to examine relationships between two core symptoms of adolescent mdd - irritability and anhedonia, assessed both quantitatively and categorically - and other clinical correlates among depressed adolescents. ninety adolescents with mdd (51 females), ages 12-20, were enrolled. anhedonia and irritability scores were quantified by summing related items on the children's depression rating scale-revised and the beck depression inventory. extremes of score distribution were defined as high or low irritability/anhedonia subgroups. a significance level of p0.01 was set to adjust for the five comparisons. despite all subjects exhibiting moderate to severe mdd, both irritability and anhedonia scores manifested a full and normally distributed severity range including the lowest values possible. however, only anhedonia severity was associated with more severe clinical outcomes, including greater overall illness severity (p0.001), suicidality scores (p0.001), episode duration (p0.006), and number of mdd episodes (p0.01). similarly, only the high-anhedonia subgroup manifested more severe outcomes; specifically, greater illness severity (p0.0001), number of mdd episodes (p0.01), episode duration (p0.01), and suicidality scores (p0.0001).","our findings suggest the significance of anhedonia as a hallmark of adolescent mdd and the need to incorporate dimensional analyses. these data are preliminary, and future prospective studies are needed to better characterize the syndrome of adolescent mdd.",Diagnosis
is enterocele correctable using the ripstein rectopexy?,"about one-third of the patients with rectal prolapse or rectal intussusception have concurrent enterocele at defecography. the purpose of this study was to evaluate the effect of the ripstein procedure on the concurrent enterocele and to study the outcome of the procedure with respect to the patients' symptoms. twenty-two patients with enterocele and either rectal prolapse or rectal intussusception at defecography were treated using the ripstein procedure. postoperatively, the patients were evaluated with clinical examination (22 patients) and defecography (16 patients). none of the patients had recurrence of enterocele, rectal prolapse, or intussusception at postoperative follow-up. continence was improved in 15 of 16 incontinent patients. emptying difficulties were unchanged in eight patients, improved in five patients, and had deteriorated in four patients.","enterocele is corrected by using the ripstein rectopexy. persisting defecation difficulties after the ripstein procedure are unlikely to be secondary to enterocele. the ripstein procedure can be an alternative in the treatment of enterocele, as a majority of these patients also have rectal prolapse or rectal intussusception.",Treatment
are hla-drb1 alleles associated with the clinical course of disease and steroid dependence in mexican patients with ulcerative colitis?,"the aim of this study was to study the association between the hla-drb1 alleles and the clinical course of ulcerative colitis (uc). seventy-five mexican patients with uc were studied. high resolution hla typing was performed using polymerase chain reaction-sequence specific oligonucleotide pcr-sso reverse dot blot and polymerase chain reaction-single specific primer pcr-ssp. molecular typing techniques were applied to define hla-drb1 alleles. seventy-five patients (36 female patients, 39 male patients) were studied. significant associations were found between some hla-drb1 alleles and the clinical course of disease: initial active and then inactive and the hla-drb114 allele (p 0.03; or 4.63; 95 ci: 1.08-21.23); and hla-drb108 allele (p 0.04; or 4.34; 95 ci: 1.9-33.3). on the other hand, the hla-drb107 (p 0.001; or 9.76 95 ci: 1.55-65.56) was significantly associated with steroid dependence in uc patients.",this study suggests that hla-drb1 alleles were associated with the clinical course of disease and steroid dependence in uc patients.,Medication
does oxytocin improve cytological and histological profiles of vaginal atrophy in postmenopausal women?,"to investigate if topical oxytocin can reverse vaginal atrophy, as assessed by cytological and histological examination of the vaginal mucosal epithelium, in postmenopausal women after 12 weeks of treatment as compared to placebo. sixty-eight postmenopausal women diagnosed with vaginal atrophy were randomized for this multicenter, double-blinded, placebo-controlled trial. thirty-three women received 600 iu vagitocin, an oxytocin containing gel, and 35 women received a placebo gel intravaginally. the dose was 600 iu daily for the first two weeks and thereafter 600 iu twice a week for 10 weeks. all participant women underwent four visits and a subgroup of 20 women had a further fifth visit. vaginal smears for cytological evaluation were collected at all visits. vaginal biopsies were taken in 20 women before and after 12 weeks of treatment for histological analysis. in these women a vaginal smear was also collected after 14 weeks. the increase in the percentage of superficial cells between 0 and 2 weeks was significantly greater after treatment with vagitocin in comparison with placebo (p 0.04). the difference in the maturation value between 0 and 12 weeks was significantly higher in the vagitocin than in the placebo group (p 0.01). the reduction in the scores of atrophy was according to the histological investigation significantly greater in the vagitocin group than in the placebo group at 12 weeks (p 0.04).",daily intravaginal treatment with vagitocin 600 iu improves expressions of vaginal atrophy as recorded by cytological investigation of vaginal smears and histological analysis of vaginal biopsies. treatment twice weekly seems to be less effective regarding the increase in superficial cells.,Medication
is charlson comorbidity index an important prognostic factor for long-term survival outcomes in korean men with prostate cancer after radical prostatectomy?,"to analyze overall survival (os), prostate cancer (pca)-specific survival (pcass), and non-pcass according to the charlson comorbidity index (cci) after radical prostatectomy (rp) for pca. data from 336 patients who had rp for pca between 1992 and 2005 were analyzed. data included age, preoperative prostate-specific antigen (psa), prostate volume, clinical stage, and pathologic stage. pre-existing comorbidities were evaluated by the cci, and patients were classified into two cci score categories (0, 1). the mean age of patients was 64.316.12 years. the median psa value (interquartile range, iqr) was 11.30 (7.35 and 21.02) ng/ml with a median follow-up period (iqr) of 96.0 (85.0 and 121.0) months. the mean cci was 0.28 (0-4). five-year os, pcass, and non-pcass were 91.7, 96.3, and 95.2, respectively. ten-year os, pcass, and non-pcass were 81.9, 92.1, and 88.9, respectively. the cci had a significant influence on os (p0.022) and non-pcass (p0.008), but not on pcass (p0.681), by log-rank test. in multivariate cox regression analysis, os was independently associated with the cci hazard ratio (hr)1.907, p0.025 and gleason score (hr2.656, p0.001). pcass was independently associated with pathologic n stage (hr2.857, p0.031), pathologic t stage (hr3.775, p0.041), and gleason score (hr4.308, p0.001). non-pcass had a significant association only with the cci (hr2.540, p0.009).","the cci was independently associated with both os and non-pcass after rp, but the cci had no impact on pcass. the comorbidities of a patient should be considered before selecting rp as a curative modality for pca.",Diagnosis
are duodenal dcytb and hephaestin mrna expression significantly modulated by variations in body iron homeostasis?,"while the upregulation of duodenal cytochrome b (dcytb) within duodenal enterocytes is reported in patients with iron deficiency, the expression of hephaestin (hp) remains controversial in altered iron metabolism states, including hfe associated hereditary hemochromatosis (hh). the effect of iron depletion therapy on the expression of these molecules is unclear. this study examines the duodenal expression of these two molecules in hh patients (prior to and following phlebotomy), in patients with iron deficiency (id) and in healthy controls. using quantitative real-time polymerase chain reaction (qrt-pcr), dcytb and hp mrna expression levels were measured in duodenal tissue of c282y homozygous hh patients, in id patients negative for the c282y mutation with a serum ferritin concentration less than 20 mug/l, and in controls negative for c282y and h63d mutations with normal iron indices. dcytb and hp mrna expression levels were not significantly different in either non-phlebotomized and phlebotomized hh patients or individuals with iron deficiency when compared with controls. there was no significant correlation between the gene expression levels and their respective serum ferritin or ts values in any of the investigated groups. in hh patients, there was no significant association between gene expression and the degree of hepatic parenchymal siderosis identified by perl's iron stain. dcytb and hp mrna levels were significantly correlated to each other when all cohorts were analyzed together and separately.",these findings demonstrate that the duodenal ferroreductase dcytb and ferroxidase hp mrna expression are not significantly altered by variations in iron homeostasis. the effect of phlebotomy-induced erythropoiesis did not alter either gene transcript mrna expression.,Treatment
is malondialdehyde-modified low-density lipoprotein a predictor of cardiac events in patients with stable angina on lipid-lowering therapy after percutaneous coronary intervention using drug-eluting stent?,"patients undergoing lipid-lowering therapy after percutaneous coronary intervention (pci) with drug-eluting stent (des) are subject to residual risk. malondialdehyde-modified low-density lipoprotein (mda-ldl) is suggested as a marker of the initiation and acceleration of atherosclerosis. this study aimed to investigate the impact of mda-ldl on clinical outcomes in patients with stable angina undergoing lipid-lowering therapy after des implantation. in this study, 332 patients whose mda-ldl was measured before pci with des were followed clinically (median 2.9 years). lipid-lowering therapy was conducted, with the target ldl 100 mg/dl. we analyzed the composite of major adverse cardiac events (mace), including cardiac death, myocardial infarction, stent thrombosis, ischemia-driven target lesion revascularization, and any revascularization. mace was observed in 64 patients (19.3). mda-ldl was significantly higher in the mace group (139.1 53.2u/l vs. 106.5 38.3u/l, p 0.01). univariate cox regression analysis indicated a significant relationship between mace and hemodialysis (hazard ratio (hr) 4.60; p 0.01), mda-ldl (per 10u/l, hr 1.14; p 0.01), multivessel disease (hr 1.78; p 0.02), and high-density lipoprotein (per 10 mg/dl, hr 0.79; p 0.03). in the multivariate model, hemodialysis (hr 4.10; p 0.01) and mda-ldl (per 10u/l, hr 1.10; p 0.01) remained significant predictors of mace. the optimal mda-ldl threshold for predicting mace was 114.1u/l, identified by the receiver operating characteristic curve.",mda-ldl was associated with future cardiac events in patients with stable angina that underwent lipid-lowering therapy after des-pci.,Treatment
do hiv-1 and il-1 regulate astrocytic cd38 through mitogen-activated protein kinases and nuclear factor-b signaling mechanisms?,"infection with human immunodeficiency virus type-1 (hiv)-1 leads to some form of hiv-1-associated neurocognitive disorders (hand) in approximately half of the cases. the mechanisms by which astrocytes contribute to hiv-1-associated dementia (had), the most severe form of hand, still remain unresolved. hiv-1-encephalitis (hive), a pathological correlate of had, affects an estimated 9-11 of the hiv-1-infected population. our laboratory has previously demonstrated that hive brain tissues show significant upregulation of cd38, an enzyme involved in calcium signaling, in astrocytes. we also reported an increase in cd38 expression in interleukin (il)-1-activated astrocytes. in the present investigation, we studied regulatory mechanisms of cd38 gene expression in astrocytes activated with hiv-1-relevant stimuli. we also investigated the role of mitogen-activated protein kinases (mapks) and nuclear factor (nf)-b in astrocyte cd38 regulation. cultured human astrocytes were transfected with hiv-1(yu-2) proviral clone and levels of cd38 mrna and protein were measured by real-time pcr gene expression assay, western blot analysis and immunostaining. astrocyte activation by viral transfection was determined by analyzing proinflammatory chemokine levels using elisa. to evaluate the roles of mapks and nf-b in cd38 regulation, astrocytes were treated with mapk inhibitors (sb203580, sp600125, u0126), nf-b interfering peptide (sn50) or transfected with dominant negative ib mutant (ibm) prior to il-1 activation. cd38 gene expression and cd38 adp-ribosyl cyclase activity assays were performed to analyze alterations in cd38 levels and function, respectively. hiv-1(yu-2)-transfection significantly increased cd38 mrna and protein expression in astrocytes (p 0.01) in a dose-dependent manner and induced astrocyte activation. il--activation of hiv-1(yu-2)-transfected astrocytes significantly increased hiv-1 gene expression (p 0.001). treatment with mapk inhibitors or nf-b inhibitor sn50 abrogated il-1-induced cd38 expression and activity in astrocytes without altering basal cd38 levels (p 0.001). ibm transfection also significantly inhibited il-1-mediated increases in cd38 expression and activity in astrocytes (p 0.001).","the present findings demonstrate a direct involvement of hiv-1 and virus-induced proinflammatory stimuli in regulating astrocyte-cd38 levels. hiv-1(yu-2)-transfection effectively induced hiv-1p24 protein expression and activated astrocytes to upregulate ccl2, cxcl8 and cd38. in astrocytes, il-1-induced increases in cd38 levels were regulated through the mapk signaling pathway and by the transcription factor nf-b. future studies may be directed towards understanding the role of cd38 in response to infection and thus its role in hand.",Medication
does ccaat/enhancer-binding protein homologous ( chop ) protein promote carcinogenesis in the den-induced hepatocellular carcinoma model?,"c/ebp homologous protein (chop) plays pro-apoptotic roles in the integrated stress response. recently, a tumor suppressive role for chop was demonstrated in lung cancer via regulation of tumor metabolism. to explore the role of chop in hepatocarcinogenesis, we induced hepatocellular carcinoma (hcc) in wild type (wt) and chop knockout (ko) mice using the carcinogen n-diethylnitrosamine (den). analysis of tumor development showed reduced tumor load, with markedly smaller tumor nodules in the chop ko animals, suggesting oncogenic roles of chop in carcinogen-induced hcc. in wt tumors, chop was exclusively expressed in tumor tissue, with minimal expression in normal parenchyma. analysis of human adenocarcinomas of various origins demonstrated scattered expression of chop in the tumors, pointing to relevance in human pathology. characterization of pathways that may contribute to preferential expression of chop in the tumor identified atf6 as a potential candidate. atf6, a key member of the endoplasmic reticulum stress signaling machinery, exhibited a similar pattern of expression as chop and strong activation in wt but not chop ko tumors. because hcc is induced by chronic inflammation, we assessed whether chop deficiency affects tumor-immune system crosstalk. we found that the number of macrophages and levels of ifn and ccl4 mrna were markedly reduced in tumors from chop ko relative to wt mice, suggesting a role for chop in modulating tumor microenvironment and macrophage recruitment to the tumor.",our data highlights a role for chop as a positive regulator of carcinogen-induced hcc progression through a complex mechanism that involves the immune system and modulation of stress signaling pathways.,Prevention
are low testosterone levels related to poor prognosis factors in men with prostate cancer prior to treatment?,"what's known on the subject? and what does the study add? prostate growth is ruled by testosterone. nevertheless, the paradigm that high testosterone levels induce prostate cancer development or lead to a poor prognosis in prostate cancer is not supported by evidence. a growing number of studies suggest that, on the contrary, low testosterone levels are related to poor prognosis features in prostate cancer such as higher prostate-specific antigen or higher gleason score. our experience shows that testosterone levels are related to risk of progression of prostate cancer - those men with lower testosterone levels are at higher risk of progression of their prostate cancer after treatment delivery. low testosterone levels have been related to a higher diagnosis of prostate cancer (pca). hormonal levels have been related to poor prognosis factors in men with pca, mainly after radical prostatectomy. our aim was to determine the relationship between hormonal levels and pca prognosis factors in men with pca prior to the onset of treatment. we prospectively analysed 137 males diagnosed in our centre with pca with 55 core prostate biopsies from february 2007 to december 2009. as part of our clinical protocol, we performed hormonal determination (testosterone and sex hormone binding globulin) following international society of andrology, international society for the study of the aging male and european association of urology recommendations. free testosterone and bioavailable testosterone were calculated using vermeulen's formula. age, prostate-specific antigen (psa), free to total psa, psa density, number of previous biopsies, digital rectal examination staging, gleason score, percentage of tumour in the biopsy sample, bilaterality of the tumour and risk of progression group were prospectively recorded. higher testosterone levels were related to lower digital rectal examination staging (p 0.02) and lower psa level (p 0.05). higher testosterone was not related to lower gleason score (p 0.08). testosterone was inversely related to pca bilaterality (p 0.01) and percentage of tumour in the biopsy (p 0.01). high testosterone levels were found in patients allocated to the low risk of progression group and inversely (p 0.03). in multivariate analysis, higher age and lower testosterone were related to higher d'amico risk of progression.",patients with pca and lower testosterone levels have poor prognosis factors and higher tumour burden before treatment onset. these findings reinforce the idea that low testosterone levels pretreatment are related to a poor prognosis in pca.,Diagnosis
does thoracic epidural anesthesia with ropivacaine compromise the tolerance of acute normovolemic anemia in pigs?,"the initial treatment of an acute blood loss with acellular fluids leads to the dilution of the red cell mass remaining in the vasculature, that is, to acute normovolemic anemia. whether the compensation and, thus, the tolerance of acute anemia, are affected by sympathetic block induced by thoracic epidural anesthesia has not yet been investigated. eighteen anesthetized and mechanically ventilated pigs were instrumented with thoracic epidural catheters and randomly assigned to receive an epidural injection of either 5-ml ropivacaine 0.2 (n 9) aiming for a th5-th10 block or saline (n 9) followed by continuous epidural infusion of 5 ml/h of either fluid. subsequently, acute normovolemic anemia was induced by replacement of whole blood with 6 hydroxyethyl starch solution until a ""critical"" limitation of oxygen transport capacity was reached as indicated by a sudden decrease in oxygen consumption. the critical hemoglobin concentration quantified at this time point was the primary endpoint; secondary endpoints were hemodynamic and oxygen transport parameters. thoracic epidural anesthesia elicited only a moderate decrease in mean arterial pressure and cardiac index and a transient decrease in oxygen extraction ratio. during progressive anemia, the compensatory increases in cardiac index and oxygen extraction ratio were not compromised by thoracic epidural anesthesia. critical hemoglobin concentration was reached at identical levels in both groups (ropivacaine group: 2.5 0.6 g/dl, saline group: 2.5 0.6 g/dl).","thoracic epidural anesthesia with ropivacaine 0.2 does not decrease the tolerance to acute normovolemic anemia in healthy pigs. the hemodynamic compensation of acute anemia is fully preserved despite sympathetic block, and the critical hemoglobin concentration remains unaffected.",Medication
are serum m30 levels associated with survival in advanced gastric carcinoma patients?,"cytokeratin 18 (ck-18) is a cytoskeleton protein of epithelial cells which are released into the circulation during necrotic or apoptotic cell death. m30 detects caspase-cleaved neo-epitope of ck-18; whereas m 65 measures whole length intact protein. we aimed to evaluate the prognostic significance of serum m65 and m30 levels in patients with gastric carcinoma. thirty eight patients with advanced disease were included in the study. thirty-two healthy people were chosen as control group. serum m65 and m30 levels were measured by quantitative elisa method. serum m65 levels were found significantly elevated in patients compared to control group (385.7/-280.6 vs. 200.2/-164.5, p0.002). serum m30 levels were significantly increased in patients compared to the control group (204.6/-245 vs. 106.5/-17.5, p0.03). patients with metastatic disease had significantly higher levels of serum m30 compared to patients with locally advanced disease (267.1/-296.1 vs. 102.3/-53.2, p0.03). serum m30 and m65 levels were evaluated in respect to survival. best cut-off value for the prediction of death for m30 antigen level was 83.8u/l. patients with higher m30 levels had significantly shorter median survival compared to patients' lower serum m30 levels. however, there was no impact of serum m65 levels on survival. serum m30 levels and clinical stage were found as the strongest variables with independent prognostic value for overall survival.",these results suggest that serum m65 and m30 levels were elevated in patients with advanced gastric carcinoma patients. serum m30 levels can be helpful to predict tumor load and also survival.,Diagnosis
does near-infrared spectroscopy in carotid artery stenting predict cerebral hyperperfusion syndrome?,"cerebral hyperperfusion syndrome (chs) following carotid artery stenting (cas) or carotid endarterectomy (cea) is rare but often fatal once intracranial hemorrhage has occurred. in particular, chs occurs significantly earlier after cas than after cea. thus a monitoring method for early detection of chs is required. near-infrared spectroscopy (nirs) provides a noninvasive monitoring technique for assessing regional cerebral oxygen saturation (rso2). this study evaluated the usefulness of transcranial nirs during cas for prediction of chs. periprocedural rso2 was monitored in 64 cases of cas (52 men, 12 women; 71 /- 6.6 years). the average degree of carotid stenosis was 76.8 /- 11.3 by north american symptomatic carotid endarterectomy trial criteria. bifrontal rso2 was monitored during the procedure using nirs. seventeen patients were symptomatic and 47 were asymptomatic. chs was diagnosed by increased cerebral blood flow by spect performed on the day after treatment with deterioration of neurologic symptoms. chs was observed in two cases (3.1). in the chs group, post-reperfusion rso2 values increased 24 from baseline until 3 minutes after reperfusion. in the non-chs group, the normal upper limit (nul) of the rso2 change was set at 10.0 at 3 minutes after reperfusion. in the chs group, rso2 at 3 minutes after reperfusion was markedly higher than the nul. in patients showing an rso2 at 3 minutes after reperfusion increased by more than 10.0, chs following cas could be predicted.",periprocedural increases in regional cerebral oxygen saturation measured by near- infrared spectroscopy can be an excellent predictor of cerebral hyperperfusion syndrome after carotid artery stenting.,Treatment
do medical students benefit from learning about patient safety in an interprofessional team?,"safe clinical practice is inextricably linked to team-working. delivering patient safety education interprofessionally heightens students' awareness of the importance of effective team-working for safe care and care delivery. we conducted a comparative study using mixed-method analysis among medical students learning about patient safety, either uni- or interprofessionally, towards the end of their training. emphasis is placed on the detailed analysis of qualitative data relating to student perceptions of the event before and afterwards. all medical students, whether working uni- or interprofessionally, increased their knowledge across all eight learning outcomes (p 0.001). although students said they felt more comfortable when learning alongside other medical students, those who learned with other disciplines gained added value from these interactions and were able to frame their thinking more clearly within the context of safe interprofessional team-working.",designing a team-based patient safety event to take place towards the end of medical education can enable students to assimilate all aspects of their curriculum relevant to safety. the link between team factors and the safety agenda is increased when students learn interprofessionally.,General
does inflammatory burden interact with conventional cardiovascular risk factors for carotid plaque formation in rheumatoid arthritis?,"patients with ra have an increased risk of atherosclerosis and cardiovascular (cv) diseases compared with the general population. the aim of this study was to evaluate the role of inflammatory burden in the formation of carotid plaques in patients with ra. we performed carotid artery us to measure the carotid intima-media thickness (imt) and plaques in 406 patients with ra and 209 age- and sex-matched healthy controls. to assess the inflammatory burden, the area under the curve (auc) of esr over time was calculated. the carotid plaque frequency and mean imt were significantly increased in patients with ra relative to controls. after adjustment for age and gender, the presence of carotid plaques in patients with ra was associated with haq score, tender joint count (tjc), swollen joint count (sjc), 28-joint das, esr, crp, lef use, current corticosteroid dose and the number of conventional cv risk factors. after multivariate regression analysis, the factors significantly associated with plaque formation were tjc (p 0.002), esr (p 0.002) and the number of conventional cv risk factors (p 0.041). among 194 ra patients with esr auc data, the presence of carotid plaque was independently associated with both the esr auc and number of conventional cv risk factors, which showed a synergistic interaction.",cumulative inflammatory burden contributes to the development of carotid atherosclerosis through a synergistic interaction with conventional cv risk factors in patients with ra.,Prevention
does combination of low doses of intrathecal ketamine and midazolam with bupivacaine improve postoperative analgesia in orthopaedic surgery?,"intrathecal ketamine produces a short period of analgesia with stable haemodynamics. midazolam with bupivacaine prolongs the duration of analgesia when administered intrathecally but does not prevent hypotension. the objective of this study was to assess the effect of a combination of intrathecal bupivacaine, ketamine and midazolam on the duration of analgesia and haemodynamic parameters. a prospective, randomized, double-blind study was carried out in 60 asa i and ii patients undergoing lower limb surgery under spinal anaesthesia. patients were divided into three groups of 20 each. patients in all the three groups received 3 ml of hyperbaric bupivacaine (0.5) intrathecally. in addition, patients in groups ii and iii received intrathecal ketamine (0.1 mg kg-1) and the same dose of ketamine along with midazolam (0.02 mg kg-1), respectively. all patients were evaluated for block characteristics, duration of pain-free period, total rescue analgesic requirement in the 24-h postoperative period, total dose of mephenteramine to treat hypotension and any central or neurological complication. no patients in group ii required mephenteramine while 40 of patients in group i and 10 in group iii required mephenteramine to maintain blood pressure after spinal anaesthesia. the mean /- standard deviation duration of pain-free period was 331.5 /- 89.9, 369.7 /- 124.2 and 730.5 /- 81.5 min in group i, ii and iii, respectively. the pain-free interval was significantly greater in group iii compared to groups i and ii (p 0.001). no patient had any complications.","a low dose of midazolam and ketamine with bupivacaine intrathecally results in prolonged analgesia and less haemodynamic fluctuations. however, the safety of this combination needs to be proved before its use in clinical practice.",Treatment
do advances in digital quantification technique enhance discrimination between mild and advanced liver fibrosis in chronic hepatitis c?,"the necessity of liver biopsy for staging fibrosis and its quantification in patients with chronic hepatitis c (chc) remains controversial. semiquantitative scoring of fibrosis is considered more subjective and less objective than digital quantification by image analysis. however, measurement of fibrosis using digital image analysis is thought to be less reliable in determining early stage fibrosis as compared with advanced fibrosis or cirrhosis. our aims were to correlate all ishak stages of fibrosis (0-6) with fibrosis percentage () using computerized digital image analysis, and thereby seek to improve discrimination between varying levels of liver fibrosis. fibrosis data were obtained by image analysis on 164 trichrome-stained liver biopsies from untreated patients with chc, representing all ishak stages of fibrosis. digital analysis of fibrosis was highly correlated with ishak scores of fibrosis (kendall's tau-beta0.86, p0.001). receiver-operator characteristic curves showed reliable discriminative capability of our digital image measurement of fibrosis when compared with semiquantitative assessments of fibrosis. excellent interobserver reliability was found.","recent advances in digital quantification of fibrosis have resulted in improved discrimination between the varying stages of liver fibrosis, including mild fibrosis. this method is reproducible, can detect early as well as advanced fibrosis or cirrhosis, may prove to be the best assessment of mild fibrosis, and may be more precise than semiquantitative estimation of changes for monitoring fibrosis progression or regression during clinical therapeutic trials.",Diagnosis
does resorcinol peel as a possible self-treatment of painful nodules in hidradenitis suppurativa?,"hidradenitis suppurativa (hs) is a chronic, inflammatory skin disease characterized by abscess formation localized to apocrine sweat gland-bearing skin. the most important factor in patients' overall assessment of disease severity is pain. the duration of abscesses takes days to weeks and are always painful. to assess the efficacy of self-treatment with topical 15 resorcinol in an open study. the case notes of 12 women with stage 1 or 2 hs treated with topical resorcinol and followed up for at least 1 year were reviewed. the patients rated the efficacy of treatment on global maximum pain of nodules and abscesses on a visual analogue scale (vas) and by self-report of the mean duration (days) of a painful lesion. all patients experienced a significant decrease in pain as assessed by vas and reported a reduction in mean duration of the painful abscesses.",topical treatment with 15 resorcinol reduced pain from painful nodules in all patients with hs. further trials are warranted to confirm these results.,Treatment
do milder liver cirrhosis and loss of serum hbeag imply lower risk for hepatocellular carcinoma development in hbv-related cirrhosis?,"serum hbeag status and liver cirrhosis severity at the time of diagnosis of hepatocellular carcinoma (hcc) in hepatitis b virus (hbv)-related cirrhosis remain inconclusive. the aim was to investigate the status of hbeag and cirrhosis severity at the time of hcc development in the natural history of hbv-related cirrhosis in mainland china. in a retrospective cross-sectional hospital-based setting, hbeag status and severity of underlying cirrhosis, estimated by meld (model for end-stage liver disease) scores and aspartate aminotransferase (ast)--to-platelet ratio index (apri), were comprehensively compared in 377 hbsag-positive compensated and decompensated liver cirrhosis and 434 with hcc patients to clarify the independent and joint effects of the factors. the majority (80.6) of the hcc patients was negative for serum hbeag. more than two-thirds of the patients with hcc had meld scores or 20, the odds ratio of hcc development in the patients with hbeag negativity and meld score 10 was 26.51 (95ci: 8.98-78.28).",a large proportion of hbv-related cirrhotic patients had negative serum hbeag and mild cirrhosis severity at the time of diagnosis of hcc.,Diagnosis
is efficacy of sandostatin lar ( long-acting somatostatin analogue ) similar in patients with untreated acromegaly and in those previously treated with surgery and/or radiotherapy?,"somatostatin analogues have been used as an adjunct to surgery and radiotherapy in the treatment of acromegaly for over 15 years, but debate surrounds their use as primary therapy. newman suggested that octreotide was equally effective as primary or adjuvant therapy, but the effects of previous surgery/radiotherapy may have led to a preselection bias. in an attempt to eliminate this bias, the efficacy of the depot somatostatin analogue sandostatin lar as primary and adjuvant therapy has been assessed using gh and igf-i levels at diagnosis as baseline values. we retrospectively analysed the gh and igf-i data from a large multicentre study in which patients' biochemical response to treatment with the depot somatostatin analogue sandostatin lar as primary and adjuvant therapy was assessed. we used gh and igf-i levels at diagnosis as baseline values to eliminate any preselection bias. in 91 patients (42 male) studied, mean serum gh fell from 36.2 /- 3.3 micro g/l (sem) at diagnosis to 2.2 /- 0.2 micro g/l after 48 weeks of treatment (p 0.0001). in the primary (n 34) and adjuvant (n 57) therapy groups, mean gh fell from 30.7 /- 5.7 to 2.6 /- 0.4 micro g/l (p 0.0001) and from 39.5 /- 4.1 to 2.0 /- 0.2 micro g/l (p 0.0001), respectively. sixty-two percent of patients in the primary therapy group and 70 in the adjuvant therapy group achieved gh 2 micro g/l. serum igf-i levels were available in 67 patients (34 male). in the primary therapy group (n 25) mean igf-i fell from 764 /- 68 to 414 /- 31 micro g/l (p 0.0001) at 48 weeks. in the adjuvant therapy group (n 42) mean igf-i was 666 /- 50 micro g/l, falling to 384 /- 30 micro g/l (p 0.0001) at 48 weeks. 72 of patients achieved normal age-related igf-i-values. there were no statistically significant differences in gh or igf-i levels between the primary and adjuvant therapy groups at diagnosis, pre sandostatin lar or after 48 weeks of treatment.","this retrospective study demonstrates that in a group of patients with similar diagnostic gh and igf-i levels, sandostatin lar was equally effective as primary therapy in acromegalic patients as in patients previously treated with surgery and/or radiotherapy.",Treatment
does selective bowel decontamination improve the survival of 90 hepatectomy in rats?,"clinically, hepatectomy is a clean procedure performed without routine antimicrobial prophylaxis, regardless of the extent of liver loss. translocation of endotoxin has been recognized as a fatal complication leading to liver failure. after extended hepatectomy, the portal hypertension, mucosal damage, intrahepatic bile acid retention, inhibited enterokinesia, and so forth are likely to contribute to enhanced endotoxin absorption. the effect of selective bowel decontamination (sbd) on the prognosis of hepatectomy were investigated. we adopted rat models of partial hepatectomy (70, phx) and subtotal hepatectomy (90, shx), gentamicin or saline of the same amount was administrated preoperatively. liver damage makers, portal and systemic lipopolysaccharide, mucosal damage, signaling pathways, liver regeneration, and bile canalicular networks reconstruction were investigated. we found that shx but not phx resulted in significantly enhanced portal and systemic endotoxin. inhibition of gastrointestinal gram-negative bacteria by gentamicin significantly reduced lipopolysaccharide levels and improved survival after shx (56 with gentamicin, 24 with saline, p 0.05). we also found sbd with gentamicin protected intestinal mucosa barrier, alleviated liver parenchymal damage, and promoted liver regeneration and bile canalicular networks reconstruction after extended liver resection.",we conclude that sbd is beneficial and necessary for extended hepatectomy.,Treatment
does bee 's honey attenuate non-alcoholic steatohepatitis-induced hepatic injury through the regulation of thioredoxin-interacting protein-nlrp3 inflammasome pathway?,"we aim to examine whether honey ameliorates hepatic injury in non-alcoholic steatohepatitis (nash) animal and cell line steatosis models. nash was induced in female sprague-dawley rat by 8-week feeding with a high-fat diet. during the experiment, 5 g/kg honey was intragastrically fed daily. rat normal hepatocyte brl-3a cell was treated with sodium palmitate (sp) to induce steatosis in the absence or presence of honey pre-treatment or specific sirna/overexpress plasmid of thioredoxin-interacting protein (txnip) or antagonist/agonist of nod-like receptor protein 3 (nlrp3). honey significantly improved the high-fat-diet-induced hepatic injury, steatosis, fibrosis, oxidative stress, and inflammation in rats. honey also inhibited the overexpression of txnip and the activation of nlrp3 inflammasome. these effects were replicated in brl-3a cell line which showed that the down-regulation of txnip or inhibition of nlrp3 contributed to the suppression of nlrp3 inflammasome activation, inflammation, and re-balanced lipid metabolism. in contrast, overexpression of txnip or agonism of nlrp3 exacerbated the cellular damage induced by sp.",suppression of the txnip-nlrp3 inflammasome pathway may partly contribute to the amelioration of hepatic injury during the progression of nash by honey. targeting hepatic txnip-nlrp3 inflammasome pathway is a potential therapeutic way for the prevention and treatment of nash.,Medication
does scintigraphy demonstrate high rate of false-positive results from glucose breath tests for small bowel bacterial overgrowth?,"breath tests for hydrogen and/or methane are used to detect small bowel bacterial overgrowth (sbbo), but false-positive results can arise from clinical conditions that accelerate small bowel transit and deliver unabsorbed glucose to the colon. we investigated the prevalence of false-positive results from glucose breath tests by also evaluating patients with scintigraphy. in a retrospective study, we reviewed data from glucose breath tests performed with concurrent scintigraphy on 139 patients with suspected sbbo at the medical college of wisconsin from january 2003 through july 2013. results from breath tests were considered abnormal (positive) if there was an increasing curve of hydrogen or methane by 15 parts per million above baseline within 90 minutes. scintigraphy was used to determine whether this increase occurred before or after the glucose bolus arrived at the cecum. data from a subset of 45 patients with prior upper gastrointestinal surgery were analyzed separately. forty-six of the patients (33) had abnormal results from breath tests. on the basis of scintigraphy findings, 22 of these patients (48) had false-positive results, which were caused by colon fermentation of unabsorbed glucose. colon fermentation caused false-positive results in 65 of patients who had undergone upper gastrointestinal surgery and 13 of patients without prior surgery. patients with false-positive results caused by colonic fermentation had shorter mean oro-cecal transit times (18 minutes) compared with patients with positive breath-test results because of sbbo (79 minutes) or negative results (86 minutes).",almost half of positive results from glucose breath tests are false because of colonic fermentation. all patients with abnormal results from breath tests should be considered for confirmatory repeat breath testing with concurrent scintigraphy to distinguish sbbo from colonic fermentation. most patients who have undergone upper gastrointestinal surgery have abnormal results from breath tests and should be assessed by using concurrent scintigraphy with the initial breath test.,Treatment
is phosphatidylinositol 3-kinase required for platelet-derived growth factor 's actions on hepatic stellate cells?,"platelet-derived growth factor (pdgf) is the most potent mitogen for hepatic stellate cells (hscs) in vitro. the aim of this study was to investigate the role of phosphatidylinositol 3-kinase (pi 3-k) activation in mediating the biological effects of pdgf on cultured hscs and its involvement in vivo. hscs were isolated from normal human livers. pi 3-k was assayed on phosphotyrosine or pdgf-receptor immunoprecipitates by in vitro kinase assay. incubation of hscs with pdgf caused a time-dependent increase in pi 3-k activity. immunoprecipitation of pdgf-alpha and -beta receptors showed that both subunits associate with active pi 3-k in pdgf-stimulated hscs. wortmannin, a specific pi 3-k inhibitor, dose-dependently blocked pi 3-k activity induced by pdgf and inhibited dna synthesis. pdgf (homodimer)-bb also stimulated hsc chemotaxis, which was inhibited by pretreatment with wortmannin. to explore the potential role of pi 3-k in vivo, liver homogenates from rats treated with ccl4 and from control rats were immunoprecipitated with anti-pdgf-beta-receptor antibodies. liver injury was associated with increased pdgf-beta-receptor autophosphorylation, and greater pi 3-k activity associated with the receptor itself.","this study shows that in cultured hscs, pi 3-k activation is necessary for both mitogenesis and chemotaxis induced by pdgf and that this pathway is up-regulated during liver injury in vivo.",Medication
does expression of the extracellular matrix protein tenascin-c vary during lactation?,"women diagnosed with pregnancy-associated breast cancer postpartum have a worse prognosis, stage for stage, than other women with breast cancer. the time of breast involution is tumor promotional. the extracellular matrix protein tenascin-c is upregulated during involution in animal models and promotes breast cancer progression. it interacts with transforming growth factor (tgf), which also is involved in breast involution and breast cancer progression. little is known about the expression of tenascin-c during human breast involution, nor its relationship to tgf. the purpose of this study was to investigate the expression of tenascin-c throughout lactation, as well as its relationship to tgf1 and tgf2. three milk samples from 25 lactating women (transitional, whole, and wean) were collected, separated into components (cells, fat, and skim), and the skim fraction analyzed for total protein, tenascin-c, tgf1, and tgf2. tenascin-c, tgf1, and tgf2 were detectable in all milk samples. highest tenascin-c levels on average were found in whole milk, whereas highest mean tgf1 and tgf2 levels were in wean milk. wean samples on average had higher levels of both tgf1 (26) and tgf2 (500) than matched transitional milk samples. tenascin-c levels in wean milk were associated with nursing length (p 0.048). combining all three milk collection time points, tenascin-c exhibited a weak inverse correlation with tgf1 and tgf2 (p 0.1). the inverse correlation at the wean time point was stronger for tgf2 than -1 (-0.37 versus -0.25). tenascin-c, a protein known to promote breast cancer progression, is expressed throughout lactation.","the inverse correlation with tgf2 in wean milk suggests a possible interaction during breast involution, which should be further investigated.",Diagnosis
do acquisition of early auditory milestones with a cochlear implant?,"speech acquisition after cochlear implant is a long process. various studies have followed the auditory milestones in the early period after implantation. the aim of the present study was to track the development of hearing skills in the early period after cochlear implantation and evaluate which factors influence the process. 195 records of children implanted in the hadassah medical center were examined retrospectively. data on etiology, age at implantation and type of implant were collected. in addition, information on the rate of progress was measured: the first time that there was detection and identification of ling sounds, the first time it was possible to obtain sdt (speech detection threshold), srt (speech reception threshold) and an audiogram, and the first accurate repetition of vcv (vowel consonant vowel) sounds. results show a consistent pattern of auditory milestone acquisition similar to that of normal development, from milestones that do not require decoding beginning with sdt, detection of ling sounds followed by an audiogram which requires cooperation, to tasks that involve decoding starting with srt and repetition of ling sounds and finally vcv repetition. the children implanted before 24 months of age achieved the auditory milestones later than children implanted between 2 and 6 years, apparently since these tasks involve cognitive abilities which are not yet developed in the youngest children. previous hearing experience improved the rate of acquisition of the auditory milestones and progress was faster in the second implanted ear compared to the first implanted ear.",more research is needed to address the relationship between acquisition of early auditory milestones and performance with the cochlear implant later on in life.,General
does proteomic study reveal plasma protein changes in congenital heart diseases?,"congenital heart disease (chd) is the most common birth defect in newborns. plasma proteins may serve as indicators of disease and are a rich source for biomarker discovery, but little has been studied in chd. we examined the hypothesis that plasma proteins may be altered and related to the pathologic changes of chd. differential protein analysis was performed in the plasma of patients with tetralogy of fallot, isolated ventricular septal defect, and normal controls by using two-dimensional electrophoresis and mass spectrometry. candidate proteins that might be related to disease processes were further confirmed by enzyme-linked immunosorbent assay in the new samples (n40). identified were 18 differentially expressed protein spots and 10 corresponding proteins or polypeptides. among those, 2 downregulated proteins, gelsolin, ficolin-3, with significant clinical relevance, were further analyzed for validation. the plasma levels of gelsolin (76.304.42 vs 131.8023.46 g/ml in control; p0.025, n40 in each group) and ficolin-3 (4.930.36 vs 10.581.58 g/ml in control; p0.001, n40 in each group) in tetralogy patients were significantly lower than those in normal controls. the ficolin-3 plasma level was also lower in the patients with isolated vsd (5.550.34 vs 10.581.58 g/ml in control g/ml; p0.003, n40 in each group).",we used proteomic methods to demonstrate for the first time the plasma protein changes in chd patients that may reveal the possible mechanisms for the prolonged bleeding time in tetralogy patients and the susceptibility to pulmonary infections in patients with chds. these findings have strong clinical implications.,Diagnosis
does genetic risk for alcoholism relate to level of response to alcohol in asian-american men and women?,"previous studies have shown that asians who possess a variant aldehyde dehydrogenase allele (aldh22) have lower rates of alcohol consumption and dependence. research in asian men has shown that those with aldh22 have greater responses to alcohol than do those without this genetic variant. the present study was designed to determine whether similar levels of response to alcohol, using objective and subjective measurements, are seen in men and women with different aldh2 genotypes. participants (n 30) were 16 men and 14 women, of whom five each were heterozygous for aldh22. they were evaluated in response to alcohol and placebo beverage challenges, dosed according to estimated body water. objective and subjective responses were measured every 30 minutes from baseline to 150 minutes after ingestion. men and women with aldh21/2 had greater pulse-rate increases, greater observed flushing responses and greater subjective feelings of being dizzy, drunk and high compared with aldh21/1 participants, despite having equivalent breath alcohol concentrations. aldh21/2 participants also reported being less likely to drive, following this level of intoxication, compared with aldh21/1 participants. some gender differences were found in subjective, but not objective, responses to alcohol, with women reporting lower levels of being high, nauseated and uncomfortable and having a lower total subjective rating scale score.",this study suggests that low risk for alcoholism based on possession of an aldh22 allele relates to greater response to alcohol in both men and women.,Symptoms
do natural regulatory t cells inhibit production of cytotoxic molecules in cd8 t cells during low-level friend retrovirus infection?,"cytotoxic t cells (ctl) play a central role in the control of viral infections. their antiviral activity can be mediated by at least two cytotoxic pathways, namely the granule exocytosis pathway, involving perforin and granzymes, and the fas-fasl pathway. it was shown that the level of friend retrovirus (fv) replication determines the cytotoxic pathway for the control of viral infection. in low-level infection only the fas pathway is active, whereas cytotoxic molecules are not produced. in the current study, we elucidate the role of cd4 regulatory t cells (tregs) in suppressing the exocytosis pathway during an asymptomatic low-level infection. we show that even a low-level retrovirus infection induced a strong activation and proliferation of natural tregs. the expanded tregs suppressed the proliferation of virus-specific cd8 t cells and the production of cytotoxic molecules by these cells. not surprisingly, the in vivo killing activity of these cd8 t cells was rather weak. selective depletion of foxp3 tregs resulted in de novo granzyme production and augmented virus-specific in vivo killing, but did not affect the low-level virus replication.",expanded natural tregs determined the cytotoxic pathways of virus-specific effector cd8 t cells during the acute phase of retroviral infection.,Medication
does mercury induce an unopposed inflammatory response in human peripheral blood mononuclear cells in vitro?,"the human immune response to mercury is not well characterized despite the body of evidence that suggests that hg can modulate immune responses, including the induction of autoimmune disease in some mouse models. dysregulation of cytokine signaling appears to play an important role in the etiology of hg-induced autoimmunity in animal models. in this study, we systematically investigated the human immune response to hg in vitro in terms of cytokine release. human peripheral blood mononuclear cells (pbmcs) were isolated from 20 volunteers who donated blood six separate times. pbmcs were cultured with lipopolysaccharide and concentrations of mercuric chloride (hgcl(2)) up to 200 nm. seven cytokines representing important pathways in physiologic and pathologic immune responses were measured in supernatants. we used multilevel models to account for the intrinsic clustering in the cytokine data due to experimental design. we found a consistent increase in the release of the proinflammatory cytokines interleukin-1beta (il-1beta) and tumor necrosis factor-alpha, and concurrent decrease in release of the antiinflammatory cytokines interleukin 1-receptor antagonist (il-1ra) and il-10 in human pbmcs treated with subcytotoxic concentrations of hgcl(2). il-4, il-17, and interferon-gamma increased in a concentration-response manner. these results were replicated in a second, independently recruited population of 20 different volunteers.","low concentrations of hgcl(2) affect immune function in human cells by dysregulation of cytokine signaling pathways, with the potential to influence diverse health outcomes such as susceptibility to infectious disease or risk of autoimmunity.",Medication
does paclitaxel affect the amounts of the n-acetylation of 2-aminofluorene and dna-2-aminofluorene adduct formation in sprague-dawley rats?,"the effects of paclitaxel on the in vivo distribution and the levels of n-acetylation of 2-aminofluorene (af) and af-dna adducts in sprague-dawley (sd) rats were studied. for in vivo examination, pretreatment with paclitaxel (50 mg/kg) 48 hours prior to the administration of af (50 mg/kg) resulted in a 28 and 43 decrease, respectively, in the urinary and fecal recovery of n-acetyl-2-aminofluorene (aaf), and a 22 decrease in the metabolic clearance of af to aaf. paclitaxel did not affect the michaelis-menten parameters for n-acetyltransferase (nat) activity in blood, liver, lung, colon and bladder. similarly, the km value for af in the examined tissues was not affected by paclitaxel. however, the vmax value estimate of liver nat activity was significantly decreased after paclitaxel pretreatment. following exposure of rats to af with and without pretreatment with paclitaxel, dna-af adducts were examined in the target tissues, liver, colon and bladder, and also in non-target tissues, lung and circulating leukocytes. the dna-af adducts in the liver, bladder, lung, colon and leukocytes were decreased by pretreatment with paclitaxel.",this is the first finding to show that paclitaxel affects af distribution and n-acetylation and dna adduct in sd rats in vivo.,General
is a novel synthetic lipopeptide allergy-protective by the induction of lps-tolerance?,"exposure to the environment of traditional farms can protect children from some allergic disease. due to this exposure, tlr2 expression in these children is increased. tlr2 ligands derived from gram-positive bacteria are found in the dust of these farms. we proved whether a synthetic lipopeptide binding to the tlr1/2 heterodimer is able to protect from allergic disease in two different murine models of allergy. we also investigated the immunological mechanisms underlying the protective properties of the lipopeptide. we synthesized a lipopeptide derived from a germination lipoprotein of bacillus cereus (lpgerd). we evaluated the immunomodulatory activity of lpgerd in a murine model of systemic sensitization (ova/alum) and in a model in which mice were sensitized with ova pulsed bone-marrow-derived dendritic cells (bmdcs) via the airways. furthermore, the induction of lps tolerance was studied. treatment of mice with lpgerd in a mouse model of asthma led to protection against sensitization and airway inflammation. similarly, bone-marrow-derived dendritic cells (bmdcs) pre-treated with lpgerd were not able to prime mice for allergic immune response. we observed that pre-treatment with lpgerd led to the induction of a lps-tolerant state in bmdcs. these cells secreted markedly lower amounts of pro-inflammatory cytokines upon lps stimulation. furthermore, we observed an up-regulation of irak-m mrna in bmdcs pre-treated with lpgerd.","our results suggest that induction of a lps-tolerant state in antigen-presenting cells (apcs) may contribute to the protective effect of a farming environment. tlr2 agonists similar to those appearing in cowshed dust extracts, such as our synthetic lpgerd, lead to the ignorance of the lps stimulus, which is important for the activation of apcs to mount a th2 immune response. this substance might be a promising candidate for allergy-preventive treatments as lpgerd had only low pro-inflammatory characteristics.",Treatment
is evidence of endothelial dysfunction in preeclampsia : decreased endothelial nitric oxide synthase expression associated with increased cell permeability in endothelial cells from preeclampsia?,"the purposes of this study were to examine endothelial nitric oxide synthase expression in endothelial cells and to determine whether the inhibition of endothelial nitric oxide synthase could impair endothelial barrier function in preeclampsia. messenger rna and protein expression for endothelial nitric oxide synthase were examined in endothelial cells that were isolated from normal and preeclamptic pregnancies. endothelial monolayer permeable response to interleukin-8 stimulation was determined. normal endothelial cells that were treated with nitric oxide inhibitor were used to test the association of endothelial nitric oxide synthase and endothelial barrier function. messenger rna expression for endothelial nitric oxide synthase was determined by reverse transcription-polymerase chain reaction, and protein expression was determined by western blot analysis. endothelial permeability was measured by horseradish peroxidase leakage through endothelial cell filters. interleukin-8 production was measured by enzyme-linked immunosorbent assay. data were presented as mean/-se and analyzed by analysis of variance or nonparametric mann-whitney test. relative messenger rna expression and protein expression for endothelial nitric oxide synthase were decreased significantly in endothelial cells from preeclampsia compared with cells from normal pregnancies (messenger rna expression, 0.191/-0.057 vs 0.508/-0.061 p 7-fold increase in normal endothelial cells, but only a 4-fold increase in preeclamptic endothelial cells in response to interleukin-8 stimulation at 25 pg/ml. the inhibition of endothelial nitric oxide synthase with n(g)-monomethyl-l-arginine resulted in an increase in interleukin-8-induced endothelial cell permeability. no difference for interleukin-8 production was observed between normal and preeclamptic endothelial cells (1.15/-0.21 ng/mg protein vs 1.29/-0.23 ng/mg protein, p.5).",increased endothelial permeability may be associated with decreased endothelial nitric oxide synthase expression and activity in endothelial cells from preeclampsia.,Symptoms
is retinoic acid a potential negative regulator for differentiation of human periodontal ligament cells?,"retinoic acid (ra) exerts a wide variety of effects on development, cellular differentiation and homeostasis in various tissues. however, little is known about the effects of ra on the differentiation of periodontal ligament cells. in this study, we investigated whether ra can affect the dexamethasone-induced differentiation of periodontal ligament cells. human periodontal ligament cells were differentiated via culturing in the presence of dexamethasone, ascorbic acid, and beta-glycerophosphate for mineralized nodule formation, as characterized by von kossa staining. continuous treatment with all-trans-ra inhibited the mineralization in a dose-dependent manner, with complete inhibition over 1 microm ra. other ra analogs, 9-cis-ra and 13-cis-ra, were also effective. furthermore, addition of ra for just the first 4 days completely inhibited the mineralization; however, as ra was added at later stages of culture, the inhibitory effect was diminished, suggesting that ra had a phase-dependent inhibition of mineralization. ra receptor (rar)-alpha agonist (am-580), but not retinoid x receptor agonist (methoprene acid), inhibited the mineralization, and reverse transcription-polymerase chain reaction analysis revealed that rar-alpha was expressed on the cells, suggesting that rar-alpha was involved in the inhibitory mechanism. this inhibition was accompanied by inhibition of alkaline phosphatase activity; however, neither expression of platelet-derived growth factor (pdgf) receptor-alpha, pdgf receptor-beta, or epidermal growth factor (egf) receptor, nor phosphorylation of extracellular signal-regulated kinases triggered by pdgf-ascorbic acid or pdgf-bb was changed, as assessed by flow cytometry or western blot analyses.",these findings suggest that ra is a potential negative regulator for differentiation of human periodontal ligament cells.,Medication
does endogenous adenosine differentially modulate 5-hydroxytryptamine release from a human enterochromaffin cell model?,"the aim was to determine whether adenosine receptors modulate camp, intracellular free calcium (ca(2)(i)), and 5-hydroxytryptamine (5-ht) release in human carcinoid bon cells. adenosine receptor (r) mrna, proteins, and function were identified by western blots, immunofluorescent labeling, fluo-4/am ca(2)(i) imaging, and pharmacologic/physiologic techniques. a1, a2, and a3rs were present in bon cells and carcinoid tumors. baseline 5-ht levels increased with adenosine deaminase, activation of a2rs, and inhibition of a3rs, whereas a3r activation decreased 5-ht. a2r antagonists or blockade of adenosine reuptake that elevates extracellular adenosine reduced mechanically evoked 5-ht release. in single bon cells, touch elevated ca(2)(i) responses were augmented by adenosine deaminase, a1, and a3r antagonists.",tonic or mechanically evoked release of endogenous adenosine is a critical determinant of differential activation of adenosine receptors and may have important implications for gut mechanosensory reflexes.,Diagnosis
does apoptotic cell death make a minor contribution to reperfusion injury in skeletal muscle in the rat?,"to determine if apoptotic cell death contributes to skeletal muscle reperfusion injury. leg ischaemia was induced in rats with a tourniquet and maintained for 4 h before reperfusion for 24 or 72 h. apoptosis was assessed by morphology, in situ end labelling of dna fragments, dna laddering, expression of p53 mrna and detection of caspase-3-like proteolytic activity. increased caspase-3-like activity was detected in muscle following ischaemia and zero, 24 h or 72 h of reperfusion. levels remained relatively low but with a highly significant difference in enzyme activity between the ischaemic and non-ischaemic legs (p 0.0001, repeated measures analysis of variance). morphological examination showed considerable oedema, disruption of muscle fibres and infiltration of white cells into tissues. muscle nuclei did not show any morphological evidence of apoptosis and were negative for dna fragmentation, while occasional neutrophils contained fragmented dna. expression of p53 was not induced by ischaemia and reperfusion and dna ladders were not detected.",the cells undergoing apoptosis were infiltrating neutrophils rather than muscle cells and reperfused muscle was damaged largely by an inflammatory process involving considerable oedema.,General
do plastic wound protectors affect wound infection rates following laparoscopic-assisted colectomy?,"wound protectors are plastic sheaths that can be used to line a wound during surgery. wound protectors can facilitate retraction of an incision without the need for other mechanical retractors and have been proposed as deterrents to wound infection. the purpose of this study was to define the ability of wound protectors to reduce the rate of infection when used in laparoscopic-assisted colectomy. we completed a retrospective review of the medical records of patients undergoing nonemergent laparoscopic-assisted colectomy between february 1999 and november 2002. all completely laparoscopic cases were excluded. the wound protector, when used, was applied to the extraction incision during the externalized portion of the procedure (colon and mesentery transection, anastomosis). outcomes for patients with and without the use of a wound protector were compared. a total of 141 patients underwent laparoscopic-assisted colectomy (98 for benign/malignant tumors, 35 for diverticular disease, and eight for crohn's disease). there were no differences between the wound protector group ( n 84) and the no wound protector group ( n 57) with respect to mean age (55 vs 58 years), average body mass index (27 vs 29 kg/m2), gender, indication for surgery, comorbidities, antibiotics used, or mean operative time (185 vs 173 min). nine patients in the wound protector group and eight in the no wound protector group developed a wound infection at the colon extraction site ( p 0.42). patients undergoing resection for crohn's disease or diverticulitis had a higher infection rate (18.6) than patients undergoing resection for polyps or cancer (9.2; p 0.05). no wound recurrence of cancer was observed in either group at a mean follow-up of 23 months (range, 3-48).","the wound protector, although useful for mechanical retraction of small wounds, does not significantly diminish the rate of wound infection at the bowel resection/anastomotic site. patients undergoing elective resection for inflammatory processes have higher infection rates than patients undergoing laparoscopic-assisted colectomy for polyps or cancer.",Treatment
is tlr4 required for host resistance in pseudomonas aeruginosa keratitis?,"to determine the role of toll-like receptor 4 (tlr4) in pseudomonas aeruginosa (p. aeruginosa) keratitis in resistant (cornea-healing) balb/c mice. corneal tlr4 mrna levels were tested by real-time pcr in balb/c mice before and after infection. clinical score, slit lamp, histopathology, bacterial counts, and polymorphonuclear neutrophil (pmn) quantitation were performed in the infected cornea of tlr4-deficient (tlr4(lps-d)) and wild-type balb/c mice. mrna for il-1beta, mip-2, ifn-gamma, il-18, inducible nitric oxide synthase (inos), and beta-defensin-2 levels were measured by real-time pcr. protein levels for il-1beta, mip-2, and ifn-gamma were tested by elisa. in resistant balb/c mice, tlr4 mrna expression was significantly upregulated in the cornea after p. aeruginosa infection. in contrast, tlr4-deficient mice were susceptible to infection with p. aeruginosa and showed increased corneal opacity, pmn infiltration, bacterial counts, and perforated infected corneas. after infection, tlr4-deficient mice also showed increased mrna expression of proinflammatory cytokines (il-1beta and mip-2) and type-1-associated cytokines (ifn-gamma and il-18) when compared with wild-type balb/c mice. elisa analyses showed that il-1beta, mip-2, and ifn-gamma protein levels also were significantly upregulated in the cornea of tlr4-deficient versus wild-type mice. in contrast, levels of inos and beta-defensin-2 were significantly decreased in tlr4-deficient compared with wild-type mice.","tlr4 is critical in host resistance to p. aeruginosa, as its deficiency results in increased pmn infiltration and proinflammatory cytokine production, decreased inos and beta-defensin-2 production, impaired bacterial killing, and a susceptible phenotype.",Medication
does abc/xyz estimate intracerebral hemorrhage volume as a percent of total brain volume in children?,"intracerebral hemorrhage volume (ichv) as a percentage of total brain volume (tbv) is a strong predictor of outcome in childhood intracerebral hemorrhage with ichv/tbv 2 associated with functional impairment. we aimed to determine whether easily performed approximations of intracerebral hemorrhage and brain volume can accurately and reliably stratify intracerebral hemorrhage by size. ct scans of 18 children with spontaneous intracerebral hemorrhage were independently reviewed by 4 neurologists. ichv as a proportion of tbv was estimated as abc/xyz expressed as a percentage: a largest axial hemorrhage diameter; blargest axial diameter perpendicular to a on the same slice; and chemorrhage vertical diameter. similarly, xlargest midline axial diameter of supratentorial brain; ylargest axial diameter perpendicular to x; and zbrain vertical diameter. interrater reliability was measured with intraclass correlation coefficients. ichv and tbv were measured using computer-assisted manual segmentation tracings to establish criterion validity. each intracerebral hemorrhage was classified as small (2 tbv). estimates of ichv, tbv, and ichv/tbv using the abc/xyz method had outstanding interrater reliability (intraclass correlation coefficient, 0.95 to 0.99). these estimates were highly correlated with volumetric measures (r20.77 to 0.96). sensitivity of the abc/xyz method for identifying an ichv 2 tbv was 100 (95 ci, 89 to 100). specificity was 95 (95 ci, 83 to 99).","the abc/xyz method accurately and reliably estimates ichv and tbv in children. these values can be used to approximate quickly and easily ichv as a percentage of tbv, which has important prognostic implications.",Diagnosis
"are passiflora actinia hydroalcoholic extract and its major constituent , isovitexin , neuroprotective against glutamate-induced cell damage in mice hippocampal slices?","to investigate whether passiflora actinia hydroalcoholic extract and its major constituent, isovitexin, protect mice hippocampal brain slices from glutamate-induced neurotoxicity. neuroprotective effect of the extract against glutamate-induced excitotoxicity (10 mm) was evaluated through cell viability of hippocampal slices. the extract or its flavonoids were directly applied to hippocampal slices and then subjected to glutamate-induced toxicity. alternatively, hippocampal slices from extract-treated mice were also subjected to the same toxicity protocol. mice supplementation with the extract protected hippocampal slices from in-vitro neurotoxicity. when directly applied to hippocampal slices, the extract showed a higher neuroprotective potential than a commercial dry extract of passiflora incarnata, which was related to p. actinia extract which had higher isovitexin and total flavonoid content expressed as isovitexin. isovitexin, but not apigenin, induced a similar neuroprotective response when applied alone, at a concentration equivalent to that found in the extract.","this study highlights new neuropharmacological activity of the passiflora genus, suggesting that it can act as modulator of the glutamatergic system. the search for improved pharmacotherapies with novel mechanisms of action has been shown of great importance for the treatment of resistant neurological and psychiatric disorders.",Medication
does a novel rantes antagonist prevent progression of established atherosclerotic lesions in mice?,"atherosclerosis is a chronic inflammatory disease that represents the primary cause of death through coronary disease and stroke. chemokines are known to play a crucial role in this disease by recruiting inflammatory leukocytes to the endothelium. recently, the chemokine variant 44aana47-rantes was shown to impair inflammatory cell recruitment in vivo by interfering with heparin binding and oligomerization. in this study we report that curative treatment with 44aana47-rantes limits atherosclerotic plaque formation in ldlr-/- mice. this was associated with reduced infiltration of t cells and macrophages and reduced production of matrix metalloproteinase (mmp)-9. by contrast, the relative smooth muscle cell and collagen content was increased, indicating a more stable plaque phenotype. in addition, we provide evidence for direct inhibition of leukocyte recruitment into aortic root lesions, attenuated leukocyte rolling and arrest in mesenteric vessels, as well as a reduced proinflammatory response following con a stimulation in vitro.","interference with chemokine oligomerization and chemokine/heparin interactions is a powerful novel approach that inhibits progression of established atherosclerosis in mice. by inhibiting leukocyte recruitment into plaques, 44aana47-rantes mediates a less inflammatory plaque phenotype and thus reduced systemic inflammatory state.",Prevention
is short stature an inflammatory disadvantage among middle-aged japanese men?,"a positive association between white blood cell count and carotid atherosclerosis has been reported. our previous study also found an inverse association between height and carotid atherosclerosis in overweight but not non-overweight men. however, no studies have reported on the association between high white blood cell (wbc) count and height accounting for body mass index (bmi) status. we conducted a hospital-based general population cross-sectional study of 3016 japanese men aged 30-59 years undergoing general health check-ups between april 2013 and march 2014. high wbc count was defined as the highest tertiles of wbc count among total subjects. independent of classical cardiovascular risk factors, height was found to be inversely associated with high wbc count, especially for subjects with a bmi 23 kg/m","independent of classical cardiovascular risk factors, height was found to be inversely associated with high wbc count, especially for those with a bmi 23 kg/m",Prevention
does high flow-mediated vasodilatation predict pulmonary edema in liver transplant patients?,"early pulmonary edema is common after orthotopic liver transplantation. associated pathogenic mechanisms might involve increased activity of cardiac-inhibitory systems due to increased vasodilator production, mainly nitric oxide (no). no is primarily responsible for flow-mediated vasodilatation (fmd). we investigated the incidence of pulmonary edema in liver transplant patients and its correlation with fmd. we prospectively evaluated traditional risk factors, doppler echocardiographic findings, derived hemodynamic data, and brachial artery nitroglycerin-induced vasodilatation (ntd) and fmd within 1 week prior to liver transplantation in 54 consecutive liver transplant patients with cirrhosis. post-transplantation chest roentgenography was performed daily. in-hospital outcomes, transfusion volume of blood components, and hemodynamic data during surgery and at the intensive care unit were analyzed. twenty-nine patients (53.7) developed radiological pulmonary edema within 1 week of transplantation. diffuse-type interstitial and alveolar pulmonary edema constituted 13 cases (24.1). patients with pulmonary edema had higher pretransplantation child-turcotte-pugh scores (p 0.01), cardiac output (p 0.03), fmd (p 0.01), ntd (p 0.01), and fmd/ntd ratio (p 0.02). although the total volume of intravenous fluid transfused was higher in the pulmonary edema group, the net fluid retention during surgery was statistically insignificant. the lengths of intensive care unit stay and hospitalization, as well as mortality rates, were not different in these groups.","the high incidence of pulmonary edema after living donor liver transplantation was associated with a high fmd and fmd/ntd ratio at pretransplantation. fmd is the only significant predictor associated with pulmonary edema. however, we observed no alteration in mortality rates.",Treatment
"is expression of the psoriasis-associated antigen , pso p27 , inhibited by traditional chinese medicine?",pso p27 is shown to be an autoantigen in psoriasis and the objective of the present study was to investigate whether traditional chinese medicine (tcm) would influence the expression of pso p27. skin biopsies obtained from psoriatic patients before and after treatment with tcm were analyzed for the presence of pso p27 antigen by indirect immunofluorescence using murine monoclonal antibodies against pso p27. a significant reduction in the amount of pso p27 in the psoriatic skin was obtained after treatment with tcm for 3 months.,the presence of pso p27 in psoriatic skin is reduced when psoriatic patients are treated with tcm.,Treatment
does effect of recombinant human erythropoietin on transfusion need in preterm infants?,"to study the efficacy, safety and cost effectiveness of recombinant human erythropoietin (r-huepo) in reducing erythrocyte transfusion needs in very low birthweight (vlbw) infants. we conducted a non-blind randomized controlled trial and assigned 100 vlbw infants, less than 33 weeks gestation, to receive either r-huepo 750 u/kg per week subcutaneously from day 5 to day 40 or no erythropoietin (epo). infants received oral iron 3-6 mg/kg per day from day 10. transfusion needs were analysed for all enrolled infants and in five weight subgroups: birthweight of less than 600 g, 600-799 g, 800-999 g, 1000-1199 g and infants more than 1200 g. vlbw infants on r-huepo attained higher reticulocyte counts and haematocrit than control infants but the mean number of transfusions and volume of erythrocyte transfused per infant were not statistically different. of infants 800-999 g at birth, the mean number of transfusions per infant was 2.1 compared with 3.5 transfusions per control infant (p 0.04). volume of erythrocytes transfused was 34.9 /- 32.1 ml/kg in r-huepo-treated infants and 56.6 /- 25.8 ml/kg in control infants (p 0.03). the cost per patient for transfusion and epo was s388 for r-huepo recipient and s438 for control infant. blood pressure, neutrophil count, platelet count and complications of prematurity were not significantly different in both groups of vlbw infants.",r-huepo at 750 u/kg per week stimulates erythropoiesis in vlbw infants but significantly reduces the need for erythrocyte transfusion only in infants weighing 800-999 g at birth.,Treatment
is the protective effect of dexmedetomidine on bupivacaine-induced sciatic nerve inflammation mediated by mast cells?,"this study was designed to assess the correlation between the neuroprotective effect of dexmedetomidine and oxidative stress, neural inflammation and mast cell stability in rats with bupivacaine-induced sciatic nerve toxicity. forty adult wistar albino rats, eight rats per group, were used. saline (0.3 ml of 0.9), dexmedetomidine (20 g/kg), 0.5 bupivacaine or 0.5 bupivacainedexmedetomidine (20 g/kg) was injected into the sciatic nerve. a control group of rats received no injection. fourteen days after injection, the sciatic nerves were harvested and total oxidant status, total anti-oxidant status, paraoxonase-1, galectin-3 and matrix metalloproteinase 2 and 9 levels were measured in the sciatic nerves. in addition, the presence and status of inflammation, edema, and mast cells were evaluated histopathologically. the combination of dexmedetomidine and bupivacaine alleviated oxidative stress. in addition, it decreased matrix metalloproteinase 9 and galectin-3 levels and increased matrix metalloproteinase 2 levels. moreover, it stabilized recruited mast cells at the injury site; however, it did not significantly decrease inflammation or edema.",dexmedetomidine may ameliorate bupivacaine-induced neurotoxicity by modulating mast cell degranulation. the neuroprotective effect of dexmedetomidine may make it a suitable adjuvant agent to local anesthetics in peripheral nerve blocks.,Medication
does chronic ethanol consumption alter recovery of spontaneously active medial septal/diagonal band of broca neurons from gaba-microiontophoresis?,"acute ethanol administration increases gaba-mediated inhibition in a variety of cerebral cortical preparations. furthermore, chronic ethanol administration blunts ethanol-induced increases in gaba-mediated inhibition and alters gaba a receptor subunit mrna and peptide expression in the cerebral cortex. the sedative hypnotic effects of ethanol are believed to be modulated by gaba-induced inhibition in medial septum/diagonal band of broca (ms/db) neurons, a brain region where acute ethanol administration increases gaba-mediated inhibition of spontaneously active neurons. chronic ethanol administration produces tolerance to the sedative effects of ethanol. however, it is unknown if chronic ethanol consumption produces alterations in gaba-mediated inhibition in the ms/db in a manner similar to that found in the cerebral cortex. animals either consumed ethanol chronically for 14 days via a liquid diet or were pair-fed an equicaloric dextrose-containing control diet. spontaneously active ms/db neurons were recorded using multibarrel glass micropipettes while the effect of gaba-microiontophoresis was investigated. the total amount of gaba-mediated inhibition at four ejection currents was analyzed, as was the recovery to spontaneous neural firing rates following gaba inhibition. in a separate group of animals, the medial septum was microdissected, and the relative expression of gaba a receptor alpha1 and alpha4 subunit peptide were analyzed via western blot analysis. chronic ethanol consumption altered recovery of spontaneous neural activity of ms/db neurons following gaba-microiontophoresis compared to premicroiontophoresis levels. specifically, the recovery of spontaneous neural activity of ms/db neurons recorded from animals that chronically consumed ethanol was slower following gaba-microiontophoresis compared to neurons recorded from control animals. this effect was temporary and reversible. furthermore, the alteration in recovery of spontaneous neural activity was not due to changes in the total amount of inhibition produced by gaba. finally, there was no significant change in gaba a receptor alpha1 and alpha4 subunit peptide levels in the ms/db.",chronic ethanol consumption alters the frequency of spontaneous ms/db neural activity following gaba microiontophoresis compared to premicroiontophoresis levels. these data suggest that the kinetics of gaba a receptors in the ms/db are altered by chronic ethanol consumption independent of changes in the total amount of inhibition or alterations in gaba a receptor alpha1 and alpha4 subunit peptide expression.,Medication
is fragile histidine triad ( fhit ) gene overexpressed in colorectal cancer?,"fhit gene, mapped at fra3b site, encodes human diadenosine triphosphate hydrolase involved in the regulation of cell cycle and nucleotide metabolism. decreased fhit gene expression was previously observed in various types of human cancer, however, quantification of fhit mrna was seldom performed. to investigate loss of heterozygosity (loh) at fra3b, expression of fhit gene at the mrna and protein levels in sporadic colorectal carcinoma (crc) and benign colon adenoma. fhit mrna was quantified by the validated realtime pcr (qpcr) in tumor samples of 84 crc patients and mucosal biopsies of 15 adenomas, in comparison to 37 control patients, whereas subgroup of 57 crc, 10 adenoma and 10 control cases were selected for immunohistochemical (ihc) detection of the native fhit protein and loh determination at fra3b. higher level of fhit mrna was found in 86 of crc (p0.001) and 60 of adenomas (p0.016). ihc showed comparable results to qpcr (p0.003), revealing the strongest presence of fhit protein in dukes' c/d stages (p0.001) and n1/n2 lymph nodes metastasis in crc (p0.04). fhit gene expression and dukes' and g staging were positively correlated in crc as analyzed by qpcr and ihc. deletion analysis of the fragile fra3b site revealed the highest loh frequency at d3s1234 in 32.5 of crc informative cases, however, loh did not correspond to qpcr, ihc or clinical-pathological variables.",our data suggest that reduction or absence of the fhit gene expression is not a prerequisite for colorectal cancer development and progression.,General
does furosemide induce mortality in a rat model of chronic heart failure?,"in an experimental heart failure model, we tested the hypothesis that furosemide causes excess mortality. post-hoc analysis of large clinical heart failure trails revealed that furosemide treatment might be associated with worsening of morbidity and even mortality in heart failure patients. myocardial infarction was induced in 7 1 week old male wistar rats by ligation of the left coronary artery. in study 1, animals were randomly assigned to treatment with furosemide (10mg/kg/d via drinking water, n33) or placebo (n33) starting 18 days after surgery. in study 2, animals received furosemide from day 18 and were then randomized to ongoing treatment with either furosemide only (n38) or furosemide plus ace-inhibitor ramipril (1mg/kg/d, n38) starting on day 42. in study 1 survival rate in the furosemide group was lower than in the placebo group (hazard ratio hr 3.39, 95 confidence interval ci 1.14 to 10.09, p0.028). the furosemide group had a lower body weight (-6, p0.028) at the end of the study and a higher sclerosis index of the glomeruli (9, p0.026) than the placebo group. wet lung weight, infarct size, and cardiac function were similar between the groups. in study 2, the furosemide group had a higher mortality rate than the furosemideramipril group (hr 4.55, 95 ci 2.0 to 10.0, p0.0003).","in our rat model of heart failure furosemide, provided at a standard dose, was associated with increased mortality. this increased mortality could be prevented by additional administration of an ace-inhibitor.",Treatment
does catheter type affect the outcome of intrauterine insemination treatment : a prospective randomized study?,"to compare the main outcome of iui with the gynetics catheter (gynetics medical products, hamont-achel, belgium) or the makler cannula (sefi-medical instruments, haifa, israel). prospective, randomized study. infertility and endocrinology unit in a university hospital. two hundred fifty-one infertile couples undergoing 784 consecutive iui treatments. patients were randomly assigned to undergo iui treatment with either the gynetics catheter (124 patients) or the makler cannula (127 patients). primary outcome measures were pregnancy and cumulative pregnancy rates. secondary outcome measures were the ease of introduction of the catheter, the presence of bleeding, and semen regurgitation after removal of the catheter. the use of the gynetics catheter resulted in similar pregnancy (10.4 vs. 9.7) and cumulative pregnancy rates (27.9 vs. 26.4) as compared with the makler cannula. difficult introduction of the catheter was more frequent in the gynetics group than in the makler group (19.4 vs. 8.0, respectively), but the frequency of bleeding did not differ between groups. sample regurgitation was observed more often in the makler group than in the gynetics group (49.9 vs. 17.9, respectively).","a lower frequency of sperm regurgitation and a higher frequency of difficult introduction was observed when the gynetics catheter was used. however, there was no significant difference in pregnancy rates with use of either the gynetics catheter or the makler cannula.",Treatment
is radial artery calcification in end-stage renal disease patients associated with deposition of osteopontin and diminished expression of alpha-smooth muscle actin?,"vascular access is the lifeline of haemodialysis patients and radial-cephalic fistula is the preferred type of access. we investigated vascular calcification in uraemia radial arteries and compared it with clinical parameters. artery specimens from 30 end-stage renal disease patients were collected, examined calcification by von kossa and alizarin red staining. expression of alpha-smooth muscle actin (alpha-sma) and the main component of bone matrix, osteopontin (op) were detected by immunohistochemistry. in uraemia vessels, calcification was mainly located in the medial layer. nineteen (63.33) patients had no evidence of calcification, six (20) had mild/moderate calcification and five (16.66) had severe calcification. upregulation of op and diminished expression of alpha-sma occurred in the medial layer, especially in the area of severe calcification. the calcification score, decreased expression of alpha-sma and upregulation of op were positively correlated with older age, serum calcium, serum phosphorus and calcium x phosphorus product (p 0.01).","vascular calcification in uraemia radial arteries is mainly located in the media layer. the risk factors appear to be older age, an elevated serum level of phosphorus, calcium and calcium x phosphorus product.",General
does foetal rise in hepatic enzymes follow decline in c-met and hepatocyte growth factor expression?,"in the embryo, rapidly proliferating hepatocytes migrate from the liver primordium into the surrounding mesenchyme, whereas foetal hepatocytes are mitotically quiescent and accumulate hepatocyte-specific enzymes. we investigated the timing and topography of this behavioural switch. the expression of the c-met receptor and its ligand, hepatocyte growth factor (hgf), was investigated in prenatal rat liver by in situ hybridization, immunohistochemistry and western-blot analysis. c-met was expressed by hepatocytes and hgf by non-parenchymal liver cells. their mrna levels peaked during embryonic day (ed) 11-13. c-met protein was weakly expressed in the entire liver during ed 11 and 12, but more abundantly at ed 13, when its expression withdrew to the hepatic periphery. simultaneously, the periportal hepatocellular marker carbamoylphosphate synthetase began to accumulate in the centre of the liver. although the definitive vascular architecture develops simultaneously, the downstream, pericentral hepatocytes began to express glutamine synthetase only 4 days later, suggesting a requirement for prior periportal hepatocyte maturation. additionally, c-met protein appeared in the connective tissue surrounding the large veins. the c-met protein/mrna ratio was substantially higher in non-epithelial cells (hepatic connective tissue, heart) than in endoderm-derived epithelia, including hepatocytes, indicating important post-transcriptional regulation.","the decline in c-met expression reflects the end of the embryonic phase and heralds the onset of the fetal, maturational phase of liver development.",Medication
is the traf1/c5 region a risk factor for polyarthritis in juvenile idiopathic arthritis?,"juvenile idiopathic arthritis (jia) is a chronic disorder in which both genetic and environmental factors are involved. recently, we identified the traf1/c5 region (located on chromosome 9q33-34) as a risk factor for rheumatoid arthritis (ra) (p(combined) 1.4 x 10(-8)). in the present study the association of the traf1/c5 region with the susceptibility to jia was investigated. a case-control association study was performed in 338 caucasian patients with jia and 511 healthy individuals. we genotyped the single nucleotide polymorphism rs10818488 as a marker for the traf1/c5 region. the a allele was associated with the susceptibility to rheumatoid factor-negative polyarthritis with an 11 increase in allele frequency (or 1.54, 95 ci 1.09 to 2.18; p 0.012). this association was stronger when combining subtypes with a polyarticular phenotype (or 1.46, 95 ci 1.12 to 1.90; p 0.004). in addition, we observed a trend towards an increase in a allele frequency in patients with extended oligoarthritis versus persistent oligoarthritis (49, 38 respectively); p 0.055.","apart from being a well replicated risk factor for ra, traf1/c5 also appears to be a risk factor for the rheumatoid factor-negative polyarthritis subtype of jia and, more generally, seems to be associated with subtypes of jia characterised by a polyarticular course.",Prevention
is stromal cell-derived factor 1/cxcr4 signaling critical for the recruitment of mesenchymal stem cells to the fracture site during skeletal repair in a mouse model?,"stromal cell-derived factor 1 (sdf-1; cxcl12/pre-b cell growth-stimulating factor) is a dominant chemokine in bone marrow and is known to be involved in inflammatory diseases, including rheumatoid arthritis. however, its role in bone repair remains unknown. the purpose of this study was to investigate the role of sdf-1 and its receptor, cxcr4, in bone healing. the expression of sdf-1 during the repair of a murine structural femoral bone graft was examined by real-time polymerase chain reaction and immunohistochemical analysis. the bone graft model was treated with anti-sdf-1 neutralizing antibody or tf14016, an antagonist for cxcr4, and evaluated by histomorphometry. the functional effect of sdf-1 on primary mesenchymal stem cells was determined by in vitro and in vivo migration assays. new bone formation in an exchanging-graft model was compared with that in the autograft models, using mice partially lacking sdf-1 (sdf-1(/-)) or cxcr4 (cxcr4(/-)). the expression of sdf1 messenger rna was increased during the healing of live bone grafts but was not increased in dead grafts. high expression of sdf-1 protein was observed in the periosteum of the live graft. new bone formation was inhibited by the administration of anti-sdf-1 antibody or tf14016. sdf-1 increased mesenchymal stem cell chemotaxis in vitro in a dose-dependent manner. the in vivo migration study demonstrated that mesenchymal stem cells recruited by sdf-1 participate in endochondral bone repair. bone formation was decreased in sdf-1(/-) and cxcr4(/-) mice and was restored by the graft bones from cxcr4(/-) mice transplanted into the sdf-1(/-) femur, but not vice versa.",sdf-1 is induced in the periosteum of injured bone and promotes endochondral bone repair by recruiting mesenchymal stem cells to the site of injury.,Treatment
do two large preoperative doses of erythropoietin reduce the systemic inflammatory response to cardiac surgery?,"cardiac surgery and cardiopulmonary bypass (cpb) induce an inflammatory reaction that may lead to tissue injury. experimental studies suggest that recombinant human erythropoietin (epo) independent of its erythropoietic effect may be used clinically as an anti-inflammatory drug. this study tested the hypothesis that 2 large doses of epo administered shortly before cpb ameliorate the systemic inflammatory response to cpb. a prospective, double-blind, placebo-controlled and randomized study at a single tertiary care hospital. patients scheduled for coronary artery bypass graft surgery with cpb. epo (epoetin alfa, 500 iu/kg intravenously, n 22) or placebo (n 21) was administered 12 to 18 hours preoperatively and again at the induction of anesthesia. cpb in both groups greatly increased plasma concentrations of tumor necrosis factor alpha (tnf-alpha), interleukin (il)-1beta, il-1beta receptor antagonist, il-6, il-10, and n-terminal probrain natriuretic peptide (nt-probnp). compared with placebo, epo at day 3 after cpb augmented the tnf-alpha response (p 0.05) and at 2 hours after cpb increased nt-probnp (p 0.05). also, epo tended to enhance the cpb-induced increase in il-1beta receptor antagonist (p 0.057). otherwise, epo had no effect on pro- and antiinflammatory mediators compared with placebo.","two large doses of epo given shortly before cpb do not reduce perioperative release of inflammatory cytokines. in contrast, epo may augment the tnf-alpha and nt-probnp response. although the long-term clinical impact remains unknown, the findings do not support use of epo as an anti-inflammatory drug in patients undergoing cardiac surgery.",Medication
does local application of isogenic adipose-derived stem cells restore bone healing capacity in a type 2 diabetes model?,"bone regeneration is typically a reliable process without scar formation. the endocrine disease type 2 diabetes prolongs and impairs this healing process. in a previous work, we showed that angiogenesis and osteogenesis-essential steps of bone regeneration-are deteriorated, accompanied by reduced proliferation in type 2 diabetic bone regeneration. the aim of the study was to improve these mechanisms by local application of adipose-derived stem cells (ascs) and facilitate bone regeneration in impaired diabetic bone regeneration. the availability of ascs in great numbers and the relative ease of harvest offers unique advantages over other mesenchymal stem cell entities. a previously described unicortical tibial defect model was utilized in diabetic mice (lepr(db-/-)). isogenic mouse adipose-derived stem cells (mascs)(db-/db-) were harvested, transfected with a green fluorescent protein vector, and isografted into tibial defects (150,000 living cells per defect). alternatively, control groups were treated with dulbecco's modified eagle's medium or mascs(wt). in addition, wild-type mice were identically treated. by means of immunohistochemistry, proteins specific for angiogenesis, cell proliferation, cell differentiation, and bone formation were analyzed at early (3 days) and late (7 days) stages of bone regeneration. additionally, histomorphometry was performed to examine bone formation rate and remodeling. histomorphometry revealed significantly increased bone formation in masc(db-/db-)-treated diabetic mice as compared with the respective control groups. furthermore, locally applied mascs(db-/db-) significantly enhanced neovascularization and osteogenic differentiation. moreover, bone remodeling was upregulated in stem cell treatment groups. local application of macss can restore impaired diabetic bone regeneration and may represent a therapeutic option for the future.",this study showed that stem cells obtained from fat pads of type 2 diabetic mice are capable of reconstituting impaired bone regeneration in type 2 diabetes. these multipotent stem cells promote both angiogenesis and osteogenesis in type 2 diabetic bony defects. these data might prove to have great clinical implications for bony defects in the ever-increasing type 2 diabetic patient population.,Treatment
is plasma fibrinogen level on admission to the intensive care unit a powerful predictor of postoperative bleeding after cardiac surgery with cardiopulmonary bypass?,"evidence regarding the behavior of fibrinogen levels and the relation between fibrinogen levels and postoperative bleeding is limited in cardiac surgery under cardiopulmonary bypass (cpb). to evaluate perioperative fibrinogen levels as a predictor of postoperative bleeding in patients undergoing cardiac surgery with cpb. in this prospective, single-center, observational cohort study of 1956 patients following cardiac surgery with cpb, fibrinogen level was measured perioperatively. excessive bleeding group was defined as patients with a 24-h chest tube output (cto) exceeded the 90th percentile of distribution. the median 24-h cto was 728.6431.1ml. a total of 189 patients (9.7) were identified as having excessive bleeding. at admission to the intensive care (day 0), the fibrinogen levels were 2.50.8g/l and 2.10.8g/l in the control and excessive bleeding groups, respectively (p0.0001). the fibrinogen level on day 0 was significantly correlated with the 24-h cto (rho-0.237; p0.0001). multivariate analysis demonstrated that the fibrinogen level at day 0 was the best perioperative standard laboratory test to predict excessive bleeding (p0.0001; odds ratio, 0.5), whereas preoperative fibrinogen level was not a predictor. using receiver operating characteristics curve analyses, the best day 0 fibrinogen level cutoff to predict postoperative bleeding was 2.2g/l.","in this large prospective study, the fibrinogen level upon admission to the intensive care unit after cpb predicted the risk of postoperative bleeding. our data add to the concern regarding the fibrinogen level threshold that might require fibrinogen concentrate infusion to reduce postoperative blood loss.",Treatment
are functional class and targeted therapy related to the survival in patients with pulmonary arterial hypertension?,"pulmonary arterial hypertension (pah) is an orphan disease showing poor prognosis. the purpose of study was to evaluate clinical factors influencing outcomes in pah. patients who were diagnosed with pah at a single center were reviewed retrospectively. forty patients (34.914.5 years, 80 of female) were enrolled. causes were congenital heart disease in 24 (60), connective tissue disease in 8 (20) and idiopathic pah in 6 (15). sixteen patients (40) were who functional class iii or iv at the time of diagnosis. twenty seven patients (67.5) received molecular targeted therapy. during follow-up (53.645.5 months), 10 patients (25) died and 1-, 2-, and 8 year survival rates were 91.3, 78.7, and 66.8, respectively. as expected, median survival of patients with functional class i or ii were significantly longer than patients with iii or iv (p0.041). interestingly, patients with molecular targeted therapy showed longer survival than conventional therapy (p0.021).","who functional class at the time of diagnosis was the strong predictor of survival, and molecular targeted therapy could significantly improve the survival. therefore, early screening and intensive management would be crucial to improve the prognosis in the patient with pah.",Treatment
do haploinsufficient bmp4 ocular phenotypes include anterior segment dysgenesis with elevated intraocular pressure?,"glaucoma is a blinding disease usually associated with high intraocular pressure (iop). in some families, abnormal anterior segment development contributes to glaucoma. the genes causing anterior segment dysgenesis and glaucoma in most of these families are not identified and the affected developmental processes are poorly understood. bone morphogenetic proteins (bmps) participate in various developmental processes. we tested the importance of bmp4 gene dosage for ocular development and developmental glaucoma. bmp4/- mice have anterior segment abnormalities including malformed, absent or blocked trabecular meshwork and schlemm's canal drainage structures. mice with severe drainage structure abnormalities, over 80 or more of their angle's extent, have elevated iop. the penetrance and severity of abnormalities is strongly influenced by genetic background, being most severe on the c57bl/6j background and absent on some other backgrounds. on the c57bl/6j background there is also persistence of the hyaloid vasculature, diminished numbers of inner retinal cells, and absence of the optic nerve.","we demonstrate that heterozygous deficiency of bmp4 results in anterior segment dysgenesis and elevated iop. the abnormalities are similar to those in human patients with developmental glaucoma. thus, bmp4 is a strong candidate to contribute to axenfeld-rieger anomaly and other developmental conditions associated with human glaucoma. bmp4 also participates in posterior segment development and wild-type levels are usually critical for optic nerve development on the c57bl/6j background. bmp4/- mice are useful for studying various components of ocular development, and may allow identification of strain specific modifiers affecting a variety of ocular phenotypes.",Medication
does periodontal treatment need in prisoners in the region of dakar ( senegal ) ?,"oral diseases qualify as major public health problems, because of their high prevalence and incidence. they usually reach the poor and socially marginalized populations. this study looked at the prisoner's population who is characterized by precarious conditions. thus the aim of this study was to assess periodontal treatment needs in prisoner's population of dakar. this was a cross sectional study which interested 375 prisoners living in camp penal, in prisons for women in liberte vi and in rufisque. the data were collected by a modified who sheet. the indicator of periodontal treatment needs (cpitn) was used. statistical analysis with stratification by sex and age was performed and the tests were significant for p or 0.05. they were 335 men (89.3) and 40 women (10.7) with a sex ratio of 8.3. the age mean was 35 years /- 11.5 with a maximum of 88 years and a minimum of 16 years. the mean stay was 39.29 months /- 17.7. the proportion of prisoners with a periodontal treatment need increased gradually according to the prison stay with significant differences (p 0.05) even after stratification.",a more developed and taking into account the environment and the prison stay would reduce the periodontal treatment needs in prisoner's population in dakar.,Treatment
does intramural delivery of bortezomib inhibit restenosis following arterial injury?,"several studies have demonstrated that the proteasome inhibitors prevent restenosis following arterial injury. the proteasome inhibitor bortezomib shows anti-inflammatory and antiproliferative effects. here, we evaluate the efficacy of bortezomib in inhibiting the restenosis following arterial injury and the effect on nuclear factor kappa b (nf-kappab) and p27. an injured iliac artery rabbit model was established by balloon over-stretching. rabbits were intramurally infused with bortezomib or normal saline by a transport coronary dilatation catheter in the bortezomib (n 20) or control (n 20) groups, respectively, and they were sacrificed on the 7th or 21th day following the arterial injury. neointimal area was measured by computer analysis of photomicrographs, while expression of nf-kappab and of p27 on day 7 were evaluated by western blotting and immunohistochemistry, respectively. expression of p27 (56.10 3.03 vs. 10.24 0.60, p 0.05) was significantly higher while that of nf-kappab (0.44 0.02 vs. 0.70 0.03, p 0.05) was significantly lower in the bortezomib group than in control group on day 7 after arterial injury. neointimal formation was significantly lower in the bortezomib group on day 21 after arterial injury (0.67 0.03 vs. 1.30 0.05 intima/media ratio, p 0.05).","intramural delivery of bortezomib reduces neointimal formation, possibly via a mechanism involving upregulation of the p27 and downregulation of the nf-kappab. bortezomib therefore may be an alternative therapeutic approach for preventing restenosis.",Medication
do cd8 cytotoxic t cells induce relapsing colitis in normal mice?,"most mouse models of ibd have emphasized an effector role of type-1 cd4 t cells in colitis. the aim of this study was to develop a model of antigen-specific relapsing colitis to investigate the relative contribution of cd4 and cd8 effectors. balb/c mice were sensitized and challenged with a suboptimal dose of 2.4 dinitrobenzene sulfonic acid to generate a colonic delayed-type hypersensitivity response. the respective role of cd4 and cd8 t cells in the initiation of colitis was analyzed by in vivo monoclonal antibody depletion and cell-transfer experiments. dynamic and function of the colitogenic effectors were studied by immunohistochemistry, fluorescence-activated cell sorter analysis, enzyme-linked immunospot assay, quantitative polymerase chain reaction, and in vivo ctl assays. relapsing colitis rapidly occurred only after challenge of previously sensitized mice. interferon-gamma-producing cytotoxic cd8 t cells (tc1) specific for hapten-modified self-proteins were generated in colon-draining lymph nodes on day 5 after sensitization, before the onset of disease. these cd8 t cells were rapidly recruited upon challenge into colon lamina propria as granzyme b-expressing effectors exerting ex vivo cytotoxicity against syngeneic hapten-modified colonic epithelial cells. colitis was prevented by in vivo antibody depletion of cd8, but not of cd4, t cells and could be induced in naive recipients within 48 hours after transfer of cd8, but not cd4, t cells purified from sensitized mice.",our data show that antigen-specific cd8 t cells can induce relapsing colitis in normal mice and suggest that the cytolytic function of cd8 tc1 against epithelial cells may initiate the intestinal inflammatory process.,Medication
are levels of circulating cellular fibronectin increased in patients with rheumatoid vasculitis?,"to investigate whether serum levels of circulating cellular fibronectin (cfn) are increased in patients with rheumatoid arthritis (ra) complicated by vasculitis. levels of serum cfn were determined by an enzyme-linked immunosorbent assay (elisa) in 26 ra patients with histologically proven vasculitis of recent onset (rv) and were compared to the levels in 47 ra patients with extraarticular manifestations of recent onset but no histological evidence of vasculitis (ra), 43 patients with uncomplicated ra (ra-), 16 patients with systemic lupus erythematosus and active disease (sle), 30 patients with active crohn's disease (cd), 21 young healthy controls (yhc) and 17 elderly healthy controls (ehc). plasma levels of cfn and von willebrand factor antigen were also determined in the ra patients. in rv patients, the median cfn level was significantly (p 0.01) higher compared to that of ra patients, and was also significantly (p 2 sd above the mean level for ehc. at an optimal cut-off titre the sensitivity of the cfn elisa in discriminating rv patients from ra patients was 90, the specificity was 46 and the accuracy was 68. plasma levels of cfn correlated significantly (r 0.62; p 0.001) with the von willebrand factor antigen levels.","increased levels of serum cfn are present in patients with ra, and are frequently found in ra patients with extraarticular manifestations, particularly in those with vasculitis.",Diagnosis
does recombinant human growth hormone accelerate wound healing in children with large cutaneous burns?,"two forms of recombinant growth hormone that accelerate the healing of skin graft donor sites in severely burned children were evaluated. growth hormone has been shown to reduce wound healing times in burned pediatric patients. through genetic engineering, several different forms have been synthesized; however, not all are marketed currently. two forms of growth hormone were used in these studies, protropin (genentech, inc., san francisco, ca), a commercially available product that possesses a n-terminal methionine residue not found in the second form nutropin (genentech, inc., san francisco, ca), which, as yet, is not commercially available. through the use of recombinant human growth hormone, rapid wound healing may reduce the hypermetabolic period, the risk of infection, and accelerate the healing of donor sites used for grafting onto burned areas. the two structurally different forms of growth hormone were tested for their efficacy in healing donor sites in severely burned children. forty-six children, with a 40 total body surface area and 20 total body surface area full-thickness burn were entered in a double-blind, randomized study to receive rhgh within 8 days of injury. twenty received (0.2 mg/kg/day) nutropin or placebo by subcutaneous or intramuscular injection beginning on the morning of the initial excision. eighteen patients who failed the entry criteria for receiving nutropin received protropin therapeutically (0.2 mg/kg/day). donor sites were harvested at 0.006 to 0.010 inches in depth and dressed with scarlet red impregnated fine mesh gauze (sherwood medical, st. louis, mo). the initial donor site healing time, in days, was reached when the gauze could be removed without any trauma to the healed site. donor sites in patients receiving nutropin (n 20) or protropin (n 18) healed at 6.8 /- 1.5 and 6.0 /- 1.5 (mean /- sd) days, respectively, whereas those receiving placebo (n 26) had a first donor site healing time of 8.5 /- 2.3 days. both groups receiving rhgh showed a significant reduction in donor site healing time compared with placebo at p 0.01. when subgroups were compared, no difference in healing times could be shown with regards to age or time of admission after injury.","our results indicate that both forms of rhgh are effective in reducing donor site healing time compared with placebo and suggest that accelerating wound healing is of clinical benefit because the patients' own skin becomes rapidly available for harvest and autografting. with this increase in the rate of wound healing, the total length of hospital stay can be reduced by more than 25.",Medication
is long latency characteristic for imported '' cases of malaria in children at a municipal hospital in vienna ?,"malaria is the most frequent tropical disease and the most important parasitic infectious disease in the world. due to high mobility by travelling and migration also in central europe malaria has to be considered also in children and youths. we report four cases of malaria being diagnosed and treated at the department of paediatrics, vienna danube hospital, a municipal centre. in all cases the latency time or incubation period respectively was long with up to one year which made the diagnosis of malaria unlikely at first glance.",taking into account the long latency or incubation period and often fragmentary report of medical history malaria has to be considered in all children after a stay in a country at risk for malaria even if this stay dates back a long time in order to diagnose and treat this disease quickly.,Treatment
does gain-of-function fhf1 mutation cause early-onset epileptic encephalopathy with cerebellar atrophy?,"voltage-gated sodium channel (nav)-encoding genes are among early-onset epileptic encephalopathies (eoee) targets, suggesting that other genes encoding nav-binding proteins, such as fibroblast growth factor homologous factors (fhfs), may also play roles in these disorders. to identify additional genes for eoee, we performed whole-exome sequencing in a family quintet with 2 siblings with a lethal disease characterized by eoee and cerebellar atrophy. the pathogenic nature and functional consequences of the identified sequence alteration were determined by electrophysiologic studies in vitro and in vivo. a de novo heterozygous missense mutation was identified in the fhf1 gene (fhf1ar114h, fhf1br52h) in the 2 affected siblings. the mutant fhf1 proteins had a strong gain-of-function phenotype in transfected neuro2a cells, enhancing the depolarizing shifts in nav1.6 voltage-dependent fast inactivation, predicting increased neuronal excitability. surprisingly, the gain-of-function effect is predicted to result from weaker interaction of mutant fhf1 with the nav cytoplasmic tail. transgenic overexpression of mutant fhf1b in zebrafish larvae enhanced epileptiform discharges, demonstrating the epileptic potential of this fhf1 mutation in the affected children.","our data demonstrate that gain-of-function fhf mutations can cause neurologic disorder, and expand the repertoire of genetic causes (fhf1) and mechanisms (altered nav gating) underlying eoee and cerebellar atrophy.",General
does knockdown of thrombomodulin enhance hcc cell migration through increase of zeb1 and decrease of e-cadherin gene expression?,"thrombomodulin (tm) is a key molecule mediating circulation homeostasis through its binding to thrombin. the tm-thrombin complex can activate protein c and thrombin-activatable fibrinolysis inhibitor to form a tight clot. in many cancer tissues, decrease of tm expression may correlate with cancer metastasis. however, the role of tm in hepatocellular carcinoma (hcc) progression is still unclear. we characterized tm expression in hcc cells (hepj5 and skhep-1 cells) using real-time polymerase chain reaction (pcr) and western blotting. we then manipulated tm expression using both tm-specific short hairpin rna (shrna) and overexpressing it in hcc cells. transwell migration assay was performed to monitor the migratory ability of hcc cells under different levels of tm expression. we found that tm was ectopically highly expressed in skhep-1 at both transcriptional and translational levels. after silencing tm expression in skhep-1 cells, we found that metastatic capability was dramatically increased. conversely, overexpression of tm in hepj5 cells decreased metastatic ability. we investigated the possible mechanism and found that decreased tm-mediated enhancement of cell migration was dependent on upregulation of zeb1, a repressor of e-cadherin.",tm may be a modulator of cancer metastasis in hcc. downregulation of tm expression may increase zeb1 and decrease e-cadherin levels.,Medication
is serum ntx a practical marker for assessing antiresorptive therapy for glucocorticoid treated patients with chronic kidney disease?,"in chronic kidney disease (ckd) patients, serum concentration of type i collagen n-telopeptide (s-ntx) increases as renal function declines because of perturbed bone metabolism by renal dysfunction itself and impaired urinary excretion of ntx. glucocorticoid (gc), which is often used for the treatment of kidney disease, may enhance bone resorption. we studied the bone resorption state in gc-treated ckd patients and the effects of bisphosphonate on s-ntx. we measured s-ntx and creatinine clearance (ccr) in 48 non-diabetic patients with declining renal function who had never received gc, vitamin d, calcium or bisphosphonate (reference group). bone markers including s-ntx and bsap (bone specific alkaline-phosphatase) in 144 patients receiving gc (prednisone equivalent of or 2.5 mg/day) for more than 6 months (gc-treated group) were measured. we compared the gc-treated group to the reference group in a cross-sectional study. in a longitudinal study, we further followed 55 patients from the gc-treated group, whose ccr was more than 60 ml/min (ckd stage 1 or 2) for 1 year after 2.5 mg/day of risedronate was commenced. in the reference group, s-ntx was correlated with ccr (s-ntx 456.6/ccr 4.5, r 0.797, p 0.0001). s-ntx values in the gc-treated group were higher than those found in the reference group at any ccr. we defined the resorption index (ri) as a ratio of measured s-ntx to estimated ntx given by the correlation curve. whereas bsap did not change significantly, s-ntx decreased significantly by risedronate treatment. ri decreased from 1.59 (baseline) to 1.54, 1.25 (p 0.01, versus baseline) and 1.23 (p 0.01) at 1, 3 and 6 months after the start of therapy, respectively, which means that s-ntx values approached the correlation curve. percent changes of s-ntx at 3 months were larger in patients with higher pretreatment s-ntx.","higher s-ntx in the gc-treated group suggests that bone resorption is enhanced by gc. in ckd patients with mild renal dysfunction, s-ntx is a practical and useful marker for monitoring bone resorption during gc treatment.",Treatment
does pim1 kinase promote angiogenesis through phosphorylation of endothelial nitric oxide synthase at ser-633?,"posttranslational modification, such as phosphorylation, plays an essential role in regulating activation of endothelial no synthase (enos). in the present study, we aim to determine whether enos could be phosphorylated and regulated by a novel serine/threonine-protein kinase pim1 in vascular endothelial cells (ecs). using immunoprecipitation and protein kinase assays, we demonstrated that pim1 specifically interacts with enos, which leads to a marked phosphorylation of enos at ser-633 and increased production of nitric oxide (no). intriguingly, in response to vegf stimulation, enos phosphorylation at ser-633 exhibits two distinct phases: transient phosphorylation occurring between 0 and 60 min and sustained phosphorylation occurring between 2 and 24 h, which are mediated by the protein kinase a (pka) and pim1, respectively. inhibiting pim1 by either pharmacological inhibitor smi-4a or the dominant-negative form of pim1 markedly attenuates vegf-induced tube formation, while pim1 overexpression significantly increases ec tube formation and migration in an no-dependent manner. importantly, pim1 expression and enos phosphorylation at ser-633 were substantially decreased in high glucose-treated ecs and in the aorta of db/db diabetic mice. increased pim1 expression ameliorates impaired vascular angiogenesis in diabetic mice, as determined by an ex vivo aortic ring assay.","our findings demonstrate pim1 as a novel kinase that is responsible for the phosphorylation of enos at ser-633 and enhances ec sprouting of aortic rings from diabetic mice, suggesting that pim1 could potentially serve as a novel therapeutic target for revascularization strategies.",Medication
is dna transfection of macaque and murine respiratory tissue greatly enhanced by use of a nuclease inhibitor?,"nuclease activity present within respiratory tissues contributes to the rapid clearance of injected dna and therefore may reduce the transfection activity of directly injected transgenes. most gene transfer technologies transduce or transfect murine tissues more efficiently than corresponding primate tissues. therefore, it is prudent to assess the utility of novel gene transfer strategies in both rodent and primate models before proceeding with further development. this study analyzed the effects of ata (a nuclease inhibitor) on the direct transfection of macaque and murine lung tissue; compared the levels of dnase activity in murine, primate, and human lung fluids; and tested the inhibitory activity of ata on the dnase activity present in these samples. fluorescent microspheres were used to detect areas of transfection in lung. intratracheal administration of a nuclease inhibitor (ata) with naked dna (0.5 microg ata/g body weight) enhanced direct transfection efficacy in macaque lung by over 86-fold and by over 54-fold in mouse lung. hematoxylin and eosin staining showed no apparent tissue toxicity. moreover, macaque, human, and mouse lung fluids were found to possess similar levels of dnase activity and this activity was inhibited by similar concentrations of ata. the authors also successfully pioneered the use of carboxylate-modified microsphere tracers to identify areas of transfection and/or treatment.","this work provides evidence that using direct nuclease inhibitors will enhance lung transfection and that nuclease activity is present in all lung fluids tested, which can be inhibited by the use of direct dnase inhibitors.",Medication
does resiliency over time of elders ' age stereotype after encountering stressful events?,"to examine whether the age stereotypes of older individuals would become more negative or else show resiliency following stressful events and to examine whether age-stereotype negativity would increase the likelihood of experiencing a stressful event (i.e., hospitalization). age stereotypes of 231 participants, 70 years and older, were assessed across 10 years, before and after the occurrence of hospitalizations and bereavements. age-stereotype negativity was resilient despite encountering stressful events. in contrast, more negative age stereotypes were associated with a 50 greater likelihood of experiencing a hospitalization.",the robustness of negative age stereotypes was expressed in their capacity to resist change as well as generate it.,General
is low-normal serum potassium associated with an increased risk of cardiovascular and all-cause death in community-based elderly?,"several studies have already reported that serum potassium (sk) correlated inversely with adverse events among patients with preexisting cardiovascular disease and impaired renal function; less is known about the prognostic value of sk at the normal range in community-based elderly individuals. this study aimed to examine whether low normal sk value was associated with cardiovascular and all-cause mortalities in elderly people. a prospective study was conducted using two independent elderly taiwanese community cohorts that included 2065 individuals with relatively normal sk values (2.8-5.6 mmol/l). the participants were grouped as follows: low (2.8-3.4 mmol/l), low-normal sk (3.5-3.8 mmol/l), normal (3.9-4.4 mmol/l), and high-normal sk (4.5-5.6 mmol/l). proportional hazards model was applied to compare the association between sk concentration groups and mortality. the relationship between baseline sk and all-cause and cardiovascular mortality was u-shaped, with the lowest mortality rates observed in patients with sk levels of 3.9-4.4 mmol/l. the low-normal sk group had significantly higher risks of all-cause (hazard ratio, 1.3; 95 confidence interval, 1.0-1.6) and cardiovascular mortality (hazard ratio, 1.6; 95 confidence interval, 1.1-2.3) than the normal sk group. the high-normal sk group had higher but nonsignificant risk compared to the normal group.",our findings suggest that low-normal sk may be used as a marker of poor survival for elderly outpatient cares.,Diagnosis
does inadequate office endometrial sample require further evaluation in women with postmenopausal bleeding and abnormal ultrasound results?,"to determine whether further histologic assessment can be omitted after office sampling produced a nondiagnostic specimen. data were retrieved from a prospective cohort study of 913 women presenting with postmenopausal bleeding. this study was limited to women with an endometrial thickness either 5 mm or greater or that could not be measured, and in whom an endometrial biopsy performed in the office yielded nondiagnostic results. endometrial thickness was nonreassuring or unknown in 516 women, of whom 403 (78.1) underwent office endometrial sampling. in 66 women the amount of tissue obtained was not sufficient for pathologic characterization. further investigation revealed an endometrial malignancy in 3 of these 66 women and atypical hyperplasia in 1.","in women with postmenopausal bleeding and a nonreassuring transvaginal ultrasound evaluation, a nondiagnostic office endometrial sample does not rule out endometrial cancer and further endometrial sampling is advisable.",Diagnosis
does nf-kappab regulate intestinal epithelial cell and bile salt-induced migration after injury?,"to determine if nf-kappa b regulates intestinal epithelial cell migration and if it has a role during bile salt-induced migration. mucosal restitution is an important repair modality in the gastrointestinal tract. the authors have shown that taurodeoxycholate (tdca) increases intestinal epithelial cell migration. nf-kappa b regulates activation of a number of genes involved in inflammatory responses. studies were conducted in iec-6 cells. i kappa b protein expression was determined by western blot analysis. sequence-specific nf-kappa b binding activity was measured by emsa shift assays and nuclear localization by immunohistochemistry. cell migration was examined by using an in vitro model that mimics the early cell division-independent stages of epithelial restitution. the process of cell migration over the wounded area was associated with a significant increase in nf-kappa b binding activity in iec-6 cells. immunohistochemistry revealed translocation of nf-kappa b into the nucleus. western blot analysis showed that injury decreased i kappa b protein expression. inhibition of the binding activity by treatment with a specific nf-kappa b inhibitor, mg-132, inhibited cell migration during restitution. further, exposure to tdca at the physiologic concentration that induces intestinal epithelial cell migration increased nf-kappa b binding activity, induced nf-kappa b translocation into the nucleus, and decreased i kappa b protein expression. mg-132 also inhibits bile salt-induced cell migration.",nf-kappa b regulates intestinal epithelial cell migration. bile salts at physiologic concentrations increase cell migration by activation of nf-kappa b. these data show that bile salts may have a role in the maintenance of intestinal mucosal integrity.,Treatment
do msp-1p42-specific antibodies affect growth and development of intra-erythrocytic parasites of plasmodium falciparum?,"antibodies are the main effector molecules in the defense against blood stages of the malaria parasite plasmodium falciparum. understanding the mechanisms by which vaccine-induced anti-blood stage antibodies work in protecting against malaria is essential for vaccine design and testing. the effects of msp-1p42-specific antibodies on the development of blood stage parasites were studied using microscopy, flow cytometry and the pldh assay. to determine allele-specific effects, if present, allele-specific antibodies and the various parasite clones representative of these alleles of msp-1 were employed. the mode of action of anti-msp-1p42 antibodies differs among the parasite clones tested: anti-msp-1p42 sera act mainly through invasion-inhibitory mechanisms against fvo parasites, by either preventing schizonts from rupturing or agglutinating merozoites upon their release. the same antibodies do not prevent the rupture of 3d7 schizonts; instead they agglutinate merozoites and arrest the development of young parasites at the early trophozoite stage, thus acting through both invasion- and growth inhibitory mechanisms. the second key finding is that antibodies have access to the intra-erythrocytic parasite, as evidenced by the labeling of developing merozoites with fluorochrome-conjugated anti-msp-1p42 antibodies. access to the parasite through this route likely allows antibodies to exert their inhibitory activities on the maturing schizonts leading to their inability to rupture and be released as infectious merozoites.",the identification of various modes of action by which anti-msp-1 antibodies function against the parasite during erythrocytic development emphasizes the importance of functional assays for evaluating malaria vaccines and may also open new avenues for immunotherapy and vaccine development.,Medication
is myocardial performance ( tei ) index normal in diastolic and systolic heart failure induced by pressure overload in rats?,"myocardial performance index (mpi), or tei index, is a doppler echocardiographic parameter defined as the sum of the isovolumic contraction and relaxation times divided by the ejection time. it is considered a reliable parameter for global left ventricular function. however, the interpretation of this index is not fully clear in diastolic dysfunction. we measured mpi in a pressure-overload model of rats with severe diastolic with or without systolic dysfunction and examined its usefulness as a parameter for cardiac function in a hypertensive heart failure model. pressure overload was created by placement of a metal clip around the thoracic aorta transverse aortic constriction (tac) at a weight of 40-50 g. transthoracic echocardiography including doppler analysis and invasive left ventricular catheter examination were performed 10 and 20 weeks after tac (n 6 for each time point). while left ventricular ejection fraction was over 50 in all tac animals after 10 weeks (56.3 2.3), it was below 50 in all tac animals after 20 weeks (45.4 1.0). e/e' was significantly larger in the tac groups at both time points and the time constant by millar catheter was also elevated in the tac groups. on the other hand, mpi was not different compared with the control groups (10 weeks: 0.47 0.09 vs. 0.44 0.04; 20 weeks: 0.38 0.03 vs. 0.46 0.07).",mpi is not a reliable parameter for the assessment of contractile function in pressure-overload heart failure. it is normal in diastolic dysfunction with or without preserved ejection fraction.,Symptoms
is debulking transplant nephrectomy leaving an intact ureter and instillation of betadine intracapsular safe nephrectomy : fifteen years ' experience?,"transplant nephrectomy has been reported to display a high morbidity (17 to 56) and considerable mortality (13 to 14). we used a debulking technique leaving an intact ureter with intracapsular instillation of betadine; it was associated with a low rate of complications. a total of 25 patients (16 males, 9 females) with failed allografted kidneys underwent transplant nephrectomy between 1991 and 2006 (group 1). all subjects had failed kidneys for 2 months or more posttransplantation. the surgical approach to allograft nephrectomy was via the same oblique incision in the iliac fossa as the original transplantation. the capsule of the allograft was exposed and incised from pole to pole for the renal parenchyma to be bluntly dissected free with an index finger. the kidney parenchyma was pulled outward, and then the pedicle was ligated with silk, and layer by layer the tissue was removed until reaching the pedicle. again it was transfixed and carefully ligated. after homeostasis, diluted betadine was instilled into the capsule and a drain inserted. the allograft ureter and capsule were left intact. all cases were followed for at least 1 year. postnephrectomy, small doses of immunosuppressive drugs were continued for at least 2 months. intracapsular nephrectomy was not associated with a significant complication.","intracapsular debulking nephrectomy, leaving the ureter and capsule intact and with intracapsular instillation of betadine, was a safe technique to remove a delayed, failed allograft.",Treatment
is a common variant near the kcnj2 gene associated with t-peak to t-end interval?,"t-peak to t-end (tpe) interval on the electrocardiogram is a measure of myocardial dispersion of repolarization and is associated with an increased risk of ventricular arrhythmias. the genetic factors affecting the tpe interval are largely unknown. to identify common genetic variants that affect the duration of the tpe interval in the general population. we performed a genome-wide association study on 1870 individuals of finnish origin participating in the health 2000 study. the tpe interval was measured from t-peak to t-wave end in leads ii, v(2), and v(5) on resting electrocardiograms, and the mean of these tpe intervals was adjusted for age, sex, and cornell voltage-duration product. we sought replication for a genome-wide significant result in the 3745 subjects from the framingham heart study. we identified a locus on 17q24 that was associated with the tpe interval. the minor allele of the common variant rs7219669 was associated with a 1.8-ms shortening of the tpe interval (p 1.1 10(-10)). the association was replicated in the framingham heart study (-1.5 ms; p 1.3 10(-4)). the overall effect estimate of rs7219669 in the 2 studies was -1.7 ms (p 5.7 10(-14)). the common variant rs7219669 maps downstream of the kcnj2 gene, in which rare mutations cause congenital long and short qt syndromes.",the common variant rs7219669 is associated with the tpe interval and is thus a candidate to modify repolarization-related arrhythmia susceptibility in individuals carrying the major allele of this polymorphism.,General
does systemic theophylline augment the blood oxygen level-dependent response to forepaw stimulation in rats?,"functional mr imaging with blood oxygen level-dependent (bold) contrast enhancement is believed to rely on changes in cerebral blood flow and deoxyhemoglobin level to estimate the location and degree of neural activation. we studied the relationship between neural activation and the observed bold response by using theophylline, an antagonist of the inhibitory neurotransmitter adenosine and a potent inhibitor of the vasodilatory response to neural activation. using a rat model with electrical forepaw stimulation, we performed fmri measurements before and after the systemic injection of either theophylline (0.1 mmol/kg) or an equivalent volume of saline. changes in the bold response were quantified by determining the number of activated voxels and the amplitude of the bold response for each animal in the theophylline and saline groups. the theophylline group had a significantly tincreased bold response (70-150 increased activated voxel count and 60-65 increased bold response amplitude) at 45 and 60 minutes after systemic injection compared with baseline. the response of the saline-injected control group did not change significantly.",the administration of systemic theophylline significantly augmented the bold response due to either an elevation of resting deoxyhemoglobin levels or the neuroexcitatory effect of theophylline. this effect potentially could be used in human fmri studies to increase the sensitivity of the bold response.,Medication
is short-term preoperative radiotherapy a safe approach for treatment of locally advanced rectal cancer?,"the swedish rectal cancer trial (srct) demonstrated that a short term regimen of high-dose preoperative radiotherapy (5x5 gy) not only reduces the risk of local recurrence but also improves overall survival rate. an increase in postoperative mortality and morbidity has also been observed, however. we therefore evaluated early postoperative complications in patients treated with neoadjuvant radiotherapy for locally advanced rectal adenocarcinoma. between 2000 and 2004, 85 patients with locally advanced rectal tumors were treated in our institution. preoperative staging was based on ct scan and, in several cases, on endorectal ultrasonography. they were 55 men and 30 women, with a median age of 68 years. they were retrospectively divided into two groups: group a, which included 40 patients undergoing preoperative radiotherapy (25 gy in five fractions) followed by surgery within 1 week, and group b, which included 45 patients with rectal cancer receiving surgery immediately after diagnosis. both groups were homogeneous regarding age, gender and preoperative stage of the disease. the two groups were compared for both technical difficulties during operation and rate of postoperative complications. no postoperative deaths were recorded in either group. low anterior resection with total mesorectal excision was performed in all group a patients, whereas eight patients in group b underwent abdominoperineal resection (p0.05). diverting stoma was performed in seven patients of group a and it was closed 3-6 months later on every occasion. postoperative morbidity was not statistically significant between the two groups (40 vs 39). the rate of postoperative hemorrhage, pelvic or abdominal wound infection, acute urinary infection, and delayed ileus was similar. the percentage of major anastomotic leak was also equivalent (5 vs 6.6).",short-term preoperative radiotherapy does not increase the rate of postoperative complications and is a safe therapeutic adjunct for the treatment of locally advanced rectal cancer.,Treatment
does ursolic acid induce cell cycle arrest and apoptosis of gallbladder carcinoma cells?,"ursolic acid (ua), a plant extract used in traditional chinese medicine, exhibits potential anticancer effects in various human cancer cell lines in vitro. in the present study, we evaluated the anti-tumoral properties of ua against gallbladder carcinoma and investigated the potential mechanisms responsible for its effects on proliferation, cell cycle arrest and apoptosis in vitro. the anti-tumor activity of ua against gbc-sd and sgc-996 cells was assessed using mtt and colony formation assays. an annexin v/pi double-staining assay was used to detect cell apoptosis. cell cycle changes were detected using flow cytometry. rhodamine 123 staining was used to assess the mitochondrial membrane potential (m) and validate ua's ability to induce apoptosis in both cell lines. the effectiveness of ua in gallbladder cancer was further verified in vivo by establishing a xenograft gbc model in nude mice. finally, the expression levels of cell cycle- and apoptosis-related proteins were analyzed by western blotting. our results suggest that ua can significantly inhibit the growth of gallbladder cancer cells. mtt and colony formation assays indicated dose-dependent decreases in cell proliferation. s-phase arrest was observed in both cell lines after treatment with ua. annexin v/pi staining suggested that ua induced both early and late phases of apoptosis. ua also decreased m and altered the expression of molecules regulating the cell cycle and apoptosis. in vivo study showed intraperitoneally injection of ua can significantly inhibited the growth of xenograft tumor in nude mice and the inhibition efficiency is dose related. activation of caspase-3,-9 and parp indicated that mitochondrial pathways may be involved in ua-induced apoptosis.","taken together, these results suggest that ua exhibits significant anti-tumor effects by suppressing cell proliferation, promoting apoptosis and inducing 7cell cycle arrest both in vitro and in vivo. it may be a potential agent for treating gallbladder cancer.",Medication
do nestin-positive progenitor cells isolated from human fetal pancreas have phenotypic markers identical to mesenchymal stem cells?,"to isolate nestin-positive progenitor cells from human fetal pancreas and to detect their surface markers and their capability of proliferation and differentiation into pancreatic islet endocrine cells in vitro. islet-like cell clusters (iccs) were isolated from human fetal pancreas by using collagenase digestion. the free-floating iccs were handpicked and cultured in a new dish. after the iccs developed into monolayer epithelium-like cells, they were passaged and induced for differentiation. reverse transcription polymerase chain reaction (rt-pcr), immunofluorescence stain, fluorescence-activated cell sorting (facs) and radioimmunoassay (ria) were used to detect the expression of cell markers. (1) the monolayer epithelium-like cells had highly proliferative potential and could be passaged more than 16 times in vitro; (2) rt-pcr analysis and immunofluorescence stain showed that these cells expressed both nestin and abcg2, two of stem cell markers; (3) facs analysis revealed that cd44, cd90 and cd147 were positive, whereas cd34, cd38, cd45, cd71, cd117, cd133 and hla-dr were negative on the nestin-positive cells; (4) rt-pcr analysis showed that the mrna expression of insulin, glucagon and pancreatic-duodenal homeobox gene-1 was detected, whereas the expression of nestin and neurogenin 3 disappeared in these cells treated with serum-free media supplemented with the cocktail of growth factors. furthermore, the intra-cellular insulin content was detected by ria after the induction culture.","nestin-positive cells isolated from human fetal pancreas possess the characteristics of pancreatic progenitor cells since they have highly proliferative potential and the capability of differentiation into insulin-producing cells in vitro. interestingly, the nestin-positive pancreatic progenitor cells share many phenotypic markers with mesenchymal stem cells derived from bone marrow.",Diagnosis
does ethanol decrease zinc transfer to the fetus in normal but not metallothionein-null mice?,"ethanol causes significant teratogenicity in normal (mt/) but not metallothionein-null (mt-/-) fetuses. impaired maternal fetal zinc (zn) transfer is indicated, because ethanol significantly reduces plasma zn concentrations in mt/ dams while increasing concentrations in mt-/- dams. in this study we examined maternal-fetal zn homeostasis in response to ethanol in mt/ and mt-/- mice and the origins of the increase in plasma zn in mt-/- mice. mice were treated with saline or ethanol (0.015 ml/g intraperitoneally at 0 and 4 hr) on day 12 of gestation. an additional subcutaneous injection of 65zn tracer was administered after the second ethanol injection before mice were killed 3 hr later. maternal liver mt levels were not different between ethanol and saline mt/ mice. both liver zn and 65zn levels were higher in mt/ mice. plasma zn concentrations were higher in mt-/- mice, with mt-/- ethanol-treated mice having levels greater than those of mt-/- saline-treated controls. mt/ ethanol-treated fetuses exhibited lower 65zn transfer and whole zn concentrations compared with mt/ and mt-/- saline and mt-/- ethanol fetuses. so we could examine changes in plasma zn after ethanol treatment, mt/ and mt-/- mice were injected with 65zn 3 days before they received ethanol treatment. muscle and skin showed a decrease in 65zn retention in both genotypes over 3 hr. there was a trend toward greater 65zn release from skin and muscle at an earlier time in mt-/- mice: 24 vs. 2 decrease (mt-/- vs. mt/) for muscle and 28 vs. 15 decrease (mt-/- vs. mt/) for skin at 2 hr.","the results show (a) that ethanol interferes with the transfer of zn to the fetus, and that this is mt dependent, and (b) that the increase in plasma zn seen in mt-/- mice after ethanol administration is a result of zn release from the skin and muscle, in the absence of hepatic zn sequestration.",Medication
does hypoxia potentiate endotoxin-induced allopregnanolone concentrations in the newborn brain?,"allopregnanolone is a neurosteroid produced in the brain that can alter the excitability of the cns. neurosteroids have neuroprotective properties, and their elevation in response to stress may protect the newborn brain following infection or hypoxia. infection, particularly of the respiratory tract, may lead to episodes of hypoxia. infection and hypoxia have been identified as factors contributing to neonatal morbidity and mortality. to determine the effect of acute episodes of hypoxia alone or in combination with lipopolysaccharide (lps) exposure on plasma and brain allopregnanolone concentrations in lambs 10-21 days old. also, to examine plasma levels of cortisol and the cytokines, tumour necrosis factor-alpha and interleutkin-6 after these challenges. allopregnanolone concentrations in the brain were markedly increased after hypoxia. hypoxia following prior lps treatment resulted in greater increases in brain allopregnanolone concentrations compared to either the lps or hypoxia treatment alone. importantly, brain regions unaffected by lps or hypoxia alone (thalamus/hypothalamus, cerebellum) showed significant increases of allopregnanolone content following the combined lps and hypoxia treatments. plasma tumour necrosis factor-alpha and interleukin-6 concentrations were increased after lps treatment with and without hypoxia, but not by hypoxia alone. in contrast, plasma cortisol concentrations were increased after both stressors.",these results show that the brain of young lambs readily responds to physiological stress by increased production of allopregnanolone. this response may protect the developing brain from the cytotoxicity following hypoxic and infectious episodes.,Medication
does diabetes prevalence estimate in schizophrenia and risk factor assessment?,"atypical antipsychotics have been indirectly associated with the diagnosis of type 2 diabetes mellitus (t2dm) in patients with schizophrenia. the purpose of this cross-sectional study was to determine the prevalence of t2dm and to examine the risk factors associated with t2dm among outpatients diagnosed with schizophrenia. the study also sought to determine which risk factors are of particular screening importance in monitoring the metabolic status of these patients. this study included 202 patients diagnosed with schizophrenia. data on a number of known and hypothesized risk factors for t2dm were collected. risk factors for t2dm identified by bivariate analyses in this sample included older age, waist-to-hip ratio 1.0, sedentary lifestyle, number of hours worked per week, hyperlipidemia, previous screening for t2dm, higher random blood glucose, and number of years on atypical antipsychotics risperidone or olanzapine. however, further scrutiny using multiple logistic regression identified only sedentary lifestyle, waist-to-hip ratio 1.0, and a diagnosis of hyperlipidemia as significant risk factors in these patients. similar to other studies, there was an 11.5 (22/192) lifetime prevalence rate of diabetes among this population.","risk factors traditionally associated with t2dm, as well as waist-to-hip ratio, are the factors most strongly associated with increased risk of diabetes in patients with schizophrenia.",Prevention
does localized intermittent delivery of simvastatin hydroxyacid stimulate bone formation in rats?,"the cholesterol-lowering drug simvastatin promotes bone formation in cell cultures and animal models. in previous studies, devices for the controlled, localized delivery of simvastatin hydroxyacid enhanced osteoblastic activity in vitro. the objective of this investigation was to determine bioactivity of the delivery system in vivo. devices for sustained or intermittent release of simvastatin hydroxyacid were formed using a blend of cellulose acetate phthalate and a poly(ethylene oxide) and poly(propylene oxide) block copolymer, and they were implanted directly over the calvarium of young male rats. drug-free devices were used as controls. after 9, 18, or 28 days, specimens were histologically evaluated for new bone formation. all three groups showed some level of new bone formation, but the extent of osteogenesis depended on the type of implant. devices delivering simvastatin hydroxyacid were associated with a 77.5 to 133 increase in new woven bone thickness compared to control devices without a drug (p0.05). furthermore, intermittent release stimulated a 32.3 greater response in bone thickness and a 74.1 greater bone area than did sustained delivery (p0.05). although a minimal thickness of woven bone was formed directly under the device (up to 36 microm), a significantly thicker layer was observed at the periphery (up to 205 microm), implying mechanical and/or chemical effects directly under the implant. the percentage of lamellar bone area for intermittent and sustained release was higher than that for the control group (p0.05).","based on the present results of enhanced bone formation, these devices for the intermittent delivery of simvastatin hydroxyacid merit further attention for localized osteogenesis.",Medication
does ibuprofen with acetaminophen for postoperative pain control following tonsillectomy increase emergency department utilization?,"to compare the performance of ibuprofen vs codeine for postoperative pain management after tonsillectomy as measured by need for emergency department (ed) treatment for pain and/or dehydration. retrospective case series with chart review. tertiary children's hospital. consecutive series of patients who underwent tonsillectomy with or without adenoidectomy at a tertiary children's hospital. patients were categorized based on the type of postoperative pain management (acetaminophen with codeine vs acetaminophen and ibuprofen). the main outcome measure was the proportion of patients requiring ed visits or inpatient admissions for inadequate pain control or dehydration. secondary measures included antibiotic use, postoperative hemorrhage, need for return to the operating room, vomiting, and oral diet tolerance. patients in the ibuprofen/acetaminophen group were younger than those in the codeine/acetaminophen group (6.2 vs 8.1 years, p .05). patients in the codeine/acetaminophen group were more likely to use antibiotics in the postoperative period (50.3 vs 5.9, p .05). the proportion of patients requiring ed visits or inpatient admission for dehydration was not significantly different between the groups (5.1 for codeine, 2.7 for ibuprofen, p .12). multivariable analysis controlling for age and antibiotic use showed no difference in ed visits or admission for dehydration (p .09). there was no difference between the groups for any of the secondary measures.",ibuprofen with acetaminophen represents a safe and acceptable analgesic alternative to codeine and acetaminophen in patients undergoing pediatric tonsillectomy.,Treatment
is cumulative exposure to ritonavir-boosted atazanavir associated with cholelithiasis in patients with hiv-1 infection?,"this study aimed to examine the effect of long-term treatment with ritonavir-boosted atazanavir (atazanavir/ritonavir) on cholelithiasis. a single-centre, cross-sectional study was conducted to elucidate the prevalence of cholelithiasis in patients with hiv-1 infection who underwent abdominal ultrasonography between january 2004 and march 2013. univariate and multivariate logistic regression analyses were applied to estimate the effects of 2 years of atazanavir/ritonavir exposure on cholelithiasis as the primary exposure. of the 890 study patients, 84 (9.4) had 2 years of atazanavir/ritonavir exposure. cholelithiasis was twice as frequent in those treated for 2 years with atazanavir/ritonavir 15 (18) of 84 patients compared with those treated for 2 years of atazanavir/ritonavir exposure and cholelithiasis (or 2.216; 95 ci 1.206-4.073; p 0.010) and the association almost persisted in multivariate analysis (adjusted or 1.806; 95 ci 0.922-3.537; p 0.085). long-term treatment (2 years) with other commonly used protease inhibitors, such as ritonavir-boosted lopinavir and ritonavir-boosted darunavir, was not associated with cholelithiasis in univariate and multivariate analysis. additional analysis showed that 1 year of exposure to atazanavir/ritonavir was significantly associated with cholelithiasis (or 1.857; 95 ci 1.073-3.214; p 0.027), whereas 1 year of exposure to ritonavir-boosted lopinavir and ritonavir-boosted darunavir was not.",long-term treatment of patients with hiv-1 infection for 2 years with atazanavir/ritonavir was associated with an increased risk of cholelithiasis compared with patients with shorter exposure. long-term exposure to atazanavir/ritonavir appears to increase the risk of cholelithiasis in patients with hiv-1 infection.,Medication
are risk of venous thromboembolism after spinal cord injury : not all levels the same?,"venous thromboembolism (vte), a diagnosis that includes both deep vein thrombosis and pulmonary embolism, is a well-recognized complication following injury. previous studies have identified multiple risk factors including spinal cord injury (sci). we hypothesized that the level of sci also influences the likelihood of vte. the national trauma data bank was queried to identify all patients with sci admitted in 2007 and 2008. rates of vte, demographics, admitting comorbidities, in-hospital complications, level of sci (divided by national trauma data bank into five groups), associated injuries, and outcome variables were abstracted. multiple regression was used to identify independent risk factors for vte. during the 2-year period, 18,302 patients were admitted with sci. the overall rate of vte was 4.3 but varied significantly depending on the level of sci injury ((2), 44.8; p 0.05). patients with high cervical spine (c1-4) injury had a rate vte of 3.4, whereas patients with high thoracic spine (t1-6) injury had the highest rate of vte at 6.3. the lowest rate of vte was in patients with lumbar injury (3.2). there were no significant differences in the preexisting comorbidities or in-hospital complications among the five sci groups with the exception of pneumonia. in a multiple logistic regression model, the level of sci was an independent risk factor for vte as was increasing age, increasing injury severity score, male gender, traumatic brain injury, and chest trauma.",the rate of vte differs with various sci levels. patients with high thoracic (t1-6) injury seem to be at the highest risk and patients with high cervical (c1-4) injury at one of the lowest. a higher index of suspicion for vte should therefore be maintained in patients with a high thoracic sci. further studies are required to elucidate the underlying mechanisms.,Prevention
is socio-economic status inversely related to bed net use in gabon?,"insecticide-treated bed nets (itns) range among the most effective measures of malaria prophylaxis, yet their implementation level in sub-saharan africa is still low. the goal of this study was to investigate the influence of socio-economic factors on the use of bed nets by mothers in gabon. a cross-sectional study was conducted completing pre-tested, interviewer-administered questionnaires exploring socioeconomic proxy measures with 397 mothers or guardians of young children. respondents were grouped according to their socio-economic situation, using scores. the condition of the bed nets was evaluated during a home visit. socio-economic factors of wellbeing were negatively associated with bed net use, such as living in a stone house (or 0.26, 95 ci 0.14-0.48), running water in the house (or 0.44, 95 ci 0.21-0.92), shower/flush toilet in the house (or 0.39/0.34, 95 ci 0.21-0.75/0.16-0.73), ownership of a freezer (or 0.50, 95 ci 0.26-0.96) and belonging to the highest group in the economic score (or 0.32, 95 ci 0.15-0.67). in contrast, similar factors were positively associated with a good maintenance condition of the bed nets: higher monthly income (or 5.64, 95 ci 2.41-13.19) and belonging to the highest group in the economic score (or 2.55, 95 ci 1.19 - 5.45).","among the poorest families in lambarn the coverage with untreated nets (utns) is the highest, but the condition of these utns is the worst. to achieve a broad implementation of itns in lambarn, there is an urgent need for educational programmes as well as need-tailored marketing strategies for itns.",Medication
is paternal smoking associated with increased risk of child malnutrition among poor urban families in indonesia?,"paternal smoking is highly prevalent in asia, and tobacco may account for a large proportion of household expenditures among poor families. we sought to characterise the relationship between paternal smoking, child malnutrition and food expenditures. data on smoking, household expenditures and child malnutrition were examined in a stratified multistage cluster sample of households in the indonesia nutrition surveillance system. main outcome measures were child wasting (weight-for-height z-score - 2), underweight (weight-for-age z-score - 2) and stunting (height-for-age z-score - 2), and severe wasting, underweight and stunting (defined by respective z-scores - 3). in total, 175,583 households from urban slum areas in indonesia. children 0-59 months of age. the prevalence of paternal smoking was 73.8. after adjusting for child gender and age, maternal age and education, and weekly per capita household expenditures, paternal smoking was associated with child stunting (odds ratio (or) 1.11, 95 confidence interval (ci) 1.08-1.14, p 0.0001), severe wasting (or 1.17, 95 ci 1.03-1.33, p 0.018) and severe stunting (or 1.09, 95 ci 1.04-1.15, p 0.001). in households where the father was a smoker, tobacco accounted for 22 of weekly per capita household expenditures, with less money spent on food compared with households in which the father was a non-smoker.","among poor families in urban slum areas of indonesia, paternal smoking diverts household money from food to tobacco and exacerbates child malnutrition.",Prevention
does ginsenoside rh2 inhibit glioma cell proliferation by targeting microrna-128?,"to examine the influence of ginsenoside rh2 (rh2), a triterpene saponin extracted from the traditional medicinal plant ginseng, on the expression of mirnas in human glioma cells. the expression profile of mirna (mir) was analyzed in human u251, t98mg and a172 glioma cells using a mirna array and quantitative real-time pcr. cell viability was assessed using a colorimetric assay (cell counting kit-8). transfection of mir-128 was performed using lipofectamine 2000. caspase 3 activity was determined using a caspase colorimetric assay kit. apoptosis was assessed using annexin v and propidium iodide staining. protein expression was determined with western blot analysis. mirna-128 targeting activity was measured using a luciferase reporter assay. in u251 cells treated with rh2 (12 g/ml), 14 of 452 human mirnas were up-regulated and 12 were down-regulated as detected with the mirna array assay. the up-regulation of mir-128 by rh2 was further verified in human u251, t98mg and a172 cells using quantitative real-time pcr. in u251 cells, transfection of a mir-128 inhibitor (50 nmol/l) prevented the overexpression of mir-128 by rh2, and significantly blunted rh2-induced cytotoxicity, apoptosis, caspase 3 activation, transcriptional activation of e2f3a, a mir-128 target gene, as well as e2f3a protein expression.",the anti-proliferative effect of rh2 in human glioma cells was mediated in part through up-regulation of mirna-128 expression.,Medication
does filaggrin-stratified transcriptomic analysis of pediatric skin identify mechanistic pathways in patients with atopic dermatitis?,"atopic dermatitis (ad; eczema) is characterized by a widespread abnormality in cutaneous barrier function and propensity to inflammation. filaggrin is a multifunctional protein and plays a key role in skin barrier formation. loss-of-function mutations in the gene encoding filaggrin (flg) are a highly significant risk factor for atopic disease, but the molecular mechanisms leading to dermatitis remain unclear. we sought to interrogate tissue-specific variations in the expressed genome in the skin of children with ad and to investigate underlying pathomechanisms in atopic skin. we applied single-molecule direct rna sequencing to analyze the whole transcriptome using minimal tissue samples. uninvolved skin biopsy specimens from 26 pediatric patients with ad were compared with site-matched samples from 10 nonatopic teenage control subjects. cases and control subjects were screened for flg genotype to stratify the data set. two thousand four hundred thirty differentially expressed genes (false discovery rate, p .05) were identified, of which 211 were significantly upregulated and 490 downregulated by greater than 2-fold. gene ontology terms for ""extracellular space"" and ""defense response"" were enriched, whereas ""lipid metabolic processes"" were downregulated. the subset of flg wild-type cases showed dysregulation of genes involved with lipid metabolism, whereas filaggrin haploinsufficiency affected global gene expression and was characterized by a type 1 interferon-mediated stress response.","these analyses demonstrate the importance of extracellular space and lipid metabolism in atopic skin pathology independent of flg genotype, whereas an aberrant defense response is seen in subjects with flg mutations. genotype stratification of the large data set has facilitated functional interpretation and might guide future therapy development.",Diagnosis
do genome-wide ancestry patterns in rapanui suggest pre-european admixture with native americans?,"rapa nui (easter island), located in the easternmost corner of the polynesian triangle, is one of the most isolated locations on the planet inhabited by humans. archaeological and genetic evidence suggests that the island was first colonized by polynesians around ad 1200, during their eastward expansion. although it remains contentious whether polynesians reached south america, suggestive evidence has been brought forward supporting the possibility of native american contact prior to the european ""discovery"" of the island in ad 1722. we generated genome-wide data for 27 rapanui. we found a mostly polynesian ancestry among rapanui and detected genome-wide patterns consistent with native american and european admixture. by considering the distribution of local ancestry tracts of eight unrelated rapanui, we found statistical support for native american admixture dating to ad 1280-1495 and european admixture dating to ad 1850-1895.",these genetic results can be explained by one or more pre-european trans-pacific contacts.,General
does plasminogen activator inhibitor type i contribute to protective immunity during experimental gram-negative sepsis ( melioidosis )?,"melioidosis is a frequent cause of sepsis in southeast asia caused by the gram-negative bacterium burkholderia pseudomallei. patients with melioidosis have elevated circulating levels of plasminogen activator inhibitor type 1 (pai-1), an important regulator of inflammation and fibrinolysis. in this study, we aimed to investigate the role of pai-1 during melioidosis. wild-type (wt) and pai-1-deficient (pai-1-/1(-/-) ) mice were intranasally infected with b. pseudomallei. mice were killed after 24, 48 or 72 h. lungs, liver and blood were harvested for measurement of bacterial loads, cytokines, clinical chemistry, histopathology, and coagulation parameters. additionally, survival studies were performed. pai-1(-/-) mice demonstrated enhanced susceptibility to b. pseudomallei infection, as shown by a strongly increased mortality rate (100 vs. 58 among wt mice, p 0.001), associated with enhanced bacterial loads in lungs, liver, and blood. additionally, pai-1(-/-) mice showed elevated levels of proinflammatory cytokines in lungs and plasma, accompanied by enhanced local and systemic coagulation activation (thrombin-antithrombin complexes and d-dimer), increased hepatocellular injury (plasma aspartate aminotransferase and alanine aminotransferase), and renal failure (plasma creatinine and urea).","pai-1 has a protective role during severe gram-negative sepsis caused by b. pseudomallei by limiting bacterial growth, inflammation, and coagulation, and probably, as a consequence thereof, distant organ injury.",Medication
does neural stem cell transplantation rescue rectum function in the aganglionic rat?,"neural stem cell (nsc) transplantation is a promising tool for restoring the nervous system in a variety of neurodegenerative disorders. the aim of this study was to determine the potential of nsc transplantation as a therapeutic strategy for neuronal replacement of the enteric nervous system of the rectum in an aganglionic rat. rat central nervous system-derived nscs (cns-nscs) obtained from the cortex of the fetal brain (e16) were transplanted into the benzalkonium chloride (bac)-induced rat aganglionic rectum. survival and differentiation of the implanted cells were assessed at 8 weeks posttransplantation using immunostaining and western blotting. the rectoanal inhibitory reflex (rair) was also be measured. eight weeks following transplantation, grafted cns-nscs differentiated into neurons and glial cells in the aganglionic rectum. the protein expression of neuronal nitric oxide synthase (nnos) and choline acetyltransferase (chat) were significantly increased and the rair restored after cell implantation.",cns-nsc transplantation may provide a viable therapeutic option for disorders of the enteric nervous system.,Treatment
is vascular endothelial growth factor 936 c/t polymorphism associated with vascular invasion in oral squamous cell carcinoma?,"the objective of this study was to analyze the relation of vegf 936 c/t polymorphisms in progression of oral squamous cell carcinoma (oscc) patients and healthy subjects in taiwan. we genotyped 218 patients with oscc, comparing the genotypes and gene frequencies with those of 121 control subjects. vegf 936 c/t polymorphisms were determined by using polymerase chain reaction and restriction fragment length polymorphism. there were no significant differences in genotype, phenotype, or gene frequency between the oscc and control groups. among patients with oscc, there were also no significant differences in the polymorphism between those with and without cervical lymph node metastases or in survival. however, 21 of the 218 patients had vascular invasion by their oscc, and these patients were significantly more likely to have a c/c (p .033) or c/t genotype (p .026) than were those without vascular invasion.",this study suggests that the vegf 936 c allele is associated with vascular invasion in oscc.,General
does lipopolysaccharide contamination of beta-lactoglobulin affect the immune response against intraperitoneally and orally administered antigen?,"microbial components in the environment are potent activators of the immune system with capacity to shift the active immune response towards priming of th1 and/or th2 cells. lipopolysaccharide (lps), a cell-wall component of gram-negative bacteria, is extensively present in food products like cow's milk. it is not well established, however, how this presence of lps affects oral tolerance induction. we studied the effect of lps contamination in a commercial preparation of the cow milk protein beta-lactoglobulin (beta-lg) on antigen-specific immune responses. igg1/igg2a production upon intraperitoneal immunization without adjuvant was measured, and oral tolerance induction against beta-lg after administration of either an aqueous solution or water-in-oil (w/o) emulsion of beta-lg was evaluated. lps contamination of beta-lg provoked a beta-lg-specific igg2a response, as well as an enhanced beta-lg-specific igg1 response upon intraperitoneal immunization. oral tolerance induction to beta-lg was induced by aqueous solutions of beta-lg with and without lps administration. conversely, oral administration of w/o-emulsified beta-lg prevented oral tolerance to beta-lg only when the beta-lg was contaminated with lps.","lps contamination of an aqueous protein solution does not affect oral tolerance induction, whereas lps present in emulsion prevents oral tolerance induction towards the food protein.",Medication
"is change in saturated fat intake associated with progression of carotid and femoral intima-media thickness , and with levels of soluble intercellular adhesion molecule-1?","a high saturated fat (sfa) intake may stimulate progression of atherosclerosis, and may be positively associated with expression of adhesion molecules. in moderately hypercholesterolaemic participants of a dietary intervention study (n103; 55/-10 years), we examined associations between reported changes in sfa intake and changes in carotid and femoral intima-media thickness (imt) and soluble intercellular adhesion molecule-1 (sicam-1) levels after 2 years. the carotid and femoral imt was assessed by high-resolution b-mode ultrasound images. after 2 years, dietary intake of sfa decreased with 1.8/-2.6 of energy (p0.01). in the lowest quintile of change in sfa intake (-5.9/-1.4 of energy), changes in carotid and femoral imt were 0.03 mm (sem 0.03) and -0.09 mm (sem 0.07), respectively, versus 0.10 mm (sem 0.03), 0.17 mm (sem 0.07) in the top quintile (1.6/-0.7 of energy) (p linear trend 0.07 (carotis), 0.02 (femoralis)). changes in sicam-1 were -19.0 ng/nl (sem 5.6) in the lowest quintile, versus 8.6 ng/ml (sem 5.3) in the top quintile (p linear trend 0.001), adjusted for baseline level, sfa intake, body mass index, age, changes in intake of fruit, polyunsaturated fat, and dietary cholesterol. adjustments for changes in established risk factors did not alter these results.","decreased sfa intake may reduce progression of atherosclerosis, as assessed by imt, and is associated with reduced levels of sicam-1 after 2 years. further research using randomised placebo-controlled trials is necessary to exclude potential confounding variables and to confirm causality.",Prevention
is phosphorylation of shox2 required for its function to control sinoatrial node formation?,"inactivation of shox2, a member of the short-stature homeobox gene family, leads to defective development of multiple organs and embryonic lethality as a result of cardiovascular defects, including bradycardia and severe hypoplastic sinoatrial node (san) and sinus valves, in mice. it has been demonstrated that shox2 regulates a genetic network through the repression of nkx2.5 to maintain the fate of the san cells. however, the functional mechanism of shox2 protein as a transcriptional repressor on nkx2.5 expression remains completely unknown. a specific interaction between the b56 regulatory subunit of pp2a and shox2a, the isoform that is expressed in the developing heart, was demonstrated by yeast 2-hybrid screen and coimmunoprecipitation. western blotting and immunohistochemical assays further confirmed the presence of phosphorylated shox2a (p-shox2a) in cell culture as well as in the developing mouse and human san. site-directed mutagenesis and in vitro kinase assays identified ser92 and ser110 as true phosphorylation sites and substrates of extracellular signal-regulated kinase 1 and 2. despite that shox2a and its phosphorylation mutants possessed similar transcriptional repressive activities in cell cultures when fused with gal4 protein, the mutant forms exhibited a compromised repressive effect on the activity of the mouse nkx2.5 promoter in cell cultures, indicating that phosphorylation is required for shox2a to repress nkx2.5 expression specifically. transgenic expression of shox2a, but not shox2a-s92as110a, mutant in the developing heart resulted in down-regulation of nkx2.5 in wild-type mice and rescued the san defects in the shox2 mutant background. last, we demonstrated that elimination of both phosphorylation sites on shox2a did not alter its nuclear location and dimerization, but depleted its capability to bind to the consensus sequences within the nkx2.5 promoter region.",our studies reveal that phosphorylation is essential for shox2a to repress nkx2.5 expression during san development and differentiation.,Diagnosis
is hla-g expression up-regulated by progesterone in mesenchymal stem cells?,"maternal immune response to fetal tissues is modified in such way that it favors the development of pregnancy. human leukocyte antigen (hla)-g, progesterone and mesenchymal stem cells (mscs) have been identified as potent immunomodulatory agents in different experimental systems and the interactions between these three factors are studies in this paper. human mscs are isolated from human adipose tissue, bone marrow and decidua are cultured in the presence of progesterone and the expression of hla-g is followed-up at protein and mrna levels. the mscs cultured in the presence of progesterone express increased levels of both cell surface and cytoplasmic hla-g when compared with the control mscs.",progesterone up-regulates the expression by mscs of hla-g which is a major player in maintenance of the immune balance between the mother and the fetus. mscs are newly detected targets of progesterone with well documented immunomodulatory activity.,General
is carotid intima-media thickness associated with markers of atherosclerosis in stroke patients?,"it has been argued that carotid intima-media thickness (imt) could better reflect an adaptive response of the vessel wall rather than being a marker of atherosclerosis. we explore this hypothesis by analyzing the artico data. the artico study was designed to evaluate the prognostic value of the pathological ankle-brachial index (abi) for the emergence of new vascular events in patients who have suffered a noncardioembolic stroke. collected variables were as follows: vascular risk factors, mean waist perimeter, quantification of carotid imt, characteristics of carotid plaques, abi, and presence of microalbuminuria. a total of 591 patients with a complete carotid evaluation were available. there was no correlation between abi and imt (spearman's, p ns). logistic regression revealed that pathological abi correlated significantly only with internal carotid artery stenosis greater than or equal to 50 (or odds ratio 2.80, 1.66-4.71, p .01) and peripheral artery disease (or 3.33, 1.63-6.78, p .01). however, multivariate regression analysis demonstrated that carotid imt was independently associated with age (or 1.05, 95 confidence interval ci 1.02-1.09, p .01), hypertension (or 1.83, 95 ci 1.02-3.26, p .04), waist circumference (or 1.03, 95 ci 1.01-1.05, p .01), and microalbuminuria (or 2.02, 95 ci 1.22-3.35, p .01).","in our patients, carotid imt does not seem to be associated with unequivocal markers of atheromatosis such as the existence of relevant carotid plaques or pathological abi. these results as well as the association of imt with age, hypertension, microalbuminuria, and mean waist perimeter support the hypothesis that imt must be considered a risk factor for general vascular disease rather than a marker of atherosclerotic burden.",Diagnosis
does rituximab adversely affect the stem cell mobilization and engraftment after high-dose therapy and autologous transplantation in patients with diffuse large b-cell lymphoma in first complete or partial remission?,"the goal was to investigate the effect of prior combined rituximab (r) and intensive chemotherapy on peripheral blood stem cell mobilization and their engraftment after stem cell transplantation (asct) in 69 patients with poor-risk, diffuse large b-cell lymphoma (dlbcl). a statistically comparable median number of cd34 stem cells was collected in both groups (13.80x10(6)/ kg in the non-r group and 7.81x10(6)/kg in the r group; p 0.110). a trend toward greater number of cfu-gm was found in the non-r group (98.1x10(4)/kg) compared to the r group (76.6x10(4)/kg; p 0.068). the non-r patients had a much higher median number of bfu-e (90.9x10(4)/kg) than the r patients (31.3x10(4)/kg; p 0.001).","hematopoietic engraftment was rapid for both groups and no different between them. the 3-year event-free survival was 90.4 in the r group and 67.2 in the non-r group (p 0.04), but there was no significant difference in the 3-year overall survival (94,7 vs 83,5 ; p 0.179).",Treatment
is accuracy of monitoring serum carcinoembryonic antigen levels in postoperative stage iii colorectal cancer patients limited to only the first postoperative year?,"the aim of the present study was to determine the accuracy of yearly postoperative monitoring of serum tumor markers to either detect or rule out recurrence in colorectal cancer patients. a total of 127 colorectal cancer patients who underwent curative surgery were enrolled. the serum carcinoembryonic antigen (cea) and carbohydrate antigen 19-9 (ca19-9) levels were assayed, and radiological examinations were performed routinely for 5 years after surgery or until recurrence was detected. yearly recurrence rates (number of recurrences/number of patients assessed in a given year), sensitivities, specificities, and likelihood ratios were calculated. post-test probabilities were calculated from these values. recurrences tended to show almost the same frequencies in the first and second year after surgery (20 of 127 patients and 18 of 107 patients, respectively). however, the post-test probability of recurrence in patients with positive and negative serum cea levels was significantly lower in the second year than in the first year (test positive: 40.0 and 76.0; test negative: 9.3 and 0.5, respectively).","measuring cea can help to identify patients likely to demonstrate recurrence with high accuracy only within the first year after surgery. another examination, such as imaging, is therefore necessary for monitoring patients at 2 or more years after surgery.",Treatment
are both the apoptotic suicide pathway and phagocytosis required for a programmed cell death in caenorhabditis elegans?,"programmed cell deaths in the nematode caenorhabditis elegans are generally considered suicides. dying cells are engulfed by neighboring cells in a process of phagocytosis. to better understand the interaction between the engulfment and death processes, we analyzed b.al/rapaav cell death, which has been previously described as engulfment-dependent and hence as a possible murder. we found that b.al/rapaav is resistant to caspase-pathway activation: the caspase-mediated suicide pathway initiates the cell-death process but is insufficient to cause b.al/rapaav death without the subsequent assistance of engulfment. when the engulfing cell p12.pa is absent, other typically non-phagocytic cells can display cryptic engulfment potential and facilitate this death.","we term this death an ""assisted suicide"" and propose that assisted suicides likely occur in other organisms. the study of assisted suicides might provide insight into non-cell autonomous influences on cell death. understanding the mechanism that causes b.al/rapaav to be resistant to activation of the caspase pathway might reveal the basis of differences in the sensitivity to apoptotic stimuli of tumor and normal cells, a key issue in the field of cancer therapeutics.",General
does polynass bioactivation of lars artificial ligament promote human ligament fibroblast colonisation in vitro?,"introduction of a new generation of artificial ligaments for acl reconstruction, the ligament augmentation and reconstruction system (lars), gives promising clinical results 1. the current literature supports the use of lars from short to medium term. to go even further to improve the biocompatibility of this biomaterial, poly(sodium styrene sulfonate) (polynass) was grafted onto its surface. studies using sheep animal model showed improvement of knee functionalities with this grafted artificial ligament and a better adhesion of human cell lines. to better understand this in vivo improvement of integration with the bioactivated artificial prosthesis, in vitro studies were leaded using human ligament fibroblasts. human ligament fibroblasts isolated from human ruptured acl were amplified and seeded onto poly(nass) grafted and non-grafted pet scaffold (lars ligament) under standard culture conditions. cellularized fibers were observed under scanning electron microscopy and histological and immunohistological studies were performed. cells are localized around the grafted pet fibers of the bioactive ligament and penetrate in the scaffold. on ungrafted fibers, cells stay around the scaffold. on grafted fibers, collagen i appears strongly organized whereas is thin and dispersed on non grafted fibers. finally, grafting altered localization of decorin.",polynass grafting enhances human ligament fibroblast organisation in vitro in contact with biomaterial and improves collagen and decorin deposits around fibers.,Treatment
do therapeutic efficacy of voriconazole against a fluconazole-resistant candida albicans isolate in a vaginal model?,"the purpose of this study was to assess the therapeutic efficacy of oral versus intravaginal voriconazole and compare it with fluconazole for the treatment of experimental vaginitis caused by a fluconazole-resistant candida albicans isolate. mice were treated with voriconazole at 5, 10 and 20 mg/kg once a day and 20 mg/kg twice a day or with fluconazole at 20 mg/kg once or twice a day orally. intravaginal treatments were evaluated with voriconazole and fluconazole at 0.5, 1 and 5 mg/kg once a day. all treatment regimens were given on days 1-5 post-challenge. one day 6, the vaginas were swabbed to assess treatment effects. mice treated orally with voriconazole at or10 mg/kg and fluconazole at or20 mg/kg showed significantly reduced fungal counts over controls (p 0.0002-0.007). significant differences were found between the groups that received voriconazole at 20 mg/kg once or twice daily and those that received fluconazole at 20 mg/kg once or twice daily, orally (p 0.010 and 0.001, respectively). mice treated with voriconazole or fluconazole administered intravaginally at or0.5 mg/kg exhibited a reduced fungal burden when compared with the control group (p 0.0002-0.007). there was no statistically significant difference in fungal burden between topical treatment with doses of 0.5, 1 and 5 mg/kg once daily of voriconazole or fluconazole. sterilization of vaginas was not observed with voriconazole and fluconazole without taking into consideration the therapeutic modality.",voriconazole could emerge as a new alternative for treatment of vaginal candidosis.,Medication
do mast cell tnf receptors regulate responses to mycoplasma pneumoniae in surfactant protein a ( sp-a ) -/- mice?,"mycoplasma pneumoniae (mp) frequently colonizes the airways of patients with chronic asthma and likely contributes to asthma exacerbations. we previously reported that mice lacking surfactant protein a (sp-a) have increased airway hyperresponsiveness (ahr) during m pneumoniae infection versus wild-type mice mediated by tnf-. mast cells (mcs) have been implicated in ahr in asthma models and produce and respond to tnf-. determine the contribution of mc/tnf interactions to ahr in airways lacking functional sp-a during mp infection. bronchoalveolar lavage fluid was collected from healthy and asthmatic subjects to examine tnf- levels and m pneumoniae positivity. to determine how sp-a interactions with mcs regulate airway homeostasis, we generated mice lacking both sp-a and mcs (sp-a(-/-)kit(w-sh/w-sh)) and infected them with m pneumoniae. our findings indicate that high tnf- levels correlate with m pneumoniae positivity in human asthmatic patients and that human sp-a inhibits m pneumoniae-stimulated transcription and release of tnf- by mcs, implicating a protective role for sp-a. mc numbers increase in m pneumoniae-infected lungs, and airway reactivity is dramatically attenuated when mcs are absent. using sp-a(-/-)kit(w-sh/w-sh) mice engrafted with tnf-(-/-) or tnf receptor (tnf-r)(-/-) mcs, we found that tnf- activation of mcs through the tnf-r, but not mc-derived tnf-, leads to augmented ahr during m pneumoniae infection when sp-a is absent. additionally, m pneumoniae-infected sp-a(-/-)kit(w-sh/w-sh) mice engrafted with tnf-(-/-) or tnf-r(-/-) mcs have decreased mucus production compared with that seen in mice engrafted with wild-type mcs, whereas burden was unaffected.",our data highlight a previously unappreciated but vital role for mcs as secondary responders to tnf- during the host response to pathogen infection.,Medication
is swallowing dysfunction a common sequelae after chemoradiation for oropharynx carcinoma?,"a retrospective review of all patients with advanced oropharynx cancer from a single institution was performed. sixty-seven patients with stage iii/iv oropharynx cancer were treated with definitive radiotherapy with or without concurrent chemotherapy from 1990 to 2004. follow-up ranged from 6 to 91 months with a median of 32 months. patients treated with concurrent chemotherapy had a statistically significant benefit for control above the clavicles, primary control, disease-free survival, and overall survival but no difference in distant control at 3 years. cox proportional regression model demonstrated the use of concurrent chemotherapy to be the only independent variable that reached significance for control above the clavicles, primary control, and overall survival. complete dysphagia for solids and/or gastrostomy tube dependence was observed in more patients who were treated with chemoradiation than those treated with radiation alone; 18 and 0, respectively (p 0.04).",concurrent chemotherapy decreases the recurrence at the primary site and above the clavicles. the most notable difference in sequelae between the 2 groups was the increase in swallowing dysfunction with concurrent chemotherapy.,Treatment
do lipopeptides from a novel bacillus methylotrophicus 39b strain suppress agrobacterium crown gall tumours on tomato plants?,"this study aims to characterise the antibacterial activity of a novel bacillus methylotrophicus strain named 39b against tumourigenic agrobacterium tumefaciens c58 and b6 strains. it also aims to identify the compound that is responsible for its activity and to evaluate its efficiency to control crown gall disease in tomato plants. b. methylotrophicus strain 39b was found to stop the growth of phytopathogenic a. tumefaciens strains in in vitro experiments. lipopeptides - surfactins, iturins and fengycins - were detected under various isoforms by mass spectrometry analysis of the methanolic extract. the active principle acting against agrobacterium strains was isolated from tlc plates and identified by mass spectrometry as surfactin. the strain was effective in reducing the weight and the number of galls induced by a. tumefaciens strains on tomato plants. total inhibition of gall formation was observed using the antibacterial compounds.",b. methylotrophicus strain 39b exhibited antibacterial activity against phytopathogenic a. tumefaciens c58 and b6 both in vitro and in vivo. lipopeptides are the main compounds that confer the biocontrol ability. this strain has the potential to be developed as a biological control agent for crown gall disease. 2016 society of chemical industry.,General
does intravenous anesthetic propofol inhibit multiple human cardiac potassium channels?,"propofol is widely used clinically for the induction and maintenance of anesthesia. clinical case reports have shown that propofol has an antiatrial tachycardia/fibrillation effect; however, the related ionic mechanisms are not fully understood. the current study investigates the effects of propofol on human cardiac potassium channels. the whole cell patch voltage clamp technique was used to record transient outward potassium current (ito) and ultrarapidly activating delayed rectifier potassium current (ikur) in human atrial myocytes and hkv1.5, human ether--go-go-related gene (herg), and hkcnq1/hkcne1 channels stably expressed in hek 293 cells. current clamp mode was used to record action potentials in human atrial myocytes. in human atrial myocytes, propofol inhibited ito in a concentration-dependent manner (ic50 33.5 2.0 m for peak current, n 6) by blocking open channels without affecting the voltage-dependent kinetics or the recovery time constant; propofol decreased ikur (ic50 35.3 1.9 m, n 6) in human atrial myocytes and inhibited hkv1.5 current expressed in hek 293 cells by preferentially binding to the open channels. action potential duration at 90 repolarization was slightly prolonged by 30 m propofol in human atrial myocytes. in addition, propofol also suppressed herg and hkcnq1/hkcne1 channels expressed in hek 293 cells.","propofol inhibits multiple human cardiac potassium channels, including human atrial ito and ikur, as well as hkv1.5, herg, and hkcnq1/hkcne1 channels stably expressed in hek 293 cells, and slightly prolongs human atrial action potential duration, which may contribute to the antiatrial tachycardia/fibrillation effects observed in patients who receive propofol.",Medication
does ast/alt ratio predict cirrhosis in patients with chronic hepatitis c virus infection?,"a liver biopsy is necessary to grade and stage chronic hepatitis c virus (hcv) infection. in a previous study of patients with nonalcoholic liver disease, an aspartate aminotransferase (ast) to alanine aminotransferase (alt) ratio 1 suggested cirrhosis. we sought to examine the value of the ast/alt ratio in distinguishing cirrhotic patients with chronic hcv infection from noncirrhotic patients and to correlate the ratio with the grade and stage of hepatitis and other biochemical indices. we retrospectively studied 139 patients with chronic hcv infection. routine biochemical indices were determined, and the histological grade of necroinflammatory activity and the stage of fibrosis of the liver biopsy specimens were scored. the mean ast/alt ratio in the cirrhotic patients (n 47) was higher than in the noncirrhotic patients (n 92) (1.06 /- 0.06 vs 0.60 /- 0.09; p or 1 had 100 specificity and positive predictive value in distinguishing cirrhotic from noncirrhotic patients, with a 53.2 sensitivity and 80.7 negative predictive value. the ratio correlated positively with the stage of fibrosis but not with the grade of activity or other biochemical indices. of the cirrhotic patients, 17 had no clinical or biochemical features suggestive of chronic liver disease except for an ast/alt ratio or 1.",the ast/alt ratio is a dependable marker of fibrosis stage and cirrhosis in patients with chronic hcv infection.,Diagnosis
does grapefruit juice reduce the oral bioavailability of fexofenadine but not desloratadine?,"certain foods, such as grapefruit juice, are known to substantially alter the bioavailability of some drugs. these effects may be mediated by interactions with enzyme systems, such as cytochrome p450, or with active transporter systems, such as p-glycoprotein and organic anion transporting polypeptides. to assess the effect of consumption of grapefruit juice on the oral bioavailability of two nonsedating antihistamines, fexofenadine and desloratadine. non-blinded, randomised, single-dose, four-way crossover study. twenty-four healthy adult volunteers. single oral doses of desloratadine 5mg and fexofenadine 60mg taken without and with grapefruit juice (pretreatment with 240ml of double-strength juice three times daily for 2 days prior to administration of study drug, plus the same amount simultaneously with, and 2 hours after, the drug dose). each treatment was separated by at least 10 days. log-transformed pharmacokinetic parameters peak plasma concentration (c(max)) and area under the curve (auc), time to maximum concentration, elimination half-life and electrocardiographic (ecg) parameters. comparing the ratio of the pharmacokinetic parameter means (c(max) and auc) with and without grapefruit juice (expressed as a percentage), the rate (c(max)) and extent (auc) of absorption of fexofenadine were reduced by 30 by consumption of grapefruit juice. in contrast, the bioavailability of desloratadine was unaffected by grapefruit juice. no clinically significant changes in ecg parameters were observed following coadministration of grapefruit juice with desloratadine or fexofenadine compared with either antihistamine given alone.","the bioavailability of drugs that do not undergo significant intestinal or hepatic metabolism, such as fexofenadine, may be altered when administered with agents that influence drug transport mechanisms.",Medication
does progesterone promote human bone marrow mesenchymal stem cells to synthesize fibronectin via erk pathway ?,"to investigate whether the progesterone can promote fibronection (fn) synthesis by human bone marrow mesenchymal stem cells (mscs) and to explore the potential underlying mechanism. the human bone marrow mscs were cultured in a serum-free medium with progesterone for 72 hours, the mtt test was performed to observe the proliferation status and adhension ability of the treated cells. western blot was used to detect the content of fn in msds with gapdh as the internal reference, the phosphorylation of erk1/2, as well as the fn content in msc treated by pd98059, a specific inhibitor of erk1/2. the progesterone at a range of certain doses not effect on the proliferation of human bone marrow mscs. progesterone (25 g/l) treatment enhanced the fn expression and adherent ability of marrow mscs. progesterone could induce prompt phosphorylation of erk 1/2 and its promoting effects on fn synthesis was reversed by pd98059.","the progesterone can promote fn synthesis by human bone marrow mscs via erk 1/2 pathway, and it might be used to culture mscs in serum-free medium.",Medication
does success of carotid endarterectomy in veterans : high medical risk equate with high surgical risk?,"the safety and efficacy of carotid endarterectomy (cea) in stroke prevention has been well documented. but ""high-risk"" patients have traditionally been excluded from these studies and may be offered alternate therapies. we examined the safety of cea in veterans, a medically high-risk group with multiple comorbidities. the records of all patients having ceas performed between 1995 and 1999 in the connecticut veterans affairs (va) hospital were reviewed. survival and freedom from stroke were determined using kaplan-meier survival analysis. the effects of risk factors on outcomes were analyzed with cox regression. there were 128 ceas performed in 120 patients, with a mean followup of 8.5 years. most patients were symptomatic preoperatively and had a high incidence of hypertension (83), coronary artery disease (64), diabetes (37), and pulmonary disease (22). incidences of perioperative (30-day) mortality (0.8), stroke (1.6), and myocardial infarction (0.8) were low. survival rates at 8.9 and 12 years were 50 and 13, respectively, with 90 patient followup. freedom from ipsilateral stroke was 90 at 12 years. age (hazards ratio hr 1.1, p0.004), hypertension (hr 2.6, p0.04), and elevated creatinine (hr 3.7, p0.001) were significant risk factors for mortality. age (hr 0.8, p0.07) and diastolic blood pressure (hr 1.2, p0.06) were predictive of ipsilateral stroke.","despite poor health and symptomatic presentation, patients treated with cea achieved excellent perioperative outcomes and were protected from stroke for the remainder of their lives. multiple medical comorbidities should not be used as exclusion criteria for cea.",Treatment
"is aes , the gene encoding the esterase b in escherichia coli , a powerful phylogenetic marker of the species?","previous studies have established a correlation between electrophoretic polymorphism of esterase b, and virulence and phylogeny of escherichia coli. strains belonging to the phylogenetic group b2 are more frequently implicated in extraintestinal infections and include esterase b2 variants, whereas phylogenetic groups a, b1 and d contain less virulent strains and include esterase b1 variants. we investigated esterase b as a marker of phylogeny and/or virulence, in a thorough analysis of the esterase b-encoding gene. we identified the gene encoding esterase b as the acetyl-esterase gene (aes) using gene disruption. the analysis of aes nucleotide sequences in a panel of 78 reference strains, including the e. coli reference (ecor) strains, demonstrated that the gene is under purifying selection. the phylogenetic tree reconstructed from aes sequences showed a strong correlation with the species phylogenetic history, based on multi-locus sequence typing using six housekeeping genes. the unambiguous distinction between variants b1 and b2 by electrophoresis was consistent with aes amino-acid sequence analysis and protein modelling, which showed that substituted amino acids in the two esterase b variants occurred mostly at different sites on the protein surface. studies in an experimental mouse model of septicaemia using mutant strains did not reveal a direct link between aes and extraintestinal virulence. moreover, we did not find any genes in the chromosomal region of aes to be associated with virulence.","our findings suggest that aes does not play a direct role in the virulence of e. coli extraintestinal infection. however, this gene acts as a powerful marker of phylogeny, illustrating the extensive divergence of b2 phylogenetic group strains from the rest of the species.",Diagnosis
does transplantation of adipose tissue-derived stem cells promote soft tissue wound repair in rats ?,"to assess the effect of local and intravenous transplantation of adipose tissue-derived stem cells (adscs) in promoting soft tissue wound healing in rats. adscs isolated from the adipose tissues of sd rats were cultured in vitro, and the third-passage cells were identified for their capacity of multipotent differentiation. eighteen sd rats with 1.8 cm dorsal full-thickness soft tissue defects (0.5 cm deep) were randomized into 3 groups to receive injection of 3.010 dii-labeled adscs via the tail vein, local injection of the cells at the wound site, or injection of saline (control). the wound healing was evaluated on days 3, 7, 11, and 14 postoperatively. on day 24 after the injury, tissue samples at the wound site were collected for fluorescent microscopy and he staining. the adscs obtained were capable of adipogenic, osteogenic, and neurogenic differentiation in vitro. adscs transplantation significantly promoted wound healing as compared to the control group. obvious wound contracture was observed in the local injection group on day 3 and in the intravenous injection group on day 7. fluorescence microscopy revealed dii-positive cells in the healing wound, and he staining showed a greater tissue thickness at the wound in the two adscs transplantation groups. compared to the control group, the two adscs transplantation groups showed more gland-like structures and better neovascularization at the wound.","adscs can significantly promote wound healing in rats, and local injection of adscs allows more rapid and obvious wound healing than tail veil injection of the stem cells.",Treatment
is the incidence of renal anomalies at full term in fetal rats synergistically increased by estradiol ( but not testosterone ) supplementation on day 18 of alcoholic gestation?,"fetal alcohol syndrome is characterized by facial dysmorphology, mental and growth retardation, and somatic anomalies including hydronephrosis. the authors sought to determine the influence of exogenous testosterone or estradiol on the incidence of hydronephrosis in a rodent model of fetal alcohol syndrome (fas). pregnant rats were fed a liquid diet containing 35 ethanol-derived calories from gestation day 6 through 15, with exogenous testosterone or estradiol supplementation on day 18. on day 20, fetal kidneys were examined for evidence of hydronephrosis, and fetal serum estradiol concentrations were determined by radioimmunoassay. maternal estrogen supplementation resulted in very high fetal serum estradiol levels that were not additionally increased by alcoholism. despite this fact, the expression of renal malformations was highest in the alcoholic, estradiol-supplemented offspring. additionally, the rate of renal malformations was significantly higher in the estrogen-supplemented alcoholic group than in the strictly estradiol animals, yet the fetal serum estradiol concentrations did not differ between the two groups.","this suggests that ethanol may act synergistically with estradiol to increase the rate of renal anomalies including hydronephrosis. such damage may persist via a suppression of normal testosterone-stimulated renal growth and development. fas includes significant renal anomalies characterized by hydronephrosis in both animal models and affected children. although the long-term functional sequelae of hydronephrosis and reflux are well known, the progression of renal disease in fas children remains to be documented.",Medication
does vitamin d enhance reactive oxygen intermediates production in phagocytic cells in term and preterm infants?,"newborn infants are endotoxin tolerant which may be responsible for their increased susceptibility to bacterial sepsis. vitamin d has an immunomodulatory effect and newborn infants are at risk of vitamin d deficiency. we examined the in vitro effect of 1, 25-dihydroxyvitamin d (1,25ohd) on whole blood phagocytic toll-like receptor 4 (tlr4), cd11b, and reactive oxygen intermediates (rois) in newborn infants during sepsis. whole blood from preterm infants 32-wk gestation, control term neonates, and adults were sampled for phagocytic expression of roi, tlr4, cd11b in response to lipopolysaccharide (lps), and 1,25ohd using flow cytometer. roi production from newborn phagocytes incubated with lps alone was decreased. pretreatment with 1,25ohd demonstrated increased (p 0.001) phagocytic roi production in newborns but not in adults. 1,25ohd did not have any effect on tlr4 and cd11b in both newborns and adults. pretreatment with roi inhibitors (apocynin (apo) and diphenyleneiodonium), phosphoinositide 3-kinase (pi3k) inhibitor, and p38 inhibitor blocked neutrophil roi production.","neonatal phagocytic cells had diminished roi production in the presence of lps, however, pretreatment with 1,25ohd reversed this hyporesponsiveness. this action by 1,25ohd was mediated by activation of nicotinamide adenine dinucleotide phosphate oxidase system through pi3k signaling enzymes.",Medication
is hiv-1 rev oligomerization obligatory in the presence of an extra basic domain?,"the hiv-1 rev regulatory protein binds as an oligomeric complex to viral rna mediating nuclear export of incompletely spliced and non-spliced viral mrnas encoding the viral structural proteins. however, the biological significance of the obligatory complex formation of rev upon the viral rna is unclear. the activity of various fusion proteins based on the negative oligomerization-defect rev mutant m4 was tested using rev dependent reporter constructs. an artificial m4 mutant dimer and an m4 mutant containing an extra basic domain from the htlv-i rex protein exhibited nearly full activity when compared to wild type rev.",rev dimerization appears to be required to expose free basic domains whilst the rev oligomeric complex remains bound to viral rna via other basic domains.,General
does stox1 overexpression in choriocarcinoma cells mimic transcriptional alterations observed in preeclamptic placentas?,"mutations in stox1 were proposed to be causal for predisposing to preeclampsia, a hypertensive disorder originating from placental defects, affecting up to 10 of human pregnancies. however, after the first study published in 2005 three other groups have dismissed the polymorphism described in the first paper as a causal mutation. in the present study, we have produced a choriocarcinoma cell line overexpressing stox1. this overexpression results in transcriptional modification of 12.5 of the genes, some of them being direct targets as shown by chromatin immunoprecipitation. stox1 overexpression correlates strongly and specifically with transcriptomic alterations in preeclamptic placentas (r 0.30, p 9.10(-7)). numerous known key modulators of preeclampsia (such as endoglin, syncytin, human chorionic gonadotrophin -hcg-, and glial cell missing homolog -gcm1-) were modified in these transformed choriocarcinoma cells.","our results contribute to reconcile contradictory data concerning the involvement of stox1 in preeclampsia. in addition, they strongly suggest that anomalies in stox1 expression are associated with the onset of preeclampsia, thus indicating that this gene should be the target of future studies. our cellular model could constitute an invaluable resource for studying specific aspects of this human disease.",General
does diethyldithiocarbamate inhibit inos expression in human lens epithelial cells stimulated by ifn-gamma and lps?,"to investigate the biological activity of human lens epithelial cells (hlec) in producing inducible nitric oxide synthase (inos) and nitric oxide (no), and to assesse the effect of diethyldithiocarbamate (ddc) on inos mrna levels and expression of nos. the human lens epithelial cell line sra 01/04 was used in this experiment. semi-quantitative reverse transcription polymerase chain reaction (rt-pcr) and western blotting were used to detect, respectively, inos mrna expression and protein production. a costimulation by interferon gamma (ifn-gamma) and lipopolysaccharide (lps) was necessary for inos expression in hlec. the expression of inos was significantly reduced in a dose-dependent manner by adding ddc from 10 micromol/l to 1 mmol/l.",the expression of inos in hlec needs co-stimulation with ifn-gamma and lps and it is inhibited by ddc.,Prevention
is invasion of salmonella into human intestinal epithelial cells modulated by hla-b27?,"to investigate the influence of the major histocompatibility complex (mhc) class i molecule hla-b27 on (i) the invasion of salmonella and yersinia into human intestinal epithelial cells, (ii) the survival of intracellular salmonella in these cells, and (iii) the production of certain inflammatory cytokines by the cells after salmonella infection. the human intestinal epithelial cell line henle-407 was transfected with hla-b27 dna. these cells and hla-b27-negative control cells were infected with salmonella or yersinia, and viable intracellular bacteria were determined as colony-forming units. cytokine production was assayed with elisa. salmonella invaded hla-b27-positive henle cells in higher numbers than hla-b27-negative control cells. however, hla-b27 did not affect the invasion of yersinia or the survival of the intracellular bacteria in these intestinal epithelial cells. salmonella infection induced production of interleukin-8 (il-8), il-6 and monocyte chemotactic protein 1 (mcp-1) by henle cells that was not affected by hla-b27 in a specific way.",these findings suggest that hla-b27 enhances the invasion of salmonella into intestinal epithelial cells. the interaction between bacteria and intestinal epithelial cells plays an important role during the early phases of rea. hla-b27-linked modulation of salmonella invasion may lead to an increased load of salmonella in intestinal tissue and thus increased susceptibility to reactive arthritis.,General
do electronic health record surveillance algorithms facilitate the detection of transfusion-related pulmonary complications?,"transfusion-related acute lung injury (trali) and transfusion-associated circulatory overload (taco) are leading causes of transfusion-related mortality. notably, poor syndrome recognition and underreporting likely result in an underestimate of their true attributable burden. we aimed to develop accurate electronic health record-based screening algorithms for improved detection of trali/transfused acute lung injury (ali) and taco. this was a retrospective observational study. the study cohort, identified from a previous national institutes of health-sponsored prospective investigation, included 223 transfused patients with trali, transfused ali, taco, or complication-free controls. optimal case detection algorithms were identified using classification and regression tree (cart) analyses. algorithm performance was evaluated with sensitivities, specificities, likelihood ratios, and overall misclassification rates. for trali/transfused ali detection, cart analysis achieved a sensitivity and specificity of 83.9 (95 confidence interval ci, 74.4-90.4) and 89.7 (95 ci, 80.3-95.2), respectively. for taco, the sensitivity and specificity were 86.5 (95 ci, 73.6-94.0) and 92.3 (95 ci, 83.4-96.8), respectively. reduced pao2 /fio2 ratios and the acquisition of posttransfusion chest radiographs were the primary determinants of case versus control status for both syndromes. of true-positive cases identified using the screening algorithms (trali/transfused ali, n 78; taco, n 45), only 11 (14.1) and five (11.1) were reported to the blood bank by physicians, respectively.","electronic screening algorithms have shown good sensitivity and specificity for identifying patients with trali/transfused ali and taco at our institution. this supports the notion that active electronic surveillance may improve case identification, thereby providing a more accurate understanding of trali/transfused ali and taco epidemiology.",Diagnosis
are outcomes in clinical trials of inhaled corticosteroids for children with asthma narrowly focussed on short term disease activity?,"little work has been done to determine which outcomes should be measured in randomised controlled trials (rcts) in children with asthma. drug regulatory authorities require that short term disease activity is measured, but other outcome domains are not mandatory for licensing and marketing purposes. we aimed to identify whether any domains were underrepresented in rcts of regular therapies for children with asthma over a 20 year period, and to examine what consistency there was between rcts in the outcomes used to assess the domains. by searching the cochrane central register of controlled trials in january 2008, we identified all parallel-group rcts, published between january 1988 and december 2007, which assessed inhaled corticosteroids (ics) as regular therapy for children with asthma. we evaluated how frequently rcts measured the following pre-defined domains: disease activity; disease damage; functional status; quality of life; health resource utilisation; and adverse effects of therapy. our initial search identified 1668 abstracts, of which 412 were retrieved in full. 159 rcts, of which 115 involved only children and 44 involved children and adults, were included in the review. disease activity was measured in 157 rcts, adverse effects of ics in 135, functional status in 25, quality of life in 21, and health resource utilisation in 17. no rct measured long term disease damage, although two used fev1 as a measure of 'lung growth'. rcts were inconsistent in the outcomes used to measure the domains.","short term disease activity is the most frequently measured outcome domain in rcts in children with asthma. effects of regular therapies on functional status, quality of life, and long term consequences of asthma are infrequently assessed. a core set of outcomes, developed using consensus techniques, would standardise the measurement of appropriate outcomes in these rcts. involving patients would identify outcomes which are most relevant from their perspective.",Medication
is permanent right-to-left shunt the key factor in managing patent foramen ovale?,"we sought to prospectively evaluate risk of stroke and impact of transcatheter patent foramen ovale (pfo) closure in patients with permanent right-to left shunt compared with those with valsalva maneuver-induced right-to-left shunt. pathophysiology and properly management of pfo still remain far from being fully clarified: in particular, the contribution of permanent right-to-left shunt remains unknown. between march 2006 and october 2010, we enrolled 180 (mean age 44 10.9 years, 98 women) of 320 consecutive patients referred to our center for transcatheter pfo closure, who had spontaneous permanent right-to-left shunt on transcranial doppler and transthoracic/transesophageal echocardiography. all patients fulfilled the standard current indications for transcatheter closure and underwent preoperative transesophageal echocardiography and brain magnetic resonance imaging, with subsequent intracardiac echocardiographic-guided transcatheter pfo closure. we compared the clinical echocardiographic characteristics of these patients (permanent group) with the rest of 140 patients with right-to-left shunt only during valsalva maneuver (valsalva group). compared with the valsalva group patients, patients of the permanent group had increased frequency of multiple ischemic brain lesions on magnetic resonance imaging, previous recurrent stroke, previous peripheral arteries embolism, migraine with aura, and-more frequently-atrial septal aneurysm and prominent eustachian valve. the presence of permanent shunt confers the highest risk of recurrent stroke (odds ratio: 5.9, 95 confidence interval: 2.0 to 12, p 0.001). no differences were recorded between the 2 groups with regard to recurrence of ischemic events after the closure procedure.","despite its small-sample nature, our study suggests that patients with permanent right-to-left shunt have potentially a higher risk of paradoxical embolism compared with those without.",Treatment
do doxorubicin and etoposide sensitize small cell lung carcinoma cells expressing caspase-8 to trail?,"trail is considered as a promising anti-cancer agent, because of its ability to induce apoptosis in cancer but not in most normal cells. however, growing evidence exist that many cancer cells are resistant to its apoptotic effects. sclc is a typical example of tumor entity where trail monotherapy is not efficient. we demonstrated that doxorubicin and etoposide markedly sensitized sclc cells expressing caspase-8 to apoptotic effects of trail. the drug-mediated sensitization of these cells was associated with increase of surface and total dr5 protein level, specific cleavage of cflipl, decrease of cflips level, and a strong activation of caspase-8. the involvement of mitochondria-mediated pathway was demonstrated by enhanced bid cleavage, bax activation, and cytochrome c release. activation of caspase-8 induced by combined treatment was shown to occur upstream of mitochondria and effector caspases.",our results highlight significant applicability of doxorubicin and etoposide in sensitization of sclc cells expressing caspase-8 to treatment with trail.,Medication
is chronic cerebrospinal venous insufficiency associated with cognitive impairment in multiple sclerosis?,"chronic cerebrospinal venous insufficiency (ccsvi) has been reported in multiple sclerosis (ms) yet its significance in relation to cognitive function is undetermined.this study measured the association between the presence and severity of ccsvi and cognitive impairment in patients with ms. ccsvi was assessed using extra-cranial and trans-cranial doppler sonography in 109 ms patients (79 with relapsing-remitting, 23 with secondary-progressive and 7 with primary-progressive disease subtype). a subject was considered ccsvi-positive if 2 venous hemodynamic criteria were fulfilled. the minimal assessment of cognitive function in ms (macfims) battery was administered assessing the full spectrum of cognitive domains known to be affected by ms. depression was quantified using the beck depression inventory fast screen (bdifs). partial correlations, analysis of variance (or covariance) and linear regression were used to examine the hypothesis that ccsvi status is related to cognition or depression after controlling for education and gender. there were 64 (58.7) patients who were considered ccsvi-positive. the regression models predicting venous hemodynamic insufficiency severity score were not statistically significant for any of the macfims predictor variables. the analysis of variance tests showed a significant effect of ccsvi-positive diagnosis on cognitive ability in only one of the 10 macfims outcomes, and that one was in the opposite direction of the tested hypothesis. there was no correspondence between ccsvi diagnosis and depression, as measured by the bdifs.",we find no evidence of an association between the presence and severity of ccsvi with cognitive impairment and depression in patients with ms.,Diagnosis
does fusarium culmorum cause strong degradation of pollen allergens in extract mixtures?,"therapeutic allergen extracts are frequently stored as mixtures to provide preparations used for specific immunotherapy. substantial protease activity, found in certain mold extracts, has been suspected to cause a loss of allergenic activity as a result of self-degradation, as well as by means of degradation of allergens from pollen and other allergenic sources. this study was performed to address possible deterioration of individual pollen allergens during storage of extract mixtures, with a mold extract as the source of proteolytic activity. aqueous birch and timothy pollen extracts were stored for 60 days at 6 degrees c with and without addition of an extract derived from the mold fusarium culmorum. the stability of the pollen allergens bet v 1, bet v 6, phl p 1, and phl p 5, as well as 2 to-date-undefined f culmorum allergens was examined by using immunoblotting analysis with sera from allergic patients and allergen-specific mabs. furthermore, the residual allergenic activity of the pollen extracts was monitored by using the rat basophilic leukemia cell-mediator release assay. proteolytic activity of extracts was determined by using a commercial protease assay and gelatinase zymography. pollen extracts were very stable, corresponding to the low proteolytic activity of these extracts. in contrast, high proteolytic activity was found for the f culmorum extract, resulting in self-degradation of mold proteins and deactivation of allergens. similarly, the mixtures showed a strong decrease of allergenic potency in the mediator release assay. bet v 1 and phl p 1 were relatively stable, whereas bet v 6 and phl p 5 were almost entirely degraded within 1 day.","proteases of the mold f culmorum clearly affected the overall allergenic activity of pollen extracts within a short time period. apart from general objections against the use of mixtures of non-cross-reacting allergens, mixing of pollen extracts with extracts derived from molds for immunotherapy is not recommended unless they are applied directly after preparation of the mixture.",Treatment
does insulin influence autophagy response distinctively in macrophages of different compartments?,"diabetes mellitus (dm) is characterized by hyperglycemia, associated to a lack or inefficiency of the insulin to regulate glucose metabolism. dm is also marked by alterations in a diversity of cellular processes that need to be further unraveled. in this study, we examined the autophagy pathway in diabetic rat macrophages before and after treatment with insulin. bone marrow-derived macrophages (bmm), bronchoalveolar lavage (bal) and splenic tissue of diabetic male wistar rats (alloxan, 42 mg/kg, i.v., 10 days) and control rats (physiological saline, i.v.). some diabetic rats were given neutral protamine hagedorn insulin (4 iu, s.c.) 8 h before experiments. for characterization of the model and evaluation of the effect of insulin on the autophagic process, the following analyzes were performed: (a) concentrations of cytokines: interleukin (il)-1, tumor necrosis factor (tnf)-, il-6, il-4, il-10, cytokine-induced neutrophil chemoattractant (cinc)-1 and cinc-2 in the bal supernatant was measured by elisa; (b) characterization of alveolar macrophage (am) of the bal as surface antigens (mhcii, pan-macrophage kim2r, cd11b) and autophagic markers (protein microtubule-associated light chain (lc)3, autophagy protein (atg)12 by flow cytometry and confocal microscopy (c) study of macrophages differentiated from the bone marrow by flow cytometry and confocal microscopy (d) histology of the spleen by immunohistochemistry associated with confocal microscopy. interestingly, insulin exerted antagonistic effects on macrophages from different tissues. macrophages from bronchoalveolar lavage (bal) enhanced their lc3 autophagosome bound content after treatment with insulin whereas splenic macrophages from red pulp in diabetic rats failed to enhance their atg 12 levels compared to control animals. insulin treatment in diabetic rats did not change lc3 content in bone marrow derived macrophages (bmm). m1 and m2 macrophages behaved accordingly to the host they were derived from. diabetic m1 bmm had their lc3 vesicle-bound content diminished and m2 bmm enhanced their lc3 levels and insulin treatment failed to rescue autophagy to control levels. insulin normalizes cinc-2 level but does not modulate autophagy markers.","taking these results together, diabetic macrophages derived from different compartments show different levels of autophagy markers compared to healthy animals, therefore, they suffer distinctively in the absence of insulin.",Medication
does maternal diabetes alter extracellular matrix protein levels in rat placentas?,"the aim of this study was to determine whether maternal diabetes affects placental levels of the extracellular matrix components fibronectin, laminin, and collagen-iv. fibronectin, laminin, and collagen-iv deposition in term (day 20) rat placentas from normal and diabetic pregnancies was detected by use of western blot, slot-blot, and immunohistochemical studies. increased placental and decreased fetal wet weight were found in offspring of manifestly diabetic rats compared with offspring of normal pregnancies. laminin deposition was reduced whereas fibronectin levels were increased in placentas from diabetic rats. no diabetes-induced changes of collagen-iv expression and deposition were found.",the diabetes-induced alterations of laminin and fibronectin protein levels in the fetal-maternal interface may affect placental development and alter gas exchange and nutrient transfer to the offspring. this may in turn contribute to the abnormal fetal development in diabetic pregnancy.,General
does 5-allyl-7-gen-difluoromethoxychrysin enhance trail-induced apoptosis in human lung carcinoma a549 cells?,"5-allyl-7-gen-difluoromethoxychrysin (afmc) is a novel synthetic analogue of chrysin that has been reported to inhibit proliferation in various cancer cell lines. tumor necrosis factor-related apoptosis-inducing ligand (trail) is a promising anti-cancer agent. the cytotoxicity of a549 and wi-38 cells were determined using colorimetry. apoptosis was detected by flow cytometry (fcm) after propidium iodide (pi) fluorescence staining and agarose gel electrophoresis. caspase activities were evaluated using enzyme-linked immunosorbent assay (elisa).the expressions of dr4 and dr5 were analyzed using fcm and western blot. subtoxic concentrations of afmc sensitize human non-small cell lung cancer (nsclc) a549 cells to trail-mediated apoptosis. combined treatment of a549 cells with afmc and trail significantly activated caspase-3, -8 and -9. the caspase-3 inhibitor zdevd-fmk and the caspase-8 inhibitor zietd-fmk blocked the apoptosis of a549 cells induced by co-treatment with afmc and trail. in addition, we found that treatment of a549 cells with afmc significantly induced the expression of death receptor 5 (dr5). afmc-mediated sensitization of a549 cells to trail was efficiently reduced by administration of a blocking antibody or small interfering rnas against dr5. afmc also caused increase of the sub-g1 cells by trail treatment and increased the expression levels of dr5 in other nsclc h460 and h157 cell lines. in contrast, afmc-mediated induction of dr5 expression was not observed in human embryo lung wi-38 cells, and afmc did not sensitize wi-38 cells to trail-induced apoptosis.",afmc synergistically enhances trail-mediated apoptosis in nsclc cells through up-regulating dr5 expression.,Medication
does trpv1 antagonist attenuate postoperative hypersensitivity by central and peripheral mechanisms?,"acute postoperative pain is one of the frequent reasons for pain treatment. however, the exact mechanisms of its development are still not completely clear. transient receptor potential vanilloid 1 (trpv1) receptors are involved in nociceptive signaling in various hypersensitive states. here we have investigated the contribution of trpv1 receptors expressed on cutaneous peripheral nociceptive fibers and in the spinal cord on the development and maintenance of hypersensitivity to thermal and mechanical stimuli following surgical incision. a rat plantar incision model was used to test paw withdrawal responses to thermal and mechanical stimuli. the effect of the trpv1 receptor antagonist sb366791 was investigated 1) by intrathecal injection 15 min before incision and 2) intradermal injection before (30 min) and immediately after the surgery. vehicle-injected rats and nave animals treated identically were used as controls. plantar incision induced mechanical allodynia and hyperalgesia and thermal hyperalgesia. a single intrathecal administration of sb366791 significantly reduced postincisional thermal hyperalgesia and also attenuated mechanical allodynia, while mechanical hyperalgesia remained unaffected. local intradermal sb366791 treatment reduced thermal hyperalgesia and mechanical allodynia without affecting mechanical hyperalgesia.",our experiments suggest that both peripheral and spinal cord trpv1 receptors are involved in increased cutaneous sensitivity following surgical incision. the analgesic effect of the trpv1 receptor antagonist was especially evident in the reduction of thermal hyperalgesia. the activation of trpv1 receptors represents an important mechanism in the development of postoperative hypersensitivity.,Treatment
is length of residence in the united states associated with a higher prevalence of cardiometabolic risk factors in immigrants : a contemporary analysis of the national health interview survey?,"cardiometabolic risk (cmr) factors including hypertension, overweight/obesity, diabetes mellitus, and hyperlipidemia are high among united states ethnic minorities, and the immigrant population continues to burgeon. hypothesizing that acculturation (length of residence) would be associated with a higher prevalence of cmr factors, the authors analyzed data on 54, 984 us immigrants in the 2010-2014 national health interview surveys. the main predictor was length of residence. the outcomes were hypertension, overweight/obesity, diabetes mellitus, and hyperlipidemia. the authors used multivariable logistic regression to examine the association between length of us residence and these cmr factors.the mean (se) age of the patients was 43 (0.12) years and half were women. participants residing in the united states for 10 years were more likely to have health insurance than those with 10 years of residence (70 versus 54, p0.001). after adjusting for region of birth, poverty income ratio, age, and sex, immigrants residing in the united states for 10 years were more likely to be overweight/obese (odds ratio or, 1.19; 95 ci, 1.10-1.29), diabetic (or, 1.43; 95 ci, 1.17-1.73), and hypertensive (or, 1.18; 95 ci, 1.05-1.32) than those residing in the united states for 10 years.","in an ethnically diverse sample of us immigrants, acculturation was associated with cmr factors. culturally tailored public health strategies should be developed in us immigrant populations to reduce cmr.",Prevention
do general anaesthetics impair developmental expression of the kcc2 potassium-chloride cotransporter in neonatal rats during the brain growth spurt?,"the developmental transition from depolarizing to hyperpolarizing -aminobutyric acid-mediated neurotransmission is primarily mediated by an increase in the amount of the potassium-chloride cotransporter kcc2 during early postnatal life. however, it is not known whether early neuronal activity plays a modulatory role in the expression of total kcc2 mrna and protein in the immature brain. as general anaesthetics are powerful modulators of neuronal activity, the purpose of this study was to explore how these drugs affect kcc2 expression during the brain growth spurt. wistar rat pups were exposed to either a single dose or 6 h of midazolam, propofol, or ketamine anaesthesia at postnatal days 0, 5, 10, or 15. kcc2 expression was assessed using immunoblotting, immunohistochemistry, or quantitative polymerase chain reaction analysis up to 3 days post-exposure in the medial prefrontal cortex. there was a progressive and steep increase in the expression of kcc2 between birth and 2 weeks of age. exposure to midazolam, propofol, or ketamine up to 6 h at any investigated stages of the brain growth spurt did not influence the expression of this cotransporter protein.",i.v. general anaesthetics do not seem to influence developmental expression of kcc2 during the brain growth spurt.,Medication
do acoustic reflex thresholds at varying click rates in children?,"previous studies conducted with young adults have shown that ipsilateral acoustic reflex thresholds improve with an increase in the click-rate. older adults also show an improvement in acoustic reflex thresholds with an increase in the click-rate. however, the click-rate induced facilitation (rif) of acoustic reflex thresholds is significantly reduced in older adults. these results suggest that slower temporal processing in older adults can be documented by measuring the click-rif of acoustic reflex thresholds. thus, the click-rif of acoustic reflex thresholds may prove to be a valuable tool for the assessment of temporal processing disorders in young children. however, click-rif of ipsilateral acoustic reflex thresholds has not been studied in young normal children. the purpose of this study was to evaluate and document the click-rif in young normal children to provide normative data for this age-group. the study included a total of 30 participants (12 male and 18 female) with normal hearing between the ages of 6 and 10 years. children with outer, middle ear, or neurological disorders were excluded from the study. ipsilateral acoustic reflex thresholds were determined in the left and right ears with clicks presented at the rate of 50 and 100 per s. the frequency of the probe tone was 226 hz and intensity was 85 db spl. a statistical analysis using a three factor mixed manova was planned to explore differences between ears, click rates and gender. the manova revealed a significant effect (p0.0000) for the click-rate. there were no differences between ears or gender and no interactions. the mean click-rif with an increase in the rate from 50 to 100 per s was 10.50 db.",comparison of these results with previous results obtained from young adults suggests that young normal children show click-rif that is similar to that apparent in young adults.,General
does nitrosative stress with hiv dementia cause decreased l-prostaglandin d synthase activity?,"the prevalence of hiv-associated neurocognitive disorders is increasing as hiv-infected individuals are living longer. the clinical manifestations of the syndrome also continue to evolve under the influence of antiretroviral drugs and comorbidities such as drugs of abuse. however, there are no surrogate markers for the disease, either to identify it de novo or to track its progression, and there is no proven treatment with the exception of antiretroviral drugs. levels of nitric oxide, nitrate, and 3-nitrotyrosine (3-nt)-modified proteins were measured in the csf of 46 patients with hiv infection stratified according to their neurocognitive status and history of iv drug use (ivd). the 3-nt-modified proteins were isolated and identified by tandem mass spectrometry, and the functional consequence of 3-nt modification of l-prostaglandin d synthase (l-pgds), the most abundant protein, was determined. 3-nt-modified proteins were significantly elevated in patients with hiv infection who had progressive neurocognitive decline over the next 6 months and in patients with a history of ivd. thirteen different proteins with 3-nt modification were identified in the csf of these patients. l-pgds was the most abundant. 3-nt modification of this protein resulted in loss of its enzymatic activity.","there is increased nitrosative stress in csf of hiv-infected patients with active dementia and in patients with a history of iv drug use, measurement of which may serve as a surrogate marker for these patients. nitrosative stress may also have important functional consequences and may impact the pathogenesis of hiv-associated neurocognitive disorders.",Medication
is prognostic significance of beta-myosin heavy chain mutations reflective of their hypertrophic expressivity in patients with hypertrophic cardiomyopathy?,"genotype-phenotype correlation studies consistently have shown that mutations are prognosticators in patients with hypertrophic cardiomyopathy (hcm). while arginine (arg)719tryptophan (trp) mutation in the beta-myosin heavy chain (myhc) gene is associated with a high incidence of sudden cardiac death (scd), the valine (val)606methionine (met) mutation in the same gene is associated with a near normal life expectancy. it is unknown whether the prognostic significance of mutations is reflective or independent of their hypertrophic expressivity. we determined the indices of left ventricular hypertrophy (lvh) in patients with beta-myhc mutations associated with high, moderate, and low incidence of scd. mutations were identified by chemical cleavage (val606met and glu930lys) or polymerase chain reaction (pcr) and mspi restriction mapping (arg719gln). left ventricular mass was determined using 2-d echocardiograms, and was indexed (lvmi) for body surface area. the extent of lvh was determined using a semiquantitative point score method that takes into account the extent of involvement of the septum, apex, and lateral wall of the left ventricle. the arg719trp, glu930lys, and val606met mutations were associated with high (14/29, 48), moderate (3/16, 19), and low (1/11, 9) risk of premature death, respectively. concordant with the incidence of premature death, the lvmi was the greatest (148.0 /- 37 g/m2) in patients with the arg719trp mutation, the smallest (111.7 /- 19 g/m2) in patients with the val606met mutation, and in between (127.1 /- 15 g/m2) in patients with the glu930lys mutation (p 0.023). similarly, the lvh score was also greater in patients with the arg719trp mutation than in those with the val606met mutation (5.92 /- 2.3 vs 3.2 /- 1.5, respectively, p 0.015). a trend toward a greater septal thickness was also present in patients with the arg719trp compared to the val606met mutations (20.7 /- 6.8 mm vs 16.2 /- 2.6 mm, p 0.077).",hypertrophic cardiomyopathy patients with the malignant arg719trp mutation have more extensive hypertrophy than those with the benign leu606val mutation. this findings suggests that the prognostic significance of beta-myhc mutations is reflective of their hypertrophic expressivity.,Diagnosis
does increased expression of estrogen receptor -36 by breast cancer oncogene ikk promote growth of er-negative breast cancer cells?,"the expression of estrogen receptor- (er) is one of the most important diagnostic and prognostic factors of breast cancer. recently, er-36 has been identified as a novel variant of er-. er-36 lacks intrinsic transcription activity and mainly mediates non-genomic estrogen signaling. the noncanonical ikk family member ikk is essential for regulating antiviral signaling pathways and is recently discovered as a breast cancer oncogene. ikk interacts with and phosphorylates er on serine 167, induces er transactivation activity and enhances er binding to dna in er-positive breast cancer cells. however, the correlation between ikk and the er-36 signaling pathway in er-negative breast cancer cells remains unclear. in this study, we show that ikk interacts with er-36 and increases its expression in breast cancer cells. as shown by western blot assays, the upregulation of er-36 by ikk was significant. in mda-mb-231 cells which are er-negative, ikk was able to increase the expression of er-36 in a dose-dependent manner, and the rna interference assay indicated the correlation between ikk and er-36 expression. moreover, ikk enhanced the growth of mda-mb-231 and mda-mb-436 cells.",these results suggest that ikk increases er-36 expression and is involved in er-36 mediated non-genomic estrogen signaling.,Medication
is interstitial fibrosis the critical determinant of impaired renal function in transplant glomerulopathy?,"transplant glomerulopathy (tg) is a feature of chronic antibody-mediated injury in the glomerular capillaries in renal transplant recipients. tg is generally associated with proteinuria; however, renal function at the diagnosis of tg varies. this study aimed to determine which morphological abnormalities are associated with renal function and proteinuria at the diagnosis of tg. a total of 871 renal transplantations were performed at tokyo women's medical university between 2005 and 2013. tg was diagnosed in 127 biopsies from 58 (6.7) recipients. renal function was evaluated by the estimated glomerular filtration rate (egfr). proteinuria was assessed by a dipstick test: positive for 1 and over. at diagnosis, of 127 biopsies, 72, 37, and 18 had mild, moderate, and severe tg (banff cg). the severity of tg was not associated with decreased egfr at the time of biopsy (cg1: 36.1 14.8, cg2-3: 38.8 14.5 ml/min per 1.73 m(2) , p 0.25), whereas the severity of interstitial fibrosis (if) (banff ci) was significantly associated with decreased egfr (ci0-1: 42.75 13.32, ci2-3: 27.69 11.94 ml/min per 1.73 m(2) , p 0.0001). the multivariate analysis revealed that if was the only independent risk factors for decreased egfr (or 4.38, p 0.0006). meanwhile, tg was identified as the only independent risk factor for the incidence of proteinuria (or 2.67, p 0.014).","interstitial fibrosis was a critical determinant of impaired renal function at the diagnosis of tg. the severity of tg was significantly associated with proteinuria, but did not contribute to renal dysfunction.",Treatment
is narrow-band ultraviolet b a useful and well-tolerated treatment for vitiligo?,"the treatment of vitiligo remains a challenge. the purpose of this article is to review our results and experience with narrow-band ultraviolet (uv) b phototherapy for vitiligo. this is a retrospective analysis of our experience and results with patients with vitiligo who were treated with narrow-band uvb between november 1998 and november 1999. narrow-band uvb phototherapy was given as monotherapy 3 times a week. the starting dose was 280 mj/cm(2), with 15 dose increments at each subsequent treatment. seven patients were able to be evaluated for the purposes of this analysis. their ages ranged from 19 to 59 years (mean, 37.6 years). three patients had fitzpatrick skin phototype iv and v, and 4 had phototypes ii and iii. five of the 7 patients achieved more than 75 repigmentation with a mean of 19 treatments; the mean duration of disease was 13 months. the remaining two patients had 50 and 40 repigmentation after 46 and 48 treatments, respectively. their mean duration of disease was 132 months. adverse effects were mild erythema and pruritus.","this treatment protocol resulted in rapid repigmentation in many patients, including those with skin phototypes iv and v. in accordance with previous studies, this report indicates that narrow-band uvb is a useful and well-tolerated therapy for vitiligo.",Treatment
are bdnf and artemin increased in drug-nave non-depressed gad patients : preliminary data?,"while the role of neuronal and glial plasticity are well established in the pathophysiology of mood disorders, the pattern and measures of neuronal and glial cell line-derived neurotrophic factors are unknown in generalized anxiety disorder (gad). the present study evaluates brain-derived neurotrophic factor (bdnf) and artemin (artn) plasma levels in gad patients. fourteen drug-nave gad patients without major depression were enrolled and plasmatic levels of bdnf and artn mrna were measured by rt-pcr, and compared to matched healthy controls. the results showed an unexpected increase in mrna levels of both bdnf and artn in patients with gad, that appeared almost doubled when compared to healthy controls. in comparison, both bdnf and artn are reduced in patients with major depressive disorder. further, the results are intriguing and might involve distinguishing pathophysiological pathways.","this is the first report of increased levels of a neurotrophic factor and of a glial cell line-derived neurotrophic factor family member in gad patients. while further studies to confirm these results and the functional meaning in terms of pathophysiology of gad are needed, the potential conceptual and clinical meanings are discussed.",Medication
does chronic iodine excess increase the incidence of hyperthyroidism : a prospective community-based epidemiological survey in china?,"an increasing incidence of hyperthyroidism has been observed when iodine supplementation has been introduced to an iodine-deficient population. moreover, the influence of chronic more than adequate or excessive iodine intake on the epidemiological features of hyperthyroidism has not been widely and thoroughly described. to investigate the influences of different iodine intake levels on the incidence of hyperthyroidism, we conducted a prospective community-based survey in three communities with mild-deficient, more than adequate (previously mild deficient iodine intake), and excessive iodine intake. in three rural chinese communities, a total of 3761 unselected inhabitants aged above 13 years participated in the original investigation and 3018 of them received identical examinations after 5 years. thyroid function, levels of thyroid peroxidase antibody (tpoab), thyroglobulin antibody and urinary iodine excretion were measured and thyroid ultrasound examination was also performed. in three communities, median urinary iodine excretion was 88, 214, and 634 microg/l (p0.05) respectively. autoimmune hyperthyroidism was predominant in thyroid hyperfunction in all the three cohorts. either positive tpoab (50 u/ml) or goiter in original healthy participants was associated with the occurrence of unsuspected hyperthyroidism in 5 years (logistic regression, or4.2 (95 ci 1.7-8.8) for positive tpoab, or3.1 (95 ci 1.4-6.8) for goiter).","iodine supplementation may not induce an increase in hyperthyroidism in a previously mildly iodine-deficient population. chronic iodine excess does not apparently increase the risk of autoimmune hyperthyroidism, suggesting that excessive iodine intake may not be an environmental factor involved in the occurrence of autoimmune hyperthyroidism.",Prevention
does perioperative blood transfusion predict short term morbidity after nephrectomy?,"to assess 30-day morbidity and mortality following partial nephrectomy (pn) and radical nephrectomy (rn) with relation to the administration of perioperative blood transfusions pbt). the national surgical quality improvement program was queried for patients with malignant renal tumors (international classification of diseases ninth revision codes 189-189.2) who underwent rn (current procedure terminology codes 50220, 50225, 50230, 50234, 50236, 50545, 50546, 50548) or pn (50240, 50543) between 2005-2013. patients were stratified by transfusion status and assessed for postoperative outcomes both separately and in composite, including morbidity, mortality, infectious complications, and pulmonary complications. univariate and multivariate analyses were performed to identify significant independent predictors of these composite outcomes. the overall transfusion rates were 15.8 and 8.2 for rn and pn, respectively. on multivariate analysis, pbt was associated with increased morbidity (rn: or 2.147, 95 ci 1.687-2.733; pn: or 2.081, 95 ci 1.434-3.022), mortality (rn: or 2.308, 95 ci 1.159-4.598; pn: or 5.166, 95 ci 1.207-22.12), infectious complications (rn: or 1.656, 95 ci 1.151-2.383; pn: or 1.945, 95 ci 1.128-3.354) and pulmonary complications (rn: or 3.040, 95 ci 2.125-4.349; or 3.771, 95 ci 2.108-6.746).","for patients undergoing rn or pn there is a significant association between receipt of pbt and 30-day postoperative outcomes, specifically overall morbidity, mortality, infectious complications, and pulmonary complications. the mechanism that underlies these effects has not been elucidated, but it most likely involves immunomodulation and acute lung injury. future research should focus on formulating comprehensive transfusion guidelines for oncologic-related nephrectomies.",Treatment
is chlorambucil an effective corticosteroid-sparing agent for recalcitrant pyoderma gangrenosum?,"pyoderma gangrenosum (pg) may fail to respond to corticosteroids. immunosuppressive and cytotoxic agents are useful in patients with recalcitrant disease. we describe our experiences with chlorambucil for pg. our purpose was to evaluate the effectiveness of oral chlorambucil in patients with pg recalcitrant to treatment with prednisone, immunosuppressive therapy, or both. six patients with recalcitrant pg were given oral chlorambucil 2 to 4 mg/day. four patients were treated with a combination of prednisone and chlorambucil, and two received chlorambucil alone. response was based on (1) a diminution in the size of the ulcers, or their complete healing, or (2) a decrease in the dose of corticosteroid therapy. beneficial effects were noted within 6 to 8 weeks in all six patients, and corticosteroids were eventually discontinued in all patients. currently only two patients are still receiving chlorambucil; the other four stopped chlorambucil after 6 to 24 months of treatment. their disease has remained in remission for 4 to 9 years. relapse of disease occurred within 1 to 4 months after stopping therapy in one of the two remaining patients or reducing the dose in the other. in both patients, the disease is again responding to treatment. minimal chlorambucil toxicity has been noted, consisting of leukopenia in one patient.",our findings suggest that chlorambucil is an effective corticosteroid-sparing agent for the control of pg.,Medication
does increased il-17a in atrial fibrillation correlate with neutrophil to lymphocyte ratio?,"atrial fibrillation (af) is the most common cardiac arrhythmia and an independent risk factor for stroke among the elderly. a role for inflammation in the atrial remodeling as well as development and recurrence of af is known. to compare il-17a between patients with different types of af and healthy individuals. il-17a was measured in sera of 112 patients and 107 healthy age/sex-matched controls using elisa assay. in sera of 26 patients with elevated il-17a (1 pg/ml), ccl5 and ccl18 levels were also measured. il-17a was significantly increased in patients with af compared to controls (1.28 3.5 vs. 0.19 0.64 pg/ml, p0.001). there was no significant difference in the level of il-17a between different types of af. il-17a was significantly higher in patients with a history of coronary artery bypass graft compared to other patients (p0.01). a significant positive correlation between il-17a and ccl18 concentration was found (p0.001). an increase in the neutrophil/lymphocyte ratio (nlr) was observed in patients with elevated serum il-17a compared to other patients (p0.006). male patients showed higher increase in nlr (p0.007) which was accompanied by a decrease in ccl5 (p0.000) and a marginal increase in ccl18 (p0.085) compared to females. there was an increase in ccl5 levels in patients receiving acetylsalicylic acid (asa) therapy (p0.046).",the increase in il-17a levels is related to the af pathology mediated by neutrophils and monocytes. the current study signifies the role of immune cells and cytokines in the pathology of af.,Prevention
does sertraline exposure lead to small left heart syndrome in adult mice?,"sertraline, a selective serotonin reuptake inhibitor (ssri), is the most commonly prescribed therapy for maternal depression. epidemiologic studies have linked ssri exposure with decreased fetal growth, altered autonomic regulation, and cardiac malformations. we hypothesized that ssri exposure decreases left-ventricular (lv) volumes and increases adult sympathetic nervous system activation, resulting in increased adult heart rates. c57bl/6 mice received saline or sertraline (5 or 15 mg/kg/day i.p.) on postnatal days 1-14. adult phenotypes were assessed at 5 mo. sertraline-exposed mice had smaller lv internal diameters in diastole (control 4.0 0.1 mm, ssri 3.7 0.1 mm, p 0.05), decreased stroke volumes (control 46 2.6 l, ssri 37 2.3 l, p 0.05), higher heart rates (control 530 13 beats per minute (bpm), ssri 567 6 bpm, p 0.05), and increased urinary excretion of noradrenaline (control 174 29.4 ng/ml, ssri 276 35.1 ng/ml, p 0.05). these changes were associated with increased cerebral serotonin transporter (5-htt) expression.","neonatal sertraline exposure causes long-term changes in cardiac morphology and physiology. we speculate that early-life ssri exposure impairs cardiomyocyte growth and central serotonin signaling, leading to a small left heart syndrome in adult mice.",Medication
does 2-h postchallenge plasma glucose predict cardiovascular events in patients with myocardial infarction without known diabetes mellitus?,"the incidence of cardiovascular events remains high in patients with myocardial infarction (mi) despite advances in current therapies. new and better methods for identifying patients at high risk of recurrent cardiovascular (cv) events are needed. this study aimed to analyze the predictive value of an oral glucose tolerance test (ogtt) in patients with acute myocardial infarction without known diabetes mellitus (dm). the prospective cohort study consisted of 123 men and women aged between 31-80 years who had suffered a previous mi 3-12 months before the examinations. the exclusion criteria were known diabetes mellitus. patients were followed up over 6.03 1.36 years for cv death, recurrent mi, stroke and unstable angina pectoris. a standard ogtt was performed at baseline. 2-h plasma glucose (hr, 1.27, 95 ci, 1.00 to 1.62; p 0.05) and smoking (hr, 3.56, 95 ci, 1.02 to 12.38; p 0.05) proved to be independent predictors of cv events in multivariate statistical analysis after adjustments for age, sex, total cholesterol, and other baseline characteristics.","in this study population, with previous mi and without known dm, 2-h pg and smoking were significant predictors of cv death, recurrent mi, stroke and unstable angina pectoris, independent of baseline characteristics and medical treatment.",Treatment
is the application of markers ( hsp70 gpc3 and gs ) in liver biopsies useful for detection of hepatocellular carcinoma?,"liver biopsy for hepatocellular carcinoma (hcc) detection is largely restricted to small hepatocellular lesions, which are often morphologically challenging, requiring careful distinction between dysplastic nodules (high-grade) and well-differentiated hcc. we investigated the diagnostic accuracy of a panel of markers (hsp70 gpc3 and gs), previously tested in resection specimens, in a series of liver biopsies of large regenerative nodules (n13), low-grade dysplastic nodules (n21), high-grade dysplastic nodules (n50), very well-differentiated (vwd) (n17), well-differentiated (wd-g1) (n40) and g2-3 (n35) hcc. almost all cases of large regenerative and low-grade dysplastic nodules did not stain while high-grade dysplastic nodules showed 1 marker (22) but never 2 or 3. for hcc detection the overall accuracy of marker combination was 60.8 (3 markers) and 78.4 (2 markers) with 100 specificity. when restricted to vwdwd-g1 hcc the accuracy was 57 (3 markers) and 72.9 (2 markers) with 100 specificity.","this panel proved useful to detect well-differentiated hcc in biopsy. two immunoreactive markers (out of 3) are recommended as the most valuable diagnostic combination for hcc detection. the diagnostic accuracy of the panel could be improved using additional markers, as suggested by studies of expression profiling in other human models.",Diagnosis
is eur-1008 pancreatic enzyme replacement safe and effective in patients with cystic fibrosis and pancreatic insufficiency?,"eur-1008 (zenpep pancrelipase) is a new, enteric-coated, porcine-derived pancreatic enzyme product (pep) developed for the treatment of cystic fibrosis (cf) patients with malabsorption associated with exocrine pancreatic insufficiency (epi). unlike currently marketed peps, eur-1008 contains the label-claimed lipase content. safety and efficacy were assessed in younger ( or 7 years) cf patients with epi. two multicenter studies were conducted: a randomized, double-blind, placebo-controlled, crossover trial in patients or 7 years of age (n34) and a supplemental, open-label study in children 7 years of age (n19). use of any medications altering gastric ph/motility was prohibited during the studies. outcome measures in the randomized trial included changes in the coefficient of fat absorption (cfa), coefficient of nitrogen absorption (cna), and signs/symptoms of malabsorption for eur-1008 vs. placebo. outcome measures in the supplemental study included safety and response (defined as no steatorrhea and no overt signs/symptoms of malabsorption) to eur-1008 vs. previous enzyme treatment. in the randomized trial, eur-1008 treatment compared to placebo resulted in a significantly higher mean cfa (88.3 vs. 62.8, respectively) and cna (87.2 vs. 65.7, respectively) (both p0.001) and reduced the incidence of malabsorption signs and symptoms in 32 evaluable patients. in the supplemental study, 11 of 19 patients met the criteria for responder with eur-1008 at the end of the study vs. 10 of 19 patients at screening (previous pep), and improvements in clinical symptoms were reported with eur-1008 treatment. eur-1008 was safe and well tolerated, and no serious drug-related aes were reported in either study.","eur-1008 was safe, well tolerated, and effective in cf patients of all ages with epi-associated malabsorption in two clinical trials. treatment led to clinically and statistically significant improvements in cfa and cna in the randomized study, and control of malabsorption and clinical symptoms in both studies.",Medication
is the major allergen of olive pollen ole e 1 a diagnostic marker for sensitization to oleaceae?,"trees of the family oleaceae are important allergen sources, with a strongly varying geographic distribution. for example, olive pollen is an important allergen source in mediterranean countries, whereas ash pollen dominates in northern and central europe and north america. the aim of this study was to compare the profiles of olive and ash pollen allergens and to study the degree of cross-reactivity using populations of allergic patients selectively exposed to olive or ash pollen. olive and ash pollen extracts were analyzed by ige immunoblotting using sera from spanish patients highly exposed to olive pollen and austrian patients without olive but ash pollen exposure. ige cross-reactivity was studied by qualitative immunoblot inhibition assays and semiquantitative elisa inhibitions using olive, ash, birch, mugwort, timothy grass pollen extracts and the major olive pollen allergen, ole e 1. spanish and austrian patients exhibited an almost identical ige-binding profile to olive and ash pollen allergens, with major reactivity directed against ole e 1, and its homologous ash counterpart, fra e 1. ige inhibition experiments demonstrated extensive cross-reactivity between olive and ash pollen allergens. however, whereas cross-reactions between profilins and calcium-binding allergens also occurred between unrelated plant species, cross-reactivity to ole e 1 was confined to plants belonging to the oleaceae.",ole e 1 is a marker allergen for the diagnosis of olive and ash pollen allergy.,Diagnosis
does cricoid pressure impede positioning and ventilation through the laryngeal mask airway?,"to assess the effect of cricoid pressure on the positioning of and ventilation through the laryngeal mask airway (lma). in a double-blind, randomized design, the lma was inserted with (cp group, n 20) or without double-handed cricoid pressure (cp- group, n 20). ventilation through the lma was assessed by measuring expiratory tidal volume and judged as adequate when a mean expiratory tidal volume of or 10 ml.kg-1 could be obtained. the lma position was examined by fibreoscopy. the position of the mask relative to the cricoid cartilage and the cervical spine was radiologically examined (n 10 in each group). ventilation was adequate in all patients in the cp- group but in only five patients (25) of the cp group (p 0.001). the glottis was visible fibreoptically below the mask aperture in all patients in the cp- group, but in only three patients in the cp group (p 0.001). fibreoscopy showed that the mask was not inserted far enough in the remaining 17 patients of the cp group. the reason for unsuccessful ventilation in the cp group was excessive gas leakage (n 2) and/or partial or complete airway obstruction (n 13), which was noted fibreoptically. the radiographs showed that the tip of the mask in the cp- group was located below the level of the cricoid cartilage (c6 or c7 vertebra). the mask tip in the cp group was above this level (c4 or c5 vertebra) (p 0.01).",cricoid pressure impedes positioning of and ventilation through the lma.,Diagnosis
does progesterone-induced mir-133a inhibit the proliferation of endometrial epithelial cells?,"this study aimed to understand the role of mir-133a in progesterone actions, explore the regulative mechanism of the progesterone receptor, and investigate the effects of mir-133a on the progesterone-inhibited proliferation of mouse endometrial epithelial cells. the expression of mir-133a induced by progesterone was detected by quantitative real-time pcr both in vivo and in vitro. ishikawa subcell lines stably transfected with progesterone receptor subtypes were used to determine the receptor mechanism of progesterone inducing mir-133a. specific mir-133a mimics or inhibitors were transfected into mouse uteri and primary cultured endometrial epithelial cells to overexpress or downregulate the mir-133a. the roles of mir-133a in the cell cycle and proliferation of endometrial epithelial cells were analysed by flow cytometry and edu incorporation analysis. the protein levels of cyclind2 in uterine tissue sections and primary cultured endometrial epithelial cells were determined by immunohistochemistry and western blot analysis. progesterone could induce mir-133a expression in a prb-dependent manner in endometrial epithelial cells. mir-133a inhibited endometrial epithelial cell proliferation by arresting cell cycle at the g",we showed for the first time that progesterone-induced mir-133a inhibited the proliferation of endometrial epithelial cells by downregulating cyclind2. our research indicated an important mechanism for progesterone inhibiting the proliferation of endometrial epithelial cells by inducing special mirnas to inhibit positive regulatory proteins in the cell cycle.,Medication
does extralevatory abdominoperineal excision ( elape ) result in reduced rate of tumor perforation or rate of positive circumferential resection margin : a nationwide database study?,"to evaluate the oncological results and possible benefits associated with extralevatory abdominoperineal excision (elape) when compared with conventional abdominoperineal excision (ape). elape was introduced in 2007 with the purpose of reducing the rate of positive resection margins after resection of low rectal cancers. preliminary studies have shown promising results. no large-scale or nationwide data have been presented. database study based on data from the danish colorectal cancer group's prospective database. data on all elapes and apes performed in denmark in the period january 1, 2009, through august 2012 were retrieved and evaluated for differences in demography, tumor characteristics, and oncological results. uni- and multivariate logistic regression analyses were performed to identify risk factors for resection with a positive circumferential resection margin (crm). a total of 554 patients were included, 301(54) were operated by elape; 253(46) by ape. sixty-three percent were men, median (interquartile range) age was 69 (61-76 years) years, and tumors removed had predominantly t-stages t2 and t3 (32 and 45, respectively). overall, crm was found in 13 of patients. when divided according to type of procedure, we found no significant differences in demography and tumor t- and n-stages. resections with a crm were more common after elape (16 vs 7; p 0.006). after uni- and multivariate logistic regression analyses, surgery by elape remained a risk factor for a crm odds ratio, 2.59 (95 confidence interval, 1.31-5.12); p 0.006).","in this nationwide study, resection of low rectal cancers by elape did not improve short-term oncological results, when compared with conventional ape.",Treatment
do overnight urinary cortisol and cortisone add new insights into adaptation to training?,"to examine the effects of training on the hpa axis using two new noninvasive tools: salivary cortisol response to awakening and overnight urinary cortisol and cortisone excretion, and on the sympathoadrenal system using overnight catecholamines excretion. to dissociate the effects of training to those of seasonal hormonal variations, endurance-trained men were compared with sedentary men. nine untrained (ut) men and 10 triathletes were followed during a 10-month season. clinical (total score of fatigue, total training load, and performances during the competition period) and hormonal parameters (overnight excretion of glucocorticoids and catecholamines, increment of saliva cortisol response to awakening) were measured. significant seasonal variations in overnight urinary glucocorticoids (decreased in june) and catecholamines (increased in june) concentrations and in saliva cortisol response to awakening were depicted in the two groups. whereas urinary cortisol excretion was similar between both groups, overnight urinary cortisone excretion was significantly higher in triathletes compared with ut men (anova: training effect: f(2,45) 9.50, p 0.0003), suggesting that during a resting day there is a higher inactivation of cortisol into cortisone in highly trained men. two triathletes developed an overtraining syndrome and presented an increased urinary cortisol/cortisone ratio (1) due to lower cortisone inactivation compared with the triathlete group.",": when not taken into account, seasonal variations may induce errors in the interpretation of hormonal variations with training. the increased intracellular inactivation of cortisol during the night in endurance-trained men uncovers subtle changes in hpa function during training. we show in this study the interest of noninvasive biological markers of the activity of the neuroendocrine system to monitor the repercussion of training load during longitudinal follow-up of athletes.",Symptoms
is maternal obesity associated with congenital anomalies of the kidney and urinary tract in offspring?,"congenital abnormalities of the kidney and urinary tract (cakut) are diagnosed in up to 1 of pregnancies and account for 20-30 of the abnormalities identified in the prenatal period. in previous studies, maternal obesity has been associated with congenital malformations in offspring. our aim was to evaluate the association between maternal obesity body mass index (bmi) 30 kg/m we conducted a population-based, case-control study using linked birth-hospital discharge records from washington state, 2003-2012. we identified 3093 cakut cases using international classification of diseases, ninth revision (icd-9) codes. controls were defined as births without any icd-9 codes denoting congenital malformations, matched to cases by year of birth in an approximate 4:1 ratio. compared to controls, mothers giving birth to infants with cakut were more likely to be obese odds ratio (or) 1.24, 95 confidence interval (ci) 1.11-1.38. we found a significant positive trend between odds of cakut in offspring and increasing severity of obesity (score test for trend of odds p 0.001). this association remained significant in offspring with isolated cakut (or 1.19, 95 ci 1.06-1.35) and upper urinary tract anomalies (or 1.26, 95 ci 1.13-1.41). maternal overweight (bmi 25-29.9 kg/m","our results demonstrate a positive association between maternal obesity and cakut in offspring, as well as between obesity severity and the odds of cakut in offspring. these findings provide additional evidence for the public health importance of obesity, particularly as a potentially modifiable risk factor.",Prevention
is history of preeclampsia more predictive of cardiometabolic and cardiovascular risk factors than obesity?,"to determine to what extent a history of preeclampsia affects traditional cardiometabolic (insulin resistance and dyslipidemia) and cardiovascular (hypertension and micro-albuminuria) risk factors of the metabolic syndrome irrespective of bmi. in a retrospective case-control study we compared 90 formerly preeclamptic women, divided in 3 bmi-classes (bmi 19.5-24.9, 25.0-29.9, 30.0kg/m(2)) to 30 controls, matched for bmi, age and parity. cardiometabolic and cardiovascular risk factors (who-criteria) were tested 6-18 months post partum. statistical analysis included unpaired t-tests, mann-whitney u test, or chi square test and two-way anova. constituents of the metabolic syndrome (glucose, insulin, homair, hdl-cholesterol, triglycerides, blood pressure, micro-albuminuria) were higher in formerly preeclamptic women than in bmi-matched controls. resultantly, traditional risk factors were more prevalent in formerly preeclamptic women than in controls (insulin resistance 80 vs 30, dyslipidemia 52 vs 3, hypertension 24 vs 0, micro-albuminuria 30 vs 0). cardiometabolic risk factors increased with bmi, to the same extent in both groups. formerly preeclamptic women had metabolic syndrome more often than their bmi-matched controls (38 vs 3, p0.001).",traditional risk factors of the metabolic syndrome are more prevalent in formerly preeclamptic women than in bmi-matched controls and increase with bmi to the same extent in both groups. a history of preeclampsia seems to be a stronger indicator of cardiovascular risk than obesity per se.,Prevention
"are peritoneal , systemic , and distant organ inflammatory responses reduced by a laparoscopic approach and carbon dioxide versus air?","advantages of laparoscopic surgery have, among other factors, been attributed to a shorter length of abdominal incision and the use of co2 versus air. an analysis of these factors taking pressure-induced alterations into account is lacking. the objective of the study was to determine the impact of laparoscopy and laparotomy with exposure to co2 and room air under a similar pressure on local, systemic, and distant organ immune responses. twenty piglets were randomized into four groups: co2 laparoscopy, air laparoscopy, co2 laparotomy, and air laparotomy. laparotomy was performed in a sterile balloon pressurized similar to laparoscopy. peritoneal interleukin-1, interleukin-6, tumor necrosis factor-a, and counts of polymorphnuclear cells (pmns), and macrophages (mfs) were determined in abdominal lavage fluids at 0, 2, and 48 h. macrophages were assessed for reactive oxygen species (ros) production. systemic responses were gauged by white blood cell count (wbc) and cytokines. alveolar lavage was performed at 48 h to determine cytokine levels, cell counts, and mf ros production. blood, lavage fluids, and mesenteric lymph nodes were tested for bacterial translocation. regarding the peritoneal response, laparotomy versus laparoscopy when performed with co2 significantly increased pmn and decreased the percentage of macrophages (mf) up to 48 h. there was a significant increase in interleukin-6, and there was a fourfold increase in mf ros production. similar differences between the procedures were found with exposure to air. the use of air versus co2 in laparoscopy, but not in laparotomy, resulted in an increase of peritoneal pmn and a decrease of the mf up to 48 h. air increased the local interleukin-6 release in both procedures and increased mf ros production fourfold. regarding the systemic response, laparotomy produced a significant increase in wbc, which was significantly more pronounced with exposure to air. no alteration of other systemic cytokines was seen. regarding the pulmonary response, the number of mfs and mf ros production were significantly increased after air versus co2 laparoscopy. there were no such differences between the laparotomy groups. regarding bacterial translocation, no bacteria were cultured from peritoneal fluids, lymph nodes, or blood.",inflammatory responses were reduced by a laparoscopic approach and by exposure to co2 versus air. peritoneal responses were affected to a larger degree than systemic parameters. laparotomy overruled the effects of co2 on chemotaxis and distant organ injury but not on peritoneal cytokine release.,Treatment
are nonsteroidal anti-inflammatory drugs an important cause of acute kidney injury in children?,"to characterize nonsteroidal anti-inflammatory drug (nsaid)-associated acute kidney injury (aki) in children. we conducted a retrospective chart review of children diagnosed with aki through the use of international classification of diseases, ninth revision diagnosis code 584.5 or 584.9 from january 1999 to june 2010. medical records were reviewed to confirm the diagnosis of aki and to quantify nsaid administration. pediatric rifle criteria were used to codify aki. patients were not classified as having nsaid-associated aki if they had a diagnosis explaining aki or comorbid clinical conditions predisposing to aki development. patients (n1015) were identified through international classification of diseases, ninth revision screening. twenty-one children had clinical, laboratory, and radiographic studies suggesting nsaid-associated acute tubular necrosis and 6 had findings suggesting nsaid-associated acute interstitial nephritis, representing 2.7 (27 of 1015) of the total cohort with aki and 6.6 when excluding complex patients with multifactorial aki. children with nsaid-associated aki had a median (range) age of 14.7 years (0.5-17.7 years); 4 patients (15) were 5 years old. fifteen of 20 children (75) for whom dosing data were available received nsaids within recommended dosing limits. patients5 years old were more likely to require dialysis (100 vs 0, p.001), intensive care unit admission (75 vs 9, p.013), and a longer length of stay (median 10 vs 7 days, p.037).",nsaid-associated aki accounted for 2.7 of aki in this pediatric population. aki typically occurred after the administration of correctly dosed nsaids. young children with nsaid-associated aki may have increased disease severity.,Medication
does investigation of crohn 's disease risk loci in ulcerative colitis further define their molecular relationship?,"identifying shared and disease-specific susceptibility loci for crohn's disease (cd) and ulcerative colitis (uc) would help define the biologic relationship between the inflammatory bowel diseases. more than 30 cd susceptibility loci have been identified. these represent important candidate susceptibility loci for uc. loci discovered by the index genome scans in cd have previously been tested for association with uc, but those identified in the recent meta-analysis await such investigation. furthermore, the recently identified uc locus at ecm1 requires formal testing for association with cd. we analyzed 45 single nucleotide polymorphisms, tagging 29 of the loci recently associated with cd in 2527 uc cases and 4070 population controls. we also genotyped the uc-associated ecm1 variant rs11205387 in 1560 cd patients and 3028 controls. nine regions showed association with uc at a threshold corrected for the 29 loci tested (p .0017). the strongest association (p 4.13 x 10(-8); odds ratio 1.27) was identified with a 170-kilobase region on chromosome 1q32 that contains 3 genes. we also found association with jak2 and replicated a recently reported association with stat3, further implicating the role of this signaling pathway in inflammatory bowel disease. additional novel uc susceptibility genes were lyrm4 and cdkal1. twenty of the loci were not associated with uc, and several appear to be specific to cd. ecm1 variation was not associated with cd.","collectively, these data help define the genetic relationship between cd and uc and characterize common, as well as disease-specific mechanisms of pathogenesis.",General
does maternal relationship during adolescence predict cardiovascular disease risk in adulthood?,"the current study investigated whether greater maternal support during adolescence is associated with lower levels of cardiovascular disease (cvd) risk in adulthood, and whether maternal support serves as a moderator or a mediator of the socioeconomic status (ses) and cvd risk association. in addition, potential moderators and mediators of the association between adult cvd risk and adolescent maternal support and ses were tested. using the national longitudinal study of adolescent to adult health (n 11,013), we examined relations between maternal support during adolescence (m 15.3 years) and cvd risk in young adulthood (m 28.7 years) via path analysis. maternal support was assessed by a composite of adolescent and mother report. cvd risk was calculated with a framingham-based prediction model that uses age, sex, body mass index, smoking, systolic blood pressure, diabetes, and use of antihypertensive medication. greater maternal support in adolescence was related to lower cvd risk in young adulthood (b -0.56, 95 ci: -0.91 to -0.20, p .05), but there was an interaction between maternal support and race such that african american adolescents were more sensitive than whites to the effects of maternal support on cvd risk (b -0.90, 95 ci: -1.56, -0.25, p .05), and there was no association between ses and maternal support (p .05), adjusting for confounders. however, the relations of adolescent maternal support and ses to adult cvd risk were mediated by young adult health behaviors and financial stress but not by depressive symptoms.",greater maternal support during adolescence appears to act independently of ses when impacting cvd risk and may operate through health behaviors and financial stress. (psycinfo database record,Medication
do alloreactive cytotoxic t cells recognize minor transplantation antigens presented by major histocompatibility complex class ib molecules?,"cytotoxic t lymphocytes (ctls) contribute to the rejection of transplanted tissues through two pathways: first, by direct recognition of foreign graft major histocompatibility complex (mhc) class i molecules; and second, by recognition of foreign graft-derived peptides presented by classical mhc class ia molecules that are matched between graft and donor. however, a number of observations suggest that additional categories of ctl recognition patterns may exist, but they remain to be defined molecularly. previous studies showed that the murine nonclassical mhc molecule h2 m3 may be involved in allorecognition. we investigated whether other members of nonclassical mhc class ib, namely qa1 and qa2, may be recognized. alloreactive ctls were generated from mice mismatched for non-mhc and/or mhc genetic backgrounds and tested using various target cells, including cells transfected with qa1 or qa2. furthermore, candidate peptides were synthesized and used to generate ctls specific for peptide presented by qa1 or qa2. the experiments demonstrate that allogeneic and xenogeneic peptides were recognized by ctls when presented on shared nonclassical mhc class ib qa1 and qa2 molecules.",the results confirm that mhc class ib molecules present peptides to ctls. this potentially important alloreactivity pathway may be functional between most individuals because sharing of mhc class ib alleles is frequent.,Treatment
does ephrin-b2 mediate trophoblast-dependent maternal spiral artery remodeling in first trimester?,"maternal spiral artery remodeling after embryo implantation is a crucial process for successful pregnancy and rely on well-controlled trophoblast functions. ephrin-b2 is found to be of great importance in various cell functions in both benign human tissue and tumors. however, its role in the regulation of trophoblast remains unknown. this study is conducted to investigate the role of ephrin-b2-induced trophoblast functions related to artery remodeling. trophoblast cell line htr-8/svneo was used to investigate the effects of ephrin-b2 inhibition on cell proliferation, apoptosis, migration, invasion and tube formation. placental-decidual co-culture (pdc) system was conducted to verify ephrin-b2-induced trophoblast functions ex vivo. factors involving in artery remodeling process, such as matrix metalloproteinases (mmps), placental growth factors (plgf) and vascular endothelial growth factor (vegf) were tested at transcriptional level. inhibition of ephrin-b2 suppressed cell proliferation and induced cell apoptosis in htr-8/svneo cells. down-regulation of ephrin-b2 impaired migration/invasion capabilities of htr-8/svneo cells and significantly decreased gene expression of mmps. also, a worse tube formation and a decrease in gene expression of plgf was observed after down-regulation of ephrin-b2. however gene expression of vegf-a did not show significantly statistical difference. these effects were further confirmed by pdc system showing an inadequate trophoblast invasion and spiral artery remodeling.",ephrin-b2 might be act as a positive regulator in maternal artery remodeling via both trophoblast invasion and endovascular formation.,General
does the human cytomegalovirus ul76 gene regulate the level of expression of the ul77 gene?,"human cytomegalovirus (hcmv) can be reactivated under immunosuppressive conditions causing several fatal pneumonitis, hepatitis, retinitis, and gastrointestinal diseases. hcmv also causes deafness and mental retardation in neonates when primary infection has occurred during pregnancy. in the genome of hcmv at least 194 known open reading frames (orfs) have been predicted, and approximately one-quarter, or 41 orfs, are required for viral replication in cell culture. in contrast, the majority of the predicted orfs are nonessential for viral replication in cell culture. however, it is also possible that these orfs are required for the efficient viral replication in the host. the ul77 gene of hcmv is essential for viral replication and has a role in viral dna packaging. the function of the upstream ul76 gene in the hcmv-infected cells is not understood. ul76 and ul77 are cistons on the same viral mrna and a conventional 5' mrna for ul77 has not been detected. the vast majority of eukaryotic mrnas are monocistronic, i.e., they encode only a single protein. to determine whether the ul76 orf affects ul77 gene expression, we mutated ul76 by orf frame-shifts, stop codons or deletion of the viral gene. the effect on ul77 protein expression was determined by either transfection of expression plasmids or infection with recombinant viruses. mutation of ul76 orf significantly increased the level of ul77 protein expression. however, deletion of ul76 upstream of the ul77 orf had only marginal effects on viral growth.","while ul76 is not essential for viral replication, the ul76 orf is involved in regulation of the level of ul77 protein expression in a manner dependent on the translation re-initiation. ul76 may fine-tune the ul77 expression for the efficient viral replication in the hcmv- infected cells.",General
does dietary vitamin k2 supplement improve bone status after lung and heart transplantation?,"osteoporosis is a problem after transplantation. studies since the last year indicate that vitamin k plays a role in optimal bone health. the aim of this randomized, double blind, prospective longitudinal study was to investigate the effect of a dietary supplement with vitamin k2 (180 microg menakinon-7) on bone mass, the first year after lung and heart transplantation. after preoperative baseline investigation of bone mass and bone-related biochemistry, 35 lung and 59 heart recipients were postoperatively randomized to vitamin k2 or placebo and reinvestigated the following year. in all recipients, 1 year after solid organ transplantation, the difference between vitamin k2 and placebo for the lumbar spine (l2-l4) bone mineral density (bmd) was 0.028 (se 0.014) g/cm(2), p0.055 and for l2 to l4 bone mineral content was 1.33 (se 1.91) g/cm(2) (p0.5). in lung recipients separately, the difference for bone mineral content was 3.39 g (se 1.65), p0.048 and in heart recipients 0.45 (se 0.02) g, p0.9 after controlling for baseline measures. in a forward stepwise linear regression analysis fitted to model differences in the l2 to l4 bmd, controlled for possible confounding variables (including use of bisphosphonate), and the only significant predictors were organ (b-0.065 g/cm(2), p0.001) and vitamin k2 (b0.034 g/cm(2), p0.019). insufficient vitamin d status was common, and the parathyroid hormone was highest in the k2 group indicating a higher need for vitamin d.",one year of vitamin k2 supplement suggest a favorable effect on lumbar spine bmd with different response in lung and heart recipients. vitamin d status should receive more attention.,Treatment
does sorafenib reverse multidrug resistance of hepatoma cells in vitro ?,"to explore the role of sorafenib in reversing multidrug resistance (mdr) in hepatoma bel-7402/fu cells and its possible mechanisms. mtt colorimetric assay was used to obtain the dose-response curve of sorafenib in bel-7402/fu cells, and flow cytometry performed to assess the effect of sorafenib on rho123 concentration in the cells. the optimal dose of sorafenib for cell treatment was determined according to the results of mtt assay and flow cytometry. mtt assay was employed to evaluate the effect of sorfenib on the cytotoxicity of the antitumor drugs, flow cytometry performed to determine the expression of cell membrane transport protein (p-gp), and rt-pcr used to detect mdr1 gene expression in the cells treated with sorafenib at the optimal dose. sorafenib at the concentration of 4 micromol/l, efficiently reversed the mdr of the cells with minimal side effects. at the concentration of 4 micromol/l, sorafenib partially reversed the drug resistance of bel-7402/fu cells to adm, 5-fu, gem and ddp, with reversal indexes of 2.98, 7.16, 1.99 and 10.08, respectively. treatment of the cells with 4 micromol/l, sorafenib also partially down-regulated p-gp expression in bel-7402/fu cells, and caused a reduction of mdr1 gene expression by 27.3 in comparison with the control cells.",sorafenib can reverse mdr in human hepatoma cells probably in association with down-regulation of mdr1 gene expression and increased accumulation of the chemotherapeutic agents in the cells.,Medication
does phosphate promote uranium ( vi ) adsorption in staphylococcus aureus lz-01?,"staphylococcus aureus lz-01 was isolated from the yellow river upstream from lanzhou which can resist and reduce chromium (vi) to chromium (iii). in this study, strain lz-01's uranium (vi) resistance and adsorption abilities were investigated. our results showed that it can resist 2 mmol l(-1) u(vi) and adsorb 96 of 2 mmol l(-1) u(vi) after 6 h incubation. transmission electron microscopy (tem) images showed that precipitates were formed on the surface of the cells. energy dispersive x-ray spectroscopy (edx) analysis indicated that the precipitates contained uranium and phosphorus. the u(vi) adsorption rate of strain lz-01 was promoted by 20 mmol l(-1) phosphate. it adsorbed 45 of 25 mmol l(-1) u(vi) in 30 min compared to 36 without phosphate (p 005). strain lz-01 can resist heavy metals and survive in nuclear waste-contaminated environments. strain lz-01 might be a potential candidate for nuclear waste remediation with phosphate added.","staphylococcus aureus lz-01 can resist 2 mmol l(-1) u(vi). it could adsorb more than 90 of the 2 mmol l(-1) u(vi) in 6 h. uranium is precipitated with phosphorus on the surface of the cells. phosphate promotes uranium adsorption in strain lz-01, and its u(vi) adsorption capacity is related to its cell availability. these results indicate that the strain lz-01 might be a potential candidate for remediation of nuclear waste when phosphate is added.",Diagnosis
is stimulation of triple negative breast cancer cell migration and metastases formation prevented by chloroquine in a pre-irradiated mouse model?,"some triple negative breast cancer (tnbc) patients are at higher risk of recurrence in the first three years after treatment. this rapid relapse has been suggested to be associated with inflammatory mediators induced by radiation in healthy tissues that stimulate cancer cell migration and metastasis formation. in this study, the ability of chloroquine (cq) to inhibit radiation-stimulated development of metastasis was assessed. the capacity of cq to prevent radiation-enhancement of cancer cell invasion was assessed in vitro with the tnbc cell lines d2a1, 4t1 and mda-mb-231 and the non-tnbc cell lines mc7-l1, and mcf-7. in balb/c mice, a single mammary gland was irradiated with four daily doses of 6 gy. after the last irradiation, irradiated and control mammary glands were implanted with d2a1 cells. mice were treated with cq (vehicle, 40 or 60 mg/kg) 3 h before each irradiation and then every 72 h for 3 weeks. migration of d2a1 cells in the mammary gland, the number of circulating tumor cells and lung metastasis were quantified, and also the expression of some inflammatory mediators. irradiated fibroblasts have increased the invasiveness of the tnbc cell lines only, a stimulation that was prevented by cq. on the other hand, invasiveness of the non-tnbc cell lines, which was not enhanced by irradiated fibroblasts, was also not significantly modified by cq. in balb/c mice, treatment with cq prevented the stimulation of d2a1 tnbc cell migration in the pre-irradiated mammary gland, and reduced the number of circulating tumor cells and lung metastases. this protective effect of cq was associated with a reduced expression of the inflammatory mediators interleukin-1, interleukin-6, and cyclooxygenase-2, while the levels of matrix metalloproteinases-2 and -9 were not modified. cq also promoted a blocking of autophagy.",cq prevented radiation-enhancement of tnbc cell invasion and reduced the number of lung metastases in a mouse model.,Prevention
are high-frequency haplotypes in the x chromosome locus tlr8 associated with both cd and uc in females?,"tnf-alpha and il-1 have been associated with mucosal inflammation in both crohn's disease (cd) and ulcerative colitis (uc). innate immune defects have been associated with cd, specifically card15/nod2. recently, toll-like receptor 8 (tlr8) signaling has been shown to enhance generation of both cytokines. interestingly, tlr8 is located on the x chromosome and inflammatory bowel disease (ibd) has been associated with abnormalities of the x chromosome. the aim was to test whether tlr8 haplotypes are associated with ibd. subjects (735 cd, 343 uc, 245 controls) were genotyped. single nucleotide polymorphisms (snps) were chosen to tag common caucasian haplotypes. both ""risk (h4)"" and ""protective (h1)"" tlr8 haplotypes were observed associated with cd in females. eighteen percent of cd females had h4 compared with 9 of controls (p 0.02). fifty-nine percent of cd females had h1 compared with 72 of controls (p 0.01). h1 was also negatively associated with uc in females (59 of uc, 72 of controls p 0.03). diplotype analysis of cd, uc, and all ibd in females revealed that 2 protective haplotypes (h1/h1) had a markedly diminished odds ratio, 0.4-0.5. the presence of a risk haplotype (h4 / not h1) had a significantly increased odds ratio, 2.0-2.2. thus, the risk for ibd was 4-5 times higher in females with 1 risk haplotype than with the protective/protective diplotype.","tlr8 is an x-linked ibd susceptibility gene with both common predisposing and protecting haplotypes. these associations further emphasize the importance of genetic variation in innate immunity as determinants, not only of cd, but of uc as well.",Medication
are contractile reserve and calcium regulation depressed in myocytes from chronically unloaded hearts?,"chronic cardiac unloading of the normal heart results in the reduction of left ventricular (lv) mass, but effects on myocyte contractile function are not known. cardiac unloading and reduction in lv mass were induced by heterotopic heart transplantation to the abdominal aorta in isogenic rats. contractility and ca(2)(i) regulation in lv myocytes were studied at both 2 and 5 weeks after transplantation. native in situ hearts from recipient animals were used as the controls for all experiments. contractile function indices in myocytes from 2-week unloaded and native (control) hearts were similar under baseline conditions (0.5 hz, 1.2 mmol/l ca(2)(o), and 36 degrees c) and in response to stimulation with high ca(2)(o) (range 2.5 to 4.0 mmol/l). in myocytes from 5-week unloaded hearts, there were no differences in fractional cell shortening and peak-systolic ca(2)(i) at baseline; however, time to 50 relengthening and time to 50 decline in ca(2)(i) were prolonged compared with controls. severe defects in fractional cell shortening and peak-systolic ca(2)(i) were elicited in myocytes from 5-week unloaded hearts in response to high ca(2)(o). however, there were no differences in the contractile response to isoproterenol between myocytes from unloaded and native hearts. in 5-week unloaded hearts, but not in 2-week unloaded hearts, lv protein levels of phospholamban were increased (345 of native heart values). protein levels of sarcoplasmic reticulum ca(2) atpase and the na()/ca(2) exchanger were not changed.","chronic unloading of the normal heart caused a time-dependent depression of myocyte contractile function, suggesting the potential for impaired performance in states associated with prolonged cardiac atrophy.",Treatment
do recombinant outer membrane vesicles carrying chlamydia muridarum htra induce antibodies that neutralize chlamydial infection in vitro?,"outer membrane vesicles (omvs) are spheroid particles released by all gram-negative bacteria as a result of the budding out of the outer membrane. since they carry many of the bacterial surface-associated proteins and feature a potent built-in adjuvanticity, omvs are being utilized as vaccines, some of which commercially available. recently, methods for manipulating the protein content of omvs have been proposed, thus making omvs a promising platform for recombinant, multivalent vaccines development. chlamydia muridarum do serine protease htra, an antigen which stimulates strong humoral and cellular responses in mice and humans, was expressed in escherichia coli fused to the ompa leader sequence to deliver it to the omv compartment. purified omvs carrying htra (cm rhtra-omv) were analyzed for their capacity to induce antibodies capable of neutralizing chlamydia infection of llc-mk2 cells in vitro. cm rhtra-omv immunization in mice induced antibodies that neutralize chlamydial invasion as judged by an in vitro infectivity assay. this was remarkably different from what observed with an enzymatically functional recombinant htra expressed in, and purified from the e. coli cytoplasm (cm rhtra). the difference in functionality between anti-cm rhtra and anti-cm rhtra-omv antibodies was associated to a different pattern of protein epitopes recognition. the epitope recognition profile of anti-cm htra-omv antibodies was similar to that induced in mice during chlamydial infection.",when expressed in omvs htra appears to assume a conformation similar to the native one and this results in the elicitation of functional immune responses. these data further support the potentiality of omvs as vaccine platform.,Medication
"is early growth response gene 1 , a trbp binding protein , involved in mirna activity of mir-125a-3p in human cells?","micrornas (mirnas) are key regulators of many cellular pathways. however, the picture for components or regulators involved in the process of mirna biogenesis and function remains to be further elucidated. early growth response gene 1 (egr1) has long been considered as tumor suppressor and transcriptional factor involved in cell proliferation and regulation of apoptosis. here we show that egr1 is able to modulate guide strand loading of certain mirnas or sirnas in human hek293 and a549 cells, which is related with thermodynamic parameters of mirna or sirna. further, we found that egr1 modulates the silencing activity of mir-125a-3p in vivo. immunoprecipitation experiment demonstrated that egr1 could bind mirna biogenesis protein tar rna-binding protein2 (trbp2), and knockdown trbp by rnai abolished the regulating effects of egr1 on mir-125a-3p efficiency. further experiments revealed that deleting sequence 97-227aa containing dsrbd b domain of trbp eliminated the binding phenomenon between egr1 and trbp and impaired the effect of egr1 on mir-125a-3p efficiency.","taken together, our study has demonstrated that egr1 is able to regulate mirna activity of mir-125a-3p in human cells through binding trbp, which highlights an unexpected function of egr1 in mirna pathway.",General
does bioconversion of plant carotenoids to vitamin a in filipino school-aged children vary inversely with vitamin a status?,"it is important to understand the factors affecting strategies to improve the vitamin a status of populations. we reported previously that a 3-d deuterated-retinol-dilution (drd) procedure might be used to indicate total body stores of vitamin a. we studied the ability of 3-d drd to detect changes in the body pool size of vitamin a and the effect of vitamin a status on the bioconversion of plant carotenoids to vitamin a. two separate, unrelated studies were conducted in 7-13-y-old children with poor or marginal serum retinol concentrations (0.32-0.93 micromol/l) by feeding them controlled diets daily for 5 d/wk for 12 wk, after treatment with an anthelmintic drug. in school 1 (n 27), lunch and 2 snacks that were provided at school contained 2258 retinol equivalents/d (mostly from orange fruit and vegetables) and 5.3 mj/d from 33 g fat, 37 g protein, and 209 g carbohydrates; in school 2 (n 25), 2 snacks provided 2.5 mj/d from 9.4 g fat, 9.6 g protein, and 119 g carbohydrates, but no carotenes. in school 1, mean serum beta-carotene increased from 0.12 to 0.62 micromol/l (p 0.0001) and serum retinol increased from 0.68 to 1. 06 micromol/l (p 0.0001). in school 2, serum beta-carotene increased from 0.06 to 0.11 micromol/l (p 0.0001) and serum retinol increased from 0.66 to 0.86 micromol/l (p 0.0001). in school 1, but not school 2, improvement in serum retinol varied inversely with baseline retinol (r -0.38, p 0.048). in both schools, 3-d drd showed reductions in the ratio of serum deuterated to nondeuterated retinol (d:h retinol) postintervention, denoting improvements in vitamin a status; the higher d:h retinol (ie, the poorer the status) at baseline, the greater the reduction in d:h retinol postintervention (school 1: r -0.99, p 0.0001; school 2: r -0.89, p 0.0001).","three-day drd can detect changes in the body pool size of vitamin a, although a predictive equation to quantitate total body stores of vitamin a with the use of 3-d data needs to be developed. bioconversion of plant carotenoids to vitamin a varies inversely with vitamin a status; improvement in status after dietary interventions is strongly influenced by total body stores of vitamin a and is influenced little or not at all by serum retinol.",Treatment
does a vertical scanning doppler probe identify blood vessels during laparoscopic surgery?,"using a conventional doppler probe, it is difficult to identify blood vessels precisely in lymph node dissection during laparoscopic surgery. for 26 patients undergoing laparoscopic colectomy and 26 patients undergoing laparoscopic subtotal gastrectomy, we used conventional and vertical scanning doppler probes to compare their ability to identify invisible blood vessels through differences in power output voltage. the vertical scanning doppler probe was 100 successful in identifying the target blood vessels regardless of the patient's body mass index (bmi), and also was superior to the conventional doppler probe in detection sensitivity. the vertical scanning doppler probe was useful for image training of recently qualified surgeons through real-time monitoring of the probe position and response on the monitor. furthermore, findings showed that the vertical scanning doppler probe was applicable to lymph node dissection as a forceps for laparoscopic usage.",the vertical scanning doppler could identify the target blood vessels regardless of the patient's bmi. it was verified to be useful as a surgical assistive device apart from being a sensor and may serve in the education of recently qualified surgeons.,Treatment
is human leukocyte antigen-g expression after heart transplantation associated with a reduced incidence of rejection?,"human leukocyte antigen (hla)-g, a nonclassic major histocompatibility complex class i molecule expressed in the extravillous cytotrophoblast at the feto-maternal interface, is known to protect the fetus from maternal cellular immunity. in a preliminary study, we showed that hla-g is expressed in the hearts of some patients after heart transplantation. in the present study, a larger number of patients was investigated to confirm this finding and to look for possible correlations between hla-g expression and the number and types of rejection. expression of hla-g in endomyocardial biopsy specimens was investigated by immunohistochemical analysis, and detection of the soluble hla-g in the serum was performed by immunoprecipitation followed by western blot analysis. hla-g was detected in the biopsy specimens and serum of 9 of 51 patients (18). the number of episodes of acute rejection was significantly lower in hla-g-positive patients (1.2/-1.1) as compared with hla-g-negative patients (4.5/-2.8) (p0.001). no chronic rejection was observed in hla-g-positive patients, whereas 15 hla-g-negative patients had chronic rejection (p0.032). a longitudinal study of these patients reveals that the status of hla-g expression was maintained after 6 months both in serum and in biopsy specimens. during this period, hla-g-positive patients did not have chronic rejection.",there is a significant correlation between rejection and hla-g expression in the heart after transplantation. hla-g expression and its effect in reducing the incidence and severity of rejection seem to be stable throughout the evolution.,Treatment
is angiotensin ii-induced protein kinase d activation regulated by protein kinase cdelta and mediated via the angiotensin ii type 1 receptor in vascular smooth muscle cells?,"angiotensin ii (ang ii), through its specific signaling cascades, exerts multiple effects on vascular smooth muscle cells (smcs). it has been shown that ang ii stimulates activation of protein kinase d (pkd), a member of a new class of serine-threonine kinases. however, little is known regarding the upstream cascade of the intracellular signaling that leads to pkd activation. in the present study, we investigated upstream molecules that mediate ang ii-induced pkd activation in smcs. protein kinase c (pkc) inhibitors completely block ang ii-induced pkd activation, and pretreatment with phorbol 12,13-dibutyrate downregulates ang ii-induced pkd activation, indicating that classical or novel isoforms of pkc mediate ang ii-induced pkd activation. furthermore, the finding that rottlerin, a pkcdelta-specific inhibitor, blocks pkd activation suggests that pkcdelta, a member of novel pkcs, mediates ang ii-induced pkd activation. by using dominant-negative approaches, our results demonstrate that expression of the dominant-negative pkcdelta, but neither the dominant-negative form of pkcepsilon nor pkczeta, inhibits pkd activation. these results further substantiate the finding that ang ii-induced pkd activation is mediated by pkcdelta. moreover, using selective ang ii receptor antagonists, our data show that the ang ii type 1 (at1) receptor but not the at2 mediates ang ii-stimulated pkd activation.",this study reveals for the first time that ang ii-induced pkd activation is mediated via at1 and regulated by pkcdelta in living cells. these data may provide new insights into molecular mechanisms involved in ang ii-induced physiological and pathological events.,Medication
is high plasma pentosidine level accompanied with cardiovascular events in hemodialysis patients?,"cardiovascular disease is a major complication in patients with end-stage renal disease (esrd). the accumulation of advanced glycation end products (ages) is facilitated in these patients. the aim of this study was to investigate the relationship between circulating ages and cardiovascular events in hemodialysis patients. the plasma level of pentosidine, a well-defined ages, was measured in 110 hemodialysis patients who were prospectively followed for 90 months. the relationship between plasma pentosidine level and cardiovascular events was assessed using kaplan-meier and cox regression analysis. thirty-nine cardiovascular events (14 coronary heart disease and 25 strokes) occurred during the follow-up period. multivariable cox proportional hazard analysis showed that plasma pentosidine levels (hr 1.040, 95 ci 1.022-1.058, p 0.01) were correlated to increased risk for cardiovascular events. when patients were divided into four groups according to plasma pentosidine levels, kaplan-meier analysis revealed that cardiovascular events in the highest pentosidine group were significantly greater than in the other groups (p 0.01 in lower and low, and p 0.05 in high pentosidine groups).",the plasma pentosidine level predicts cardiovascular events in hemodialysis patients. the effects of lowering circulating age levels on cardiovascular events should be examined in esrd patients.,Medication
are higher pentraxin-3 levels associated with inflammation in familial mediterranean fever?,"circulating levels of pentraxin-3 (ptx3) have been shown to increase in several inflammatory conditions. however, there is no information about the levels of ptx3 in patients with familial mediterranean fever (fmf). this study was designed to evaluate the serum ptx3 levels in patients with fmf during attack and free-attack periods. twenty fmf patients in attack and free-attack period, and 20 age-, sex-, and body mass index-matched healthy controls were included in the study. blood samples were obtained within the first 24 h of the attack period and between attacks, and levels of white blood cell, erythrocyte sedimentation rate, fibrinogen, high sensitive crp, and ptx3 were determined. ptx3 levels during the attack period were not significantly different from those in free-attack patients (4.9 4.6 ng/ml vs. 2.8 1.4 ng/ml, p 0.05). however, both attack and free-attack patients had significantly higher ptx3 levels than healthy controls (4.9 4.6 ng/ml vs. 1.8 0.8 ng/ml, p 0.001; 2.8 1.4 ng/ml vs. 1.8 0.8 ng/ml, p 0.025, respectively).","ptx3 levels were not markedly affected from fmf attacks, but high level of ptx3 in free-attack period of fmf patients shows ongoing subclinical inflammation. however, further studies are needed to determine its usefulness as a marker in clinical practice.",Symptoms
does an online quiz uncover limitations of morphology in equivocal lung cytology?,equivocal atypia in respiratory cytology can be a diagnostic challenge. in such cases fluorescence in situ hybridization (fish) may be used for the analysis of chromosomal aberrations and often allows a reliable distinction of benign and malignant cells. an online picture gallery of 30 respiratory cytologic preparations comprising 23 specimens with equivocal cytology as well as 5 positive and 2 negative controls was prepared (www.unibas.ch/patho/lungenzyto/loesung). the final diagnoses were confirmed by clinical follow-up or biopsy or both. each of the illustrated cell groups was analyzed by multitarget fish after pap image capturing and automatic relocalization. the online questionnaire was completed by 137 cytomorphologists from all continents. the control cases were assessed accurately to a significantly higher percentage than the equivocal cases. in equivocal cases participants more often made false-positive than false-negative diagnoses. in 2 patients with benign conditions (tuberculosis and pulmonary capillaritis) the rate of false-positive answers was remarkably high (31.4 and 62.8 respectively). the result of the 20 best-performing participants for the 5 cases with the highest percentage of inaccurate answers was not better than if they had chosen their answer by chance.,these data illustrate that single cells or cell clusters of a subgroup of equivocal lung cytology are a diagnostic challenge even for highly experienced morphologists. internet-based tests are able to reveal limitations of cytomorphology.,Diagnosis
does neutrophil to lymphocyte ratio predict perioperative mortality following open elective repair of abdominal aortic aneurysms?,"this study assesses the predictive value of neutrophil to lymphocyte ratio (nlr) in relation to 30-day and overall mortality following open abdominal aortic aneurysm (aaa) repairs. in addition, it assess assesses any correlation between nlr and age, size of the aaa and gender. patients undergoing elective or urgent open repair of their aaa by a single surgeon during a 10-year period were included. a pre-operative nlr of 5 was regarded as abnormal. 350 consecutive patients underwent aaa repair. 52 had an nlr5. 30-day mortality rate was 12/52 (23) in the nlr5 group and 20/298 (6.7) in the nlr5 group were due to myocardial infarction. the median nlr was higher in those that died within 30 days at 4.2 iqr: 2.6-7.5 versus 2.8 iqr: 2.1-3.8 (p 0.0001). overall mortality at 10 years, in the nlr5 group - 26/52 (50) was significantly greater than that of the nlr5 at 3.2 (iqr 2.5-4.6) versus 2.6 (iqr: 2.0-3.6) in those surviving (p 0.00004). no difference was found between nlr and age, aneurysm size or gender.",pre-operative nlr5 appears to be a significant predictor of both 30-day mortality and long-term outcome in elective and urgent open aaa surgery. it is plausible the nlr is identifying a group with sub-clinical cardiovascular disease at risk of peri-operative myocardial infarction.,Treatment
"is the oocyte spindle preserved by 1,2-propanediol during slow freezing?","to investigate the specific changes in oocyte spindle subjected to severe challenges of low temperature, as well as to examine the effect of cryoprotectants in preserving oocyte spindle during cryopreservation. in vitro experimental study. academic research laboratory. b6d2f1 (c57bl/6 x dba/2) mice. mouse oocytes were cryopreserved using a slow freezing method in a sodium-depleted medium with 1.5 mol/l 1,2-propanediol (proh) and 0.3 m sucrose. to examine the spindle, oocytes were fixed before, during, and after cryopreservation, and oocytes were analyzed by immunocytochemistry and confocal microscopy. the mii spindle was preserved during the slow freezing, because the cryoprotectant proh was found to support the organization of mii spindle in resisting the subzero temperature. in contrast, the mii spindle was disassembled gradually during the thawing process with or without proh. most of the oocytes were able to recover the mii spindle after thawing, but a portion of thawed oocytes could not sustain the meiotic spindle because of parthenogenetic activation.","1,2-propanediol can support the organization of mii spindle to defy the subphysiologic temperature; however, the proh cannot sustain oocyte spindle structure after the subsequent thawing process.",General
does protamine affect the formation of cgmp or camp in pig vascular smooth muscle cells in response to vasodilators?,"protamine has recently been shown to have a direct vasodilator action in isolated vascular tissue. as one possible mechanism for this action, it has been hypothesized that protamine might increase the response of vascular smooth muscle to the endothelium-derived relaxing factor, nitric oxide. in this study, we tested this hypothesis and examined the effect of protamine on other guanosine 3'5'-cyclic monophosphate (cgmp)- and adenosine 3'5'-cyclic monophosphate (camp)-dependent processes. prospective, repeated measures analysis of concentration-response curves. anesthesia research laboratory in an academic medical center. cultured coronary artery smooth muscle cells from pig heart. sodium nitroprusside was used to mimic the action of the endothelium-derived relaxing factor by stimulating the soluble guanylyl cyclase and increasing intracellular cgmp. atrial natriuretic peptide was used to stimulate the particulate guanylyl cyclase. isoproterenol and forskolin were used to increase intracellular camp. the responses to these agents were determined in the presence and absence of protamine. in cultured vascular smooth muscle cells, sodium nitroprusside increased cgmp, the second messenger for endothelium-derived relaxing factor, in a concentration-dependent manner. in cells treated with protamine (32 to 250 micrograms/ml), we could detect no effect of protamine on basal intracellular levels of cgmp until a concentration of 250 micrograms/ml of protamine was used. at this concentration, protamine increased basal cgmp concentrations from 4.2 /- 0.3 to 9.0 /- 0.6 pmol/mg protein (p .001). the response of intracellular cgmp to sodium nitroprusside in cells treated with 250 micrograms/ml or other concentrations of protamine was not different from control. likewise, we could detect no effect of protamine on intracellular cgmp stimulated with the atrial natriuretic peptide or on camp stimulated with the beta-adrenergic receptor agonist, isoproterenol, or with forskolin.","these experiments show that protamine does not alter the responses of the intracellular second messengers, cgmp and camp, to the vasodilators sodium nitroprusside, atrial natriuretic peptide, isoproterenol, and forskolin. these results do not support the hypothesis that protamine sensitizes vascular smooth muscle cells to the endothelium-derived relaxing factor, nitric oxide.",Medication
is growth hormone secretion impaired in amyotrophic lateral sclerosis?,"als is the most common motor neurone disorder in human adults. scanty data on endocrine abnormalities have been reported. the aim of the present study was to investigate the gh-igf-i axis in als patients. twenty-two als patients (12 men, 10 women), mean age 61 years, and 25 normal age- and sex-matched subjects. no patient was under riluzole therapy. patients and controls underwent a ghrh plus arginine test. igf-i was determined at baseline. a complete evaluation of pituitary function was also performed. mean (/- sd) basal gh levels were significantly reduced compared with normal controls (0.2 /- 0.3 vs 1.6 /- 1.8 ng/ml, p 0.01), as well as peak gh concentrations after ghrh arginine administration (12.6 /- 8.9 vs 39.9 /- 18.7 ng/ml, p 0.001). six (27) patients showed a normal gh response to stimulus; 7 (32) patients displayed a moderate gh deficiency; in 9 (40) patients gh response was markedly deficient. igf-i levels were normal in the majority of patients (mean /- sd: 143.6 /- 63.8 ng/ml). no significant correlation was observed between peak gh concentrations and age, bmi, disease duration, severity or clinical form. a higher incidence of gh deficiency was observed in male compared to female patients (83vs 60), with a peak gh response in males significantly lower than in females (8.9 /- 6.6 vs 17 /- 9.6 ng/ml, p 0.03). eighteen patients repeated the test after 5 months and similar results were obtained.",the present data indicate a reduction of gh secretion in als patients.,Treatment
does trans-fatty acid promote thrombus formation in mice by aggravating antithrombogenic endothelial functions via toll-like receptors?,"since excessive intake of trans-fatty acid (tfa) increases the risk of myocardial infarction, we investigated the effects of tfa on thrombus formation using animal and cell culture experiments. c57bl/6 mice were fed a diet containing tfa or cis-fatty acid (5 each of total calories) or a chow diet for 4 weeks, and thrombus formation was induced in the carotid artery by he-ne laser irradiation. the high-tfa diet significantly promoted thrombus formation in the carotid artery compared to the chow or cis-fatty acid diet. tfa activated the inflammatory signaling pathway in cultured endothelial cells and in mice; aortic gene expression levels of antithrombogenic molecules, including thrombomodulin and tissue factor pathway inhibitor, were decreased, and the expression levels of prothrombogenic molecules were increased in tfa-treated mice. tfa markedly upregulated the prothrombogenic molecules and downregulated the antithrombogenic molecules in endothelial cells. in addition, tfa induced phosphorylation of c-jun n-terminal kinase, extracellular signal-regulated kinase, and nuclear factor-b. the tfa-activated signal pathways and prothrombogenic phenotypic changes of endothelial cells were inhibited by genetic or pharmacological inactivation of toll-like receptors 2 and 4.",tfa aggravates the antithrombogenic phenotypes of vascular endothelial cells via toll-like receptors and promotes thrombus formation in mice.,Medication
is susceptibility of gr/gr rearrangements to azoospermia or oligozoospermia dependent on daz and cdy1 gene copy deletions?,"the purpose of this study was to determine the association of azfc subdeletions (gr/gr, b1/b3 and b2/b3) and deletion of daz and cdy1 gene copies with male infertility three hundred twelve controls, 172 azoospermic and 343 oligozoospermic subjects were subjected to azfc subdeletion typing by sts pcr. deletion of daz and cdy1 gene copies was done using sequence family variant analysis. sperm concentration and motility were compared between men with and without azfc subdeletions. effect of the azfc subdeletions on icsi outcome was evaluated. amongst the three azfc subdeletions, the frequency of gr/gr was higher in oligozoospermic (10.5 ) and azoospermic (11.6 ) men as compared to controls (5.1 ). in men with azfc subdeltions, loss of two daz and one cdy1 gene copy made them highly susceptible to azoospermia and severe oligozoospermia with or of 29.7 and 26, respectively. these subdeletions had no effect on icsi outcome, albeit there were an increased number of poor quality embryos in azfc subdeleted group.","azfc subdeletions are a major risk factor for male infertility in the indian population. in the subjects with azfc subdeletions, the deletion of daz and cdy1 gene copies increases its susceptibility to azoospermia or severe oligozoospermia. since these deletions can be vertically transmitted to the future male offspring by icsi, it will be essential to counsel the couples for the transmission of the genetic defect in the male offspring born after assisted reproduction and the risk of perpetuating infertility in future generation.",General
does antidepressant use be associated with an increased risk of developing microbleeds?,"serotonin-specific antidepressants may increase the risk of adverse bleeding events. in a previous cross-sectional study, we did not observe an association between antidepressant use and presence of subclinical cerebral bleedings. in this study, we investigated longitudinally whether antidepressant use is associated with an increased risk of new subclinical cerebral microbleeds. in total, 2559 participants aged 45 years of the population-based rotterdam study, all without microbleeds at baseline, underwent baseline and repeat brain magnetic resonance imaging between 2005 and 2013 (mean time interval, 3.9 years; sd, 0.5) to determine the incidence of microbleeds. antidepressant use (yes versus no) was assessed between baseline and follow-up scan. in additional analyses, antidepressants were classified as low, intermediate, or high affinity for the serotonin transporter, and alternatively as selective serotonin reuptake inhibitors or non-selective serotonin reuptake inhibitors. we used multivariable logistic regression models to investigate the association of antidepressants with incident microbleeds. antidepressant use was associated with a higher cerebral microbleed incidence (odds ratio, 2.22; 95 confidence interval, 1.31-3.76) than nonuse. when stratified by affinity for the serotonin transporter, intermediate serotonin affinity antidepressant use was associated with an increased risk of developing microbleeds (odds ratio, 3.07; 95 confidence interval, 1.53-6.17). finally, selective serotonin reuptake inhibitor and non-selective serotonin reuptake inhibitor use were both associated with increased microbleed incidence.",antidepressant use was associated with an increased risk of developing microbleeds. our results may support findings from previous clinical studies about increased intracranial and extracranial bleeding risk in antidepressant users.,Medication
is adequacy of food spending related to housing expenditures among lower-income canadian households?,"a number of studies have pointed to the pressure that housing costs can exert on the resources available for food. the objectives of the present study were to characterise the relationship between the proportion of income absorbed by housing and the adequacy of household food expenditures across the canadian population and within income quintiles; and to elucidate the impact of receipt of a housing subsidy on adequacy of food expenditures among low-income tenant households. the 2001 survey of household spending, conducted by statistics canada, was a national cross-sectional survey that collected detailed information on expenditures on goods and services. the adequacy of food spending was assessed in relation to the cost of a basic nutritious diet. canada. the person with primary responsibility for financial maintenance from 15 535 households from all provinces and territories. as the proportion of income allocated to housing increased, food spending adequacy declined significantly among households in the three lowest income quintiles. after accounting for household income and composition, receipt of a housing subsidy was associated with an improvement in adequacy of food spending among low-income tenant households, but still mean food spending fell below the cost of a basic nutritious diet even among subsidised households.",this study indicates that housing costs compromise the food access of some low-income households and speaks to the need to re-examine policies related to housing affordability and income adequacy.,Prevention
are high concentrations of n-bnp related to non-infectious severe sirs associated with cardiovascular dysfunction occurring after off-pump coronary artery surgery?,"procalcitonin (pct) blood concentrations are known to be an appropriate marker of severe systemic inflammatory response syndrome (sirs) induced by coronary artery surgery with and without cardiopulmonary bypass. pro-brain natriuretic peptide (n-bnp) is a newly described cardiac hormone considered to be an effective marker of severity and prognosis of acute coronary syndromes and congestive heart failure. we evaluated the perioperative time courses of pct and n-bnp and investigated their role as early markers of severe sirs (sirs with cardiovascular dysfunction) induced by off-pump coronary artery bypass (opcab). sixty-three patients were prospectively included. the american college of chest physicians classification was used to diagnose sirs and organ system failure to define severe sirs. serum concentrations of pct and n-bnp were determined before, during and after surgery. receiver operating characteristic curves and cut-off values were used to assess the ability of these markers to predict postoperative severe sirs. sirs occurred in 25 (39) patients. nine of them (14) showed severe sirs. significantly higher serum concentrations of n-bnp and pct were found in patients with severe sirs with peak concentrations respectively at 8887 pg ml(-1) (range 2940-29372 pg ml(-1)) for n-bnp and 9.50 ng ml(-1) (range 1-65 ng ml(-1)) for pct. the area under the curve using n-bnp to detect postoperative severe sirs was 0.799 before surgery (0.408 for pct; p0.01) and 0.824 at the end of surgery (0.762 for pct; p0.05).",n-bnp may be an appropriate marker indicating the early development of non-infectious postoperative severe sirs after opcab.,Treatment
does ro-3306 prevent postovulatory aging-mediated spontaneous exit from m-ii arrest in rat eggs cultured in vitro?,"postovulatory aging-mediated spontaneous exit from metaphase-ii (m-ii) arrest deteriorates egg quality and limits assisted reproductive technologies outcome (art) outcome. present study was aimed to find out whether ro-3306, specific cyclin dependent kinase 1 (cdk1) inhibitor could protect against postovulatory aging-mediated spontaneous exit from m-ii arrest in rat eggs cultured in vitro. freshly ovulated m-ii arrested eggs were exposed to various concentrations of ro-3306 for 3h in vitro. the morphological changes, percentage of spontaneous exit from m-ii arrest, total and specific phosphorylation status of cdk1, cyclin b1 level and cdk1 activity were analyzed. data suggest that ro-3306 protected postovulatory aging-mediated spontaneous exit from m-ii arrest in a concentration-dependent manner. postovulatory aging increased thr14/tyr15 phosphorylated cdk1 level, decreased thr161 phosphorylated cdk1 as well as cyclin b1 levels and increased cdk1 activity in aged eggs cultured in vitro. on the other hand, ro-3306 protected postovulatory aging-induced changes in specific phosphorylation of cdk1, cyclin b1 level, inhibited the kinase activity and prevented spontaneous exit from m-ii arrest.","our results suggest that postovulatory aging destabilizes mpf by modulating specific phosphorylation of cdk1 and cyclin b1 level. ro-3306 prevented these changes and maintained m-ii arrest in rat eggs cultured in vitro. hence, maintenance of m-ii arrest in ovulated eggs using ro-3306 could be beneficial to increase the number of eggs available for various art programs.",Prevention
does overexpression of coupling factor 6 cause cardiac dysfunction under high-salt diet in mice?,"reactive oxygen species are involved in the pathogenesis of congestive heart failure. we recently showed that coupling factor 6, a component of adenosine trisphosphate (atp) synthase, induces hypertension by intracellular acidosis, which is related to reactive oxygen species generation. we investigated the effect of high-salt diet on the cardiac performance and reactive oxygen species generation in coupling factor 6-overexpressing transgenic mice. baseline echocardiographic findings, reactive oxygen species generation, protein expression of sarcoplasmic/endoplasmic reticulum of ca-atpase 2 and phospholamban, and atp content in the heart were similar between 7-week-old transgenic and wild-type mice. when the mice were fed with 8 salt diet for 20-24 weeks, fractional shortening of the left ventricle was decreased in transgenic mice compared with wild-type mice and was recovered by intraperitoneal administration of anticoupling factor 6 antibody. nicotinamide adenine dinucleotide phosphate oxidase activity in the heart was increased in transgenic mice after the high-salt diet concomitantly with c-src activation. the level of 8-iso-prostaglandin f2 was increased in transgenic heart compared with wild-type heart. the protein expression of sarcoplasmic/endoplasmic reticulum of ca-atpase 2 was decreased and that of phospholamban was increased in transgenic heart. in cdna microarray analysis, the genes related to atp synthesis and glycolysis were decreased in transgenic heart, concomitantly with the decrease in atp content and the increase in -myosin heavy chain.",these suggest that coupling factor 6 induces the development of systolic dysfunction and upregulation of nicotinamide adenine dinucleotide phosphate oxidase in the heart under the high-salt diet.,Prevention
is cpg methylation of a silent controlling element in the murine avy allele incomplete and unresponsive to methyl donor supplementation?,"the viable yellow allele of agouti (a(vy)) is remarkable for its unstable and partially heritable epigenetic state, which produces wide variation in phenotypes of isogenic mice. in the a(vy) allele an inserted intracisternal a particle (iap) acts as a controlling element which deregulates expression of agouti by transcription from the ltr of the iap; the phenotypic state has been linked to cpg methylation of the ltr. phenotypic variation between a(vy) mice indicates that the epigenetic state of the iap is unstable in the germline. we have made a detailed examination of somatic methylation of the iap using bisulphite allelic sequencing, and find that the promoter is incompletely methylated even when it is transcriptionally silent. in utero exposure to supplementary methyl donors, which alters the spectrum of a(vy) phenotypes, does not increase the density of cpg methylation in the silent ltr.","our findings suggest that, contrary to previous supposition, methyl donor supplementation acts through an indirect mechanism to silence a(vy). the incomplete cytosine methylation we observe at the somatically silent a(vy) allele may reflect its unstable germline state, and the influence of epigenetic modifications underlying cpg methylation.",Medication
does proximal fluid proteome profiling of mouse colon tumors reveal biomarkers for early diagnosis of human colorectal cancer?,"early detection of colorectal cancer (crc) and its precursor lesions is an effective approach to reduce crc mortality rates. this study aimed to identify novel protein biomarkers for the early diagnosis of crc. proximal fluids are a rich source of candidate biomarkers as they contain high concentrations of tissue-derived proteins. the fabplcre;apc(15lox/) mouse model represents early-stage development of human sporadic crc. proximal fluids were collected from normal colon and colon tumors and subjected to in-depth proteome profiling by tandem mass spectrometry. carcinoembryonic antigen (cea) and chi3l1 human serum protein levels were determined by elisa. of the 2,172 proteins identified, quantitative comparison revealed 192 proteins that were significantly (p 5-fold) more excreted by tumors than by controls. further selection for biomarkers with highest specificity and sensitivity yielded 52 candidates, including s100a9, mcm4, and four other proteins that have been proposed as candidate biomarkers for human crc screening or surveillance, supporting the validity of our approach. for chi3l1, we verified that protein levels were significantly increased in sera from patients with adenomas and advanced adenomas compared with control individuals, in contrast to the crc biomarker cea.","these data show that proximal fluid proteome profiling with a mouse tumor model is a powerful approach to identify candidate biomarkers for early diagnosis of human cancer, exemplified by increased chi3l1 protein levels in sera from patients with crc precursor lesions.",Diagnosis
does body mass index affect systematic d2 lymph node dissection and postoperative morbidity in gastric cancer patients?,"the extent of standard lymph node dissection (d1, d2, or d3) in gastric cancer patients is still controversial. several prospective european trials attained contradictory results. a generally increased body mass index (bmi) of the european patients was assumed to be one of the major causes for postoperative morbidity. we evaluated the effect of bmi on the quality of routine d2 lymph node dissection and on postoperative morbidity in patients with gastric cancer who underwent a potentially curative total gastrectomy. a total of 199 consecutive gastric cancer patients who underwent a total gastrectomy and a routine d2 lymph node dissection between 1992 and 2001 were included in the study. according to bmi, they were assigned to three groups: group a, with bmi 30 kg/m(2) (obesity). parameters such as complete histopathological staging, intraoperative blood loss, length of operation, and surgical and nonsurgical morbidity were recorded and correlated within the different groups. no significant differences were found with regard to the number of examined lymph nodes, blood loss, length of operation, surgical complications, or length of stay in the intensive care unit.","in contrast to comparable japanese studies, our analysis reveals that even for overweight patients, a standard d2 lymph node dissection is justified without significantly increased morbidity.",Treatment
does miltefosine induce metacaspase and parp genes expression in leishmania infantum?,"apoptosis is the process of programmed cell death (pcd) that occurs in both animal and plant cells. protozoan parasites possess metacaspase and these caspase-related proteases could be involved in the pcd pathways in these organisms. therefore we analyzed the activities of metacaspase and parp genes in leishmania infantum (mcan/ir/96/lon49) treated with miltefosine. anti-leishmania activity of miltefosine was studied by treatment of cultured promastigotes with various concentration of miltefosine. mtt assay and annexin-v fluos staining by using facs flow cytometry methods were used. cytotoxic potential of hepc on the amastigots of l.infantum was evaluated in j774 cell line. in addition, metacaspase and parp genes expression of treated l. infantum were studied. miltefosine led to dose-dependent death of l. infantum with features compatible with apoptosis. over expression of metacaspase and parp was seen 6 hr after treatment.",our study showed that miltefosine exerts cytotoxic effect on l. infantum via an apoptotic-related mechanism.,Medication
do community- and family-level factors influence care-giver choice to screen blood lead levels of children in a mining community?,"bunker hill, in kellogg, idaho, formerly a lead mine (1884-1981) and smelter (1917-1981), is now a superfund site listed on the environmental protection agency's (epa) national priorities list. lead contamination from the site is widespread due to past smelter discharges to land, water, and air, placing children at risk for both exposure to lead and resultant health effects of lead. since 1983, the epa has used child blood lead levels to inform the clean-up standards for the bunker hill superfund site. this study was undertaken to examine factors that have contributed to the significant fall-off in the rates and numbers of children being screened for blood lead in kellogg (number screened decreased from 195 to 8 from 2002 to 2007). the goal of this research project was to define community- and family-level factors which influence care-giver choice to screen blood lead levels of their children in this environment. this formative research study used mixed methods and was comprised of three research components: (1) preliminary interviews using community-based participatory research methods to define key research questions of relevance to community members, government and ngos working in relation to the bunker hill clean-up; (2) a quantitative analysis of a cross-sectional household survey conducted with adult care-givers about child blood lead screening in kellogg; and (3) ethnographic community rapid assessment methods formed the in-depth interview process and qualitative analysis. the survey showed the likelihood of blood lead screening that for children under the age of 18 years increases 34 with each one-year increase in current age of the child (95 ci, 1.08-1.67, p-value0.009), and decreases 45 with annual household income greater than 10,000 (95 ci, 0.35-0.88, p-value0.013). sibling birth order increased the likelihood of blood lead screening by 61 (95 ci, 1.04-2.48, p-value0.032) for each successive child. female children were rated by their care-givers as 3.7 times less agitated or easily angered than male children (95 ci, 1.5-8.8, p-value0.005). across all levels of interviews, regulators, residents, and non-governmental organization representatives reported that kellogg's long history as a mining town has continued to influence attitudes and actions of care-givers to access blood lead screening for their children. the mining context has been described as instilling stigmas, parental blame and a sense of shame about lead exposure and resultant health effects.","children under 6 years of age are currently the least likely to have been screened for lead in kellogg and screening rates decreased in the 2000s. according to most indicators, socio-economic status did not influence the likelihood of a care-giver to screen children's blood lead levels. however, children in homes with an annual income below 10,000 were more likely to have been screened than the rest of the population. former concerted screening efforts, including outreach, support, follow-up, and financial incentives in the 1980s-1990s to screen children, may have influenced low-income residents. programmatic outreach for children under 6 years of age in kellogg should focus on increasing female child and first child blood lead screening, rather than targeting only low-income families, by improving approaches to promotion, implementation and environmental follow-up for child lead screening. some families have resided in kellogg for five to six generations, and the long-term mining context influences community values and perceptions of lead exposure and screening for children through a conflicted combination of pride in the mining history, attachment to the past economy that supported the community in juxtaposition to the personalized blame, shame, guilt, and stigma associated with children having high blood lead levels. health communication and other programs should prioritize methods of reducing parental feelings of blame, shame and guilt, and stigmas associated with the health effects of lead in a way that respects the pride of former mine workers, their families, and the history of the town.",Diagnosis
does nicotine induce tissue factor expression in cultured endothelial and smooth muscle cells?,"cigarette smoking is associated with an increased risk to develop myocardial infarction and ischemic stroke. however, the mechanisms responsible for these effects are still poorly understood. to investigate whether nicotine, the major component of cigarette smoking, and its main metabolite, cotinine, might induce a pro-thrombotic state via stimulation of tissue factor (tf) expression in two cell population widely represented in the arterial wall such as endothelial cells (ecs), and smooth muscle cells (smcs). incubation of ecs and smcs with nicotine and cotinine induced tf expression in both cell types in a dose-dependent fashion, exerting its effect at the transcriptional level, as demonstrated by semiquantitative and by real-time pcr. nicotine- and cotinine-induced tf expression was mediated by the activation of the transcription factor, nuclear factor-kappa b (nf-kappab), as demonstrated by electrophoretic mobility shift assay and by the suppression of tf expression by the nf-kappab inhibitor, pyrrolidine dithio carbamate ammonium.","these data indicate that nicotine and cotinine exert direct effects on ecs and smcs, shifting them toward a pro-thrombotic state via induction of tf expression. these effects on cells of the vessel wall might explain, at least in part, the deleterious cardiovascular consequences of cigarette smoking.",Medication
does pathway analysis reveal functional convergence of gene expression profiles in breast cancer?,"a recent study has shown high concordance of several breast-cancer gene signatures in predicting disease recurrence despite minimal overlap of the gene lists. it raises the question if there are common themes underlying such prediction concordance that are not apparent on the individual gene-level. we therefore studied the similarity of these gene-signatures on the basis of their functional annotations. we found the signatures did not identify the same set of genes but converged on the activation of a similar set of oncogenic and clinically-relevant pathways. a clear and consistent pattern across the four breast cancer signatures is the activation of the estrogen-signaling pathway. other common features include brca1-regulated pathway, reck pathways, and insulin signaling associated with the er-positive disease signatures, all providing possible explanations for the prediction concordance.",this work explains why independent breast cancer signatures that appear to perform equally well at predicting patient prognosis show minimal overlap in gene membership.,Medication
does cerebral -amyloid deposition predict hiv-associated neurocognitive disorders in apoe 4 carriers?,"the apolipoprotein e (apoe) 4 allele enhances cerebral accumulation of -amyloid (a) and is a major risk factor for sporadic alzheimer's disease. we hypothesized that hiv-associated neurocognitive disorders (hand) would be associated with the apoe 4 genotype and cerebral a deposition. clinicopathological study of hiv-infected adults from four prospective cohorts in the us national neuroaids tissue consortium. we used multivariable logistic regressions to model outcomes a plaques (immunohistochemistry) and hand (standard criteria) on predictors apoe 4 (allelic discrimination assay), older age (50 years), a plaques, and their two-way interactions and comorbid factors. isocortical a deposits generally occurred as diffuse plaques and mild-to-moderate amyloid angiopathy. isocortical phospho-tau-immunoreactive neurofibrillary lesions were sparse. the apoe 4 and older age were independently associated with the presence of a plaques adjusted odds ratio (or) 10.16 and 5.77, 95 confidence interval (ci) 2.89 - 35.76 and 1.91-17.48, p 0.0003 and 0.0019, respectively, n 96. the probability of hand was increased in the presence of a plaques among apoe 4 carriers (adjusted or 30.00, 95 ci 1.41-638.63, p 0.029, n 15), but not in non-4 carriers (n 57).","the apoe 4 and older age increased the likelihood of cerebral a plaque deposition in hiv-infected adults. generally, a plaques in hiv brains were immunohistologically different from those in symptomatic alzheimer's disease brains. nonetheless, a plaques were associated with hand among apoe 4 carriers. the detection of apoe 4 genotype and cerebral a deposition biomarkers may be useful in identifying living hand patients who could benefit from a-targeted therapies.",Prevention
does bilateral l1 and l2 dorsal root ganglion block for discogenic low-back pain?,"it is possible that interruption of nociceptive input from intervertebral discs can be modulated through bilateral l1 and l2 dorsal root ganglia (drg) blockade. in order to test this hypothesis, we prospectively collected data from patients with low-lumbar pain, accurately diagnosed as discogenic using provocation discography. twelve patients were recruited with a mean (sd) symptom duration of 13.7 (8.2) years. bilateral drg blocks of l1 and l2 were performed using methylprednisolone 80 mg, clonidine 75 microg and 0.5 bupivacaine 4 ml in each patient. analysis of brief pain inventories showed no significant change in pain scores.",we conclude that blocks of this nociceptive pathway in humans using bilateral drg blocks has no therapeutic value.,Symptoms
"does acute improvement of pulmonary hemodynamics alleviate cheyne-stokes respiration in chronic heart failure-a randomized , controlled , double-blind , crossover trial?","this randomized, controlled trial aimed to investigate whether acute improvement of pulmonary congestion would reduce the severity of cheyne-stokes respiration (csr) in patients with chronic heart failure (chf). twenty-one consecutive patients with chf and csr (apnea-hypopnea index ahi 15/h) underwent right heart catheterization with titration of intravenous (iv) glyceryltrinitrate (gtn) to a maximum tolerable dosage and inhalation of iloprost 10 g/ml after a washout phase. maximum tolerable dosages of gtn and iloprost were randomly applied during full cardiorespiratory polysomnography within two split-night procedures and compared with iv or inhaled sodium chloride (nacl) 0.9 , respectively. gtn (6.2 1.5 mg/h) and iloprost significantly lowered mean pulmonary artery pressure (20.1 9.0 to 11.6 4.2 mmhg, p 0.001 and 16.9 7.9 to 14.2 6.4 mmhg, p 0.01, respectively). pulmonary capillary wedge pressure was only reduced by gtn (14.0 5.6 to 7.2 3.9 mmhg, p 0.001), and there was no significant change in the cardiac index. sleep studies revealed no significant improvement in markers of csr severity, including ahi, central apnea index, and csr cycle length following gtn or iloprost treatment. significant decreases in blood pressure, mean oxygen saturation, and s3 sleep were documented during gtn infusion.","acute improvement of pulmonary congestion by gtn had no immediate impact on csr severity. future investigations must therefore include longer treatment periods and treatment regimens that have positive, rather than negative, additional effects on peripheral and central chemoreceptors and sleep structure.",Medication
does plasminogen initiate and potentiates the healing of acute and chronic tympanic membrane perforations in mice?,"most tympanic membrane (tm) perforations heal spontaneously, but approximately 10-20 remain open as chronic tm perforations. chronic perforations can lead to an impaired hearing ability and recurrent middle ear infections. traditionally, these perforations must be surgically closed, which is costly and time consuming. therefore, there is a need for simpler therapeutic strategies. previous studies by us have shown that plasminogen (plg) is a potent pro-inflammatory regulator that accelerates cutaneous wound healing in mice. we have also shown that the healing of tm perforations is completely arrested in plg-deficient (plg(-/-)) mice and that these mice develop chronic tm perforations. in the present study, we investigated the therapeutic potential of local plg injection in acute and chronic tm perforation mice models. plg(-/-) mice and wild-type mice were subjected to standardized tm perforations followed by local injection of plg into the soft tissue surrounding the tm. tm perforations with chronic characteristics were induced by leaving tm perforations in plg(-/-) mice untreated for 9 days before treatment. the healing process was observed through otomicroscope and finally confirmed by immunostaining. the quality of tm healing was evaluated based on the morphology of the tm. daily local injections of plg into the soft tissue surrounding the tm restored the ability to heal tm perforations in plg-/- mice in a dose-dependent manner, and potentiated the healing rate and quality in wild-type mice. a single local injection of plg initiated the healing of the chronic-like tm perforations in these mice, resulting in a closed tm with a continuous but rather thick outer keratinocyte layer. however, three plg injections led to a completely healed tm with a thin keratinizing squamous epithelium covering a connective tissue layer.",our data suggests that plg is a promising drug candidate for the treatment of chronic tm perforations in humans.,Treatment
does eszopiclone prevent excitotoxicity and neurodegeneration in the hippocampus induced by experimental apnea?,"this study was designed to determine the effects of eszopiclone on apnea-induced excitotoxic synaptic processes and apoptosis in the hippocampus. recurrent periods of apnea, which consisted of a sequence of apnea (75 spo2), followed by ventilation with recovery to normoxia ( 95 spo2), were induced for a period of three hours in anesthetized guinea pigs. the ca3 schaffer collateral pathway in the hippocampus was stimulated and the field excitatory postsynaptic potential (fepsp) response was recorded in ca1. animals in the experimental group received an intravenous injection of eszopiclone (3 mg/kg) 10 min prior to the initiation of the periods of recurrent apnea, and once every 60 min thereafter; control animals received comparable injections of vehicle. at the end of the 3-h period of recurrent apnea, the animals were perfused, and hippocampal sections were immunostained in order to determine the presence of apoptosis, i.e., programmed cell death. analyses and results: apnea resulted in a persistent increase in synaptic responsiveness of ca1 neurons as determined by analyses of the fepsp. eszopiclone antagonized the apnea-induced increase in the fepsp. morphological analyses revealed significant apoptosis of ca1 neurons in control animals; however, there was no significant apoptosis in eszopiclone-treated animals.","eszopiclone was determined to suppress the apnea-induced hyperexcitability of hippocampal ca1 neurons, thereby reducing/eliminating neurotoxicity. these data lend credence to our hypothesis that eszopiclone, exclusive of its hypnotic actions, has the capacity to function as a potent neuroprotective agent.",Prevention
does prognosis of rectal cancer patients improve with downstaging by intensified neoadjuvant radiochemotherapy - a matched pair analysis?,"neoadjuvant radiochemotherapy has been proven superior to adjuvant treatment in reducing the rate of local recurrence without impairing cancer related survival or the incidence of distant metastases in standard protocols of neoadjuvant radiochemotherapy. the present study aimed at addressing the effects of an intensified neoadjuvant radiochemotherapy on long term cancer related and disease free survival. a total of 387 patients underwent oncologic resection for rectal cancer in our institution between january 2000 and december 2009. there were 106 patients (27.4) who received an intensified radiochemotherapy protocol completely and without excluding criteria (study group). a matched pair analysis was performed by comparing the study group with patients undergoing primary surgery and postoperative radiochemotherapy, if necessary and possible (control group). matching was carried out in descending order for uicc stage, r-status, tumor height, t-, n-, v-, l-, m- and g-category of the tnm-system according to the histopathological staging. follow-up data included local recurrence rate, cancer related and disease free survival. in the study group histopathological work-up of the specimen revealed a treatment response in terms of tumor regression in 92.5 (98/106) of these patients. undergoing intensified neoadjuvant rct the actuarial cancer related and disease free survival was 67.9 and 70.4, local recurrence was 5.7 after an observation period of 4.3 2.55 years. in the control group cancer related and disease free survival was 71.7 and 82.7, local recurrence was 4.7 after an observation period of 3.8 3.05 years revealing no statistical significant difference between the two groups. moreover, estimated 5-year results of cancer related survival (66.7 vs 67.9 (controls)), the disease free survival (66.7 vs 79.9 (controls)) as well as subgroup analysis of uicc 0-iii and uicc iv patients showed no difference between the study and control group as well.","in our study, intensified neoadjuvant radio-chemotherapy shows a high rate of tumor regression. the resulting inferior histopathological tumor stage shows the same long term local control and systemic tumor control as the control group with a primary more favorable tumor stage.",Treatment
are endometriomas more frequent on the left side?,"to investigate whether asymmetry exists in the left- and right-distribution of ovarian cystic lesions in women with endometriosis. we evaluated operative reports of women who underwent surgical treatment of endometrioma(n 253) from january 1999 to december 2003. we included only those cases that had not been previously operated on (n 234). data of all operative findings consisted of a written report and a diagram, fulfilling the revised american fertility society classification of endometriosis. endometrioma was found in the left ovary in 113 women, in the right ovaryin 67, and bilaterally in 54. left ovarian unilateral endometrioma was found more frequently (62.8) than right endometrioma (p 0.001, odds ratio (or) 2.8, 95 confidence interval (ci) 1.9, 4.4). the frequencies of left and right ovarian endometrioma were compared with the expected 50 using pearson's chi(2)-test. the results confirmed asymmetry(p 0.001). we found 4 cases of ovarian cancer associated with left endometrioma without histological proof of transition.","our results confirm a left lateral predisposition of endometrioma. this predisposition may be caused by the presence of the sigmoid colon in the left side of the pelvis, which decreases peritoneal fluid movement. our findings may support the transplantation theory of the origin for endometriosis.",Treatment
does bacillus calmette guerin induce fibroblast activation both directly and through macrophages in a mouse bladder cancer model?,"bacillus calmette-guerin (bcg) is the most effective treatment for non-muscle invasive bladder cancer. however, a failure in the initial response or relapse within the first five years of treatment has been observed in 20 of patients. we have previously observed that in vivo administration of an inhibitor of nitric oxide improved the response to bcg of bladder tumor bearing mice. it was described that this effect was due to a replacement of tumor tissue by collagen depots. the aim of the present work was to clarify the mechanism involved in this process. we demonstrated that bcg induces nih-3t3 fibroblast proliferation by activating the mapk and pi3k signaling pathways and also differentiation determined by alpha-smooth muscle actin (alpha-sma) expression. in vivo, intratumoral inoculation of bcg also increased alpha-sma and collagen expression. oral administration of l-name enhanced the pro-fibrotic effect of bcg. peritoneal macrophages obtained from mb49 tumor-bearing mice treated in vivo with combined treatment of bcg with l-name also enhanced fibroblast proliferation. we observed that fgf-2 is one of the factors released by bcg-activated macrophages that is able to induce fibroblast proliferation. the involvement of fgf-2 was evidenced using an anti-fgf2 antibody. at the same time, this macrophage population improved wound healing rate in normal mice and fgf-2 expression was also increased in these wounds.","our findings suggest that fibroblasts are targeted by bcg both directly and through activated macrophages in an immunotherapy context of a bladder murine model. we also described, for the first time, that fgf-2 is involved in a dialog between fibroblasts and macrophages induced after bcg treatment. the fact that l-name administration improves the bcg effect on fibroblasts, no inhibition, might represent a new approach to add to the conventional bcg therapy.",Medication
does ct substitute derived from mr images reconstructed with parallel imaging?,"computed tomography (ct) substitute images can be generated from ultrashort echo time (ute) mri sequences with radial k-space sampling. these ct substitutes can be used as ordinary ct images for pet attenuation correction and radiotherapy dose calculations. parallel imaging allows faster acquisition of magnetic resonance (mr) images by exploiting differences in receiver coil element sensitivities. this study investigates whether non-cartesian parallel imaging reconstruction can be used to improve ct substitutes generated from shorter examination times. the authors used gridding as well as two non-cartesian parallel imaging reconstruction methods, spirit and cg-sense, to reconstruct radial ute and gradient echo (ge) data into images of the head for 23 patients. for each patient, images were reconstructed from the full dataset and from a number of subsampled datasets. the subsampled datasets simulated shorter acquisition times by containing fewer radial k-space spokes (1000, 2000, 3000, 5000, and 10,000 spokes) than the full dataset (30,000 spokes). for each combination of patient, reconstruction method, and number of spokes, the reconstructed ute and ge images were used to generate a ct substitute. each ct substitute image was compared to a real ct image of the same patient. the mean absolute deviation between the ct number in ct substitute and ct decreased when using spirit as compared to gridding reconstruction. however, the reduction was small and the ct substitute algorithm was insensitive to moderate subsampling ( 5000 spokes) regardless of reconstruction method. for more severe subsampling ( 3000 spokes), corresponding to acquisition times less than a minute long, the ct substitute quality was deteriorated for all reconstruction methods but spirit gave a reduction in the mean absolute deviation of down to 25 hounsfield units compared to gridding.","spirit marginally improved the ct substitute quality for a given number of radial spokes as compared to gridding. however, the increased reconstruction time of non-cartesian parallel imaging reconstruction is difficult to motivate from this improvement. because the ct substitute algorithm was insensitive to moderate subsampling, data for a ct substitute could be collected in as little as minute and reconstructed with gridding without deteriorating the ct substitute quality.",Treatment
is detrusor after-contraction associated with bladder outlet obstruction?,"the aims of this study were to determine how we can differentiate detrusor after-contraction (dac) from artifacts, and to understand the clinical implications and significance of dac. a retrospective analysis was performed on 2,309 patients with neurogenic or non-neurogenic voiding dysfunction. investigators asked patients to cough when detrusor contraction occurred following cessation of urinary flow. no simultaneous change of detrusor pressure (p(det) ) could confirm that p(det) increase could be regarded as true dac. patients were subcategorized according to the presence of large postvoid urine volume, increase of electromyographic activity, the amount of p(det) change, and multiplicity. detrusor contraction occurred after cessation of urinary flow in 245 patients (10.6). the contractions of 57 patients (23.3) were regarded as artifacts. dac was identified in 188 patients (132 males, 5.7 and 56 females, 2.4). the mean increase in p(det) from the initiation of dac to the maximal p(det) of dac was 22.6 11.2 cmh(2) o in males, and 18.6 7.9 cmh(2) o in females. dac occurred more frequently as males became older. detrusor pressures at maximal flow were higher in patients with dac. patients of both genders with bladder outlet obstruction (boo) had an increased risk of developing dac. males with benign prostatic hyperplasia had an increased risk of developing dac.",dac should be differentiated from artifacts using cough test and the presence of dac was significantly correlated to the presence of boo.,Symptoms
does peri-procedural povidone-iodine rectal preparation reduce microorganism counts and infectious complications following ultrasound-guided needle biopsy of the prostate?,"the purpose of the study was to evaluate whether a peri-procedural povidone-iodine rectal preparation (pirp) prior to transrectal ultrasound-guided prostate needle biopsy (trus pnb) can reduce microorganism colony counts and infectious complications. our institutional trus pnb database was reviewed to identify infectious post-biopsy complications (defined as fever 38.5 c with positive culture). the last 570 biopsy patients were divided into those administered only preoperative oral and/or parenteral antibiotics (n 456; chronologically cohorts a-d) versus men receiving peri-procedural pirp in conjunction with standard preoperative antibiotics (n 114; cohort e). rectal cultures were obtained in the pirp cohort to quantify changes in microorganism colony counts. mean baseline psa for patients was 11.6 ng/ml, 63 were undergoing an initial biopsy, and 17 had documented use of antibiotic therapy within the previous 6 months. a reduction in infectious complications was observed when comparing the conventional antibiotic (cohorts a-d) versus pirp (cohort e) group (1.8 vs. 0 ), with the largest magnitude of decline occurring in the concurrent contemporary cohorts (cohort d-5.3 vs. cohort e-0 , p 0.03). rectal cultures obtained in 92 men before and after pirp administration noted a 97 reduction in microorganism colonies (2.1 10(5) vs. 6.3 10(3) cfu/ml, p 0.001). no adverse reactions to the pirp were reported by patients 7 days post-biopsy.","peri-procedural pirp decreased microorganism colony counts and effectively reduced infectious complications following trus pnb. this safe, cheap, and simple strategy may be a reasonable alternative to systemic or targeted antibiotic therapy to reduce post-biopsy infections.",Diagnosis
is survival of patients with hpv-positive oropharyngeal cancer after radiochemotherapy significantly enhanced?,"the purpose of this study was to evaluate the incidence and clinical significance of hpv (human papilloma virus) infection in patients with head and neck cancer who had received radiotherapy in eastern austria. 88 patients with head and neck cancer including 26 patients with oral cavity cancer, 45 patients with oropharyngeal cancer, seven patients with laryngeal carcinoma and ten patients with carcinoma of the hypopharynx were screened for high risk hpv by immunohistochemistry, pcr (polymerase chain reaction) and in-situ hybridization. 29 out of 45 patients with a squamous cell carcinoma of the oropharynx received radiotherapy alone, radiotherapy in combination with cisplatin or cetuximab. of the investigated 29 patients with oropharyngeal cancer receiving conservative treatment, 11 had a hpv-positive and 18 a hpv-negative tumor. patients received radiation cisplatin or cetuximab, where the hpv-positive patients had a significant better response to treatment and overall survival (p 0.015) as well as disease-free survival (p 0.001) after therapy.",patients with oropharyngeal carcinoma and a positive hpv status respond considerably better to radiochemotherapy than patients with hpv-negative tumors. hpv screening is a simple procedure and can easily be implemented in routine pathology investigations and should be included in standard operational procedures for the diagnosis and therapy of head and neck cancer patients.,Treatment
does inhibition of csn3 expression induce growth arrest and apoptosis of hepatocellular carcinoma cells?,"csn3 (or csn3) encodes the third subunit of an eight-subunit complex, the cop9 signalosome (csn), which acts as a protein kinase and a deneddylase in mammalian cells. previous studies have shown that csn3 is essential for maintenance of cell proliferation in the mouse embryonic epiblast and associated with the tumorigenesis process in osteosarcoma. however, its correlation with hepatocellular carcinoma (hcc) has not been explored yet. the expression of csn3 in hcc (n 30), cirrhosis (n 30), and normal tissues (n 30) was detected using immunohistochemical analysis. the impacts of lentivirus-mediated inhibition of csn3 on hcc cells were detected using mtt, brdu incorporation assay, and flow cytometric analysis. in addition, the colony formation and tumor growth ability in nude mice were detected to define the role of csn3 in tumorigenesis. knockdown of csn3 expression in hcc cell lines (smmc-7721 and hep3b) significantly inhibits the tumor growth both in vitro and in vivo. further investigation indicates that this growth inhibition effect may be mediated through cell cycle arrest in g0/g1 phase and inductions of pro-apoptotic proteins bik and caspase-8. in addition, knockdown of csn3 expression evidently suppresses tumor growth in a xenograft nude mice model.","collectively, this study demonstrates csn3 as an oncogene that regulates the tumorigenesis process in hcc cells.",General
do subinhibitory concentrations of penicillin increase the mutation rate to optochin resistance in streptococcus pneumoniae?,"the aim of this work was to study the effect of subinhibitory concentrations of penicillin, chloramphenicol and erythromycin on the mutation rate of streptococcus pneumoniae. the mutation rate to rifampicin and optochin resistance was estimated using fluctuation analysis in three capsulated s. pneumoniae strains, cultured both with and without different subinhibitory antibiotic concentrations. the atpac and rpob mutations that conferred optochin and rifampicin resistance, respectively, were identified by dna sequencing. the exposure to subinhibitory concentrations of penicillin increased the mutation rate (expressed as mutation per cell division) to optochin resistance between 2.1- and 3.1-fold for all three strains studied. in contrast, the rifampicin resistance assay showed no significant variations. to analyse the putative cause of the different responses between the optochin and rifampicin tests, mutations that conferred resistance in both cases were analysed. the difference may be explained by the genetic nature of the atpac mutations, mostly transversions, which are not efficiently repaired by the hexab mismatch repair system.","we demonstrated that subinhibitory concentrations of penicillin significantly increased the mutation rate of s. pneumoniae, suggesting that exposure to this antibiotic could help this pathogen to acquire mutations that confer resistance to other antibiotics. the optochin test was useful to detect this phenomenon and it should be considered for further mutability analysis in s. pneumoniae.",Medication
is 1p36 deletion a marker for tumour dissemination in microsatellite stable stage ii-iii colon cancer?,"the clinical behaviour of colon cancer is heterogeneous. five-year overall survival is 50-65 with all stages included. recurring somatic chromosomal alterations have been identified and some have shown potential as markers for dissemination of the tumour, which is responsible for most colon cancer deaths. we investigated 115 selected stage ii-iv primary colon cancers for associations between chromosomal alterations and tumour dissemination. follow-up was at least 5 years for stage ii-iii patients without distant recurrence. affymetrix snp 6.0 microarrays and allele-specific copy number analysis were used to identify chromosomal alterations. fisher's exact test was used to associate alterations with tumour dissemination, detected at diagnosis (stage iv) or later as recurrent disease (stage ii-iii). loss of 1p36.11-21 was associated with tumour dissemination in microsatellite stable tumours of stage ii-iv (odds ratio 5.5). it was enriched to a similar extent in tumours with distant recurrence within stage ii and stage iii subgroups, and may therefore be used as a prognostic marker at diagnosis. loss of 1p36.11-21 relative to average copy number of the genome showed similar prognostic value compared to absolute loss of copies. therefore, the use of relative loss as a prognostic marker would benefit more patients by applying also to hyperploid cancer genomes. the association with tumour dissemination was supported by independent data from the the cancer genome atlas.",deletions on 1p36 may be used to guide adjuvant treatment decisions in microsatellite stable colon cancer of stages ii and iii.,Diagnosis
is coronary flow reserve impaired in patients with adult growth hormone ( gh ) deficiency?,"relationship between adult growth hormone deficiency (aghd) and increased cardiovascular disease risk is very well known in hypopituitary patients treated with conventional hormone replacement therapy other than growth hormone (gh) administration. endothelial dysfunction, an early and reversible event in pathogenesis of atherosclerosis, is associated with increased vascular smooth muscle tone, arterial stiffening and intima-media thickness (imt). coronary flow reserve (cfr) measurement by transthoracic doppler echocardiography (ttde) reflects coronary microvascular and endothelial functions, as a cheaper and an easy screening test. we have used ttde to evaluate endothelial function and coronary microvascular function in aghd. cross-sectional observational study. a total of 10 gh-deficient adults on conventional replacement therapy other than gh (4 males, 6 females; mean age 37 /- 11 years) and 15 healthy subjects (7 males, 8 females; mean age 41 /- 11 years) were studied. patients and controls were all nonsmokers, normotensive and nondiabetic. igf-1, free t4, lipid profile, insulin, glucose, insulin resistance (ir), anthropometrical and physical parameters were recorded. cfr recordings and imt measurements were performed using the vivid 7 echocardiography device. imt were significantly higher in patients than controls (0.70 0.19 mm and 0.53 0.13 mm, respectively; p 0.02). cfr was significantly lower in patients than in controls (1.96 /- 0.35 and 2.62 /- 0.45, respectively; p 0.001). cfr was positively correlated with igf-1 levels (r 0.54, p 0.005).",cfr is significantly lower in adults with gh deficiency than in controls. direct correlation between cfr and igf-1 concentrations suggests gh replacement could improve microvascular function and thereby could decrease cardiovascular morbidity and mortality in aghd.,Treatment
does canalicular magnetic stimulation lack specificity to differentiate idiopathic facial palsy from borreliosis in children?,"to investigate the role of transcranial magnetic stimulation (tms) to differentiate between idiopathic facial nerve palsy (ifnp) and facial nerve palsy due to borreliosis (bfnp). transcranial and intracanalicular magnetic and peripheral electrical stimulation of the facial nerve together with clinical grading according to the house and brackmann scale were performed in 14 children and adolescents with facial palsy (median age 11.5 yr, range 4.6-16.5 yr). serum and cerebrospinal fluid (csf) were evaluated for antibodies against borrelia burgdorferi and csf cell count, glucose and protein content were screened with methods of routine laboratory testing. data of patients were compared with normal values established in 10 healthy subjects (median age 10.2 yr, range 5.1-15.3 yr). patients with ifnp showed a significant decrease in mep amplitude to canalicular magnetic stimulation compared with healthy controls (p0.03). however, mep amplitude did not discriminate sufficiently between the two groups, because the ranges of dispersion of mep amplitudes overlapped. patients with bfnp had normal mep amplitudes to canalicular magnetic stimulation compared with normal subjects.",diagnostic assessment by tms failed to provide a reliable diagnostic criterion for distinguishing between ifnp and bfnp in children and adolescents.,Diagnosis
is tumor necrosis factor alpha necessary for granulocyte-macrophage-colony-stimulating-factor-induced eosinophil transendothelial migration?,"we have previously shown that granulocyte macrophage-colony stimulating factor (gm-csf) was capable of inducing eosinophil migration across naked filters but not endothelial monolayers. tumor necrosis factor alpha (tnf-alpha) has been shown to be a key factor in granulocyte adhesion and transendothelial migration. we, therefore, pretreated human umbilical vein endothelial cell (huvec) monolayers with tnf-alpha and studied whether tnf-alpha could support gm-csf-induced eosinophil transendothelial migration. we found that tnf-alpha supported gm-csf-induced eosinophil transendothelial migration and that this process was: (1) dependent upon gm-csf and tnf-alpha dose; (2) time-dependent; (3) not due to tnf-alpha having a chemotactic effect itself; (4) not due to tnf-alpha-induced soluble factor production by endothelium, and (5) inhibitable by actinomycin d. we next studied the specificity of this response. neutrophils did not migrate across tnf-alpha-pretreated endothelium in response to gm-csf. tnf-alpha pretreatment of a549 human type-ii-like epithelial lung cells (a549) did not support gm-csf-induced transepithelial migration. neither interleukin (il)-1 nor gm-csf pretreatment of the huvec supported gm-csf-induced transendothelial migration. however, il-5 induced eosinophil migration through naked filters as well as tnf-alpha-pretreated huvec in a manner analogous to gm-csf. antibodies to icam-1, but not vcam-1 significantly inhibited this response. although il-1 did not support gm-csf-induced eosinophil transendothelial migration, il-1 and tnf-alpha induced equivalent expression of icam-1 on huvec.","thus, tnf-alpha-supported eosinophil transendothelial migration in response to gm-csf (and il-5) is dependent upon icam-1, and is both specific and complex.",Medication
do armband activity monitor data correlate with reported pain scores in patients receiving vertebroplasty?,"prior research on the efficacy of vertebroplasty has focused primarily on subjective, patient-reported outcomes. to apply an armband activity monitor (sensewear by bodymedia inc, usa) to patients presenting for consideration for vertebroplasty and to determine the correlation between patient-reported outcomes and quantitative activity metrics at baseline and 30 days after presentation. nineteen patients were enrolled (15 receiving vertebroplasty, 4 not receiving vertebroplasty). patients reported their average pain over the past 24 hours and completed the roland-morris disability questionnaire at baseline and 30 days. patients wore the sensewear armband activity monitor for a median of 4 days at baseline and at the 30-day time period to assess steps, metabolic equivalents expended, sedentary activity time, moderate activity time, sleep efficiency, and total sleep time. pain and disability scores were correlated with activity monitor metrics using linear regression analysis. changes in reported average pain in the past 24 hours and disability scores were not significantly different between vertebroplasty and non-vertebroplasty groups (p0.05). changes in activity monitor data were not significantly different between the vertebroplasty and non-vertebroplasty groups (p0.05). none of the correlations between the reported pain or disability scores and the activity monitor data were significant.",activity monitors can be used to objectively record changes in activity following vertebroplasty procedures. patient-reported pain or disability scores do not correlate with activity monitor-measured activity or sleep metrics.,Symptoms
is oxidative stress an early event in hydrostatic pressure induced retinal ganglion cell damage?,"to determine whether oxidative adduct formation or heme oxygenase-1 (ho-1) expression are altered in retinal ganglion cell (rgc) cultures exposed to elevated hydrostatic pressure and in a mouse model of glaucoma. cultured rgc-5 cells were subjected to 0, 30, 60, or 100 mm hg hydrostatic pressure for 2 hours, and the cells were harvested. parallel experiments examined the recovery from this stress, the effect of direct 4-hydroxy-2-nonenal (hne) treatment, and the effect of pretreatment with resveratrol or quercetin. mice were anesthetized and intraocular pressure was increased to 30, 60, or 100 mm hg for 1 hour; then the retinas were harvested. hne adduct formation and ho-1 expression were assessed by immunocytochemistry and immunoblotting. increases of hne-protein adducts (up to 5-fold) and ho-1 expression (up to 2.5 fold) in pressure-treated rgc-5 cells were dose dependent. during recovery experiments, hne-protein adducts continued to increase for up to 10 hours; in contrast, ho-1 expression decreased immediately. hne, at a concentration as low as 5 mum, led to neurotoxicity in rgc-5 cells. hne adducts and ho-1 expression increased in the mouse retina and optic nerve after acute iop elevation up to 5.5-fold and 2-fold, respectively. antioxidant treatment reduced the oxidative stress level in pressure-treated rgc-5 cells.",this study demonstrates that oxidative stress is an early event in hydrostatic pressure/iop-induced neuronal damage. these findings support the view that oxidative damage contributes early to glaucomatous optic neuropathy.,Medication
does carboxyhemoglobin formation in preterm infants be related to the subsequent development of bronchopulmonary dysplasia?,"to evaluate the usefulness of carboxyhemoglobin (co-hb) levels as a biomarker to predict the development and severity of bronchopulmonary dysplasia (bpd). twenty-five infants born at 33 wk of gestational age or with a birth weight of 1,500 g were enrolled. co-hb levels were measured between postnatal days 5 and 8, 12 and 15, 19 and 22, and 26 and 29. urinary levels of 8-hydroxydeoxyguanosine (8-ohdg), advanced oxidation protein products, and n-(hexanoyl) lysine were measured between postnatal days 5 and 8 and 26 and 29. receiver operating characteristic (roc) analysis was used to compare the biomarkers' predictive values. compared with infants in the no-or-mild bpd group, infants with moderate-to-severe bpd exhibited higher co-hb levels during the early postnatal period and higher 8-ohdg levels between postnatal days 5 and 8. using roc analysis to predict the development of moderate-to-severe bpd, the area under the curve (auc) for co-hb levels between postnatal days 5 and 8 was higher than aucs for the urinary markers.",co-hb levels during the early postnatal period may serve as a practical marker for evaluating oxidative stress and the severity of subsequently developing bpd.,Diagnosis
does hemoglobin a1c predict heart failure hospitalization independent of baseline cardiac function or b-type natriuretic peptide level?,"diabetes is a major risk factor for heart failure (hf). we examined whether baseline hba1c level predicts hf incidence independent of other hf risk factors, including baseline cardiac structural and functional abnormalities. in patients with type 2 diabetes, multivariable cox regression models were constructed to examine the independent association between baseline hba1c and future hf hospitalization. in 608 subjects (mean age, 66.5 years; men, 68; mean hba1c, 9.1 (76 mmol/mol)), 92 were hospitalized for hf during a median follow-up of 6 years. for a 1 (11 mmol/mol) increase in baseline hba1c, the hazard ratio for hf was 1.23 (95 confidence interval, 1.1-1.7, p0.001) with adjustment for age, sex, body mass index, blood pressure and plasma b-type natriuretic peptide (bnp) level. the effect of hba1c on hf was independent of baseline left ventricular (lv) ejection fraction, the ratio of peak early to late diastolic filling velocity, and prevalent/incident coronary heart disease (chd), and was more evident in patients with enlarged lv, decreased systolic function, prevalent chd, or prevalent hf.","in patients with type 2 diabetes, hba1c significantly predicts future hf hospitalization independent of baseline bnp level or echocardiographic parameters.",Prevention
does interference of osteopontin expression inhibit the invasion and metastasis of human hepatocellular carcinoma cell lines ?,"to investigate the effect of osteopontin (opn) on the invasion and metastasis of human hapatocellular carcinoma (hcc). hcc cell lines (hcc-lm3) were transfected with the chemically synthesized small interfering rna (sirna). real-time pcr and western blot were used to quantify the mrna and opn protein levels. the malignant phenotypes including cellular growth, colony formation and invasion capability of the hcc cells were analyzed. the opn mrna and proteins levels were decreased by 75 and 80 in opn sirna treated cells. colony formation and migratory capability were reduced in opn sirna treated cells (p 0.05).",the specific sirna is able to reduce the opn expression at both the mrna and protein levels and significantly inhibits the invasiveness of hcc cells.,Treatment
does oxidation of cellular thiols by hydroxyethyldisulphide inhibit dna double-strand-break rejoining in g6pd deficient mammalian cells?,"we investigated the effect of protein- and non protein-thiol oxidation on dna double-strand-break (dsb) rejoining after irradiation and its relevance in the survival of cho cells. we used mutant cells null for glucose 6 phosphate dehydrogenase (g6pd) activity since reducing equivalents, required for reduction of oxidized thiols, are typically generated through g6pd regulated production of nadph. cellular thiols were oxidized by pre-incubating the cells with hydroxyethyldisulphide (heds), the oxidized form of mercaptoethanol (me). the concentrations of the intracellular and extracellular non-protein thiols (npsh), glutathione, cysteine and mercaptoethanol were quantitated by hplc. protein thiols (psh) were estimated using ellman's reagent. cell survival was determined by clonogenic assay. the induction and rejoining of dsb in cells was quantitated by pulse field gel electrophoresis after exposure to ionizing radiation. much lower bioreduction of heds was found in the g6pd deficient mutants (e89) than in the wild-type cells (k1). a 1 h treatment of e89 cells with heds produced almost complete depletion of non-protein thiol (npsh) and a 26 decrease in protein thiols. only minor changes were found under similar conditions with k1 cells. when exposed to gamma radiation in the presence of heds, the g6pd null mutants exhibited a higher cell killing and decreased rate and extent of rejoining of dsb than were observed in k1 cells. moreover, when the g6pd deficient cells were transfected with the gene encoding wild-type g6pd (a1a), they recovered close to wild-type cellular thiol status, cell survival and dsb rejoining.",these results suggest that a functioning oxidative pentose phosphate pathway is required for dsb rejoining in cells exposed to a mild thiol oxidant.,Treatment
is reported condom use associated with incidence of sexually transmitted diseases in malawi?,"to establish frequency of reported condom use and validate reliability of self-reporting among urban women in malawi. cross-sectional survey in antenatal women in 1989 and 1993. prospective study in cohort first surveyed in 1989. a total of 6561 women in 1989 and 2460 women in 1993 answered questions about condom use and sexual activity, had a physical examination and were screened for hiv. a subset of women from the 1989 screening were administered a questionnaire and tested for syphilis, neisseria gonorrhoeae and trichomonas vaginalis infections every 6 months. although between the two cross-sectional studies intermittent condom use increased from 6 to 15 (p 0.001) with no difference according to hiv infection, consistent use was reported by less than 1. in the prospective study, women reported a higher condom use at any visit than either group assessed cross-sectionally. consistent condom use peaked at 62 in the first 6 months, but declined to as low as 8 in the second year of follow-up. condom use at each visit, either intermittent or consistent, was higher in hiv-seropositive than hiv-seronegative women. overall, the incidence of gonorrhea, trichomoniasis and syphilis did not decline in women reporting consistent condom use.","in prospectively followed women reports of consistent condom use was substantially higher than in cross-sectional surveys, but rapidly decreased over time, irrespective of hiv status. the presence of new sexually transmitted diseases suggests that this population of urban women overreports condom use or underreports sexual activity, or both. intensive and sustained education is needed to achieve consistent condom use. biologic markers of sexual activity are useful in interpreting reported condom use.",Medication
does flagellin induce the expression of thymic stromal lymphopoietin in human keratinocytes via toll-like receptor 5?,"thymic stromal lymphopoietin (tslp), highly expressed by keratinocytes in skin lesions of atopic dermatitis patients and bronchial epithelial cells in asthma, plays a key role in allergic diseases. information on triggers for the release of tslp in keratinocytes is still limited. keratinocytes express toll-like receptor (tlr) 5, the ligand for which is flagellin, the major structural protein of the flagella of gram-negative bacteria. il-4, il-13 and tnf- (th2/tnf) are associated with allergic diseases. tgf-, one of the ligands for the epidermal growth factor receptor, is overexpressed in keratinocytes in atopic dermatitis. we investigated the induction of tslp expression in keratinocytes stimulated with flagellin and its modulation by the th2/tnf cytokines and tgf-. primary human keratinocytes were stimulated with flagellin with or without cytokines. the tslp released was measured by elisa. gene expression was analyzed by quantitative real-time pcr. stimulation of keratinocytes with flagellin induced the release of tslp protein and upregulation of the gene expression of tslp and other pro-inflammatory molecules. the flagellin-induced release of tslp was enhanced by the th2/tnf cytokines or tgf-. small interfering rna-mediated knockdown of tlr5 expression suppressed the flagellin-induced tslp gene expression.","flagellin induces tslp expression in keratinocytes via tlr5 and the expression can be upregulated by a cytokine milieu with th2/tnf or tgf-, suggesting that exposure of barrier-defective skin to gram-negative bacteria or environmental flagellin contributes to the initiation and/or amplification of th2-type skin inflammation including atopic dermatitis through the induction of tslp expression in keratinocytes.",Medication
is prophylactic plasma transfusion before interventional radiology procedures associated with reduced bleeding complications?,"to determine the association between prophylactic plasma transfusion and periprocedural red blood cell (rbc) transfusion rates in patients with elevated international normalized ratio (inr) values undergoing interventional radiology procedures. in this retrospective cohort study, adult patients undergoing interventional radiology procedures with a preprocedural inr available within 30 days of the procedure during a study period of january 1, 2009, to december 31, 2013, were eligible for inclusion. baseline characteristics, coagulation parameters, transfusion requirements, and procedural details were extracted. univariate and multivariable propensity-matched analyses were used to assess the relationships between prophylactic plasma transfusion and the outcomes of interest, with a primary outcome assessed a priori of rbc transfusion occurring during the procedure or within the first 24 hours postprocedurally. a total of 18,204 study participants met inclusion criteria for this study, and 1803 (9.9) had an inr of 1.5 or greater before their procedure. of these 1803 patients, 196 patients (10.9) received prophylactic plasma transfusion with a median time of 1.9 hours (interquartile range iqr, 1.1-3.2 hours) between plasma transfusion initiation and procedure initiation. in multivariable propensity-matched analysis, plasma administration was associated with increased periprocedural rbc transfusions (odds ratio, 2.20; 95 ci, 1.38-3.50; p.001) and postprocedural intensive care unit admission rates (odds ratio, 2.11; 95 ci, 1.41-3.14; p.001) as compared with those who were not transfused preprocedurally. similar relationships were seen at higher inr thresholds for plasma transfusion.","in patients undergoing interventional radiology procedures, preprocedural plasma transfusions given in the setting of elevated inr values were associated with increased periprocedural rbc transfusions. additional research is needed to clarify this potential association between preprocedural plasma transfusion and periprocedural rbc transfusion.",Treatment
is postural change during venous blood collection a major source of bias in clinical chemistry testing?,"to investigate the influence of different phlebotomy postures on clinical chemistry testing. nineteen volunteers were recruited from the laboratory staff. a first set of samples was drawn after 25 min of resting in supine position, a second after 20 min in sitting position, and a third after 20 min in upright position. clinical chemistry testing was performed on roche cobas c501. the plasma volume change (pvc) was -3.4 from supine to sitting, -14.1 from supine to standing and -9.7 from sitting to standing. compared to quality specifications for bias, hemoglobin, hematocrit, albumin and total proteins exhibited meaningful increases from supine to sitting, whereas meaningful increases were observed for hemoglobin, hematocrit, albumin, alkaline phosphatase (alp), amylase, aspartate aminotransferase (ast), total bilirubin, calcium, total and high-density lipoprotein (hdl) cholesterol, gamma-glutamyl transferase (ggt), glucose, lactate dehydrogenase (ldh), magnesium, total protein and triglycerides from sitting to standing. the parameters with meaningful bias from sitting to upright were hemoglobin, hematocrit, albumin, alp, total bilirubin, calcium, total and hdl cholesterol, glucose, ldh and total protein.",these results provide further support to the need of standardizing patient's posture during phlebotomy.,General
do complex receptor-ligand dynamics control the response of the vegf system to protease injury?,"vascular homeostasis and response to injury are dependent on the coordinated activity of growth factors such as vascular endothelial growth factor-a (vegf). vegf signaling is mediated by vegf receptors 1 (vegfr1) and 2 (vegfr2). vegf also binds to extracellular matrix (ecm) and neuropilin (np), a cell surface glycoprotein that enhances vegf binding to vegfr2 while inhibiting vegf-vegfr1 interactions. proteases such as neutrophil elastase release vegf bound to ecm; however, this results in proteolytic processing of vegf to a smaller species termed vegf fragment (vegff). we hypothesized that the generation and presence of vegff would have significant effects on the binding distribution of vegf. we show that vegff, unlike vegf, does not bind ecm, fibronectin, or np-1. using computational simulations, we find that excess vegff can lead to increased binding of vegf to vegfr2 through vegff binding to vegfr1 and subsequent liberation of np-1. we show experimentally that vegf-induced migration has a biphasic response to conversion of vegf to vegff. simulations suggest that a simple change in vegfr1 or vegfr2 complexes are unlikely to be responsible and that a more complex integration of signals is more likely involved.",these findings suggest that proteolytic damage at sites of tissue injury and inflammation has the potential to modulate the vegf system through a complex process and highlight the need for quantitative analysis to reveal mechanisms of growth factor control.,Medication
do patients ' descriptions of visual sensations during pars plana vitrectomy under retrobulbar anesthesia?,"to investigate the visual sensations experienced by patients during vitrectomy under retrobulbar anesthesia. cross-sectional study. fifty-six men and 45 women with a mean age of 62.2 /- 11.9 years (range, 30 to 89 years) were studied. twenty-two eyes had an idiopathic epiretinal membrane, 10 had an idiopathic macular hole, 29 had macular edema (16 resulting from diabetic retinopathy and 13 resulting from retinal vein occlusion), 14 had proliferative diabetic retinopathy, 13 had rhegmatogenous retinal detachment, four had proliferative vitreoretinopathy, and nine had other retinal diseases. the patients were questioned about their visual sensations during and within three hours after vitrectomy, which was performed under retrobulbar anesthesia using 2 lidocaine hydrochloride. visual sensations perceived by the patients during surgery were reviewed. ninety-one of the 101 patients experienced some type of visual sensation during the vitrectomy. ninety-one (90.1) patients reported seeing lights, 73 (72.3) patients reported seeing one or more colors, and 57 (56.4) patients reported seeing movements or moving objects. of these latter 57 patients, 54 saw instruments and nine (8.9) saw the surgeon's fingers or hands. in the 94 cases that had triamcinolone-assisted vitrectomy, 35 (37.2) reported seeing many diffuse whirling black spots. six patients (5.9) found the visual experiences frightening.","visual sensations are experienced by approximately 90 of the patients despite full pain control, and surgeons should warn patients of these possibilities because they can be frightening. this should minimize patients' anxiety and stress during the surgery.",Medication
does preservation solution impact physiologic function and cellular viability of human saphenous vein graft?,"recent clinical data suggest intraoperative preservation of human saphenous vein (hsv) in normal saline is associated with vein graft failure. we evaluated the influence of several preservation media on acute physiologic function and cellular viability of hsv conduit. unprepared (up) hsv obtained from coronary artery bypass graft patients was characterized on a muscle bath after 2-hour storage in 6 solutions: plasma-lyte a, 0.9 nacl (normal saline), university of wisconsin solution, celsior solution, autologous whole blood, or glutathione-ascorbic acid l-arginine (gala) solution. vascular smooth muscle contractility was assessed after exposure to depolarizing kcl and phenylephrine. the relaxation of phenylephrine-precontracted hsv to sodium nitroprusside and carbachol (endothelial-independent and -dependent relaxation, respectively) was also assessed. cellular viability was determined via the methyl thiazolyl tetrazolium (mtt) assay. rat aortae were used to assess the effect of ph during graft preservation on endothelial-dependent relaxation. preservation of hsv in normal saline and autologous whole blood impaired contractile responses to kcl relative to up tissues, whereas preservation in university of wisconsin solution and celsior solution enhanced contractile responses (p .05). relative to up tissues, responses to phenylephrine were decreased with preservation in normal saline, whereas preservation in university of wisconsin solution, celsior solution, and gala all potentiated these responses (p .05). only preservation in normal saline impaired endothelial-independent relaxation (p .005). preservation in plasma-lyte a (p .02), normal saline (p .002), and university of wisconsin solution (p .02) impaired endothelial-dependent relaxation. normal saline preservation decreased mtt viability index relative to up tissues (0.02 0.002 mg(-1)0.5 ml(-1) vs 0.033 0.005 mg(-1)0.5 ml(-1); p .03). endothelial function was impaired by acidic ph in rat aorta.",preservation of hsv in normal saline causes graft injury leading to impaired physiologic function and decreased viability of the hsv. this harm is mitigated by the use of buffered salt solutions as preservation media.,General
is maternal oct-4 a potential key regulator of the developmental competence of mouse oocytes?,"the maternal contribution of transcripts and proteins supplied to the zygote is crucial for the progression from a gametic to an embryonic control of preimplantation development. here we compared the transcriptional profiles of two types of mouse mii oocytes, one which is developmentally competent (miisn oocyte), the other that ceases development at the 2-cell stage (miinsn oocyte), with the aim of identifying genes and gene expression networks whose misregulated expression would contribute to a reduced developmental competence. we report that: 1) the transcription factor oct-4 is absent in miinsn oocytes, accounting for 2) the down-regulation of stella, a maternal-effect factor required for the oocyte-to-embryo transition and of which oct-4 is a positive regulator; 3) eighteen oct-4-regulated genes are up-regulated in miinsn oocytes and are part of gene expression networks implicated in the activation of adverse biochemical pathways such as oxidative phosphorylation, mitochondrial dysfunction and apoptosis.",the down-regulation of oct-4 plays a crucial function in a sequence of molecular processes that leads to the developmental arrest of miinsn oocytes. the use of a model study in which the mii oocyte ceases development consistently at the 2-cell stage has allowed to attribute a role to the maternal oct-4 that has never been described before. oct-4 emerges as a key regulator of the molecular events that govern the establishment of the developmental competence of mouse oocytes.,Symptoms
is blood pressure variability more important than blood pressure level in determination of end-organ damage in rats?,"this study was designed to determine how important a novel risk factor of elevated blood pressure variability (bpv) is in the determination of end-organ damage by comparison with the classic risk factor of a high blood pressure (bp) level. the effects of haemodynamics on cardiovascular morphology were evaluated by univariate and multivariate regression analysis in two different rat models with an enlarged distribution of haemodynamics. in male sham-operated and sinoaortic-denervated wistar-kyoto rats and spontaneously hypertensive rats (n 34), bpv was more important than bp in cardiac and renal damage and aortic hypertrophy. bpv and bp had independent effects, explaining 59.4 of the variation in damage to these organs. in male (n 44) and female (n 46) f1 hybrids of sprague-dawley rats and spontaneously hypertensive rats, the greater importance of bpv than bp was further demonstrated in left ventricular hypertrophy, glomerular damage and aortic hypertrophy. the phenomenon was more evident in females than males for cardiovascular hypertrophy. bpv and bp or bpv alone had independent effects, explaining 46.9 (male) or 37.5 (female) of the variation in damage to these organs.","bpv is a more critical determinant than bp level for cardiac damage, renal lesions and aortic hypertrophy in rats, strongly suggesting the significance of bpv control for the protection of these organs.",Prevention
is metabolic syndrome associated with faster degeneration of bioprosthetic valves?,"several studies have reported similarities between calcification of the native aortic valve and atherosclerosis. recent studies also suggested that hypercholesterolemia may be a risk factor for calcific degeneration of bioprosthetic valves. the metabolic syndrome (ms) is associated with a higher risk of vascular atherosclerosis. we thus hypothesized that the atherogenic features of ms could accelerate bioprosthetic valve degeneration. we included 217 patients who underwent aortic valve replacement with a bioprosthetic valve in the study. of these patients, 71 patients (33) had ms defined according to the modified criteria proposed by the national cholesterol education program adult treatment panel iii. the annualized increase in mean transprosthetic gradient and the worsening of transprosthetic regurgitation measured by doppler echocardiography were used to assess the deterioration of valve hemodynamic function. patients with ms had higher progression of gradient (4/-5 mm hg/year versus 2/-2 mm hg/year, p or 1/3 degree worsening of regurgitation (25 versus 12, p0.02), and higher proportion of valve function deterioration defined as regurgitation worsening and/or or 3 mm hg/year increase in gradient (41 versus 25, p0.02) when compared with patients without ms. on multivariate analysis, ms was an independent predictor of gradient progression (p0.01), regurgitation worsening (p0.02), and valve function deterioration (p0.02). the other independent predictors were diabetes, renal insufficiency, and higher mean gradient at baseline.",this is the first study to report that the ms is independently associated with faster bioprosthetic valve degeneration. this study could pave the way for the development of a new medical therapy able to significantly reduce the structural valve deterioration of bioprostheses.,Prevention
does traf3ip2 mediate atherosclerotic plaque development and vulnerability in apoe ( -/- ) mice?,"atherosclerosis is a major cause of heart attack and stroke. inflammation plays a critical role in the development of atherosclerosis. since the cytoplasmic adaptor molecule traf3ip2 (traf3-interacting protein 2) plays a causal role in various autoimmune and inflammatory diseases, we hypothesized that traf3ip2 mediates atherosclerotic plaque development. traf3ip2/apoe double knockout (dko) mice were generated by crossing traf3ip2(-/-) and apoe(-/-) mice. apoe(-/-) mice served as controls. both dko and control mice were fed a high-fat diet for 12 weeks. plasma lipids were measured by elisa, atherosclerosis by en face analysis of aorta and plaque cross-section measurements at the aortic valve region, plaque necrotic core area, collagen and smooth muscle cell (smc) content by histomorphometry, and aortic gene expression by rt-qpcr. the plasma lipoprotein profile was not altered by traf3ip2 gene deletion in apoe(-/-) mice. while total aortic plaque area was decreased in dko female, but not male mice, the plaque necrotic area was significantly decreased in dko mice of both genders. plaque collagen and smc contents were increased significantly in both female and male dko mice compared to respective controls. aortic expression of proinflammatory cytokine (tumor necrosis factor , tnf), chemokine (chemokine (c-x-c motif) ligand 1, cxcl1) and adhesion molecule (vascular cell adhesion molecule 1, vcam1; and intercellular adhesion molecule 1, icam1) gene expression were decreased in both male and female dko mice. in addition, the male dko mice expressed markedly reduced levels of extracellular matrix (ecm)-related genes, including timp1 (tissue inhibitor of metalloproteinase 1), reck (reversion-inducing-cysteine-rich protein with kazal motifs) and adam17 (a disintegrin and metalloproteinase 17).","traf3ip2 plays a causal role in atherosclerotic plaque development and vulnerability, possibly by inducing the expression of multiple proinflammatory mediators. traf3ip2 could be a potential therapeutic target in atherosclerotic vascular diseases.",Medication
do morphine-tolerant mice exhibit a profound and persistent cardioprotective phenotype?,"morphine and other opioids continue to be used as the major treatment for acute pain both before and after surgery. in this regard, much research has focused on the mechanisms of morphine tolerance and dependence in the central nervous system; however, few studies have examined the effect of morphine on peripheral organs, such as the heart, in morphine-tolerant animals. here, we examine the effect of tolerance to the analgesic effect of morphine on ischemic tolerance in mice after prolonged morphine exposure and withdrawal. male c57/bl6 mice were implanted subcutaneously with either placebo or morphine pellets (25 or 75 mg). after prolonged exposure to and/or withdrawal from morphine or placebo, the hearts were excised and subjected to 25 minutes of ischemia and 45 minutes of reperfusion. morphine-tolerant mice exhibited a markedly improved functional recovery compared with placebo and mice subjected to acute morphine. lactate dehydrogenase release was also significantly reduced. the protection observed was equieffective 48 hours after withdrawal of pellet, whereas the onset of protection preceded analgesic tolerance.",these data demonstrate that chronic exposure to morphine unexpectedly results in a profound and persistent cardioprotective phenotype.,Medication
does lr-90 a new advanced glycation endproduct inhibitor prevent progression of diabetic nephropathy in streptozotocin-diabetic rats?,"advanced glycation and lipoxidation endproducts have been implicated in the pathogenesis of diabetic complications, including diabetic nephropathy. lr-90, a new advanced glycation endproduct inhibitor, was investigated for its effects on the development of renal disease in diabetic rats. diabetic animals were randomly allocated into groups receiving lr-90 or vehicle (untreated). age- and weight-matched non-diabetic rats were studied concurrently. body weight, plasma glucose, glycated haemoglobin, urinary albumin and creatine excretions were measured serially. kidney histopathology, age accumulation in cells and tissues, protein oxidation, were also examined. in vitro assays were used to assess the possible mechanism of action of lr-90. lr-90 inhibited the increase in albumin and creatinine concentrations, and concentrations of circulating age in diabetic rats without any effect on glycaemic control. lr-90 treated-rats also showed higher body weights than untreated diabetic rats. lr-90 prevented glomerulosclerosis, tubular degeneration and collagen deposition in the kidney. age-induced cross-linking and fluorescence of tail collagen were reduced by lr-90 treatment. lr-90 also decreased age accumulation in kidney glomeruli and nitrotyrosine deposition in the renal cortex. in vitro, lr-90 was capable of reacting with reactive carbonyl compounds and was a more potent metal chelator than pyridoxamine and aminoguanidine.","lr-90 reduces in vivo age accumulation, age-protein cross-linking and protein oxidation, and could be beneficial in preventing the progression of diabetic nephropathy. the age inhibitory and therapeutic effects of lr-90 could be attributed, at least in part, to its ability to react with reactive carbonyl species and/or potent metal chelating activity that inhibits glycoxidative-age formation.",Prevention
is epilepsy a mandatory feature of stxbp1 associated ataxia-tremor-retardation syndrome?,"mutations in the stxbp1 gene (munc18-1) were first described to cause ohtahara syndrome (early infantile epileptic encephalopathy, eiee)(12-14) characterized by very early infantile epileptic encephalopathy with frequent tonic spasms and a suppression-burst pattern on electroencephalogram. in the following years a wider phenotype was recognized having milder forms of epilepsies. all patients showed also intellectual disability and movement disorders. here, we present three female patients with an ataxia-tremor-retardation syndrome caused by a de novo stxbp1 mutation. two of the girls were diagnosed through next-generation-sequencing as mutations in stxbp1 were not suspected. the third patient was diagnosed by targeted genetic testing due to its clinical features strikingly similar to the first two girls. the characteristic feature of our three patients is the lack of epilepsy which is in contrast to the majority of the patients with stxbp1 mutation.","hence, epilepsy is not a mandatory feature of patients with a stxbp1 mutation.",Diagnosis
is preoperative fibrinogen plasma concentration associated with perioperative bleeding and transfusion requirements in scoliosis surgery?,"prospective observational study. to investigate the potential association between fibrinogen, bleeding, and transfusion requirements after scoliosis surgery. bleeding complications during and after orthopedic surgery are associated with increased morbidity and mortality. early identification of patients with increased risk of excessive bleeding offers the possibility to initiate countermeasures. fibrinogen is a key protein in the coagulation cascade, and thus a potential biomarker for bleeding risk. a total of 82 otherwise healthy patients (mean age: 15 3 years, 85 girls) undergoing surgery for adolescent idiopathic scoliosis were included in the study. patient variables (age, gender, operation time, and thrombosis prophylaxis), preoperative laboratory variables (hemoglobin, platelet count, activated partial thromboplastin time aptt, prothrombin time pt, and fibrinogen), peroperative and postoperative bleeding volume, and transfusions were registered. correlations between laboratory variables and bleeding volume were calculated with pearson test. patient variables and laboratory variables were compared with student t test between patients with bleeding volume in the upper quartile (""bleeders"") and the remaining patients, and between patients with extensive transfusion (defined as 2 u of packed red cells) and no or limited transfusions ( 2 u). mean fibrinogen concentration was 3.0 0.7 g/l (range, 1.3- 4.9). mean total perioperative bleeding volume was 1552 1019 ml (range, 100-5800 ml). total bleeding volume correlated significantly with preoperative fibrinogen concentration (r -0.31, p 0.005) but neither with platelet count, aptt, nor pt (p 0.61, 0.46, and 0.57, respectively). bleeders had significantly lower preoperative fibrinogen plasma concentration (2.6 0.6 vs. 3.1 0.6 g/l, p 0.002). of total, 16 (13/82) of the patients were transfused with 2 u of packed red cells. patients with extensive transfusions had significantly lower preoperative fibrinogen plasma concentration (2.5 0.7 vs. 3.1 0.6 g/l, p 0.002), while preoperative platelet count, aptt, and pt did not differ.",the results indicate that preoperative fibrinogen concentration is a limiting factor for postoperative hemostasis during and after scoliosis surgery. preoperative measurement of fibrinogen concentration provides more information about bleeding volume and transfusion requirements than standard screening tests.,Treatment
is tonsillar colonization unlikely to play important role in helicobacter pylori infection in children?,"to determine (i) seroprevalence of helicobacter pylori (hp) infection in children undergoing tonsillectomy, (ii) possible hp colonization on tonsils of children and its importance in hp transmission, and (iii) if four examined socio-economic factors are the risk factors for hp transmission and hp colonization on tonsils in children. rapid urease test (rut) of tonsils, and serologic blood tests for hp were performed in 77 children (aged 4-14 years) in bosnia and herzegovina (b-h), undergoing tonsillectomy. rut positive tonsils were cultured for hp. rut positive children were tested using (13)carbon-urea breath test ((13)c-ubt). information about socio-economic potential risk factors was obtained from the parents. out of 139 pharyngeal and palatine tonsils, 17 palatine tonsils in 14 children were rut positive and had negative hp culture. eight children had positive both rut and (13)c-ubt. there was no significant difference between children with hypertrophy and those with recurrent tonsillitis comparing their serologic tests results. there was no significant difference between seronegative (n61) and seropositive (n16) children comparing their age, sex, parental education level, owning a family courtyard, attending a children's collective, and owning a pet cat.",the results in this prospective study do not support the notion that tonsils are an important reservoir for hp transmission in children in b-h. the examined socio-economic factors did not enhance hp seropositivity rate in children.,Prevention
does rg1 prevent myocardial hypoxia/reoxygenation injury by regulating mitochondrial dynamics imbalance via modulation of glutamate dehydrogenase and mitofusin 2?,"mitochondrial dysfunction is a prominent feature of ischemia heart disease but the underlying mechanism of dynamics (fusion/fission) is still unclear. here we investigated a novel function and underlying mechanism of rg1 on an in vitro cardiomyocyte model of hypoxia/reoxygenation (h/r). cellular cytotoxicity was evaluated by mtt, mitochondrial viable staining, and cardiac marker detection. mitochondrial function was evaluated by atp content measurement, mmp determination, ros, ocr and ecar assay. mitochondrial dynamics was investigated by live-cell imaging with time-lapse fluorescence microscopy and morphological features were evaluated by the high-content image analysis. mitochondrial fusion and fission-related proteins, gdh were determined by western blot, rt-pcr and immunofluorescence. rg1 moderated gdh dysregulation and then protected against h/r-induced cellular damage and mitochondrial dysfunction in a dose-dependent manner. rg1 significantly increased mitochondrial length, reduced the number of cells with fragmented mitochondria and up-regulated the mfn2 expression finally leading to preventing the imbalance of mitochondrial dynamics following h/r. knock-down of mfn2 by specific sirna completely abolished the ability of rg1 to cell survival by h/r.",rg1 through modulation of gdh and mfn2 maintained mitochondrial dynamics that resulted in protection against h/r-induced cardiomyocyte injury. all these results put forward a new protective mechanism of rg1 on the therapeutic potential in cardiac i/r disorders.,Prevention
do clinical and histological results of septoplasty with a resorbable implant?,"the use of a resorbable implant connected with septal cartilage would facilitate external septoplasty, offering mechanical stability until the cartilage fragments heal. to study the histological and clinical results of septoplasty with a resorbable implant (polydioxanone pds; ethicon, norderstedt, germany) in conjunction with cartilage. to provide histological information in 5 rabbits, pds foil was implanted into the outer ear in conjunction with an artificial cartilage defect. observations were made at 2, 5, 10, 15, and 25 weeks. resorption of the implant was investigated, including the time to complete elimination. in addition, septoplasty with pds foil was performed on 71 patients with severe septal deformities. surgery consisted of excision of the quadrilateral cartilage and division into straight fragments, which were sutured to the pds foil and replaced as a free graft. ear, nose, and throat department of the general district hospital steyr, steyr, austria. histological examination showed that the foil remained unchanged for at least 10 weeks and was completely resorbed after 25 weeks with minimal remaining scar tissue. newly formed cartilage developed bordering the cartilage defect. in the clinical study, all patients experienced varying degrees of improvement in nasal blockage. no immediate or long-term complications occurred.","the use of pds foil in connection with cartilage facilitates surgical correction of severe septal deformities, additionally providing support for the nasal dorsum. the histological examination showed that no inflammatory or foreign body reaction occurred. cartilage regeneration was even found. the foil was completely resorbed within 25 weeks, avoiding the long-term complications that occur with other artificial implants.",Treatment
does tamoxifen induce apoptosis in fas tumor cells by upregulating the expression of fas ligand?,"tamoxifen (tam), a nonsteroidal anticancer agent, is used in the treatment of breast cancer. in the current study, we investigated whether tam induces apoptosis in tumor cells by altering the expression of fas and fas ligand (fasl). several tumor cell lines were used to test the ability of tam to induce apoptosis, which was studied using the tunel assay. the effect of tam on the expression of fas and fasl was analyzed using a flow cytometer. tam was found to suppress the growth of an estrogen receptor-positive human mammary tumor cell line (t-47d) by inducing apoptosis. interestingly, tam also induced apoptosis in an estrogen receptor-negative murine t cell lymphoma cell line, el-4. the ability of tam to induce apoptosis in t-47d and el-4 tumor cells correlated with the increased expression of fasl but not fas on the tumor cells. similar to tam, a metalloproteinase (mp) inhibitor, which is known to increase the expression of membrane-bound fasl, was found to induce apoptosis in both t-47d and el-4 tumor cells by increasing the expression of fasl but not fas. furthermore, both tam and the mp inhibitor failed to induce apoptosis in l1210 tumor cell lines that failed to express fasl.",the current study demonstrates that tam can induce apoptosis in fas() tumor cells by upregulating fasl.,Medication
does histone deacetylase inhibit the growth and migration of human osteosarcoma cells ?,"to explore the effects of histone deacetylase inhibitors (hdacis) on human osteosarcoma in vitro and in vivo. hdaci suberoylanilide hydroxamic acid (saha) and sodium butyrate (sb) were employed to examine the effects on human osteosarcoma in vitro and in vivo. the in vitro effects of hdaci saha and sb were evaluated in saos2 and u2os human osteosarcoma cell lines. cell growth, cell cycle progression and histone acetylation were examined by methyl tolyl sulfide (mts), flow cytometry and western blot respectively.in addition, saha or sb was administered for 4 weeks in a murine xenograph model for assessing the in vitro effects. mts assay revealed that saha and sb significantly suppressed the growth of saos2 and u2os cells in a concentration-dependent manner.western blot analysis indicated that the levels of acetylated h3 increased after hdaci treatment.flow cytometry showed that saha arrested the cell cycle in g1 and g2/m phase, while sb arrested the cell cycle in g2/m phase. the tumor growth of murine xenograph model with saos2 was inhibited by saha and sb compared with vehicle control.","hdaci saha and sb significantly inhibit the growth of human osteosarcoma cells and induce cell cycle arrest. meanwhile, the tumor inhibitory effects were also validated in a murine xenograft model.",Medication
is red cell distribution width associated with cardiovascular risk and disease parameters in rheumatoid arthritis?,"since red cell distribution width (rdw) has been associated with cardiovascular (cv) disease and inflammation in several conditions, the main aim of this study was to evaluate its prognostic value in ra patients and its potential associations with clinical features. the history of cv events was retrospectively reviewed in 160 ra patients and rdw was recorded at disease onset and 6 and 12 months after diagnosis to calculate the accumulated value area under the curve (auc) rdw and change during the first year (rdw). in addition, rdw was analysed in 110 patients with established disease in relation to clinical features. increased rdw at diagnosis and auc rdw were able to predict the occurrence of cv events in ra patients hazard ratio (hr) 1.247 (95 ci 1.079, 1.441), p 0.003 and hr 1.038 (95 ci 1.018, 1.059), p 0.0001, respectively after adjusting by potential confounding factors. receiver operating characteristic curve analyses revealed a better power of discrimination for the auc rdw (p 3.394 10(-5)). in addition, an increase in rdw during the first year was associated with poor cv outcome (p 0.010). on the other hand, rdw in patients with established ra was significantly associated with disease activity, acute phase reactants and severity.","rdw at disease onset may be used as an early marker of cv risk in ra, whereas in patients with established disease it was related to the activity of the disease. these findings suggest that rdw can be considered as a surrogate marker of inflammation and, consequently, cv risk in ra patients.",Diagnosis
do an update on complex regional pain syndromes in children and adolescents?,"complex regional pain syndrome (crps) is a chronic pain condition typically involving a limb, which is characterized by neuropathic pain, sensory abnormalities and neurovascular findings. the exact cause of crps is unknown; however, proposed theories include alterations in the sympathetic and central nervous system (cns), small fibre changes in the peripheral nervous system and psychological factors. although this condition was previously considered rare among children and adolescents, it has been increasingly recognized in paediatric patients and can result in significant disability. the diagnosis of paediatric crps is based upon clinical criteria obtained from a thorough history and physical examination. other possible causes, such as orthopaedic, infectious, vascular and rheumatologic disorders, should be ruled out prior to making the diagnosis. treatment focuses on a rehabilitative strategy consisting of physical therapy, occupational therapy and cognitive-behavioural therapy with an overall focus on return to functioning.","crps in children and adolescents is characterized by a painful, mottled appearing, swollen limb with allodynia and hyperalgesia. for most patients, pain is severe, resulting in significant functional disability. more recent evidence suggests that a rehabilitative programme results in improvement in both pain and functional measures.",Symptoms
does pramipexole at a low dose induce beneficial effect in the harmaline-induced model of essential tremor in rats?,"the aim of the study was to examine the effects of preferential agonists of dopamine d3 receptors: pramipexole and 7-oh-dpat on the harmaline-induced tremor in rats (a model of essential tremor, et). to study receptor mechanisms of these drugs, rats were pretreated with dopamine d3 receptor antagonists--sb-277011-a and sr-21502, an antagonist of presynaptic d2/d3 receptors--amisulpride, or a nonselective antagonist of d2-like receptors, haloperidol, at a postsynaptic dose. for tremor measurement, fully automated force plate actimeters were used and data were analyzed using fast fourier transform. harmaline (15 mg/kg ip)-triggered tremor was manifested by an increase in the power within 9-15 hz band (ap2). pramipexole administered at a low (0.1 mg/kg sc), but not higher doses (0.3 and 1 mg/kg sc), and 7-oh-dpat (0.1, 0.3, and 1 mg/kg sc) reversed the harmaline-increased ap2. none of the examined dopamine antagonists: sb-277011-a (10 mg/kg ip), sr-21502 (15 mg/kg ip), haloperidol (0.5 mg/kg ip), or amisulpride (1 mg/kg ip) influenced the above effect of dopamine agonists.","the present study indicates that pramipexole reduces the harmaline-induced tremor, which may suggest its beneficial effects in et patients. however, mechanisms underlying its action are still unclear and need further examination.",Medication
do local anesthetics modulate neuronal calcium signaling through multiple sites of action?,"local anesthetics (las) are known to inhibit voltage-dependent na channels, as well as k and ca2 channels, but with lower potency. since cellular excitability and responsiveness are largely determined by intracellular ca2 availability, sites along the ca2 signaling pathways may be targets of las. this study was aimed to investigate the la effects on depolarization and receptor-mediated intracellular ca2 changes and to examine the role of na and k channels in such functional responses. effects of bupivacaine, ropivacaine, mepivacaine, and lidocaine (0.1-2.3 mm) on evoked ca2(i) transients were investigated in neuronal sh-sy5y cell suspensions using fura-2 as the intracellular ca2 indicator. potassium chloride (kcl, 100 mm) and carbachol (1 mm) were individually or sequentially applied to evoke increases in intracellular ca2. coapplication of la and na/k channel blockers was used to evaluate the role of na and k channels in the la effect on the evoked ca2(i) transients. all four las concentration-dependently inhibited both kcl- and carbachol-evoked ca2(i) transients with the potency order bupivacaine ropivacaine lidocaine / mepivacaine. the carbachol-evoked ca2(i) transients were more sensitive to las without than with a kcl prestimulation, whereas the la-effect on the kcl-evoked ca2(i) transients was not uniformly affected by a carbachol prestimulation. na channel blockade did not alter the evoked ca2(i) transients with or without a la. in the absence of la, k channel blockade increased the kcl-, but decreased the carbachol-evoked ca2(i) transients. a coapplication of la and k channel blocker resulted in larger inhibition of both kcl- and carbachol-evoked ca2(i) transients than by la alone.","different and overlapping sites of action of las are involved in inhibiting the kcl- and carbachol-evoked ca2(i) transients, including voltage-dependent ca2 channels, a site associated with the caffeine-sensitive ca2 store and a possible site associated with the ip(3)-sensitive ca2 store, and a site in the muscarinic pathway. k channels, but not na channels, seem to modulate the evoked ca2(i) transients, as well as the la-effects on such responses.",Medication
is previous immunosuppressive therapy a risk factor for immune reconstitution inflammatory syndrome in whipple 's disease?,"whipple's disease is a rare chronic infection caused by tropheryma whipplei. although most patients respond to antibiotics, in some of them the start of the treatment is followed by recurrence of inflammation. since polymerase chain reaction is negative for tropheryma whipplei, this reinflammation cannot be a relapse of whipple's disease itself. very recently, it has been recognised as a complication of whipple's disease and defined immune reconstitution inflammatory syndrome (iris). our aim is to study the prevalence and the clinical features of iris in italian patients with whipple's disease. evidence of iris was retrospectively revaluated in the clinical notes of 22 patients with whipple's disease. patients with no evidence of iris served as controls for the clinical findings. recurrence of arthralgia and/or fever allowed a diagnosis of iris in 5/22 patients. one patient died. previous immunosuppressive therapy was found in all patients with iris but only in 7/17 controls (fisher test, p0.039). age at diagnosis and diagnostic delay were higher in patients with iris compared to controls. however, statistical significance was not reached.",iris is a frequent complication of whipple's disease and it can be fatal. the risk of iris is greatly increased in patients previously treated with immunosuppressive therapy.,Treatment
does electroporation-mediated transfer of plasmid dna encoding il-10 attenuate orthotopic tracheal allograft stenosis in rats?,"electroporation has been shown to increase the efficacy of intramuscular injection of plasmid dna, resulting in a higher level of foreign gene expression. using this technique, we examined the effect of viral il-10 gene transfer on the prevention of tracheal allograft stenosis in an animal model. on the day of tracheal transplantation, recipient lewis rats were intramuscularly injected with either plasmid pcaggs-lacz or plasmid pcaggs-viral il-10, followed immediately by electroporation. tracheas from brown norway donors were transplanted into the backs of lewis recipients, and the histology of the grafts were assessed 2 and 4 weeks after transplantation. the serum level of il-10 peaked at 2000 pg/ml one day after injection; the level then slowly decreased, but was maintained above 1000 pg/ml until 8 days after injection. at day 28, the airway lumina of the tracheal allografts were almost completely obliterated by fibroproliferative tissue in the control pcaggs-lacz-treated rats. in rats injected once with pcaggs-viral il-10, luminal obliteration was significantly decreased compared with the control pcaggs-lacz-treated rats (mean luminal opening 46.8 vs 0 p0.05). the loss of epithelial cells lining the airway was also decreased in the il-10-treated group (mean epithelial coverage 42 vs 5 p0.05). multiple injections with pcaggs-viral il-10 did not further improve the histological changes.",il-10 gene transfer by intramuscular injection using electroporation attenuated tracheal allograft stenosis associated with mild epithelial injury.,Medication
is stromal cell-derived factor-1-3 ' a polymorphism associated with decreased risk of myocardial infarction and early endothelial disturbance?,"genome-wide association studies have identified single-nucleotide polymorphisms at the 10q11 locus as risk factors for myocardial infarction (mi). this locus lies upstream (80 kb) of the stromal cell-derived factor-1 (sdf1) gene that codify for a chemokine with protective atherogenetic effects and with a major role in the mobilization, homing, and differentiation of endothelial progenitor cells (epcs). the purpose of this study was to investigate the possible association of sdf1-3'a polymorphism, that upregulates sdf1 protein expression, with mi and early endothelial dysfunction and atherosclerosis in young healthy subjects. 200 patients (181 men age 57.3 7.7 years) and 230 healthy controls (96 men, age 52 11.9 years) were recruited to investigate the association between mi and sdf1-3'a polymorphism. the relationship between sdf1-3'a polymorphism and brachial artery flow-mediated dilation and the number of circulating epcs was examined in 50 healthy young adults. a significant difference in sdf1-3'a genotype distribution was observed between patients and controls (p 0.006). patients carrying the a allele had a significantly reduced mi risk compared with subjects with gg genotype (odds ratio 0.5, 95 ci 0.3-0.9, p 0.001). sdf1-3'a polymorphism presented a significant interaction with other cardiovascular risk factors (pinteraction 0. 0001). controls carrying the a allele showed significantly higher flow-mediated dilation (13.9 4.9 vs 10.8 4.3, p 0.03) and significantly higher values of epcs (0.029 0.009 vs 0.022 0.008, p 0.02) compared with gg homozygotes.","sdf1-3'a polymorphism is associated with a decreased risk of mi and early endothelial dysfunction, strongly confirming the important atherogenic role of sdf1 gene at clinical level.",Prevention
do apoptosis levels increase after castration in the cwr22 human prostate cancer xenograft?,"the role of apoptosis in the regression of human prostate cancer after androgen deprivation therapy remains controversial. detection of caspase-3, an ubiquitous effector of apoptosis, is a highly specific technique for in vivo evaluation of apoptosis. apoptotic rates were evaluated in the androgen-dependent cwr22 human prostate cancer xenograft in tumors that represented time points throughout the progression from androgen-stimulated to recurrent prostate cancer. caspase-3 levels in formalin-fixed, paraffin-embedded specimens were quantified using immunohistochemical detection and video image analysis. western blot analysis was used to confirm the results of immunodetection. expression of caspase-3 reached a maximum on day 2 after castration, decreased on day 6, and remained low until tumor recurrence. the percentage of tumor area expressing caspase-3 increased from 2.51 /- 0.44 in tumors from intact mice to 20.84 /- 1.75 on day 2 after castration. among immunopositive cells, the intensity of caspase-3 expression measured using the mean optical density (mod) increased 45 (0.3762 /- 0.003 to 0.5461 /- 0.001) on day 2 after castration compared to levels detected in tumors from intact mice.",apoptosis contributes to tumor regression after castration in the cwr22 human prostate cancer xenograft model.,Treatment
does adenovirus-mediated sirna targeting c-met inhibit proliferation and invasion of small-cell lung cancer ( sclc ) cells?,"the hepatocyte growth factor receptor c-met and its ligand hepatocyte growth factor (hgf) have been reported to be involved in cellular motility, growth, and invasion by activating mitogenic signaling pathways. the overexpression of c-met gene has been found in many malignant cancers, but the roles of c-met overexpression in sclc tumors still remain unclear. the aim of the present study was to explore its roles and potential as a therapeutic target for sclc. quantitative real-time rt-pcr and immunohistochemistry assays were performed to detect the expression of c-met mrna and protein in sclc tissue or corresponding non-tumor lung tissue samples. adenovirus-mediated small interfering rna (sirna) was employed to down-regulate the expression of c-met gene in sclc cell line (nci-h446). mtt and colony formation assays were performed to detect in vitro proliferation of nci-h446 cells. in vitro wound-healing and transwell invasion assays were performed to detect in vitro invasion and metastasis of nci-h446 cells. finally, in vivo tumorigenicity and metastasis assays were done to analyze in vivo proliferation and metastasis of nci-h446 cells in a xenograft model. we showed that the levels of c-met mrna expression were significantly higher in sclc tissue samples (0.970.08) than those in corresponding non-tumor lung tissue samples (0.210.02; p0.05). additionally, the immunostaining of c-met protein in sclc tissues was stronger than that in corresponding non-tumor tissues. adenovirus-mediated sirna targeting c-met could significantly down-regulate c-met expression, and the specific down-regulation of c-met expression in sclc cells could strongly inhibit proliferation of sclc cells both in vitro and in vivo. moreover, c-met down-regulation could also reduce invasion capacity in vitro and metastasis capacity in vivo of sclc cells.","taken together, our results indicated that the overexpression of c-met gene played an important role in the progression and development of sclc, and adenovirus-mediated sirna targeting c-met could potentially be an experimental approach for sclc gene therapy.",Medication
does suppression of aurora-a-flj10540 signaling axis prohibit the malignant state of head and neck cancer?,"head and neck cancer (hnc) is a highly invasive cancer. aurora-a has been reported for a number of malignancies. however, the identity of downstream effectors responsible for its aggressive phenotype in hnc remains underinvestigated. the mrna and protein expression levels of aurora-a and flj10540 were assessed in hnc specimens and cell lines using rt-qpcr, western blot, oncomine, and microarray database analysis. the downstream molecular mechanisms of aurora-a were confirmed by rt-qpcr, western blot, luciferase reporter, confocal microscopy analyses, immunoprecipitation, colony formation, cell viability, and xenograft model. cellular functions in response to aurora-a-modulated downstream targets such as flj10540 and mmps were examined in vitro and in vivo, including cell growth, motility and chemosensitivity. aurora-a/flj10540/mmps expression was determined in cancer and adjacent normal tissues from hnc patients by immunohistochemistry approach. in the current study, aurora-a exhibited similar gene expression profiles with flj10540 by using accessibly public microarray and oncomine database analysis, raising the possibility that these molecules might coordinately participate in cancer progression and metastasis of hnc. these two molecules connection were also examined in cell lines and tissues of hnc. aurora-a overexpression could not only bind to the promoter of flj10540 to induce flj10540 expression, but also increase both mrna and protein levels of mmp-7 and mmp-10 in hnc cells. conversely, depletion of aurora-a expression by using sirna or aurora-a kinase inhibitor, mln8237, suppressed flj10540, mmp-7 and mmp-10 mrna and protein expressions in vitro and in vivo. in addition, the flj10540-pi3k complex was destroyed by inhibition the aurora-a kinase activity. forced overexpression of flj10540 in aurora-a-depleted or in mln8237-treated hnc cells attenuated the effect on cytotoxicity to cisplatin. elevated aurora-a expression in hnc cells led to the characteristics of more aggressive malignancy, including enhanced chemoresistance and increased the abilities of proliferation, migration and invasion, which was required for flj10540/mmp-7 or flj10540/mmp-10 expressions. finally, immunohistochemical analysis of human hnc specimens showed a significant positively correlation among aurora-a, flj10540, mmp-7 and mmp-10 expressions.","together, our findings define a novel mechanism by which aurora-a promotes cell malignancy, with potential implications for understanding the clinical action of aurora-a.",Medication
do evaluation of the reliability of thiophen-2-carboxylic acid hydrazine result for the identification of mycobacterium bovis ?,"to evaluate the reliability of thiophen-2-carboxylic acid hydrazine (tch) test for identification of mycobacterium bovis (m. bovis). a total of 4069 clinically isolated strains were identified by p-nitrobenzoic acid medium (500 mg/l) and tch medium (5 mg/l). mycobacterium tuberculosis (m. tuberculosis) complex strains susceptible to 5 mg/l tch were further tested for susceptibility to 2 mg/l tch. spacer oligonucleotide typing (spoligotyping) and multi-loci pcr were also performed to identify tch susceptible strains. among the 4069 isolated strains there were 3929 strains belonging to m. tuberculosis complex (mtbc) of which 245 were susceptible to 5 mg/l tch. of these 245 strains, 20 were also susceptible to 2 mg/l tch, while only 1 strain was identified to be m. bovis by both spoligotyping and multi-loci pcr.",tch susceptibility test (either 5 mg/l or 2 mg/l) is not a reliable method for identification of m. bovis.,General
does the h2o2 scavenger ebselen decrease ethanol-induced locomotor stimulation in mice?,"in the brain, the enzyme catalase by reacting with h(2)o(2) forms compound i (catalase-h(2)o(2) system), which is the main system of central ethanol metabolism to acetaldehyde. previous research has demonstrated that acetaldehyde derived from central-ethanol metabolism mediates some of the psychopharmacological effects produced by ethanol. manipulations that modulate central catalase activity or sequester acetaldehyde after ethanol administration modify the stimulant effects induced by ethanol in mice. however, the role of h(2)o(2) in the behavioral effects caused by ethanol has not been clearly addressed. the present study investigated the effects of ebselen, an h(2)o(2) scavenger, on ethanol-induced locomotion. swiss rjorl mice were pre-treated with ebselen (0-50mg/kg) intraperitoneally (ip) prior to administration of ethanol (0-3.75g/kg; ip). in another experiment, animals were pre-treated with ebselen (0 or 25mg/kg; ip) before caffeine (15mg/kg; ip), amphetamine (2mg/kg; ip) or cocaine (10mg/kg; ip) administration. following these treatments, animals were placed in an open field to measure their locomotor activity. additionally, we evaluated the effect of ebselen on the h(2)o(2)-mediated inactivation of brain catalase activity by 3-amino-1,2,4-triazole (at). ebselen selectively prevented ethanol-induced locomotor stimulation without altering the baseline activity or the locomotor stimulating effects caused by caffeine, amphetamine and cocaine. ebselen reduced the ability of at to inhibit brain catalase activity.","taken together, these data suggest that a decline in h(2)o(2) levels might result in a reduction of the ethanol locomotor-stimulating effects, indicating a possible role for h(2)o(2) in some of the psychopharmacological effects produced by ethanol.",Prevention
are high risk hpv types 18 and 16 potent modulators of oral squamous cell carcinoma phenotypes in vitro?,"human papillomavirus (hpv) has been confirmed as the primary etiological factor that transforms cervical epithelia into cancer. the presence of hpv in oral cancers suggests that hpv may play a similar role in transforming the oral epithelia. a high degree of variability in the prevalence of hpv in oral cancers has been found, however, raising questions regarding its role in the transformation and development of oral cancers. the goal of this study was to test our hypothesis that high-risk hpv strains hpv16 and hpv18 will alter the phenotype of transformed oral squamous cell carcinoma cell lines, cal27, scc-15 and scc-25 in vitro. cal27 cells transfected with hpv18, hpv16, as well as hpv16/18 co-transfectants, demonstrated significant increases in proliferation, adhesion and cell spreading compared with non-transfected controls. these observed differences were correlated with a small level of increased cell survival. scc-15 cells, however, displayed a differential response to hpv transfection, with only hpv18-transfectants demonstrated changes to proliferation. interestingly, scc-25 cells displayed a more complex response, with hpv16-induced increases in cell proliferation, viability and cell spreading, while hpv18- and 16/18-transfectants exhibited reduced adhesion and proliferation.","determining the potential of specific high-risk hpv strains to alter phenotypic behaviors of already transformed oral carcinomas is a critical step in providing more accurate prognosis and treatment options for oral cancer patients. the identification of differential responses to specific hpv strains among oral cancers suggests a more significant, complex and multifactorial role of hpv, not only in transforming, but also in modulating, the phenotype and treatment responsiveness of precancerous and cancerous oral lesions. this study provides some of the first evidence to help identify the important molecular markers for pathways that could be used to determine the most effective and appropriate treatment plans for oral cancer patients with concomitant oral hpv infections.",Diagnosis
is cells in pseudointimal hyperplasia migrated from extravascular space?,"the aim of this study was to investigate the origin of the pseudointima (pi) formed in polytetrafluoroethylene (ptfe) tube grafts after implantation into the inferior vena cava (ivc) of rabbits. a segment of the ivc of rabbits was replaced by ptfe tube graft (3 cm long, 3 mm inner diameter, 30 microns internodal distance, 0.3 mm thickness). the experimental group was divided into two groups as follows: (group a) non-wrapped, (group b) wrapped the outer wall of ptfe with impermeable vinyl. grafts were harvested at three weeks after implantation and subjected to the following studies: patency, ultrastructural studies by light microscopy (lm) and immunostaining, scanning and transmission electron microscopy (sem tem). the grafts were patient but the lumen of the control group was narrowed by pi. lm and immunostaining studies revealed the presence of thick pi composed of spindle-type cells in group a, bust almost no pi in group b. only few erythrocytes, macrophage and protein-fibrin matrix was found in group b. endothelial like cell coverage, judged by sem, was observed in only group a. only some macrophages and platelets were shown in the graft surface in group b. tem of pi revealed the presence of vsmcs, myofibroblasts and outer surface of grafts revealed the presence of myofibroblast in group a.",the formation of pi suppressed by blocking the cellular migration from perigraft space suggest that pi was mainly originated by myofibroblast located in the perigraft space.,General
are high vitamin b12 levels associated with increased mortality risk for icu patients after adjusting for liver function : a cohort study?,"recent research has suggested that high vitamin b12 levels may be associated with increased mortality after icu admission. however, it is known that impaired liver function may lead to elevated b12 since b12 is metabolized through the liver, and therefore high b12 levels may serve as a proxy for poor liver function. the aim of this study is to assess the impact that liver function and liver disease have on the relationship between high vitamin b12 levels and mortality in the icu. we performed an observational cohort study using icu data that were collected from patients admitted to four icu types (medical, surgical, cardiac care and cardiac surgery recovery) in one large urban hospital from 2001 to 2008. we analyzed the medical records of 1,684 adult patients (age 18 years) who had vitamin b12 and liver function measurements up to 14 days prior to icu admission or within 24 hours after admission. while we found an association between high b12 and mortality when we did not control for any potential confounders, after we adjusted for liver function and liver disease, no significant association existed between b12 and mortality using multivariable logistic regression (30-day mortality: or1.18, 95 ci 0.81 to 1.72, p0.3890; 90-day mortality: or1.20, 95 ci 0.84 to 1.71, p0.3077).","elevated b12 levels are not a significant predictor of mortality after icu admission when liver function is controlled for, and may instead be a proxy for poor liver function.",Treatment
is polymorphism of 270 a g in brap associated with lower ankle-brachial index in a taiwanese population?,"the single nucleotide polymorphism (snp) rs11066001 of brap has been shown to be associated with myocardial infarction (mi), coronary atherosclerosis and carotid atherosclerosis, but it is not clear whether it also plays a role in peripheral artery disease (pad). the ankle-brachial index (abi) is often used as a non-invasive measure of pad; therefore, the aim of this study was to test for a relationship between the snp rs11066001 and abi. a total of 537 high-risk subjects with a family history of mi or stroke completed a health survey, including a physical examination, blood test and measurement of abi. among them, 523 subjects had the genotypes. association analyses between the genotype of brap and abi were performed by multiple linear and logistic regressions with adjustment for covariates. we found that the gg genotype is significantly associated with a lower abi value. for the lowest abi tertile, the gg genotype had an or of 2.87 (p 0.018) when compared with the middle abi tertile, and or of 2.92 (p 0.015) when compared to the highest abi tertile. women with the gg genotype had a lower abi value than men with the same genotype (p 0.012). accordingly, women carrying this gg risk genotype may have a higher risk for pad.",our findings provide additional evidence that support the genetic effect of brap on diverse cardiovascular phenotypes.,General
is adenocarcinoma of the rectum in patients under age 40 increasing : impact of signet-ring cell histology?,"overall, the incidence of colorectal cancer appears to be stable or diminishing. however, based on our practice pattern, we observed that the incidence of rectal cancer in patients under 40 is increasing and may be associated with a prominence of signet-ring cell histology. the aim of this study was to verify the rising trend in rectal cancer in patients under 40 and describe the histology prominent in that cohort. this is a retrospective cohort study. we performed a retrospective cohort study of all patients diagnosed with rectal adenocarcinoma from 1980 to 2010 using the surveillance, epidemiology, and end results cancer registry. rectal cancer incidence, histology, and associated staging characteristics were the primary outcomes measured. although the incidence of rectal cancer for all ages remained stable from 1980 to 2010, we observed an annual percent change of 3.6 in the incidence of rectal cancer in patients under 40. the prevalence of signet cell histology in patients under 40 was significantly greater than in patients over 40 (3 vs 0.87, p 0.01). a multivariate regression analysis revealed an adjusted odds ratio of 3.6 (95 ci, 2.6-5.1) for signet cell histology in rectal adenocarcinoma under age 40. signet cell histology was also significantly associated with a more advanced stage at presentation, poorly differentiated tumor grade, and worse prognosis compared with mucinous and nonmucinous rectal adenocarcinoma.","the study was limited by its retrospective nature and the information available in the surveillance, epidemiology, and end results database.",Diagnosis
does apoe influence vasospasm and cognition of noncomatose patients with subarachnoid hemorrhage?,"to determine the influence of the apoe genotype on functional and cognitive outcome and on the incidence and prognosis of clinical vasospasm (delayed ischemic neurologic deficit dind) in noncomatose patients with aneurysmal subarachnoid hemorrhage (sah). the authors reviewed the data of patients admitted for sah to the neurosurgical departments of the san gerardo hospital of monza (january 1996 to december 2001) and the ospedali riuniti of bergamo (january 2002 to september 2003). the authors considered only noncomatose patients and evaluated outcome by means of the rankin disability index and the mini-mental state examination at least 6 months after the sah. uni- and multivariate logistic regression. the authors included 101 patients. they found the epsilon4 allele in 26 patients (25.7). the presence of the epsilon4 allele negatively affected the overall outcome (functional morbidity or cognitive morbidity, or both) (p 0.0087) and, particularly, cognitive morbidity (p 0.0028). those with an epsilon4 allele had delayed ischemic neurologic deficit dinds more frequently (p 0.024) and, in the presence of dind, they were more likely to show permanent neurologic deficits (p 0.0051).",apoe4 negatively affects cognitive morbidity and delayed ischemic neurologic deficit recovery. the presence of an epsilon4 allele increases the risk of delayed ischemic neurologic deficit.,Diagnosis
"are cathepsin b , k , and s expressed in cerebral aneurysms and promote the progression of cerebral aneurysms?","a cerebral aneurysm (ca) causes catastrophic subarachnoid hemorrhage. degradation of extracellular matrix in arterial walls is a prominent feature of cerebral aneurysms. we investigated the expression and role of cysteine cathepsins, collagen- and elastin- degrading proteinases, in ca progression. cas were induced in sprague-dawley rats with or without cysteine cathepsin inhibitor, nc-2300. expression of cathepsin b, k, s, and cystatin c, an endogenous inhibitor of cysteine cathepsins, in aneurysmal walls was examined in quantitative rt-pcr and immunohistochemistry. the activity of cysteine cathepsins and collagenase i and iv in aneurysmal walls was also assessed. finally, expression of cysteine cathepsins and cystatin c in human cas was examined. quantitative rt-pcr and immunohistochemistry revealed upregulated expression of cathepsin b, k, and s in the late stage of aneurysm progression. in contrast, cystatin c expression was reduced with aneurysm progression. treatment with nc-2300 resulted in the decreased incidence of advanced cas. the activity of cysteine cathepsins and collagenase i and iv in aneurysmal walls was reduced and elastin content was increased in the nc-2300-treated group. finally, immunohistochemistry for cysteine cathepsins and cystatin c expression in human cas showed the same expression pattern as in the rat study.",data obtained by using nc-2300 revealed an important role of cysteine cathepsins in the progression of cas. our findings strongly suggest that an imbalance between cysteine cathepsins and their inhibitor may cause the excessive breakdown of extracellular matrix in the arterial walls leading to the progression and rupture of cas.,Medication
do nmda receptors mediate olfactory learning and memory in drosophila?,"molecular and electrophysiological properties of nmdars suggest that they may be the hebbian ""coincidence detectors"" hypothesized to underlie associative learning. because of the nonspecificity of drugs that modulate nmdar function or the relatively chronic genetic manipulations of various nmdar subunits from mammalian studies, conclusive evidence for such an acute role for nmdars in adult behavioral plasticity, however, is lacking. moreover, a role for nmdars in memory consolidation remains controversial. the drosophila genome encodes two nmdar homologs, dnr1 and dnr2. when coexpressed in xenopus oocytes or drosophila s2 cells, dnr1 and dnr2 form functional nmdars with several of the distinguishing molecular properties observed for vertebrate nmdars, including voltage/mg(2)-dependent activation by glutamate. both proteins are weakly expressed throughout the entire brain but show preferential expression in several neurons surrounding the dendritic region of the mushroom bodies. hypomorphic mutations of the essential dnr1 gene disrupt olfactory learning, and this learning defect is rescued with wild-type transgenes. importantly, we show that pavlovian learning is disrupted in adults within 15 hr after transient induction of a dnr1 antisense rna transgene. extended training is sufficient to overcome this initial learning defect, but long-term memory (ltm) specifically is abolished under these training conditions.","our study uses a combination of molecular-genetic tools to (1) generate genomic mutations of the dnr1 gene, (2) rescue the accompanying learning deficit with a dnr1 transgene, and (3) rapidly and transiently knockdown dnr1 expression in adults, thereby demonstrating an evolutionarily conserved role for the acute involvement of nmdars in associative learning and memory.",Medication
do oxygenated perfluorocarbons protect the intestine from the ischemia/reperfusion injury in rabbits?,"to investigate whether intraluminal administration of oxygenated perfluorocarbons (pfcs) protects the enterocyte from acute ischemia-reperfusion (i/r) injury. twenty rabbits were divided in 4 groups: sham-operated controls (group a), acute i/r (group b), acute i/r plus infusion of oxygenated pfcs 30 minutes before ischemia (group c), and acute i/r plus infusion of oxygenated pfcs 30 minutes before reperfusion (group d). serum creatine phosphokinase (cpk) and mucosal disaccharidase activity were examined. intestinal biopsies were obtained for electron microscopy study. group b cpk mean values are 3495.2 157.35 and 4855 350.21 u/l. group c: 2674.6 265.87 and 3231 232.30. group d: 2382.2 102.90 and 3217.6 185.61 at 120 and 180 minutes (p.05). at 180 minutes, maltase and sucrose values were 33.63, 51.88, 8.45, and 19.91, and 17.99, 22.87, 6.62, and 14.24 mol/min per g for groups a, b, c, and d, respectively (p.05). histopathology showed the least cellular deterioration in pfc groups.",oxygenated pfcs protect the enterocyte during bowel i/r.,Medication
does narrowband uv-b produce superior clinical and histopathological resolution of moderate-to-severe psoriasis in patients compared with broadband uv-b?,"to compare the therapeutic effectiveness of daily exposure to narrowband (nb) uv-b vs broadband (bb) uv-b with and without tar. half-body exposures to nb uv-b or bb uv-b were given daily for 4 weeks in this comparative treatment study. narrowband uv-b was delivered from tl-01 fluorescent bulbs and bb uv-b from conventional bulbs in the same phototherapy cabinet. narrowband uv-b was compared using a paired treatment approach to bb uv-b above the waist and to bb uv-b with tar (goeckerman treatment) below the waist. general clinical research center of a university hospital inpatient unit. twenty-two patients with moderate-to-severe plaque-type psoriasis completed the study. clinical efficacy was measured weekly using psoriasis severity scoring. therapeutic outcomes after 4 weeks were compared in paired biopsy samples from treated lesions using objective histopathological measures (quantitative reduction in epidermal acanthosis and keratin 16 expression). clinical resolution of psoriasis was achieved on 86 of paired sites treated with nb uv-b vs 73 treated with bb uv-b. histopathological resolution of epidermal hyperplasia (marked by keratin 16 expression) was achieved in 88 of lesions treated with nb uv-b vs 59 treated with bb uv-b. epidermal acanthosis was reduced more completely by nb uv-b treatment. clinical resolution of psoriatic lesions occurred more rapidly following nb uv-b treatment, with some patients achieving complete resolution after 2 to 3 weeks of treatment.","narrowband uv-b offers a significant therapeutic advantage over bb uv-b in the treatment of psoriasis, with faster clearing and more complete disease resolution. the erythema response to nb uv-b treatment was significantly more intense and persistent compared with bb uv-b. considerably more necrotic keratinocytes were observed in histopathological sections of skin treated with nb uv-b after a single 2.0-minimum erythema dose exposure. treatment should be coupled with obligate minimum erythema dose testing to nb uv-b and close clinical observation during dose increases.",Treatment
does television viewing in early childhood predict adult body mass index?,"to examine the effects of duration, timing and type of television (tv) viewing at age 5 years on body mass index (bmi) in adult life. 1970 british birth cohort, followed up at 5 (n13,135), 10 (n14,875), and 30 years (n11,261). weekday and weekend tv viewing at 5 years, type of programs, and maternal attitudes toward tv at age 5 years. bmi z-score at 10 and 30 years. mean daily hours of tv viewed at weekends predicted higher bmi z-score at 30 years (coefficient0.03, 95 ci: 0.01, 0.05, p.01) when adjusted for tv viewing and activity level at 10 years, sex, socioeconomic status, parental bmis, and birth weight. each additional hour of tv watched on weekends at 5 years increased risk of adult obesity (bmi or 30 kg/m2) by 7 (or1.07, 95 ci 1.01, 1.13, p.02). weekday viewing, type of program and maternal attitudes to tv at 5 years were not independently associated with adult bmi z-score.",weekend tv viewing in early childhood continues to influence bmi in adulthood. interventions to influence obesity by reducing sedentary behaviors must begin in early childhood. interventions focusing on weekend tv viewing may be particularly effective.,Prevention
is predictive value of low bmd for 1-year fracture outcomes similar for postmenopausal women ages 50-64 and 65 and older : results from the national osteoporosis risk assessment ( nora )?,"the relationship of low bone mass and fracture in younger postmenopausal women has not been extensively studied. in a large cohort of postmenopausal women or 50 years of age, we found the relationship of bmd measured at peripheral sites and subsequent 1-year fracture risk to be similar between women or 65 years of age. low bone mass and fractures are prevalent in older postmenopausal women. however, the frequency of low bone mass and fracture in younger postmenopausal women has not been studied extensively. there are very limited data regarding the association between bmd measurements and fractures in postmenopausal women who are between the ages of 50 and 64. in the national osteoporosis risk assessment (nora) we studied the frequency of low bone mass and its association with fracture in women 50-64 years of age in comparison with women or 65 of age. nora enrolled 200,160 postmenopausal women or 50 years of age who had no prior diagnosis of osteoporosis. baseline bmd was measured at the heel, forearm, or finger. a 1-year follow-up survey requesting incident fractures since baseline was completed by 163,935 women, 87,594 (53) of whom were 50-64 years of age. the association between bmd and fracture was assessed using logistic regression, adjusted for important covariates. thirty-one percent of women 50-64 years of age had low bone mass (t scores or 65 years of age. during the first year of follow-up, 2440 women reported fractures of wrist/forearm, rib, spine, or hip, including 440 hip fractures. nine hundred four women 50-64 years of age reported fractures, including 86 hip fractures, accounting for 37 of fractures and 20 of hip fractures reported in the entire nora cohort. relative risk for osteoporotic fracture was 1.5 for each sd decrease in bmd for both the younger and older groups of women.",low bmd in younger postmenopausal women 50-64 years of age showed a 1-year relative risk of fracture similar to that found in women or 65 years of age.,Diagnosis
is frontal p3 event-related potential related to brain glutamine/glutamate ratio measured in vivo?,"the auditory p3 event-related potential (erp) is thought to index cognitive processing relevant to attention and working memory processes. drug challenge studies suggest that glutamate neurotransmission plays an important role in modulating p3 erp. however, while direct links between glutamate activity and p3 erp response in humans are suspected, mechanistic details remain largely unknown. we investigated here the relationships between p3 erp and indices of glutamatergic processing measured in vivo with proton magnetic resonance spectroscopy ((1)h mrs). we hypothesized that a higher index of glutamatergic processing (glutamine/glutamate ratio; abbreviated gln/glu) in the anterior cingulate (acc) and in the parietal-occipital (poc) cortices would associate with larger frontal p3a and parietal p3b amplitudes, respectively. frontal p3a (fz) and parietal p3b (pz) were collected from 32 healthy participants who performed an auditory oddball task. resting glutamate (glu), glutamine (gln), and gln/glu (an index of glutamatergic processing) measures were obtained on a 4t mr scanner using j-resolved mr spectroscopy. linear regression and partial correlations were used for statistical analysis. significant positive correlations were found between frontal p3a amplitude and acc gln/glu ratio (partial r0.57; p0.001) and between frontal p3a amplitude and acc gln concentration (partial r0.43; p0.02). relationships between parietal p3b and the glutamate indices in the poc were not significant.","these results indicate a specific connection between an index of glutamate neurotransmitter function in acc and frontal p3 erp, providing a novel insight into the neurochemistry underlying scalp recorded eeg response. abnormalities in glutamate neurotransmission have been observed in schizophrenia and other psychiatric conditions and may underlie illness related deficits of p3 erp.",Medication
does the fxr agonist 6ecdca reduce hepatic steatosis and oxidative stress induced by ethanol and low-protein diet in mice?,"excessive ethanol consumption can lead to development of hepatic steatosis. since the fxr receptor regulates adipose cell function and liver lipid metabolism, the aim of this work was to examine the effects of the fxr agonist 6ecdca on alcoholic liver steatosis development and on oxidative stress induced by ethanol consumption. swiss mice (n24) received a low-protein diet (6) and a liquid diet containing 10 ethanol or water for 6weeks. in the last 15days mice received oral treatment with 6ecdca (3mgkg(-1)) or 1 tween (vehicle). the experimental groups (n6) were: watertween, water6ecdca, ethanoltween and ethanol6ecdca. moreover, as a diet control, we used a basal group (n6), fed by a normal-proteic diet (23) and water. after the treatment period, the animals were anesthetized for sample collection to perform plasma biochemistry assays, hepatic oxidative stress assays, hepatic cholesterol and triglycerides measurements, liver histology and hepatic gene expression. ethanol associated with low-protein diet induced hepatic oxidative stress, increased plasma transaminases and induced hepatic lipid accumulation. many of these parameters were reversed by the administration of 6ecdca, including amelioration of lipid accumulation and lipoperoxidation, and reduction of reactive oxygen species. these effects were possibly mediated by regulation of srebpf1 and fas gene expression, both reduced by the fxr agonist.",our data demonstrated that 6ecdca reverses the accumulation of lipids in the liver and decreases the oxidative stress induced by ethanol and low-protein diet. this fxr agonist is promising as a potential therapy for alcoholic liver steatosis.,Medication
is early treatment with rutoside and ascorbic acid highly effective for progressive pigmented purpuric dermatosis?,"progressive pigmented purpuric dermatosis (pppd, schamberg disease) is a rare benign, but chronic dermatosis frequently misdiagnosed as vasculitis or bleeding disorder. although affected patients experience significant impairment in quality of life no effective treatment has been established. the aim of our two center case series was to evaluate efficacy and tolerability of the antioxidants rutoside and ascorbic acid as combination treatment for pppd. a retrospective review was performed on 35 patients with pppd treated with 2 50 mg rutoside and 1,000 mg ascorbic acid daily between 2004 until 2011. the mean treatment duration was 8.2 months. 71.4 of the participants experienced complete clearance and 20.0 an improvement of more than 50, accompanied by increased quality of life. nine participants (25.1) relapsed after discontinuation. in seven, rutoside and ascorbic acid was re-initiated, and all responded again. only three participants reported mild adverse effects. participants with shorter disease duration showed better therapeutic success, shorter time to response and lower risk of recurrence.",oral rutoside and ascorbic acid may be an efficient and well tolerated treatment for pppd. early treatment is recommended to achieve best clinical outcome.,Treatment
do urinary albumin excretion from spot urine samples predict all-cause and stroke mortality in africans?,"increased urinary albumin excretion reflects general vascular damage and predicts adverse cardiovascular and renal outcomes. albuminuria can be determined from easily collected spot urine samples, especially in low-resource settings. however, no prognostic evidence exists for africans. we followed clinical outcomes in 1,061 randomly selected non diabetic, human immunodeficiency virus (hiv)-negative africans (mean age: 51.5 years; 62.0 women). baseline urinary albumin-to-creatinine ratio was assessed from spot urine samples. over a median follow-up of 4.52 years, 132 deaths occurred, of which 47 were cardiovascular related. the urinary albumin-to-creatinine ratio averaged 6.1 g/mg (5th to 95th percentile interval; 1.2-70.0). in multivariable-adjusted analyses, urinary albumin excretion predicted all-cause mortality (hazard ratio (hr), 1.26; 95 confidence interval (ci), 1.07-1.48; p 0.006), and a tendency existed for cardiovascular mortality (hr, 1.26; 95 ci, 0.97-1.63; p 0.087), which seemed to be driven by fatal stroke (hr, 1.72; 95 ci, 1.17-2.54; p 0.006) rather than cardiac mortality (hr, 0.67; 95 ci, 0.41-1.07; p 0.094). the predictive value remained in 528 hypertensives for both all-cause (hr, 1.38; 95 ci, 1.13-1.69; p 0.001) and cardiovascular (hr, 1.45; 95 ci, 1.07-1.96; p 0.017) mortality, again driven by stroke. our findings also remained significant after we excluded participants with macroalbuminuria, those on antihypertensive treatment, as well as participants who died within 1 year after enrollment.","in nondiabetic hiv-negative africans, albuminuria predicts all-cause and stroke mortality.",Medication
does aspirin synergistically potentiate isoflurane minimum alveolar concentration reduction produced by morphine in the rat?,"the combination of opioids and nonsteroidal antiinflammatory drugs is more analgesic than the summed effect of each drug administered separately. this synergism has been used to obtain analgesia in the postoperative period at doses at which side effects are minimal. the aim of this study is to evaluate the analgesic interaction between aspirin and morphine in the rat during isoflurane anesthesia. the reduction in minimum alveolar concentration of isoflurane (mac(iso)) was used as an objective measure of the analgesic potency of individual drugs and their use in combination. thirty-seven male wistar rats were anesthetized with isoflurane in oxygen, and the mac(iso) was determined before and after the intravenous administration of aspirin and morphine. rats were administered morphine alone (1, 3, and 10 mg/kg) or morphine (1 and 3 mg/kg) and aspirin (30 mg/kg). the mac(iso) was determined from alveolar gas samples at the time of tail clamp. the duration of mac(iso) reduction was recorded. aspirin did not have an effect on mac(iso), (average, 1.35/-0.1), whereas the combination of morphine (1 and 3 mg/kg) and aspirin (30 mg/kg) produced a reduction in the dose of morphine needed to produce the same degree of mac(iso) reduction. actual mac(isodrug) data were as follows: 1 mg/kg morphine, 1.17/-0.14; 3 mg/kg morphine, 0.98/-0.15; 1 mg/kg morphine plus aspirin, 0.90/-0.04; 10 mg/kg morphine, 0.63/-0.13; and 3 mg/kg morphine plus aspirin, 0.64/-0.06.","the synergistic effects of aspirin and morphine allow a clinically significant reduction in the requirements of isoflurane and isoflurane plus morphine, and these drug combinations may decrease the side effects associated with the use of single higher, equianalgesic doses of these drugs.",Medication
is tap73 one of the genes responsible for the lack of response to chemotherapy depending on b-raf mutational status?,"although there have been many studies on the p73 gene, some of its functions still remain unclear. there is little research on the relationship between p73 gene transcription and its protein expression and the response to certain drugs such as oxaliplatin and cetuximab, which are drugs currently used in colorectal cancer.the purpose of this study was to evaluate the impact of tap73 expression on oxaliplatin and cetuximab-based chemotherapy in colorectal cancer cell lines with different k-ras and b-raf mutational status. tap73 was analyzed in three colorectal tumor cell lines ht-29, sw-480 and caco-2. mrna tap73 was determined using real time pcr; tap73 protein by immunoblotting and cell viability was analyzed by the mtt method. we found that mrna and tap73 protein were decreased in cells treated with oxaliplatin (in monotherapy or combined with cetuximab) when b-raf is mutated. this was statistically significant and was also associated with higher cell viability after the treatment.","here, for the first time we report, that there is a signaling loop between b-raf activation and p73 function.low expression of tap73 in colorectal cancer cell lines with mutated b-raf may be involved in the lack of response to oxaliplatin in monotherapy or combined with cetuximab.",Medication
do increases in p-wave dispersion predict postoperative atrial fibrillation after coronary artery bypass graft surgery?,"atrial fibrillation (af) is a common complication after coronary artery bypass graft (cabg) surgery. in this study we examined the effect of surgery on atrial electrophysiology as measured by p-wave characteristics and to determine the potential predictive value of p-wave characteristics on the incidences of postoperative af in patients undergoing cabg surgery. patients undergoing elective cabg surgery were monitored by continuous electrocardiogram (ecg) telemetry during the in-hospital period until discharge for the occurrence of postoperative af. differences in p-wave characteristics (p-wave duration, amplitude, axis, dispersion, pr interval, segment depression, and dispersion) were compared between the pre- and postoperative 12-lead ecg measurements, and also between patients with and without postoperative af. the association of postoperative af and potential clinical predictors and p-wave characteristics were determined by multivariate logistic regression. postoperative af occurred in 81 (27) of 300 patients. univariate analysis showed that patients who subsequently developed postoperative af compared with those without af were significantly older (mean age 68 /- 8 versus 63 /- 10 yr, p 0.0001), had a larger body surface area (bsa) (2.03 /- 0.24 versus 1.92 /- 0.22 m(2), p 0.0002), were more likely to have a history of af (8 of 81 versus 1 of 219, p 0.003), used preoperative antiarrhythmic medications more frequently (7 of 81 versus 4 of 219, p 0.01), and had a more frequent rate of return to the operating room for postoperative complications (9 of 81 versus 9 of 219, p 0.029). furthermore, the postoperative p-wave duration decreased to a larger extent (mean change -11.3 /- 0.1 ms versus -8.4 /- 0.1 ms, p 0.0001), and the p-wave dispersion increased postoperatively to a larger extent (3.1 /- 15.5 ms versus -1.6 /- 14.6 ms, p 0.028) in those who subsequently developed af compared with those without af. multivariate logistic regression showed age (odds ratio or 1.1, 95 confidence interval ci: 1.06-1.15, p 0.0001), bsa (or 38.1, 95 ci: 8.2-176, p 0.0001), and an increase in postoperative p-wave dispersion (or 1.03, 95 ci: 1.01-1.05, p 0.01) to be independent predictors of postoperative af. no surgical factor was identified to be responsible for this postoperative change in atrial electrophysiology.","in addition to clinical factors, such as advanced age and body surface area, we demonstrated that electrophysiologic changes involving an increase in p-wave dispersion postoperatively independently predict atrial fibrillation after coronary artery bypass graft surgery.",Treatment
does dynamic exercise normalize resting blood pressure in mildly hypertensive premenopausal women?,"dynamic exercise acutely and transiently lowers resting blood pressure in hypertensive men and is termed postexercise hypotension (peh). we examined 18 premenopausal women (7 hypertensive and 11 normotensive) to determine if peh occurs in women and to elucidate possible hemodynamic and hormonal mechanisms. patients wore an ambulatory blood pressure monitor throughout the day after 40 minutes of a rest sham session and 40 minutes of cycle exercise, of which 30 minutes was performed at 60 of maximal oxygen consumption. cardiac output and total systemic vascular resistance were determined by doppler echocardiography before and 15 minutes after sham and exercise. catecholamines, plasma renin activity, and beta-endorphin were measured over this same period. peh occurred only in the hypertensive women. systolic, diastolic, and mean arterial blood pressure decreased in the hypertensive women by a mean of 9.5 /- 2. 8 mm hg (p .05). after exercise, total systemic vascular resistance was lower (p .01), and cardiac output, catecholamines, and plasma renin activity were greater (p .01) than before exercise in both groups of women.",peh was observed for up to 7 hours after exercise in mildly hypertensive women and was not explained by the hemodynamic and hormonal adjustments that occurred after exercise. the magnitude and duration of peh may be sufficient to normalize the blood pressure of certain hypertensive women throughout most of the day.,Prevention
does a multifaceted intervention for patients with anaphylaxis increase epinephrine use in adult emergency department?,"studies have documented inconsistent emergency anaphylaxis care and low compliance with published guidelines. to evaluate anaphylaxis management before and after implementation of an emergency department (ed) anaphylaxis order set and introduction of epinephrine autoinjectors, and to measure the effect on anaphylaxis guideline adherence. a cohort study was conducted from april 29, 2008, to august 9, 2012. adult patients in the ed who were diagnosed with anaphylaxis were included. ed management, disposition, self-injectable epinephrine prescriptions, allergy follow-up, and incidence of biphasic reactions were evaluated. the study included 202 patients. the median age of the patients was 45.3 years (interquartile range, 31.3-56.4 years); 139 (69) were women. patients who presented after order set implementation were more likely to be treated with epinephrine (51 vs 33; odds ratio or 2.05 95 ci, 1.04-4.04) and admitted to the ed observation unit (65 vs 44; or 2.38 95 ci, 1.23-4.60), and less likely to be dismissed home directly from ed (16 vs 29, or 0.47 95 ci, 0.22-1.00). eleven patients (5) had a biphasic reaction. of these, 5 (46) had the biphasic reaction in the ed observation unit; 1 patient was admitted to the intensive care unit. six patients (55) had reactions within 6 hours of initial symptom resolution, of whom 2 were admitted to the intensive care unit.",significantly higher proportions of patients with anaphylaxis received epinephrine and were admitted to the ed observation unit after introduction of epinephrine autoinjectors and order set implementation. slightly more than half of the biphasic reactions occurred within the recommended observation time of 4 to 6 hours. analysis of these data suggests that the multifaceted approach to changing anaphylaxis management described here improved guideline adherence.,Treatment
does blockade of advanced glycation end product formation attenuate bleomycin-induced pulmonary fibrosis in rats?,"advanced glycation end products (ages) have been proposed to be involved in pulmonary fibrosis, but its role in this process has not been fully understood. to investigate the role of age formation in pulmonary fibrosis, we used a bleomycin (blm)-stimulated rat model treated with aminoguanidine (ag), a crosslink inhibitor of age formation. rats were intratracheally instilled with blm (5 mg/kg) and orally administered with ag (40, 80, 120 mg/kg) once daily for two weeks. ages level in lung tissue was determined by elisa and pulmonary fibrosis was evaluated by ashcroft score and hydroxyproline assay. the expression of heat shock protein 47 (hsp47), a collagen specific molecular chaperone, was measured with rt-pcr and western blot. moreover, tgfbeta1 and its downstream smad proteins were analyzed by western blot. ages level in rat lungs, as well as lung hydroxyproline content and ashcroft score, was significantly enhanced by blm stimulation, which was abrogated by ag treatment. blm significantly increased the expression of hsp47 mrna and protein in lung tissues, and ag treatment markedly decreased blm-induced hsp47 expression in a dose-dependent manner (p 0.05). in addition, ag dose-dependently downregulated blm-stimulated overexpressions of tgfbeta1, phosphorylated (p)-smad2 and p-smad3 protein in lung tissues.","these findings suggest age formation may participate in the process of blm-induced pulmonary fibrosis, and blockade of age formation by ag treatment attenuates blm-induced pulmonary fibrosis in rats, which is implicated in inhibition of hsp47 expression and tgfbeta/smads signaling.",Medication
does magnesium reduce myocardial infarct size via enhancement of adenosine mechanism in rabbits?,"clinical impact of magnesium (mg) therapy remains controversial in acute myocardial infarction. we investigated the infarct size limiting effects of mg and its mechanism in rabbits. anesthetized rabbits underwent 30 min coronary occlusion and 3 h reperfusion in ten groups: (1) control, (2) low mg, (3) mg, (4) high mg, (5) calcium (ca), (6) mgca, (7) 8-phenyltheophylline (8pt), an adenosine receptor blockade, (8) 8ptmg, (9) alpha, beta-methylene-adenosine diphosphate (aopcp), a selective inhibitor of ecto-5'-nucleotidase, and (10) aopcpmg groups. infract size (is) to area at risk (ar) was measured by triphenyltetrazorium chloride method. the is/ar ratio was significantly smaller in mg, 27/-3 (p0.05) and high mg, 24/-2 (p0.05) compared to control, 50/-3 and low mg, 42/-4. the is limiting effects of mg were abolished in 8ptmg, aopcpmg and mgca. the is/ar ratio correlated with neither rate-pressure products nor incidence of arrhythmia.","magnesium administration has an infarct size limiting effect independent of its effects on myocardial oxygen consumption and incidence of arrhythmia in rabbits. the infarct size limiting effect of magnesium is attributable, at least in part, to augmentation of adenosine mechanism.",Medication
does parallactic movement beat binocularity in the presence of external visual noise?,"binocular vision provides a considerable advantage over monocular vision when stationary particles partly obstruct the view. such situations occur in real life, e.g., when drivers are trying to identify objects through a windshield dotted with snowflakes. in the process of driving, any bumpiness of the road will bring about a parallactic movement of particles on the windshield with respect to the visual object. we investigated whether this parallactic movement diminishes the advantage of binocular over monocular vision. using computer graphics, we simulated a driving situation with snowflakes represented by noise particles on the windshield. ten observers tried to identify a landolt ring (8 possible orintations, gap always 2.5 arcmin) presented for 2 s at a viewing distance of 2 m. the partly obstructing noise particles, either stationary or moving vertically at three sinusoidal velocities, were presented at a viewing distance of 0.8 m, corresponding to a stereodisparity well beyond panum's fusional area. we compared the percentage of correct responses and the reaction time between binocular and monocular vision. when the 'snowflakes' were stationary, binocular vision yielded more correct responses than monocular vision (52.2 1.8 vs 39.7 1.7). when the 'snowflakes' were moving, the task was much easier and the binocular advantage less pronounced (95.8 1.4 vs 85.3 5.2). the reaction time with stationary noise was 1.25 s for binocular and 1.31 s for monocular vision. with moving noise, averaged over all three velocities, the reaction time was 1.23 s for binocular and 1.36 s for monocular vision.",parallactic movement of partly obstructing particles reduces the advantage of binocular over monocular vision to practically irrelevant values.,General
is the vad-dcep sequence an effective pre-transplant therapy in untreated multiple myeloma?,"standard treatment for patients with multiple myeloma is debulking chemotherapy with non-alkylating agents followed by a regimen to mobilize peripheral blood stem cells (pbsc) and the transplantation of the mobilized, autologous pbsc. the aim of this study was to evaluate the efficacy of a new regimen and compare it with that of a previous regimen. in a large cohort of 106 patients (group i) we administered a new pre-transplant program which includes 2 courses of pulsed-vad (vincristine, adriamycin, dexamethasone) followed by 2 courses of dcep (dexamethasone, cyclophosphamide, etoposide and cis-platinum). we compared the efficacy of this new vad-dcep sequence, in terms of mobilizing capacity, toxicity and anti-myeloma activity in comparison with that of the previous vad-high-dose cyclophosphamide program (group ii, 40 patients). in group i 81/106 (76.4) patients yielded or 4x10(6)/kg cd34 cells, as did 30/40 (75) in group ii but with a significantly higher toxicity in this latter group. in detail, 9 patients in group i (8.5) had who grade iii neutropenia versus 35 in group ii (87.5), 5 patients of group i (4.7) had grade iii thrombocytopenia versus 12 patients in group ii (30), and 8 patients in group i (7.5) experienced an infections fever versus 9 patients in group ii (22.5). therefore, nearly all patients in group ii had to be admitted to hospital (39/40, 97.5). there was a higher percentage of responses (crvgprpr) in group i than in group ii: 73 versus 50 (p0.02).","the vad-dcep sequence has an adequate mobilizing capacity, without significant toxicity, and a good anti-myeloma activity, and therefore represents a safe and effective therapeutic approach for multiple myeloma patients at the onset of their disease.",Treatment
does classical positioning decrease the cross-sectional area of the subclavian vein?,"the classic position for subclavian venipuncture is the trendelenberg position, with the head turned away and placement of a shoulder roll (sr). the purpose of this study was to determine whether this position results in the largest cross-sectional area (csa) of the subclavian vein (sv). adult volunteers underwent ultrasound imaging of the right sv in supine and trendelenberg positioning in the following four head and shoulder positions: head neutral with the chin midline (nl), head turned away (ta), head neutral with an sr, and head ta with an sr (ta/sr). the mean csa of the sv in each position was calculated. statistical significance was determined using student's t, wilcoxon signed rank, and bonferroni test. eighteen adults participated in the study. trendelenberg positioning significantly increased the csa of the sv in all positions except nl compared to supine positioning (p .03). an sr significantly decreased sv csa in all positions. the largest sv csa was obtained in the ta/trendelenberg position (1.41 /- .06 cm(2)). the classic positioning for subclavian cannulation, ta/sr/trendelenberg, resulted in a significantly smaller csa than ta/trendelenberg position (1.27 /- .06 cm(2), 15 reduction, p .01).",the classic recommended maneuvers of turning the head and placing an sr significantly reduce the csa of the sv. positioning patients in trendelenberg with the head turned away without an sr optimizes sv size. positioning patients in this manner may serve to reduce the morbidity associated with percutaneous access of the sv.,Diagnosis
"is insurance status , not race , a determinant of outcomes from vehicular injury?","hypothesizing that outcomes from specific injury mechanisms should not vary by race or socioeconomic status, we analyzed the relationship of race and ethnicity to fatality in motor vehicle crash victims treated during 2008 and 2009. logistic regression analysis of pooled administrative data assessed the contribution of patient demographics and injury severity to outcome, defined as mortality during acute hospitalization. demographic factors included age, sex, race, ethnicity, and insurance. severe injury was defined using icd-9 injury severity score (survival probability) p 0.85, presence of up to 3 comorbidities, and/or diagnosis of spinal cord injury and/or traumatic brain injury. mortality was stratified by survival time after trauma center arrival to death within 24 hours or thereafter. factors contributing to outcomes were tested using chi square analysis of the calculated model estimate. for 8,758 motor vehicle crash victims treated in state-designated trauma centers, age, sex, injury severity, and 2 or more comorbidities consistently predicted survival. neither race nor ethnicity was associated with increased mortality risk. being uninsured was related to death within 24 hours (p 0.001). the majority of the uninsured who died within 24 hours had an icd-9 injury severity score p 0.5. mortality risk after 24 hours was driven by traumatic brain injury and comorbidities.","the results of this study indicated that higher immediate mortality of the uninsured is a behavioral and socioeconomic rather than physiologic marker. this higher mortality is driven by increased injury severity that increases cost of care in uninsured survivors. this disparity suggests that risk-taking behavior, especially relating to safety practices and licensing regulations, is an important etiologic factor. improved outcomes require better public education and enforcement in conjunction with improvements in processes of care.",Treatment
is beta-cell dysfunction rather than insulin resistance the main contributing factor for the development of postrenal transplantation diabetes mellitus?,"our study was undertaken to investigate the pathogenesis and possible risk factors for postrenal transplantation diabetes mellitus (ptdm). we recruited 114 patients with normal glucose tolerance (ngt) and performed both 75-g oral glucose tolerance tests (ogtt) and short insulin tolerance tests 1 week before and 9-12 months after transplantation. the subjects were classified into three groups by world health organization criteria on the basis of ogtt after transplantation: (a) 36 (31.6) subjects with normal glucose tolerance; (b) 51 (45.7) subjects with impaired glucose tolerance (igt); and (c) 27 (23.7) subjects with postrenal transplantation diabetes mellitus. dosages of steroid and cyclosporine were equivalent among the three groups. before transplantation, the fasting and 2-hr plasma glucose and proinsulin/insulin (pi/i) ratios were significantly higher in the igt and ptdm groups than in the ngt group, but the insulin sensitivity index (isi) was not significantly different among the three groups. in addition, the area under the curve-insulin on ogtt was significantly lower in the ptdm group than in the ngt group. after transplantation, however, the isi was increased in all groups. furthermore, the isi and pi/i ratios revealed significantly higher values in the ptdm group than in the ngt group after transplantation.","these results revealed that fasting and 2-hr plasma glucose levels, as well as the proinsulin/insulin ratio before transplantation, are both possible indicators of beta-cell dysfunction and may be predictors for the development of ptdm. furthermore, beta-cell dysfunction, rather than insulin resistance, was proven to be the main factor for the pathogenesis of ptdm.",Medication
does docosahexaenoic acid promote differentiation of developing photoreceptors in culture?,"the purpose of this work was to study the effects of diverse fatty acids on the composition, metabolism, differentiation, and characteristics of opsin expression in retina photoreceptors. cultures of rat retinal neurons were incubated with or without 22:6 n-3, 22:5 n-3, 20:4 n-6, 18:1 n-9, and 16:0, labeled and unlabeled. in photoreceptor cells incubated with 22:6 n-3 and 22:5 n-3, the proportions of these fatty acids in phospholipids increased four- to sixfold. the remaining fatty acids did not change lipid acyl chain composition. the labeled fatty acids were all actively esterified in neuronal lipids, particularly in phosphatidylcholine. addition of unlabeled 22:6 n-3 did not affect the distribution among lipids of the other fatty acids but displaced 3h20:4 n-6 from phosphatidylcholine and phosphatidylethanolamine. these results suggest that retinal neurons have specific mechanisms for processing fatty acids of different lengths and degrees of unsaturation and that 22:6 n-3 incorporation takes priority. of all fatty acids, 22:6 n-3 was the most effective in promoting photoreceptor differentiation. in 22:6-sufficient photoreceptors, new apical processes formed, the expression of opsin augmented, and its localization improved, concentrating in the apical processes of the cells.","the advancement in differentiation selectively elicited by 22:6 correlates with the fact that 22:6 n-3, but none of the other fatty acids, delays significantly the onset of apoptosis in photoreceptors in culture. the synthesis of 22:6-containing phospholipid molecules could be required for the proper localization of opsin. this could contribute to furthering the differentiation of photoreceptors, preventing their apoptosis, and extending their survival.",General
does poly ( adp-ribose ) polymerase inhibition improve erectile function in diabetic rats?,"erectile dysfunction (ed) is a common and hard-to-treat complication of diabetes mellitus (dm). multiple lines of evidence have shown that poly(adp-ribose) polymerase (parp) activation plays an important role in neurovascular dysfunction in diabetes, which is the crucial mechanism for diabetic ed. to investigate the preventive benefit of a parp inhibitor in a rat model of ed induced by diabetes. established streptozotocin-diabetic male sprague-dawley rats were given pj-34, a selective parp inhibitor, by oral gavage at a dose of 10 mg/kg twice daily for 8 weeks. erectile responses under electrical stimulation of the cavernous nerve, parp activity and reactive oxygen species (ros) production were measured. nitric oxide synthase (nos) isoforms were evaluated by western blot and real-time quantitative pcr. nuclear factor-kappa b activition and apoptosis in corpus cavernosa (cc) were also investigated. the effects of parp inhibition on the development of diabetic ed were determined. diabetes markedly attenuated the erectile responses (intracavernosal pressure/mean systemic arterial blood pressure) and these were partially prevented by pj-34 treatment. promoted oxidative stress associated parp activation was found in cc from vehicle-treated diabetic rats. pj-34 blocked parp activity and the diabetes-associated ros generation. decreased expression and activity of constitutive nos (cnos), including endothelial nos (enos) and neuronal nos (nnos), associated with enhanced inducible nos (inos) expression and activity were observed in vehicle-treated diabetic rats. although pj-34 had no effect on enos expression, it significantly prevented the decrease in nnos expression and cnos activity, and inhibited inos expression and activity in diabetic rats. parp blockade by pj-34 to some extent prevented diabetes-associated apoptosis and nf-b activation.",our results indicate that parp activation plays an important role in the pathogenesis of diabetic ed and parp inhibition may be a promising strategy to prevent development of diabetic ed.,Medication
does cleome arabica leaf extract have anticancer properties in human cancer cells?,"cleome arabica l. (capparidaceae) is a desert plant widely distributed in the north part of africa whose leaves are used in traditional medicine as a sedative for abdominal and rheumatic pains. the anticancer activity of methanol cleome arabica leaf extracts (cale) is investigated in different human cancer cell lines. five different human cancer cell lines, representative of the most common cancers in western countries (i.e., breast adenocarcinoma, colon carcinoma, neuroblastoma, hepatoma, cervix carcinoma) were treated with different concentrations of cale (i.e., 1, 5, 10, 25, 50, 100 and 200 g/ml). cell viability and cell cycle were measured by using a hemocytometer chamber and a cytofluorimeter, respectively. epidermal growth factor (egf) was used as a positive control. western blots were performed to evaluate the cale effects on pathways involved in cell growth regulation and on apoptotic cascade activation.","our results confirm that cale has a high content of polyphenolic compounds (i.e., 32.21 3.44), mainly as flavonoids (24.56 4.67). in all tested cell lines cale treatment reduces cell number in a dose-dependent manner (ed50 175 30 g/ml). cale (100 and 200 g/ml) increases by three-fold the activation of the apoptotic cascade involving caspase-3 activation and the cleavage of its substrate poly(adp-ribose) polymerase (parp). intriguingly, cale treatment (200 g/ml) also blocks egf-induced cell growth by preventing the growth factor-triggered akt and erk phosphorylation. as a whole, these data strongly suggest that cale possesses anticancer effects in all tested cancer cell lines.",Medication
are pulmonary immune responses against aspergillus fumigatus characterized by high frequencies of il-17 producing t-cells?,"in healthy individuals and in patients with invasive aspergillosis, aspergillus-specific t-cells in peripheral blood display mainly a thelper1 phenotype. although in other fungal infections thelper17 immunity is important, it was suggested that in aspergillus infection thelper17 cells do not play a role or may even be detrimental. to compare the cytokine profiles of aspergillus-specific cd4 t-cells in peripheral blood and in the lung. to investigate the thelper phenotype at the primary location of a. fumigatus exposure. lung-derived t-cells and peripheral blood t-cells from copd-patients were stimulated with overlapping peptides of 6 a. fumigatus proteins. aspergillus-specific t-cells were identified on the basis of the activation marker cd154 and production of tnf. in addition, production of the cytokines ifn, il-17, il-4 and il-5 by the aspergillus-specific t-cells was measured. the majority of lung-derived aspergillus-specific t-cells displayed a thelper17 phenotype, and only low percentages of cells produced ifn. in contrast, in the peripheral blood of copd patients aspergillus-specific t-cells displayed a thelper1 phenotype, similar as peripheral blood-derived aspergillus-specific t-cells from healthy individuals.","these data demonstrate that in a. fumigatus infection, similar as in other fungal infections, thelper17 cells may play a more important role in the immune response than was appreciated until now.",Diagnosis
does isoflurane decrease self-renewal capacity of rat cultured neural stem cells?,"in models, isoflurane produces neural and behavioral deficits in vitro and in vivo. this study tested the hypothesis that neural stem cells are adversely affected by isoflurane such that it inhibits proliferation and kills these cells. sprague-dawley rat embryonic neural stem cells were plated onto 96-well plates and treated with isoflurane, 0.7, 1.4, or 2.8, in 21 oxygen for 6 h and fixed either at the end of treatment or 6 or 24 h later. control plates received 21 oxygen under identical conditions. cell proliferation was assessed immunocytochemically using 5-ethynyl-2'-deoxyuridine incorporation and death by propidium iodide staining, lactate dehydrogenase release, and nuclear expression of cleaved caspase 3. data were analyzed at each concentration using an anova; p 0.05 was considered significant. isoflurane did not kill neural stem cells by any measure at any time. isoflurane, 1.4 and 2.8, reduced cell proliferation based upon 5-ethynyl-2'-deoxyuridine incorporation, whereas isoflurane, 0.7, had no effect. at 24 h after treatment, the net effect was a 20-30 decrease in the number of cells in culture.","isoflurane does not kill neural stem cells in vitro. at concentrations at and above the minimum alveolar concentrations required for general anesthesia (1.4 and 2.8), isoflurane inhibits proliferation of these cells but has no such effect at a subminimum alveolar concentration (0.7). these data imply that dosages of isoflurane at and above minimum alveolar concentrations may reduce the pool of neural stem cells in vivo but that lower dosages may be devoid of such effects.",Treatment
does formation of stat5/ppargamma transcriptional complex modulate angiogenic cell bioavailability in diabetes?,"circulating angiogenic cells (cacs) expansion is a multistage process requiring sequential activation of transcriptional factors, including stat5. stat5, in concert with peroxisome proliferator-activated receptors (ppars), seems to induce discrete biological responses in different tissues. in the present study we investigated the role of stat5 and ppargamma in regulating cac expansion in normal and diabetic settings. normal and diabetic cacs were used. sirna technology, emsa, and chromatin immunoprecipitation (chip) assay as well as site-directed mutagenesis of the stat5 response element in the ppargamma promoter enabled us to demonstrate that stat5 transcriptional activity controls ppargamma expression. moreover, facs analysis, coimmunoprecipitation experiments, and chip assay revealed that a stat5/ppargamma transcriptional complex controls cyclin d1 expression and cac progression into the cell-cycle. conversely, ppargamma agonists, by preventing the expression of stat5 and the formation of the stat5/ppargamma heterodimeric complex failed to promote cac expansion. finally, we demonstrated that diabetic cac functional capability can be recovered by molecules able to activate the stat5/ppargamma transcriptional complex.",our data identify the stat5/ppargamma heterodimers as landmark of cac expansion and provide evidences for a mechanism that partially rescues cac bioavailability in diabetic setting.,Medication
does chronic psychosocial stress exacerbate impairment of cognition and long-term potentiation in beta-amyloid rat model of alzheimer 's disease?,"alzheimer's disease (ad) is a degenerative disorder that leads to progressive cognitive decline. alzheimer's disease develops as a result of over-production and aggregation of beta-amyloid (abeta) peptides in the brain. the reason for variation in the gravity of symptoms among ad patients is unknown and might result from patient-related factors including lifestyle. individuals suffering from chronic stress are at an increased risk for developing ad. this study investigated the effect of chronic psychosocial stress in abeta rat model of ad. psychosocial stress was induced with a rat intruder model. the rat model of ad was induced by 14-day osmotic pump infusion of a mixture of 300 pmol/day abeta(1-40)/abeta(1-42). the effect of chronic stress on the severity of abeta-induced spatial learning and memory impairment was tested by three approaches: behavioral testing in the radial arm water maze, in vivo electrophysiological recording in anesthetized rat, and immunoblot analysis to determine protein levels of learning- and memory-related molecules. a marked impairment of learning and memory developed when stress was combined with abeta, more so than that caused by abeta alone. additionally, there was a significantly greater impairment of early-phase long-term potentiation (e-ltp) in chronically stressed/abeta-treated rats than in either the stressed or abeta-treated rats. this might be a manifestation of the reduction in protein levels of calcium/calmodulin-dependent protein kinase ii (camkii) and the abnormal increase in calcineurin levels.",chronic stress significantly intensified abeta-induced deficits of short-term memory and e-ltp by a mechanism involving decreased camkii activation along with increased calcineurin levels.,Symptoms
are amplitude and strength of muscle contraction reduced in experimental tears of the rotator cuff?,"chronic tendon tears lead to retraction, fatty infiltration, and atrophy of the respective muscle. these muscle changes are decision-making criteria in rotator cuff tear management. to investigate the functional implications of these morphological changes in a sheep rotator cuff tear model. controlled laboratory study. the authors established chronic retraction of the musculotendinous unit accompanied with fatty infiltration and atrophy of the infraspinatus muscle in 20 sheep. the contractile force and passive tension of the muscle as a function of its length were measured and the active work capacity determined. after tendon release and chronic retraction (by 5.7 0.9 cm), fatty infiltrated and atrophied infraspinatus muscles (with a density of 22.4 10.4 hounsfield units hu and a cross-sectional area of 65 16 of the contralateral control side) had a mean contractile amplitude and strength of 2.7 0.4 cm and 235 71 n compared with the contralateral control shoulder of 4.1 0.7 cm and 485 78 n (p .05), respectively. the mean active work of the muscle was 2.8 0.9 nm for retracted and 8.8 2.4 nm for control muscles (p .05). the correlation of total active work to fatty infiltration (r 0.78, p .001) was significant.","chronic tendon tears are associated not only with retraction, fatty infiltration, and atrophy but also with loss of strength and contractile amplitude. the functional changes can only indirectly and approximately be predicted by computed tomography imaging findings.",Treatment
is chronic exposure to nicotine associated with reduced reward-related activity in the striatum but not the midbrain?,"the reinforcing effects of nicotine are mediated by brain regions that also support temporal difference error (tde) processing; yet, the impact of nicotine on tde is undetermined. dependent smokers (n 21) and matched control subjects (n 21) were trained to associate a juice reward with a visual cue in a classical conditioning paradigm. subjects subsequently underwent functional magnetic resonance imaging sessions in which they were exposed to trials where they either received juice as temporally predicted or where the juice was withheld (negative tde) and later received unexpectedly (positive tde). subjects were scanned in two sessions that were identical, except that smokers had a transdermal nicotine (21 mg) or placebo patch placed before scanning. analysis focused on regions along the trajectory of mesocorticolimbic and nigrostriatal dopaminergic pathways. there was a reduction in tde-related function in smokers in the striatum, which did not differ as a function of patch manipulation but was predicted by the duration (years) of smoking. activation in midbrain regions was not impacted by group or drug condition.","these data suggest a differential effect of smoking status on the neural substrates of reward in distinct dopaminergic pathway regions, which may be partially attributable to chronic nicotine exposure. the failure of transdermal nicotine to alter reward-related functional processes, either within smokers or between smokers and control subjects, implies that acute nicotine patch administration is insufficient to modify reward processing, which has been linked to abstinence-induced anhedonia in smokers and may play a critical role in smoking relapse.",Medication
does houttuynia cordata induce expression of human beta-defensin-2 mrna in pulmonary epithelial cells in vitro ?,"to explore the effects of houttuynia cordata on expression of human beta-defensin-2 (hbd-2) in pulmonary epithelial cells (spc-a-1) in vitro; and to observe the correlationship between the level of hbd-2 mrna and the concentrations or treatment times of houttuynia cordata. the spc-a-1 cells were cultured with different concentrations of houttuynia cordata in vitro, including 0, 12.5, 25, 50, 100 and 200 microg/ml. and then, the spc-a-1 cells were cultured with the optimal concentration of houttuynia cordata in different lengths of time, including 1, 2, 4, 8, 16 and 24 hours. after the treatment, the mrna level of hbd-2 in pulmonary epithelial cells was detected by means of semi-quantitative reverse transcription polymerase chain reaction (rt-pcr). after being cultured with houttuynia cordata, the expression of hbd-2 mrna had positive correlation with the stimulus concentrations (rs0.829, p0.042) and stimulus time (rs0.914, p0.003). the highest expression of hbd-2 mrna was induced by 100 microg/ml houttuynia cordata after 8-hour treatment. in comparison with the normal control group and the interleukin-1beta group, 100 microg/ml houttuynia cordata could significantly up-regulate the expression of hbd-2 mrna in spc-a-1 cells after 8-hour treatment (p0.01).","houttuynia cordata can up-regulate expression of hbd-2 mrna in spc-a-1 cells, and the highest expression level of hbd-2 mrna can be obtained by culture with 100 microg/ml houttuynia cordata for 8 hours.",Treatment
do glucocorticoids interact with cholinergic system in impairing memory reconsolidation of an inhibitory avoidance task in mice?,"recent studies suggest that glucocorticoids modulate memory reconsolidation. moreover, cholinergic system is involved in memory reconsolidation. since glucocorticoids interact with brain cholinergic system in modulating memory processing, we investigated whether glucocorticoid influences on the reconsolidation of emotionally arousing training depend on the cholinergic system. mice were trained (1ma, 3s footshock) in an inhibitory avoidance task. forty-eight hours after training, memory reactivation was occurred (test 1), and different treatments were given. two (test 2), five (test 3), and seven days (test 4) after memory reactivation (test 1), animals were retested for fear memory retention. in the first experiment, we observed that administration of corticosterone (cort, 0.3, 1 and 3 mg/kg) following memory reactivation impaired subsequent expression of memory in a dose-dependent manner. in the second experiment, we found that cort-induced impairment of memory reconsolidation was reversed by the muscarinic receptor antagonist atropine (0.5 and 2 mg/kg). in the third experiment, the nicotinic receptor antagonist mecaylamine (0.5 or 2 mg/kg) was not able to block the corticosterone response.",these findings indicate that glucocorticoids impair memory reconsolidation by a muscarinic cholinergic mechanism.,Medication
does isoflurane depress electroencephalographic and medial thalamic responses to noxious stimulation via an indirect spinal action?,"anesthetics such as isoflurane act in the spinal cord to suppress movement in response to noxious stimulation. spinal anesthesia decreases hypnotic/sedative requirements, possibly by decreasing afferent transmission of stimuli. we hypothesized that isoflurane action in the spinal cord would similarly depress the ascending transmission of noxious input to the thalamus and cerebral cortex. in six isoflurane-anesthetized goats, we measured electroencephalographic (eeg) and thalamic single-unit responses to a clamp applied to the forelimb. cranial bypass permitted differential isoflurane delivery to the torso and cranial circulations. when the cranial-torso isoflurane combination was 1.3 /- 0.2-1.0 /- 0.4 the noxious stimulus did not evoke significant changes in the eeg or thalamic activity: 389 (153-544) to 581 (172-726) impulses/min, (median, 25th-75th percentile range, p: 0.05). when the cranial-torso isoflurane combination was 1.3 /- 0.2-0.3 /- 0.2, noxious stimulation increased thalamic activity: 804 (366-1162) to 1124 (766-1865) impulses/min (p: 0.05), or eeg activity. the indirect torso effect of isoflurane on evoked eeg total power (12.6 /- 2.7 microv(2)/vol, mean /- se) was quantitatively similar to the direct cranial effect (17.7 /- 3.0 microv(2)/vol; p: 0.05). these data suggest that isoflurane acts in the spinal cord to blunt the transmission of noxious inputs to the thalamus and cerebral cortex, and thus might indirectly contribute to anesthetic endpoints such as amnesia and unconsciousness.","isoflurane action in the spinal cord diminished the transmission of noxious input to the brain. because memory and consciousness are likely dependent on the ""arousal"" state of the brain, this indirect action of isoflurane could contribute to anesthetic-induced amnesia and unconsciousness.",Medication
does c-reactive protein predict tumor necrosis factor-alpha blocker retention rate in axial ankylosing spondylitis?,"in ankylosing spondylitis (as), tumor necrosis factor (tnf) blockers are recommended for patients with high symptomatic disease activity. few data are available about objective signs of inflammation such as increased c-reactive protein (crp). we assessed the retention rate of tnf blockers in patients with axial as, according to baseline crp and other potentially predictive measures. a retrospective study of all patients treated with tnf blockers for axial as. retention rate was evaluated using a survival-data analysis technique with discontinuation of the drug because of inefficacy (kaplan-meier method). potential factors explaining the retention rates (demographic and clinical indicators and crp) were evaluated using log-rank tests and a cox proportional-hazards regression model. for axial as, 175 patients received tnf blockers (men 78, mean disease duration 12.4 /- 9.1 yrs); 100 patients (of 143 with available data) had an increased crp ( 10 mg/l). an increased crp at baseline was the only variable explaining the retention rate in the cox model (p 0.003, hazard ratio 3.3, 95 ci 1.5-7.3).","interruption for expert opinion of inefficacy was more frequent for patients with low baseline crp; however, even in these patients retention was high. increased crp should not be considered mandatory for proposing tnf blocker treatment in axial as.",Medication
is a history of ischemic heart disease a common cause of wheezing in the elderly of a japanese local community?,"we conducted a cross-sectional study to investigate which factors have a significant impact on wheezing and qol in the elderly of a japanese local community. in 2008, 527 participants (250 participants aged 45 to 64 years and 277 participants aged 65 to 88 years) responded to the questionnaire regarding wheezing and disease history. qol was evaluated by the short form-8. the participants underwent airway reversibility testing. the plasma levels of ige were measured. the plasma levels of n-terminal-pro-b-type natriuretic peptide were measured in twenty-one participants with a history of ischemic heart disease and in thirty-five age-matched participants without that history. wheezing was reported by 50 (9.5) participants and was associated with a lower score of qol. in multivariate analysis, wheezing was associated with sex (or 3.12, ci 1.10-9.67) and a history of bronchial asthma (or 22.3, ci 6.50-84.0) among participants aged 45 to 64 years. among participants aged 65 and over, wheezing was associated with a history of bronchial asthma (or 4.86, ci 1.39-15.1) and ischemic heart disease (or 5.12, ci 1.61-15.0). participants with both a history of ischemic heart disease and wheezing showed higher levels of n-terminal-pro-b-type natriuretic peptide. airway reversibility was only associated with a history of ischemic heart disease (or 4.65, ci 1.26-17.6).",it is suggested that bronchial asthma and heart disease are both significant causes of wheezing and affect the qol in the elderly of a japanese local community.,Medication
do cardiovascular risk factors predict survival in middle-aged men during 50 years?,"we aimed at studying the expectancy of life in middle-aged men as a function of several personal characteristics and risk factors. a sample of 1712 italian men aged 40-59, first examined in 1960, was followed-up for mortality for 50 years. the length of survival was estimated as a function of 48 personal characteristics and risk factors using the multiple linear regression. in 50 years 1672 men died (97.7) and 40 survived (2.3). twenty risk factors, most of which were never measured in previous studies of such duration, proved to be significant, for the estimation of survival with an overall adjusted r(2) of 0.3236. they were: age, 4 anthropometric measurements (body mass index, and its squared term, laterality-linearity index, shoulder/pelvis shape), mean blood pressure, father and mother history of premature (65-year) death, marital status, arm circumference, 2 respiratory measurements (vital capacity and forced expiratory volume), serum cholesterol, corneal arcus, xantelasma, cancer, cardiovascular diseases, diabetes and chronic bronchitis. coefficients of 5 suitable risk factors became definitely larger after adjustment for regression dilution bias with 5 year data. all 40 cases of survival were located in the higher 5 deciles of estimated survival and 25 (62.5) were in the upper decile.","a small number of risk factors and personal characteristics, mainly known as cardiovascular risk factors and measured once in middle-aged men, are strongly associated with the length of survival in a 50-year follow-up.",Prevention
does gene therapy attenuate the elevated blood pressure and glucose intolerance in an insulin-resistant model of hypertension?,"fructose feeding in male sprague-dawley (sd) rats results in a mild hypertension and glucose intolerance. although the mechanism of this glucose intolerance and hypertension is not completely understood, a role for the renin-angiotensin system (ras) has been proposed. in the current study our aim was to test the hypothesis that intervention of the ras with a gene therapy approach would be effective in preventing the development of hypertension and glucose intolerance in this animal model. five-day-old sd rats were administered either an empty retroviral vector (lnsv) or retroviral vector containing at1 receptor antisense dna (at1r-as). the virus (25 microl, 8 x 10(9) cfu/ml) was injected into the heart and the animals were returned to their mothers. after weaning, half the animals from each group were placed on breeder's chow or a 60 fructose diet. indirect blood pressures (bp) were determined and an oral glucose tolerance test (ogtt) was performed when the animals had been on the respective diets for 2 months. fructose-fed animals developed mild hypertension (145 /- 3 versus 132 /- 4 mmhg) by 6 weeks of dietary intervention. this increase in bp was prevented by at1r-as treatment (125 /- 3 mmhg). at 2 months of age, fasting blood glucose was comparable among the four groups; however, the glucose excursion during the ogtt was significantly greater and more prolonged in the lnsv-treated, fructose-fed group than the other three groups. at1r-as treatment significantly prevented glucose intolerance in the fructose rat to levels observed in the controls.","early fructose dietary treatment results in moderate hypertension and glucose intolerance, which is prevented by a single neonatal treatment with at1r-as. these results suggest that the ras is involved in the glucose intolerance associated with fructose feeding and that genetic intervention is effective in this rat model.",Medication
does star-shaped tetraspermine enhance cellular uptake and cytotoxicity of t-oligo in prostate cancer cells?,"an oligonucleotide termed 't-oligo' having sequence homology with telomere overhang has shown cytotoxicity in multiple cancers. we have demonstrated that t-oligo can induce apoptosis in androgen independent prostate cancer cell line du-145. in this report, we evaluate the use of star-shaped tetraspermine (ssts) for delivery of t-oligo. ssts was synthesized from spermine and its intrinsic cytotoxicity towards du-145 cells was compared with spermine and branched polyethyleneimine (bpei). atomistic molecular dynamic (md) simulations were conducted to understand binding and complexation of spermine and ssts with t-oligo. complexation was also determined using gel electrophoresis and sybr gold assay. complexes were characterized for size, cellular uptake and antiproliferative effect. ssts exhibited significantly lower toxicity than spermine and bpei. its affinity towards t-oligo was significantly higher than spermine as determined by experimental studies and confirmed by md simulations and it formed stable complexes (tonps) with t-oligo. tonps facilitated cellular uptake and nuclear accumulation of t-oligo and their cytotoxic potential was observed at concentration several folds lower than that required for t-oligo alone.",ssts significantly enhanced therapeutic benefits associated with the use of t-oligo and can be developed as a delivery vehicle for its in-vivo therapeutic applications.,Medication
does epitope analysis following active immunization with tau proteins reveal immunogens implicated in tau pathogenesis?,"abnormal tau hyperphosphorylation and its accumulation into intra-neuronal neurofibrillary tangles are linked to neurodegeneration in alzheimer's disease and similar tauopathies. one strategy to reduce accumulation is through immunization, but the most immunogenic tau epitopes have so far remained unknown. to fill this gap, we immunized mice with recombinant tau to build a map of the most immunogenic tau epitopes. non-transgenic and rtg4510 tau transgenic mice aged 5 months were immunized with either human wild-type tau (wt, 4r0n) or p301l tau (4r0n). each protein was formulated in quil a adjuvant. sera and splenocytes of vaccinated mice were collected to assess the humoral and cellular immune responses to tau. we employed a peptide array assay to identify the most effective epitopes. brain histology was utilized to measure the effects of vaccination on tau pathology and inflammation. humoral immune responses following immunization demonstrated robust antibody titers (up to 1:80,000 endpoint titers) to each tau species in both mice models. the number of ifn- producing t cells and their proliferation were also increased in splenocytes from immunized mice, indicating an increased cellular immune response, and tau levels and neuroinflammation were both reduced. we identified five immunogenic motifs within either the n-terminal (9-15 and 21-27 amino acids), proline rich (168-174 and 220-228 amino acids), or the c-terminal regions (427-438 amino acids) of the wild-type and p301l tau protein sequence.","our study identifies five previously unknown immunogenic motifs of wild-type and mutated (p301l) tau protein. immunization with both proteins resulted in reduced tau pathology and neuroinflammation in a tau transgenic model, supporting the efficacy of tau immunotherapy in tauopathy.",Medication
"is fifth vaccination with dipthteria , tetanus and acellular pertussis beneficial in four- to six-year-olds?","diphtheria, tetanus and pertussis serum antibody titers were assessed before a fifth dose of diphtheria-tetanus-acellular pertussis (dtap) or diphtheria-tetanus-whole cell pertussis (dtwp) vaccination at age 4 to 6 years. healthy children who had participated in a series of national institutes of health-sponsored trials assessing dtwp and dtap vaccines provided prevaccination sera before a fifth dose of dtwp or dtap. the trial design was prospective, randomized and double blind. diphtheria, tetanus and pertussis antibody titers were measured by enzyme-linked immunosorbent assay. pertussis results are expressed in enzyme-linked immunosorbent assay units/ml based on us food and drug administration reference sera. tetanus and diphtheria toxin concentrations are expressed in iu/ml with a who international reference sera as a standard. for diphtheria 100 of the children had antibody titers above the minimum protective level of 0.01 iu/ml and 86 to 100 (depending on prior vaccine product) had titers 0.1 iu/ml. however, only 0 to 40 of the children had antibody titers or 1.0 iu/ml, a titer associated with more certain durable protection. for tetanus none of the children had an antibody titer below 0.01 iu/ml, and 93 to 100 had titers or 0.1 iu/ml, a titer associated with more certain, durable protection. for pertussis the geometric mean concentrations of antibody before booster were uniformly very low, and the percentage of children exceeding the minimum detectable titer of antibody by 4-fold was also low.","before a 4- to 6-year-old booster, a large proportion of children have titers of antibody to diphtheria below the certain, durable protective level. because serologic correlates and minimum protective titers of antibody to pertussis antigens have not been established, the relevance of the low titers determined in the current study is unknown but a potential concern.",Medication
is the defect of both angiogenesis and lymphangiogenesis involved in preeclampsia?,"pre-eclampsia (pe) is characterized by failed remodeling of maternal vessels perfusing the placenta. blood vessels and lymphatic system are involved in vessel remodeling and flow homeostasis in the uterus during pregnancy. this study aims to investigate the involvement of angiogenesis and lymphangiogenesis in pe. placental and decidual tissues were obtained from pregnancies with pe (n 90), including pe cases with decidual vasculopathy (dv) (n 52) and without dv (n 38), and healthy pregnancies (control, n 20). the clinical characteristics of these groups were analyzed. the expression levels of vegf1, cd34, prox-1, vegfr3, and cd31 in the placenta and decidua were detected through immunohistochemistry, reverse-transcription polymerase chain reaction, and western blot. the lymphangiogenic markers prox-1 and vegfr3 were negatively expressed in the placenta but positively expressed in the decidua. the expression levels of the angiogenic markers vegf1 and cd34 and the panendothelial marker cd31 were significantly lower in the placenta and decidua of the pe group than in those of the control group. the expression levels of vegf1, cd34, and cd31 were significantly lower in the placenta and decidua with dv than in those without dv. furthermore, the expression trends of prox-1 and vegfr3 was similar to those of vegf1, cd34, and cd31 among the groups.","lymphangiogenesis occurred in the decidua but not in the placenta. impaired angiogenesis and lymphangiogenesis were associated with pe, particularly in the presence of dv.",Diagnosis
does cardiac pet/ct misregistration cause significant changes in estimated myocardial blood flow?,"misregistration of cardiac pet/ct data can lead to misinterpretation of regional myocardial perfusion. however, the effect of misregistration on the quantification of myocardial blood flow (mbf) has not been studied. cardiac (82)rb-pet/ct scans of 10 patients with normal regional myocardial perfusion were analyzed. realignment was done for the baseline and stress pet/ct images as necessary, and mbf was obtained from dynamic data. then, the stress images were misregistered by 5 mm along the x-axis (left) and z-axis (cranial) and again by 10 mm. a 10-mm misregistration in the opposite direction (-10 mm along the x-axis right and z-axis caudal) was also tested. stress mbf was recalculated for 5-, 10-, and -10-mm misregistrations. stress mbf of the left ventricle decreased by 10 6 (p 0.005) after 5-mm misregistration and by 24 15 (p 0.001) after 10-mm misregistration. in descending order, the most important stress mbf changes occurred in the anterior (39 9), lateral (34 9), apical (20 16), inferior (12 10), and septal (10 12) walls after 10-mm misregistration. lesser changes were observed after 5-mm misregistration, with the same wall distribution. in contrast, -10-mm misregistration increased global mbf by 9 6 (p 0.004). in descending order, the overestimation of estimated mbf after -10-mm misregistration occurred in the lateral (15 8), apical (15 18), anterior (9 5), and inferior (9 11) walls.",misregistration of the stress pet/ct dataset leads to significant global and regional artifactual alterations in the estimated mbf. quantitative error was observed throughout the myocardium and was not confined to those heart regions that extended into the lung on misregistered ct.,Diagnosis
is telomere length a determinant of emphysema susceptibility?,"germline mutations in the enzyme telomerase cause telomere shortening, and have their most common clinical manifestation in age-related lung disease that manifests as idiopathic pulmonary fibrosis. short telomeres are also a unique heritable trait that is acquired with age. we sought to understand the mechanisms by which telomerase deficiency contributes to lung disease. we studied telomerase null mice with short telomeres. although they have no baseline histologic defects, when mice with short telomeres are exposed to chronic cigarette smoke, in contrast with controls, they develop emphysematous air space enlargement. the emphysema susceptibility did not depend on circulating cell genotype, because mice with short telomeres developed emphysema even when transplanted with wild-type bone marrow. in lung epithelium, cigarette smoke exposure caused additive dna damage to telomere dysfunction, which limited their proliferative recovery, and coincided with a failure to down-regulate p21, a mediator of cellular senescence, and we show here, a determinant of alveolar epithelial cell cycle progression. we also report early onset of emphysema, in addition to pulmonary fibrosis, in a family with a germline deletion in the box h domain of the rna component of telomerase.","our data indicate that short telomeres lower the threshold of cigarette smoke-induced damage, and implicate telomere length as a genetic susceptibility factor in emphysema, potentially contributing to its age-related onset in humans.",Symptoms
does persistent downregulation of hippocampal creb mrna parallel a y-maze deficit in adolescent rats following semi-chronic amphetamine administration?,"we investigated possible differences in the impact of chronic amphetamine administration during adolescence and adulthood on aspects of behaviour and brain chemistry. adult (n32) and adolescent (n32) male sprague-dawley rats were given either d-amphetamine sulphate (10 mg kg(-1) daily, i.p.) or saline (1 ml kg(-1), i.p.) for 10 days. rats were subsequently tested for anxiety-like behaviour, learning and memory, and sensorimotor gating. nine weeks later, rats received saline (1 ml kg(-1)) or acute amphetamine challenge (1.5 mg kg(-1)) and the expression levels of mrna for tyrosine kinase b (trkb) or camp response element-binding protein (creb) were measured in the hippocampus. the adolescent amphetamine pretreated group revealed a deficit in exploration on the y-maze during a 6 h retention test. the frequency of visits to the novel arm was 35 lower for the amphetamine group compared with controls. in parallel, a 43 decrease in hippocampal creb mrna, but not trkb mrna, was observed in periadolescent rats treated chronically with amphetamine 9 weeks earlier. none of the effects were detected in the adult treated cohort.","chronic amphetamine treatment during periadolescence resulted in altered behaviour on the y-maze and persistent downregulation of hippocampal creb mrna expression. given that this group had intact spatial learning and reference memory, it would appear that the deficits observed on the y-maze reflect a dysfunction in response to novelty. because no effects of amphetamine treatment were observed in the adult cohort, these data suggest idiosyncratic sensitivity of periadolescence to the long-term effects of psychostimulants.",Treatment
is pioglitazone inhibition of lipopolysaccharide-induced nitric oxide synthase associated with altered activity of p38 map kinase and pi3k/akt?,"previous studies have suggested that peroxisome proliferator activated receptor-gamma (ppar-gamma)-mediated neuroprotection involves inhibition of microglial activation and decreased expression and activity of inducible nitric oxide synthase (inos); however, the underlying molecular mechanisms have not yet been well established. in the present study we explored: (1) the effect of the ppar-gamma agonist pioglitazone on lipopolysaccharide (lps)-induced inos activity and nitric oxide (no) generation by microglia; (2) the differential role of p38 mitogen-activated protein kinase (p38 mapk), c-jun nh(2)-terminal kinase (jnk), and phosphoinositide 3-kinase (pi3k) on lps-induced no generation; and (3) the regulation of p38 mapk, jnk, and pi3k by pioglitazone. mesencephalic neuron-microglia mixed cultures, and microglia-enriched cultures were treated with pioglitazone and/or lps. the protein levels of inos, p38 mapk, jnk, ppar-gamma, pi3k, and protein kinase b (akt) were measured by western blot. different specific inhibitors of inos, p38mapk, jnk, pi3k, and akt were used in our experiment, and no generation was measured using a nitrite oxide assay kit. tyrosine hydroxylase (th)-positive neurons were counted in mesencephalic neuron-microglia mixed cultures. our results showed that pioglitazone inhibits lps-induced inos expression and no generation, and inhibition of inos is sufficient to protect dopaminergic neurons against lps insult. in addition, inhibition of p38 mapk, but not jnk, prevented lps-induced no generation. further, and of interest, pioglitazone inhibited lps-induced phosphorylation of p38 mapk. wortmannin, a specific pi3k inhibitor, enhanced p38 mapk phosphorylation upon lps stimulation of microglia. elevations of phosphorylated ppar-gamma, pi3k, and akt levels were observed with pioglitazone treatment, and inhibition of pi3k activity enhanced lps-induced no production. furthermore, wortmannin prevented the inhibitory effect of pioglitazone on the lps-induced no increase.","we demonstrate that pioglitazone protects dopaminergic neurons against lps insult at least via inhibiting inos expression and no generation, which is potentially mediated via inhibition of p38 mapk activity. in addition, the pi3k pathway actively participates in the negative regulation of lps-induced no production. our findings suggest that ppar-gamma activation may involve differential regulation of p38 mapk and of the pi3k/akt pathway in the regulation of the inflammatory process.",Medication
does cyr61 downregulation correlate with tumor progression by promoting mmp-7 expression in human gastric carcinoma?,"cyr61 (cysteine-rich 61) belongs to the ccn (cyr61/ctgf/nov) protein family and is involved in tumorigenesis. we have previously confirmed that the level of cyr61 protein is decreased in gastric carcinoma compared with nontumoral mucosa, by conducting proteome-based analyses. in this study, we examine the relationship between cyr61 expression and clinicopathological data of mmp-7 expression in human gastric mucosae and tumors. immunohistochemical and/or immunofluorescence analyses were performed to examine the histological expression of cyr61 in normal gastric mucosa, intestinal metaplasia, 33 adenomas, and 127 carcinomas. seven gastric carcinoma cell lines were used to examine the expression of cyr61 and mmp-7 by western blotting. the cyr61-expressing cells mostly coincided with the serotonin-containing cells, not only in nontumoral epithelia, but also among tumor cells. cyr61 expression was positive (labeling index: 2) in 43 of 49 early gastric carcinomas (87.8) and in 19 of 78 advanced gastric carcinomas (24.4), the frequency being significantly lower in the latter (p 0.001). all the normal mucosae, intestinal metaplasias and adenomas were in the positive group. the reduction in cyr61 expression correlated significantly with histological differentiation (p 0.05), depth of invasion (p 0.001), lymphatic invasion (p 0.001), venous invasion (p 0.001), lymph node metastasis (p 0.001) and clinical stage (p 0.001). immunohistochemistry and western blotting revealed the expression of cyr61 to be inversely correlated with that of mmp-7 (p 0.001).","cyr61 is expressed in serotonin-containing cells, and downregulation of the expression might contribute to the progression of cancer by promoting mmp-7 expression in human gastric carcinomas.",General
does epidemiological progress of hemorrhagic fever with renal syndrome in china?,"to summarize the major achievements of chinese work on the epidemiology and prevention of hemorrhagic fever with renal syndrome (hfrs) in recent years, and to give a general review on the present situation of hfrs in china. reviews and papers published in chinese journals, relevant to the objectives, written or collected by the author; and the research work of the author. an outline was drafted according to the purpose given above, and the relevant materials and data were grouped together into different items outlined. all the materials and data extracted were published or specially assessed. hfrs was first recognized in the northeastern china in 1931. it has been found prevalent also in many other parts of china since 1955, and presently, 28 out of 31 provinces (autonomous regions, or municipalities) have been proved to be its endemic areas. the total number of cases is 1,256,431 from 1950 to 1997, with 44,304 death (3.53). 50-100 thousands of cases could be registered annually since 1981 when the presence of the rattus-type hfrs was first identified serologically in china, with the highest peak in 1986 (115,985 cases). three types of endemicity have been differentiated: the apodemus-type, the rattus-type and the mixed type of the two, by their peculiar seasonal distributions of cases and by methods of serotyping (hi, mabs serotyping kits). the epidemiologic features of the rattus-type hfrs are quite different from that of the apodemus-type. 67 species of vertebrates were found to harbor hantavirus antigen or antibodies, but the chief or primary reservoir hosts are apodemus agrarius and rattus norvegicus only. besides the commonly recognized enzootic mode of transmission (via contacts with the reservoir rodents or their excreta), mite transmission (including certain species of gamasid mites, and chigger mites) has been identified as the potential vectors and reservoir hosts with hfrs. vertical transmission had been found in pregnant patients with hfrs, and in all three chief host rodents (apodemus agrarius, rattus norvegicus, the laboratory rats). the relatively high inapparent infection rates in the population of endemic areas of the rattus-type hfrs after big outbreaks (8-20) are suggested to play a significant role in the gradual decline of the incidence of hfrs in that areas. three kinds of inactivated vaccines against hfrs (the golden hamster kidney cell vaccine, the mongolian gerbil kidney cell vaccine and the purified suckling mouse brain vaccine) have been successively developed and proved highly effective in the prevention of hfrs.","chinese workers on the epidemiology and prevention of hfrs in china have accomplished great achievements since 1981. as the relatively high annual incidence of hfrs sustained in recent years, control measures have to be reinforced. many problems of hfrs and hantavirus infections are still not well understood or unclear, such as the poly-host nature, and the multi-modes of transmission, the natural history of hantaviruses and their genetic variation occurred in nature etc. the task for effective control of hfrs and the research on its epidemiology in china should be held on a high priority.",Prevention
does synthetic retinoid cd437 induce s-phase arrest and apoptosis in human prostate cancer cells lncap and pc-3?,"exposure of prostate carcinoma cell lines to retinoids, which function through the classical retinoic acid nuclear receptor, (rars) or retinoid x receptors (rxrs), results in minimal cytostatic inhibition of cell proliferation. growth inhibition and various regulatory responses were investigated in two human prostate carcinoma cell lines (lncap and pc-3) treated with or without a synthetic retinoid, cd 437. incubation of prostate carcinoma cell lines with a novel retinoid cd437 resulted in the marked inhibition of proliferation. lncap and pc-3 possessed ic50 values for cd437 of 375 nm and 550 nm, respectively. incubation with 1 microm cd437 for 24 hr resulted in 100 and 60 inhibition of growth in lncap and pc-3 cells, respectively. simultaneously, cell flow cytometric analyses revealed a dramatic increase of the cell population in s phase, in both lncap (from 38.6 up to 86.7) and pc-3 (27.9 to 55.7), and a decreased proportion of cells in g2 phase, in lncap (from 23.7 down to 1.2) and pc-3 (14.9 to 2.2), indicating a significant s-phase arrest. the cell growth inhibition and s-phase arrest in these cells were followed by apoptosis, as revealed by the acquisition of the characteristic cell morphology including the appearance of apoptotic bodies, and further confirmed by cellular dna fragmentation. cd437-induced-s phase arrest was associated with upregulated mrna levels of p21waf1/cip1/sdi1 in both lncap (p53/) and pc-3 (53-/-) cells.","cd437 represents a unique retinoid that induces s-phase arrest and apoptosis in both androgen-dependent (lncap) and -independent (pc-3) human prostate cancer cells, suggesting a potential role of cd437 in the treatment of human prostate cancer.",Medication
is new prognostic indicator useful for predicting the survival of patients with unresectable advanced colorectal cancer?,"complete resection of tumors is possible after heavy chemotherapy in a few patients with unresectable colorectal cancer (ucrc). this study evaluated the ability of new prognostic score to identify such patients. four peripheral blood markers were evaluated in 50 patients diagnosed with ucrc at the time of patients' first visit to the hospital: c-reactive protein (crp), albumin (alb), neutrophil/lymphocyte ratio (nlr), and carcinoembryonic antigen (cea). each was scored 1 or 0 for that marker. for example, when patient shows crp 1.0 mg/dl, alb 3.5 g/dl, nlr 5, and cea 10 ng/ml, his score is 4. thus, patients' scores could range from 0 to 4. the median survival time (mst) of the 15 patients with scores 0 and 1 was longer than that of the 35 with scores 2, 3, and 4 (35 vs. 6 months, p 0.001). r0 operation after treatment was performed in 2 patients (4) with score 0 and 1.",our prognostic score is useful in selecting patients with ucrc who will survive.,Diagnosis
do current termination of resuscitation ( tor ) guidelines predict neurologically favorable outcome in japan?,"it is unclear whether the basic life support (bls) and advanced life support (als) pre-hospital termination of resuscitation (tor) rules developed in north america can be applied successfully to patients with out-of-hospital cardiac arrest (ohca) in other countries. to assess the performance of the bls and als tor in japan. retrospective nationwide, population-based, observational cohort study of consecutive ohca patients with emergency responder resuscitation attempts from 1 january 2005 to 31 december 2009 in japan. the bls tor rule has 3 criteria whereas the als tor rule includes 2 additional criteria. we extracted ohca patients meeting all criteria for each tor rule, and calculated the specificity and positive predictive value (ppv) of each tor rule for identifying ohca patients who did not have neurologically favorable one-month survival. during the study-period, 151,152 cases were available to evaluate the bls tor rule, and 137,986 cases to evaluate the als tor rule. of 113,140 patients that satisfied all three criteria for the bls tor rule, 193 (0.2) had a neurologically favorable one-month survival. the specificity of bls tor rule was 0.968 (95 ci: 0.963-0.972), and the ppv was 0.998 (95 ci: 0.998-0.999) for predicting lack of neurologically favorable one-month survival. of 41,030 patients that satisfied all five criteria for the als tor rule, just 37 (0.1) had a neurologically favorable one-month survival. the specificity of als tor rule was 0.981 (95 ci: 0.973-0.986), and the ppv was 0.999 (95 ci: 0.998-0.999) for predicting lack of neurologically favorable one-month survival.","the prehospital bls and als tor rules performed well in japan with high specificity and ppv for predicting lack of neurologically favorable one-month survival in japan. however, the specificity and ppv were not 1000 and we have to develop more specific tor rules.",Diagnosis
is quality of life before and after heart valve surgery influenced by gender and type of valve?,"quality of life (qol) in valvular surgery may differ according to the underlying pathology and surgical technique used. 82 adults undergoing their first elective surgery for valve repair (vp; n 9) or valve replacement (vr) with a mechanical valve (mvr; n 57) or bioprosthesis (bvr; n 16) were assessed before surgery and three months afterwards. delta scores (postoperative-preoperative) on qol measures (quality of life systemic inventory (qlsi) and sf-36). paired t tests and ancovas with age and preoperative qol scores as covariates. qol improves after surgery according to most subscales. according to group comparisons, patients with an mvr improve more than those with a bvr on the mental health subscale. in physical roles, patients with an mvr improve while those with a bvr deteriorate. in emotional roles, patients with a vr improve while those with a vp deteriorate. however, they are similar on all other subscales. women improve more than men on leisure, affectivity and social functioning while the opposite holds true for mental health.","qol improves after surgery. however, significant differences between groups are small because of a lack of statistical power.",Treatment
is routine review of ascites fluid from patients with cirrhosis or hepatocellular carcinoma a low-yield procedure : an observational study?,"patients with cirrhosis develop ascites for physiologic reasons that are unrelated to malignant progression. however, physicians performing paracentesis in these patients, often send fluid to the cytology laboratory, sometimes specifically looking for hepatocellular carcinoma (hcc). we have investigated the diagnostic yield of these specimens. a computerized pathology database search for all ascites fluid cases submitted to the cytology laboratory at a major liver transplant center between november 2004 and april 2008 was performed. clinical history was obtained for each case. patients with cirrhosis, with or without hcc, were included in the study. cytologic diagnoses were compiled and follow-up information was obtained for cases with non-negative findings. a total of 167 specimens from 133 patients ranging from 29 to 85 years of age (mean 56 years) were submitted over the said time period. the causes of cirrhosis included: alcohol - 44; hepatitis c - 30; hepatitis b - 6; non-alcoholic steatohepatitis - 7; cryptogenic - 18; other single causes - 6; and multifactorial (alcohol and hepatitis viruses) - 22. hepatocellular carcinoma (hcc) was present or strongly suspected in 17 patients and had been previously resected in two others. the status of fifteen patients was post liver transplant, with recurrent liver failure. human immunodeficiency virus was present in seven patients and eight patients had a history of non hepatic malignancies. among the specimens, 162 were negative, two had atypical lymphocytes worked up for lymphoma, and three had atypical epithelioid cells; none was positive for hcc. immunohistochemistry demonstrated a mesothelial origin for the atypical epithelioid cells in two cases; in the third case, the patient died shortly after the specimen was collected, with no radiological evidence of hcc.","ascites fluid cytology specimens in patients with cirrhosis, even those known or suspected to have hcc, are almost always negative. atypical cells seen in such specimens should be treated with skepticism since the likelihood that they represent peritoneal spread of hcc is low..",Treatment
does trail induce apoptosis in human colorectal adenoma cell lines and human colorectal adenomas?,"recombinant human (rh) tumor necrosis factor-related apoptosis-inducing ligand (trail) is a potential new anticancer drug which can induce apoptosis in colorectal cancer cell lines. the aim of this study was to investigate whether it is possible to induce apoptosis in human adenoma cell lines and human adenomas using rhtrail. two human adenoma cell lines were exposed to 0.1 microg/ml of rhtrail for 5 hours. apoptosis and caspase activation in cell lines were evaluated using immunocytochemistry, fluorimetric caspase assays, and western blotting. short-term explant cultures were established from freshly removed human adenomas (n 38) and biopsies of normal colon epithelium (n 15), and these were incubated for 5 hours in the presence or absence of 1 microg/ml of rhtrail. apoptosis was determined in paraffin-embedded tissue using morphologic criteria and cleaved caspase-3 staining. in the adenoma cell lines, rhtrail induced up to 55 apoptosis. this coincided with caspase-8 and caspase-3 activation and could be inhibited by a pan-caspase inhibitor. rhtrail induced caspase-dependent apoptosis in adenomas with high-grade dysplasia (n 21) compared with the paired untreated counterparts (apoptotic index, 34 /- 5 versus 17 /- 2, mean /- se; p 0.002), but not in adenomas with low-grade dysplasia (n 17) or in normal colon epithelium (n 15).","colorectal adenoma cell lines and adenomas with high-grade dysplasia are sensitive to rhtrail-induced apoptosis, whereas normal colon epithelium is not. this suggests the potential application of rhtrail in the treatment of adenomas with high-grade dysplasia.",Medication
does iterative sub-network component analysis enable reconstruction of large scale genetic networks?,"network component analysis (nca) became a popular tool to understand complex regulatory networks. the method uses high-throughput gene expression data and a priori topology to reconstruct transcription factor activity profiles. current nca algorithms are constrained by several conditions posed on the network topology, to guarantee unique reconstruction (termed compliancy). however, the restrictions these conditions pose are not necessarily true from biological perspective and they force network size reduction, pruning potentially important components. to address this, we developed a novel, iterative sub-network component analysis (isnca) for reconstructing networks at any size. by dividing the initial network into smaller, compliant subnetworks, the algorithm first predicts the reconstruction of each subnetwork using standard nca algorithms. it then subtracts from the reconstruction the contribution of the shared components from the other subnetwork. we tested the isnca on real, large datasets using various nca algorithms. the size of the networks we tested and the accuracy of the reconstruction increased significantly. importantly, foxa1, atf2, atf3 and many other known key regulators in breast cancer could not be incorporated by any nca algorithm because of the necessary conditions. however, their temporal activities could be reconstructed by our algorithm, and therefore their involvement in breast cancer could be analyzed.","our framework enables reconstruction of large gene expression data networks, without reducing their size or pruning potentially important components, and at the same time rendering the results more biological plausible. our isnca method is not only suitable for prediction of key regulators in cancer studies, but it can be applied to any high-throughput gene expression data.",Treatment
is overexpression of cks1 associated with poor survival by inhibiting apoptosis in breast cancer?,"the present study was undertaken to examine the amplification and expression status of cks1 in breast cancer and its significance. the amplification and expression status of cks1 gene was examined by fish, real-time pcr and immunohistochemistry, respectively. rna interference was used to detect the effects of cks1 on migration, invasion, cell cycle progress and apoptosis of breast cancer cells. cks1 gene amplification was highly correlated with protein overexpression. overexpression of cks1 was strongly associated with lymph node metastasis and poor prognosis (p 0.000, 95 ci (0.00-0.02); p 0.008, 95 ci (0.001-0.05), respectively). knockdown of cks1 expression by rna interference inhibited the cell cycle progress, migration and invasion ability of breast cancer cells. moreover, overexpression of cks1 inhibited apoptosis of breast cancer cells through mek-erk pathway.",cks1 may be considered as potential novel prognostic markers and targets for the future development of specific therapeutic interventions in breast cancer.,Diagnosis
does high resolution optical mapping reveal conduction slowing in connexin43 deficient mice?,"analysis of mice with genetically altered expression of cardiac connexins can provide insights into the role of individual gap junction channel proteins in cell-to-cell communication, impulse propagation, and arrhythmias. however, conflicting results have been reported regarding conduction velocity slowing in mice heterozygous for a null mutation in the gene encoding connexin43 (cx43). high-resolution optical mapping was used to record action potentials from 256 sites, simultaneously, on the ventricular surface of langendorff perfused hearts from 15 heterozygous (cx43/-) and 8 wildtype (cx43/) mice (controls). a sensitive method for measuring epicardial conduction velocity was developed to minimize confounding influences of subepicardial breakthrough and virtual electrode effects. epicardial conduction velocity was significantly slower (23 to 35, p0.01) in cx43/- mice compared to wildtype. there was no change in conduction patterns or anisotropic ratio (cx43/- 1.54/-0.33; cx43/ 1.57/-0.17) suggesting that cx43 expression was reduced uniformly throughout myocardium. the magnitude of reductions in conduction velocity and cx43 protein expression (45) were similar in mice in which the null allele occurred in a pure c57bl/6j genetic background versus a mixed (c57bl/6j x 129) background. action potential duration did not differ between mice of different genotypes.",a approximately 50 reduction of cx43 expression causes significant conduction velocity slowing in the cx43/- mouse heart. the apparent lack of conduction velocity changes reported in previous studies may be related to technical factors rather than variations in genetic background. high-resolution optical mapping is a powerful tool for investigating molecular determinants of propagation and arrhythmias in genetically engineered mice.,General
is the combination of tumor necrosis factor-related apoptosis-inducing ligand ( trail/apo2l ) and genistein effective in inhibiting pancreatic cancer growth?,"our previous studies have shown that, contrary to many other human pancreatic adenocarcinoma cell lines, aspc1 cells are resistant to the apoptotic effect of the tumor necrosis factor-related apoptosis-inducing ligand, also called apo2l (trail/apo2l). in our in vitro studies, the combination of trail/apo2l and protein synthesis inhibitor, genistein, but not genistein alone, was, however, effective in inducing apoptosis in aspc1 cells. in the present study, we examined the effect of trail/apo2l with genistein on the growth of aspc1 cells in vitro and in vivo. mice with orthotopically transplanted aspc1 cells were treated either with trail/apo2l, genistein (gen) or a combination of both (trail/apo2l gen) for 14 days. after 14 days, the size and weight of the tumors were registered and the apoptosis of the tumor cells were determined by the tunel method. in vitro, the effect of combination treatment on cytotoxicity was assessed by mtt assay and apoptosis was assessed by dapi staining. fadd, caspase 3, and parp proteins were determined by western blot. no toxic side effects were observed in either group. the tumor volume was significantly smaller and the apoptotic ratio was higher in the trail gen group than in the other 2 groups. the apoptotic effect was associated with the caspase-3 activation. z-vad-fmk partially inhibited apoptosis by trail gen.","these results indicate that the combination of trail/apo2l with genistein presents a promising therapeutic approach for the treatment of pancreatic cancer. further detail investigations are needed, however, to verify the mechanisms of this combination therapy.",Medication
are dna sequence losses on chromosomes 11p and 18q associated with clinical outcome in lymph node-negative ductal breast cancer?,"histological and other markers alone cannot predict the risk of disease progression in node-negative breast cancer. several genomic aberrations have been linked to clinical outcome in breast cancer. in this study, comparative genomic hybridization was applied to screen for specific dna copy number gains and losses in 20 pt1/pt2 node-negative invasive ductal carcinomas with no disease recurrence with at least 8 years of follow-up and in 20 pt1/pt2 node-negative tumors with distant disease recurrence. the number of genomic aberrations (copy number gains and losses) per tumor was significantly higher in tumors with disease recurrence (p 0.05). the number of genomic aberrations was associated with histological grade (p 0.02). within the group of tumors with disease recurrence, the total number of genetic aberrations per tumor (p 0.02) and the number of dna sequence losses per tumor (p 0.01) were significantly associated with poor survival. of the individual loci involved, only losses at chromosomes 11p (p 0.002) and 18q (p 0.004) were associated with poor survival in the recurrence group. histological grade and loss of 18q were independent prognostic variables in multivariate analysis.","this genome-wide analysis by comparative genomic hybridization suggests that node-negative ductal breast cancers with a high number of genomic aberrations have an increased risk of disease recurrence. the number of dna sequence losses, particularly losses of chromosomes 11p and 18q, were associated with poor prognosis. genes on chromosomes 11p and 18q may play a role in the progression of ductal breast carcinoma.",Diagnosis
is habitual physical activity a meaningful predictor of well-being in mid-life women : a longitudinal analysis?,"to examine whether physical-activity patterns over a period of 4 years are associated with well-being. a sample of 399 women aged 50-60 years participated in the study. measures included rate of physical activity and other life style behaviors, well-being, health status, and interpersonal stress. sufficient and insufficient exercisers were identified, and the association of this dichotomy with well-being, along with the contribution of the other variables, was examined. the distribution of physical-activity patterns remained stable over the 4 years of the study, with 40 of the women exercising leisurely and 15-20 exercising vigorously four to seven times a week. approximately 50 of the women were considered sufficiently active in terms of public recommendations. random effects regression analysis revealed that sufficient exercise along with a low frequency of daily hassles, relatively few menopausal symptoms, and a low level of interpersonal stress significantly contributed to the variability of well-being.",these data evoke the need for a better understanding of exercise behavior and its promising potential contribution to the well-being of middle-aged women.,Prevention
does promoting angiogenesis protect severely hypertrophied hearts from ischemic injury?,"myocardial hypertrophy is associated with progressive contractile dysfunction, increased vulnerability to ischemia-reperfusion injury, and is, therefore, a risk factor in cardiac surgery. during the progression of hypertrophy, a mismatch develops between the number of capillaries and cardiomyocytes per unit area, suggesting an increase in diffusion distance and the potential for limited supply of oxygen and nutrients. we hypothesized that promoting angiogenesis in hypertrophied hearts increases microvascular density, thereby improves tissue perfusion and substrate availability, maintains myocardial function, and improves postischemic recovery. left ventricular hypertrophy was created in 10-day-old rabbits by aortic banding and progression was monitored by echocardiography. at 4 weeks (compensated hypertrophy), 2 microg of vascular endothelial growth factor (vegf) or placebo was administered intrapericardially. after 2 weeks, microvascular density, coronary flow (cf), and glucose uptake (gu) were measured. tolerance to ischemia was determined by cardiac function measurements before and after ischemia-reperfusion using an isolated heart preparation. microvascular density increased significantly following vegf treatment (1.43 /- 0.08/nuclei/field vs 1.04 /- 0.06/nuclei/field untreated hypertrophy). concomitantly, there was an increase in cf (7 /- 0.5 vs 5 /- 0.4 ml/min/g) and gu (1.24 /- 0.2 vs 0.69 /- 0.2 micromoles/g/30 minutes; p or 0.05). in vivo contractile function (-0.08 /- 0.48 vs -1.39 /- 0.35 untreated hypertrophy; p or 0.05) and postischemic myocardial recovery ( recovery: 93 /- 2.0 vs 73 /- 6.8 untreated hypertrophy; p or 0.05) were significantly improved in vegf-treated hearts compared to untreated hypertrophied hearts.","treatment of hypertrophied hearts with vegf resulted in an increase of microvascular density, improved tissue perfusion, and glucose delivery. promoting angiogenesis proved useful in preserving myocardial function in late hypertrophy and improving postischemic recovery of contractile function.",Treatment
does serum he4 detect recurrent endometrial cancer in patients undergoing routine clinical surveillance?,"the purpose of this study was to evaluate serum he4 as a biomarker to detect recurrent disease during follow-up of patients with endometrial adenocarcinoma (eac). we performed a retrospective analysis of 98 eac patients treated at innsbruck medical university, between 1999 and 2009. twenty-six patients developed recurrent disease. median follow-up was 5 years. serum he4 and ca125 levels were analyzed using the architect assay (abbott, wiesbaden, germany) pre-operatively (baseline), post-operative (interval) and after histological confirmation of recurrent disease or when patients returned for clinical review with no evidence of recurrent disease (recurrence/final)). receiver operator curves (roc), spearman rank correlation coefficient, chi-squared and mann-whitney tests were used for statistical analysis. he4 levels decreased after initial treatment (p 0.001) and increased again at recurrence (p 0.002). he4 was elevated (70 pmol/l) in 21 of 26 (81) and ca125 was elevated (35 u/ml) in 12 of 26 (46) patients at recurrence. in endometrioid histology (n 69) serum he4 measured during follow up (area under the curve (auc) 0.87, 95ci 0.79-0.95) was a better indicator of recurrence than ca125 (auc 0.67, 95ci 0.52-0.83). a he4 level of 70 pmol/l was associated with a sensitivity of 84, a specificity of 74 and a negative predictive value of 93 when assessing for recurrent endometrioid eac.",this is a preliminary description of he4 serum levels measured during routine follow up of eac patients. serum he4 measured during clinical follow-up may identify recurrent disease particularly in patients with endometrioid histology. further prospective validation of he4 is warranted.,Diagnosis
is fetuin-a associated with calcified coronary artery disease?,"fetuin-a is a circulating glycoprotein that is involved in various stages of atherosclerosis. despite the fact that emerging evidence suggests fetuin-a acts as a calcification inhibitor that protects against advanced calcified atherosclerosis in dialyzed patients, the role of fetuin-a in cardiovascular disease is still controversial. as diabetes and uremia make the role of fetuin-a in cardiovascular disease uncertain, we investigated the association between fetuin-a and calcified coronary artery disease in participants without diabetes and renal dysfunction. serum fetuin-a levels were measured in 92 participants who underwent coronary angiography. the number of diseased vessels and the presence of calcification were evaluated. fetuin-a levels significantly decreased in patients with advanced three-vessel disease compared with those without stenosis (245.5/-50.9, 289.0/-71.8 microg/ml, respectively; p0.05). likewise, fetuin-a levels were significantly lower in patients with coronary artery calcification compared with those without coronary artery calcification (257.1/-49.7, 288.0/-63.1 microg/ml, respectively; p 0.010). multivariate logistic regression analysis revealed that fetuin-a levels inversely correlated with the presence of coronary artery calcification (odds ratio: 0.54; 95 confidence interval: 0.31-0.92; p 0.025).",serum fetuin-a levels inversely correlated with advanced calcified coronary artery disease.,Medication
are long-term outcomes of the bronchial artery embolization diagnosis dependent?,"bronchial artery embolization (bae) is an established, safe, and effective procedure for the treatment of hemoptysis but long-term outcomes of the bae have never been investigated before. to retrospectively analyze long-term outcomes of the bae. a retrospective chart analysis was done from the hospital central database for all patients undergoing the bae over a consecutive 14-year period (january 2000-february 2014). a total of 58 patients were identified from the database. eight patients were excluded due to the lack of follow-up. data such as patient demographics, reason for hemoptysis, medical imaging results, bronchoscopy findings, recurrence rates, and morbidity/mortality rates after the bae were collected. eighty three embolizations were performed in 50 patients. the median follow-up was of 2.2 years. cystic fibrosis (cf) bronchiectasis was the most common etiology (21/50), followed by non-cf bronchiectasis (9/50). cavitary lung disease occurred in 12/50 patients, an additional 4/50 had cancer (primary lung and metastatic), and one patient had antineutrophil cytoplasmic antibody (anca) vasculitis. in three patients the etiology was unknown. postprocedural complications occurred in 5/83 (6) patients, two patients with two major complications - stroke (one) and paraplegia (one) - and three patients with minor complications - chest pain (two) and bronchial artery dissection (one). a total of 15/50 patients died during the follow-up. three patients died of hemoptysis, and the remaining deaths were unrelated to the procedure or hemoptysis. twenty four patients had recurrent hemoptysis. a kaplan-meier analysis revealed an excellent long-term survival that was 85 at 10 years.",the bae is a safe and effective procedure with excellent overall long-term survival.,Diagnosis
is the parathyroid hormone-2 receptor expressed on human leukocytes and down-regulated in hyperparathyroidism?,"parathyroid hormone (pth) has specific effects on function, migration and proliferation of human leukocytes. these effects may contribute to accelerated atherosclerosis and impaired immune response observed in patients with renal insufficiency. recently, a new g protein-coupled receptor with substantial implications for vascular function--the pth2 receptor (pth2-r)--has been identified, however, expression and distribution in humans and a possible regulation has not yet been studied. we therefore investigated the expression of the pth2 receptor on human leukocytes in healthy subjects and in patients with hyperparathyroidism. pth2 receptor expression was quantified by flow cytometry (facs) analysis on monocytes, lymphocytes and granulocytes that were isolated from peripheral blood (hypotonic density gradient centrifugation) and by immunohistochemistry using a specific alpha-pth2-r antibody produced in rabbit. results of 22 patients with hyperparathyroidism (12 renal allograft recipients, 10 hemodialysis patients, mean age 43 /- 8 years) were compared to 22 age and sex-matched healthy controls. mean relative antigen density of the pth2 receptor and percentage of positive cells in healthy subjects was 19 /- 5 and 90 /- 6 on granulocytes, 5 /- 2 and 55 /- 19 on monocytes, and 24 /- 7 and 21 /- 7 on lymphocytes. in patients with hyperparathyroidism, mean antigen density was significantly lower on granulocytes and monocytes (17 /- 4 and 3 /- 1, p 0.01, respectively). the percentage of positive cells and mean expression on lymphocytes was not significantly different. a significant and inverse correlation was found between plasma pth concentrations and the mean pth2 receptor expression on granulocytes (r -0.41, p 0.05).",the pth2 receptor is expressed on human granulocytes and--to a lesser degree--on monocytes and lymphocytes. in patients with hyperparathyroidism the pth2 receptor is down-regulated as function of plasma pth levels.,Medication
is autonomous motivation associated with hearing aid adoption?,"to use the self-determination theory of motivation to investigate whether different forms of motivation were associated with adults' decisions whether or not to adopt hearing aids. a quantitative approach was used in this cohort study. participants completed the treatment self-regulation questionnaire (tsrq), which measured autonomous and controlled motivation for hearing aid adoption. sociodemographic data and audiometric information were also obtained. participants were 253 adults who had sought information about their hearing but had not consulted with a hearing professional. participants were categorized as hearing aid adopters if they had been fitted with hearing aids 4-6 months after completing the tsrq, and as non-adopters if they had not. multivariate logistic regression was used to examine associations between autonomous and controlled motivation, sociodemographic and audiometric variables, and hearing aid adoption (n 160). three factors were significantly associated with increased hearing aid adoption when the influence of other variables was accounted for: autonomous motivation, perceived hearing difficulty, and poorer hearing. controlled motivation was not found to influence hearing aid adoption.",these empirical findings that link autonomous motivation to decisions of hearing help-seekers have implications for the ways practitioners may evaluate motivation and could inform discussions with clients about hearing aid adoption.,Treatment
does varenicline potentiate alcohol-induced negative subjective responses and offsets impaired eye movements?,"varenicline (var) is a partial nicotinic receptor agonist that is an effective smoking cessation medication. preliminary evidence indicates that it may also reduce alcohol consumption, but the underlying mechanism is not clear. for example, var may reduce alcohol consumption by attenuating its subjectively rewarding properties or by enhancing its aversive effects. in this study, we examined the effects of an acute dose of var upon subjective, physiological, and objective responses to low and moderate doses of alcohol in healthy social drinkers. healthy men and women (n 15) participated in 6 randomized sessions; 3 sessions each with 2 mg var and placebo (pl) followed 3 hours later by a beverage containing pl, low-dose alcohol (0.4 g/kg), or high-dose alcohol (0.8 g/kg). subjective mood and drug effects (i.e., stimulation, drug liking), physiological measures (heart rate, blood pressure), and eye tracking tasks were administered at various intervals before and after drug and alcohol administration. var acutely increased blood pressure, heart rate, ratings of dysphoria and nausea, and also improved eye tracking performance. after alcohol drinking (vs. pl), var increased dysphoria and tended to reduce alcohol liking ratings. it also attenuated alcohol-induced eye-tracking impairments. these effects were independent of the drug's effects on nausea before drinking.","our data support the theory that var may reduce drinking by potentiating aversive effects of alcohol. var also offsets alcohol-induced eye movement impairment. the evidence suggests that var may decrease alcohol consumption by producing effects, which oppose the rewarding efficacy of alcohol.",Medication
"is household food insecurity associated with self-reported pregravid weight status , gestational weight gain , and pregnancy complications?","household food insecurity is positively associated with weight among women. the association between household food insecurity and pregnancy-related weight gain and complications is not well understood. to identify whether an independent association exists between household food insecurity and pregnancy-related complications. data from the pregnancy, infection, and nutrition prospective cohort study were used to assess household food insecurity retrospectively using the us department of agriculture 18-item core food security module among 810 pregnant women with incomes or 400 of the income/poverty ratio, recruited between january 2001 and june 2005 and followed through pregnancy. self-reported pregravid body mass index, gestational weight gain, second trimester anemia, pregnancy-induced hypertension, and gestational diabetes mellitus. multivariate linear, multinomial logistic, and logistic regression analyses. among 810 pregnant women, 76 were from fully food secure, 14 were from marginally food secure, and 10 were from food insecure households. in adjusted models, living in a food insecure household was significantly associated with severe pregravid obesity (adjusted odds ratio 2.97, 95 confidence intervals cis 1.44 to 6.14), higher gestational weight gain (adjusted beta coefficient 1.87, 95 ci 0.13 to 3.62), and with a higher adequacy of weight gain ratio (adjusted beta .27, 95 ci 0.07 to 0.50). marginal food security was significantly associated with gestational diabetes mellitus (adjusted odds ratio 2.76, 95 ci 1.00 to 7.66).",this study highlights the possibility that living in a food insecure household during pregnancy may increase risk of greater weight gain and pregnancy complications.,Prevention
do sea water or its components alter experimental irritant dermatitis in man?,"ocean bathing has been considered ""healthy"" for skin, but its efficacy remains testimonial in nature. our aim was to evaluate the effects of sea water and its main components on experimental irritant contact dermatitis induced by sodium lauryl sulphate (sls) cumulative irritation. after open application of 2 sls for 10 min on volar forearm sites, solutions of sea water, 500 mm nacl, 10 mm kcl, 55 mm mgcl2, 10 mm cacl2, or deionized water were separately applied using filter paper discs for 20 min. the procedures were repeated daily for 2 weeks. the effects of the treatment were assessed daily using measurements of transepidermal water loss (tewl), as an indicator of epidermal barrier function, and capacitance, as a parameter of stratum corneum water content. sea water, nacl, and kcl significantly inhibited the increase of tewl as compared with deionized water (p 0.003, p 0.05, p 0.05, respectively). sea water and nacl inhibited the decrease of capacitance as well (p 0.03, p 0.01).","the effect of sea water may be attributed to skin barrier preservation by nacl and kcl, and an emollient effect by nacl.",Treatment
does liver biopsy analysis have a low level of performance for diagnosis of intermediate stages of fibrosis?,"there is controversy about the performance of noninvasive tests such as fibrotest in diagnosing intermediate stages of fibrosis. we investigated whether this controversy results from limitations of biopsy analysis for intermediate-stage fibrosis and inappropriate determination of the standard area under the receiver-operator characteristic curve (auroc). to determine whether biopsy has a lower diagnostic performance for fibrosis stage f2 (few septa) vs f1 (fibrosis without septa), compared with its performance for f1 vs f0 or f4 vs f3, we determined the fibrotic areas of large surgical samples collected from 20 consecutive patients with chronic liver disease or normal liver tissue that surrounded tumors. we analyzed digitized images of 27,869 virtual biopsies of increasing length and also analyzed data from 6500 patients with interpretable fibrotest results who also underwent biopsy analysis. the overall performance of biopsy analysis (by obuchowski measure) increased with biopsy length from 0.885 for 5-mm to 0.912 for 30-mm samples (p .0001). the performance of biopsy was lower for the diagnosis of f2 vs f1 samples (weighted auroc wauroc 0.505) than for f1 vs f0 (wauroc 0.773; 53 difference; p .0001) or f4 vs f3 (wauroc 0.700; 39 difference; p .0001), even when 30-mm biopsy samples were used. the performance of fibrotest was also lower for the diagnosis of f2 vs f1 samples (wauroc 0.512) than for f1 vs f0 samples (wauroc 0.626; 22 difference; p .0001) or f4 vs f3 (wauroc 0.628; 23 difference; p .0001). however, the fibrotest had smaller percentage differences among wauroc values than biopsy.","biopsy has a low level of diagnostic performance for fibrosis stages f2 and f1. the recommendation for biopsy analysis, instead of a validated biomarker panel such as fibrotest, for the diagnosis of intermediate stages of fibrosis is therefore misleading.",Diagnosis
are all adverse events in autologous blood donors with cardiac disease necessarily caused by blood donation?,"autologous blood donation before elective cardiac surgery has become a standard of care at many institutions. however, the safety of autologous blood donations by patients with cardiac disease is subject to controversy. two life-threatening cardiac arrests and one fatal myocardial infarction that occurred in three patients who were scheduled to donate blood for autologous use in elective cardiac surgery are reported. all three patients met the institution's selection criteria for autologous blood donors, and all of them had given written informed consent for their participation in the autologous blood donation program. one of the two cardiac arrests and the myocardial infarction occurred in the patients prior to any blood donations, and the other cardiac arrest occurred 7 days after the patient donated blood uneventfully.",life-threatening and fatal adverse events may occur during the donation period in autologous blood donors with cardiac disease. not all adverse events are necessarily caused by blood donation.,Treatment
does peroxisome proliferator-activated receptor gamma negatively regulate allergic rhinitis in mice?,"peroxisome proliferator-activated receptor gamma(ppar-gamma) has been shown to play an important role in the control of inflammatory responses acting on macrophages, mast cells, t cells, and eosinophils. the present study was aimed at investigating the effects of ppar-gamma agonist on nasal symptoms and eosinophil accumulations in nasal mucosa by using a murine allergic rhinitis model. furthermore, we examined the expression of ppar-gamma in the nasal mucosa in mice. balb/c mice were sensitized and challenged intranasally with ovalbumin. ciglitazone, a ppar-gamma agonist, was administered orally 6 hours before each nasal challenge. administration of ppar-gamma agonist significantly decreased the number of nasal rubs, nasal histamine responsiveness, serum ige, il-5 production from the spleen, and eosinophilic infiltration in the nasal mucosa. furthermore, ppar-gamma was expressed in eosinophils and epithelial cells in the nasal mucosa by immunohistochemistry.","ppar-gamma was expressed in eosinophils and epithelial cells in the nasal mucosa. also, the oral administration of ciglitazone is effective in upper airway allergic inflammation in mice.",Medication
does phylogenetic analysis of the complete mitochondrial genome of madurella mycetomatis confirm its taxonomic position within the order sordariales?,"madurella mycetomatis is the most common cause of human eumycetoma. the genus madurella has been characterized by overall sterility on mycological media. due to this sterility and the absence of other reliable morphological and ultrastructural characters, the taxonomic classification of madurella has long been a challenge. mitochondria are of monophyletic origin and mitochondrial genomes have been proven to be useful in phylogenetic analyses. the first complete mitochondrial dna genome of a mycetoma-causative agent was sequenced using 454 sequencing. the mitochondrial genome of m. mycetomatis is a circular dna molecule with a size of 45,590 bp, encoding for the small and the large subunit rrnas, 27 trnas, 11 genes encoding subunits of respiratory chain complexes, 2 atp synthase subunits, 5 hypothetical proteins, 6 intronic proteins including the ribosomal protein rps3. in phylogenetic analyses using amino acid sequences of the proteins involved in respiratory chain complexes and the 2 atp synthases it appeared that m. mycetomatis clustered together with members of the order sordariales and that it was most closely related to chaetomium thermophilum. analyses of the gene order showed that within the order sordariales a similar gene order is found. furthermore also the trna order seemed mostly conserved.","phylogenetic analyses of fungal mitochondrial genomes confirmed that m. mycetomatis belongs to the order of sordariales and that it was most closely related to chaetomium thermophilum, with which it also shared a comparable gene and trna order.",General
does specific-wavelength visible light irradiation inhibit bacterial growth of porphyromonas gingivalis?,"the effects of laser irradiation on porphyromonas gingivalis have been reported, but the results are still controversial regarding the efficiency because of the differences of the light sources and irradiation conditions. the aim of this study was to determine the wavelength and irradiation conditions under which the most effective inhibitory effect on p. gingivalis growth was seen without any photosensitizers. using an okazaki large spectrograph, monochromatic light spectra ranging from 400 to 700 nm were evaluated to determine which spectra effectively inhibited bacterial growth. moreover, using a monochromatic 405-nm irradiating device, the effects of various irradiating conditions on p. gingivalis growth were examined. growth of bacteria irradiated at 400 nm and 410 nm was significantly suppressed compared with a nonirradiated control, whereas wavelengths of 430 nm and longer produced no significant inhibition. a constant energy density of 15 j/cm2 was found to be enough to show an inhibitory effect. significant inhibition of bacterial growth was found after only 1 min at 50 mw/cm2 irradiation.","these results indicate that p. gingivalis growth is specifically suppressed by 405-nm light irradiation, suggesting that visible blue light irradiation is a promising means for eradicating periodontopathogenic bacteria from periodontal lesions.",Medication
is tspy4 a novel sperm-specific biomarker of semen exposure in human cervicovaginal fluids ; potential use in hiv prevention and contraception studies?,"developing an objective, reliable method to determine semen exposure in cervicovaginal fluids is important for accurately studying the efficacy of vaginal microbicides and contraceptives. y-chromosome biomarkers offer better stability, sensitivity, and specificity than protein biomarkers. tspy4 belongs to the tspy (testis-specific protein y-encoded) family of homologous genes on the y-chromosome. using a multiplex pcr amplifying tspy4, amelogenin, and sex-determining region in the y chromosome (sry), our objective was to determine whether a gene in the tspy family was a more sensitive marker of semen exposure in cervicovaginal fluids than sry. the multiplex polymerase chain reaction (pcr) was developed using sperm and vaginal epithelial (female) dna. diluted sperm dna and mixed male/female dna was used to determine the sensitivity of the multiplex pcr. potential interference of tspy4 amplification by components in cervicovaginal and seminal fluids was determined. tspy4 and sry amplification was also investigated in women participating in a separate irb-approved clinical study in which cervicovaginal swab dna was collected before semen exposure and at various time points after exposure. tspy4, sry, and amelogenin were amplified in sperm dna, but only amelogenin in female dna. the limit of sperm dna from which tspy4 could be amplified was lower than sry (4 pg vs 80 pg). tspy4 could also be amplified from mixed male/female dna. amplification was not affected by cervicovaginal and seminal components. using cervicovaginal swab dna from three women before and after semen exposure, tspy4 was detected up to 72 h post exposure while sry detection was observed up to 24-48 h. tspy4 was detected up to 7 days post exposure in one out of three women.","we have demonstrated that tspy4 is a new sensitive, and sperm-specific biomarker. the multiplex pcr incorporating this new biomarker has potential to be an objective measure for determining semen exposure in clinical trials of vaginal products such as contraceptives and hiv pre/post-exposure prophylaxis agents.",Diagnosis
does intrauterine use of hyperconcentrated platelet concentrate collected with trima accel in a case of neonatal alloimmune thrombocytopenia?,"due to the threat of serious or fatal bleedings, fetuses with neonatal alloimmune thrombocytopenia (nait) may need intrauterine platelet (plt) transfusions. to prevent a volume overload or an abo minor mismatch, standard plt concentrates need to be washed to increase the plt concentration and to reduce the plasma content. hyperconcentrated single-donor plt concentrates (hcps) are a therapeutic alternative. the first case of nait successfully treated with hcps collected with the trima accel (ta; gambro bct) is reported. a 31-year-old woman with a history of nait in the preceding pregnancy underwent cordocentesis three times during her third pregnancy (30th, 31st, and 32nd weeks of gestation). nait was confirmed by marked fetal thrombocytopenia, a maternal anti-human plt antigen (hpa)-1a-immunoglobulin g (titer 1:128), and the appropriate hpa genotype of the fetus and the parents. on each cordocentesis procedure, a distinct volume of a hpa-1a-negative hcp with a plt concentration of 3 x 10(6) plts per microl was transfused resulting in high corrected count increments after 2 hours. the hcps were transfused within 10 hours after collection. one day after the last cordocentesis procedure, a cesarean section was performed. the newborn did not show any bleeding signs, and the plt count remained on normal levels and no further plt transfusions were needed.","hcps collected with ta are a useful alternative to washed standard plt concentrates without the need for further manipulation of the product after collection. further in vitro and in vivo studies are needed, however, to make definite recommendations for the shelf life of these hcp.",Treatment
does the use of cylindrical coordinate for treatment planning parameters of an elongated 192ir source?,"the doses given to the intima, media, and adventitia are very crucial quantities in intravascular brachytherapy. to facilitate accurate computerized treatment planning calculations, we have determined dose distributions in away-and-along table format around an 192ir wire source and developed pertinent dosimetric parameters in cylindrical coordinates. the monte carlo method (mcnp4c code) was used to calculate the dose distributions for the angiorad 192ir wire source (model sl-77hs, interventional therapies). the calculations were carried out for photon, beta, and electron (conversion and auger) contributions for radial distances from 0.03 to 2.0 cm with 0.01-cm increments, and up to 2.24 cm from the source center in the longitudinal direction with 0.04-cm resolution. dose rate values are determined in away-and-along format (cylindrical coordinates) and then converted to spherical coordinate format. dosimetric parameters, such as the geometry factor, g(r, theta), and anisotropy function, f(r, theta), are generated in both cylindrical (r, z, phi) and spherical (r, theta, phi) coordinates. the use of a cylindrical coordinate system for treatment planning parameters is proposed as a more suitable approach for accurate calculations. the photon contribution to dose varies nearly inversely with radial distance (from the source center) along the perpendicular bisector with 0.199 x 10(-3) cgy u(-1) s(-1) (0.802 cgy ci(-1) s(-1)) at 1 cm. the beta and electron contributions start at very high values of about 35.5 x 10(-3) cgy u(-1) s(-1) and 11.0 x 10(-3) cgy u(-1) s(-1), respectively, at 0.03 cm and fall off exponentially to negligible amount near 0.2 cm. the total dose rate at 0.2 cm is 1.428 x 10(-3) cgy u(-1) s(-1) (5.754 cgy ci(-1) s(-1)). the radial dose function, g(r), is nearly unity between 0.2 cm and 2 cm. due to the beta and electron dose contributions, g(r) increases steeply to 5.5 as radial distance decreases from 0.2 cm down to 0.03 cm. the f(r, z) values are close to unity for the majority of the region of interest. in contrast, f(r, theta) experiences a steep rise as shallow angles are approached (closer to the source), related to the beta dose contributions. accurate treatment planning calculations would be possible with linear interpolation of f(r, z), but difficult with f(r, theta) in the spherical coordinate system and the original normalization point as recommended in the american association of physicists in medicine task group 60 (aapm tg-60) formalism.","the angiorad 192ir wire source, model sl-77hs, was completely characterized dosimetrically using monte carlo methods. the use of cylindrical coordinates and a modified anisotropy function normalization point for dosimetric parameters of an elongated 192ir source is more suitable for accurate computerized treatment planning calculations in intravascular brachytherapy.",Treatment
are calmodulin antagonists involved in mouse sperm capacitation ?,"to investigate the possible involvement of calmodulin in mouse sperm capacitation. calmodulin antagonists w7 at the concentrations of 50, 100 and 200 micromol/l and calmidazolium (cz) at the concentrations of 10, 20 and 30 micromol/ l, were coincubated with mouse sperm for 2 hours, respectively. the percentage of pattern b sperm was measured by chlorotetracycline staining. then the sperm were coincubated with 100 micromol/l w7 or 10 micromol/l calmidazolium (cz) before acrosome reaction was induced by 5 micromol/l progesterone and evaluated by the same method. after the treatment of the sperm with different concentrations of cz or w7, the percentages of pattern b sperm decreased in a dose-dependent manner, significantly different from the control (p 0.05). there was a statistic difference in the rate of acrosome reaction between the experiment and the control group (p 0.01).",calmodulin is a key protein involved in mouse sperm capacitation.,Medication
do subtle microscopic abnormalities in hippocampal sclerosis predict clinical features of temporal lobe epilepsy?,"subtle microdysplastic features are found in some patients with hippocampal sclerosis (hs) and refractory temporal lobe epilepsy. the significance of these findings is unknown. we investigated their frequency, relation to the pattern of hs, and clinical associations. one-hundred forty patients with histologically confirmed hs (mean age at operation, 35 years; 85 women) were analyzed. the presence of hs and subtle structural abnormalities (ssas) in the mesial temporal lobe and in the lateral neocortical tissue was assessed in detail. antecedents, seizure characteristics, two verbal memory tests, and outcome in hs patients with and without ssas were determined. ssas were found in 60 (43) of the 140 hs patients, being mesial only in 32 of the 60 cases, and lateral only in nine cases; the remaining 19 cases had both mesial and lateral abnormalities. the frequency of ssa was not related to the pattern of hs or other tested variables. prolonged febrile convulsions were present in 26 (44) patients with ssas, and in 26 (34) patients (not significant) without ssas. the outcome after surgery did not differ between patients with ssas (incidence rate ratio for seizure recurrence, 0.9; 95 confidence interval, 0.5-1.6) compared with patients without ssas (reference ratio, 1).","forty-three percent of hs patients have ssas in their lobectomy specimens. the presence of ssas does not predict clinical characteristics, such as presence of prolonged febrile convulsions, postsurgical outcome, or neuropsychological performance, nor does it correlate with the histologic pattern of hs.",Treatment
are placental antiangiogenic prolactin fragments increased in human and rat maternal diabetes?,"the role of the placenta in diabetic mothers on fetal development and programming is unknown. prolactin (prl) produced by decidual endometrial cells may have an impact. although full-length prl is angiogenic, the processed form by bone morphogenetic protein-1 (bmp-1) and/or cathepsin d (ctsd) is antiangiogenic. the objectives were to investigate the involvement of decidual prl and its antiangiogenic fragments in placentas from type-1 diabetic women (t1d) and from pregnant diabetic rats with lower offspring weights than controls. prl, bmp-1, and ctsd gene expressions and prl protein level were assessed in t1d placentas (n8) at delivery and compared to controls (n5). wistar rats received, at day 7 of pregnancy, streptozotocin (stz) (n5) or nicotinamide (nct) plus stz (n9) or vehicle (n9). placental whole-genome gene expression and prl western blots were performed at birth. in human placentas, prl (p0.05) and bmp-1 (p0.01) gene expressions were increased with a higher amount of cleaved prl (p0.05) in t1d than controls. in rats, diabetes was more pronounced in stz than in nct-stz group with intra-uterine growth restriction. decidual prolactin-related protein (dprp) (p0.01) and bmp-1 (p0.001) genes were up-regulated in both diabetic groups, with an increased cleaved prl amount in the stz (p0.05) and nct-stz (p0.05) groups compared to controls. no difference in ctsd gene expression was observed in rats or women.",alterations in the levels of the prl family are associated with maternal diabetes in both rats and t1d women suggesting that placental changes in these hormones impact on fetal development.,General
does fat digestion modulate gastrointestinal sensations induced by gastric distention and duodenal lipid in humans?,"it is unclear whether fat digestion is required for the induction of gastrointestinal sensations and whether different fats have different effects. we investigated the effect of fat digestion and of medium-chain triglycerides (mcts; c 16) on gastrointestinal sensations. in a double-blind study, 15 healthy subjects were studied on 5 occasions during which lct or mct emulsions (2 kcal/min), with or without 120 mg tetrahydrolipstatin (thl, lipase inhibitor), or sucrose polyester (spe, nondigestible fat) were infused intraduodenally in randomized order. after 30 minutes, the proximal stomach was distended in 1 mm hg steps/min. intensity of gastrointestinal sensations (on a 0-10 visual analog scale), plasma cholecystokinin (cck) levels, and gastric volumes were assessed throughout. lct and mct increased gastric volume at baseline pressure compared with spe, and lct more than mct. thl entirely abolished this effect (volumes ml: lct, 213 /- 19; lct-thl, 39 /- 3; mct, 155 /- 12; mct-thl, 43 /- 5; spe, 44 /- 5). only lct increased plasma cck levels (pmol/l per 30 minutes: lct, 21 /- 2; lct-thl, 9 /- 1; mct, 9 /- 1; mct-thl, 11 /- 1; spe, 9 /- 1). during distentions, intragastric volumes were greater during infusion of lct and mct than during the respective thl conditions or spe, but plasma cck levels did not change. the intensity of sensations increased (hunger decreased) more with lct than with mct. during infusion of thl or spe, the effects were smaller than during lct or mct.",fat digestion is required for the modulation of gastrointestinal sensations during gastric distention. the effects of fat depend on the fatty acid chain length and are not entirely explained by release of cck.,Medication
is laparoscopic sleeve gastrectomy a safe and effective bariatric procedure for the lower bmi ( 35.0-43.0 kg/m2 ) population?,"the laparoscopic vertical sleeve gastrectomy (lsg) is derived from the biliopancreatic diversion with duodenal switch operation (marceau et al., obes surg 3:29-35, 1993; hess and hess, obes surg 8:267-82, 1998; chu et al., surg endosc 16:s069, 2002). later, lsg was advocated as the first step of a two-stage procedure for super-obese patients (regan et al., obes surg 13:861-4, 2003; cottam et al., surg endosc 20:859-63, 2006). however, recent support is mounting that continues to establish lsg as the definitive procedure for surgical treatment of morbid obesity. we will report our experience with the lsg as a primary bariatric procedure and evaluate if this operation is suitable as a stand-alone procedure. the study is a nonrandomized retrospective analysis of 204 patients from a single surgeon operated between july 2006 and april 2010. the study comprises of 155 women and 49 men with a mean age of 45 years (range, 19-70 years), a mean preoperative weight of 126.6 kg, and body mass index (bmi) of 45.7 kg/m(2). the mean percent excess weight loss (ewl) was 49.9 (n 159), 64.2 (n 138), 67.9 (n 77), 62.4 (n 34), and 62.2 (n 9) at 3, 6, 12, 24, and 36 months, respectively. for patients with bmi 43.0, the mean postoperative ewl was 58.9 (n 72), 74.1 (n 67), 75.8 (n 39), 72.1 (n 17), and 78.7 (n 5) at 3, 6, 12, 24, and 36 months, respectively. operative complications include leak (0.0), abscess (0.5), hemorrhage (1.0), sleeve stricture (1.0), and severe gastroesphogeal reflux disease with need to convert to laparoscopic roux-en-y gastric bypass (0.5).","lsg yields excellent outcomes with low complication rates for morbidly obese patients. we advocate lsg as a safe and effective stand-alone procedure, especially with the lower bmi population (bmi 35.0-43.0 kg/m(2)).",Treatment
does tuberosity position correlate with fatty infiltration of the rotator cuff after hemiarthroplasty for proximal humeral fractures?,"this study investigates the correlation between tuberosity positioning, fatty infiltration of the rotator cuff, and clinical outcome after hemiarthroplasty for proximal humeral fracture. twenty patients with a mean age of 70.8 /- 9.9 years were evaluated at a mean of 19.8 /- 9.4 months. evaluation included assessment of the constant score (cs); disabilities of the arm, shoulder and hand (dash) score; radiographic evaluation; and computed tomography to classify healing of the tuberosities and changes in the rotator cuff. fatty degeneration of the cuff was classified according to the goutallier classification as stage 0 to 4. tuberosity positioning was classified as mal-positioning of less than 0.5 cm., 0.5 to 1 cm., 1.0 cm., or not healed. the mean constant score (cs) of patients with greater tuberosity displacement of or 0.5 cm displacement and non-united greater tuberosities. the cs of patients with greater tuberosity displacement of 0.5 to 1 cm was significantly higher than that in patients with non-united greater tuberosities. for the lesser tuberosity, patients with displacement of 1 cm and non-united lesser tuberosities. there was a significant correlation between fatty infiltration of the supraspinatus and infraspinatus muscles and greater tuberosity malposition and between fatty infiltration of the subscapularis and lesser tuberosity malposition.",fatty infiltration of the cuff was significantly associated with lower clinical scores. tuberosity positioning and healing are critical for improved clinical outcomes after hemiarthroplasty for proximal humeral fractures.,Diagnosis
does a novel method of 2-channel dual-pulse gastric electrical stimulation improve solid gastric emptying in dogs?,"gastric electrical stimulation (ges) is known to improve vomiting with short pulses, normalize dysrhythmia with long pulses, and accelerate gastric emptying with 2 channels. the aim of this study was to assess the effects of a new method ges, namely, 2-channel ges with dual pulses on gastric emptying of solids as well as gastric dysrhythmia and emetic responses. seven beagle dogs implanted with 4 pairs of electrodes were studied. a novel method of ges was proposed: 2-channel dual-pulse ges in which each stimulus was composed of a short pulse followed with a long pulse, and stimulation was delivered at 2 different locations. the study was performed to test the effects of this new method of ges on vasopressin-induced delayed gastric emptying of solids, gastric dysrhythmia, and emetic responses. (1) vasopressin-induced gastric dysrhythmia and emetic responses, as well as delayed gastric emptying of solids (p .01). (2) two-channel, but not 1-channel, dual-pulse ges was able to accelerate vasopressin-induced delayed gastric emptying of solids. (3) both 1- and 2-channel dual-pulse ges was capable of improving dysrhythmia and emetic responses (p .01).",the novel method of 2-channel dual-pulse ges is capable of accelerating gastric emptying of solids and improving dysrhythmia and emetic responses induced by vasopressin. this new method of ges may have a potential for gastroparesis.,Symptoms
is serum albumin predictive of 30-day survival after percutaneous endoscopic gastrostomy?,"percutaneous endoscopic gastrostomy (peg) tubes have been used since 1980 in patients who require prolonged enteral feeding. to identify factors associated with poor survival (defined as survival or 3.0 g/dl survived 30 days compared with 58 with an albumin 3.0, a difference of 25 (95 ci, -2 to 54; p .07).","in conclusion, serum albumin appears to be a predictor of early survival in individuals undergoing percutaneous endoscopic gastrostomy tube placement.",General
are narcolepsy-like sleep disturbance in orexin knockout mice normalized by the 5-ht1a receptor agonist 8-oh-dpat?,"orexin knockout (ko) mice exhibit a phenotype that is similar to human narcolepsy, and monoamine-related compounds, such as psychostimulants and 5-ht uptake inhibitors, have been used for the treatment of narcoleptic disorders. however, little information is available regarding the pathophysiological features of orexin ko mice, particularly with respect to their narcoleptic-like disorder and how it is affected by monoamine-related compounds. the present study was designed to investigate both the nature of the neuronal changes in orexin ko mice and the therapeutic effects of monoamine-related compounds on the sleep disorder in orexin ko mice. a decrease in locomotor activity in the dark phase was observed in orexin ko mice, and psychostimulants and 5-ht-related compounds, such as 8-oh-dpat (5-ht1a receptor agonist) and doi (5-ht2 receptor agonist), inhibited this hypolocomotion. we also found that 5-ht1a receptor mrna levels, but not those for 5-ht2 or dopamine receptors, were significantly decreased in the prefrontal cortex of orexin ko mice in the dark period and were accompanied by compromising the increase in 5-ht metabolite levels. in addition, the sleep disorder in orexin ko mice, as analyzed by a polysomnography during the dark period, was completely normalized by 8-oh-dpat.","these results suggest that a dysfunction of 5-ht1a receptors is involved in the narcoleptic-like sleep dysfunction in orexin ko mice, and such dysfunction may participate in orexin deficiency-induced sleep disorders. further, the use of 5-ht1a receptor agonist could be useful for treating the sleep disorder under a deficiency of orexin.",Medication
does sunitinib cause dose-dependent negative functional effects on myocardium and cardiomyocytes?,"to examine the acute effects of sunitinib on inotropic function, intracellular ca(2) transients, myofilament ca(2) sensitivity and generation of reactive oxygen species (ros) in human multicellular myocardium and isolated mouse cardiomyocytes. to search for micrornas as suitable biomarkers for indicating toxic cardiac effects. after exposure to sunitinib (0.1-10 g/ml) developed force, diastolic tension and kinetic variables were assessed in isolated human myocardium. changes in myocyte sarcomere length, whole-cell calcium transients, myofilament force-ca(2) relationship, and ros generation were examined in isolated ventricular mouse cardiomyocytes. microarray and realtime-pcr were used to screen for differentially expressed micrornas in cultured cardiomyocytes that were exposed for 24 h to sunitinib. we found that higher concentrations of sunitinib (1 and 10 g/ml) decreased developed force at 30 minutes 76.9 2.8 and 54.5 6.3, compared to 96.1 2.6 in controls (p 0.01). sunitinib exposure significantly decreased sarcomere shortening and ca2 transients. myofilament ca(2) sensitivity was not altered, while ros levels were significantly increased after exposure to the drug. microrna expression patterns were not altered by sunitinib.","sunitinib elicits a dose-dependent negative inotropic effect in myocardium, accompanied by a decline in intracellular ca(2) and increased ros generation. in clinical practice, these cardiotoxic effects should be considered in cases where cardiac concentrations of sunitinib could be increased.",Medication
does the gut microbiome contribute to a substantial proportion of the variation in blood lipids?,"evidence suggests that the gut microbiome is involved in the development of cardiovascular disease, with the host-microbe interaction regulating immune and metabolic pathways. however, there was no firm evidence for associations between microbiota and metabolic risk factors for cardiovascular disease from large-scale studies in humans. in particular, there was no strong evidence for association between cardiovascular disease and aberrant blood lipid levels. to identify intestinal bacteria taxa, whose proportions correlate with body mass index and lipid levels, and to determine whether lipid variance can be explained by microbiota relative to age, sex, and host genetics. we studied 893 subjects from the life-lines-deep population cohort. after correcting for age and sex, we identified 34 bacterial taxa associated with body mass index and blood lipids; most are novel associations. cross-validation analysis revealed that microbiota explain 4.5 of the variance in body mass index, 6 in triglycerides, and 4 in high-density lipoproteins, independent of age, sex, and genetic risk factors. a novel risk model, including the gut microbiome explained 25.9 of high-density lipoprotein variance, significantly outperforming the risk model without microbiome. strikingly, the microbiome had little effect on low-density lipoproteins or total cholesterol.","our studies suggest that the gut microbiome may play an important role in the variation in body mass index and blood lipid levels, independent of age, sex, and host genetics. our findings support the potential of therapies altering the gut microbiome to control body mass, triglycerides, and high-density lipoproteins.",Prevention
does preoperative brain natriuretic peptide predict late mortality and functional class but not hospital readmission after cardiac surgery?,"n-terminal brain natriuretic peptide (nt-probnp) is an established biomarker of heart failure and has been found to predict mortality and morbidity after cardiac surgery. the aim of this study was to investigate whether preoperative nt-probnp can predict postoperative new york heart association (nyha) functional class and hospital readmission in addition to morbidity and mortality. retrospective. university hospital. all patients undergoing aortic valve replacement for aortic stenosis and coronary artery bypass grafting from january to december 2008 (n 390). preoperative nt-probnp was recorded prospectively. five-year mortality was obtained through national registries. postoperative functional class, morbidity, and hospital readmission were obtained through telephone interviews. patients were divided into quartiles based on preoperative nt-probnp; the medians of each quartile were 103 ng/l, 291 ng/l, 825 ng/l and 2,375 ng/l. increased preoperative nt-probnp was associated with reduced postoperative functional class. in the first quartile, 7 (7/97) were in nyha functional class iii-iv compared to 26 (25/97) in the fourth quartile (p0.01). increased preoperative nt-probnp was also associated with reduced long-term survival (p0.01). the covariate adjusted hazard ratio for mortality in the fourth quartile was 2.9 (1.61-5.08; p0.01) compared to the other quartiles. no association was found between preoperative nt-probnp and postoperative hospital readmission.","increased preoperative nt-probnp is associated with reduced long-term survival and functional class but not hospital readmission post-cardiac surgery. thus, nt-probnp might have additive value to established risk factors in the preoperative assessment of patients undergoing cardiac surgery.",Treatment
is early full weight bearing safe in open-wedge high tibial osteotomy?,"in open-wedge, valgus osteotomy of the upper tibia, there are concerns regarding the initial stability and ability to retain the correction. rehabilitation protocols vary depending on the osteotomy technique and the fixation method. angle-stable implants offer superior initial stability. early full weight bearing appears to be possible using these implants. in this prospective cohort study, we measured migration in open-wedge osteotomy in patients following an early full weight bearing protocol and compared the results to those from a historical cohort of open-wedge osteotomy patients who followed a standard protocol (full weight bearing after 6 weeks) using radiostereometry. 14 open-wedge osteotomies fixated with the angle-stable tomofix implant were performed; patients were allowed full weight bearing as soon as pain and wound healing permitted. radiostereometry was used to measure motion across the osteotomy at regular intervals. improvement in pain and functional outcome were assessed postoperatively. the results were compared to those from a group of 23 patients who had undergone the same operation but had used a standard rehabilitation protocol. there were no adverse effects because of the early full weight bearing protocol. there were no differences in motion at the osteotomy between groups as measured by radiostereometry. in both groups, pain and function improved substantially without any differences between groups. patients in the early weight bearing group achieved the same result but in a shorter time.",tomofix-plate-fixated open-wedge high tibial osteotomy allows early full weight bearing without loss of correction.,Treatment
"is porphyromonas gingivalis resistance to polymyxin b determined by the lipid a 4'-phosphatase , pgn0524?","to elucidate the genetic basis for the pronounced resistance that the oral pathogen, porphyromonas gingivalis (p. gingivalis), exhibits towards the cationic antimicrobial peptide, polymyxin b. a genetic screen of p. gingivalis clones generated by a tn4400'-based random insertion mutagenesis strategy was performed to identify bacteria harboring novel genetic mutations that render p. gingivalis susceptible to killing by the cationic antimicrobial peptide, polymyxin b (pmb, 50 microg x ml(-1)). p. gingivalis (atcc 33277) is unusually resistant to the cationic antimicrobial peptide, pmb at relatively high concentrations (200 microg x ml(-1)). approximately 2,700 independent tn4400'-derived mutants of p. gingivalis were examined for increased sensitivity to pmb killing at a relatively low dose (50 microg x ml(-1)). a single pmb-sensitive mutant was obtained in this phenotypic screen. we determined that the tn4400' transposon was integrated into the gene encoding the lipid a 4'-phosphatase, pgn0524, demonstrating that this insertion event was responsible for its increased susceptibility of this clone to pmb-dependent killing. the resulting mutant strain, designated 0524-tn4400', was highly sensitive to pmb killing relative to wild-type p. gingivalis, and exhibited the same sensitivity as the previously characterized strain, 0524ko, which bears a genetically engineered deletion in the pgn0524 locus. positive ion mass spectrometric structural (maldi-tof ms) analyses revealed that lipid a isolates from 0524-tn4400' and 0524ko strains displayed strikingly similar maldi-tof ms spectra that were substantially different from the wildtype p. gingivalis lipid a spectrum. finally, intact 0524-tn4400' and 0524ko mutant bacteria, as well as their corresponding lps isolates, were significantly more potent in stimulating toll-like receptor 4 (tlr4)-dependent e-selectin expression in human endothelial cells relative to intact wild-type p. gingivalis or its corresponding lps isolate.","the combined molecular evidence provided in this report suggests that pgn0524, a lipid a 4'-phosphatase, is the sole genetic element conferring the ability of the periodontopathogen, p. gingivalis, to evade the killing activity of cationic antimicrobial peptides, such as pmb. these data strongly implicate pgn0524 as a critical virulence factor for the ability of p. gingivalis to evade front-line host innate defenses that are dependent upon cationic antimicrobial peptide activity and tlr 4 sensing.",Medication
is higher mean platelet volume determined shortly after the symptom onset in acute ischemic stroke patients associated with a larger infarct volume on ct brain scans and with worse clinical outcome?,"mean platelet volume (mpv) determined shortly after the onset of acute ischemic stroke represents the pre-stroke values. data on its relationship to stroke severity/outcome have been conflicting. we related mpv to infarct volume on ct brain scans and risk of death/dependence 7 days and 3 months post-stroke. mpv (within 30h since stroke onset), infarct volume (13-83h since stroke onset) and clinical outcomes were evaluated in 81 consecutive patients (32 men, age 52-91 years, 10 small artery occlusion, 10 large artery atherosclerosis, 29 cardioembolic, 32 multiple probable/possible etiology). higher mpv was independently associated with larger ln-infarct volume estimate 0.259, 95 confidence interval (ci) 0.004-0.513, p0.046, greater risk of death/dependence 7 days post-stroke relative risk (rr)1.077, 95 ci 1.005-1.115, p0.036, and greater risk of death/dependence 3 months post-stroke (rr1.077, 95 ci 1.001-1.158, p0.048). considered covariates: stroke etiology, ct scan timing, platelet count and other hematological parameters, demographic variables, history of cerebrovascular, cardiac or cardiovascular diseases, diabetes, serum chemistry, previous antiplatelet and statin use and treatments delivered after the index event.",data support the view about mpv as a determinant of severity/outcome of the acute ischemic stroke.,Symptoms
is zinc a negative regulator of hepatitis c virus rna replication?,"hepatitis c virus (hcv) infection is a significant global public health problem. in clinical studies, zinc has been closely related to the pathogenesis of chronic hepatitis c. however, the role of zinc in both viral replication and the expression of viral proteins remains unclear. we aimed to clarify the effect of zinc on the replication of hcv in vitro. we incubated subgenomic hcv replicon cells (so) and genome-length hcv rna-replicating cells (o) treated with several chemicals including trace elements. total rnas were collected and subjected to real-time reverse-transcriptase polymerase chain reaction in order to examine the level of hcv rna replication, and western blotting was performed to confirm the expression of viral proteins. iron salts and interferon-alpha suppressed hcv rna replication and protein expression in both so and o cells. zinc salts effectively reduced the viral replication in the genome-length hcv rna replication system but not in the subgenomic hcv replicon system.",we demonstrated that zinc may play an important role as a negative regulator of hcv replication in genome-length hcv rna-replicating cells. zinc supplementation thus appears to offer a novel approach to the development of future strategies for the treatment of intractable chronic hepatitis c.,Prevention
does cold crystalloid perfusion provide cardiac preservation superior to cold storage for donation after circulatory death?,"we previously showed that donation after circulatory death (dcd) canine hearts can be resuscitated if perfused with warm blood. however, clinical application of this technique is complex and difficult. we have developed a simplified system of cold crystalloid perfusion and compared it with standard cold storage for dcd heart preservation. anesthetized greyhounds underwent 30 minutes dcd by withdrawal of ventilation followed by assignment to either 4 hours of perfusion (n 6) or cold storage (n 7). nonpreserved hearts (n 5) served as a normal reference group. perfusion hearts were reperfused with a protective solution then perfused for 4 hours with a novel oxygenated, nutrient-containing solution at 20 ml/min at 4c to 10c. cold storage hearts were flushed with st thomas' cardioplegic solution and stored in ice. after preservation, the recovery of the hearts was assessed on a blood-perfused working heart rig. during preservation, perfusion hearts consumed oxygen (0.09 0.01 ml/100 g per minute) and showed decreasing lactate production in the perfusate (initial: 0.031 0.004 vs final: 0.007 0.002 mmol/min; p 0.001). after preservation, compared to cold storage hearts, perfusion hearts had higher cardiac output (p 0.004), lv dp/dt max (p 0.003) and myocardial oxygen efficiency (p 0.01), with lower blood perfusate lactate (p 0.007). hemodynamic values of perfused hearts reached 60 or more those in the normal reference group.","continuous cold crystalloid perfusion in a canine model of dcd: (1) facilitates aerobic metabolism and resuscitates the dcd heart, (2) provides functional and metabolic recovery superior to cold storage, (3) shows promise for improved clinical preservation of dcd and marginal donor hearts.",General
does fusion rates after thoracoscopic release and bone graft substitute in idiopathic scoliosis?,"a retrospective assessment of fusion rates using either morselized allograft bone or demineralized bone matrix (dbm) following video-assisted thoracoscopic surgery (vats) in idiopathic scoliosis. to compare fusion rates between allograft bone and demineralized bone matrix (grafton dbm flex) following vats using on standard standing lateral spine radiographs. both vats and bone graft substitutes are accepted surgical techniques. however, their concomitant use in spinal deformity surgery has not been previously reported. bone graft substitute has the advantage of decreasing operative time, blood loss, and donor site morbidity associated with autografts. anterior thoracic discectomies were performed using vats. forty patients with 1 year or more follow-up were evaluated-12 with morselized allograft bone (allograft group) and 28 with folded grafton dbm flex (dbm group). factors analyzed included age, number of anterior levels fused, operative time, anterior perioperative blood loss, curve correction, and fusion rates. clinical and radiographic evaluations were performed before surgery and at month, 1 year, and at most recent follow-up. interbody fusion was assessed on standing lateral radiographs using the newton et al 4-level grading scale. there were no significant differences in age at surgery, number of anterior vertebral levels fused, anterior operative time per level, anterior intraoperative blood loss, chest tube drainage and duration, or total perioperative anterior blood loss between the 2 groups. percent curve correction from before surgery to the most recent follow-up were very similar in both allograft (68) and dbm groups (67). at most recent assessment, 60 of 73 disc spaces (82) in the allograft group and 100 of 109 disc spaces (92) in the dbm group were rated as radiographically fused (newton et al grade i and ii). there was no significant difference between the 2 groups (p 0.088). no patients were observed to have crankshaft, pseudoarthrosis or hardware failure. there were no complications related to the bone graft material used.",demineralized bone matrix (grafton dbm flex) seem to be an effective bone graft substitute in thoracoscopic surgery for idiopathic scoliosis.,Treatment
does the hypothalamus mediate the effect of cerebellar fastigial nuclear glutamatergic neurons on humoral immunity?,"we explored effect of glutamatergic neurons in the fastigial nucleus (fn), one of three cerebellar nuclei, on humoral immunity and revealed that this effect was mediated by the hypothalamus via fn-hypothalamic glutamatergic transmission. rats were immunized with bovine serum albumin (bsa). on the third day after the immunization, 6-diazo-5-oxo-l-norleucine (don), an inhibitor of glutaminase for glutamate synthesis, was microinjected in bilateral fn and d,l-threo--hydroxyaspartic acid (tha), an inhibitor of glutamate transporters on plasma membrane, was microinjected in both sides of lateral hypothalamic area (lha). glutamate content in the hypothalamus was examined by high-performance liquid chromatography (hplc). flow cytometry and enzyme-linked immunosorbent assay (elisa) were used to measure b lymphocyte percentage in mononuclear cells of peripheral blood and levels of anti-bsa igm and igg antibodies in the serum, respectively. don injection in bilateral fn reduced b lymphocyte percentage and anti-bsa igm and igg levels, and simultaneously decreased glutamate content in the hypothalamus. combined treatment with don in the fn and with tha in the lha elevated b cell number and anti-bsa igm and igg levels and increased hypothalamic glutamate content compared with don treatment alone. however, combined treatment with don in the fn and with tha in the ventrolateral thalamic nuclei (vl) did not significantly alter don-dependent changes in b cell number and antibody levels, although the co-treatment altered don-dependent glutamate content in the thalamus.",cerebellar fn glutamatergic neurons participate in modulation of humoral immunity and this effect is mediated by the hypothalamus via fn-hypothalamic glutamatergic transmission.,Medication
does parathyroidectomy reduce cardiovascular events and mortality in renal hyperparathyroidism?,"secondary hyperparathyroidism (shpt) and its associated abnormalities in mineral metabolism increase the risk of cardiovascular morbidity and death in chronic renal failure (crf). the effect of parathyroidectomy (ptx) on the incidence of major cardiovascular events in crf patients with shpt is unknown. we tested the hypothesis that ptx reduces the incidence of cardiovascular complications and death in crf patients with severe shpt scheduled for ptx, comparing the outcome of patients treated or not treated by ptx. the study comprised 118 crf patients with shpt on maintenance hemodialysis, unresponsive to medical treatment and scheduled for ptx. patients underwent comprehensive cardiovascular evaluations at baseline. they were followed up until death, occurrence of major cardiovascular events, or kidney transplantation. no deaths related to ptx occurred. after a median follow-up of 30 months, 50 patients (42) had undergone ptx whereas 68 (58) had not. the groups were comparable in terms of age, sex, race, serum parathyroid hormone, calcium or phosphate, calcium x phosphate product, and all major cardiovascular variables, except diastolic blood pressure. ptx was associated with a reduced incidence of major cardiovascular events (p .02) and overall mortality (p / .001). cox proportional multivariate analysis showed that variables associated independently with events were no-ptx (rr 2.36, ci 1.11-6.32, p .02) and age (rr 1.07, ic 1.02-1.14, p .009). all-cause mortality was related to no-ptx (rr 2.34, ci 1.25-5.14, p .007) and hematocrit (rr 1.15, ci 1.03-1.29, p .01).",ptx confers protection against future major cardiovascular events and death in select crf patients with severe refractory shpt.,Treatment
does cd48 on blood leukocytes and in serum of asthma patients vary with severity?,"cd48 is a membrane receptor (mcd48) on eosinophils and mast cells and exists in a soluble form (scd48). cd48 has a pivotal role in murine asthma and in the proinflammatory interactions of mast cells with eosinophils via its ligand cd244. thus, cd48 might be important in human asthma. therefore, two separate cohorts (il and uk) comprising mild, moderate, and severe asthma and healthy volunteers were evaluated for blood leukocyte mcd48 expression and scd48 in serum. asthmatic bronchial biopsies were immunostained for cd48. scd48 effect on cd244-dependent eosinophil activation was evaluated. eosinophil mcd48 expression was significantly elevated in moderate while downregulated in severe asthma. mcd48 expression on b, t, and nk cells and monocytes in severe asthma was significantly increased. scd48 levels were significantly higher in mild while reduced in severe asthma. scd48 optimal cutoff values for differentiating asthma from health were identified as 1482 pg/ml (il) and 1619 pg/ml (uk). in asthmatic bronchial biopsies, mcd48 was expressed predominantly by eosinophils. scd48 inhibited anti-cd244-induced eosinophil activation.",mcd48 and scd48 are differentially expressed in the peripheral blood of asthma patients of varying severity. scd48 inhibits cd244-mediated eosinophil activation. these findings suggest that cd48 may play an important role in human asthma.,Medication
does montelukast have no ergogenic effect on cycle ergometry in cold temperature?,"to examine the effects of a single 10-mg dose of ml on physical performance in eib- and eib athletes. twenty-four male college ice hockey players performed two 6-min maximal work accumulation bouts on an electronically braked cycle ergometer in subfreezing conditions (-2.5 /- 0.4 degrees c) 6-8 h after either ml or placebo (pl) to obtain total work accumulated (kj); subjects were evaluated for eib after each exercise trial. eight (33) subjects were identified as eib (23.5 /- 13.35 fall in fev1); 16 were eib- (1.8 /- 3.03 fall in fev1). ml provided an approximately 50 protection against postexercise fall in fev1. no significant differences in kj were found between pl and ml trials for pooled subjects (95.3 /- 13.69 and 94.8 /- 13.27 kj, respectively), eib- subjects (99.6 /- 13.26 and 99.0 /- 11.81 kj, respectively), or eib subjects (86.8 /- 10.67 and 86.5 /- 12.72 kj, respectively). total work accumulated for eib- subjects was significantly greater than for eib subjects for both pl and ml (p 0.05).","a single 10-mg dose of ml had no ergogenic effect for eib- and eib subjects performing short-duration high-intensity exercise in subfreezing temperature, supporting the use of ml as eib prophylaxis during international sport competition.",Medication
"does down-regulation of core 1 beta1,3-galactosyltransferase and cosmc by th2 cytokine alter o-glycosylation of iga1?","patients with iga nephropathy (igan) have an increased amount of abnormally o-glycosylated iga1 in circulation, in glomerular deposits and produced by tissue cells in vitro. although increased production of th2 cytokines by peripheral blood lymphocytes and a functional abnormality of core 1 1,3-galactosyltransferase (c13gal-t) have been proposed as mechanisms underlying pathogenesis of igan, they are still obscure and are not connected. to clarify the effect of t-cell cytokines, we analysed the mrna levels of c13gal-t and its molecular chaperone cosmc, c13gal-t activity and subsequent o-glycosylation of iga1 in a human b-cell line stimulated with these cytokines. the surface iga1-positive human b-cell line was cultured with recombinant human ifn-, il-2, il-4 or il-5. the production and glycosylation of iga1 were determined by sandwich elisa and enzyme-linked lectin binding assay, respectively. the mrna levels of c13gal-t and cosmc were quantitatively measured by real-time pcr. c13gal-t activity was analysed using high-performance liquid chromatography. iga1 production by il-4-stimulated cells was significantly higher than controls or after ifn- or il-5. the terminal glycosylation of secreted iga1 was altered in response to il-4. il-4 stimulation significantly decreased the mrna levels of both c13gal-t and cosmc and of c13gal-t activity. il-4 stimulation was clearly blocked by recombinant human il-4 soluble receptor.",it appears that th2 cytokine il-4 may play a key role in controlling glycosylation of the iga1 hinge region.,Medication
does theophylline inhibit the cough reflex through a novel mechanism of action?,"theophylline has been used in the treatment of asthma and chronic obstructive pulmonary disease for more than 80 years. in addition to bronchodilator and anti-inflammatory activity, clinical studies have suggested that theophylline acts as an antitussive agent. cough is the most frequent reason for consultation with a family doctor, and treatment options are limited. determining how theophylline inhibits cough might lead to the development of optimized compounds. we sought to investigate the inhibitory activity of theophylline on vagal sensory nerve activity and the cough reflex. using a range of techniques, we investigated the effect of theophylline on human and guinea pig vagal sensory nerve activity in vitro and on the cough reflex in guinea pig challenge models. theophylline was antitussive in a guinea pig model, inhibited activation of single c-fiber afferents in vivo and depolarization of human and guinea pig vagus in vitro, and inhibited calcium influx in airway-specific neurons in vitro. a sequence of pharmacological studies on the isolated vagus and patch clamp and single-channel inside-out experiments showed that the effect of theophylline was due to an increase in the open probability of calcium-activated potassium channels. finally, we demonstrated the antitussive activity of theophylline in a cigarette smoke exposure model that exhibited enhanced tussive responses to capsaicin.","theophylline inhibits capsaicin-induced cough under both normal and ""disease"" conditions by decreasing the excitability of sensory nerves through activation of small- and intermediate-conductance calcium-activated potassium channels. these findings could lead to the development of optimized antitussive compounds with a reduced side effect potential.",Symptoms
do serum hepatitis b virus-dna levels correlate with long-term adverse outcomes in spontaneous hepatitis b e antigen seroconverters?,"hepatitis b e antigen (hbeag) status and serum hepatitis b virus (hbv) dna levels are major factors affecting the prognosis of adult hbv carriers; however, the impact of viral load on long-term outcomes after spontaneous hbeag seroconversion remains unclear. a total of 390 spontaneous hbeag seroconverters with a long-term follow-up were enrolled. serum hbv-dna levels at 1 year after hbeag seroconversion were determined, and their correlation with long-term adverse outcomes was explored. in a mean follow-up of 6.8 years, the average annual incidence rates were 4.4 and 1.9 for hbeag-negative hepatitis and hepatitis flare, respectively. compared with patients with hbv-dna levels 200 iu/ml, the adjusted hazard ratios of hbeag-negative hepatitis were 2.4 (95 confidence interval, 1.3-4.4), 3.6 (1.8-7.2), and 5.3 (2.8-10.0), respectively, for serum hbv-dna level of 2000 -2 10(4), 2 10(4) -2 10(5), and 2 10(5) iu/ml. in addition, serum hbv-dna levels were independently associated with hbeag-negative hepatitis flare, which confirmed their impact on the immune active hepatitis after hbeag seroconversion.",hbeag seroconversion may not always confer favorable outcomes. serum hbv-dna levels 2000 iu/ml at 1 year post hbeag seroconversion correlate with increased risk of hbeag-negative hepatitis and hepatitis flare.,Diagnosis
does continuous infusion of nitroglycerin improve pulmonary graft function of non-heart-beating donor lungs?,"the warm ischemic period of lungs harvested from a non-heart-beating donor (nhbd) results in an increased ischemia-reperfusion injury after transplantation. the intravenous application of nitroglycerin (ntg), a nitric oxide (no) donor, proved to be beneficial during reperfusion of lung grafts from heart-beating donors. the objective of the present study was to investigate the effect of nitroglycerin on ischemia-reperfusion injury after transplantation of long-term preserved nhbd-lungs. sixteen pigs (body weight, 20-30 kg) underwent left lung transplantation. in the control group (n5), lungs were flushed (perfadex, 60 ml/kg) and harvested immediately after cardiac arrest. in the nhbd group (n5) and the nhbd-ntg group (n6), lungs were flushed 90 min (warm ischemia) after cardiac arrest. after a total ischemia time of 19 hr, lungs were reperfused and graft function was observed for 5 hr. recipient animals in the nhbd-ntg group received 2 microg/kg/min of ntg administered intravenously during the observation period starting 5 min before reperfusion. tissue specimens and bronchoalveolar lavage fluid (balf) were obtained at the end of the observation period. compared with the control group, pulmonary gas exchange was significantly impaired in the nhbd group, whereas graft function in the nhbd-ntg group did not change. leukocyte fraction and protein concentration in the balf and histologic alteration of the nhbd-ntg group were not different from controls.",continuous infusion of ntg in the early reperfusion period improves pulmonary graft function of nhbd lungs after long-term preservation. the administration of an no donor during reperfusion may favor the use of nhbd lungs to alleviate the critical organ shortage in lung transplantation.,Medication
is seropositivity to multiple sexually transmitted infections common?,"seropositivity for several sexually transmitted infections (stis) is often used as a surrogate measure of sexual behavior. the authors assessed the concomitant seropositivity for stis in women. to estimate the excess of concomitant seropositivity for four stis among fertile-aged women assuming no coinfections above what would be expected at random. antibodies to herpes simplex virus type 2, human papillomavirus type 16, hiv, chlamydia trachomatis, and treponema pallidum were determined from a random sample of 1110 pregnant women in tallinn, estonia. a total of 310 combinations of the concomitant seropositivity were observed, whereas only 193 were expected by chance. among persons seropositive for two stis, 78 extra combinations were observed, whereas for three stis, 35 extra combinations were observed. for four stis, 3.8 extra combinations were found.","seropositivity to multiple stis is not common. this fits the concept of different transmission probabilities and the spread of the stis, and suggests that seropositivity alone should be used with caution as a surrogate to sexual behavior in women.",General
is motility-induced but not vasoactive intestinal peptide-induced increase in luminal alkalinization in rat duodenum dependent on luminal cl ( - )?,"to investigate whether the motility- and the vasoactive intestinal peptide (vip)-induced increase in luminal alkalinization in the duodenum is dependent on luminal cl(-). experiments were performed in anaesthetized rats in vivo. the proximal duodenum was perfused luminally with an isotonic solution, containing zero or low cl(-) and the effects on luminal alkalinization, motility, fluid flux and epithelial permeability were determined. parecoxib, a cox-2 inhibitor, was used to induce duodenal contractions. control rats lacked duodenal wall contractions while parecoxib-treated ones exhibited contractions throughout the experiment. most animals had a net fluid absorption during the perfusion with isotonic nacl. luminal alkalinization was about 100 higher in parecoxib-treated rats than in controls. cl(-) -free solutions did not affect epithelial permeability or motility but decreased luminal alkalinization by 50 and decreased net fluid absorption in both control and parecoxib-treated animals. reduction in luminal cl(-) decreased alkalinization in a concentration-dependent manner. the parecoxib-induced increase in alkalinization was markedly reduced in the absence of luminal cl(-) . vip increased luminal alkalinization and induced fluid secretion. the lack of luminal cl(-) did not affect the vip-induced increase in alkalinization but reduced fluid secretion.","the parecoxib-induced increase in luminal alkalinization is highly dependent on luminal cl(-) and it is proposed that cox-2 inhibition, via induction of duodenal motility, enhances hco(3) (-) efflux through stimulation of apical cl(-) /hco(3) (-) exchange in duodenal epithelial cells. although the vip-induced stimulation of fluid secretion is partly dependent on luminal cl(-) , the vip-induced increase in luminal alkalinization is not.",Medication
does normalization of vital signs reduce the probability of acute pulmonary embolism in symptomatic emergency department patients?,"in a patient with symptoms of pulmonary embolism (pe), the presence of an elevated pulse, respiratory rate, shock index, or decreased pulse oximetry increases pretest probability of pe. the objective of this study was to evaluate if normalization of an initially abnormal vital sign can be used as evidence to lower the suspicion for pe. this was a prospective, noninterventional, single-center study of diagnostic accuracy conducted on adults presenting to an academic emergency department (ed), with at least one predefined symptom or sign of pe and one risk factor for pe. clinical data, including the first four sets of vital signs, were recorded while the patient was in the ed. all patients underwent computed tomography pulmonary angiography (ctpa) and had 45-day follow-up as criterion standards. diagnostic accuracy of each vital sign (pulse rate, respiratory rate, shock index, pulse oximetry) at each time was examined by the area under the receiver operating characteristic curve (auc). a total of 192 were enrolled, including 35 (18) with pe. all patients had vital signs at triage, and 174 (91), 135 (70), and 106 (55) had second to fourth sets of vital signs obtained, respectively. the initial pulse oximetry reading had the highest auc (0.63, 95 confidence interval ci 0.50 to 0.76) for predicting pe, and no other vital sign at any point had an auc over 0.60. among patients with an abnormal pulse rate, respiratory rate, shock index, or pulse oximetry at triage that subsequently normalized, the prevalences of pe were 18, 14, 19, and 33, respectively.",clinicians should not use the observation of normalized vital signs as a reason to forego objective testing for symptomatic patients with a risk factor for pe.,Symptoms
is olfactory impairment correlated with confabulation in alcoholism : towards a multimodal testing of orbitofrontal cortex?,"olfactory abilities are now a flourishing field in psychiatry research. as the orbitofrontal cortex appears to be simultaneously implicated in odour processing and executive impairments, it has been proposed that olfaction could constitute a cognitive marker of psychiatric states. while this assumption appears promising, very few studies have been conducted on this topic among psychopathological populations. the present study thus aimed at exploring the links between olfaction and executive functions. these links were evaluated using two tasks of comparable difficulty, one known to rely on orbitofrontal cortex processing (i.e., a confabulation task), and one not associated with this area (i.e., stop-signal task). twenty recently detoxified alcoholic individuals and twenty paired controls took part in an experiment evaluating olfactory abilities and executive functioning (i.e., stop-signal task and confabulation task). comorbidities and potential biasing variables were also controlled for. alcoholic individuals exhibited impaired performance for high-level olfactory processing and significant confabulation problems as compared to controls (but no deficit in stop-signal task), even when the influence of comorbidities was taken into account. most importantly, olfactory abilities and confabulation rates were significantly correlated in both groups.","alcoholism jointly leads to olfactory and memory source impairments, and these two categories of deficits are associated. these results strongly support the proposition that olfactory and confabulation measures both index orbitofrontal functioning, and suggest that olfaction could become a reliable cognitive marker in psychiatric disorders. moreover, it underlines the need to take into account these olfactory and source memory impairments in a clinical context.",Diagnosis
does n-acetyl-cysteine treatment improve insulin sensitivity in women with polycystic ovary syndrome?,"to evaluate the effect of n-acetyl-cysteine (nac) on insulin secretion and peripheral insulin resistance in subjects with polycystic ovary syndrome (pcos). prospective data analysis. volunteer women in an academic research environment. six lean and 31 obese subjects, aged 19-33 years. patients were treated for 5-6 weeks with nac at a dose of 1.8 g/day orally. a dose of 3 g/day was arbitrarily chosen for massively obese subjects. six of 31 obese patients with pcos were treated with placebo and served as controls. before and after the treatment period, the hormonal and lipid blood profile and insulin sensitivity, assessed by an hyperinsulinemic euglycemic clamp, were evaluated and an oral glucose tolerance test (ogtt) was performed. fasting glucose, fasting insulin, and glucose area under curve (auc) were unchanged after treatment. insulin auc after ogtt was significantly reduced, and the peripheral insulin sensitivity increased after nac administration, whereas the hepatic insulin extraction was unaffected. the nac treatment induced a significant fall in t levels and in free androgen index values (p.05). in analyzing patients according to their insulinemic response to ogtt, normoinsulinemic subjects and placebo-treated patients did not show any modification of the above parameters, whereas a significant improvement was observed in hyperinsulinemic subjects.",nac may be a new treatment for the improvement of insulin circulating levels and insulin sensitivity in hyperinsulinemic patients with polycystic ovary syndrome.,Medication
is dual b cell immunotherapy superior to individual anti-cd20 depletion or baff blockade in murine models of spontaneous or accelerated lupus?,"to determine whether a combination of b cell depletion and baff blockade is more effective than monotherapy in treating models of spontaneous or accelerated systemic lupus erythematosus (sle) in (nzb nzw)f1 mice. clinical parameters such as disease progression-free survival, proteinuria, and renal injury were assessed in models of spontaneous, interferon- (ifn)-accelerated, or pristane-accelerated lupus in (nzb nzw)f1 mice. treatment arms included anti-cd20 (b cell depletion), b lymphocyte stimulator receptor 3 fusion protein (br-3-fc) (baff blockade), the combination of anti-cd20 and br-3-fc, isotype control, or cyclophosphamide. in models of spontaneous, ifn-accelerated, or pristane-accelerated lupus, mice were treated for 24 weeks, 8 weeks, or 12 weeks, respectively. peripheral and resident b cell subsets and various autoantibodies were examined. compared to b cell depletion or baff blockade alone, combined therapy significantly improved disease manifestations in all 3 lupus models. in addition, marginal zone b cells, plasmablasts, and circulating and tissue plasma cells were decreased more effectively. dual b cell immunotherapy also reduced multiple classes of pathogenic autoantibodies, consistent with its observed effectiveness in reducing immune complex-mediated renal injury.","dual immunotherapy via b cell depletion and baff blockade is more efficacious than single agent immunotherapy in murine sle models, and this combination treatment is predicted to be an effective strategy for immunotherapy in human sle.",Treatment
does pretreatment but not treatment with probiotics abolish mouse intestinal barrier dysfunction in acute pancreatitis?,"intestinal barrier failure during acute pancreatitis (ap) is associated with translocation of luminal bacteria, resulting in infectious complications. we examined the effects of multispecies probiotics on the intestinal barrier impairment in a murine model of ap. mice were injected with cerulein to induce ap and were sacrificed 11 (early ap) or 72 hours (late ap) after start of induction. ap and associated systemic effects were confirmed by histology of pancreas and lung. animals received daily probiotics starting 2 days prior to ap induction (pretreatment) or at the moment of ap induction (treatment). mucosal barrier function of the distal ileum was assessed in ussing chambers by measurement of the epithelial electrical resistance and the permeability to na-fluorescein. histological analysis revealed pancreatic injury in both phases of ap, and lung damage in the early phase. epithelial resistance of the ileum was reduced and permeability increased in both phases of ap, indicating impairment of the intestinal barrier. pretreatment had no effect on resistance or permeability in the early phase of ap. in the late phase of ap, pretreatment but not treatment abolished the ap induced resistance decrease and permeability increase. administration of probiotics as such (ie, without induction of ap) had no effect on intestinal barrier function.","pretreatment with multispecies probiotics for 2 days abolishes intestinal barrier dysfunction in the late phase of ap, while treatment does not. the effectiveness of probiotics in this model depends on the timing of administration. clinical trials with probiotics should seek conditions where treatment can be started prior to onset of disease or elective surgical intervention.",Treatment
do am-pac 6-clicks '' functional assessment scores predict acute care hospital discharge destination?,"physical therapists and occupational therapists practicing in acute care hospitals play a crucial role in discharge planning. a standardized assessment of patients' function could be useful for discharge recommendations. the study objective was to determine the accuracy of ""6-clicks"" basic mobility and daily activity measures for predicting discharge from an acute care hospital to a home or institutional setting. the study was retrospective and observational. ""6-clicks"" scores obtained at initial visits by physical therapists or occupational therapists and patients' discharge destinations were used to develop and validate receiver operating characteristic curves for predicting discharge destination. positive predictive values (ppv), negative predictive values (npv), and likelihood ratios were calculated. areas under the receiver operating characteristic curves for basic mobility scores were 0.857 (95 confidence interval ci0.852, 0.862) and 0.855 (95 ci0.850, 0.860) in development and validation samples, respectively. areas under the curves for daily activity scores were 0.846 (95 ci0.841, 0.851) and 0.845 (95 ci0.840, 0.850) in development and validation samples, respectively. cutoff scores providing the best accuracy for determining discharge destination were 42.9 for basic mobility and 39.4 for daily activity. for basic mobility, the ppv was 0.748 and the npv was 0.801 in both development and validation samples. for daily activity, the ppvs were 0.787 and 0.784 and the npvs were 0.748 and 0.746 in development and validation samples, respectively.","limitations included lack of information on the rater reliability of ""6-clicks"" instruments, use of surrogate data for some discharge designations, and use of a clinical database for research purposes.",Treatment
does universal health insurance coverage eliminate inequities in access to cardiac procedures after acute myocardial infarction?,"it remains unclear whether socioeconomic status (ses) influences access to invasive cardiac procedures after acute myocardial infarction (ami) in a universal health care system. the objective of this study was to evaluate the effect of ses on access to cardiac procedure after ami in a universal health care system. this was an observational cohort study of all patients with a first ami in the province of quebec, canada, between 1985 to 1995. information on treatment was obtained from the discharge and physicians' claims databases. ses was obtained from census data by linking postal codes. ses-independent predictors of use were identified, then incorporated in hierarchical models to predict use in low, medium, and high ses areas. the main outcome measures were rates of cardiac catheterization, percutaneous coronary intervention (pci), and coronary artery bypass graft surgery (cabg) as a function of ses. ses data were available for 62,364 individuals with a first ami. of these, 65 were men and the mean age was 64 /- 13 years. rates of cardiac procedures rose with an increase in several ses measures. after adjustment for individual-level predictors of use of cardiac catheterization, average rent, (odds ratio per 100 difference: 1.57, 95 credible interval: 1.36 to 1.80) and proportion of renters, (odds ratio, 2.2; 95 ci: 1.21 to 3.73) in the area were independent ses predictors. patients in low ses areas (median family income: 30,809 cdn) were less likely to undergo cardiac catheterization than patients in high ses areas (92,169 cdn) (men: 33; compared with 47; women: 18; compared with 47). however, among patients with cardiac catheterization, ses was not associated with the use of revascularization procedures. for example, pci rates for men within 90 days after ami were 26, compared with 25 in low and high ses areas, respectively. cabg rates were 15, compared with 19.","we found that in the universal health care system of canada, access to cardiac catheterization after ami varied according to ses. among those with cardiac catheterization, ses did not appear to influence further use of revascularization procedures.",Treatment
does resistance exercise affect the serum concentrations of cell adhesion molecules?,"cell adhesion molecules are proteins expressed on the surface of a variety of cells and mediate the leucocyte response to inflammation. some of these molecules are released to the plasma as soluble forms, whose presence indicates the degree of vascular endothelial activation or dysfunction. increased concentrations of soluble adhesion molecules are thought to hamper the immune response and mediate the atherosclerotic inflammatory process. studies on the effect of exercise on the concentrations of soluble adhesion molecules have almost exclusively used aerobic exercise. to assess the effect of resistance exercise on the serum concentrations of five cell adhesion molecules during and immediately after 30 min of exercise in lean and obese participants. fourteen healthy young men (eight lean and six obese) performed 3 sets of 10 resistance exercises with 10-12 repetitions at 70-75 of one repetition maximum in a circuit training fashion. venous blood samples were drawn at baseline and at the end of the first, second and third sets. the serum concentrations of vascular cell adhesion molecule-1, intercellular cell adhesion molecule-1, e-selectin, p-selectin and l-selectin were measured in a biochip array analyser. no significant changes were observed in the concentrations of these cell adhesion molecules during exercise, or between lean and obese participants.","our data indicate that resistance exercise of moderate to high intensity does not affect the serum concentrations of cell adhesion molecules in healthy young lean or obese men, suggesting no considerable negative effect on immune function.",Prevention
is diabetic hdl dysfunctional in stimulating endothelial cell migration and proliferation due to down regulation of sr-bi expression?,"diabetic hdl had diminished capacity to stimulate endothelial cell (ec) proliferation, migration, and adhesion to extracellular matrix. the mechanism of such dysfunction is poorly understood and we therefore sought to determine the mechanistic features of diabetic hdl dysfunction. we found that the dysfunction of diabetic hdl on human umbilical vein endothelial cells (huvecs) was associated with the down regulation of the hdl receptor protein, sr-bi. akt-phosphorylation in huvecs was induced in a biphasic manner by normal hdl. while diabetic hdl induced akt phosphorylation normally after 20 minutes, the phosphorylation observed 24 hours after diabetic hdl treatment was reduced. to determine the role of sr-bi down regulation on diminished ec responses of diabetic hdl, mouse aortic endothelial cells (maecs) were isolated from wild type and sr-bi (-/-) mice, and treated with normal and diabetic hdl. the proliferative and migratory effects of normal hdl on wild type maecs were greatly diminished in sr-bi (-/-) cells. in contrast, response to diabetic hdl was impaired in both types suggesting diminished effectiveness of diabetic hdl on ec proliferation and migration might be due to the down regulation of sr-bi. additionally, sr-bi down regulation diminishes diabetic hdl's capacity to activate akt chronically.","diabetic hdl was dysfunctional in promoting ec proliferation, migration, and adhesion to matrix which was associated with the down-regulation of sr-bi. additionally, sr-bi down regulation diminishes diabetic hdl's capacity to activate akt chronically.",Symptoms
does positive end-expiratory pressure aggravate left ventricular diastolic relaxation further in patients with pre-existing relaxation abnormality?,"positive end-expiratory pressure (peep) has been known to adversely influence cardiac output. even though left ventricular (lv) diastolic function significantly contributes to lv performance, the effects of peep on lv diastolic function remains controversial. we, therefore, aimed to examine the effects of peep on lv diastolic function by use of pulsed wave doppler tissue imaging in patients with pre-existing lv relaxation abnormality. seventeen patients with peak early diastolic velocity of lateral mitral annulus (e') 8.5 cm s(-1) among patients who underwent coronary artery bypass graft surgery were evaluated. echocardiographic and haemodynamic variables were measured with 0, 5, and 10 cmh2o of peep. e' and deceleration time (dt) of peak early transmitral filling velocity (e) were used as echocardiographic indicators of lv diastolic function. mean arterial blood pressure decreased during 10 cmh2o peep, compared with that during 0 cmh2o peep. e' showed a gradual and significant decrease with an incremental increase in peep (6.9 0.9, 5.8 0.9, and 5.2 1.2 cm s(-1) during 0, 5, and 10 cmh2o peep, respectively), and dt of e was prolonged during 10 cmh2o peep, compared with that during 0 cmh2o peep.",increasing peep led to a progressive decline in lv relaxation in patients with pre-existing lv relaxation abnormality.,Treatment
is extent of cell electrofusion in vitro and in vivo cell line dependent?,"electric pulses delivered to cells that are in close contact may induce cell fusion, by a process termed electrofusion. recently it has been shown that electrofusion in tumours in vivo depends on tumour type. the aim of this work was to examine the differences in electrofusion in various cell lines, both in vivo and in vitro. lpb, b16f10 and dc-3f cells in vitro and llc tumours in vivo were exposed to various electric pulses. the number of fused cells was then evaluated. cell electropermeabilization was confirmed to be a necessary but non-exclusive condition to obtain a high level of cell electrofusion. the extent of electrofusion depends both on the degree of permeabilization and cell type.","it was observed that metastatic tumour cells easily electrofuse, suggesting that cell type-specific membrane properties and/or secretion of proteases determine the extent of electrofusion.",General
does chek2 repress breast stromal fibroblasts and their paracrine tumor-promoting effects through suppressing sdf-1 and il-6?,"active fibroblasts, the predominant and the most active cells of breast cancer stroma, are responsible for tumor growth and spread. however, the molecular mediators and pathways responsible for stromal fibroblast activation, and their paracrine pro-carcinogenic effects are still not well defined. the chek2 tumor suppressor gene codes for a protein kinase, which plays important roles in the cellular response to various genotoxic stresses. immunoblotting, quantitative rt-pcr and immunofluorescence were used to assess the expression of chek2 in different primary breast fibroblasts and in tissues. the effect of chek2 on the expression and secretion of sdf-1 and il-6 was evaluated by immunoblotting and elisa. the wst-1 colorimetric assay was used to assess cell proliferation, while the bd biocoat matrigel invasion chambers were utilized to determine the effects of chek2 on the migratory and the invasiveness capacities of breast stromal fibroblasts as well as breast cancer cells. we have shown that chek2 is down-regulated in most cancer-associated fibroblasts (cafs) as compared to their corresponding tumor counterpart fibroblasts (tcfs) at both the mrna and protein levels. interestingly, chek2 down-regulation using specific sirna increased the expression/secretion of both cancer-promoting cytokines sdf-1 and il-6, and transdifferentiated stromal fibroblasts to myofibroblasts. these cells were able to enhance the proliferation of non-cancerous epithelial cells, and also boosted the migration/invasion abilities of breast cancer cells in a paracrine manner. the later effect was sdf-1/il-6-dependent. importantly, ectopic expression of chek2 in active cafs converted these cells to a normal state, with lower migration/invasion capacities and reduced paracrine pro-carcinogenic effects.","these results indicate that chek2 possesses non-cell-autonomous tumor suppressor functions, and present the chk2 protein as an important mediator in the functional interplay between breast carcinomas and their stromal fibroblasts.",General
is video-assisted thoracoscopic surgery a promising treatment for solitary fibrous tumor of the pleura?,"solitary fibrous tumors of the pleura (sftps) are slow-growing neoplasms. approximately 800 cases have been reported in the literature to date. the aim of this study was to address our experience with the management of sftps and to evaluate the advantage of video-assisted thoracoscopic surgery (vats) in sftp treatment. retrospective analysis of our experience. department of thoracic and cardiovascular surgery, nara medical university. from january 1992 to august 2002, 13 patients with a sftp were referred to us for surgical resection after vats was adopted in our hospital. the study group consisted of seven men and six women with a mean age of 49.8 years (age range, 37 to 72 years). surgical excision was performed with vats only in nine patients, with vats plus a small thoracotomy in three patients, and by a posterolateral thoracotomy without vats in one patient. the mean chest-drain duration was 1.3 days (range, 1 to 3 days), and the mean duration of hospital stay was 8.6 days (range, 3 to 30 days). eleven tumors, originating from the visceral pleura, were pedunculate, and 2 tumors from the parietal pleura were not pedunculate. two cases were focally characterized by a mitotic count in excess of four mitoses per 10 high-power fields and by cellular pleomorphism. follow-up periods ranged from 6 to 120 months, with a mean of 49.7 months and a median of 42 months. all patients have remained well with no recurrence or metastasis.","complete surgical resection is the treatment of choice for sftps. for the pedunculate tumors, therefore, vats is a powerful and useful approach. even when it is necessary to perform a small thoracotomy in addition to vats for the removal of a large tumor, vats may play an important role in reducing the size of the thoracotomy incision, which results in less invasive surgery. to minimize postoperative morbidity, vats may be the most promising surgical approach for the resection of sftps.",Treatment
does a complex case management system provide optimal care for all patients?,"to describe the complex case management system developed by optical express, a large corporate provider of laser vision correction, and to detail the benefits this system offers for managing the surgical complications of laser vision correction. the classification scheme optical express uses to categorize surgical complications is described, and the various pathways patients can take through the complex case system are detailed. this process is illustrated with a case study describing the treatment of a patient with postoperative lasik ectasia. the benefits of the complex case system are also discussed. a total of 1363 eyes were treated in the complex case management system during the 5-year period between january 1, 2004 and december 31, 2008. these 1363 eyes represent a small fraction (0.45) of the approximately 300,000 eyes treated during this period. the optical express complex case management system organizes complications based on severity and urgency. grade a complications (40 eyes, 2.9 of all complications) are the most serious and urgent, followed by grade b (327 eyes, 24.0), and grade c (996 eyes, 73.1). for each complication, the patient's journey through the complex case system starts with an evaluation by an optometrist. depending on the severity of the complication, the patient may then be referred to the treating surgeon, a regional complex case surgeon, or an external consultant. a complex case manager coordinates care and logistics throughout this process.",the complex case management system used by optical express provides clinical care and support for patients who experience a surgical complication.,Treatment
are patients presenting at the emergency department with acute abdominal pain less likely to be admitted to inpatient wards at times of access block : a registry study?,"also known as access block, shortage of inpatient beds is a common cause of emergency department (ed) boarding and overcrowding, which are both associated with impaired quality of care. recent studies have suggested that access block not simply causes boarding in eds, but may also result in that patients are less likely to be admitted to the hospital from the ed. the present study's aim was to investigate whether this effect remained for patients with acute abdominal pain, for which different management strategies have emerged. access block was defined in terms of hospital occupancy and the appropriateness of ed discharges addressed as 72 h revisits to the ed. as a registry study of ed administrative data, the study examined a population of patients who presented with acute abdominal pain at the ed of a 420-bed hospital in southern sweden during 2011-2013. associations between exposure and outcomes were addressed in contingency tables and by logistic regression models. crude analysis revealed a negative association between access block and the probability of inpatient admission (38.6 admitted at 0-95 occupancy, 37.8 at 95-100 occupancy, and 35.0 at 100 occupancy) (p .001). no significant associations between exposure and 72 h revisits emerged. multivariable models indicated an odds ratio of inpatient admission of 0.992 (95 ci: 0.986-0.997) per percentage increase in hospital occupancy.","study findings indicate that patients with acute abdominal pain are less likely to be admitted to the hospital from the ed at times of access block and that other management strategies are employed instead. no association with 72 h revisits was seen, but future studies need to address more granular outcomes in order to clarify the safety aspects of the effect.",Symptoms
do concomitant nitrates enhance clopidogrel response during dual anti-platelet therapy?,"despite advances in modern anti-platelet strategies, clopidogrel still remains the cornerstone of dual anti-platelet therapy (dapt) in patients undergoing percutaneous coronary interventions (pci). there is some inconclusive evidence that response after clopidogrel may be impacted by concomitant medications, potentially affecting clinical outcomes. sustained released nitrates (srn) are commonly used together with clopidogrel in post-pci setting for mild vasodilatation and nitric oxide-induced platelet inhibition. we prospectively enrolled 458 patients (64.5 9.6 years old, and 73.4 males) following pci undergoing dapt with clopidogrel and aspirin. platelet reactivity was assessed by the verifynow p2y12 assay at the maintenance outpatient setting. concomitant srn (n266) significantly (p0.008) enhanced platelet inhibition after dapt (251.6 80.9pru) when compared (232.1 73.5pru) to the srn-free (n192) patients. multivariate logistic regression analysis with the cut-off value of 253 pru for defining heightened platelet reactivity confirmed independent correlation of more potent platelet inhibition during dapt and use of srn (relative risk1.675; odds ratio 1.059-2.648; p0.027). in contrast, statins, calcium-channel blockers, beta blockers, angiotensin receptor blockers, ace-inhibitors, diuretics, and anti-diabetic agents did not significantly impact platelet inhibition following dapt.","the synergic ability of srn to enhance response during dapt may have important clinical implications with regard to better cardiovascular protection, but extra bleeding risks, requiring further confirmation in a large randomized study.",Medication
are plasma osteoprotegerin levels decreased in smoker chronic periodontitis patients?,"the aim of this study was to evaluate plasma levels of soluble receptor activator of nuclear factor-kappa b ligand (srankl) and osteoprotegerin (opg) in smoker versus non-smoker chronic periodontitis patients. plasma samples were obtained from 13 smoker and 31 non-smoker systemically healthy chronic periodontitis patients, as well as 13 smoker and 29 non-smoker systemically and periodontally healthy subjects. before commencing any periodontal intervention, venous blood samples were obtained and whole-mouth clinical periodontal measurements were recorded. srankl and opg concentrations in plasma samples were determined by enzyme-linked immunosorbent assay (elisa) technique. data were tested statistically by student's t test, wilcoxon matched pairs test, and spearman's correlation analysis. all clinical periodontal measurements were significantly higher in chronic periodontitis groups than the healthy controls (p 0.05). smoker chronic periodontitis patients exhibited significantly lower (p 0.007) plasma opg concentrations and higher srankl/opg ratio (p 0.01) than smoker healthy controls.","within the limits of this study, periodontal inflammation in smoker chronic periodontitis patients seems to lower plasma osteoprotegerin levels and thereby increase the rankl/opg ratio, and possibly play a role in the increased susceptibility for alveolar bone destruction in smoker subjects.",Medication
is helicobacter pylori infection associated with type 2 diabetes among a middle- and old-age chinese population?,"although the association of helicobacter pylori (h. pylori) infection with diabetes mellitus has been evaluated, findings are controversial. this study investigated the association in a chinese population. a cross-sectional study, including a total of 30 810 subjects from the dongfeng-tongji cohort study, was conducted. h. pylori status was measured via (14) c urea breath test. association analysis was performed by logistic regression, with multivariable adjustment for sex, age, body mass index, smoking, alcohol consumption, family history of diabetes, physical activity and the use of antibiotics. among a middle-age and old-age chinese population, individuals with h. pylori infection also had a higher prevalence of type 2 diabetes (21.3 versus 20.2, p 0.026). h. pylori infection was associated with higher risk of type 2 diabetes odds ratio, 1.08 (95 confidence interval: 1.02-1.14); p 0.008 after adjustment for other confounders. the association was significant among women, those who were above 65 years old, not overweight or obese, and those who did not smoke, did not consume alcohol and without family history of diabetes. however, there was no interaction between h. pylori infection and other traditional risk factors on type 2 diabetes risk. subjects with h. pylori infection had a lower level of high-density lipoprotein cholesterol (p 0.0001) and higher levels of blood pressure (p 0.001), total cholesterol, hba1c and fasting blood glucose (p 0.0001) than those who did not.","these findings suggested that h. pylori infection was associated with the risk of type 2 diabetes in a middle-age and old-age chinese population. copyright 2015 john wiley sons, ltd.",Prevention
does chronic stimulation of the tone of endogenous anandamide reduce cue- and stress-induced relapse in rats?,"the endogenous cannabinoid system plays an important role in motivation, stress, and drug abuse. pharmacologically, the endocannabinoid system can be stimulated by either agonists of cb1 receptors or inhibition of metabolic degradation of endogenous cannabinoids and consequent increases in their brain levels. here, we investigated whether chronic administration during a period of withdrawal of the fatty acid amide hydrolase inhibitor urb597, which increases anandamide levels, would decrease the risks of relapse to cocaine seeking. rats were allowed to self-administer cocaine and then they underwent forced withdrawal for 28 days, during which they were treated with urb597 or vehicle. one day after the last injection, we investigated cocaine seeking in one 6h extinction session and relapse triggered by re-exposure to drug-associated cues or a pharmacological stressor. we found that administration of urb597 significantly decreases cocaine-seeking behavior and cue- and stress-induced relapse.",these results suggest that stimulation of the endocannabinoid system could be helpful to prevent relapse to cocaine addiction.,Medication
does treatment with lenalidomide modulate t-cell immunophenotype and cytokine production in patients with chronic lymphocytic leukemia?,"lenalidomide, an immunomodulatory agent, has activity in lymphoproliferative disorders. the authors, therefore, evaluated its effects on t-cell immunophenotype and cytokine production in patients with chronic lymphocytic leukemia (cll). to study the immunomodulatory effects of lenalidomide in cll, the authors recruited 24 patients with untreated cll enrolled in a phase 2 clinical trial of lenalidomide and obtained peripheral blood specimens for immunologic studies consisting of enumeration of t cells and assessing their ability to synthesize cytokines after activation through t-cell receptor (tcr). after 3 cycles of therapy, patients had a significant reduction in percentage () and absolute lymphocyte count (alc) and an increase in percentage of t cells, percentage of activated cd8() t cells producing ifn-, and percentage of regulatory t (t(r) ) cells when compared with their respective levels before treatment. after 15 cycles of treatment, responder patients had significant reduction in percentage of lymphocytes and alc, percentage of activated cd4() t cells producing il-2, ifn-, or tnf-, and percentage of t(r) cells when compared with their perspective levels after 3 cycles of treatment. furthermore, the numbers of activated cd4() t cells producing il-2, ifn-, or tnf-, activated cd8() t cells producing ifn-, and t(r) cells normalized to the range of healthy subjects.","treatment with lenalidomide resulted in the normalization of functional t-cell subsets in responders, suggesting that lenalidomide may modulate cell-mediated immunity in patients with cll.",Treatment
does heat shock factor 1 inhibit nuclear factor-kappab nuclear binding activity during endotoxin tolerance and heat shock?,"sepsis, endotoxin tolerance, and heat shock (hs) all display down-regulation of innate immunity. we hypothesize that hs factor 1 (hsf-1) induces competitive inhibition of nuclear factor-kappab (nf-kappab)-induced signal transduction in both endotoxin tolerance and hs. we compared endotoxin tolerance and hs in raw 264.7 cells. we transfected cells with an hs protein 70 (hsp70) plasmid to test whether hsp70 is the mediator of hs-induced nf-kappab inhibition. we studied the effects of endotoxin stimulation and hs, both separately and together, on ""wild-type"" cells, cells transfected with the hsp70 plasmid, and cells transfected with vehicle. heat shock protein 70 plasmid-transfected cells had increased hsp70 expression and demonstrated decreased nitric oxide (no) release and inducible no synthase messenger rna expression in response to endotoxin compared with wild-type and empty plasmid-transfected cells. heat shock completely abolished subsequent no and inducible no synthase messenger rna expression in wild-type cells. heat shock factor 1 reached maximum expression 60 to 90 minutes after hs. heat shock protein 70-transfected cells still displayed endotoxin-induced nf-kappab nuclear binding, whereas endotoxin tolerance, hs, and exposure to hsf-1, but not exposure to an unrelated promoter, inhibited nf-kappab nuclear binding.","endotoxin tolerance and hs appear to share a common immune suppressive effect, possibly through hsf-1-mediated competitive inhibition of nf-kappab nuclear binding.",General
is quality of life before intensive care unit admission a predictor of survival?,"predicting whether a critically ill patient will survive intensive care treatment remains difficult. the advantages of a validated strategy to identify those patients who will not benefit from intensive care unit (icu) treatment are evident. providing critical care treatment to patients who will ultimately die in the icu is accompanied by an enormous emotional and physical burden for both patients and their relatives. the purpose of the present study was to examine whether health-related quality of life (hrqol) before admission to the icu can be used as a predictor of mortality. we conducted a prospective cohort study in a university-affiliated teaching hospital. patients admitted to the icu for longer than 48 hours were included. close relatives completed the short-form 36 (sf-36) within the first 48 hours of admission to assess pre-admission hrqol of the patient. mortality was evaluated from icu admittance until 6 months after icu discharge. logistic regression and receiver operating characteristic analyses were used to assess the predictive value for mortality using five models: the first question of the sf-36 on general health (model a); hrqol measured using the physical component score (pcs) and mental component score (mcs) of the sf-36 (model b); the acute physiology and chronic health evaluation (apache) ii score (an accepted mortality prediction model in icu patients; model c); general health and apache ii score (model d); and pcs, mcs and apache ii score (model e). classification tables were used to assess the sensitivity, specificity, positive and negative predictive values, and likelihood ratios. a total of 451 patients were included within 48 hours of admission to the icu. at 6 months of follow up, 159 patients had died and 40 patients were lost to follow up. when the general health item was used as an estimate of hrqol, area under the curve for model a (0.719) was comparable to that of model c (0.721) and slightly better than that of model d (0.760). when pcs and mcs were used, the area under the curve for model b (0.736) was comparable to that of model c (0.721) and slightly better than that of model e (0.768). when using the general health item, the sensitivity and specificity in model d (sensitivity 0.52 and specificity 0.81) were similar to those in model a (0.45 and 0.80). similar results were found when using the mcs and pcs.","this study shows that the pre-admission hrqol measured with either the one-item general health question or the complete sf-36 is as good at predicting survival/mortality in icu patients as the apache ii score. the value of these measures in clinical practice is limited, although it seems sensible to incorporate assessment of hrqol into the many variables considered when deciding whether a patient should be admitted to the icu.",Diagnosis
does biodentine reduce tumor necrosis factor alpha-induced trpa1 expression in odontoblastlike cells?,"the transient receptor potential (trp) ion channels have emerged as important cellular sensors in both neuronal and non-neuronal cells, with trpa1 playing a central role in nociception and neurogenic inflammation. the functionality of trp channels has been shown to be modulated by inflammatory cytokines. the aim of this study was to investigate the effect of inflammation on odontoblast trpa1 expression and to determine the effect of biodentine (septodent, paris, france) on inflammatory-induced trpa1 expression. immunohistochemistry was used to study trpa1 expression in pulp tissue from healthy and carious human teeth. pulp cells were differentiated to odontoblastlike cells in the presence of 2 mmol/l beta-glycerophosphate, and these cells were used in quantitative polymerase chain reaction, western blotting, calcium imaging, and patch clamp studies. immunofluorescent staining revealed trpa1 expression in odontoblast cell bodies and odontoblast processes, which was more intense in carious versus healthy teeth. trpa1 gene expression was induced in cultured odontoblastlike cells by tumor necrosis factor alpha, and this expression was significantly reduced in the presence of biodentine. the functionality of the trpa1 channel was shown by calcium microfluorimetry and patch clamp recording, and our results showed a significant reduction in tumor necrosis factor alpha-induced trpa1 responses after biodentine treatment.","in conclusion, this study showed trpa1 to be modulated by caries-induced inflammation and that biodentine reduced trpa1 expression and functional responses.",Medication
do influence of implant number on the movement of mandibular implant overdentures?,"the rotational movement of an implant overdenture (iod) has a negative effect on the perceived masticatory ability of the denture wearer. however, the influence of implant number on the movement of iods has not been investigated. the purpose of this in vitro study was to evaluate the denture movement of mandibular iods anchored by different numbers of implants. an edentulous mandibular test model with artificial mucosa and 5 experimental overdentures (n5) was fabricated. the locator attachment system with blue nylon inserts was chosen for this study. three implant positions were prepared: anterior midline (1-iod), bilateral lateral incisor regions (2-iod), and anterior midline and bilateral canine regions (3-iod). vertical loads of 50 n were applied to the mid-anterior region, the left canine region, the left premolar region, and the left first molar region. the vertical and horizontal displacements at the right distal edge and the vertical displacements at the loading point were measured. the displacement values were statistically analyzed using a 1-way analysis of variance and the post hoc tukey honest significant difference test with the implant number as a factor. in addition, the values of the vertical and horizontal displacements at the distal edge of the overdenture were statistically compared using a paired t test, and the values of the vertical displacement at the distal edge of the overdenture were statistically analyzed by a repeated measures analysis of variance and the post hoc tukey honest significance difference test with the loading point as a factor (a.05). upon anterior loading, the 2-iod showed significantly larger vertical displacements at the right distal edge than the 1-iod or 3-iod (p.05).","within the limitations of this in vitro study, the following conclusions were drawn: during mastication with the anterior teeth, the use of 2 implants for anchoring an iod increased the rotation of the denture base more than the use of 1 or 3 implants. the horizontal movements of the iods were small compared with the vertical movements. denture movement under the occlusal force in the molar region was smaller than that in the anterior region.",General
does mineral and/or milk supplementation of fruit beverages help in the prevention of h2o2-induced oxidative stress in caco-2 cells?,"fruit beverages are commonly supplemented with milk, vitamins and/or minerals in order to improve their healthy effects by providing some bioactive components that can act additively or synergistically against oxidative stress. to test whether iron, zinc, and milk added to fruit beverages do not affect the cytoprotective effect against oxidative damage to caco-2 cells through gsh-related enzymes induction and cell cycle progression preservation, in comparison with non-supplemented fruit beverage. caco-2 cells were incubated 24 h with the bioaccessible fraction (bf) of eight fruit beverages with/without iron and/or zinc, and/or milk, and then challenged with h2o2 (5 mmol l-1 -2 h). mitochondrial enzyme activities (mtt test), gsh-rd and gsh-px enzyme activities, cell cycle progression and caspase-3 activity were measured.","fruit beverages prevented the deleterious effect of h2o2 on cell viability, with almost all samples reaching control basal levels. only independent iron or zinc supplementation with/without milk exerted positive effects upon gsh-rd activity. both minerals with milk, afforded improved preservation of gsh-px activity. all samples prevented the decrease in the g1 phase of cell cycle induced by h2o2, except iron supplemented samples with/without milk, but none of them avoided the increase in sub-g1 phase. however, this fact was not associated to caspase-3 activity, with a probable positive effect of zinc upon this parameter.",Prevention
are white matter hyperintensities rather than lacunar infarcts associated with depressive symptoms in older people : the ladis study?,"both white matter hyperintensities (wmh) and lacunar infarcts have been associated with the development of depression in older subjects, although the relative importance of the two and the influence of lesion location and concomitant vascular disease are unclear. this study investigates the relationship between location and burden of wmh and lacunes on depressive features in older people. in a pan-european multicenter study of 626 older subjects, the authors examined the relationship between regional magnetic resonance imaging white matter hyperintensities, number of lacunar infarcts, depressive symptoms as assessed by the 15-item geriatric depression scale (gds), cognitive status (mini-mental status examination), hypertension, and self-perceived health quality of life (qol). the authors found depressive symptoms to be correlated with wmh rating in the frontal (n626; spearman's rho0.161, p 0.001) and temporal (rho0.14, p 0.001) but not occipitoparietal region (rho0.07, p0.07). basal ganglia lacunes were only weakly correlated with gds (rho0.09, p0.03), and lacunes in other regions showed no association. in a ordinal logistic regression model (controlling for qol, mini-mental status examination, age, and with an interaction between wmh and hypertension), temporal wmh in the absence of hypertension independently predicted gds, whereas neither history of stroke nor number of lacunar infarcts did. the authors compared left- versus right-sided wmh and found no effect of laterality on depressive symptoms.","the results suggest that in this population of nondisabled older people, wmh have a greater influence on depressive symptoms than infarcts.",Symptoms
does caffeine attenuate liver fibrosis via defective adhesion of hepatic stellate cells in cirrhotic model?,"several epidemiological studies have shown that coffee intake attenuates the progression of liver fibrosis; however, the mechanism is unclear. we investigated the direct effects of caffeine on hepatic stellate cells (hscs) and assessed whether caffeine attenuated intrahepatic fibrosis in rat model of liver cirrhosis. human hepatic stellate cell line, an immortalized human hscs line, was used in in vitro assay system. cell migration and proliferation were assessed in presence of various caffeine concentrations (0, 1, 5, and 10 mmol), and levels of procollagen type ic and -smooth muscle actin (-sma) were measured by western blot. severity of liver inflammation and fibrosis were compared between thioacetamide-treated rats with and without caffeine supplementation. caffeine increased hscs apoptosis and intracellular f-actin and cyclic adenosine monophosphate expression. caffeine also inhibited procollagen type ic and -sma expression in a dose- and time-dependent manner. in rat model, caffeine decreased periportal inflammation, levels of inflammatory cells (1.4 0.52 vs 2.6 0.46, p 0.05), and fibrosis (2.1 0.35 vs 2.9 0.84, p 0.05). transforming growth factor- and -sma expressions were also reduced by caffeine.",caffeine attenuates the progression of liver fibrosis by inhibiting hscs adhesion and activation.,Medication
does rosiglitazone reverse mitomycin c resistance in human gastric cancer cells?,"to explore the mechanisms of rosiglitazone (ros), a selective peroxisome proliferator-activated receptor gamma ligand, in reversing mitomycin c (mmc) resistance in a human drug-resistant gastric cancer cell line. the vincristine-resistant human gastric cancer cell line sgc7901/vcr and its parental cell line sgc7901 were treated with ros, mmc (negative control), cyclosporine ammc (positive control) or rosmmc. a tetrazolium blue (methyl thiazolyl tetrazolium) assay was used to evaluate the sensitivity to these treatments. flow cytometry analysis and acridine orange-ethidium bromide (ao-eb) fluorescent staining were used to determine the effects of ros on mmc-induced apoptosis. reverse transcription polymerase chain reaction and western blotting were used to measure the expression of multidrug resistant 1 (mdr1), livin and p-glycoprotein (p-gp). ros administration dose dependently increased the reversal index in mmc-treated scg7901/vcr cells. ros increased apoptosis in sgc7901/vcr cells compared with the blank group and mmc group. rosmmc also increased apoptosis in sgc7901/vcr cells compared with other groups (p 0.05 or p 0.01). the mrna expression of mdr1 and livin and the protein expression of p-gp in sgc7901/vcr cells were significantly higher than those in sgc7901 cells (p 0.01). however, ros or rosmmc treatment markedly upregulated the mrna expression of mdr1 and livin and the protein expression of p-gp in sgc7901/vcr cells (p 0.01).","ros reverses mmc resistance in human gastric cancer sgc7901/vcr cells by reducing expression of mdr1, livin and p-gp and increasing apoptosis.",Medication
do insulin use and smoking jointly increase the risk of bladder cancer mortality in patients with type 2 diabetes?,"whether insulin use predicts bladder cancer mortality has not been investigated. furthermore, it is not known whether insulin use and smoking jointly influence the risk. a total of 86,939 patients (40,014 men, 46,925 women) with type 2 diabetes mellitus (t2dm) and aged 25 years in a nationally representative cohort were followed prospectively from 1995 to 2006 for bladder cancer mortality. cox regression was used considering the following independent variables: age, sex, diabetes duration, body mass index, smoking, insulin use, and area of residence. the models were created for patients aged 25 and 65 years, separately; and sensitivity analyses were conducted after excluding (1) patients with duration between onset of diabetes and bladder cancer mortality 5 years, and (2) patients with diabetes duration at recruitment 3 years. the joint effect of insulin use and smoking was evaluated. patients who died of bladder cancer were characterized by older age, male predominance, longer diabetes duration, smoking, and insulin use. in multivariable cox models, age, male sex, and insulin use were consistently predictive for bladder cancer mortality in all analyses, whereas the other variables were not. the adjusted hazard ratios for bladder cancer mortality for insulin users vs. nonusers ranged from 1.877 to 2.502 in different models (all p values .05). insulin use and smoking jointly increased the adjusted hazard ratio to 3.120 (95 confidence interval, 1.329-7.322).",insulin use is significantly predictive for bladder cancer mortality in patients with t2dm. insulin use and smoking jointly increase the risk.,Medication
is serum bilirubin inversely associated with insulin resistance and metabolic syndrome among children and adolescents?,bilirubin is a potent antioxidant and a cyroprotectant. low serum bilirubin is associated with atherosclerosis. little is known about its role in metabolic syndrome (ms) among children and adolescents. we examined 4723 children and adolescents aged 12-17 years with reliable measures of various serum hepatic profiles and metabolic risks from health and nutrition examination survey 1999-2004. the results showed that the prevalence of the ms was from 6.6/-1.2 in the lowest quartile to 2.1/-1.9 in the highest quartile of the concentration of total bilirubin. the graded association remained significant after the adjustment of other co-variates. the odds ratios for the ms were around 0.29 (0.08-0.99) and 0.23 (0.08-0.65) for the upper two quartiles when using the lowest quartile as reference for the concentration of total bilirubin. the quartiles of the serum total bilirubin levels were inversely correlated with the homeostasis model assessment (homa-ir) and insulin while not associated with the serum c-reactive protein (crp) levels.,the serum total bilirubin levels are inversely correlated with the prevalence of the ms. the mechanism of the association between ms and total bilirubin may be related to the insulin resistance status.,Medication
does loss of tissue expression of interleukin-10 promote the disease progression of colorectal carcinoma?,"interleukin-10 (il-10) is a unique cytokine that is thought to be a potent immunostimulatory and immunosuppressive factor. the aim of this study was to investigate il-10 expression in colorectal cancer, and clarify its relationship to the clinicopathological findings and prognosis. tissue samples were collected from 92 patients with colorectal cancer and adjacent normal mucosa. the expression of il-10 in colorectal cancer tissues was evaluated by immunohistochemistry. tissue levels of il-10 were measured by enzyme-linked immunosorbent assay. the mean concentration of il-10 did not significantly differ between the cancer tissue and adjacent normal mucosa. the il-10 concentration in cancer tissue with positive staining immunohistochemically was significantly higher than that without il-10 staining. the il-10 level in cancer tissue decreased in accordance with advanced-stage serosal invasion and lymph node involvement, and thus predicted poor survival in patients undergoing surgery with curative intent. a cox multivariate analysis demonstrated that a decreased il-10 level in cancer tissue was an independent risk factor for poor survival.","the tumor il-10 level in colorectal cancer was inversely correlated with serosal invasion and lymph node metastasis, which thus reflected tumor progression. evaluating the tumor expression of il-10 may therefore provide valuable information for predicting the long-term survival in patients undergoing surgery with curative intent.",Prevention
does an integrative review of factors associated with fall during post-stroke rehabilitation?,"our aims were to evaluate evidence of risk factors for falls among patients in stroke rehabilitation and to offer recommendations for clinical practice and future research. we conducted an integrative review of the literature published from 1990 to 2009 that describes empirical investigations of risk factors for post-stroke falls during inpatient rehabilitation. we searched medline, the cumulative index to nursing and allied health literature (cinahl), psycinfo, and embase databases, using the search terms ""accidental falls,""""fall risk,""""risk factors,""""risk assessment,""""stroke,"" and ""cerebrovascular disorders."" we extracted information regarding study design, sample, potential risk factors, analytic methods, findings, and limitations from the 14 articles that met our inclusion criteria, and we rated the level of evidence for each study. available empirical evidence points to impaired balance, visuospatial hemineglect, and impaired performance of activities of daily living as risk factors for falls during inpatient rehabilitation for stroke. associations between falls and cognitive function, incontinence, visual field deficits, and stroke type were less clear, while relationships between falls and age, gender, stroke location, and impaired vision and hearing were not supported.","the relatively sparse literature pertaining to risk factors for falls among stroke rehabilitation inpatients indicates that deficits affecting balance, perception, and self-care significantly increase the likelihood of falls. particularly intriguing is the less well established role of post-stroke cognition in falls in this population. a conceptual model is needed to guide scientific inquiry and clinical practice in this area.",Treatment
do alpha-actinin and filamin cooperatively enhance the stiffness of actin filament networks?,"the close subcellular proximity of different actin filament crosslinking proteins suggests that these proteins may cooperate to organize f-actin structures to drive complex cellular functions during cell adhesion, motility and division. here we hypothesize that alpha-actinin and filamin, two major f-actin crosslinking proteins that are both present in the lamella of adherent cells, display synergistic mechanical functions. using quantitative rheology, we find that combining alpha-actinin and filamin is much more effective at producing elastic, solid-like actin filament networks than alpha-actinin and filamin separately. moreover, f-actin networks assembled in the presence of alpha-actinin and filamin strain-harden more readily than networks in the presence of either alpha-actinin or filamin.","these results suggest that cells combine auxiliary proteins with similar ability to crosslink filaments to generate stiff cytoskeletal structures, which are required for the production of internal propulsive forces for cell migration, and that these proteins do not have redundant mechanical functions.",General
is reverse remodelling through exercise training more pronounced in non-ischemic heart failure?,"most training studies in patients with chronic heart failure (chf) do not consider chf aetiology in the interpretation of the results. about 60 of the patients in those studies have ischemic chf (ihf) and 40 non-ischemic chf (nhf). recently, we conducted a randomized controlled trial to study three different training modalities in 60 patients with severe chf, with a similar distribution of ihf and nhf patients. in the present post hoc analysis we compared the differences in training results between ischemic and non-ischemic patients. left ventricular ejection fraction (ef), end diastolic volume (edv), end systolic volume (esv), measured with radionuclide ventriculography (rnv) and echocardiography, nt-pro bnp, peak oxygen uptake (peak v(o)(2)), working capacity and muscular volume were analyzed before and after training in 45 patients training for 40 sessions, 3 times per week. fifteen patients served as control group. the outcome was analyzed considering the aetiology of chf, either ischemic or non-ischemic. there were no significant differences in improvements of peak v(o)(2), working capacity and muscular volume between ihf and nhf patients. in nhf patients, ef increased while edv and esv decreased after training. these parameters remained unchanged in ihf patients after training. nt-pro bnp decreased significantly in nhf patients and increased in ihf patients after training. in the control group, patients showed a mild improvement of ef and a decrease of nt-pro bnp.","this post hoc analysis shows that training intervention is associated with significant reverse remodelling in nhf, but not in ihf patients, whereas v(o)(2) peak and muscle volume improve regardless of chf aetiology. future prospective studies are needed to confirm our findings.",Prevention
does pulsed electromagnetic fields stimulation prevent steroid-induced osteonecrosis in rats?,"pulsed electromagnetic fields (pemf) stimulation has been used successfully to treat nonunion fractures and femoral head osteonecrosis, but relatively little is known about its effects on preventing steroid-induced osteonecrosis. the purpose of the study was to investigate the effects of pemf stimulation on the prevention of steroid-induced osteonecrosis in rats and explore the underlying mechanisms. seventy-two male adult wistar rats were divided into three groups and treated as follows. (1) pemf stimulation group (pemf group, n 24): intravenously injected with lipopolysaccharide (lps, 10 g/kg) on day 0 and intramuscularly injected with methylprednisolone acetate (mpsl, 20 mg/kg) on days 1, 2 and 3, then subjected to pemf stimulation 4 h per day for 1 to 8 weeks. (2) methylprednisolone-treated group (mpsl group, n 24): injected the same dose of lps and mpsl as the pemf group but without exposure to pemf. (3) control group (ps group, n 24): injected 0.9 saline in the same mode at the same time points. the incidence of osteonecrosis, serum lipid levels and the mrna and protein expression of transforming growth factor 1 (tgf-1) in the proximal femur were measured 1, 2, 4 and 8 weeks after the last mpsl (or saline) injection. the incidence of osteonecrosis in the pemf group (29) was significantly lower than that observed in the mpsl group (75), while no osteonecrosis was observed in the ps group. the serum lipid levels were significantly lower in the pemf and ps groups than in the mpsl group. compared with the mpsl and ps groups, the mrna expression of tgf-1 increased, reaching a peak 1 week after pemf treatment, and remained high for 4 weeks, then declined at 8 weeks, whereas the protein expression of tgf-1 increased, reaching a peak at 2 weeks after pemf treatment, and remained high for 8 weeks.","pemf stimulation can prevent steroid-induced osteonecrosis in rats, and the underlying mechanisms involve decreased serum lipid levels and increased expression of tgf-1.",Prevention
is fgf23 protein expression in coronary arteries associated with impaired kidney function?,"fibroblast growth factor 23 (fgf23) levels are elevated in chronic kidney disease (ckd) and elevated values have been associated with both heart disease and mortality. recent studies show that fgf23, a protein synthesized by osteocytes, is also present in calcified atherosclerotic plaques and may be induced by heart disease. whether vascular expression of fgf23 is associated with progressive ckd, however, remains unknown. therefore, the relationship between kidney function, vascular calcification and fgf23 expression was evaluated in patients with heart disease. immunohistochemistry for fgf23 was performed in coronary arteries of all patients undergoing heart transplantation at ucla between february 2008 and 2010. immunohistochemical staining for klotho, dmp1, fgfr1, and fgfr3; calcium deposition; and rna expression of klotho and dmp1 were assessed in a subset of eight samples. fgf23 was detected by immunohistochemistry in 56 of the coronary artery specimens. vascular fgf23 expression correlated with declining kidney function, as evidenced by reduced creatinine clearance. fgfr1 and fgfr3 were detected throughout the vascular tissue and in calcified plaques. calcium deposition, klotho expression and dmp1 expression correlated with fgf23 immunoreactivity.",the findings suggest that the klotho-fgf23-fgfr system is active in coronary arteries and its upregulation correlates with impaired renal function and matrix calcium deposition.,Treatment
does npc1 repression contribute to lipid accumulation in human macrophages exposed to environmental aryl hydrocarbons?,"aryl hydrocarbons (ahs), such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (tcdd) and benzo(a)pyrene (bp), are environmental contaminants promoting the development of atherosclerosis-related cardiovascular diseases. in order to identify molecular mechanisms involved in these effects, we have analysed ah-mediated regulation of the lipid trafficking niemann-pick type c1 protein (npc1) and its contribution to ah-induced macrophage lipid accumulation. exposure of primary human macrophages to tcdd and bp decreased npc1 mrna expression in a time-dependent manner. npc1 protein expression and npc1-related acid sphingomyelinase activity were reduced in parallel. npc1 was also similarly down-regulated in mice exposed to bp. moreover, tcdd and bp were demonstrated to trigger lipid accumulation in human macrophages, as assessed by oil red o and nile red staining and cholesterol determination. such lipid loading occurred at least partly in endosomal/lysosomal compartments as demonstrated by immunolabelling of lipid vesicles by the lysosome-associated membrane protein 1. these cellular phenotypic effects were found to be similar to those triggered by knock-down of npc1 expression using sirnas and were counteracted by npc1 overexpression, thus supporting the contribution of npc1 to ah-mediated lipid accumulation in macrophages. finally, both npc1 down-expression and lipid accumulation in response to tcdd were found to be abolished through knock-down of the ah receptor (ahr), a ligand-activated transcription factor mediating many effects of ahs.","our data have shown that contaminants such as tcdd and bp repress npc1 expression in macrophages in an ahr-dependent manner, which likely contributes to macrophage lipid accumulation caused by these environmental chemicals. thus, npc1 appears to be a new molecular target regulated by environmental ahs and putatively involved in their deleterious cardiovascular effects.",Medication
does detection of sonographic markers of fetal aneuploidy depend on maternal and fetal characteristics?,"the purpose of this study was to determine factors that influence the detection rate of sonographic markers of fetal aneuploidy (smfa). we reviewed the sonographic images of 160 consecutive second-trimester trisomic fetuses for the presence of smfa, either structural anomalies or sonographic soft markers. one hundred forty-nine (93.1) records were complete and analyzed; 78 cases (52.3) were identified with 1 or more smfa. sonographic markers of fetal aneuploidy were detected in 42.7, 75.0, and 90.9 of trisomies 21, 18, and 13, respectively (p.005). the detection rate of smfa had a positive linear correlation with gestational age (adjusted r(2)0.64; p.002). sonographic markers of fetal aneuploidy were detected in 43.7 of fetuses of less than 18.0 weeks' gestation and 64.5 of fetuses of 18.0 weeks' gestation or greater (likelihood ratio6.4; p.01). sonographic markers of fetal aneuploidy were detected in 23.5 of patients with suboptimal image quality versus 58.3 of the others (likelihood ratio7.5; p.05). the rate of structural malformation was similar between the male and female fetuses, whereas that of soft markers was 49.4 in male and 30.0 in female fetuses (odds ratio2.3; range, 1.2-4.5; p.02). factor analysis showed that some soft markers and some structural anomalies tended to appear together.","the type of fetal trisomy, gestational age, sex, and quality of images influence the detection rate of smfa. the highest detection rate for smfa in the second trimester is at or above 18 weeks' gestational age. certain markers are detected in clusters. these findings may explain, in part, the variability in reported rates of detection of smfa among trisomic fetuses. these findings need to be prospectively tested in the general population of pregnancies for applicability to sonographic risk calculations for fetal trisomies.",Diagnosis
do age and diet affect gene expression profiles in canine liver tissue?,"the liver plays a central role in nutrient and xenobiotic metabolism, but its functionality declines with age. senior dogs suffer from many of the chronic hepatic diseases as elderly humans, with age-related alterations in liver function influenced by diet. however, a large-scale molecular analysis of the liver tissue as affected by age and diet has not been reported in dogs. liver tissue samples were collected from six senior (12-year old) and six young adult (1-year old) female beagles fed an animal protein-based diet (apb) or a plant protein-based diet (ppb) for 12 months. total rna in the liver tissue was extracted and hybridized to affymetrix genechip canine genome arrays. using a 2.0-fold cutoff and false discovery rate 0.10, our results indicated that expression of 234 genes was altered by age, while 137 genes were differentially expressed by diet. based on functional classification, genes affected by age and/or diet were involved in cellular development, nutrient metabolism, and signal transduction. in general, gene expression suggested that senior dogs had an increased risk of the progression of liver disease and dysfunction, as observed in aged humans and rodents. in particular for aged liver, genes related to inflammation, oxidative stress, and glycolysis were up-regulated, whereas genes related to regeneration, xenobiotic metabolism, and cholesterol trafficking were down-regulated. diet-associated changes in gene expression were more common in young adult dogs (33 genes) as compared to senior dogs (3 genes).","our results provide molecular insight pertaining to the aged canine liver and its predisposition to disease and abnormalities. therefore, our data may aid in future research pertaining to age-associated alterations in hepatic function or identification of potential targets for nutritional management as a means to decrease incidence of age-dependent liver dysfunction.",Prevention
are eosinophil granulocytes activated during the remission phase of ulcerative colitis?,"the aim of this study was to establish a method of investigating intestinal eosinophil and neutrophil granulocytes by flow cytometry, and to compare the distribution and activity of these cells in different stages of ulcerative colitis (uc). biopsy samples were taken from six locations of the entire colon and from the terminal ileum in 10 patients with active total uc, 10 patients with inactive total uc, eight patients with active distal uc, and 11 control subjects. cell suspensions from biopsies and from peripheral blood were incubated with fluorophore conjugated monoclonal antibodies. the use of scatter plot-gating and specific antibodies was established in a flow cytometry assay. eosinophils were more numerous and more active in patients with active uc than in controls. interestingly, during inactive uc, the number of activated eosinophils was even larger. eosinophil activity was high in the rectum of patients with distal colitis but was also slightly elevated in the proximal colon. neutrophils were increased in number and activity during active but not inactive uc. in patients with distal colitis, activated neutrophils were only found in the sigmoid colon and rectum.","with this method, we confirm that neutrophils participate in the inflammatory process during active uc, and that they express a resting phenotype during remission. the finding of activated eosinophils in inflamed intestine strengthens the view of these cells as proinflammatory and tissue damaging. nevertheless, our new finding of high eosinophil activation during inactive uc suggests that eosinophils play a role in repair of injured epithelium.",Diagnosis
does transfer time to a high-volume center for patients with subarachnoid hemorrhage affect outcomes?,"the objective of our study was to examine patients with aneurysmal subarachnoid hemorrhage transferred and directly admitted to our institution in order to determine how transfer time affects outcomes. a retrospective cohort study was performed of all patients undergoing treatment for aneurysmal subarachnoid hemorrhage between 2005 and 2012 at the university of michigan. variables, including transfer time, were tested for their independent association with the primary outcomes of symptomatic vasospasm and 12-month outcome as well as secondary outcomes of aneurysm rebleeding and 12-month mortality. during the study period, 263 (87.4) patients were transferred to our institution and 38 (12.6) were directly admitted for treatment of aneurysmal subarachnoid hemorrhage. transfer time was not associated with the occurrence of symptomatic vasospasm, 12-month outcome, rebleeding, or 12-month mortality. higher hunt-hess grade was associated with the occurrence of symptomatic vasospasm as well as with poorer 12-month outcome.","transfer time was not associated with the occurrence of symptomatic vasospasm, 12-month outcome, rebleeding, or 12-month mortality. we believe our data argue that protocols should emphasize early resuscitation and stabilization followed by safe transfer rather than a hyperacute transfer paradigm. however, transfer time should be minimized as much as possible so as not to delay time to definitive treatment.",Treatment
is coronary artery disease detected by coronary computed tomography angiography associated with red cell distribution width?,"increased red blood cell distribution width (rdw) is associated with severity of coronary artery disease (cad). the aim of the present study was to retrospectively evaluate the relationship between cad detected by coronary computed tomography angiography (ccta) and rdw. records of 291 patients who underwent 16-slice ccta due to the presence of angina-like chest pain were retrospectively evaluated. exclusion criteria were applied. clinical characteristics, risk factors for cad, and rdw values on ccta were noted. rdw levels in patients with cad were significantly higher than in those with normal coronary arteries (ncas) (15.501.57 compared to 14.801.41, p0.001). diabetes mellitus, hypertension, and history of smoking were significantly more common in the cad group (p0.018, p0.007, and p0.013, respectively). on multivariate logistic regression analysis, rdw (p0.009 odds ratio (or): 1.352; 95 confidence interval (ci): 1.081-1.683), age (p0.001 or: 1.063; 95 ci 1.031-1.090), and history of smoking (p0.003 or: 2.672; 95 ci: 1.360-5.232) were shown to be independent predictors for cad detected by ccta.",the present results suggest that higher rdw levels are independently associated with presence of cad detected by ccta in patients without known cad. further studies are warranted to clarify the exact role of rdw in risk stratification.,Prevention
do reactive oxygen species mediate endotoxin-induced human dermal endothelial nf-kappab activation?,"microvascular endothelial cell ""activation"" by endotoxin is an early and critical phenomenon underlying organ dysfunction related to sepsis. dermal endothelial cells contribute to many of the manifestations of septic shock, such as cutaneous interstitial edema and loss of peripheral vasomotor regulation. human dermal endothelial cell activation by endotoxin (lipopolysaccharide lps) is characterized by the generation of reactive oxygen species (ros) that enhance nuclear translocation of the transcription factor kappa-b (nf-kappab). we tested our hypothesis by stimulating human dermal microvascular endothelial cells (hmec.1) with endotoxin and assaying for endothelial generation of ros and nuclear translocation of nf-kappab subunits. hmec.1 cultures were treated individually with lps, hydrogen peroxide, or xanthine, xanthine oxidase, and ferrous sulfate (xanthine/xo/fe(2)). nuclear proteins were isolated and consensus sequence binding was assessed by electrophoretic mobility shift assay (emsa). 2',7'-dichlorofluorescin diacetate and confocal microscopy were used to examine ros production in lps-stimulated hmec.1. nuclear translocation of the p65/p50 nf-kappab heterodimer was detectable 30 min after stimulation with lps alone or the xanthine/xo/fe(2) combination, but not with hydrogen peroxide. antioxidant n-acetylcysteine (nac) inhibited lps-stimulated ros production in hmec.1. antioxidant prior to or simultaneously with lps exposure, but not following lps, also prevented nf-kappab activation. nac was ineffective at inhibiting nf-kappab translocation at increased lps concentrations.","dermal endothelial cells, a microvascular cell type that may contribute to the systemic response to blood-borne endotoxemia, generate ros in the absence of other inflammatory cells. these lps-activated endothelial cells, in turn, rapidly translocate transcription factor nf-kappab to cell nuclei, a process regulated in part by intracellular ros.",Symptoms
does a maternal high salt diet disturb cardiac and vascular function of offspring?,"high salt intake is an environmental factor that promotes increased blood pressure. we previously demonstrated that high salt diet causes aggravation of hypertension and impaired vasodilation in response to nitric oxide (no) in young spontaneously hypertensive rats (shr), which exhibit low sensitivity to salt in adulthood. changes in offspring blood pressure and cardiovascular structures have been reported. however, it remains unclear to what extent a maternal high salt intake may affect cardiac and/or vascular function in offspring. therefore, we investigated influence of exposure to a maternal high salt diet during gestation and lactation on offspring's cardiac and arterial functions in shr. shr dams were fed either a high salt diet or a control diet. after weaning, the offspring were fed the high salt diet or control diet for 8weeks. compared with offspring of control diet-fed dams, at 12weeks of age, offspring of the high-salt diet-fed dams had lower blood pressure, heart rate, indices of both left ventricular systolic and diastolic function, and a decreased aortic vasodilation response to no. postnatal high salt intake did not affect blood pressure, vasodilatory response, or cardiac function in offspring of high-salt diet-fed dams. neither maternal nor postnatal dietary salt altered levels of lipid peroxide, superoxide dismutase, or angiotensinogen mrna in serum and ventricle of the offspring.",exposure to high maternal dietary salt induces cardiac and vascular dysfunction in offspring. these results point to the possible importance of avoiding excess dietary salt during gestation and lactation.,Prevention
is t-cell profile in adipose tissue associated with insulin resistance and systemic inflammation in humans?,"the biological mechanisms linking obesity to insulin resistance have not been fully elucidated. we have shown that insulin resistance or glucose intolerance in diet-induced obese mice is related to a shift in the ratio of pro- and anti-inflammatory t cells in adipose tissue. we sought to test the hypothesis that the balance of t-cell phenotypes would be similarly related to insulin resistance in human obesity. healthy overweight or obese human subjects underwent adipose-tissue biopsies and quantification of insulin-mediated glucose disposal by the modified insulin suppression test. t-cell subsets were quantified by flow cytometry in visceral (vat) and subcutaneous adipose tissue (sat). results showed that cd4 and cd8 t cells infiltrate both depots, with proinflammatory t-helper (th)-1, th17, and cd8 t cells, significantly more frequent in vat as compared with sat. t-cell profiles in sat and vat correlated significantly with one another and with peripheral blood. th1 frequency in sat and vat correlated directly, whereas th2 frequency in vat correlated inversely, with plasma high-sensitivity c-reactive protein concentrations. th2 in both depots and peripheral blood was inversely associated with systemic insulin resistance. furthermore, th1 in sat correlated with plasma interleukin-6. relative expression of associated cytokines, measured by real-time polymerase chain reaction, reflected flow cytometry results. most notably, adipose tissue expression of anti-inflammatory interleukin-10 was inversely associated with insulin resistance.",cd4 and cd8 t cells populate human adipose tissue and the relative frequency of th1 and th2 are highly associated with systemic inflammation and insulin resistance. these findings point to the adaptive immune system as a potential mediator between obesity and insulin resistance or inflammation. identification of antigenic stimuli in adipose tissue may yield novel targets for treatment of obesity-associated metabolic disease.,Medication
does acute stretch perception alteration contribute to the success of the pnf contract-relax '' stretch?,"some researchers have suggested that an alteration of stretch perception could be responsible for the success of the contract-relax (cr) stretch, a stretch technique derived from proprioceptive neuromuscular facilitation (pnf). this study was conducted to determine if the alteration of the stretch perception is a possible explanation for the range of motion (rom) gains of the cr stretch. eighteen subjects performed two stretches in randomized order: the slow stretch and the cr stretch. the stretch intensity was controlled. the stretch force was measured and compared between the slow stretch and cr stretch. there was a significant difference between the stretch force that could be applied in the pnf stretch (126.0 n) and the slow stretch (108.4 n); p 0.00086. the average stretch tolerance progressively increased with successive trials from 120.6 n in the first trial to 132.4 n in the fourth trial.",the alteration of stretch perception plays a role in the success of the cr form of pnf stretching. at least four repetitions of the cr stretch are recommended to get the greatest rom gain.,General
do human basophils express amphiregulin in response to t cell-derived il-3?,"amphiregulin, a member of the epidermal growth factor family, is expressed by activated mouse t(h)2 cells. amphiregulin produced by mouse hematopoietic cells contributes to the elimination of a nematode infection by a type 2 effector response. to identify the human peripheral blood cell population expressing amphiregulin. amphiregulin-expressing cells were identified by flow cytometry of cell surface markers and histologic staining. histamine and amphiregulin in supernatants were measured by enzyme immunoassay. quantitative real-time pcr was used to measure mrna expression. stimulation of human pbmcs by anti-cd3 anti-cd28 antibodies induced expression of amphiregulin mrna and protein by a non-t-cell population. the amphiregulin-producing cells were basophils, as judged by morphology and expression of cd203c and cd123 (il-3 receptor chain). activated mouse basophils also produced amphiregulin. amphiregulin expression by basophils in response to anti-tcr stimulation required il-3 produced by t cells, and il-3 alone induced high levels of amphiregulin expression by purified basophils. amphiregulin was expressed at much higher levels when human basophils were stimulated by il-3 than by ige cross-linking, whereas the opposite was true for il-4 expression and histamine release. heparin-binding epidermal growth factor-like growth factor was also expressed by il-3-stimulated human basophils. pbmcs from human subjects with asthma contained significantly higher numbers of basophils able to produce amphiregulin compared with controls with or without allergy.","il-3 can induce basophils to express high levels of amphiregulin, which may contribute to tissue remodeling during type 2 immune responses such as asthma.",Medication
is bap1 a good prognostic factor in advanced non-small cell lung cancer?,"non-small cell lung cancer (nsclc) is the leading worldwide source of cancer-related deaths. although some drugs targeting epidermal growth factor receptor (egfr) mutations have been developed, most advanced nsclc is still incurable and new targets for anticancer drugs are in demand. brca1-associated protein-1 (bap1) is a component of the ubiquitin proteasome system (ups). ups has emerged as a potential target for anticancer drugs. the aim of the present study was to investigate the expression of bap1 protein in patients with nsclc. bap1 expression was measured using western blot analysis in 103 cases patients with advanced nsclc. results revealed 49 (47.5) patients were classified with high expression of bap1. squamous cell carcinomas were more likely to be observed in bap1 high expressers compared with adenocarcinomas (55.8 vs. 32.3, p 0.001). high bap1 expression was associated with no lymph node metastasis (p 0.002). there was also a significant association between bap1 expression and histological type (p 0.014), while expression of bap1 was not correlated with other clinical or pathological characteristics. kaplan-meier survival analysis showed that patients with high bap1 expression had a longer median survival compared with patients with low bap1 expression (23.2 vs. 14.7 months, p 0.021). multivariate analysis revealed that high bap1 expression was an independent lower risk for all 103 patients (hr 0.61, 95 ci 0.32-0.71, p 0.003).",bap1 may be a useful prognostic factor of nsclc patients and potential target for anticancer drugs.,Diagnosis
does pulsed electromagnetic fields dosing impact postoperative pain in breast reduction patients?,"pulsed electromagnetic fields (pemf) reduce postoperative pain and narcotic requirements in breast augmentation, reduction, and reconstruction patients. pemf enhances both calmodulin-dependent nitric oxide and/or cyclic guanosine monophosphate signaling and phosphodiesterase activity, which blocks cyclic guanosine monophosphate. the clinical effect of these competing responses on pemf dosing is not known. two prospective, nonrandomized, active cohorts of breast reduction patients, with 15 min pemf per 2 h; ""q2 (active)"", and 5 min pemf per 20 min; ""5/20 (active)"", dosing regimens were added to a previously reported double-blind clinical study wherein 20 min pemf per 4 h, ""q4 (active)"", dosing significantly accelerated postoperative pain reduction compared with q4 shams. postoperative visual analog scale pain scores and narcotic use were compared with results from the previous study. visual analog scale scores at 24 h were 43 and 35 of pain at 1 h in the q4 (active) and q2 (active) cohorts, respectively (p 0.01). pain at 24 h in the 5/20 (active) cohort was 87 of pain at 1 h, compared with 74 in the q4 (sham) cohort (p 0.451). concomitantly, narcotic usage in the 5/20 (active) and q4 (sham) cohorts was not different (p 0.478), and 2-fold higher than the q4 (active) and q2 (active) cohorts (p 0.02).","this prospective study shows q4/q2, but not 5/20 pemf dosing, accelerated postoperative pain reduction compared with historical shams. the 5/20 (active) regimen increases no 4-fold faster than the q4 (active) regimen, possibly accelerating phosphodiesterase inhibition of cyclic guanosine monophosphate sufficiently to block the pemf effect. this study helps define the dosing limits of clinically useful pemf signals.",Treatment
is the expression of thyroid hormone receptors ( thr ) regulated by the progesterone receptor system in first trimester placental tissue and in bewo cells in vitro?,"thyroid hormones are essential for the maintenance of pregnancy and a deficiency in maternal thyroid hormones has been associated with early pregnancy losses. the aim of this study was a systematic investigation of the influence of mifepristone (ru 486) on the expression of the thyroid hormone receptor (thr) isoforms thr1, thr2, thr1 and thr2 on protein and mrna-level. samples of placental tissue were obtained from patients with mifepristone induced termination of pregnancy (n13) or mechanical induced termination of normal pregnancy (n20), each from the 4th to 13th week of pregnancy. expression of thr1, thr2, thr1 and thr2 was analysed on protein level by immunohistochemistry and on mrna level by real time rt-pcr (taqman). the influence of progesterone on thr gene expression was analysed in the trophoblast tumour cell line bewo by real time rt-pcr (taqman). nuclear expression of thr1, thr2 and thr1 is downregulated on protein level in mifepristone (ru 486) treated villous trophoblast tissue. in decidual tissue, we found a significant downregulation only for thr1 in mifepristone treated tissue. on mrna level, we also found a significantly reduced expression of thra but no significant downregulation for thrb in placental tissue. the gene thra encodes the isoform thr and the gene thrb encodes the isoform thr. the majority of cells expressing the thyroid hormone receptors in the decidua are decidual stromal cells. in addition, in vitro experiments with trophoblast tumour cells showed that progesterone significantly induced thra but not thrb expression.","termination of pregnancy with mifepristone (ru 486) leads to a downregulation of thr1, thr2 and thr1 in villous trophoblasts and in addition to a decreased expression of thra in placental tissue. decreased expression of thr1 induced by ru486 could also be found in the decidua. therefore inhibition of the progesterone receptor may be responsible for this downregulation. this assumption is supported by the finding, that stimulation of the progesterone receptor by progesterone itself up-regulated thra in trophoblast cells in vitro.",Medication
is flow cytometry a promising and rapid method for differentiating between freely suspended escherichia coli and e. coli attached to clay particles?,"a standard procedure does not exist to distinguish between attached and unattached micro-organisms. in this study, we compared two methods to quantify between escherichia coli attached to clay particles and e. coli freely suspended in solution: flow cytometry (attachment assay and viability assay) and settling (or centrifugation followed by settling). methods were tested using three environmental strains collected from swine facilities (a, b and c) and one purchased modified pathogenic strain (atcc 43888); four clay particles: hectorite, kaolinite, ca-montmorillonite, montmorillonite k-10; and a range of surface area ratios (particle surface area to e. coli surface area). when comparing the two methods, the per cent attached obtained from the flow cytometry was lower, but not significantly different from the per cent attached obtained from the settling method for all conditions except when the particle was hectorite or montmorillonite k-10; when the strain was c; and when the surface area ratio was below 100. differences between the methods are likely because traditional culture-based methods cannot detect the viable but nonculturable (vbnc) population, whereas flow cytometry can detect the fraction of vbnc with intact membranes.",our results indicate that flow cytometry is a rapid and culture-independent method for differentiating between attached and unattached micro-organisms.,Treatment
are polymorphic variants in hereditary pancreatic cancer genes associated with pancreatic cancer risk?,"inherited risk of pancreatic cancer has been associated with mutations in several genes, including brca2, cdkn2a (p16), prss1, and palb2. we hypothesized that common variants in these genes, single nucleotide polymorphisms (snp), may also influence risk for pancreatic cancer development. a clinic-based case-control study in non-hispanic white persons compared 1,143 patients with pancreatic adenocarcinoma with 1,097 healthy controls. twenty-eight genes directly and indirectly involved in the fanconi/brca pathway (includes brca1, brca2, and palb2) were identified and 248 tag snps were selected. in addition, 11 snps in cdkn2a, prss1, and prss2 were selected. association studies were done at the gene level by principal components analysis, whereas recursive partitioning analysis was used to investigate pathway effects. at the individual snp level, adjusted additive, dominant, and recessive models were investigated, and gene-environment interactions were also assessed. gene level analyses showed no significant association of any genes with altered pancreatic cancer risk. multiple single snp analyses showed associations, which will require replication. exploratory pathway analyses by recursive partitioning showed no association between snps and risk for pancreatic cancer.","in a candidate gene and pathway snp association study analysis, common variations in the fanconi/brca pathway and other candidate familial pancreatic cancer genes are not associated with risk for pancreatic cancer.",General
does curcumin inhibit the adverse effects of sodium arsenite in mouse epididymal sperm?,"the aim of this study was to investigate the effects of curcumin on epididy- mal sperm parameters in adult male navel medical research institute (nmri) mice ex- posed to sodium arsenite. in this experimental study, we divided the animals into four groups: control, sodium arsenite (5 mg/kg), curcumin (100 mg/kg) and curcuminsodium arsenite. exposures were performed by intraperitoneal injections for a 5-week period. after the exposure period, we recorded the animals' body and left testes weights. the left caudal epididymis was used to count the sperm number and analyze motility, viability, morphological abnormalities, acrosome reaction, dna integrity, and histone-protamine replacement in the spermatozoa. one-way analysis of variance (anova) followed by the tukey's test was used to assess the statistical significance of the data with spss 16.0. p0.05 was considered significant. mice exposed to sodium arsenite showed a significant decrease in the num- ber, motility, viability, normal sperm morphology and acrosome integrity of spermato- zoa compared to the control group. in the curcuminsodium arsenite group, curcumin significantly reversed these adverse effects to the point where they approximated the control. in addition, the application of curcumin alone had no significant difference in these parameters compared to the control and curcuminsodium arsenite groups. however, we observed no significant differences in the body and the testis weight as well as the dna integrity and histone-protamine replacement in the spermatozoa of the four groups.",curcumin compensated for the toxic effects of sodium arsenite on a number of sperm parameters in adult mice.,Medication
are elevated plasma pentraxin 3 levels associated with development and progression of diabetic retinopathy in korean patients with type 2 diabetes mellitus?,"to evaluate the association between elevated levels of plasma pentraxin 3 (ptx3) and the development and/or progression of diabetic retinopathy (dr). in this case-control study, 92 diabetic patients with dr (group 3), 30 diabetic patients without dr (group 2), and 41 normal subjects (group 1) were enrolled. log-transformed values of plasma ptx3 and high-sensitivity c-reactive protein (hscrp) concentrations were measured and used in our analysis. for subgroup analysis, group 3 was divided into four subgroups: mild, moderate, severe nonproliferative, and proliferative dr. in our 163 participants, average plasma ptx3 levels were 916.1 532.2, 1093.7 1034.2, and 1817.9 1776.9 pg/ml for groups 1, 2, and 3, respectively. the duration of diabetic mellitus (dm), glycated hemoglobin (hba1c), log hscrp, and log ptx3 were significantly different between the three groups (p 0.008, p 0.001, p 0.046, and p 0.001, respectively). in subgroup analysis, plasma log ptx3 levels increased in correlation with the severity of dr (r 0.372, p 0.001). multivariate logistic analysis showed that the correlation between dr development and duration of dm and log ptx3 values was significant (p 0.014 and p 0.025, respectively), whereas correlation with log hscrp values was not significant in univariate analysis (p 0.129). the receiver operating characteristic curves of dr development were plotted using log ptx3 and log hscrp values, and the area under the curves was found to be 0.721 (p 0.001) and 0.614 (p 0.087), respectively.","plasma ptx3 is positively associated with dr development and progression, and may be a more accurate predictor of dr development than hscrp.",Diagnosis
does vitamin a status modulate intestinal adaptation after partial small bowel resection?,"intestinal adaptation after loss of functional small bowel surface area is characterized by cellular hyperplasia and increased absorptive function. interventions to enhance the adaptive response are needed to decrease the morbidity and mortality associated with short bowel syndrome. retinoic acid was shown to stimulate crypt cell proliferation in the adapting remnant rat ileum by 6 hours after resection. thus, vitamin a, which is required for normal epithelial cell proliferation and differentiation and which can modulate programmed cell death, may play an important role in the adapting intestine. on the basis of these observations, the effects of vitamin a deficiency on intestinal morphology, epithelial cell proliferation, and apoptosis in the adapting intestine after resection were investigated. weanling male sprague-dawley rats fed either a vitamin a-deficient or -sufficient diet for 58 days underwent 70 proximal small bowel resection. the deficient rats were divided into cohorts that were either maintained on the experimental diet after surgery or replenished with vitamin a 20 hours before surgery and switched to the control diet after surgery. ten days after resection, vitamin a-deficient rats exhibited a markedly blunted adaptive response. the adaptive increase in villus height and crypt depth was absent in the deficient rats. however, adaptive increases in crypt cell proliferation were not attenuated by vitamin a deficiency, and there were no differences in apoptotic indices.","vitamin a deficiency inhibits the adaptive response to partial small bowel resection, supporting a role for vitamin a in the adaptive process. changes in cellular proliferation or programmed cell death are not sufficient to account for this inhibition. this model system will be useful for examining the role of other mechanisms, such as changes in cell-cell and cell-extracellular matrix interactions, and rates of epithelial cell migration and cell extrusion.",Treatment
does mitochondrial cytochrome c oxidase biogenesis be regulated by the redox state of a heme-binding translational activator?,"mitochondrial cytochrome c oxidase (cox), the last enzyme of the respiratory chain, catalyzes the reduction of oxygen to water and therefore is essential for cell function and viability. cox is a multimeric complex, whose biogenesis is extensively regulated. one type of control targets cytochrome c oxidase subunit 1 (cox1), a key cox enzymatic core subunit translated on mitochondrial ribosomes. in saccharomyces cerevisiae, cox1 synthesis and cox assembly are coordinated through a negative feedback regulatory loop. this coordination is mediated by mss51, a heme-sensing cox1 mrna-specific processing factor and translational activator that is also a cox1 chaperone. in this study, we investigated whether mss51 hemylation and mss51-mediated cox1 synthesis are both modulated by the reduction-oxidation (redox) environment. we report that cox1 synthesis is attenuated under oxidative stress conditions and have identified one of the underlying mechanisms. we show that in vitro and in vivo exposure to hydrogen peroxide induces the formation of a disulfide bond in mss51 involving cpx motif heme-coordinating cysteines. mss51 oxidation results in a heme ligand switch, thereby lowering heme-binding affinity and promoting its release. we demonstrate that in addition to affecting mss51-dependent heme sensing, oxidative stress compromises mss51 roles in cox1 mrna processing and translation. h2o2-induced downregulation of mitochondrial translation has so far not been reported. we show that high h2o2 concentrations induce a global attenuation effect, but milder concentrations specifically affect cox1 mrna processing and translation in an mss51-dependent manner.","the redox environment modulates mss51 functions, which are essential for regulation of cox biogenesis and aerobic energy production.",General
is ultrasound-guided thrombin injection the treatment of choice for femoral pseudoaneurysms?,"ultrasound-guided injection of thrombin is the treatment of choice for femoral pseudoaneurysms. a prospective study of patients undergoing a single form of treatment for femoral pseudoaneurysms. patients were treated at 2 tertiary care, university-affiliated hospitals. forty consecutive patients with femoral pseudoaneurysms resulting from diagnostic and therapeutic catheterizations for peripheral arterial, coronary arterial, and cerebrovascular diseases were evaluated. thrombin was injected directly into the pseudoaneurysms under ultrasonographic guidance. thrombosis of the pseudoaneurysm following thrombin injection was the goal of treatment. all 40 patients had initial complete thrombosis of their femoral pseudoaneurysms. in each case, except for one, the aneurysm was noted to have thrombosed on follow-up duplex ultrasonogram. there was one complication.",ultrasound-guided thrombin injection is the treatment of choice for femoral pseudoaneurysms.,Treatment
does addition of tanshinone iia to uw solution decrease skeletal muscle ischemia-reperfusion injury?,"to investigate whether tanshinone iia could improve the effect of uw solution for skeletal muscle preservation and to determine the dose range of tanshinone iia providing optimal protection during ischemia and reperfusion. ischemic rat limbs were perfused with uw solution or uw plus tanshinone iia (uwt, 0.05, 0.1, or 0.2 mg/ml) for 0.5 h before reperfusion; controls (i/r) received no perfusion. serum creatine phosphokinase (cpk), aspartate aminotransferase (ast), and lactate dehydrogenase (ldh) were measured pre-ischemia and after reperfusion (2-h, 4-h, and 6-h). muscle water content, superoxide dismutase (sod), malondialdehyde (mda), adenosine triphosphatase (atpase) were assessed pre-reperfusion and after 6-h reperfusion. intercellular adhesion molecule-1 (icam-1) and apoptosis were detected after 6-h reperfusion. reperfusion blood flow was monitored during reperfusion period. uw and uwt prevented luxury perfusion during reperfusion and inhibited icam-1 expression and apoptosis after 6-h reperfusion. serum cpk, ast, and ldh levels in uw rats were significantly less than those in controls after 2-h reperfusion (no difference, 4-h or 6-h reperfusion). after 4-h ischemia, there were significant differences in water content, mda, sod, and atpase between uw and controls, but no difference after 6-h reperfusion. all tests with uwt rats were significantly different from control results at corresponding durations. higher tanshinone doses improved results.","uw plus tanshinone iia increased protection against i/r injury, suggesting that tanshinone iia has clinical value.",Medication
does risk factors for fall in the thai elderly in an urban community?,"instability or falls in the elderly are a health condition meeting all criteria for prevention i.e. high frequency, evidence of preventability and a high burden of morbidity. the consequences of a fall affect not only the elderly per se such as fractures and various kinds of physical and mental impairment, but also the family and the society as a whole in terms of the financial expenditure involved. the need for a comprehensive study to identify the risk factors for falls among the thai elderly is, therefore, crucial for further management. to identify the significant risk factors for falls among the thai elderly for further prevention and management. a cross-sectional study in the urban community around siriraj hospital, bangkok. 1,043 community-dwelling people aged or 60 years were recruited. a structured questionnaire, including mental test and physical examinations as well as various laboratory tests, were used to identify the risk factors for falls between faller and control groups. the overall prevalence of falls among elderly thais in an urban area was 19.8 per cent during a period of 6 months. however, the prevalence was 24.1 per cent in women but only 12.1 per cent in men. older people who were likely to fall also had a lower bone mass which predisposed them to future fractures. the independent risk factors for falls after multiple logistic regression analysis were: female gender, hypertension, deafness, poor memory, poor self-perceived health status, poor performance in the instrumental activities of daily living, kyphoscoliosis, use of spectacles, rapid pulse rate after a 5 minute rest, higher serum transferrin and poor nutrition in terms of low lean body mass and reduced serum albumin level.","special sense, activity of daily living, nutritional status, kyphoscoliosis, hypertension and cognitive ability were six important factors determining the likelihood of fall among the elderly in an urban area.",Prevention
does a systematic review of troponin t and i value as a prognostic tool for patients with chest pain?,"the accuracy of the troponin t and i test as a prognostic tool for patients with chest pain varies considerably depending on the patient population, the cutoff for an abnormal test result, and other factors. the goal of our systematic review was to synthesize the best available evidence on this topic. we searched the medline database, bibliographies of identified articles, and articles identified from a previous meta-analysis of diagnosis. we included cohort studies that had at least 80 follow-up and reported useful data. data from each study were abstracted by 2 investigators. we calculated sensitivity and specificity for the prediction of death, fatal or nonfatal myocardial infarction (mi), or any cardiac event for each combination of patient population, troponin test, interval from admission to blood draw, and cutoff for an abnormal test result. for patients with chest pain and a normal electrocardiogram, the peak troponin i level drawn 6 or more hours after the onset of chest pain is useful for identifying patients at low risk of death or nonfatal mi at 30 days (negative likelihood ratio0.07; probability of outcome0.3 with a negative test, given a pretest probability of 4.4). for patients with unstable angina, the sensitivity of troponin i for the identification of patients who die or have a nonfatal mi in the next 30 days is only 59, and the specificity is only 79. the sensitivity and specificity varied widely for patients with unstable angina or non-q-wave mi depending on the inclusion criteria, cutoff used, timing of the blood draw, duration of follow-up, aim other factors.","if the peak troponin t or i level measured at least 6 hours after the onset of chest pain symptoms is in the normal range in a patient with a normal electrocardiogram, it is very unlikely that the patient will die or have a nonfatal mi in the next 30 days ( or 1). the initial troponin value is not as helpful as the peak value at least 6 hours after the onset of chest pain. an abnormal troponin test result for patients with unstable angina or non-q-wave mi identifies a subset at greater risk of death.",Diagnosis
do radiotherapy doses at special reference points correlate with the outcome of cervical cancer therapy?,"the authors analyzed the correlation between radiotherapy doses at reference points on the uterine edge and the rectal wall and both pelvic control and late rectal complications of cervical cancer therapy. between 1997 and 2005, 57 patients with stages ib-iva cancer of uterine cervix were treated with a combination of external beam radiotherapy and high-dose-rate intracavitary brachytherapy. their high-dose-rate intracavitary brachytherapy was planned by dose-point optimization at six dose points located on the edge of uterus by computed tomography. a rectal reference point located on the anterior wall of the rectum by computed tomography was also used. the pelvic control rate and the rate of late rectal complications were calculated according to the biologically effective dose (bed) at each point and several clinical parameters. the overall 3-year pelvic control rate was 69.4. the patients with a bed 80 gy10 at the point on the edge of the uterine cervix had better pelvic control (78.4 at 3 years) than the patients with a bed or 2 late rectal complications (median, 178 gy) was significant. chemotherapy was a borderline significant parameter in regard to correlation with pelvic control and late rectal complications, but there were no correlations with other dosimetric or clinical parameters.","the radiotherapy dose at the reference point on the edge of the cervix affected pelvic control more than the clinical parameters, and the dose at the rectal reference point was more strongly correlated with the occurrence of late rectal complications.",Treatment
do hsp90 inhibitors cause g2/m arrest associated with the reduction of cdc25c and cdc2 in lung cancer cell lines?,"hsp90, a molecular chaperone, is involved in folding, assembly, maturation, and stabilization of the client proteins which regulate survival of cancer cells, and thus hsp90 inhibitors may be potential molecular targeting agents for cancer treatment. we investigated whether hsp90 inhibitors have therapeutic value in lung cancer. first, expression levels of hsp90 in lung cancer cells were examined by western blotting and immunohistochemical analyses. next, the effect of hsp90 inhibitors, geldanamycin and 17-allylaminogeldanamycin (17-aag), on lung cancer cell growth was examined. remarkable high expression of hsp90 protein in lung cancer cell lines and a more intense signal for hsp90 by immunohistochemistry in males, patients with smoking index over 600, and squamous cell carcinoma were observed. both hsp90 inhibitors dose dependently inhibited the growth of lung cancer cell lines and induced g2/m arrest concomitant with decreased protein levels of cdc25c and cdc2. moreover, combination of an hsp90 inhibitor and irradiation had an additive effect on cell growth inhibition and reduction of cdc25c and cdc2 protein levels.","hsp90 inhibitor is thus a therapeutic tool for lung cancer based on its target proteins, which are involved in tumor progression and antiproliferative activity in lung cancer cells.",Medication
does dre-mir-2188 targets nrp2a and mediate proper intersegmental vessel development in zebrafish embryos?,"micrornas (mirnas) are a class of small rnas that are implicated in the control of eukaryotic gene expression by binding to the 3'utr of target mrnas. several algorithms have been developed for mirna target prediction however, experimental validation is still essential for the correct identification of mirna targets. we have recently predicted that neuropilin2a (nrp2a), a vascular endothelial growth factor receptor which is essential for normal developmental angiogenesis in zebrafish, is a dre-mir-2188 target. here we show that dre-mir-2188 targets the 3'-untranslated region (3'utr) of nrp2a mrna and is implicated in proper intersegmental vessel development in vivo. over expression of mir-2188 in zebrafish embryos down regulates nrp2a expression and results in intersegmental vessel disruption, while its silencing increases nrp2a expression and intersegmental vessel sprouting. an in vivo gfp sensor assay based on a fusion between the gfp coding region and the nrp2a 3'utr confirms that mir-2188 binds to the 3'utr of nrp2a and inhibits protein translation.",we demonstrate that mir-2188 targets nrp2a and affects intersegmental vessel development in zebrafish embryos.,Medication
does evolution of pattern of breathing during a spontaneous breathing trial predict successful extubation?,"rapid shallow breathing may occur at any time during spontaneous breathing trials (sbt), questioning the utility of a single determination of the rapid shallow breathing index (rsbi). we hypothesize that change in rsbi during sbt may more accurately predict successful extubation than a single determination. prospective observational study. seventy-two subjects were extubated. at 24 h, 63/72 remained extubated (extubation success), and 9 were re-intubated (extubation failure). respiratory rate (rr), tidal volume (vt) and rsbi were measured every 30 min during 2-h t-piece sbt. change in respiratory parameters was assessed as percent change from baseline. initial rsbi was similar in extubation success and extubation failure groups (77.0 /- 4.8, 77.0 /- 4.8, p ns). nevertheless, rsbi tended to remain unchanged or decreased in the extubation success group; in contrast rsbi tended to increase in the extubation failure group because of either increased rr and/or decreased vt (p or20 at any time during the sbt. in contrast, in the extubation failure group, rsbi increased in all subjects during the sbt, and eight of nine subjects demonstrated an increase greater than 20. thus, with a 2-h sbt the optimal threshold was a 20 increase (sensitivity 89, specificity 89). similar results were obtained at 30 min (threshold 5 increase). percent change of rsbi predicted successful extubation even when initial values were or105.",percent change of rsbi during an sbt is a better predictor of successful extubation than a single determination of rsbi.,Diagnosis
does the hepatotoxic metabolite of acetaminophen directly activate the keap1-nrf2 cell defense system?,"the transcription factor nrf2 regulates the expression of numerous cytoprotective genes in mammalian cells. we have demonstrated previously that acetaminophen activates nrf2 in mouse liver following administration of non-hepatotoxic and hepatotoxic doses in vivo, implying that nrf2 may have an important role in the protection against drug-induced liver injury. nrf2 activation has been proposed to occur through the modification of cysteine residues within keap1, the cytosolic repressor of nrf2. we hypothesized that acetaminophen activates nrf2 via the formation of its reactive metabolite n-acetyl-p-benzoquinoneimine (napqi), which may disrupt the repression of nrf2 through the modification of cysteine residues within keap1. here, we show that napqi can directly activate the nrf2 pathway in mouse liver cells, inducing an adaptive defense response that is antagonized by rna interference targeted against nrf2. furthermore, mass spectrometric analysis shows that napqi selectively modifies cysteine residues in keap1, both in recombinant protein in vitro and in cells ectopically expressing keap1. using this cell-based model, we demonstrate that activation of nrf2 by napqi and a panel of probe molecules dexamethasone 21-mesylate, 15-deoxy-delta-((12,14))-prostaglandin j(2), 2,4-dinitrochlorobenzene, and iodoacetamide correlates with the selective modification of cysteine residues located within the intervening region of keap1. however, substantial depletion of glutathione (to less than 15 of basal levels) by buthionine sulfoximine, which does not directly modify keap1, is also sufficient to activate nrf2.","nrf2 can be activated via the direct modification of cysteine residues located within the intervening region of keap1, but also via the substantial depletion of glutathione without the requirement for direct modification of keap1. it is possible that both of these mechanisms contribute to the activation of nrf2 by acetaminophen.",Medication
is stress-induced hyperthermia in the 5-ht ( 1a ) receptor knockout mouse normal?,"several studies on serotonin 1a (5-ht(1a)) receptor knockout mice in different genetic backgrounds indicate that such mice display a more anxious phenotype than their corresponding wild types. we hypothesized that the 5-ht(1a) receptor knockout mice would show a different phenotype than the wild type mice in the stress-induced hyperthermia (sih) paradigm, which tests putative anxiolytic effects of drugs. moreover, on pharmacologic challenges with the 5-ht(1a) receptor agonist flesinoxan we expected an absence of the functional response in knockout mice relative to wild type mice. effects of the 5-ht(1a) receptor agonist flesinoxan, alone or in combination with the 5-ht(1a) receptor antagonist way-100635, and the gamma-aminobutyric acid a (gaba(a))-benzodiazepine receptor agonist diazepam were studied in the sih paradigm in male 129/sv 5-ht(1a) receptor knockout and wild type mice. in addition, the effects of flesinoxan on plasma corticosterone concentrations were determined. plasma corticosterone concentrations were dose dependently elevated by flesinoxan in wild type mice but not in knockout mice. flesinoxan dose dependently decreased sih in wild type mice but not in knockout mice. the flesinoxan effect in wild type mice was blocked by way-100635. furthermore, diazepam decreased sih in both genotypes. there were no differences in basic sih responses between wild type and knockout mice.","5 -ht(1a) receptor knockout mice display a normal sih response, and results indicate, based on the sih, that the gaba(a)-benzodiazepine receptor complex functions normally.",Medication
is serum sulfatase activity more elevated in colonic adenomas than cancers?,"elucidation of molecular basis of the adenomatous polyps (ap) and colorectal cancer (crc) development is crucial for their prevention, early detection, and treatment. according to the recent discoveries, sulfatases are implied in extracellular matrix remodeling and degradation and also in the regulation of certain signaling pathways. however, their exact role in carcinogenesis remains unclear. because the majority of crcs arise from ap, the aim of our studies was the investigation of sulfatase activity in adenomas and adenocarcinomas and verification of possible usefulness of sulfatase activity determination as an indicator of the presence and discrimination between adenomas and carcinomas. patient-methods: one hundred twenty individuals were enrolled in the study. we assayed serum sulfatase activity in 79 patients with colorectal neoplasms (38 crc and 41 ap) and 41 controls. enzyme activity was determined colorimetrically. we found statistically higher serum sulfatase activity in patients with colonic neoplasms than in controls (124; 112-139 vs. 79.5; 73-87 u). the activity was more elevated in adenomas (149; 128-173 u) than in cancers (103; 90-112 u). sulfatase activity exceeded the cutoff value in 71 of ap and 47 of crc patients. it increased with number of adenomas and tended to decrease with tumor progression.",sulfatases seem to be involved in the early stages of colonic neoplastic transformation which is reflected in their serum activity. the likelihood of elevated sulfatase activity is almost ten times higher in subjects with than without polyps. sulfatase upregulation in majority of adenomas and their correlation tendencies warrants reconsideration of sulfatase determination as a possible diagnostic tool.,Prevention
does social integration prospectively predict changes in heart rate variability among individuals undergoing migration stress?,"poor social integration increases risk for poor health. the psychobiological pathways underlying this effect are not well-understood. this study utilized a migration stress model to prospectively investigate the impact of social integration on change in high-frequency heart rate variability (hf-hrv), a marker of autonomic functioning. sixty new international students were recruited shortly after their arrival in the host country and assessed 2 and 5 months later. at each assessment period, participants provided information on social integration and loneliness and had their resting hf-hrv evaluated. there was an overall decrease in hf-hrv over time. the magnitude of the within-person and between-person effects of social integration on hrv increased over time, such that greater social integration was associated with higher hf-hrv at later follow-ups.",these results suggest that altered autonomic functioning might represent a key pathway linking social integration to health outcomes.,Diagnosis
is tph1 a218 allele associated with suicidal behavior in turkish population?,"serotonergic dysfunction is implicated in depression, psychiatric disorders and suicidal behaviors. the first and rate-limiting step in the synthesis of serotonin is catalyzed by tryptophan hydroxylase (tph) which is encoded by tph1 and thp2 genes. genetic association studies have revealed contradictory results about the effect of the tph1 a218c (rs1800532) polymorphism on suicidal behavior in different populations. in this study, we investigated a218c polymorphism in 109 suicide attempters and 98 healthy controls. socio-demographic characteristics of participants were obtained through questionnaire. dna was extracted from peripheral blood and genotyping was performed by real time pcr. fisher's exact test was used to evaluate the significance of the difference among the independent variables. hardy-weinberg equilibrium was tested using pearson's goodness-of-fit chi-squared test. the frequency of a allele was significantly higher in suicide attempters than controls (46.33 vs. 35.71, p0.0357). however, there were no differences in genotype frequencies of this locus between participants having attempted suicide and controls (p0.05). among males, frequencies of cc genotype and c allele were found to be significantly higher in controls (p0.0125, p0.0298). with regard to the female subjects and female controls, no significant association was detected between suicidal behavior and genotype/allele frequencies (p0.05).",our results provide evidence that a allele of tph1 a218c polymorphism may be associated with suicidal behavior in turkish population.,Symptoms
is glycine n-methyltransferase a favorable prognostic marker for human cholangiocarcinoma?,"glycine n-methyltransferase (gnmt) is a susceptibility gene for human hepatocellular carcinoma (hcc). we previously reported that gnmt expression is diminished in hcc. here we report our examination of gnmt expression patterns in cholangiocarcinoma and the relationship between its expression and prognosis. we analyzed gnmt expression in tumor tissues from 33 cholangiocarcinoma patients (19 male) using immunohistochemistry (ihc) procedures with a gnmt monoclonal antibody (mab 4-17). gnmt expression intensity and percentages were scored on a scale of 0 to 6. the association between gnmt expression and survival was analyzed using the kaplan-meier method, and prognostic factors were evaluated with a multivariate cox proportional hazards regression model. high gnmt expression was found in epithelial cells of normal bile ducts. six of 33 (18.2) cholangiocarcinoma tissues had no gnmt expression. a statistically significant difference was noted in gnmt expression between male and female patients (68.4 vs 100, p 3, the death hazard ratio for patients with gnmt scores or 3 was 3.68 (95 confidence interval 1.17-11.59, p 0.05).",gnmt expression is a favorable prognosis predictor for cholangiocarcinoma.,Diagnosis
does birth weight predict blood pressure in a young working population : a sharp ( scottish heart and arterial disease risk prevention ) study?,"we sought to assess the association between birth weight and adult systolic blood pressure in a relatively young, healthy, working population with prospectively collected birth data and blood pressure consistently recorded. detailed information on pregnancy and birth came from the walker cohort, a database of babies born in dundee, scotland 1952-1966. follow-up was conducted through record linkage to demographic and health information from the sharp (scottish heart and arterial disease risk prevention) cohort, a working population screened for cardiovascular risk factors between 1991 and 1993. there were 1158 (56 male) subjects with a mean age of 32.1 years. multivariable regression analysis showed no association between birth weight and systolic blood pressure when adjusted for age, gender, body mass index (bmi), cigarettes and alcohol, and social class b0.04 (95 confidence interval -1.37, 1.45). a decrease of 0.1 mm hg for each 1-kg increase in birth weight was observed after additional adjustment for parental high blood pressure but was not statistically significant. bmi and male gender were predictors of increasing blood pressure. a parental history of high blood pressure showed an increase in systolic blood pressure of 4.1 mmhg (maternal) and 3.0 mm hg (paternal).","we were unable to demonstrate an inverse association between birth weight and systolic blood pressure. in this cohort, bmi and male sex remain consistent influences on blood pressure.",Prevention
does expression of lkb1 tumor suppressor in non-small cell lung cancer determine sensitivity to 2-deoxyglucose?,"targeted therapy promises to improve patient outcome in non-small cell lung cancer. biomarkers can direct targeted therapy toward patients who are most likely to respond, thus optimizing benefit. a novel agent with antineoplastic potential is the glucose analog, 2-deoxyglucose. 2-deoxyglucose targets tumor cells, owing to their increased glucose uptake, inhibiting cellular metabolism and inducing energetic stress, resulting in decreased cellular viability. the tumor suppressor lkb1 is activated by energetic stress, and cells that lack lkb1 fail to respond and undergo cell death, suggesting that lkb1-null non-small cell lung cancer may have an increased susceptibility to 2-deoxyglucose. inasmuch as somatic loss of lkb1 is a frequent event in non-small cell lung cancer, lkb1 expression could be used as a biomarker for directing 2-deoxyglucose therapy in patients with this type of cancer. lkb1-positive and lkb1-negative non-small cell lung cancer cell lines were evaluated for cell viability, markers of apoptosis, and gene expression after 2-deoxyglucose treatment and compared with vehicle control. lkb1-negative cells treated with 2-deoxyglucose displayed a significant decrease in cell viability compared with lkb1-positive cells. gene expression profiles of 2-deoxyglucose treated cells revealed changes in apoptotic markers in lkb1-negative cells, correlating with activation of apoptosis. re-expression of lkb1 prevented 2-deoxyglucose mediated apoptosis, demonstrating the critical role of lkb1 in mediating 2-deoxyglucose toxicity.","lkb1 loss increases susceptibility to 2-deoxyglucose treatment in non-small cell lung cancer lines, even at low doses. thus, determination of lkb1 status may help direct therapy to those patients most likely to benefit from this novel approach, making it useful in the treatment of patients with non-small cell lung cancer.",Diagnosis
do gene expression patterns of dengue virus-infected children from nicaragua reveal a distinct signature of increased metabolism?,"infection with dengue viruses (denv) leads to a spectrum of disease outcomes. the pathophysiology of severe versus non-severe manifestations of denv infection may be driven by host responses, which could be reflected in the transcriptional profiles of peripheral blood immune cells. we conducted genome-wide microarray analysis of whole blood rna from 34 denv-infected children in nicaragua collected on days 3-6 of illness, with different disease manifestations. gene expression analysis identified genes that are differentially regulated between clinical subgroups. the most striking transcriptional differences were observed between dengue patients with and without shock, especially in the expression of mitochondrial ribosomal proteins associated with protein biosynthesis. in the dengue hemorrhagic fever patients, one subset of differentially expressed genes encode neutrophil-derived anti-microbial peptides associated with innate immunity. by performing a meta-analysis of our dataset in conjunction with previously published datasets, we confirmed that denv infection in vivo is associated with large changes to protein and nucleic acid metabolism. additionally, whereas in vitro infection leads to an increased interferon signature, this was not consistently observed from in vivo patient samples, suggesting that the interferon response in vivo is relatively transient and was no longer observed by days 3-6 of illness.","these data highlight important differences between different manifestations of severity during denv infection as well as identify some commonalities. compilation of larger datasets in the future across multiple studies, as we have initiated in this report, may well lead to better prediction of disease manifestation via a systems biology approach.",Symptoms
does norovirus non-structural protein p20 lead to impaired restitution of epithelial defects by inhibition of actin cytoskeleton remodelling?,"norovirus is the most common cause of acute gastroenteritis in humans worldwide. typical symptoms are vomiting, nausea and severe watery diarrhea. because of the lack of cell lines susceptible to human norovirus infection, pathomechanisms and replication cycle are largely unknown. here, we address the issue of how norovirus infection could lead to epithelial barrier dysfunction. expression of the non-structural norovirus protein p20 in the epithelial cell line ht-29/b6 was activated through a tetracycline sensitive promoter. tight junction proteins were studied by western blot and confocal laser scanning microscopy. apoptoses were detected in tunel stainings. epithelial restitution was monitored by conductance scanning after induction of single cell lesions. changes in the expression or localization of the tight junction proteins occludin and/or claudin-1, -2,- 3, -4, -5, -7 and -8 could be ruled out to mediate epithelial barrier modulation. cell motility was also unaltered by p20. investigation of epithelial apoptosis revealed an accumulation of apoptic cells in epithelial monolayers after induction of p20 expression. in epithelial cell restitution assays, an arrest was identified in p20 expressing cells. fluorescence microscopy revealed an inability for condensation and redistribution of cellular actin, which led to a reduced transepithelial electrical resistance.",functional data for norovirus protein p20 suggest a role in modulation of the actin cytoskeleton leading to barrier dysfunction through impairment of restitution of epithelial defects.,Symptoms
do fibroblasts and transforming growth factor beta induce organization and differentiation of t84 human epithelial cells?,"the gut epithelium in the crypt-villus axis represents a continuous developmental system in which the role of fibroblast-epithelial interactions is obvious. the aim of this study was to establish an in vitro method whereby fibroblast-guided differentiation of crypt-like gut epithelial cells can be studied. intestinal epithelial cells (t84 and ht-29) were cultured within type i collagen gel together were fibroblasts without cell-to-cell contact. t84 cells were also grown in the presence of transforming growth factor beta and hepatocyte growth factor. the gels were studied using light and electron microscopy and histochemical and immunohistochemical methods. the epithelial cells formed unorganized cell clusters within the gels, but when given fibroblast support, 76 of the t84 cell colonies (not ht-29) organized into luminal formations, and basement membranes including laminin were well deposited. the cells in the columnar single cell-layer luminal formations (49 of all colonies) were differentiated, showing microvilli, up-regulated alkaline phosphatase brush border activity, and mucin profiles typical for small intestine. this fibroblast-induced organization and differentiation was induced by transforming growth factor beta.",crypt-like t84 epithelial cells are able to differentiate when grown three-dimensionally together with fibroblasts or transforming growth factor beta. this method may be used for mesenchymal-epithelial cell cross-talk studies.,General
is impaired fasting glucose a risk factor for atherosclerosis?,"to determine a new category of dysfunctional glucose homeostasis - impaired fasting glucose (ifg) - introduced by the american diabetes association (ada) and the world health organization (who) defining those with abnormal but nondiabetic fasting glucose values and with a possible risk for developing diabetes. it is not known whether ifg is a risk factor for atherosclerosis, as is impaired glucose tolerance (igt). in this case-control cross-sectional study in which the oral glucose tolerance (75-g ogtt) and the carotid intima-media thickness (imt) with b mode ultrasound, as a marker of atherosclerosis, were measured, together with hba1c, lipids, plasminogen activator (pai), insulin and proinsulin concentrations in blood plasma. out of 788 subjects of the risk factors in igt for atherosclerosis and diabetes (riad) study we found 104 ifg cases that were compared to 104 controls with fasting plasma glucose (fpg) or 11.1 mmol/l were excluded. the rest were subdivided into those with 2h plasma glucose 7.8 mmol/l and 11.1 mmol/l (41 pairs, igt). the case and control groups showed no significant differences in the major risk factors except for waist-to-hip ratio (whr) which was higher in the ifg with ngt. ifg with ngt exhibited significantly higher levels of hba1c, true insulin and proinsulin. in ifg with igt, only hba1c and proinsulin were significantly increased vs. controls. imt was in the same range for cases and controls in both subgroups. however, imt mean and imtmax were significantly increased in ifg with igt vs. ifg with ngt (0.95 mm vs. 0.80 mm and 1.10 mm vs. 0.90 mm). cumulative distribution analysis of imt illustrates that imt in ifg with igt is more shifted to higher artery wall thickness than in ifg with ngt.",in our case-control study ifg alone was not related to increased imt. only ifg in a combination with igt exhibited atherosclerotic changes of the carotid arteries. ifg is not analogous to igt as a risk factor for atherosclerosis.,Prevention
do zerovalent bismuth nanoparticles inhibit streptococcus mutans growth and formation of biofilm?,"despite continuous efforts, the increasing prevalence of resistance among pathogenic bacteria to common antibiotics has become one of the most significant concerns in modern medicine. nanostructured materials are used in many fields, including biological sciences and medicine. while some bismuth derivatives has been used in medicine to treat vomiting, nausea, diarrhea, and stomach pain, the biocidal activity of zerovalent bismuth nanoparticles has not yet been studied. the objective of this investigation was to analyze the antimicrobial activity of bismuth nanoparticles against oral bacteria and their antibiofilm capabilities. our results showed that stable colloidal bismuth nanoparticles had 69 antimicrobial activity against streptococcus mutans growth and achieved complete inhibition of biofilm formation. these results are similar to those obtained with chlorhexidine, the most commonly used oral antiseptic agent. the minimal inhibitory concentration of bismuth nanoparticles that interfered with s. mutans growth was 0.5 mm.",these results suggest that zerovalent bismuth nanoparticles could be an interesting antimicrobial agent to be incorporated into an oral antiseptic preparation.,Symptoms
is plate augmentation with retention of intramedullary nail effective for resistant femoral shaft non-union?,"non-union after intramedullary nail fixation of femur shaft fractures is although infrequent but a challenging condition to treat. the treatment options available to deal with such a situation include exchange nailing, removal of nail and re-osteosynthesis with plating, or ilizarov fixation. we believe that rotational instability, in the presence of a nail, is one of the main reasons for most of the non-union. we present our experience of plate augmentation leaving the nail in situ for non-union of femoral shaft fracture. in this retrospective study, we had operated 16 cases of the femoral shaft non-union, which were treated by plate augmentation and bone grafting (if needed) with retention of the intramedullary interlocking nail in situ. the cases of infected non-union and any fracture less than one-year duration were excluded from the study. bone grafting was done only in 4 cases with atrophic non-union. we could achieve union in all the cases at an average time of 6.25 months. the average time of surgery between the primary surgery of interlocking nail fixation and the plate augmentation was 13 months. mean surgical time for plate augmentation and bone grafting was 71 min. no major complication or implant failure was encountered. an average residual shortening of the limb was 0.9 cm and average range of motion of the knee was 115.","plate augmentation seems an effective, reliable, safe and an easy procedure for the treatment of femoral shaft non-union after an intramedullary nailing.",Treatment
do profound high-frequency sensorineural hearing loss treatment with a totally implantable hearing system?,"this study seeks to assess the efficacy of the envoy esteem totally implantable hearing device in treating profound high-frequency sensorineural hearing loss. five patients with profound high-frequency hearing loss participating in a prospective, multi-center, nonrandomized food and drug administration clinical trial. implantation with esteem totally implantable hearing device and comparison to baseline unaided and aided conditions. speech reception threshold and word recognition scores (wrs) at 50 db hl presentation level. preoperative speech reception threshold improved from an unaided 65 db and aided 48 db average to 26 db with the esteem at 12 months. wrs at 50 db scores improved from an unaided 10 and aided 23 average to 78 postoperatively.",the esteem totally implantable middle ear hearing device provides appreciable functional gain and improvement in wrs to rehabilitate hearing in patients with a profound high-frequency sensorineural hearing loss.,Treatment
is cxcr4 highly expressed at the tumor front but not in the center of prostate cancers?,"to evaluate the expression of cxcr4, its ligand sdf-1, -catenin and e-cadherin throughout the local tumor microenvironment of prostate cancer. a total of 64 prostate cancer specimens, 24 frozen and 40 paraffin-embedded sections, were obtained from patients treated with radical prostatectomy for clinically localized cancer. real-time rt-pcr was used for mrna quantification of cxcr4 and sdf-1 in the tumor center (t), tumor front (f) and distant peritumoral tissue (d). immunohistochemical analysis was used to investigate the expression patterns of cxcr4, e-cadherin and -catenin. clinical records of these patients were studied for follow-up data, and the prognostic value of these molecules' expression was statistically assessed. cxcr4 mrna and protein were significantly increased at the tumor front as compared to distant tissue or tumor center. in comparison, sdf-1 mrna level gradually increased from the tumor center to the distant peritumoral tissue. high cxcr4 at the tumor front was associated with high gleason score. low sdf-1 at the tumor front was associated with locally advanced cancer and disease recurrence. moreover, high cxcr4 staining at the tumor front and increased cytosolic e-cadherin expression in the same location was associated with locally advanced disease.","cxcr4 seems overexpressed at the tumor front of prostate tumors, where it potentially promotes cell migration toward the sdf-1 centrifugal attracting gradient, as well as epithelial-mesenchymal transition. high cxcr4 and low sdf-1 levels at tumor front were both associated with adverse histological features.",Treatment
does genome-wide rare copy number variation screening in ulcerative colitis identify potential susceptibility loci?,"ulcerative colitis (uc), a complex polygenic disorder, is one of the main subphenotypes of inflammatory bowel disease. a comprehensive dissection of the genetic etiology of uc needs to assess the contribution of rare genetic variants including copy number variations (cnvs) to disease risk. in this study, we performed a multi-step genome-wide case-control analysis to interrogate the presence of disease-relevant rare copy number variants. one thousand one hundred twenty-one german uc patients and 1770 healthy controls were initially screened for rare deletions and duplications employing snp-array data. quantitative pcr and high density custom array-cgh were used for validation of identified cnvs and fine mapping. two main follow-up panels consisted of an independent cohort of 451 cases and 1274 controls, in which cnvs were assayed through quantitative pcr, and a british cohort of 2396 cases versus 4886 controls with cnv genotypes based on array data. additional sample sets were assessed for targeted and in silico replication. twenty-four rare copy number variants (14 deletions and 10 duplications), overrepresented in uc patients were identified in the initial screening panel. follow-up of these cnv regions in four independent case-control series as well as an additional public in silico control group (totaling 4439 uc patients and 15,961 healthy controls) revealed three copy number variants enriched in uc patients; a 15.8 kb deletion upstream of abcc4 and cldn10 at13q32.1 (0.43 cases, 0.11 controls), a 119 kb duplication at 7p22.1, overlapping rnf216, znf815, ocm and ccz1 (0.13 cases, 0.01 controls) and a 134 kb large duplication upstream of the kcnk9 gene at 8q24.3 (0.22 carriers among cases, 0.03 carriers among controls). the trend of association with uc was present after the p-values were corrected for combining data from different subpopulations. break-point mapping of the deleted region suggested non-allelic homologous recombination as the mechanism underlying its formation.",our study presents a pragmatic approach for effective rare cnv screening of snp-array data sets and implicates the potential contribution of rare structural variants in the pathogenesis of uc.,Diagnosis
does inhibition of p38 mitogen-activated protein kinase attenuate butyrate-induced intestinal barrier impairment in a caco-2 cell monolayer model?,"butyrate is well known to induce apoptosis in differentiating intestinal epithelial cells. the present study was designed to examine the role of p38 mitogen-activated protein kinase (mapk) in butyrate-induced intestinal barrier impairment. the intestinal barrier was determined by measuring the transepithelial electrical resistance (ter) in a caco-2 cell monolayer model. the permeability was determined by measuring transepithelial passage of fluorescein isothiocyanate-conjugated inulin (inulin-fitc). the morphology of the monolayers was examined with scanning electron microscopy. the apoptosis status was determined by annexin v-fitc labeling and flow cytometry. the activity of p38 mapk was determined by the phosphorylation status of p38 with western blotting. butyrate at 5 mm increases the apoptosis rate of caco-2 cells and induces impairment of intestinal barrier functions as determined by decreased ter and increased inulin-fitc permeability. butyrate treatment activates p38 mapk in a concentration- and time-dependent manner. sb203580, a specific p38 inhibitor, inhibits butyrate-induced caco-2 cell apoptosis. treatment of sb203580 significantly attenuates the butyrate-induced impairment of barrier functions in the caco-2 cell monolayer model.",p38 mapk can be activated by butyrate and is involved in the butyrate-induced apoptosis and impairment of intestinal barrier function. inhibition of p38 mapk can significantly attenuate butyrate-induced intestinal barrier dysfunction.,Medication
does rosiglitazone reduce the accelerated neointima formation after arterial injury in a mouse injury model of type 2 diabetes?,"hyperglycemia (hg) and hyperinsulinemia (hi) may be factors enhancing the atherosclerotic complications of diabetes. we hypothesized that specific feeding of c57bl/6 apolipoprotein (apo) e-/- mice would alter their metabolic profiles and result in different degrees of neointima (ni) formation. we additionally hypothesized that an insulin-sensitizing agent (rosiglitazone) would prevent the development of type 2 diabetes and reduce neointima formation after carotid wire injury measured at 28 days. fasting glucose and insulin levels were elevated in the western diet (wd) group, with a trend toward higher insulin levels and euglycemia in the fructose diet (fd)--fed mice. ni formation was exaggerated in the wd group compared with the fd or chow control groups. in the wd mice given rosiglitazone, glucose and insulin levels remained normal and ni formation was significantly reduced, as was ni macrophage content.","these findings demonstrate that apoe-/- mice fed a wd develop type 2 diabetes with an exaggerated ni response to injury. fd mice maintain euglycemia but develop insulin resistance, with an intermediate degree of ni growth compared with chow diet controls. rosiglitazone prevents the development of hyperglycemia and hyperinsulinemia and normalizes the insulin release profile in the apoe-/-, wd-fed mouse and significantly reduces ni formation by 65 after carotid wire injury while reducing macrophage infiltration. these data support the hypothesis that type 2 diabetes in the setting of elevated cholesterol accelerates the response to vascular injury and suggest that agents that improve insulin sensitivity may have therapeutic value in reducing restenosis in type 2 diabetes.",Prevention
is forced-air warming no more effective than conventional methods for raising postoperative core temperature after cardiac surgery?,"to determine whether postoperative forced-air warming of cardiac bypass patients in the intensive care unit (icu) results in faster rate of warming and improved outcomes compared with more conventional icu warming methods. prospective randomized effectiveness study. three hundred fifty-bed university-affiliated hospital. sixty consenting randomized patients from a consecutive series of 84 patients undergoing routine adult cardiac surgery. one group of patients received usual patient care, which includes warm blankets and overhead heat lamps. patients in the other group were placed under forced-air warming devices on arrival in the icu. sixty consenting patients (30 in each group) were randomly assigned to one or the other method of warming. the remaining 24 patients refused randomization and self-selected a treatment group. results are presented for the randomized groups. core temperature, measured by pulmonary artery catheter thermistor, increased in both groups at the rate of 0.25 degree c per hour. no statistically or clinically significant differences were found between the group for whom the warming device was used and the standard care group in the incidence of postoperative cardiac arrhythmia, duration of time in the icu, or any other clinical variable.",there is no evidence from this study to warrant use of forced-air warming devices for the care of postoperative cardiac surgical patients in the icu.,Treatment
does pharmacological ascorbic acid suppress syngeneic tumor growth and metastases in hormone-refractory prostate cancer?,"the aim of this study was to test for the influence of ascorbic acid on tumorigenicity and metastases of implanted paiii prostate cancer adenocarcinoma cells in syngeneic lw rats. hormone-refractory prostate cancer paiii cells were implanted subcutaneously into immunologically intact, lobund-wistar (lw) rats. intraperitoneal pharmacological doses of ascorbic acid were administered each day for the ensuing 30 days. on the 40th day, animals were sacrificed. local tumor weights were measured, and metastases were counted. at the end of the 40 day experimental period, the primary tumors were found to be significantly reduced in weight (p0.026). in addition, sub-pleural lung metastases were even more profoundly reduced in number and size (p0.009). grossly enlarged ipsilateral lymph node metastases declined from 7 of 15 rats to 1 of 15 rats.",pharmacological doses of ascorbic acid suppress tumor growth and metastases in hormone-refractory prostate cancer.,Medication
does mitomycin c reduce haze formation in rabbits after excimer laser photorefractive keratectomy?,"to investigate the effects of mitomycin c on haze after photorefractive keratectomy (prk). twenty of 24 rabbits underwent bilateral 193-nm excimer laser prk to correct -10.00 d of myopia; the remaining four rabbits were not operated (no prk group). the right eyes of the 20 rabbits were treated with 0.02 mitomycin c during surgery (prkmmc group) and the left eyes did not receive 0.02 mitomycin c (prk alone group). clinical and histopathologic examinations were performed. the most severe haze in the prk alone group after prk reached grade 3; the prkmmc group did not exceed grade 1 haze. statistically significant differences were found between the prkmmc and prk alone groups from week 2 to week 26 after treatment (p.05). a marked reduction of keratocytes in the anterior stroma of the prkmmc group was observed. at week 1, 2, and 4 after prk, keratocytes of the prkmmc group were only 3.1/-2.6, 6.8/-4.7, and 12.4/-5.7 keratocytes x 10(4)/microm2, respectively, while those of the prk alone group were 41.2/-80, 42.3/-7.8, and 40.0/-3.3 keratocytes x 10(4)/microm2, respectively. there were statistically significant differences between the two groups (p.001).",a single intraoperative application of topical mitomycin c during prk in rabbits reduced corneal haze by inhibiting the proliferation of keratocytes.,Treatment
is erk5 a mediator to tgf1-induced loss of phenotype and function in human podocytes?,"podocytes are highly specialized cells integral to the normal functioning kidney, however, in diabetic nephropathy injury occurs leading to a compromised phenotype and podocyte dysfunction which critically produces podocyte loss with subsequent renal impairment. tgf1 holds a major role in the development of diabetic nephropathy. erk5 is an atypical mitogen-activated protein (map) kinase involved in pathways modulating cell survival, proliferation, differentiation, and motility. accordingly, the role of erk5 in mediating tgf1-induced podocyte damage was investigated. conditionally immortalized human podocytes were stimulated with tgf1 (2.5 ng/ml); inhibition of erk5 activation was conducted with the chemical inhibitor bix02188 (10 m) directed to the upstream mek5; inhibition of alk5 was performed with sb431542 (10 m); ras signaling was inhibited with farnesylthiosalicylic acid (10 m). intracellular signaling proteins were investigated by western blotting; phenotype was explored by immunofluorescence; proliferation was assessed with a mts assay; motility was examined with a scratch assay; barrier function was studied using electric cell-substrate impedance sensing; apoptosis was studied with annexin v-fitc flow cytometry. podocytes expressed erk5 which was phosphorylated by tgf1 via mek5, whilst not involving ras. tgf1 altered podocyte phenotype by decreasing p-cadherin staining and increasing -sma, as well as reducing podocyte barrier function; both were prevented by inhibiting erk5 phosphorylation with bix02188. tgf1-induced podocyte proliferation was prevented by bix02188, whereas the induced apoptosis was not. podocyte motility was reduced by bix02188 alone and further diminished with tgf1 co-incubation.",these results describe for the first time the expression of erk5 in podocytes and identify it as a potential target for the treatment of diabetic renal disease.,Medication
does antibody-dependent enhancement infection facilitate dengue virus-regulated signaling of il-10 production in monocytes?,"interleukin (il)-10 levels are increased in dengue virus (denv)-infected patients with severe disorders. a hypothetical intrinsic pathway has been proposed for the il-10 response during antibody-dependent enhancement (ade) of denv infection; however, the mechanisms of il-10 regulation remain unclear. we found that denv infection and/or attachment was sufficient to induce increased expression of il-10 and its downstream regulator suppressor of cytokine signaling 3 in human monocytic thp-1 cells and human peripheral blood monocytes. il-10 production was controlled by activation of cyclic adenosine monophosphate response element-binding (creb), primarily through protein kinase a (pka)- and phosphoinositide 3-kinase (pi3k)/pkb-regulated pathways, with pka activation acting upstream of pi3k/pkb. denv infection also caused glycogen synthase kinase (gsk)-3 inactivation in a pka/pi3k/pkb-regulated manner, and inhibition of gsk-3 significantly increased denv-induced il-10 production following creb activation. pharmacological inhibition of spleen tyrosine kinase (syk) activity significantly decreased denv-induced il-10 production, whereas silencing syk-associated c-type lectin domain family 5 member a caused a partial inhibition. ade of denv infection greatly increased il-10 expression by enhancing syk-regulated pi3k/pkb/gsk-3/creb signaling. we also found that viral load, but not serotype, affected the il-10 response. finally, modulation of il-10 expression could affect denv replication.","these results demonstrate that, in monocytes, il-10 production is regulated by ade through both an extrinsic and an intrinsic pathway, all involving a syk-regulated pi3k/pkb/gsk-3/creb pathway, and both of which impact viral replication.",Medication
do low levels of bile acids increase bacterial uptake in colonic biopsies from patients with collagenous colitis in remission?,"patients with collagenous colitis have an impaired mucosal barrier. moreover, collagenous colitis is associated with bile acid malabsorption. bile acids can increase bacterial mucosal uptake in humans. mucosal barrier function was investigated by exposing colonic biopsies to chenodeoxycholic acid (cdca) or deoxycholic acid (dca) in ussing chamber experiments. to find if low levels of bile acids increase bacterial uptake in colonic biopsies from collagenous colitis patients. the study comprised 33 individuals; 25 with collagenous colitis (14 in clinical remission without treatment, 11 with active disease and 10 examined in clinical remission resulting from treatment with 6 mg budesonide); eight healthy individuals undergoing screening colonoscopy served as controls. endoscopic biopsies from the sigmoid colon were mounted in modified ussing chambers and assessed for short-circuit current (isc), potential difference, trans-epithelial resistance and transmucosal passage of escherichia coli k12 after adding 100 mol/l cdca or dca. when adding 100 mol/l cdca or dca, bacterial uptake increased fourfold in biopsies of patients in remission; cdca 6.5 units 2.5-9.8 and dca 6.2 units 2.1-22 (median iqr), compared with uptake in biopsies without added bile acids 1.6 units 1.1-3 (p0.004 and p0.01 respectively). in active disease and in patients in remission due to budesonide treatment, bile acids did not affect bacterial uptake. confocal microscopy revealed trans-epithelial passage of e. coli k12 within 30 min.","low concentrations of dihydroxy-bile acids exacerbate mucosal barrier dysfunction in colonic biopsies of patients with collagenous colitis in remission. this allows a substantially increased bacterial uptake, which may contribute to recurrence of inflammation.",Treatment
does the antipsoriatic drug dimethylfumarate strongly suppress chemokine production in human keratinocytes and peripheral blood mononuclear cells?,"the effectiveness of systemic treatment of psoriasis with fumaric acid esters has been proven, but their mode of action at the cellular and molecular level has not yet been fully elucidated. to study the effect of dimethylfumarate (dmf) on the production of the chemokines cxcl1, cxcl8, cxcl9, cxcl10 and cxcl11, formerly known as groalpha, interleukin-8, mig, ip-10 and ip-9/i-tac, respectively, in human keratinocytes and peripheral blood mononuclear cells (pbmc). cultured keratinocytes were stimulated with interferon (ifn) -gamma to produce cxcl9, cxcl10 and cxcl11 and with phorbol myristate acetate to produce cxcl1 and cxcl8 in the absence and presence of dmf (5, 15 and 45 micromol l(-1)). pbmc were stimulated with either ifn-gamma to produce cxcl9 and cxcl10 or lipopolysaccharide to produce cxcl8, in the absence and presence of dmf (5, 15 and 45 micromol l(-1)). rna preparations from isolated keratinocytes were analysed by northern blotting; protein production by keratinocytes and pbmc was monitored by an enzyme-linked immunosorbent assay. northern blot analysis on isolated keratinocyte rna preparations showed a dose-dependent inhibition of cxcl1, cxcl8, cxcl9, cxcl10 and cxcl11 transcription by dmf. at 45 micromol l(-1) the inhibition was almost complete. in addition, keratinocytes and pbmc showed in the presence of dmf a dose-dependent inhibition of cxcl8, cxcl9 and cxcl10 protein production.","these results show the ability of dmf to inhibit the production of chemokines that may be critically involved in the development and perpetuation of psoriatic lesions. this might explain, at least in part, the beneficial effects of treatment with fumaric acid esters in psoriasis patients.",Medication
does clinical iron deficiency disturb normal human responses to hypoxia?,"iron bioavailability has been identified as a factor that influences cellular hypoxia sensing, putatively via an action on the hypoxia-inducible factor (hif) pathway. we therefore hypothesized that clinical iron deficiency would disturb integrated human responses to hypoxia. we performed a prospective, controlled, observational study of the effects of iron status on hypoxic pulmonary hypertension. individuals with absolute iron deficiency (id) and an iron-replete (ir) control group were exposed to two 6-hour periods of isocapnic hypoxia. the second hypoxic exposure was preceded by i.v. infusion of iron. pulmonary artery systolic pressure (pasp) was serially assessed with doppler echocardiography. thirteen id individuals completed the study and were age- and sex-matched with controls. pasp did not differ by group or study day before each hypoxic exposure. during the first 6-hour hypoxic exposure, the rise in pasp was 6.2 mmhg greater in the id group (absolute rises 16.1 and 10.7 mmhg, respectively; 95 ci for difference, 2.7-9.7 mmhg, p 0.001). intravenous iron attenuated the pasp rise in both groups; however, the effect was greater in id participants than in controls (absolute reductions 11.1 and 6.8 mmhg, respectively; 95 ci for difference in change, -8.3 to -0.3 mmhg, p 0.035). serum erythropoietin responses to hypoxia also differed between groups.","clinical iron deficiency disturbs normal responses to hypoxia, as evidenced by exaggerated hypoxic pulmonary hypertension that is reversed by subsequent iron administration. disturbed hypoxia sensing and signaling provides a mechanism through which iron deficiency may be detrimental to human health.",Medication
is cyclin h expression increased in gist with very-high risk of malignancy?,"risk estimation of gastrointestinal stromal tumours (gist) is based on tumour size and mitotic rate according to the national institutes of health consensus classification. the indication for adjuvant treatment of patients with high risk gist after r0 resection with small molecule inhibitors is still a controversial issue, since these patients represent a highly heterogeneous population. therefore, additional prognostic indicators are needed. here, we evaluated the prognostic value of cyclin h expression in gist. in order to identify prognostic factors of gist we evaluated a single centre cohort of ninety-five gist patients. first, gists were classified with regard to tumour size, mitotic rate and localisation according to the nih consensus and to three additional suggested risk classifications. second, cyclin h expression was analysed. of ninety-five patients with gist (53 female/42 male; median age: 66.78a; range 17-94a) risk classification revealed: 42 high risk, 20 intermediate risk, 23 low risk and 15 very low risk gist. in patients with high risk gist, the expression of cyclin h was highly predictive for reduced disease-specific survival (p 0.038). a combination of cyclin h expression level and high risk classification yielded the strongest prognostic indicator for disease-specific and disease-free survival (p or 0.001). moreover, in patients with tumour recurrence and/or metastases, cyclin h positivity was significantly associated with reduced disease-specific survival (p 0.016) regardless of risk-classification.","our data suggest that, in addition to high risk classification, cyclin h expression might be an indicator for ""very-high risk"" gist.",Treatment
do adolescent girls ' personal experience with baby think it over infant simulator?,"to explore adolescent girls' personal experience with an infant simulator that had to be cared for over a period of 1 to 2 weeks. this qualitative study employed the phenomenological approach and utilized colaizzi's method of analysis. participants were nine adolescent high school girls who were interviewed and audiotaped. interview data were coded using nudist 4 software. three themes emerged from the data. they were (1) a parenting journey incorporating intellectual, emotive, and physical faculties; (2) recognizing the illusionary nature of previously held ideas about parenting an infant; and (3) offering counsel based on the btio experience.","the new perspectives gained by the participants about parenting a newborn infant differed markedly from the romantic fantasies they held prior to the experience. the teens started thinking more seriously about the consequences of sexual activity. used for 1 to 2 weeks, in conjunction with budgeting exercises and provocative small-group discussions, the btio shows promise as an effective tool in helping to modify unrealistic and idealized teen views of adolescent pregnancy and parenting.",General
do vegf-c and vegf-a synergistically enhance lymph node metastasis of gastric cancer?,"vascular endothelial growth factor c (vegf-c) is the most important molecule in lymphangiogenesis and its relationship with lymph node metastasis has attracted considerable interest. we investigated the relationship of vegf-c or vegf-a with clinicopathological factors in gastric cancer patients. eighty gastric cancer patients who underwent gastric resection were analyzed immunohistochemically for expression of vegf-c and vegf-a protein. positive immunoreactivity of vegf-c and vegf-a was observed in 75 (93.8) and 41 (51.3) patients, respectively. vegf-a expression was significantly correlated with tumor differentiation (p0.0017) and vascular invasion (p0.0004). and positive relationship of vegf-c expression was only demonstrated with tumor differentiation (p0.0168). interestingly, however, the frequency of lymph node metastasis was significantly higher in the patients with expression of both vegf-c and vegf-a (strong positive expression, p0.036). furthermore, the expression of both was also significantly correlated with depth of tumor invasion, tumor differentiation, lymphatic invasion, and vascular invasion.","the present results suggest that strong expression of vegf-a in addition to vegf-c expression is essential in lymph node metastasis, presumably because enhanced metastatic potential including lymphangiogenesis induced by both vegf-a and vegf-c is vital in lymph node metastasis of gastric cancer.",Treatment
does acetylcholine activate protein kinase c-alpha in pulmonary venous smooth muscle?,"the authors investigated whether acetylcholine-induced contraction in pulmonary venous smooth muscle (pvsm) is associated with the activation of specific protein kinase c (pkc) isoforms. isolated canine pulmonary venous rings without endothelium were suspended in modified krebs-ringer's buffer for measurement of isometric tension. the effects of nonspecific pkc inhibition (bisindolylmaleimide i; 3 x 10 m) and conventional pkc isoform inhibition (g7936 10 m) on the acetylcholine dose-response relation were assessed. the expression of conventional pkc isoforms (alpha, beta, gamma), novel pkc isoforms (delta, epsilon, theta), and atypical pkc isoforms (zeta, iota, mu) was measured in pvsm cells by western blot analysis. the immunofluorescence technique and confocal microscopy were used to localize the cellular distribution of pkc isoforms before and after the addition of acetylcholine. acetylcholine caused dose-dependent contraction in e-pulmonary veins. pretreatment with bisindolylmaleimide i or g7936 attenuated acetylcholine contraction. pkc-alpha, -iota, -mu, and -zeta were expressed, whereas pkc-beta, -gamma, -delta, -epsilon;, and -theta were not expressed in pvsm cells. immunofluorescence staining for pkc isoforms showed that in unstimulated cells, pkc-alpha and pkc-mu were detected only in the cytoplasm. pkc-iota and pkc-zeta also exhibited a cytoplasmic immunofluorescence pattern, which was especially abundant in the perinuclear zone. activation with acetylcholine induced translocation of pkc-alpha from cytoplasm to membrane, whereas acetylcholine had no effect on the other pkc isoforms. translocation of pkc-alpha in response to acetylcholine was blocked by the muscarinic receptor antagonist, atropine.",acetylcholine contraction is attenuated by pkc inhibition in pvsm. acetylcholine induces translocation of pkc-alpha from cytoplasm to membrane in pvsm. these results suggest that pkc-dependent acetylcholine contraction in pvsm may involve activation and translocation of pkc-alpha.,Medication
do only a fraction of new hiv infections occur within identifiable stable discordant couples in sub-saharan africa?,"to estimate the contribution of hiv-1 sero-conversions among stable hiv sero-discordant couples (sdcs) to total hiv population-level incidence in sub-saharan africa. we constructed a mathematical model, grounded in nationally representative demographic and epidemiological data, that estimates the annual number of hiv-1 transmissions from the infected partners to the uninfected partners among established sdcs, and compares its value to an estimate for the overall hiv population-level incidence in 20 countries in sub-saharan africa. we defined identifiable hiv-1 transmissions among sdcs as those that a hypothetical screening and intervention program would have the potential to avert. uncertainty and sensitivity analyses were incorporated to assess the robustness of the findings. across the 20 countries, an average of 29 (range: 10-52) of new hiv-1 infections occurred in which one partner in an identifiable sdc infected the other. the percentage of total hiv new infections in a country that occurred within such identifiable sdcs tended to be lower in countries with larger general population hiv epidemics. for most countries, hiv-1 incidence among sdcs is unlikely to exceed 50 of new hiv infections in the whole population.","only a fraction of hiv-1 heterosexual transmissions occur within identifiable sdcs. prevention within sdcs at scale requires a series of potentially challenging programmatic requirements to be met. despite the importance of prevention programs aiming at protecting the sero-negative partner in an sdc, a wider strategy utilizing the full range of prevention modalities, which would limit the original generation of sdcs, is also needed.",Diagnosis
is initial treatment response essential to improve survival in patients with hepatocellular carcinoma who underwent curative radiofrequency ablation therapy?,"this study was undertaken to assess the outcome of potentially curative radiofrequency ablation (rfa) therapy for early-stage hepatocellular carcinoma (hcc) in patients with child-pugh stage a cirrhosis. this study retrospectively evaluated clinical outcomes in a cohort of 171 child-pugh stage a cirrhotic patients who received rfa for nave hcc within the milan criteria. the median follow-up period was 36.7 months. cumulative survival rates estimated by the kaplan-meier method for all patients were 98.8, 91.1 and 76.8 at 1, 3 and 5 years, respectively. cumulative probabilities of local tumor recurrence at 1, 2 and 3 years were 9.0, 14.1 and 17.7, respectively. cumulative survival rates in patients without local tumor recurrence were 96.6, 94.6 and 84.4 at 1, 3 and 5 years, respectively, compared with patients with local tumor recurrence (96.6, 74.8 and 42.1 at 1, 3 and 5 years, respectively; p 0.0002). cox regression analysis showed that low serum albumin (p 0.009, rr 3.04, ci 1.32-6.98), high range of pivka-ii (prothrombin induced by vitamin k absence or agonist ii) (p 0.025, rr 2.57, ci 1.13-5.89), with multiple (less than 3) nodules (p 0.021, rr 2.61, ci 1.15-5.91), and with local tumor recurrence (p 0.004, rr 3.62, ci 1.51-8.69) were significant risk factors for death.","initial complete response of curative rfa therapy in patients with child-pugh stage a cirrhosis and early-stage hcc is associated with improved survival. therefore, clinicians should aim to achieve complete ablation of all detectable hcc nodules with adequate safety margins.",Treatment
do inflammation markers correlate with common carotid intima-media thickness in patients perinatally infected with human immunodeficiency virus 1?,"to investigate common carotid intima-media thickness in a cohort of patients who were vertically infected with human immunodeficiency virus 1 (hiv-1). we conducted a cross-sectional observational study. human immunodeficiency virus 1-infected patients were compared with age-, sex-, and body mass index-matched healthy participants. common carotid intima-media thickness was measured in all participants on both sides of the neck, and the mean intima-media thickness was calculated. metabolic parameters and markers of inflammation were measured only in hiv-1-infected patients. statistical analysis was performed by multiple regression and by a matrix of pearson correlation coefficients. the student t test was used to compare mean common carotid intima-media thickness values between groups. forty patients (21 female) with hiv-1 infection acquired from birth with a mean age sd of 16.3 4.7 years and 27 healthy participants (11 female) with a mean age of 17.7 4.6 years were included in the study. mean common carotid intima-media thickness in the hiv-1-infected group (0.450 0.088 mm) was significantly higher (p .05) than in the control group (0.407 0.079 mm). no significant association was found between intima-media thickness and a specific antiretroviral regimen, exposure to combined antiretroviral agents, and hiv status. in multiple regression analyses, higher levels of insulin (p .007) and elevated levels of glycated hemoglobin (p .01) were associated with intima-media thickness changes.",patients perinatally infected with hiv have increased common carotid intima-media thickness compared with healthy individuals. these changes were more pronounced with increasing age and inflammation markers. interventions that improve cardiovascular risk profiles should be considered in hiv-infected young adults.,Diagnosis
does characterization of the equine skeletal muscle transcriptome identify novel functional responses to exercise training?,"digital gene expression profiling was used to characterize the assembly of genes expressed in equine skeletal muscle and to identify the subset of genes that were differentially expressed following a ten-month period of exercise training. the study cohort comprised seven thoroughbred racehorses from a single training yard. skeletal muscle biopsies were collected at rest from the gluteus medius at two time points: t(1) - untrained, (9 /- 0.5 months old) and t(2) - trained (20 /- 0.7 months old). the most abundant mrna transcripts in the muscle transcriptome were those involved in muscle contraction, aerobic respiration and mitochondrial function. a previously unreported over-representation of genes related to rna processing, the stress response and proteolysis was observed. following training 92 tags were differentially expressed of which 74 were annotated. sixteen genes showed increased expression, including the mitochondrial genes acadvl, mrps21 and slc25a29 encoded by the nuclear genome. among the 58 genes with decreased expression, mstn, a negative regulator of muscle growth, had the greatest decrease.functional analysis of all expressed genes using fatiscan revealed an asymmetric distribution of 482 gene ontology (go) groups and 18 kegg pathways. functional groups displaying highly significant (p 0.0001) increased expression included mitochondrion, oxidative phosphorylation and fatty acid metabolism while functional groups with decreased expression were mainly associated with structural genes and included the sarcoplasm, laminin complex and cytoskeleton.","exercise training in thoroughbred racehorses results in coordinate changes in the gene expression of functional groups of genes related to metabolism, oxidative phosphorylation and muscle structure.",Prevention
does resiniferatoxin combined with antidepressants preferentially prolong sensory/nociceptive block in rat sciatic nerve?,"current techniques of peripheral nerve block have major limitations, including lack of differentiation between motor and sensory fibers and potential toxicity of local anesthetics. recent studies have suggested that a nociceptive-selective nerve block can be achieved via a transient receptor potential vanilloid type 1 activator (capsaicin) along with local anesthetics. we hypothesized that the combination of potent transient receptor potential vanilloid type 1 agonist resiniferatoxin (rtx) and selected antidepressants (amitriptyline, doxepin, and fluoxetine, also potent sodium channel blockers) would produce prolonged and predominantly sensory nerve block. rats were anesthetized with isoflurane, and 0.2 ml of amitriptyline, doxepin, or fluoxetine was deposited next to the surgically exposed sciatic nerves (n 8 per group). some animals received a second injection containing rtx (n 8 per group). the effect of nerve block was assessed by neurobehavioral tests of the motor function (extensor postural thrust) and the nocifensive reaction (mechanical pinch). a single application of rtx produced nociceptive-selective sciatic nerve block, whereas antidepressants produced nociceptive and motor block. the combined administration of rtx and antidepressant resulted in a predominantly nociceptive nerve block. compared with antidepressants or rtx alone, the combination prolonged the nociceptive nerve block more than the motor block.","the combined application of rtx and antidepressants produced a markedly prolonged nociceptive peripheral nerve block in rat sciatic nerves compared with either agent alone. however, the 2-drug regimen also elicited prolonged blockade of the motor function, although disproportionately less compared with the nociceptive modality, suggesting the existence of nontransient receptor potential vanilloid type 1-mediated mechanisms. the mechanisms through which rtx affects nociceptive signal transduction/transmission have yet to be fully elucidated.",Medication
does salt reduction in vegetable soup affect saltiness intensity and liking in the elderly and children?,"reduction of added salt levels in soups is recommended. we evaluated the impact of a 30 reduction of usual added salt in vegetable soups on elderly and children's saltiness and liking evaluation. subjects were elderly and recruited from two public nursing homes (29 older adults, 79.78.9 years), and preschool children recruited from a public preschool (49 children, 4.51.3 years). this study took place in institutional lunchrooms. through randomization and crossover, the subjects participated in two sensory evaluation sessions, on consecutive days, to assess perceived saltiness intensity (elderly sample) and liking (elderly and children samples) of a vegetable soup with baseline salt content and with a 30 salt reduction. elderly rated perceived liking through a 10 cm visual analogue scale 'like extremely' (1) to 'dislike extremely' (10) and children through a five-point facial scale 'dislike very much' (1) to 'like very much' (5). after 30 added salt reduction in vegetable soup, there were no significant differences in saltiness noted by the elderly (p0.150), and in perceived liking by children (p0.160) and elderly (p0.860).",a 30 salt reduction in vegetable soup may be achieved without compromising perceived saltiness and liking in children and the elderly.,General
does allicin induce calcium and mitochondrial dysregulation causing necrotic death in leishmania?,"allicin has shown antileishmanial activity in vitro and in vivo. however the mechanism of action underlying its antiproliferative effect against leishmania has been virtually unexplored. in this paper, we present the results obtained in l.infantum and a mechanistic basis is proposed. exposure of the parasites to allicin led to high ca2 levels and mitochondrial reactive oxygen species (ros), collapse of the mitochondrial membrane potential, reduced production of atp and elevation of cytosolic ros. the incubation of the promastigotes with sytox green revealed that decrease of atp was not associated with plasma membrane permeabilization. annexin v and propidium iodide (pi) staining indicated that allicin did not induce phospholipids exposure on the plasma membrane. moreover, dna agarose gel electrophoresis and tunel analysis demonstrated that allicin did not provoke dna fragmentation. analysis of the cell cycle with pi staining showed that allicin induced cell cycle arrest in the g2/m phase.","we conclude that allicin induces dysregulation of calcium homeostasis and oxidative stress, uncontrolled by the antioxidant defense of the cell, which leads to mitochondrial dysfunction and a bioenergetic catastrophe leading to cell necrosis and cell cycle arrest in the premitotic phase.",General
does early plasma exchange improve outcome in pr3-anca-positive renal vasculitis?,"plasma exchange (pe) has been shown to improve renal outcome in anti-neutrophil cytoplasm antibody (anca)-associated vasculitis (aav) and severe renal failure; however the effect of pe in aav with moderate renal impairment is controversial. a single-centre, retrospective one-year follow-up study, including patients with renal aav and egfr 60 ml/min/1.73 m2. since 2007, all patients with renal aav and egfr 60 ml/min/1.73 m2 had pe in addition to induction therapy with cyclophosphamide and prednisolone. patients admitted from 1999 to 2007 that did not receive pe served as controls. the primary outcome was the combination of death, end-stage renal disease, and relapses after one year. a significant reduction in the primary endpoint was observed following the addition of pe (25 vs. 43, p0.04). furthermore, a greater improvement in renal function after one year was observed among surviving pe treated patients not on dialysis (egfr 36.1 vs. 19.7 ml/min, p0.03). there was a significant reduction in serious adverse events in the pe treated group (4 vs. 30, p0.02) despite no differences in types and doses of induction immunosuppressive therapy. the advantageous effect of pe was related to the presence of anti-proteinase3 (pr3)-antibodies and also evident among patients with plasma creatinine less than 500 m.",this study suggests the use of pe in addition to standard induction treatment with cyclophosphamide and glucocorticoids to patients with renal pr3-aav and an estimated-gfr 60 ml/min/1.73m2.,Treatment
does hypothermia augment nf-kappab activity and the production of il-12 and ifn-gamma?,"the differentiation of th1 and th2 is strictly regulated by humoral and cellular factors. the imbalance between th1 and th2 is considered to be the pathogenesis of allergic and autoimmune disorders. it is important to elucidate the effect of environmental factors, such as temperature, on the expression of cytokines of th1 and th2. we investigated the expression of ifn-gamma, il-4, il-5, il-10 and il-12 from lps- or pha-stimulated pbmcs at 30 degrees c or 37 degrees c using elisa and real-time pcr. we measured the change of nf-kappab activity at 30 degrees c or 37 degrees c with lps stimulation using the reporter gene assay. ifn-gamma production from lps-stimulated pbmcs at 30 degrees c was up-regulated compared with 37 degrees c. il-5 and il-10 production from pha-stimulated pbmcs at 30 degrees c were down-regulated compared with 37 degrees c. this augmented ifn-gamma production was caused by the up-regulation of il-12 production from cd14 blood monocytes. both il-12 mrna and il12 protein at 30 degrees c were up-regulated compared with 37 degrees c. nf-kappab, the key molecule for the expression of il-12, was also augmented at 30 degrees c compared with 37 degrees c.",hypothermia up-regulated the expression of il-12 and ifn-gamma due to the augmented nf-kappab activity. it is suggested that hypothermia modifies the pattern of cytokine gene expression.,General
do baseline gray- and white-matter volume predict successful weight loss in the elderly?,the purpose of this study was to investigate whether structural brain phenotypes could be used to predict weight loss success following behavioral interventions in older adults with overweight or obesity and cardiometabolic dysfunction. a support vector machine with a repeated random subsampling validation approach was used to classify participants into the upper and lower halves of the weight loss distribution following 18 months of a weight loss intervention. predictions were based on baseline brain gray matter and white matter volume from 52 individuals who completed the intervention and a magnetic resonance imaging session. the support vector machine resulted in an average classification accuracy of 72.62 based on gray matter and white matter volume. a receiver operating characteristic analysis indicated that classification performance was robust based on an area under the curve of 0.82.,findings suggest that baseline brain structure was able to predict weight loss success following 18 months of treatment. the identification of brain structure as a predictor of successful weight loss was an innovative approach to identifying phenotypes for responsiveness to intensive lifestyle interventions. this phenotype could prove useful in future research focusing on the tailoring of treatment for weight loss.,Prevention
does autonomic dysfunction independently predict poor cardiovascular outcomes in asymptomatic individuals with type 2 diabetes in the diad study?,"the primary aim of this secondary analysis was to determine whether cardiac autonomic neuropathy independently predicted adverse cardiac outcomes in asymptomatic individuals with type 2 diabetes. additional aims include the determination of the correlation of standard autonomic testing measures and power spectral analysis of heart rate variability, and the association of diabetes-related and cardiac risk factors with cardiac autonomic neuropathy measures. cardiac autonomic neuropathy was assessed at the study entry into the detection of ischemia in asymptomatic diabetics study, using autonomic heart rate and blood pressure testing, and power spectral analysis of heart rate variability. all participants were prospectively followed for the composite clinical outcome of cardiac death, acute coronary syndromes, heart failure, or coronary revascularization. over 5 years of follow-up, 94 of 1119 (8.4) subjects developed symptomatic cardiac disease. in unadjusted bivariate analyses, abnormalities in several cardiac autonomic neuropathy tests, including lower valsalva and standing heart rate ratios, higher resting heart rate, greater systolic blood pressure decrease on standing, and lower low-frequency power, were predictive of symptomatic disease. independent predictors of poor cardiac outcome were a lower valsalva heart rate ratio, non-black ethnicity, longer diabetes duration, higher glycated hemoglobin (hba1c), insulin use, reported numbness in the extremities, higher pulse pressure, family history of coronary artery disease, and higher waist-to-hip ratio. clinical factors independently associated with a lower valsalva heart rate ratio were insulin use, clinical proteinuria, higher pulse pressure, use of angiotensin-converting enzyme inhibitor and non-black ethnicity.",cardiac autonomic neuropathy predicted adverse cardiac outcomes in asymptomatic type 2 diabetes without known cardiac disease. clinical variables may help to identify patients who might have cardiac autonomic neuropathy and warrant consideration for autonomic testing.,Symptoms
does strontium ranelate inhibit key factors affecting bone remodeling in human osteoarthritic subchondral bone osteoblasts?,"in osteoarthritis (oa) the progression of cartilage degeneration has been associated with remodeling of the subchondral bone. human oa subchondral bone osteoblasts were shown to have an abnormal phenotype and altered metabolism leading to an abnormal resorptive process. bone resorption is suggested to occur, at least in part, through the increased levels of two proteolytic enzymes, mmp-2 and mmp-9, and rankl, which are mainly produced by osteoblasts. in this study, we investigated in human oa subchondral bone osteoblasts the modulatory effect of strontium ranelate on the above key factors. human subchondral bone osteoblasts were cultured in a medium containing 0.1, 1 and 2 mm of strontium ranelate for 18 h for mrna and 72 h for protein determination. the effect of strontium ranelate was evaluated on the expression (qpcr) of mmp-2, mmp-9, opg, rankl (total), rankl-1, and rankl-3, on the production of opg (elisa), membranous rankl (flow cytometry), and mt1-mmp, adam17, and adam19 (western blot). after incubation of osteoblasts with pre-osteoclasts (i.e., differentiated human peripheral blood mononuclear cells), the resorbed surface was measured using a sub-micron synthetic calcium phosphate thin film. firstly, the expression levels of mmp-2, mmp-9, opg, and rankl were determined in normal and oa subchondral bone osteoblasts. as expected, the gene expression of mmp-9 and rankl were not detectable in normal cells, whereas mmp-2 was very low but detectable and opg demonstrated high gene expression. further experiments looking at the effect of strontium ranelate on expression levels, except for opg, were performed only on the oa subchondral bone osteoblasts. in oa cells, the expression levels of mmp-2 and mmp-9 were significantly decreased by strontium ranelate at 1mm (p0.005, p0.02, respectively) and 2 mm (p0.003, p0.007), and for mmp-9 only at 0.1 mm (p0.05). in normal cells, the expression of opg was increased with strontium ranelate at 2 mm, and in oa both the expression (p0.02) and synthesis (p0.002) of opg were significantly increased with strontium ranelate at 1 and 2 mm. rankl (total) as well as the isoforms rankl-1 and rankl-3 were significantly increased by strontium ranelate at 1 and 2 mm. of note, it is known that the different rankl isoforms differentially regulate rankl membranous localization: rankl-3, in contrast to rankl-1, prevents such membranous localization. this is reflected by the significant (p0.02) reduction in the level of membranous rankl by strontium ranelate at 2 mm. this latter finding was not likely to be related to a proteolytic cleavage of membranous rankl, as the enzymes known to cleave it, mt1-mmp, adam17 and adam19, were unaffected by strontium ranelate. in addition, oa osteoblasts treated with strontium ranelate induced a significant (p0.002) decrease in resorbed surface at the three tested concentrations.","this study provides new insights into the mode of action of strontium ranelate on the metabolism of human oa subchondral bone osteoblasts. these data suggest that strontium ranelate may exert a positive effect on oa pathophysiology by inhibiting, in these cells, the synthesis of key factors leading to bone resorption, a feature associated with the oa process.",Prevention
"are malnutrition ( subjective global assessment ) scores and serum albumin levels , but not body mass index values , at initiation of dialysis independent predictors of mortality : a 10-year clinical cohort study?","to examine the associations between demographic, clinical, lifestyle, and nutritional parameters at the start of dialysis and mortality, including the combined effects on nutritional parameters, which were seldom investigated in the literature. ten-year retrospective clinical cohort study. dialysis unit of a metropolitan tertiary teaching hospital in sydney, australia. incident dialysis patients (n 167; hemodialysis, 57.5; male, 61.7; age, 65.3 13.6 years; diabetic, 24.5) who commenced on a planned dialysis program. associations were examined between all-cause mortality and baseline demographics, including age and gender; clinical and lifestyle characteristics, including glomerular filtration rate, smoking habits, presence of comorbidities (e.g., coronary artery disease, diabetes mellitus, and peripheral vascular disease); and nutritional parameters, including body mass index (bmi), serum albumin (s-albumin) levels, and subjective global assessment score (sga). associations with combination values for malnutrition, s-albumin (65 years, p .0001), presence of peripheral vascular disease (p .0001), reduced s-albumin levels (p .01), and malnutrition scores (p .02) independently predicted mortality. being overweight and obese (bmi: 26 kg/m(2)) did not show any advantage on survival (p .73). being malnourished and overweight (or obese) was associated with a 3-fold increase in mortality risk (adjusted hazard ratio hr, 2.96; 95 confidence interval ci, 1.12 to 7.33; p .02) compared with being well nourished with a bmi 26 kg/m(2) (referent). compared with being well nourished (sga a), being malnourished with normal or low s-albumin was associated with higher risk (hr, 2.06; 95 ci, 1.06 to 4.00; p .03 and hr, 2.86; 95 ci, 1.65 to 4.94; p .0001, respectively). there was no statistical difference between mortality risks through any combination of s-albumin and bmi values (p .54).","malnutrition and reduced s-albumin levels were found to be independent predictors of mortality, whereas being overweight and obese did not show protective effects.",Treatment
does nuclear expression of phosphorylated traf2- and nck-interacting kinase in hepatocellular carcinoma is associate with poor prognosis?,"traf2- and nck-interacting kinase (tnik) is a member of the germinal center kinase family and a transcription factor 4 (tcf4) interactor is recruited to promoters of wnt target genes via phosphorylation of the tcf/-catenin complex. the aim of this study was to evaluate the tnik, the active form of tnik (p-tnik), and -catenin expression in hepatocellular carcinoma (hcc), and to identify the prognostic significance of p-tnik. we assessed the expression status of tnik, p-tnik, and -catenin by using immunohistochemical analysis of 302 hccs in 8 tissue microarray blocks, and we evaluated their clinicopathologic features and survival rates based on their p-tnik expression. of 302 hccs, 92.7 stained positive for tnik in the cytoplasm. nuclear expression of p-tnik was identified in 7.9 hccs. aberrant cytoplasmic expression of -catenin was identified in 77.2 and nuclear expression in 3.3. p-tnik nuclear staining was positively correlated to -catenin nuclear expression (p0.036). cytoplasmic and nuclear expression of p-tnik was more frequently observed in high edmondson-steiner (es) nuclear grade groups (p0.030). nuclear p-tnik expression was also associated with pathological m1 stage (pm1 stage) patients (p0.0001). aberrant cytoplasmic expression of -catenin was more frequently identified in larger tumors (p0.014). univariate (dfs, p0.049; os, 0.037) and multivariate analysis (dfs, p0.006; os, p0.003) confirmed the independent prognostic significance of nuclear p-tnik expression.","this is the first time that nuclear p-tnik expression was studied in hcc, and p-tnik nuclear expression was associated with poor prognosis and is a candidate prognostic marker for hcc.",Diagnosis
is cd10 useful to identify gastrointestinal contamination in endoscopic ultrasound-guided fine needle aspiration ( eus-fna ) cytology from pancreatic ductal adenocarcinoma?,"endoscopic ultrasound-guided fine needle aspiration (eus-fna) cytology is an effective tool to diagnose pancreatic ductal adenocarcinoma (pda). standard morphological criteria are usually reliable. when contaminating gastrointestinal (gi) epithelial cells are prevalent among neoplastic cells, these can be highlighted by carcinoembryonic antigen (cea) staining. cd10 is a cell-surface metallopeptidase normally expressed by the gi epithelial apical border, whose expression is decreased or lost in pda. we included cd10 in a panel, together with cea, to discriminate the gi contaminant cells from pda cells on cell blocks. eight cases of eus-fna of pda, featuring both contaminating gi cells and neoplastic cells, whose corresponding cell blocks were available for immunostaining, were selected. cd10 and cea were stained on cell blocks by standard methods. cd10 strongly labelled only the gi cells, with a well-defined apical membrane signal; conversely, gi cells did not show cea staining; benign duodenal cells were faintly labelled in only one case. malignant cells were positive for cea and negative for cd10, with the exception of one case with labelled neoplastic cells with weak diffuse cytoplasmic positivity. cd10 apical membrane staining was a feature only seen in benign gi cells.","as a loss of cd10 is a consistent feature of pda, this marker can be useful, together with cea, to aid the cytopathologist to identify neoplastic cells in a background rich in gi contaminant cells.",Diagnosis
does arbitrary starting point of separation affect morphology of the 2 bundles of anterior cruciate ligament at insertion sites?,"to explore whether changes in the starting point of separation affect the morphology of the 2 bundles of the anterior cruciate ligament (acl) at insertion. ten cadaveric knees were used to separate the acl fibers into 2 bundles from 3 different starting points that were located at the proximal one fifth, two fifths, and three fifths of the inter-bundle mark line. the dividing lines between the 2 bundles at insertion and the area of the anteromedial (am) bundle resulting from these different separations were compared, with data collected in groups i, ii, and iii, respectively. the angle of the dividing line and the long axis of the femoral footprint was 67.24 degrees /- 11.94 degrees, 91.01 degrees /- 11.16 degrees, and 116.03 degrees /- 9.01 degrees in groups i, ii, and iii, respectively, and the percentage of the am bundle area in the whole femoral footprint was 38.64 /- 5.55, 52.22 /- 6.76, and 65.09 /- 4.53, respectively. at the tibial insertion sites, the angle between the dividing line and the sagittal plane was 110.17 degrees /- 13.26 degrees, 127.72 degrees /- 8.94 degrees, and 149.28 degrees /- 18.80 degrees in groups i, ii, and iii, respectively, and the percentage of the am bundle area in the whole footprint was 25.72 /- 3.82, 40.41 /- 3.73, and 60.56 /- 6.59, respectively. there were statistical differences between the angle and the area data of each of the 2 groups at either the tibial or femoral insertion site.","in an anatomic study of the acl, changes in the point from which separation started resulted in noticeably different bundle morphology at the insertion.",General
is stepwise sedation safe and effective for the insertion of central venous catheters?,"the introduction of a central venous catheter in haemodialysis patients is an unpleasant procedure for the patient. intravenous sedation is accepted practice in complicated endoscopic procedures but not often used in haemodialysis patients. we developed a protocol for the use of stepwise sedation in these patients with the use of midazolam and fentanyl. stepwise sedation with midazolam and fentanyl was used in 155 procedures. no or minor movements were observed in 94 of 154 procedures. 88 of the 155 procedures were graded as very easy or easy. no or only very slight recall of the procedure were noted in 86 of 133 procedures. only in 7 of 132 procedures were the patients able to recollect most of the procedure. no, or only a small amount of pain was recollected in 93 of 131 procedures. the most important complication was a slight decrease in oxygen saturation in 23 procedures. in the second part of the study we compared the effects of sedation with midazolam alone versus the combination of midazolam and fentanyl for the introduction of tesio catheters. amnesia, ease of procedure and the recollection of pain were equivalent. oxygen desaturation occurred significantly less often with the use of midazolam alone.",we conclude that stepwise sedation is effective and safe in haemodialysis patients and leads to a complete amnesia for the procedure.,Medication
does normothermic continuous blood cardioplegia improve electrophysiologic recovery after open heart surgery?,"myocardial protection during open heart surgery is based on administration of oxygenated blood cardioplegia, the preferred temperature of which is still under debate. the current randomized study was designed to prospectively evaluate the quality of myocardial protection and the functional recovery of the heart with either normothermic (group n) or hypothermic (group h) oxygenated blood cardioplegia. under continuous electrocardiographic holter monitoring, 42 patients were randomly scheduled to receive either normothermic (33.5 degrees c) or hypothermic (10 degrees c) cardioplegia solutions during coronary bypass grafting surgery. blood samples for creatinine phosphokinase, creatinine phosphokinase-mb, lactate, epinephrine, and norepinephrine were withdrawn during cardiopulmonary bypass via a coronary sinus cannula. active cooling in group h on initiation of cardiopulmonary bypass was characterized by transition through ventricular fibrillation in 75 of patients, whereas in group n atrial fibrillation occurred in 65 of patients. on myocardial reperfusion, sinus rhythm spontaneously resumed in 95 of group n patients compared to 25 in group h (p 0.0003). in the latter, 75 of patients developed ventricular fibrillation often followed by complete atrioventricular block, which necessitated temporary pacing for a mean duration of 168 /- 32 min. both groups showed a similar incidence of intraventricular block and st segment changes. however, the incidence of ventricular premature beats in the first 16 h after cardiopulmonary bypass was significantly greater in group h (p 0.05), 20 /- 26/h, compared to 3 /- 5/h in group n. blood concentrations of lactate, creatinine phosphokinase, epinephrine, and norepinephrine increased gradually during the operation, but the differences between the groups were not significant.","the current prospective human study suggests that the increased susceptibility for ventricular fibrillation and dysrhythmia, and the delayed recovery of the conduction system after hypothermic myocardial protection, are related to temperature-induced changes in vital cellular functions of the conduction tissue in the postischemic period. both cardioplegic methods provide adequate myocardial protection but normothermic oxygenated blood cardioplegia may accelerate recovery of the heart after cardiopulmonary bypass.",Treatment
is early renin-angiotensin system intervention more beneficial than late intervention in delaying end-stage renal disease in patients with type 2 diabetes?,"to develop and validate a model to simulate progression of diabetic kidney disease (dkd) from early onset until end-stage renal disease (esrd), and to assess the effect of renin-angiotensin system (ras) intervention in early, intermediate and advanced stages of dkd. we used data from the benedict, irma-2, renaal and idnt trials that assessed effects of ras intervention in patients with type 2 diabetes. we built a model with discrete disease stages based on albuminuria and estimated glomerular filtration rate (egfr). using survival analyses, we assessed the effect of ras intervention on delaying esrd in early egfr60 ml/min/1.73 m(2) and albumin:creatinine ratio (acr) 300 mg/g) stages of dkd for patients in different age groups. for patients at early, intermediate and advanced stage of disease, whose mean age was 60 years and who received placebo, the median time to esrd was 21.4, 10.8 and 4.7 years, respectively. ras intervention delayed the predicted time to esrd by 4.2, 3.6 and 1.4 years, respectively. the benefit of early ras intervention was more pronounced in younger patients; for example, for patients with a mean age of 45 years, ras intervention at early, intermediate or advanced stage delayed esrd by 5.9, 4.0 and 1.1 years versus placebo.",ras intervention early in the course of proteinuric dkd is more beneficial than late intervention in delaying esrd.,Treatment
are bicycle helmets highly protective against traumatic brain injury within a dense urban setting?,"new york city (nyc) has made significant roadway infrastructure improvements, initiated a bicycle share program, and enacted vision zero, an action plan to reduce traffic deaths and serious injuries. the objective of this study was to examine whether bicycle helmets offer a protective advantage against traumatic brain injury (tbi) within a contemporary dense urban setting with a commitment to road safety. a prospective observational study of injured bicyclists presenting to a level i trauma centre was performed. all bicyclists arriving within 24 h of injury were included. data were collected between february, 2012 and august, 2014 and included demographics, imaging studies (e.g. computed tomography (ct)), injury patterns, and outcomes including glasgow coma scale (gcs) and injury severity score. of 699 patients, 273 (39.1) were wearing helmets at the time of injury. helmeted bicyclists were more likely to have a gcs of 15 (96.3 95 confidence interval (ci), 93.3-98.2 vs. 87.6 95 ci, 84.1-90.6) at presentation. helmeted bicyclists underwent fewer head cts (40.3 95 ci, 34.4-46.4 vs. 52.8 95 ci, 48.0-57.6) and were less likely to sustain intracranial injury (6.3 95 ci, 2.6-12.5 vs. 19.7 14.7-25.6), including skull fracture (0.9 95 ci, 0.0-4.9 vs. 15.3 95 ci, 10.8-20.7) and subdural hematoma (0.0 95 ci, 0.0-3.2 vs. 8.1 95 ci, 4.9-12.5). helmeted bicyclists were significantly less likely to sustain significant tbi, i.e. head ais 3 (2.6 95 ci: 0.7-4.5 vs.10.6 7.6-12.5). four patients underwent craniotomy while three died; all were un-helmeted. a multivariable logistic regression model showed that helmeted bicyclists were 72 less likely to sustain tbi compared with un-helmeted bicyclists (adjusted odds ratio 0.28, 95 ci 0.12-0.61).","despite substantial road safety measures in nyc, the protective impact of simple bicycle helmets in the event of a crash remains significant. a re-assessment of helmet laws for urban bicyclists is advisable to most effectively translate vision zero from a political action plan to public safety reality.",Diagnosis
are lactase persistence and milk consumption associated with body height in swedish preadolescents and adolescents?,"body height is a classic polygenic trait. about 80-90 of height is inherited and 10-20 owed to environmental factors, of which the most important ones are nutrition and diseases in preadolescents and adolescents. the aim of this study was to explore potential relations between the lct (lactase) ct-13910 polymorphism, milk consumption, and body height in a sample of swedish preadolescents and adolescents. in a cross-sectional study, using a random sample of preadolescents and adolescents (n 597), dietary intakes were determined. anthropometric measurements including sexual maturity (tanner stage) and birth weight were assessed. parental body height and socio-economic status (ses) were obtained by questionnaires. genotyping for the lct ct-13910 polymorphism that renders individuals lactase persistent (lp) or lactase non-persistent (lnp) was performed by dna sequencing. stepwise backward multivariate linear regression was used. milk consumption was significantly and positively associated with body height ( 0.45; 95 ci: 0.040, 0.87, p 0.032). adjustments were performed for sex, parental height, birth weight, body mass index (bmi), ses, and tanner stage. this model explains 90 of the observed variance of body height (adjusted r(2) 0.89). the presence of the -13910 t allele was positively associated with body height ( 2.05; 95 ci: 0.18, 3.92, p 0.032).",milk consumption is positively associated with body height in preadolescents and adolescents. we show for the first time that a nutrigenetic variant might be able to explain in part phenotypic variation of body height in preadolescents and adolescents. due to the small sample size further studies are needed.,Prevention
does semi-automatic software increase ct measurement accuracy but not response classification of colorectal liver metastases after chemotherapy?,"this study evaluates intra- and interobserver variability of automatic diameter and volume measurements of colorectal liver metastases (crlm) before and after chemotherapy and its influence on response classification. pre-and post-chemotherapy ct-scans of 33 patients with 138 crlm were evaluated. two observers measured all metastases three times on pre-and post-chemotherapy ct-scans, using three different techniques: manual diameter (md), automatic diameter (ad) and automatic volume (av). recist 1.0 criteria were used to define response classification. for each technique, we assessed intra- and interobserver reliability by determining the intraclass correlation coefficient (-level 0.05). intra-observer agreement was estimated by the variance coefficient (). for inter-observer agreement the relative measurement error () was calculated using bland-altman analysis. in addition, we compared agreement in response classification by calculating kappa-scores () and estimating proportions of discordance between methods (). intra-observer variability was 6.05, 4.28 and 12.72 for md, ad and av, respectively. inter-observer variability was 4.23, 2.02 and 14.86 for md, ad and av, respectively. chemotherapy marginally affected these estimates. agreement in response classification did not improve using ad or av (md 0.653, ad 0.548, av 0.548) and substantial discordance between observers was observed with all three methods (md 17.8, ad 22.2, av 22.2).","semi-automatic software allows repeatable and reproducible measurement of both diameter and volume measurements of crlm, but does not reduce variability in response classification.",Medication
do systemic postganglionic adrenergic studies distinguish parkinson 's disease from multiple system atrophy?,"multiple system atrophy (msa) affects the preganglionic adrenergic neuron and parkinson's disease (pd) involves the postganglionic counterpart. widespread postganglionic denervation should result in denervation supersensitivity and a failure of the axon to release norepinephrine (ne). we examined if pharmacological dissection of the adrenergic neuron can distinguish between msa and pd. we measured blood pressure, heart rate, and plasma ne responses to direct (phenylephrine) and indirect (tyramine) acting adrenergic agonists in 15 patients with probable msa, 16 patients with idiopathic pd, and 16 age- and gender-matched controls. baroreflex sensitivity was impaired in msa and intact in pd. pressor responses to phenylephrine (direct acting) were higher in msa (p0.01) and pd patients (p0.04) than in controls. blood pressure responses to tyramine (indirect acting) were increased in msa only (p0.01). tyramine increased plasma catecholamine levels in all groups with no significant differences between groups.","there is denervation supersensitivity in pd patients that is, however, insufficient to shift the dose-response curve to the left. the excessive pressor responses to both tyramine and phenylephrine in msa are due to baroreflex failure. we conclude that this diagnostic approach lacks sufficient sensitivity to differentiate pd and msa.",Medication
does beraprost sodium protect against chronic brain injury in aluminum-overload rats?,"aluminum overload can cause severe brain injury and neurodegeneration. previous studies suggest that prostacyclin synthase (pgis) expression and prostacyclin receptor (ip) activation are beneficial for treatment of acute traumatic and ischemic brain injury. however, the potential value of pgis/ip signaling pathway to chronic brain injury is still unclear. in this study, we investigated the change of pgis/ip signaling pathway and the effect of beraprost sodium (bps) on chronic brain injury in chronic aluminum-overload rats. rat model of chronic cerebral injury was established by chronic intragastric administration of aluminum gluconate(al3 200 mg/kg per day,5d a week for 20 weeks). the methods of elisa, qrt-pcr and western blotting were used to detect the pgi2 level and the pgis and ip mrna and protein levels in hippocampi of chronic aluminum-overload rats, respectively. rat hippocampal superoxide dismutase (sod) activity and malondialdehyde (mda) content also were measured. the effects of bps (6, 12 and 24 gkg(-1)) on brain injury in chronic aluminum-overload rats were evaluated. compared with the control group, pgis mrna expression, pgi2 level, and the ip mrna and protein expressions significantly increased in hippocampi of chronic aluminum-overload rats. administration of bps significantly improved spatial learning and memory function impairment and hippocampal neuron injury induced by chronic aluminum overload in rats. meanwhile, administration of bps resulted in a decrease of pgi2 level and downregulation of pgis and ip expressions in a dose-dependent manner. aluminum overload also caused a decrease of sod activity and an increase of mda content. administration of bps significantly blunted the decrease of sod activity and the increase of mda content induced by aluminum overload in rats.",bps has a significant neuroprotective effect on chronic brain injury induced by aluminum overload in rats. remodeling the balance of pgis/ip signaling pathway and inhibition of oxidative stress involve in the neuroprotective mechanism of bps in aluminum-overload rats. the pgis/ip signaling pathway is a potential therapeutic strategy for chronic brain injury patients.,Medication
does darbepoetin-alpha promote microvascular thrombus formation in mice : role of enos-dependent protection through platelet and endothelial cell deactivation?,"erythropoietin (epo) treatment has become the standard treatment of renal anemia. though a link between hematopoiesis-stimulating drugs and thrombosis has not been proven, it is generally assumed that systemic application of epo and its analogues increases the risk for thrombotic events. here we show in c57bl/6j mice that 4-week treatment with the long-lasting epo analogue darbepoetin-alpha (dpo) at a dose of 10 microg/kg/week induces a reduction of platelet reactivity using flow cytometry and western blot analysis of tyrosine-specific platelet phosphorylation. additionally, immunohistochemistry of endothelial adhesion molecule expression and elisa of circulating endothelial activation markers demonstrated a reduced endothelial activation. immunohistochemistry and rt-pcr analysis revealed a significant (p0.05) increase of enos expression. further, dpo did not exert prothrombogenic effects in a murine intravital microscopic thrombosis model of the cremaster muscle. the role of enos in prevention of dpo-mediated microvascular thrombosis is further underlined by a significantly accelerated thrombus formation on dpo treatment in enos (-/-) mice.","thus, dpo-related erythropoiesis with a raised hematocrit is not associated with an increased risk for thrombosis as long as endothelial no production serves as compensatory mechanism.",Medication
is a frequent hypofunctional irak2 variant associated with reduced spontaneous hepatitis c virus clearance?,"patients carrying very rare loss-of-function mutations in interleukin-1 receptor-associated kinase 4 (irak4), a critical signaling mediator in toll-like receptor signaling, are severely immunodeficient, highlighting the paramount role of irak kinases in innate immunity. we discovered a comparatively frequent coding variant of the enigmatic human irak2, l392v (rs3844283), which is found homozygously in 15 of caucasians, to be associated with a reduced ability to induce interferon-alpha in primary human plasmacytoid dendritic cells in response to hepatitis c virus (hcv). cytokine production in response to purified toll-like receptor agonists was also impaired. additionally, rs3844283 was epidemiologically associated with a chronic course of hcv infection in two independent hcv cohorts and emerged as an independent predictor of chronic hcv disease. mechanistically, irak2 l392v showed intact binding to, but impaired ubiquitination of, tumor necrosis factor receptor-associated factor 6, a vital step in signal transduction.",our study highlights irak2 and its genetic variants as critical factors and potentially novel biomarkers for human antiviral innate immunity.,Medication
does tobacco smoking increase the risk for death from pneumococcal pneumonia?,"active smoking increases the risk of developing community-acquired pneumonia (cap) and invasive pneumococcal disease, although its impact on mortality in pneumococcal cap outcomes remains unclear. the aim of this study was to investigate the influence of current smoking status on pneumococcal cap mortality. we performed a multicenter, prospective, observational cohort study in 4,288 hospitalized patients with cap. the study group consisted of 892 patients with pneumococcal cap: 204 current smokers (22.8), 387 nonsmokers (43.4), and 301 exsmokers (33.7). mortality at 30 days was 3.9: 4.9 in current smokers vs 4.3 in nonsmokers and 2.6 in exsmokers. current smokers with cap were younger (51 years vs 74 years), with more alcohol abuse and fewer cardiac, renal, and asthma diseases. current smokers had lower curb-65 (confusion, uremia, respiratory rate, bp, age 65 years) scores, although 40 had severe sepsis at diagnosis. current smoking was an independent risk factor (or, 5.0; 95 ci, 1.8-13.5; p .001) for 30-day mortality of pneumococcal cap after adjusting for age (or, 1.06; p .001), liver disease (or, 4.5), sepsis (or, 2.3), antibiotic adherence to guidelines, and first antibiotic dose given 6 h. the independent risk effect of current smokers remained when compared only with nonsmokers (or, 4.0; 95 ci, 1.3-12.6; p .015) or to exsmokers (or, 3.9; 95 ci, 1.09-4.95; p .02).","current smokers with pneumococcal cap often develop severe sepsis and require hospitalization at a younger age, despite fewer comorbid conditions. smoking increases the risk of 30-day mortality independently of tobacco-related comorbidity, age, and comorbid conditions. current smokers should be actively targeted for preventive strategies.",Medication
are plasma levels of interleukin-6 and its soluble receptor associated with prostate cancer progression and metastasis?,"elevated circulating levels of interleukin 6 (il-6) have been associated with cancer metastasis. il-6 binds either to membrane or to soluble il-6 receptor (il-6sr), which then induces homodimerization of gp130 that activates downstream signaling. we tested the hypothesis that preoperative plasma il-6 and il-6sr levels are associated with prostate cancer stage, progression, and metastasis after radical prostatectomy. plasma levels of il-6 and il-6sr were measured in 120 consecutive patients who underwent radical prostatectomy for clinically localized prostate cancer, 44 healthy men without any cancer, 19 men with prostate cancer metastatic to the regional lymph nodes, and 10 men with prostate cancer metastatic to bone. plasma il-6 and il-6sr levels were highest in patients with bone metastases (p 0.001). the preoperative il-6 and il-6sr levels were associated with the preoperative prostate-specific antigen (psa) level (p /0.041), prostatectomy tumor volume (p /0.048), and final gleason sum (p /0.042). the preoperative il-6 and il-6sr levels and biopsy gleason sum were independent predictors of psa progression (p /0.029). however, in a model that included both il-6 and il-6sr, only il-6sr and the biopsy gleason sum predicted progression (p /0.040). in patients whose disease progressed, the preoperative il-6 and il-6sr levels were highest in those with presumed aggressive failure (p /0.042).","plasma il-6 and il-6sr levels were dramatically elevated in the men with prostate cancer metastatic to bone. in patients with clinically localized prostate cancer, the preoperative plasma il-6 and il-6sr levels independently predicted biochemical progression after surgery, presumably because of an association with occult metastatic disease present at the time of radical prostatectomy.",Medication
do mesenchymal stromal cells prolong the lifespan in a rat model of amyotrophic lateral sclerosis?,"amyotrophic lateral sclerosis (als) is a progressive neurodegenerative disorder characterized by the loss of brain and spinal cord motor neurons (mn). the intraspinal and systemic grafting of mesenchymal stromal cells (msc) was used to treat symptomatic transgenic rats overexpressing human superoxide dismutase 1 (sod1) in order to alleviate the disease course and prolong the animals' lifespan. at the age of 16 weeks (disease onset) the rats received two grafts of msc expressing green fluorescent protein (gfp() msc) on the same day, intraspinally (10(5) cells) and intravenously (2 10(6) cells). sham-treated animals were injected with phosphate-buffered saline (pbs). motor activity, grip strength and body weight were tested, followed by immunohistochemical analysis. the combined grafting of msc into symptomatic rats had a significant effect on motor activity and grip strength starting 4 weeks after transplantation. the lifespan of animals in the treated group was 190 3.33 days compared with 179 3.6 days in the control group of animals. treated rats had a larger number of mn at the thoracic and lumbar levels; these mn were of larger size, and the intensity of terminal deoxynucleotidyltransferase-mediated dutp-biotin nick-end labeling (tunel) staining in the somas of apoptotic mn at the thoracic level was much lower than in sham-treated animals. transplanted gfp() msc survived in the spinal cord until the end stage of the disease and migrated both rostrally and caudally from the injection site.",intraspinal and intravenous transplantation of msc has a beneficial and possibly synergistic effect on the lifespan of als animals.,Medication
do newborn weight charts underestimate the incidence of low birthweight in preterm infants?,"the objective of the study was to compare sonographic fetal weight estimates with newborn weight charts and analyze the predictive accuracy of the ponderal index (pi) in preterm infants. we generated sonographic reference curves for fetal weight and pi estimates from a database of fetal biometric records from 12,589 term deliveries. we then plotted sonographic and newborn weight and pi of 2406 preterm newborns on these curves and compared them with published newborn weight charts. the third centiles of sonographic and newborn weights diverged markedly between 25 and 36 weeks of gestation and by more than 400 g at 32-33 weeks. in contrast, sonographic and newborn pi values were similar despite uncertainties as to fetal length.",we suggest using sonographic reference fetal weights to screen preterm newborns for low birthweight. uncertainties in fetal length threaten the reliability of the pi.,Diagnosis
is the pxr a drug target for chronic inflammatory liver disease?,"pxr activators are used to treat pruritus in chronic inflammatory liver diseases such as primary biliary cirrhosis (pbc). the aims of this study were to determine whether pxr activators could have an additional benefit of inhibiting inflammation in the liver, and determine whether cyclosporin a - which more effectively prevents pbc recurrence in transplanted patients than fk506 - is a pxr activator. in sjl/j mice (which have constitutively high levels of hepatic portal tract inflammatory cell recruitment), feeding a pxr activator inhibited inflammation, tnfalpha and il-1alpha mrna expression in sjl/j-pxr(/), but not sjl/j-pxr(-/-). monocytic cells - a major source of inflammatory mediators such as tnfalpha - expressed the pxr and pxr activators inhibited endotoxin-induced nf-kappab activation and tnfalpha expression. pxr activation also inhibited endotoxin-stimulated tnfalpha secretion from liver monocytes/macrophages isolated from pxr(/) mice, but not from cells isolated from pxr(-/-) mice. to confirm that pxr activation inhibits nf-kappab in vivo, 3x-kappab-luc fibrotic mice (which express a luciferase gene regulated by nf-kappab) were imaged after treatment with the hepatotoxin ccl(4). pxr activator inhibited the induction of hepatic nf-kappab activity without affecting ccl(4) toxicity/hepatic damage. using a pxr reporter gene assay, cyclosporin a - but not fk506 - was shown to be a direct pxr activator, and also to induce expression of the classic pxr-regulated cyp3a4 gene in human hepatocytes and in a cell line null for the fxr, a nuclear receptor with similar properties to the pxr.","pxr activation is anti-inflammatory in the liver and the effects of cyclosporin a in pbc disease recurrence may be mediated in part via the pxr. since pxr activation promotes hepatocyte growth and is also anti-fibrogenic, the pxr may be an excellent drug target for the treatment of chronic inflammatory liver disease.",Medication
is effector function of ctls increased by irradiated colorectal tumor cells that modulate ox-40l and 4-1bbl and is reversed following dual blockade?,"sub-lethal doses of ionizing radiation (ir) can alter the phenotype of target tissue by modulating genes that influence effector t cell activity. previous studies indicate that cancer cells respond to radiation by up-regulating surface expression of death receptors, cell adhesion molecules and tumor-associated antigens (taa). however, there is limited information available regarding how t cells themselves are altered following these interactions with irradiated tumor cells. here, several human colorectal tumor cell lines were exposed to radiation (0-10 gy) in vitro and changes in the expression of molecules costimulatory to effector t cells (4-1bbl, ox-40l, cd70, icosl) were examined by flow cytometry. t cell effector function was assessed to determine if changes in these proteins were directly related to the changes in t cell function. we found ox-40l and 4-1bbl to be the most consistently upregulated proteins on the surface of colorectal tumor cells post-ir while icosl and cd70 remained largely unaltered. expression of these gene products correlated with enhanced killing of irradiated human colorectal tumor cells by taa-specific t-cells. importantly, blocking of both ox-40l and 4-1bbl reversed radiation-enhanced t-cell killing of human tumor targets as well as t-cell survival and activation.","overall, results of this study suggest that, beyond simply rendering tumor cells more sensitive to immune attack, radiation can be used to specifically modulate expression of genes that directly stimulate effector t cell activity.",Medication
does congenital nos2 deficiency protect mice from lps-induced hyporesponsiveness to inhaled nitric oxide?,"in animal models, endotoxin (lipopolysaccharide) challenge impairs the pulmonary vasodilator response to inhaled nitric oxide (no). this impairment is prevented by treatment with inhibitors of no synthase 2 (nos2), including glucocorticoids and l-arginine analogs. however, because these inhibitors are not specific for nos2, the role of this enzyme in the impairment of no responsiveness by lipopolysaccharide remains incompletely defined. to investigate the role of nos2 in the development of lipopolysaccharide-induced impairment of no responsiveness, the authors measured the vasodilator response to inhalation of 0.4, 4, and 40 ppm no in isolated, perfused, and ventilated lungs obtained from lipopolysaccharide-pretreated (50 mg/kg intraperitoneally 16 h before lung perfusion) and untreated wild-type and nos2-deficient mice. the authors also evaluated the effects of breathing no for 16 h on pulmonary vascular responsiveness during subsequent ventilation with no. in wild-type mice, lipopolysaccharide challenge impaired the pulmonary vasodilator response to 0.4 and 4 ppm no (reduced 79 and 45, respectively, p 0.001), but not to 40 ppm. in contrast, lipopolysaccharide administration did not impair the vasodilator response to inhaled no in nos2-deficient mice. breathing 20 ppm no for 16 h decreased the vasodilator response to subsequent ventilation with no in lipopolysaccharide-pretreated nos2-deficient mice, but not in lipopolysaccharide-pretreated wild-type, untreated nos2-deficient or untreated wild-type mice.","in response to endotoxin challenge, no, either endogenously produced by nos2 in wild-type mice or added to the air inhaled by nos2-deficient mice, is necessary to impair vascular responsiveness to inhaled no. prolonged no breathing, without endotoxin, does not impair vasodilation in response to subsequent no inhalation. these results suggest that no, plus other lipopolysaccharide-induced products, are necessary to impair responsiveness to inhaled no in a murine sepsis model.",Medication
is stool microbiota composition associated with the prospective risk of plasmodium falciparum infection?,"in humans it is unknown if the composition of the gut microbiota alters the risk of plasmodium falciparum infection or the risk of developing febrile malaria once p. falciparum infection is established. here we collected stool samples from a cohort composed of 195 malian children and adults just prior to an intense p. falciparum transmission season. we assayed these samples using massively parallel sequencing of the 16s ribosomal rna gene to identify the composition of the gut bacterial communities in these individuals. during the ensuing 6-month p. falciparum transmission season we examined the relationship between the stool microbiota composition of individuals in this cohort and their prospective risk of both p. falciparum infection and febrile malaria. consistent with prior studies, stool microbial diversity in the present cohort increased with age, although the overall microbiota profile was distinct from cohorts in other regions of africa, asia and north america. age-adjusted cox regression analysis revealed a significant association between microbiota composition and the prospective risk of p. falciparum infection; however, no relationship was observed between microbiota composition and the risk of developing febrile malaria once p. falciparum infection was established.","these findings underscore the diversity of gut microbiota across geographic regions, and suggest that strategic modulation of gut microbiota composition could decrease the risk of p. falciparum infection in malaria-endemic areas, potentially as an adjunct to partially effective malaria vaccines.",General
is vasoactive intestinal polypeptide gene expression characteristically higher in opossum gastrointestinal sphincters?,"vasoactive intestinal polypeptide (vip) has been suggested to be an inhibitory neurotransmitter in the sphincteric and nonsphincteric smooth muscles of the gut. however, the relative gene expression of vip in these functionally diverse regions is not known. the gastrointestinal smooth muscle sphincters of opossums were excised from the adjoining nonsphincteric smooth muscles. rnas were isolated and subjected to blot hybridizations with vip complementary dna probe. relative expression of vip gene was quantitated using the densitometric scanning of the vip messenger rna (mrna) transcripts. the cellular specificity of vip gene expression was investigated in cultures of neuroblastoma cells and myenteric plexuses and compared with those of the smooth muscle cells. the data showed higher levels of vip mrna in the sphincteric than the adjoining nonsphincteric tissues. vip mrna were found in significantly higher amounts in the myenteric neurons and neuroblastoma cells than in the smooth muscle cells.",vip gene expression was significantly higher in the sphincteric smooth muscle regions than in the nonsphincteric regions of the gut. the studies provide further evidence for the role of vip in neurotransmission of the gut.,Medication
is neonatal interleukin-12 capacity associated with variations in allergen-specific immune responses in the neonatal and postnatal periods?,"a reduced capacity of antigen presenting cells (apc) to provide pro-t helper 1 (th1) signals, such as il-12, to t cells during early life may be implicated in the development of t helper 2 (th2)-mediated allergic disease. in this study we examined the relationships between the capacity for il-12 responses in the neonatal period and atopic risk (family allergy), in vitro t cell responses to allergens, and the subsequent development of allergic disease at 6 years. the capacity of circulating neonatal (and maternal) apc to produce il-12 p70 in response to lps (and ifn-gamma) stimulation was assessed in a group of 60 children with previously well-characterized immune responses to allergens and atopic outcomes. the il-12 responses were compared with allergen-induced lymphoproliferation (to house dust mite (hdm) ovalbumin (ova), cat and beta-lactoglobulin (blg)) and il-13 and ifn-gamma cytokine responses (to ova, hdm and phytohaemaglutinin (pha)) in the neonatal and postnatal periods. il-12 responses were also compared according to atopic risk and atopic outcomes (doctor-diagnosed asthma, eczema, food allergies and sensitization as evidenced by skin prick testing) at 6 years clinical follow-up. maternal peripheral blood mononuclear cells (pbmc) synthesized significantly greater amounts of il-12 than neonatal pbmc, though within maternal-infant pairs il-12 responses were significantly correlated (r 0.4, p 0.019). moreover, neonatal il-12 responses were positively correlated with neonatal allergen proliferation for hdm (r 0.6, p 0.0001), ova (r 0.55, p 0.0001), cat (r 0.5, p 0.003) and blg (r 0.55, p 0.001), but negatively correlated with neonatal il-13 responses to both allergens tested (hdm: r - 0.4, p 0.03 and ova: r - 0.5, p 0.001). both neonatal and maternal il-12 responses were positively correlated with postnatal ifn-gamma responses to hdm at 12, 18 and 24 months of age (responses after age of 2 years were not assessed). there was no relationship between atopic risk and il-12 capacity in the neonatal period, but there was a (non-significant) trend for neonatal il-12 responses to be lower in the high-risk children who developed clinical allergy at 6 years (compared with the low risk group) although the number in this analysis was small.","reduced apc il-12 production in the perinatal period was associated with reduced t cell activation (lymphoproliferation), stronger neonatal th2 responses, and weaker th1 responses to allergen in the postnatal period. this supports the notion that variations in apc function in early life may contribute to altered allergen-specific cytokine responses associated with later allergy.",Diagnosis
does glucosamine exposure reduce proteoglycan synthesis in primary human endothelial cells in vitro?,"glucosamine (glcn) supplements are promoted for medical reasons, for example, for patients with arthritis and other joint-related diseases. oral intake of glcn is followed by uptake in the intestine, transport in the circulation and thereafter delivery to chondrocytes. here, it is postulated to have an effect on synthesis and turnover of extracellular matrix constituents expressed by these cells. following uptake in the intestine, serum levels are transiently increased, and the endothelium is exposed to increased levels of glcn. we investigated the possible effects of glcn on synthesis of proteoglycans (pgs), an important matrix component, in primary human endothelial cells. primary human endothelial cells were cultured in vitro in medium with 5 mm glucose and 0-10 mm glcn. pgs were recovered and analysed by western blotting, or by sds-page, gel chromatography or ion-exchange chromatography of (35)s-pgs after (35)s-sulphate labelling of the cells. the synthesis and secretion of (35)s-pgs from cultured endothelial cells were reduced in a dose- and time-dependent manner after exposure to glcn. pgs are substituted with sulphated glycosaminoglycan (gag) chains, vital for pg function. the reduction in (35)s-pgs was not related to an effect on gag chain length, number or sulphation, but rather to the total expression of pgs.","exposure of endothelial cells to glcn leads to a general decrease in (35)s-pg synthesis. these results suggest that exposure to high levels of glcn can lead to decreased matrix synthesis, contrary to what has been claimed by supporters of such supplements.",Medication
is rhinitis associated with a greater risk of intermittent claudication in adults?,"chronic inflammatory airway disorders have been reported to be associated with vascular diseases of the heart and central nervous system, but their association with peripheral arterial disease (pad), a high-prevalence vascular illness, has not been investigated. to evaluate the association of asthma and rhinitis with intermittent claudication, which is a typical symptom of pad. the data were collected in the gene-environment interaction in respiratory disease survey, a population-based, multicase-control study. participants underwent a standardized interview, skin prick tests and pulmonary function tests. the associations between respiratory diseases and intermittent claudication (i.e. pain in the leg during walking that disappears within 10 min when standing still) were estimated through relative risk ratios (rrr) by multinomial logistic regression models. 1174 subjects (aged 20-64 years, of which 52 were females) underwent clinical examinations and were classified into four groups: asthma only (n 81), asthma-rhinitis overlap (n 292), rhinitis only (n 299) and controls (n 345). the prevalence of intermittent claudication in these groups was, respectively, 2.5, 3.4, 6.4 and 2.3. after adjusting for smoking habits and a wide range of established and potential vascular risk factors, rhinitis without asthma was associated with intermittent claudication (rrr:4.63, 95 ci:1.72-12.5), whereas no significant association was found with asthma alone (rrr:1.45, 95 ci:0.27-7.76) or asthma-rhinitis overlap (rrr:2.89, 95 ci:0.91-9.18). atopy did not modify the observed association between intermittent claudication and rhinitis.","our findings suggest that rhinitis is associated with pad, a predictor of future cerebrovascular and cardiovascular events, independently of the presence of atopy.",Symptoms
does liver dysfunction markedly decrease the inhibition of cytochrome p450 1a2-mediated theophylline metabolism by fluvoxamine?,"in vivo inhibition of cytochrome p450 (cyp) 1a2 by fluvoxamine causes a reduction in the clearance of the high-extraction drug lidocaine, which decreases in proportion to the degree of liver dysfunction. the objectives of this study were (1) to evaluate the effect of liver cirrhosis on the inhibition by fluvoxamine of the metabolic disposition of theophylline, a cyp1a2 substrate with a low-extraction ratio, to assess whether decreased sensitivity to cyp1a2 inhibition in liver disease is a general characteristic of cyp1a2 substrates, regardless of their pharmacokinetic properties, and (2) to investigate the mechanism(s) underlying the effect of liver dysfunction on cyp1a2 inhibition. the study was carried out in 10 healthy volunteers and 20 patients with cirrhosis, 10 with mild liver dysfunction (child class a) and 10 with severe liver dysfunction (child class c), according to a randomized, double-blind, 2-phase, crossover design. in one phase all participants received placebo for 7 days; in the other phase they received one 50-mg fluvoxamine dose for 2 days and two 50-mg fluvoxamine doses, 12 hours apart, in the next 5 days. on day 6, 4 mg/kg of theophylline was administered orally 1 hour after the morning fluvoxamine dose. concentrations of theophylline and its metabolites, 3-methylxanthine, 1-methyluric acid, and 1,3-dimethyluric acid, were then measured in plasma and urine up to 48 hours. fluvoxamine-induced inhibition of theophylline clearance decreased from 62 in healthy subjects to 52 and 12 in patients with mild cirrhosis and those with severe cirrhosis, respectively. cyp1a2-mediated formations of 3-methylxanthine and 1-methyluric acid were almost totally inhibited in control subjects, whereas they were only reduced by one third in patients with child class c cirrhosis. inhibition of 1,3-dimethyluric acid formation, which is catalyzed by cyp1a2 and cyp2e1, progressively decreased from 58 in healthy subjects to 43 and 7 in patients with mild cirrhosis and those with severe cirrhosis, respectively.","the effect of liver dysfunction on the inhibition of cyp1a2-mediated drug elimination is a general phenomenon, independent of the pharmacokinetic characteristics of the cyp1a2 substrate. therefore, for any drug metabolized by cyp1a2, the clinical consequences of enzyme inhibition are expected to become less and less important as liver function worsens. two mechanisms, as follows in order of importance, are responsible for the effect of liver dysfunction: (1) decreased sensitivity to fluvoxamine of cyp1a2-mediated biotransformations in the cirrhotic liver, probably resulting from reduced uptake of the inhibitory drug, and (2) reduced hepatic expression of cyp1a2, which makes its contribution to overall drug elimination less important.",Symptoms
does notch2 signaling promote biliary epithelial cell fate specification and tubulogenesis during bile duct development in mice?,"intrahepatic bile duct (ihbd) development begins with the differentiation of hepatoblasts into a single continuous biliary epithelial cell (bec) layer, called the ductal plate. during ductal plate remodeling, tubular structures arise at distinct sites of the ductal plate, forming bile ducts that dilate into the biliary tree. alagille syndrome patients, who suffer from bile duct paucity, carry jagged1 and notch2 mutations, indicating that notch2 signaling is important for ihbd development. to clarify the role of notch2 in bec differentiation, tubulogenesis, and bec survival, we developed a mouse model for conditional expression of activated notch2 in the liver. we show that expression of the intracellular domain of notch2 (notch2icd) differentiates hepatoblasts into becs, which form additional bile ducts in periportal regions and ectopic ducts in lobular regions. additional ducts in periportal regions are maintained into adulthood and connect to the biliary tight junction network, resulting in an increased number of bile ducts per portal tract. remarkably, notch2icd-expressing ductal plate remnants were not eliminated during postnatal development, implicating notch2 signaling in bec survival. ectopic ducts in lobular regions did not persist into adulthood, indicating that local signals in the portal environment are important for maintaining bile ducts.","notch2 signaling regulates bec differentiation, the induction of tubulogenesis during ihbd development, and bec survival.",General
does therapy with proton-pump inhibitors for gastroesophageal reflux disease reduce the risk for severe exacerbations in copd?,"gastroesophageal reflux disease (gerd) symptoms are associated with a higher risk of chronic obstructive pulmonary disease (copd) exacerbation. we hypothesize that treatment with proton pump inhibitors reduces the risk of exacerbation in patients with stable copd. a total of 638 patients with stable copd for 6 weeks, 10 pack-years of smoking and global initiative for chronic obstructive lung disease ii-iv seeking care in tertiary hospitals in eight european countries in the predicting outcome using systemic markers in severe exacerbations-copd cohort was prospectively evaluated by us. comorbidities including associated medical treatment were assessed at baseline, at exacerbation and at biannual visits. median observation time was 24 months. the primary study outcomes were exacerbation and/or death. a total of 85 (13.3) of copd patients were on anti-gerd therapy. these patients had higher annual and higher severe exacerbation rates (p 0.009 and p 0.002), decreased quality of life (sf-36: activity score p 0.004, st. george's respiratory questionnaire: physical functioning p 0.013 and social functioning p 0.007), higher body mass airflow obstruction, dyspnea and exercise capacity index (p 0.033) and modified medical research council scores (p 0.002), shorter 6-min walking distance (p 0.0004) and a higher adjusted charlson score (p 0.0001). anti-gerd therapy was associated with a shorter time to severe exacerbation (hr 2.05 95 ci 1.37-3.08). using three multivariable cox-regression models, this association was independent of the following: (i) adjusted charlson score and fev1 predicted (hr 1.91 95 ci 1.26-2.90); (ii) adjusted charlson score, body mass, airflow obstruction, dyspnea and exercise capacity index and modified medical research council (hr 1.62 95 ci 1.04-2.54); and (iii) adjusted charlson score, fev1 predicted and nine classes of medication for comorbidities (hr 1.63 95 ci 1.04-2.53).",these findings suggest that patients with stable copd receiving acid-suppressive therapy with proton pump inhibitors remain at high risk of frequent and severe exacerbations.,Medication
do genome variations account for different response to three mineral elements between medicago truncatula ecotypes jemalong a17 and r108?,"resequencing can be used to identify genome variations underpinning many morphological and physiological phenotypes. legume model plant medicago truncatula ecotypes jemalong a17 (j. a17) and r108 differ in their responses to mineral toxicity of aluminum and sodium, and mineral deficiency of iron in growth medium. the difference may result from their genome variations, but no experimental evidence supports this hypothesis. a total of 12,750 structure variations, 135,045 short insertions/deletions and 764,154 single nucleotide polymorphisms were identified by resequencing the genome of r108. the suppressed expression of mtaact that encodes a putative aluminum-induced citrate efflux transporter by deletion of partial sequence of the second intron may account for the less aluminum-induced citrate exudation and greater accumulation of aluminum in roots of r108 than in roots of j. a17, thus rendering r108 more sensitive to aluminum toxicity. the higher expression-level of mtzpt2-1 encoding a tfiiia-related transcription factor in j. a17 than r108 under conditions of salt stress can be explained by the greater number of stress-responsive elements in its promoter sequence, thus conferring j. a17 more tolerant to salt stress than r108 plants by activating the expression of downstream stress-responsive genes. ysls (yellow stripe-likes) are involved in long-distance transport of iron in plants. we found that an ysl gene was deleted in the genome of r108 plants, thus rendering r108 less tolerance to iron deficiency than j. a17 plants.",the deletion or change in several genes may account for the different responses of m. truncatula ecotypes j. a17 and r108 to mineral toxicity of aluminum and sodium as well as iron deficiency. uncovering genome variations by resequencing is an effective method to identify different traits between species/ecotypes that are genetically related. these findings demonstrate that analyses of genome variations by resequencing can shed important light on differences in responses of m. truncatula ecotypes to abiotic stress in general and mineral stress in particular.,Medication
is inspiratory muscle weakness associated with autonomic cardiovascular dysfunction in patients with type 2 diabetes mellitus?,"diabetic autonomic neuropathy is a complication of diabetes mellitus (dm) that can cause cardiovascular and respiratory abnormalities. the association between respiratory muscle weakness and autonomic cardiovascular neuropathy has not yet been studied. the aims of the present study were to assess respiratory muscle strength, pulmonary function, and heart rate (hr) variability in diabetic patients with and without diabetic autonomic neuropathy. twenty-four patients with type 2 dm were divided into two groups: those without diabetic autonomic neuropathy (c group, n 12); and those with diabetic autonomic neuropathy (dan group, n 12). we evaluated pulmonary function, maximum static inspiratory pressure (pimax), maximum static expiratory pressure (pemax), and hr variability. the results of the pulmonary function tests were similar in both the groups. pimax was lower in the dan group (80 24 vs. 102 24 cmh(2)o, p 0.03), but pemax was similar in both the groups. rr intervals (878 122 vs. 743 88 ms; p 0.01), standard deviation of rr intervals (28 11 vs. 14 4 ms; p 0.01) and squared root of the sum of successive differences of squared rr intervals (15 6 vs. 8 5 ms; p 0.01) were higher in the c group. in the dan group, resting hr was higher (82 10 vs. 69 9 bpm; p 0.01) than in the c group. there was a positive correlation between pimax and rr intervals (r 0.452, p 0.02) and a negative correlation between pimax and resting hr (r -0.482, p 0.01), and pimax and dm duration (r -0.463, p 0.02).",patients with type 2 dm and autonomic neuropathy showed reduced respiratory muscle strength and less hr variability. respiratory muscle weakness may be associated with autonomic dysfunction in these patients.,Symptoms
does lonicerae japonicae flos attenuate diabetic retinopathy by inhibiting retinal angiogenesis?,"lonicerae japonicae flos (jin-yin-hua) is a well-known traditional chinese medicine used for clearing away heat and toxic material. this study aims to observe the attenuation of aqueous extract of lonicerae japonicae flos (fl) against streptozotocin (stz)-induced diabetic retinopathy (dr) and its engaged mechanism. stz-induced proliferative dr (pdr) for 5 month in c57bl/6 mice was used in this study. retinal vessels were observed by immunofluorescence staining with cluster of differentiation 31 (cd31) and histopathological evaluation. enzyme-linked immunosorbent assay (elisa) was used to detect serum vascular endothelial growth factor (vegf) content. cell proliferation was detected by 3-(4, 5-dimethylthiazol-2-yl) 2, 5-diphenyltetrazolium bromide (mtt) assay in choroid-retinal endothelial rf/6a cells. vegf-induced tube formation in rf/6a cells was observed. the contents of chlorogenic acid (cga), caffeic acid (ca), and luteolin in fl were detected by high-performance liquid chromatography (hplc). histopathological evaluation demonstrated that retinal vessels were increased in stz-induced pdr mice, whereas fl decreased such increase. the results of cd31 staining also showed that fl decreased the increased number of retinal vessels in stz-induced pdr mice. in addition, fl reduced the increased serum vegf content in stz-induced pdr mice. fl reduced vegf-induced rf/6a cell proliferation in the concentration-dependent manner, but had no obvious effect on rf/6a cell viability without vegf stimulation. vegf-induced tube formation in rf/6a cells was inhibited by different concentrations of fl. cga, ca and luteolin all inhibited vegf-induced tube formation in rf/6a cells, and the lowest effective concentration of cga and ca was both 0.625m, but of luteolin was 5m. furthermore, the results of hplc demonstrated that the amount of cga was the highest in fl.",fl ameliorates stz-induced pdr by inhibiting retinal angiogenesis. phenolic acid cga is the main compound contributing to the inhibition of fl on retinal angiogenesis.,General
does ten-year review reveal changing trends and severity of allergic reactions to nuts and other foods?,"over the past few decades, the incidence of food allergies has risen and sweden has increased its import of peanuts and exotic nuts, such as cashew nuts, which may cause severe allergic reactions. this study aimed to retrospectively investigate paediatric emergency visits due to food reactions over a 10-year period, focusing on reactions to peanuts and tree nuts. emergency visits to uppsala university children's hospital, sweden, between september 2001 and december 2010, were reviewed, and cases containing diagnostic codes for anaphylaxis, allergic reactions or allergy and hypersensitivity not caused by drugs or biological substances were retrieved. we analysed 703 emergency visits made by 578 individuals with food allergies. peanuts and tree nuts accounted for 50 of the food allergies and were more frequently associated with adrenaline treatment and hospitalisation than other foods. cashew nut reactions increased over the study period, and together with peanuts, they were responsible for more anaphylactic reactions than hazelnuts.",peanut and tree nut reactions were more likely to result in adrenaline treatment and hospitalisation than other food reactions. peanut and cashew nut reactions were more likely to cause anaphylaxis than hazelnuts. cashew nut reactions increased during the study period.,Medication
does clinical and treatment correlate of access to section 8 certificates for homeless mentally ill persons?,"the study assessed how clients' housing preference and other variables were related to the acquisition of section 8 certificates, facilitating independent living, for homeless persons with severe mental illness who were being served by an experimental assertive community treatment team. for 77 clients, demographic and clinical differences between receivers and nonreceivers of certificates were examined, and correlates of time from referral to the team to completion of the section 8 application were analyzed. reasons clients did not receive certificates and housing outcomes were summarized in relation to client preference. the 34 clients who received certificates (44 percent) had significantly less psychopathology after three months than did nonreceivers and tended to have affective disorders rather than schizophrenia. of the 43 nonreceivers, the two largest groups were 19 clients who did not want certificates and ten clients who wanted certificates but whom staff considered unable to live safely in an unsupervised apartment. the mean /- sd length of time for application for a certificate was 5.7 /- 5.8 months. longer time to apply was significantly associated with having schizophrenia, having the team as a representative payee, and showing increased psychotic symptoms at referral and at three months.","the study suggests that it is possible to honor the housing preferences of the majority of homeless persons with severe mental illness if adequate resources are provided. however, staff may view persons who have schizophrenia and more symptoms as needing more supervision than those clients prefer. homeless mentally ill persons may also take longer than more symptomatic persons to pursue independent living through a section 8 certificate.",Treatment
"are hippocampal abnormalities of glutamate/glutamine , n-acetylaspartate and choline in patients with depression related to past illness burden?","smaller hippocampal volumes in major depressive disorder (mdd) have been linked with earlier onset, previous recurrences and treatment refractoriness. the aim of our study was to investigate metabolite abnormalities in the hippocampus associated with past depressive illness burden. glutamate/glutamine (glx), n-acetylaspartate (naa) and choline (cho), potential markers of glial/neuronal integrity and membrane turnover, respectively, were measured in adults with depression and healthy controls using a 3 t magnetic resonance spectroscopy scanner. voxels were placed in the head of the right and left hippocampus. we controlled for systematic differences resulting from volume-of-interest (voi) tissue composition and total hippocampal volume. our final sample comprised a total of 16 healthy controls and 52 adult patients with depression in different stages of the illness (20 treatment-resistant/chronic, 18 remitted-recurrent and 14 first-episode), comparable for age and sex distribution. patients with treatment-resistant/chronic and remitted-recurrent depression had significantly lower levels of glx and naa than controls, especially in the right hippocampal region (p 0.025). diminished levels of glx were correlated with longer illness duration (left voi r -0.34, p 0.01). by contrast, cho levels were significantly higher in patients with treatment-resistant/chronic depression than those with first-episode depression or controls in the right and left hippocampus (up to 19 higher; all p 0.025) and were consistently related to longer illness duration (right voi r 0.30, p 0.028; left voi r 0.38, p 0.004) and more previous episodes (right voi r 0.46, p 0.001; left voi r 0.44, p 0.001).",the cross-sectional design and the inclusion of treated patients are the main limitations of the study.,Treatment
do asymptomatic high flow subclavian steal in a patient with hemodialysis access?,"subclavian steal phenomenon due to proximal subclavian artery stenosis or occlusion is not un-common but often remains asymptomatic. we describe the case of a 66-year-old man with end-stage renal disease hemodialysed through a brachio-brachial loop graft of the left forearm. echo-doppler precerebral examination showed a high reversed flow of 570 ml/min in the ipsilateral vertebral artery. after successful endovascular recanalization of the subclavian artery, access blood flow increased and vertebral flow decreased to 30 ml/min. complete neurological examination was normal both before and after endovascular treatment.",this case demonstrates how high a subclavian steal can be without causing symptoms and how well precerbral and cerebral circulation can adapt to hemodynamic changes.,Treatment
does the corticosterone synthesis inhibitor metyrapone prevent hypoxia/ischemia-induced loss of synaptic function in the rat hippocampus?,"ischemia is accompanied by abundant corticosterone secretion, which could potentially exacerbate brain damage via activation of glucocorticoid receptors. we addressed whether manipulating steroid levels during ischemia affects hippocampal synaptic function along with neuronal structure. moreover, we established whether pretreatment with the glucocorticoid receptor antagonist ru38486 is as effective in preventing deleterious effects after ischemia as is the steroid synthesis inhibitor metyrapone. rats underwent 20 minutes of unilateral hypoxia/ischemia (hi). convulsions were monitored after hi, and 24 hours later, field potentials were recorded in vitro in the hippocampal ca1 area in response to stimulation of the schaffer collateral/commissural fibers. morphological alterations were determined in brain slices from the same animals. data were correlated with steroid treatment before hi. metyrapone suppressed plasma corticosteroid levels during hi, whereas corticosterone treatment significantly elevated plasma steroid levels. these treatments affected the incidence of visible seizures after hi: corticosterone treatment resulted in the highest incidence, whereas metyrapone attenuated the occurrence of seizures. moreover, the hi-induced impairment in synaptic transmission in the ca1 area in vitro was exacerbated by concomitant corticosteroid treatment and alleviated by pretreatment with metyrapone. in parallel, degenerative changes in the hippocampus after hi were most pronounced after corticosterone treatment, whereas metyrapone reduced these alterations. ru38486 was effective only in reducing the incidence of seizures shortly after ischemia.",we tentatively conclude that synaptic function along with cellular integrity is preserved after hi by preventing the ischemia-evoked rise in corticosteroid levels rather than blocking the glucocorticoid receptor.,Medication
does heart failure after myocardial infarction be associated with increased risk of cancer?,"heart failure (hf) is associated with excess morbidity and mortality for which noncardiac causes are increasingly recognized. the authors previously described an increased risk of cancer among hf patients compared with community controls. this study examined whether hf was associated with an increased risk of subsequent cancer among a homogenous population of first myocardial infarction (mi) survivors. a prospective cohort study was conducted among olmsted county, minnesota, residents with incident mi from 2002 to 2010. patients with prior cancer or hf diagnoses were excluded. a total of 1,081 participants (mean age 64 15 years; 60 male) were followed for 5,327 person-years (mean 4.9 3.0 years). a total of 228 patients developed hf, and 98 patients developed cancer (excluding nonmelanoma skin cancer). incidence density rates for cancer diagnosis (per 1,000 person-years) were 33.7 for patients with hf and 15.6 for patients without hf (p 0.002). the hazard ratio (hr) for cancer associated with hf was 2.16 (95 confidence interval ci: 1.39 to 3.35); adjusted for age, sex, and charlson comorbidity index; hr: 1.71 (95 ci: 1.07 to 2.73). the hrs for mortality associated with cancer were 4.90 (95 ci: 3.10 to 7.74) for hf-free and 3.91 (95 ci: 1.88 to 8.12) for hf patients (p for interaction 0.76).","patients who develop hf after mi have an increased risk of cancer. this finding extends our previous report of an elevated cancer risk after hf compared with controls, and calls for a better understanding of shared risk factors and underlying mechanisms.",Diagnosis
is utilization of intravenous thrombolysis increasing in the united states?,"evaluating recombinant tissue plasminogen activator utilization rates is important, as many studies have demonstrated that administration of recombinant tissue plasminogen activator to qualified patients significantly improves prognosis. we investigated recent trends in the utilization and outcomes of administration of intravenous recombinant tissue plasminogen activator in the united states using the national inpatient sample between 2001 and 2008. we identified patients with a primary diagnosis of acute ischemic stroke who underwent treatment with intravenous recombinant tissue plasminogen activator and studied utilization rates and clinical outcomes: discharge to long-term facility (morbidity), in-hospital death (mortality), and intracranial hemorrhage. information on demographics, hospital characteristics, and comorbidities was collected. a multivariate logistic regression analysis was performed to determine independent predictors of morbidity, mortality, and intracranial hemorrhage. intravenous recombinant tissue plasminogen activator utilization increased from 13 in 2001 to 35 in 2008. on multivariate analysis, variables associated with increased morbidity after intravenous recombinant tissue plasminogen activator administration included advanced age (p 0001), female gender (p 0001), and comorbidities of atrial fibrillation (p 0001) and hypertension (p 0001). increased mortality was associated with increased age (p 0001) and comorbidities of atrial fibrillation, congestive heart failure, coronary artery disease, and diabetes (p 0001 for all comorbidities).",intravenous recombinant tissue plasminogen activator utilization rates increased between 2001 and 2008. advanced age and atrial fibrillation were significantly associated with increased morbidity and mortality among patients treated with intravenous recombinant tissue plasminogen activator.,Medication
are plasma asymmetric dimethylarginine levels increased in neonates with bronchopulmonary dysplasia-associated pulmonary hypertension?,"to test the hypothesis that levels of the endogenous inhibitor of nitric oxide production, asymmetric dimethylarginine (adma), would be greater in preterm infants with bronchopulmonary dysplasia (bpd)-associated pulmonary hypertension (ph) than in infants with bpd alone. a case-control study of 23 patients with both bpd and ph (cases) and 95 patients with bpd but no evidence of ph (controls). levels of adma were compared between cases and controls by t test. patients with both bpd and ph had greater plasma levels of adma than patients with bpd alone (p .04). in samples drawn before 28 days of life, greater levels of adma were again found in cases compared with controls (p .02). the plasma arginine-to-adma ratio was lower in cases than in controls (p .03), suggesting a greater likelihood of inhibition of nitric oxide production in patients with both bpd and ph than in patients with bpd alone.","in this neonatal bpd cohort, adma levels are increased in patients with bpd who develop ph. we speculate that adma may be both a biomarker and a potential therapeutic target for preterm infants with bpd-associated ph.",Medication
is melatonin receptor 1b ( mtnr1b ) gene polymorphism associated with the occurrence of adolescent idiopathic scoliosis?,"a genetic association study to comprehensively investigate variations of melatonin receptor 1b gene polymorphism by a set of tagging single nucleotide polymorphisms (tagsnps) derived from the international hapmap project. to determine whether melatonin receptor 1b (mtnr1b) gene polymorphisms are associated with the predisposition and/or disease severity of adolescent idiopathic scoliosis (ais). linkage studies suggested a genetic predisposition for ais. in addition, evidence showed that ais might be related to melatonin deficiency and dysfunction of melatonin signaling pathway. locating in one of the chromosomal regions linked to ais, mtnr1b gene is a potential candidate gene for ais. this study was carried out in 2-stage case-control analysis: 1) initial screening (472 cases and 304 controls) and 2) separate replication test (342 cases and 347 controls) to confirm results in the screening. in the first screening stage, 5 tagsnps were selected to cover most of the genetic variation in the mtnr1b gene. in the second stage, snps showing association in the screening stage were studied in a separate replication sample set to confirm the association. genotyping was performed by pcr-rflp. the first stage showed a putative association between rs4753426 and ais, which was confirmed in the replication sample set. by meta-analysis, the frequency of c allele of this snp locating in the promoter was significantly higher in the cases than controls (p 0.006 aftermeta-analysis). subjects with the cc genotype had an odds ratio of 1.29 for ais. another snp rs741837 in promoter region, being moderate linkage disequilibrium with rs4753426, was also marginally associated with ais.","polymorphisms of the promoter of mtnr1b gene were associated with ais, but not with the curve severity in ais patients. this suggested that mtnr1b was an ais predisposition gene.",Medication
do plasmacytoid dendritic cells play a key role in promoting atherosclerosis in apolipoprotein e-deficient mice?,"clinical studies have identified that reduced numbers of circulating plasmacytoid dendritic cells (pdcs) act as a predictor of cardiovascular events in coronary artery disease and that pdcs are detectable in the shoulder region of human atherosclerotic plaques, where rupture is most likely to occur. results from animal models are controversial, with pdcs seen to inhibit or promote lesion development depending on the experimental settings. here, we investigated the role of pdcs in atherosclerosis in apolipoprotein e-deficient mice. we demonstrated that the aorta and spleen of both apolipoprotein e-deficient and c57bl/6 mice displayed similar numbers of pdcs, with similar activation status. in contrast, assessment of antigen uptake/presentation using the e/y-ae system revealed that aortic pdcs in apolipoprotein e-deficient(-) mice were capable of presenting in vivo systemically administered antigen. continuous treatment of apolipoprotein e-deficient mice with anti-mouse plasmacytoid dendritic cell antigen 1 (mpdca-1) antibody caused specific depletion of pdcs in the aorta and spleen and significantly reduced atherosclerosis formation in the aortic sinus (by 46; p0.001). depletion of pdcs also reduced macrophages (by 34; p0.05) and increased collagen content (by 41; p0.05) in aortic plaques, implying a more stable plaque phenotype. additionally, pdc depletion reduced splenic t-cell activation and inhibited interleukin-12, chemokine (c-x-c motif) ligand 1, monokine induced by interferon-, interferon -induced protein 10, and vascular endothelium growth factor serum levels.",these results identify a critical role for pdcs in atherosclerosis and suggest a potential role for pdc targeting in the control of the pathology.,Medication
do contrast media inhibit exogenous surfactant therapy in rats with acute respiratory distress syndrome?,"to test the effects of various contrast media on the pulmonary surfactant system. in a rat model of acute respiratory distress syndrome (ards) induced by lung lavage, the effects of surfactant suspended in saline were compared with surfactant suspended in the contrast media visipaque, gastrografin, omnipaque, telebrix m, telebrix and hexabrix, to establish their influence on oxygenation and lung mechanics. after the induction of ards, surfactant instillation improved oxygenation, total lung capacity (tlc(35)), volume at 5 cm h(2)o end-expiration (v(5)) and gruenwald index. the effects of visipaque and gastrografin were comparable with those of surfactant alone from 90 min onwards and at 120 min, respectively. surfactant suspended in the other contrast media resulted in significantly lower values in the above-mentioned parameters. surface tension was lowest in surfactant suspended in saline alone. surfactant suspended in visipaque and gastrografin had lower surface tension compared with surfactant suspended in the other contrast media.","the ionic and non-ionic contrast media used in this study, cause an impairment of the physico-chemical behaviour of exogenous surfactant. therefore, these contrast media cannot be regarded as safe in case of accidental exposure.",Treatment
is hypermethylation of the cpg islands in the promoter region flanking gstp1 gene a potential plasma dna biomarker for detecting prostate carcinoma?,"to investigate the possibility of identifying dna hypermethylation in the circulation of prostate cancer patients. plasma dna samples were extracted from 36 prostate cancer patients and 27 benign prostate hyperplasia (bph) cases. after extensive methylation-sensitive restriction enzyme digestion, the dna samples were subjected to the real-time quantitative pcr amplification. dissociation curve analysis was applied to determine if hypermethylation occurred in the promoter region flanking the gstp1 gene, a well-documented epigenetic event among prostate cancer cells, in these plasma dna samples. 11 of 36 prostate cancer patients showed positive peak pattern, indicating methylation changes occurred. concordant data were obtained from the corresponding paraffin-embedded tissue samples available from the tumor bank. twenty-five of the 27 bph cases showed negative results, suggesting no methylation changes happened in the cpg islands in these cases.","we have successfully identified prostate cancer genome hypermethylation in the peripheral circulation in prostate cancer patients with this protocol. this method can effectively distinguish bph from prostate neoplasm. although a larger number of samples are necessary to validate the capability of the protocol in practice, using plasma dna sample is an ideal non-invasive approach for prostate neoplasm detection.",Diagnosis
do amaryllidaceae alkaloids inhibit nuclear-to-cytoplasmic export of ribonucleoprotein ( rnp ) complex of highly pathogenic avian influenza virus h5n1?,"few drugs are currently licensed to treat influenza a infection, and new therapies are needed, especially for highly pathogenic strains. traditional medicinal plants, such as lycoris radiata, are a potential source of new antiviral agents. to test 15 amaryllidaceae alkaloids isolated from the bulbs of l. radiata in vitro for antiviral activities against influenza virus type a, a/chicken/guangdong/178/2004 (h5n1, 178). antiviral activities of the compounds were tested in time-of-addition assays, hemagglutination inhibition (hi) assays, neuraminidase (na) activity assays, and viral entry inhibition assays using h5n1-hiv pseudoviruses. effects of the compounds on localization and activity of the viral ribonucleoprotein (rnp) were determined by immunofluorescence and an rnp minigenome assay, respectively. among the alkaloids, lycorine (aa1), hippeastrine (aa2), hemanthamine (aa3) and 11-hydroxy vittatine (aa4) exhibited antiviral activities, with ec90 values of 052, 8207, 415, and 1345 m, respectively. these compounds did not affect the function of the outer membrane proteins or the viral entry process and viral rnp activity. as aa1 and aa3 exhibited stronger antiviral activities, they were further analyzed. intracellular nucleoprotein (np) localization showed that aa1 and aa3 inhibited the rnp complex in the nucleus at an early stage of a single-round and multi-round of replication.","four amaryllidaceae alkaloids were first determined that could exert anti-influenza activities after virus entry into cells. furthermore, aa1 and aa3 could inhibit nuclear-to-cytoplasmic export of the rnp complex of virus replication. thus, these compounds may be developed further as anti-influenza drug candidates.",Medication
does recombinant gene transfer of endothelial nitric oxide synthase augment coronary artery relaxations during hypoxia?,"coronary arteries respond to hypoxia with transient relaxations, which increases coronary blood flow, in part, by release of nitric oxide. we hypothesized that increased expression of nitric oxide synthase might further augment blood vessel relaxation during hypoxia. the present study examined the effect of adenovirus-mediated transfer of bovine endothelial nitric oxide synthase (enos) on hypoxia-induced transient relaxations in canine coronary arteries. paired segments of coronary arteries were exposed to vehicle (phosphate-buffered saline with albumin) or an adenovirus encoding either e coli beta-galactosidase (ad.cmvlacz, viral control; 10(10) pfu/ml) or enos (ad.cmvenos; 10(10) pfu/ml) for 2 hours at 37 degrees c. immunohistochemistry with a monoclonal antibody specific for enos documented both endothelial and adventitial expression in ad.cmvenos arteries, whereas vehicle and viral controls demonstrated only constitutive expression. levels of cgmp were increased 5-fold in ad.cmvenos arteries compared with controls. in arteries exposed to ad.cmvenos, maximum contraction to prostaglandin f(2alpha) was reduced compared with viral controls, and this effect was eliminated by pretreatment with a competitive inhibitor of enos (n(g)-monomethyl-l-arginine, 10(-3) mol/l). hypoxia-induced transient relaxation (95 n(2)-5 co(2)) in ad.cmvenos arteries (45.2/-8.8, n6) was augmented compared with vehicle (26.3/-6.0) or viral (27.2/-7.1) controls.",adenovirus-mediated gene transfer of nitric oxide synthase reduces receptor-dependent contractions and augments hypoxia-induced relaxations in canine coronary arteries; this method of augmentation of no production might be advantageous for reduction of coronary artery vasospasm.,Medication
does contractile reserve assessed by dobutamine test identify super-responders to cardiac resynchronization therapy?,"in this study, we sought to determine whether myocardial contractile reserve (cr) assessed by dobutamine stress echocardiography (dse) can identify patients who experience nearly complete normalization of left ventricular (lv) function after the implantation of a cardiac resynchronization therapy (crt) pacemaker. the study group consisted of 55 consecutive patients with non-ischemic dilated cardiomyopathy, lv ejection fraction (lvef) 50 and reduction in left ventricular end-systolic dimension to 40 mm 12 months following the crt implantation. a total of 7 patients (12.7) were identified as super-responders to crt. when compared to non-super-responders, these patients had significantly higher values of the dobutamine-induced change in wmsi (1.031 0.120 vs. 0.49 0.371, p 0.01), and ef (17.9 2.2 vs. 8.8 6.2, p 0.01). receiver operating characteristic analysis showed that dobutamine-induced changes in wmsi 0.7 and 14 for ef are the best discriminators for a super-response. patients with wmsi 0.7 and ef 14 are significantly less often hospitalized (p 0.01) for worsening of heart failure during 28.5 3.0 months of the follow-up.",contractile reserve assessed by dse can identify patients with dilated cardiomyopathy who are likely to experience near normalization of lv function following crt.,Treatment
is respiratory syncytial virus-positive bronchiolitis in hospitalized infants associated with thrombocytosis?,"secondary thrombocytosis is associated with a variety of clinical conditions, one of which is lower respiratory tract infection. however, reports on thrombocytosis induced by viral infections are scarce. to assess the rate of thrombocytosis (platelet count 500 x 10(9)/l) in hospitalized infants with bronchiolitis and to investigate its potential role as an early marker of respiratory syncytial virus infection. clinical data on 469 infants aged or 4 months who were hospitalized for bronchiolitis were collected prospectively and compared between rsv-positive and rsv-negative infants. the rate of thrombocytosis was significantly higher in rsv-positive than rsv-negative infants (41.3 vs. 29.2, p0.031). the odds ratio of an infant with bronchiolitis and thrombocytosis to have a positive rsv infection compared to an infant with bronchiolitis and a normal platelet count was 1.7 (p 0.023, 95 confidence interval 1.07-2.72). there was no significant difference in mean platelet count between the two groups.",rsv-positive bronchiolitis in hospitalized young infants is associated with thrombocytosis.,Diagnosis
does skin application of isoflurane attenuate the responses to a mechanical and an electrical stimulation?,"this prospective randomized crossover study was performed to test the potential of an analgesic effect of isoflurane after its local application to the skin. we evaluated the local analgesic effect of isoflurane solution in 31 healthy volunteers. the right or left forearm of each subject was exposed to isoflurane and the contralateral forearm to water for 30 min. then, the response of both forearms to a mechanical stimulus of 650 gr and an electrical stimulus of 2 hz was tested. the procedure was repeated the next day with the forearms exposed to anaesthetic or water in an inverse way. the averaged responses to the mechanical and electrical stimuli obtained from both forearms after exposure to isoflurane were expressed on a vas scale and compared with the averaged responses obtained after exposure to water, using the wilcoxon signed-ranks matched-pairs test. the average vas scores obtained from both forearms after the mechanical stimulus were decreased after isoflurane compared with water (3.5 /- 2.1 cm vs 4.3 /- 2.2 cm, p 0.0001). after the electrical stimulus local application of isoflurane was associated with a decrease in the vas scores obtained from both the right and left forearms (3.6 /- 2.0 cm) when compared with water, (5.2 /- 2.1 cm, p 0.0001).","these data suggest that isoflurane may have an analgesic effect in the peripheral tissues, which may interfere with the mac determination as well with decreased responses to other nociceptive stimuli.",Medication
is motor control of the vastus medialis oblique and vastus lateralis muscles disrupted during eccentric contractions in subjects with patellofemoral pain?,inappropriate control of the vastus medialis oblique and vastus lateralis muscles by the central nervous system can contribute to maltracking of the patella. the activation timing and amplitude of the vastus medialis oblique and vastus lateralis muscles will be different between normal subjects and patients with patellofemoral pain. controlled laboratory study. subjects with patellofemoral pain and asymptomatic control subjects performed maximum voluntary knee extension contractions initiated from a flexed and an extended position. the activation timing and amplitude of the vastus lateralis and vastus medialis oblique muscles were quantified from the recorded electromyographic signals. there were no between-group differences in activation timing. the activation amplitude of the vastus medialis oblique and vastus lateralis muscles of the patellofemoral pain subjects was altered to the greatest extent during eccentric contractions and differed significantly from that of control subjects.,the activation amplitudes of the vastus medialis oblique and vastus lateralis muscles of subjects with patellofemoral pain are consistent with a laterally tracking patella during eccentric contractions.,Symptoms
does whey protein modify gene expression related to protein metabolism affecting muscle weight in resistance-exercised rats?,"the aim of this study was to evaluate the effects of resistance exercise on the mrna expression of muscle mammalian target of rapamycin (mtor), muscle-specific ring finger-1 (murf-1), and muscle atrophy f-box (mafbx) in the presence or absence of whey protein ingestion. we hypothesized that resistance exercise in combination with whey protein ingestion alters the gene expression of proteins related to muscle protein synthesis (mtor) and/or degradation (murf-1 and mafbx), thus affecting muscle weight gain in rats. thirty-two male fischer rats were randomly assigned to the following four experimental groups (n 8/group): control sedentary, control exercised, whey protein sedentary, and whey protein exercised. exercise consisted of inducing the animals to perform sets of jumps for 8 wk. body weight gain, muscle weights, food intake, and feeding efficiency were evaluated. gene expressions were analyzed by quantitative real-time reverse transcription polymerase chain reaction. statistical evaluation was performed using a two-way analysis of variance with a tukey post hoc test. whey protein exercised rats exhibited higher body and muscle weight gain compared with control-exercised rats (p 0.032). the expression of mtor was reduced by exercise but increased when whey protein was consumed as a dietary protein (p 0.005). murf-1 expression was reduced by exercise (p 0.001), whereas mafbx was reduced only by whey protein ingestion (p 0.008) independent of exercise.",a reduction in mafbx gene transcription induced by whey protein and the interaction between exercise and whey protein ingestion on mtor gene expression contributed significantly to differences in body and muscle weight gain.,Prevention
does red ginseng treatment for two weeks promote fat metabolism during exercise in mice?,"red ginseng (rg) has been reported to improve the blood and organ lipid profile when combined with exercise. however, the effect of rg on energy metabolism during exercise is poorly understood. therefore, this study was designed to investigate whether rg treatment alters fat utilization during exercise; we used seven-week-old icr mice (n 42). rg (1 g/kg) was administered orally daily during two weeks of endurance training. all mice were randomized into two groups: training only group (con group) and training with rg group (rg group). endurance training consisted of 2025 m/min on a slope of 8 for one hour five times a week. after a two-week experimental period, we measured substrate utilization during exercise at the same intensity and duration of training using a respiratory calorimetry chamber. mice were dissected for glycogen measurement of muscles and liver before, immediately after, and one hour after the exercise; fat oxidation during the initial 20 min of the one-hour exercise significantly increased in the rg group compared to the con group. in addition, the liver glycogen stores significantly decreased immediately after the one-hour exercise compared to at rest in the rg group, but did not differ between immediately after the one-hour exercise and at rest in the rg group. the glycogen concentration in white and red gastrocnemius muscle did not differ between the groups immediately after the one-hour exercise;",these results suggest that rg treatment for two weeks promotes fat oxidation and a glycogen-sparing effect during exercise. this might lead to a delay in peripheral fatigue during endurance exercise performance.,Treatment
is ability to regulate emotion predicted by depressive symptoms and cognitive function in a cardiac sample?,"reduced ability to regulate emotion is exhibited in depressed individuals as well as patients with neurocognitive change. given that patients with cardiovascular disease (cvd) often exhibit both cognitive and mood changes, these could, in combination, lead to increased volatility of emotion. the current study examined the association between ability to regulate emotion, depressive symptoms, and cognitive function in a sample of patients with cvd. ninety-one cvd patients referred for outpatient stress testing completed brief cognitive testing and self-report measures of emotion regulation and depressive symptoms. hierarchical multiple regression analyses revealed that depressive symptoms (p .001) and executive function (p .05) independently contribute to emotion regulation. the interaction between these variables demonstrates that elevated depressive symptoms and decreased executive function predict increased emotion dysregulation.","findings suggest that in combination, elevated depressive symptoms and executive dysfunction contribute to poorer ability to regulate emotion in patients with cvd. given the prevalence of depression and cognitive change in this population, these findings underscore the importance of clinician awareness of these issues in this population and suggest clinical implications for treatment of mental health issues, especially emotion regulation, in this population.",Symptoms
does soluble st2 monitoring provide additional risk stratification for outpatients with decompensated heart failure?,"the novel biomarker st2 provides diagnostic information in a variety of clinical settings. the objective was to determine whether measurement of the soluble st2 (sst2) concentration improves risk stratification in outpatients with decompensated heart failure (hf). the concentrations of sst2 and n-terminal probrain natriuretic peptide (nt-probnp) and a heart failure severity score (hfss), based on framingham criteria, were determined at baseline and 2 weeks later in 48 outpatients with decompensated hf. the ratio of the value of each variable at week 2 relative to baseline was determined. patients were followed for 1 year and cardiac events (i.e. death, hf admission and heart transplantation) were recorded. by 1 year, 56 of patients had experienced a cardiac event. the sst2 ratio was significantly lower in patients who did not have a cardiac event (0.6 0.39 vs. 1.39 0.92; p0.75 and a baseline nt-probnp level 1000 ng/l, 72 had a cardiac event (p.018), while no events occurred in patients with marker values below these reference levels.",determination of the sst2 concentration in serial samples provided additional risk stratification in outpatients with decompensated hf. repeated measurement of sst2 may aid clinical decision-making.,Diagnosis
does hormone replacement therapy improve arterial stiffness in normotensive postmenopausal women?,"aortic stiffness, determined by the pulse wave velocity (pwv), is an independent marker of cardiovascular risk. pwv is mainly influenced by age-associated alterations of arterial wall structure and blood pressure (bp). to determine the impact of hormone replacement therapy (hrt) on arterial compliance in normotensive, postmenopausal women, we examined the effects of hrt on pwv. fifty-six postmenopausal women aged 50-70 years were recruited into the present retrospective study from the patients visiting our menopause clinic. twenty-seven women who were prescribed hrt (14 on estrogen alone and 13 on estrogen plus progestogen) for several months to 6 years and an age-matched group of 29 women not on hrt were studied (study 1). nine postmenopausal women were also studied before and at 4 weeks of the treatment of estrogen replacement therapy (ert) (study 2). brachial to ankle pwv (bapwv), which is correlated with aortic pwv, was determined using an automatic device, bp-203pre. in study 1, pwv was significantly correlated with age in both groups (controls: r0.392, p0.035; hrt group: r0.471, p0.013), and hrt significantly lowered the pwv value at all ages examined (mean/-s.d. of bapwv in controls: 1382.2/-114.1; hrt: 1245.3/-124.8, p0.0001). in study 2, bapwv decreased significantly after ert (p0.05), without a significant change in systolic bp (p0.851).",estrogen appears to improve arterial compliance independently of bp within 4 weeks.,Treatment
"are expressions of putative cancer stem cell markers abcb1 , abcg2 , and cd133 correlated with the degree of differentiation of gastric cancer?","the present study was carried out to determine whether a quantitative relationship exists between the expressions of 3 cancer stem cell (csc) markers and the degree of differentiation of gastric cancer. the expressions of 3 putative csc markers, abcb1, abcg2, and cd133, were detected in 90 human gastric adenocarcinoma cases by immunofluorescence assay. the differentiation statuses of 3 gastric cancer cell lines (the undifferentiated gastric cancer cell line hgc-27, the poorly differentiated gastric cancer cell line bgc-823, and the moderately-poorly differentiated gastric adenocarcinoma cell line sgc-7901) were observed and compared by performing the 3-4,5-dimethylthiazol-2yl-2,5-diphenyl tetrazolium bromide (mtt) assay. gastric xenotransplant cancers in nude mice were constructed to compare the malignancy of the 3 variously differentiated gastric cancer cell lines. the expressions of the 3 putative csc markers were also detected in the 3 gastric cancer cell lines in vitro by flow cytometric analysis and in the 3 gastric xenotransplant cancers in vivo by immunofluorescence staining. the expressions of abcb1, abcg2, and cd133 were generally correlated with the degree of differentiation of the gastric cancers. in the human gastric adenocarcinomas and in the cancer cell lines, the expressions of abcb1, abcg2, and cd133 increased with the increases in the malignancy grades of the gastric cancers. in the human gastric adenocarcinomas, poorly differentiated adenocarcinoma expressed more abcb1, abcg2, and cd133 than well-differentiated adenocarcinoma. in addition, the expressions of abcb1 and cd133 were higher in the diffuse type than in the intestinal type of human gastric cancers. the undifferentiated cell line hgc-27 expressed more putative csc markers than the moderately-poorly differentiated cell line sgc-7901. similar results were observed in the xenotransplant tumors that arose from the 3 gastric cancer cell lines.","the expressions of the csc markers abcb1, abcg2, and cd133 differed in the gastric cancers with various degrees of differentiation, with poorly differentiated gastric cancer expressing relatively more csc markers.",Diagnosis
does endothelin-1 contribute to the progression of renal injury in sickle cell disease via reactive oxygen species?,"endothelin-1 (et-1) is increased in patients with sickle cell disease and may contribute to the development of sickle cell nephropathy. the current study was designed to determine whether et-1 acting via the eta receptor contributes to renal injury in a mouse model of sickle cell disease. adult, humanized hbss (homozygous for sickle hb) mice had increased et-1 mrna expression in both the cortex and the glomeruli compared with mice heterozygous for sickle and hb a (hbas controls). in the renal cortex, eta receptor mrna expression was also elevated in hbss (sickle) mice although etb receptor mrna expression was unchanged. ligand binding assays confirmed that sickle mice had increased eta receptors in the renal vascular tissue when compared with control mice. in response to pkc stimulation, reactive oxygen species production by isolated glomeruli from hbss sickle mice was increased compared with that from hbsa controls, an effect that was prevented by 1 week in vivo treatment with the selective eta antagonist, abt-627. protein and nephrin excretion were both elevated in sickle mice, effects that were also significantly attenuated by abt-627. finally, eta receptor antagonism caused a significant reduction in mrna expression of nadph oxidase subunits, which may contribute to nephropathy in sickle cell disease.","these data support a novel role for et-1 in the progression of sickle nephropathy, specifically via the eta receptor, and suggest a potential role for eta receptor antagonism in a treatment strategy.",Medication
is basal endothelial nitric oxide release preserved in overweight and obese adults?,"impaired basal nitric oxide release is associated with a number of cardiovascular disorders including hypertension, arterial spasm, and myocardial infarction. we determined whether basal endothelial nitric oxide release is reduced in otherwise healthy overweight and obese adult humans. seventy sedentary adults were studied: 32 normal weight (bmi or 25 or 30 kg/m(2)). forearm blood flow (fbf) responses to intra-arterial infusions of n(g)-monomethyl-l-arginine (5 mg/min), a nitric oxide synthase inhibitor, were used as an index of basal nitric oxide release. n(g)-monomethyl-l-arginine elicited significant reductions in fbf in the normal weight (from 4.1 /- 0.2 to 2.7 /- 0.2 ml/100 ml tissue/min), overweight (4.1 /- 0.1 to 2.8 /- 0.2 ml/100 ml tissue/min), and obese (3.9 /- 0.3 to 2.7 /- 0.2 ml/100 ml tissue/min) subjects. importantly, the magnitude of reduction in fbf (approximately 30) was similar among the groups.",these results indicate that the capacity of the endothelium to release nitric oxide under basal conditions is not compromised in overweight and obese adults.,Medication
does the icf comprehensively cover the spectrum of health problems encountered by health professionals in patients with musculoskeletal conditions?,"the objective of this study was to investigate, whether the international classification of functioning, disablity and health (icf) comprehensively covers the spectrum of health problems encountered by medical doctors and physiotherapists in patients with musculoskeletal conditions. a worldwide e-mail survey with questionnaires that requested lists of relevant areas in the icf components-body functions, body structures, activities and participation, and environmental factors-in patients with rheumatoid arthritis, osteoarthritis, low back pain and osteoporosis was conducted. the suitability of linking the named concepts to the icf as well as the precision of the linking was characterized by assigning the concepts to six groups. all concepts that were named by the experts could be linked to the icf, with the exception of personal factors. between 32 (environmental factors) and 51 (activities and participation) of the named concepts were linked to an icf category with an identical meaning and the same grade of precision. all other named concepts were linked to icf categories with a lower level of precision, or encompassed more than one icf category, or were linked to an icf category with a related, but not identical meaning.",the icf covers comprehensively the spectrum of problems encountered in patients with musculoskeletal conditions by clinical experts throughout the world. this strengthens the validity of the icf in the view of the users and will encourage the use of icf-based applications such as the icf checklist and the now-developed icf core sets.,Treatment
does cocaine disrupt both behavioural inhibition and conditional discrimination in rats?,"stimulant addicts exhibit increased behavioural disinhibition under the influence of the drug. in laboratory animals, however, the effects of amphetamine on behavioural disinhibition are equivocal, and the effects of cocaine have not been investigated. the current set of experiments was designed to test the effects of cocaine on behavioural disinhibition and to assess whether the possible impairments are due to deficits in conditional discrimination or attention. separate groups of rats were trained to respond in an asymmetrically reinforced go/no-go task, a conditional discrimination task or a vigilance task. upon reaching criterion performance, animals were treated with cocaine (0-20 mg/kg) immediately prior to testing. cocaine (15 mg/kg) increased no-go interval responses, indicating an increase in behavioural disinhibition. conditional discrimination was also impaired by cocaine (15 and 20 mg/kg); animals made more incorrect trials per completed trial. cocaine-treated animals also made more premature responses in this task, indicating increased behavioural disinhibition independent of a conditional discrimination deficit. finally, cocaine (0-20 mg/kg) had no effect on vigilance.","administration of moderate to high doses of cocaine increases behavioural disinhibition, and this increase may be independent of an impairment in conditional discrimination.",Medication
does anterolateral rectopexy for correction of rectoceles lead to good anatomical but poor functional results?,"several different surgical repair procedures for symptomatic rectocele have been described with variable results. in our clinic, a modified anterolateral rectopexy is used. in this article we evaluate our results, with emphasis on patient satisfaction. from 2001 until 2003, twenty patients with a symptomatic rectocele were treated by anterolateral rectopexy. the preoperative dynamic defecogram and anorectal complaints were analyzed and compared to postoperative outcome via a standardized questionnaire. after surgery, all rectoceles were restored as shown by postoperative defecogram. anorectal symptoms (incomplete evacuation, continuous urge, prolapse, digital evacuation) were improved in 40. as new-onset symptoms, dyspareunia (50), digital support (55) and incomplete evacuation (75) were mentioned frequently. most of the patients with larger rectoceles (3.5 cm) had increased anorectal complaints after surgery.","anterolateral rectopexy for treatment of rectocele give limited improvement of anorectal complaints. besides, many patients developed new complaints postoperatively and hence overall satisfaction was low.",Treatment
does omega-3 polyunsaturated fatty acid supplementation confer long-term neuroprotection against neonatal hypoxic-ischemic brain injury through anti-inflammatory actions?,"current available therapies for neonatal hypoxia/ischemia (h/i) brain injury are rather limited. here, we investigated the effect of omega-3 polyunsaturated fatty acids on brain damage and long-term neurological function after h/i in neonates. female rats were treated with or without an omega-3 polyunsaturated fatty acids-enriched diet from the second day of pregnancy until 14 days after parturition. seven-day-old neonates were subjected to h/i and euthanized 5 weeks later for evaluation of tissue loss. neurological impairment was assessed progressively for 5 weeks after h/i by grid walking, foot fault, and morris water maze. activation of microglia and production of inflammatory mediators were examined up to 7 days after h/i. omega-3 polyunsaturated fatty acid supplementation significantly reduced brain damage and improved long-term neurological outcomes up to 5 weeks after neonatal h/i injury. omega-3 polyunsaturated fatty acids exerted an anti-inflammatory effect in microglia both in an in vivo model of h/i and in in vitro microglial cultures subjected to inflammatory stimuli by inhibiting nf-b activation and subsequent release of inflammatory mediators.","our results suggest that omega-3 polyunsaturated fatty acids confer potent neuroprotection against neonatal h/i brain injury through, at least partially, suppressing a microglial-mediated inflammatory response.",Medication
does entecavir allow an unexpectedly high residual replication of hbv mutants resistant to lamivudine?,"entecavir is an efficient inhibitor of hbv reverse transcriptase (rt) and widely used for therapy of chronic hepatitis b. entecavir treatment of hbv patients with lamivudine-resistant viral strains, however, often fails, but the mechanism of cross-resistance development is not fully understood. using non-linear regression models, dose-response curves of cloned hbv strains from patients pre-treated with rt inhibitors were established in human hepatoma cell lines after transfection with hbv genomes containing hbv polymerase genes from patient isolates. 50 and 90 inhibitory concentrations (ic50 and ic90) and corresponding antiviral resistance factors (rf50 and rf90) were calculated. the entecavir dose-response curve of lamivudine-resistant hbv rt mutants rtm204 for the replication of hbv decreased less than expected with increasing drug dose. remarkably, due to the flat dose-response curves, rf90 values against entecavir of samples with rtm204 substitutions were up to 30 higher than their rf50 values.","the unexpectedly high ic90 indicates a strong residual replication capacity of lamivudine-resistant hbv rtm204 variants under entecavir therapy, although ic50 values are initially within the therapeutic range of entecavir. this characteristic favours rapid selection of additional mutants with overt resistance against entecavir. thus, the current phenotypic resistance assays should include determination of ic90.",Medication
does assessment of local mosquito species incriminate aedes aegypti as the potential vector of zika virus in australia?,"within the last 10 years zika virus (zikv) has caused unprecedented epidemics of human disease in the nations and territories of the western pacific and south america, and continues to escalate in both endemic and non-endemic regions. we evaluated the vector competence of australian mosquitoes for zikv to assess their potential role in virus transmission. mosquitoes were exposed to infectious blood meals containing the prototype african zikv strain. after 14 days incubation at 28c and high relative humidity, infection, dissemination and transmission rates were assessed. infection in culex annulirostris and cx. sitiens could not be detected. 8 of cx. quinquefasciatus were infected, but the virus did not disseminate in this species. despite having infection rates 50, aedes notoscriptus and ae. vigilax did not transmit zikv. in contrast, ae. aegypti had infection and transmission rates of 57 and 27, respectively. in susceptibility trials, the virus dose required to infect 50 (id50) of ae. aegypti was106.4 tissue culture infectious dose50 (tcid50)/ml. additionally, a threshold viral load within the mosquito of at least 105.1 tcid50 equivalents/ml had to be reached before virus transmission occurred.","we confirmed ae. aegypti to be the most likely mosquito vector of zikv in australia, although the restricted distribution of this species will limit the receptive zone to northern queensland where this species occurs. importantly, the role in zikv transmission of culex and other aedes spp. tested will be negligible. despite being the implicated vector, the relatively high id50 and need for a high titer disseminated infection in ae. aegypti suggest that high mosquito population densities will be required to facilitate epidemic zikv transmission among the currently immunologically nave human population in australia.",Medication
is the nuclear factor i/a ( nfia ) gene associated with the asthma plus rhinitis phenotype?,"a previous genome-wide linkage scan in 295 families of the french epidemiological study on the genetics and environment of asthma (egea) showed strong evidence of linkage of the 1p31 region to the combined asthma plus allergic rhinitis (ar) phenotype. our purpose was to conduct fine-scale mapping of the 1p31 linkage region to identify the genetic variants associated with asthma plus ar. association analyses with the asthma plus rhinitis phenotype were first conducted in the egea family sample using the family-based association method (fbat) and logistic regression. the test of homogeneity of association between asthma plus ar versus asthma alone or ar alone was also applied. replication of egea findings was sought in french-canadian and united kingdom family samples. we found a significant association between asthma plus rhinitis and a 1p31 genetic variant (p 2 10(-5) for rs12122228, which reached the multiple testing-corrected threshold) in egea using fbat. there was evidence of heterogeneity of association between asthma plus ar versus asthma alone or ar alone (p .03). a meta-analysis of fbat results from egea and french-canadian families improved evidence for both association and heterogeneity (p 5 10(-6) and p .008, respectively), whereas a meta-analysis of egea, french-canadian, and united kingdom samples based on logistic regression slightly increased the evidence for heterogeneity.","the single nucleotide polymorphism specifically associated to asthma plus rhinitis is located in the flanking 5' untranslated region of the nuclear factor i/a (nfia) gene, a strong candidate gene for asthma and ar.",Prevention
do randomized controlled clinical trial of kang'ai injection in gastrointestinal cancerchemotherapy patients ?,"to study the influence of kang'ai injection on quality of life among gastrointestinal cancer chemotherapy patients. fourty-two gastrointestinal cancer patients were randomly divided into the treatment group (n22) and the control group (n20). the treatment group was treated with chemotherapy and kang'ai injection, and the control group was only treated with chemotherapy. their quality of life, improvement of clinical symptoms and adverse effects were observed. the disease control rates of the treatment group and the control group were 91 and 30 ,while their effective rates of kps were 59 and 30 respectively. they had one case and six cases with side effects above iii degree.","kang'ai injection can mitigate syndromes of gastrointestinal cancer chemotherapy patient, improve their quality of life and have an effect of reducing toxic and enhancing efficacy for chemotherapy.",Medication
is augmentation of left ventricular torsion with exercise attenuated with age?,"left ventricular torsion, resulting from the rotation of the base and apex of the ventricle in opposite directions, may be an important component of normal cardiac function both at rest and with exercise. the effect of exercise on torsion in the general population and the influence of aging on changes in torsion with exercise are not known. analysis of torsion, positive and negative torsion velocities, and negative torsion acceleration was performed using speckle tracking imaging on 33 stress echocardiograms using supine bicycle stress. resting and postexercise torsion could be assessed in 14 patients (42). a total of 19 patients who were significantly older and larger (mean age 57 years, mean body mass index 28.2, both p .03) were excluded as a result of inadequate frame rate and image quality after exercise. after exercise, significant increases in peak torsion (10.3 /- 0.8 vs 13.3 /- 1.3 degrees, p .04), peak positive torsion (54.2 /- 5.6 vs 113.6 /- 12.3 degrees/s, p .0001), and peak negative torsion (-56.3 /- 7.9 vs -100.8 /- 14.8 degrees/s, p .03) velocities were observed. ejection fraction correlated with torsion both at rest and after exercise (r 0.63, p .0004). at rest, torsion was greater in older individuals (8.9 /- 0.6 vs 11.6 /- 1.2 degrees, p .04). with increasing age, exercise resulted in less augmentation of torsion (r 0.59, p .02) and positive torsion velocity (r -0.79, p .003), and decreased negative torsional acceleration (r 0.60, p .035).",exercise results in increased cardiac plecotropy (the augmentation of torsion parameters in response to load or stimulus) but this effect is attenuated with aging. further investigation is required to determine whether impairment of plecotropy contributes to the reduced exercise capacity associated with aging.,Prevention
is paced qrs fragmentation associated with spontaneous ventricular fibrillation in patients with brugada syndrome?,"conduction abnormalities are involved in the pathogenesis of ventricular fibrillation (vf) in patients with brugada syndrome (brs). we investigated whether right ventricular apical pacing (rvap) could enhance the conduction abnormality and predict the susceptibility to vf in patients with brs. twenty patients with brs (n 15) or early repolarization syndrome (ers) (n 5) having an implantable cardioverter-defibrillator and 11 patients with complete atrioventricular block having a pacemaker were studied. in brs, 7 patients had a history of spontaneous vf vf() group and the remaining 8 did not vf(-) group. the number of spikes in fragmented qrs was counted during sinus rhythm and rvap at rates of 80 and 110 beats/min, respectively. patients with complete atrioventricular block had no spikes during rvap. during sinus rhythm, no significant difference was observed in qrs spike numbers among vf(), vf(-), and ers groups. during rvap at 110 beats/min, the sum of spike numbers in leads v1 and v2 increased and the duration of qrs fragmentation increased in the vf() group as compared with vf(-) and ers groups vf(): 10.7 3.7, 2.4 3.2, and 2.4 1.8 ms; p .001; vf(-): 173 32, 45 44, and 49 45 ms; p .001. according to the receiver operating characteristic analysis, the cutoff value of the sum of spike numbers in leads v1 and v2 to best discriminate between vf() and vf(-) groups was 4 in patients with brs.","rvap manifested qrs fragmented spikes, which could be associated with spontaneous vf in patients with brs.",General
do monocyte-derived dendritic cells over-express cd86 in patients with systemic lupus erythematosus?,"dendritic cells (dcs) play a key role in regulating immune responses, especially in priming nave t-cells. recently, dcs have been suggested to be involved in systemic lupus erythematosus (sle) development by activating autoreactive t-helper lymphocytes. as a consequence, we compared the activation state of human monocyte-derived dcs (mddcs) obtained from lupus patients and normal individuals. the mddcs were generated in vitro from blood from healthy donors and lupus patients. immature and mature mddcs were analysed by flow cytometry for several cell surface molecules. in parallel, cytokine secretion was determined by elisa before and after mddc activation. in each experiment, lupus dcs were compared with normal dcs. here, we show for the first time that lupus mddcs spontaneously over-express cd86 in the absence of any dc activation signal as compared with normal mddcs (p 0.025). moreover, activation-induced il-6 secretion was increased in lupus dcs with high cd86 over-expression as compared with normal dcs (p 0.010). interestingly, the percentage of mddcs in lupus preparations is negatively correlated with disease activity scores (sledai; p 0.031).",lupus mddcs are pre-activated suggesting that they might be more efficient antigen-presenting cells. this result might partly explain how the peripheral tolerance is broken in sle.,General
do role of visual integration in gaze perception and emotional intelligence in schizophrenia?,"individuals with schizophrenia demonstrate a wide range of social cognitive deficits that significantly compromise functioning. early visual processing is frequently disrupted in schizophrenia, and growing evidence suggests a role of perceptual dysfunctions in socioemotional functioning in the disorder. this study examined visual integration (the ability to effectively integrate individual, local visual features into a holistic representation), a target construct of basic perception identified by the cognitive neuroscience treatment research to improve cognition in schizophrenia initiative, and its relationship with eye- contact perception and emotional intelligence in schizophrenia. twenty-nine participants with schizophrenia (scz) and 23 healthy controls (hc) completed tasks measuring visual integration (coherent motion task, contour integration task), an eye-contact perception task, and a measure of emotional intelligence. scz participants showed compromised visual integration as suggested by poorer performance on the contour integration task relative to hc. visual integration was a significant predictor of eye-contact perception and emotional intelligence among scz. the amounts of variances in these 2 social cognitive areas accounted for by visual integration were comparable to and overlapped with those accounted for by the diagnosis of schizophrenia.","individuals with schizophrenia showed compromised visual integration, and this may play a significant role in the observed deficits in higher level processing of social information in the disorder.",Treatment
do intraoperative joint gaps affect postoperative range of motion in tkas with posterior-stabilized prostheses?,"joint gaps and mediolateral (ml) soft tissue balance have long been known to affect clinical scores and patient function after tka, but the relationship between gaps and soft tissue balance remain poorly defined. if specific relationships exist between soft tissue tension and patient function, then objective targets could be established to assist surgeons in achieving more consistent postoperative knee function. by performing instrumented gap measurements during tka, we sought to quantify the relationships between intraoperative soft tissue tension and clinical scores and patient function. we prospectively followed 57 patients with 63 primary tkas with posterior-stabilized prostheses. joint gaps and ml soft tissue balance were measured intraoperatively from 0 to 135 with the patella reduced after independent bone cuts and soft tissue releases. we determined the relationships between these intraoperative measurements and postoperative rom and knee society scores at minimum 2-year followup. larger joint gaps at 120 and 135 flexion predicted larger postoperative knee flexion (r0.296 and r0.393, respectively), whereas larger gaps at 10 flexion predicted greater postoperative knee extension (r0.285). knees with rectangular joint gaps did not show better rom or knee society scores compared with knees with trapezoidal joint gaps. in the range of normal surgical variation, neither joint gaps nor gap asymmetry affected the incidence of postoperative instability.",avoiding small joint gaps in extension and in deep flexion should allow patients who undergo tkas to obtain maximum rom.,Treatment
do serum thioredoxin reductase levels increase in response to chemically induced acute liver injury?,"mammalian thioredoxin reductases (trxr) are selenoproteins with important roles in antioxidant defense and redox regulation, principally linked to functions of their main substrates thioredoxins (trx). all major forms of trxr are intracellular while levels in serum are typically very low. serum trxr levels were determined with immunoblotting using antibodies against mouse trxr1 and total enzyme activity measurements were performed, with serum and tissue samples from mouse models of liver injury, as triggered by either thioacetamide (taa) or carbon tetrachloride (ccl4). trxr levels in serum increased upon treatment and correlated closely with those of alanine aminotransferase (alt), an often used serum biomarker for liver damage. in contrast, trx1, glutathione reductase, superoxide dismutase or selenium-containing glutathione peroxidase levels in serum displayed much lower increases than trxr or alt.",serum trxr levels are robustly elevated in mouse models of chemically induced liver injury.,Treatment
does the degree of bandemia in septic ed patients predict inpatient mortality?,"a delay in diagnosis of sepsis and appropriate treatment increases subsequent mortality. an association with the degree of bandemia, or the presence of immature neutrophils in the white blood cell count, has not been explored in septic patients presenting to the emergency department (ed). we hypothesized that the presenting band levels would be higher in septic patients who die in hospital compared with survivors. this study reviewed charts of ed patients presenting with sepsis to a single urban, academic, tertiary care ed with an annual census of 80,000 visits. patients were included if they had bandemia assessed and were eligible for early goal-directed therapy. reviewers blinded to the study purpose abstracted data using predetermined definitions. the band level was compared between patients who died and those who survived to discharge using the mann-whitney u test. logistic regression was used to estimate the effect of bandemia levels on the odds of death. ninety-six patients meeting inclusion criteria were enrolled; 2 were excluded with incomplete data. mean age was 59 years, 53 were white, and 51 were male. thirty-two patients (34) died during admission. the median band levels in patients who died was 17 (range, 0-67); and in patients surviving to discharge, the median band level was 9 (range, 0-77) (difference in medians, 8; ci(95), -27.04 to 11.04; p .222).",the band level on presentation was not found to be associated with inpatient mortality in ed patients with sepsis who are eligible for early goal-directed therapy.,Treatment
are rotator cuff fatty infiltration and atrophy associated with functional outcomes in anatomic shoulder arthroplasty?,"shoulder arthroplasty provides reliable pain relief and restoration of function. however, the effects of fatty infiltration and atrophy in the supraspinatus and infraspinatus muscles on functional outcomes are not well understood. the purposes of this study were to (1) compare preoperative with postoperative fatty infiltration and atrophy of the supraspinatus and infraspinatus muscles after primary shoulder arthroplasty; and (2) identify any associations between these variables and outcome measures. a retrospective analysis was undertaken of 62 patients with a mean age of 67 years (range, 34-90 years) who underwent shoulder arthroplasty. ct scans were conducted preoperatively and at 12 months postoperatively. outcome variables included the degree of supraspinatus and infraspinatus fatty infiltration (percent fatty infiltration and goutallier grade), muscle area (percent muscle area and warner atrophy grade), shoulder strength, and the western ontario osteoarthritis score (woos), american shoulder and elbow surgeons score, and constant outcome score. preoperatively, the mean percent fatty infiltration (fi) within the supraspinatus and infraspinatus was identical at 14. one year after shoulder arthroplasty, both muscles had less fatty infiltration (6 and 7, respectively; p0.251). preoperatively, greater supraspinatus percent fi was negatively associated with preoperative shoulder strength (r0.37, p0.001) and constant score (r0.38, p0.001). postoperative infraspinatus percent fi was negatively associated with postoperative strength (r0.3, p0.021) and constant score (r0.3, p0.04). multivariable regression analysis of possible predictive factors demonstrated that preoperative supraspinatus percent muscle area (p0.016) and the diagnosis of osteoarthritis (p0.017) were associated with better followup woos scores, and preoperative supraspinatus strength was associated with postoperative strength (p0.0024). higher degrees of preoperative percent fi were not associated with worse patient-reported outcomes postoperatively.","supraspinatus and infraspinatus fatty infiltration improves after shoulder arthroplasty, whereas muscle area remains unchanged. although further study of these variables is required, the negative associations identified between preoperative supraspinatus atrophy and the diagnosis of rheumatoid arthritis and postoperative quality-of-life outcome scores may aid the clinician in selecting the best treatment option for glenohumeral arthrosis and in the management of patient expectations.",Diagnosis
does the antioxidant alpha-lipoic acid improve endothelial dysfunction induced by acute hyperglycaemia during ogtt in impaired glucose tolerance?,"impaired glucose tolerance (igt) is considered a transitional phase in the development of type 2 diabetes, and is also independently associated with the occurrence of cardiovascular disease. endothelial dysfunction (ed) represents a very early step in the development of atherosclerosis. the aim of the present study was to examine ed in the fasting state and after a glucose challenge as well as after administration of an antioxidant agent. the study subjects included 42 igt patients and 26 healthy individuals (control group). the igt patients were randomly divided into two groups, 21 in each group (the alpha-lipoic acid group and the placebo group). in the alpha-lipoic acid group, 300 mg of alpha-lipoic acid was administrated before an oral glucose tolerance test (ogtt); in the placebo group, 250 ml of 0.9 sodium chloride was administrated before the ogtt. in addition, 250 ml of 0.9 sodium chloride was also administrated to the control subjects before the ogtt (control group), and then vascular function was examined in the fasting state and repeated 1 and 2 h after the glucose load. high-resolution ultrasound was used to measure flow-mediated endothelium-dependent arterial dilation (fmd) and glyceryltrinitrate (gtn)-induced endothelium-independent arterial dilation. in the fasting state, and at 60 and 120 min, fmd in both the placebo and alpha-lipoic acid groups was significantly lower than in the controls (p 0.05). in the placebo group, fmd decreased significantly at 60 min after glucose loading (p 0.01) and increased markedly from 60 to 120 min (p 0.01). the alpha-lipoic acid-treated patients showed fmd values intermediate between the control subjects and the igt patients treated with placebo, at both 60 and 120 min, and the differences were significant (p 0.01). in multiple regression analysis, fmd was significantly correlated to fasting blood glucose (fbg), low density lipoprotein cholesterol (ldl-c), lipoprotein (a) lp(a), c-reactive protein (crp), thiobarbituric acid reactive substances (tbars) and age in igt patients at baseline (p 0.01). spearman's analysis showed a significant negative correlation between fmd and plasma glucose levels, and between fmd and tbars during the ogtt in igt patients (placebo group) (p 0.01). there was also a significant correlation between fmd and plasma glucose levels, and between fmd and tbars during the ogtt in igt patients treated with alpha-lipoic acid (p 0.05), although the power of association decreased.","in subjects with igt, fmd was impaired both in the fasting state and after a glucose challenge, probably through increased production of oxygen-derived free radicals. the ed observed after a glucose challenge is related to the extent of hyperglycaemia and tbars, and an antioxidant agent can improve the impairment of endothelial function induced by acute hyperglycaemia.",Symptoms
does scf/c-kit signaling promote invasion of t24 cells via pi3k pathway ?,"to explore the role of scf/c-kit signaling in the invasion of bladder cancer t24 cells. western blotting was used to detect the expression of c-kit and pi3k pathway activation stimulated by stem cell factor (scf) in t24 cells. the invasiveness of t24 cells before and after scf stimulation and wortmannin (aspecific pi3k inhibitor) treatment was evaluated using transwell invasion assay (direct and indirect counting methods). t24 cells expressed c-kit protein and showed obvious akt phosphorylation after stimulation with scf (1 ng/ml) for 24 h. compared to the control group, scf stimulation (1 ng/ml) caused a greater number of t24 cells to migrate through the polycarbonate film (p0.01), and this effect was blocked by the application of wortmannin before the stimulation.","scf/c-kit signaling promotes the invasiveness of t24 cells, and this effect is mediated by the pi3k pathway.",Medication
does cd10 expression help to differentiate basal cell carcinoma from trichoepithelioma?,"the distinction between basal cell carcinoma (bcc) and trichoepithelioma (te) may be very difficult in some cases because of the close similarities of these two lesions clinically and histopathologically. the purpose of this study is to investigate the usefulness of cd10 in distinguishing bcc and te. the immunohistochemical expression of cd10 was evaluated in an archived group of 30 bccs and 12 tes in a retrospective cross sectional study. the localization of anti-cd10 to the tumoral and/or stromal cells was determined in each case and was compared between these two tumors using fisher's exact test. in bcc cases, the expression of cd10 was noted in tumoral cells in 26 cases (83.2). of these, 3 cases showed positivity of the stromal and basaloid cells, two cases demonstrated stromal expression alone and two bccs were not immunoreactive. on the other hand, 10 out of 12 (83.3) tes showed positive stromal immunoreactivity. of these, one case also showed positivity of the basaloid cells. one te demonstrated epithelial expression alone and one te was not immunoreactive. the pattern of staining of basaloid cells and stromal cells in bcc and trichoepithelioma was statistically different (p 0.001).",we conclude that cd10 is a useful marker in the differential diagnosis of bcc versus te.,General
is p53-insensitive puma down-regulation essential in the early phase of liver regeneration after partial hepatectomy in mice?,"liver regeneration after partial hepatectomy involve proliferation and apoptosis of hepatocytes. puma, the well-known proapoptotic member of the bcl-2 family, can respond to distinct stimuli. this study explores the role of puma and its relationship with other bcl-2 family members in this process. the expression patterns of puma and its related proteins were investigated in livers after 70 hepatectomies. the contributions of puma to liver regeneration were assessed by manipulating its expression levels using adenovirus vectors. the differences in puma expression levels in human normal livers and hepatitis, as well as hepatoma tissues were characterised. during the first 72h after hepatectomy, puma was highly down-regulated transcriptionally, while the levels of p53, slug, bax, and bcl-x(l) proteins increased continuously. highly induced expression of puma in the liver by ad-puma caused lethal fulminant hepatitis 48h after treatment. slightly induced expression was enough to impair liver regeneration, with an elevation of post-hepatectomy mortality, an increase of apoptosis, a decrease of proliferation, an up-regulation of bax levels, an induction of inflammatory chemokines (kc and macrophage inflammatory protein-2), and an increase in the neutrophil infiltration relative to the control. in contrast to the results from the regenerating liver, puma expression showed an increased trend in human hepatitis and hepatoma tissues.","sharply p53-insensitive down-regulation of puma, coupled with bcl-x(l) up-regulation, may play a cytoprotective role in liver regeneration after hepatectomy. furthermore, the increased expression of puma in hepatitis and hepatoma may indicate misregulation of the apoptotic network in these diseases.",Treatment
does inspiratory resistive loading increase sympathetic tone in copd?,"neurohumoral activation has been shown to be present in patients with chronic obstructive pulmonary disease (copd). the increase in respiratory muscle work might be responsible for the observed elevation of sympathetic tone via a respiratory muscle ergoreflex in these patients. the aim of this study is to investigate whether moderately increasing inspiratory resistive loading will impact on sympathetic activity in healthy subjects and copd patients. efferent muscle sympathetic nerve activity, blood pressure, heart rate and respiratory movements were continuously measured in 15 patients and 15 healthy control subjects. in order to increase work of breathing as evaluated by the tension-time index, inspiratory resistive loading was performed while patients were breathing through a spirometer. at baseline, sympathetic nerve activity was significantly elevated in patients. resistive loading increased work of breathing (tension-time index) by roughly 110 (copd) and 130 (controls) but did not significantly alter blood gases or sympathetic activity in either group.",doubling the work of breathing does not affect sympathetic activation in copd patients or healthy control subjects. thus in copd the respiratory muscle ergoreflex does not seem to play a major role in sympathoexcitation.,General
does relative hyperoxia augment lipopolysaccharide-stimulated cytokine secretion by murine macrophages?,"increased systemic levels of inflammatory mediators are seen after open abdominal operations. macrophages that are exposed to lipopolysaccharide secrete cytokines. peritoneal macrophages normally reside in a po(2) of 40 mm hg. we hypothesize that exposure of lipopolysaccharide-stimulated macrophages to ""non-physiologic"" po(2) augments cytokine secretion. murine macrophages were preconditioned to a po(2) of 40 mm hg for 24 hours. the medium then was discarded and exchanged for a medium containing a po(2) of 40, 150, or 440 mm hg. macrophages were incubated in the desired po(2) for 6 and 24 hours while stimulated with lipopolysaccharide (0 to 100 ng/ml). the effect of po(2) was compared. supernatant tumor necrosis factor (tnf) and interleukin-6 were measured with enzyme-linked immunosorbent assay. statistics were performed with analysis of variance. we found dose-dependent lipopolysaccharide-stimulated tnf and interleukin-6 production with macrophages incubated at physiologic po(2). higher po(2) did not stimulate tnf and interleukin-6 in the absence of lipopolysaccharide. however, a po(2) of 150 and 440 mm hg significantly (p .05) increased lipopolysaccharide-stimulated tnf and interleukin-6 production versus 45 mm hg.",our data suggest synergy between increased po(2) and lipopolysaccharide for macrophage tnf and interleukin-6 production. similar po(2) elevations may occur with an open peritoneum or high supplemental o(2). cytokines from peritoneal macrophages may contribute to the increased systemic inflammation after open operations.,Medication
does rna sequencing identify crucial genes in papillary thyroid carcinoma ( ptc ) progression?,"the study aims to uncover molecular mechanisms of ptc (papillary thyroid carcinoma) progression and provide therapeutic biomarkers. the paired tumor and control tissues were obtained from 5 ptc patients. rna was extracted and cdna libraries were constructed. rna-sequencing (rna-seq) was performed on the illumina hiseq2000 platform using paired-end method. after preprocessing of the rna-seq data, gene expression value was calculated by rpkm. then the differentially expressed genes (degs) were identified with edger. functional enrichment and protein-protein interaction (ppi) network analyses were conducted for the degs. module analysis of the ppi network was also performed. transcription factors (tfs) of degs were predicted. a cohort of 496 up-regulated degs mainly correlating with the ecm degradation pathways, and 440 down-regulated degs predominantly enriching in transmembrane transport process were identified. hub nodes in the ppi network were rrm2 and a set of collagens (col1a1, col3a1 and col5a1), which were also remarkable in module 3 and module 5, respectively. genes in module 3 were associated with cell cycle pathways, while in module 5 were related to ecm degradation pathways. plau, psg1 and egr2 were the crucial tfs with higher transcriptional activity in ptc than in control.","several genes including col1a1, col3a1, rrm2, plau, and egr2 might be used as biomarkers of ptc therapy. among them, col1a1 and col3a1 might exert their functions via involving in ecm degradation pathway, while rrm2 through cell cycle pathway. plau might be an active tf, whereas egr2 might be a tumor suppressor.",Diagnosis
does prevalence and correlate of anomalous experiences in a large non-clinical sample?,"anomalous experiences occur in many psychiatric conditions, but are also reported by non-patients. given the continuum account of psychiatric symptoms and reports of dissociation between delusions and anomalous experiences, we predicted that anomalous experiences in a large non-clinical sample would (1) associate with delusion-like beliefs but not with socio-cultural beliefs and (2) that anomalous experiences would also show examples of dissociation with anomalous beliefs. a particular focus was the association between beliefs and experiences theoretically predicted to co-occur in capgras syndrome. the study examined the distribution and correlates of differential levels of self-reported anomalous experience in a british sample of 1,000 individuals. anomalous experiences were found to be relatively common in the general population and were reported (occurring sometimes/often) by 48 of the sample. being female and endorsing a non-christian religion were the only two demographic factors related to higher experience scores. significant relationships were found between anomalous experiences and anomalous beliefs (i.e., delusion-like and paranormal/religious), but not general societal beliefs. dissociations between anomalous experiences and anomalous beliefs also were present but not common. no significant relationship was found between capgras-type beliefs and experiences.","this large scale study demonstrated significant association between anomalous experiences and anomalous beliefs in the general population. the relationship was not, however present in all cases similar to cases reported in the clinical literature.",Diagnosis
does androgen receptor cag repeat length polymorphism modify the impact of testosterone on insulin sensitivity in men?,"low circulating testosterone concentrations have been associated with insulin resistance (ir). androgen action is mediated by the androgen receptor (ar) whose activity is modulated by a polymorphic cag repeat sequence within exon 1. an interaction between testosterone and cag repeat length (cag length) with respect to ir has been described in women. we investigated such a putative interaction between testosterone and the cag length with respect to ir in men with normal glucose tolerance. cross-sectional study. in 113 non-diabetic men calculated free testosterone, the cag length, and a multiplicative interaction term were investigated by multiple linear regression analysis for an association with ir, as indicated by homeostasis model assessment (homa s). in a multivariate regression analysis adjusted for age and body mass index, free testosterone, cag length, and a multiplicative interaction term were significantly associated with ir (p0.001, p0.001, p0.01 respectively). the model explained 36.6 of the variation of ir and predicted that in carriers with a cag length of 23, changes in testosterone would only minimally affect ir. for cag lengths longer than 23, however, an increase in testosterone would improve ir, namely the longer the cag length, the greater the effect. in contrast, in the case of cag lengths shorter than 23, the effect of increasing testosterone would be the opposite.","in men, testosterone and the ar cag repeat length polymorphism interacted with respect to ir. the interpretation of the association between testosterone and ir seems to require consideration of the ar cag repeat polymorphism.",Medication
does induction therapy improve survival for clinical stage t2n0 esophageal cancer?,"this study compared survival after initial treatment with esophagectomy as primary therapy to induction therapy followed by esophagectomy for patients with clinical t2n0 (ct2n0) esophageal cancer in the national cancer database (ncdb). predictors of therapy selection for patients with ct2n0 esophageal cancer in the ncdb from 1998 to 2011 were identified with multivariable logistic regression. survival was evaluated using kaplan-meier and cox proportional hazards methods. surgery was used in 42.9 (2057 of 4799) of ct2n0 patients. of 1599 esophagectomy patients for whom treatment timing was recorded, induction therapy was used in 44.1 (688). pretreatment staging was proven accurate in only 26.7 of patients (210 of 786) who underwent initial surgery without induction treatment and had complete pathologic data available: 41.6 (n 327) were upstaged and 31.7 (n 249) were downstaged. adjuvant therapy (chemotherapy or radiation therapy) was given to 50.2 of patients treated initially with surgery who were found after resection to have nodal disease. there was no significant difference in long-term survival between strategies of primary surgery and induction therapy followed by surgery (median 41.1 versus 41.9 months, p 0.51). in multivariable analysis, induction therapy was not independently associated with risk of death (hazard ratio hr, 1.16, p 0.32).","current clinical staging for early-stage esophageal cancer is highly inaccurate, with only a quarter of surgically resected ct2n0 patients found to have had accurate pretreatment staging. induction therapy for patients with ct2n0 esophageal cancer in the ncdb is not associated with improved survival.",Treatment
do crispr loci reveal networks of gene exchange in archaea?,"crispr (clustered, regularly, interspaced, short, palindromic repeats) loci provide prokaryotes with an adaptive immunity against viruses and other mobile genetic elements. crispr arrays can be transcribed and processed into small crrna molecules, which are then used by the cell to target the foreign nucleic acid. since spacers are accumulated by active crispr/cas systems, the sequences of these spacers provide a record of the past ""infection history"" of the organism. here we analyzed all currently known spacers present in archaeal genomes and identified their source by dna similarity. while nearly 50 of archaeal spacers matched mobile genetic elements, such as plasmids or viruses, several others matched chromosomal genes of other organisms, primarily other archaea. thus, networks of gene exchange between archaeal species were revealed by the spacer analysis, including many cases of inter-genus and inter-species gene transfer events. spacers that recognize viral sequences tend to be located further away from the leader sequence, implying that there exists a selective pressure for their retention.","crispr spacers provide direct evidence for extensive gene exchange in archaea, especially within genera, and support the current dogma where the primary role of the crispr/cas system is anti-viral and anti-plasmid defense.",General
is self-reported habitual short sleep duration associated with endothelial fibrinolytic dysfunction in men : a preliminary report?,"habitual short sleep duration is associated with increased cardiovascular disease morbidity and mortality resulting from atherothrombotic events. the mechanisms responsible for this heightened cardiovascular risk are not fully understood. the capacity of the endothelium to release tissue-type plasminogen activator (t-pa), the primary activator of the fibrinolytic system, is a key endogenous defense mechanism against intravascular fibrin deposition and thrombosis. we tested the hypothesis that endothelial t-pa release is impaired in adults who sleep less than 7 h/night compared with adults who sleep between 7 and 9 h/night. thirty adult men were stratified based on average nightly habitual sleep duration: 15 with normal sleep duration (age: 55 2 years; sleep duration: 7.6 h/night) and 15 with short sleep duration (56 2 years; 6.1 h/night). net endothelial release of t-pa was determined, in vivo, in response to intra-brachial infusions of bradykinin (12.5-50.0 ng/100 ml tissue/min) and sodium nitroprusside (1.0-4.0 g/100 ml tissue/min). net endothelial t-pa release to bradykinin was significantly lower (25) in the short (from 0.4 0.8 to 41.5 4.3 ng/100 ml tissue/min) compared with the normal (0.4 0.5 to 64.9 6.7 ng/100 ml/tissue/min) sleep duration group. furthermore, there was an inverse relation between average nightly sleep duration and peak t-pa release to bradykinin (r 0.36, p 0.05).",endothelial t-pa release is impaired in adults who report short habitual sleep duration. impaired endothelial fibrinolytic function may underlie the increased atherothrombotic risk associated with chronic short sleep.,Symptoms
does short-term exposure to low concentrations of thapsigargin inhibit replication of cultured human vascular smooth muscle cells?,"central to the pathophysiology of stenosis following balloon angioplasty and arterial bypass surgery is proliferation of vascular smooth muscle cells (vsmcs). to investigate the role of calcium (ca2) in vsmc proliferation, the effect of thapsigargin, ca2 ionophore a23187, ionomycin, cyclopiazonic acid and di-tert-butylhydroquinone (all of which raise intracellular ca2 levels) on the proliferation of cultured human vsmcs was observed. cultured vsmcs from human saphenous vein were treated with calcium-modulating drugs and proliferation was assessed by determining 3hthymidine and 5-bromo-2'-deoxyuridine incorporation and cell number. over a 48-h exposure, thapsigargin inhibited vsmc replication (median 50 per cent maximal inhibitory concentration 2 nmol/l) whereas the other drugs were much less effective. short-term exposure (5, 10, 30 and 60 min) to thapsigargin elicited a significant dose-dependent inhibition of vsmc replication whereas, again, the other drugs were without significant effect.",thapsigargin-sensitive intracellular ca2 pools play a key role in controlling vsmc proliferation and specialized means of administering thapsigargin may constitute a possible approach to preventing stenosis.,Medication
does personal protection by long-lasting insecticidal hammocks against the bite of forest malaria vectors?,"in southeast asia, malaria vectors bite outside the houses before bedtime, and forest dwellers rarely use insecticide-treated nets (itns). thus, we tested the protection of long-lasting insecticidal hammocks (llih) using olyset technology against exophagic vectors in two forest villages of cambodia. in each village, we conducted two entomological surveys (middle and end of the rainy season), each lasting 10 consecutive nights. these comprised human landing collections during the whole night by people sitting outside in the hammocks. five households were selected per village, and for each household, two fixed positions were allocated: one for the control and one for the treated hammock. in total, 6449 mosquitoes were collected from control hammocks compared to 4481 in treated hammocks. personal protection conferred by the hammocks was 46 (ci 95: 35-55) against the bites of anopheles minimus. a significant reduction of an. dirus bites (46 ci 95: 25-62) was only observed at the end of the rainy season. an. maculatus and culicines bites were only reduced in one of the two study sites.","even if this llih is not inducing full protection against the bites of malaria vectors, it could prove effective in protecting forest workers and villagers before sleeping time. llih can be an additional and valuable tool in eliminating artemisinin-resistant malaria in the region.",Treatment
does thoracic epidural bupivacaine attenuate supraventricular tachyarrhythmias after pulmonary resection?,"supraventricular tachyarrhythmias after pulmonary surgery are well described. some investigators suggest that tachyarrhythmias after thoracic operations may result from the relative sympathotonic status produced by injury to the cardiac parasympathetic nerves. we examined whether postoperative thoracic sympathetic blockade by thoracic epidural bupivacaine might reduce the tachyarrhythmias after pulmonary resection. fifty patients with lung cancer were randomized to receive epidural bupivacaine (group b) or epidural morphine (group m). patients in group b were given 6 to 10 ml of 0.25 bupivacaine epidurally, followed by epidural infusion at 3 to 5 ml/h for 3 days, and patients in group m were given 2 to 3 mg morphine epidurally, followed by morphine infusion at a rate of 0.2 mg/h. tachyarrhythmias were diagnosed by using the continuous heart rate trend and arrhythmia trend with a central monitoring system. postoperative analgesia was not statistically different between groups. however, the incidence of postoperative tachyarrhythmias in group b was significantly less than in group m (1 of 23 vs 7 of 25, p 0.0497, fisher's exact test). the continuous infusion of thoracic epidural bupivacaine can reduce supraventricular tachyarrhythmias compared with epidural morphine infusion, presumably because of attenuation of the sympathotonic status after pulmonary resection.",we examined whether postoperative thoracic sympathetic blockade by thoracic epidural bupivacaine after pulmonary resection might reduce the tachyarrhythmias that may result from the relative sympathotonic status produced by injury to the cardiac parasympathetic nerves. the continuous infusion of thoracic epidural bupivacaine was shown to reduce supraventricular tachyarrhythmias.,Treatment
does transfer of the interleukin-1 receptor antagonist gene into rat liver abrogate hepatic ischemia-reperfusion injury?,"the anti-inflammatory cytokine interleukin-1 receptor antagonist (il-1ra) is known to reduce hepatic ischemia-reperfusion injury. therefore, we wished to examine the effect of il-1ra gene delivery into the rat liver on hepatic ischemia-reperfusion injury. il-1ra cdna was delivered into the rat liver by a single injection of the transgene vector into the portal vein using either the plasmid-cationic liposome or the recombinant adenoviral vector. at 24 hours after the gene delivery, rats were subjected to partial liver ischemia for 90 minutes followed by reperfusion. liver tissue and serum samples were taken at 180 minutes of reperfusion, and the degree of the liver injury as well as the expression level of pro-inflammatory cytokines in the serum and tissue were investigated. in addition, we assessed the effect of il-1ra gene delivery on the 7-day survival rate when the nonischemic liver lobe was partially excised immediately following reperfusion. in both cases of delivery methods, gene transfer of il-1ra resulted in significant elevation of serum il-1ra concentration, which reached maximal levels at 24 hours following the delivery. however, the highest serum concentration with the adenoviral vector was 1,000-fold of that in the liposome-treated animals. in the il-1ra delivered rats, liver damage, as well as production of pro-inflammatory cytokines, at 180 minutes of reperfusion was significantly reduced in a concentration-dependent manner of the circulating il-1ra protein. rats subjected to the adenoviral vector gene delivery had higher 7-day survival rates compared with control animals.",il-1ra gene delivery into the liver may be of therapeutic use for abrogating hepatic ischemia-reperfusion injury after transplantation.,Medication
does mucous fistula refeeding decrease parenteral nutrition exposure in postsurgical premature neonates?,"premature neonates can develop intraabdominal conditions requiring emergent bowel resection and enterostomy. parenteral nutrition (pn) is often required, but results in cholestasis. mucous fistula refeeding allows for functional restoration of continuity. we sought to determine the effect of refeeding on nutrition intake, pn dependence, and pn associated hepatotoxicity while evaluating the safety of this practice. a retrospective review of neonates who underwent bowel resection and small bowel enterostomy with or without mucous fistula over 2years was undertaken. patients who underwent mucous fistula refeeding (rf) were compared to those who did not (ost). primary outcomes included days from surgery to discontinuation of pn and goal enteral feeds, and total days on pn. secondary outcomes were related to pn hepatotoxicity. thirteen rf and eleven ost were identified. there were no significant differences among markers of critical illness (p0.20). in the interoperative period, rf patients reached goal enteral feeds earlier than ost patients (median 28 versus 43days; p0.03) and were able to have pn discontinued earlier (median 25 versus 41days; p0.04). following anastomosis, the magnitude of effect was more pronounced, with rf patients reaching goal enteral feeds earlier than ost patients (median 7.5 versus 20days; p0.001) and having pn discontinued sooner (30.5 versus 48days; p0.001).",rf neonates reached goal feeds and were able to be weaned from pn sooner than ost patients. a prospective multicenter trial of refeeding is needed to define the benefits and potential side effects of refeeding in a larger patient population in varied care environments.,Prevention
do why londoners have low death rates from ischaemic heart disease and stroke?,"to explain the low death rates from cardiovascular disease in london. london and the other counties of england and wales. women living in london during 1901-10 and people in london dying during 1968-78. at the beginning of the twentieth century young women aged 15-34 in london had remarkably low death rates, largely because of low rates for tuberculosis and other infectious diseases and low mortality during childbirth. their low death rates contrasted with the high rates in girls under 15 years.","large numbers of young women had migrated into london from agricultural counties in southern england and went into domestic service, where the diet was usually very good. recent findings suggest that a mother's nutrition and health has a major effect on the risk of cardiovascular disease in the next generation. the low cardiovascular mortality in london is consistent with this, and contrasts with the high mortality from other common diseases.",General
does overexpression of matrix metalloproteinase-9 promote intravascular thrombus formation in porcine coronary arteries in vivo?,"matrix metalloproteinases (mmps) cause extracellular matrix degradation and may be involved in the rupture of atherosclerotic plaques by degrading fibrous cap, resulting in the intravascular thrombus formation. here we examined whether local overexpression of mmp-9 alters the characteristics of arteriosclerotic vascular lesions and promotes thrombosis after balloon injury in porcine coronary arteries in vivo. balloon angioplasty was performed in the left coronary arteries followed by injection of adenovirus vector solution encoding either mmp-9 or beta-galactosidase (beta-gal) gene into the injured coronary arteries. three weeks after the gene transfer, histological examination demonstrated that macroscopic intravascular thrombus formation was noted at the mmp-9-transfected site but not at the beta-gal-transfected site. microscopic intramural thrombus area was significantly larger at the mmp-9-transfected site as compared to the beta-gal-transfected site. co-transfection of tissue inhibitor of metalloproteinase-1 (timp-1) with mmp-9 prevented the intravascular thrombus formation in vivo. western blot analysis revealed the reduced expression of intact tissue factor pathway inhibitor-1 and the increased tissue factor (tf) expression at the mmp-9-transfected sites.",these results provide the first in vivo evidence that overexpression of mmp-9 promotes intravascular thrombus formation after balloon injury due in part to the activation of tf-mediated coagulation cascade.,Medication
do serum liver fatty acid binding protein levels correlate positively with obesity and insulin resistance in chinese young adults?,"liver fatty acid-binding protein (fabp1) plays an inconclusive role in adiposity. we investigated the association of serum fabp1 levels with obesity and insulin resistance in chinese young people under 30 years old. cross-sectional analysis including 200 obese and 172 normal-weight subjects matched for age and sex, anthropometric measurements were performed and serum fabp1 and biochemical characteristics were measured. insulin resistance was determined by homeostasis model assessment of insulin resistance (homa-ir) and by the insulin sensitivity index (s(i)) derived from bergman's minimal model. fabp1 levels in obese subjects were significantly higher than those in normal-weight subjects (p0.001) and the significance remained after adjustment for age, gender, alanine and aspartate aminotransferases (p0.001). serum fabp1 levels were significantly correlated with many metabolic-related parameters, with bmi and triglycerides as the independent determinants. fabp1 levels remained an independent risk factor of insulin resistance assessed by binary s(i) (or 1.868 per sd unit, 95 ci 1.035-3.373, p 0.038) after adjustment for age, sex, bmi, waist circumference, systolic blood pressure, serum triacylglycerol, total cholesterol, hdl- and ldl-cholesterol,. fabp1 levels were also elevated with an increasing number of components of the metabolic syndrome (p for trend 0.001). multiple regression modeling for the mets and its components demonstrated that hypertriglyceridemia and low hdl-cholesterol were significantly correlated to serum fabp1 levels.",serum fabp1 correlates positively with obesity and insulin resistance in chinese young adults. our data supports the fact that fabp1 might be an important mediator participating in fatty acid metabolism and energy balance.,Prevention
is tissue hemoglobin monitoring unable to follow variations of arterial hemoglobin during transitions from pulsatile to constant flow in cardiac surgery?,"to test whether the variations of tissue hemoglobin concentration (thb) measured by the fore-sight(tm) cerebral oximeter can accurately detect changes in arterial hemoglobin concentration (ahb) before, during, and after cardiopulmonary bypass. a prospective clinical study. cardiac surgery operating room. thirty patients scheduled for cardiac surgery. tissue hemoglobin concentration (thb) was recorded continuously via 2 sensors applied on the forehead and connected to the cerebral oximeter. arterial hemoglobin concentration (ahb) was measured in a hematology analyzer laboratory. hemodynamic and respiratory parameters as well as epidemiologic data also were noted. data were collected at 3 perioperative times: after induction of anesthesia, 10 minutes after cardioplegia, and at the end of the surgery. ninety pairs of data were collected. the coefficient of linear regression between thb and ahb was 0.4 (p0.001). after exclusion of hb variations5, the trending ability of thb to predict ahb was 87. however, the bland and altman plot graph for thb and ahb showed major limits of agreement (2.4 times the standard deviation). central venous pressure and carbon dioxide tension were linked independently and positively with thb (p 0.03).","continuous monitoring of thb cannot accurately track variations of ahb during the transition from pulsatile to continuous flow and vice versa in cardiac surgery. local hemodynamic factors such as paco2 and vasodilation significantly impact thb. in this setting, thb monitoring should not be used to guide eventual blood transfusion management.",Treatment
do plethysmographic dynamic indices predict fluid responsiveness in septic ventilated patients?,"in septic patients, reliable non-invasive predictors of fluid responsiveness are needed. we hypothesised that the respiratory changes in the amplitude of the plethysmographic pulse wave (deltap(plet)) would allow the prediction of changes in cardiac index following volume administration in mechanically ventilated septic patients. prospective clinical investigation. an 11-bed hospital medical intensive care unit. twenty-three deeply sedated septic patients mechanically ventilated with tidal volume or8 ml/kg and equipped with an arterial catheter and a pulse oximetry plethysmographic sensor. respiratory changes in pulse pressure (deltapp), deltap(plet) and cardiac index (transthoracic doppler echocardiography) were determined before and after volume infusion of colloids (8 ml/kg). twenty-eight volume challenges were performed in 23 patients. before volume expansion, deltapp correlated with deltap(plet) (r2 0.71, p0.001). changes in cardiac index after volume expansion significantly (p0.001) correlated with baseline deltapp (r2 0.76) and deltap(plet) (r2 0.50). the patients were defined as responders to fluid challenge when cardiac index increased by at least 15 after the fluid challenge. such an event occurred 18 times. before volume challenge, a deltapp value of 12 and a deltap(plet) value of 14 allowed discrimination between responders and non-responders with sensitivity of 100 and 94 respectively and specificity of 70 and 80 respectively. comparison of areas under the receiver operator characteristic curves showed that deltapp and deltap(plet) predicted similarly fluid responsiveness.",the present study found deltap(plet) to be as accurate as deltapp for predicting fluid responsiveness in mechanically ventilated septic patients.,Medication
do diarrhea- and constipation-predominant ibs patients differ in postprandial autonomic and cortisol responses?,"as the primary link between brain and gut, autonomic and endocrine dysfunction may play a role in the pathophysiology of the irritable bowel syndrome (ibs). the aim of this study was to assess autonomic, endocrine, and symptomatic responses to food intake in diarrhea-predominant and constipation-predominant ibs patients, compared to normals. twelve women with diarrhea-predominant or alternating ibs (ibs-d), 12 women with constipation predominant ibs (ibs-c), and 20 healthy women participated. gi symptoms, saliva cortisol concentration, heart rate, and heart rate variability were assessed at baseline and after a meal. spectral analysis of heart rate variability was used as a measure of the sympathovagal regulation of the heart rate. both groups of ibs patients showed a significant postprandial increase in gi symptoms. ibs-d showed a significant increase in the low frequency/high frequency band ratio and a decrease in the high frequency band power during the first postmeal period, which was significantly different, not only from controls, but also from ibs-c. ibs-d also showed a significant postprandial increase in cortisol, which was not evident in controls or ibs-c. there was a significant correlation between the vagal response and the postprandial increase in gi symptoms in ibs-d (r 0.6, p 0.05).","these findings support the notion that the ibs symptom groups are characterized by different physiological responses to visceral stimuli, and point to a role of autonomic pathways in ibs symptomatology.",Symptoms
are thiazolidione derivatives targeting the histidine kinase yycg effective against both planktonic and biofilm-associated staphylococcus epidermidis?,"to evaluate the efficacies of six derivatives of compound 2, a novel yycg histidine kinase inhibitor with the thiazolidione core structure in the treatment of medical device-related biofilm infections. the minimal inhibitory concentration (mic) of the derivatives was determined using the macrodilution broth method, and the minimal bactericidal concentration (mbc) was obtained via sub-culturing 100 l from each negative tube from the mic assay onto drug-free mueller-hinton agar plates. biofilm-killing effect for immature (6 h-old) biofilms was examined using a semiquantitative plate assay, and the effect on mature (24 h-old) biofilms was observed under a confocal laser scanning microscope (clsm). the derivatives potently suppressed the growth of staphylococcus epidermidis. the mic values of the derivatives h2-10, h2-12, h2-20, h2-29, h2-27, and h2-28 on s epidermidis atcc 35984 were 24.3, 6.5, 6.2, 3.3, 3.1, and 1.5 g/ml, respectively. the mbc values of these derivatives were 48.6, 52.2, 12.4, 52.6, 12.4, and 6.2 g/ml, respectively. the derivatives killed all bacteria in immature (6 h-old) biofilms and eliminated the biofilm proliferation. the derivatives also displayed strong bactericidal activities toward cells in mature (24 h-old) biofilms, whereas they showed low cytotoxicity and hemolytic activity toward vero cells and human erythrocytes.",the bactericidal and biofilm-killing activities of the new anti-yycg compounds were significantly better than the parent compound 2.,Medication
do clinical predictors of mechanical ventilation in fisher/guillain-barr overlap syndrome?,"some patients with fisher syndrome (fs) developed subsequent descending tetraparesis (fisher/guillain-barr overlapping syndrome: fs/gbs). the assumption is that such descending progression may frequently lead to respiratory failure. to investigate whether patients with fs/gbs more often require artificial ventilation than those with typical gbs and which clinical and serological findings are useful predictors. medical records were reviewed of patients who had acute ophthalmoplegia, ataxia and areflexia, as well as subsequent tetraparesis with monophasic course. forty-five patients fulfilled the fs/gbs criteria. clinical and serological features were analysed, and clinical predictors of mechanical ventilation were investigated. fs/gbs patients more frequently required mechanical ventilation than did gbs patients (24 vs 10, p 0.04). the former also needed artificial ventilation earlier than the latter (p 0.03), but none of the fs patients required it. as the initial symptom, ventilated fs/gbs patients more frequently showed titubation than non-ventilated patients (55 vs 18, p 0.04). during the course of the illness, descending tetraparesis was more common in 11 ventilated fs/gbs patients than in the other 34 non-ventilated patients (64 vs 21, p 0.02). the need for artificial ventilation was not associated with anti-gq1b igg antibodies, monospecific anti-gt1a igg antibodies or igg antibodies to various ganglioside complexes.",fs/gbs patients significantly needed mechanical ventilation more often. such patients showing titubation and descending tetraparesis need to be carefully monitored as the illness progresses because those clinical features are helpful predictors of respiratory failure.,Symptoms
does the analgesic agent tapentadol inhibit calcitonin gene-related peptide release from isolated rat brainstem via a serotonergic mechanism?,"in this study we tested the hypothesis that tapentadol inhibits ggrp release from the rat brainstem through a mechanism mediated by the inhibition of na reuptake; as a second alternative hypothesis, we investigated whether tapentadol inhibits ggrp release via the inhibition of 5-ht reuptake. rat brainstems were explanted and incubated in short-term experiments. cgrp released in the incubation medium was taken as a marker of cgrp release from the central terminals of trigeminal neurons within the brainstem. cgrp levels were measured by radioimmunoassay under basal conditions or in the presence of tapentadol; na, 5-ht, clonidine, yohimbine and ondansetron were used as pharmacological tools to investigate the action mechanism of tapentadol. the 2-antagonist yohimbine failed to counteract the effects of tapentadol. moreover, neither na nor the 2-agonist clonidine per se inhibited k()-stimulated cgrp release, thereby indicating that the effects of tapentadol are nor mediated through the block of na reuptake. further experiments showed that 5-ht and tramadol, which inhibits both na and 5-ht reuptake, significantly reduced k()-stimulated cgrp release. moreover, the 5-ht3 antagonist ondansetron was able to counteract the effects of tapentadol in this system.",this study provided pharmacological evidence that tapentadol inhibits stimulated cgrp release from the rat brainstem in vitro through a mechanism involving an increase in 5-ht levels in the system and the subsequent activation of 5-ht3 receptors.,Medication
does oxidative stress regulate left ventricular pde5 expression in the failing heart?,"phosphodiesterase type 5 (pde5) inhibition has been shown to exert profound beneficial effects in the failing heart, suggesting a significant role for pde5 in the development of congestive heart failure (chf). the purpose of this study is to test the hypothesis that oxidative stress causes increased pde5 expression in cardiac myocytes and that increased pde5 contributes to the development of chf. myocardial pde5 expression and cellular distribution were determined in left ventricular samples from patients with end-stage chf and normal donors and from mice after transverse aortic constriction (tac)-induced chf. compared with donor human hearts, myocardial pde5 protein was increased approximately equal 4.5-fold in chf samples, and the increase of myocardial pde5 expression was significantly correlated with myocardial oxidative stress markers 3'-nitrotyrosine or 4-hydroxynonenal expression (p0.05). histological examination demonstrated that pde5 was mainly expressed in vascular smooth muscle in normal donor hearts, but its expression was increased in both cardiac myocytes and vascular smooth muscle of chf hearts. myocardial pde5 protein content and activity also increased in mice after tac-induced chf (p0.05). when the superoxide dismutase (sod) mimetic m40401 was administered to attenuate oxidative stress, the increased pde5 protein and activity caused by tac was blunted, and the hearts were protected against left ventricular hypertrophy and chf. conversely, increased myocardial oxidative stress in superoxide dismutase 3 knockout mice caused a greater increase of pde5 expression and chf after tac. in addition, administration of sildenafil to inhibit pde5 attenuated tac-induced myocardial oxidative stress, pde5 expression, and chf.",myocardial oxidative stress increases pde5 expression in the failing heart. reducing oxidative stress by treatment with m40401 attenuated cardiomyocyte pde5 expression. this and selective inhibition of pde5 protected the heart against pressure overload-induced left ventricular hypertrophy and chf.,Medication
does cardiopulmonary resuscitation performed by bystanders increase adverse effects as assessed by chest radiography?,"important adverse effects of bystander cardiopulmonary resuscitation (cpr) are well known. we describe the number of nonmedical professional cpr-related complications in patients surviving cardiac arrest, as assessed by chest radiograph. within 2 yr, all consecutive patients admitted to the department of emergency medicine at a university hospital who had a witnessed, nontraumatic, normothermic cardiac arrest were studied. radiologically evaluated adverse effects were compared with mann-whitney u-tests between patients who received bystander basic life support (bystander group) and patients who did not receive bystander basic life support before advanced life support was started (als group). for assessment of bystander cpr-associated complications, chest radiographs were used. of 224 patients, 173 were eligible. the median age was 58 yr (interquartile range, 51-71 yr), and 126 patients (73) were men. the incidence of adverse effects associated with assisted-ventilation maneuvers and external chest compressions did not differ significantly between groups (severe gastric insufflation, 17 vs 18 between the bystander group n 59 and the als group n 96, respectively; suspicion of aspiration, 22 vs 17, respectively; soft tissue emphysema, 2 vs 1, respectively; and serial rib fractures, 8 vs 8, respectively). cpr administered by nonmedical personnel did not increase the number of life support-related adverse effects in patients surviving cardiac arrest as assessed by means of chest radiograph on admission.","complications related to cardiopulmonary bypass (cpr) are not increased when cpr is administered by nonmedical personnel, as assessed by chest radiograph. these data may be valuable in motivating lay people to perform basic life support.",Medication
does inhibition of calcium-independent phospholipase a2 activity in rat hippocampus impair acquisition of short- and long-term memory?,"phospholipase a(2) (pla(2)) is a family of enzymes that cleave membrane phospholipids generating important lipid mediators in signal transduction. in rat hippocampal slices, both intracellular cytosolic ca(2)-dependent pla(2) (cpla(2)) and ca(2)-independent pla(2) (ipla(2)) have been implicated in mechanisms of synaptic plasticity underlying memory processes. in mice, intraperitoneal injections of a selective ipla(2) inhibitor impaired spatial learning. accordingly, reduced cpla(2) and ipla(2) activities were found in postmortem hippocampus of patients with alzheimer's disease. this study investigates the effects of injections of pla(2) inhibitors directly into rat hippocampus on the acquisition of short-term (stm) and long-term memory (ltm) of a one-trial step-down inhibitory avoidance (ia) task. wistar rats were bilaterally implanted with cannulae in the ca1 region of the dorsal hippocampus. after surgery, the rats received bilateral injections of a vehicle, or of dual cpla(2) and ipla(2) inhibitors (mafp or pacocf(3)), or a selective ipla(2) inhibitor (bromoenol lactone) before training in ia. the animals were tested 1.5 h (for stm) and 24 h (for ltm) after training. significant inhibition of ipla(2) activity in rat hippocampus impaired acquisition of stm and ltm. memory impairment did not result from neuronal death after ipla(2) inhibition. moreover, ia training per se increased significantly hippocampal pla(2) activity.",the present results suggest a functional effect of hippocampal pla(2) on the neurochemistry of memory acquisition and support the hypothesis that reduced pla(2) activity may contribute to memory impairment in alzheimer's disease.,Medication
do treatment of a resistant port-wine stain with a new variable pulse-duration pulsed-dye laser?,"because of the heterogeneity in port-wine stains, a number of them prove resistant to treatment with the pulsed-dye laser (pdl). a new variable pulse-duration pdl improves a refractory port-wine stain. a 26-year-old man with a congenital port-wine stain underwent eight treatments with the 1.5-ms pulse-duration pdl resulting in minimal improvement. a single treatment was then administered with the 3-ms pulse-duration pdl. initial results of treatment with the 3-ms pulse-duration pdl on this patient's port-wine stain show dramatic clearance in areas previously treated with significantly higher fluences, an identical spot size, but with a pulse duration half as long.",vessel heterogeneity may require changing pulse durations once a port-wine stain or a portion of a port-wine stain becomes refractory to given pulse-duration.,Treatment
are th17 cells and activated dendritic cells increased in vitiligo lesions?,"vitiligo is a common skin disorder, characterized by progressive skin de-pigmentation due to the loss of cutaneous melanocytes. the exact cause of melanocyte loss remains unclear, but a large number of observations have pointed to the important role of cellular immunity in vitiligo pathogenesis. in this study, we characterized t cell and inflammation-related dermal dendritic cell (dc) subsets in pigmented non-lesional, leading edge and depigmented lesional vitiligo skin. by immunohistochemistry staining, we observed enhanced populations of cd11c myeloid dermal dcs and cd207 langerhans cells in leading edge vitiligo biopsies. dc-lamp and cd1c sub-populations of dermal dcs expanded significantly in leading edge and lesional vitiligo skin. we also detected elevated tissue mrna levels of il-17a in leading edge skin biopsies of vitiligo patients, as well as il-17a positive t cells by immunohistochemistry and immunofluorescence. langerhans cells with activated inflammasomes were also noted in lesional vitiligo skin, along with increased il-1 mrna, which suggest the potential of langerhans cells to drive th17 activation in vitiligo.","these studies provided direct tissue evidence that implicates active th17 cells in vitiligo skin lesions. we characterized new cellular immune elements, in the active margins of vitiligo lesions (e.g. populations of epidermal and dermal dendritic cells subsets), which could potentially drive the inflammatory responses.",General
does comparative genomic analysis reveal evidence of two novel vibrio species closely related to v. cholerae?,"in recent years genome sequencing has been used to characterize new bacterial species, a method of analysis available as a result of improved methodology and reduced cost. included in a constantly expanding list of vibrio species are several that have been reclassified as novel members of the vibrionaceae. the description of two putative new vibrio species, vibrio sp. rc341 and vibrio sp. rc586 for which we propose the names v. metecus and v. parilis, respectively, previously characterized as non-toxigenic environmental variants of v. cholerae is presented in this study. based on results of whole-genome average nucleotide identity (ani), average amino acid identity (aai), rpob similarity, mlsa, and phylogenetic analysis, the new species are concluded to be phylogenetically closely related to v. cholerae and v. mimicus. vibrio sp. rc341 and vibrio sp. rc586 demonstrate features characteristic of v. cholerae and v. mimicus, respectively, on differential and selective media, but their genomes show a 12 to 15 divergence (88 to 85 ani and 92 to 91 aai) compared to the sequences of v. cholerae and v. mimicus genomes (ani 95 and aai 96 indicative of separate species). vibrio sp. rc341 and vibrio sp. rc586 share 2104 orfs (59) and 2058 orfs (56) with the published core genome of v. cholerae and 2956 (82) and 3048 orfs (84) with v. mimicus mb-451, respectively. the novel species share 2926 orfs with each other (81 vibrio sp. rc341 and 81 vibrio sp. rc586). virulence-associated factors and genomic islands of v. cholerae and v. mimicus, including vsp-i and ii, were found in these environmental vibrio spp.","results of this analysis demonstrate these two environmental vibrios, previously characterized as variant v. cholerae strains, are new species which have evolved from ancestral lineages of the v. cholerae and v. mimicus clade. the presence of conserved integration loci for genomic islands as well as evidence of horizontal gene transfer between these two new species, v. cholerae, and v. mimicus suggests genomic islands and virulence factors are transferred between these species.",Diagnosis
is low health literacy associated with hiv test acceptance?,"the centers for disease control and prevention has proposed increasing the proportion of people who learn their hiv serostatus. the health care setting represents a logical site to accomplish this goal. however, little is known about factors that determine acceptability of hiv testing in health care settings, particularly patients' health literacy. to evaluate the association between patients' health literacy and acceptance of hiv testing among individuals at an urgent care center (ucc). as part of a prospective study that sought to increase hiv testing at a ucc located in an inner-city hospital serving an indigent population, we surveyed patients who had been offered an hiv test by their providers and had accepted or refused testing. pretest counseling was provided using a low-literacy brochure given to patients upon registration into the clinic. we measured health literacy level using the rapid estimate of adult literacy in medicine (realm) scale. three hundred seventy-two patients were enrolled in the study. in univariate analysis, no statistically significant difference between hiv test acceptors or refusers was found for gender, race/ethnicity, marital status, income, type of health insurance, educational level, or type of test offered. acceptors were more likely to have a low literacy level (odds ratio or, 1.763; 95 confidence interval ci, 1.084 to 2.866) and be less than 40 years old (or, 1.639; 95 ci, 1.085 to 2.475). in multivariate analysis, low health literacy was shown to be a predictor of hiv test acceptance controlling for age and education (or, 2.017; 95 ci, 1.190 to 3.418).","low health literacy was shown to be a predictor of hiv test acceptance. patients presenting to a ucc with poorer health literacy appear more willing to comply with health care providers' recommendations to undergo hiv testing than those with adequate health literacy when an ""opt-out"" strategy combined with a low-literacy brochure is used.",Prevention
does obesity increase complication rate of percutaneous epicardial access?,"percutaneous epicardial access for ablative therapies is an increasingly common technique utilized for refractory ventricular arrhythmias. there are, however few known data on obesity and complication rates associated with this procedure. we retrospectively reviewed the charts of subjects undergoing epicardial access at mayo clinic between january 2004 and june 2013. baseline clinical and echocardiographic data were collected for each subject, who was then classified into body mass index (bmi) categories as underweight, normal weight, overweight, and obese based on a bmi of 18.5, 18.5-24.99, 25-29.99, and 30, respectively. events and complications were recorded, and procedural and clinical success rates were determined. there was no statistically significant difference in access approach, procedural or clinical outcomes, or complications among the bmi categories. note that 95.1, 91.7, and 93.1 derived procedural success among the normal weight, overweight, and obese categories, respectively (p value 0.81). similarly, there was no difference in clinical outcomes with success rates of 68.3, 66.7, and 75.9 between the respective groups (p value 0.54). at 5 years, there was a trend toward increased mortality among obese individuals (28.8) compared to normal weight (8.8) and overweight (9.8) patients (p value 0.139).","percutaneous epicardial access, mapping, and ablation can be performed in obese individuals with similar outcomes to those of lower weight category. obesity should not preclude the use of percutaneous epicardial access when clinically indicated.",Prevention
do serum uric acid levels show a ' j-shaped ' association with all-cause mortality in haemodialysis patients?,"although elevated serum levels of uric acid are common in patients with kidney disease or in those receiving maintenance dialysis therapy, the clinical impact of uric acid on mortality in haemodialysis (hd) patients remains unclear. this work was designed to explore the predictive value of serum uric acid levels on all-cause mortality of hd patients. we retrospectively analysed mortality rates in 146 chronic hd patients that were treated with hd three times per week at our hd unit for a period of one full year. the analysed parameters included demographic characteristics, aetiology of end-stage renal disease, co-morbid conditions, duration (at least 1 year) and delivered dose of hd, normalized protein catabolic rate, serum albumin concentration, haematocrit, serum uric acid (ua) levels and other laboratory parameters. a multivariate cox proportional hazards model, which included adjustment for the above factors, was applied to identify the predictive value of ua levels on patient mortality. a cox proportional hazards model revealed that decreased serum albumin, underlying diabetic nephropathy (dmn) and ua groups ( or 80th percentiles; p 0.016) were all significant, independent predictors of all-cause mortality in hd patients. the hazard ratios of death were: serum albumin (per 0.5 g/dl decrease), 3.10 95 confidence interval (95 ci), 1.80-5.34, p or 80th percentile, 5.67 (95 ci, 1.71-18.78, p 0.004).",these preliminary observations suggest that hd patients in the lowest and highest quintiles of ua levels would face higher risk of mortality. further studies with larger sample sizes will be needed to confirm these findings.,Treatment
does improved perioperative blood pressure control lead to reduced hospital costs?,"perioperative hypertension affects 80 of cardiac surgery patients and is associated with an increased risk of complications. to determine the relationship between perioperative blood pressure (bp) control and hospital costs for cardiac surgery in the united states (us) and estimate the potential cost reductions associated with effective therapies. the analysis estimated hospitalization costs (2011 us dollars (usd)) for cardiac surgery when bp was controlled with intravenous (iv) antihypertensives. patient characteristics, hospital length of stay, and clinical event rates during the initial hospitalization and post-discharge 30 days after study drug infusion were based on the eclipse (evaluation of clevidipine in the perioperative treatment of hypertension assessing safety events) trials. these clinical trial data were combined with data from the massachusetts acute hospital case mix database 2007 - 2009 (ma case mix database) to estimate total hospitalization costs. effective perioperative bp control in patients requiring iv antihypertensives was associated with a 7 decrease in hospital costs compared with less effective bp control. reductions in total hospital costs associated with clevidipine versus other iv antihypertensives averaged 394 per patient overall. cost savings with clevidipine exceeded 500 per patient versus sodium nitroprusside and nitroglycerin, but only 22 compared to nicardipine.","improved perioperative bp control may reduce hospital costs. given the low cost of iv antihypertensives, the total hospital cost reductions may offset any incremental cost increases associated with newer, more effective therapies.",Treatment
do they think surgery is just a quick fix ''?,"to prevent weight regain, patients undergoing weight loss surgery are encouraged to change their exercise and dietary habits. building on previous research, the aim of this study was to explore women's experiences of changing exercise habits - focusing on women participating in a group based rehabilitation program including surgical as well as non-surgical participants. based on interviews with the 11 women included in this study, as well as participant observation, two themes were identified; 1) pushing ones tolerance limits, and 2) rebutting the ""quick fix"" fallacy. taken together, the findings showcase how being a part of this mixed group involved having to relate to social stigmas, as well as notions regarding successful and non-successful surgical outcomes. although such notions may be useful in identifying potential challenges related to changing exercise habits, they do not illuminate the complexity of undergoing such changes following weight loss surgery.","the findings point to the need of acknowledging patients' own exceriences to determine how successful they are after surgery. given the findings, i argue for the need to reconsider the notion of success in relation to group based interventions.",Treatment
"is fibulin-1 required during cardiac ventricular morphogenesis for versican cleavage , suppression of erbb2 and erk1/2 activation , and to attenuate trabecular cardiomyocyte proliferation?","trabeculation is an integral component of cardiac ventricular morphogenesis and is dependent on the matrix metalloproteinase, adamts1. a substrate of adamts1 is the proteoglycan versican which is expressed in the developing ventricle and which has been implicated in trabeculation. fibulin-1 is a versican and adamts1-binding extracellular matrix protein required for ventricular morphogenesis. here we investigated the involvement of fibulin-1 in adamts1-mediated cleavage of versican in vitro, and the involvement of fibulin-1 in versican cleavage in ventricular morphogenesis. we show that fibulin-1 is a cofactor for adamts1-dependent in vitro cleavage of versican v1, yielding a 70-kda amino-terminal fragment. furthermore, fibulin-1-deficiency in mice was found to cause a significant reduction (90) in ventricular levels of the 70-kda versican v1 cleavage product and a 2-fold increase in trabecular cardiomyocyte proliferation. decreased versican v1 cleavage and augmented trabecular cardiomyocyte proliferation in fibulin-1 null hearts is accompanied by increased ventricular activation of erbb2 and erk1/2. by contrast, versican deficiency was found to lead to decreased cardiomyocyte proliferation and reduced ventricular trabeculation.",we conclude that fibulin-1 regulates versican-dependent events in ventricular morphogenesis by promoting adamts1 cleavage of versican leading to suppression of trabecular cardiomyocyte proliferation mediated by the erbb2-map kinase pathway.,General
do the effect of dressing with fresh kiwifruit on burn wound healing?,"this study was designed to evaluate the wound healing effects of kiwifruit in the treatment of second-degree burn wounds in rats. sixty rats were each randomly assigned to 1 of 3 groups. a deep second-degree burn was created on the lateral flank of each rat with a standard burning procedure in the form of applying a heated plaque. in the control group (group c; n 20) burns were dressed with vaseline sterile gauze after normal saline irrigation. in group s (n 20), the lesions were treated with silver sulfadiazine cream after normal saline irrigation. in the third group (group k; n 20), the burn wounds were dressed with kiwifruit. the dressings were changed twice a day in all groups. the response to treatments was assessed histologically at day 21 postburn and microbiologically on days 7 and 21. macroscopic evaluation was performed every day to determine wound closure rate, measure burn wound area, and investigate macroscopic edema, hyperemia, and epithelialization. histopathologic evaluation included monitoring of epithelialization, vascularization, granulation tissue formation, and inflammatory cell response. on day 21, the wounds in the group k healed completely in comparison to other groups (p .0001). there was significant reduction in wound area size in the group k in all evaluation days as compared with groups s and c (p .0001). microscopic evaluation revealed a high grade of neovascularization in group k lesions in contrast with groups s and c (p .0001). wound infection was dramatically less common in the group k compared with the other 2 groups (p .05).","we suggest that the dramatic antibacterial, debridement, wound contracture, and angiogenic effect of kiwifruit induced a significant wound healing in burn ulcers and might be useful in treating chronic ulcers, such as bedsores.",Treatment
is calcified plaque resorptive status as determined by high-resolution ultrasound predictive of successful conservative management of calcific tendinosis?,"in patients with calcific tendinosis, the morphology of calcified plaques is associated with response to conservative management. we aimed to determine changes in pain and morphology of plaques in patients with calcific tendinosis and non-arc-shaped plaques identified by high-resolution ultrasonography who received only conservative treatment. a total of 33 patients with a mean age of 63.310.3 years were included. pain scores at the time of first and follow-up ultrasound were recorded, and the degree of plaque resolution was calculated. at follow-up, 90.9 (30 of 33) of patients reported improvement in pain, and 84.8 (28 of 33) patient had more than 50 elimination of plaques. most of increased vascularity observed in color doppler ultrasonography during 1st visit disappeared at follow-up.","in patients with calcific tendinosis, non-arc-shaped plaques determined by high-resolution ultrasonography are likely to resolve and conservative management is warranted.",Treatment
does intraoperative endoscopy decrease postoperative complications in laparoscopic roux-en-y gastric bypass?,"leak or stenosis following laparoscopic roux-en-y gastric bypass (lrygb) can lead to a major morbidity. we aim to evaluate whether the routine use of intraoperative endoscopy (ioe) can reduce this morbidity. all cases of lrygb in 2009-2014 were reviewed. in all cases, we perform an ioe. if ioe shows a leak, the area of the leak is re-enforced and ioe is repeated. if the leak persisted, a feeding tube and drains are placed. during the study period, we performed 342 lrygb cases. primary lrygb represented 82 (282/342). average bmi 48 kg/m(2) (range was 35-92) and females represented 76 (261/342). our clinical leak rate was 3/342 (0.88 ) in lrygb (0.4 in primary and 3.3 in revisional lrygb). ioe showed a positive air leak test in six lrygb cases (1.75 ). we were able to achieve a negative leak test after re-enforcement in 5/6 (83 ) cases, and all those patients had no clinical leak. the patient with persistent air leak test had a clinical leak after surgery. ioe was negative in 336 lrygb cases and we had two clinical leaks in this group (0.59 ). our stenosis rate at the gastrojejunostomy was 3/342 (0.88 ). the positive predictive value (ppv) of the performing ioe to detect leaks in lrygb was 75 while the negative predictive value was 99.5 .",routine ioe has led to a change in the operative strategy and could be one reason for our low leak and stenosis in laparoscopic roux-en-y gastric bypass.,Treatment
"is growth hormone effective in treatment of short stature associated with short stature homeobox-containing gene deficiency : two-year results of a randomized , controlled , multicenter trial?","the short stature homeobox-containing gene, shox, located on the distal ends of the x and y chromosomes, encodes a homeodomain transcription factor responsible for a significant proportion of long-bone growth. patients with mutations or deletions of shox, including those with turner syndrome (ts) who are haplo-insufficient for shox, have variable degrees of growth impairment, with or without a spectrum of skeletal anomalies consistent with dyschondrosteosis. our objective was to determine the efficacy of gh in treating short stature associated with short stature homeobox-containing gene deficiency (shox-d). fifty-two prepubertal subjects (24 male, 28 female; age, 3.0-12.3 yr) with a molecularly proven shox gene defect and height below the third percentile for age and gender (or height below the 10th percentile and height velocity below the 25th percentile) were randomized to either a gh-treatment group (n 27) or an untreated control group (n 25) for 2 yr. to compare the gh treatment effect between subjects with shox-d and those with ts, a third study group, 26 patients with ts aged 4.5-11.8 yr, also received gh. between-group comparisons of first-year and second-year height velocity, height sd score, and height gain (cm) were performed using analysis of covariance accounting for diagnosis, sex, and baseline age. the gh-treated shox-d group had a significantly greater first-year height velocity than the untreated control group (mean /- se, 8.7 /- 0.3 vs. 5.2 /- 0.2 cm/yr; p 0.001) and similar first-year height velocity to gh-treated subjects with ts (8.9 /- 0.4 cm/yr; p 0.592). gh-treated subjects also had significantly greater second-year height velocity (7.3 /- 0.2 vs. 5.4 /- 0.2 cm/yr; p 0.001), second-year height sd score (-2.1 /- 0.2 vs.-3.0 /- 0.2; p 0.001) and second-year height gain (16.4 /- 0.4 vs. 10.5 /- 0.4 cm; p 0.001) than untreated subjects.","this large-scale, randomized, multicenter clinical trial in subjects with shox-d demonstrates marked, highly significant, gh-stimulated increases in height velocity and height sds during the 2-yr study period. the efficacy of gh treatment in subjects with shox-d was equivalent to that seen in subjects with ts. we conclude that gh is effective in improving the linear growth of patients with various forms of shox-d.",Treatment
is conventional pituitary irradiation effective in normalising plasma igf-i in patients with acromegaly?,"for patients in whom acromegaly persists despite pituitary surgery, conventional pituitary irradiation represents an additional treatment option. a 30-60 cure rate is described in the literature, but these studies did not utilise strict rules of remission, such as ""safe"" gh levels 2.5 microg/l, and age-adjusted normal igf-i levels. we report the outcome of 41 patients with acromegaly who received pituitary conventional external irradiation. the median follow-up time was 12.8 years (3.7-43.4 years) post-radiotherapy. the median pre-irradiation gh level was 31.0 microg/l (7.0-210 microg/l). information on igf-i levels was only available for 6 patients prior to therapy. utilising strict rules of remission, one-third (14/41) of our patients had normal biochemical parameters, i.e. ""safe"" gh (0.5 microg/l (range 0.2-1.6 microg/l)) and normal age-adjusted igf-i levels (multiple of upper limit of normal range (xuln); 0.45 (0.2-1.0)) at the end of the follow-up period. an additional 9 patients achieved normal levels with adjunctive drug therapy. furthermore, disease activity was reduced in a considerable proportion of the 18 patients who did not achieve normal biochemical levels (gh: 3.6 microg/l (1.9-15.7 microg/l); xuln of igf-i: 1.6 (0.9-2.6)). in retrospect, remission is unlikely in patients who had a gh level greater than 52 microg/l (mean2 s.d. of cured patients) prior to radiotherapy. in addition to the 12 patients with pre-irradiation pituitary functional deficiency, another 11 patients developed symptoms of panhypopituitarism during the 3-year period following irradiation. within a 6-year period, partial pituitary insufficiency was observed in a further 7 patients, thus necessitating hormone substitution treatment.","using strict rules of remission, in our cohort we found both a normalisation of igf-i and safe gh levels in 34 of patients treated for acromegaly with conventional irradiation therapy.",Treatment
does acceleration/ejection time ratio in the fetal pulmonary artery predict fetal lung maturity?,"the aim of this study was to determine whether sonographic fetal pulmonary artery flow velocity waveforms correlate with amniotic fluid biomarkers of fetal lung maturity. we studied women with singleton pregnancies undergoing clinically indicated amniocentesis for fetal lung maturity at yale-new haven hospital. fetal pulmonary artery flow velocity measurements, including systolic/diastolic ratio, pulsatility index, resistance index, and acceleration-time/ejection-time ratio were obtained using spectral doppler ultrasound. pearson's correlation coefficient was used to determine the association between fetal pulmonary artery flow velocity parameters and the lecithin/sphingomyelin ratio. twenty-nine subjects met study criteria. the acceleration-time/ejection-time ratio was inversely correlated with the lecithin/sphingomyelin ratio (r -0.76; p or .001). this relationship was maintained after controlling for potential confounders. other fetal pulmonary artery flow velocity measurements were not associated with the lecithin/sphingomyelin ratio.",there is an inverse correlation between the acceleration-time/ejection-time ratio in the fetal pulmonary artery and the amniotic fluid lecithin/sphingomyelin ratio. this suggests that ultrasound evaluation of fetal pulmonary artery blood flow may be a promising new noninvasive technique to evaluate fetal lung maturity.,Diagnosis
is the virtual reality endourologic simulator realistic and useful for educational purposes?,"to examine the educational value of uro mentor, a virtual reality simulator for endourologic procedures, by establishing its face and content validity. eighty-nine urologists and residents in urology performed a urethrocystoscopy task (bladder inspection, biopsy, and coagulation) or a ureterorenoscopy task (manipulation of a distal ureter stone) using the uro mentor. they completed an evaluation questionnaire about these tasks. questionnaire bias related to task performance on uro mentor was analyzed as well (hawthorne effect). the overall rating of the uro mentor was 7.3 on a 10-point scale (1 poor, 10 excellent). regression analysis showed that ratings were not related to previous experience or task performance using the uro mentor. of all subjects, 25 rated the realism of uro mentor as or3.5 on a five-point scale, and 82 rated its usefulness as an educational tool as or3.5 on a five-point scale. more than 73 of all participants said they would purchase a uro mentor if financial means were available; participants who needed more time to complete the task were less positive in their answers to this question.",uro mentor appears to be a realistic and useful training model for endourologic procedures.,Treatment
does exercise training lead to a reduction of elevated myostatin levels in patients with chronic heart failure?,"in chronic heart failure (chf), cardiac cachexia is often associated with the terminal stage of this disease. in animal studies it has been demonstrated that myostatin, a key regulator of skeletal muscle mass, is elevated in advanced stages of this syndrome. the aim of the present study was to investigate the expression of myostatin in patients with late stage chf (nyha iiib) in comparison to healthy subjects. furthermore the effects of physical exercise on myostatin were analyzed. twenty-four patients were either randomized to a sedentary control group (chf-s) or exercise training (chf-e). at baseline and after 12 weeks mrna and myostatin protein in the peripheral skeletal muscle as well as myostatin serum concentration were measured. furthermore 12 age-matched healthy men were compared to all patients at baseline (hc). chf patients showed a two-fold increase of myostatin mrna (p 0.05) and a 1.7-fold (p 0.01) augmentation of protein content in skeletal muscle compared to healthy subjects. in late-stage chf, exercise training led to a 36 reduction of the mrna and a 23 decrease of the myostatin protein compared to baseline. the serum concentration of myostatin revealed no significant alteration between the groups.","in the skeletal muscle, myostatin increases significantly in the course of chf. the observed effects of a significant reduction of myostatin in skeletal muscle after 12 weeks of exercise training demonstrate the reversibility of molecular changes that might be able to halt the devastating process of muscle wasting in chronic heart failure.",Prevention
does mitochondrial translocation of p53 modulate neuronal fate by preventing differentiation-induced mitochondrial stress?,"apoptosis regulatory proteins, such as p53, play a pivotal role in neural differentiation, through mechanisms independent of cell death. in addition, p53 has been identified as an important regulator of mitochondrial survival response, maintaining mitochondrial dna (mtdna) integrity and oxidative protection. the aim of this study was to determine the role of mitochondrial p53 in organelle damage and neural differentiation. our results show that mitochondrial apoptotic events such as reactive oxygen species production, mitochondrial membrane permeabilization, and cytochrome c release are typical of early-stage mouse neural stem cell differentiation, which occurs 3-18 h after induction of differentiation, with no evidence of cell death. in addition, decreased mtdna content, lipidated lc3 (lc3-ii), colocalization of mitochondria and lc3-ii puncta, and mitochondria-associated parkin are consistent with activation of mitophagy. importantly, at early stages of neural differentiation, p53 was actively translocated to mitochondria and attenuated mitochondrial oxidative stress, cytochrome c release, and mitophagy. forced mitochondrial translocation of p53 increased neurogenic potential and neurite outgrowth.","in conclusion, our results reveal a novel role for mitochondrial p53, which modulates mitochondrial damage and apoptosis-related events in the context of neural differentiation, thus enhancing neuronal fate.",Prevention
"is term labor associated with a core inflammatory response in human fetal membranes , myometrium , and cervix?","identify overlap of the transcriptome of myometrium and cervix in association with human labor. the transcriptional profile of myometrial and cervical biopsies obtained from women in spontaneous labor at term (n 9) and not in labor (n 9) were characterized by affymetrix v2 u133 plus 2 arrays. common canonical pathways and functional groups were identified by ingenuity pathway analysis. one hundred ten genes (false discovery rate 1) were commonly up-regulated by myometrium and cervix in association with labor and 29 genes (false discovery rate 1) down-regulated. fold change in expression of up-regulated genes was strongly correlated; myometrium vs cervix (r 0.51; p .001), with no relationship in down-regulated genes (r 0.26; p .16). canonical pathway analysis established up-regulation of inflammatory pathway signaling, with greatest increases in cellular movement and immune response gene ontology groups.","gestational tissues exhibit a core inflammatory response in association with human parturition, with pathways regulating cellular trafficking dominating.",General
is increase in use of non-invasive ventilation for infants with severe bronchiolitis associated with decline in intubation rates over a decade?,"to redress the paucity of studies evaluating non-invasive respiratory support in bronchiolitis patients. following ethics committee approval, the clinical database of a tertiary 23-bed paediatric intensive care unit (picu) was reviewed for bronchiolitis admissions from january 2000 to december 2009. length of stay (los), ventilatory requirements and risk factors, including prematurity, respiratory syncytial virus (rsv) status, chronic lung, neuromuscular, immune and congenital heart disease, were analysed. of 8,288 admissions, 520 (6.27 ) had bronchiolitis with 343 (65.9 ) having rsv. median (sd) age and los were 2.78 months and 2.68 (4.32) days. one (0.2 ) patient died. assisted ventilation was required for 399 (76.7 ) patients. a total of 114 (28.6 ) patients were intubated directly and 285 (71.4 ) had a trial of non-invasive ventilation (niv). significant increase in the use of niv was seen (2.8 /year) with decline in intubation rates (1.9 / year) (p 0.002). of niv patients, 237 (83.2 ) needed only niv and 48 (16.8 ) failed and therefore needed intubation. the median los was shorter in those who succeeded niv (2.38 2.43 days) compared to those with invasive ventilation (5.19 6.34 days) and those who failed niv (8.41 3.44 days). presence of a risk factor increased the chances of failing niv from 6 to 10 .","niv was successful in the vast majority of patients, particularly in those without risk factors and halved the los in intensive care. failure of niv was associated with increased duration of invasive ventilation and picu los. a prospective study comparing different techniques of niv will be helpful in defining the risks of failure of niv.",Prevention
does low-dose creatine supplementation enhance fatigue resistance in the absence of weight gain?,"we examined the effects of 6 wk of low-dose creatine supplementation on body composition, muscle function, and body creatine retention. twenty healthy men and women (21 2 y old) were randomized to receive creatine (0.03 g kg(-1) d(-1); n 10, 4 women) or placebo (n 10, 4 women) for 6 wk in a double-blind placebo-controlled fashion. participants were tested on two occasions before supplementation to establish a reliable baseline, and then were retested after supplementation. testing included body composition, maximal strength (three-repetition maximal concentric knee extension at 180 degrees/s), muscle fatigue (five sets of 30 concentric knee extensions at 180 degrees/s), and plasma creatine concentration. there were no significant differences in body mass, fat-free mass, fat mass, body fat percentage, total body water, or maximal strength in either group from before to after supplementation (all p 0.05). after supplementation, plasma creatine increased significantly in the creatine group (182, p 0.03), with no difference in the placebo group. compared with baseline values, creatine-supplemented volunteers were more resistant to fatigue during sets 2 (7), 3 (9), 4 (9), and 5 (11) (all p 0.05).",ingesting a low dose (2.3 g/d) of creatine for 6 wk significantly increased plasma creatine concentration and enhanced resistance to fatigue during repeated bouts of high-intensity contractions.,Medication
does simvastatin preserve the structure of coronary adventitial vasa vasorum in experimental hypercholesterolemia independent of lipid lowering?,"previous studies have demonstrated that experimental hypercholesterolemia leads to neovascularization in the coronary artery vasa vasorum (vv). recent evidence suggests that hmg-coa reductase inhibitors (statins) have beneficial effects independent of lipid lowering. we aimed to determine the effect of simvastatin on coronary vv neovascularization, in the absence of cholesterol lowering. pigs were randomized to 3 groups fed a normal (n), high cholesterol (hc), or hcsimvastatin (hcs) diet for 12 weeks. the proximal left anterior descending artery was isolated, scanned with micro-ct, and reconstructed. quantification of the vv density in serial cross-sections along the vessel was then performed. ldl cholesterol was similarly increased in hc and hcs compared with n. there was an increase in both vv density (4.7/-0.3 versus 2.7/-0.2 n/mm(2); p0.05) and vessel wall area (3.1/-0.2 versus 1.8/-0.1 mm(2); p0.05) in hc compared with n. the vv density in hcs was preserved compared with hc (3.0/-0.2 n/mm(2); p0.05), despite similar increase in vessel wall area compared with n (2.5/-0.1 mm(2); p0.05). coronary artery tissue expression of vegf was increased in hc but not in hcs compared with n. in parallel, immunoreactivity for hif-1alpha, vegf, mmp-2, and mmp-9 was accentuated in the outer media in hc but not in hcs compared with n.","this study demonstrates that simvastatin attenuates hypoxia in the coronary artery wall and vv neovascularization in experimental hypercholesterolemia, despite no change in plasma lipids. these data are consistent with an additional mechanism for the vascular effects of the statins, independent of cholesterol lowering.",Medication
does chemokine ligand 20 enhance progression of hepatocellular carcinoma via epithelial-mesenchymal transition?,"to identify the mechanisms of chemokine ligand 20 (ccl20)-induced hepatocellular carcinoma (hcc) metastasis and evaluate it as a prognostic marker. expression of ccl20 was evaluated by immunohistochemistry in hcc tissues from 62 patients who underwent curative resection. the relationship between ccl20 expression and clinicopathologic features was analyzed. univariate and multivariate analyses were performed to evaluate its predictive value for recurrence and survival of hcc patients. the expression levels of epithelial-mesenchymal transition (emt)-and signaling pathway-related proteins were evaluated by western blotting and immunocytochemistry. the effects of ccl20 on hcc cell proliferation and migration were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenoltetrazolium bromide (mtt) and transwell assays. ccl20 immunoreactivity was detected in all 62 patient specimens. ccl20 expression was associated with preoperative alpha-fetoprotein level (p 0.043), tumor size (p 0.000), tumor number (p 0.008), vascular invasion (p 0.014), and tumor differentiation (p 0.007). patients with high ccl20 expression had poorer recurrence-free and overall survivals compared to those with low ccl20 expression (both p 0.001). ccl20 induced emt-like changes in hcc cells and increased their proliferation and migration ability (p 0.05). western blotting and immunofluorescence staining showed that ccl20 induced an emt-like phenotype in hcc cells, and increased expression of phosphorylated akt, -catenin and vimentin, and decreased e-cadherin expression (p 0.05). the correlation analysis revealed that high ccl20 expression in hcc tissue specimens was negatively correlated with e-cadherin expression (13.33, 4/30), and positively correlated with vimentin (90.0, 27/30), -catenin (96.67, 29/30) and p-akt (76.67, 23/30) expression.",ccl20 expression is associated with hcc recurrence and patient survival and promotes hcc cell proliferation and migration by inducing emt-like changes via pi3k/akt and wnt/-catenin pathways.,Diagnosis
is the severity of retinal degeneration in rp1h gene-targeted mice dependent on genetic background?,"the severity of disease in patients with retinitis pigmentosa (rp) can vary significantly, even among patients with the same primary mutations. it is hypothesized that modifier genes play important roles in determining the severity of rp, including the retinitis pigmentosa 1 (rp1) form of disease. to investigate the basis of variation in disease expression for rp1 disease, the authors generated congenic mice with a gene-targeted retinitis pigmentosa 1 homolog (rp1h) allele (rp1h(tm1eap)) on several different genetic backgrounds and analyzed their retinal phenotypes. the rp1h(tm1eap) allele was placed onto the c57bl/6j, dba1/j, and a/j backgrounds. retinal function of the resultant congenic mice was evaluated using electroretinographic analyses. retinal structure and ultrastructure were evaluated using light and electron microscopy. rp1h protein location was determined with immunofluorescence microscopy. analysis of the retinal phenotype of incipient congenic (n6) b6.129s-rp1h(/tm1eap), dba.129s(b6)-rp1h(/tm1eap), and a.129s(b6)-rp1h(/tm1eap) mice at 1 year of age showed retinal degeneration only in the a.129s(b6)-rp1h(/tm1eap) mice. further analyses revealed that the photoreceptors of the fully congenic a.129s(b6)-rp1h(/tm1eap) mice show evidence of degeneration at 6 months of age and are almost completely lost by 18 months of age. in contrast, the photoreceptor cells in the fully congenic b6.129s-rp1h(/tm1eap) mice remain healthy up to 18 months.",the severity of the retinal degeneration caused by the rp1h(tm1eap) allele is notably dependent on genetic background. the development and characterization of the b6.129s-rp1h(/tm1eap) and a.129s(b6)-rp1h(/tm1eap) congenic mouse lines will facilitate identification of sequence alterations in genes that modify the severity of rp1 disease.,General
does low-intensity exercise increase skeletal muscle protein expression of ppardelta and ucp3 in type 2 diabetic patients?,"physical exercise provides health benefits for people with type 2 diabetes mellitus, partly by enhancing skeletal muscle insulin action. we tested the hypothesis that changes in expression of key genes in skeletal muscles relate to exercise-induced improvements in type 2 diabetic patients. we determined mrna expression of 20 selected genes following a self-supervised program of walking ( 150 min per week) over a 4-month period. this level of physical activity improved clinical parameters in approximately half the participants, as determined by reduced hypertension and enhanced insulin sensitivity (defined by reduced plasma-insulin levels and improved homeostasis model assessment (homa)). skeletal muscle mrna expression of cbl-associated protein (cap), diacylglycerol kinase (dgk)delta, uncoupling protein (ucp) 3, nuclear respiratory factor (nrf)-1, and peroxisome proliferator-activated receptor (ppar)delta tended to increase in type 2 diabetic patients with an improved clinical profile. skeletal muscle protein expression of ppardelta and ucp3 was increased significantly after physical exercise in patients with an improved clinical profile, but were unchanged in patients who did not show exercise-mediated improvements in clinical parameters.","this study provides clinical evidence that improvements in insulin sensitivity can be achieved in type 2 diabetic patients after individually executed low-intensity exercise training. moreover, the positive clinical response to exercise is correlated with changes in skeletal muscle proteins involved in the regulation of mitochondrial biogenesis and metabolism. these changes in skeletal muscle gene expression offer a possible molecular explanation for the improvements in clinical outcomes.",Prevention
does the royal college of nursing 's information need survey of nurses and health professionals?,"to find out about the nursing community's needs in the following areas: information or knowledge to improve practice in the clinical area; information to support lifelong learning and formal study. a questionnaire was circulated in summer 2004 containing questions on types of information source used for particular types of problem or question; specific sources used; ease of access to various information sources including computers and the internet, and local health library; and workplace culture and environment. a total of 1715 usable questionnaires were completed and returned. significant numbers of the nursing community have currently no or limited access to computers. nursing staff in the independent sector had less access to computers and the internet than those working for the national health service (nhs). workplace culture was as important as access to it equipment.","as a result of the survey, the royal college of nursing (rcn) is working with the nhs and the independent health sector to improve access and provide complementary services for the whole nursing community.",General
does a controlled trial of antimicrobial prophylaxis for lyme disease after deer-tick bite?,"borrelia burgdorferi, which causes lyme disease, is transmitted by deer ticks (lxodes dammini) in the northeastern and midwestern united states. although deer-tick bites are common in areas in which the disease is endemic, there is uncertainty about how to manage the care of persons who are bitten. to assess the risk of infection with b. burgdorferi and the efficacy of prophylactic antimicrobial treatment after a deer-tick bite, we conducted a double-blind, placebo-controlled trial in an area of southeastern connecticut in which lyme disease is endemic. children and adults who had been bitten by deer ticks were randomly assigned to receive either amoxicillin or placebo for 10 days. subjects were followed for one year for clinical manifestations of lyme disease. serum samples obtained at enrollment and six weeks and three months later were tested for antibodies against b. burgdorferi. of the 387 subjects, 205 (53 percent) were assigned to receive amoxicillin and 182 (47 percent) to receive placebo. of 344 deer ticks submitted and analyzed by the polymerase chain reaction, 15 percent were infected with b. burgdorferi. erythema migrans developed in two subjects, both of whom had received placebo. there were no asymptomatic seroconversions and no late manifestations of lyme disease. the risk of infection with b. burgdorferi in the placebo-treated subjects was 1.2 percent (95 percent confidence interval, 0.1 to 4.1 percent), which was not significantly different (p 0.22) from the risk in the amoxicillin-treated subjects (0 percent; 95 percent confidence interval, 0 to 1.5 percent).","even in an area in which lyme disease is endemic, the risk of infection with b. burgdorferi after a recognized deer-tick bite is so low that prophylactic antimicrobial treatment is not routinely indicated.",Medication
does gap junction protein cx37 interact with endothelial nitric oxide synthase in endothelial cells?,"the gap junction protein connexin37 (cx37) plays an important role in cell-cell communication in the vasculature. a c1019t cx37 gene polymorphism, encoding a p319s substitution in the regulatory c terminus of cx37 (cx37ct), correlates with arterial stenosis and myocardial infarction in humans. this study was designed to identify potential binding partners for cx37ct and to determine whether the polymorphism modified this interaction. using a high-throughput phage display, we retrieved 2 binding motifs for cx37ct: whk ... k,rxp ... and fhk ... k,rxxp ... , the first being more common for cx37ct-319p and the second more common for cx37ct-319s. one of the peptides (whrtprlpppvp) showed 77.7 homology with residues 843 to 854 of endothelial nitric oxide synthase (enos). in vitro binding of this peptide or of the homologous enos sequence to both cx37ct isoforms was confirmed by cross-linking and surface plasmon resonance. electrophysiological analysis of cx37 single channel activity in transfected n2a cells showed that enos-like and enos(843-854) increased the frequency of events with conductances higher than 300 ps. we demonstrated that enos coimmunoprecipitated with cx37 in a mouse endothelial cell (ec) line (bend.3), human primary ecs, and a human ec line transfected with cx37-319p or cx37-319s. cx37 and enos colocalized at ec membranes. moreover, a dose-dependent increase in nitric oxide production was observed in ecs treated with cx37 antisense.","overall, our data show for the first time a functional and specific interaction between enos and cx37. this interaction may be relevant for the control of vascular physiology both in health and in disease.",Medication
does tak1 inhibition-induced rip1-dependent apoptosis in murine macrophages rely on constitutive tnf- signaling and ros production?,"transforming growth factor- (tgf-)-activated kinase 1 (tak1) is a key regulator of signal cascades of tnf- receptor and tlr4, and can induce nf-b activation for preventing cell apoptosis and eliciting inflammation response. tak1 inhibitor (taki) can decrease the cell viability of murine bone marrow-derived macrophages (bmdm), raw264.7 and bv-2 cells, but not dermal microvascular endothelial cells, normal human epidermal keratinocytes, thp-1 monocytes, human retinal pigment epithelial cells, microglia chme3 cells, and some cancer cell lines (cl1.0, hela and hct116). in bmdm, taki-induced caspase activation and cell apoptosis were enhanced by lipopolysaccharide (lps). moreover, taki treatment increased the cytosolic and mitochondrial reactive oxygen species (ros) production, and ros scavengers nac and bha can inhibit cell death caused by taki. in addition, rip1 inhibitor (necrostatin-1) can protect cells against taki-induced mitochondrial ros production and cell apoptosis. we also observed the mitochondrial membrane potential loss after taki treatment and deterioration of oxygen consumption upon combination with lps. notably tnf- neutralization antibody and inhibitor enbrel can decrease the cell death caused by taki.","taki-induced cytotoxicity is cell context specific, and apoptosis observed in macrophages is dependent on the constitutive autocrine action of tnf- for rip1 activation and ros production.",Medication
is a differential cytokine expression profile induced by highly purified human menopausal gonadotropin and recombinant follicle-stimulating hormone in a pre- and postovulatory mouse follicle culture model?,"to compare the differential effects of highly purified (hp) hmg or recombinant fsh (rfsh) on cytokine expression before and after ovulation in an in vitro mouse ovarian follicle model. a prospective laboratory in vitro study. a university-based reproductive biology laboratory. material(s): mechanically isolated mouse preantral follicles from 14-day-old prepubertal mouse ovaries (f1 hybrids: c57bl/6jxcba/ca). randomly distributed mouse early preantral follicles were exposed to two hyperstimulation conditions with either hp-hmg or rfsh. an ovulatory stimulus was given using hcg/epidermal growth factor. conditioned media from the two culture conditions were collected on the days before and after in vitro ovulation. conditioned media were compared for their relative cytokine profile content as measured by a cytokine antibody array analysis. relative concentrations of 62 cytokines in conditioned media before and after ovulation. statistically significant increase in the production of a number of cytokines was found after hp-hmg stimulation compared with rfsh: 14 and 24 pre- and post-rhcg, respectively. cytokines with the largest significant difference (more than 5 times) before and after ovulation included thymus-expressed cytokine (teck), stnfri, and sdf-1alpha. the cytokines that are most strongly related to oocyte and embryo quality and implantation and that have been related to oocyte yield and maturation were significantly higher with hp-hmg.",the significant differences in follicular cytokine production induced by hp-hmg and rfsh before and after in vitro ovulation might explain the difference in treatment outcome.,Diagnosis
are abcc8 polymorphisms associated with triglyceride concentration in type 2 diabetics on sulfonylurea therapy?,"the failure of therapy with oral hypoglycemic drugs leads to not only poorly regulated glycemic status, but also dyslipidemia and increased body weight and body mass index (bmi). sulfonylureas act as insulin secretagogues by binding to the sulfonylurea receptor (sur-1) encoded by the gene abcc8. the aim of this study was to explore whether there is an association of abcc8 polymorphisms sur1 exon 16 (-3c/t), sur-1 exon 31 (arg1273arg), and sur-1 exon 33 (s1369a) with lipid concentration and bmi in type 2 diabetics on sulfonylurea therapy. this study included 251 unrelated type 2 diabetics on sulfonylurea therapy. height and weight were measured for bmi calculation. all polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism methods. lipid concentrations and bmi were measured at inclusion into the study and after 6 months of follow-up. wild-type allele carriers for the sur-1 exon 31 polymorphism (arg1273arg) had a significantly higher triglyceride (tg) concentration when compared with the carriers of two variant alleles (p0.023). polymorphic allele carriers of the sur-1 exon 16 (-3c/t) polymorphism were more frequent in the subgroup of patients with the tg concentration increase after 6 months (p for genotype and allelic differences: 0.024 and 0.015, respectively).",abcc8 polymorphisms in exon 16 and 31 are associated with the tg concentration in type 2 diabetics on sulfonylurea therapy.,Treatment
are cervicovaginal levels of proinflammatory cytokines increased during chlamydial infection in bacterial vaginosis but not in lactobacilli-dominated flora?,"the purpose of this study was to assess the cervicovaginal levels of proinflammatory cytokines in women with chlamydia trachomatis (ct) infection in the presence of bacterial vaginosis (bv) and normal flora and to compare with those negative for ct. in this cross-sectional study, nonpregnant women were enrolled at 2 outpatient clinics and at 1 primary medical care unit in so paulo state, brazil. cervicovaginal samples from 256 women with bv, of which 68 (26.6) had concomitant ct infection and 188 (73.4) were ct-negative, were measured for interleukin-1 (il-1), il-6, and il-8 by enzyme-linked immunosorbent assay. a matching number of samples from women with normal flora, ct-positive (n 68) and negative (n 188), were evaluated as control. cytokine levels were compared by mann-whitney test and differences were considered significant at p .05. in ct-negative women, il-1 was increased in bv (p .001) when compared to normal flora, while the levels of il-6 and il8 were unchanged. the presence of ct infection was not associated with differences on cytokine levels in women with normal flora. however, women with bv had higher levels of il-1 (p .02), il-6 (p .02), and il-8 (p .03) in the presence of ct when compared to those who tested negative for ct.","detection of endocervical ct is associated with increased cervicovaginal il-1, il-6, and il-8 levels in women with concomitant bv but not in those with normal flora.",General
do effects of switching statins on lipid and apolipoprotein ratios in the mercury i study?,"lipid ratios are clinically useful markers of coronary artery disease (cad) risk. the effects of rosuvastatin, atorvastatin, simvastatin, and pravastatin on lipid ratios were investigated in the measuring effective reductions in cholesterol using rosuvastatin therapy (mercury) i trial. this trial was conducted in 3140 hypercholesterolemic patients with cad, atherosclerosis, type 2 diabetes mellitus, or a 20 10-year risk for cad. patients were randomized to rosuvastatin 10 mg, atorvastatin 10 or 20 mg, simvastatin 20 mg, or pravastatin 40 mg for 8 weeks; all patients except those receiving rosuvastatin 10 mg either were switched to rosuvastatin 10 or 20 mg or remained on initial treatment for 8 more weeks. at 8 weeks, reductions in total cholesterol (tc):high-density lipoprotein cholesterol (hdl-c), low-density lipoprotein cholesterol:hdl-c, non-hdl-c:hdl-c, and apolipoprotein (apo) b:apo a-i ratios with rosuvastatin 10 mg were significantly greater than those with atorvastatin 10 mg, atorvastatin 20 mg, simvastatin 20 mg, and pravastatin 40 mg (p0.0001 for all). at week 16, switching to rosuvastatin 10 mg from atorvastatin 10 mg, simvastatin 20 mg, and pravastatin 40 mg and to rosuvastatin 20 mg from atorvastatin 20 mg produced significantly greater reductions in all lipid ratios (p or 0.0001 for all). switching to rosuvastatin 10 mg from atorvastatin 20 mg produced significantly greater reductions in tc:hdl-c (p0.025) and apo b:apo a-i (p0.01).",rosuvastatin 10 mg reduces lipid ratios more than equivalent and higher doses of other statins; switching to equal or lower doses of rosuvastatin produces significantly improved reductions in lipid ratios.,Medication
is prolactin elevation of the antipsychotic risperidone predominantly related to its 9-hydroxy metabolite?,"treatment with the antipsychotic risperidone is frequently associated with hyperprolactinemia. the aim of this study was to evaluate the role of the main compound risperidone and its active 9-hydroxy metabolite on elevating prolactin levels. twenty patients with psychotic disorders, on therapy with risperidone, were studied. all patients had been receiving risperidone for at least 2.5 months, and the median daily dose of risperidone was 3 mg (range 1-10). morning serum samples for prolactin were analyzed and investigated in relation to the serum concentrations of risperidone and 9-hydroxyrisperidone. elevated prolactin levels were found in 17 (85) of the patients. levels of prolactin were positively correlated to the 9-hydroxyrisperidone serum concentration (r(s) 0.48, p 0.03) and to the daily dose of risperidone (r(s) 0.51, p 0.03), but did not correlate to the risperidone serum concentration.",the present results suggest that 9-hydroxyrisperidone and not risperidone is the main contributor to the increased serum levels of prolactin observed in many risperidone-treated patients.,Treatment
does dna-pkcs expression be a predictor of biochemical recurrence after permanent iodine 125 interstitial brachytherapy for prostate cancer?,"predictive factors for biochemical recurrence (bcr) in localized prostate cancer (pca) after brachytherapy are insufficient to date. cellular radiosensitivity depends on dna double-strand breaks, mainly repaired by the nonhomologous end-joining (nhej) system. we analyzed whether the expression of nhej proteins can predict bcr in patients treated by brachytherapy for localized pca. from 983 pca cases treated by brachytherapy between march 2000 and march 2012, 167 patients with available biopsy material suitable for in situ analysis were included in the study. the median follow-up time was 47 months. twenty-nine patients experienced bcr. all slides were reviewed to reassess the gleason score. expression of the key nhej proteins dna-pkcs, ku70, and ku80, and the proliferation marker ki67, was studied by immunohistochemistry performed on tissue microarrays. the gleason scores after review (p.06) tended to be associated with bcr when compared with the score initially reported (p.74). both the clinical stage (p.02) and the pretreatment prostate-specific antigen level (p.01) were associated with biochemical failure. whereas the expression of ku80 and ki67 were not predictive of relapse, positive dna-pkcs nuclear staining (p.003) and higher ku70 expression (p.05) were associated with bcr. on multivariate analysis, among pretreatment variables, only dna-pkcs (p.03) and clinical stage (p.02) remained predictive of recurrence. none of the patients without palpable pca and negative dna-pkcs expression experienced biochemical failure, compared with 32 of men with palpable and positive dna-pkcs staining that recurred.","our results suggest that dna-pkcs could be a predictive marker of bcr after brachytherapy, and this might be a useful tool for optimizing the choice of treatment in low-risk pca patients.",Treatment
is angiotensin-converting enzyme insertion/deletion polymorphism a risk factor for thoracic aortic aneurysm in patients with bicuspid or tricuspid aortic valves?,"the angiotensin-converting enzyme (ace) is highly expressed in the aneurysmal vascular wall, in both animal models and human disease. genetic variations in ace could be crucial in determining the risk of thoracic aortic aneurysm (taa). the aim of the present study was to examine the role of ace insertion/deletion polymorphism on the risk of taa in patients with bicuspid aortic valves or tricuspid aortic valves. we enrolled 216 patients (158 men; age, 58.914.9 years) with taa, associated with bicuspid aortic valves (n105) and tricuspid aortic valves (n111) compared with 312 patients (252 men; age, 54.611.0 years) with angiographically proven coronary artery disease and 300 healthy controls (91 men; age, 40.410.5 years). the genotype distribution of ace insertion/deletion was significantly different between the patients with taa compared with both the control group (p.0005) and the coronary artery disease group (p.03). the genotypes were not different between the control group and the coronary artery disease group (p.3). compared with the controls, both the bicuspid aortic valve patients (p.0008) and tricuspid aortic valve patients (p.0001) had a greater frequency of allele d. the aortic diameters were significantly different among the three genotypes (48.36.6, 45.38.9, 39.98.7 for the dd, di, and ii genotypes, respectively; p.0002). a synergistic effect between the ace d allele and hypertension was found for both an increased aortic diameter (p.003) and the risk of taa (p.001). on multivariate logistic regression analysis, d allele (odds ratio, 3.0; 95 confidence interval, 1.1-8.1; p.03) was a significant predictor of taa.",ace insertion/deletion polymorphism represents a genetic biomarker for taa. these findings could have a significant effect on both the early detection and effective pharmacologic treatment of aortic disease.,Prevention
is increased protein intake associated with uncontrolled blood pressure by 24-hour ambulatory blood pressure monitoring in patients with type 2 diabetes?,"to analyze possible associations of dietary components, especially protein intake, with blood pressure (bp) during ambulatory bp monitoring (abpm) in patients with type 2 diabetes. in this cross-sectional study, bp of outpatients with type 2 diabetes was evaluated by 24-hour abpm (spacelabs 90207) and usual diet by 3-day weighed diet records. patients were divided into 2 groups according to their daytime abpm: uncontrolled bp (systolic bp 135 mmhg or diastolic bp 85 mmhg) and controlled bp (systolic bp 135 mmhg and diastolic bp 85 mmhg). logistic regression models unadjusted and adjusted for possible confounders (covariates) were used to analyze the association of protein and uncontrolled bp. a total of 121 patients with type 2 diabetes aged 62.3 years, 54.5 of whom were women, were studied. the uncontrolled bp group had higher glycated hemoglobin (hba1c) values (8.4 2.0 vs 7.6 1.3; p 0.04) and consumed more protein (20.0 3.8 vs 18.2 3.6 of energy; p 0.01) and meat, (2.6 1.45, 2.95 vs 2.0 1.49, 2.90 g/kg weight; p 0.04) than the controlled bp group. in a multivariate analysis, protein intake ( of energy) increased the chance for uncontrolled bp (odds ratio or 1.16; 95 confidence interval ci, 1.02, 1.30; p 0.02), adjusted for body mass index (bmi), hba1c, low-density lipoprotein (ldl) cholesterol, number of antihypertensive medications, and ethnicity. meat consumption higher than 3.08 g/kg weight/day more than doubled the chance for uncontrolled bp (or 2.53; 95 ci, 1.01, 7.60; p 0.03).",high protein intake and meat consumption were associated with high daytime abpm values in patients with type 2 diabetes. reducing meat intake might represent an additional dietary intervention in hypertensive patients with type 2 diabetes.,Medication
does zoledronic acid inhibit primary bone tumor growth in ewing sarcoma?,"zoledronic acid has been shown to be effective in the treatment of osteoporosis, hypercalcemia, and metastatic bone tumors. the efficacy of zoledronic acid on primary bone tumors has not been investigated. a primary bone tumor mouse model was established. intratibia injection of tc71 cells resulted in an osteolytic bone tumor. four days after injection the mice were treated with zoledronic acid alone, paclitaxel alone, or zoledronic acid plus paclitaxel. control mice were treated with phosphate-buffered saline. bone tumor growth was assessed using a faxitron specimen radiography system. the gene expression was detected by reverse-transcription polymerase chain reaction (rt-pcr), elisa, and immunohistochemistry. osteoclast formation was determined by tartrate-resistant acid phosphatase (trap) staining. zoledronic acid induced apoptosis in tc71 human ewing sarcoma cells and inhibited cell proliferation. five weeks after injection, 89 of mice in the control group developed osteolytic bone tumors. paclitaxel had little effect on bone tumor growth, with 78 of mice developing tumors. by contrast, 44 of mice treated with zoledronic acid developed bone tumors. the most effective treatment was zoledronic acid plus paclitaxel. tumor incidence in the combination therapy group was only 22. osteoclasts were quantified using trap staining. there was a decrease in trap-positive osteoclasts in tumor tissues from zoledronic acid-treated animals compared to control animals. rt-pcr, immunohistochemistry, and elisa assay demonstrated that zoledronic acid up-regulated osteoprotegerin expression.",these results suggest that zoledronic acid induces apoptosis and inhibits primary bone tumor growth in ewing sarcoma through a mechanism involving the up-regulation of osteoprotegerin. zoledronic acid may provide a novel therapeutic approach for the treatment of patients with ewing sarcoma.,Treatment
is carotid artery wall stiffness increased in patients with small vessel disease : a case-control study?,"cerebral ischemic small-vessel disease (svd), causing lacunar infarcts and white matter hyperintensities on brain magnetic resonance imaging (mri), is a progressive disease associated with an increased risk of stroke, dementia and death. increased arterial stiffness has been associated with ischemic stroke and cerebral svd independently of common vascular risk factors. the aim of the study was to analyze arterial stiffness in our patients with symptomatic svd. in a cross-sectional study design we included 30 patients with clinical and mri evidence of cerebral svd and 30 age-, gender- and risk factor-matched control subjects with no neurological diseases. patients were evaluated at the ultrasound laboratory at the neurology clinic, clinical center of serbia in belgrade, during a three-month period (from september 1st to december 1st 2012). baseline demographic and vascular risk factors were recorded. all patients underwent standard carotid ultrasound scans with measuring of intima-media thickness (imt) and analysis of atheromatous plaques. internal carotid artery stiffness was evaluated with the use of e-tracking option as beta stiffness index (bsi) value. there were no differences between study groups in regard to degree of carotid stenosis and type of carotid plaques (p 0.05). patients in svd group had significantly higher mean imt (p 0.0093) and mean bsi (p 0.0001) than subjects in the control group. no significant correlation was detected between imt and bsi in svd group (r 0.168; p 0.376). brain lesions severity correlated with bsi (r 0.733; p 0.0001).","arterial stiffness is increased in symptomatic patients with svd, independently of vascular risk factors and imt.",Diagnosis
does pretreatment of bapta-am suppress the genesis of repetitive endocardial focal discharges and pacing-induced ventricular arrhythmia during global ischemia?,"in isolated rabbit hearts, repetitive endocardial focal discharges (refds) were consistently observed during ventricular fibrillation (vf) with prolonged (5 minutes) global ischemia (gi). we hypothesized that bapta-am, a calcium chelator, can suppress these refds. using a two-camera optical mapping system, we simultaneously mapped endocardial (left ventricle, lv) and epicardial (both ventricles) activations during ventricular arrhythmia with gi. in 5 hearts (protocol i), we infused tyrode's solution (no bapta-am) for 30 minutes before the onset of no-flow gi. in 7 additional hearts (protocol ii), bapta-am (20 mol/l) was infused for 30 minutes before the initiation of gi. in protocol i, sustained vf (30 seconds) was successfully induced in all 5 hearts with prolonged gi. refds were present in 85 of recording time. in protocol ii, however, ventricular arrhythmia was not inducible and refds were not observed after 5-minute gi in 5 hearts. effects of bapta-am on intracellular calcium (ca(i) ) at the lv endocardium were also evaluated in 5 hearts (protocol iii) using dual ca(i) /membrane potential mapping. gi, both without and with bapta-am pretreatment, caused a decrease of ca(i) amplitude during s(1) pacing. however, this effect was more pronounced in the hearts with bapta-am pretreatment (p 0.001). gi, without bapta-am pretreatment, caused broadening of ca(i) transient. in contrast, gi, with bapta-am pretreatment, caused narrowing of ca(i) transient.","bapta-am pretreatment attenuates ca(i) transient, suppressing the genesis of refds and pacing-induced ventricular arrhythmia during gi. these findings support the notion that ca(i) dynamics is important in the maintenance of refds.",Treatment
does sorafenib sensitize head and neck squamous cell carcinoma cells to ionizing radiation?,"there is a great need to improve the outcome of locoregionally advanced squamous cell carcinomas of the head and neck (hnscc). standard treatment includes a combination of surgery, radio- and chemotherapy. the addition of molecular targeting agents to conventional treatment may improve outcomes. in this study the raf inhibitor sorafenib was used to increase the radiosensitivity of hnscc cell lines. in a panel of six cell lines (a549, fadu, utscc 60a, utscc 42a, utscc 42b, utscc 29) radiosensitivity was measured by colony formation assay and apoptosis and cell cycle analysis were performed by flow cytometry. dna repair was analyzed by 53bp1 immunohistochemistry. sorafenib added prior to irradiation resulted in an increased cellular radiosensitivity (def0.51.11-1.84). radiosensitization was not caused by an enhanced rate of apoptosis or cell cycle effects. in contrast, sorafenib was shown for the first time to block the repair of dna double-strand breaks (dsb).",our data suggest that sorafenib may be used to overcome the radioresistance of hnscc through the inhibition of dsb repair.,Treatment
is inadequate calcium intake highly prevalent in korean children and adolescents : the korea national health and nutrition examination survey ( knhanes ) 2007-2010?,"the present study aimed to assess the adequacy of ca intake and major food sources of ca in korean children and adolescents. a cross-sectional study. data from the korean national health and nutrition examination survey (knhanes) 2007-2010. we analysed the daily ca intake, major food sources of ca and the prevalence of inadequate ca intake in the study population. ca intake was categorized as inadequate when the participant's daily ca intake was less than the estimated average requirement. subject the study population consisted of 7233 children and adolescents (3973 boys, 3260 girls; aged 1-18 years). mean ca intake was 5102 mg/d in boys and 4317 mg/d in girls. overall, 750 of adolescents (boys 716 , girls 791 ) had inadequate ca intake. the prevalence of inadequate ca intake increased significantly from toddlers (45-55 ) to adolescents (78-86 ) in both genders. the highest ranked food sources for ca were dairy products (350 ), followed by vegetables (173 ), grains (113 ) and seafood (99 ). ca intake from dairy products decreased significantly from 57 in toddlers to 30 in adolescents, while ca intakes from other foods increased with age.",inadequate ca intake is highly prevalent and increased with age in korean children and adolescents. it should be emphasized to encourage children and adolescents to eat more ca-rich products to meet their ca needs.,Prevention
does reduced expression of toll-like receptor 4 inhibit human breast cancer cells proliferation and inflammatory cytokines secretion?,"tumor cell expression of toll-like receptors (tlrs) can promote inflammation and cell survival in the tumor microenvironment. toll-like receptor 4 (tlr4) signaling in tumor cells can mediate tumor cell immune escape and tumor progression, and it is regarded as one of the mechanisms for chronic inflammation in tumorigenesis and progression. the expression of tlr4 in human breast cancer cell line mda-mb-231 and its biological function in the development and progression of breast cancer have not been investigated. we sought to characterize the expression of tlr1-tlr10 in the established human breast cancer cell line mda-mb-231, and to investigate the biological roles of tlr4 in breast cancer cells growth, survival, and its potential as a target for breast cancer therapy. tlrs mrna and protein expressions were detected in human breast cancer cell line mda-mb-231 by rt-pcr, real-time pcr and flow cytometry (fcm). rna interference was used to knockdown the expression of tlr4 in mda-mb-231. mda-mb-231 transfected with the vector pgenesil-1 and the vector containing a scrambled sirna were as controls. recombinant plasmids named tlr4asirna, tlr4bsirna and tlr4csirna specific to tlr4 were transfected into human breast cancer cell line mda-mb-231 with lipfectamine 2000 reagent. tlr4 mrna and protein expressions were investigated by rt-pcr, real-time pcr, fcm and immunofluorescence after silence. mtt analysis was performed to detect cell proliferation and fcm was used to detect the secretion of inflammatory cytokines in supernatant of transfected cells. the human breast cancer cell line mda-mb-231 was found to express tlr1-tlr10 at both the mrna and protein levels. tlr4 was found to be the highest expressed tlr in mda-mb-231. tlr4asirna, tlr4bsirna and tlr4csirna were found to significantly inhibit tlr4 expression in mda-mb-231 at both mrna and protein levels as compared to vector control(vector transfected cells). tlr4asirna mediated the strongest effect. knockdown of tlr4 gene in mda-mb-231 resulted in a dramatic reduction of breast cancer cell viability. the cytokines which were secreted by the tlr4 silenced cells, such as il-6 and il-8, also decreased significantly as compared with vector control. no significant difference was observed in sirna control (recombinant plasmid named scrambledsirna transfected cells) compared to vector control.","these studies identified the expression levels of multiple tlrs in human breast cancer cell line mda-mb-231 and demonstrated that knockdown of tlr4 could actively inhibit proliferation and survival of breast cancer cells. taken together, our results suggest rnai-directed targeting of tlr4 may be a beneficial strategy for breast cancer therapy.",Medication
does genome sequencing of sporisorium scitamineum provide insights into the pathogenic mechanisms of sugarcane smut?,"sugarcane smut can cause losses in cane yield and sugar content that range from 30 to total crop failure. losses tend to increase with the passage of years. sporisorium scitamineum is the fungus that causes sugarcane smut. this fungus has the potential to infect all sugarcane species unless a species is resistant to biotrophic fungal pathogens. however, it remains unclear how the fungus breaks through the cell walls of sugarcane and causes the formation of black or gray whip-like structures on the sugarcane plants. here, we report the first high-quality genome sequence of s. scitamineum assembled de novo with a contig n50 of 41 kb, a scaffold n50 of 884 kb and genome size 19.8 mb, containing an estimated 6,636 genes. this phytopathogen can utilize a wide range of carbon and nitrogen sources. a reduced set of genes encoding plant cell wall hydrolytic enzymes leads to its biotrophic lifestyle, in which damage to the host should be minimized. as a bipolar mating fungus, a and b loci are linked and the mating-type locus segregates as a single locus. the s. scitamineum genome has only 6 g protein-coupled receptors (gpcrs) grouped into five classes, which are responsible for transducing extracellular signals into intracellular responses, however, the genome is without any pth11-like gpcr. there are 192 virulence associated genes in the genome of s. scitamineum, among which 31 expressed in all the stages, which mainly encode for energy metabolism and redox of short-chain compound related enzymes. sixty-eight candidates for secreted effector proteins (cseps) were found in the genome of s. scitamineum, and 32 of them expressed in the different stages of sugarcane infection, which are probably involved in infection and/or triggering defense responses. there are two non-ribosomal peptide synthetase (nrps) gene clusters that are involved in the generation of ferrichrome and ferrichrome a, while the terpenes gene cluster is composed of three unknown function genes and seven biosynthesis related genes.","as a destructive pathogen to sugar industry, the s. scitamineum genome will facilitate future research on the genomic basis and the pathogenic mechanisms of sugarcane smut.",Medication
is corticotropin releasing hormone correlated with tumorigenesis of gastric cancer?,"the etiology of gastric cancer is unclear; its therapeutic effect is poor; the anatomical factor and lack of specific diagnostic markers are part of the reason. recent reports indicate corticotropin releasing hormone (crh) is associated with the pathogenesis of cancer. this study is designed to assess the levels of crh in gastric tissue of a group of patients with gastric cancer and gastric chronic inflammation. fifty-two patients with gastric cancer (gc) and 213 patients with gastric chronic inflammation were recruited into this study. the levels of crh in the gastric biopsies were assessed. the correlation between the levels of crh in the gastric biopsies and the tumorigenesis was assessed. high levels of (458.6 pg/mg protein) crh were detected in the biopsies of 52 patients with gastric cancer, which were also detected in the gastric biopsies of 213 patients with chronic gastritis (less than 100 pg/mg protein). crh was below the detectable levels in the normal gastric mucosa. of the 213 patients with chronic gastritis, 50 patients developed into cancer 3-5 years after the first diagnosis of chronic gastric cancer.",crh may be involved in the pathogenesis of gastric cancer.,Diagnosis
is chlamydia pneumoniae persistent infection associated with primary iga nephropathy ?,"to explore the correlations between chlamydia pneumoniae (cp) infection and iga nephropathy (igan). seventy patients with primary igan were enrolled in the study. seventy serum specimens from healthy blood donors and twelve renal autopsy specimens from accidental death bodies were regarded as control groups. serum cp igg and cp iga antibody titers were detected by indirect immunofluorescence. cp dna of renal tissue was measured by fluorescent quantitative pcr. finally, using statistical methods, we analyzed the correlations of cp infection and cp dna of renal tissue with clinical manifestations and kidney pathological changes of igan patients. the rate of cp persistent infection in igan group was higher than that of healthy blood donor group (p0.05). it was higher in the patients with gross proteinuria and/or durative renal insufficiency than in non-gross proteinuria patients (p0.05). the scores of glomerular patholopical and tubulointerstitial injury of cp persistent infection patients were higher than those of non-persistent infection ones (p0.05). the renal injury of cp persistent infection patients was more severe than that of non-persistent infection ones. the positive rate of cp dna in gross proteinuria and/or renal insufficiency patients was higher than that of non-gross proteinuria patients (p0.05). the scores of glomerular pathological and tubulointerstitial injury of positive cp dna patients were respectively higher than those of negative cp dna ones (p0.05, p0.01). the renal injury of patients with positive cp dna was more severe than that of negative cp dna ones. cp persistent infection was obviously correlated with renal cp dna (p0.01).","primary igan is associated with cp persistent infection, but not with cp previous infection or cp acute infection.",Symptoms
does qdr 4500a dual-energy x-ray absorptiometer underestimate fat mass in comparison with criterion methods in adults?,"dual-energy x-ray absorptiometry (dxa) has become one of the most frequently used methods for estimating human body composition. although the dxa technique has been validated for the measurement of fat-free mass and fat mass, differences in calibration between instruments produced by different manufacturers, as well as between different models produced by the same manufacturer, have been reported. the objective was to compare the calibration of the qdr 4500a against criterion methods in a large heterogeneous population. dxa-derived body-composition data were obtained from 7 studies: 6 data sets were provided by the investigators, one of which was published. the data included fat mass and fat-free mass measured with a qdr 4500a and criteria measurements of body composition from total body water by dilution at 4 centers, densitometry from 1 center, and four-compartment analysis at 2 centers. in the cohort of 1195 subjects, 602 men and 593 women aged 19-82 y with a body mass index (in kg/m2) of 16-44, the fan-beam dxa overestimated fat-free mass (p 0.05). a significant difference was observed in all 7 data sets, and the mean (/-se) was 5 /- 1.",it is recommended that the lean soft tissue mass estimate with the fan-beam qdr 4500a be reduced by 5 and that for fat mass be increased by that same mass. this finding is particularly important because the national health and nutrition examination survey is using the qdr 4500a to assess body composition in a nationally representative sample of persons in the united states.,Diagnosis
do osteopontin and galectin-3 predict the risk of ventricular tachycardia and fibrillation in heart failure patients with implantable defibrillators?,"myocardial extracellular matrix remodelling provides electrical heterogeneity entailing ventricular tachycardia/fibrillation (vt/vf) in heart failure (hf) patients. osteopontin (opn) and galectin-3 (gal-3) are fibrosis markers and may reflect the extension of the arrhythmogenic substrate. we assessed whether plasma opn and gal-3 predict the risk of sustained vt/vf in a cohort of hf patients with implantable cardioverter-defibrillator (icd). a total of 75 hf patients underwent pre-icd implantation clinical evaluation and assessment of plasma opn and gal-3. the primary endpoint was the time to the occurrence of the first sustained vt/vf. hazard ratios (hr) were derived from cox proportional-hazards analysis. patients with coronary artery disease (cad) had higher plasma opn (79.8 44.0 ng/ml vs. 66.0 31.8 ng/ml; p 0.04). both gal-3 (r -0.38; p 0.01) and opn (r -0.27; p 0.01) were negatively related to estimated glomerular filtration rate. after 29 17 months, 20 patients (27) reached the primary endpoint. patients with vt/vf had higher plasma opn and gal-3 (97.4 51.7 ng/ml vs. 65.9 31.3 ng/ml; p 0.002 and 19.7 8.5 ng/ml vs. 16.2 6.2 ng/ml; p 0.05). in univariate analysis, opn (log-opn, hr: 32.4; 95ci: 3.9-264.7; p 0.001) and gal-3 (hr: 1.05; 95ci: 1.00-1.11; p 0.04) predicted sustained vt/vf. in multivariable analysis, both opn (hr: 41.4; 95ci: 3.8-441.9; p 0.002) and gal-3 (hr: 1.06; 95ci: 1.00-1.12; p 0.03) retained their prognostic power after correction for age, sex, history of mi, ef, nyha class, egfr, use of ace-i, and amiodarone.",plasma opn and gal-3 predict sustained vt/vf in hf patients at high risk for scd. larger prospective studies should outline the role of these biomarkers in predicting scd on top of conventional risk stratification.,Diagnosis
does a melanoma cell state distinction influence sensitivity to mapk pathway inhibitors?,"most melanomas harbor oncogenic braf(v600) mutations, which constitutively activate the mapk pathway. although mapk pathway inhibitors show clinical benefit in braf(v600)-mutant melanoma, it remains incompletely understood why 10 to 20 of patients fail to respond. here, we show that raf inhibitor-sensitive and inhibitor-resistant braf(v600)-mutant melanomas display distinct transcriptional profiles. whereas most drug-sensitive cell lines and patient biopsies showed high expression and activity of the melanocytic lineage transcription factor mitf, intrinsically resistant cell lines and biopsies displayed low mitf expression but higher levels of nf-b signaling and the receptor tyrosine kinase axl. in vitro, these mitf-low/nf-b-high melanomas were resistant to inhibition of raf and mek, singly or in combination, and erk. moreover, in cell lines, nf-b activation antagonized mitf expression and induced both resistance marker genes and drug resistance. thus, distinct cell states characterized by mitf or nf-b activity may influence intrinsic resistance to mapk pathway inhibitors in braf(v600)-mutant melanoma.","although most braf(v600)-mutant melanomas are sensitive to raf and/or mek inhibitors, a subset fails to respond to such treatment. this study characterizes a transcriptional cell state distinction linked to mitf and nf-b that may modulate intrinsic sensitivity of melanomas to mapk pathway inhibitors.",Medication
are dental injuries in pediatric patients with facial fractures frequent and severe?,"this study was carried out to identify the occurrence, type, location, and severity of dental injuries (dis), as well as predictors for dis, in pediatric patients with facial fractures. this study examined the files of patients aged 16 years or less who had sustained facial fractures during a 12-year period. the outcome variable was di. the explanatory variables included gender, age, trauma mechanism, and type of facial fracture. data analysis was carried out with the (2) test and logistic regression analysis. a total of 200 patients, 119 (59.5) of whom were boys, met the inclusion criteria. the mean age was 12.6 years. a total of 45 patients (22.5) had dis. crown fracture, the most common type of di, occurred in 59.9 of all dis. the most common location of crown fractures was in the premolars (37.4 of all crown fractures). multiple dis occurred in 71.1 of those with dis and severe di in 66.7. dis were significantly associated with motor vehicle collision (mvc) (p .02) and mandibular fracture (p .03).","dis are common in pediatric patients with facial fracture, often being both multiple and severe. in association with pediatric facial fracture, facial surgeons should be especially alert for crown fractures in the lateral parts of the jaws.",General
"is implementation of the strategy clean care safer care '' in a third level hospital in medelln , colombia ?","hand hygiene is the most cost-effective and simple measure of preventing healthcare associated infections (hai). the approach to improve low compliance must be through multimodal interventions such as the ""clean care is safer care"" strategy (who). to estimate the efficacy of a multimodal strategy in improving hand hygiene in five wards of a tertiary care hospital in medelln, colombia (2008-2010). quasi-experimental before-after study. hand hygiene compliance significantly increased after the intervention (82 to 89, p 0.007). the knowledge score increased from a median of 26 (iqr22-28) to 30 (iqr26-32, p 0.001). alcohol-based hand rub consumption increased significantly from 10.5 liters to 58.1 liters per 1000 patient-days incidence ratio (ir) 2.39, 95 ci 1.99; 2.88. monthly hai rates showed no significant variations during the same period ir 0.90, 95 ci 0.71; 1.13.","this and other recent studies demonstrate that implementing a multimodal strategy for hand hygiene significantly increases compliance with this measure, irrespective of type of health worker or hospital department.",Prevention
does prolonged respiratory disorder predict adverse prognosis in infants with end-stage kidney disease?,"among comorbidities, pulmonary hypoplasia (ph) is known as a significant risk factor for mortality in infants with end-stage kidney disease (eskd). however, the final outcomes of infants with both eskd and ph are still not well defined, as the diagnosis modality, and definition of ph severity remain ambiguous. children initiating peritoneal dialysis during infancy from 1990 to 2015 were followed until death, date of last contact, or the end of 2015. we examined the long-term outcome of children with congenital pulmonary disorders by studying infants with prolonged respiratory disorders of greater than 28 days duration after birth and evaluated risk factors for mortality. forty-six children were followed (median follow-up, 9.23 years), and classified as children without (n 38; group a) or with (n 8; group b) a prolonged respiratory disorder. overall actuarial 5 year survival rate in this cohort was 79.5 . the survival curve in group b showed a significant decline compared with group a. prolonged respiratory disorder was significantly associated with mortality by multivariate analysis (hazard ratio, 8.32).","infants who initiate peritoneal dialysis complicated by prolonged respiratory disorders have increased adverse risk factors for mortality; therefore, withholding aggressive treatment should be considered.",Diagnosis
do patients with seasonal affective disorder have lower odor detection thresholds than control subjects?,"behavioral changes in patients with seasonal affective disorder resemble seasonal changes in photoperiodic animals. because the olfactory system has a modulatory role in seasonal photoperiodic responses in certain species, we hypothesized that olfactory function may differ between patients with seasonal affective disorder and healthy control subjects. fourteen patients who had winter seasonal affective disorder and 16 healthy volunteers were studied once in winter and once in the subsequent summer. we administered a phenyl ethyl alcohol detection threshold test to each side of the nose in a counterbalanced order, with the nostril contralateral to the tested site occluded. patient and control data were compared using a 4-way repeated measure analysis of covariance (with group and gender as between-subjects factors, season and side-of-the-nose as within-subjects factors, and age as a covariate). the patients exhibited lower thresholds than did the controls (f(1,25) 9.2; p .006). there was no main effect of season.","in humans, marked seasonal behavioral rhythms with recurrent winter depression may be associated with a more acute sense of smell.",Medication
is the surgical procedure the most important factor affecting continence recovery after laparoscopic radical prostatectomy?,"we analyzed factors associated with early recovery of continence after laparoscopic radical prostatectomy. among 467 patients treated with laparoscopic radical prostatectomy for localized prostate cancer between 2007 and 2012, 249 patients who underwent a preoperative urodynamic study were enrolled. the patients' age, prostate volume, preoperative serum prostate-specific antigen (psa), gleason score, pathologic stage, and preoperative urodynamic parameters were recorded. the preoperative membranous and prostatic urethral length on magnetic resonance image, nerve sparing technique, and type of surgical procedure (extrafascial and intrafascial) were analyzed. patients were considered to have early recovery of continence when they needed no pad in 3 months or less after surgery. ninety-two patients were in the early recovery group and 157 were in the late recovery group. the membranous urethral lengths were 12.062.56 and 11.812.87 mm, and prostatic urethral lengths were 36.396.15 and 37.457.55 mm in each group, respectively. the membranous-posterior urethral length ratios were 0.250.06 and 0.240.06, and prostatic-posterior urethral length ratios were 0.750.06 and 0.760.06, respectively. in and of themselves, the membranous and prostatic urethral lengths were not associated with recovery duration however, the membranous-total and prostatic-total urethral length ratios were related (p0.024 and 0.024, respectively). none of the urodynamic parameters correlated with continence recovery time. in the multivariate analysis, the type of surgical procedure (odds ratio or, 7.032; 95 confidence interval ci, 2.660 to 18.590; p0.001) and membranous urethral length (or, 0.845; 95 ci, 0.766 to 0.931; p0.001) were significantly related to early recovery of continence.",the current intrafascial surgical procedure is the most important factor affecting early recovery of continence after laparoscopic radical prostatectomy.,Treatment
does ct perfusion predict secondary cerebral infarction after aneurysmal subarachnoid hemorrhage?,"to prospectively assess the diagnostic accuracy of ct perfusion (ctp) and transcranial doppler sonography (tcd) for the prediction of secondary cerebral infarction (sci) after aneurysmal subarachnoid hemorrhage (sah). during 2 weeks after sah, 38 consecutive patients completed an average of 3.5 ct/ctp and 10.7 tcd examinations at regular intervals as required by the study protocol. sci was defined as delayed infarction on native ct between 3 and 14 days after sah and developed in n 14 patients (n 24 without sci). analysis was based on examination dates before sci. common measures of diagnostic accuracy were calculated for qualitative ctp (visual color-map ratings from two blinded observers) and tcd assessments (mean flow velocity 120 cm/s in anterior, middle, and posterior cerebral artery territories). quantitative measures, which for ctp were obtained from cortical a priori regions of interest corresponding to the vascular territories, were analyzed by binary logistic regression. time of prediction for sci by ctp was at a median of 3 days (range 2 to 5 days) before manifestation of complete infarction on native ct. visual assessment of time-to-peak (ttp) color maps performed best for the prediction of sci with 0.93 sensitivity (95 ci: 0.7 to 1.0) and 0.67 specificity (95 ci: 0.53 to 0.7). on quantitative analysis, the odds ratio (or) for 1 second of side-to-side delay in ttp was 1.4 (p 0.01, wald chi(2) 8.57, ci: 1.07 to 1.82). daily tcd measures were not significantly related to sci at any time before complete infarction on native ct.",time to peak as indicated by ct perfusion is a sensitive and early predictor of secondary cerebral infarction.,Diagnosis
is short-term survival of the trabecular metal cup similar to that of standard cups used in acetabular revision surgery?,"the use of trabecular metal (tm) cups in revision surgery has increased worldwide during the last decade. since the introduction of the tm cup in sweden in 2006, this design has gradually replaced other uncemented designs used in sweden. according to data from the swedish hip arthroplasty register (shar) in 2012, one-third of all uncemented first-time cup revisions were performed using a tm cup. we compared the risk of reoperation and re-revision for tm cups and the 2 other most frequently used cup designs in acetabular revisions reported to the shar. the hypothesis was that the performance of tm cups is as good as that of established designs in the short term. the study population consisted of 2,384 patients who underwent 2,460 revisions during the period 2006 through 2012. the most commonly used cup designs were the press-fit porous-coated cup (n 870), the trabecular metal cup (n 805), and the cemented all-polyethylene cup (n 785). 54 of the patients were female, and the median age at index revision was 72 (19-95) years. reoperation was defined as a second surgical intervention, and re-revision-meaning exchange or removal of the cup-was used as endpoint. the mean follow-up time was 3.3 (0-7) years. there were 215 reoperations, 132 of which were re-revisions. the unadjusted and adjusted risk of reoperation or re-revision was not significantly different for the tm cup and the other 2 cup designs.","our data support continued use of tm cups in acetabular revisions. further follow-up is necessary to determine whether trabecular metal cups can reduce the re-revision rate in the long term, compared to the less costly porous press-fit and cemented designs.",Treatment
does systematic functional interrogation of rare cancer variants identify oncogenic alleles?,"cancer genome characterization efforts now provide an initial view of the somatic alterations in primary tumors. however, most point mutations occur at low frequency, and the function of these alleles remains undefined. we have developed a scalable systematic approach to interrogate the function of cancer-associated gene variants. we subjected 474 mutant alleles curated from 5,338 tumors to pooled in vivo tumor formation assays and gene expression profiling. we identified 12 transforming alleles, including two in genes (pik3cb, pot1) that have not been shown to be tumorigenic. one rare kras allele, d33e, displayed tumorigenicity and constitutive activation of known ras effector pathways. by comparing gene expression changes induced upon expression of wild-type and mutant alleles, we inferred the activity of specific alleles. because alleles found to be mutated only once in 5,338 tumors rendered cells tumorigenic, these observations underscore the value of integrating genomic information with functional studies.","experimentally inferring the functional status of cancer-associated mutations facilitates the interpretation of genomic information in cancer. pooled in vivo screen and gene expression profiling identified functional variants and demonstrated that expression of rare variants induced tumorigenesis. variant phenotyping through functional studies will facilitate defining key somatic events in cancer. cancer discov; 6(7); 714-26. 2016 aacr.see related commentary by cho and collisson, p. 694this article is highlighted in the in this issue feature, p. 681.",General
does rate at 120/min provide qualified chest compression during cardiopulmonary resuscitation?,"the quality of cardiopulmonary resuscitation (cpr) is a very important prognostic factor for cardiac arrest. chest compression is thought to be one of the most important aspects of high-quality cpr. recent studies have prompted that there may be an interaction between chest compression rate and other factors related to the quality of chest compression. we aimed to investigate the effect of different compression rates on chest compression depth, recoil, and rescuers' fatigue point during cpr. participants performed 2 minutes of chest compression-only cpr after the guiding sounds, at 3 rates (100, 120, and 140 compressions/min) in random sequence. a repeated-measures analysis of variance was used to compare the average chest compression depth and other factors related to the quality of chest compression among the groups. as the chest compression rate increases through all the 3 rates, the fractions of chest compressions with complete release and the fractions of chest compressions with sufficient depth were deteriorated at the rate of 140 compressions/min (p .05). of note, the fatigue point at 140 compressions/min happened significantly (p .05) sooner.",our study supported the concern of some that there may be a risk of increasing recommended chest compression rate without providing an upper limit. an appropriate choice may be 120 compressions/min.,Diagnosis
does combination of mtor inhibitors augment potency while activating pi3k signaling in pituitary tumors?,"despite the success in treating some cancers, the efficacy of the mtor inhibitors rapalogs as anti-cancer therapeutics has been limited. we undertook to examine the effects of torin1, a second-generation selective atp-competitive mtor inhibitor, in non-functioning pituitary tumor cells. during characterization of the molecular mechanisms that mediate torin1 actions, there seemed to be a rationale for combining it with rapalogs. proliferation assays, flow cytometry and western blotting were applied to assess the effects of torin1, rad001 and their combination on an mtt/e pituitary cell line and human-derived non-functioning pituitary tumor cells. combined long treatments of torin1 and rad001 induced a pronounced reduction in cell growth and viability of both mtt/e pituitary cells and human-derived non-functioning pituitary tumor cells, superior to each drug alone. this was remarkable in the 10 nm combination and was reflected in a triggered decrease of cyclin d3 and p21/cip expression. interestingly, akt-thr308 and sin1-thr86 phosphorylations were robustly elevated in the combined treatment, accompanied by a reduction in pten expression. phosphorylation of p70s6k was abolished in all individual and combined treatments. akt-ser473 phosphorylation, induced by rad001, was reduced by the combined treatment to the same extent as when treated by torin1 alone.",our results suggest that the differential signaling mechanisms induced by these compounds eventually converge to lead to an efficient blockade of the pi3k/akt/mtor pathway in pituitary tumor cells and may facilitate a reduction in treatment dosage.,Medication
does bepridil reverse atrial electrical remodeling and l-type calcium channel downregulation in a canine model of persistent atrial tachycardia?,"this study tested whether bepridil, a multichannel blocker, would reverse electrical remodeling induced by persistent atrial tachycardia. fourteen dogs were subjected to rapid atrial pacing at 400 bpm for 6 weeks after atrioventricular block was created to control the ventricular rate. during the study period, seven dogs were given placebo for 6 weeks (control group), and seven were given placebo for 3 weeks, followed by 3 weeks of bepridil (10 mg/kg/day, bepridil group). the atrial effective refractory period (erp) and the inducibility and duration of atrial fibrillation (af) were determined on a weekly basis. after 6 weeks, expression of l-type calcium channel alpha1c messenger ribonucleic acid (mrna) was quantified by real-time reverse transcription-polymerase chain reaction. in the control group, erp was shortened and the inducibility and duration of af increased through the 6-week period. in the bepridil group, the same changes occurred during the first 3 weeks, but were gradually reversed with bepridil. after 6 weeks, erp was longer, af inducibility was lower, and af duration was shorter in bepridil group than in the control group. expression of alpha1c mrna was decreased by 64 in the control group (p 0.05 vs sham), but in the bepridil group, it was not different compared with the sham dogs. as a whole group of dogs, erp was positively correlated with alpha1c mrna expression.",bepridil reverses the electrophysiological consequences of atrial remodeling to some extent and l-type calcium channel downregulation in a canine model of atrial tachycardia.,General
does extent of mgmt promoter methylation correlate with outcome in glioblastomas given temozolomide and radiotherapy?,"epigenetic silencing of o(6)-methylguanine-dna-methyltransferase (mgmt) by promoter methylation is associated with improved survival in glioblastomas treated with alkylating agents. in this study, we investigated mgmt promoter methylation in glioblastomas treated with temozolomide and radiotherapy in a single uk treatment centre. quantitative methylation data at individual cpg sites were obtained by pyrosequencing for 109 glioblastomas. median overall survival (os) was 12.4 months with 2-year survival of 17.9. pyrosequencing data were reproducible with archival samples yielding data for all glioblastomas. variation in methylation patterns of discrete cpg sites and intratumoral methylation heterogeneity were observed. a total of 58 out of 109 glioblastomas showed average methylation non-neoplastic brain in at least one clinical sample; 86 had homogeneous methylation status in multiple samples. methylation was an independent prognostic factor associated with prolonged progression-free survival (pfs) and os. cases with methylation more than 35 had the longest survival (median pfs 19.2; os 26.2 months, 2-year survival of 59.7). significant differences in pfs were seen between those with intermediate or high methylation and unmethylated cases, whereas cases with low, intermediate or high methylation all showed significantly different os.","these data indicate that mgmt methylation is prognostically significant in glioblastomas given chemoradiotherapy in the routine clinic; furthermore, the extent of methylation may be used to provide additional prognostic stratification.",Treatment
do farnesyl transferase inhibitors induce extended remissions in transgenic mice with mature b cell lymphomas?,"we have used a mouse model based on overexpression of c-myc in b cells genetically engineered to be self-reactive to test the hypothesis that farnesyl transferase inhibitors (ftis) can effectively treat mature b cell lymphomas. ftis are undergoing clinical trials to treat both lymphoid and non-lymphoid malignancies and we wished to obtain evidence to support the inclusion of b cell lymphomas in future trials. we report that two ftis, l-744,832 and sch66336, blocked the growth of mature b cell lymphoma cells in vitro and in vivo. the fti treatment affected the proliferation and survival of the transformed b cells to a greater extent than nave b cells stimulated with antigen. in syngeneic mice transplanted with the transgenic lymphoma cells, l-744,832 treatment prevented the growth of the tumor cells and the morbidity associated with the resulting lymphoma progression. tumors that arose from transplantation of the lymphoma cells regressed with as little as three days of treatment with l-744,832 or sch66336. treatment of these established lymphomas with l-744,832 for seven days led to long-term remission of the disease in approximately 25 of animals.","fti treatment can block the proliferation and survival of self-reactive transformed b cells that overexpress myc. in mice transplanted with mature b cell lymphomas, we found that fti treatment led to regression of disease. ftis warrant further consideration as therapeutic agents for mature b cell lymphomas and other lymphoid tumors.",Medication
do drivers of overweight mothers ' food choice behaviors depend on child gender?,"national data suggest a higher prevalence of obesity among boys. one possible cause could be the food choices made by parents on behalf of their children. this study sought to determine whether and how mothers' food choices for their children differ by child gender and to understand the drivers of these differences. data were analyzed from a randomized controlled trial conducted using a virtual reality-based buffet restaurant. overweight mothers filled out questionnaires and received an information module. they were then immersed in a virtual buffet restaurant to select a lunch for their 4- to 5-year-old child. of the 221 overweight mothers recruited, 55 identified their daughters as the child for whom they would be choosing the food. the caloric content of boys' meals was 43 calories higher than girls' (p .015). this difference was due to extra calories from the less healthy food category (p .04). multivariate analyses identified more predictors of calorie choices for daughters' than sons' meals. predictors of calories chosen for girls included: having both biological parents overweight ( 0.26; p .003), mother's weight ( 0.17; p .05), mother's education ( -0.28; p .001), her restriction of her child's food intake ( -0.20; p .02), and her beliefs about the importance of genetics in causing obesity ( 0.19; p .03). mother's weight was the sole predictor of boys' meal calories ( 0.20; p .04).",differences in dietary choices made for young girls and boys may contribute to lifelong gender differences in eating patterns. a better understanding of differences in feeding choices made for girls versus boys could improve the design of childhood obesity prevention interventions.,Prevention
does pre-surgery disability compensation predict long-term disability among workers with carpal tunnel syndrome?,"we sought to identify early risk factors for work disability compensation prior to and after carpal tunnel syndrome (cts) surgery, and to determine whether pre-surgery disability compensation is associated with long-term disability. washington state workers' compensation administrative data and data from interviews with workers 18 days (median) after submitting new workers' compensation claims for cts were examined. baseline risk factors for pre-surgery disability compensation and for long-term disability (365 days of work disability compensation prior to 2 years after claim filing) were evaluated for workers who underwent cts surgery and had at least 1 day of disability compensation (n 670). after adjustment for baseline long-term disability risk factors, workers with pre-surgery disability compensation had over five times the odds of long-term disability. baseline factors in multiple domains, including job, psychosocial, clinical, and worker pain and function, were associated with both pre-surgery disability compensation and long-term disability.","risk factors for work disability prior to and after cts surgery are similar, and early work disability is a risk factor for long-term cts-related disability. an integrated approach to cts-related disability prevention could include identifying and addressing combined risk factors soon after claim filing, more efficient use of conservative treatments and appropriate work modifications to minimize early work loss, and, when indicated, timely surgical intervention.",Treatment
does three-dimensional reconstruction allow accurate quantification and length measurements of coronary artery stenoses?,"the aim of this prospective study was to evaluate the feasibility and accuracy of a recently developed 3d system (cardiop-b; paieon medical ltd., israel) as compared to a validated quantitative coronary angiography (qca) system (siemens quantcor, siemens medical solutions). in patients scheduled for heart catheterisation, minimal lumen diameter (mld) and diameter-derived percent stenosis (dps) were obtained for cas (50) using both qca and the 3d-system. to estimate stenosis length, a non-inflated balloon was inserted into the stenosis and the distance between balloon markers was measured using both methods and then compared to the known distance between the markers. in 61 patients 79 lesions were analysed. mld measurements showed a good agreement between qca and 3d with a mean difference of 0.08/-0.035 mm. reference diameter was 2.61/-0.67 for 3d and 2.42/-0.61 mm for qca and 54.79/-9.20 vs. 58.75/-8.15 for the -stenosis range, respectively. the mean true balloon length was 12.8 mm/-3.8 mm. lengths determined by the 3d system were 13.0/-4.0 mm and 11.3/-3.8 mm by qca, respectively.","evaluation of cas using the novel 3d system was feasible and showed equivalent results to validated qca measurements. length measurements seemed to be more accurate by the 3d system as compared to qca. therefore, this 3d-system can be used to guide decisions in interventional cardiology.",Treatment
is active methamphetamine use associated with transmitted drug resistance to non-nucleoside reverse transcriptase inhibitors in individuals with hiv infection of unknown duration?,"frequent methamphetamine use among recently hiv infected individuals is associated with transmitted drug resistance (tdr) to non-nucleoside reverse transcriptase inhibitors (nnrti); however, the reversion time of tdr to drug susceptible hiv may exceed 3 years. we assessed whether recreational substance use is associated with detectable tdr among individuals newly diagnosed with hiv infection of unknown duration. cross-sectional analysis. subjects were enrolled at the university california, san diego early intervention program. demographic, clinical and substance use data were collected using structured interviews. genotypic resistance testing was performed using geneseq, monogram biosciences. we analyzed the association between substance use and tdr using bivariate analyses and the corresponding transmission networks using phylogenetic models. between april 2004 and july 2006, 115 individuals with genotype data were enrolled. the prevalence of alcohol, marijuana and methamphetamine use were 98, 71 and 64 respectively. only active methamphetamine use in the 30 days prior to hiv diagnosis was independently associated with tdr to nnrti (or: 6.6; p0.002).","despite not knowing the duration of their hiv infection, individuals reporting active methamphetamine use in the 30 days prior to hiv diagnosis are at an increased risk of having hiv strains that are resistant to nnrti.",Medication
is meld score a better prognostic model than child-turcotte-pugh score or discriminant function score in patients with alcoholic hepatitis?,"the aim of the present study was to compare meld score, child-turcotte-pugh (ctp) score, modified maddrey's discriminant function (df) score, and the related variables in predicting in-hospital mortality of patients with alcoholic hepatitis. a retrospective chart review and statistical analyses were done on 202 patients consecutively admitted for alcoholic hepatitis from 1997 to 2002 at the liver unit at rancho los amigos medical center. twenty-nine patients died during the hospitalization. admission meld score (or 1.1, p0.005), first week meld score (or 1.2, p/20 had the best sensitivity (91) and specificity (85) compared with admission or first week change meld score.","the present study indicates that in patients with alcoholic hepatitis, admission, first week, and first week change in meld score are significantly independent predictors for in-hospital mortality. meld score is a more valuable model than ctp or df score in patients admitted with alcoholic hepatitis.",Diagnosis
does caffeine intake enhance the benefits of sodium glucose transporter 2 inhibitor?,"the effect of sodium glucose transporter 2 (sglt-2) inhibitors is dependent on the glomerular filtration rate. it has been reported that caffeine intake increases glomerular filtration rate. however, the effect of caffeine intake on urinary glucose excretion in patients who take sglt-2 inhibitors is unclear. six patients with type 2 diabetes took part in a randomized, open-label, crossover pilot study. the patients took sglt-2 inhibitors (ipragliflozin) for 9 days. on day 3, 6 and 9, the patients were assigned to one of three studies: water 500, patients drank 500 ml of water in 3 h; water 1500, patients drank 1500 ml of water in 3 h; and caffeine 500, patients drank 500 ml of water with 400 mg of caffeine in 3 h. in all of the studies, the patients' urine was collected over a 6-h period. in addition, we enrolled 60 patients with type 2 diabetes who newly took sglt-2 inhibitors in a 3-month follow-up cohort study to investigate the effect of caffeine intake on glucose control. caffeine intake was evaluated using questionnaires. the 6-h median (interquartile range) urinary glucose excretion was 9.5 (8.5-9.7) g in water 500, 12.2 (10.3-27.2) g in water 1500 and 15.7 (11.4-21.4) g in caffeine 500 (p 0.005 vs water 500). in the cohort study, multiple regression analysis demonstrated that log (caffeine intake) was associated with a change in hba","caffeine intake enhanced the effect of sglt-2 inhibitors. copyright 2016 john wiley sons, ltd.",Medication
does low-salt diet increase no bioavailability and cox-2 vasoconstrictor prostanoid production in spontaneously hypertensive rats?,"the ability of dietary sodium restriction to reduce the incidence of cardiovascular mortality and improve vascular function in hypertension still remains poorly understood. the aim of this study was to observe the effects of a long period of salt restriction on the vascular reactivity of mesenteric resistance arteries of shrs. male shrs received either standard-salt diet (0.3 nacl) or low-salt diet (0.03 nacl) for 28weeks. vascular reactivity was studied in mesenteric artery segments and the influence of cyclooxygenase-2 (cox-2), reactive oxygen species (ros) and participation of the renin-angiotensin system were analyzed. decreased salt intake did not affect phenylephrine-induced vasoconstriction but increased acetylcholine-induced vasodilatation and also increased the response to phenylephrine after inhibition of no synthase by l-name (100m) and inos protein expression was elevated. cyclooxygenase inhibitor indomethacin (10m) and cox-2 inhibitor ns 398 (1m) decreased the reactivity to phenylephrine in low-salt-treated group, and cox-2 protein expression was elevated in low-salt group. the effects of apocynin (10m); superoxide anion scavenger, tiron (1mm); hydrogen peroxide scavenger, catalase (1000uml(-1)); and ace and at1 receptor blockers, enalapril (10m) and losartan (10m) on vascular reactivity were not different between two groups. the levels of at1 protein expression were similar in both groups.","low-salt diet modulates mesenteric vascular responses via increased no bioavailability suggested by increased inos protein expression and vasoconstrictor prostanoid production via cox-2 pathway, in shrs. neither ros nor the local renin-angiotensin system is involved in these responses.",Prevention
does angiopoietin-like protein3 regulate plasma hdl cholesterol through suppression of endothelial lipase?,"a low level of high-density lipoprotein (hdl) in plasma has been recognized as an aspect of metabolic syndrome and as a crucial risk factor of cardiovascular events. however, the physiological regulation of plasma hdl levels has not been completely defined. current studies aim to reveal the contribution of angiopoietin-like protein3 (angptl3), previously known as a plasma suppressor of lipoprotein lipase, to hdl metabolism. angptl3-deficient mice showed low plasma hdl cholesterol and hdl phospholipid (pl), and which were increased by angptl3 supplementation via adenovirus. in vitro, angptl3 inhibited the phospholipase activity of endothelial lipase (el), which hydrolyzes hdl-pl and hence decreases plasma hdl levels, through a putative heparin-binding site in the n-terminal domain of angptl3. post-heparin plasma in angptl3-knockout mice had higher phospholipase activity than did that in wild-type mice, suggesting that the activity of endogenous el is elevated in angptl3-deficient mice. furthermore, we established an elisa system for human angptl3 and found that plasma angptl3 levels significantly correlated with plasma hdl cholesterol and hdl-pl levels in human subjects.",angptl3 acts as an inhibitor of el and may be involved in the regulation of plasma hdl cholesterol and hdl-pl levels in humans and rodents.,Medication
does tbx1 genetically interact with the transforming growth factor-/bone morphogenetic protein inhibitor smad7 during great vessel remodeling?,"growth and remodeling of the pharyngeal arch arteries are vital for the development of a mature great vessel system. dysmorphogenesis of the fourth arch arteries can result in interruption of the aortic arch type b, typically found in digeorge syndrome. tbx1 haploinsufficient embryos, which model digeorge syndrome, display fourth arch artery defects during formation of the vessels. recovery from such defects is a documented yet unexplained phenotype in tbx1 haploinsufficiency. to understand the nature of fourth arch artery growth recovery in tbx1 haploinsufficiency and its underlying genetic control. we categorized vessel phenotypes of tbx1 heterozygotes as hypoplastic or aplastic at the conclusion of pharyngeal artery formation and compared these against the frequency of vessel defects scored at the end of great vessel development. the frequency of hypoplastic vessels decreased during embryogenesis, whereas no reduction of vessel aplasia was seen, implying recovery is attributable to remodeling of hypoplastic vessels. we showed that smad7, an inhibitory smad within the transforming growth factor- pathway, is regulated by tbx1, is required for arch artery remodeling, and genetically interacts with tbx1 in this process. tbx1 and tbx1;smad7 haploinsufficiency affected several remodeling processes; however, concurrent haploinsufficiency particularly impacted on the earliest stage of vascular smooth muscle cell vessel coverage and subsequent fibronectin deposition. conditional reconstitution of smad7 with a tbx1cre driver indicated that the interaction between the 2 genes is cell autonomous.",tbx1 acts upstream of smad7 controlling vascular smooth muscle and extracellular matrix investment of the fourth arch artery.,Medication
is hepatitis c virus ns4b carboxy terminal domain a membrane binding domain?,"hepatitis c virus (hcv) induces membrane rearrangements during replication. all hcv proteins are associated to membranes, pointing out the importance of membranes for hcv. non structural protein 4b (ns4b) has been reported to induce cellular membrane alterations like the membranous web. four transmembrane segments in the middle of the protein anchor ns4b to membranes. an amphipatic helix at the amino-terminus attaches to membranes as well. the carboxy-terminal domain (ctd) of ns4b is highly conserved in hepaciviruses, though its function remains unknown. a cytosolic localization is predicted for the ns4b-ctd. however, using membrane floatation assays and immunofluorescence, we now show targeting of the ns4b-ctd to membranes. furthermore, a profile-profile search, with an hcv ns4b-ctd multiple sequence alignment, indicates sequence similarity to the membrane binding domain of prokaryotic d-lactate dehydrogenase (d-ldh). the crystal structure of e. coli d-ldh suggests that the region similar to ns4b-ctd is located in the membrane binding domain (mbd) of d-ldh, implying analogy in membrane association. targeting of d-ldh to membranes occurs via electrostatic interactions of positive residues on the outside of the protein with negative head groups of lipids. to verify that anchorage of d-ldh mbd and ns4b-ctd is analogous, ns4b-ctd mutants were designed to disrupt these electrostatic interactions. membrane association was confirmed by swopping the membrane contacting helix of d-ldh with the corresponding domain of the 4b-ctd. furthermore, the functionality of these residues was tested in the hcv replicon system.","together these data show that ns4b-ctd is associated to membranes, similar to the prokaryotic d-ldh mbd, and is important for replication.",General
does ezetimibe inhibit lymphatic transport of esterified cholesterol but not free cholesterol in thoracic lymph duct-cannulated rats?,"ezetimibe has been shown to inhibit dietary cholesterol absorption in animal models and humans, but studies on lymphatic lipid transport have not yet been performed. rats subjected to permanent lymph duct cannulation were used to investigate the effects of ezetimibe on lipid transport. rats were fed diets with and without ezetimibe (5.0 mg/kg), and their lymph was collected after feeding to quantify lymphatic lipid levels. total cholesterol content in the intestinal mucosa was also measured. rats that consumed ezetimibe had significantly lower lymphatic total cholesterol transport with the reduction of esterified cholesterol transport. according to the calculation based on cholesterol consumption, ezetimibe reduced the total cholesterol lymphatic recovery rate by 54 . we also determined that ezetimibe significantly reduced the total cholesterol content in the intestinal mucosa.","this is the first direct evidence that ezetimibe inhibits esterified but not free cholesterol lymphatic transport in thoracic duct-cannulated rats. the results also indicate that ezetimibe is not involved in the lymphatic transport of triacylglycerols, phospholipids, or -tocopherol.",Prevention
does evolutionary rate depend on number of protein-protein interactions independently of gene expression level?,whether or not a protein's number of physical interactions with other proteins plays a role in determining its rate of evolution has been a contentious issue. a recent analysis suggested that the observed correlation between number of interactions and evolutionary rate may be due to experimental biases in high-throughput protein interaction data sets.,"the number of interactions per protein, as measured by some protein interaction data sets, shows no correlation with evolutionary rate. other data sets, however, do reveal a relationship. furthermore, even when experimental biases of these data sets are taken into account, a real correlation between number of interactions and evolutionary rate appears to exist.",General
does tamoxifen suppress the growth of malignant pleural mesothelioma cells?,"malignant pleural mesothelioma (mpm) is a rare but highly aggressive malignancy most often associated with exposure to asbestos. recent evidence points to oestrogen receptor (er)- having a tumour-suppressor role in mpm progression, and this raises the question of whether selective modulators of ers could play a role in augmenting mpm therapy. we investigated the action of tamoxifen in inhibiting the growth and modulating the cisplatin sensitivity of four mpm cell lines. tamoxifen inhibited the growth of mpm cells and also modulated their sensitivity to cisplatin. the mpm cell lines expressed er, but the actions of tamoxifen were not blocked by antagonism of nuclear ers. tamoxifen treatment repressed the expression of cyclins by mpm cells, resulting in cell-cycle arrest and caspase-3-coupled apoptosis signaling.",the er-independent actions of tamoxifen on mpm cell proliferation and cell-cycle progression may have clinical benefits for a subset of patients with mpm.,Treatment
does nitric oxide stimulate early egress of toxoplasma gondii tachyzoites from human foreskin fibroblast cells?,"egress is a vital step in the life cycle of toxoplasma gondii which attracts attentions of many groups. previous studies have shown that exogenous nitric oxide (no) stimulates the early egress of t. gondii from infected peritoneal macrophages, a kind of immune cells. however, because toxoplasma forms cysts in brain and muscle tissues, the development of autonomous immunity in non-immune cells is vital for limiting parasite burden and cyst formation. therefore, we attempted to investigate whether exogenous no could induce the early egress of t. gondii from infected non-immune cells. t. gondii tachyzoites were cultured in human foreskin fibroblast (hff) cells and were then treated with no released by sodium nitroferricyanide (iii) dihydrate (snp). the egressed parasites were analysed by flow cytometry. the results showed that no induced the early egress of parasites from hff cells before completing their intracellular life cycles. we also found that the occurrence of egress was dependent on intracellular calcium (ca(2)) levels and the mobility of the parasite. compared with freshly isolated tachyzoites, the developmental ability and virulence of egressed tachyzoites presented no difference.","taken together, our findings demonstrate a novel assay for the analysis of egress signalling mechanisms and an avenue of parasite clearance by hosts of t. gondii.",Treatment
does 334 a functional screen identify mirnas that induce radioresistance in glioblastomas?,"the efficacy of radiotherapy in many tumor types is limited by normal tissue toxicity and by intrinsic or acquired radioresistance. an unbiased functional microrna screen identified 4 mirnas (mir1, mir125a, mir150, and mir425) that induced glioblastoma radioresistance. we employed gain and loss of function approaches to validate the critical importance of these mirnas as determinants of glioblastoma radiation resistance. overexpression of mir1, mir125a, mir150, and/or mir425 in glioblastoma promotes radioresistance through upregulation of the cell-cycle checkpoint response. conversely, antagonizing with antagomirs sensitizes glioblastoma cells to irradiation, suggesting their potential as targets for inhibiting therapeutic resistance. analysis of glioblastoma data sets from the cancer genome atlas (tcga) revealed that these mirnas are expressed in glioblastoma patient specimens and correlate with transforming growth factor (tgf) signaling. finally, it is demonstrated that expression of mir1 and mir125a can be induced by tgf and antagonized by a tgf receptor inhibitor. together, these results identify and characterize a new role for mir425, mir1, mir125, and mir150 in promoting radioresistance in glioblastomas and provide insight into the therapeutic application of tgf inhibitors in radiotherapy.",systematic identification of mirs that cause radioresistance in gliomas is important for uncovering predictive markers for radiotherapy or targets for overcoming radioresistance.,Diagnosis
does development of a risk index for prediction of abnormal pap test result in serbia?,"serbia is one of the countries with highest incidence and mortality rates for cervical cancer in central and south eastern europe. introducing a risk index could provide a powerful means for targeting groups at high likelihood of having an abnormal cervical smear and increase efficiency of screening. the aim of the present study was to create and assess validity ofa index for prediction of an abnormal pap test result. the study population was drawn from patients attending departments for women's health in two primary health care centers in serbia. out of 525 respondents 350 were randomly selected and data obtained from them were used as the index creation dataset. data obtained from the remaining 175 were used as an index validation data set. age at first intercourse under 18, more than 4 sexual partners, history of std and multiparity were attributed statistical weights 16, 15, 14 and 13, respectively. the distribution of index scores in index-creation data set showed that most respondents had a score 0 (54.9). in the index-creation dataset mean index score was 10.3 (sd-13.8), and in the validation dataset the mean was 9.1 (sd13.2).","the advantage of such scoring system is that it is simple, consisting of only four elements, so it could be applied to identify women with high risk for cervical cancer that would be referred for further examination.",Diagnosis
do helicobacter pylori 's virulence and infection persistence define pre-eclampsia complicated by fetal growth retardation?,"to better understand the pathogenic role of helicobacter pylori (h. pylori) in pre-eclampsia (pe), and whether it is associated or not with fetal growth retardation (fgr). maternal blood samples were collected from 62 consecutive pregnant women with a diagnosis of pe and/or fgr, and from 49 women with uneventful pregnancies (controls). serum samples were evaluated by immunoblot assay for presence of specific antibodies against h. pylori antigens virulence: cytotoxin-associated antigen a (caga); ureases; heat shock protein b; flagellin a; persistence: vacuolating cytotoxin a (vaca). maternal complete blood count and liver enzymes levels were assessed at delivery by an automated analyzer. a significantly higher percentage of h. pylori seropositive women were found among pe cases (85.7) compared to controls (42.9, p 0.001). there were no differences between pregnancies complicated by fgr without maternal hypertension (46.2) and controls. importantly, persistent and virulent infections (vaca/caga seropositive patients, intermediate leukocyte blood count and aspartate aminotransferase levels) were exclusively associated with pre-eclampsia complicated by fgr, while virulent but acute infections (caga positive/vaca negative patients, highest leukocyte blood count and aspartate aminotransferase levels) specifically correlated with pe without fgr.","our data strongly indicate that persistent and virulent h. pylori infections cause or contribute to pe complicated by fgr, but not to pe without feto-placental compromise.",Diagnosis
does functional blockade of 51 integrin induce scattering and genomic landscape remodeling of hepatic progenitor cells?,"cell scattering is a physiological process executed by stem and progenitor cells during embryonic liver development and postnatal organ regeneration. here, we investigated the genomic events occurring during this process induced by functional blockade of 51 integrin in liver progenitor cells. cells treated with a specific antibody against 51 integrin exhibited cell spreading and scattering, over-expression of liver stem/progenitor cell markers and activation of the erk1/2 and p38 mapks signaling cascades, in a similar manner to the process triggered by hgf/sf1 stimulation. gene expression profiling revealed marked transcriptional changes of genes involved in cell adhesion and migration, as well as genes encoding chromatin remodeling factors. these responses were accompanied by conspicuous spatial reorganization of centromeres, while integrin genes conserved their spatial positioning in the interphase nucleus.","collectively, our results demonstrate that 51 integrin functional blockade induces cell migration of hepatic progenitor cells, and that this involves a dramatic remodeling of the nuclear landscape.",Treatment
are the proinflammatory cxc-chemokines gro-alpha/cxcl1 and mig/cxcl9 concomitantly expressed in ulcerative colitis and decrease during treatment with topical corticosteroids?,"ulcerative colitis is characterized by relapsing mucosal inflammation where the lesions include tissue-damaging granulocytes. in addition, t cells and natural killer (nk) cells play important pathophysiologic roles. chemokines are a large family of peptides that play key roles in the regulation of inflammation. the cxc-chemokines, growth-related oncogene (gro)-alpha/cxcl1 and interleukin (il)-8/cxcl8, both recruit neutrophils and possess mitogenic properties, whereas the interferon-dependent cxc-chemokines monokine induced by gamma-interferon (mig)/cxcl9, interferon-gamma inducible protein of 10 kd/cxcl10, and ifn-inducible t cell alpha chemoattractant/cxcl11 recruit and activate t cells and nk cells. the expression of cxc-chemokines was studied in eight controls and in 11 patients suffering from ulcerative colitis in the distal part of the colon, before and during topical treatment with corticosteroids. perfusates (obtained before, after 7 days, and after 28 days of treatment) and pinch biopsies (obtained before and after 28 days of treatment) were collected by colonoscopy. the rectal release of gro-alpha and mig was determined by enzyme-linked immunosorbent assay (elisa), and tissue expression of the chemokines was detected in colonic tissue by immunohistochemistry. in perfusates, high levels of gro-alpha, il-8, and mig were detected compared with controls (p0.02, 0.005, and p0.03, respectively). during treatment with corticosteroids, both gro-alpha and mig decreased. in clinical nonresponders, characterized by sustained inflammation, the levels of gro-alpha and mig remained elevated. both epithelial cells and granulocytes, present in the submucosa, expressed gro-alpha and mig as detected by immunohistochemistry.","cxc-chemokines are likely to be important in the pathophysiology of ulcerative colitis and may become targets for novel treatment strategies. in addition, gro-alpha may serve as a marker of disease activity.",Medication
does neonatal screening for cystic fibrosis affect time to first infection with pseudomonas aeruginosa?,"newborn screening for cystic fibrosis was introduced in the piedmont region of italy in the year 2000. our aim with this study was to estimate the effect of newborn screening on the risk of pseudomonas aeruginosa infection at the regional cystic fibrosis pediatric reference center. the time to first infection with p aeruginosa within the historical cohort of cystic fibrosis children diagnosed between january 1, 1997, and june 30, 2004, was investigated, comparing survival functions and the adjusted hazard ratio of children diagnosed before and after newborn screening introduction. the role of pancreatic insufficiency was also concurrently investigated. overall, 71 children diagnosed with cystic fibrosis were identified, 27 cases were clinically diagnosed before newborn screening introduction, and 5 of them presented with meconium ileus, whereas 44 were identified by newborn screening. among them 35 needed pancreatic enzyme supplementation, whereas 34 children were infected with p aeruginosa. both the nonparametric and semiparametric survival estimates failed to show any significant increase in the risk of p aeruginosa infection among screened children compared with historical controls. however, the median time from cystic fibrosis diagnosis to p aeruginosa infection among screened children was significantly shorter (183 vs 448 days). children with impaired pancreatic function were at high risk of p aeruginosa infection.",the results of the study suggest that health authorities should regard newborn screening for cystic fibrosis as an opportunity to improve care and outcomes among affected children and shift the focus from whether it is appropriate to screen to how to optimize biomedical and psychosocial outcomes of screening.,Diagnosis
is interferon-gamma required for lupus nephritis in mice treated with the hydrocarbon oil pristane?,"although the precise mechanisms leading to lupus nephritis remain obscure, both th1 and th2 cytokines have been implicated. the present study examined the roles of interleukin (il)-4 and interferon-gamma (ifn-gamma) in a novel inducible form of lupus that develops in non-autoimmune mice treated with the hydrocarbon oil pristane. balb/c il-4 or ifn-gamma deficient mice (il-4 -/-, ifngamma -/-) and wild type controls (/) received either pristane or phosphate-buffered saline (pbs) ip. serial sera were analyzed for anti-dna/chromatin, anti-rnp/sm, and total immunoglobulin levels. proteinuria was measured and kidneys were examined by direct immunofluorescence and light microscopy. renal disease did not develop in pristane-treated ifn-gamma -/- mice, as assessed by the absence of capillary immune deposits, glomerular pathology and proteinuria whereas il-4 -/- mice developed renal disease similar to / mice. production of igg anti-single stranded dna and anti-chromatin antibodies was abrogated in ifn-gamma -/- mice. in contrast, these autoantibodies were produced at similar or higher frequencies and levels by il-4 -/- versus wild-type mice. the frequency of anti-nrnp/sm was markedly reduced in ifn-gamma -/- mice. il-4 deficiency had little effect on the production of anti-dna/chromatin and anti-nrnp/sm.","ifn-gamma is essential for the induction of nephritis and anti-dna/chromatin following pristane exposure in balb/c mice, suggesting that genetic or environmental factors influencing th1-th2 balance could be an important determinant of renal disease in lupus.",Treatment
does gene therapy with mitochondrial heat shock protein 70 suppress visual loss and optic atrophy in experimental autoimmune encephalomyelitis?,"to rescue visual loss and optic neuropathy in experimental autoimmune encephalomyelitis (eae). encephalomyelitis was induced in mice that received intravitreal injections of aav2-mthsp70flag or aav2-cox8-mcherry. additional mice were injected with aav2-cox8-mcherry, but not sensitized for eae. visual function was assessed by pattern electroretinograms (perg) at 1, 3, and 6 months post injection (mpi). optical coherence tomography (oct) evaluated the thickness of the inner plexiform layer nerve fiber layers at 1, 3, and 6 mpi. retinas and optic nerves (ons) of mice euthanized 6 mpi were processed for light and electron microscopy. expression of mthsp70flag in the retina and ons was evaluated by rt-pcr, immunofluorescence, and western blotting. the activities of respiratory complexes i and iii, as well as mitochondrial protein import were quantitated. expression: immunofluorescence revealed punctate and perinuclear expression of mthsp70flag that colocalized with mitochondrial porin in thy1.2 labeled retinal ganglion cells (rgcs). immunoblotting and rt-pcr confirmed mthsp70flag expression in the retina and on. rescue: treatment with mthsp70flag resulted in a 44 increase in perg amplitude and less delays in latency relative to the eae-mcherry group that also showed progressive inner retinal thinning. at 6 mpi, the almost 50 loss of rgcs and optic nerve axons in eae mice was suppressed by mthsp70flag. in addition, retinas of eae-mthsp70flag mice showed nearly complete rescue of complex i and iii activities that was reduced by one-third in the eae-mcherry retinas. lastly, reductions in import of cox8-mcherry into mitochondria of mice sensitized for eae improved by 30 with mthsp70flag gene therapy.",mitochondrial hsp70 ameliorates mitochondrial dysfunction that culminates in irreversible visual loss and atrophy of the optic nerve in eae suggesting that it may be useful to prevent irreversible disability in patients with optic neuritis and multiple sclerosis (ms).,Treatment
does dietary threonine reduce plasma phenylalanine levels in patients with hyperphenylalaninemia?,"in order to achieve normal intellectual development, the plasma phe-nylalanine (phe) levels of patients with hyperphenylalaninemia should not exceed toxic levels. this goal is usually accomplished by employing special diets in which the patient's protein intake is in the form of phe-free mixtures of amino acids. there is evidence from our own observations in animals and a preliminary observation in patients with hyperphenylalaninemia that supplemental dietary threonine (thr) might decrease plasma phe concentrations. in this placebo-controlled crossover study, the effect of supplemental oral thr on the plasma amino acid concentrations of 12 patients with hyperphenylalaninemia was investigated. before starting the first treatment period of this cross-over study, the patients were randomly assigned to one of two groups supplemented either with approximately 50 mg thr/kg per day or with a similar amount of maltodextrin as placebo. after a feeding period of 8 weeks and a wash-out period of 8 weeks, the supplements were crossed over and the study continued for an additional 8 weeks. blood was obtained at the start and the end of each supplementation period. dietary thr supplementation of approximately 50 mg/kg per day resulted in a significant decrease of plasma phe levels ( p 0.0234). there was a close positive correlation between plasma and urinary phe concentrations ( p 0.001) indicating that the lower plasma phe levels in the thr supplemented patients were not caused by higher urinary excretion of phe.","the data of the present study show that oral thr supplementation has a clear plasma-phe-reducing effect but they do not allow any conclusion about the mechanisms responsible for the observed effect. although it seems attractive on the basis of the present data to use thr supplementation in patients with hyperphenylalaninemia, the mechanism of the observed effect should be clarified before introduction of such a treatment in these patients.",Prevention
do incidence and etiology of mortality in polytrauma patients in a dutch level i trauma center?,"earlier studies assessing mortality in polytrauma patients have focused on improving trauma care and reducing complications during hospital stay. the same studies have shown that the complication rate in these patients is high, often resulting in death. the aim of this study was to assess the incidence and causes of mortality in polytrauma patients in our institute. secondarily, we assessed the donation and autopsy rates and outcome in these patients. all polytrauma patients (injury severity score16) transported to and treated in our institute during a period of 6 years were retrospectively analyzed. we included all patients who died during hospital stay. prehospital and in-hospital data were collected on patients' condition, diagnostics, and treatment. the chance of survival was calculated according to the triss methodology. patients were categorized according to the complications during treatment and causes of death. logistic regression analysis was used to design a prediction model for mortality in major trauma. a statistical analysis was carried out. of the 1073 polytrauma patients who were treated in our institute during the study period, 205 (19.1) died during hospital stay. the median age of the deceased patients was 58.8 years and 125 patients were men. their mean injury severity score was 30.4. the most common mechanism of injury involved fall from height, followed by bicycle accidents. almost 50 of the patients underwent an emergency intervention. almost 92 of the total population died because of the effects of the accident (primary trauma). of these, 24 died during primary assessment in the emergency department. most patients died because of the effects of severe head injury (63.4), followed by exsanguination (17.6). the most common type of complications causing death during treatment was respiratory failure (6.3), followed by multiple organ failure (1.5). autopsy was performed in 10.4. organ donation procedure was performed in 14.5. permission for donation was not provided in almost 20 of the population.",the mortality rate in polytrauma patients in our institute is considerable and comparable with the international literature. most patients die because of the effects of the accident (primary trauma). autopsy and organ donation rates are low in our institution and leave room for substantial improvements in the future.,Treatment
does elevated expression of fgf-2 cause prostate cancer progression in lncap cells?,"androgen-independent (ai) prostate cancer (cap) resulting from progression of disease is untreatable. such progression may relate to upregulation and autocrinicity of growth factor expression. we studied one candidate growth factor, basic fibroblast growth factor (fgf-2). lncap cells made autocrine for fgf-2 by stable transfection with fgf-2 were examined for cancer progression, measured by 1) altered response to androgen, 2) ability to grow more quickly when cocultured with bone cells in vitro or to form tumors when coinoculated with bone cells in vivo, or 3) increase in metastatic ability. stably transfected lines differed in fgf-2 protein expression. lncap-hf (high production of fgf-2) expressed more fgf-2 than lncap-lf (low production of fgf-2); controls were negative. in vitro, compared with lncaps, lncap-hf cells showed a slightly increased growth rate, reduced proliferation in response to androgen but not to estrogen or progesterone, and a decreased proliferative response to epidermal growth factor (egf) and fgf-2. although giving a slightly faster take rate, lncap-hf cells without matrigel only formed small, fast-regressing tumors in male nude mice, and with matrigel, did not differ from lncaps in growth rate or tumor size. no metastases occurred. no tumors grew in females. mixed growth of fgf-2 transfectants with human fetal osteoblasts failed to cross-stimulate in vitro, or to allow tumor formation in vivo.","although fgf-2 is overexpressed in ai caps, our experiments show that upregulation of fgf-2 expression is not sufficient to cause androgen independence, tumorigenicity, or metastases production (i.e., prostate cancer progression) in lncap cells.",General
does accuracy of pointing movements rely upon a specific tuning between anticipatory postural adjustments and prime mover activation?,"equilibrium-perturbing forces associated with a voluntary upper-limb movement can be strong enough to displace the whole-body centre of mass. in this condition, anticipatory postural adjustments (apas), developing in muscles other than the prime mover, are essential in maintaining the whole-body balance. here, we test the hypothesis that apas preceding an upper-limb target-reaching movement could play a role also in controlling the movement accuracy. standing subjects (10) were asked to flex the right shoulder and touch with the index fingertip the centre of a target positioned in front of them. the reaching task was also performed while wearing and after doffing prismatic lenses (shifting the eye field rightward). emgs from different upper- and lower-limb muscles and the mechanical actions to the ground were recorded. (i) before wearing prisms, subjects were very accurate in hitting the target, and the pointing movements were accompanied by apas in quadriceps (q) and tibialis anterior (ta) of both sides, and in right hamstrings (h) and soleus (sol). (ii) after donning prisms, rightward pointing errors occurred, associated with a significant apa increase in right q and ta, but without changes in the recruitment of right anterior deltoid (prime mover) and biceps brachii. (iii) these pointing errors were progressively compensated in about 10 trials, indicating a sensorimotor adaptation, and apas returned to values recorded before wearing prisms. (iv) after doffing prisms, pointing errors occurred in the opposite direction but changes in apas did not reach significance.","we propose that, besides preserving the whole-body balance, apas are also tailored to obtain an accurate voluntary movement.",Diagnosis
do interventions using foreign material to treat congenital heart disease in children increase the risk for infective endocarditis?,"congenital heart disease (chd) is a risk factor for infective endocarditis (ie). we aimed to assess the impact of cardiac interventions on the frequency and microbial profile of ie in children with chd. episodes of ie were analyzed in children aged or 18 years with chd between 1995 and 2005 with respect to cardiac surgery or catheter interventions with or without implantation of foreign material. diagnosis of ie was made in 14 (0.36) of 3826 children with chd including native ie in 6 and postinterventional ie in 8 patients. during the period 3029 cardiac interventions (1944 surgeries; 1085 catheters) were performed; foreign material was implanted in 1360 interventions (1139 surgeries; 221 catheters) including all 8 patients with postinterventional ie. cardiac intervention by itself did not change the risk for ie compared with no intervention. the risk of ie after implantation of foreign material was higher than following intervention without implantation (odds ratio, 21.0; 95 confidence interval, 1.2-365; p 0.05). pacemaker implantation was associated with the highest risk for ie (odds ratio, 11.0; 95 confidence interval, 2.6-46.5; p 0.001). staphylococci were the most frequently isolated organisms in foreign material-associated ie.","cardiac intervention in children with chd does not increase the risk for ie. postinterventional ie in children with chd is strongly linked to implantation of foreign material, especially of pacemaker.",Treatment
does endogenous endothelin-1 mediate cardiac hypertrophy and switching of myosin heavy chain gene expression in rat ventricular myocardium?,"we investigated the role of endogenous endothelin-1 in the development of cardiac hypertrophy in vivo under pressure overload conditions. endothelin-1, a potent vasoconstrictor peptide, has recently been shown to act as a growth factor of myocardial cells in culture. we examined the effect of an endothelin-a receptor antagonist (fr139317) on the development of right ventricular hypertrophy in rats with monocrotaline-induced pulmonary hypertension. three groups of rats were studied: those given monocrotaline alone or monocrotaline plus fr139317 and those given vehicle alone (control group). the ratio of right ventricular systolic pressure to aortic systolic pressure was similarly elevated in rats treated with monocrotaline and monocrotaline plus fr139317. the right ventricular/left ventricular weight ratio was increased in monocrotaline-treated rats but lower in rats treated with monocrotaline plus fr139317 than in those treated with monocrotaline alone (p 0.01). as a biochemical marker of hypertrophy, the isoform ratio of beta-myosin heavy chain protein was determined for the right ventricular tissue samples. this ratio was increased in all monocrotaline-treated rats but was lower (p 0.01) in rats given monocrotaline plus fr139317 than in those given monocrotaline alone. the isoform ratio of beta-myosin heavy chain messenger ribonucleic acid quantitated by s1 nuclease mapping also was lower (p 0.025) in rats receiving monocrotaline plus fr139317 than in those receiving monocrotaline alone.","these data suggest that blocking the action of endothelin-1 with a receptor antagonist ameliorates cardiac hypertrophy in this model system, and that this action is not mediated by ameliorating hemodynamic changes.",Medication
does a2a adenosine receptor activation improve survival in mouse models of endotoxemia and sepsis?,"sepsis is currently treated with antibiotics and various adjunctive therapies that are not very effective. mouse survival (4-5 days) and peritoneal and blood bacteria counts were determined after challenge with intraperitoneal lipopolysaccharide (lps) or live escherichia coli. the a(2a) adenosine receptor (ar) agonist 4-3-6-amino-9-(5-ethylcarbamoyl-3, 4-dihydroxy-tetrahydro-furan-2-yl)-9h-purin-2-yl-prop-2-ynyl-cyclohexanecarboxylic acid methyl ester (atl146e; 0.05-50 mu g/kg) protected mice from challenge with lps, and protection occurred when treatment was delayed up to 24 h after challenge. deletion of the a (2a) ar gene, adora2a, inhibited protection by atl146e. a putative a (3)ar agonist, n(6)-3-iodobenzyladenosine-5'-n-methyluronamide (ib-meca; 500 mu g/kg but not 5 or 50 mu g/kg) protected mice from challenge with lps. the protective effects of both atl146e and ib-meca were counteracted by the a(2a) ar selective antagonist 4-(2-7-amino-2-2-furyl1,2,4triazolo2,3-a1,3,5triazin-5-yl-aminoethyl)-phenol. in the live e. coli model, treatment with atl146e (50 mu g/kg initiated 8 h after infection) increased survival in mice treated with ceftriaxone (5 days) from 40 to 100. treatment with atl146e did not affect peritoneal numbers of live e. coli at the time of death or 120 h after infection but did increase numbers of peritoneal neutrophils and decreased the number of live e. coli in blood.",ar agonists increase mouse survival in endotoxemia and sepsis via a(2a) ar-mediated mechanisms and reduce the number of live bacteria in blood.,Medication
is meconium amniotic fluid associated with endomyometritis?,"this study aimed to determine whether msaf is associated with endometritis after delivery. this cohort study was conducted from 2012 to 2013 in kosar hospital of qazvin, iran. all women with cesarean delivery (1239 women) beyond 37 weeks of gestational age participated in the study. data were collected on rates of endomyometritis, quality of amniotic fluid and were analyzed with bivariate and multivariate statistics. probability values of .05 were considered statistically significant. we found that among 1239 women with cesarean delivery at term 2.34 were diagnosed with endometritis. compared with deliveries with clear amniotic fluid, those with msaf had higher rates of endomyometritis (1.5 vs 3.2 , p .04).",we found that the presence of msaf is associated with puerperal infection even when being controlled for confounders.,Diagnosis
do antioxidant and calcium channel blockers counteract endothelial barrier injury induced by acute pancreatitis in rats?,"multiple organ failure is the major mortality-related complication in severe acute pancreatitis. endothelial barrier injury may be involved in its pathophysiology. the present study evaluated alterations in endothelial barrier integrity in different organs/tissues 12 h after induction of acute pancreatitis by intraductal infusions of bile. potential effects of oxygen free radicals and calcium influx were evaluated by pretreatment with an antioxidant, n-acetyl-l-cysteine, and calcium channel antagonists, verapamil and diltiazem. tissue edema, reflected by an increase in tissue water content, was noted in the stomach, proximal small intestine, cecum, spleen, pancreas, kidneys, liver, lungs, heart, and brain in rats with pancreatitis. also, an increased endothelial barrier permeability, as evidenced by the leakage of radiolabeled human serum albumin from blood to tissues, occurred in the stomach, proximal small intestine, colon, peritoneum, spleen, pancreas, kidneys, liver, lungs, and heart, accompanied by altered liver functions, increased levels of pancreatic enzymes, compromised renal function, and delayed intestinal motility. n-acetyl-l-cysteine prevented tissue edema and endothelial permeability changes in most organs/tissues, whereas the effects of verapamil and diltiazem were less marked. the preventive effects occurred in an organ-dependent manner.",endothelial barrier injury is found in all investigated organs/tissues in acute experimental pancreatitis. oxygen free radicals and calcium influx may play a role in the development of these changes.,Medication
does local brain activity persist during apparently generalized postictal eeg suppression?,"postictal generalized eeg suppression (pges) frequently occurs after generalized convulsive seizures (gcs) and may be involved in the pathophysiology of sudden unexpected death in epilepsy (sudep). it is usually determined using conventional scalp eeg which is likely to miss cerebral activity in deeper brain structures. here, we examined intracranial eeg activity after gcs to unravel the pattern and extent of local brain activity during apparent pges on scalp eeg (s-pges). we retrospectively reviewed electroencephalographic data of people with chronic epilepsy who had gcs during presurgical video-eeg monitoring using simultaneous intracranial and scalp eeg (10-20 system) electrodes. twenty-five gcs (20 with s-pges) of 15 patients with an average number of 8842 intracranial electrode contacts were included. the majority of gcs with s-pges (18 of 20) displayed persisting or reemerging intracranial eeg activity during apparent pges on scalp eeg. three patterns were identified: pattern 1 (11 gcs, 6 patients) consisted of continuous local interictal activity; pattern 2 (5 gcs, 5 patients) displayed suppressed eeg activity at all intracranial contacts in the early phase of s-pges, but reemerging local brain activity before s-pges dissolved; and pattern 3 (2 gcs, 2 patients) showed persistent local ictal activity during s-pges. persisting intracranial eeg activity at pges onset on scalp eeg was present in 1014 (range: 0 to 42) of all intracranial contacts and mostly in the temporal lobe.","our results reveal that, during apparently generalized postictal eeg suppression, local brain activity persists or reemerges in most gcs. possible implications of this localized neuronal activity in the context of sudep are discussed in the paper.",Diagnosis
is metronomic oral topotecan with pazopanib an active antiangiogenic regimen in mouse models of aggressive pediatric solid tumor?,"low dose metronomic (ldm) chemotherapy, combined with vegf signaling pathway inhibitors, is a highly effective strategy to coordinately inhibit angiogenesis and tumor growth in many adult preclinical cancer models. we have tested the efficacies of daily oral ldm topotecan alone and in combination with pazopanib, a vegf receptor inhibitor, in three pediatric extracranial solid tumor mouse models. in vitro dose-response study of topotecan and pazopanib was conducted on several neuroblastoma, osteosarcoma, and rhabdomyosarcoma cell lines. in vivo antitumor efficacies of the ldm topotecan and pazopanib as single agents and in combination were tested on 4 subcutaneous xenograft models and on 2 neuroblastoma metastatic models. circulating angiogenic factors such as circulating endothelial cells (cec), circulating endothelial pro genitor cells (cep), and microvessel densities were used as surrogate biomarker markers of antiangiogenic activity. in vitro, topotecan caused a dose-dependent decrease in viabilities of all cell lines, while pazopanib did not. in vivo, combination of topotecan pazopanib (tp pz) showed significant antitumor activity and significant enhancement in survival compared with the respective single agents in all models. reductions in viable cep and/or cec levels and tumor microvessel density were correlated with tumor response and therefore confirmed the antiangiogenic activity of the regimens. pharmacokinetic studies of both drugs did not reveal any drug-drug interaction.",metronomic administration of tp pz showed a statistically significant antitumor activity compared with respective single agents in pediatric tumor mouse models and represent a valid option as a maintenance therapy in aggressive pediatric solid tumors.,Medication
does the joint council on thoracic surgery education coronary artery assessment tool have high interrater reliability?,"barriers to incorporation of simulation in cardiothoracic surgery training include lack of standardized, validated objective assessment tools. our aim was to measure interrater reliability and internal consistency reliability of a coronary anastomosis assessment tool created by the joint council on thoracic surgery education. ten attending surgeons from different cardiothoracic residency programs evaluated nine video recordings of 5 individuals (1 medical student, 1 resident, 1 fellow, 2 attendings) performing coronary anastomoses on two simulation models, including synthetic graft task station (low fidelity) and porcine explant (high fidelity), as well as in the operative setting. all raters, blinded to operator identity, scored 13 assessment items on a 1 to 5 (low to high) scale. each performance also received an overall pass/fail determination. interrater reliability and internal consistency were assessed as intraclass correlation coefficients and cronbach's , respectively. both interrater reliability and internal consistency were high for all three models (intraclass correlation coefficients 0.98, 0.99, and 0.94, and cronbach's 0.99, 0.98, and 0.97 for low fidelity, high fidelity, and operative setting, respectively). interrater reliability for overall pass/fail determination using were 0.54, 0.86, 0.15 for low fidelity, high fidelity, and operative setting, respectively.","even without instruction on the assessment tool, experienced surgeons achieved high interrater reliability. future resident training and evaluation may benefit from utilization of this tool for formative feedback in the simulated and operative environments. however, summative assessment in the operative setting will require further standardization and anchoring.",Treatment
do low oxygen tension and autologous plasma enhance t-cell proliferation and cd49d expression density in serum-free media?,"as cellular immunotherapy with ex vivo expanded cells becomes more widely used to treat a variety of illnesses, optimization of culture parameters, to maximize cell production and function, is essential for continued success. the effects of reduced oxygen tension and autologous plasma on t-cell expansion, receptor expression, apoptosis, and cytolytic activity in serum-free media were investigated. pbmcs derived from whole blood samples were activated with anti-cd3 and anti-cd28 mab in serum-free (aim v) medium containing il-2, and maintained at 5 and 20 oxygen tension. in some cases cultures were supplemented with 2 autologous plasma. low oxygen enhanced t-cell expansion 13- and 4.8-fold in serum-free and plasma-supplemented media, respectively. autologous plasma also had a beneficial effect on t-cell cultures. plasma-supplemented cultures expanded 74-fold more than serum-free cultures at low oxygen tension, and 43-fold more at high oxygen tension. several samples expanded very poorly under serum-free conditions, and reasonable cell numbers were obtained only from plasma-supplemented cultures. cd49d expression density increased 3-fold to 4-fold in cultures supplemented with plasma. in contrast to our previous findings in serum-containing media, il-2 receptor expression kinetics were unaffected by oxygen tension. no effects caused by oxygen tension or autologous plasma on expression of other surface antigens (cd4, cd8, cd44, cd95) were observed.","low oxygen tension and autologous plasma greatly increase expansion of t cells, thereby decreasing the time needed for production of cells for prophylaxis. increased cd49d expression density may translate into improved migration and cytotoxicity.",Medication
does juniper oil inhibit the heat shock-induced apoptosis via preventing the caspase-3 activation in human astrocytes ccf-sttg1 cells?,brain astrocytes play a pivotal role in neuronal activities. an investigation was undertaken to determine whether juniper oil inhibits heat shock-induced apoptosis of astrocytes. juniper oil inhibited the heat shock-induced apoptosis in human astrocyte ccf-sttg1 cells. pretreatment of the cells with juniper oil inhibited the heat shock-induced dna fragmentation and condensation of nuclear chromatin. juniper oil alone did not affect the apoptosis. juniper oil inhibited the heat shock-induced caspase-3 activation and poly-adp-ribose polymerase (parp) fragmentation in the human astrocytes.,juniper oil may inhibit the apoptosis of astrocytes by preventing the caspase-3 activation.,Prevention
is glucose variability an independent predictor of mortality in hospitalized patients treated with total parenteral nutrition?,"hyperglycemia is associated with increased mortality in critically ill patients treated with total parenteral nutrition (tpn). the role of glucose variability (gv) in predicting outcomes in these patients is not known. this retrospective study included medical and surgical patients receiving tpn in a community teaching hospital. gv was calculated by standard deviation (sd) of blood glucose (bg) values and by mean bg daily () change (daily max - daily minimum). a total of 276 medical and surgical patients (mean age: 51 18 years), 19 with a history of diabetes mellitus (dm), and 74 with intensive care unit (icu) admission were treated with tpn. during tpn, the mean daily bg was 142.9 33 mg/dl; frequencies of hypoglycemia 70 and 40 mg/dl were 41 and 3, respectively; and hospital mortality was 27.2. the mean gv by sd was 38 21 mg/dl and by mean (d) change 58 34 mg/dl. gv was significantly higher in deceased patients (sd: 48 25 vs. 34 18 mg/dl and change: 75 39 vs. 51 29 mg/dl, both p .01) than surviving patients. multivariate analysis adjusted for age, dm status, gender, apache (acute physiology and chronic health evaluation) score, mean daily glucose, and hypoglycemia revealed that gv was an independent predictor of hospital mortality (p .05). the association between gv and mortality was limited to patients without a history of dm and was not present in patients with dm.",high gv is associated with increased hospital mortality independent of the presence and severity of hyperglycemia or hypoglycemia during tpn therapy. prospective randomized trials are needed to determine if reduction in gv with intensive glycemic control improves clinical outcomes in patients treated with tpn.,Treatment
does body adiposity dictate different mechanisms of increased coronary reactivity related to improved in vivo cardiac function?,"saturated fatty acid-rich high fat (hf) diets trigger abdominal adiposity, insulin resistance, type 2 diabetes and cardiac dysfunction. this study was aimed at evaluating the effects of nascent obesity on the cardiac function of animals fed a high-fat diet and at analyzing the mechanisms by which these alterations occurred at the level of coronary reserve. rats were fed a control (c) or a hf diet containing high proportions of saturated fatty acids for 3 months. thereafter, their cardiac function was evaluated in vivo using a pressure probe inserted into the cavity of the left ventricle. their heart was isolated, perfused iso-volumetrically according to the langendorff mode and the coronary reserve was evaluated by determining the endothelial-dependent (edv) and endothelial-independent (eiv) vasodilatations in the absence and presence of endothelial nitric oxide synthase and cyclooxygenase inhibitors (l-name and indomethacin). the fatty acid composition of cardiac phospholipids was then evaluated. although all the hf-fed rats increased their abdominal adiposity, some of them did not gain body weight (hf- group) compared to the c group whereas other ones had a higher body weight (hf). all hf rats displayed a higher in vivo cardiac activity associated with an increased edv. in the hf- group, the improved edv was due to an increase in the endothelial cell vasodilatation activity whereas in the hf group, the enhanced edv resulted from an improved sensitivity of coronary smooth muscle cells to nitric oxide. furthermore, in the hf- group the main pathway implicated in the edv was the nos pathway while in the hf group the cox pathway.",nascent obesity-induced improvement of cardiac function may be supported by an enhanced coronary reserve occurring via different mechanisms. these mechanisms implicate either the endothelial cells activity or the smooth muscle cells sensitivity depending on the body adiposity of the animals.,Medication
does matrix metalloproteinase-3 inhibitor retard treadmill running-induced cartilage degradation in rats?,"the effect of intra-articular injection of matrix metalloproteinase (mmp)-3 inhibitor was investigated in a rat model to understand the role of mmp-3 in cartilage degradation induced by excessive loading from running. a total of 24 male wistar rats were randomly assigned into groups of sedentary control (sed), high-intensity running (hir), hir low dosage of mmp-3 inhibitor i (hiri1), and hir high dosage of mmp-3 inhibitor i (hiri2). rats in the hir, hiri1 and hiri2 groups were intensively trained for six weeks on the treadmill. those in hiri1 and hiri2 groups were provided bilateral intra-articular injections of 80 l of 0.2 mm and 2 mm mmp-3 inhibitor i in knee joints once a week, respectively. blood samples were collected to measure serum mmp-3 level using elisa. femoral condyles were collected to observe cartilage characteristics by histochemistry, and mmp-3 as well as collagen ii was measured by immunohistochemistry. in addition, cartilage samples were obtained to assess mmp-3 mrna expression by rt-pcr. histological examination showed osteoarthritic changes in rats after six weeks of high intensity running. in comparison to the sed group, significant decreases in glycosaminoglycans (gag) and collagen content were found in the hir group, which corresponded to significant increase in serum mmp-3 level, cartilage mmp-3 activity and gene expression. however, such a degradative process was considerably retarded by intra-articular injection of mmp-3 inhibitor at higher dosage. statistical differences were found between the hir and hiri2 groups with regard to gag and collagen ii content, serum mmp-3 level, cartilage mmp-3 activity and gene expression.",high-intensity running for six weeks may lead to cartilage degradation in a rat model. it was shown that the chrondroprotective effect was offered by the use of intra-articular injection of mmp-3 inhibitor. mmp-3 acts as the key mediator of this catabolic change under such mechanical condition. the results also showed that mmp-3 selective inhibitor may be an effective option for retarding such osteoarthritic changes.,Medication
is hypermethylation of cpg sites at the promoter region associated with deregulation of mitochondrial atpsyn- and chemoresistance in acute myeloid leukemia?,"aberrant dna methylation status of some genes has been shown to be involved in chemoresistance of acute myeloid leukemia (aml). we have recently found that down-regulation of the subunit of mitochondrial atp synthase (atpsyn-) leads to adriamycin resistance in acute and chronic myeloid leukemia cells, and hypermethylation of the atpsyn- gene promoter is associated with chemoresistance in chronic myeloid leukemia. to further investigate the relationship between methylation of atpsyn- gene, mrna expression as well as chemoresistance in aml. quantitative rt-pcr and methylation specific pcr were performed to assess mrna expression and methylation status of atpsyn- gene on primary bone marrow nuclear cells (bmmcs), and cell proliferation assay was used to determine the sensitivity of bmmcs to adriamycin. hypermethylation status of atpsyn- gene promoter existed in those relapsed/refractory aml patients, and this hypermethylation of the gene was associated with a suppressed mrna expression levels. four patients at diagnosis and relapse underwent gene methylation status shift from hypermethylation to hypomethylation, which was accompanied by reduced mrna expression of the gene. 5-azacitidine(5-aza)- a demethylating agent, could restore atpsyn- mrna expression and increase the adriamycin sensitivity of primary leukemic cells from seven relapsed/ refractory aml patients.",hypermethylation of atpsyn- gene promoter is associated with a down-regulated mrna expression and chemoresistance in aml patients.,Diagnosis
does high-frequency oscillatory ventilation following prone positioning prevent a further impairment in oxygenation?,"the improvement in oxygenation with prone positioning is not persistent when patients with acute respiratory distress syndrome (ards) are turned supine. high-frequency oscillatory ventilation (hfov) aims to maintain an open lung volume by the application of a constant mean airway pressure. the aim of this study was to show that hfov is able to prevent the impairment in oxygenation when ards patients are turned back from the prone to the supine position. prospective, comparative randomized study. a medical intensive care unit. forty-three ards patients with a pao2/fio2 ratio or 5 cm h2o. after an optimization period, the patients were assigned to one of three groups: a) conventional lung-protective mechanical ventilation in the prone position (12 hrs) followed by a 12-hr period of conventional lung-protective mechanical ventilation in the supine position (cv(prone)-cv(supine)); b) conventional lung-protective mechanical ventilation in the supine position (12 hrs) followed by hfov in the supine position (12 hrs) (cv(supine)-hfov(supine)); or c) conventional lung-protective mechanical ventilation in the prone position (12 hrs) followed by hfov in the supine position (cv(prone)-hfov(supine) group). pao2/fio2 ratio was higher at the end of the study period in the cv(prone)-hfov(supine) group than in the cv(prone)-cv(supine) group (p .02). venous admixture at the end of the study period was lower in the cv(prone)-hfov(supine) group than in the two other groups.",hfov maintained the improvement in oxygenation related to prone positioning when ards patients were returned to the supine position.,Prevention
does administration of low-dose heparin in total nutrient admixture prevent central venous catheter-related infections in neonates ?,"peripherally inserted central catheter (picc) is widely used to provide a long-term access for the administration of total parenteral nutrition and medications. catheter-related infections (cri) are common complications of picc. the purpose of this retrospective study was to investigate the role of low-dose heparin added to the total nutrient admixture (ctna) in the prevention of cri. eighty-three neonates who underwent picc received tna with (heparin group, n43) or without heparin (0.5 u/ml) (control group, n40). the incidence of cri was compared between the two groups. the incidences of catheter obstruction (5 vs 20) and the catheter-tip colonization (2 vs 18) in the heparin group were significantly lower than those in the control group (p0.05). none of the neonates in the heparin group had clinical evidence of catheter-related bloodstream infection, but 5 cases in the control group (p0.05).",the administration of low-dose heparin in tna may decrease the incidences of catheter obstruction and cri.,Medication
does local osteoprotegerin gene transfer inhibit relapse of orthodontic tooth movement?,"in orthodontic treatment, teeth can relapse after tooth movement without retention. the aim of this study was to evaluate the inhibition effects of local osteoprotegerin (opg) gene transfer on orthodontic relapse. eighteen male wistar rats were divided into 3 groups. the maxillary right first molars of all animals were subjected to orthodontic force and moved mesially. three weeks later, the force was removed, and the teeth relapsed. during the 2-week relapse period, the 3 groups of rats received local opg gene transfer (experimental group), mock vector transfer (mock group), and no injections (control group). tooth movement and relapse were measured by using palatal superimpositions of 3-dimensional digital models. histomorphometric analysis was used to quantify osteoclasts, and microcomputed tomography analysis was done to quantify the alveolar bone and the tibia. relapse was significantly inhibited and the number of osteoclasts was reduced in the experimental group. on the other hand, bone mineral density and bone volume fraction of alveolar bone were significantly increased. bone mineral density and bone volume fraction of the tibia showed no significant difference between the groups.","local opg gene transfer to periodontal tissues could inhibit relapse after orthodontic tooth movement, through the inhibition of osteoclastogenesis.",Medication
does warm htk donor pretreatment reduce liver injury during static cold storage in experimental rat liver transplantation?,"organ shortage has led to an increased number of transplantations from extended criteria donors. these organs are more vulnerable to ischemia-reperfusion injury. thus, improvement of organ preservation is needed. htk is a widely used preservation solution for static cold storage in liver transplantation. the present study was to investigate the beneficial effect of warm htk donor pretreatment on liver preservation. male inbred wistar rats (weighing 230-260 g) served as donors and recipients (n6/group). donors of treatment groups received i.v. 0.01 ml/g body weight (bw) warm (21 degree centigrade) htk systemically 15 minutes prior to cold perfusion. control groups received 0.01 ml/g bw warm (21 degree centigrade) nacl 0.9. following pretreatment, donors were flushed with 4 degree centigrade cold htk, livers were explanted and stored in 4 degree centigrade htk for six hours. thereafter orthotopic liver transplantation was performed. recipients were harvested four hours, two and five days after reperfusion and blood and liver tissue samples were obtained. blood samples were analyzed for ast, alt, lactate dehydrogenase and bilirubin. liver histological analysis as well as tissue analysis for pro-mmp2, mmp2 and pro-mmp9 using zymography was conducted. treatment groups showed significantly lower alt and lactate dehydrogenase levels as well as significantly lower activities of pro-mmp2, mmp2 and pro-mmp9. histological analysis revealed only minor damage in all groups.",the new concept of warm htk pretreatment significantly reduced ischemia-reperfusion injury. the reduced ischemia-reperfusion injury was due to mmp inhibition. warm htk donor pretreatment is easy to handle and could further improve htk's potency in liver preservation.,Treatment
is ppi therapy equally effective in well-defined non-erosive reflux disease and in reflux esophagitis : a meta-analysis?,"symptomatic response to proton pump inhibitor (ppi) therapy in patients with non-erosive reflux disease (nerd) is often reported as lower than in patients with erosive reflux disease (erd). however, the definition of nerd differs across clinical trials. this meta-analysis aims to estimate the rate of symptom relief in response to ppi in nerd patients. medline (1966-2010), cochrane comprehensive trial register (1997-2010) and embase (1985-2010) databases were searched and manual searches from studies' references were performed. randomized clinical trials were selected that included patients with heartburn, and analyzed the effect of short-term ppi treatment. the primary outcome of selected studies was defined as complete or partial heartburn relief. two reviewers independently extracted data and assessed study quality of selected articles. random effects models and meta-regression were used to combine and analyze results. the pooled estimate of complete relief of heartburn after 4 weeks of ppi therapy in patients with erd was 0.72 (95 ci 0.69-0.74) (32 studies), vs 0.50 (0.43-0.57) (eight studies) in empirically treated patients, 0.49 (0.44-0.55) (12 studies) in patients defined as non-erosive by negative endoscopy, and 0.73 (0.69-0.77) (two studies) in patients defined as non-erosive by both negative endoscopy and a positive ph-test.","in well-defined nerd patients, the estimated complete symptom response rate after ppi therapy is comparable to the response rate in patients with erd. the previously reported low response rate in studies with patients classified as nerd is likely the result of inclusion of patients with upper gastrointestinal symptoms that do not have reflux disease.",Treatment
is estrogen receptor beta the predominant isoform expressed in the brain of adult and fetal sheep?,the objective of this study was to examine the expression of estrogen receptors alpha and beta in the cerebral cortex of the adult and fetal sheep. a reverse transcriptase-polymerase chain reaction-based approach was used to examine the expression of ovine estrogen receptor alpha and estrogen receptor beta in the cerebral cortex of 4 adult and 2 fetal sheep. estrogen receptor beta was expressed in the 4 adult and 2 fetal brain samples. estrogen receptor alpha expression was seen in only 1 adult brain and 1 fetal brain.,estrogen receptor beta is the predominant isoform expressed in the cerebral cortex of both adult and fetal sheep. these data may have implications for the many important actions of estrogen in the adult and developing ovine brain.,Medication
does zolpidem improve neuropsychiatric symptoms and motor dysfunction in a patient with parkinson 's disease after deep brain stimulation?,"to illustrate the beneficial effect of zolpidem on the neuropsychiatric and motor symptoms in a patient with parkinson disease (pd) after bilateral subthalamic nucleus deep brain stimulation. the 61-year-old housewife was diagnosed to have pd for 12 years with initial presentation of clumsiness and rest tremor of right limbs. she was referred to our hospital in march 2009 due to shortening of drug beneficial period since 3 years ago and on-phase dyskinesia in recent 2 years. bilateral stn dbs was conducted on 18 june, 2009. fluctuating spells of mental confusion were developed on the next day after surgery. electric stimuli via dbs electrodes were delivered with parameters of 2 volts, 60 s, 130 hz on bilateral stn 32 days after dbs. the incoherent behaviors and motor fluctuation remained to occur. the beneficial effect of zolpidem on her neuropsychiatric and motor symptoms was detected incidentally in early july 2009. she could chat normally with her caregiver and walk with assistance after taking zolpidem. the beneficial period may last for 2 hours. zolpidem was then given in dosage of 10 mg three times per day. the neuropsychiatric inventory was scored 56 during zolpidem 'off' and 30 during zolpidem 'on'. to understand the intriguing feature, we conducted fdg-pet during 'off' and 'on' zolpidem conditions. the results revealed that the metabolism was decreased in the right frontal, parietal cortex and caudate nucleus during zolpidem 'off'. these cool spots can be partially restored by zolpidem.","zolpidem ameliorated the neuropsychiatric and parkinsonian motor symptom in the pd patient. since gabaa benzodiazepine receptors are widely distributed throughout the central nervous system, zolpidem probably acts via modulating structures lying within the cortico-subcortical loop or by direct effect on these cortical regions.",Symptoms
does additional ect increase bdnf-levels in patients suffering from major depressive disorders compared to patients treated with citalopram only?,"in patients suffering from major depressive disorders (mdd), improvements in mdd are related to increased activation of brain-derived neurotrophic factor (bdnf), an endogenous protein that facilitates neural functioning. to treat patients suffering from severe mdd, electroconvulsive therapy (ect) is considered an efficacious and safe intervention, though the impact of ect on plasma bdnf levels has thus far barely been investigated. the aim of the present study was therefore to assess plasma bdnf levels and depression of patients suffering from severe mdd treated with additional ect compared to patients treated with citalopram only. a total of 40 patients (mean age: m 31.45 years; females 30) suffering from mdd and all receiving 40 mg/d citalopram were assigned either to a control group (n 20), or to a target group (n 20) undergoing additional 12 sessions of ect. plasma bdnf and symptom severity were assessed at baseline and four weeks later. plasma bdnf increased in both groups over time, though the significant time by group-interaction revealed an increase of 101 in the target group as compared to the control group. symptom severity significantly decreased in both groups over time, though without being related to plasma bdnf levels.","data from the present study suggest that, in patients suffering from severe mdd, treatment with citalopram was associated both with an increase of plasma bdnf and amelioration of depression, while additional ect was associated with even higher plasma bdnf levels. further studies should focus on possible cognitive and behavioral consequences.",Treatment
does the diagnostic apathia scale predict the ability to return to work following depression or anxiety?,"the aim of this study was to evaluate the validity of a new apathy rating scale in predicting the ability to return to work (rtw) in patients with depression or anxiety a year after discharge from a psychiatric hospital. we evaluated 56 patients with depression or anxiety, who participated in an on-going randomised clinical trial using rtw as primary outcome. the degree of apathy was measured by the diagnostic apathia scale, which contains six items covering the following neuropsychological symptoms: concentration/memory problems, difficulties in decision making, lassitude, tiredness/fatigue, insomnia, and reduced ability to work and engage in personal interests. the scale was analysed for psychometric validity (scalability) and for its ability to predict rtw. finally, the predictive validity of the diagnostic apathia scale regarding rtw was compared with scales measuring severity of depression/anxiety symptoms, disability, and psychological well-being. the diagnostic apathia scale displayed sufficient scalability, that is, the total score was a psychometrically valid measure of apathy. only the diagnostic apathia scale, and not the scales measuring severity of symptoms, disability, or psychological well-being, had predictive validity regarding rtw. thus, 76 with 'clinically significant apathy' at baseline were unable to rtw versus 50 of the patients without apathy (p0.05).",the diagnostic apathia scale was found to have an acceptable predictive validity in terms of patients' ability to rtw 1 year after discharge from hospitalisation for depression or anxiety.,Diagnosis
does protein kinase c control type 2 innate lymphoid cell and?,"protein kinase c (pkc) , a serine/threonine kinase, is involved in t we hypothesized that pkc- contributes to ilc2 activation and might be necessary for ilc2s to instruct the t prkcq gene expression was assessed in innate lymphoid cell subsets purified from human pbmcs and mouse lung ilc2s. ilc2 activation and eosinophil recruitment, t here we report that pkc- is expressed in both human and mouse ilc2s. mice lacking pkc- had reduced ilc2 numbers, t",therefore our findings identify pkc- as a critical factor for ilc2 activation that contributes to t,General
"are germline brca mutations associated with higher risk of nodal involvement , distant metastasis , and poor survival outcomes in prostate cancer?","to analyze the baseline clinicopathologic characteristics of prostate tumors with germline brca1 and brca2 (brca1/2) mutations and the prognostic value of those mutations on prostate cancer (pca) outcomes. this study analyzed the tumor features and outcomes of 2,019 patients with pca (18 brca1 carriers, 61 brca2 carriers, and 1,940 noncarriers). the kaplan-meier method and cox regression analysis were used to evaluate the associations between brca1/2 status and other pca prognostic factors with overall survival (os), cause-specific os (css), css in localized pca (cssm0), metastasis-free survival (mfs), and css from metastasis (cssm1). pca with germline brca1/2 mutations were more frequently associated with gleason 8 (p .00003), t3/t4 stage (p .003), nodal involvement (p .00005), and metastases at diagnosis (p .005) than pca in noncarriers. css was significantly longer in noncarriers than in carriers (15.7 v 8.6 years, multivariable analyses mva p .015; hazard ratio hr 1.8). for localized pca, 5-year css and mfs were significantly higher in noncarriers (96 v 82; mva p .01; hr 2.6; and 93 v 77; mva p .009; hr 2.7, respectively). subgroup analyses confirmed the poor outcomes in brca2 patients, whereas the role of brca1 was not well defined due to the limited size and follow-up in this subgroup.",our results confirm that brca1/2 mutations confer a more aggressive pca phenotype with a higher probability of nodal involvement and distant metastasis. brca mutations are associated with poor survival outcomes and this should be considered for tailoring clinical management of these patients.,Diagnosis
does endothelin-1 ( 1-31 ) induce spreading depolarization in rats?,"the vasoconstrictor endothelin-1(1-21) (et-1) seems to induce cerebral vasospasm after aneurismal subarachnoid hemorrhage (asah). moreover, et-1 causes spreading depolarization (sd) via vasoconstriction/ischemia. et-1(1-31) is an alternate metabolic intermediate in the generation of et-1. our aim was to investigate whether endothelin-1(1-31) causes sd in a similar fashion to et-1. increasing concentrations of either et-1, et-1(1-31) or vehicle were brain topically applied in 29 rats. each concentration was superfused for one hour while regional cerebral blood flow (rcbf) and direct current electrocorticogram (dc-ecog) were recorded. in response to the highest concentration of 10(-6) m, all animals of both et groups developed typical sd. at concentrations below 10(-6) m only et-1 induced sd (n14 of 19 rats). thus, the efficacy of et-1(1-31) to induce sd was significantly lower (p0.001, two-tailed fisher's exact test).","our findings suggest that et-1(1-31) less potently induces sd compared to et-1 which implicates that it is a less potent vasoconstrictor. speculatively, it could be interesting to shift the metabolic pathway towards the alternate intermediate et-1(1-31) after asah as an alternative strategy to eta receptor inhibition. this could decrease et-induced vasoconstriction and sd generation while a potentially beneficial basal eta receptor activation is maintained.",Medication
does integration of health services improve multiple healthcare outcomes among hiv-infected people who inject drugs in ukraine?,"people who inject drugs (pwid) experience poor outcomes and fuel hiv epidemics in middle-income countries in eastern europe and central asia. we assess integrated/co-located (icl) healthcare for hiv-infected pwid, which despite international recommendations, is neither widely available nor empirically examined. a 2010 cross-sectional study randomly sampled 296 hiv-infected opioid-dependent pwid from two representative hiv-endemic regions in ukraine where icl, non-co-located (ncl) and harm reduction/outreach (hro) settings are available. icl settings provide onsite hiv, addiction, and tuberculosis services, ncls only treat addiction, and hros provide counseling, needles/syringes, and referrals, but no opioid substitution therapy (ost). the primary outcome was receipt of quality healthcare, measured using a quality healthcare indicator (qhi) composite score representing percentage of eight guidelines-based recommended indicators met for hiv, addiction and tuberculosis treatment. the secondary outcomes were individual qhis and health-related quality-of-life (hrqol). on average, icl-participants had significantly higher qhi composite scores compared to ncl- and hro-participants (71.9 versus 54.8 versus 37.0, p0.001) even after controlling for potential confounders. compared to ncl-participants, icl-participants were significantly more likely to receive antiretroviral therapy (49.5 versus 19.2, p0.001), especially if cd4 200 (93.8 versus 62.5 p0.05); guideline-recommended ost dosage (57.3 versus 41.4, p0.05); and isoniazid preventive therapy (42.3 versus 11.2, p0.001). subjects receiving ost had significantly higher hrqol than those not receiving it (p0.001); however, hrqol did not differ significantly between icl- and ncl-participants.","these findings suggest that ost alone improves quality-of-life, while receiving care in integrated settings collectively and individually improves healthcare quality indicators for pwid.",Medication
is external hydrogen peroxide indispensable for experimental induction of lipid peroxidation via fenton reaction in porcine ovary homogenates?,"substrates of fenton reaction (fe(2)h(2)o(2)--fe(3)ohoh-) may be used to experimentally induce oxidative damage to macromolecules. the study aimed at evaluating effects of fe(2) and/or h(2)o(2) on lipid peroxidation in porcine ovary homogenates. ovary homogenates were incubated in the presence of either h2o2 (100, 50, 25, 10, 5.0, 2.5, 1.0, 0.5, 0.25, 0.01, 0.001 mm) or feso(4) (fe2) (300, 150, 75, 30, 15, 7.5, 3.0, 1.5, 0.75 microm), or of those two factors used together: fe(2) (30 microm) plus h(2)o(2) (concentrations as above), or h(2)o(2) (0.5 mm) plus fe(2) (concentrations as above). the concentration of malondialdehyde4-hydroxyalkenals constituted the lipid peroxidation index. h(2)o(2) alone did not affect lipid peroxidation in porcine ovary homogenates at all, whereas fe(2) (300, 150, 75, 30, and 15 microm) alone increased lipid peroxidation in a concentration dependent manner. when fe(2) and h(2)o(2) were applied together, lipid peroxidation increased significantly without any concentration related effect of h(2)o(2), but with a clear concentration dependent effect of fe(2); the damaging effect of fe(2), used together with h(2)o(2), was the same as the one, obtained after fe(2) was applied alone.","in conclusion, external h(2)o(2) is not indispensable for experimental induction of lipid peroxidation by fenton reaction in porcine ovary homogenates.",General
is instability of igf-igfbp complex as a cause of the different performance of serum and edta-plasma after storage : edta-plasma preferable for evaluating bioactive igf especially in the mouse?,"the insulin-like growth factor (igf) signaling pathway is recognized as a potential target for treating several cancers, and strategies targeting the igf type 1 receptor (igf-1r) have been evaluated in many clinical trials. these suggested that the pretreatment level of circulating free igf gives an estimate of igf bioactivity and might be a predictive biomarker of the response to anti-igf-1r antibodies. however, there is no defined protocol for measuring free and bioactive igf concentrations, partly because the measurement procedures, including sample collection and handling, have not been standardized. we investigated the effects of sample collection methods and storage conditions on bioactive igf measurement using a modified kinase receptor activation (kira) assay in human and mouse samples. blood samples were obtained from healthy men and women, and from healthy male and female wild-type balb/c mice. serum and ethylenediaminetetraacetic acid (edta)-plasma samples were collected and used immediately or stored in small quantities at 4 c or -80 c for 3, 7, or 14 days. a bioassay directed against the phosphorylated igf-1r using western blot analysis was developed as a modification of the kira assay, in which the level of phosphorylation of igf-1r represented the igf bioactivity in blood samples. the levels of bioactive igfs in mouse serum stored at 4 c increased markedly in a time-dependent manner; the increase was slightly reduced in samples stored at -80 c. analysis of mouse edta-plasma stored at 4 c showed a similar pattern, but the time-dependent increase was less than in the serum samples. by contrast, the levels of bioactive igfs in edta-plasma stored at -80 c were stable over 14 days. the levels of human bioactive igfs in both serum and edta-plasma stored at 4 c increased slightly with time, but the increases were much smaller than in mouse samples. the levels of human bioactive igf in both serum and edta-plasma stored at -80 c were stable over 14 days.","the use of edta-plasma avoids the problems with long-term storage. therefore, edta-plasma should be used when measuring circulating igf bioactivity, especially in mouse samples. all samples should be stored at -80 c when long-term storage is unavoidable. because of the large difference in the stability of the igf-igf-binding protein complex between the human and mouse in vitro, all samples should be handled carefully to ensure the accurate evaluation of igf bioactivity, especially in mouse samples.",Medication
does social cognition make an independent contribution to peer relations in children with specific language impairment?,"language is important for developing and maintaining social relationships, and also for understanding others minds. separate studies have shown that children with specific language impairment (sli) present difficulties in both abilities, although the role of social cognition (sc) on peers' perception remains unexplored. the present study aims to assess specific sociometric features of children with sli through peer nominations of liking and disliking, and also to explore their relationship to the children's sc. thirty-five children with sli attending ordinary schools (3;10 to 8;00 years old) and thirty-five age-matched children (am) were assessed with language, sc and sociometric measures. sli group received more disliked nominations and had lower scores on sc tasks compared to the am group. after controlling for age and language, sc made an independent contribution to disliked nominations within the sli group.","difficulties with peers of children with sli are related to their language level but also with their sc abilities. consequently, only resolving language impairments will not necessarily improve early peer acceptance in children with sli.",General
does left ventricular mass predict left atrial appendage thrombus in persistent atrial fibrillation?,"atrial fibrillation (af) can result in the development of left atrial appendage (laa) thrombi. we sought to examine demographic and echocardiographic predictors of laa thrombus in patients with persistent af. one hundred and sixty-five patients in persistent af (36 with laa thrombus and 129 without thrombus) were studied. demographic and cardiovascular risk factors were retrospectively examined. transthoracic (tte) and transoesophageal echocardiography (toe) were performed to assess the size and function of the left ventricle (lv), left atrium (la), laa, and spontaneous echo contrast (sec) in the la and right atrium (ra). univariate demographic predictors of la thrombus included systolic blood pressure, ischaemic heart disease and congestive heart failure. indexed lv mass and septal e' velocity on tte and mean laa emptying velocity and the presence of sec in both the la and ra on toe were predictors of thrombus. in a multiple logistic regression analysis the only independent predictor of thrombus was indexed lv mass (p 0.001). receiver operator characteristic curve analysis also demonstrated that indexed lv mass had the highest area under the curve (auc: 0.98).","in the present study, increased lv mass was the strongest predictor of laa thrombus in persistent af. la sec and ra sec were univariate predictors of laa thrombus but did not add predictive value to a multivariate model including lv mass. this study highlights the importance of diagnosing and treating lv hypertrophy associated with persistent af, which may reduce the risk of laa thrombus and thrombo-embolic stroke.",Prevention
does diagnostic glenohumeral arthroscopy fail to fully evaluate the biceps-labral complex?,"the purpose of this study was to define the limits of diagnostic glenohumeral arthroscopy and determine the prevalence and frequency of hidden extra-articular ""bicipital tunnel"" lesions among chronically symptomatic patients. eight fresh-frozen cadaveric specimens underwent diagnostic glenohumeral arthroscopy with percutaneous tagging of the long head of the biceps tendon (lhbt) during maximal tendon excursion. the percentage of visualized lhbt was calculated relative to the distal margin of subscapularis tendon and the proximal margin of the pectoralis major tendon. then, a retrospective review of 277 patients who underwent subdeltoid transfer of the lhbt to the conjoint tendon were retrospectively analyzed for lesions of the biceps-labral complex. lesions were categorized by anatomic location (inside, junctional, or bicipital tunnel). inside lesions were labral tears. junctional lesions were lhbt tears visualized during glenohumeral arthroscopy. bicipital tunnel lesions were extra-articular lesions hidden from view during standard glenohumeral arthroscopy. seventy-eight percent of lhbt were visualized relative to the distal margin of the subscapularis tendon and only 55 relative to the proximal margin of the pectoralis major tendon. no portion of the lhbt inferior to the subscapularis tendon was visualized. forty-seven percent of patients had hidden bicipital tunnel lesions. scarring was most common and accounted for 48 of all such lesions. thirty-seven percent of patients had multiple lesion locations. forty-five percent of patients with junctional lesions also had hidden bicipital tunnel lesions. the only offending lesion was in the bicipital tunnel for 18 of patients.",diagnostic glenohumeral arthroscopy fails to fully evaluate the biceps-labral complex because it visualizes only 55 of the lhbt relative to the proximal margin of the pectoralis major tendon and did not identify extra-articular bicipital tunnel lesions present in 47 of chronically symptomatic patients.,Diagnosis
is genetic variation in ucp2 ( uncoupling protein-2 ) associated with energy metabolism in pima indians?,"uncoupling protein-2 (ucp2) is thought to play a role in insulin secretion and the development of obesity. in this study, we investigated the effects of genetic variation in ucp2 on type 2 diabetes and obesity, as well as on metabolic phenotypes related to these diseases, in pima indians. the coding and untranslated regions of ucp2, and approximately 1 kb of the 5' upstream region, were sequenced in dna samples taken from 83 extremely obese pima indians who were not first-degree relatives. five variants were identified: (1) a -866g/a in the 5' upstream region; (2) a g/a in exon 2; (3) a c/t resulting in an ala55val substitution in exon 4; and (4, 5) two insertion/deletions (ins/del; 45-bp and 3-bp) in the 3' untranslated region. among the 83 subjects whose dna was sequenced, the -866g/a was in complete genotypic concordance with the ala55val and the 3-bp ins/del polymorphism. the g/a polymorphism in exon 2 was extremely rare. to capture the common variation in this gene for association analyses, the -866g/a variant (as a representative of ala55val and the 3-bp ins/del polymorphism) and the 45-bp ins/del were also genotyped for 864 full-blooded pima indians. neither of these variants was associated with type 2 diabetes or body mass index. however, in a subgroup of 185 subjects who had undergone detailed metabolic measurements, these variants were associated with 24-h energy expenditure as measured in a human metabolic chamber (p0.007 for the 45-bp ins/del and p0.03 for the -866g/a after adjusting for age, sex, family membership, fat-free mass and fat mass).","our data indicate that variation in ucp2 may play a role in energy metabolism, but this gene does not contribute significantly to the aetiology of type 2 diabetes and/or obesity in pima indians.",Medication
does characterization of outbreak response strategies and potential vaccine stockpile need for the polio endgame?,"following successful eradication of wild polioviruses and planned globally-coordinated cessation of oral poliovirus vaccine (opv), national and global health leaders may need to respond to outbreaks from reintroduced live polioviruses, particularly vaccine-derived polioviruses (vdpvs). preparing outbreak response plans and assessing potential vaccine needs from an emergency stockpile require consideration of the different national risks and conditions as they change with time after opv cessation. we used an integrated global model to consider several key issues related to managing poliovirus risks and outbreak response, including the time interval during which monovalent opv (mopv) can be safely used following homotypic opv cessation; the timing, quality, and quantity of rounds required to stop transmission; vaccine stockpile needs; and the impacts of vaccine choices and surveillance quality. we compare the base case scenario that assumes aggressive outbreak response and sufficient mopv available from the stockpile for all outbreaks that occur in the model, with various scenarios that change the outbreak response strategies. outbreak response after opv cessation will require careful management, with some circumstances expected to require more and/or higher quality rounds to stop transmission than others. for outbreaks involving serotype 2, using trivalent opv instead of mopv2 following cessation of opv serotype 2 but before cessation of opv serotypes 1 and 3 would represent a good option if logistically feasible. using mopv for outbreak response can start new outbreaks if exported outside the outbreak population into populations with decreasing population immunity to transmission after opv cessation, but failure to contain outbreaks resulting in exportation of the outbreak poliovirus may represent a greater risk. the possibility of mopv use generating new long-term poliovirus excretors represents a real concern. using the base case outbreak response assumptions, we expect over 25 probability of a shortage of stockpiled filled mopv vaccine, which could jeopardize the achievement of global polio eradication. for the long term, responding to any poliovirus reintroductions may require a global ipv stockpile. despite the risks, our model suggests that good risk management and response strategies can successfully control most potential outbreaks after opv cessation.",health leaders should carefully consider the numerous outbreak response choices that affect the probability of successfully managing poliovirus risks after opv cessation.,Medication
does cannabinoid receptor 1 blockade ameliorate albuminuria in experimental diabetic nephropathy?,"cannabinoid receptor 1 (cb1) is localized in the central nervous system and in peripheral tissues involved in energy metabolism control. however, cb1 receptors are also expressed at low level within the glomeruli, and the aim of this study was to investigate their potential relevance in the pathogenesis of proteinuria in experimental type 1 diabetes. streptozotocin-induced diabetic mice were treated with n-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,3-dichlorophenyl)-4-methyl-1h-pyrazole-3-carboxamide (am251), a selective cb1-receptor antagonist, at the dosage of 1 mg x kg(-1) x day(-1) via intraperitoneal injection for 14 weeks. urinary albumin excretion was measured by enzyme-linked immunosorbent assay. cb1 receptor expression was studied by immunohistochemistry, immunoblotting, and real-time pcr. expression of nephrin, podocin, synaptopodin, and zonula occludens-1 (zo-1) was assessed by immunofluorescence and real-time pcr. fibronectin, transforming growth factor-beta1 (tgf-beta1), and connective tissue growth factor (ctgf) mrna levels were quantitated by real-time pcr. in diabetic mice, the cb1 receptor was overexpressed within the glomeruli, predominantly by glomerular podocytes. blockade of the cb1 receptor did not affect body weight, blood glucose, and blood pressure levels in either diabetic or control mice. albuminuria was increased in diabetic mice compared with control animals and was significantly ameliorated by treatment with am251. furthermore, cb1 blockade completely prevented diabetes-induced downregulation of nephrin, podocin, and zo-1. by contrast overexpression of fibronectin, tgf-beta1, and ctgf in renal cortex of diabetic mice was unaltered by am251 administration.","in experimental type 1 diabetes, the cb1 receptor is overexpressed by glomerular podocytes, and blockade of the cb1 receptor ameliorates albuminuria possibly via prevention of nephrin, podocin, and zo-1 loss.",Medication
is susceptibility to murine experimental autoimmune oophoritis associated with genes outside the major histocompatibility complex ( mhc )?,"neonatal thymectomy induces experimental autoimmune oophoritis in certain strains of mice, and this serves as a model for human autoimmune oophoritis. because strong mhc associations have been noted in human autoimmune conditions, we investigated the role of mhc in determining susceptibility to murine experimental autoimmune oophoritis. strain a mice are highly susceptible to post-thymectomy autoimmunity, whereas strain b10 mice are relatively resistant. the availability of congenic strains of mice makes it possible to separate the effects of genetic background and specific h-2 haplotype we neonatally thymectomized a and b10 background female mice, and their h-2 congenic counterparts, and then evaluated the resulting ovarian disease at age 6 weeks. a. by mice, which have the a background and the h-2b haplotype, developed severe disease equivalent to strain a mice. similarly, b10.a mice, which have the b background and the h-2a haplotype, failed to develop disease. thus, h-2a haplotype did not convey disease susceptibility.","our findings suggest that immune-regulatory regions outside the h-2 locus play an important role in determining susceptibility to murine post-thymectomy autoimmune oophoritis. this is in accord with our previous findings in women that showed no association between mhc and premature ovarian failure. thus, in this respect this model is similar to human autoimmune ovarian failure. this suggests that the non-mhc genes conveying susceptibility to autoimmune oophoritis in mice might represent similar predisposing genes for premature ovarian failure in women.",General
does ankle arthritis predict polyarticular disease course and unfavourable outcome in children with juvenile idiopathic arthritis?,"to evaluate the occurrence, clinical characteristics and prognostic factors associated with ankle arthritis in children with juvenile idiopathic arthritis (jia). 440 children with jia were followed for eight years in a prospective nordic population-based cohort study. data on remission was available for 427 of these children. occurrence of clinically assessed ankle arthritis was analysed in relation to jia category, clinical characteristics and remission data eight years after disease onset. in 440 children with jia, 251 (57) experienced ankle arthritis during the first eight years of disease. ankle arthritis was least common in the persistent oligoarticular category (25) and most common in children with extended oligoarticular (83) and polyarticular rf-negative (85) jia. children who developed ankle arthritis during the first year of disease were younger at disease onset (median age 4.9 (iqr 2.1-8.8) vs. 6.6 (iqr 2.8-10.1) years, p0.003) and had more cumulative affected joints at 8-year follow-up (median involved joints 10 (iqr 6-16) vs. 3 (iqr 2-9), p0.001). the odds ratio for not achieving remission eight years after disease onset, if the ankle joint was involved during the first year of disease was 2.0 (95 ci:1.3-3.0, p0.001). hind-, mid- and forefoot involvements were more common compared to patients without ankle arthritis.","in this nordic population-based 8-year follow-up study, occurrence of ankle arthritis during the first year was associated with an unfavourable disease outcome. we suggest that ankle arthritis should be recognised in the assessment of prognosis and choice of treatment strategy in jia.",Diagnosis
does osteoporosis change the amount of vertebral trabecular bone at risk of fracture but not the vertebral load distribution?,"a finite-element study to investigate the amount of trabecular bone at risk of fracture and the distribution of load between trabecular core and cortical shell, for healthy, osteopenic, and osteoporotic vertebrae. to determine differences between healthy, osteopenic, and osteoporotic vertebrae with regard to the risk of fracture and the load distribution. the literature contains no reports on the effects of osteopenia and osteoporosis on load distribution in vertebral bodies, nor any reports on the amount of trabecular bone at risk of fracture. computed tomography data of vertebral bodies were used to construct patient-specific finite-element models. these models were then used in finite-element analyses to determine the physiologic stresses and strains in the vertebrae. for all three classes of vertebrae the contribution of the trabecular core to the total load transfer decreased from about 70 near the endplates to about 50 in the midtransverse region. the amount of trabecular bone that is at risk of fracture was about 1 for healthy vertebrae, about 3 for osteopenic vertebrae, and about 16 for osteoporotic vertebrae.","our finite-element models indicated that neither osteopenia nor osteoporosis had any effect on the contribution of the trabecular core to the total load placed on the vertebra. the trabecular core carried about half the load. our finite-element models indicated that osteoporosis had a significant effect on the amount of trabecular bone at risk of fracture, which increased from about 1 in healthy vertebrae to about 16 for osteoporotic vertebrae.",General
is loss of heterozygosity at chromosome 14q associated with poor prognosis in head and neck squamous cell carcinomas?,"loss of heterozygosity (loh) in a chromosomal location indicates the presence of an inactivated tumor suppressor gene (tsg). inactivation of tsg has a functional role in the tumorigenesis of head and neck squamous cell carcinoma (hnscc). based on the recent evidences of a putative tsg on chromosome 14, we examined loh on chromosome 14q using eight polymorphic microsatellite markers in 50 cases of hnsccs. three regions were detected to have a high loh rate which included 14q21.2-22.3 (42.5), 14q31 (55), and 14q32.1 (37). the correlation between loh and clinicopathological findings was investigated through statistical analyses. a strong correlation was observed between the highest loh marker and the overall and disease-free survival.","the results suggest that the distal part of chromosome 14 may host a tsg that may lead to the development and/or progression of hnsccs. several genes such as ches1, bmp4, sav, and pnn have arisen as candidate tumor suppressors in the region.",Diagnosis
does skin surface hydration decrease rapidly during long distance flights?,"dehydration of the stratum corneum leads to sensations and symptoms of 'dry skin' such as skin tightness and itchiness. as these complaints are frequently experienced by airline travellers, the aim of this study was to investigate the changes in skin surface hydration during long distance flights. the study was performed on four healthy caucasian, and on four japanese women aged 29-39 years, travelling on long distance flights. they had stopped using skin care products at least 12 h before, and did not apply them during the flights. the air temperature and relative humidity inside the cabin, as well as skin capacitance of the face and forearm of participants, were registered at several time points before and during the flights. relative humidity of the aircraft cabin dropped to levels below 10 within 2 h after take-off and stayed at this value throughout the flight. skin capacitance decreased rapidly on both the face and forearms with most pronounced changes on the cheeks where it decreased by up to 37.","our results demonstrate that during long distance flights, the aircraft cabin environment leads to a rapid decrease in stratum corneum hydration, an alteration, which probably accounts for the discomfort experienced by long distance aircraft travellers.",Symptoms
is longitudinal linear growth and final height impaired in childhood acute lymphoblastic leukemia survivors after treatment without cranial irradiation?,"to evaluate long-term growth and final height (fh) in survivors of childhood acute lymphoblastic leukemia (all) who were treated without cranial radiation therapy and underwent evaluation of growth hormone (gh) status at the end of treatment. data on longitudinal growth (collected at the start of treatment, end of treatment, and 1 year thereafter) and fh of 67 adult survivors of childhood all who had been treated according to european organisation for research and treatment of cancer 58831/2 protocols with chemotherapy as the only treatment modality were reviewed retrospectively. height data were expressed as sds for national references. the relative role of sex, age at diagnosis, intensity of chemotherapeutic regimen, and gh status at the end of treatment as contributing factors were analyzed. a modest but significant loss in fh (change in sds sds -0.59 0.86; p .001) was found. two-thirds of the height deficit observed from diagnosis until fh occurred during treatment. the height deficit was more severe in the male patients (p .036). the sds for height from diagnosis to fh was not correlated with age at diagnosis or intensity of treatment. no correlation was found between the results of the gh stimulation test and sds for height from diagnosis or the end of treatment to fh.",adult survivors of childhood all treated with chemotherapeutic regimens of moderate intensity without cranial radiation therapy exhibit a modest loss in sds for height at fh irrespective of gh status at the cessation of treatment.,Treatment
do highly sensitive cardiac troponin t values remain constant after brief exercise- or pharmacologic-induced reversible myocardial ischemia?,"using a new precommercial high-sensitivity cardiac troponin t (hstnt) assay, we evaluated whether hstnt increases after reversible myocardial ischemia. in 195 patients undergoing nuclear stress testing (st) using single-photon emission computed tomography (spect) for suspected ischemic heart disease, we measured hstnt before and 18 min, 4 h, and 24 h after the stress test. thirty patients were excluded before st because of cardiac troponin t (ctnt) 30 ng/l (0.03 mug/l) as measured by the fourth-generation commercial test. another 65 patients were excluded because of a combination of fixed and reversible perfusion defects (pds) after spect. we studied 18 patients with reversible pds, 41 patients with fixed pds, and 41 patients without any pds. of these 100 patients, 61 received dynamic st and 39 pharmacological st. median baseline hstnt concentrations (25th, 75th percentile) were comparable in patients with reversible, fixed, and no pds 5.57 (2.47, 12.60), 8.01 (4.55, 12.44), and 6.90 (4.63, 10.59) ng/l, respectively. after st, median hstnt concentrations did not change in the reversible, fixed, or no pd groups from baseline to 18 min -0.41 (-0.81, 0.01), 0.01 (-0.75, 0.79), and 0.36 (-0.42, 1.01) ng/l or from baseline to 4 h -0.56 (-1.82, 0.74), 0.24 (-0.60, 1.45), and 0.23 (-0.99, 1.15) ng/l. median baseline hstnt concentrations tended to be higher in patients undergoing pharmacological vs dynamic st; however, there were no significant increases in hstnt concentrations after either type of st.",elevation of ctnt is rather a consequence of irreversible myocyte death than reversible myocardial ischemia after exercise or pharmacologic myocardial ischemia.,Medication
does myeloperoxidase serve as a redox switch that regulates apoptosis in epithelial ovarian cancer?,"resistance to apoptosis is a key feature of cancer cells and is believed to be regulated by nitrosonium ion (no())-induced s-nitrosylation of key enzymes. nitric oxide (no), produced by inducible nitric oxide synthase (inos), is utilized by mpo to generated no(). we sought to investigate the expression of myeloperoxidase (mpo) and inos in epithelial ovarian cancer (eoc) and determine their effect on s-nitrosylation of caspase-3 and its activity as well as apoptosis. mpo and inos expression were determined using immunofluorescence in skov-3 and mdah-2774 and eoc tissue sections. s-nitrosylation of caspase-3 and its activity, levels of mpo and inos, as well as apoptosis, were evaluated in the eoc cells before and after silencing mpo or inos genes with specific sirna probes utilizing real-time rt-pcr, elisa, and tunel assays. mpo and inos are expressed in eoc cell lines and in over 60 of invasive eoc cases with no expression in normal ovarian epithelium. indeed, silencing of mpo or inos gene expression resulted in decreased s-nitrosylation of caspase-3, increased caspase-3 activity, and increased apoptosis but with a more significant effect when silencing mpo.","mpo and inos are colocalized to the same cells in eoc but not in the normal ovarian epithelium. silencing of either mpo or inos significantly induced apoptosis, highlighting their role as a redox switch that regulates apoptosis in eoc. understanding the mechanisms by which mpo functions as a redox switch in regulating apoptosis in eoc may lead to future diagnostic tools and therapeutic interventions.",General
do sex and strain influence the effect of ethanol on central monoamines?,"we recently investigated the effects of etoh on the mesolimbic dopamine and serotonin systems in male and female c57bl/6 (b6) and dba/2j (d2) mice. male and female rodents from the b6 and d2 mouse strains (n 11 per strain, sex and dose) were used in this study. doses of etoh (vs saline) administered were 1.0, 2.0 or 3.0 g/kg. treatment with saline or etoh produced both strain- and sex-dependent differences in patterns of monoamine response. for example, d2s exhibited significantly higher overall dopamine (da) levels than did b6s in the frontal cortex (fc), nucleus accumbens (na) and caudate-putamen (cp). in the fc, female d2 evinced elevated 5hiaa at 1.0 g/kg. in the na, d2 females showed dose related increases in levels of da up to 3.0 g/kg, whereas in the d2 males and in b6 males and females we observed no response. also in the na, b6 males showed increases in dihydroxyphenyacetic acid (dopac) at 1.0 and 3.0 g/kg. in the cp, b6 males showed higher da levels than b6 females at the saline, and all etoh doses. for serotoninergic activity in the cp as well as the na, etoh produced a distinctive triphasic response, with the 1.0 and 3.0 g/kg doses of etoh producing higher levels than saline and 2.0 g/kg of 5hiaa in b6 males than in b6 females.","our findings indicate strain and sex differences in monoamine response to acute doses of ethanol, and further implicate (via changes in dopac) presynaptic mechanisms in the effects of ethanol on dopamine.",Medication
"is phospholipid scramblase 1 , an interferon-regulated gene located at 3q23 , regulated by snon/skil in ovarian cancer cells?","treatment of advanced stage ovarian cancer continues to be challenging due to acquired drug resistance and lack of early stage biomarkers. genes identified to be aberrantly expressed at the 3q26.2 locus (i.e. snon/skil) have been implicated in ovarian cancer pathophysiology. we have previously shown that snon expression is increased in advanced stage ovarian cancers and alters cellular response to arsenic trioxide (as2o3). we now demonstrate increased dna copy number levels (tcga data) of phospholipid scramblase 1 (plscr1, located at 3q23) whose transcript expression in ovarian cell lines is highly correlated with snon mrna. interestingly, snon can modulate plscr1 mrna levels in the absence/presence of interferon (ifn-2). both ifn-2 and as2o3 treatment can modulate plscr1 mrna levels in ovarian carcinoma cells. however, snon sirna does not lead to altered plscr1 protein implicating other events needed to modulate its protein levels. in addition, we report that plscr1 can modulate aspects of the as2o3 cellular response.",our findings warrant further investigation into the role of plscr1 in ovarian cancer development and chemoresistance.,Medication
is osteoprotegerin a better serum biomarker of coronary artery calcification than osteocalcin in type 2 diabetes?,"coronary artery calcification (cac) is a prominent feature of atherosclerosis and is associated with cardiovascular events. in vitro studies have suggested that osteoprotegerin (opg) and osteocalcin (oc) exert anticalcification potential in the vessel wall. the objective of this study was to investigate the association of cac and serum bone biomarkers in persons with type 2 diabetes. we examined 50 individuals with type 2 diabetes. cac imaging was performed by multidetector computed tomography. cac scores 10, expressed in agatston units, were considered abnormal. oc, undercarboxylated oc (ucoc), and opg levels were determined by enzyme-linked immunosorbent assay. abnormal cac scores were found for 64 of the study cohort. opg levels were significantly elevated (5.5 2.0 pmol/l vs. 4.2 1.7 pmol/l; p .026) for those with abnormal cac scores. no univariate differences were found for oc or ucoc. logistic regression analyses revealed that an increase in serum opg level was significantly associated with an increase in cac score (odds ratio, 3.324; 95 confidence interval, 1.321 to 8.359; p .011). longer duration of diabetes was a significant covariate (p .026), whereas nonsignificant covariates in the final model were age, gender, systolic blood pressure, body mass index, insulin resistance determined by the homeostasis model assessment for insulin resistance, leptin, adiponectin, and glycemic control. the nagelkerke r2 for the model was 0.66. neither oc nor ucoc were significantly associated with elevated cac scores.",our results suggest that opg is a more useful serum biomarker than oc or ucoc for identifying those at increased risk of arterial calcification in type 2 diabetes.,Diagnosis
is anterior cingulum white matter altered in tobacco smokers?,"the anterior cingulate cortex (acc) is hypothesized to be involved in decision making and emotion regulation. previous observations of drug dependent individuals indicate that substance dependence may be associated with cingulum white matter abnormalities. the present study evaluated cingulum white matter in cigarette smokers. diffusion tensor imaging (dti) in adult tobacco smokers and healthy non-smoker controls (total n 70) was performed in a 3t siemens trio mri scanner. analyses of dti tractography of the cingulum in tobacco-smoking individuals and controls indicated that tobacco abusers have significantly reduced fractional anisotropy (fa) in the right cingulum. in addition, fa in the left cingulum white matter was negatively associated with the number of cigarettes smoked per day and the fagerstrom test for nicotine dependence, a self-report measure of tobacco dependence severity.","the white matter of the cingulum is altered in a non-symmetrical way in tobacco smokers. an inverse relationship between fa and reported number of cigarettes per day was observed. previous studies have also noted altered neural connectivity in cigarette smokers using similar methods. similar white matter differences in the cingulum have been observed in methamphetamine dependent individuals and patients with dementia, which suggests that the cingulum may be altered by mechanisms not specific to tobacco exposure.",Diagnosis
is waist circumference associated with pitch pattern sequence score in older male adults?,"while obesity may increase the risk for neurodegenerative diseases such as alzheimer's disease, the relationship between waist circumference (wc) and central auditory dysfunction is unknown. we aimed to investigate the relationship of wc and pitch pattern sequence (pps) score in adults. the association of wc with pps score was analysed. volunteer helpers at a community hospital, 391 adults 40 years, with normal or symmetrical sensorineural hearing loss were randomly selected. after adjusting for age, gender, pure-tone average, systemic diseases, and habits, wc was significantly negatively associated with pps. in a subgroup analysis by gender and age, the pps score was negatively associated with wc only for males who were older than 55 years old, but not for males who were younger than 55 years old or females in either age group. meanwhile, central obesity showed positive association with abnormal pps recognition ability (pps score 90) of borderline significance only for males who were older than 55 years old, but not for males who were younger than 55 years old or females in both age groups.","wc or central obesity is an independent risk factor for poor central auditory function, especially in older male subjects.",Prevention
do magnetic resonance imaging study in a normal bengal tiger ( panthera tigris ) stifle joint?,"the purpose of this study was to describe the normal appearance of the bony and soft tissue structures of the stifle joint of a bengal tiger (panthera tigris) by low-field magnetic resonance imaging (mri), and the use of gross anatomical dissections performed as anatomical reference. a cadaver of a mature female was imaged by mri using specific sequences as the spin-echo (se) t1-weighting and gradient-echo (ge) stir t2-weighting sequences in sagittal, dorsal and transverse planes, with a magnet of 0.2 tesla. the bony and articular structures were identified and labelled on anatomical dissections, as well as on the magnetic resonance (mr) images. mr images showed the bone, articular cartilage, menisci and ligaments of the normal tiger stifle. se t1-weighted sequence provided excellent resolution of the subchondral bones of the femur, tibia and patella compared with the ge stir t2-weighted mr images. articular cartilage and synovial fluid were visualised with high signal intensity in ge stir t2-weighted sequence, compared with se t1-weighted sequence where they appeared with intermediate intensity signal. menisci and ligaments of the stifle joint were visible with low signal intensity in both sequences. the infrapatellar fat pad was hyperintense on se t1-weighted images and showed low signal intensity on ge stir t2-weighted images.",mri provided adequate information of the bony and soft tissues structures of bengal tiger stifle joints. this information can be used as initial anatomic reference for interpretation of mr stifle images and to assist in the diagnosis of diseases of this region.,Diagnosis
does postexercise peripheral oxygen saturation after completion of the 6-minute walk test predict successfully reaching the summit of aconcagua?,"the 6-minute walk test (6mwt) is a single measurement of functional status in patients with cardiovascular disease. it has not been studied at high altitude. we investigate the screening value of 6-minute walk distance (6mwd) and postexercise vital sign (vs) measurements as predictors of successfully reaching the summit or development of acute mountain sickness (ams) on aconcagua (6962 m). prospective observational cohort in aconcagua provincial park, argentina. adults climbing the normal route who registered with base camp physicians were included. there were no exclusion criteria. vss were measured before (resting) and after (postexercise) completion of 6mwt while volunteers acclimatized at plaza de mulas base camp (4365 m). volunteers proceeded towards the summit at their own pace and upon descent returned a questionnaire with maximum altitude reached and lake louise ams self-report score (llself). one hundred twenty-four volunteers completed the 6mwt. sixty-four volunteers (51.6) completed questionnaires; 56 summited. median llself was 4 (iqr: 3.0-6.5). there was no association between any resting or postexercise vs measurements and ams. however, mean postexercise spo(2) was 80.8 in summiters and 76.4 in nonsummiters, a difference of -4.4 (95 ci: -6.7 to -2.0, p 0.0005). postexercise spo(2) 75 had 97.2 sensitivity and negative likelihood ratio of 0.086 in predicting the outcome of successfully reaching the summit: only one climber with spo(2) 75 successfully reached the summit.",this study provides the first published data on 6mwd recorded in the field at high altitude. postexercise spo(2) 75 may be a useful screening test for predicting the outcome of successfully reaching the summit of aconcagua.,Diagnosis
does tumour hypoxia determine the potential of combining mtor and autophagy inhibitors to treat mammary tumours?,"hypoxia can activate autophagy, a self-digest adaptive process that maintains cell turnover. mammalian target of rapamycin (mtor) inhibitors are used to treat cancer but also stimulate autophagy. human mammary cancer cells and derived xenografts were used to examine whether hypoxia could exacerbate autophagy-mediated resistance to the mtor inhibitor rapamycin. rapamycin exerted potent antitumour effects in mcf-7 and mda-mb-231 mammary tumours through a marked inhibition of angiogenesis, but the autophagy inhibitor chloroquine (cq) failed to further sensitise tumours to mtor inhibition. rapamycin treatment actually led to tumour reoxygenation, thereby preventing the development of autophagy. chloroquine alone, however, blocked the growth of mcf-7 tumours and in vitro blunted the hypoxia-induced component of autophagy in these cells. finally, when initiating cq treatment in large, hypoxic tumours, a robust antitumour effect could be observed, which also further increased the antiproliferative effects of rapamycin.","the mtor inhibitor rapamycin significantly contributes to tumour growth inhibition and normalisation of the tumour vasculature through potent antiangiogenic effects. the resulting reduction in hypoxia accounts for a lack of sensitisation by the autophagy inhibitor cq, except if the tumours are already at an advanced stage, and thus largely hypoxic at the initiation of the combination of rapamycin and cq treatment.",Medication
is mass distribution of azithromycin for trachoma control associated with short-term reduction in risk of acute lower respiratory infection in young children?,"we evaluated the effect of a single mass distribution of azithromycin for trachoma on the risk of acute lower respiratory infection (alri) during a 6-month period among young children living in 8 communities in rural tanzania. in 8 communities, a cohort of randomly selected children (n 1036) was followed for incidence of alri episodes. mass treatment for trachoma using a single dose of oral azithromycin was provided in 4 of the 8 communities where trachoma prevalence was .10. all children were followed with biweekly surveillance at home for 6 months. incidence of alri episodes was calculated for 0 to 1 month, 1 to 3 months, and 3 to 6 months posttreatment and in comparable time points in the nontreated villages. in the multivariate analysis, living in a mda village was associated with a 38 (rate ratio 5 0.62, 95 confidence interval ci 0.43-0.91) decreased risk of alri in the 0- to 1-month follow-up period as compared with those in the untreated communities after adjusting for covariates and clustering. there were no significant differences in alri incidence by exposure status in the 1- to 3-month (rate ratio 0.91, 95 ci 0.69-1.20) and in the 3- to 6-month (rate ratio 1.00, 95 ci 0.76-1.30) follow-up periods.",mass distribution of a single dose of oral azithromycin for trachoma is associated with a significant short-term reduction in alri morbidity among young children.,Medication
does secretory expression vector v-plncx-s-hri inhibit the growth of mouse b16 melanoma ?,"human ribonuclease inhibitor (hri) extracted and purified from human placenta has been shown to remarkably inhibit some solid tumors in mice. this study was to construct v-plncx-s-hri, a secretory expression vector, and explore its inhibition effects on the growth of mouse b16 melanoma cells. the hri gene sequence conjugated with the synthesized signal peptide of mouse igg was cloned into the retroviral vector v-plncx to construct v-plncx-s-hri. the pa317 cells were used for viral package and nih3t3 cells were employed to determine the viral titer. the expression of hri gene was detected by rt-pcr and western blot. the content of ri was determined by enzyme-linked immunoabsorption assay (elisa). the model of b16 melanoma-carrying mouse was established and received different treatments. the tumor weight and microvessle density (mvd) were assessed. normal saline (ns), v-plncx, and v-plncx-hri were used as controls. the infection efficiency of v-plncx-s-hri on cultured b16 cells reached 38.5. mrna and protein levels of hri were detected in b16 cells infected by v-plncx-s-hri. the hri content in the supernatant of infected b16 cells reached 0.228 microg/ml. the hri content in the peripheral blood of experimental mice was significantly higher in the v-plncx-s-hri group (0.249 microg/ml) than in the ns group (0.035 microg/ml), v-plncx group (0.028 microg/ml) and v-plncx-hri group (0.169 microg/ml) (p0.01).",v-plncx-s-hri can effectively infect b16 cells and induce high expression of hri. v-plncx-s-hri is superior to v-plncx-hri in inhibiting the growth of b16 cells.,Medication
does alpha 2a-adrenergic receptor signaling underlie synergistic enhancement of ethanol-induced behavioral impairment by clonidine?,"we tested the hypothesis that central alpha(2a)-adrenergic receptor (alpha(2a)ar) signaling plays a key role in clonidine-ethanol evoked synergistic behavioral impairment. male sprague-dawley rats, with intracisternal and jugular vein cannulae implanted 6 days earlier, were tested for drug-induced behavioral impairment. the latter was assessed as the duration of loss of righting reflex (lorr) and rotorod performance every 15 minutes until the rat recovered to the baseline walk criterion (180 seconds). in a separate cohort, c-fos expression in locus coeruleus (lc) and cerebellum was determined as a marker of neuronal activity following drug treatment. rats that received clonidine (60 microg/kg, i.v.) followed by ethanol (1 g/kg, i.v.) exhibited synergistic impairment of rotorod performance and lorr. the mixed alpha(2a)ar and i(1)-imidazoline receptor agonist clonidine (30, 60, and 90 microg/kg) synergistically and dose-dependently enhanced behavioral impairment elicited by ethanol (1 g/kg). possible involvement of i(1)-imidazoline receptors was ruled out because selective i(1)-agonist rilmenidine (300 microg/kg, i.v.) did not cause behavioral impairment alone or enhance ethanol-evoked behavioral impairment. pharmacological blockade of central alpha(2a)ar (rx821002, 0.3 mg i.c.) abolished the synergy between clonidine and ethanol; the behavioral response caused by the drug combination was similar to that caused by ethanol alone. conversely, involvement of central alpha(2b)ar in the interaction was ruled out because blockade of central alpha(2b)ar (arc-239) independently evoked a strong sedative effect. clonidine (60 microg/kg) or ethanol (1 g/kg) alone increased, but their combination decreased, c-fos levels in lc, while inconsistent c-fos responses were observed in cerebellum.","central alpha(2a)ar, but not i(1)-imidazoline or alpha(2b)ar, signaling is implicated in the synergistic enhancement of ethanol-evoked behavioral impairment by clonidine. although the mechanism of c-fos response remains to be investigated, this neurochemical response highlights the lc as a neuroanatomical target for clonidine-ethanol behavioral interaction.",Medication
does a modified glenn shunt reduce right ventricular stroke work during left ventricular assist device therapy?,"right ventricular (rv) failure is a major cause of morbidity and mortality after left ventricular assist device (lvad) placement and remains hard to predict. we hypothesized that partial surgical exclusion of the rv with a modified glenn shunt during lvad treatment would reduce rv stroke work. an lvad was implanted in eight pigs and a modified glenn shunt was constructed. a conductance pressure-volume catheter was placed in the right ventricle through the apex. haemodynamic data and pressure-volume loops were obtained at the following time periods: (i) baseline, (ii) open shunt, (iii) lvad with closed shunt and (iii) lvad and open shunt. during lvad therapy, the right atrial (ra) pressure increased from 9 mmhg (9-9) to 15 mmhg (12-15), p 0.01. rv stroke volume increased from 30 ml (29-40) to 51 ml (42-53), p 0.01. also, rv stroke work increased to 708 mmhg ml (654-1193) from 535 mmhg ml (424-717), p 0.04, compared with baseline. during lvad therapy in combination with a glenn shunt, the ra pressure decreased from 15 mmhg (12-15) to 10 mmhg (7-11) when compared with lvad therapy only, p 0.01. a decrease in rv stroke work from 708 mmhg ml (654-1193) to 465 mmhg ml (366-711), p 0.04, was seen when the lvad was combined with a shunt, not significantly different from the baseline value (535 mmhg ml). the developed pressure in the right ventricle decreased from 29 mmhg (26-32) to 21 mmhg (20-24), p 0.01. the pressure-volume loops of the rv show a significant reduction of rv stroke work during the use of the shunt with lvad treatment.","a modified glenn shunt reduced rv volumes, rv stroke work and ra pressure during lvad therapy in an experimental model of heart failure in pigs.",Treatment
are quality of life and acquired organ damage intimately related to activity limitations in patients with systemic lupus erythematosus?,"systemic lupus erythematosus (sle) is an autoimmune multi-organ disease, characterized by episodes of disease flares and remissions over time, which may restrain affected patients' ability to perform daily activities. the purpose of the present study was to characterize variation in activity limitations among well-defined sle patients, and to describe disease phenotypes, acquired organ damage and their relations to activity limitation and self-reported health, respectively. the disease phenotypes were organized into 4 different clinical groups and logistic regression analyses were used to identify how an elevated health assessment questionnaire (haq) score was related to disease variables such as phenotypes, disease activity and damage accrual. correlation and multiple linear regression analyses were used to examine the association between each group of variables - background variables, disease variables and self-reported measurements - and the degree of elevated haq. we found a higher proportion of activity limitation in patients with skin and joint involvement compared to others. the presence of activity limitation, as detected by the haq instrument, was significantly associated with quality of life (euroqol-5d) and accrual of organ damage using the systemic lupus international collaborative clinics/acr damage index.",the findings highlight the differing requirements of the multi-professional rehabilitation interventions for the various sle phenotypes in order to optimize the clinical care of the patients.,General
does dynamic hyperinflation correlate with exertional oxygen desaturation in patients with chronic obstructive pulmonary disease?,"dynamic hyperinflation (dh) causes exercise limitation and exertional dyspnea in patients with chronic obstructive pulmonary disease (copd). exertional desaturation (ed) also occurs commonly in copd but neither routine physiologic parameters nor imaging predict ed accurately. in this study we evaluated the relationship between dh and ed during 6-min walk testing (6mwt). we measured ed and dh in patients with stable copd. spo2 was measured by continuous pulse oximetry during 6mwt. ed was defined as a decline in spo2 (spo2) 4 . dh was determined by measuring inspiratory capacity (ic) before and after the 6mwt using a handheld spirometer. dh was defined as ic 0.0 l. we correlated dh and ed with clinical and pulmonary physiologic variables by regression analysis, (2), and receiver operator curve (roc) analysis. thirty males age 65 9.4 years, fev1 predicted 48 14 , and dlco predicted 50 21 (mean sd) were studied. spo2 correlated with ic (r 0.49, p 0.005) and age (r 0.39, p 0.03) by univariate analysis; however, only ic correlated on multivariate regression analysis (p 0.01). spo2 did not correlate with fev1, fvc, fef25-75, rv, dlco predicted, bmi, smoking, borg score, or distance covered in 6mwt. dh strongly correlated with ed (p 0.001). on roc analysis, dh had an area under the curve of 0.92 for the presence of ed (sensitivity 90 ; specificity 77 , p 0.001).",routine pulmonary function test results and clinical variables did not correlate with ed in patients with stable copd. dynamic hyperinflation strongly correlates with exertional desaturation and could be a reason for this desaturation.,Diagnosis
do parents and primary care physicians have different views about copying medical letters to parents after paediatric outpatient visits?,"we assessed how satisfied parents were when they received a copy of the letter sent to their primary care physician after their child attended a hospital outpatient clinic and compared their views with those of the primary care physician. anonymised questionnaires were sent to parents, and their primary care physician, after their child had visited a paediatric nephrology unit. we received responses from 112 parents (46) and 69 primary care physicians (93). most parents (97) were satisfied with the process, 94 thought that the letter was a true reflection of the outpatient consultation and easy to understand, and 55 read it to their child. however, 21 would have preferred a simpler letter. more than a third (37) of the primary care physicians did not approve of the parents being sent the letter, and 30 felt that the letter was difficult for the parents to understand and should be replaced with a simpler letter.","most parents (97) appreciated receiving a copy of the letter following their child's outpatient clinic visit, and 95 understood its contents. more than half (55) read the letter to their child. however, 37 of primary care physicians did not approve of the practice.",General
do selective cyclooxygenase inhibitors increase paclitaxel sensitivity in taxane-resistant ovarian cancer by suppressing p-glycoprotein expression?,"the purpose of this study was to investigate whether selective cyclooxygenase (cox) inhibitors promote paclitaxel-induced apoptosis in taxane-resistant ovarian cancer cells by suppressing mdr1/p-glycoprotein (p-gp) expression. taxane-resistant ovarian cancer cells were cultured with paclitaxel alone or combined with a selective cox inhibitors. the expression patterns of mdr1/p-gp and the ability of cox inhibitors to inhibit growth of taxane-resistant ovarian cancer cells were measured. the efficacy of prostaglandin e2 (pge2) supplementation was measured to evaluate the mechanisms involved in suppressing mdr1 gene expression. p-gp was upregulated in taxane-resistant ovarian cancer cells compared to paired paclitaxel-sensitive ovarian cancer cells. an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (mtt) assay showed that selective cox inhibitors significantly enhanced the cytotoxic effects of paclitaxel in taxane-resistant ovarian cancer cells via a prostaglandin-independent mechanism. these increased apoptotic effects were further verified by measuring an increased percentage of cells in sub-g1 stage using flow cytometry. selective cox inhibitors suppressed mdr1 and p-gp expression. moreover, combined treatment with paclitaxel and selective cox inhibitors increased poly (adp-ribose) polymerase (parp) cleavage in taxane-resistant ovarian cancer cells.","selective cox inhibitors significantly promote paclitaxel-induced cell death in taxane-resistant ovarian cancer cells in a prostaglandin-independent manner. cox inhibitors could be potent therapeutic tools to promote paclitaxel sensitization of taxane-resistant ovarian cancers by suppressing mdr1/p-gp, which is responsible for the efflux of chemotherapeutic agents.",Medication
does kiss-1 inhibit the proliferation and invasion of gastric carcinoma cells?,"to investigate the function of the kiss-1 gene in gastric carcinoma cells and to explore its potential mechanism. a kiss-1 eukaryotic expression vector was constructed and transfected into bgc-823 cells. resistant clones were obtained through g418 selection. reverse transcription-polymerase chain reaction and western blotting were used to detect kiss-1 and matrix metalloproteinase-9 (mmp-9) expression in transfected cells. the growth of transfected cells was investigated by 3-(4, 5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (mtt) proliferation assays, and the cells' invasive potential was analyzed by basement membrane (matrigel) invasion assays. the anti-tumor effects of kiss-1 were tested in vivo using allografts in nude mice. the expression level of kiss-1 mrna and protein in bgc-823/kiss-1 transfected cells were significantly higher than in bgc-823/pcdna3.1 transfected cells (p 0.05) or the parental bgc-823 cell line (p 0.05). the expression level of mmp-9 mrna and protein in bgc-823/kiss-1 were significantly less than in bgc-823/pcdna3.1 (p 0.05) or bgc-823 cells (p 0.05). mtt growth assays show the proliferation of bgc-823/kiss-1 cells at 48 h (0.642 0.130) and 72 h (0.530 0.164) were significantly reduced compared to bgc-823/pcdna3.1 (0.750 0.163, 0.645 0.140) (p 0.05) and bgc-823 cells (0.782 0.137, 0.685 0.111) (p 0.05). invasion assays indicate the invasive potential of bgc-823/kiss-1 cells (16.50 14.88) is significantly reduced compared to bgc-823/pcdna3.1 (20.22 14.87) (p 0.05) and bgc-823 cells after 24 h (22.12 16.12) (p 0.05). in vivo studies demonstrate the rate of pcdna3.1-kiss-1 tumor growth is significantly slower than pcdna3.1 and control cell tumor growth in nude mice. furthermore, tumor volume of pcdna3.1-kiss-1 tumors (939.38 82.08 mm(3)) was significantly less than pcdna3.1 (1250.46 44.36 mm(3)) and control tumors (1284.36 55.26 mm(3)) (p 0.05). moreover, the tumor mass of pcdna3.1-kiss-1 tumors (0.494 0.84 g) was significantly less than pcdna3.1 (0.668 0.55 g) and control tumors (0.682 0.38 g) (p 0.05).",kiss-1 may inhibit the proliferation and invasion of gastric carcinoma cells in vitro and in vivo through the downregulation of mmp-9.,General
does curcumin reduce streptococcus mutans biofilm formation by inhibiting sortase a activity?,"sortase a is an enzyme responsible for the covalent attachment of pac proteins to the cell wall in streptococcus mutans. it has been shown to play a role in modulating the surface properties and the biofilm formation and influence the cariogenicity of s. mutans. curcumin, an active ingredient of turmeric, was reported to be an inhibitor for staphylococcus aureus sortase a. the aim of this study was to investigate the inhibitory ability of curcumin against s. mutans sortase a and the effect of curcumin for biofilm formation. the antimicrobial activity of the curcumin to the s. mutans and inhibitory ability of the curcumin against the purified sortase a in vitro were detected. western-blot and real-time pcr were used to analysis the sortase a mediated pac protein changes when the s. mutans was cultured with curcumin. the curcumin on the s. mutans biofilm formation was determined by biofilm formation analysis. curcumin can inhibit purified s. mutans sortase a with a half-maximal inhibitory concentration (ic50) of (10.20.7)mol/l, which is lower than minimum inhibitory concentration (mic) of 175mol/l. curcumin (15mol/l) was found to release the pac protein to the supernatant and reduce s. mutans biofilm formation.",these results indicated that curcumin is an s. mutans sortase a inhibitor and has promising anti-caries characteristics through an anti-adhesion-mediated mechanism.,Medication
does linc-ror confer gemcitabine resistance to pancreatic cancer cells via inducing autophagy and modulating the mir-124/ptbp1/pkm2 axis?,"in this study, we investigated the regulation of linc-ror on autophagy and gemcitabine resistance of pancreatic cancer cells and further studied the underlying involvement of the mir-124/ptbp1/pkm2 axis in this regulation. pancreatic cancer cell lines panc-1 and miapaca-2 cells were used as in vitro model. autophagy was assessed by western blot of lc3 i/ii and observation gfp-lc3 puncta. cell viability was examined using cck-8 assay. cell apoptosis was examined by flow cytometric analysis of annexin v/pi staining. qrt-pcr, rna fluorescence in situ hybridization and dual luciferase assay were used to study the expression and the binding between linc-ror and mir-124. linc-ror sirna significantly sensitized panc-1 and miapaca-2 cells to gemcitabine, while linc-ror overexpression significantly reduced the sensitivity. linc-ror knockdown reduced basal autophagy, while linc-ror overexpression markedly increased basal autophagy in the cells. linc-ror sirna showed similar effect as 3-ma on enhancing gemcitabine-induced cell apoptosis and also reduced pkm2 expression. mir-124 overexpression restored pkm1 and reduced pkm2 levels in the cells. in addition, mir-124 mimics also alleviated autophagy in pancreatic cancer cells. both mir-124 mimics and pkm2 sirna enhanced gemcitabine-induced cell apoptosis. in both pancreatic cell lines and padc tissues, linc-ror is negatively correlated with mir-124 expression. in addition, dual luciferase assay verified two 8mer binding sites between mir-124 and linc-ror.",linc-ror confers gemcitabine resistance to pancreatic cancer cells at least partly via inducing autophagy. there is a linc-ror/mir-124/ptbp1/pkm2 axis involved in regulation of gemcitabine resistance in pancreatic cancer cells.,Diagnosis
do the presence and duration of overweight are associated with low-grade inflammation in prepubertal chilean children?,"overweight is associated with low-grade inflammation, but it is under debate whether the effect of fat mass accumulation is acute or chronic. we aimed to study the association of overweight duration with low-grade inflammation in children in whom overweight initiation can be established. observational longitudinal study, including a subsample of 250 chilean children from the growth and obesity cohort study followed-up yearly since preschool age (n 1195). at 4 years, 324 children provided blood. from those, 272 participants were evaluated at 7 years. the current analysis includes 250 children with a blood sample at 4 and 7 years of age and c-reactive protein (crp) 5 mg/l. anthropometric data (0-4 years) were obtained from health records and measured thereafter; sex- and age-specific body mass index z-scores (baz) were computed. among overweight (baz 1) participants at 7 years, the duration of overweight (time since diagnosis) was computed and categorized according to tertiles: 36, 36-72, or 72 months. the independent association between overweight (diagnosis and duration) and low-grade inflammation (crp 1 mg/l) was studied (logistic regression models). overweight was associated with crp 1 mg/l at 7 years odds ratio (or) 2.93 confidence interval (95 ci 1.60-5.38), but not at 4 years or 1.26 (95 ci 0.71-2.26). an overweight duration 36 m was independently associated with crp 1 mg/l or 3.53 (95 ci 1.21-10.28) (reference normal weight), whereas longer overweight durations (36-72 or 72 m) were not associated with crp 1 mg/l or 1.35 (95 ci 0.41-4.40) and or 1.21 (95 ci 0.35-4.18), respectively.",overweight at 7 years of age was associated with low-grade inflammation only in the case of recent onset. inflammatory disturbances may be associated with the early phases of excess weight.,Prevention
"does vorapaxar , an oral par-1 receptor antagonist , affect the pharmacokinetics of rosiglitazone?","to evaluate the potential effects of vorapaxar on the pharmacokinetics and safety of rosiglitazone. this was an open-label, two-period, two-treatment, fixed-sequence study in 18 healthy subjects. on day 1, period 1, subjects received a single dose of rosiglitazone 8 mg. in period 2, subjects received vorapaxar 40 mg on day 1, vorapaxar 7.5 mg once-daily on days 2-7, and a single dose of rosiglitazone 8 mg on day 7. rosiglitazone and n-desmethylrosiglitazone pharmacokinetics were assessed alone (period 1) and after coadministration with vorapaxar (period 2). vorapaxar and its m20 metabolite pharmacokinetics were assessed on day 7, period 2. safety and tolerability were assessed throughout the study. coadministration of rosiglitazone with vorapaxar had no effect on rosiglitazone or n-desmethylrosiglitazone pharmacokinetics. the ratio of geometric means (gmr) and 90 confidence intervals (ci) of the coadministration versus monotherapy for cmax (gmr 95; 90 ci 88, 103) and auc0-24 h (gmr 103; 90 ci 98, 108) were within the 80-125 bioequivalence criteria. the metabolite-to-parent exposure ratio with and without vorapaxar was unaltered. coadministration of vorapaxar with rosiglitazone was generally well tolerated.",coadministration of vorapaxar with rosiglitazone or drugs metabolized via cyp2c8 is unlikely to cause a significant pharmacokinetic interaction.,Medication
is left-ventricular electromechanical delay prolonged in patients with postoperative atrial fibrillation?,"although several risk factors for postoperative atrial fibrillation (af) have been proposed, it remains the most common complication after cardiac surgery, even in low-risk patients. there is still no single reliable and reproducible parameter for predicting af, and no standardized recommendation exists for this issue. electromechanical delay (excitation-contraction coupling delay) is the time delay from the electrical activation to the actual systolic motion, and it reflects abnormality in calcium-handling proteins, which is considered one mechanism of postoperative af. we hypothesized that left-ventricular electromechanical delay (lvemd) is correlated to postoperative af and serially examined it by echocardiography. we prospectively included 16 patients with relatively low risk for af, who underwent cardiac surgery. the inclusion criteria were younger than 80 years, an ejection fraction greater than 45, a left-atrial dimension less than 50mm, and a brain natriuretic peptide (bnp) value less than 250 pg ml. postoperative af for 10 postoperative days was monitored by 24-h electrocardiogram. the lvemd was assessed by pulse-wave tissue doppler echocardiography before and 1, 3, and 7 days after the operation. serum bnp, adrenalin, and noradrenalin levels were also examined at the same time. postoperative af was detected in six (37.5) patients. there was no significant difference in heart rate, qrs duration, and serum hormones between the non-af (n 10) and af (n 6) groups. although the preoperative lvemd was comparable, that on postoperative day 1 of the af group was significantly longer than that of the non-af group (in the septal wall, 174 50 vs 101 36 ms, p 0.020; in the lateral wall, 195 71 and 111 37 ms, p 0.029). a lvemd on postoperative day 1 greater than 150 ms well predicted postoperative af (sensitivity, 75 and 75; specificity, 100 and 86, in septal and lateral lvemds, respectively).",lvemd is prolonged in patients with postoperative af. this could be a new predicting parameter for af in low-risk patients.,Treatment
does i148m variant in pnpla3 reduce central adiposity and metabolic disease risks while increasing nonalcoholic fatty liver disease?,"the i148m variant because of the substitution of c to g in pnpla3 (rs738409) is associated with the increased risk of nonalcoholic fatty liver disease (nafld). in liver, i148m variant reduces hydrolytic function of pnpla3, which results in hepatic steatosis; however, its association with the other clinical phenotype such as adiposity and metabolic diseases is not well established. to identify the impact of i148m variant on clinical risk factors of nafld, we recruited 1363 generally healthy korean males after excluding alcoholic and secondary causes of hepatic steatosis. central adiposity was assessed by computed tomography, and hepatic steatosis was evaluated by abdominal ultrasonography. the participants were predominantly middle-aged (49.0 7.1 years; range 30-60 years), and the frequency of nafld was 44.2. the rs738409-g allele carriers had a 1.19-fold increased risk for nafld (minor allele frequency 0.43; allelic odds ratio 1.38; p 4.3 10(-5) ). interestingly, the rs738409 gg carriers showed significantly lower levels of visceral and subcutaneous adiposity (p 0.001 and 0.015, respectively), bmi (p 0.001), triglycerides (p 0.001) and insulin resistance (p 0.002) compared to cc carriers. these negative associations between clinical risk factors and rs738409-g dosage were more prominent in non-nafld group compared to those in nafld group.","the i148m variant, although increasing the risk of nafld, was associated with reduced levels of central adiposity, bmi, serum triglycerides and insulin resistance, suggesting differential roles in fat storage and distribution according to cell types and metabolic status.",Medication
does lack of c-kit receptor promote mammary tumors in n-nitrosomethylurea-treated ws/ws rats?,"c-kit is expressed in various cell types during development and it has been linked to the promotion of cellular migration, proliferation and/or survival of melanoblasts, hematopoietic progenitors and primordial germ cells. several reports have proposed a role for the c-kit gene on carcinogenesis. gain-of-function mutations are associated with diseases such as mastocytosis and gastrointestinal stromal tumors among others. however, very little is known about pathologies associated with loss-of-function mutations. regarding breast cancer, c-kit protein and mrna are highly expressed in normal breast but their expression decreases or is absent in the presence of breast cancer. we studied the role of c-kit in mammary carcinogenesis in the ws/ws rats carrying spontaneous lack-of-function mutation in the c-kit gene. fifty day-old virgin female ws/ws rats and their wild type counterparts were injected with either 50 mg/kg body weight of the chemical carcinogen n-nitrosomethylurea or with vehicle. the animals were followed-up for 6 months. fisher 344 rats were used as positive controls for tumor development. eleven weeks after treatment, palpable tumors were detected in the ws/ws rats. the tumor incidence was 80 in ws/ws rats, while no tumors were observed in the wild type rats (p 0.006). our data show that the lack of c-kit is permissive for the development of mammary tumor in ws/ws rats treated with carcinogen.","we conclude that the lack of c-kit may contribute to an imbalanced homeostatic state in the mammary gland either by affecting signaling between stroma and epithelium, or through the lack of mast cells.",Medication
does hsp27 act as a master molecular chaperone and plays an essential role in hepatocellular carcinoma progression?,"hsp27, a master molecular chaperone, plays an important role in cancer. however, the specific co-chaperones that partner with hsp27 and the role of hsp27 in hepatocellular carcinoma (hcc) are not fully enumerated. the present study focuses on the role of hsp27 in hcc and explores its potential co-chaperones in hcc development. gene overexpression or knockdown was used to observe the role of hsp27 in hcc. co-immunoprecipitation and mass spectrometry were used to explore apoptosis resistance by regulating multiple co-chaperones of hsp27. hsp27 protein-protein interaction (ppi) networks were constructed by the metacore software. hsp27 was upregulated in hcc tissues, and hsp27 overexpression significantly facilitated formation of hcc cell colony and invasion in normoxia and tolerance in hypoxia by interacting with hif-1. next, the analysis of microarrays revealed that hsp27 regulated several cellular signaling pathways, including wnt, erbb and tgf- signaling. moreover, we characterized the hsp27 ppi map, which indicated that hsp27 along with its co-chaperones formed different complexes and exerts transcription regulation activity by activating sp1, c-myc, p53 and esr1.","hsp27 along with its co-chaperones was related to the development of hcc by regulating multiple signaling pathways, and drugs that target hsp27 along with its co-chaperones may be a potential therapy for hcc.",General
does novel scn3b mutation associated with brugada syndrome affect intracellular trafficking and function of nav1.5?,"brugada syndrome (brs) is characterized by specific alterations on ecg in the right precordial leads and associated with ventricular arrhythmia that may manifest as syncope or sudden cardiac death. the major causes of brs are mutations in scn5a for a large subunit of the sodium channel, nav1.5, but a mutation in scn3b for a small subunit of sodium channel, nav3, has been recently reported in an american patient. a total of 181 unrelated brs patients, 178 japanese and 3 koreans, who had no mutations in scn5a, were examined for mutations in scn3b by direct sequencing of all exons and adjacent introns. a mutation, val110ile, was identified in 3 of 178 (1.7) japanese patients, but was not found in 480 japanese controls. the scn3b mutation impaired the cytoplasmic trafficking of nav1.5, the cell surface expression of which was decreased in transfected cells. whole-cell patch clamp recordings of the transfected cells revealed that the sodium currents were significantly reduced by the scn3b mutation.","the val110ile mutation of scn3b is a relatively common cause of scn5a-negative brs in japan, which has a reduced sodium current because of the loss of cell surface expression of nav1.5.",Diagnosis
do mentor 's hand hygiene practices influence student 's hand hygiene rates?,"there were 3 objectives for this prospective quasiexperimental study. the first was to determine the effect of mentor's hand hygiene practices on student's hand hygiene rates during clinical rotations. the second was to assess the difference in hand hygiene rates for students with and without prior medical experience. the third was to assess the student's opinion and beliefs regarding hand hygiene. sixty students enrolled in a certified nursing program were selected to participate in the study. each study group was observed twice during the 30-day span. the first observational period was conducted on day 1 of clinical rotation. the second observational period was conducted on day 30 of clinical rotation. students were observed for hand hygiene. also assessed were medical experience, sex, gloving, age, and mentor's hand hygiene practices. after observational period 2, a brief questionnaire was given to students to determine their opinion and beliefs regarding hand hygiene. the questionnaire was divided into 5 sections: student's commitment to hand hygiene, their perception of hand hygiene inconvenience, the necessity of hand hygiene, the student's ability to perform hand hygiene, and their opinion on the frequency of medical staff's hand hygiene. the mentor's practice of hand hygiene was the strongest predictor of the student's rate of hand hygiene for both observational periods (p .01). furthermore, students without prior medical experience had a significant increase in hand hygiene rates when comparing observational period 1 to observational period 2 (p .01). glove usage was associated with increased hand hygiene rates by 50 during observational period 1 (p .01) and 44 during observational period 2 (p .01). male students during observational period 1 practiced hand hygiene 30 less often than female students (p .01); however, during observational period 2, there was no significant difference between hand hygiene rates for males and females (p .82). questionnaires were completed by 47 students, who reported a strong commitment to hand hygiene, belief in its necessity, and ability to perform hand hygiene (with scores in the high 90s on a 10 to 100 rating scale).","mentor's use of hand hygiene and glove usage was associated with increased hand hygiene among students. even though students reported strongly positive attitudes toward hand hygiene, students had a low overall rate of hand hygiene.",Prevention
is serum immunoglobulin a concentration an independent predictor of liver fibrosis in nonalcoholic steatohepatitis before the cirrhotic stage?,"the similarity of alcoholic liver disease and nonalcoholic steatohepatitis (nash) in terms of pathogenic mechanisms suggests that immunoglobulin a (iga) may play an important role in the pathogenesis of nash. we aimed to determine whether serum iga concentrations allow a diagnosis of liver fibrosis in nash. we compared serum iga concentrations between 108 patients with stages 0-2 nash and 19 patients with stage 3 nash. in a univariate analysis, age (p 0.0001), gender (p 0.0039), serum albumin level (p 0.0192), ast (p 0.0001), ast/alt ratio (p 0.0001), platelet count (p 0.0027), hyaluronic acid level (p 0.0001), fasting blood sugar (fbs) (p 0.0013), iri (p 0.0001), prothrombin time () (p 0.0287), iga (p 0.0001), total sum of igg, iga, and igm (p 0.0049), and iga/(igg iga igm) (p 0.0105) were significantly elevated in severe-stage nash patients compared with the early-stage nash group. multiple logistic regression analysis showed that in severe-stage nash patients, only serum iga concentrations were significantly elevated (p 0.0225) relative to early-stage nash patients. the area under the curve (auc) of serum iga concentrations was 0.758 for detecting severe-stage nash compared with early-stage nash.",serum iga concentration could be a useful independent predictor for assessing the pre-cirrhotic progression of nash.,Diagnosis
are neurological soft signs associated with attentional dysfunction in children with attention deficit hyperactivity disorder?,"inattention is one of the core symptoms of attention deficit hyperactivity disorder (adhd). most of patients with adhd show motor impairment, consisting in the persistence of neurological soft signs (nss). our aim was to evaluate attentional and motor functioning in an adhd sample and healthy children (hc) and possible link between attentional dysfunction and motor impairment in adhd. twenty-seven drug-naive patients with adhd and 23 hc were tested with a test battery, measuring different aspects of attention. motor evaluation has provided three primary variables: overflow movements (om), dysrhythmia and total speed of timed activities. compared to hc, patients were impaired in a considerable number of attentional processes and showed a greater number of nss. significant correlations between disturbances of attention and motor abnormalities were observed in adhd group.","our findings suggest that attentional processes could be involved in the pathophysiology of the nss and add scientific evidence to the predictive value of nss as indicators of the severity of functional impairment in adhd. given the marked improvement or complete resolution of nss following treatment with methylphenidate, we suggest that evaluation of nss is useful to monitor the effectiveness of pharmacological treatment with mph in adhd.",Symptoms
is albumin administration associated with acute kidney injury in cardiac surgery : a propensity score analysis?,"the risk of acute kidney injury (aki) with the use of albumin-containing fluids compared to starches in the surgical intensive care setting remains uncertain. we evaluated the adjusted risk of aki associated with colloids following cardiac surgery. we performed a retrospective cohort study of patients undergoing on-pump cardiac surgery in a tertiary care center from 2008 to 2010. we assessed crystalloid and colloid administration until 36 hours after surgery. aki was defined by the rifle (risk, injury, failure, loss and end-stage kidney disease) risk and acute kidney injury network (akin) stage 1 serum creatinine criterion within 96 hours after surgery. our cohort included 984 patients with a baseline glomerular filtration rate of 72 19 ml/min/1.73 m(2). twenty-three percent had a reduced left ventricular ejection fraction (lvef), thirty-one percent were diabetics and twenty-three percent underwent heart valve surgery. the incidence of aki was 5.3 based on rifle risk and 12.0 based on the akin criterion. aki was associated with a reduced lvef, diuretic use, anemia, heart valve surgery, duration of extracorporeal circulation, hemodynamic instability and the use of albumin, pentastarch 10 and transfusions. there was an important dose-dependent aki risk associated with the administration of albumin, which also paralleled a higher prevalence of concomitant risk factors for aki. to address any indication bias, we derived a propensity score predicting the likelihood to receive albumin and matched 141 cases to 141 controls with a similar risk profile. in this analysis, albumin was associated with an increased aki risk (rifle risk: 12 versus 5, p 0.03; akin stage 1: 28 versus 13, p 0.002). we repeated this methodology in patients without postoperative hemodynamic instability and still identified an association between the use of albumin and aki.",albumin administration was associated with a dose-dependent risk of aki and remained significant using a propensity score methodology. future studies should address the safety of albumin-containing fluids on kidney function in patients undergoing cardiac surgery.,Treatment
does rho-kinase inhibitor fasudil suppress high glucose-induced h9c2 cell apoptosis through activation of autophagy?,"cardiac cell apoptosis plays a crucial role in the progression of diabetic cardiomyopathy. recent studies have shown that fasudil, a rho-kinase (rock) inhibitor, inhibits cardiac cell apoptosis; however, the underlying mechanism remains unclear. this study aimed to investigate whether fasudil protects h9c2 cells from high glucose-induced apoptosis via activation of autophagy. rat cardiomyocyte h9c2 cells were treated with high glucose and used as a diabetic cardiomyopathy model. cell survival rate, apoptosis, and subcellular morphology were examined using the mtt assay, flow cytometry, and electron microscopy, respectively. rock1 and rock2 mrna levels were determined using quantitative real-time pcr. bcl-2 and bax, myosin phosphatase target subunit-1 (mypt-1), phosphorylated (p)-mypt1, lc3-ii/lc3-i, beclin-1, soluble and insoluble p62 protein levels were determined by western blot analysis. fasudil reversed the high glucose-induced inhibition of cell proliferation and suppressed high glucose-induced early apoptosis. fasudil also reversed the high glucose-suppressed bcl-2 levels and decreased the high glucose-induced bax levels. further, fasudil suppressed rock levels, expression, promoted autophagy via increasing the lc3-ii/lc3-i ratio, beclin-1 expression, and the number of autophagosomes in h9c2 cells treated with high glucose. these effects of fasudil were abrogated by 3-methyladenine (3-ma), an autophagy inhibitor.",fasudil inhibited high glucose-induced apoptosis in rat h9c2 cells through activating autophagy.,Medication
are rare variants in sos2 and lztr1 associated with noonan syndrome?,"noonan syndrome is an autosomal dominant, multisystemic disorder caused by dysregulation of the ras/mitogen activated protein kinase (mapk) pathway. heterozygous, pathogenic variants in 11 known genes account for approximately 80 of cases. the identification of novel genes associated with noonan syndrome has become increasingly challenging, since they might be responsible for very small fractions of the cases. a cohort of 50 brazilian probands negative for pathogenic variants in the known genes associated with noonan syndrome was tested through whole-exome sequencing along with the relatives in the familial cases. families from the usa and poland with mutations in the newly identified genes were included subsequently. we identified rare, segregating or de novo missense variants in sos2 and lztr1 in 4 and 8, respectively, of the 50 brazilian probands. sos2 and lztr1 variants were also found to segregate in one american and one polish family. notably, sos2 variants were identified in patients with marked ectodermal involvement, similar to patients with sos1 mutations.","we identified two novel genes, sos2 and lztr1, associated with noonan syndrome, thereby expanding the molecular spectrum of rasopathies. mutations in these genes are responsible for approximately 3 of all patients with noonan syndrome. while sos2 is a natural candidate, because of its homology with sos1, the functional role of lztr1 in the ras/mapk pathway is not known, and it could not have been identified without the large pedigrees. additional functional studies are needed to elucidate the role of lztr1 in ras/mapk signalling and in the pathogenesis of noonan syndrome.",General
does kir6.2 e23k polymorphism is relate to secondary failure of sulfonylureas in non-obese patients with type 2 diabetes?,"the kir6.2 e23k polymorphism was studied with a special reference to secondary sulfonylurea (su) failure in non-obese patients with type 2 diabetes. we recruited 278 non-obese (body mass index 30.0 kg/m(2)) japanese patients with type 2 diabetes who had a history of su treatment (for 11.2 6.3 years) and compared the frequency of the secondary su failure among the genotypes of the polymorphism. genotyping of the kir6.2 e23k was carried out by polymerase chain reaction-restriction fragment length polymorphism. the genotype frequencies of the polymorphism were similar to those previously reported in japanese patients with type 2 diabetes. the frequency with which patients deteriorated into secondary su failure was significantly higher in those with the kk genotype than those with ee or ek genotypes. among 214 patients who eventually received insulin therapy because of secondary su failure, the period of su treatment in those with the kk genotype was significantly shorter than those with the ee or ek genotype, although the period from diagnosis to the start of su treatment was not significantly different.",these data suggest that the kir6.2 e23k polymorphism is related to the acceleration of secondary su failure in non-obese japanese patients with type 2 diabetes.,Treatment
are sequence memory skills in spastic bilateral cerebral palsy age independent as in normally developing children?,"to study the development of sequence memory skills in a group of participants with spastic bilateral cerebral palsy (cp) and their matched controls (td). sequence memory skills are defined as a blend of implicit and explicit competences that are crucial for the acquisition and consolidation of most adaptive skills along the lifespan. a computerized sequence learning task was administered to 51 participants with cp (age range: 4.1-14.7) and their controls. general performance, accuracy and learning strategy were analyzed, as well as cognitive competencies (iq and explicit visual spatial memory). explicit learning developed along with age in all participants. sequence learning skills were age independent and unevenly distributed among cp participants: most td (96.1) and only about half (58.8) of cp participants succeeded in sequence learning, in dynamic relation with cognitive and manipulation abilities.","sequence memory skills should be verified to plan therapeutic strategies. therapeutic plans based on implicit learning (more resistant to disruption and stress) could be effective and highly advantageous for most but not for all cp children. independently from age, many cp children could fix sequences more efficiently by explicit strategies, a more effortful but probably more effective way.",Medication
is type 2 diabetes associated with decreased pgc1 expression in epicardial adipose tissue of patients with coronary artery disease?,"although recent studies indicate that epicardial adipose tissue expresses brown fat-like genes, such as pgc1, ucp1 and prdm16, the association of these genes with type 2 diabetes mellitus (dm2) in coronary artery disease (cad) remains unknown. pgc1, ucp1, and prdm16 mrnas expression levels were measured by real-time pcr in epicardial and thoracic subcutaneous adipose tissue from 44 cad patients (22 with dm2 cad-dm2 and 22 without dm2 cad-ndm2) and 23 non-cad patients (ncad). the cad-dm2 patients had significantly lower pgc1 and ucp1 expression in epicardial adipose tissue than the cad-ndm2 and ncad patients. however, pgc1 and ucp1 mrna trended upward in subcutaneous adipose tissue from cad-dm2 patients. at multiple regression analysis, age, body mass index, left ventricular ejection fraction, ucp1 expression of epicardial adipose tissue and diabetes came out to be independent predictors of pgc1 levels. epicardial adipose tissue pgc1 expression was dependent on the number of injured coronary arteries and logistic regression analysis showed that pgc1 expression in epicardial adipose tissue could exert a protective effect against coronary lesions.","dm2 is associated with decreased expression of pgc1 and ucp1 mrna in epicardial adipose tissue of patients with cad, likely reflecting a loss of brown-like fat features. decreased expression of pgc1 in human epicardial adipose tissue is associated with higher prevalence of coronary lesions.",General
does minocycline prevent abeta ( 25-35 ) -induced reduction of somatostatin and neprilysin content in rat temporal cortex?,"tetracyclines have been demonstrated to inhibit formation of beta-amyloid (abeta) aggregates and to disassemble preformed fibrils. minocycline, a semi-synthetic second-generation tetracycline, can reverse abeta-induced impairment of cognitive functions. since somatostatin is involved in cognition and we recently showed that abeta(25-35) lowers somatostatin expression in the rat temporal cortex, our aim here was to analyze the effects of minocycline on somatostatin immunoreactivity and mrna levels in the temporal cortex of abeta(25-35)-infused and healthy rats. moreover, since brain levels of neprilysin, an abeta-degrading enzyme, decrease with age, favoring the appearance of senile neuritic plaques, we tested whether minocyline could affect neprilysin expression. wistar rats were thus injected with minocycline twice on the first day of treatment. on the following day, and during 14 days, abeta(25-35) or vehicle were administered. minocycline was injected once again on days 13 and 14. all animals were sacrificed 24 h after the last drug injection. minocycline abrogated the abeta(25-35)-induced decrease of somatostatin-like immunoreactive content, somatostatin mrna levels, phosphorylated-creb content and neprilysin levels. minocycline alone enhanced these targets.",our findings indicate that minocycline prevents the deleterious effects of abeta(25-35) on srif and neprilysin expression in the rat temporal cortex and that it has protective effects per se on these parameters.,Prevention
is neovascularization in the carotid atherosclerotic plaque associated with inflammatory cell aggregation?,"monocytes and macrophages in atherosclerotic plaque lead to plaque instability. the aim of the study was to determine if plaque neovascularization led to inflammation. patients were consecutively enrolled if their carotid intimal media thickness was 2 mm, as revealed by duplex ultrasound. the patients then underwent dynamic contrast enhanced magnetic resonance imaging (dce mri) and fluorine-18 fluorodeoxyglucose ((18)f-fdg) positron emission tomography combined with computed tomography (pet ct). a target to background ratio (tbr) of 1.25 or 1.25 served as the cutoff point for the presence and absence of inflammation, respectively. twenty-six patients underwent bilateral carotid dce mri and 24 patients also underwent pet ct. one hundred and fifty-five plaques were evaluated by both dce mri and pet ct. there was no significant difference in plaque morphology between the tbr 1.25 (n 61) and tbr 1.25 (n 94) groups. no significant differences were found in plasma volume and transfer constant between the tbr 1.25 and tbr 1.25 groups.",our study did not find a significant correlation between plaque neovascularization and the aggregation of inflammatory cells.,Diagnosis
does large-artery stiffness contribute to the greater prevalence of systolic hypertension in elderly women?,"to determine whether sex differences in large-artery stiffness contribute to the greater prevalence of systolic hypertension in elderly women than in elderly men. during a single visit arterial stiffness was assessed in the unmedicated state using four parameters. three hundred seventy-four women with a mean age/-standard deviation of 72/-5 and 296 men aged 71/-5 participated. hypertensive patients were recruited from general practice as part of the second australian national blood pressure study in melbourne, australia. large-artery stiffness was assessed using multiple methodologies, including aortic arch stiffness (beta-index) using m-mode ultrasound and arterial compliance and augmentation index using noninvasive carotid pressure and aortic flow measurements. women had greater carotid and brachial pulse pressure (pp) than men (p.001), despite higher mean arterial pressure in men. mean arterial compliance was lower in women (0.20/-0.12 vs 0.28/-0.16 ml/mmhg, p.001) even after correction for aortic area, and aortic arch stiffness was higher (30/-36 vs 23/-22; p.01). consistent with both a stiffer proximal circulation and a shorter distance to reflection sites, women had higher augmentation index (38/-11 vs 29/-12, p.001). in multivariate analysis, sex was an independent determinant of all arterial stiffness indices.","independently of known confounders, elderly hypertensive women have stiffer large arteries, greater central wave reflection, and higher pp than elderly men. stiffer large arteries likely contribute to the greater prevalence of systolic hypertension in elderly women and may partly explain the acceleration in postmenopausal cerebrovascular and cardiac complications.",Diagnosis
does recombinant anti-vascular endothelial growth factor fusion protein efficiently suppress choridal neovasularization in monkeys?,"kh902 is a fusion protein which combines ligand binding elements taken from the extracellular domains of vascular endothelial growth factor (vegf) receptors 1 and 2 and the fc portion of igg1. this study is designed to examine the inhibitory effect of kh902 in the choroidal neovascularization (cnv) monkey model. the binding affinity with vegf was measured by using the human vegf elisa kit, and the biological activity effect of kh902 was assayed by an in vitro inhibition experiment on human umbilical vein endothelial cell proliferation that was induced by vegf. the experimental cnv was induced by causing perimacular laser injury in the eyes of rhesus monkeys and confirmed by fluorescence fundus angiography (ffa), optical coherence tomography (oct), and multifocal electroretinograms (mf-erg) 20 days after the infliction of the laser injury. kh902 was delivered to the animals through intravitreal injection at various doses. monkeys were observed four weeks after injection by ophthalmic examination, ffa, oct, mf-erg, histopathology, and immunohistochemistry analysis. kh902 binds vegf at a high affinity with a mean of ic(50) of 10 pm. kh902 at 41 nm can completely block vegf-induced cell proliferation and kh902 at 10.7 nm can block 82.6 of cell growth. in the eyes of the treatment group, which received 300 microg and 500 microg kh902, choroidal neovascularization leakage was obviously less than before injection, and no leakage was observed at the end of the observation after injection. no high reflect light echogenic mass was detected by oct. however, in the 0.1 mg kh902-treated and control eyes, the leakage and high reflect light echogenic mass still existed. the reduction of experimental cnv was greater in eyes treated with 300 microg and 500 microg kh902 than in eyes treated with 0.1 mg kh902 and the control eyes. there were fiber-vasculosa membrane proliferation in the 100 microg kh902-treated eyes and control eyes but not in the 300 microg and 500 microg kh902-treated eyes under histopathologic observation. the results of mf-erg demonstrated that there was greater improvement in the 300 microg and 500 microg kh902-treated eyes than in the 100 microg kh902-treated eyes and control eyes.",kh902 presents high affinity with vegf and inhibitory activity on the proliferation of human umbilical vein endothelial cells (huvecs) induced by vegf. a single 300 microg or 500 microg kh902 intravitreal injection effectively inhibited leakage and growth of the cnv in rhesus monkeys without evidence of toxicity. this study suggests that kh902 has promise as a local antiangiogenic treatment of cnv.,Medication
is use of tranquilizers and sleeping pills among cancer patients associated with a poorer quality of life?,"to evaluate the association between sleeping pill/tranquilizer (sp/t) use and quality of life (qol) among cancer patients. oncology patients (n 909) in three israeli hospitals were interviewed in clinics, day centers and in-patient departments regarding sp/t use in the previous week. crude and adjusted qol scores, measured using the european organisation for research and treatment of cancer quality of life questionnaire-c30 (eortc qlq-c30), were compared in users vs. non-users. sleeping pill/tranquilizer use was self-reported by 234 (25.7) participants, but rarely documented in medical charts. factors associated with sp/t use were female gender (adjusted odds ratio, or: 1.79; 95 confidence interval, ci: 1.22-2.62, age (or: 4.6; 95 ci: 1.66-12.53 for age 70), place of birth (or: 1.97; 95 ci: 1.19-3.26 for eastern europe compared with israel), concomitant use of painkillers (or: 2.88; 95 ci: 1.97-4.20) and presence of cardiovascular disease (or: 2.41; 95 ci: 1.48-3.91). controlling these factors as well as disease status, users had a poorer qol on all functional scales (p 0.001) as well as global qol. furthermore, users reported increased severity of symptoms, especially fatigue, insomnia, pain, dyspnea and constipation (p 0.01), compared to non-users.","use of sp/t, reported by one fourth of cancer patients, was associated with substantially poorer qol and increased severity of symptoms. causal inference is not possible given the cross-sectional design. periodic inquiry regarding use of these medications in the oncology clinic is recommended since it may identify patients with poor qol and unmet needs.",Medication
is low socioeconomic status a risk factor for preeclampsia : the generation r study?,"to examine whether maternal socioeconomic status, as indicated by maternal educational level, is associated with preeclampsia, and if so, to what extent known risk factors for preeclampsia mediate the effect of educational level. in the generation r study, a population-based cohort study, we examined data of 3547 pregnant women. odds ratios of preeclampsia for low, mid-low and mid-high educational level compared with high educational level were calculated after adjustment for confounders and additional adjustment for a selection of potential mediators (family history, material factors, psychosocial factors, substance use, working conditions, preexisting medical conditions, maternal anthropometrics and blood pressure at enrollment) that individually caused more than 10 change in the odds ratio for low education. adjusted for the confounding effects of age, gravidity and multiple pregnancy, women with low educational level were more likely to develop preeclampsia (odds ratio 5.12; 95 confidence interval: 2.20, 11.93) than women with high educational level. after additional adjustment for financial difficulties, smoking in pregnancy, working conditions, body mass index and blood pressure at enrollment, the odds ratio was 4.91 (95 confidence interval: 1.93, 12.52).",low maternal socioeconomic status is a strong risk factor for preeclampsia. only a small part of this association can be explained by the mediating effects of established risk factors for preeclampsia. further research is needed to disentangle the pathway from low socioeconomic status to preeclampsia.,Prevention
does geriatric nutritional risk index be a simple predictor of mortality in chronic hemodialysis patients?,"malnutrition is common in hemodialysis (hd) patients, and it is associated with increasing risk of mortality. the geriatric nutritional risk index (gnri) has been developed as a tool to assess the nutritional risk. the aim of this study was to examine the reliability of the gnri as a mortality predictor in a japanese hd cohort. we prospectively examined the gnri of 332 maintenance hd patients aged 65.4 13.2, 213 males, and followed up on them for 36 months. the patients were divided into quartiles (q) according to gnri values (q1: 102.3). predictors for all-cause mortality were examined using kaplan-meier and cox proportional-hazards analyses. the gnri presented a normal distribution. during the follow-up period of 36 months, 76 patients died. the overall mortality at the end of the 3-year observational period was 22.3. at the 3-year follow-up period, kaplan-meier survival rates for all-cause mortality were 72.3, 79.3, 84.9 and 92.6 in q1, q2, q3, and q4, respectively (p 0.0067). multivariate cox proportional-hazards analysis demonstrated that the gnri was a significant predictor of adjusted all-cause mortality (hr 0.958; 95 ci 0.929-0.989, p 0.0073).","the results of the present study demonstrate that the gnri is a strong predictor of overall mortality in hd patients. however, cardiovascular mortality was not associated with gnri values, and did not differ among the gnri quartiles. the gnri score can be considered a simple and reliable marker of predictor for mortality risk in japanese hd patients.",Prevention
does immunosuppressive therapy increase operative morbidity in patients with crohn 's disease?,"the aim of this study was to examine the impact of immunosuppressive therapy on the morbidity of intestinal surgery in patients with crohn's disease. an increasing number of immunomodulating agents are being used in the treatment of crohn's disease. the effect of these medications on surgical morbidity is controversial. we performed a retrospective review of our prospectively maintained database of patients with crohn's disease who underwent intestinal surgery between june 1999 and may 2010. the effect of perioperative immunomodulation on postoperative outcomes, specifically anastomotic complications, was evaluated. predictors of postoperative morbidity among demographic and surgical variables were identified. length of hospitalization and rate of hospital readmission were compared between groups. comparisons were made using student t test and fisher exact test. one hundred ninety-six intestinal procedures were performed. one hundred twenty-seven (64.8) of these were performed among patients who received perioperative immunomodulation. forty-six (23.5) procedures were in patients who received 1 immunomodulating medication perioperatively. complications occurred in 45 (23.0) cases. there were 20 (10.2) anastomotic complications, including 8 (4.1) intra-abdominal abscesses, 8 (4.1) anastomotic leaks, and 4 (2) enterocutaneous fistulas. preoperative treatment with steroids (p0.21), 6-mp (p0.10), and anti-tumor necrosis factor biologics (p1.0) was not associated with increased postoperative anastomotic complications. combination immunosuppressive therapy also did not increase morbidity (p0.39).","in our series, single agent and combination immunosuppressive therapy given around the time of intestinal surgery did not increase the incidence of surgical complications in patients with crohn's disease.",Treatment
does overexpression of the homeobox gene hoxc8 in human prostate cancer correlate with loss of tumor differentiation?,"homeobox (hox)-containing proteins have been identified as regulators controlling the coordinated expression of genes involved in development and differentiation. recent data also suggest a possible involvement of hox genes in malignant transformation and/or progression. we have previously shown that hoxc8 expression was selectively turned on in human cervix cancer cells compared with normal keratinocytes, suggesting that hoxc8 may be involved in the process leading to the transformation of cervix keratinocytes alami et al.: biochem biophys res commun 257:738-745, 1999. rt-pcr and in situ hybridization experiments were performed to investigate the expression and cell type localization of hoxc8 transcripts in human prostate cancer cell lines and tissues. in situ hybridization was performed with the use of an hoxc8 anti-sense digoxigenin-labeled probe to investigate hoxc8 mrna expression in 27 prostate cancer tissue specimens. out of the three human prostate cancer cell lines tested, du-145 and pc3 but not lncap cells expressed detectable amount of hoxc8 transcripts. results from in situ hybridization experiments demonstrated that hoxc8 gene was expressed mainly in malignant epithelial cells. furthermore, the staining intensity in epithelial cells was significantly increased in high gleason score carcinomas (scores 7-9, n 12; labeling intensity 2 to 3 ) compared with the one observed in low and intermediate gleason score tumors (scores 3-6, n 15; labeling intensity 0 and 1 ) (anova test, p 0.0001).",our data showing that hoxc8 overexpression is associated with the loss of tumor differentiation in human prostate cancer suggests that hoxc8 may play a role in the acquisition of the invasive and metastatic phenotype of this malignancy.,General
are rising ca-125 levels in a patient with ovarian cancer always indicative of disease recurrence ?,"a 64-year-old woman was diagnosed as suffering from ovarian cancer. at that time, in 1984, she was treated with chemotherapy and complete remission was achieved. the disease recurred 2.5 years later and chemotherapy was delivered again. the patient remained disease free for 9 years. at that point a routine blood examination revealed a high serum level of the marker ca-125. a second recurrence of ovarian cancer was assumed. nonetheless, work up revealed that the rise in ca-125 was related to the presence of a non-hodgkins lymphoma (nhl).",this case together with our review of the literature highlights the emerging roll of the ca-125 marker in the diagnosis and follow-up of non-hodgkins lymphoma. our case also illustrates that physicians should be aware of the fact that markers may be misleading.,Medication
are whip use and race progress associated with horse falls in hurdle and steeplechase racing in the uk?,"falls during racing present a risk of injury to both horse and jockey and a risk of fatality to horses. to use video recordings of races to describe the circumstances surrounding horse falls at hurdle and steeplechase fences and to identify and quantify within-race risk factors for horse falls in national hunt racing in the uk. a retrospective, matched, nested case-control study using video recordings of races was conducted on 6 uk racecourses. cases and controls were matched on both race type and jump number at which the fall occurred. conditional logistic regression analysis was used to examine the univariable and multivariable relationship between predictor variables and the risk of falling. the risk of falling was significantly associated with whip use and race progress. horses which were being whipped and progressing through the race were at greater than 7 times the risk of falling compared to horses which were not being whipped and which had no change in position or lost position through the field.",this study has identified whip use and the position of the horse with respect to others in the field as potential risk factors for horse falls.,Prevention
does inflammation enhance resection-induced intestinal adaptive growth in il-10 null mice?,"surgical resection of the ileum, cecum, and proximal right colon (icr) is common in the management of crohn's disease, yet little is known about the effect of active inflammation on the adaptive response following intestinal loss. we recently developed a surgical model of icr in germ-free (gf) il-10 null mice that develop small intestinal inflammation only when mice undergo conventionalization with normal fecal microflora (conv) before surgical intervention. in this study, we examined the effects of postsurgical small bowel inflammation on adaptive growth after icr. gf 129svev il-10 null mice, 8-10 wk old, were allocated to gf or conv groups. nonoperated gf and conv mice provided baseline controls. two wk later, gf and conv mice were further allocated to icr or sham operation. small intestine and colon were harvested 7 d after surgery for histological analysis. all mice within the gnotobiotic facility maintained gf status and did not develop small intestinal or colonic inflammation. conv resulted in colitis in all groups, whereas small intestinal inflammation was only observed following icr. resection-induced small intestinal inflammation in conv mice was associated with increases in proliferation, crypt depth, and villus height compared with gf mice after icr. resection-induced increases in crypt fission only occurred in conv mice.",icr-dependent small intestinal inflammation in conv il-10 null mice dramatically enhances early adaptive growth of the small intestine. additional studies utilizing our model may provide clinical insight leading to optimal therapies in managing ibd patients after surgical resection.,Treatment
does whole exome sequencing identify de novo mutations in gata6 associated with congenital diaphragmatic hernia?,"congenital diaphragmatic hernia (cdh) is a common birth defect affecting 1 in 3000 births. it is characterised by herniation of abdominal viscera through an incompletely formed diaphragm. although chromosomal anomalies and mutations in several genes have been implicated, the cause for most patients is unknown. we used whole exome sequencing in two families with cdh and congenital heart disease, and identified mutations in gata6 in both. in the first family, we identified a de novo missense mutation (c.1366ct, p.r456c) in a sporadic cdh patient with tetralogy of fallot. in the second, a nonsense mutation (c.712gt, p.g238) was identified in two siblings with cdh and a large ventricular septal defect. the g238 mutation was inherited from their mother, who was clinically affected with congenital absence of the pericardium, patent ductus arteriosus and intestinal malrotation. deep sequencing of blood and saliva-derived dna from the mother suggested somatic mosaicism as an explanation for her milder phenotype, with only approximately 15 mutant alleles. to determine the frequency of gata6 mutations in cdh, we sequenced the gene in 378 patients with cdh. we identified one additional de novo mutation (c.1071delg, p.v358cfs34).","mutations in gata6 have been previously associated with pancreatic agenesis and congenital heart disease. we conclude that, in addition to the heart and the pancreas, gata6 is involved in development of two additional organs, the diaphragm and the pericardium. in addition, we have shown that de novo mutations can contribute to the development of cdh, a common birth defect.",General
"is postovariectomy weight gain in female rats reversed by estrogen receptor alpha agonist , propylpyrazoletriol?","the objective of this study was to distinguish the role of specific estrogen receptors (ers), eralpha and erbeta, on body weight regulation using a rat model of weight gain subsequent to menopause. ovariectomized rats were utilized as the animal model to simulate the postmenopause weight gain. the rats were ovariectomized and subcutaneously injected daily with vehicle, estradiol-17beta (e2), propylpyrazoletriol (ppt; eralpha agonist) and diarylpropionitrile (dpn; erbeta agonist). to further control for the possible effect of estrogen secreted from adrenals, a second experiment was conducted during which the rats were adrenalectomized and ovariectomized. ovariectomy significantly increased (p .05) body weight, whereas treatment of ovariectomized rats with e2 and ppt, but dpn decreased (p .05) body weight. the results from the second study with ovariectomized/adrenalectomized rats were consistent with the first experiment.",these results suggest that the activation of eralpha is important in regulating body weight.,Medication
is a ghrelin receptor agonist an effective colokinetic in rats with diet-induced constipation?,"despite constipation being a common problem, the treatments that are available have side effects and are only partly effective. recent studies show that centrally penetrant ghrelin receptor agonists cause defecation in humans and other species. here, we describe some features of a rat model of low fiber-induced constipation, and investigate the effectiveness of the ghrelin agonist, capromorelin. rats were given low-fiber diets for 5 weeks. their colorectal responsiveness to distension and to a behavioral test, water avoidance and colon histology were compared to those of rats on a standard diet. after the low-fiber diet, distension of the colon produced fewer propulsive contractions, behaviorally induced defecation was reduced, and the lining of the colorectum was inflamed. however, capromorelin was similarly effective in causing defecation in constipated and non-constipated rats.","low-fiber diet in rats produces a constipation phenotype, characterized by reduced responsiveness of the colorectum to distension and to a behavioral stimulus of defecation, water avoidance. the effectiveness of capromorelin suggests that centrally penetrant ghrelin receptor stimulants may be effective in treating constipation.",Medication
does l-arginine-enriched preservation solution decrease ischaemia/reperfusion injury in canine kidneys after long-term cold storage?,"kidneys stored hypothermically for transplantation show varying degrees of tissue injury, depending on the duration of preservation. the causes of injury are not entirely clear. we investigated the quality of renal functional recovery in canine kidneys after 72 h hypothermic preservation in custodiol solution or custodiol solution plus l-arginine. kidneys obtained from mongrel dogs, weighing 18-25 kg, were subjected to 72-h cold ischaemia after flushing. animals were divided into two groups (n18/group). a flush solution of either custodiol solution or custodiol solution plus l-arginine 1 mmol/l was used for each group. after 72-h cold storage all animals had a contralateral nephrectomy, and autotransplantation was performed to external iliac artery and vein. survivals were evaluated at 3 days. renal damage was assessed by kidney function tests, serum creatinine (scr), blood urea nitrogen (bun) and light histology. malondialdehyde (mda) was measured as an index of lipid peroxidation. scr and bun (24, 48 and 72 h) were significantly different from the control and l-arginine groups. histological damage was less in the l-arginine group. mda levels were significantly different with the lower levels in the l-arginine group.","on the basis of these data, we concluded that exogenous l-arginine (a substrate for no synthesis) has a beneficial and protective effect on long-term (72 h) hypothermic ischaemical damage in canine kidneys.",Treatment
is alpha2-antiplasmin involved in the production of transforming growth factor beta1 and fibrosis?,"fibrotic disease occurs in most tissues. transforming growth factor (tgf)-beta is the major inducer of fibrosis. the fibrinolytic system is considered to play an important role in the degradation of extracellular matrices. however, the detailed mechanism of how this system affects fibrosis remains unclear. we examined experimental fibrosis in mice with a deficiency of alpha(2)-antiplasmin (alpha2ap), which is a potent and specific plasmin inhibitor. we found that the lack of alpha2ap attenuated bleomycin-induced tgf-beta(1) synthesis and fibrosis. in addition, the production of tgf-beta(1) from the explanted fibroblasts of alpha2ap(-/-) mice decreased dramatically as compared to that in wild-type mice. moreover, we found that alpha2ap specifically induces the production of tgf-beta(1) in fibroblasts.","the lack of alpha2ap attenuated tgf-beta(1) synthesis, thereby resulting in attenuated fibrosis. this is the first report to describe the crucial role that alpha2ap plays in tgf-beta(1) synthesis during the process of fibrosis. our results provide new insights into the role of alpha2ap in fibrosis.",Medication
is high triglyceride level associated with severe coronary artery disease in hypertensive subjects?,"the contribution of triglycerides (tg) to the extent of coronary artery disease (cad) in hypertensive patients remained unclear. consecutive 821 (aged 64.5/-11.5 years, 482 males) hypertensive patients undergoing coronary angiography were included. the relationship of tg levels ( or 150 mg/dl) to the extent of cad in all patients was examined by multiple logistic regression, adjusting for other cad risk factors. in the lipid group, low levels of hdl were also adjusted. higher levels of tg were found in subjects with severe cad compared to those with no or minimal cad. the adjusted odds ratios for high levels of tg in the severe cad subgroup versus the no or minimal cad subgroup were 5.20 (95 ci, 3.13 to 8.63) in all patients and 7.51 (95 ci, 3.19 to 17.65) in the lipid group.",high levels of tg are strong clinical markers of greater extent of cad in hypertensive subjects undergoing coronary angiography. the results may have clinical relevance for physicians in therapeutic decision making.,Prevention
does ischemic conditioning ( delay phenomenon ) improve esophagogastric anastomotic wound healing in the rat?,"esophagogastric anastomotic leaks are a major source of morbidity after esophagectomy. occult ischemia of the mobilized gastric fundus is an important etiological factor for this failure of healing. to test the hypothesis that ischemic conditioning (delay phenomenon) could improve esophagogastric anastomotic healing, anastomotic healing was studied in a rodent model of partial gastric devascularization. thirty-four sprague-dawley rats (two groups of 17 rats) underwent partial gastric devascularization and creation of esophagogastric anastomoses. in the acute ischemia group, devascularization and anastomosis were done at the same laparotomy. in the ischemic conditioned group, devascularization was done 3 weeks before anastomosis. gastric tissue perfusion was assessed by laser-doppler flowmetry before and after devascularization in both groups, and 3 weeks after devascularization in the ischemic conditioned group. all rats were killed 4 days after anastomosis, and the wounds assessed for dehiscence, breaking strength, and hydroxyproline concentration. gastric tissue perfusion, measured in tissue perfusion units (tpu) decreased immediately after devascularization (before: 73.6 /- 12.1 tpu; after: 25.0 /- 6.5 tpu; p 0.001). after 3 weeks, gastric tissue perfusion returned to baseline values in the ischemic conditioned rats (before: 72.3 /- 11.0 tpu; 3 weeks, 71.1 /- 15.1 tpu; p 0.80). ischemic conditioned rats had fewer anastomotic leaks (2 vs. 9, p 0.023) and higher anastomotic wound breaking strengths (2.35 /- 1.05 n vs. 1.56 /- .76 n, p 0.02) than the acute ischemic rats. anastomotic would hydroxy-proline concentration was not significantly different in the two groups (acute ischemic--0.111 /- .033 mumol/mg, ischemic conditions--0.097 /- .026 mumol/mg, p 0.20).","in this rodent model of partial gastric devascularization, ischemic conditioning (delay phenomenon) ameliorated the harmful effect of ischemic on esophagogastric anastomotic wound healing.",General
is mandibular tori size related to obstructive sleep apnea and treatment success with an oral appliance?,"obstructive sleep apnea (osa) is a common disorder characterized by repetitive upper airway obstruction during sleep. we aimed to investigate whether mandibular tori, exostoses that appear on the lingual surface of the lower jaw, are related to osa and the effect of an oral appliance (oa) in osa patients. six hundred snoring patients with a mean age of 52 years (range 23-75 years) and a mean respiratory disturbance index (rdi) of 15 (range 0-76), who were consecutively referred for oa treatment, were included. the size of the tori was measured on plaster casts with a digital sliding caliper. twenty-seven percent of the patients had mandibular tori, with a similar prevalence in snorers and patients with mild, moderate and severe osa. tori size differed between severity groups. thick tori (2.9 mm) were associated with an rdi of 30, odds ratio (or) 4.7 (p 0.01), adjusted for age, gender and body mass index (bmi; kg/m(2)). complete treatment response with oa was related to thick tori, or 2.5 (p 0.02), adjusted for disease severity, age, gender, bmi (kg/m(2)), weight changes (kg) and mandibular repositioning.",patients with milder disease are more likely to have larger tori than patients with severe osa. treatment success with an oa occurs more frequently in patients with larger tori than in patients with no tori or small tori.,Treatment
does panel of emerging cardiac biomarkers contribute for prognosis rather than diagnosis in chronic heart failure?,"as complex disease, heart failure is associated with various pathophysiological and biochemical disorders. no single biomarker is able to display all these characteristics. therefore, we evaluated a multimarker panel together with the biochemical gold-standard nt-probnp. part of the panel are markers for angiogenesis (endostatin, ibp-4, ibp-7, sflt-1 as antiangiogenetic factors and plgf as angiogenectic factor), myocyte stress (gdf-15), extracellular matrix remodelling (galectin-3, mimecan and timp-1), inflammation (galectin-3) and myocyte injury (hs-tnt). all markers (roche diagnostics, penzberg, germany) were assessed in a cohort of 149 patients with chronic heart failure and 84 healthy controls. all markers were positively correlated with ln nt-probnp (each p 0.05). furthermore, they were significantly elevated in patients with chronic heart failure (each p 0.05). all markers increased significantly with severity of lv dysfunction and severity of new york heart association class (each p 0.05), except for plgf and mimecan (each p ns). with the exception of endostatin, mimecan and plgf, all other markers were further significant predictors for all-cause mortality in a 3-year follow-up. in a multimarker approach of the five biomarkers with the best performance (nt-probnp, hs-tnt, timp-1, gdf-15 and ibp-4), the event rate was superior to nt-probnp alone and increased significantly and progressively with the number of elevated biomarkers.","all emerging markers increased stepwise with the severity of symptoms and lv dysfunction and offer important prognostic information in chronic heart failure, except for plgf and mimecan. five biomarkers with different pathophysiological background incorporated additive prognostic value in heart failure. prognostication in heart failure may be further improved through a multimarker approach.",Diagnosis
is bax the heterodimerization partner necessary for sustained anti-photoreceptor-cell-death activity of bcl-2?,"ectopic expression of bcl-2 in photoreceptors of certain mouse models of retinitis pigmentosa (rp) temporarily slows disease progression. the temporary effect produced by bcl-2 may result from insufficient levels of functional complexes between bcl-2 and additional proteins necessary for maintaining the anti-apoptotic activity of bcl-2. although the overexpression of bax generally induces apoptosis, bax exerts anti-apoptotic properties when complexed with bcl-2 in certain cell culture systems. these studies were designed to determine whether coexpression of bcl-2 and bax would improve the neuroprotective effect provided by bcl-2 alone in photoreceptors of mice with autosomal dominant rp (adrp). transgenic mice were produced that overexpressed bax and bcl-2 specifically in photoreceptor cells, using the murine opsin promoter to drive transgene expression. these mice were crossed with an adrp mouse model to assess the effect of coexpression of bax and bcl-2 on retinal degeneration. morphologic analysis was performed on retinas isolated at various developmental times to monitor disease progression. ectopic expression of bax in photoreceptors resulted in extensive rod cell death dependent on the level of bax transgene expression. although bcl-2 was able to inhibit bax-induced photoreceptor cell death, the coexpression of bcl-2 and bax in photoreceptors of mice with adrp did not enhance the protective effect against photoreceptor cell death exerted by bcl-2 alone.","coexpression of bax and bcl-2, at the levels produced in the transgenic lines, does not extend the temporary neuroprotective effect produced by bcl-2 in photoreceptors of mice with adrp.",General
do prevalence of triceps tendon tears on mri of the elbow and clinical correlation?,"triceps tendon injuries are reported to be very rare. to our knowledge, there have been no studies describing its prevalence or injury patterns on mr imaging. the purpose of this retrospective study was to determine the prevalence and patterns of triceps injuries based on a large series of consecutive mr examinations. clinical correlation was obtained. from 801 consecutive elbow mr examinations over a 15-year period, 28 patients with 30 triceps tendon injuries were identified and graded as partial tendon tear and complete tendon tear. the patients' medical records were reviewed to determine age, gender, cause of tears, and management. the prevalence of triceps tendon injuries was 3.8. there were 5 women and 23 men with partial or complete tears (mean age: 46.6 years; range: 2.7 to 75.1 years). the most common injury was partial tear, found in 18 patients. there were 10 patients with 12 complete tears (2 had re-torn following surgical repair). a tear was suspected in 12 out 28 (43) patients prior to the mri. the most common presenting symptom was pain. the most common cause was athletic injury (8 patients 29, including weightlifting 2 patients). tendon tear was found to be a complication of infection in 6 patients, and in 3 patients the tears were a complication of steroid use. thirteen tendon tears were surgically repaired (8 of these were complete tears).",triceps tendon injury is not as rare as commonly reported and may often be clinically underdiagnosed.,Diagnosis
does maximizing tissue response in selected subjects with anterior open bite?,"open bites are challenging malocclusions with a multifactorial etiology, varying clinical severity, and questionable stability. the aim of this article is to describe a method for maximizing tissue response in the treatment of selected subjects with anterior open bites. twelve subjects with an anterior open bite and insufficient incisor display underwent a limited corticotomy to augment alveolar bone response by creating an anteroposterior intra-arch anchorage differential. cephalometric radiographs were taken before treatment (t1) and 1 month after open bite closure (t2). the change in perceived smile esthetics was assessed by a visual analog scale. all open bites were closed after a mean of 6 weeks. radiographic evaluation showed significant maxillary incisor extrusion and retrusion. there was a notable improvement in smile esthetics after treatment.",it is possible to close anterior open bites rapidly with significant improvement in smile esthetics in a selected group of anterior open-bite subjects.,Diagnosis
does computer-controlled cardiopulmonary bypass increase jugular venous oxygen saturation during rewarming?,"conventional roller pump apulsatile cardiopulmonary bypass (cpb) was compared with computer-controlled pulsatile bypass, which was designed to recreate biological variability (return of beat-to-beat variability in rate and pressure with superimposed respiratory rhythms). the degree of jugular venous oxygen saturation (sjvo2) less than 50 during rewarming from hypothermic cpb was compared for the two bypass techniques. an sjvo2 less than 50 during rewarming from hypothermic cpb is correlated with cognitive dysfunction in humans. pigs were placed on cpb for 3 hours using a membrane oxygenator with alpha-stat acid-base management and arterial filtration. after baseline measurements and normothermic cpb, the animals were randomized to apulsatile cpb (n 12) or computer-controlled pulsatile cpb (roller pump speed adjusted by an average of 2.9 voltage output modulations/s; n 12). the animals were then cooled to a nasopharyngeal temperature of 28 degrees c. during rewarming to stable normothermic temperatures, sjvo2 was measured at 5-minute intervals. the mean and cumulative areas for an sjvo2 less than 50 were determined for all animals. no between-group differences in temperature were noted during hypothermic cpb or during rewarming. the rate of rewarming was not different between groups. mean arterial pressure, partial pressure of oxygen in arterial blood, and partial pressure of carbon dioxide in arterial blood also did not differ between groups. the hemoglobin concentration was within 0.4 g/dl between groups at all time periods. mean pulse pressure was 10.0 /- 4.8 mm hg in the apulsatile cpb group and 20.7 /- 5.2 mm hg in the pulsatile cpb group (p 0.0002; unpaired t test). markedly greater mean and cumulative areas under the curve for sjvo2 less than 50 were seen with apulsatile cpb (164 /- 209 versus 1.9 /- 3.6 x min, p 0.021; and 1,796 /- 2,263 versus 23 /- 45 x min, p 0.020, respectively).","computer-controlled pulsatile cpb was associated with significantly greater sjvo2 during rewarming from hypothermic cpb. both the mean and cumulative areas under the curve for sjvo2 less than 50 exceeded a ratio of 75:1 for apulsatile versus computer-controlled pulsatile cpb. these experiments suggest that cerebral oxygenation was better preserved during rewarming from moderate hypothermia with computer-controlled pulsatile cpb, which returned biologic variability to the flow pattern.",Treatment
does gastric electrical stimulation result in improved metabolic control in diabetic patients suffering from gastroparesis?,"symptoms of gastroparesis possess a heavy impact on the quality of life; delayed gastric emptying may result in poor metabolic control in diabetics. gastric electrical stimulation (ges) has recently been introduced as a treatment option in patients with drug refractory gastroparesis to increase the quality of life by alleviating nausea and vomiting frequencies. however, the effect of ges on metabolic control has not been assessed yet. we performed a prospective single center study on the long-term effect (12 months) of continuous high-frequency/low-energy ges on symptoms, gastric emptying (measured scintigraphically), and metabolic control (hba1c) in insulin-dependent diabetic subjects suffering from drug-refractory gastroparesis for more than one year. seventeen (12 female, 5 male) patients entered the study; all were available for analysis at all time points. no therapy-associated adverse events occurred. weekly vomiting and nausea frequencies decreased significantly at 6 and 12 months. gastric retention rates improved significantly from 83 (2 h) and 38 (4 h) to 35 (2 h)/14 (4 h) and 25 (2 h)/17 (4 h) at 6 and 12 months, respectively. hba1c values were lowered in all 17 subjects; initially, all hba1c values were above 7.5 ; at 6 and 12 months, mean values had significantly decreased from 8.6 to 6.2 and 6.5 , respectively.","gastric electrical stimulation offers symptom control in diabetics with drug-refractory gastroparesis and decreases gastric retention. this study, for the first time, documents a positive effect of this therapy on metabolic control as indicated by hba1c, a surrogate marker of the risk of diabetic complications.",Symptoms
does strictureplasty in selected crohn 's disease patients result in acceptable long-term outcome?,"strictureplasty is an alternative to resection in patients with crohn's disease. the objective of this study was to evaluate the long-term results of patients who have undergone strictureplasty. this is a retrospective cohort study. this study was conducted at a tertiary referral center, mount sinai hospital, toronto, ontario, canada. all patients who had a strictureplasty of the small bowel between 1985 and 2010 were identified from a prospective database. the main outcomes were short-term complications, need for further surgery, and surgery-free survival. multivariate analysis was performed to determine factors affecting the need for further surgery. quality of life was measured by use of the short version of the inflammatory bowel disease questionnaire. ninety-four patients (42 women; age at first strictureplasty, 33.4 9.7 years) underwent 119 operations (range per patient, 1-4). the number of strictureplasties was 278 (range, 1-11), including 9 in the duodenum and 269 in the jejunum-ileum. the most common type of procedure was the heineke-mickulicz (258, 92.8). median follow-up of the patients was 94 months (interquartile range, 27-165 months). the surgery-free survival at 5 and 10 years was 70.7 (95 ci 59.8, 81.7) and 26.6 (95 ci 13.6, 39.6). in multivariate analysis, only age at the time of first strictureplasty was associated with the need for further surgery. fifty-seven (64.8) patients returned the questionnaire. the average score was 5.2 1.2 (range, 2.2-7.0) with no significant differences between patients with or without previous surgery (p 0.22), with or without simultaneous resection (p 0.71) or with or without further surgery (p 0.11).",this study was limited by its sample size and retrospective design.,Treatment
is raloxifene pharmacodynamics influenced by genetic variants in the rankl/rank/opg system and in the wnt signaling pathway?,"raloxifene is a selective estrogen receptor (er) modulator (serm) used for the treatment of osteoporosis. however, its efficacy and also its safety vary greatly among treated patients, and it might be influenced by the individuals' genetic background. as the receptor activator of the nuclear factor b (rank) ligand (rankl)/rank/osteoprotegerin (opg) system is essential for osteoclastogensis and wnt signaling pathway for osteoblastogenesis, we decided to evaluate the raloxifene treatment in regard to selected polymorphisms in key genes of these two main bone regulatory pathways. fifty-six osteoporotic postmenopausal women treated with raloxifene were genotyped for 11 polymorphisms located in six genes: -290ct, -643ct, and -693gc in tumor necrosis factor receptor superfamily member 11 (tnfsf11), 34694ct, 34901ga, and 35966insdelc in tumor necrosis factor receptor superfamily member 11a (tnfrsf11a), k3n and 245tg in tumor necrosis factor receptor superfamily member 11b (tnfrsf11b), a1330v in lrp5, i1062v in lrp6, and -1397-1396insgga in sost. for evaluation of treatment efficacy, bone mineral density (bmd) and biochemical markers of bone turnover were measured. one-year change in total hip bmd was associated with 34901ga in tnfrsf11a (p0.040), whereas, for lumbar spine bmd, the association was shown for -1397-1396insgga in sost (p0.015). c-terminal crosslinking telopeptides of type i collagen (ctx) concentrations showed significant association with -643ct single nucleotide polymorphism (snp) in tnfsf11 (p0.049) and 34694ct in tnfrsf11a (p0.022). no other association was found between 1-year change in bmds or biochemical markers and the studied snps.","we have shown that, in postmenopausal osteoporotic women treated with raloxifene, the efficacy of raloxifene treatment might be influenced by 34901ga in tnfrsf11a gene and -1397-1396insgga in the sost gene as well as -643ct in tnfsf11 gene and 34694ct in tnfrsf11a gene. however, these findings need additional functional and clinical confirmation for potential pharmacogenetic use in the future.",Medication
is polymyalgia rheumatica associated with extensor tendon tenosynovitis but not with synovitis of the hands : a magnetic resonance imaging study?,"to study with mri the hands of consecutive pmr patients, who were not selected on the basis of peripheral arthritis, with a correlation to clinical and laboratory findings. twenty-six hands of 15 pmr patients and 26 hands of 13 healthy controls were studied by extremity-dedicated mri for the presence of synovitis, tenosynovitis, soft-tissue oedema, bone marrow oedema and erosions. sixteen (61.6) of the 26 pmr hands and 4 (15.4) of the 26 control hands showed tenosynovitis (p 0.001). extensor tendon tenosynovitis was seen in 9 (34.6) of the 26 pmr hands, but in only 1 (3.8) control hand (p 0.002) and flexor tenosynovitis was seen in 12 (46.1) of the 26 pmr hands and in 4 (15.4) of the 26 control hands (p 0.03). all other features were similar in the two groups.","our data support the view that tenosynovitis, especially of the extensor tendons, is a frequent event in pmr, unrelated to clinical involvement of the hand. this finding is in agreement with the concept of pmr as a disease of extra-articular structures.",Diagnosis
do epigenetic changes in basal cell carcinoma affect shh and wnt signaling components?,"the genetic background of basal cell carcinoma (bcc) has been studied extensively, while its epigenetic makeup has received comparatively little attention. epigenetic alterations such as promoter hypermethylation silence tumor suppressor genes (tsg) in several malignancies. we sought to analyze the promoter methylation status of ten putative (tumor suppressor) genes that are associated with sonic hedgehog (shh), wnt signaling and (hair follicle) tumors in a large series of 112 bcc and 124 healthy control samples by methylation-specific pcr. gene promoters of shh (p 0.016), adenomatous polyposis coli (apc) (p 0.003), secreted frizzled-related protein 5 (sfrp5) (p 0.004) and ras association domain family 1a (rassf1a) (p 0.023) showed significantly more methylation in bcc versus normal skin. mrna levels of these four genes were reduced for apc and sfrp5 in bcc (n 6) vs normal skin (n 6). down regulation of shh, apc and rassf1a could be confirmed on protein level as well (p0.001 for all genes) by immunohistochemical staining. increased canonical wnt activity was visualized by -catenin staining, showing nuclear -catenin in only 28/101 (27.7) of bcc. absence of nuclear -catenin in some samples may be due to high levels of membranous e-cadherin (in 94.1 of the samples).","we provide evidence that promoter hypermethylation of key players within the shh and wnt pathways is frequent in bcc, consistent with their known constitutive activation in bcc. epigenetic gene silencing putatively contributes to bcc tumorigenesis, indicating new venues for treatment.",General
do paramedic interventions increase the rate of return of spontaneous circulation in out of hospital cardiac arrests?,"to determine whether paramedic interventions increased the rate of return of spontaneous circulation in the victims of out of hospital cardiac arrest. a retrospective analysis of 276 out of hospital cardiac arrests was made. data analysed included age, sex, presenting rhythm, ambulance response time, presence of a pulse at any point, interventions performed by the ambulance crews, and survival to discharge. 146 patients were treated by paramedics and 130 by technicians. there was no difference in the rate of return of spontaneous circulation or survival to discharge in patients presenting in ventricular fibrillation (vf). in non-vf arrests there was no increase in survival to discharge, but 15 of patients in non-vf arrests achieved a return of spontaneous circulation when treated by paramedics compared to none treated by technicians. there were no other significant differences in any of the variables assessed.","out of hospital cardiac arrests presenting in vf are managed equally well by paramedics and technicians. however, in non-vf arrests there is a significantly increased rate of return of spontaneous circulation in those patients attended by paramedics.",Treatment
do coated platelet levels correlate with bleed volume in patients with spontaneous intracerebral hemorrhage?,"coated platelets are produced on dual agonist stimulation with collagen and thrombin. these highly procoagulant platelets are critical to normal hemostasis, and an earlier study demonstrated decreased coated platelet production in patients with spontaneous intracerebral hemorrhage. we have expanded this observation to investigate if coated platelet levels correlate with bleed volume in spontaneous intracerebral hemorrhage. coated platelet levels and bleed volume were determined in 45 patients with a diagnosis of spontaneous intracerebral hemorrhage. there was an inverse relationship between coated platelet levels and bleed volume (r-0.38, p0.01).",these data support a link between decreased coated platelet synthesis and the severity of spontaneous intracerebral hemorrhage.,Symptoms
do strength and comprehensiveness of district school wellness policies predict policy implementation at the school level?,"in 2006, all local education agencies in the united states participating in federal school meal programs were required to establish school wellness policies. this study documented the strength and comprehensiveness of 1 state's written district policies using a coding tool, and tested whether these traits predicted school-level implementation and practices. school wellness policies from 151 connecticut districts were evaluated. school principal surveys were collected before and after the writing and expected implementation of wellness policies. sociodemographic variables were assessed for each district, including enrollment, population density, political climate, racial composition, and socioeconomic status. changes in school-level policy implementation before and after the federal wellness policy mandate were compared across districts by wellness policy strength; policies were compared based on district-level demographics. statewide, more complete implementation of nutrition and physical activity policies at the school level was reported after adoption of written policies. districts with stronger, more comprehensive policies were more successful in implementing them at the school level. some sociodemographic characteristics predicted the strength of wellness policies.",written school wellness policies have the potential to promote significant improvements in the school environment. future regulation of school wellness policies should focus on the importance of writing strong and comprehensive policies.,Prevention
is hiv an important risk factor for human papillomavirus types 16 and 18 seropositivity among sexually active men who have sex with men?,"the aim of this study was to investigate whether hiv infection is a main risk factor for human papillomavirus (hpv)-16 and hpv-18 seropositivity in men who have sex with men (msm), and what other risk factors are associated with hpv-16 and hpv-18 seropositivity in this population. men who have sex with men visiting a sexually transmitted infection (sti) clinic in amsterdam in 2008 to 2009 answered questions concerning demographics and sexual behavior. sera were tested for hpv antibodies to the major hpv capsid protein l1 by luminex-based multiplex serology. as it is known that site of exposure is associated with seropositivity, this analysis was restricted to msm who reported receptive anal sex during the preceding 6 months. using multivariable logistic regression, we examined whether hiv was associated with hpv serostatus. included in the study were 415 hiv-negative and 205 hiv-positive msm reporting receptive anal sex. median age of the study population was 39 years (interquartile range, 31-44). human papillomavirus seroprevalence differed significantly between hiv-negative and hiv-positive msm: 31 versus 65 (p 0.001) for hpv-16 and 28 versus 51 (p 0.001) for hpv-18. after adjusting for important risk factors hpv-16 (adjusted odds ratio, 2.80; 95 confidence interval, 1.75-4.49) and hpv-18 (adjusted odds ratio, 1.78; 95 confidence interval, 1.11-2.85), seropositivity was significantly more common in hiv-positive than in hiv-negative msm. we could not identify other consistent risk factors for hpv-16 and hpv-18 seropositivity.",hiv infection is an important risk factor for hpv-16 and hpv-18 seropositivity among msm reporting receptive anal sex in the preceding 6 months.,Prevention
does glucosamine inhibit il-1beta-induced nfkappab activation in human osteoarthritic chondrocytes?,"glucosamine sulfate (gs) is a commonly used drug for the treatment of osteoarthritis. the mechanism of the action of this drug does, however, remain to be elucidated. in human osteoarthritic chondrocytes (hoc) stimulated with a proinflammatory cytokine, we studied whether gs could modify the nfkappab activity and the expression of cox-2, a nfkappab-dependent gene. using hoc in culture stimulated with interleukin-1 beta (il-1beta), the effects of gs on nfkappab activation, nuclear translocation of nfkappab/rel family members, cox-1 and cox-2 expressions and syntheses and prostaglandin e2 (pge2) concentration were studied. gs significantly inhibited nfkappab activity in a dose-dependent manner, as well as the nuclear translocation of p50 and p65 proteins. furthermore, gs-preincubated il-1beta-stimulated hoc showed an increase in ikappabalpha in the cell cytoplasm in comparison with hoc incubated with il-1beta alone. gs also inhibited the gene expression and the protein synthesis of cox-2 induced by il-1beta, while no effect on cox-1 synthesis was seen. gs also inhibited the release of pge2 to conditioned media of hoc stimulated with il-1beta.",gs inhibits the synthesis of proinflammatory mediators in hoc stimulated with il-1beta through a nfkappab-dependent mechanism. our study further supports the role of gs as a symptom- and structure-modifying drug in the treatment of oa.,Medication
are two renal veins a contraindication for retroperitoneoscopic right-side donor nephrectomy?,"to evaluate the results of right-donor nephrectomy with kidneys having two or more renal veins. between september 2004 and august 2007 50 right-side donor nephrectomies were performed. eight donors had two or more renal veins; in seven patients multiple renal veins were an intraoperative finding, while in one case preoperative evaluation had revealed two renal veins. four-port retroperitoneoscopic donor nephrectomy was performed. an endo-ta stapler was used to control renal veins in all donors. donor nephrectomy was uncomplicated in all cases. two renal veins were present in seven patients, while one donor had four renal veins. mean operative time, blood loss, and warm ischemia time were 148.7 minutes, 86.8 ml, and 269 seconds, respectively. the mean nadir serum creatinine value was 0.98 mg.",retroperitoneoscopic donor nephrectomy on the right side with two or more renal veins is feasible and safe.,Medication
are patients with poor baseline walking capacity most likely to improve their functional status with multimodal prehabilitation?,"evidence suggests that multimodal prehabilitation programs comprising interventions directed at physical activity, nutrition, and anxiety coping can improve functional recovery after colorectal cancer operations; however, such programs may be more clinically meaningful and cost-effective if targeted to specific subgroups. this study aimed to estimate the extent to which patients with poor baseline functional capacity improve their functional capacity. data for 106 participants enrolled in a multimodal, prehabilitation program before colorectal operations were analyzed. low baseline functional capacity was defined as a 6-minute walking test distance (6mwd) of less than 400 m. participants were categorized as higher fitness (6mwd 400 m, n 70) or lower fitness (6mwd 400 m, n 36). changes in 6mwd over the preoperative period, and 4 weeks and 8 weeks after the operation were compared between groups. secondary outcomes included patient-reported physical activity and health status, postoperative complications, duration of hospital stay, and readmissions. less-fit patients were then compared with subjects in the rehabilitation arm of the original studies who had a baseline 6mwd 400 m. participants with lower baseline fitness had greater improvements in functional walking capacity with prehabilitation compared to patients with higher fitness (46.5 standard deviation 53.8 m vs 22.6 standard deviation 41.8 m, p .012). at 4 weeks postoperatively, patients with lower baseline fitness were more likely to be recovered to their baseline 6mwd than those with higher fitness. (74 vs 50, p .029). there were no differences in secondary outcome. less-fit patients had a greater improvement through all the preoperative period compared to the control group.",patients with lower baseline walking capacity are more likely to experience meaningful improvement in physical function from prehabilitation before and after a colorectal cancer operation.,Treatment
does lipopolysaccharide significantly influence the hepatic triglyceride metabolism in growing pigs?,"in the practical commercial pig farms, inflammation is a perennial problem, yet most of studies on inflammation are focused on immune response. actually, inflammation can induce body metabolism disorder which will finally influence animals' growth. in this study, we investigated the effect of acute inflammation on the triglyceride (tg) metabolism in the liver of growing pigs and the possible underlying mechanisms. twelve male growing pigs were randomly divided into two groups, a control group (received saline) and a lps group (intramuscular injected with 15 g/kg lps). six hours after lps injection, the pigs were euthanized and sampled. biochemical indexes, inflammation factors, lipid metabolism related parameters and mitochondrial function were evaluated. the relationship between glucocorticoid receptor (gr) and the key enzymes of de novo lipogenesis were also investigated by chromatin immunoprecipitation assay (chip). lps induced a serious inflammation in the liver of growing pigs proved by liver morphologic changes, the up-regulated plasma cortisol, tumor necrosis factor- (tnf-) content and gene expression of inflammation related genes in liver. for de novo lipogenesis, lps significantly decreased the gene expression of fatty acid synthase (fas), acetyl-coa carboxylase-1 (acc-1) and stearoyl-coa desaturase-1 (scd-1), and the protein expression of acc-1 and scd-1. for lipolysis, only the gene expression of adipose triglyceride lipase (atgl) was decreased. lps did nothing to the gene expression of hormone-sensitive lipase (hsl) and the lipolytic enzymes activities. for -oxidation, lps significantly increased the protein expression of cpt-1, but the gene expression of mitochondrial dna-encoded genes and the activities of mitochondrial complex iv and v demonstrated no obviously changes. furthermore, chip results showed that lps significantly decreased the level of gr binding to acc-1 promoter.","lps infection has a profound impact on hepatic tg metabolism. this impact is mainly demonstrated by the significantly deceased de novo lipogenesis, and gr may involve in its regulation.",Medication
is a fetal circle of willis associated with a decreased deep white matter lesion load?,to investigate the relationship between morphologic differences in the circle of willis and the presence and location of white matter lesions (wmls). two hundred forty-three consecutive patients with clinical manifestations of atherosclerotic disease underwent mri of the brain and mr angiography of the circle of willis. subjects with a fetal configuration of the circle of willis demonstrated a decreased load of small (p 0.01) and medium (p 0.01) deep wmls compared with subjects with a nonfetal configuration of the posterior part of the circle of willis.,a fetal configuration of the posterior part of the circle of willis may be an important protecting determinant in the etiology of white matter lesions.,Diagnosis
does heat shock protein a12b protect against sepsis-induced impairment in vascular endothelial permeability?,"as a common and life-threatening infectious syndrome, sepsis contributes significantly to morbidity and mortality in clinical settings. vascular endothelial injury and hyperpermeability play an important role in the development of sepsis-induced organ dysfunction. heat shock protein a12b (hspa12b) is one of the hsp70 superfamily members and is mainly expressed in vascular endothelial cells. the present study was performed to investigate the role of hspa12b in endothelial barrier dysfunction during sepsis. human umbilical vein endothelial cells (huvecs) were stimulated with 1 g/ml of lipopolysaccharide (lps) and harvested at 0, 3, 6, 9, 12, and 24 h. the messenger rna and protein levels of hspa12b were detected by real time-polymerase chain reaction and western blot. upregulation of hspa12b was induced by transfection of pires2-egfp plasmid carrying the hspa12b complementary dna. the in vitro effect of hspa12b overexpression on endothelial permeability was manifested by the transendothelial electrical resistance value, expression of the adhesion molecules ve-cadherin, and the level of permeability-related kinase myosin light chain, src, and cdc42. mice received cecal ligation and puncture surgery followed by nasal inhalation of nano-polymer-mediated sirna. lung endothelial permeability was assessed via intrajugular vein injection of evans blue 30 h after cecal ligation and puncture. after lps induction, the messenger rna and protein level of hspa12b in huvecs increased and peaked at 12 h, whereas they returned to the baseline level at 24 h. overexpression of hspa12b can reduce the permeability of huvec stimulated by lps in vitro, while increasing the expression of ve-cadherin, myosin light chain, and cdc42. on the other hand, downregulating the expression of hspa12b can significantly increase lung permeability in mice with sepsis-induced vascular injury.",hspa12b plays a protective role in vascular endothelial barrier dysfunction by preserving the endothelial permeability during sepsis.,Medication
does metformin regulate differentiation of bone marrow-derived endothelial progenitor cells via multiple mechanisms?,"the aim of this study was to investigate the effect of metformin on endothelial progenitor cells (epcs) differentiation and the possible mechanisms. epcs were treated with metformin and differentiation, migration and tube formation of epcs were evaluated. moreover, we also assessed the ampk-mtor-p70s6k pathway, ampk related autophagy pathway and enos-no pathway to explore the mechanisms. metformin treatment could significantly increase differentiation of epcs. on the mechanisms, increased level of ampkand enos phosphorylation, lc3 expression and no production, and decreased mtor, p70 s6k as well as tgf- expression were found in epcs. the ampk inhibitor compound c, atg5 knocking-down and enos inhibitor l-name could reverse the effect exerted by metformin.",our results here showed that metformin could regulate the differentiation of epcs. autophagy related pathway and ampk-enos-no pathway were involved in the mechanisms.,Medication
is cerebral autoregulation impaired in cardioinhibitory carotid sinus syndrome?,"to compare changes in cerebral autoregulation in response to controlled, lower body negative pressure-induced hypotension in patients with carotid sinus syndrome (css) and case controls. prospective case controlled study. secondary and tertiary referral falls and syncope service. 17 consecutive patients with css and 11 asymptomatic controls. hypotension insufficient to cause syncope induced by lower body negative pressure (minimum 30 mm hg fall in systolic blood pressure (sbp)) during concomitant transcranial doppler ultrasonography. cerebral autoregulation (systolic, diastolic and mean middle cerebral arterial blood flow velocities and cerebrovascular resistance) with continuous end-tidal carbon dioxide and haemodynamic monitoring. cerebral autoregulatory indices differed significantly between patients with css and controls. systolic, diastolic and middle cerebral arterial blood flow velocities were, respectively, 9.2 m/s (95 confidence interval (ci) 2.9 to 15.4 m/s), 4.7 m/s (95 ci 1.5 to 7.9 m/s) and 6.9 m/s (95 ci 2.5 to 11.4 m/s) slower in patients with css. cerebrovascular resistance was significantly greater in patients with css than in controls at sbp nadir and suction release; differences were 0.9 mm hg/m/s (95 ci 0.0 to 1.7 mm hg/m/s) and 0.8 mm hg/m/s (95 ci 0.0 to 1.7 mm hg/m/s), respectively. end-tidal carbon dioxide and systemic haemodynamic variables were similar for patients and controls at baseline and during lower body negative pressure.",cerebral autoregulation is altered in patients with css. this difference may have aetiological implications in the differential presentation with falls and drop attacks rather than syncope.,General
is biochemical investigation no substitute for clinical examination?,"toxic shock syndrome has been shown previously to be associated with hyperamylasaemia. however, serum amylase levels do not usually exceed three times upper limit of normal in these cases. we report a case of a young girl of 17 years who presented with upper abdominal pain, severe shock and raised serum amylase level of 3,898 u/l, giving an impression of severe acute pancreatitis. it was only after finding a tampon in her vagina, and subsequently growing staphylococcus aureus in her blood cultures, did the diagnosis of toxic shock syndrome become apparent. she recovered fully with supportive treatment and appropriate antibiotics.","toxic shock syndrome with such a high level of serum amylase has not been previously reported. this case exemplifies the importance of repeated clinical evaluation of patients in this era of multiple investigations, and not simply relying on biochemical values for diagnosis.",Medication
is inadequate dietary intake but not renal tubular acidosis associated with bone demineralization in primary biliary cirrhosis?,"metabolic bone disease associated with primary biliary cirrhosis (pbc) is inadequately characterized. renal tubular acidosis (rta) may lead to bone loss through chronic mobilization of skeletal calcium salts to buffer increased acid load. to evaluate the prevalence of rta in pbc and establish the relationships among bone mineral density (bmd), renal function and nutritional status. we enrolled 69 female patients with compensated pbc and 35 control patients with chronic hepatitis c. rta was searched in all patients, and 24-h dietary recalls were collected at enrolment. bmd was measured by dual-energy x-ray absorptiometry at the femur neck, lumbar spine and radius ultradistalis sites. no patients received a diagnosis of rta. bmd values (z-scores) showed only little deviation from normal population with no difference between pbc and controls. osteopoenic pbc patients (t-score 1) showed significantly lower daily phosphorus intake median: 672 (288-1374) vs. 921 (253-1923) mg/day; p 0.037, with a trend towards lower caloric intake than their nonosteopoenic counterparts.",renal tubular acidosis is uncommon in compensated pbc. cholestasis is not associated with an increased risk of bone demineralization. inadequate dietary intake may be a preventable factor contributing to bone loss in pbc.,Prevention
are umbilical sp-selectin levels different in preeclamptic pregnancies with intrauterine normal growth and growth restricted fetus?,"the aim of this study was the analysis of the umbilical cord serum sp-selectin levels in pregnancies complicated by severe preeclampsia with and without intrauterine growth restriction and in normotensive pregnancies. the study was carried out on 18 patients with singleton pregnancies complicated by severe preeclampsia with appropriate-for-gestational-age weight infants (group p) and 18 pregnant patients with severe preeclampsia complicated by intrauterine fetal growth restriction (iugr) (group pi). the control group consisted of 34 patients with singleton uncomplicated pregnancies (group c). umbilical serum sp-selectin concentrations were estimated using a sandwich elisa assay according to the manufacturer's instruction (elisa kit bender medsystems vienna, austria). our study revealed different concentrations of soluble p-selectin in the umbilical cord in our both studied groups of preeclamptic women with and without iugr. the umbilical cord levels of sp-selectin were decreased in the group with preeclampsia complicated by iugr and increased in the preeclamptic women with the normal intrauterine fetal growth. the mean values of umbilical sp-selectin were 839.008 625.703 ng/ml in group p, 275.873 174.339 ng/ml in group pi, and 288.719 199.039 ng/ml in the control group, respectively.","higher levels of the umbilical sp-selectin may confirm the presence of platelet and endothelial cell activation and confirm a hypercoagulant state in preeclamptic disorder, especially in preeclampsia without iugr.",General
does 3-hydroxybutyrate inhibit noradrenaline-induced thermogenesis in lean but not in obese zucker rats?,"to determine the effect of 3-hydroxybutyrate (3ohb) on the thermogenic response to noradrenaline (na) in lean and genetically obese zucker fa/fa rats. rats were infused with 18.7 nmol x kg(-1) x min(-1) of na, supplemented, for 15 min, with 66.7 micromol x kg(-1) x min(-1) of r-3-hydroxybutyrate (3ohb). pentobarbital-anaesthetized lean and obese zucker rats. aortic and interscapular brown adipose tissue (bat) temperature; plasma na, 3ohb, glucose and insulin levels during infusion. the na-induced increase in aortic and bat temperature was more marked in lean than in obese rats. in lean rats, the rise was arrested by 3ohb; but in obese rats 3ohb had no effect. infusion of saline, glucose or 3ohb in the absence of na did not induce changes in either temperature. na infusion resulted in a rapid increase in plasma na to 45-50 nm in both groups; this plateau was maintained for up to 60 min. the presence of 3ohb decreased the plasma na of lean rats, but did not affect the plasma na of the obese rats. blood 3ohb rose to 1.2 mm during 3ohb infusion in both groups, and decreased on cessation of infusion. blood glucose levels increased with na infusion in both groups; the presence of high 3ohb levels decreased glucose levels only in lean rats.","the changes in na levels induced by 3ohb may help explain the effects observed on temperature and glucose. the defective thermogenic system of obese rats cannot be modulated by 3ohb, unlike thermogenesis in lean rats, on which 3ohb has a marked effect.",Medication
are interleukin-10 ( -592 c/a ) and interleukin-12b ( 16974 a/c ) gene polymorphisms and the interleukin-10 ata haplotype associated with periodontitis in a taiwanese population?,"single nucleotide polymorphisms are assumed to be associated with the differential production of cytokines. we evaluated gene polymorphisms of interleukin-10 (-592ca, -819ct and -1082ga) and interleukin-12b (16974) in patients with chronic periodontitis (n 145) and generalized aggressive periodontitis (n 65) in comparison with healthy controls (n 126). gene promoter polymorphisms were analyzed by polymerase chain reaction with sequence-specific primers. genotype and allele frequencies were analyzed using the chi-square test and logistic regression analysis. the interleukin-10 -592 polymorphism showed significant differences among the three groups (p 0.0330). the genotype frequencies of the -592 locus between the chronic periodontitis and healthy control groups were significantly different (ac vs. aa: odds ratio 0.33). the combination ata/ata seemed to be associated with susceptibility to generalized aggressive periodontitis (p 0.0276). patients with the composite ata/acc were less likely to develop chronic periodontitis (p 0.0248). the cc genotype of interleukin-12b (16974) was related to chronic periodontitis (cc vs. aa, p 0.0211; cc vs. aaac, p 0.0187). the ac heterozygosity of interleukin-12b was significantly lower in chronic periodontitis vs. healthy controls (p 0.0500).","the interleukin-10 gene polymorphism at position -592ca may be associated with a lower risk for development of chronic periodontitis. the interleukin-10 haplotype ata is associated with generalized aggressive periodontitis. on the other hand, interleukin-12b genetic variants at position 16974 are associated with susceptibility to chronic periodontitis.",Diagnosis
does use of predefined biochemical admission profiles reduce the number of tests or total cost : a randomized-controlled pilot study?,"the objective of this pilot study was to evaluate whether the use of predefined biochemical profiles as an alternative to individually ordered blood tests by the treating physicians resulted in fewer tests or a lower total cost. this was a randomized-controlled trial of 191 adult patients admitted to a medical admission unit. upon admission, the patients were randomized to have their blood tests determined by either using a predefined profile (used routinely and designed by the department head) or ordered individually by the treating physician. all patients were initially assessed by junior physicians. we compared the number of tests, estimated total cost, and length of stay. data are presented as median (interquartile range). differences were compared using the wilcoxon rank-sum test and fishers' exact test. ninety-two patients were men, median age 65 years. patients randomized to the use of the predefined profile had median 17 (14-22) blood tests drawn and patients randomized to physician discretion had median 17 (12-21) tests drawn (p0.3). the median total cost of tests in the profile group was 618 dkk (493-803) and the cost in the physician group was 564 dkk (434-812) (p0.19). length of stay in the profile group was a median of 4 days (2-6 days) and 2 days (2-6 days) in the physician group (p0.08).","the use of a predefined blood test panel did not significantly affect the number of tests, total cost, or length of stay for acutely admitted medical patients compared with tests ordered at the discretion of the treating physician.",Treatment
does mekk1-mkk4-jnk-ap1 pathway negatively regulate rgs4 expression in colonic smooth muscle cells?,"regulator of g-protein signaling 4 (rgs4) plays an important role in regulating smooth muscle contraction, cardiac development, neural plasticity and psychiatric disorder. however, the underlying regulatory mechanisms remain elusive. our recent studies have shown that upregulation of rgs4 by interleukin (il)-1 is mediated by the activation of nfb signaling and modulated by extracellular signal-regulated kinases, p38 mitogen-activated protein kinase, and phosphoinositide-3 kinase. here we investigate the effect of the c-jun n-terminal kinase (jnk) pathway on rgs4 expression in rabbit colonic smooth muscle cells. cultured cells at first passage were treated with or without il-1 (10 ng/ml) in the presence or absence of the selective jnk inhibitor (sp600125) or jnk small hairpin rna (shrna). the expression levels of rgs4 mrna and protein were determined by real-time rt-pcr and western blot respectively. sp600125 or jnk shrna increased rgs4 expression in the absence or presence of il-1 stimulation. overexpression of mekk1, the key upstream kinase of jnk, inhibited rgs4 expression, which was reversed by co-expression of jnk shrna or dominant-negative mutants for mkk4 or jnk. both constitutive and inducible upregulation of rgs4 expression by sp600125 was significantly inhibited by pretreatment with the transcription inhibitor, actinomycin d. dual reporter assay showed that pretreatment with sp600125 sensitized the promoter activity of rgs4 in response to il-1. mutation of the ap1-binding site within rgs4 promoter increased the promoter activity. western blot analysis confirmed that il-1 treatment increased the phosphorylation of jnk, atf-2 and c-jun. gel shift and chromatin immunoprecipitation assays validated that il-1 increased the in vitro and ex vivo binding activities of ap1 within rabbit rgs4 promoter.",activation of mekk1-mkk4-jnk-ap1 signal pathway plays a tonic inhibitory role in regulating rgs4 transcription in rabbit colonic smooth muscle cells. this negative regulation may aid in maintaining the transient level of rgs4 expression.,Medication
does tumour necrosis factor-alpha affect blood-brain barrier permeability and tight junction-associated occludin in acute liver failure?,"cerebral oedema leading to cerebral herniation is a major cause of death during acute liver failure (alf), but the underlying mechanism is not clear. we investigated the role of tumour necrosis factor (tnf)-alpha in changing the permeability of the blood-brain barrier (bbb) during alf. alf animal models were generated by administering d-galactosamine (galn) and lipopolysaccharide, or galn and tnf-alpha. alf induction was blocked by first administering anti-tnf-alpha-igg or anti-tnf-alpha-r1. we investigated the bbb permeability with evans blue staining, and the structure with electron microscopy. bbb permeability increased in alf mice and correlated with elevated serum tnf-alpha levels. no vascular endothelial cell (ec) apoptosis was detected, but electron microscopy of cells from human and mouse alf tissues revealed tight junction (tj) disruptions and ec shrinkage, as well as increased vesicles and vacuoles. in addition, the expression of the tj-associated protein occludin was significantly decreased in both alf mice and patients, although the expression of occludin mrna did not change. changes in bbb permeability, brain tissue ultrastructure and occludin expression in alf-induced mice could be prevented by prophylaxis treatment with either antibody to tnf-alpha-igg or antibody to tnf-alpha-r1.","our results suggest that tnf-alpha plays a critical role in the development of brain oedema in alf, and that both vasogenic and cytotoxic mechanisms may be involved. increased bbb permeability may be because of the disruption of tjs, and loss of the tj-associated protein occludin.",Prevention
does a new color vep procedure disclose asymptomatic visual impairments in optic neuritis and glaucoma suspects?,"to evaluate the reliability of visual evoked potentials obtained with a set of multiple chromatic and achromatic patterns (c-veps) in differentiating asymptomatic perifoveal retinal impairment from central conduction impairment. we propose a set of colored pattern stimuli that allows relatively differential activation of the magnocellular and parvocellular pathways. the system runs on a standard pentium pc with peripherals that present stimuli and collect, analyze and print data. p1 latencies of c-veps obtained with achromatic (black/white) and chromatic (blue/black and red/black isocontrast) checkerboards were evaluated in normal subjects and patients with subclinical retinal impairment (glaucoma suspects) or mild neural conduction impairment (optic neuritis), none of whom had subjective visual defects. the procedure evoked robust cortical signals and statistically distinguished the 3 groups of subjects. the achromatic and chromatic stimuli used distinguished controls from glaucoma suspects and patients with optic neuritis. glaucoma suspects had greater impairment of c-veps to blue/black checkerboards whereas patients with optic neuritis had greater impairment of responses to red/black stimuli.","our data suggest that chromatic patterns (color/ black, red and blue), that may activate the parvocellular and magnocellular systems differentially but not selectively, can distinguish between mild perifoveal or foveal conduction impairment. they have the additional advantage of evoking large, stable responses across all the subjects.",Treatment
does attaching unit cost to australia 's national survey of mental health and wellbeing?,"in mental health, policy-makers and planners are increasingly being asked to set priorities. this means that health economists, health services researchers and clinical investigators are being called upon to work together to define and measure costs. typically, these researchers take available service utilisation data and convert them to costs, using a range of assumptions. there are inefficiencies, as individual groups of researchers frequently repeat essentially similar exercises in achieving this end. there are clearly areas where shared or common investment in the development of statistical software syntax, analytical frameworks and other resources could maximise the use of data. this paper reports on an australian project in which we calculated unit costs for mental health admissions and community encounters. in reporting on these calculations, our purpose is to make the data and the resources associated with them publicly available to researchers interested in conducting economic analyses, and allow them to copy, distribute and modify them, providing that all copies and modifications are available under the same terms and conditions (i.e., in accordance with the 'copyleft' principle). within this context, the objectives of the paper are to: (i) introduce the 'copyleft' principle; (ii) provide an overview of the methodology we employed to derive the unit costs; (iii) present the unit costs themselves; and (iv) examine the total and mean costs for a range of single and comorbid conditions, as an example of the kind of question that the unit cost data can be used to address. we took relevant data from the australian national survey of mental health and wellbeing (nsmhwb), and developed a set of unit costs for inpatient and community encounters. we then examined total and mean costs for a range of single and comorbid conditions. we present the unit costs for mental health admissions and mental health community contacts. our example, which explored the association between comorbidity and total and mean costs, suggested that comorbidly occurring conditions cost more than conditions which occur on their own.","our unit costs, and the materials associated with them, have been published in a freely available form governed by a provision termed 'copyleft'. they provide a valuable resource for researchers wanting to explore economic questions in mental health.",Prevention
does brain state-dependent transcranial magnetic closed-loop stimulation controlled by sensorimotor desynchronization induce robust increase of corticospinal excitability?,"desynchronization of sensorimotor rhythmic activity increases instantaneous corticospinal excitability, as indexed by amplitudes of motor-evoked potentials (mep) elicited by transcranial magnetic stimulation (tms). the accumulative effect of cortical stimulation in conjunction with sensorimotor desynchronization is, however, unclear. the aim of this study was to investigate the effects of repetitive pairing event-related desynchronization (erd) with tms of the precentral gyrus on corticospinal excitability. closed-loop single-pulse tms was controlled by beta-band (16-22 hz) erd during motor-imagery of finger extension and applied within a brain-computer interface environment in eleven healthy subjects. the same number and pattern of stimuli were applied in a control group of eleven subjects during rest, i.e. independent of erd. to probe for plasticity resistant to depotentiation, stimulation protocols were followed by a depotentiation task. brain state-dependent application of approximately 300 tms pulses during beta-erd resulted in a significant increase of corticospinal excitability. by contrast, the identical stimulation pattern applied independent of beta-erd in the control experiment resulted in a decrease of corticospinal excitability. these effects persisted beyond the period of stimulation and the depotentiation task.",these results could be instrumental in developing new therapeutic approaches such as the application of closed-loop stimulation in the context of neurorehabilitation.,General
do clinical observe of the middle ear malformation ?,"to analyze the diagnosis and therapeutic effect of the middle ear abnormalities. 65 ears from 1967 to 1996 were reviewed. the degrees of the ossicular abnormalities were analyzed, operative effect were valued. in the 65 ears, incus abnormalities was 57 ears (87.7), stapes was 55 ears (84.6), mixed malformation was dominant. 47 ears were operated with ossicular chain reconstruction. 44 ears (93.6) had hearing improvement, 32 ears (68.1) had obviously improvement ( 20 db). they were followed up over one year, 44 ears had steadily hearing and had not any complications.","if diagnosis and interference were all proper, operation would obtain good result.",Treatment
are cardioprotective properties of sevoflurane in patients undergoing coronary surgery with cardiopulmonary bypass related to the modalities of its administration?,"experimental studies have related the cardioprotective effects of sevoflurane both to preconditioning properties and to beneficial effects during reperfusion. in clinical studies, the cardioprotective effects of volatile agents seem more important when administered throughout the procedure than when used only in the preconditioning period. the authors hypothesized that the cardioprotective effects of sevoflurane observed in patients undergoing coronary surgery with cardiopulmonary bypass are related to timing and duration of its administration. elective coronary surgery patients were randomly assigned to four different anesthetic protocols (n 50 each). in a first group, patients received a propofol based intravenous regimen (propofol group). in a second group, propofol was replaced by sevoflurane from sternotomy until the start of cardiopulmonary bypass (sevo pre group). in a third group, propofol was replaced by sevoflurane after completion of the coronary anastomoses (sevo post group). in a fourth group, propofol was administered until sternotomy and then replaced by sevoflurane for the remaining of the operation (sevo all group). postoperative concentrations of cardiac troponin i were followed during 48 h. cardiac function was assessed perioperatively and during 24 h postoperatively. postoperative troponin i concentrations in the sevo all group were lower than in the propofol group. stroke volume decreased transiently after cardiopulmonary bypass in the propofol group but remained unchanged throughout in the sevo all group. in the sevo pre and sevo post groups, stroke volume also decreased after cardiopulmonary bypass but returned earlier to baseline values than in the propofol group. duration of stay in the intensive care unit was lower in the sevo all group than in the propofol group.","in patients undergoing coronary artery surgery with cardiopulmonary bypass, the cardioprotective effects of sevoflurane were clinically most apparent when it was administered throughout the operation.",Treatment
does bactericidal/permeability-increasing protein preserve leukocyte functions after major liver resection?,"to analyze postoperative leukocyte functions in patients undergoing hemihepatectomy, and to assess the effect of treatment with the endotoxin-neutralizing agent bactericidal/permeability-increasing protein (rbpi21). extensive liver resection is associated with a high incidence of infectious complications. because elimination of pathogenic microorganisms occurs mainly by leukocytes, this increased rate of infections is most likely due to an impaired function of these cells. endotoxin, translocated from the gut into the systemic circulation as a result of increased gut permeability and reduced hepatic clearance function after major liver resection, may play an important role in the impairment of posthepatectomy leukocyte function. to investigate whether hemihepatectomy results in impaired leukocyte functions and to determine the role of endotoxin in this process, leukocyte oxidative burst and leukocyte antigen expression were studied in three groups of patients: patients undergoing a hemihepatectomy and receiving rbpi21 treatment, patients undergoing hemihepatectomy and receiving placebo, and as an extra control group patients undergoing other major abdominal surgeries. blood samples were collected before surgery, 2 hours after surgery, and at days 1, 2, 5, and 7. phorbol myristate acetate-stimulated oxidative burst was measured using dihydrorhodamine, and leukocyte surface expression of the antigens cd11b, cd16, and cd14 was investigated by indirect immunofluorescence. both oxidative burst and membrane surface expression were quantified by flow cytometry. an indication of the antiendotoxin effect of rbpi21 treatment was provided by assessment of plasma lipopolysaccharide binding protein (lbp) levels by enzyme-linked immunosorbent assay. the oxidative burst in the hemihepatectomized patients receiving placebo and the controls increased 2 hours after surgery, whereas it decreased in the rbpi21-treated patients, resulting in significant differences between the groups. on day 1, neutrophil cd11b expression and monocyte cd14 expression in the rbpi21-treated patients and controls were significantly lower than in the placebo group. at 2 hours, cd16 expression in the placebo-treated patients was significantly higher than in the rbpi21-treated patients and controls. on day 5 and day 7, plasma lbp levels were significantly higher in the placebo-treated patients compared with the rbpi21-treated patients.","the results of this study show that patients undergoing major liver resection have an increased activation of leukocytes compared with those undergoing other major abdominal surgery. this enhanced activation may contribute to the increased risk of infection in these patients. administration of the endotoxin-neutralizing agent rbpi21 to hemihepatectomy patients was shown to reduce plasma lbp levels, to preserve leukocyte functions partially, and to reduce leukocyte activation to the level of other, nonhepatic abdominal surgery.",Treatment
are limited professional guidance and literature available to guide the safe use of neuromuscular block in infants?,"neuromuscular blocking agents (nmbas) are used in a range of critical illnesses in neonates and infants, despite a lack of guidelines and professional standards. this study reviewed the current evidence base and ascertained uk practice regarding the continuous use of these agents in this age range. we reviewed the literature and carried out a telephone questionnaire of all tertiary units in england and specialist children's hospital neonatal units in the uk. no best practice guidelines or general consensus statements were found, and the only randomised trial to feature an nmba protocol expressed concerns about its use in such young babies. of the 56 units contacted, 54 (96.4) shared information. only three of the 56 (5.4) used intermittent boluses of nmbas, 91.1 used nmba infusions, 11 (19.6) routinely used regular neuromuscular blocker pause to assess depth, and only one (1.8) used peripheral nerve stimulation monitoring. all the units carried out clinical assessments, but only one (1.8) had a written protocol.","there is a paucity of literature and professional standards to guide the safe use of nmbas in infants. of the 54 units who participated in the survey, only one had a protocol for using nmbas in babies.",Medication
does overexpression of human decoy receptor 3 in mice result in a systemic lupus erythematosus-like syndrome?,"decoy receptor 3 (dcr3), a tumor necrosis factor receptor family member, is a secreted protein that can enhance cell survival by interfering with multiple apoptosis pathways. this study was undertaken to investigate the role of dcr3 in the pathogenesis of autoimmune disease. we generated transgenic mice with actin promoter-driven expression of human dcr3 and investigated the development of autoimmune disease in these mice. t cell immune responses were compromised in young dcr3-transgenic mice. beyond 5-6 months of age, transgenic mice developed a systemic lupus erythematosus (sle)-like syndrome, with numerous features of the disease. they produced autoantibodies against double-stranded dna. their kidneys showed pathologic changes indicative of glomerular nephritis and igg and c3 deposition, and proteinuria, leukocyturia, and hematuria, were evident. aged transgenic mice also developed skin lesions and lymphocyte infiltration in the liver, and exhibited leukopenia, anemia, and thrombocytopenia. the sle-like syndrome penetrance in dcr3-transgenic mice was sex associated, occurring in approximately 60 of females versus 20 of males. exogenous recombinant dcr3 or endogenous dcr3 produced by transgenic t cells effectively protected t cells against activation-induced apoptosis in vitro. probably as a consequence of this, cd4 cells with a phenotype of previous activation were increased in the peripheral blood of transgenic mice beyond 6 months of age.",these results show that dcr3 overexpression could lead to an sle-like syndrome in mice.,Medication
does cystamine ameliorate ventricular hypertrophy associated with modulation of il-6-mediated signaling in lupus-prone mice?,"the aim of this study is to investigate the protective effects of cystamine on lupus-associated cardiac hypertrophy. balb/c and lupus-prone nzb/w-f1 mice were individually randomized into sham group (saline, n16) and cystamine group (n16). mice received saline or cystamine (100 mmol in 100 l saline) by daily intraperitoneal injection for 2 consecutive weeks. morphological, histological, and biochemical alterations were investigated. cystamine decreased both left ventricular (lv) mass and lv mass/tissue-to-blood ratio (tbr) in nzb/w-f1 mice (p0.05), whereas slight effects were observed in balb/c mice. moreover, cystamine reduced levels of atrial natriuretic peptide (anp), c-reactive protein (crp), heart type-fatty acid binding protein (h-fabp), creatine kinase-mb (ck-mb) and il-6 in lv tissues of nzb/w-f1 mice (p0.05). additionally, in lv tissues of nzb/w-f1 mice, suppression of hypertrophic signaling mediated by il-6 in response to administration of cystamine was revealed, including phosphorylation of mek5, erk5, c-jun n-terminal kinase (jnk) and p38 mitogen-activated protein kinase (p38) (p0.05).",cystamine alleviated lv hypertrophy in nzb/w-f1 mice as a result of decrease in hypertrophic mediators and suppression of il-6 mediated hypertrophic signaling.,Medication
"is risk for premenstrual dysphoric disorder associated with genetic variation in esr1 , the estrogen receptor alpha gene?","premenstrual dysphoric disorder (pmdd) is a heritable mood disorder that is triggered by gonadal steroids during the luteal phase in susceptible women. we performed haplotype analyses of estrogen receptors alpha and beta (esr1 and esr2) in 91 women with prospectively confirmed pmdd and 56 control subjects to investigate possible sources of the genetic susceptibility to affective dysregulation induced by normal levels of gonadal steroids. we also examined associations with the valine (val)158methionine (met) single nucleotide polymorphism (snp) of the gene for catechol-o-methyltransferase (comt), an enzyme involved in estrogen metabolism and prefrontal cortical activation. four snps in intron 4 of esr1 showed significantly different genotype and allele distributions between patients and control subjects. significant case-control differences were seen in sliding-window analyses of two-, three-, and four-marker haplotypes but only in those haplotypes containing snps in intron 4 that were positive in the single-locus analysis. no significant associations were observed with esr2 or with the comt val158met polymorphism, although the significant associations with esr1 were observed only in those with the val/val genotype.",these are the first positive (albeit preliminary) genetic findings in this reproductive endocrine-related mood disorder and involve the receptor for a hormone that is pathogenically relevant.,Medication
does olanzapine enhance cognition in non-agitated and non-psychotic patients with mild to moderate alzheimer 's dementia?,"this was an exploratory study of olanzapine as potential treatment for improvement in cognition in patients with alzheimer's disease without prominent psychobehavioral symptoms. non-psychotic/non-agitated patients (n 268) with alzheimer's disease, who had baseline mini-mental state examination (mmse) scores of 14-26 were randomized to treatment with olanzapine (2.5 to 7.5 mg/d) or placebo for 26 weeks. the primary objectives were to determine if treatment with olanzapine improved cognition as indexed by the alzheimer's disease assessment scale for cognition (adas-cog) and the clinician's interview-based impression of change (cibic) after 26 weeks of therapy. patients treated with olanzapine vs placebo experienced significant worsening adas-cog scores at weeks 12 (p 0.03) and 26 (p 0.004). changes in cibic scores were not significantly different between treatment groups at either assessment. a post hoc analysis revealed that olanzapine-treated patients with more cognitive impairment at baseline (mmse scores of 14-18) (n 35) experienced significantly greater deterioration in adas-cog performance than patients in the placebo group (n 24; p 0.001); whereas in patients with less cognitive impairment (n 78, baseline mmse scores of 23-26) between-group adas-cog changes were not significant.",in this 26-week study non-psychotic/non-agitated patients with alzheimer's disease treated with olanzapine experienced significant worsening of cognition as compared to placebo.,Treatment
does ultra-sensitive molecular mri of vascular cell adhesion molecule-1 reveal a dynamic inflammatory penumbra after strokes?,"our aim was to assess the spatiotemporal evolution of the cerebrovascular inflammation occurring after ischemic and hemorrhagic strokes using a recently developed, fast, and ultra-sensitive molecular mri method. we first assessed longitudinally the cerebrovascular inflammation triggered by collagenase-induced hemorrhage and by permanent/transient middle cerebral artery occlusion in mice, using mri after injection of microparticles of iron oxide targeted to vascular cell adhesion molecule-1 (mpios-vcam-1). thereafter, we used this method to study the anti-inflammatory effects of celecoxib, atorvastatin, and dipyridamole after stroke. using multiparametric mri, we demonstrated that the level and the kinetics of cerebrovascular vcam-1 expression depend on several parameters, including stroke pathogenesis, the natural history of the disease, and the administration of inflammation-modulating drugs. interestingly, in transient middle cerebral artery occlusion and intracranial hemorrhage models, vcam-1 expression was maximal at 24 hours and almost returned to baseline 5 days after stroke onset. in contrast, after permanent middle cerebral artery occlusion, vcam-1 overexpression was sustained between 24 hours and 5 days, and was particularly significant in the peri-infarct areas. our results suggest that these perilesional areas expressing vcam-1 constitute an inflammatory penumbra that is recruited by the ischemic core during the subacute phase. using mpios-vcam-1-enhanced imaging, we also provided evidence that celecoxib and atorvastatin (but not dipyridamole) alleviate vcam-1 overexpression after stroke and prevent formation of the inflammatory penumbra.","mpios-vcam-1-enhanced imaging seems to be promising in the detection of individuals presenting with severe cerebrovascular responses after stroke, which could therefore benefit from anti-inflammatory treatments.",Diagnosis
do the influence of a sports drink on the postexercise metabolism of elite athletes as investigated by nmr-based metabolomics?,"the aim of this study is to evaluate the systemic effects of an isotonic sports drink on the metabolic status of athletes of the italian olympic rowing team during recovery after strenuous and prolonged physical exercise by means of nuclear magnetic resonance (nmr)-based metabolomics analysis on plasma and urine. forty-four male athletes of the italian olympic rowing team were enrolled in a double-blind crossover study. all subjects underwent 2 evaluations at 1-week intervals. the evaluation was performed on a rowing ergometer after strenuous physical exercise to produce a state of dehydration. afterward, the athletes were rehydrated either with a green tea-based carbohydrate-hydroelectrolyte drink or with oligomineral water. three blood samples were drawn for each subject: at rest, after the exercise, and following rehydratation, while 2 urine samples were collected: at rest and after the rehydratation period. biofluid samples were analyzed by high-resolution (1)h nmr metabolic profiling combined with multilevel simultaneous data-analysis (msca) and partial-least squares-discriminant analysis (pls-da). the between-subject variations, as evaluated by msca, reflected the variations of lactate levels induced by the physical exercise. analysis of the within-individual variance using multilevel pls-da models of plasma and urine metabolic profiles showed an effect of the green tea-based sports drink on glucose, citrate, and lactate levels in plasma and on acetone, 3-oh-butyrate, and lactate levels in urine. the increase of caffeine and hippuric acid levels in urine indicated the absorption of green tea extract components.",nmr-based metabolomics allowed the complex effects of a green tea extract-based carbohydrate/hydroelectrolyte beverage on the energy metabolism of athletes during recovery by postexercise rehydration to be evaluated.,Prevention
is immunohistochemical expression of phospho-mtor associated with poor prognosis in patients with gallbladder adenocarcinoma?,"advanced gallbladder carcinoma (gbc) is a highly fatal disease with poor prognosis and few therapeutic alternatives. the mammalian target of rapamycin (mtor) is a serine/threonine kinase that plays a central role in cell growth and homeostasis. its regulation is frequently altered in various tumors and is an attractive target for cancer therapy; however, its status in gbc remains unclear. to characterize immunohistochemical expression and prognostic significance of phospho-mtor in advanced gallbladder carcinoma. phospho-mtor expression was examined by immunohistochemistry in tissue microarrays containing 128 advanced gbcs and 99 cases of chronic cholecystitis, which were divided into 2 groups according to the presence or absence of metaplasia. to evaluate the association of the level of phospho-mtor expression with clinical variables and patient survival, the advanced gbcs were classified as having low or high expression. statistical analysis was performed by using a significance level of p .05, and kaplan-meier curves were constructed for survival analysis. immunostaining for phospho-mtor was positive in 82 of 128 tumors (64.1) and in 24 of chronic cholecystitis cases (16 nonmetaplasia and 32 with metaplasia) (p .001). survival analysis indicated that a high phospho-mtor immunohistochemical expression was associated with poorer prognosis in patients with advanced gbc (p .02).","metaplasia is a common finding in chronic cholecystitis and is considered a precursor lesion of dysplasia. our results suggest that the activation of mtor occurs very early during the development of gbc, contributing to the carcinogenesis process. phospho-mtor expression is correlated with poor survival, supporting the potential of mtor for targeted therapy.",Diagnosis
is the ala45thr polymorphism of neurod1 associated with type 1 diabetes in brazilian women?,"neurod1 encodes a transcription factor expressed in the endocrine pancreas, and involved in beta-cell development, function and mechanisms of apoptosis. in this study, we investigated the association of a frequent polymorphism in exon 2 of neurod1 (g a; ala45thr) with type 1 diabetes in brazilian subjects. a population/association study comprising 246 unrelated type 1 diabetic and 275 nondiabetic white brazilian subjects. the ala45thr variant was genotyped by a pcr-rflp method. the frequency of the thr allele was significantly higher in patients with type 1 diabetes than in controls (42.3 vs 35.3, p0.02). stratification by gender showed that homozygosity for the thr allele was associated with type 1 diabetes in women with odds ratio of 3.66 (95 c.i. 1.43-10.11, p0.009) as compared to homozygosity for the ala allele. this effect was not observed in men.",we found a gender-specific association of the ala45thr variant of neurod1 with type 1 diabetes in brazilian women. our results suggest that gender as well as ethnicity might modulate the association of neurod1 with type 1 diabetes.,General
does vampire bat salivary plasminogen activator ( desmoteplase ) inhibit tissue-type plasminogen activator-induced potentiation of excitotoxic injury?,"in contrast to tissue-type plasminogen activator (tpa), vampire bat (desmodus rotundus) salivary plasminogen activator (desmoteplase dspa) does not promote excitotoxic injury when injected directly into the brain. we have compared the excitotoxic effects of intravenously delivered tpa and dspa and determined whether dspa can antagonize the neurotoxic and calcium enhancing effects of tpa. the brain striatal region of wild-type c57 black 6 mice was stereotaxically injected with n-methyl-d-aspartate (nmda); 24 hour later, mice received an intravenous injection of tpa or dspa (10 mg/kg) and lesion size was assessed after 24 hours. cell death and calcium mobilization studies were performed using cultures of primary murine cortical neurons. nmda-mediated injury was increased after intravenous administration of tpa, whereas no additional toxicity was seen after administration of dspa. unlike dspa, tpa enhanced nmda-induced cell death and the nmda-mediated increase in intracellular calcium levels in vitro. moreover, the enhancing effects of tpa were blocked by dspa.","intravenous administration of tpa promotes excitotoxic injury, raising the possibility that leakage of tpa from the vasculature into the parenchyma contributes to brain damage. the lack of such toxicity by dspa further encourages its use as a thrombolytic agent in the treatment of ischemic stroke.",Medication
is ct hypotension complex ( shock bowel ) always due to traumatic hypovolemic shock?,the purpose of our study was to review the clinical and ct findings in a substantial series of 41 patients with the shock bowel sign to determine if there is an association between shock bowel (and other ct signs of hypotension) and conditions other than post-traumatic hypovolemic shock.,"the shock bowel sign and the ct hypotension complex are frequently associated with hypotension from causes other than trauma-induced hypovolemic shock, such as severe head or spine injury, cardiac arrest, septic shock, bacterial endocarditis, and diabetic ketoacidosis. other elements of the ct hypotension complex such as flattening of the inferior vena cava and aorta, abnormal pancreatic enhancement and peripancreatic fluid, and hypoperfusion of the spleen and liver are variably associated with shock bowel whether due to posttraumatic hypovolemia or other causes of hypotension. the ct hypotension complex (shock bowel) has important prognostic and therapeutic implications and can probably be distinguished from bowel trauma and other forms of bowel injury in most cases.",General
does an analysis of near miss identified by anesthesia providers in the intensive care unit?,"learning from adverse events and near misses may reduce the incidence of preventable errors. current literature on adverse events and near misses in the icu focuses on errors reported by nurses and intensivists. icu near misses identified by anesthesia providers may reveal critical events, causal mechanisms and system weaknesses not identified by other providers, and may differ in character and causality from near misses in other anesthesia locations. we analyzed events reported to our anesthesia near miss reporting system from 2009 to 2011. we compared causative mechanisms of icu near misses with near misses in other anesthesia locations. a total of 1,811 near misses were reported, of which 22 (1.2 ) originated in the icu. five causal mechanisms explained over half of icu near misses. compared to near misses from other locations, near misses from the icu were more likely to occur while on call (45 vs. 19 , p 0.001), and were more likely to be associated with airway management (50 vs. 12 , p 0.001). icu near misses were less likely to be associated with equipment issues (23 vs. 48 , p 0.02).","a limited number of causal mechanisms explained the majority of icu near misses, providing targets for quality improvement. errors associated with airway management in the icu may be underappreciated. specialist consultants can identify systems weaknesses not identified by critical care providers, and should be engaged in the icu patient safety movement.",Medication
are activities of asymmetric dimethylarginine-related enzymes in white adipose tissue associated with circulating lipid biomarkers?,"asymmetric ng,ng-dimethylarginine (adma), an endogenous inhibitor of nitric oxide synthase, is regulated by the enzymatic participants of synthetic and metabolic processes, i.e., type i protein n-arginine methyltransferase (prmt) and dimethylarginine dimethylaminohydrolase (ddah). previous reports have demonstrated that circulating adma levels can vary in patients with type 1 and type 2 diabetes mellitus (t2dm). white adipose tissue expresses the full enzymatic machinery necessary for adma production and metabolism; however, modulation of the activities of adipose adma-related enzymes in t2dm remains to be determined. a rodent model of t2dm using 11- and 20-week old goto-kakizaki (gk) rats was used. the expression and catalytic activity of prmt1 and ddah1 and 2 in the white adipose tissues (periepididymal, visceral and subcutaneous fats) and femur skeletal muscle tissue were determined by immunoblotting, in vitro methyltransferase and in vitro citrulline assays. non-obese diabetic gk rats showed low expression and activity of adipose prmt1 compared to age-matched wistar controls. adipose tissues from the periepididymal, visceral and subcutaneous fats of gk rats had high ddah1 expression and total ddah activity, whereas the ddah2 expression was lowered below the control value. this dynamic of adma-related enzymes in white adipose tissues was distinct from that of skeletal muscle tissue. gk rats had lower levels of serum non-esterified fatty acids (nefa) and triglycerides (tg) than the control rats. in all subjects the adipose prmt1 and ddah activities were statistically correlated with the levels of serum nefa and tg.","activities of prmt1 and ddah in white adipose tissues were altered in diabetic gk rats in an organ-specific manner, which was reflected in the serum levels of nefa and tg. changes in adipose adma-related enzymes might play a part in the function of white adipose tissue.",Diagnosis
does acoustic monitoring of lung sound for the detection of one-lung intubation?,"monitoring methods for the early diagnosis of one-lung intubation (oli) are nonspecific and controversial. in this study, we evaluated a new acoustic monitoring system for the detection of oli. lung sounds were collected from 24 adult surgical patients scheduled for routine surgical procedures. four piezoelectric microphones attached to the patients' backs were used to sample lung sounds during induction of anesthesia and endotracheal tube positioning. to achieve oli, the endotracheal tube was inserted and advanced down the airway so that diminished or no breath sounds were heard on the left side of the chest. the tube was then withdrawn stepwise until equal breath sounds were heard. fiberoptic bronchoscopy confirmed the tube's final position. acoustic analyses were preformed by a new algorithm which assumes a multiple input multiple output system, in which a multidimensional auto-regressive model relates the input (lungs) and the output (recorded sounds) and a classifier, based on a generalized likelihood ratio test, indicates the number of ventilated lungs without reconstructing the original lung sounds from the recorded samples. this algorithm achieved an oli detection probability of 95.2 with a false alarm probability of 4.8.",higher detection values can be achieved at the price of a higher incidence of false alarms.,Diagnosis
does prolonged in vitro expansion partially affect phenotypic features and osteogenic potential of ovine amniotic fluid-derived mesenchymal stromal cells?,"ovine amniotic fluid mesenchymal stromal cells (oafmscs) are an emerging alternative source of stem cells to develop pre-clinical cell replacement protocols. for tissue engineering purposes, oafmscs can be used either immediately after isolation or after in vitro expansion. however, detailed studies are still required to investigate the advantages and drawbacks of their in vitro expansion. the phenotype and osteogenic differentiation potential of oafmscs were analyzed in relation to in vitro expansion that was carried out for 20 consecutive passages. expanded oafmscs were analyzed for proliferation index, expression profiles of several surface, pluripotency-associated and hla antigens, global dna methylation, telomere length and karyotype. the osteogenic differentiation ability of expanded oafmscs was assessed by qualitative and quantitative methods. expanded oafmscs reduced their proliferative activity after 10 passages and partially modified the expression of surface antigens and the intracellular distribution of pluripotency-associated markers (nanog, sox2 and tert) after 20 passages. the phenotypic alteration of cultured oafmscs was associated with a reduction of in vitro osteogenic plasticity. in detail, after 20 passages of cellular expansion, oafmscs lost the ability to increase osteocalcin and decreased collagen type i messenger rna expression. also, a lower percentage of cells displayed intracellular calcium release after stimulation with salmon calcitonin.","the results presented here suggest that long-term in vitro expansion may cause significant alterations in phenotypic features and plasticity of oafmscs, suggesting a careful re-evaluation of in vitro cultural and temporal conditions before employing expanded oafmscs for therapeutic purposes.",Diagnosis
is trial therapy with proton pump inhibitors a suitable test for gastroesophageal reflux disease ; a meta-analysis of the diagnostic test characteristics ?,"to determine the value of successful trial therapy with proton-pump inhibitors (ppis) as a diagnostic test for gastro-oesophageal reflux disease (gerd). systematic review and meta-analysis. studies were included in which the clinical response to a short course (1-4 weeks) of ppi therapy could be related to abnormal results of 24-hr ph monitoring, gastroscopy, and/or diagnostic questionnaires. the sensitivity and specificity of the trial therapy were calculated. the roc method was used to summarize the test characteristics across studies. with 24-hr ph monitoring as the reference standard, the positive likelihood ratio of the diagnosis 'reflux disease' ranged from 1.63 to 1.87 and the combined estimates of sensitivity and specificity in the various studies were 0.78 (95 ci: 0.66-0.86) and 0.54 (0.44-0.65), respectively. these values were lower with the other reference standards.","although there were insufficient data to determine the effect of varying dosages of ppis and duration of therapy on the test characteristics, successful short-term treatment with ppis in patients suspected of having gerd provides insufficient certainty as to the diagnosis.",Diagnosis
does ondansetron attenuate hepatic injury via p38 mapk-dependent pathway in a rat haemorrhagic shock model?,"ondansetron is a 5-ht3 receptor antagonist with potent antiemetic, analgesic, and antiphlogistic effects. recent evidence suggests that the co-existence of 5-ht3 receptors in various cell types is involved in inflammation. however, the effects that 5-ht3 antagonists produce in haemorrhagic shock and resuscitation remain unknown. in this study, we hypothesized that ondansetron administration in male rats, after haemorrhagic shock, decreases cytokine production and protects against hepatic injury through a p38 mitogen-activated protein kinase (mapk) pathway. male sprague-dawley rats underwent haemorrhagic shock (mean arterial blood pressure 40 mm hg for 90 min), followed by resuscitation. various doses of ondansetron (0.1, 0.3, 1, 3 mg kg(-1)) or a single dose of ondansetron (1 mg kg(-1)) with or without a p38 mapk inhibitor (sb-203580, 2 mg kg(-1)) or vehicle were administered intravenously during resuscitation. plasma aspartate aminotransferase (ast) and alanine aminotransferase (alt) concentrations and various liver proinflammatory parameters were measured at 24h after resuscitation. results show that haemorrhagic shock increases plasma ast and alt concentrations, hepatic myeloperoxidase activity, cytokine-induced neutrophil chemoattractant (cinc)-1, cinc-3, intercellular adhesion molecule-1 (icam-1), interleukin-6 (il-6) and tumor necrosis factor (tnf-) levels. these parameters were significantly improved in the ondansetron-treated rats subjected to haemorrhagic shock. ondansetron treatment restored phos-p38 mapk expression as compared with vehicle-treated haemorrhaged rats. coadministration of sb-203580 prevented the beneficial effects of ondansetron on postresuscitation proinflammatory responses and hepatic injury.","ondansetron attenuates hepatic injury following haemorrhagic shock, which is, at least in part, to be due to its anti-inflammatory effect via p38 mapk signal pathway.",Medication
do trauma surgeon mortality rates correlate with surgeon time at institution?,"trauma centers have been created to bring traumatized patients together with experienced surgeons. we reviewed our outcomes to determine if mortality rates for high injury severity scores (or 35) correlate with surgeon experience at our trauma center. using our prospectively collected database, we compared our results with mean mortality for high-volume american college of surgeon-certified trauma centers reporting to the national trauma data bank. mortality rates for our 11 trauma surgeons were correlated with years of experience as faculty surgeons at our institution during a 2-year period. statistical analysis was done with chi-square or weighted linear regression; significance was defined as p or 35 (weighted linear regression, p 0.05). it took, on average, 7.9 years of experience at our trauma center to reach benchmark mortality rates.","mortality rates for severely injured patients correlate significantly with surgeon experience at our institution. the training process does not end with fellowship or surgical residency, and surgeons new to an institution should be closely monitored and mentored to minimize mortality rates of severely injured patients. even at a very high volume trauma center with overall results substantially better than mean expected survival, we can demonstrate that experience makes a difference.",General
are renal effects of urodilatin in healthy subjects independent of blockade of the cyclooxygenase and angiotensin ii receptor?,"little is known about the role of the renin-angiotensin-aldosterone system and the renal prostaglandins in modulating the renal vasoconstrictive and natriuretic effects of synthetic urodilatin (uro) in healthy humans. twelve volunteers were pretreated in a randomized, single-blind, crossover study with losartan 50 mg a day or placebo for 5 days. another 12 healthy subjects received indomethacin 25 mg three times a day or placebo for 4 days and a single dose on day 5. all subjects received a uro infusion (15 ng kg(-1) min(-1)) on day 5. radioactive tracers and the lithium clearance technique were used. the effective renal plasma flow (erpf) decreased significantly during uro infusion: losartan pretreatment 573/-63 to 461/-76 ml/min versus placebo 540/-89 to 432/-90 ml/min. the urinary sodium excretion rate (una) increased significantly during uro infusion: losartan 335/-115 to 502/-134 umol/min (micromol/min) (una) versus placebo 386/-142 to 476/-137 umol/min (micromol/min) (una). in the indomethacin pretreated subjects, erpf decreased significantly from 530/-109 to 446/-55 ml/min versus 533/-89 to 449/-69 ml/min in the placebo group. una increased significantly from 395/-142 to 768/-254 umol/min (micromol/min) (una) in the indomethacin group versus 282/-117 to 552/-242 umol/min (micromol/min) (una) in placebo.",the renal vasoconstrictive and natriuretic effects of synthetic uro are not modified by sustained inhibition of the angiotensin ii receptor or the cyclooxygenase in man in a sodium replete state.,Medication
is soluble ctla-4 receptor an immunological marker of graves ' disease and severity of ophthalmopathy associated with ctla-4 jo31 and ct60 gene polymorphisms?,"graves' disease (gd) is an autoimmune disorder with genetic and environmental background. ctla-4 is a candidate gene for thyroid autoimmunity. increased serum levels of soluble ctla-4 (sctla-4) were found in some autoimmune diseases. the aim of the study was to evaluate the relation between sctla-4 level and clinical manifestation of graves' ophthalmopathy (go), thyroid status, and ctla-4 gene polymorphisms. serum sctla-4 concentrations were determined in 93 go patients and 93 healthy controls. in the go group, ctla-4 gene was genotyped in five polymorphic sites: g.319ct, c.49ag, ct60 by means of prc-rflp, jo31, and g.642at(833) by means of minisequencing assay. serum sctla-4 level was significantly higher in the go group than in controls (median: 7.94 vs 0.00 ng/ml, p0.000001). this level was higher in severe than in nonsevere go (median: 10.3 vs 5.6 ng/ml, p0.01). sctla-4 concentration was related neither to the activity of go nor to thyroid function. elevated sctla-4 levels were observed in carriers jo31g allele (genotype gggt) as compared with subjects with an absence of the g allele (tt genotype; median: 9.18 vs 4.0 ng/ml, p0.02). also patients possessing ct60g allele (genotype ggga) had higher serum sctla-4 levels than subjects who lack the g allele (aa genotype; median: 8.73 vs 2.28 ng/ml, p0.03).",it was shown for the first time that increased serum concentration of sctla-4 correlate with the severity of go. genetic variation in the ctla-4 gene region in gd patients at least partially determines the level of sctla-4.,Medication
is pre-existing disease associated with a significantly higher risk of death in severe respiratory syncytial virus infection?,"600,000 deaths worldwide are estimated to be directly or indirectly attributable to respiratory syncytial virus (rsv). to determine: (1) the mortality rate; and (2) risk factors for death in children with severe rsv infection. 20-bed, regional, multidisciplinary, tertiary, paediatric intensive care unit (picu) in a university-affiliated children's hospital. cohort study of all children with severe rsv infection covering eight consecutive rsv seasons (1999-2007), using picu admission as a marker of severity. of the 406 rsv-positive patients that were admitted to picu: 98.5 required mechanical ventilation; 35 children died--median age 5.1 months (interquartile range (iqr) 2.4-13.6), length of picu stay 16 days (iqr 8-31) and 371 survived--median age 2.5 months (iqr 1.2-9), length of picu stay 5 days (iqr 4-9). the overall picu rsv mortality was 8.6 with a standardised mortality ratio of 0.76. during the study period 2009 rsv-positive patients were admitted to the children's hospital, giving a hospital rsv mortality rate of 1.7. of the deaths, 18 were directly rsv related (rsv bronchiolitis-related mortality picu 4.4 and hospital 0.9) as the patients were still rsv positive when they died and 17 children died from non-pneumonitis causes after becoming rsv negative. all of the rsv deaths had pre-existing medical conditions--chromosomal abnormalities 29, cardiac lesions 27, neuromuscular 15, chronic lung disease 12, large airway abnormality 9, and immunodeficiency 9. nineteen children (56) had pre-existing disease in two or more organ systems (relative risk (rr) 4.38). predisposing risk factors for death were pre-existing disease (rr 2.36), cardiac anomaly (rr 2.98) and nosocomial/hospital-acquired rsv infection (rr 2.89). there is an interaction effect between pre-existing disease, nosocomial/hospital-acquired rsv infection and mortality (p0.001).","pre-existing disease/comorbidity, in particular multiple pre-existing diseases and cardiac anomaly, is associated with a significantly higher risk of death from severe rsv infection. nosocomial/hospital-acquired rsv infection is an additional major risk factor for death in children with severe rsv infection.",Prevention
is preoperative tumor marker doubling time a useful predictor of recurrence and prognosis after hepatic resection of hepatocellular carcinoma?,"it is important to identify prognostic factors in patients with hepatocellular carcinoma (hcc) before hepatectomy. no previous studies have addressed the predictive efficacy of the preoperative doubling times of alpha-fetoprotein (afp) and protein induced by vitamin k absence (pivka-ii). a total of 210 hcc patients who underwent a hepatic resection between 1998 and 2006 were prospectively evaluated. serum afp and pivka-ii levels were measured at least twice before surgery to calculate the doubling times. nineteen clinical factors that can be examined preoperatively, including the doubling times of afp and pivka-ii were investigated to identify prognostic factors for disease-free and overall survival after hepatectomy. there was no relationship between preoperative levels and doubling times of afp and pivka-ii. in a multivariate analysis, patients with a doubling time of afp 30 days and pivka-ii 16 days showed a significantly worse disease-free (p 0.02, p 0.03, respectively) and overall survival (p 0.0001, p 0.03, respectively).","in hcc patients, the doubling times of preoperative serum afp or pivka-ii levels are useful tools to predict early postoperative recurrence and a poor prognosis.",Diagnosis
does low serum triiodothyronine in acute myocardial infarction indicate major heart injury?,"in patients with acute myocardial infarction (mi), low serum triiodothyronine (t3) concentration is commonly associated with a severe clinical course. the aim of this prospective study was to investigate whether a severe clinical course in patients with low t3 is related to the magnitude of myocardial injury assessed by echocardiography. out of 635 patients with mi we enrolled 100 consecutive patients. they were divided in two subgroups: group a, 81 patients without clinical hard events (death, resuscitation following ventricular tachycardia/vertricular fibrillation, new mi) and group b, 19 patients in whom at least one of the above hard events occurred during hospital stay. thyroid function tests were performed on day 1, 4 and 7, echocardiographic examinations measuring asynergic area (aa), and wall motion score index (wmsi) between day 1 and 5 (median 3). a negative correlation was found between plasma free triiodothyronine (ft3), concentration and aa (p0.001), ft3 and wmsi (p0.001) values at all time points. ft3 concentration was lower in group b than group a at all time points (p0.001).","in patients with acute mi, low ft3 state is related to the extent of myocardial damage.",General
does immediate inguinal lymph node dissection improve survival in patients of penile cancer ?,"to investigate the clinical outcome of immediate inguinal lymph node dissection on the survival of the patients with penile carcinoma. a total of 67 patients of penile carcinoma whose inguinal lymph nodes (iln) were initial clinically impalpable, received inguinal lymph node dissection (ilnd) from dec 2008 to april 2014. among them, 33 patients received immediate ilnd within 1 month after the resection of penile cancer, while 34 patients underwent delayed ilnd which was performed when iln was found clinically apparent during follow-up. the kaplan-meier survival analysis was performed. the prognostic factors was evaluated by log-rank test, including age, morphology, location, t stage, grade of primary tumor, clinical status of iln before ilnd, lymphatic pathology, time to ilnd. cox proportional hazard model was used to find the independent risk factors on survival. the median age was 50 year-old (range 26 to 84 year-old). the median follow-up time was 23 months (range 3-76 months). the 3-year and 5-year overall survival were 70.1 and 65.4, respectively, the 5-year survival rate in immediate ilnd and delayed ilnd group were 93.1, and 33.7 respectively. positive iln metastasis was found in 7 patients from immediate ilnd group but 26 patients from delayed ilnd group that the prognostic factors included t stage, tumor grade, clinical status of inguinal lymph nodes before ilnd, and lymphatic pathology. cox model found the status of inguinal lymph nodes was independent prognostic factor for the survival.",inguinal lymph node metastasis is the important prognostic indicator of the survival of penile cancer. immediate ilnd could improve survival for the patients with clinically impalpable lymph nodes.,Prevention
does tyrosine-mutant aav8 delivery of human mertk provide long-term retinal preservation in rcs rats?,"the absence of mertk in rcs rats results in defective rpe phagocytosis, accumulation of outer segment (os) debris in the subretinal space, and subsequent death of photoreceptors. previous research utilizing mertk gene replacement therapy in rcs rats provided proof of concept for treatment of this form of recessive retinitis pigmentosa (rp); however, the beneficial effects on retinal function were transient. in the present study, we evaluated whether delivery of a mertk transgene using a tyrosine-mutant aav8 capsid could lead to more robust and longer-term therapeutic outcomes than previously reported. an aav8 y733f vector expressing a human mertk cdna driven by a rpe-selective promoter was administrated subretinally at postnatal day 2. functional and morphological analyses were performed at 4 months and 8 months post-treatment. retinal vasculature and mller cell activation were analyzed by quantifying acellular capillaries and glial fibrillary acidic protein immunostaining, respectively. electroretinographic responses from treated eyes were more than one-third of wild-type levels and os were well preserved in the injection area even at 8 months. rescue of rpe phagocytosis, prevention of retinal vasculature degeneration, and inhibition of mller cell activation were demonstrated in the treated eyes for at least 8 months.",this research describes a longer and much more robust functional and morphological rescue than previous studies. we also demonstrate for the first time that an aav8 mutant capsid serotype vector has a substantial therapeutic potential for rpe-specific gene delivery. these results suggest that tyrosine-mutant aav8 vectors hold promise for the treatment of individuals with mertk-associated rp.,Treatment
does urgent laparoscopic cholecystectomy in the management of acute cholecystitis : timing influence conversion rate?,"the optimal treatment of acute cholecystitis is urgent laparoscopic cholecystectomy. most reports suggest that a delay of 72 or 96 h from onset of symptoms leads to a higher conversion rate. this study assessed the conversion rate in relation to the timing of urgent laparoscopic cholecystectomy for acute cholecystitis. during a 12 month period, 112 patients received laparoscopic cholecystectomy for acute cholecystitis at a tertiary care university hospital in central taiwan. data were collected prospectively. the overall conversion rate was 3.6 (4/112). of 62 procedures performed within 72 h from onset of symptoms, 2 were converted, as compared with 2 of 50 procedures after 72 h. of 76 procedures performed within 96 h from onset of symptoms, 3 were converted, as compared with 1 of 36 procedures after 96 h. there were no mortalities or common bile duct injuries.",the conversion rate for urgent laparoscopic cholecystectomy among patients with acute cholecystitis can be as low as 3.6. the timing of urgent laparoscopic cholecystectomy has no impact on the conversion rate.,Treatment
do cardiac troponin i release in acute pulmonary embolism in relation to the duration of symptoms?,"to evaluate the release of cardiac troponin i in normotensive patients with acute pulmonary embolism in relation to the duration of symptoms. fifty-seven normotensive patients with acute pulmonary embolism were included in the study. patients were divided into two groups based on the duration of symptoms at presentation: symptoms of 72 h, group b. serum cardiac troponin i levels were measured at presentation. mean age was 63/-18 years and 23 (40) patients were males. thirty-three (58) patients had symptoms of 72 h (group b). both groups had similar prevalence of right ventricular dysfunction on echocardiography (55 n18 in group a vs. 42 n10 in group b, pns). sixteen patients had elevated serum cardiac troponin i (mean/-s.d. 3.3/-2.3 ng/ml, range 0.6-8.3 ng/ml). elevated serum cardiac troponin i was strongly associated with right ventricular dysfunction (p0.015). all patients with elevated serum cardiac troponin i (n16) were in group a (p0.0001). twelve of 18 (67) patients with (p0.0005) and 4 of 15 (27) patients without (pns) right ventricular dysfunction had elevated serum cardiac troponin i. thirteen of 16 (81) patients with elevated serum cardiac troponin i had duration of symptoms or 24 h at presentation.","the dynamics of cardiac troponin i release in acute pulmonary embolism in patients who present with symptoms of or 72 h duration could be different from those who present with longer duration of symptoms. therefore, the use of cardiac troponin i in risk stratification of acute pulmonary embolism might be limited to the patients presenting within 72 h of the onset of symptoms.",Symptoms
does the congenital diaphragmatic hernia composite prognostic index correlate with survival in left-sided congenital diaphragmatic hernia?,"we developed the congenital diaphragmatic hernia congenital prognostic index (cdh-cpi) to incorporate all known prognostic variables into a single composite index to improve prognostic accuracy. the purpose of this study is to examine the ability of the cdh-cpi to predict survival in patients with left-sided congenital diaphragmatic hernia and to determine if the index has a stronger correlation with survival than each of the individual components. a retrospective review of patients with left-sided congenital diaphragmatic hernia between 2004 and 2010 was conducted. ten prenatal parameters of the cdh-cpi were collected, total score was tabulated, and patients stratified according to total score and survival. sixty-four patients with a prenatal diagnosis of left-sided congenital diaphragmatic hernia were identified. patients with a cdh-cpi score of 8 or higher had a significantly higher survival than patients with a cdh-cpi score of lower than 8. the cdh-cpi has the strongest correlation with survival compared with the individual parameters measured. the cdh-cpi correlates with extracorporeal membrane oxygenation use, and 75 of patients with a score of 5 or lower were placed on extracorporeal membrane oxygenation.",the cdh-cpi accurately stratifies survival in left-sided congenital diaphragmatic hernia. the amalgamation of 10 prenatal parameters of the cdh-cpi may be a better prenatal predictor than any single prognostic variable currently used.,Diagnosis
does the peroxisomal multifunctional protein interact with cortical microtubules in plant cells?,"the plant peroxisomal multifunctional protein (mfp) possesses up to four enzymatic activities that are involved in catalyzing different reactions of fatty acid beta-oxidation in the peroxisome matrix. in addition to these peroxisomal activities, in vitro assays revealed that rice mfp possesses microtubule- and rna-binding activities suggesting that this protein also has important functions in the cytosol. we demonstrate that mfp is an authentic microtubule-binding protein, as it localized to the cortical microtubule array in vivo, in addition to its expected targeting to the peroxisome matrix. mfp does not, however, interact with the three mitotic microtubule arrays. microtubule co-sedimentation assays of truncated versions of mfp revealed that multiple microtubule-binding domains are present on the mfp polypeptide. this indicates that these regions function together to achieve high-affinity binding of the full-length protein. real-time imaging of a transiently expressed green fluorescent protein-mfp chimera in living plant cells illustrated that a dynamic, spatial interaction exits between peroxisomes and cortical microtubules as peroxisomes move along actin filaments or oscillate at fixed locations.","plant mfp is associated with the cortical microtubule array, in addition to its expected localization in the peroxisome. this observation, coupled with apparent interactions that frequently occur between microtubules and peroxisomes in the cell cortex, supports the hypothesis that mfp is concentrated on microtubules in order to facilitate the regulated import of mfp into peroxisomes.",Diagnosis
is the 5-ht2 antagonist ketanserin an open channel blocker of human cardiac ether--go-go-related gene ( herg ) potassium channels?,"ketanserin, a selective 5-ht receptor antagonist, prolongs the qt interval of ecg in patients. the purpose of the present study was to determine whether ketanserin would block human cardiac ether--go-go-related gene (herg) potassium channels. whole-cell patch voltage-clamp technique was used to record membrane currents in hek 293 cells expressing wild type or mutant herg channel genes. ketanserin blocked herg current (i(herg)) in a concentration-dependent manner (ic500.11 microm). the drug showed an open channel blocking property, the block increasing significantly at depolarizing voltages between 10 to 60 mv. voltage-dependence for inactivation of herg channels was negatively shifted by 0.3 microm ketanserin. a 2.8 fold attenuation of inhibition by elevation of external k concentration (from 5.0 to 20 mm) was observed, whereas the inactivation-deficient mutants s620t and s631a had the ic50s of 0.84 /- 0.2 and 1.7 /-0.4 microm (7.6 and 15.4 fold attenuation of block). in addition, the herg mutants in pore helix and s6 also significantly reduced the channel block (2-59 fold) by ketanserin.",these results suggest that ketanserin binds to and blocks the open herg channels in the pore helix and the s6 domain; channel inactivation is also involved in the blockade of herg channels. blockade of herg channels most likely contributes to the prolongation of qt intervals in ecg observed clinically at therapeutic concentrations of ketanserin.,Medication
does 5-fluorouracil-based chemotherapy enhance the antitumor activity of a thymidylate synthase-directed polyepitopic peptide vaccine?,"thymidylate synthase (ts), a key enzyme in dna synthesis, is often overexpressed in cancer cells. some chemotherapeutic agents, such as 5-fluorouracil (5-fu), act by inhibiting ts expression. we evaluated whether a novel 28-amino acid multiepitope peptide, ts/pp, that contains the sequences of three ts-derived epitopes with binding motifs for hla-a()02.01 could induce a ts-directed cytotoxic t-lymphocyte (ctl) response with antitumor activity. ts/pp peptide immunologic activity in ctl lines derived from human leukocyte antigen (hla)-a()02.01 peripheral blood mononuclear cells (pbmcs) was tested in the presence of interleukin-2 and autologous ts/pp peptide-loaded dendritic cells. immunologic and antitumor activities of ts/pp and its toxicity were also evaluated in vivo in hla-a()02.01 transgenic (hhd) mice that were vaccinated with ts/pp, control, or ts-peptide cocktail and treated with or without 5-fu chemotherapy. the mice were also inoculated subcutaneously with ts-expressing el-4/hhd lymphoma cells to assess immune response against these tumor cells. ts/pp-specific ctl lines showed a ts-multiepitopic specificity and were able to kill ts/hla-a()02.01 breast and colon carcinoma cells. the killing ability against target cells previously exposed to sublethal doses of 5-fu was statistically significantly greater than against untreated target cells (43.5 versus 26.5 at 25/1 effector to target ratio difference diff 17.0; 95 confidence interval ci 12.6 to 20.4) for mda-mb-231 breast carcinoma cells and 73.5 versus 48.5 (diff 25.0; 95 ci 16.2 to 33.8) for the sw-1463 colon carcinoma cells. hhd mice vaccinated with ts/pp manifested a ts-peptide-specific ctl response with no sign of autoimmunity or toxicity. furthermore, treatment of these mice with 5-fu delayed or prevented the occurrence of tumors formed by inoculation with autologous (ts)el-4/hhd lymphoma cells.",the multiepitopic ts/pp vaccine induces a tumor-specific immune response in mice and is especially potent when used in combination with 5-fu-based chemotherapy.,Medication
does n-acetylcycsteine attenuate the deleterious effects of radiation therapy on inci-sional wound healing in rats?,"during preoperative radiotherapy, effective doses of ionizing radiation occasionally cause wound complications after subsequent surgery. this study was designed to determine the effects of intraperitoneally or orally administered n-acetylcysteine (nac) on anastomotic healing of irradiated rats. forty wistar albino rats were randomized into four groups containing 10 rats each. a 3 cm long surgical full-thickness midline laparotomy was performed to all groups (groups 1-4). group 1 was designed as a control group without radiation therapy and nac treatment. groups 2, 3 and 4 received a single abdominal dose of 10 gy irradiation before laparotomy and groups 3 and 4 received oral and intraperitoneal nac, respectively. group comparisons demonstrated that breaking strength was significantly higher in nac treated rats. a statistically significant difference was determined in terms of superoxide dismutase (sod), malondealdehyde (mda) and glutation (gsh) values between groups (p0.001). nevertheless, advanced oxidation protein products (aopp) levels were found to be similar between groups (p0.163). serum gsh and sod levels were significantly higher in groups 3 and 4 when compared to group 2 (p 0.05). similarly, there was a significant increase in serum mda concentration, predicting lipid peroxidation, in group 2 when compared to groups 1, 3 and 4 (p 0.05). there was not a significant difference between groups 3 and 4 regarding gsh, mda, sod, and aopp levels. histopathological analysis revealed that nac administration, either orally or intraperitoneally, leads to a better incisional healing in terms of inflammation, granulation, collagen deposition, reepithelization and neovascularization.",the present study supports the hypothesis that nac administration alleviates the negative effects of radiotherapy on incisional wound healing by means of reducing oxidative stress markers and improving histologic parameters independent of the route of administration.,Treatment
do target lesion characteristics in failing vein grafts predict the success of endovascular and open revision?,"this study examined the association of anatomic and temporal characteristics of graft-threatening lesions with the efficacy of percutaneous and open graft revision for failing infrainguinal vein grafts. consecutive open and endovascular revisions for graft threatening lesions were reviewed. we evaluated graft durability and individual target lesion response to open and endovascular treatment to determine characteristics that may influence outcomes. treatment failure was defined as target lesion restenosis or graft occlusion. eighty-four (58 endovascular, 26 open) infrainguinal vein graft revisions were performed in 67 failing, nonthrombosed infrainguinal vein grafts. primary assisted graft patency at 5 years was 63 (95 confidence interval ci, 46 to 77). follow-up was 29.5 /- 19.2 months. grafts treated for early lesions (6 months) failed (occlusion or need for additional interventions) more frequently than those with late occurring lesions (p .03). overall target lesion revascularization patency was 45 (95 ci, 32 to 58) at 3 years. average time to target lesion revascularization failure was 7.5 months, with no significant difference noted between endovascular and open treatment groups. overall target lesion revascularization patency at 3 years was also not significantly different between open and endovascular groups at 54 (95 ci, 30 to 73) vs 41 (95 ci, 25 to 56; p .15). when divided by early and late-occurring target lesions, endovascular treatment of early lesions was associated with inferior patency compared with open procedures; no difference in patency was seen between treatment groups for late lesions. when divided by target lesion location (anastomotic vs mid-graft), treatment for both proximal and distal anastomotic target lesion was associated with inferior patency compared with mid-graft revision at 32 (95 ci, 17 to 47) vs 62 (95 ci, 37 to 87) at 3 years (p .03). in addition, although results of anastomotic target lesion treatment significantly favored open repair, even open repair of anastomotic target lesions was associated with a 50 patency rate at 3 years. in contrast, mid-graft target lesions treated with open revisions were uniformly successful compared with a 54 patency at 3 years with endovascular treatment (p .24). short lesions (2 cm) fared equally well with either endovascular or open treatment. univariate analysis noted only anastomotic treatment was associated with significantly increased odds of failure.","grafts that develop early lesions fare poorly regardless of treatment modality. lesions involving anastomoses of failing grafts are better treated with open revision, but patency after treatment of such lesions is still worse than treatment of mid-graft lesions. in contrast, the method of treatment does not influence outcome after treatment of mid-graft target lesions. thus, endovascular therapy should be reserved for focal, late-appearing lesions involving the mid-graft.",Treatment
"is cholesteatoma epithelium characterized by increased expression of ki-67 , p53 and p21 , with minimal apoptosis?","to investigate differences in cell proliferation, cell cycle arrest and apoptosis between cholesteatoma and control skin. immunohistochemical sections of 15 cholesteatoma and 15 paired control retro-auricular skin samples were examined for ki-67, p53, p21 and active caspase 3, using image analysis, as well as for dna fragmentation. the retro-auricular skin samples contained 5.7 /- 3.6, ki-67-positive cells and showed a normal expression pattern. in the cholesteatoma epithelium 11.7 /- 9.5 of the cells were ki-67-positive and these cells were dominantly expressed in the basal and parabasal cell layers. retro-auricular skin contained 5.8 /- 5.4 p53-positive cells and 1.0 /- 0.9, p21-positive cells. in the cholesteatoma epithelium 17.8 /- 12.3 of the cells were p53-positive and 14.3 /- 11.6 were p21-positive the expression of ki-67, p53 and p21 differed significantly between the two groups (p 0.05). in the cholesteatoma epithelium a positive correlation was found between p53 and p21 expression (p 0.016). active caspase 3 positivity and dna fragmentation were rarely seen in the cholesteatoma epithelium.","our results indicate that increased cell proliferation in cholesteatoma epithelium is accompanied by an increase in p53 and p21 protein levels, whilst apoptosis is minimal.",General
does alcohol abuse among u.s. navy recruit who were maltreated in childhood?,"to examine relationships between childhood maltreatment and alcohol-related problems among u.s. navy recruits. an anonymous sample of 5697 navy recruits completed a survey regarding their alcohol consumption, alcohol problems (binge drinking, drinking until drunk, alcohol dependence, alcohol-related arrests), and experiences of childhood physical and sexual abuse. most of the recruits used alcohol, and a substantial proportion reported histories of childhood maltreatment. recruits who had been victimized as children were more likely to use alcohol. furthermore, among drinkers, those who had been abused were more likely to exhibit alcohol problems than were non-abused drinkers.",substantial numbers of personnel with alcohol-related problems may be using alcohol to self-medicate due to a history of childhood abuse. attention to the association between alcohol abuse and childhood maltreatment might help improve the efficacy of military alcohol reduction programs.,General
does ascorbic acid prevent cigarette smoke injury to endothelium-dependent arterial relaxation?,"arterial endothelium-dependent acetylcholine relaxation is impaired by smoking, and this injury may be mediated by oxygen free radicals. the purpose of this study was to examine the effect of ascorbic acid (aa) treatment on this injury. new zealand white rabbits (n 6, each group) were placed in a 240-ft3 airflow chamber for 3 h per day, 5 days per week over an 8-week period. animals were divided into four groups and fed rabbit chow and water or rabbit chow and aa (250 ml/kg)-supplemented water. the control-smoke rabbit group and the ascorbic acid-smoke rabbit group were exposed to mainstream cigarette smoke from a robotic smoke generator for the 3-h period, while the control-no smoke rabbit group and ascorbic acid-no smoke rabbit group were similarly placed in the chamber without smoke. at the end of 8 weeks, rabbits were sacrificed and segments of their superficial femoral arteries were suspended from tension transducers and the maximal contraction was determined. the remaining rings were contracted to 50 of the maximum and relaxation was determined by adding acetylcholine. groups were compared using one-way anova. rings from control-smoke (5.13 /- 0.21 g) and aa-smoke rabbits (6. 24 /- 0.46 g) exhibited increased mean contraction to kcl (p 0. 05) compared to control-no smoke rabbits (3.86 /- 0.40 g). acetylcholine-dependent relaxation was significantly reduced in the rings from the control-smoke rabbits compared to control-no smoke rabbits (acetylcholine, 5 x 10(-7) m: 24.7 /- 2.7 versus 55.3 /- 8.0; acetylcholine, 7 x 10(-7) m: 27.5 /- 2.3 versus 56.3 /- 9. 2). the aa-smoke group (acetylcholine, 5 x 10(-7) m: 61.8 /- 12. 4; 7 x 10(-7) m: 67.9 /- 11.4) had significantly increased relaxation compared to the control-smoke group (p 0.05). there was no statistical difference in the mean percentage ring relaxation between the control-no smoke, aa-no smoke, and aa-smoke groups.",ascorbic acid protected the artery from cigarette smoke-induced endothelial injury.,Prevention
do cell-density-dependent changes in mitochondrial membrane potential and reactive oxygen species production in human skin cells post sunlight exposure?,"solar ultraviolet radiation (uvr) is the principal etiological factor in skin carcinogenesis. in vivo and in vitro studies have demonstrated previously that oxidative dna damage, mitochondrial mass and mitochondrial membrane potential (mmp) changes are associated with skin cell response to uvr stress. spontaneously immortalized human skin keratinocytes were irradiated with increasing sub-lethal doses of simulated sunlight irradiation (ssi) using a q-sun solar simulator. the effects of ssi on reactive oxygen species (ros) formation, mitochondrial mass and mmp were then determined. ssi induced mitochondrial mass increase post low ssi (0.25-2.5 j/cm), whereas higher ssi doses (5.0 and 7.5 j/cm) decreased mitochondrial mass. mitochondrial mass increased with time post 5.0 j/cm irradiation and all changes in mass were independent of cell density status. changes in ros and mmp were cell density dependent. additionally, an inverted dose-dependent decrease in ros formation was observed 3 h post ssi with the lower ssi dose (0.25 j/cm).",observations from the present study suggest that changes in the cell's microenvironment (modeled through varying cell density) influence changes in mmp and ros detoxifying responses in sun-exposed skin cells.,Medication
do lactobacillus reuteri 6475 increases bone density in intact females only under an inflammatory setting?,"we previously demonstrated that short-term oral administration of the probiotic lactobacillus reuteri 6475 enhanced bone density in male but not female mice. we also established that l. reuteri 6475 enhanced bone health and prevented bone loss in estrogen-deficient female mice. in this study, we tested whether a mild inflammatory state and/or a long-term treatment with the probiotic was required to promote a positive bone effect in estrogen-sufficient female mice. a mild inflammatory state was induced in female mice by dorsal surgical incision (dsi). following dsi animals were orally supplemented with l. reuteri or vehicle control for a period of 8 weeks. gene expression was measured in the intestine and bone marrow by qpcr. distal femoral bone density and architecture was analyzed by micro-ct. we report that 8 weeks after dsi there is a significant increase in the weight of spleen, thymus and visceral (retroperitoneal) fat pads. expression of intestinal cytokines and tight junction proteins are also altered 8 weeks post-dsi. interestingly, l. reuteri treatment was found to display both intestinal region- and inflammation-dependent effects. unexpectedly we identified that 1) l. reuteri treatment increased bone density in females but only in those that underwent dsi and 2) dsi benefited cortical bone parameters. in the bone marrow, dorsal surgery induced cd4 t cell numbers, a response that was unaffected by l. reuteri treatment, whereas expression of rankl, opg and il-10 were significantly affected by l. reuteri treatment.","our data reveals a previously unappreciated effect of a mild surgical procedure causing a long-lasting effect on inflammatory gene expression in the gut and the bone. additionally, we demonstrate that in intact female mice, the beneficial effect of l. reuteri on bone requires an elevated inflammatory status.",Treatment
does tacrolimus have less fibrogenic potential than cyclosporin a in a model of renal ischaemia-reperfusion injury?,"cyclosporin is associated with significant chronic nephrotoxicity, manifest in the long term mainly as renal fibrosis. there have been claims that tacrolimus is a less fibrotic drug than cyclosporin, and this study was designed to determine the effect of the two drugs on the expression of fibrosis-associated genes. male wistar rats underwent clamping of the right renal pedicle for 45 min together with left nephrectomy; this model has previously been shown to be associated with upregulation of fibrosis-associated genes. experimental groups (six animals per group) received cyclosporin a 10 mg/kg daily, tacrolimus 0.2 mg/kg daily or no treatment. animals were killed at 16 weeks, and the renal cortical expression of fibrosis-associated genes was studied by means of quantitative reverse transcriptase-polymerase chain reaction. tacrolimus-treated animals developed significantly less proteinuria and had lower serum creatinine levels than those receiving cyclosporin. tacrolimus administration also significantly reduced the expression of transforming growth factor beta and tissue inhibitor of metalloproteinases 1, both the products of genes associated with fibrosis. although cyclosporin treatment reduced levels of the matrix-degrading enzymes, matrix metalloproteinase (mmp) 2 and mmp-9, this was not statistically significant.","tacrolimus has less nephrotoxicity than cyclosporin in this model. it also appears to have less fibrogenic potential, and this may have implications for the choice of long-term immunosuppressant in renal transplantation.",Medication
do tlc analysis of harpagoside in devil claw extract and its tablets ?,"to set up a method for tlc identification of the devil claw extract and its tablets, and make a quantitative analysis of harpagoside the main active constituent in the extract. a characteristic tlc chromatogram was obtained by using pre-coated silica gel 60f254 plate, chloroform-ethyl acetate-methanol-water as the solvent system and 5 vanillin-sulfuric acid solution or 10 sulfuric acid-ethanol solution as the spray reagent; and quantitative analysis was carried out using silica gel plate modified by 1 sodium hydroxide, and uv absorptive scanning at 283 nm. the regression equation is y 20.33x 92.72, r 0.9993, linear range between 16.8-151.2 ng, and average recovery 101.2.","this method has been validated by linearity, stability, sensitivity and reproducibility tests, and proved to be accordant with the requirement for quantitative analysis of the herbal medicine in question.",Medication
does classic mitral valve prolapse cause enlargement in left ventricle even in the absence of significant mitral regurgitation?,"the aim of this study was to evaluate whether left ventricular size was increased in patients with classic bileaflet mitral valve prolapse (mvp) in the absence of significant mitral regurgitation (mr). patients with classic bileaflet mvp were included as the case group. two different control groups were established. the first control group was composed of the patients with mild mr caused by the reasons except mvp. the second control group consisted of healthy individuals whose echocardiograms were normal. the patients with moderate or severe mr and having abnormality in the other valves were excluded. there were 20 patients in each group. systolic and diastolic diameters and volumes of left ventricle (lv) in the mvp group were significantly higher than those in the control groups. in 10 of the patients in the mvp group, lv internal diastolic diameter (lvidd) values were measured as 5.7 cm, whereas increased lvidd value was detected in only one patient in the other two control groups. there was a significant difference in terms of the presence of increased lvidd values between the mvp group and the control groups. despite this enlargement in the lv dimension, the lv ejection fractions were found similar in all groups. furthermore, it was found that the lengths of both anterior and posterior mitral leaflets in mvp group were significantly higher than those in the control groups.",the lv diameters and volumes of patients with classic bileaflet mvp were found to be increased even in the absence of significant mr. these results need to be supported by large-scale clinical studies.,General
does oral glutamine supplementation protect female mice from nonalcoholic steatohepatitis?,"genetic factors, a diet rich in fat and sugar, and an impaired intestinal barrier function are critical in the development of nonalcoholic steatohepatitis (nash). the nonessential amino acid glutamine (gln) has been suggested to have protective effects on intestinal barrier function but also against the development of liver diseases of various etiologies. the effect of oral gln supplementation on the development of western-style diet (wsd)-induced nash in mice was assessed. female 6- to 8-wk-old c57bl/6j mice were pair-fed a control (c) diet or a wsd alone or supplemented with 2.1 g l-gln/kg body weight for 6 wk (cgln or wsdgln). indexes of liver damage, lipid peroxidation, and glucose metabolism and endotoxin concentrations were measured. although gln supplementation had no effect on the loss of the tight junction protein occludin, the increased portal endotoxin and fasting glucose concentrations found in wsd-fed mice, markers of liver damage (e.g., nonalcoholic fatty liver disease activity score and number of neutrophils in the liver) were significantly lower in the wsdgln group than in the wsd group (47 and 60 less, respectively; p 0.05). concentrations of inducible nitric oxide synthase (inos) protein and 3-nitrotyrosin protein adducts were significantly higher in livers of wsd-fed mice than in all other groups (8.6- and 1.9-fold higher, respectively, compared with the c group; p 0.05) but did not differ between wsdgln-, c-, and cgln-fed mice. hepatic tumor necrosis factor and plasminogen activator inhibitor 1 concentrations were significantly higher in wsd-fed mice (1.6- and 1.8-fold higher, respectively; p 0.05) but not in wsdgln-fed mice compared with c mice.",our data suggest that the protective effects of oral gln supplementation on the development of wsd-induced nash in mice are associated with protection against the induction of inos and lipid peroxidation in the liver.,Medication
do bone perforation and placement of collagen sponge facilitate bone augmentation?,"bone perforation may induce bone marrow cell migration into a collagen sponge onlay implant. this study investigated the efficacy of bone perforation and collagen sponge onlay placement with regard to new bone formation. one hundred sixty femurs of 80 wistar male rats were used in four groups: bone perforation and sponge (ps) group: after perforating the femur, fibrillar and heat-denatured collagen (fc-hac) sponges were placed on the femur; sponge (s) group: a fc-hac sponge was placed directly on the femur without bone perforation; perforation (p) group: femur perforation without collagen sponge placement; and control (c) group: neither bone perforation nor sponge placement was used. histologic and histomorphometric analyses were performed after the surgery. numerous osteoblastic and fibroblastic cells were seen during the early repopulation in and at the periphery of the sponge in the ps group. these cells were seen only at the periphery of the sponge in the s group. in the ps group, angiogenesis was noted frequently, and it exhibited significantly greater new bone area compared to the other groups at days 14 and 28.",the use of the fc-hac sponge on the bone perforation area seemed to promote bone augmentation by possibly acting as a scaffold for the bone marrow cells as well as maintaining the space that is necessary for bone growth to occur.,Treatment
does carbohydrate augment exercise-induced protein accretion versus protein alone?,"we tested the thesis that cho and protein coingestion would augment muscle protein synthesis (mps) and inhibit muscle protein breakdown (mpb) at rest and after resistance exercise. nine men (age23.01.9 yr, body mass index24.22.1 kgm) performed two unilateral knee extension trials (four sets8-12 repetitions to failure) followed by consumption of 25 g of whey protein (pro) or 25 g of whey protein plus 50 g of maltodextrin (procarb). muscle biopsies and stable isotope methodology were used to measure mps and mpb. the areas under the glucose and insulin curves were 17.5-fold (p0.05) and 5-fold (p0.05) greater, respectively, for procarb than for pro. exercise increased mps and mpb (both p0.05), but there were no differences between pro and procarb in the rested or exercised legs. phosphorylation of akt was greater in the procarb than in the pro trial (p0.05); phosphorylations of akt (p0.05) and acetyl coa carboxylase- (p0.05) were greater after exercise than at rest. the concurrent ingestion of 50 g of cho with 25 g of protein did not stimulate mixed mps or inhibit mpb more than 25 g of protein alone either at rest or after resistance exercise.",our data suggest that insulin is not additive or synergistic to rates of mps or mpb when cho is coingested with a dose of protein that maximally stimulates rates of mps.,Prevention
do disparities in receipt of specialty services among children with mental health need enrolled in the cmhi?,"the study assessed racial-ethnic differences in receipt of mental health services among children enrolled in systems of care under the children's mental health initiative (cmhi). survey data for 3,920 cmhi enrollees were used to estimate the association between race-ethnicity and the number of days in the 12 months postenrollment during which the child received individual psychotherapy, family and group psychotherapy, medication monitoring, assessment and evaluation, case management, residential treatment, and inpatient care. two-part regressions with fixed site effects were estimated to adjust for geography and baseline population differences, including child and caregiver characteristics. compared with white non-latino children, african americans had lower odds of using any individual psychotherapy (odds ratio or.73, p.019), family and group psychotherapy (or.79, p.043), and medication monitoring (or.51, p.001); among users of each service, african americans had lower utilization of individual psychotherapy (incidence rate ratio irr.79, p.001), family and group psychotherapy (irr.86, p.011), and inpatient care (irr.75, p.026). latino children had lower odds of receiving medication monitoring (or.70, p.007) and assessment and evaluation services (or.75, p.027); among users, latinos had lower utilization of individual (irr.91, p.044) and family and group (irr.88, p.044) psychotherapy. pacific islanders who received medication monitoring used services at a lower rate (irr.60, p.009) than white children. no other associations with race-ethnicity were significant.","racial-ethnic disparities in children's mental health treatment persist within systems of care. further work is necessary to understand the role of individual program components, their interactions with community characteristics, and how they might affect mental health services use.",Treatment
are calcium channel blockers independently associated with short sleep duration in hypertensive patients with obstructive sleep apnea?,"obstructive sleep apnea (osa) and hypertension (hyp) frequently coexist and have additive harmful effects on the cardiovascular system. there is also growing evidence that short sleep duration may contribute independently to poor cardiovascular outcome. the aim of this study was to evaluate the potential influence of antihypertensive medication on sleep parameters objectively measured by standard polysomnography in hypertensive patients with osa. we evaluated consecutive patients with a recent diagnosis of osa by full polysomnography (apnea hypopnea index 5 events/h) and hyp. smokers, patients with diabetes mellitus, heart failure, or using hypnotics and benzodiazepines were excluded. we evaluated 186 hypertensive patients with osa, 64 men. all patients were on at least one antihypertensive medication, including angiotensin-converting enzyme inhibitors (37), beta-blockers (35), angiotensin receptor blockers (32), diuretics (29) and calcium channel blockers (21). backward multiple regression analysis showed that age (p 0.001) and the use of calcium channel blockers (p 0.037) were the only factors inversely associated with lower total sleep time. sleep efficiency was inversely associated only with age (p 0.001), whereas the use of calcium channel blockers had a nonsignificant trend (p 0.092). use of calcium channel blockers was associated with significant reduction in total sleep time (-41 min, p 0.005) and 8 lower sleep efficiency (p 0.004). no other antihypertensive medication, including diuretics and beta-blockers, was associated with sleep impairment.",calcium channel blockers may impact negatively on sleep duration in hypertensive patients with osa. the mechanisms and significance of this novel finding warrants further investigation.,Medication
does correlation of fingerstick blood glucose measurements with glucowatch biographer glucose result in young subjects with type 1 diabetes?,"the purpose of this study was to compare measurements of glucose obtained via iontophoretic extraction with the glucowatch automatic glucose biographer (cygnus, inc., redwood city, ca) with capillary blood glucose values that were determined 1) in a controlled outpatient clinic setting and 2) in a home setting. there were 76 glucowatch biographers used on 28 different young adults (21 women and 7 men) with type 1 diabetes (age 30.9 /- 6.9 years and duration of diabetes 18.4 /- 8.1 years mean /- sd) in a controlled outpatient clinic setting. some subjects participated on multiple days. subjects wore two glucowatch biographers, each on the forearm (ventral aspect). comparisons were made to hemocue blood glucose analyzer (aktiebolgat leo, helsingborg, sweden) capillary blood glucose measurements. in addition, glucowatch biographers (one each day for 3 consecutive days) were used by 12 subjects (8 women, 4 men) in a home setting. comparisons were made to capillary blood glucose values determined using the one touch profile meter (johnson johnson, new brunswick, nj). glucowatch biographer glucose values correlated well with capillary blood glucose values determined using the hemocue analyzer in the clinic setting (r 0.90, 1,554 paired data points) and using the one touch profile meter in the home setting (r 0.85, 204 paired data points). when 36 subjects wore two biographers simultaneously, the correlation between the two biographers was r 0.94. the error grid analysis demonstrated that 96 of biographer glucose values determined in the clinic or home setting were in the clinically acceptable a and b regions.",this study confirms the accuracy and precision of glucose values as determined using the glucowatch biographer in clinic and home settings.,General
does piperine enhance the efficacy of trail-based therapy for triple-negative breast cancer cells?,"triple-negative breast cancer (tnbc) is most the aggressive type of breast cancer and is poorly responsive to endocrine therapeutics; however, one of the most attractive treatments is tumor necrosis factor-related apoptosis-inducing ligand (trail)-based therapies. to identify compounds that enhance the efficacy of trail-based therapies, we screened 55 compounds from natural products in combination with trail in tnbc cells. human tnbc cells, mda-mb-468 and mda-mb-231, and murine tnbc cells, 4t1, were used. cell viability, apoptotic cells, and cell cycle were quantified by the wst-1 assay, annexin-v/7-amino-actinomycind (7-aad) staining and propidium iodide (pi) staining, respectively. in vivo effects of piperine were evaluated in the orthotopic-inoculated 4t1-luc mouse model. after screening, we identified piperine as the most potent adjuvant at enhancing the efficacy of trail-based therapies in tnbc cells in vitro and in vivo, which might be mediated through inhibition of survivin and p65 phosphorylation.",piperine may enhance trail-based therapeutics for tnbc.,Treatment
does motor training reduce surround inhibition in the motor cortex?,"surround inhibition (si) is thought to facilitate focal contraction of a hand muscle by keeping nearby muscles silent. unexpectedly, si is reduced in skilled pianists. we tested whether repeated practice of focal contraction in non-pianists could reduce si. motor-evoked potentials were elicited by transcranial magnetic stimulation in the relaxed abductor digiti minimi randomly at the onset and 5s after offset of a 2s focal contraction (10 maximum) of the first dorsal interosseous (fdi). over 5 blocks of 40 trials participants obtained points for increasing contraction speed and stability in fdi. in a final block, the interval between contractions was varied randomly to increase attention to the task. over the first 5 blocks, si declined as performance (points scored) improved. in the final ""attention"" block si increased towards baseline without affecting performance.","although si may be useful during the early stages of learning, skilled focal finger movement does not require si to prevent activity in non-involved muscles. this could be due to better targeting of the excitatory command to move. results from the final block suggest that increased attention can re-engage si when task parameters change.",General
"are the immunosuppressive properties of the hiv vpr protein linked to a single highly conserved residue , r90?","a hallmark of aids progression is a switch of cytokines from th1 to th2 in the plasma of patients. il-12, a critical th1 cytokine secreted by antigen presenting cells (apcs) is suppressed by vpr, implicating it as an important virulence factor. we hypothesize that vpr protein packaged in the virion may be required for disabling apcs of the first infected mucosal tissues. consistent with this idea are reports that defects in the c-terminus of vpr are associated with long-term non-progression. vpr rna amplified from various sources was electroporated into monocyte-derived dc and il-12 levels in supernatants were analyzed. the analysis of previously reported c-terminal vpr mutations demonstrate that they do not alleviate the block of il-12 secretion. however, a novel single conservative amino acid substitution, r90k, reverses the il-12 suppression. analysis of 1226 vpr protein sequences demonstrated arginine (r) present at position 90 in 98.8, with other substitutions at low frequency. furthermore, none of sequences report lysine (k) in position 90. vpr clones harboring the reported substitutions in position 90 were studied for their ability to suppress il-12. our data demonstrates that none of tested substitutions other than k relieve il-12 suppression. this suggests a natural selection for sequences which suppress il-12 secretion by dc and against mutations which relieve such suppression. further analyses demonstrated that the r90k, as well as deletion of the c-terminus, directs the vpr protein for rapid degradation.","this study supports vpr as an hiv virulence factor during hiv infection and for the first time provides a link between evolutionary conservation of vpr and its ability to suppress il-12 secretion by dc. dc activated in the presence of vpr would be defective in the production of il-12, thus contributing to the prevailing th2 cytokine profile associated with progressive hiv disease. these findings should be considered in the design of future immunotherapies that incorporate vpr as an antigen.",General
"is -tocopherol bioavailability lower in adults with metabolic syndrome regardless of dairy fat co-ingestion : a randomized , double-blind , crossover trial?","increasing dietary fat intake is expected to improve -tocopherol bioavailability, which could be beneficial for improving -tocopherol status, especially in cohorts at high cardiometabolic risk who fail to meet dietary -tocopherol requirements. our objective was to assess dose-dependent effects of dairy fat and metabolic syndrome (mets) health status on -tocopherol pharmacokinetics in plasma and lipoproteins. a randomized, crossover, double-blind study was conducted in healthy and mets adults (n 10/group) who ingested encapsulated hexadeuterium-labeled (d6)-rrr--tocopherol (15 mg) with 240 ml nonfat (0.2 g fat), reduced-fat (4.8 g fat), or whole (7.9 g fat) milk before blood collection at regular intervals for 72 h. compared with healthy participants, those with mets had lower (p 0.05) baseline plasma -tocopherol (mol/mmol lipid) and greater oxidized low-density lipoprotein (ldl), interleukin (il)-6, il-10, and c-reactive protein. regardless of health status, d6--tocopherol bioavailability was unaffected by increasing amounts of dairy fat provided by milk beverages, but mets participants had lower estimated d6--tocopherol absorption (sem) than did healthy participants (26.1 1.0 compared with 29.5 1.1). they also had lower plasma d6--tocopherol auc from 0 to 72 h, as well as maximal concentrations (cmax: 2.04 0.14 compared with 2.73 0.18 mol/l) and slower rates of plasma disappearance but similar times to cmax. mets participants had lower d6--tocopherol auc from t 0-12 h (auc0- t final) in lipoprotein fractions chylomicron, very-low-density lipoprotein (vldl), ldl, high-density lipoprotein. percentages of d6--tocopherol auc0- t final in both the chylomicron (r -0.46 to -0.52) and vldl (r -0.49 to -0.68) fractions were inversely correlated with oxidized ldl, il-10, il-6, and c-reactive protein.","at dietary intakes equivalent to the recommended dietary allowance, -tocopherol bioavailability is unaffected by dairy fat quantity but is lower in mets adults, potentially because of greater inflammation and oxidative stress that limits small intestinal -tocopherol absorption and/or impairs hepatic -tocopherol trafficking. these findings support higher dietary -tocopherol requirements for mets adults. this trial was registered at www.clinicaltrials.gov as nct01787591.",Medication
is tolerance of bacteriuria after urinary diversion linked to antimicrobial peptide activity?,"to compare the cationic antimicrobial peptide gene expression profiles and urinary cationic antimicrobial activities of patients after urinary diversion according to their urinary tract infection (uti) status. ileal conduit urinary diversion joins the bacterial-tolerant ileal epithelium and intolerant urothelium. after this procedure, one quarter of patients develop repeated symptomatic utis. such development might reflect the altered innate immune mechanisms centered on epithelial expression and urinary activity of cationic antimicrobial peptides, such as defensins. ileal and ureteral biopsy specimens from ileal conduit subjects with (n 18) and without (n 18) recurrent symptomatic utis were assessed for cationic antimicrobial peptide gene expression using quantitative reverse transcriptase polymerase chain reaction. overnight urine collections were analyzed for antimicrobial activity against a laboratory escherichia coli strain, and infecting organisms were isolated from individual subjects. overall, the ureteral epithelium showed increased expression of human -defensin 5 and decreased expression of the human -defensin 1 after urinary diversion (p .05). no significant changes were seen for the ileal epithelium. the expression levels of both defensins also did not differ significantly according to uti status. urinary cationic activity against infecting bacterial isolates from the individual subjects was significantly greater in those with symptomatic uti (p .001), and the activities against the laboratory e. coli strain were similar.",the changes in the human -defensin 1 and human -defensin 5 expression profiles and the link between symptomatic infection and high urinary antimicrobial activity suggest that innate mechanisms play significant roles in balancing bacterial tolerance and killing after ileal conduit urinary diversion. future work needs to determine whether these changes can be therapeutically modulated to benefit the patients.,Medication
does yes-associated protein regulate the hepatic response after bile duct ligation?,"human chronic cholestatic liver diseases are characterized by cholangiocyte proliferation, hepatocyte injury, and fibrosis. yes-associated protein (yap), the effector of the hippo tumor-suppressor pathway, has been shown to play a critical role in promoting cholangiocyte and hepatocyte proliferation and survival during embryonic liver development and hepatocellular carcinogenesis. therefore, the aim of this study was to examine whether yap participates in the regenerative response after cholestatic injury. first, we examined human liver tissue from patients with chronic cholestasis. we found more-active nuclear yap in the bile ductular reactions of primary sclerosing cholangitis and primary biliary cirrhosis patient liver samples. next, we used the murine bile duct ligation (bdl) model to induce cholestatic liver injury. we found significant changes in yap activity after bdl in wild-type mice. the function of yap in the hepatic response after bdl was further evaluated with liver-specific yap conditional deletion in mice. ablating yap in the mouse liver not only compromised bile duct proliferation, but also enhanced hepatocyte necrosis and suppressed hepatocyte proliferation after bdl. furthermore, primary hepatocytes and cholangiocytes isolated from yap-deficient livers showed reduced proliferation in response to epidermal growth factor in vitro. finally, we demonstrated that yap likely mediates its biological effects through the modulation of survivin expression.",our data suggest that yap promotes cholangiocyte and hepatocyte proliferation and prevents parenchymal damage after cholestatic injury in mice and thus may mediate the response to cholestasis-induced human liver disease.,General
is rat pancreatic level of cystathionine -lyase regulated by glucose level via specificity protein 1 ( sp1 ) phosphorylation?,"cystathionine -lyase (cse) catalyses the endogenous production of hydrogen sulphide (h(2)s) in pancreatic beta cells, and h(2)s has been shown to inhibit insulin release from these cells. as altered pancreatic h(2)s production modulated by glucose has been previously shown, we hypothesised that the cse gene could be regulated by glucose level in insulin-secreting cells. the effects of glucose on cse protein level and mrna level were analysed in ins-1e cells. glucose effect on cse promoter activity was tested by constructing a proximal cse promoter vector including specificity protein 1 (sp1) consensus sequence. high glucose (20 mmol/l) inhibited h(2)s production in ins-1e cells and freshly isolated rat pancreatic islets. cse mrna expression, cse activity and protein abundance were also profoundly reduced by high glucose. the involvement of sp1 in basal and high-glucose-regulated cse production was demonstrated. sp1-knockdown abolished a large portion of cse production at basal glucose. phosphorylation of sp1 stimulated by high glucose was inhibited by p38 mitogen-activated protein kinase (mapk) inhibitors sb203580 and sb202190. after blocking p38 mapk phosphorylation, the inhibitive effects of high glucose on cse protein production and promoter activity in ins-1e cells were also virtually abolished.","glucose stimulates the phosphorylation of sp1 via p38 mapk activation, which leads to decreased cse promoter activity and subsequent downregulation of cse gene expression. inhibited h(2)s production through glucose-mediated cse activity and production alterations may be involved in the fine control of glucose-induced insulin secretion.",Diagnosis
do sphingosine-kinase 1 and 2 contribute to oral sensitization and effector phase in a mouse model of food allergy?,"sphingosine-1-phosphate (s1p) influences activation, migration and death of immune cells. further, s1p was proposed to play a major role in the induction and promotion of allergic diseases. however, to date only limited information is available on the role of s1p in food allergy. we aimed to investigate the role of sphingosine-kinase (sphk) 1 and 2, the enzymes responsible for endogenous s1p production, on the induction of food allergy. human epithelial colorectal caco2 cells stimulated in vitro with s1p revealed a decrease of transepithelial resistance and enhanced transport of fitc labeled ova. we studied the effect of genetic deletion of the enzymes involved in s1p production on food allergy induction using a mouse model of food allergy based on intragastrically (i.g.) administered ovalbumin (ova) with concomitant acid-suppression. wild-type (wt), sphk1(-/-) and sphk2(-/-) mice immunized with ova alone i.g. or intraperitoneally (i.p.) were used as negative or positive controls, respectively. sphk1- and sphk2-deficient mice fed with ova under acid-suppression showed reduced induction of ova specific ige and igg compared to wt mice, but had normal responses when immunized by the intraperitoneal route. flow cytometric analysis of spleen cells revealed a significantly reduced proportion of cd4() effector t-cells in both sphk deficient animals after oral sensitization. this was accompanied by a reduced accumulation of mast cells in the gastric mucosa in sphk-deficient animals compared to wt mice. furthermore, mouse mast cell protease-1 (mmcp-1) levels, an ige-mediated anaphylaxis marker, were reliably elevated in allergic wt animals.",modulation of the s1p homeostasis by deletion of either sphk1 or sphk2 alters the sensitization and effector phase of food allergy.,Medication
is helicobacter pylori gastric infection a protection factor for gastroesophageal reflux disease ?,"to know the relationship between endoscopic esophagitis and h. pylori infection. the incidence of gastric cancer and peptic ulcer disease has declined in recent years, while gerd, barrett esophagus, and distal esophageal adenocarcinoma have increased. some authors think these epidemiologic changes are related to the simultaneous decrease in h. pylori colonization. from 1997 to 1999, 192 patients underwent gastrointestinal endoscopy and detection of h. pylori (rapid urease test and/or seric antibodies and/or histologic examination and/or c13 marked urea). patients were retrospectively divided according to endoscopic diagnosis of esophagitis (savary-miller) and positivity of any h. pylori test. both groups were compared using fisher exact test and odds ratio (or) with 95 confidence intervals (ci 95). a total of 80 (40.6) were h. pylori-positive without esophagitis, and 18 (9.4) had esophagitis and h. pylori positivity (p 0.01) or 0.39 (ci 95 0.15-0.62). of the remaining 133 patients, after separating those who received treatment that could modify gerd (n 59), and 50 (37.6), were h. pylori without positive without esophagitis) 18 (13.5) had esophagitis and h. pylori positivity maintaining significance p 0.003) or 0.32 (ci 95 (-0.1)-0.8). the severity of the esophagitis (savary-miller) was compared with the presence of helicobacter pylori, but no relationship was found (p 0.3).","1) helicobacter pylori infection seems to be a protective factor for the presence of endoscopic esophagitis. 2) when esophagitis is present, the degree of damage appears to be independent of the h. pylori infection.",Prevention
"does phosphatidylinositol 4,5-bisphosphate depletion fail to affect neurosteroid modulation of gabaa receptor function?","neurosteroids and likely other lipid modulators access transmembrane sites on the gabaa receptor (gabaar) by partitioning into and diffusing through the plasma membrane. therefore, specific components of the plasma membrane may affect the potency or efficacy of neurosteroid-like modulators. here, we tested a possible role for phosphatidylinositol 4,5-bisphosphate (pip2), a phospholipid that governs activity of many channels and transporters, in modulation or function of gabaars. in these studies, we sought to deplete plasma-membrane pip2 and probe for a change in the strength of potentiation by submaximal concentrations of the neurosteroid allopregnanolone (35p) and other anesthetics, including propofol, pentobarbital, and ethanol. we also tested for a change in the behavior of negative allosteric modulators pregnenolone sulfate and dipicrylamine. we used xenopus oocytes expressing the ascidian voltage-sensitive phosphatase (ci-vsp) to deplete pip2. voltage pulses to positive membrane potentials were used to deplete pip2 in ci-vsp-expressing cells. gabaars composed of 122l and 42 subunits were challenged with gaba and 35p or other modulators before and after pip2 depletion. kv7.1 channels and nmda receptors (nmdars) were used as positive controls to verify pip2 depletion. we found no evidence that pip2 depletion affected modulation of gabaars by positive or negative allosteric modulators. by contrast, ci-vsp-induced pip2 depletion depressed kv7.1 activation and nmdar activity.","we conclude that despite a role for pip2 in modulation of a wide variety of ion channels, pip2 does not affect modulation of gabaars by neurosteroids or related compounds.",Medication
does platycodin d from platycodonis radix enhance the anti-proliferative effects of doxorubicin on breast cancer mcf-7 and mda-mb-231 cells?,"it has been demonstrated that platycodin d (pd) exhibits anti-cancer activities. this study aims to investigate the anti-proliferative effects of the combination of pd and doxorubicin (dox) on human breast cancer cells (mcf-7 and mda-mb-231 cells). the anti-proliferative effects of different dosages of pd, dox, and pd dox on mcf-7 and mda-mb-231 cells were determined by the mtt assay. the 10 m pd, 5 m dox, and 10 m pd 5 m dox induced-protein expression of apoptosis-related molecules on mcf-7 and mda-mb-231 cells were detected by western blot. the 10 m pd, 5 m dox and 10 m pd 5 m dox-induced mitochondrial membrane potential changes on mcf-7 and mda-mb-231 cells were stained with jc-1 before visual determination. the intracellular accumulations of dox, induced by 10 m pd, 5 m dox and 10 m pd 5 m dox, were detected by flow cytometry. pd enhanced anti-cancer activities of dox were observed in both mcf-7 and mda-mb-231 cell lines. compared with mono treatment, the combined treatment increased the protein expression of cleaved poly (adp-ribose) polymerase and decreased the mitochondrial membrane potential. the combined treatment with pd did not obviously increase the accumulation of dox in mcf-7 cells (1.66 0.13 in dox-treated group, and 1.69 0.06 in pd dox-treated group, p 0.76), but it significantly increased the accumulation of dox in mda-mb-231 cells (1.76 0.17 in dox-treated group, 2.09 0.02 in pd dox-treated group, p 0.027).",the combined treatment of dox and pd exhibited stronger anti-proliferative effects on mcf-7 and mda-mb-231 cells than dox and pd treatment did.,Medication
does ratio of hepatic arterial flow to recipient body weight predict biliary complications after deceased donor liver transplantation?,"adequate hepatic arterial (ha) flow to the bile duct is essential in liver transplantation. this study was conducted to determine if the ratio of directly measured ha flow to weight is related to the occurrence of biliary complications after deceased donor liver transplantation. a retrospective review of 2684 liver transplants carried out over a 25-year period was performed using data sourced from a prospectively maintained database. rates of biliary complications (biliary leaks, anastomotic and non-anastomotic strictures) were compared between two groups of patients with ha flow by body weight of, respectively, 5 ml/min/kg (n 884) and 5 ml/min/kg (n 1800). patients with a lower ratio of ha flow to weight had higher body weight (92 kg versus 76 kg; p 0.001) and lower ha flow (350 ml/min versus 550 ml/min; p 0.001). a lower ratio of ha flow to weight was associated with higher rates of biliary complications at 2 months, 6 months and 12 months (19.8, 28.2 and 31.9 versus 14.8, 22.4 and 25.8, respectively; p 0.001).",a ratio of ha flow to weight of 5 ml/min/kg is associated with higher rates of biliary complications. this ratio may be a useful parameter for application in the prevention and early detection of biliary complications.,Treatment
does variability of p-wave morphology predict the outcome of circumferential pulmonary vein isolation in patients with recurrent atrial fibrillation?,"severe atrial structural remodeling may reflect irreversible damage of the atrial tissue in patients with atrial fibrillation (af) and is associated with changes of p-wave duration and morphology. our aim was to study whether variability of p-wave morphology (pmv) is associated with outcome in patients with af after circumferential pv isolation (cpvi). 70 consecutive patients (aged 609years, 46 men) undergoing cpvi due to symptomatic af were studied. after cessation of antiarrhythmic therapy, standard 12-lead ecg during sinus rhythm was recorded for 10min at baseline and transformed to orthogonal leads. beat-to-beat p-wave morphology was subsequently defined using a pre-defined classification algorithm. the most commonly observed p-wave morphology in a patient was defined as the dominant morphology. pmv was defined as the percentage of p waves with non-dominant morphology in the 10-min sample. at the end of follow-up, 53 of 70 patients had no arrhythmia recurrence. pmv was greater in patients without recurrence (19.517.1 vs. 8.26.7, p0.001). in the multivariate logistic regression model, pmv20 (upper tertile) was the only independent predictor of ablation success (or11.4, 95 ci 1.4-92.1, p0.023). a pmv20 demonstrated a sensitivity of 41.5, a specificity of 94.1, a ppv of 96.7, and an npv of 34.0 for free of af after cpvi.",we report a significant association between increased pmv and 6-month cpvi success. pmv may help to identify patients with very high likelihood of freedom of af 6-months after cpvi.,Diagnosis
is hypertension an independent risk factor for contrast nephropathy after percutaneous coronary intervention?,"the administration of radiographic contrast agents is an important cause of acute renal failure. we hypothesised that hypertension is an independent risk factor for the development of contrast nephropathy in patients undergoing percutaneous coronary intervention. 1383 consecutive patients scheduled for elective or emergency percutaneous coronary intervention were randomly assigned to receive isotonic or half-isotonic hydration. contrast nephropathy was defined as a rise in serum creatinine of at least 44 micromol/l (0.5 mg/dl) within 48 h of the procedure. hypertension was defined as self-reported history of treated or untreated diagnosed high blood pressure. the prevalence of hypertension was 63. patients with hypertension were significantly older, were more often female, smoked less and had a higher incidence of 3-vessel disease than patients without hypertension. the estimated glomerular filtration rate was slightly lower in hypertensive patients. there was no difference in preventive hydration regimen, type and quantity of contrast medium used, or quantity of intravenous fluids given. contrast nephropathy developed in 17 of 874 hypertensive patients (2) compared to 2 of 509 patients (0.4) without hypertension (p 0.016). when contrast nephropathy was defined as a 25 rise in baseline creatinine, the disease developed in 103 patients (12) with and 36 patients (7) without hypertension (p 0.005). after adjustment for confounders, arterial hypertension remained an independent predictor of contrast nephropathy (odds ratio 4.6, 95 ci 1.0-20.5, p 0.046).",hypertension is an independent risk factor for the development of contrast nephropathy. further preventive strategies to lower the incidence of contrast nephropathy in hypertensive patients are warranted.,Treatment
is cytokine-induced beta-cell death independent of endoplasmic reticulum stress signaling?,"cytokines contribute to beta-cell destruction in type 1 diabetes. endoplasmic reticulum (er) stress-mediated apoptosis has been proposed as a mechanism for beta-cell death. we tested whether er stress was necessary for cytokine-induced beta-cell death and also whether er stress gene activation was present in beta-cells of the nod mouse model of type 1 diabetes. ins-1 beta-cells or rat islets were treated with the chemical chaperone phenyl butyric acid (pba) and exposed or not to interleukin (il)-1beta and gamma-interferon (ifn-gamma). small interfering rna (sirna) was used to silence c/ebp homologous protein (chop) expression in ins-1 beta-cells. additionally, the role of er stress in lipid-induced cell death was assessed. cytokines and palmitate triggered er stress in beta-cells as evidenced by increased phosphorylation of pkr-like er kinase (perk), eukaryotic initiation factor (eif)2alpha, and jun nh(2)-terminal kinase (jnk) and increased expression of activating transcription factor (atf)4 and chop. pba treatment attenuated er stress, but jnk phosphorylation was reduced only in response to palmitate, not in response to cytokines. pba had no effect on cytokine-induced cell death but was associated with protection against palmitate-induced cell death. similarly, sirna-mediated reduction in chop expression protected against palmitate- but not against cytokine-induced cell death. in nod islets, mrna levels of several er stress genes were reduced (atf4, bip binding protein, grp94 glucose regulated protein 94, p58, and xbp-1 x-box binding protein 1 splicing) or unchanged (chop and edem1 er degradation enhancer, mannosidase alpha-like 1).","while both cytokines and palmitate can induce er stress, our results suggest that, in contrast to lipoapoptosis, the perk-atf4-chop er stress-signaling pathway is not necessary for cytokine-induced beta-cell death.",Treatment
is cytoplasmic poly ( adenosine diphosphate-ribose ) polymerase expression predictive and prognostic in patients with breast cancer treated with neoadjuvant chemotherapy?,"poly(adenosine diphosphate-ribose) polymerase (parp) plays a key role in dna repair and cellular stress response. inhibitors of parp show promising clinical activity in metastatic, triple-negative or brca-mutated breast cancer. we investigated cytoplasmic parp (cparp) and nuclear parp (nparp) expression by immunohistochemistry in 638 pretreatment biopsies from patients on the gepartrio study and evaluated its predictive and prognostic value after neoadjuvant anthracycline/taxane-based chemotherapy. cparp expression was high in 23.7, intermediate in 50.9, and negative in 25.4 of tumors. high cparp expression was significantly correlated with nonlobular histology (p .001), undifferentiated grade (p .001), positive nodal status (p .049), and negative hormone receptor (hr) status (p .001) but not with human epidermal growth factor receptor 2 (her2) status. expression was high in 35.5 of triple-negative tumors, 24.6 of her2-positive tumors, and 18.0 of hr-positive/her2-negative tumors (p .001). pathologic complete response (pcr) rates were 26.5, 19.1, and 8.0 in patients with high, intermediate, or negative expression, respectively (p .001). this predictive effect was most prominent in hr-positive tumors (p .035) or her2-negative tumors (p .001). high cparp expression was a negative, but not independent, prognostic factor for disease-free survival (dfs; p .0025) and overall survival (os; p .0022). cparp expression was highly prognostic in patients without a pcr (dfs, p .001; os, p .001) and in patients with hr-positive tumors (dfs, p .001; os, p .001). no such correlations were found for nparp expression.","high cparp expression correlates with aggressive tumor pattern and predicts high sensitivity to neoadjuvant taxane/anthracycline-based chemotherapy but also unfavorable long-term prognosis. as a potential target for parp inhibitors, cparp-positive breast cancer might become a new, clinically relevant entity.",Medication
does interaction of monocytes with vascular smooth muscle cells regulate monocyte survival and differentiation through distinct pathways?,"vascular smooth muscle cells (vsmcs) may regulate monocyte functions within atherosclerotic lesions. we investigated the impact of vsmc/monocyte interactions on monocyte apoptosis and scavenger receptor cd36 expression, key events related to monocyte survival and differentiation. serum deprivation significantly increased thp-1 and human peripheral blood monocyte apoptosis. however, this was significantly reversed by physical binding to human vsmcs (hvsmcs). on binding to hvsmcs, antiapoptotic kinase akt and its downstream targets were phosphorylated, and bcl-2 expression was enhanced. binding-mediated suppression of apoptosis and akt phosphorylation were attenuated by a phosphoinositide 3-kinase inhibitor and also by an antibody to vascular cell adhesion molecule-1. cd36 expression was also significantly increased in thp-1 cells and in human peripheral blood monocytes after binding to hvsmcs, and this was mediated by both direct contact and soluble factors. extracellular signal-regulated kinase 1/2 (erk1/2) mitogen-activated protein kinase phosphorylation was increased in thp-1 cells after hvsmc coculture. furthermore, an erk1/2 inhibitor blocked monocyte cd36 upregulation. contact-dependent cd36 induction and erk1/2 phosphorylation in monocytes were inhibited by blocking vascular cell adhesion molecule-1 on hvsmc, whereas soluble factor-induced cd36 expression was attenuated by a monocyte chemoattractant protein-1 neutralizing antibody.",these data provide evidence of novel vsmc-dependent local regulation mechanisms for monocyte survival and differentiation in atherosclerosis.,Medication
does short term wear of high dk soft contact lenses alter corneal epithelial cell size or viability?,"current contact lenses (cls) when worn on an extended wear basis cause corneal epithelial alterations. the aim of this study was to evaluate changes in corneal epithelial cell morphology and physiology following short term (3 months) wear of highly oxygen permeable cls and to compare this with disposable cls. subjects were wearers of highly oxygen permeable cls (n11, wearing cls on a 30 night schedule), disposable cl users (n6, wearing cls on a 6 night schedule), and non-cl wearers (n20). mean cl wear experience was 3 months. epithelial cells were harvested using corneal cytology and were stained using acridine orange and ethidium bromide. epithelial cell size and viability were determined. the majority of epithelial cells recovered were non-viable (71), and the mean longest cell diameter was 38 (sd 8) microm. disposable cls caused an increase in cell size (42 (7) microm) compared with both non-wear (39 (7) microm, p0.01) and wear of highly oxygen permeable cls (37 (10) microm, p0.0049). there was no difference in cell viability between groups.",extended wear of disposable cls caused an 8 increase in cell diameter in harvested corneal epithelial cells following 3 months of cl wear. cells harvested following 3 months' wear of highly oxygen permeable cls were indistinguishable from those recovered from non-cl wearers.,General
is hypoglycemia associated with intensive care unit mortality?,"the implementation of intensive insulin therapy in the intensive care unit is accompanied by an increase in hypoglycemia. we studied the relation between hypoglycemia on intensive care unit mortality, because the evidence on this subject is conflicting. retrospective database cohort study. an 18-bed medical/surgical intensive care unit in a teaching hospital (onze lieve vrouwe gasthuis hospital, amsterdam, the netherlands). a total of 5961 patients admitted to from 2004 to 2007 were analyzed. readmissions and patients with a withholding care policy or with hypoglycemia on the first glucose measurement were excluded. patients were treated with a computerized insulin algorithm (target glucose range, 72-126 mg/dl). none. all first episodes of hypoglycemia (glucose or 45 mg/dl) were derived from 154,015 glucose values. using poisson regression, the incidence rates for intensive care unit death and incidence rate ratio comparing exposure and nonexposure to hypoglycemia were calculated. patients were considered to be exposed to hypoglycemia from the event until the end of intensive care unit admittance. we corrected for severity of disease using the daily sequential organ failure assessment score. age, sex, cardiothoracic surgery, sepsis, and diabetes mellitus were also included as possible confounders. two hundred eighty-eight (4.8) patients experienced at least one episode of hypoglycemia. median age was 68 yrs (range, 58-75 yrs), 66 were male, and 6.4 died in the intensive care unit. the incidence rate of death in patients exposed to hypoglycemia was 40 per 1000 intensive care unit days compared with 17 per 1000 intensive care unit days in patients without exposure. the adjusted incidence rate ratio for intensive care unit death was 2.1 (95 confidence interval, 1.6-2.8; p .001).","hypoglycemia is related to intensive care unit mortality, also when adjusted for a daily adjudicated measure of disease severity, indicating the possibility of a causal relationship.",Treatment
does interferon alfa induce leukocyte capillary trapping in rat retinal microcirculation?,"interferon alfa has been suggested as a possible treatment for choroidal neovascularization. however, retinal complications following interferon therapy have been reported. to evaluate the effects of interferon alfa on leukocyte dynamics in the rat retinal microcirculation. interferon alfa of different doses was intravenously administered in rats. leukocyte dynamics were observed with acridine orange digital fluorography, which uses a nuclear fluorescent dye of acridine orange and scanning laser ophthalmoscopy. this technique allows visualization of leukocyte movements in the retinal microcirculation in vivo. after interferon alfa was administered, leukocytes adhered to vascular walls and became trapped in the retinal microcirculation. leukocyte trapping was dose-dependent.","interferon alfa increased leukocyte adherence to vascular endothelium and subsequent leukocyte trapping in the retinal capillaries. interferon alfa may activate leukocytes, and activated leukocytes may be involved in the pathogenesis of microinfarction associated with interferon-induced retinopathy.",Medication
does elective resection for ongoing diverticular disease significantly improve quality of life?,"although the risks of elective resection for diverticular disease are well studied, studies on subjective improvement are scarce. this study aims to investigate subjective improvement. all patients who underwent elective resection for recurring or persisting complaints after an episode of diverticulitis were identified from an in-hospital database. patients with at least 1 year of follow-up were sent visual analogue scales (vas) to grade their quality of life (qol) and the degree of discomfort caused by abdominal pain, abnormal defecation and fatigue before and after resection. one hundred and five patients responded to the questionnaire (response rate 76.6). the median follow-up was 33 (15-53) months. elective resection improved general qol (median vas improvement 40) and reduced discomfort caused by abdominal pain (median vas improvement 60) in up to 89.3 and 87.5 of patients, respectively. the effects of elective resection are less profound for discomfort caused by abnormal defecation (77.1, median vas improvement 33) and fatigue (75.2, median vas improvement 30).","elective resection of the sigmoid for persisting or recurring symptoms after an episode of diverticulitis improves general qol and discomfort caused by abdominal pain, abnormal defecation and fatigue in the vast majority of patients.",Treatment
does pten loss predict for response to rad001 ( everolimus ) in a glioblastoma orthotopic xenograft test panel?,"hyperactivation of the phosphatidylinositol 3-kinase/akt signaling through disruption of pten function is common in glioblastoma multiforme, and these genetic changes are predicted to enhance sensitivity to mammalian target of rapamycin (mtor) inhibitors such as rad001 (everolimus). to test whether pten loss could be used as a predictive marker for mtor inhibitor sensitivity, the response of 17 serially transplantable glioblastoma multiforme xenografts was evaluated in an orthotopic therapy evaluation model. of these 17 xenograft lines, 7 have either genomic deletion or mutation of pten. consistent with activation of akt signaling, there was a good correlation between loss of pten function and elevated levels of akt phosphorylation. however, of the 7 lines with disrupted pten function, only 1 tumor line (gbm10) was significantly sensitive to rad001 therapy (25 prolongation in median survival), whereas 1 of 10 xenograft lines with wild-type pten was significantly sensitive to rad001 (gs22; 34 prolongation in survival). relative to placebo, 5 days of rad001 treatment was associated with a marked 66 reduction in the mib1 proliferation index in the sensitive gbm10 line (deleted pten) compared with a 25 and 7 reduction in mib1 labeling index in the insensitive gbm14 (mutant pten) and gbm15 (wild-type pten) lines, respectively. consistent with a cytostatic antitumor effect, bioluminescent imaging of luciferase-transduced intracranial gbm10 xenografts showed slowed tumor growth without significant tumor regression during rad001 therapy.",these data suggest that loss of pten function is insufficient to adequately predict responsiveness to mtor inhibitors in glioblastoma multiforme.,Treatment
is the nuclear-factor kappab pathway activated in pterygium?,"pterygium is a prevalent ocular surface disease with unknown pathogenesis. the authors investigated the role of nuclear factor kappa b (nf-b) transcription factors in pterygium. surgically excised primary pterygia were studied compared with uninvolved conjunctiva tissues. nf-b activation was evaluated using western blot analysis, elisa, and dna-binding assays. primary pterygium fibroblasts were treated with tnf- (20 ng/ml), and nf-b activation was evaluated using immunocytochemistry, western blot analysis, phospho-ib elisa, and dna-binding assays. tnf- stimulation of nf-b target genes relb, nfkb2, rantes, mcp-1, ena-78, mmp-1, mmp-2, and mmp-3 in pterygium fibroblasts was compared with that in primary tenon fibroblasts by real-time pcr. phosphorylation of ib (ser32) was increased in pterygia tissues compared with uninvolved conjunctiva tissues, as determined by western blot analysis and elisa. ib expression was decreased, whereas nuclear rela and p50 dna-binding capacities were increased. within 30 minutes of treatment with tnf-, pterygium fibroblasts showed increased ib phosphorylation and nuclear translocation of rela and p50. treatment with tnf- beyond 12 hours resulted in increased nuclear expression of relb, p100, and p52. furthermore, the upregulation of rantes, mcp-1, ena-78, mmp-1, mmp-2, and mmp-3 expression was more pronounced in tnf--treated pterygium fibroblasts than in tenon fibroblasts.",the nf-b pathway is shown for the first time to be activated in pterygia tissues compared with normal conjunctiva tissues. stimulation by the inflammatory cytokine tnf- can activate both canonical and noncanonical nf-b pathways in pterygium fibroblasts with concomitant upregulation of nf-b target genes.,Treatment
is introgression of apomixis into sexual species inhibited by mentor effects and ploidy barriers in the ranunculus auricomus complex?,"apomictic plants maintain functional pollen, and via pollination the genetic factors controlling apomixis can be potentially transferred to congeneric sexual populations. in contrast, the sexual individuals do not fertilize apomictic plants which produce seeds without fertilization of the egg cells. this unidirectional introgressive hybridization is expected finally to replace sexuality by apomixis and is thought to be a causal factor for the wide geographical distribution of apomictic complexes. nevertheless, this process may be inhibited by induced selfing (mentor effects) of otherwise self-incompatible sexual individuals. here whether mentor effects or actual cross-fertilization takes place between diploid sexual and polyploid apomictic cytotypes in the ranunculus auricomus complex was tested via experimental crosses. diploid sexual mother plants were pollinated with tetra- and hexaploid apomictic pollen donators by hand, and the amount of well-developed seed compared with aborted seed was evaluated. the reproductive pathways were assessed in the well-developed seed via flow cytometric seed screen (fcss). the majority of seed was aborted; the well-developed seeds have resulted from both mentor effects and cross-fertilization at very low frequencies (1.3 and 1.6 of achenes, respectively). pollination by 4x apomictic pollen plants results more frequently in cross-fertilization, whereas pollen from 6x plants more frequently induced mentor effects.","it is concluded that introgression of apomixis into sexual populations is limited by ploidy barriers in the r. auricomus complex, and to a minor extent by mentor effects. in mixed populations, sexuality cannot be replaced by apomixis because the higher fertility of sexual populations still compensates the low frequencies of potential introgression of apomixis.",Diagnosis
does insulin sensitivity at childhood predict changes in total and central adiposity over a 6-year period?,"to examine the associations of insulin resistance at childhood with adiposity changes over a 6-year period (from 9 to 15 years) in a sample of 659 swedish and estonian children (52.7 girls) participating in the european youth heart study. we measured weight, height, waist circumference, biceps, triceps, subscapular, suprailiac, and medial calf skinfolds, and we calculated body mass index (bmi), sum of five skinfolds, and body fat percentage. fasting plasma glucose and insulin were measured and homeostasis model assessment of insulin resistance (homa-ir) was calculated. changes in puberty stage, sex, centre and the corresponding baseline adiposity values were used as confounders in all analysis. homa-ir at childhood was significantly and positively associated with changes in bmi (0.265; p0.024), sum of five skinfolds (0.3445; p0.003), body fat percentage (1.042; p0.016) and waist circumference (0.806; p0.002) from childhood to adolescence. these relationships persisted when overweight children were excluded from the analysis. bmi, sum of five skinfolds, body fat percentage and waist circumference at childhood were not significantly associated with changes in homa-ir (p for all 0.1).",these results give further support to the concept that lower insulin sensitivity at childhood may predict subsequent total and central adiposity gain at adolescence. these findings enhance the role of insulin sensitivity as a target of obesity prevention already from the first decades of life.,Medication
does emotional considerations and attending involvement ameliorate organ donation in brain dead pediatric trauma victims?,"the purpose of this study was to ascertain a strategy for maximizing parental consent for organ donation in traumatically injured children suffering from brain death. our hypothesis was that appropriate attending surgeon involvement and delay in evaluating children for brain death leads to an increased percentage of organ donors. from january 1993 to august 1999, the records of all children who died in a level i trauma center were evaluated. those children suffering brain death that were suitable for organ donation were entered into the study. cases were reviewed for patient demographics, time to entry into brain death protocol (measured from time of admission), time to parent notification about brain death (measured from time of admission), specific attending involved in the case (with level of involvement), and success of organ donation request. in all, 43 charts were reviewed. of 43 deaths, 33 were deemed suitable for donation. age of suitable donors ranged from 1 month to 18 years. in all, 11 attending physicians were involved in the care of these children. overall, 20 of 33 were organ donors (60). when the attending surgeon was involved, donation success for organ retrieval was 86, whereas if the attending was not involved personally, the success rate dropped to 23 (p 0.04). one senior pediatric surgeon obtained a success rate of 12 of 12 children. it was this surgeon's policy to not initiate brain death protocols in children immediately on entry into the emergency room, but rather to delay initiation until family could be gathered and spend time with the affected child in order that the family could recover from the initial shock of trauma (always at least overnight). when time to initiation of brain death protocol was examined, success was obtained when a delay of 15.5 hours was respected, versus 7.0 hours when donation was requested but denied (p 0.03).",these data indicate that attending involvement is important when parents of brain dead children are asked about organ retrieval (p 0.04). delay in initiating brain death protocols in order for family members to deal with the shock of the initial trauma appears to increase willingness to participate in organ donation.,General
does cumulative hypoxemia during sleep predict vascular endothelial dysfunction in patients with sleep-disordered breathing?,"sleep-disordered breathing (sdb) is associated with repeated intermittent hypoxemia, and it is known as one of the risk factors for cardiovascular diseases. previous studies assessing the effects of frequency and depth of hypoxemia on cardiovascular diseases have shown conflicting results. the aim of the current study was to clarify what sdb-related parameters most predict endothelial dysfunction to better understand the pathogenesis of endothelial dysfunction in patients with sdb. we conducted polysomnography (psg) and measured flow-mediated vasodilation response (fmd) in 50 outpatients suspected of sdb. evaluated indices included: apnea-hypopnea index (ahi), 3 oxygen desaturation index (3odi), averaged arterial oxygen saturation (averaged spo2), lowest arterial oxygen saturation (lowest spo2), ratio of arterial oxygen saturation 90 (spo2 90), and averaged time desaturation summation index (tds: 100-averaged spo2 total sleep time). significant differences were observed only in the tds between the first and third (p 0.03) and between the first and forth (p 0.04) quartile groups, stratified by fmd. the fmd showed a significant relationship with tds ( -0.47, p 0.001), even after adjusting for confounding factors ( -0.33, p 0.02). in contrast, ahi, 3odi, averaged spo2, lowest spo2, and spo2 90 showed no significant relationships.","this study shows the validity of tds in predicting endothelial damage in patients with sdb. cumulative hypoxemia, rather than the frequency of hypoxemic events presented as ahi, may be a greater contributing factor in causing endothelial dysfunction. a simple index like tds may be a useful and novel indicator of the influence of sdb on the vasculature.",Symptoms
does direct contact with endoderm-like cells efficiently induce cardiac progenitors from mouse and human pluripotent stem cells?,"pluripotent stem cell-derived cardiac progenitor cells (cpcs) have emerged as a powerful tool to study cardiogenesis in vitro and a potential cell source for cardiac regenerative medicine. however, available methods to induce cpcs are not efficient or require high-cost cytokines with extensive optimization due to cell line variations. based on our in-vivo observation that early endodermal cells maintain contact with nascent pre-cardiac mesoderm, we hypothesized that direct physical contact with endoderm promotes induction of cpcs from pluripotent cells. to test the hypothesis, we cocultured mouse embryonic stem (es) cells with the endodermal cell line end2 by co-aggregation or end2-conditioned medium. co-aggregation resulted in strong induction of flk1() pdgfra() cpcs in a dose-dependent manner, but the conditioned medium did not, indicating that direct contact is necessary for this process. to determine if direct contact with end2 cells also promotes the induction of committed cardiac progenitors, we utilized several mouse es and induced pluripotent (ips) cell lines expressing fluorescent proteins under regulation of the cpc lineage markers nkx2.5 or isl1. in agreement with earlier data, co-aggregation with end2 cells potently induces both nkx2.5() and isl1() cpcs, leading to a sheet of beating cardiomyocytes. furthermore, co-aggregation with end2 cells greatly promotes the induction of kdr() pdgfra() cpcs from human es cells.","our co-aggregation method provides an efficient, simple and cost-effective way to induce cpcs from mouse and human pluripotent cells.",Medication
is vaginal lubrication after cervicovaginal stimulation facilitated by phosphodiesterase type 5 inhibition in ovariectomized mice?,"nitric oxide synthases (noss) and estrogen receptors are expressed in the vagina. we aimed to assess the impact of sildenafil on vaginal lubrication according to the hormonal status and to determine the role of the neuronal isoform of nos (nnos). four-week-old c57/bl6 female mice were sham operated or ovariectomized. at 10 weeks of age, they were injected intraperitoneally by any combination of sildenafil, 7-nitroindazole (7-ni)--a potent selective nnos inhibitor--or the corresponding vehicles. vaginal lubrication was induced in a physiological manner by cervical vaginal probing and quantified depending on the hormonal and pharmacological conditions. the animals were then sacrificed for vaginal histomorphometry. the main outcome measure is the quantification of vaginal transudate after cervicovaginal stimulation and vaginal histomorphometry. sildenafil increased cervicovaginal probing-induced vaginal lubrication in ovariectomized and sham-operated animals. ovariectomized mice exhibited decreased vaginal lubrication as compared with sham-operated mice. when taking into account the presence of severe vaginal atrophy, a threefold increase in transudate per gram of vagina wet weight was revealed in ovariectomized animals. castration markedly reduced the thickness of the vaginal wall. nnos inhibition by 7-ni had no impact on vaginal lubrication.","irrespective of the hormonal status, sildenafil increased vaginal lubrication. the vaginal effect of sildenafil was independent of the nnos pathway and more pronounced in ovariectomized animals.",Medication
is echocardiographic epicardial fat thickness related to altered blood pressure responses to exercise stress testing?,"hypertensive response at peak exercise and blunted blood pressure (bp) recovery, altered bp responses obtained from exercise stress testing, have been suggested as risk factors for future onset of hypertension in previous studies. epicardial fat, a new cardiometabolic risk factor, has been linked to hypertension in some recent studies. in this study, we tested the primary hypothesis suggesting that the epicardial fat thickness (eft) is related to altered bp responses to treadmill exercise testing. we also evaluated the sensitivity and specificity of the eft as a predictor of hypertensive response to peak exercise. normotensive subjects underwent to treadmill stress testing and transthoracic echocardiography. hypertensive response to peak treadmill exercise testing was defined as 210/105 mmhg and 190/105 mmhg at peak exercise in males and females, respectively. bp recovery index (bpri) was defined as the ratio of the bp at the 3rd minute of the recovery phase to bp at peak exercise. eft was measured by echocardiography. thirty-two subjects with hypertensive response to peak exercise constituted group 1 and 48 subjects with normal response constituted group 2. the mean eft of subjects in group 1 was significantly higher (8.2 1.1 mm vs 5.1 1.5 mm; p 0.0001) than subjects in group 2. in correlation analysis performed in group 1, eft was found to be significantly correlated with bpri (r 0.51, p 0.003). an eft of 6.5 mm predicted the hypertensive response to peak exercise test with 68.8 sensitivity and 87.5 specificity (receiving operator characteristic area under curve: 0.879, 95 ci 0.793-0.965, p 0.001). patients with eft 6.5 mm showed a significantly increased bpri (0.89 0.07 vs 0.74 0.09, p 0.0001) and peak systolic bp (198.4 15.3 mmhg vs 169.4 19.8 mmhg, p 0.0001). there were significant differences in metabolic equivalents, maximum heart rate, homeostatic model assessment of insulin resistance, high-density lipoprotein-cholesterol, waist circumference and age values between two patients groups dichotomized according to the cut-off value of eft. bpri was the only independent variable related to eft in the multivariate analysis (odds ratio 1.4, 95 ci 2.75-7.16, p 0.001).",eft was found to be related to altered bp responses to exercise stress testing. the echocardiographic measurement of eft may serve as a useful non-invasive indicator of heightened risk of future hypertension.,Prevention
do learners favour high resolution oesophageal manometry with better diagnostic accuracy over conventional line tracings?,"high resolution manometry (hrm) provides a colourful representation of oesophageal motility. novice and intermediate learners were tested to compare hrm clouse plots and conventional manometry for accuracy, ease of interpretation and knowledge retention. 36 learners evaluated 60 randomised motility sequences (30 hrm clouse plots with corresponding line tracings) 4 months apart, following a tutorial. learners rated prior knowledge of oesophageal pathophysiology and manometry and scored ease and speed of interpretation on 10 cm visual analogue scales (vas). understanding of oesophageal pathophysiology was low in all cohorts (2.90.4 on vas) and knowledge of hrm and conventional motility studies was even lower (1.90.4 and 1.80.3, respectively, pns). after the tutorial, diagnostic accuracy was significantly higher with hrm clouse plots than with line tracings (p0.001). hrm gains in diagnostic accuracy were evident over line tracings (43.1), particularly with aperistalsis (36.1), oesophageal body hypomotility (25.8) and relaxation of the lower oesophageal sphincter (21.0) (p0.001 for each comparison); these were maintained at the second evaluation. gains were independent of academic level (f0.56, p0.5) and did not correlate with prior experience of learners (r-0.18, p0.29). learners favoured hrm clouse plots (80.6) over line tracings and reported faster interpretation (94.4).","hrm clouse plots provide ease of interpretation that translates into higher diagnostic accuracy and better knowledge retention in novice and intermediate learners of oesophageal manometry. these results implicate the value of pattern recognition in hrm interpretation, irrespective of academic level and prior understanding of oesophageal motor function.",Diagnosis
does an icu preanesthesia evaluation form reduce missing preoperative key information?,"a comprehensive preoperative evaluation is critical for providing anesthetic care for patients from the intensive care unit (icu). there has been no preoperative evaluation form specific for icu patients that allows for a rapid and focused evaluation by anesthesia providers, including junior residents. in this study, a specific preoperative form was designed for icu patients and evaluated to allow residents to perform the most relevant and important preoperative evaluations efficiently. the following steps were utilized for developing the preoperative evaluation form: 1) designed a new preoperative form specific for icu patients; 2) had the form reviewed by attending physicians and residents, followed by multiple revisions; 3) conducted test releases and revisions; 4) released the final version and conducted a survey; 5) compared data collection from new icu form with that from a previously used generic form. each piece of information on the forms was assigned a score, and the score for the total missing information was determined. the score for each form was presented as mean standard deviation (sd), and compared by unpaired of 52 anesthesiologists (19 attending physicians, 33 residents) responding to the survey, 90 preferred the final new form; and 56 thought the new form would reduce perioperative risk for icu patients. forty percent were unsure whether the form would reduce perioperative risk. over a three month period, we randomly collected 32 generic forms and 25 new forms. the average score for missing data was 23 10 for the generic form and 8 4 for the new form (p 2.58e-11).",a preoperative evaluation form designed specifically for icu patients is well accepted by anesthesia providers and helped to reduce missing key preoperative information. such an approach is important for perioperative patient safety.,Medication
does vein wall remodeling after deep vein thrombosis involve matrix metalloproteinases and late fibrosis in a mouse model?,"deep venous thrombosis (dvt) confers vein wall injury associated with fibrosis and extracellular matrix (ecm) turnover, likely mediated by matrix proteases. this study investigated the expression of proteases and collagen involved in early vein wall remodeling. in the mouse, dvt was produced by ligation of the infrarenal inferior vena cava (ivc) or sham operation, and tissue was harvested at 4, 8, and 12 days. the vein wall tissue was processed for real-time reverse transcriptase-polymerase chain reaction (6 to 8 per time point), western immunoblotting (5 per time point), and gelatin zymography (5 per time point). analysis of variance was used for multiple comparisons, and a p .05 was significant. thrombus resolution was documented by a 38 decrease in the thrombosed ivc weight from day 4 to day 12 (p .007). total vein wall collagen increased over time, with a corresponding increase in procollagen i and iii, and expression peaked at 12 days (24-fold and 6.1-fold, respectively, p .02). matrix metalloproteinase-2 (mmp-2) gene expression was 23-fold greater at 12 days after thrombus formation compared with sham or 4 days after thrombosis (p .05). total mmp-2 activity was also significantly elevated at 12 days compared with sham (p .05). mmp-9 expression was 19-fold and 27-fold higher at days 4 and 8, respectively, relative to sham (p .05), with no difference in activity. mmp-14 expression was twofold to 3.6-fold greater at day 12 compared with earlier time points and shams (p .001), but no differences in protein levels were found. urokinase-type plasminogen activator (upa) and plasminogen activator inhibitor-1 (pai-1) protein levels were not significantly different from sham over time; however, the ratio of upa to pai-1 was decreased through 8 days.","vein wall remodeling after dvt is similar to wound healing and is associated with increased procollagen gene expression and total collagen. it is also associated with increased early mmp-9 expression, followed by mmp-2 expression and activity after dvt resolution.",Medication
does exogenous l-arginine affect angiotensin ii-induced renal vasoconstriction in man?,"it has been suggested that provision of the substrate of nitric oxide (no) synthesis, l-arginine, might influence the effects of renal vasoconstrictors. we have therefore studied the effects of pretreatment or concomitant administration of l-arginine on angiotensin ii (ang ii)-increased renovascular resistance. the study was conducted in a double-blind, randomized, cross-over design. eight healthy subjects were assigned to placebo or a continuous intravenous coinfusion of ang ii (5.0 ng kg-1 min-1, infusion period 75 min) with l-arginine (17 mg kg-1 min-1, infusion period 30 min). nine further subjects received a continuous infusion of ang ii with or without pretreatment of l-arginine. changes in renal plasma flow (rpf) were estimated by the steady state clearance of pah. l-arginine alone increased rpf to 110 /- 10 over baseline (p 0.003). the ang ii-induced decrease in rpf was not affected by pretreatment or coinfusion of l-arginine.","our results demonstrate that a counterregulatory response of the renal vasculature to high levels of ang ii does not depend on exogenous l-arginine. in healthy subjects, this lack of functional antagonism at the renal vasculature is therefore not a result of no substrate availability.",Medication
do chromosome 9p deletions identify an aggressive phenotype of clear cell renal cell carcinoma?,"the authors investigated whether deletion of chromosome 9p in clear cell renal cell carcinoma (ccrcc) predicted worse disease-specific survival (dss) and recurrence-free survival (rfs) and whether it was associated with more aggressive behavior in small renal masses. in total, 703 ccrcc tumors were analyzed using fluorescence in situ hybridization (316 tumors) and cytogenetics (388 tumors). tumor grade, classification, and size; 9p status; eastern cooperative oncology group performance status (ecog ps); lymph node involvement; and the presence of metastasis were recorded. outcomes were stratified by 9p status, and a cox proportional hazards models was constructed using tnm staging, ecog ps, tumor size, tumor grade, and 9p status. deletions of 9p were detected in 97 tumors (13.8). at presentation, 9p-deleted tumors were larger and were more likely to be high grade (grade 3 or 4), to have a high tumor (t) classification (t3-t4), and to have lymph node or distant metastases (p .01). the median dss for patients with and without 9p deletions was 37 months and 82 months, respectively (p .01). in patients with localized disease, the median rfs in those who had 9p deletions was 53 months and was not reached in those without 9p deletions (p .01). in patients who had localized lesions that measured 4 cm in greatest dimension, 9p-deleted tumors were more likely to recur (19 vs 2; p .01).","deletion of chromosome 9p in ccrcc occurred in 14 of patients and was associated with higher grade and t classification, and the presence of lymph node and distant metastases. in addition, 9p deletion independently conferred a worse prognosis for patients with localized ccrcc, and most noteworthy, in patients with localized, small renal masses. preoperatively identifying patients with 9p deletions will improve risk stratification and will help to select appropriate patients for surveillance protocols or aggressive treatment.",General
is intracavernous alprostadil alfadex ( edex/viridal ) effective and safe in patients with erectile dysfunction after failing sildenafil ( viagra )?,"sildenafil (viagra), an oral treatment for erectile dysfunction, has proved popular since its introduction in 1998. however, not all patients respond to this form of therapy. consequently, this study investigated the efficacy of intracavernous alprostadil alfadex (edex/viridal) treatment in patients not responding to sildenafil. in an open-label, multicenter study, patients with erectile dysfunction were treated with sildenafil for 4 weeks. the initial dose was 50 mg, which was increased to 100 mg if no response was achieved. patients not responding to treatment, measured using the international index of erectile function (iief) questionnaire, entered an alprostadil alfadex in-office titration phase, to determine the optimal dose, up to 40 microgram. a 6-week alprostadil alfadex at-home treatment phase followed. in 67 patients who did not respond satisfactorily to sildenafil, the alprostadil alfadex at-home therapy resulted in improvements in questions 3 and 4 of the iief in 60 (89.6) and 57 (85.1) patients, respectively. the mean improvement in iief score for these patients was 2.75 and 2.63 for questions 3 and 4, respectively. the most common side effect was penile pain in 25 (29. 4) of 85 patients treated with alprostadil alfadex in-office and at home.",alprostadil alfadex therapy can be used effectively and safely in men who fail initial therapy with sildenafil.,Symptoms
does use of an image acquisition stabilizer improve sidestream dark field imaging of the serosa during open gastrointestinal surgery?,to investigate whether an image acquisition stabilizer (ias) mounted on the sidestream dark field camera (sdf) during gastrointestinal surgery improves image stability and acquisition. serosal sdf imaging was compared with sdf imaging combined with an ias (sdf ias) during gastrointestinal surgery. stability was assessed as the image drift in pixels and the time to obtain stable images. the success rate was determined as the percentage of analyzable images after recording. the effect of negative pressure from the ias was determined during single-spot measurements and by comparing microvascular parameters between groups. data are presented as mean sd. sixty serosal measurements were performed per group; 87 were successful in the sdf group and 100 in the sdf ias group (p 0.003). image drift in the sdf group was 148 36 versus 55 15 pixels in the sdf ias group; p 0.001. time to stable image was 96 60 s in the sdf group versus 57 31 s in the sdf ias group; p 0.03. no effect of negative pressure was seen.,the use of an ias mounted on an sdf camera during serosal microvascular assessment improves the success rate of image acquisition and stability and reduces the time to stable image with no effect on the microcirculation.,Treatment
does nerve growth factor prevent both neuroretinal programmed cell death and capillary pathology in experimental diabetes?,"chronic diabetes causes structural changes in the retinal capillaries of nearly all patients with a disease duration of more than 15 years. acellular occluded vessels cause hypoxia, which stimulates sight-threatening abnormal angiogenesis in 50 of all type i diabetic patients. the mechanism by which diabetes produces acellular retinal capillaries is unknown. in this study, evidence of programmed cell death (pcd) was sought in the retinas of early diabetic rats, and the effect of nerve growth factor (ngf) on pcd and capillary morphology was evaluated. diabetes induced pcd primarily in retinal ganglion cells (rgc) and muller cells. this was associated with a transdifferentiation of muller cells into an injury-associated glial fibrillary acidic protein (gfap)-expressing phenotype, and an up-regulation of the low-affinity ngf receptor p75ngfr on both rgc and muller cells. ngf treatment of diabetic rats prevented both early pcd in rgc and muller cells, and the development of pericyte loss and acellular occluded capillaries.","these data provide new insight into the mechanism of diabetic retinal vascular damage, and suggest that ngf or other neurotrophic factors may have potential as therapeutic agents for the prevention of human diabetic retinopathy.",Prevention
do neutralizing antibodies induced by cell culture-derived hepatitis c virus protect against infection in mice?,"hepatitis c virus (hcv) infection is a major cause of liver cancer, so strategies to prevent infection are needed. a system for cell culture of infectious hcv particles (hcvcc) has recently been established; the inactivated hcvcc particles might be used as antigens in vaccine development. we aimed to confirm the potential of hcvcc as an hcv particle vaccine. hcvcc derived from the j6/jfh-1 chimeric genome was purified from cultured cells by ultrafiltration and ultracentrifugation purification steps. purified hcv particles were inactivated and injected into female balb/c mice with adjuvant. sera from immunized mice were collected and their ability to neutralize hcv was examined in naive huh7.5.1 cells and urokinase-type plasminogen activator-severe combined immunodeficiency mice (upa(/)-scid mice) given transplants of human hepatocytes (humanized livers). antibodies against hcv envelope proteins were detected in the sera of immunized mice; these sera inhibited infection of cultured cells with hcv genotypes 1a, 1b, and 2a. immunoglobulin g purified from the sera of hcv-particle-immunized mice (ihcv-igg) inhibited hcv infection of cultured cells. injection of igg from the immunized mice into upa(/)-scid mice with humanized livers prevented infection with the minimum infectious dose of hcv.","inactivated hcv particles derived from cultured cells protect chimeric liver upa(/)-scid mice against hcv infection, and might be used in the development of a prophylactic vaccine.",Medication
does antidepressant stimulation of cdp-diacylglycerol synthesis require monoamine reuptake inhibition?,"recent studies demonstrate that diverse antidepressant agents increase the cellular production of the nucleolipid cdp-diacylglycerol and its synthetic derivative, phosphatidylinositol, in depression-relevant brain regions. pharmacological blockade of downstream phosphatidylinositide signaling disrupted the behavioral antidepressant effects in rats. however, the nucleolipid responses were resistant to inhibition by serotonin receptor antagonists, even though antidepressant-facilitated inositol phosphate accumulation was blocked. could the neurochemical effects be additional to the known effects of the drugs on monoamine transmitter transporters? to examine this question, we tested selected agents in serotonin-depleted brain tissues, in pc12 cells devoid of serotonin transporters, and on the enzymatic activity of brain cdp-diacylglycerol synthase - the enzyme that catalyzes the physiological synthesis of cdp-diacylglycerol. imipramine, paroxetine, and maprotiline concentration-dependently increased the levels of cdp-diacylglycerol and phosphatidylinositides in pc12 cells. rat forebrain tissues depleted of serotonin by pretreatment with p-chlorophenylalanine showed responses to imipramine or maprotiline that were comparable to respective responses from saline-injected controls. with fluoxetine, nucleolipid responses in the serotonin-depleted cortex or hippocampus were significantly reduced, but not abolished. each drug significantly increased the enzymatic activity of cdp-diacylglycerol synthase following incubations with cortical or hippocampal brain tissues.","antidepressants probably induce the activity of cdp-diacylglycerol synthase leading to increased production of cdp-diacylglycerol and facilitation of downstream phosphatidylinositol synthesis. phosphatidylinositol-dependent signaling cascades exert diverse salutary effects in neural cells, including facilitation of bdnf signaling and neurogenesis. hence, the present findings should strengthen the notion that modulation of brain phosphatidylinositide signaling probably contributes to the molecular mechanism of diverse antidepressant medications.",Medication
does in utero undernutrition reduce diabetes incidence in non-obese diabetic mice?,"observational studies in humans suggest that low birthweight may decrease the risk of type 1 diabetes, but the mechanism is unknown. we hypothesised that antenatal undernutrition would decrease the incidence of type 1 diabetes in non-obese diabetic (nod) mice. a 40 restriction of energy intake was applied to pregnant nod dams from day 12.5 to day 18.5 of gestation, resulting in intrauterine growth retardation of offspring. all mice were fed a standard diet after weaning. control and undernourished female offspring were followed to assess diabetes incidence. male nod mice were treated with cyclophosphamide to accelerate development of diabetes. glucose homeostasis, body composition and pancreatic histology were compared in control and undernourished offspring. mean birthweight was lower in undernourished than in control mice (p 0.00003). at 24 weeks of age, the cumulative incidence of spontaneous diabetes in female mice was 73 in control and 48 in undernourished mice (p 0.003). in cyclophosphamide-treated male mice, antenatal undernutrition also tended to reduce the development of diabetes (p 0.058). maternal leptin levels were lower in undernourished dams on day 18.5 of pregnancy (p 0.039), while postnatal leptin levels were significantly higher in undernourished offspring at 4, 20 and 27 weeks of life (p 0.05). beta cell mass was similar in both groups (control 0.4 mg; undernourished 0.54 mg; p 0.24). histological evidence of apoptosis at 20 weeks was greater in control than in undernourished mice (control 6.3 /- 1.4; undernourished 4.2 /- 0.3, p 0.05).","antenatal undernutrition reduces the incidence of diabetes in nod mice, perhaps via alterations in apoptosis.",Prevention
do the combination of external high-frequency oscillation and pressure support ventilation in acute respiratory failure?,"effective gas exchange can be maintained in animals by using external high-frequency oscillation (ehfo). the present study evaluates the effect of relatively long-term duration ehfo combined with pressure support ventilation (psv) in patients with acute respiratory failure. twelve patients were ventilated with ehfo combined with psv for 8 h at 60 oscillations.min-1, with a cuirass pressure of 36 cm h2o: -26 to 10 cm h2o (27 mm hg: -19.5 to 7.5 mm hg) and an inspiratory-to-expiratory ratio of 1:1. blood gas values and hemodynamic parameters were measured. significant increases were noted in cardiac index (3.0 /- 0.7 to 3.2 /- 0.7 1.min-1.m-2, p 0.05) and stroke volume index (32 /- 14 to 35 /- 13 ml.m-2, p 0.05) without changes in pulmonary artery wedge pressure at 1 h after ehfo. pao2 (kpa)/fio2 and paco2 improved from 21.9 /- 7.5 to 26.8 /- 8.0 (p 0.05) at 2 h and from 6.9 /- 1.7 to 6.1 /- 0.9 (p 0.01) at 30 min after ehfo, respectively. breath sounds could be heard well throughout the lung fields after institution of ehfo. the mucous rales also decreased.","as a method of ventilation for patients with acute respiratory failure, ehfo combined with psv may have potential advantages over conventional mechanical ventilation when drainage of secretions if facilitated. beneficial effects of ehfo may appear after several hours.",General
does results of a pilot study with a signal enhancement algorithm for hire 120 cochlear implant users?,"cochlear implant users still experience severe limitations regarding sound quality, music appreciation, and speech perception in adverse listening situation. to improve hearing in noisy environments, the incorporation of signal enhancement algorithms was initiated. the study group consisted of 13 postlingually deafened adults using hires 120. participants were fitted with 2 versions of the noise reduction algorithm: a moderate and a strong setting. in an immediate session, the hsm sentence test in speech-shaped noise was administered using the clinical program as well as both noise reduction programs. participants were asked to try all 3 programs in everyday listening situations at home and provide a rating of sound quality and speech perception via a questionnaire (abbreviated profile of hearing aid benefit). during the fitting, no difficulties were encountered, and all participants accepted the noise reduction programs without any acclimatization. all participants achieved better results with both noise reduction programs in the hsm sentence test in noise compared with the clinical program. group mean speech perception scores were highly significantly better for the clearvoice settings compared with the clinical program score. the majority preferred one of the clearvoice conditions, with 4 participants for the strong and 3 for the moderate setting.","our results demonstrate a real potential benefit for noise reduction algorithms in cochlear implant processors. although algorithm parameters were not optimized individually, a significant improvement could still be achieved. further investigation is required to develop fitting guidelines and achieve parameter optimization.",Medication
are energy intake adaptations to acute isoenergetic active video games and exercise similar in obese adolescents?,"although the impact of passive video games (pvgs) on energy intake has been previously explored in lean adolescents, data are missing on the nutritional adaptations to passive and active video games (avgs) in obese adolescents. it is also unknown whether isoenergetic avgs and exercise (ex) differently affect food consumption in youth. nineteen obese adolescent boys (12-15 years old) had to complete four 1-hour sessions in a crossover manner: control (con; sitting on a chair), pvg (boxing game on xbox 360), avg (boxing game on xbox kinect 360) and ex (cycling). the ex was calibrated to generate the same energy expenditure as the avg session. energy expenditure was measured using a k4b2 portable indirect calorimeter. ad libitum food intake (buffet-style meal) and appetite sensations (visual analogue scales) were assessed after the sessions. as expected, mean energy expenditure was similar between avg (3704 kcal) and ex (3583 kcal), both of which were significantly higher than pvg (1257 kcal) and con (985 kcal) (p0.001). however, ad libitum food intake after the sessions was not significantly different between con (1174282 kcal), pvg (1124281 kcal), avg (1098265 kcal) and ex (1091290 kcal). likewise, the energy derived from fat, carbohydrate and protein was not significantly different between sessions, and appetite sensations were not affected.","energy intake and food preferences after an hour of avg or pvg playing remain unchanged, and isoenergetic sessions of avg and ex at moderate intensity induce similar nutritional responses in obese adolescent boys.",Prevention
is the voice of the patients : allergic rhinitis a trivial disease?,"patient and physician perspectives on the impact of allergic rhinitis have previously been studied in the general population. we evaluated the burden of allergic rhinitis among patients from the members of european allergy patient organizations. the patient voice allergy survey was a quantitative, self-completion survey of 3562 patients with allergic rhinitis (16 years and older). background information on allergic rhinitis, severity of allergic rhinitis symptoms and their impact on lives, nonmedical measures for relieving of symptoms, types of medications, and concomitant conditions were evaluated. almost 50 of the responders reported symptoms lasting for more than a season. preventive household adjustments are expensive with little perceived benefit. sleep and emotional life are affected by allergic rhinitis. most patients are satisfied with the current allergic rhinitis medications; at least one-fifth report dissatisfaction. patients perceive that allergic rhinitis worsens other concomitant allergic diseases.","future management guidelines for allergic rhinitis must take into account the results of this survey. such guidelines must promote relief from the emotional burden of allergic rhinitis and from the negative impact on daily activities, encourage patient education, and maintain and build on the strong partnership between patients and healthcare professionals.",Medication
is endotoxemia during supraceliac aortic crossclamping associated with suppression of the monocyte cd14 mechanism : possible role of transforming growth factor-beta1?,"monocyte cd14 and its soluble form (scd14) mediate the proinflammatory response to endotoxemia. the aim of this study was to measure the changes to these factors after major aortic surgery and the possible inhibitory role of transforming growth factor-beta(1) (tgf-beta(1)) during these procedures. twenty-four patients with supraceliac aortic crossclamping during thoracoabdominal aortic aneurysm (taaa) repair and 12 patients with infrarenal aortic crossclamping as part of infrarenal aneurysm repair (aaa) were studied. blood was collected at incision, aortic clamping, and reperfusion and at 1, 8, and 24 hours after reperfusion. samples were assayed for endotoxin, peripheral blood monocyte cd14 expression, scd14, tumor necrosis factor-alpha, and tgf-beta(1). although there was significant endotoxemia on reperfusion in both groups of patients, peak plasma endotoxin levels were significantly higher in patients with taaa (p .001). monocyte cd14 and plasma scd14 were significantly decreased in patients with taaa at reperfusion and 1 hour after reperfusion (p .01, both points). in patients with aaa, a significant upregulation of cd14 was observed at 24 hours after reperfusion (p .01), but no significant changes in scd14 were observed. tnf-alpha showed no significant changes during the study period in both groups. in patients with taaa, tgf-beta(1) showed significant elevation at all time points (p .01); whereas in patients with aaa, tgf-beta(1) showed no significant changes.",splanchnic ischemia reperfusion in patients who undergo supraceliac aortic clamping is associated with peripheral blood monocyte cd14 suppression and significant elevation of tgf-beta(1). tgf-beta(1) may play an important role in modulating the immune response to endotoxemia during major aortic aneurysm surgery.,Treatment
does proximal arterial occlusion protect the distal lower limb vessels?,"to test the hypothesis that chronic arterial occlusion protects the distal vessels from disease progression. peripheral angiograms from the radiology film store filed under 1997-1999 were reviewed. those showing unilateral iliac occlusion and those showing unilateral femoro-popliteal occlusion were selected. the severity of arterial disease distal to the occlusion was compared with the patent side. subsequently, in a subgroup of patients undergoing repeat angiography, the frequency and distribution of disease progression was recorded and related to the initial disease distribution. in the presence of a unilateral iliac occlusion, femoro-popliteal occlusion was less likely on the side of the iliac occlusion than on the opposite side (difference in proportion 10. 95 c.i.: 1-18). in the presence of a unilateral occlusion proximal to the knee joint, there were more patent calf vessels on the side of the occlusion than on the opposite side (difference in proportion 9. 95 c.i.: 4-14). when angiography was repeated, progression of calf vessel disease was less common in the limbs with untreated proximal occlusion than in those with no proximal occlusion.",proximal arterial occlusion protects the distal vessels from the risk of progressive arterial disease.,General
does serial sectioning of the fallopian tube allow for improved identification of primary fallopian tube carcinoma?,"serial sectioning of the fallopian tube in women undergoing risk reducing surgery has been shown to increase the detection rate of occult malignancy in brca mutation carriers. we undertook this study to determine whether this protocol at the time of surgery for ovarian cancer (ov) or primary peritoneal malignancies (pp) changes the detection rate of fallopian tube carcinoma (ft). we secondarily investigated where this difference affects patient outcomes. a retrospective review of 130 patients treated at the university of chicago medical center for ovarian, peritoneal or fallopian tube carcinoma was conducted. sixty five patients diagnosed with ov, pp or ft who had serial sectioning of the fallopian tubes at the time of diagnoses (ss) were compared to 65 patients whose fallopian tubes were sectioned in a standard fashion (pss). serial sectioning of the fallopian tube at the time of pathologic examination in women with presumed ov or pp led to an increase in the number of women diagnosed with ft as the primary site of origin (p0.001). clinical or pathologic risk factors leading to an increased risk of ft were not identified. survival between the two groups was similar.","in women with presumed ov or pp, serial sectioning identifies women with ft. ft may be more common than previously noted; however distinct biologic or clinical behavior to differentiate it from ov or pp could not be identified. clinical management of ft should continue to be the same as that of ov or pp.",Treatment
is protection by ozone preconditioning mediated by the antioxidant system in cisplatin-induced nephrotoxicity in rats?,"acute renal failure is a dose-limiting factor of cisplatin chemotherapy. here, we show the protective effect of ozone oxidative preconditioning against cisplatin-induced renal dysfunction in rats. ozone oxidative preconditioning is a prophylactic approach, which favors the antioxidant-pro-oxidant balance for preservation of the cell redox state by increasing antioxidant endogenous systems in various in vivo and in vitro experimental models. to analyze the protective role of ozone oxidative preconditioning against cisplatin-induced nephrotoxicity. male sprague-dawley rats were pretreated with 15 intrarectal applications of ozone/oxygen mixture at 0.36, 0.72, 1.1, 1.8 and 2.5 mg/kg before cisplatin intraperitoneal injection (6 mg/kg). serum and kidneys were extracted and analyzed 5 days after cisplatin treatment for determinations of the renal content of glutathione, thiobarbituric acid-reactive substances, renal concentration and enzymatic activities of catalase, superoxide dismutase and glutathione peroxidase. ozone pretreatment prevented the increase in serum creatinine levels, the glutathione depletion and the inhibition of superoxide dismutase, catalase and glutathione peroxidase activities induced by cisplatin in the rat kidney. also, the renal content of thiobarbituric acid-reactive substances was decreased by ozone therapy. these protective effects of ozone were dose dependent.",intrarectal ozone therapy prevented effectively the renal antioxidant unbalance induced by cisplatin treatment.,Medication
does four-dimensional single breathhold magnetic resonance imaging using kt-blast enable reliable assessment of left- and right-ventricular volumes and mass?,"to prospectively determine the accuracy of four-dimensional (4d) kt-broad-use linear acquisition speed-up technique (blast) accelerated mri (kt-blast) for the assessment of left-ventricular (lv) volumes and mass as well as right-ventricular (rv) volumes in comparison to standard multiple breathhold cine imaging. a total of 40 patients with suspected or known coronary artery disease (cad) underwent cardiac mri. in each patient a standard multislice cine steady-state free precession (ssfp) sequence was performed with complete ventricular coverage during multiple breathholds. additionally, a kt-blast-accelerated 4d sequence with complete ventricular coverage was acquired during one single breathhold. for comparison of ssfp and kt-blast, the following lv parameters were determined: end-diastolic and end-systolic volumes, ejection fraction, end-diastolic diameter and mass. for comparison of rv dimensions, end-diastolic and end-systolic volumes and ejection fraction were assessed. lv volumes, ejection fraction, diameter, and mass showed a strong correlation between ssfp and kt-blast (r0.98-0.99; p0.01). in addition, rv parameters demonstrated a high correlation (r0.97-0.98; p0.01). for all parameters, the calculated bias between both methods was found to be minimal (0.4-4).","4d kt-blast-accelerated mri enabled the accurate assessment of lv and rv quantitative parameters during one single breathhold when compared to standard multislice, multiple breathhold ssfp imaging.",Diagnosis
does intensive insulin therapy decrease urinary mcp-1 and icam-1 excretions in incipient diabetic nephropathy?,"nowadays, intensive insulin treatment has been widely used in type 2 diabetics who have poor control of blood glucose, to reduce the risk of chronic complications of diabetes. recently, some scholars have paid more attention to the pivotal role of inflammation involved in type 2 diabetes and its complications. monocyte chemoattractant protein-1 (mcp-1) and intercellular adhesion molecule-1 (icam-1), which are two important inflammatory chemokines, have been documented to participate in the onset and development of type 2 diabetes and its complications, such as diabetic nephropathy (dn). in the current study, we recruited 30 type 2 diabetics with microalbuminuria to be treated with multiple insulin injections daily for 2 weeks. random spot urine samples (corrected for creatinine-cr) were collected for the examination of urinary mcp-1, icam-1 and albumin (alb) levels before and after the intensive insulin therapy. changes in their levels were observed to test the hypothesis that type 2 diabetes with microalbuminuria is associated with elevated urinary concentrations of mcp-1 and icam-1, and intensive insulin therapy can result in a decline of alb by reducing the inflammatory reaction. the urinary mcp-1/cr and urinary icam-1/cr ratios in type 2 diabetic patients with microalbuminuria were much higher than those in normal controls, and intensive insulin treatment could decrease significantly the urinary mcp-1/cr, icam-1/cr and alb/cr ratios in type 2 diabetics with microalbuminuria.",intensive insulin treatment may protect against renal injury in early dn by reducing the urinary mcp-1 and icam-1 excretions.,Medication
does the cyclophilin-inhibitor alisporivir stimulate antigen presentation thereby promoting antigen-specific cd8 ( ) t cell activation?,"cyclophilin-inhibitors have potent antiviral activity against hepatitis c virus (hcv) and are promising candidates for broad-spectrum antiviral therapy. cyclosporine a (csa) acts immunosuppressive by blocking t cell activation and antigen presentation. alisporivir, a non-immunosuppressive csa analog in clinical development, does not inhibit t cell activation. in this study we explored the impact of alisporivir on antigen presentation. hepatoma cells endogenously expressing the epitope-restricting major histocompatibility complex-class i (mhc-i) allele hla-a2 and constitutively expressing a viral antigen were established to study the impact of cyclophilin-inhibitors on antigen presentation. antigen-specific cd8() t cell activation and mhc-i surface expression were measured to quantify antigen presentation. our work establishes a novel cell culture model to study antigen presentation in liver-derived cells. authentic regulation of antigen presentation was ensured by the action of pro- and anti-inflammatory cytokines. alisporivir pretreatment stimulated antigen presentation by hepatoma target cells, leading to enhancement of antigen-specific cd8() t cell activation by 40. alisporivir, as well as a panel of other cyclophilin-inhibitors, induced an increase of mhc-i and beta-2 microglobulin on the surface of several cell lines. the drug neither enhanced mhc-i transcript or protein levels nor affected surface expression of other proteins or protein trafficking in general. proteasome-inhibitors completely blocked the alisporivir-directed enhancement of surface mhc-i, suggesting an influence of the drug on peptide-availability.","alisporivir stimulates antigen presentation by inducing enhanced mhc-i surface expression, thereby promoting antigen-specific cd8() t cell activation. this immunostimulatory function might further contribute to the antiviral activity of non-immunosuppressive cyclophilin-inhibitors.",Medication
does weight loss therapy improve pancreatic endocrine function in obese older adults?,"obesity and aging increase the risk of type 2 diabetes (t2d). we evaluated whether weight loss therapy improves pancreatic endocrine function and insulin sensitivity in obese older adults. twenty-four obese (bmi: 38 /- 2 kg/m(2)) older (age: 70 /- 2 years) adults completed a 6-month randomized, controlled trial. participants were randomized to diet and exercise (treatment group) or no therapy (control group). beta-cell function (assessed using the c-peptide minimal model), alpha-cell function (assessed by the glucagon response to an oral glucose load), insulin sensitivity (assessed using the glucose minimal model), and insulin clearance rate were evaluated using a 5-h modified oral glucose tolerance test. body weight decreased in the treatment group, but did not change in the control group (-9 /- 1 vs. 0 /- 1; p 0.05), the disposition index (di), which adjusts beta-cell insulin response to changes in insulin sensitivity, improved in the treatment group compared with the control group (100 /- 47 vs. -22 /- 9; p 0.05), but insulin clearance rate increased (51 /- 25; p 0.05), resulting in lower plasma insulin concentrations.","weight loss therapy concomitantly improves beta-cell function, lowers plasma glucagon concentrations, and improves insulin action in obese older adults. these metabolic effects are likely to reduce the risk of developing t2d in this population.",Prevention
does overexpression of laptm4b-35 attenuate epirubucin-induced apoptosis of gallbladder carcinoma gbc-sd cells?,"it was shown previously that laptm4b promoted growth of gallbladder carcinoma (gbc) cells and predicted poor prognosis in gbc; however, its roles and relative mechanisms in apoptosis of gbc cells remain unknown. the plasmids, pcdna3-ae, containing the complete open reading frame of laptm4b and mock (pcdna3), were transfected transiently into gbc-sd cells, followed by induction of apoptosis by epirubicin. cell apoptosis was determined by hoechst 33258 staining, propidium iodide (pi) staining, and annexin v/pi double staining flow cytometry. protein expression was detected by immunoblotting. overexpression of laptm4b-35 was observed in cells transfected with pcdna3-ae. these cells possessed significantly less apoptosis ratios compared with cells transfected with the mock plasmid, although the values were still greater than those in parent cells. of the apoptosis-related molecules, expression of bcl-2 and bcl-xl was up-regulated in cells transfected with pcdna3-ae, whereas expressions of bax, bid, and cleaved caspase-9 and -3 were down-regulated compared with their expression in other kinds of cells.","our data show that laptm4b-35 attenuated epirubicin-induced apoptosis of gbc-sd cells in vitro through a mitochondria-dependent pathway. therefore, the protein laptm4b-35 might be associated with the chemoresistance of gbc.",Diagnosis
is bmpr2 expression suppressed by signaling through the estrogen receptor?,"studies in multiple organ systems have shown cross-talk between signaling through the bone morphogenetic protein receptor type 2 (bmpr2) and estrogen pathways. in humans, pulmonary arterial hypertension (pah) has a female predominance, and is associated with decreased bmpr2 expression. the goal of this study was to determine if estrogens suppress bmpr2 expression. a variety of techniques were utilized across several model platforms to evaluate the relationship between estrogens and bmpr2 gene expression. we used quantitative rt-pcr, gel mobility shift, and luciferase activity assays in human samples, live mice, and cell culture. bmpr2 expression is reduced in lymphocytes from female patients compared with male patients, and in whole lungs from female mice compared with male mice. there is an evolutionarily conserved estrogen receptor binding site in the bmpr2 promoter, which binds estrogen receptor by gel-shift assay. increased exogenous estrogen decreases bmpr2 expression in cell culture, particularly when induced to proliferate. transfection of increasing quantities of estrogen receptor alpha correlates strongly with decreasing expression of bmpr2.","bmpr2 gene expression is reduced in females compared to males in live humans and in mice, likely through direct estrogen receptor alpha binding to the bmpr2 promoter. this reduced bmpr2 expression may contribute to the increased prevalence of pah in females.",Medication
do dendritic cells limit fibroinflammatory injury in nonalcoholic steatohepatitis in mice?,"nonalcoholic steatohepatitis (nash) is the most common etiology of chronic liver dysfunction in the united states and can progress to cirrhosis and liver failure. inflammatory insult resulting from fatty infiltration of the liver is central to disease pathogenesis. dendritic cells (dcs) are antigen-presenting cells with an emerging role in hepatic inflammation. we postulated that dcs are important in the progression of nash. we found that intrahepatic dcs expand and mature in nash liver and assume an activated immune phenotype. however, rather than mitigating the severity of nash, dc depletion markedly exacerbated intrahepatic fibroinflammation. our mechanistic studies support a regulatory role for dcs in nash by limiting sterile inflammation through their role in the clearance of apoptotic cells and necrotic debris. we found that dcs limit cd8() t-cell expansion and restrict toll-like receptor expression and cytokine production in innate immune effector cells in nash, including kupffer cells, neutrophils, and inflammatory monocytes. consistent with their regulatory role in nash, during the recovery phase of disease, ablation of dc populations results in delayed resolution of intrahepatic inflammation and fibroplasia.",our findings support a role for dcs in modulating nash. targeting dc functional properties may hold promise for therapeutic intervention in nash.,Medication
does gemcitabine-based adjuvant chemotherapy improve survival after aggressive surgery for hilar cholangiocarcinoma?,"the prognosis of hilar cholangiocarcinoma is dismal although aggressive surgery including major hepatectomy has been performed. the aim of this study was to clarify useful prognostic factors and the usefulness of gemcitabine-based adjuvant chemotherapy for patients with hilar cholangiocarcinoma who had undergone aggressive surgical resection. medical records of 42 patients with hilar cholangiocarcinoma who underwent surgical resection were reviewed retrospectively. univariate and multivariate models were used to analyze the effect of various clinicopathological factors on long-term survival. overall 1-, 3-, and 5-year survival rates of the 42 patients with hilar cholangiocarcinoma were 81, 42, and 30, respectively (median survival time, 21.5 months). univariate analysis revealed that adjuvant gemcitabine-based chemotherapy, tumor differentiation, lymph node metastasis, and surgical margin status were associated significantly with long-term survival (p 0.05). furthermore, use of a cox proportional hazards regression model indicated that only adjuvant gemcitabine-based chemotherapy was a significant independent predictor of a favorable prognosis (p 0.035). the toxicity of adjuvant gemcitabine-based chemotherapy was mild. five-year actuarial survival rates of patients who did or did not receive adjuvant gemcitabine-based chemotherapy were 57 and 23, respectively (p 0.026).",postoperative adjuvant gemcitabine-based chemotherapy may be a promising strategy to improve survival after surgical resection for hilar cholangiocarcinoma. a prospective randomized study should be done to confirm the results of this study.,Medication
is the novel small molecule drug rabeximod effective in reducing disease severity of mouse models of autoimmune disorders?,"autoimmune diseases such as rheumatoid arthritis (ra) and multiple sclerosis (ms) affect a relatively large portion of the population, leading to severe disability if left untreated. even though pharmaceutics targeting the immune system have revolutionised the therapy of these diseases, there is still a need for novel, more effective therapeutic substances. one such substance is the new chemical entity 9-chloro-2,3 dimethyl-6-(n,n-dimthylamino-2-oxoethyl)-6h-indolo 2,3-b quionoxaline, rabeximod, currently being investigated for efficiency in treatment of human ra. in this study we aimed to evaluate rabeximod as a treatment for autoimmune diseases, using animal models. in the present investigation we have evaluated rabeximod as a treatment for autoimmune diseases using mouse models of ra and ms, ie, collagen-induced arthritis, collagen antibody induced arthritis and experimental autoimmune encephalomyelitis. rabeximod efficiently prevented arthritis and encephalomyelitis in mice. in addition, this effect correlated to the timepoint when cells migrate into the joints.",we conclude that rabeximod reduces disease severity in animal models of autoimmunity and should be considered as a new therapeutic substance for ms and ra.,Medication
are increased plasma levels of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in lung and breast cancer altered during chest radiotherapy?,"does the release of plasma matrix metalloproteinase-9 (mmp-9) by radiation-activated airway epithelial cells and infiltrating inflammatory cells play a role in the radiation damage or repair process in the lungs? we evaluated lung damage by ionizing radiation using plasma levels of mmp-9, tissue inhibitor of metalloproteinase-1 (timp-1), and mmp-3 as biologic markers of tissue damage, and also their relationship to changes in pulmonary epithelial permeability, clinical signs and symptoms, and lung structural changes. seven serial studies were conducted in each of 8 patients undergoing chest radiotherapy (rt) for lung or breast cancer, beginning before the first treatment (baseline) and then biweekly to approximately 100 days during and after rt. chest radiographs were monitored for each patient. sandwich enzyme-linked immunoassays (elisa) were used to measure plasma mmp-3, mmp-9, and timp-1 levels. lung permeability was evaluated by measuring the rate of epithelial clearance of approximately 150 microci ( approximately 5.6 mbq) inhaled (99m)tc diethylenetriamine pentaacetate aerosol (dtpa). lung and breast cancer resulted in very high plasma levels of mmp-9 (126-893 ng/ml) and timp-1 (496-8985 ng/ml) in all subjects studied before initiation of rt. this compares with plasma mmp-9 and timp-1 values in healthy volunteers of 29 /- 11 ng/ml and 436 /- 86 ng/ml, respectively. rt was followed by a sharp decrease in plasma mmp-9 within the first 2 weeks, but without a corresponding change in timp-1. in contrast, plasma mmp-3 levels, which are generally increased with inflammation, were elevated in only 1 of 5 subjects.","lung and breast cancer are associated with high plasma levels of mmp-9 and timp-1. these high baseline plasma levels of mmp-9 were reduced in the first 2 weeks of rt in 7 of 8 subjects, and timp-1 plasma levels remained high in all subjects. the decrease in plasma mmp-9 after initiation of chest rt appears to reflect a suppressive effect on cancer-induced cellular responses rather than a primary role for mmp-9 in radiation-induced lung damage. likewise, the lack of a rise in plasma mmp-3 levels does not support a role for mmp-3 in tissue injury or repair in the lung. it remains to be determined whether plasma mmp-9 measurements will serve as a useful parameter in predicting cancer relapse.",Medication
is functional recovery after coronary revascularization for chronic coronary artery disease dependent on maintenance of oxidative metabolism?,"this study was performed to define the importance of maintenance of oxidative metabolism as a descriptor and determinant of functional recovery after revascularization in patients with left ventricular dysfunction attributable to chronic coronary artery disease. although myocardial accumulation of 18f-fluorodeoxyglucose indicates the presence of tissue that is metabolically active, it may not identify those metabolic processes required for restoration of myocardial contractility. experimental studies suggest that, under conditions of ischemia and reperfusion, maintenance of myocardial oxidative metabolism is an important metabolic determinant of the capacity for functional recovery. in 16 patients positron emission tomography was performed to characterize myocardial perfusion (with h(2)15o), oxidative metabolism (with 11c-acetate) and utilization of glucose (with 18f-fluorodeoxyglucose). dysfunctional but viable myocardium was differentiated from nonviable myocardium on the basis of assessments of regional function before and after coronary revascularization. to define the importance of coronary revascularization on myocardial perfusion and metabolism, tomography was repeated in 11 patients after revascularization. before revascularization, perfusion in 24 dysfunctional but viable myocardial segments and 29 nonviable segments averaged 79 and 74, respectively, of that in 42 normal myocardial segments (both p less than 0.01). dysfunctional but viable myocardium exhibited oxidative metabolism comparable to that in normal myocardium. in contrast, in nonviable myocardium, oxidative metabolism was only 66 of that in normal (p less than 0.01) and 69 of that in reversibly dysfunctional myocardium (p less than 0.003). regional utilization of glucose normalized to regional perfusion in dysfunctional but viable myocardium was greater than that in normal myocardium (p less than 0.01). however, in both reversibly and persistently dysfunctional myocardium, utilization of glucose normalized to relative perfusion was markedly variable.","the results indicate that preservation of oxidative metabolism is a necessary condition for recovery of function after coronary recanalization in patients with chronic coronary artery disease. consequently, approaches that measure myocardial oxygen consumption, such as dynamic positron emission tomography with 11c-acetate, should facilitate the identification of those patients most likely to benefit from coronary revascularization.",Symptoms
is elevated osteopontin level of synovial fluid and articular cartilage associated with disease severity in knee osteoarthritis patients?,"to investigate osteopontin (opn) levels in both synovial fluid and articular cartilage of patients with primary knee osteoarthritis (oa) and their relationship with severity of the disease. fifty patients aged 48-81 years with knee oa and 10 healthy controls were enrolled in this study. anteroposterior knee radiographs or/and mankin score were taken to determine the disease severity of the affected knee. the radiographic grading of oa in the knee was performed by using the kellgren-lawrence criteria. opn levels in synovial fluid were measured using enzyme-linked immunosorbent assay. opn levels in articular cartilage were assessed by immunohistochemical methods. compared to healthy controls, oa patients had higher opn concentration in synovial fluid (4519.60/-1830.37, 95ci 3999.42-5039.79 vs 1179.70/-303.39, 95ci 1035.53-1438.74 pg/ml, p0.001)and articular cartilage(0.6/-0.06, 95ci 0.59-0.62 vs 0.43/-0.07, 95ci 0.38-0.48, p0.01). in addition, synovial fluid opn levels showed a positive correlation with articular cartilage opn levels (r0.411, 95ci 0.150-0.619, p0.003). subsequent analysis showed that synovial fluid opn levels significantly correlated with severity of disease (spearman's rho0.581, 95ci 0.335-0.726, p0.001). furthermore, the articular cartilage levels of opn also correlated with disease severity (spearman's rho0.675, 95ci 0.500-0.808, p0.001).",opn in synovial fluid and articular cartilage is associated with progressive joint damage and is likely to be a useful biomarker for determining disease severity and progression in knee oa.,Diagnosis
do ratio of myeloid and plasmacytoid dendritic cells and th2 skew in crs with nasal polyps?,"the role of myeloid and plasmacytoid dendritic cells and its consequences for the t(h)2 skew in chronic rhinosinusitis (crs) with nasal polyps (crsnp()) should be detailed. in 18 crs patients without nasal polyps (crsnp(-)), 35 crsnp() patients and 22 patients with nasal structural abnormalities without rhinosinusitis (controls), dendritic cells (dc) were differentiated into myeloid (mdc) and plasmacytoid (pdc) subtypes using an antibody cocktail including cd1c (bdca-1) and cd303 (bdca-2) in peripheral blood mononuclear cells (pbmc) and single cell preparations of sinonasal mucosa by flow cytometry. moreover, cells were analysed for expression of cd45, cd3, cd4, cxcr3 (t(h)1) and ccr4 (t(h)2) and ifn-gamma, il-5, tgf-beta1, tgf-beta2, ecp and total ige in nasal secretions were determined. as a possible confounder, staphylococcus aureus in nasal lavages was detected. the tissue mdc/pdc-ratio was 1.7 (1.0-2.4) in controls, 3.0 (1.8-4.0) in crsnp(-) and 0.8 (0.6-1.0) in crsnp() (p 0.01). in tissue samples, the t(h)1/t(h)2 ratio was 12.6 (6.4-16.0) in controls, 12.5 (6.9-21.2) in crsnp(-) and 1.8 (1.3-3.6) in crsnp() (median and interquartile range, p 0.001). less pronounced differences were found in pbmc. s. aureus detection rates or tgf-beta levels did not differ between patient groups and s. aureus detection had no influence on the parameters investigated.",a significant t(h)2 skew in crsnp() could be confirmed on the cellular level. it was driven by low myeloid dendritic cell numbers. the t(h)2 skew did not correlate with s. aureus detection. the data support the concept that crsnp() and crsnp(-) are pathophysiologically distinct.,General
is exercise hyperventilation in chronic heart failure caused by systemic lactic acidosis?,"patients with heart failure have an abnormally high ventilatory response to exercise associated with gas exchange defects and reduced arterial pco(2). we examined the possibility of lactic acidosis as the stimulus to this increased ventilation that abnormally depresses pco(2) during exercise in heart failure. we studied 18 patients with chronic heart failure. we measured ve/vco(2) slope during exercise, arterial blood gases and lactate concentrations during cardiopulmonary exercise testing (rest, peak exercise and one minute after the end of exercise). neither ve/vco(2) slope nor arterial pco(2) were related to arterial lactate concentrations at peak exercise (r -0.16, p 0.65 and r -0.15, p 0.6). during early recovery, patients with a high ve/vco(2) slope had a particularly pronounced rise in arterial lactate and hydrogen ion concentrations (r 0.57, p 0.05 and r 0.84, p 0.0001) and yet their arterial pco(2) rose rather than fell (r 0.79, p 0.001). the rise in arterial pco(2) correlated with the increase in arterial hydrogen concentration (r 0.78, p 0.001) and with arterial pco(2) at peak exercise (r -0.76, p 0.001).",in heart failure ve/vco(2) slope and low arterial pco(2) at peak exercise are not related to the degree of systemic lactic acidosis. lactic acidosis is therefore not a plausible mechanism of exercise induced hyperventilation.,Prevention
is gas6-induced tissue factor expression in endothelial cells mediated through caveolin-1-enriched microdomains?,"gas6 has been shown to interact with axl in endothelial cells and to induce several signaling pathways involved in cell survival and proliferation. however, the interaction of gas6/axl with lipid raft/caveolin-1 in endothelial cells and its role in thrombosis are unknown. we tested whether axl and/or caveolin-1 is involved in gas6-induced akt, erk1/2, and c-src activation leading to altered tissue factor expression in endothelial cells. gas6-treated endothelial cells were transfected with small interfering rna (sirna) for axl, caveolin-1, c-src, and akt or treated with pharmacological inhibitors of c-src and erk1/2. sucrose gradient centrifugation and confocal microscopy were used to study lipid raft/caveolin-1-enriched fractions. akt, erk1/2, p38, and c-src activation was analyzed by western blot analysis. tissue factor expression was assessed by real-time quantitative polymerase chain reaction and immunofluorescence.","gas6 induced axl and c-src localization into lipid raft/caveolin-1-enriched fractions. gas6 increased the phosphorylation of akt, erk1/2, and c-src but not p38. using sirna, we demonstrated that axl is required for akt, erk1/2, and c-src activation after gas6 stimulation. sirna for caveolin-1 blocked gas6-induced phosphorylation of akt, erk1/2, and c-src. c-src downregulation inhibited gas6-induced akt but not erk1/2 phosphorylation. finally, gas6 increased tissue factor mrna and protein expression in endothelial cells. tissue factor expression was blocked by sirna for axl, caveolin-1, or akt as well as c-src inhibition. these data demonstrate that the signaling pathway gas6/axl/caveolin-1/c-src/akt is required for tissue factor expression in endothelial cells, providing mechanistic insight into how gas6 exerts its prothrombotic role in the vasculature.",Medication
does parental consanguinity increase congenital heart diseases in south india?,"congenital heart diseases (chds) are the commonest single group of congenital abnormalities with a prevalence ranging from 1.0 to 50.89 per 1000 live births in the world population including india, whereas mysore has a prevalence of 11.08 per 1000 live births. one of the risk factors for the occurrence of chds is parental consanguinity, in particular first-cousin marriage between parents. the present study examined the role of consanguineous marriages in causing chds in mysore, south india. a total of 144 confirmed chd cases with an age range of 1 day to 23 years and a control group of 200 families from different localities of mysore city were considered for the present study. methods included the establishment of a genetic register and pedigree analysis followed by statistical analysis by logistic regression. the findings revealed that first-cousin marriages (44.68) and uncle-niece marriages (46.81) are equally significant in increasing chds. the subtypes of chds associated with consanguinity were found to be atrial septal defect (asd) and patent ductus arteriosus (pda). these findings emphasize the important role played by segregation of recessive genes in the offspring resulting in the causation of chds.","therefore, for every incidence of parental consanguinity, the risk (odds) of birth of a child with chd increases. there is an urgent need to educate the public on the deleterious effects of inbreeding, especially in india, which has high overall consanguinity.",Prevention
does neurosphere formation enhance the neurogenic differentiation potential and migratory ability of umbilical cord-mesenchymal stromal cells?,"the human umbilical cord (uc) is a rich source of mesenchymal stromal cells (mscs), which have been reported to have multi-lineage potential. the objectives of this study were to investigate the characteristics and capacity of uc-msc neurosphere formation and whether this event enhances the propensity of uc-mscs to undergo neural differentiation. uc-mscs were collected by the improved explant method. uc-mscs and neurosphere-forming uc-mscs (uc-msc-neurospheres) were induced to undergo neurogenic differentiation, the latter of which were induced by suspension culturing in the presence of epidermal growth factor and basic fibroblast growth factor. the differentiation and migratory capacities of the individual cultures were then compared on the basis of the expression of neural markers, as measured by immunocytochemistry, immunoblotting and quantitative real-time polymerase chain reaction and transwell assays, respectively. both uc-mscs and uc-msc-neurospheres were capable of differentiating into neurogenic cells when cultured in neurogenic differentiation medium. however, pre-conditioned uc-msc-neurospheres exhibited significantly higher expression of neural markers--including microtubule-associated protein (map2), musashi1, glial fibrillary acidic protein (gfap), and nestin--compared with those derived from uc-mscs directly. moreover, uc-msc-neurospheres expressed significantly higher levels of the stemness markers nanog, klf4 and oct4 than did uc-mscs. migration assays also revealed that both uc-mscs and uc-msc-neurospheres actively migrate toward glucose-depleted cells.","neurogenic differentiation potential probably is greater in uc-msc-neurospheres than in uc-mscs. thus, uc-msc-neurospheres may serve as a better source of cells for neurogenic regenerative medicine.",Diagnosis
does tamoxifen enhance the cytotoxic effects of nelfinavir in breast cancer cells?,"the hiv protease inhibitor nelfinavir is currently under investigation as a new anti-cancer drug. several studies have shown that nelfinavir induces cell cycle arrest, endoplasmic reticulum stress, autophagy, and apoptosis in cancer cells. in the present article, the effect of nelfinavir on human breast cancer cells is examined and potential combination treatments are investigated. the effects of nelfinavir and tamoxifen on the human breast cancer cell lines mcf7, t47 d, mda-mb-453, and mda-mb-435 were tested by analysing their influence on cell viability (via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay), apoptosis (annexin binding, poly(adp-ribose) polymerase cleavage), autophagy (autophagy marker light chain 3b expression), endoplasmic reticulum stress (binding protein and activating transcription factor 3 expression), and the occurrence of oxidative stress (intracellular glutathione level). nelfinavir induced apoptosis in all four breast cancer cell lines tested, although the extent of autophagy and endoplasmic reticulum stress varied among the cell lines. the concentration of nelfinavir needed for an efficient induction of apoptosis in breast cancer cells could be reduced from 15 g/ml to 6 g/ml when combined with tamoxifen. at a concentration of 6 g/ml, tamoxifen substantially enhanced the endoplasmic reticulum stress reaction in those cell lines that responded to nelfinavir with binding protein (bip) upregulation (mcf7, t47d), and enhanced autophagy in cell lines that responded to nelfinavir treatment with autophagy marker light chain 3b upregulation (mda-mb-453). although tamoxifen has been described to be able to induce oxidative stress at concentrations similar to those applied in this study (6 g/ml), we observed that nelfinavir but not tamoxifen reduced the intracellular glutathione level of breast cancer cells within hours of application by up to 32, suggesting the induction of oxidative stress was an early event and an additional cause of the apoptosis induced by nelfinavir.","the results demonstrate that nelfinavir may be an effective drug against breast cancer and could be combined with tamoxifen to enhance its efficacy against breast cancer cells. moreover, the cytotoxic effect of a tamoxifen and nelfinavir combination was independent of the oestrogen receptor status of the analysed breast cancer cells, suggesting a potential benefit of a combination of these two drugs even in patients with no hormone-responsive tumours. we therefore recommend that clinical studies on nelfinavir with breast cancer patients should include this drug combination to analyse the therapeutic efficacy as well as the safety and tolerability of this potential treatment option.",Medication
are plasma omentin-1 levels related to exercise performance in obese women and increase upon aerobic endurance training?,"omentin-1 is an adipokine that is primarily released from visceral adipose tissue stromal cells. the effects of exercise on omentin-1 regulation are not clear so far. therefore, the effect of endurance training on circulating omentin-1 levels and its relation to exercise performance was assessed in obese women. 13 obese women (age: 44.83.3 years; bmi: 37.81.3 kgm(-2)) participated in a 6-week endurance training program. omentin-1, metabolic traits (glucose, insulin, homa-ir, lipids profile), and exercise performance (cardiopulmonary exercise test (vo2,peak, wpeak), 6 min walking test, 6mwt) were assessed before and after the training. after the training program circulating omentin-1 were 10.4 higher than before the program (69050 ngml(-1) vs. 61842; p0.04), while body weight remained unchanged (p0.9). before training, omentin-1 levels were significantly correlated with wpeak (given in absolute and relative values) as well as with 6mwt (all r0.603; all p0.029) and the correlations with absolute as well as relativevo2,peak approached significance (both r0.534; both p0.060). after training, respective correlations were generally weaker and did not reach significance any longer (all r0.465; all p0.109). neither before nor after the training program were significant correlations found between omentin-1 levels and the other measured metabolic blood markers (all p0.157).",data show a rather strong relationship between exercise performance and circulating omentin-1 levels as well as an increase of the adipokine in response to 6-week of endurance training in obese women. our findings may hint to a skeletal muscle-adipose tissue crosstalk in regard of omentin-1 regulation.,Prevention
is the level of adam12-s in maternal serum an early first-trimester marker of fetal trisomy 18?,"adam12-s is a pregnancy-associated insulin-like growth factor binding protein-3 (igfbp-3) and igfbp-5 protease present in human gestational serum. recently, maternal serum levels of adam12-s were found to be markedly reduced during the first trimester of pregnancies with a down syndrome (ds) fetus. on the basis of this finding, it was suggested that adam12-s might be a useful maternal serum marker of fetal chromosomal disease. retrospective examination of the use of adam12-s as a marker for fetal trisomy 18. serum samples were obtained from ten women during the first semester of their pregnancies with fetuses that had trisomy 18. an elisa was used to determine the levels of adam12 in maternal serum. results were compared to adam12-s levels, previously measured in the serum of 170 women carrying normal pregnancies during the first trimester. in all cases, the adam12-s concentration in maternal serum samples was lower in trisomy 18 pregnancies than in normal pregnancies, with a median multiple of the median (mom) of 0.28 (p 0.001)","a reduced concentration of adam12-s in maternal serum is a promising marker for foetal trisomy 18, as well as for ds.",Diagnosis
do polymorphisms in maternal folate pathway genes interact with arsenic in drinking water to influence risk of myelomeningocele?,"arsenic induces neural tube defects in many animal models. additionally, studies have shown that mice with specific genetic defects in folate metabolism and transport are more susceptible to arsenic-induced neural tube defects. we sought to determine whether 14 single-nucleotide polymorphisms in genes involved in folate metabolism modified the effect of exposure to drinking water contaminated with inorganic arsenic and posterior neural tube defect (myelomeningocele) risk. fifty-four mothers of children with myelomeningocele and 55 controls were enrolled through clinical sites in rural bangladesh in a case-control study of the association between environmental arsenic exposure and risk of myelomeningocele. we assessed participants for level of myelomeningocele, administered questionnaires, conducted biological and environmental sample collection, and performed genotyping. inductively coupled plasma mass spectrometry was used to measure inorganic arsenic concentration in drinking water. candidate single-nucleotide polymorphisms were identified through review of the literature. drinking water inorganic arsenic concentration was associated with increased risk of myelomeningocele for participants with 4 of the 14 studied single-nucleotide polymorphisms in genes involved in folate metabolism: the aa/ag genotype of rs2236225 (mthfd1), the gg genotype of rs1051266 (slc19a1), the tt genotype of rs7560488 (dnmt3a), and the gg genotype of rs3740393 (as3mt) with adjusted odds ratio of 1.13, 1.31, 1.20, and 1.25 for rs2236225, rs1051266, rs7560488, and rs3740393, respectively.",our results support the hypothesis that environmental arsenic exposure increases the risk of myelomeningocele by means of interaction with folate metabolic pathways.,Medication
does blood mrna expression profiling predict survival in patients treated with tremelimumab?,"tremelimumab (ticilimumab, pfizer), is a monoclonal antibody (mab) targeting cytotoxic t lymphocyte-associated antigen-4 (ctla-4). ipilimumab (yervoy, bms), another anti-ctla-4 antibody, is approved by the u.s. federal drug administration (fda). biomarkers are needed to identify the subset of patients who will achieve tumor control with ctla-4 blockade. pretreatment peripheral blood samples from 218 patients with melanoma who were refractory to prior therapy and receiving tremelimumab in a multicenter phase ii study were measured for 169 mrna transcripts using reverse transcription polymerase chain reaction (rt-pcr). a two-class latent model yielded a risk score based on four genes that were highly predictive of survival (p 0.001). this signature was validated in an independent population of 260 treatment-nave patients with melanoma enrolled in a multicenter phase iii study of tremelimumab. median follow-up was 297 days for the training population and 386 days for the test population. expression levels of the 169 genes were closely correlated across the two populations (r 0.9939). a four-gene model, including cathepsin d (ctsd), phopholipase a2 group vii (pla2g7), thioredoxin reductase 1 (txnrd1), and interleukin 1 receptor-associated kinase 3 (irak3), predicted survival in the test population (p 0.001 by log-rank test). this four-gene model added to the predictive value of clinical predictors (p 0.0001).","expression levels of ctsd, pla2g7, txnrd1, and irak3 in peripheral blood are predictive of survival in patients with melanoma treated with tremelimumab. blood mrna signatures should be further explored to define patient subsets likely to benefit from immunotherapy.",Treatment
is genetic polymorphism at val80 ( rs700518 ) of the cyp19a1 gene associated with aromatase inhibitor associated bone loss in women with er breast cancer?,"polymorphisms in the cyp19a1 (aromatase) gene have been reported to influence disease-free survival and the incidence of musculoskeletal complaints in patients taking aromatase inhibitors (ais) for estrogen receptor positive (er) breast cancer. bone loss and fractures are well-recognized complications from ai therapy. the objective of this study is to determine the influence of polymorphisms in the cyp19a1 gene on bone loss among patients taking aromatase inhibitors for er breast cancer. the subjects consisted of 97 postmenopausal women with er breast cancer who were initiated on third-generation ais. bone mineral density (bmd) was measured by dual energy x-ray absorptiometry at baseline and at 6 and 12 months. twenty-four hour urine n-telopeptide (ntx) was measured by elisa and serum estradiol was measured by ultrasensitive radioimmunoassay at baseline, and at 6 months. genotyping was done by taqman snp allelic discrimination assay. women with the aa genotype for the rs700518 (g/a at val(80)) developed significant bone loss at the lumbar spine and the total hip at 12 months relative to patients carrying the g allele (ga/gg); both p 0.03. there was a borderline greater increase in urinary ntx in those with the aa genotype compared to patients with the g allele, p 0.05; but no significant difference in changes in estradiol levels among the genotypes.",patients with the aa genotype for the rs700518 polymorphism in the cyp19a1 gene are at risk for ai-associated bone loss and deserve close follow-up during long-term ai therapy.,Medication
do genomic diversity and introgression in o. sativa reveal the impact of domestication and breeding on the rice genome?,"the domestication of asian rice (oryza sativa) was a complex process punctuated by episodes of introgressive hybridization among and between subpopulations. deep genetic divergence between the two main varietal groups (indica and japonica) suggests domestication from at least two distinct wild populations. however, genetic uniformity surrounding key domestication genes across divergent subpopulations suggests cultural exchange of genetic material among ancient farmers. in this study, we utilize a novel 1,536 snp panel genotyped across 395 diverse accessions of o. sativa to study genome-wide patterns of polymorphism, to characterize population structure, and to infer the introgression history of domesticated asian rice. our population structure analyses support the existence of five major subpopulations (indica, aus, tropical japonica, temperate japonica and groupv) consistent with previous analyses. our introgression analysis shows that most accessions exhibit some degree of admixture, with many individuals within a population sharing the same introgressed segment due to artificial selection. admixture mapping and association analysis of amylose content and grain length illustrate the potential for dissecting the genetic basis of complex traits in domesticated plant populations.","genes in these regions control a myriad of traits including plant stature, blast resistance, and amylose content. these analyses highlight the power of population genomics in agricultural systems to identify functionally important regions of the genome and to decipher the role of human-directed breeding in refashioning the genomes of a domesticated species.",General
is carotid intima-media thickness in type 2 diabetes more strongly related to serum apoprotein a-i in females?,"dyslipidemia in type 2 diabetes has been shown to be related to the incidence of macrovascular events. increased carotid intima-media thickness is considered to be a marker of macrovascular disease. to investigate a possible relationship between lipoprotein levels and carotid intima-media thickness as a marker of early atherosclerosis in patients with type 2 diabetes. seventy-one consecutively selected eligible patients (31 males, 40 females) with type 2 diabetes were studied. common carotid intima-media thickness was measured bilaterally by high-resolution ultrasound and the mean value from both sides was used for further analysis. fasting blood samples were taken from each individual and their serum was analyzed for lipoprotein levels. in the entire group of patients, intima-media thickness was inversely related to apoprotein a-i (r -0.33, p 0.008) and hdl cholesterol (r -0.23, p 0.059) in univariate correlation analysis, and a positive correlation between intima-media thickness and apoprotein b/apoprotein a-i ratio was found (r 0.33, p 0.007). when genders were analyzed separately, intima-media thickness was significantly correlated with apoprotein a-i and apoprotein b/apoprotein a-i ratio in females, while no significant correlation of any lipid variable with intima-media thickness was observed in males. in multiple linear regression analysis, age (p 0.005), male gender (p 0.002) and apoprotein a-i (p 0.035) were the only risk factors in the entire group of diabetic patients, which significantly predicted carotid intima-media thickness in models adjusted for demographic and other known risk factors. as was the case in the univariate analysis, no risk factor significantly predicted carotid intima-media thickness in males while age, apoprotein a-i and b significantly predicted intima-media thickness in females.","in the present study, low serum apoprotein a-i, a major protein component of hdl, was found to be related to increased carotid intima-media thickness. this relationship was stronger in females than in males, which suggests possible gender differences in the relationship between apoprotein a-1 and early atherosclerotic lesions in subjects with type 2 diabetes mellitus.",Diagnosis
does radiofrequency ablation combined with systemic chemotherapy in nasopharyngeal carcinoma liver metastases improve response to treatment and survival outcomes?,"systemic chemotherapy is the major treatment modality for nasopharyngeal carcinoma (npc) liver metastases. we investigated the effectiveness of radiofrequency ablation (rfa) treatment, which has not been well explored in this disease. one-hundred and thirty-four cases of npc with liver metastases treated with chemotherapy, chemotherapy with rfa, or rfa alone were retrospectively analyzed. patient survival was evaluated by the log-rank test. survival was analyses using the kaplan-meier method. cox multivariate analyses of clinicopathological features and different treatment approaches were conducted. local response rates were 58 in the rfa group, 78 in the chemotherapy group and 93 in the chemotherapy with rfa group (p 1), the dimension of the largest liver metastases (3 cm vs. 3 cm), evaluation of treatment (response vs. no response) and disease-free survival (12 months vs. 12 months) were independent prognostic factors.","rfa combined with chemotherapy is a promising treatment for npc metastatic liver disease with improved local response, pfs, and os compared to current chemotherapy protocols.",Medication
does simultaneously increased fraction of exhaled nitric oxide levels and blood eosinophil count relate to increased asthma morbidity?,"we have previously described that fraction of exhaled nitric oxide (feno) levels and blood eosinophil counts offer additive information in relation to asthma and asthma exacerbations when analyzing data from a large population study. we sought to investigate increased feno levels and blood eosinophil counts in relation to lung function, bronchial hyperresponsiveness (bhr), and asthma control in a cohort of young asthmatic patients. measurements of feno levels and blood eosinophil counts were available in 406 subjects (208 women) aged 10 to 35 years. asthma control was assessed through the asthma control test. moderate-to-severe bhr was defined as a cumulative dose of methacholine of less than 0.3 mg causing an fev subjects with simultaneously increased feno levels (20-25 ppb) and blood eosinophil counts (0.3 10",we have shown that simultaneously increased local (feno) and systemic (blood eosinophil) markers of type 2 inflammation related to a higher likelihood of bhr and uncontrolled asthma in a large cohort of young asthmatic patients.,Medication
does ultra-low dose beta-irradiation induce constriction of rabbit carotid arteries via the endothelium?,"to investigate the action of ultra-low dose beta-radiation (uldbr) on isolated segments of blood vessels. we used the pharmacological model of isolated rabbit carotid arteries with intact or mechanically removed endothelium. specific vascular responses to beta-irradiation were registered after addition of (90)sr in the concentration range between 12 and 96 microci l(-1) to the organ bath containing physiological salt solution (pss). intact vascular rings, preconstricted with 20 mm k()-pss, developed an additional constriction upon the addition of (90)sr depending on the absorbed radiation dose (21.5, 42.9, 85.8, and 171.6 microgy) and the dose rate (51.5, 103.0, 206.0 and 412.0 microgy h(-1)). the vasoconstriction due to (90)sr was absent in the endothelium-denuded vascular segments indicating the endothelium dependent action of uldbr. irradiation did not alter the endothelium dependent relaxation of rabbit carotid arteries induced by acetylcholine. the endothelium dependent responses to uldbr were abolished after increasing the extra-cellular k() to 40 mm.",uldbr acts on rabbit carotid arteries as a pharmacological signalling agent because uldbr effects were completely reversible. uldbr-mediated contractile responses of the vessels are endothelium dependent. the resistance of acetylcholine endothelium-dependent relaxation of rabbit carotid arteries to uldbr indicates that the polyphosphoinositide-nitric oxide (no) signalling cascade is not impaired by uldbr in endothelial cells.,Medication
do texture feature ratios from relative cbv maps of perfusion mri are associated with patient survival in glioblastoma?,"texture analysis has been applied to medical images to assist in tumor tissue classification and characterization. in this study, we obtained textural features from parametric (relative cbv) maps of dynamic susceptibility contrast-enhanced mr images in glioblastoma and assessed their relationship with patient survival. mr perfusion data of 24 patients with glioblastoma from the cancer genome atlas were analyzed in this study. one- and 2d texture feature ratios and kinetic textural features based on relative cbv values in the contrast-enhancing and nonenhancing lesions of the tumor were obtained. receiver operating characteristic, kaplan-meier, and multivariate cox proportional hazards regression analyses were used to assess the relationship between texture feature ratios and overall survival. several feature ratios are capable of stratifying survival in a statistically significant manner. these feature ratios correspond to homogeneity (p .008, based on the log-rank test), angular second moment (p .003), inverse difference moment (p .013), and entropy (p .008). multivariate cox proportional hazards regression analysis showed that homogeneity, angular second moment, inverse difference moment, and entropy from the contrast-enhancing lesion were significantly associated with overall survival. for the nonenhancing lesion, skewness and variance ratios of relative cbv texture were associated with overall survival in a statistically significant manner. for the kinetic texture analysis, the haralick correlation feature showed a p value close to .05.",our study revealed that texture feature ratios from contrast-enhancing and nonenhancing lesions and kinetic texture analysis obtained from perfusion parametric maps provide useful information for predicting survival in patients with glioblastoma.,Diagnosis
do wnt proteins regulate acetylcholine receptor clustering in muscle cells?,"the neuromuscular junction (nmj) is a cholinergic synapse that rapidly conveys signals from motoneurons to muscle cells and exhibits a high degree of subcellular specialization characteristic of chemical synapses. nmj formation requires agrin and its coreceptors lrp4 and musk. increasing evidence indicates that wnt signaling regulates nmj formation in drosophila, c. elegans and zebrafish. in the study we systematically studied the effect of all 19 different wnts in mammals on acetylcholine receptor (achr) cluster formation. we identified five wnts (wnt9a, wnt9b, wnt10b, wnt11, and wnt16) that are able to stimulate achr clustering, of which wnt9a and wnt11 are expressed abundantly in developing muscles. using wnt9a and wnt11 as example, we demonstrated that wnt induction of achr clusters was dose-dependent and non-additive to that of agrin, suggesting that wnts may act via similar pathways to induce achr clusters. we provide evidence that wnt9a and wnt11 bind directly to the extracellular domain of musk, to induce musk dimerization and subsequent tyrosine phosphorylation of the kinase. in addition, wnt-induced achr clustering requires lrp4.","these results identify wnts as new players in achr cluster formation, which act in a manner that requires both musk and lrp4, revealing a novel function of lrp4.",Medication
is hypothalamic volume loss associated with reduced melatonin output in parkinson 's disease?,"recent studies have suggested that melatonin-a hormone produced by the pineal gland under circadian control-contributes to pd-related sleep dysfunction. we hypothesized that degenerative changes to the neural structures controlling pineal function (especially the suprachiasmatic nuclei of the anterior hypothalamus) may be responsible for reduced melatonin output in these patients. we compared hypothalamic volumes in pd patients with matched controls and determined whether volume loss correlated with reduced melatonin output in the pd group. a total of 12 pd patients and 12 matched controls underwent magnetic resonance imaging to determine hypothalamic volume. in addition, pd patients underwent 24-hour blood sampling in a controlled environment to determine serum melatonin concentrations using enzyme-linked immunosorbent assays. pd patients had significantly reduced hypothalamic gray matter volume when compared with matched controls. melatonin levels were significantly associated with hypothalamic gray matter volume and disease severity in pd patients.","melatonin levels are associated with hypothalamic gray matter volume loss and disease severity in pd patients. this provides anatomical and physiological support for an intrinsic sleep and circadian phenotype in pd. 2016 the authors. movement disorders published by wiley periodicals, inc. on behalf of international parkinson and movement disorder society.",Diagnosis
do trends in cholesterol levels in the adult population of so jos do rio preto ?,"to develop a survey about risk factors for atherosclerosis in a or 20-year-old population from so jos do rio preto, and compare the results with those obtained in a similar survey in 1991. quantitative survey with sample stratified by sex and age. the individuals (a total of 646, 303 men) where contacted in outpatient facilities from the health secretary and other populated sites, distributed by geographic zone and social class of different neighborhoods. the standard error of the survey was 4, and the confidence interval was 95. a) mean hdl-cholesterol (only in 1997): male gender 43.7 /- 15 mg/dl, female gender 49.6 /- 13.5 mg/dl (p 0.001, 95 ci 3.7 a 8.1). b) mean total cholesterol in 1991 vs 1997: for the global population 192.5 /- 48.9 mg/dl vs 190.5 /- 42.5 mg/dl (p ns); for men 187.6 /- 53.3 mg/dl vs 190.5 /- 42.5 mg/dl (p ns); for women 196.8 /- 40 mg/dl vs 187.6 /- 37.8 mg/dl (p 0.008, 95 ci 2.4 a 15.9). c) by regression analysis, the variables that correlated significantly with cholesterol levels, in both surveys, were: age (p 0.001), systolic (p 0.001) and diastolic (p 0.001) arterial pressure, diet (p 0.001). female gender showed correlation only in the 1991 survey (p 0.011), and sedentarism only in 1997 (p 0.014).","the mean cholesterol levels in the adult population of so jos do rio preto are very favorable and, in female gender, showed a significant decrease in the 1997 survey, relatively to the 1991 survey.",Prevention
does psychological stress-induced accelerated colonic transit in rats involve hypothalamic corticotropin-releasing factor?,"brain corticotropin-releasing factor (crf) is involved in stress-induced accelerated colonic transit. brain sites of action of crf to stimulate colonic transit were investigated in conscious fed rats. bilateral guide cannulae were chronically implanted into the paraventricular nucleus of the hypothalamus (pvn) or central amygdala for peptide microinjection and a catheter into the proximal colon to measure colonic transit. crf (0.6 nmol/rat) injected into the pvn reduced colonic transit time by 84 and stimulated fecal pellet output 20-fold, whereas crf injected into sites outside of the pvn or the central amygdala had no effect. crf stimulatory action was prevented by chlorisondamine, and atropine methyl nitrate but not by bretylium. the stress of avoiding water by standing on a small cube reduced colonic transit time by 75 and increased fecal output by 7-fold. bilateral microinjection of crf antagonist, alpha-helical-crf, into the pvn abolished the colonic response to stress. the crf antagonist had no effect on basal colonic transit time in nonstressed rats.",psychological stress-induced stimulation of colonic motor function in fed rats involves crf pathways in the pvn.,Medication
does zingiber officinale ameliorate allergic asthma via suppression of th2-mediated immune response?,"ginger has been used commonly in the traditional system of medicine for the treatment of respiratory disorders. the present study investigates the immunosuppressive activity of ginger by using the mouse model of ovalbumin-induced allergic asthma. treatment with ethanol extract (500 mg/kg) and aqueous extract (720 mg/kg) of rhizomes, and methylprednisolone (5 mg/kg) was initiated 1 week after second sensitization of mice with ovalbumin and continued for 7 d. rt-pcr followed by gel electrophoresis and elisa were used for the evaluation of mrna expression levels and protein levels of th2 type markers, respectively. lung tissue histopathology was conducted by using he and pas staining. we observed significant reduction in goblet cell hyperplasia (0.83 0.17 and 1.0 0.26), infiltration of inflammatory cells in airways (0.67 0.33 and 1.0 0.37), and edema with vascular congestion (1.0 0.26 and 1.2 0.17) by both ethanol and aqueous extracts, respectively. a highly significant reduction of total and differential count of eosinophils and neutrophils in balf, and eosinophil count in blood were also observed. both extracts significantly inhibited th2-mediated immune response, which is evident by a decrease in mrna expression levels of il-4 and il-5. protein levels of il-4 and il-5 in balf, along with total serum ige levels, were also significantly suppressed by both extracts.","our study validated the traditional use of ginger in respiratory disorders and suggests that ginger reduces allergic airway inflammation, possibly by the suppression of th2-mediated immune response.",Diagnosis
does vascular endothelial growth factor augment the healing of demineralized bone matrix grafts?,"to produce a totally allogeneic graft material that would eliminate the need for harvesting the autogenous bone from patients. thirty-six (10x5mm) defects were created in the parietal bones of 18 rabbits. two experimental groups of 12 defects each were grafted with dbm(im) alone and vegfdbm(im), respectively. the remaining 12 defects were left empty as controls, and sacrificed on days 14, 30 and 60. two rabbits, with four defects, of each group were sacrificed on day 14, 30 and 60 post grafting. the defects were retrieved for histological evaluation and quantitative analysis. no bone formed across the defect in the controls. the difference in the amount of new bone formation between experimental groups was significant especially 30 and 60days post grafting (p0.0001), which were 149 and 100 respectively.","vegfdbm(im) powder is a promising graft material, and warrants further clinical investigation.",General
is radiographic measurement of the posterior femoral offset precise?,"the posterior femoral offset may significantly impact the final flexion range after total knee arthroplasty (tka). the purpose of the present study was to compare a conventional, radiologic-based technique with an intra-operative, surgical navigation-based technique for the measurement of posterior femoral offset. the tested hypothesis was that the two measurement techniques produce different results both before and after tka. one-hundred consecutive cases referred for end-stage knee osteoarthritis have been studied. posterior femoral offsets, measured pre- and post-tka from radiographs, as well as those measured from a navigation system intra-operatively, were analysed. the pre-tka measured offsets, post-tka measured offsets and the changes (pre- vs. post-tka) in the offsets were statistically compared between the radiologic and the navigated measurement techniques at a 0.05 level of significance. the mean paired difference between pre-tka radiologic and navigated measurement was 4 4 mm (p 0.001). there was a significant and moderate positive correlation with a good coherence between the two measurements. the mean paired difference between post-tka radiologic and navigated measurement was 6 5 mm (p 0.001). there was a significant and moderate positive correlation but a poor coherence between the two measurements.","the conventional radiologic technique for the measurement of the posterior femoral offset cannot be reliably used either for pre-tka planning of the posterior femoral resection and antero-posterior sizing of the femoral component, or for post-tka quality control of the reconstruction of the posterior femoral offset.",Diagnosis
are the 1-h oral glucose tolerance test glucose and insulin values associated with markers of clinical deterioration in cystic fibrosis?,"cystic fibrosis (cf) is associated with the emergence of cf-related diabetes (cfrd). cfrd is associated with increased risk of accelerated weight and/or lung function loss (clinical degradation). data in the cf pediatric population reported an association between higher 60-min oral glucose tolerance test (ogtt) plasma glucose values and reduced lung function. our objective was to evaluate the relationship between the 60-min ogtt insulin and glucose values and markers of clinical degradation in adult patients with cf. this study was based on an ongoing observational cohort of cf adult patients (18 years). all patients underwent a 2-h ogtt with 30-min interval sample measurements. plasma insulin and glucose levels were measured. adult patients (n 240) were categorized based on the 60-min ogtt median values of glucose (g60, 11.0 mmol/l) and/or insulin (i60, 43.4 u/ml). a negative association was observed between the 60-min ogtt glucose value and pulmonary function (fev1; p 0.001), whereas 60-min ogtt insulin values were positively associated with bmi (p 0.004). patients with high g60 values displayed lower fev1 than patients with low g60 values (p 0.025). patients with higher i60 values demonstrated higher values of both fev1 (p 0.022) and bmi (p 0.003) than patients with low i60 values. more importantly, when adjusting for bmi, the difference in fev1 between both groups no longer existed (p 0.166).",both insulin and glucose values at 60-min ogtt are associated with indicators of clinical degradation in adult patients with cf. future prospective analyses are essential in establishing the clinical utility of these indicators.,Medication
do intellectual and functional outcome of children 3 years old or younger who have cns malignancies?,"to evaluate the impact of tumor location, clinical parameters, and therapy on neurocognitive, neuroendocrine, and functional outcomes in children or 5 years after diagnosis, 71.4 of csi recipients compared with 23 of local rt recipients had iq less than 70 (p .021). patients undergoing csi were more likely to develop endocrinopathies (p .0001) and to require special education (p .0007).","in young children with cns tumors, csi and hemispheric location are associated with significant declines in iq scores.",Treatment
does antenatal glucocorticoid administration increase corticotrophin-releasing hormone in maternal plasma?,"this study was designed to determine whether maternal corticotrophin-releasing hormone (crh) concentrations are altered after maternal betamethasone administration for fetal lung maturity in women with threatened preterm labour and whether these effects are dependent on gestational age. our study included 49 women with threatened preterm labour who received prenatal betamethasone for fetal lung maturity between 24 and 31 weeks of gestational age and 11 women who did not. maternal blood was taken before and after glucocorticoid administration or at 24 hours after initial sampling. plasma crh, adrenocorticotrophin (acth) and cortisol concentrations were determined by radioimmunoassays. the women were stratified into 24-25 weeks, 26-27 weeks, 28-29 weeks, and 30-31 weeks completed gestation. at each gestational age, maternal cortisol concentrations decreased by approximately 85 after glucocorticoid administration. overall mean cortisol values fell from 580.0 (sd, 351.8) to 89.7 (96.6) nmol/l (n 40, p 0.001). overall mean acth values decreased from 9.9 (4.7) to 5.0 (3.4) pmol/l (n 43, p 0.001), and the approximate 50 decrease was similar at each gestational age. in marked contrast, overall mean crh values increased from 58.0 (37.0) to 87.8 (68.6) pmol/l (n 49, p 0.001) after betamethasone administration. there was no change in maternal cortisol, acth or crh values over 24 hours in women who did not receive betamethasone.",we conclude that maternal betamethasone administration increases maternal plasma crh values between 24 and 31 completed weeks of gestation.,General
are lipopolysaccharide-induced intestinal motility disturbances mediated by c-jun nh2-terminal kinases?,"lipopolysaccharide (lps) is a causative agent of sepsis. many alterations, such as intestinal motility disturbances, have been attributed to lps. here we investigated the role of c-jun nh(2)-terminal kinases (jnk) in the effect of lps on intestinal motility, the oxidative stress status and the cyclooxygenese-2 (cox-2) expression. rabbits were injected with either (1) saline, (2) lps, (3) sp600125, a specific jnk inhibitor, or (4) sp600125lps. duodenal contractility was studied in an organ bath. the formation of products of oxidative damage to proteins (carbonyls) and lipids malondialdehyde (mda) and 4-hydroxyalkenals (4-hda) was quantified by spectrophotometry in the intestine and plasma. the protein expression of p-jnk, total jnk, and cox-2 was measured by western blot, and p-jnk was localized by immunohistochemistry. lps decreased the contractions evoked by acetylcholine and prostaglandin e(2) and kcl-induced contractions. lps increased phospho-jnk and cox-2 expressions and the levels of carbonyls and mda4-hda. sp600125 blocked the effect of lps on the acetylcholine, prostaglandin e(2), and kcl-induced contractions, the levels of carbonyls and mda4-hda, and the p-jnk and cox-2 expressions. p-jnk was detected in the smooth muscle cells of duodenum.",our results suggest that jnk is involved in the mechanism of action of lps in the intestine.,Medication
do anthocyanin-derived phenolic acids form glucuronides following simulated gastrointestinal digestion and microsomal glucuronidation?,"current research indicates that anthocyanins are primarily degraded to form phenolic acid products. however, no studies have yet demonstrated the metabolic conjugation of these anthocyanin-derived phenolic acids in humans. within the present study, a simulated gastrointestinal digestion model was used to evaluate the potential degradation of anthocyanins post-consumption. subsequently, cyanidin (cy) and pelargonidin and their degradation products, protocatechuic acid and 4-hydroxybenzoic acid, were incubated in the presence of human liver microsomes to assess their potential to form hepatic glucuronide conjugates. for structural conformation, phenolic glucuronides were chemically synthesised and compared to the microsomal metabolites. during the simulated gastric digestion, anthocyanin glycosides (200 m) remained stable however their aglycone derivatives were significantly degraded (20 loss), while during subsequent pancreatic/intestinal digestion only pelargonidin-3-glucoside remained stable while cyanidin-3-glucoside (30 loss) and cy and pelagonidin aglycones were significantly degraded (100 loss, respectively). following microsomal metabolism, pelargonidin formed 4-hydroxybenzoic acid, which was further metabolised (65) to form two additional glucuronide conjugates, while cy formed protocatechuic acid, which was further metabolised (43) to form three glucuronide conjugates.","we propose that following ingestion, anthocyanins may be found in the systemic circulation as free or conjugated phenolic acids, which should be a focus of future dietary interventions.",General
does preinfarction angina affect infarct size in stemi patients undergoing primary angioplasty?,"several clinical studies have demonstrated that anginal attacks shortly before the onset of stemi limit infarct size and improve short- and long-term outcomes. however, the clinical significance of preinfarction angina in stemi patients treated by primary pci is still controversial. therefore, the aim of the current study was to evaluate the impact of preinfarction angina on scintigraphic infarct size in stemi patients undergoing primary pci. our population is represented by 430 stemi patients undergoing primary pci. infarct size was evaluated at 30 days by technetium-99m-sestamibi. preinfarction angina was associated with more advanced age, a larger prevalence of family history for cad, smoking, and longer ischemia time. no difference was observed in other clinical or angiographic characteristics. preinfarction angina did not affect either the rate of postprocedural timi 3 flow or infarct size (19 15.5 vs 16 13.9, p 0.18). similar results were observed in subanalyses according to infarct location (anterior stemi: 22.7 14.8 vs 19.2 16.1, p 0.36; non-anterior stemi: 16.1 15.7 vs 13.8 11.6, p 0.36), gender (female gender: 15.6 14.5 vs 11.5 13.2, p 0.30; male gender 20.4 16 vs 17.2 13.8, p 0.3) or ischemia time ( or 4 h) (17.6 15.6 vs 15.8 14.1, p 0.52; 21.6 15.5 vs 16.7 13.3, p 0.18). the absence of any impact of preinfarction angina on infarct size was confirmed after correction for baseline characteristics, such as age, smoking, family history for cad and ischemia time (or 95 ci 1.26 0.66-2.41, p 0.48).",this study shows that among stemi patients undergoing primary pci preinfarction angina does not affect infarct size.,Treatment
does manual exfoliation of fresh tissue obviate the need for frozen sections for molecular profiling?,"simple, rapid tissue processing that preserves macromolecules will enhance translational research capabilities. traditional fixative-based approaches for specimen preservation are ideal for histologic evaluation but are not conducive to molecular studies of nucleic acids and protein. tissue cryosections preserve macromolecule integrity, but the process is labor intensive and technically challenging. to the authors' knowledge to date, an alternative method capable of retrieving cells while providing adequate histologic detail yet preserving macromolecule integrity has been lacking. in the current study, the authors evaluated the utility of using manual exfoliation of clinical tissue samples as a means of obtaining cells for molecular analysis. this technique possesses the advantages of fixed and frozen tissue sections without their drawbacks. this simple, rapid, nonfixative based technique is capable of preparing cells from human clinical material for further isolation without compromising the preservation of macromolecules in the tissue. cells from a variety of clinical resection specimens from solid tumors were directly scraped from the tissue samples using the edge of a glass microscope slide and smeared onto another slide for cytologic evaluation. the manually exfoliated cells were evaluated microscopically for cytologic quality and cellular quantity. pure cell populations were procured by laser capture microdissection (lcm) with subsequent extraction of nucleic acids and proteins. the integrity and suitability of the recovered nucleic acids and proteins for molecular analysis were evaluated using the polymerase chain reaction (pcr), reverse transcriptase-pcr, and reverse-phase protein microarray, respectively. manual exfoliation permits the selection of homogeneous cell populations by lcm based on well established cytologic characteristics. dna and mrna, of comparable quality to frozen sections, can be amplified from the manual exfoliation cells. proteins of similar quality can be recovered using this technique and quantitated via reverse-phase protein microarray.","molecular macromolecules of high quality and sufficient quantity can be retrieved from human clinical samples using manual exfoliation and lcm to procure specific cell populations. the manual exfoliation technique does not destroy the original tissue source, thereby allowing subsequent formalin tissue fixation. the technique of manual exfoliation in conjunction with lcm can enable the molecular profiling of a sampled selected cell population. because it does not destroy the original tissue, histologic correlation can be combined with molecular profiling.",Treatment
is a planar qrs-t angle 90 degrees associated with multivessel coronary artery disease in patients undergoing coronary angiography?,the aim of the study was to investigate the severity of coronary artery disease (cad) in patients who had a planar qrs-t angle 90 degrees versus 50 obstruction of or1 major coronary artery. all qrs-t angle measurements were made from a 12-lead electrocardiogram by 2 authors who agreed on the measurement and who were blinded to the coronary angiographic findings. a qrs-t angle 90 degrees was considered abnormal. obstructive cad of 2 or 3 vessels was present in 309 of 495 patients (62) with a planar qrs-t angle 90 degrees and in 250 of 734 patients (34) with a planar qrs-t angle or30 kg/m2 (odds ratio 1.5).,the prevalence of 2- or 3-vessel obstructive cad was significantly higher in patients with a planar qrs-t angle 90 degrees than in patients with a planar qrs-t angle or90 degrees (p0.0001).,General
does peak aerobic capacity predict prognosis in patients with coronary heart disease?,"it is unknown if contemporary preventive treatments such as statins or primary percutaneous coronary intervention in patients with coronary heart disease (chd) have rendered obsolete the use of measured exercise capacity for assessment of future risk and prognosis. using a sample of patients from 2 clinical sites, most of whom were taking beta-blockade, antiplatelet, and statin therapy, we hypothesized that peak oxygen consumption (vo(2)) would remain a strong and independent predictor of all-cause and cardiovascular-specific mortality in men and women with chd. we studied 2,812 patients with chd between 1996 and 2004. all-cause and cardiovascular disease-specific mortality served as end points. in all men and women and in a subgroup of patients following evidence-based care, peak vo(2) remained a strong predictor of all-cause death, with every 1 ml x kg(-1) x min(-1) increase in peak vo(2) associated with an approximate 15 decrease in risk of death. among men, a peak vo(2) (ml x kg(-1) x min(-1)) below approximately 15 was associated with the highest risk, whereas a peak vo(2) above approximately 19 was associated with a low rate and risk for annual all-cause mortality. among women, a peak vo(2) below approximately 12 was associated with the highest risk, whereas a peak vo(2) above approximately 16.5 was associated with the lowest rate and risk for annual all-cause mortality.","in men and women with chd, peak vo(2) remains an independent predictor of all-cause and cardiovascular-specific mortality.",Diagnosis
does oral folic acid improve endothelial dysfunction in cigarette smokers?,"endothelial dysfunction is an early manifestation of the atheromatous process and is evident without overt clinical signs or symptoms of the disease. cigarette smoking has been shown to be associated with endothelial dysfunction in otherwise healthy adults. although cessation of smoking is the ideal objective, it is not always attainable, and therefore any strategy to prevent early endothelial dysfunction is desirable. folic acid is currently under review as a rational therapeutic agent in hyperhomocysteinemia. however, folic acid may modify endothelial function independent of its effect on homocysteine. we therefore investigated the effect of folic acid on endothelial function in young otherwise healthy cigarette smokers. volunteer cigarette smokers (n 10) and control lifelong nonsmokers were enrolled in the study. baseline folate, vitamin b12, homocysteine, and cholesterol levels were analyzed. flow-mediated dilatation, an endothelial-dependent phenomenon, was assessed using ultrasonography. this scan was performed at baseline and following 4 weeks of folic acid supplementation (5 mg/day). there were no significant differences in the baseline hematological investigations between the groups. homocysteine levels were within normal limits in both groups and did not change following folic acid supplementation. cigarette smokers demonstrated significant endothelial dysfunction compared to controls (p 0.005). this difference was significantly attenuated by folic acid supplementation (p 0.005).",folic acid significantly improves endothelial function in otherwise healthy cigarette smokers. this provides a potential therapeutic tool in attenuating the atheromatous process in this group.,Symptoms
does surface acoustic wave patch therapy affect tissue oxygenation in ischemic feet?,"transcutaneous oxygen pressure (tcpo2) less than 30 mm hg at the toe leads to local tissue hypoxia and nonhealing wounds. studies regularly illustrate that tcpo2 values are strong predictors of healing and can accurately demonstrate altered levels when extremities have restricted blood flow. the objective of this study was to evaluate the effectiveness of surface acoustic wave (saw) in ischemic feet on local tissue oxygenation. ten patients, ranging from 40-75 years of age and suffering from critical limb ischemia (cli) were selected from a vascular surgery clinic to undergo evaluation with a painshield saw patch device (nanovibronix inc, melville, ny). patients were treated once with 96 khz of saw for 30 minutes. all patients had an ankle brachial index of 0.4 mm hg. two patients (patients 1 and 8) had necrosis of at least 2 toes on the affected limb and were given the device for nightly use for 1 month. through usage of saw there was a significant increase in all patients' saturation values. the recorded baseline in both patients with necrotic toes almost doubled and during usage there was still a measurable increase in oxygen saturation. in both of these patients the subjective pain measures dropped significantly. pain, as assessed by the visual analog scale, dropped from 9 to 2 for patient 1 and from 8 to 3 for patient 8. patient 1 went from 5 methadone treatments per day to only 1 per day starting in week 3. patient 8 did not change their pain medication regimen.","surface acoustic waves as delivered in this study had a positive effect on tissue oxygenation and saturation in ischemic feet. in lower extremities that are not surgical candidates or are either in the pre- or postsurgical environment, an saw patch device is a good therapy in elevating the extremities' o2 saturation.",Treatment
does ketamine suppress lps-induced bile reflux and gastric bleeding in the rat?,"although ketamine has many beneficial effects in a rat model of noninfectious inflammation with lipopolysaccharide (lps), its effects on gut ileus are unknown. we hypothesized that ketamine would improve lps-induced ileus and therefore examined its effects on gastric emptying and intestinal transit as well as duodenogastric bile reflux and associated gastric bleeding. male rats received saline or ketamine (7 mg/kg ip) 1 hour before saline or lps (20 mg/kg ip) for 5 hours. thirty minutes before killing, rats received orogastric rhodamine b isothiocyanate-labeled dextran and 5 minutes later fluorescein isothiocyanate-labeled dextran via a duodenal catheter. gi contents were collected for dye, bile acid, and hemoglobin (index of bleeding) determinations. lps significantly impaired intestinal transit and increased duodenogastric bile reflux and gastric luminal hemoglobin content. ketamine improved intestinal transit, prevented lps-induced bile reflux, and diminished gastric bleeding. in mechanistic studies, ketamine also attenuated lps-induced upregulation of the proinflammatory genes inducible nitric oxide synthase and cyclo-oxygenase-2 in the stomach but preserved expression of the anti-inflammatory gene heme-oxygenase-1 (western blot).","these data suggest that ketamine may prevent lps-induced gastric bleeding by decreasing bile reflux through improved intestinal transit or by local changes in nitric oxide, prostaglandin, and carbon monoxide metabolism.",Symptoms
do sevoflurane and isoflurane impair edrophonium reversal of vecuronium-induced neuromuscular block?,"a dose-response relationship study for edrophonium to examine the modification of volatile anaesthetics on reversal of vecuronium block. one hundred and twenty asa (i-ii) patients were anaesthetized with sevoflurane, isoflurane (1 minimum alveolar anaesthetic concentration mac end-tidal concentration), or fentanyl-diazepam anaesthesia, in combination with 66 nitrous oxide (n 40 for each group). the evoked electromyogram (emg) response of the abductor digiti minimi was monitored at 20 sec intervals following train-of-four (tof) stimulation of the ulnar nerve. the initial neuromuscular block was produced by vecuronium 100 micrograms.kg-1. when the amplitude of the first response (t1) had spontaneously recovered to 10 of the control, edrophonium (0, 125, 400, 700 or 1000 micrograms.kg-1; eight patients each) was randomly administered, and the ratio of the fourth tof to the first response (tofr) was monitored at one minute intervals for 10 min. sevoflurane and isoflurane impaired the edrophonium-assisted tofr recovery in an edrophonium dose and time dependent manner. the dose-response curves at 10 min exhibited a greater shift to the right in the sevoflurane and isoflurane groups than in the fentanyl-diazepam-nitrous oxide group (p 1000 micrograms.kg-1) and isoflurane groups (851 micrograms.kg-1) were observed than in the fentanyl-diazepam-nitrous oxide group (339 micrograms.kg-1) (p 0.05).",one mac sevoflurane and isoflurane anaesthesia impair edrophonium reversal of vecuronium block to a similar degree.,Medication
does efavirenz outperform boosted atazanavir among treatment-naive hiv-1-infected persons in routine clinical care?,"effectiveness of antiretroviral therapy (art) in a routine clinical care may result different from the clinical trials. we assessed the virologic outcomes in treatment-naive persons who received either efavirenz (efv) or atazanavir/ritonavir (atv/r) with a backbone of tenofovir/emtricitabine (tdf/ftc) as their combination art (cart). this was a retrospective cohort study conducted at the washington university hiv outpatient clinic from january 2004 to june 2009. predictors of virologic suppression (hiv rna level 400 copies/ml) by week 48 were assessed by multivariate cox proportional hazards regression models. of 324 persons, 221(68) received efv and 103 (32) received atv/r. persons on efv had 1.4-fold increased likelihood of virologic suppression (95 confidence interval, 1.0-1.8) when compared to atv/r after adjustment with primary drug resistance, pre-cart opportunistic infection, hiv rna levels, and timing to start cart.","in routine clinical care settings, efv had higher likelihood of achieving virologic suppression than atv/r with backbone of tdf/ftc.",Treatment
does hypoxia confer protection against apoptosis via the pi3k/akt pathway in endothelial progenitor cells?,"the recruitment of endothelial progenitor cells (epc) to ischemia has recently been suggested as an important mechanism of tissue repair. although tissue ischemia can facilitate epc mobilization, recruitment, and retention at the hypoxic site, the effects of hypoxia on epc survival are not well known. in the present study, we examined whether hypoxia (2 o2) would suppress apoptosis induced by serum withdrawal and whether survival signals, such as the phosphatidylinositol 3-kinase (pi3k)/akt and extracellular signal-regulated protein kinase (erk) pathways, were involved in this process. after being serum-starved for 24 h, epc were cultured under normoxic or hypoxic conditions (2 o2) for 24 h. cell survival was assessed by 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, annexin v-propidium iodide dual-color flow cytometry, and terminal deoxynucleotidyl transferase-mediated digoxigenin-dutp nick-end labeling assay. the expressions of signaling proteins were evaluated by western blot analysis. under hypoxic conditions, epc were resistant to apoptosis induced by serum starvation. the inhibition of the pi3k/akt pathway using the ly294002 inhibitor prevented hypoxia-inhibited apoptosis in epc and altered the phosphorylation state of glycogen synthase kinase-3beta, an effector protein involved in regulation of epc apoptosis. however, erk inhibitor pd98059 had no significant effect on cell survival.","our data demonstrated that hypoxia inhibited serum withdrawal-induced apoptosis in epc, which might be associated with the activation of the pi3k/akt pathway.",Medication
do ten-year results from the natrelle 410 anatomical form-stable silicone breast implant core study?,"silicone breast implants have long been used for breast augmentation and reconstruction. during this time, these medical devices have gone through a number of modifications to improve their safety, quality, and clinical outcome performance. the authors conducted a 10-year study to determine the safety and effectiveness of natrelle 410 silicone breast implants. this prospective, multicenter study enrolled 941 subjects who were undergoing either augmentation, augmentation revision, reconstruction, or reconstruction revision. data on complications, reoperations, explantations, and subject satisfaction were collected at annual clinic visits, and one-third of subjects underwent biennial magnetic resonance imaging (mri) to screen for implant rupture. the authors used the kaplan-meier estimator to calculate risk rates for local complications, reoperations, and explantations. capsular contracture rates increased approximately 1 per year from the previously reported 6-year rates. the rates were significantly lower than those from the natrelle round gel core study. the overall rate of confirmed ruptured implants in subjects who underwent mri was 5.7. eleven late seromas were reported. the most common reason for explantation was a subject requesting a size or style change. satisfaction rates remained high through 10 years, with most subjects saying they were somewhat or definitely satisfied with their implants.",this 10-year prospective trial demonstrated the long-term safety and effectiveness of natrelle 410 anatomical form-stable implants. the complication rates were low and the satisfaction rates were high. level of evidence 1: therapeutic.,Diagnosis
does multicolor banding remain an important adjunct to array cgh and conventional karyotyping?,"array comparative genomic hybridization (cgh) for high resolution detection of chromosome imbalance, and karyotype analysis using g-banded chromosomes for detection of chromosome rearrangements, provide a powerful diagnostic armoury for clinical cytogenetics. however, abnormalities detected by karyotype analysis cannot always be characterised by scrutinising the g-banded pattern alone, and imbalance detected by array cgh cannot always be visualised in the context of metaphase chromosomes. in some cases further techniques are needed for detailed characterisation of chromosomal abnormalities. we investigated seven cases involving structural chromosome rearrangements detected by karyotype analysis, and one case where imbalance was primarily detected by array cgh. multicolor banding (mcb) was used in all cases and proved invaluable in understanding the detailed structure of the abnormalities. karyotype analysis detected structural chromosome rearrangements in 7 cases and mcb was used to help refine the karyotype for each case. array cgh detected imbalance in an eighth case, where previously, g-banded chromosome analysis had reported a normal karyotype. karyotype analysis of a second tissue type revealed this abnormality in mosaic form; however, mcb was needed in order to characterise this rearrangement. mcb provided information for the delineation of small deletions, duplications, insertions and inversions and helped to assign breakpoints which were difficult to identify from g-banded preparations due to ambiguous banding patterns.","despite the recent advance of array cgh in molecular cytogenetics we conclude that fluorescence in situ hybridization, including mcb, is still required for the elucidation of structural chromosome rearrangements, and remains an essential adjunct in modern diagnostic laboratories.",Diagnosis
is development of neuropathic pain in the rat spared nerve injury model prevented by a peripheral nerve block?,"the mechanisms responsible for initiation of persistent neuropathic pain after peripheral nerve injury are unclear. one hypothesis is that injury discharge and early ectopic discharges in injured nerves produce activity-dependent irreversible changes in the central nervous system. the aim of this study was to determine whether blockade of peripheral discharge by blocking nerve conduction before and 1 week after nerve injury could prevent the development and persistence of neuropathic pain-like behavior in the spared nerve injury model. bupivacaine-loaded biodegradable microspheres embedded in fibrin glue were placed in a silicone tube around the sciatic nerve to produce a conduction block. after sensory-motor testing of block efficacy, a spared nerve injury procedure was performed. development of neuropathic pain behavior was assessed for 4 weeks by withdrawal responses to stimulation (i.e., von frey filaments, acetone, pinprick, radiant heat) in bupivacaine microspheres-treated animals (n 12) and in controls (n 11). bupivacaine microspheres treatment produced conduction blockade with a complete lack of sensory responsiveness in the sural territory for 6 to 10 days. once the block wore off, the degree of hypersensitivity to stimuli was similar in both groups.",peripheral long-term nerve blockade has no detectable effect on the development of allodynia or hyperalgesia in the spared nerve injury model. it is unlikely that injury discharge at the time of nerve damage or the early onset of ectopic discharges arising from the injury site contributes significantly to the persistence of stimulus-evoked neuropathic pain in this model.,Prevention
is plasma timp1 level a prognostic factor in patients with liver metastases?,"timp1 (tissue inhibitor of metalloproteinases 1) regulates extracellular matrix turnover and also promotes cell growth and has anti-apoptotic activity, which promotes malignant processes in tumor tissue. the aim of our study was to evaluate the relation of plasma timp1 protein levels with prognosis in patients with liver metastases, with particular regard to possible early-prediction of recurrence of the disease. we studied a group of 87 patients with metastatic liver disease (mostly from colorectal cancer) who underwent surgery for liver metastases, and assessed their preoperative plasma timp1 levels. these levels were evaluated according to prognosis. furthermore, we measured plasma timp1 in the post-operative period and tried to relate the changes with the diagnosis of relapse. we found preoperative plasma timp1 levels to be related to overall survival in the group of all patients with metastatic liver disease (p0.0047), with a higher level being associated with an adverse outcome; the cut-off value was set at 165 ng/ml. this applied to all patients, regardless of the type of surgery. assessment of the post-operative dynamics of timp1 was not found to be statistically significant to indicate disease recurrence.",we found there to be a relationship between higher plasma levels of timp1 and an adverse prognosis in patients with liver metastases. the assessment of plasma timp1 levels could help the detection of patients with worse outcome.,Diagnosis
does overexpression of calcineurin in mouse cause sudden cardiac death associated with decreased density of k channels?,"overexpression of calcineurin in transgenic (tg) mice results in cardiac hypertrophy and unexpected deaths. none of the tg survived beyond 24 weeks (n38) whereas all of the wildtype (wt, n47) survived. prolongation of repolarization preceded the development of sustained pleomorphic ventricular tachycardia and high degree atrioventricular block, which occurred during spontaneous sudden deaths. since depolarization-activated k() channels contribute dominantly to repolarization in mice, we hypothesized that the tg would decrease these k() currents and that the in vivo administration of cyclosporin a (csa), a calcineurin inhibitor, would reduce this effect. csa reversed cardiac hypertrophy: capacitance measurements of wt left ventricular myocytes (127/-7 pf; n45) and csa-treated tg (129/-14 pf; n17) were significantly lower than in placebo-treated tg (220/-11 pf; n41; p0.001 by anova). independent of whether the data fit a bi- or a tri-exponential model, the density of i(tof) was significantly reduced in tg versus wt and csa reversed this effect. while i(tos) and i(kslow) were also reduced in tg, csa does not reverse this change because long-term in vivo csa treatment of wt also reduces i(tos) and i(kslow.) to assess whether the decreased 'repolarization reserve' contributed to arrhythmogenesis, the residual i(kr) was blocked by dofetilide precipitating pleomorphic ventricular tachycardias.","since the downregulation of i(tof) was observed with overexpression of calcineurin and was also reversed by the calcineurin inhibitor csa, we conclude that downregulation of i(tof) is a consequence of calcineurin overexpression.",Medication
does linezolid have unique immunomodulatory effects in post-influenza community acquired mrsa pneumonia?,"post influenza pneumonia is a leading cause of mortality and morbidity, with mortality rates approaching 60 when bacterial infections are secondary to multi-drug resistant (mdr) pathogens. staphylococcus aureus, in particular community acquired mrsa (cmrsa), has emerged as a leading cause of post influenza pneumonia. linezolid (lzd) prevents acute lung injury in murine model of post influenza bacterial pneumonia. mice were infected with hini strain of influenza and then challenged with cmrsa at day 7, treated with antibiotics (lzd or vanco) or vehicle 6 hours post bacterial challenge and lungs and bronchoalveolar lavage fluid (bal) harvested at 24 hours for bacterial clearance, inflammatory cell influx, cytokine/chemokine analysis and assessment of lung injury. mice treated with lzd or vanco had lower bacterial burden in the lung and no systemic dissemination, as compared to the control (no antibiotic) group at 24 hours post bacterial challenge. as compared to animals receiving vanco, lzd group had significantly lower numbers of neutrophils in the bal (910(3) vs. 2.310(4), p 0.01), which was associated with reduced levels of chemotactic chemokines and inflammatory cytokines kc, mip-2, ifn-, tnf- and il-1 in the bal. interestingly, lzd treatment also protected mice from lung injury, as assessed by albumin concentration in the bal post treatment with h1n1 and cmrsa when compared to vanco treatment. moreover, treatment with lzd was associated with significantly lower levels of pvl toxin in lungs.",linezolid has unique immunomodulatory effects on host inflammatory response and lung injury in a murine model of post-viral cmrsa pneumonia.,Medication
is cadherin 17 frequently expressed by 'sclerosing variant ' pancreatic neuroendocrine tumour?,"recently, we described a series of pancreatic neuroendocrine tumours (pannets) featuring prominent stromal fibrosis, which we called sclerosing pannets. the aim of this study was to examine the pathological, immunophenotypic and clinical differences between sclerosing and non-sclerosing pannets. one hundred and six pannets were identified, of which 15 (14) were sclerosing nets. tissue microarrays containing 44 non-sclerosing and five sclerosing pannets, as well as sections from 10 additional sclerosing tumours, were immunohistochemically labelled for serotonin, cdx2, cdh17, and islet 1. sclerosing pannets were smaller (p 0.045) and more likely to show an infiltrative growth pattern (p 0.001) than non-sclerosing pannets. they were frequently associated with a large pancreatic duct, causing duct stenosis. additionally, we found significantly increased expression of the small intestinal net markers serotonin, cdx2 and cdh17 in sclerosing pannets (p 0.001) as compared with non-sclerosing pannets. no difference in clinical outcome was found; however, more sclerosing pannets were stage iib or above (p 0.035), with lymph node metastasis being seen in three of nine sclerosing pannets with a tumour size of 20 mm.","sclerosing pannets have distinct pathological features and biomarker expression profiles. in addition, lymph node metastasis can be present even with small sclerosing pannets.",Diagnosis
is elevated plasma proinsulin/insulin ratio a marker of reduced insulin secretory capacity in healthy young men?,"to examine whether reduced insulin secretory capacity or increased insulin secretory demand is associated with elevated ratio of plasma proinsulin to immunoreactive insulin (pi/iri ratio) in non-diabetic subjects. we measured various indices of insulin secretory function and insulin sensitivity by frequently sampled intravenous glucose tolerance test (fsigt) and hyerglycemic glucose clamp in 21 healthy young men. we then examined the relationships between these indices and pi, iri, or pi/iri ratio in the fasting state. insulin sensitivity index (si) measured by fsigt correlated inversely with basal iri (r-0.53, p 0.01) and pi levels (r-0.57, p 0.01), but there was no significant correlation between si and pi/iri ratio (r0.26, ns). on the other hand, pi/iri ratio correlated inversely with insulin secretory indices, such as acute insulin responses during fsigt (r -0.46, p 0.01) and hyperglycemic glucose clamp (r-0.54, p 0.01) and submaximum insulin response during hyperglycemic glucose clamp (r-0.59, p 0.01).",these results indicate that elevated pi/iri ratio may serve as a marker of reduced insulin secretory function in non-diabetic subjects.,Medication
are operating lung volumes affected by exercise mode but not trunk and hip angle during maximal exercise?,"despite vopeak being, generally, greater while running compared to cycling, ventilation (ve) during maximal exercise is less while running compared to cycling. differences in operating lung volumes (olv) between maximal running and cycling could be one explanation for previously observed differences in v e and this could be due to differences in body position e.g., trunk/hip angle during exercise. we asked whether olv differed between maximal running and cycling and if this difference was due to trunk/hip angle during exercise. eighteen men performed three graded maximal exercise tests; one while running, one while cycling in the drop position (i.e., extreme hip flexion), and one while cycling upright (i.e., seated with thorax upright). resting flow-volume characteristics were measured in each body position to be used during exercise. tidal flow-volume loops were measured throughout the exercise. v e during maximal running (148.8 18.9 l min(-1)) tended to be lower than during cycling in the drop position (158.5 24.7 l min(-1); p 0.07) and in the upright position (158.5 23.7 l min(-1); p 0.06). end-inspiratory and end-expiratory lung volumes (eilv, eelv) were significantly larger during drop cycling compared to running (87.1 4.1 and 35.8 6.2 vs. 83.9 6.0 and 33.0 5.7 fvc), but only eilv was larger during upright cycling compared to running (88.2 3.5 fvc). olv and v e did not differ between cycling positions.","since olv are altered by exercise mode, but cycling position did not have a significant impact on olv, we conclude that trunk/hip angle is likely not the primary factor determining olv during maximal exercise.",Prevention
does orally administered diflunisal stabilize transthyretin against dissociation required for amyloidogenesis?,"rate-limiting transthyretin (ttr) tetramer dissociation and monomer misfolding enable misassembly into numerous aggregate morphologies including amyloid, a process genetically linked to and thought to cause amyloid pathology. t119m ttr trans-suppressor subunit inclusion into tetramers otherwise composed of disease-associated subunits ameliorates human amyloidosis by increasing the tetramer dissociation barrier. diflunisal binding to the 99 unoccupied l-thyroxine binding sites in ttr also increases the tetramer dissociation barrier; hence, we investigated the feasibility of using diflunisal for the treatment of human ttr amyloidosis using healthy volunteers. diflunisal (125, 250 or 500 mg bid) was orally administered to groups of 10 subjects for 7 days to evaluate serum diflunisal concentration, diflunisal binding stoichiometry to ttr, and the extent of diflunisal imposed ttr kinetic stabilization against urea- and acid-mediated ttr denaturation in human serum. the rates of urea-mediated tetramer dissociation and acid-mediated aggregation as a function of diflunisal concentration were also evaluated in vitro, utilizing physiologically relevant concentrations identified by the above experiments. in the 250 mg bid group, 12 h after the 13th oral dose, the diflunisal serum concentration of 146 /- 39 microm was sufficient to afford a ttr binding stoichiometry exceeding 0.95 /- 0.13 ( approximately 1.75 corrected). diflunisal binding to ttr at this dose slowed urea-mediated dissociation and acid-mediated ttr aggregation at least, threefold (p 0.05) in serum and in vitro, consistent with kinetic stabilization of ttr.","diflunisal-mediated kinetic stabilization of ttr should ameliorate ttr amyloidoses, provided that the nonsteroidal anti-inflammatory drug liabilities can be managed clinically.",Medication
does late reduction in cyclosporine dosage improve renal function in pediatric heart transplant recipients?,"to determine the relation between cyclosporine (csa) dosage and late renal function in pediatric heart transplant recipients. in this retrospective study, pediatric patients were observed for at least 3 years after transplantation, with serial measurement of renal glomerular filtration rate (gfr). patient variables examined included pre-existing disease (cardiomyopathy or congenital heart disease), age at transplantation, duration of follow-up, and csa dosage and trough levels at 3 months after transplantation and yearly until the latest follow-up. for each patient, the least squares regression method was used to estimate the average rate of change per year (slope value) for gfr and csa dosage during follow-up. twenty-five patients who met the study criteria underwent transplantation at a median age of 11.7 years (interquartile range iqr, 6.8-14.5 years) and were observed for a median of 6.0 years (iqr, 4-7). the median gfr at 1 year after transplantation was 73 ml/min/1.73 m(2) (iqr, 50-89) and at latest follow-up was 75 ml/min/1.73 m(2) (iqr, 57-98). the median csa dosage and trough level at 1 year after transplantation were 6.1 mg/kg/day and 234 ng/ml, and at latest follow-up were 3.45 mg/kg/day and 141 ng/ml, respectively. the median rate of change in gfr was 1.6 ml/year of observation (95 confidence interval, -0.9, 4.7) and was inversely related to measured gfr at 1 year after transplantation. the rate of change of gfr was unrelated to any other patient variables including csa dosages and levels at the specified time intervals and the rate of change of csa dosage.",measured gfr in pediatric cardiac transplant recipients treated with csa is moderately depressed at 12 months after transplantation and does not change significantly during subsequent years. no evidence suggests that the usual progressive reduction in csa dosage influences renal function beyond 1 year after transplantation.,Medication
do slow gait speed and rapid renal function decline are risk factors for postoperative delirium after urological surgery?,"the aim of this study was to identify risk factors associated with postoperative delirium in patients undergoing urological surgery. we prospectively evaluated pre- and postoperative risk factors for postoperative delirium in consecutive 215 patients who received urological surgery between august 2013 and november 2014. preoperative factors included patient demographics, comorbidities, and frailty assessment. frailty was measured by handgrip strength, fatigue scale of depression, fall risk assessment, and gait speed (the timed get-up and go test). postoperative factors included types of anesthesia, surgical procedure, renal function and serum albumin decline, blood loss, surgery time, highest body temperature, and complications. uni- and multivariate logistic regression analyses were performed to assess pre- and postoperative predictors for the development of postoperative delirium. median age of this cohort was 67 years. ten patients (4.7) experienced postoperative delirium. these patients were significantly older, had weak handgrip strength, a higher fall risk assessment score, slow gait speed, and greater renal function decline compared with patients without delirium. multivariate analysis revealed slow gait speed (13.0 s) and rapid renal function decline (30) were independent risk factors for postoperative delirium.",slow gait speed and rapid renal function decline after urological surgery are significant factors for postoperative delirium. these data will be helpful for perioperative patient management. this study was registered as a clinical trial: umin: r000018809.,Treatment
does peptide yy attenuate transcription factor activity in tumor necrosis factor-alpha-induced pancreatitis?,"acute pancreatitis (ap) is a disease characterized by inflammation. nuclear factor (nf)-kappab, smad proteins, and the steroid hormone family peroxisome proliferator-activated receptors (ppars) are involved in regulation of gene transcription during the disease process. peptide yy (pyy), a gastrointestinal hormone, inhibits nf-kappab translocation to acinar nuclei in tumor necrosis factor (tnf)-alpha-induced ap. we investigated tnf-alpha induction of smad proteins, pparalpha/gamma, and nf-kappab by tnf-alpha, and hypothesized that pyy would attenuate this effect. rat acinar cells were treated with recombinant tnf-alpha (200 ng/ml). pyy (3 to 36) was added at 500 pm at 30 minutes after tnf-alpha treatment until cell harvest at 2 hours. western blot analysis and intracellular staining of the p65 subunit of nf-kappab were performed. nf-kappab, smad3/4, and pparalpha/gamma binding activities were determined by protein/dna array analysis and verified by electrophoretic-mobility shift assay and densitometry. cellular localization of nf-kappab p65 showed nuclear staining within 2 hours, with controls stained in the cytoplasm. with pyy, p65 stained in the cytoplasm. nuclear p65 was increased significantly (p 0.05) by tnf-alpha at 2 hours and pyy reduced it. array analysis revealed upregulation of nf-kappab, pparalpha/gamma, and smad3/4 with tnf-alpha. tnf-alpha stimulated nf-kappab activation sevenfold, and binding was enhanced (p 0.05). pyy reduced nf-kappab binding to control levels. ppar binding increased 51 after tnf-alpha treatment and was reduced to 33 with pyy. smad3/4 binding was increased (p 0.05) above controls with tnf-alpha and pyy reduced it by 40.","tnf-alpha increases early nuclear translocation of the p65 subunit of nf-kappab in acinar cells. exposure to tnf-alpha activates transcription factors nf-kappab, smad3/4, and pparalpha/gamma. pyy reduces this activation. treatment with pyy may have therapeutic potential in improving ap.",Medication
does biomarker robustness reveal the pdgf network as driving disease outcome in ovarian cancer patients in multiple studies?,"ovarian cancer causes more deaths than any other gynecological cancer. identifying the molecular mechanisms that drive disease progress in ovarian cancer is a critical step in providing therapeutics, improving diagnostics, and affiliating clinical behavior with disease etiology. identification of molecular interactions that stratify prognosis is key in facilitating a clinical-molecular perspective. the cancer genome atlas has recently made available the molecular characteristics of more than 500 patients. we used the tcga multi-analysis study, and two additional datasets and a set of computational algorithms that we developed. the computational algorithms are based on methods that identify network alterations and quantify network behavior through gene expression.we identify a network biomarker that significantly stratifies survival rates in ovarian cancer patients. interestingly, expression levels of single or sets of genes do not explain the prognostic stratification. the discovered biomarker is composed of the network around the pdgf pathway. the biomarker enables prognosis stratification.","the work presented here demonstrates, through the power of gene-expression networks, the criticality of the pdgf network in driving disease course. in uncovering the specific interactions within the network, that drive the phenotype, we catalyze targeted treatment, facilitate prognosis and offer a novel perspective into hidden disease heterogeneity.",Diagnosis
does extracurricular physical activity participation modify the association between high tv watching and low bone mass?,"to examine whether different sedentary behaviours are associated with the risk of low bone mineral content in adolescents, and if so, whether extracurricular physical-sporting activity influences this association. a total of 277 adolescents from zaragoza (168 females and 109 males) aged 13.0-18.5 yr within frame work of the multicentre avena study participated in this study. bone mineral content (bmc), lean mass, and fat mass were measured with dxa. physical activity and sedentary independent variables: participation in extracurricular physical-sporting activity (pa), h/d of television watching, playing video/computer games during school days and on weekend days and doing homework/studying. they all were assessed by questionnaire. the main outcome was low bmc, as defined by bmc z-score for age and sex or 3 h/d was associated with an increased risk for low bmc in males (or, 95 ci: 7.01, 1.73 to 28.40), after controlling for sexual maturation. when pa was in the models, television watching was not any longer associated with low bmc, while pa was so (or, 95 ci: 0.23, 0.09 to 0.55). involvement in such activity reduced the risk of low bone mass by 76 (p0.01) independently of body mass, height and fat mass, but not of the lean mass.","watching television for 3 or more h/d seems to be associated with an increased risk for low bmc in male adolescents. however, this association is mediated by participation in pa, suggesting that negative consequences of excessive television watching on adolescent bone health could be counteracted by sport participation. longitudinal data and randomized controlled trials will confirm or contrast our findings.",Prevention
do effect of tooth-bleaching methods on gloss and color of resin composites?,"the purpose of the study was to evaluate gloss and color changes of resin composites after exposure to different bleaching agents. products used, were: nite white acp (10 carbamide peroxide gel), crest classic and supreme whitestrip (6.5 and 14 hydrogen peroxide strips, accordingly). a hybrid (herculite xrv) and a nanohybrid (premise) resin composite were exposed to the bleaching agents. twenty-four disk-shaped specimens per composite were subjected to bleaching by each of the agents (n8) for up to 2 weeks. color changes using cie-lab system (50:50 acceptability threshold: e3.3) were recorded after 1 and 2 weeks bleaching cycles relative to baseline measurements. in addition, gloss measurements (in gloss units) were performed at the same bleaching intervals and gloss changes were calculated. all bleaching agents tested provided decrease in gloss of both composites after 2-week bleaching (p0.05). no differences were detected among the three bleaching regimens, for up to 2-week application, in terms of color and gloss changes on both composites. after the 2-week bleaching period, hybrid composite presented higher gloss reduction () than nanohybrid regardless of the bleaching agent (p0.05). color change (e) was lower than 3.3 for all composite-bleaching agent combinations. after 1- and 2-week bleaching time, the nanohybrid composite provided higher color change than the hybrid under all bleaching procedures (p0.05). no strong correlation was proved between color (e) and gloss changes caused by bleaching treatments.","after 2-week bleaching cycles, composites showed significant gloss reduction (p0.05). color alteration was below the 50:50 acceptability threshold (e3.3) and it was product-depended. there was no significant difference in color and gloss changes between the evaluated bleaching strips and 10 carbamide peroxide gel.",Treatment
is performance status a predictor of overall survival of elderly patients with muscle invasive bladder cancer?,"elderly patients with muscle invasive bladder cancer often present treatment challenges due to concomitant comorbidities and psychosocial factors. this study examines patterns of treatment in this population and evaluates the impact of these factors on overall survival in a contemporary population. common components of geriatric assessment were reviewed in 152 consecutive patients 70 years old or older presenting with nonmetastatic muscle invasive bladder cancer from january 1995 to december 2004 (median followup of 41 months). overall survival was evaluated using kaplan-meier methods and a multivariate cox model. mean patient age was 76 years. most patients underwent definitive treatment, with 114 (75) opting for cystectomy including 29 of 114 (25) with planned neoadjuvant chemotherapy. only 15 were treated with palliative intent. patients with a karnofsky performance status of 80 or less or prior weight loss underwent bladder preservation more often than cystectomy (p 0.01). overall survival was greatest in patients 80 years old or older compared to younger cohorts (p 0.05) and in those treated with bladder preservation compared to other treatments (p 0.04). in a multivariate analysis patients with a karnofsky performance status of 80 or less had 1.8 times the risk of death compared to patients with a karnofsky performance status of 90 or greater (95 ci 1.0-3.2, p 0.05).","most elderly patients with muscle invasive bladder cancer tolerate curative therapy. however, functional status must be seriously considered. karnofsky performance status is an important predictor of overall survival in this population, with a karnofsky performance status of 90 or greater providing a significant survival advantage regardless of treatment type. thus, karnofsky performance status should be routinely incorporated into treatment planning.",Medication
do amino acids counteract the inhibitory effect of fentanyl on hepatocyte oxidative metabolism?,"hypothermia is common after major surgery in newborns and can be triggered by intraoperative fentanyl analgesia. recent studies have found that fentanyl inhibits hepatocyte mitochondrial oxidative metabolism, which is proportional to thermogenesis. in adults it has been shown that amino acids have a thermogenic effect, although the biochemical basis of this phenomenon is not known. the aim of this study was to test the hypothesis that amino acids counteract the inhibition of neonatal hepatocyte oxygen consumption by fentanyl. hepatocytes were isolated from suckling rats, and o2 consumption was measured polarographically. in experiment a hepatocytes were incubated with (1) palmitate alone (control), (2) palmitate plus fentanyl, (3) palmitate plus fentanyl plus amino acids, and (4) palmitate plus amino acids. in experiment b the effects of essential and nonessential amino acids were tested separately. in experiment c, to investigate whether the effect of amino acids is intramitochondrial, hepatocytes were incubated with amino acids plus inhibitors of mitochondrial respiration. in experiment a, fentanyl significantly inhibited o2 consumption (p .006). this inhibition was reversed by amino acids (p .001). in experiment b, both essential and nonessential amino acids reversed the effect of fentanyl (p .001). in experiment c, there was no difference in o2 consumption in the presence of myxothiazol among the groups indicating that amino acids affect intramitochondrial o2 consumption.",(1) amino acids abolish the inhibitory effect of fentanyl on hepatocyte oxidative metabolism. (2) amino acids affect intramitochondrial o2 consumption and therefore thermogenesis. (3) perioperative administration of amino acids in neonates may help to prevent hypothermia and its deleterious effects.,Medication
are molecular subtypes of clear cell renal cell carcinoma associated with sunitinib response in the metastatic setting?,"selecting patients with metastatic clear-cell renal cell carcinoma (m-ccrcc) who might benefit from treatment with targeted tyrosine kinase inhibitors (tki) is a challenge. our aim was to identify molecular markers associated with outcome in patients with m-ccrcc treated with sunitinib. we performed global transcriptome analyses on 53 primary resected ccrcc tumors from patients who developed metastatic disease and were treated with first-line sunitinib. we also determined chromosome copy-number aberrations, methylation status, and gene mutations in von hippel-lindau and pbrm1. molecular data were analyzed in relation with response rate (rr), progression-free survival (pfs), and overall survival (os). validation was performed in 47 additional ccrcc samples treated in first-line metastatic setting with sunitinib. unsupervised transcriptome analysis identified 4 robust ccrcc subtypes (ccrcc1 to 4) related to previous molecular classifications that were associated with different responses to sunitinib treatment. ccrcc1/ccrcc4 tumors had a lower rr (p 0.005) and a shorter pfs and os than ccrcc2/ccrcc3 tumors (p 0.001 and 0.0003, respectively). these subtypes were the only significant covariate in the multivariate cox model for pfs and os (p 0.017 and 0.006, respectively). ccrcc1/ccrcc4 tumors were characterized by a stem-cell polycomb signature and cpg hypermethylation, whereas ccrcc3 tumors, sensitive to sunitinib, did not exhibit cellular response to hypoxia. moreover, ccrcc4 tumors exhibited sarcomatoid differentiation with a strong inflammatory, th1-oriented but suppressive immune microenvironment, with high expression of pdcd1 (pd-1) and its ligands.","ccrcc molecular subtypes are predictive of sunitinib response in metastatic patients, and could be used for personalized mrcc treatment with tkis, demethylating or immunomodulatory drugs.",Treatment
is quality of evidence a key determinant for making a strong grade guidelines recommendation?,"the objective of the study was to assess the association between grading of recommendations assessment, development and evaluation (grade) factors and the strength of recommendations. the study was conducted as part of the development of clinical practice guideline (cpg) by american association of blood banking related to role of prophylactic vs. therapeutic transfusion for the management of thrombocytopenia. the association between grade factors and strength of recommendations was assessed using logistic regression and multilevel mixed effect logistic regression model. seventeen members of the cpg panel participated in the recommendation process. the quality of evidence was the only statistically significant (odds ratio 4.5; p 0.001) grade factor associated with the strength of recommendations. the predictive model showed that there is about 90 probability that panelists would issue the same (strong) recommendation when confidence in the effects of intervention is high vs. 10 when the quality of evidence is very low.",the results showed that quality of evidence is a key determinant for making a strong vs. a weak recommendation.,Treatment
is lymphovascular invasion associated with oncologic outcomes following radical cystectomy for squamous cell carcinoma of the urinary bladder?,"to evaluate the association of lymphovascular invasion (lvi) with oncologic outcomes of squamous cell carcinoma (scc) of the urinary bladder following radical cystectomy (rc). we performed a retrospective analysis of 1,280 patients who underwent rc for invasive bladder cancer between 1997 and 2003 in mansoura, egypt. only patients with pure urothelial carcinoma of the bladder (ucb) or scc pathology were included. using multivariate cox regression analyses and kaplan-meier analyses, prognostic significance of lvi in disease-free survival and cancer-specific survival was evaluated for patients with ucb and scc. our cohort included 519 (59) patients with ucb and 360 (41) with scc. median patient age and follow-up were 55 years (20-87) and 64 months (0-128), respectively. median number of lymph nodes (ln) retrieved was 19 (4-70). lvi was present in 288 (32.8) patients (241 46.4 ucb vs. 47 13.1 scc; p0.001). lvi was an independent predictor of oncologic outcomes in both ucb and scc groups; however, lvi had more prognostic significance in scc. ln negative, lvi positive (lvi/ln-) patients with scc had higher risk of recurrence and cancer-specific mortality compared to ln positive, lvi negative (lvi-/ln) patients with scc (hazard ratio 2.8 vs. 1.9 and hazard ratio 3.6 vs. 2.2, respectively).",the presence of lvi is an independent predictor of poor oncologic outcomes after rc and had greater prognostic significance in patients with scc compared to ucb.,Diagnosis
does a single dose of beetroot juice enhance cycling performance in simulated altitude?,"increasing nitric oxide bioavailability via supplementation with nitrate-rich beetroot juice (br) has been shown to attenuate the negative effect of hypoxia on peripheral oxygen saturation and exercise tolerance. we investigated the effects of a single dose of concentrated br on the physiological responses to submaximal exercise and time trial (tt) performance in trained cyclists exposed to moderate simulated altitude (approximately 2500 m). nine competitive amateur male cyclists (age, 28 8 yr; vo2peak at altitude, 51.9 5.8 mlkgmin) completed four exercise trials consisting of an initial graded test to exhaustion and three performance trials on a cycle ergometer. the performance trials comprised 15 min of submaximal steady-state exercise at 60 maximum work rate and a 16.1-km tt. the second and third trials were preceded by ingestion of either 70 ml of br or nitrate-depleted br (pla) 3 h before exercise. plasma nitrate (pla, 39.1 3.5 m; br, 150.5 9.3 m) and nitrite (pla, 289.8 27.9 nm; br, 678.1 103.5 nm) measured immediately before exercise were higher after ingestion of br compared with that after pla (p 0.001, p 0.004). vo2 during steady-state exercise was lower in the br trial (2542 114 mlmin) than that in the pla trial (2727 85 mlmin, p 0.049). tt performance was significantly faster after br (1664 14 s) than that after pla (1702 15 s, p 0.021).","a single dose of br lowered vo2 during submaximal exercise and enhanced tt performance of trained cyclists in normobaric hypoxia. consequently, ingestion of br may be a practical and effective ergogenic aid for endurance exercise at altitude.",Medication
is maintenance of heterogeneity of capillary spacing essential for adequate oxygenation in the soleus muscle of the growing rat?,"normal muscle growth is accompanied by capillary proliferation, which usually lags behind the increase in muscle size, causing a decline in mean capillary density (cd). it is not known, however, how the capillary distribution is affected and what impact it has on the oxygenation of the muscle. the capillarization of soleus muscles of rats (64-425 g) was determined with the method of capillary domains. as well as quantifying cd, capillary to fiber ratio (c:f), and fiber size, this method provides a measure of the heterogeneity of capillary spacing. capillary locations were used to mathematically model oxygenation levels within the muscle. the increase in muscle mass was largely attributable to 5-fold increase in fiber size, accompanied by a more than 3-fold rise in c:f. the mismatch between rates of angiogenesis and muscle growth resulted in a decrease in cd. however, the heterogeneity of capillary spacing was unaffected (heterogeneity index logrsd: 0.091 /- 0.013; mean /- sd) as was muscle po2, with modal values between 4 and 60 mmhg (0.5 and 8 kpa).","angiogenesis during normal muscle growth does not maintain cd, but with similar heterogeneity of capillary spacing it preserves the potential for adequate intramuscular oxygenation.",General
do tsh receptor antibodies alter the function of gonadotropin receptors stably expressed in eukaryotic cells?,"tsh receptor (tshr) mediates the activating action of tsh on the thyroid gland resulting in the growth and proliferation of thyrocytes and thyroid hormone production. tshr is a major autoantigen in graves' disease (gd) and is the target for tshr antibodies. in gd, thyroid-stimulating antibodies (tsab) are competitive agonists of tsh. in atrophic thyroiditis (at), thyroid-stimulating blocking antibodies (tshbab) are tsh antagonists. the tshr together with the lh receptor (lhr) and fsh receptor (fshr) are g-protein-coupled receptors with considerable amino acid homologies in the extracellular domain. we studied the cross-reactivity of the antibodies measured in sera from patients with gd or at on the lhr and fshr function. we tested the activity of tsab and tshbab in cell lines expressing the lhr and the fshr. to this purpose a psvl-fshr construct was transfected in cho cells and one clone was used. twenty-eight sera from patients with gd and four from patients with at, known to contain tshr antibodies measured with a radioreceptor assay, were selected. tsab and tshbab activities were measured in cho cells expressing the tshr (cho-tshr). tsab and tshbab were then tested with the cell lines expressing the lhr and the fshr for their ability to elicit camp accumulation or inhibit fsh/lh-induced camp production. none of the tsab identified was able to stimulate camp increase in cho-lhr or cho-fshr. similarly, none of the tshbab was able to block the camp response induced by fsh or lh in the respective cell lines.",our results confirm the notion of the organ-specific nature of the tshr antibodies.,Medication
do alcohol and polyphenolic grape extract inhibit platelet adhesion in flowing blood?,"moderate and prolonged alcohol consumption has been associated with decreased cardiovascular morbidity and mortality. inhibition of platelet function in suspension attributes to these effects. whether alcohol, red wine, or polyphenolic grape extracts (pge) inhibit platelet adhesion is not known. we investigated platelet adhesion to fibrinogen and collagen in whole blood under standardised flow. before perfusion was started, citrated whole blood from 95 volunteers was preincubated for five min with different alcohol concentrations, unfractioned red wine and pge. then, blood was perfused in a single-passage flow chamber over coverslips coated with human fibrinogen or collagen type iii at shear rates of 300 s(-1) and 1600 s(-1). alcohol inhibited platelet adhesion to human fibrinogen at high shear rate (concentrations or 0.15 per thousand) and low shear rate (only at a concentration of 4.8 per thousand), whereas red wine (concentrations or 0.15 per thousand) inhibited platelet adhesion to human fibrinogen at both shear rates. in contrast, pge (concentrations or 0.0225 g l(-1)) inhibited platelet adhesion to human fibrinogen only at low shear rate. none of these incubations affected adhesion to collagen.","alcohol, red wine and pge inhibit adhesion to fibrinogen but not to collagen. this inhibition might contribute to the cardioprotective effects of moderate alcohol consumption.",General
are emotion regulation difficulties relevant to persecutory ideation?,"persecutory delusions are preceded and accompanied by negative emotions, which may be prolonged or even amplified by difficulties in the ability to regulate negative emotions. this study aims to gain insight into emotion regulation difficulties in persecutory ideation. a correlational approach was adopted to explore bivariate and multivariate associations between emotion regulation difficulties and persecutory ideation in a subclinical sample. furthermore, general psychopathology as well as positive symptoms of schizophrenia were assessed in order to estimate the specificity of emotion regulation difficulties. data from 151 participants acquired via an internet-based survey were analyzed. there were substantial bivariate correlations between paranoid ideation and emotion regulation difficulties. however, only impulse control difficulties were specific to persecutory ideation after controlling for general psychopathology. additionally, a multivariate analysis revealed unexpected positive associations between the acceptance of emotional responses and paranoid ideation as well as positive symptoms.","besides the general difficulties in regulating emotion that are common to many clinical disorders and were associated with overall psychopathology, subclinical psychotic symptoms seem to be specifically associated with certain aspects of emotion regulation. emotion regulation difficulties are likely to contribute to symptom formation and maintenance in persecutory delusions and might therefore present a valuable treatment target.",Diagnosis
does prophylactic pancreatectomy for intraductal papillary mucinous neoplasm negatively impact quality of life : a preliminary study?,"uncertainties remain over whether prophylactic surgery or surveillance is the better management option for intraductal papillary mucinous neoplasm of the pancreas. the aim of this preliminary study was to determine if differences in anxiety and quality of life exist between patients who have surgery or undergo surveillance. recruited patients were given the hospital anxiety and depression scale, a general survey that evaluates anxiety, and the functional assessment of cancer therapy-pancreas, a disease-specific survey that assesses quality of life. questionnaires were scored by standardized algorithms and compared using student's t test or wilcoxon rank-sum test. sixteen patients had surgery and 16 patients were undergoing surveillance. mean age was 66.8 19.9 years. responses from both groups were remarkably similar. surgery patients scored higher on the anxiety questionnaire than surveillance patients, although not statistically significant (p 0.09). surgery patients scored lower on the functional well-being domain of the quality-of-life instrument (p 0.03), though there were no differences in overall quality of life.","prophylactic surgery does not reduce quality of life, and a protocol of surveillance does not appear to generate undue anxiety in this select patient group. further investigation with more patients is required to validate these findings.",Prevention
do interleukin-6-deficient mice resist development of autoimmune myocarditis associated with impaired upregulation of complement c3?,"interleukin (il)-6 regulates various aspects of the immune response. in the context of heart diseases, it has been recognized as a prognostic factor for dilated cardiomyopathy, which often results from myocarditis. using il-6-deficient mice, we studied the role of il-6 in a model of autoimmune myocarditis resulting from immunization with a peptide derived from cardiac alpha-myosin. prevalence and severity of myocarditis were markedly reduced in the absence of il-6. cd4 t cells from immunized il-6-deficient mice proliferated poorly on restimulation with specific antigen in vitro and did not mediate disease on adoptive transfer into il-6-competent rag-2-deficient mice, which otherwise lack b cells and t cells. production of complement c3, a crucial factor for the development of myocarditis, was strongly upregulated in il-6/ but not in il-6-deficient mice after immunization.","our results demonstrate that il-6 is required for the expansion of autoimmune cd4 t cells and the pathogenesis of autoimmune myocarditis, possibly by upregulation of complement c3.",Medication
do a daily glass of red wine and lifestyle changes affect arterial blood pressure and heart rate in patients with carotid arteriosclerosis after 4 and 20 weeks?,"regular consumption of small amounts of red wine improves blood lipids. however, there is concern whether this beneficial effect might be counterbalanced by an increase in blood pressure (bp) and heart rate (hr), which are risk factors for cerebro-cardiovascular disease. in particular, we studied whether regular consumption of red wine with and without lifestyle changes (lc; healthy diet and physical activity advice) results in an increase in bp and hr. a prospective, unblinded randomized trial was performed in 108 patients (67 men) with carotid atherosclerosis documented by ultrasound, a mean bp of 122/79 mm hg and a mean hr of 71 bpm at inclusion in the study. sixty-eight percent were known and treated hypertensives. the mean 24-hour bp at baseline was 122/79 mm hg. half of the study participants, the control group, was seen by a nurse at baseline, after 4 and after 20 weeks, and was instructed not to change their eating and physical activity habits. in the other half, a dietician performed five sessions of 30 min each (at baseline, after 1 week and after 2, 3 and 4 weeks) giving advice on healthy eating based on a mediterranean diet and physical exercise. the recommendations given were the following: 5 portions of fruit/vegetables per day, a diet low in absolute fat, a preference of vegetable oil (olive or rapeseed oil), whole-grain products, poultry, low-fat dairy products, 1 fat and 1 lean fish meal per week, reduced consumption of red meat, and avoidance of pork, ready-made meals, sugar and excessive salt intake. in addition, regular consumption of 1 bar of dark chocolate (25 g, 70 of cacao), 1-2 tomatoes, and 3-5 walnuts as well as at least 30 min of moderate daily physical activity were recommended. within these two groups, half of the patients were randomized either to avoid alcohol completely or to drink 100 ml (women) or 200 ml of red wine (men) daily. neither lc nor red wine had an effect on the mean systolic and diastolic 24-hour bp and hr after 4 and 20 weeks, as analyzed by general linear modeling. no difference was found for diurnal and nocturnal values.","the possible beneficial effect of regular consumption of small amounts of red wine is not counterbalanced in the long term by an increase in the mean bp or hr in mainly normotensive and well-treated hypertensive patients with carotid atherosclerosis, neither in the patients given healthy lifestyle advice nor in those with a standard lifestyle. yet, we remain cautious about actively advice patients to drink alcohol regularly given the well-known risks.",Prevention
does excretion of pyridinium crosslinks correlate with disease activity and appendicular bone loss in early rheumatoid arthritis?,"to establish if urinary excretion rates of the collagen crosslinks pyridinoline and deoxypyridinoline, which are known to be elevated in established rheumatoid arthritis (ra), are useful markers of bone loss in this disease. eight hour urine collections on all patients and 52 controls were performed, and the rates of pyridinoline and deoxypyridinoline excretion were measured. bone mineral density (bmd), by dual energy x-ray absorption, and full laboratory and clinical assessments were performed. the rates of excretion of pyridinoline and deoxypyridinoline were significantly increased in patients compared with controls (p 0.001). pyridinoline excretion was associated with increased disease activity (esr/crp) but not disability (haq score/functional grade), and correlated with bmd loss at the femoral neck (p 0.01).",the excretion of collagen crosslinks may be useful as markers of bone and cartilage turnover in patients with ra.,Diagnosis
is a polymorphism in the gene for microsomal epoxide hydrolase associated with pre-eclampsia?,"microsomal epoxide hydrolase is an important enzyme involved in the metabolism of endogenous and exogenous toxicants. polymorphic variants of the human epoxide hydrolase gene vary in enzyme activity. we determined whether genetic variability in the gene encoding for microsomal epoxide hydrolase contributes to individual differences in susceptibility to the development of pre-eclampsia with or without the syndrome of haemolysis, elevated liver enzymes, and low platelets (hellp). a total of 183 non-pregnant women with a history of pre-eclampsia, 96 of whom had concurrently developed the hellp syndrome, and 151 healthy female controls were genotyped for the 113tyr--his polymorphism in exon 3 and the 139his--arg polymorphism in exon 4 of the epoxide hydrolase gene by a polymerase chain reaction-restriction fragment length polymorphism assay. chi-square analysis was used for statistical evaluation of differences in polymorphic rates. in pre-eclampsia a higher frequency (29) of the high activity genotype tyr113 tyr113 in exon 3 was found as compared to controls (16, or 2.0, 95 ci 1.2-3.7). there was no difference between groups for the 139his--arg polymorphism. in women with a history of pre-eclampsia, no difference in epoxide hydrolase genotypes was found between women who either did or did not develop the hellp syndrome. in addition, a significant association was found between predicted ephx activity and pre-eclampsia.","women with the high activity genotype in exon 3, which could reflect differences in metabolic activation of endogenous or exogenous toxic compounds, may have enhanced susceptibility to pre-eclampsia. however, polymorphisms in the epoxide hydrolase gene do not seem to influence the risk for concurrent development of the hellp syndrome.",General
does advanced age remain an achilles heel for liver resections?,"as the general population is aging, surgery in elderly patients has become a major public health issue. this basic question is especially true for liver resection (lr). the aim of this study was to evaluate the operative risks of lr in the elderly. retrospective analysis of a large recent and monocentric database of lr was performed between january 1, 2005 and may 31, 2011. patients were categorized into three groups (60, 60-74, and 75 years old) to analyze postoperative outcomes and 1-year mortality. clinicopathologic factors likely to influence outcomes were assessed by univariate and multivariate analysis. altogether, 1,001 consecutive lrs were performed in 912 patients (mean age 62 13 years). the distribution of the lr by age was 372 (37.2 ), 477 (47.6 ), and 152 (15.2 ) in patients 60, 60-74, and 75 years, respectively. the overall morbidity and mortality rates were 33.3 and 2.5 , respectively. age 75 years was independently associated with postoperative mortality odds ratio (or) 4.75, 95 confidence interval (ci) 1.5-15.1; p 0.008 and 1-year mortality (or 2.8, 95 ci 1.2-6.6; p 0.015). the postoperative complication rate (p 0.216) was not increased, even for major complications (p 0.09). the other independent risk factors for mortality were a cirrhotic liver (p 0.017), preoperative arterial chemoembolization (p 0.001), caval vein clamping (p 0.001), and intraoperative blood transfusion (p 0.044).",age beyond 75 years represent a risk factor of death after lr and should be avoided after chemoembolization or in cirrhotic patients. a specific assessment using geriatric indexes might be the key to success in this population.,Treatment
is the glasgow prognostic score an independent prognostic predictor of hepatocellular carcinoma following radical resection?,"some prognostic evaluation systems were developed to postoperatively predict the outcome of hepatocellular carcinoma (hcc) patients, mainly based on the cancer itself and the underlying liver diseases. however, none of these prognostic evaluation systems have so far been universally accepted. a simple and feasible scoring system is still lacking for the prediction of prognosis of hcc patients following resection. we aimed to uncover the correlation between the preoperative glasgow prognostic score (gps) and the clinical outcome of hcc patients after radical resection. the patients were separated into 3 subgroups on the basis of their gpss. the prognostic significance of the gps in the patient cohort was evaluated by survival analysis. on univariate analysis, the levels of c-reactive protein and albumin, the child-pugh class, vascular invasion, tumor number, tumor size, the tumor/node/metastasis (tnm) stage, and the gps were associated with overall survival and time to recurrence of hcc patients after radical resection. on multivariate analysis, the tumor size, albumin level, and gps were independently associated with the outcome of hcc postoperatively.",the gps is an independent biomarker for prognostic prediction of hcc following radical resection.,Treatment
are higher levels of cell apoptosis and abnormal e-cadherin expression in the urothelium associated with inflammation in patients with interstitial cystitis/painful bladder syndrome?,"to investigate the relationships between suburothelial inflammation and urothelial dysfunction in interstitial cystitis/painful bladder syndrome (ic/pbls). immunofluorescence staining of ki-67 (to assess cell proliferation), junction protein e-cadherin, tryptase (to assess mast cell activation) and tunel (to assess urothelial apoptosis) were performed in bladder tissues from 20 patients with ic/pbls and from 6 control patients. the fluorescence intensity of e-cadherin was measured using the imagej method. the percentage of apoptotic cells, proliferated cells and activated mast cells were measured and quantified as positive cells (sd) per area unit (4 m(2)). the ratio of ki-67-positive cells in the bladder tissue of the patients with ic/pbls was significantly down-regulated compared with that of the control patients (0.559 0.658 vs. 1.23 1.28, p 0.001). tunel staining revealed a significantly higher number of apoptotic cells in the ic/pbls bladder tissue compared with control bladder tissue (2.26 2.04 v 0.051 0.124, p 0.000). the tryptase signal was significantly stronger in the ic/pbls bladder tissue compared with that of control patients (6.16 4.35 v 1.15 0.436, p 0.000). the apoptotic cell number in ic/pbls bladder tissue correlated significantly with mast cell activation (p 0.021). immunofluorescence also showed a significantly lower distribution of e-cadherin in ic/pbls bladder tissue compared with that of control patients (8.50 6.83 v 17.2 11.9, p 0.000). lower expression of e-cadherin in ic/pbls bladder tissue was significantly correlated with higher visual analogue pain scores in patients with ic/pbls (p 0.008).","the results of the present study suggest that urothelial homeostasis in ic/pbls bladders was impaired, and abnormal urothelial function was significantly associated with chronic inflammation. the junctions between urothelial cells in ic/pbls bladders were abnormal, which was associated with the patient's self-report pain scales.",Symptoms
does solubilization of phytosterols in diacylglycerol versus triacylglycerol improve the serum cholesterol-lowering effect?,"this study was performed to investigate the difference in the serum-cholesterol- and triglyceride-lowering activities between phytosterols dissolved in diacylglycerol (ps/dg) and dispersed in triacylglycerol (ps/tg). the effects of the solvent on the concentrations of serum beta-sitosterol and campesterol were examined. the study had a randomised crossover design. twelve healthy normocholesterolemic or moderately hypercholesterolemic men aged 29-50 y participated in this study. for 2 weeks before the test period (designated as the control period), all subjects consumed control mayonnaise (ps free) daily with supper and were randomly assigned to two groups for the 2 week test period; one group was given mayonnaise containing ps (500 mg/day) dissolved in dg (10 g/day), and the other mayonnaise containing ps (500 mg/day) dispersed in tg (10 g/day). after a wash out period consuming control ps-free mayonnaise for 4 weeks, the groups were reversed for 2 weeks. ps/tg feeding had no effect on the serum cholesterol level. in contrast, ps/dg feeding significantly reduced the total and ldl cholesterol levels from the initial value of 5.57 to 5.31 mmol/l (4.7; p0.05) and from 3.69 to 3.39 mmol/l (7.6; p0.05), respectively. moreover, the degree of total cholesterol reduction induced by ps/dg feeding in the test period was significantly greater than that induced by ps/tg feeding (p0.05). in addition, the serum beta-sitosterol and campesterol concentrations did not change during the ps/tg or ps/dg feeding periods.",dissolution of ps in dg had a better serum cholesterol lowering effect than dissolution in tg.,General
is ppnrg1 a transcriptional repressor for glucose and glycerol repression of aox1 promoter in methylotrophic yeast pichia pastoris?,"the regulator in glycerol repression of pichia pastoris aox1 promoter (p aox1 ) is still unclear. a cys2his2 zinc finger transcriptional repressor ppnrg1 localized to nucleus and participated in the repression of p aox1 in p. pastoris in glucose and glycerol. quantitative real-time pcr revealed that ppnrg1 repressed expression of numerous genes involved in methanol utilization and peroxisome biogenesis in 0.02 glucose and 1 (v/v) glycerol. electrophoretic mobility shift assay and dnase i footprinting assay revealed that ppnrg1 bound to five sites of p aox1 , including two binding sites of ppmxr1, which is an indispensable activator of p aox1 in p. pastoris.","transcriptional repressor ppnrg1 suppresses p aox1 in glucose and glycerol by directly binding to five sites of p aox1 , including two binding sites of transcriptional activator ppmxr1.",General
does proteomic profiling of human keratinocytes undergoing uvb-induced alternative differentiation reveal tripartite motif protein 29 as a survival factor?,"repeated exposures to uvb of human keratinocytes lacking functional p16(ink-4a) and able to differentiate induce an alternative state of differentiation rather than stress-induced premature senescence. a 2d-dige proteomic profiling of this alternative state of differentiation was performed herein at various times after the exposures to uvb. sixty-nine differentially abundant protein species were identified by mass spectrometry, many of which are involved in keratinocyte differentiation and survival. among these protein species was tripartite motif protein 29 (trim29). increased abundance of trim29 following uvb exposures was validated by western blot using specific antibody and was also further analysed by immunochemistry and by rt-pcr. trim29 was found very abundant in keratinocytes and reconstructed epidermis. knocking down the expression of trim29 by short-hairpin rna interference decreased the viability of keratinocytes after uvb exposure. the abundance of involucrin mrna, a marker of late differentiation, increased concomitantly. in trim29-knocked down reconstructed epidermis, the presence of picnotic cells revealed cell injury. increased abundance of trim29 was also observed upon exposure to dna damaging agents and pkc activation. the uvb-induced increase of trim29 abundance was dependent on a pkc signaling pathway, likely pkcdelta.",these findings suggest that trim29 allows keratinocytes to enter a protective alternative differentiation process rather than die massively after stress.,Diagnosis
is alcohol consumption before sleep associated with severity of sleep-disordered breathing among professional japanese truck drivers?,"alcohol consumption as well as overweight is known to aggravate the severity of sleep-disordered breathing (sdb), but little is known about alcohol consumption in truck drivers. the aim of this study was to examine the relationship between alcohol consumption and sdb among truck drivers. we conducted a cross-sectional study of 1,465 men aged 20-69 years who were registered with the japanese trucking association. the 3 oxygen desaturation index (3odi) was selected as an indicator of sdb, representing the number of desaturation events per hour of recording time in which blood oxygen fell by or 3 based on overnight pulse-oximetry. participants completed a self-administered questionnaire including alcohol consumption on the same night for sdb assessment. the prevalence of 3odi or 5, or 10, and or 15/h was 25.4, 11.1, and 6.6 respectively. the multivariable odds ratios (or) of 3odi or 10/h were 1.5(0.9-2.5) for 0.5 to or 1.0 g of alcohol intake/kg compared with non-drinkers. similar associations with alcohol consumption were observed for 3odi or 5 and or 15/h. the relation between alcohol consumption ( or 1.0 g of alcohol intake/kg) and 3odi or 10/h tended to be more evident among men with body mass index (bmi) or 23.4 kg/m(2) 11.4 (3.2-41) vs. 1.2 (0.6-2.7), p 0.18 for interaction. a similar trend was observed for 3odi or 5/h.",the prevalence of undiagnosed sdb and the significant association of alcohol consumption with sdb severity emphasize the need for sdb screening and alcohol modification as well as weight control to prevent and control sdb among truck drivers.,Medication
does epidermal growth factor receptor inhibition attenuate early kidney enlargement in experimental diabetes?,"renal enlargement is an early feature of both human and experimental diabetes. although the precise mechanisms underlying its development are incompletely understood, locally active growth factors have been suggested to have a key role. having previously documented increased expression of the proproliferative and antiapoptotic growth factor, epidermal growth factor (egf), in early diabetes-related kidney growth, the present study sought to evaluate its pathogenetic role by blocking its action with a specific inhibitor. sprague-dawley rats were randomized to receive streptozotocin (diabetic) or buffer (control) and then further randomized to receive either vehicle or the inhibitor of the egf receptor tyrosine kinase, pki 166 (100 mg/kg/day) for 2 days and 3 weeks following streptozotocin administration. experimental diabetes was associated with an increase in kidney weight and tubular epithelial cell proliferation as identified by increased expression of proliferating cell nuclear antigen (pcna) and 5-bromo-2'-deoxyuridine (brdu) incorporation. pki 166 resulted in a 30 reduction in kidney weight in diabetic rats (p 0.01) and reduced tubular epithelial cell proliferation (p 0.01). in addition, egf receptor inhibition also led to a 40 increase in tubular epithelial cell apoptosis at 3 weeks (p 0.01). diabetes-associated glomerular enlargement was similarly attenuated by pki 166, although glomerular hyperfiltration was unaffected.","these findings suggest that the egf-egf receptor (egfr) axis has a significant role in the development of early diabetes-related kidney growth. the impact of egfr inhibition on the later development of renal dysfunction, however, remains to be determined.",Medication
is gbv-c viremia associated with reduced cd4 expansion in hiv-infected people receiving haart and interleukin-2 therapy?,"interleukin-2 (il-2) is a cytokine with multiple effects on lymphocytes including induction of cd4 t-cell proliferation. il-2 administration has been shown to increase cd4 cell counts in hiv-infected people receiving antiretroviral therapy. gb virus c (gbv-c) is an apparently nonpathogenic flavivirus that replicates in cd4 t cells and inhibits hiv replication in vitro by mechanisms including downregulation of hiv entry coreceptors (ccr5 and cxcr4) and induction of chemokines (rantes, mip-1alpha, mip-1 beta, and sdf-1). gbv-c replication is significantly inhibited in vitro by activation of primary cd4 cell cultures with il-2 and phytohemagglutinin. we sought to determine if there is an interaction between gbv-c and il-2 in vivo. gbv-c viremia status was characterized in 92 hiv-infected individuals participating in a randomized trial of il-2 and antiretroviral therapy aids clinical trials group study (actg) 328. changes in cd4 cell counts and hiv rna levels in individuals assigned il-2 were compared with those in individuals assigned antiretroviral therapy alone. individuals lacking gbv-c viremia had a significantly greater rise in cd4 cell count with il-2, compared with gbv-c viremic individuals (by 511 cells/microl at week 84; interaction p 0.02): gbv-c viremic individuals assigned il-2 did not demonstrate a significant increase in cd4 cell count compared with individuals not assigned to receive il-2 (95 ci for difference -255 to 397 cells/microl).","gbv-c viremia was associated with a block in cd4 cell expansion following il-2 therapy in the actg 328 study, and gbv-c status may be an important factor in il-2 treatment response.",Treatment
does liver enpp1 protein increase with remission of type 2 diabetes after gastric bypass surgery?,"type 2 diabetes mellitus (t2dm) is a progressive disease resulting from increasing insulin resistance and reduced pancreatic -cell insulin secretion. ectonucleotide pyrophosphatase/phosphodiesterase 1 (enpp1) inhibits insulin signalling and may contribute to the pathogenesis of t2dm. others have found elevated enpp1 levels in muscle, fat, and skin tissues from insulin resistant individuals, but similar data on liver enpp1 is lacking. the purpose of this study was to compare expression and protein concentrations of enpp1 in liver between patients with and without t2dm. roux-en-y gastric bypass surgery (rygb) results in remission of insulin resistance and t2dm thus presenting an opportunity to examine some critical aspects of these conditions. we measured liver enpp1 gene and protein expression in individuals with or without t2dm at rygb and on average 17 (5.6) months later. we found liver enpp1 protein abundance was lower in individuals with t2dm than in those with normal glucose tolerance, and increased after rygb surgery in those individuals who had remission of t2dm. enpp1 positively correlated with insulin sensitivity at the liver (as measured by homa-ir), which is contrary to what others have reported in other insulin target tissues.","liver enpp1 expression in t2dm is the reverse of that expected based on expression in other tissues and is likely due to the unique role the liver has in insulin clearance. the work presented here adds another dimension to the role of enpp1, and supports the hypothesis that enpp1 may act as a natural modulator of insulin signalling in the liver.",Treatment
does mid-term outcome after carotid artery stenting depend on presence of coronary artery disease?,"longer-term outcome of patients following carotid artery revascularization depends predominantly on cardiac events rather than neurological events. to assess the longer-term outcomes of patients with known coronary artery morphology undergoing carotid artery stenting. in a prospective observational study including 549 consecutive patients undergoing carotid artery stenting, a coronary angiography was performed in a single session unless a recent angiogram was available. following the intervention, patients were followed prospectively to determine neurological events as well as major adverse coronary events (mace) during long-term follow-up. coronary artery disease was present in 378 patients including 92 patients without current significant stenosis. the mace rate was 6.4 in patients without coronary artery disease compared to 28.3 in patients with coronary artery disease (p0.00001). cardiac and all-cause mortality were statistically significantly higher in patients with a significant coronary stenosis than in patients without coronary artery disease (p0.001 and p0.01). cardiac mortality and all-cause mortality were 2.3 and 7.6 in patients without coronary artery disease (patient group i), 7.6 and 13.0 in patients with coronary artery disease but no current significant stenosis (patient group ii), and 10.5 and 16.1 in patients with significant coronary stenosis (patient group iii). neurological events, however, were distributed equally among the three patient groups.","in the longer term, outcomes in patients undergoing carotid artery stenting depend on concomitant coronary artery disease rather than neurological events, cardiac mortality and even all-cause mortality depending on a significant coronary artery stenosis.",Treatment
is saline volume in transvesical intra-abdominal pressure measurement : enough enough?,"the objective was to determine the minimum volume of instillation fluid for intra-abdominal pressure (iap) measurement, and to evaluate the effect of instillation volume on transvesically measured iap. prospective cohort study twenty-two-bed surgical icu of the ghent university hospital. twenty patients at risk of intra-abdominal hypertension (iah). transvesical iap measurement using volumes from 10 to 100 ml. minimal volume at which an iap was measured was recorded (iap(min)), as well as iap at 50 and 100 ml of instillation volume (iap(50) and iap(100)). the percentage difference for iap(50) and iap(100) was calculated. the minimal volume for iap measurement was 10 ml in all patients. mean iap(min) was 12.8 mmhg (/- 4.9), mean iap(50 )15 mmhg (/- 4.5) and mean iap(100) 17.1mmhg (/- 4.7). the mean percentage difference for iap(50) was 21 (/- 17), and 40 (/-29) for iap(100.) twelve patients were categorised as suffering from iah when 10 ml of saline was used for iap measurement, increasing to 15 and 17 patients respectively when using 50 and 100 ml. in patients with iah, there was a significant correlation between the duration of bladder drainage and percentage difference for iap(100) (pearson correlation coefficient 0.60, p 0.03).","using 50 or 100 ml of saline for iap measurement in critically ill patients results in higher iap values compared with the use of 10 ml, and possibly, in overestimation of the incidence of intra-abdominal hypertension.",Treatment
does threshold crossing of device-based intrathoracic impedance trends identify relatively increased mortality risk?,"threshold crossings of impedance trends detected by implanted devices have been associated with clinically relevant heart failure events, but long-term prognosis of such events has not been demonstrated. the aim of this study is to examine the relationship between alterations in intrathoracic impedance and mortality risk in patients with implantable devices. we reviewed remote monitoring data in the de-identified medtronic carelink() discovery link that captured intrathoracic impedance trends for 6 months. the initial 6 months of the cardiac and impedance trends were used as the observation period to create the patient groups and cross-referenced with the social security death index for mortality data. in our study cohort of 21 217 patients, 36 experienced impedance threshold crossing within the initial 6 months of monitoring (defined as the 'early threshold crossing' group). patients with early threshold crossings demonstrated an increased risk of age- and gender-adjusted all-cause mortality hazard ratio (hr) 2.15, 95 confidence interval (ci) 1.95-2.38, p 0.0001. increased mortality risk remained significant when analysed in subgroups of patients without defibrillator shock (hr 2.10, 95 ci 1.90-2.34, p 0.0001, n 1621) or within those patients without device-detectable atrial fibrillation (af) during the initial 6 months of monitoring (hr 2.09, 95 ci 1.86-2.34, p 0.0001, n 17 235). both the number and the duration of early threshold crossings of impedance trends detectable by implanted devices were associated with increased mortality risk. furthermore, the improvement of altered impedance trends portends more favourable prognosis.","threshold crossing of impedance trends detectable by implanted devices is associated with relatively increased mortality risk even after adjusted for demographic, device-detected af, or defibrillator shocks.",Diagnosis
do transesophageal echocardiographic assessment of right heart hemodynamics during high-frequency jet ventilation?,"to evaluate right ventricular dimensions and function by echocardiography in anesthetized patients during superimposed high-frequency jet ventilation (hfjv). prospective clinical study. university hospital operating room. 20 asa physical status i patients undergoing elective minor otorhinolaryngological surgery, and undergoing conventional mechanical ventilation with subsequent superimposed hfjv. two-dimensional transesophageal echocardiography with a 5-mhz multiplane transducer to determine right ventricular dimensions and function from a mid-esophageal view. insertion of a radial artery catheter for monitoring blood pressure and blood gases. heart rate, mean arterial blood pressure, and right ventricular end-diastolic and end-systolic volumes determined by echocardiography, stroke volume, and ejection fraction. measurements were performed after 10 minutes of conventional positive pressure ventilation (control) and after 10 minutes of subsequent superimposed hfjv at similar peak and positive end-expiratory airway pressures. right ventricular systolic and diastolic volumes, stroke volume, and ejection fraction did not reveal statistical significant differences after transition to hfjv. interventricular septum did not show any abnormalities in motion. in contrast, interatrial septum demonstrated momentary mid-systolic bows toward the left atrium in 9 of 17 patients (53) during conventional ventilation, but in 15 of 17 patients (88) during jet ventilation. heart rate and mean arterial blood pressure remained unchanged, but arterial oxygen tension values were higher and arterial carbon dioxide tension values lower during hfjv.","transesophageal echocardiographic evaluation of right heart hemodynamics did not show any significant difference after transition of ventilation to superimposed hfjv applying similar airway pressures. furthermore, superimposed hfjv was safe and effective, it improved oxygenation, and it facilitated carbon dioxide elimination.",Treatment
do development and implementation of a quality assurance program for a hormonal contraceptive implant?,"the importance of the distribution of safe, effective and cost-effective pharmaceutical products in resource-constrained countries is the subject of increasing attention. fhi 360 has developed a program aimed at evaluating the quality of a contraceptive implant manufactured in china, while the product is being registered in an increasing number of countries and distributed by international procurement agencies. the program consists of (1) independent product testing; (2) ongoing evaluation of the manufacturing facility through audits and inspections; and (3) post-marketing surveillance. this article focuses on the laboratory testing of the product. the various test methods were chosen from the following test method compendia, the united states pharmacopeia (usp), british pharmacopeia (bp), international organization for standardization (iso), the american society for testing and materials (astm), or lot release tests mandated by chinese regulatory requirements. each manufactured lot is independently tested prior to its distribution to countries supported by this program. in addition, a more detailed annual testing program includes evaluation of the active ingredient (levonorgestrel), the final product and the packaging material. over the first 4 years of this 5-year project, all tested lots met the established quality criteria.",the quality assurance program developed for this contraceptive implant has helped ensure that a safe product was being introduced into developing country family planning programs. this program provides a template for establishing quality assurance programs for other cost-effective pharmaceutical products that have not yet received stringent regulatory approval and are being distributed in resource-poor settings.,General
do a significant proportion of elderly patients develop hormone-dependant luminal-b '' tumours associated with aggressive characteristics?,"to investigate the influence of ageing on the incidence of breast cancer (bc) molecular subtypes, patient age at diagnosis was correlated with bio-pathological data collected retrospectively from 2723 consecutive patients diagnosed/treated at our institute between 2000 and 2003. according to their bio-characteristics, 61 of the samples could be assigned to a molecular subtype: the ""her-2"", the ""er her2 negative"" or one of the two ""luminal-like"" subtypes divided according to their histological grade (""a"" her-2-/er/grade 1-2 and ""b"" her-2-/er/grade 3).","age is highly influencing the incidence of bc molecular subtypes. patients younger than 40 develop a statistically higher rate of high grade proliferating ""her-2"" (27) and ""er her2 negative"" (31) bc whereas patients older than 50 develop mostly less aggressive hormone-dependant ""luminal-a"" bc (67). nevertheless, a significant proportion of patients older than 70 develop ""luminal-b"" (19) tumours associated with high proliferation, high grade, large size and nodal invasion.",Treatment
are mouse mammary tumor virus-like gene sequences present in lung patient specimens?,"previous studies have reported on the presence of murine mammary tumor virus (mmtv)-like gene sequences in human cancer tissue specimens. here, we search for mmtv-like gene sequences in lung diseases including carcinomas specimens from a mexican population. this study was based on our previous study reporting that the iner51 lung cancer cell line, from a pleural effusion of a mexican patient, contains mmtv-like env gene sequences. the mmtv-like env gene sequences have been detected in three out of 18 specimens studied, by pcr using a specific set of mmtv-like primers. the three identified mmtv-like gene sequences, which were assigned as iner6, hz101, and hz14, were 99, 98, and 97 homologous, respectively, as compared to genbank sequence accession number ay161347. the iner6 and hz-101 samples were isolated from lung cancer specimens, and the hz-14 was isolated from an acute inflammatory lung infiltrate sample. two of the env sequences exhibited disruption of the reading frame due to mutations.","in summary, we identified the presence of mmtv-like gene sequences in 2 out of 11 (18) of the lung carcinomas and 1 out of 7 (14) of acute inflamatory lung infiltrate specimens studied of a mexican population.",General
does interaction between tie receptors modulate angiogenic activity of angiopoietin2 in endothelial progenitor cells?,"ischemia-dependent upregulation of angiopoietin2 (ang2) led us to hypothesize the potentially proangiogenic ang2-tie2 signaling in endothelial progenitor cells (epcs). given the well-known vascular destabilizing action of ang2 in mature endothelium, we investigated the yet unidentified mechanism behind cell-dependent differential activity of ang2. both in vitro and in vivo experiments showed that ang2 promoted angiogenicity of human cord blood-derived epcs, where ang2 directly activated tie2 and its related downstream signaling molecules. however, ang2 had no such effect in fully differentiated human umbilical vein endothelial cells (huvecs) under the same condition. such a cell-dependent tie2 activation by ang2 was explained by comparing epcs and huvecs, where most tie2 receptors in epcs were found to be present unbound to tie1, whereas those in huvecs existed as heterocomplexes with tie1. when tie2 in huvecs was prevented from forming heterocomplexes by silencing tie1 expression, they underwent rapid phosphorylation upon ang2 treatment, as shown in epcs.","in contrast with its roles in mature endothelial cells, ang2 has proangiogenic activities in epc directly through tie2 signaling pathway. such a cell-dependent differential reactivity of ang2 was for the first time found to be modulated by physical association between tie1 and tie2, which inhibited ang2-mediated tie2 activation.",Medication
does suppression subtractive hybridization identify bacterial genomic regions that are possibly involved in hbd-2 regulation by enterocytes?,"human -defensin 2 (hbd-2) is an inducible antimicrobial peptide synthesized by the epithelium to counteract bacterial adherence and invasion. it has been suggested that probiotic bacteria sustain gut barrier function via induction of defensins. the goals of this study were (i) to evaluate the potential immunomodulatory effects of 11 different lactobacillus fermentum strains isolated from kimere, an african fermented pearl millet (pennisetum glaucum) dough, on the hbd-2 secretion by human intestinal caco-2 cell line and (ii) to examine genetic differences between two strains of l. fermentum (k2-lb4 and k11-lb3) which differed in their effect on the production of hbd-2 in this study. totally, 46 strains of l. fermentum from kimere were isolated and characterized using molecular biology methods including pulsed-field gel electrophoresis patterns. after performing time- and dose-experiments, caco-2 cells were incubated with or without bacteria for 12 h. l. fermentum pz1162 was included as the positive control. cell-free supernatants were analyzed for hbd-2 protein by enzyme-linked immunosorbent assay (elisa). to identify potential bacterial genes associated with hbd-2 regulation, suppression subtractive hybridization (ssh) was used. among the 11 strains tested, only two strains of bacteria, k11-lb3 and k2-lb6, significantly induced the production of hbd-2 by caco-2 cells. this effect was strain-specific, dose-dependent and particularly seems to be bacterial genomic-dependent as manifested by ssh. l. fermentum strains with and without hbd-2 inducing effect differed in genes encoding proteins involved in glycosylation of cell-wall proteins e.g. glycosyltransferase, udp-n-acetylglucosamine 2-epimerase, rod shape-determining protein mrec, lipoprotein precursors, sugar abc transporters, and glutamine abc transporter atp-binding protein.","this study implies that certain strains of l. fermentum isolated from kimere may stimulate the intestinal innate defense through the induction of hbd-2. the molecular basis of hbd-2 induction by l. fermentum strain k11-lb3 may be based on glycosylated cell-surface structures synthesized with the aid of glycosyltransferase, udp-n-acetylglucosamine 2-epimerase, and rod shape-determining protein mrec.",Medication
does putrescine decrease cytochrome p450 3a4 levels during liver regeneration in the rat?,"the mechanism by which many cytochrome p450 (cyp) isozymes decrease during liver regeneration is unclear. peptides and growth factors are thought to be involved. putrescine, the first polyamine synthesised by ornithine decarboxylase, peaks early following partial hepatectomy and is known to play an essential role in hepatic regeneration. gamma amino butyric acid was reported as a physiologic inhibitor of ornithine decarboxylase. in this work we studied the possible involvement of putrescine in the cyp reduction during liver regeneration. hepatectomised, putrescine-treated sham, and gaba-treated hepatectomised rats were used throughout. total hepatic cytochrome p450, o-dealkylase activities (cyp1a1 and cyp2b1/2), nifedipine oxidase activity (cyp3a4), and western blot assays of their respective apoproteins were analysed in liver microsomes. putrescine levels in hepatic tissue were also measured. partial hepatectomy and putrescine treatment induced a significant diminution in total cyp (50 and 30 of sham-operated rats, respectively). gamma amino butyric acid treatment prevented this decrease in partially hepatectomised rats. nifedipine oxidase activity of partially hepatectomised and putrescine-treated rats significantly decreased to 43 and 60 of that in sham-operated rats, respectively. again, gamma amino butyric acid prevented the diminution in partially hepatectomised rats. no significant changes were observed in o-dealkylase activities.","these results show that inducible cyp1a1 and cyp2b1/2, which are important in carcinogen metabolisation, are preserved after partial hepatectomy. however, constitutive cyp3a4, which represents 50 of total cyp and metabolises drugs like nifedipine, warfarin, acetaminophen, cyclosporin and fk-506, is reduced during liver regeneration. our experiments suggest that endogenous putrescine is, at least, partly responsible for this decrease.",Medication
does vsl 3 probiotic-mixture induce remission in patients with active ulcerative colitis?,"intestinal bacteria have been implicated in the initiation and perpetuation of ibd; in contrast, ""probiotic bacteria"" have properties possibly effective in treating and preventing relapse of ibd. we evaluated the safety and efficacy of vsl3 and the components, and the composition of the biopsy-associated microbiota in patients with active mild to moderate ulcerative colitis (uc). thirty-four ambulatory patients with active uc received open label vsl3, 3,600 billion bacteria daily in two divided doses for 6 wk. the presence of biopsy-associated bacteria was detected using a nucleic acid-based method and the presence of vsl3 species confirmed by dna sequencing of 16s rrna. thirty-two patients completed 6 wk of vsl3 treatment and 2 patients did not have the final endoscopic assessment. intent to treat analysis demonstrated remission (ucdai or 3, but final score or 3) in 24 (n 8); no response in 9 (n 3); worsening in 9 (n 3); and failure to complete the final sigmoidoscopy assessment in 5 (n 2). there were no biochemical or clinical adverse events related to vsl3. two of the components of vsl3 were detected by pcr/dgge in biopsies collected from 3 patients in remission.","treatment of patients with mild to moderate uc, not responding to conventional therapy, with vsl3 resulted in a combined induction of remission/response rate of 77 with no adverse events. at least some of the bacterial species incorporated in the probiotic product reached the target site in amounts that could be detected.",Medication
"does epidural analgesia influence anastomotic leakage incidence after open colorectal surgery for cancer : a retrospective study on 1,474 patients?","anastomotic leakage is a major cause of morbidity after colorectal surgery. epidural analgesia is the most effective method for postoperative pain relief after major abdominal surgery. anyhow, its effect on anastomotic leakage rate is still controversial. this study aimed to compare epidural versus intravenous analgesia as risk factor for anastomotic leakage requiring reoperation in patients undergoing open colorectal surgery for cancer. a retrospective study on 1,474 patients was performed. the cox proportional hazards model was used to study the relation between primary and secondary factors of risk and anastomotic leakage occurrence within 30 days after elective operation. overall 30-day anastomotic leakage requiring reoperation was 4.9 (95ci: 3.8-6.0). no difference in anastomotic leakage occurrence was observed between the epidural analgesia group and the intravenous analgesia group (hazard ratio: 0.94; 95ci: 0.53-1.67; p 0.8338). females had a rate of anastomotic leakage 43 lower than males (p 0.0301). the diverting stoma resulted to be protective for anastomotic leakage occurrence (p 0.0052). al significantly increased postoperative median length of stay but not in-hospital mortality.",epidural analgesia does not influence the al risk after open colorectal surgery for cancer.,Treatment
does polymorphism rs11085226 in the gene encoding polypyrimidine tract-binding protein 1 negatively affect glucose-stimulated insulin secretion?,"polypyrimidine tract-binding protein 1 (ptbp1) promotes stability and translation of mrnas coding for insulin secretion granule proteins and thereby plays a role in -cells function. we studied whether common genetic variations within the ptbp1 locus influence insulin secretion, and/or proinsulin conversion. we genotyped 1,502 healthy german subjects for four tagging single nucleotide polymorphisms (snps) within the ptbp1 locus (rs351974, rs11085226, rs736926, and rs123698) covering 100 of genetic variation with an r(2)0.8. the subjects were metabolically characterized by an oral glucose tolerance test with insulin, proinsulin, and c-peptide measurements. a subgroup of 320 subjects also underwent an ivgtt. ptbp1 snp rs11085226 was nominally associated with lower insulinogenic index and lower cleared insulin response in the ogtt (p0.04). the other tested snps did not show any association with the analyzed ogtt-derived secretion parameters. in the ivgtt subgroup, snp rs11085226 was accordingly associated with lower insulin levels within the first ten minutes following glucose injection (p 0.0103). furthermore, snp rs351974 was associated with insulin levels in the ivgtt (p 0.0108). upon interrogation of magic homa-b data, our rs11085226 result was replicated (magic p 0.018), but the rs351974 was not.",we conclude that common genetic variation in ptbp1 influences glucose-stimulated insulin secretion. this underlines the importance of ptbp1 for beta cell function in vivo.,Medication
does stability of cytadherence-related proteins p140/p110 in mycoplasma genitalium require mg218 and unidentified factors?,"tip-mediated cytadherence in mycoplasma genitalium requires the structural and functional stability of the p140 adhesin, its operon-related protein p110, and the high molecular weight protein mg218 (190-kda). disruption mutants of mg218 unable to express mg218 exhibit both a non-cytadhering phenotype and p140/p110 instability, while disruption mutants that synthesize a truncated mg218 (160 kda) retain the stability of p140/p110 and are 95 cytadhering. however, the origin of the mg218 truncated protein in these mutants is unclear. therefore, we attempted to identify the origin of the truncated mg218 protein and to evaluate whether this truncated protein possessed the c-terminal part of mg218. in addition, we used spontaneous mutants lacking p140 to assess the role of mg218 in the stability of p140/p110. rna from m. genitalium mutant producing truncated mg218 was subjected to primer extension analysis to identify the origin of expression of truncated mg218. extracts of this mutant were examined for the presence of the c-terminal region of mg218 by immunoblot. in addition, pulse-chase analysis was performed to assess the role of mg218 in the stability of p140/p110 in spontaneous p140 mutants. primer extension analysis identified a transcriptional start point adjacent to the gentamycin-resistance gene in disrupted mg218 mutants. antibodies directed against the c-terminal region (amino acids 1651-1666) of mg218 bound to truncated mg218 protein from mutants. spontaneous p140 mutants subjected to pulse chase analysis indicated that solely class i mutants exhibited instability of p140/p110 in the presence of intact mg218.","expression of truncated mg218 in m. genitalium mg218 mutants appears to be due to the presence of a putative promoter upstream to the point of mg218 disruption; this truncated protein possesses the c-terminal region of mg218. however, pulse chase results from spontaneously arising, non-cytadhering p140-deficient m. genitalium mutants suggest that the stability of p140 and p110 requires not only mg218 but also additional factors.",General
is erythrocyte insulin receptor tyrosine kinase activity increased in glyburide-treated patients with type 2 diabetes in good glycaemic control?,"the goal of this study was to test the hypothesis that insulin receptor tyrosine kinase activity of isolated erythrocytes would be greater in glyburide-treated patients with type 2 diabetes in good glycaemic control (n 13) than in untreated patients (n 12) with significant fasting hyperglycaemia. the two groups were similar in age, sex distribution, and body mass index. by selection, glyburide-treated patients had significantly (p 0.001) lower (mean /- s.e.m.) fasting glucose (6.9/-0.4 vs. 13.9/-0.8 mmol/l) and hba(ic) (7.4/-0.2 vs. 11.8/-0.9) concentrations. in addition, insulin-stimulated tyrosine kinase activity was increased in erythrocytes from glyburide -treated patients (p 0.01). although insulin receptor number was similar in solubilized erythrocytes from the two groups, tyrosine kinase activity per insulin receptor was significantly (p 0.02) greater in erythrocytes from glyburide-treated patients with type 2 diabetes.","these findings are quite similar to previously published data in metformin-treated patients. as such, it is suggested that decreases in insulin receptor tyrosine kinase activity may contribute to the loss of insulin sensitivity in hyperglycaemic subjects (glucotoxicity), and that an improvement in glycaemic control, irrespective of how it is achieved, will help rectify this abnormality.",Medication
does modulation of matrix metalloproteinase activity by edta prevent posterior capsular opacification?,"to evaluate the effect of ethylenediaminetetraacetic acid (edta) on posterior capsular opacification (pco) of rabbits and to assess its effect on intraocular tissues. modulation of matrix metalloproteinase (mmp) activity in the aqueous following cataract surgery in rabbits and its prevention by different doses of edta was determined by zymography. for evaluation of pco, lensectomized rabbits were intracamerally injected with single dose of either 5 mg edta or normal saline. after one month, the degree of pco was determined by slitlamp biomicroscopy, miyake-apple view, and histology of the lens capsule. the effect of edta on intra ocular pressure (iop), corneal endothelial cells, and the retina was evaluated by tonometry, specular microscopy and scanning electron microscopy, and electroretinography. the concentration of edta in the aqueous was determined by high performance liquid chromatography (hplc) at different time points. the mmp activity was significantly increased in the aqueous of the operated eyes, and edta reduced the degree of increase in a dose-dependent manner. edta treatment significantly reduced the degree of pco (p0.05). histopathology of the lens capsule showed a reduction in the number of proliferating and migrating cells as well as mmp2 expression in the edta-treated eyes. edta treatment did not change the iop; density, morphology and ultrastructure of the corneal endothelial cells; and electroretinography (erg). edta was detectable in the aqueous humor up to 72 h following a single intracameral injection.",edta reduces the degree of pco by suppressing the mmp activity and it is not toxic to intra ocular structures at the concentration used.,Prevention
does a processed metabolite of luteinizing hormone-releasing hormone have proliferative effects in endometrial cells?,"the purpose of this study is to determine the possible role of the processed peptide of lhrh, lhrh-(1-5), in regulating growth of endometrial cancer cells. an endometrial cancer cell line, the ishikawa cell line, was cultured under standard conditions and treated in a dose-dependent manner with 1 of 2 hormones, lhrh and lhrh-(1-5) to determine the ability of these peptides to regulate cellular growth. a tetrazolium-based assay was used to determine the effect these peptides have on cell proliferation. furthermore, enzyme-linked immunosorbent assay (elisa)-based assays were used to determine the expression of caspase-3/7 and perk-1/2. statistical analyses were conducted using an analysis of variance followed by fisher lsd as the post-hoc test. the results show that lhrh is anti-proliferative whereas lhrh-(1-5) is proliferative on the cells. furthermore, lhrh-(1-5) decreased caspase-3/7 and perk1/2 expression.",this is the first time lhrh-(1-5) is shown to have proliferative effects on cells.,Medication
are mandibular advancement devices an alternative and valid treatment for pediatric obstructive sleep apnea syndrome?,"orthodontic and craniofacial abnormalities have often been reported in pediatric sleep-disordered breathing (sdb). while the reversibility of these craniofacial abnormalities by means of adenotonsillectomy has yet to be established, orthodontic treatment based on oral appliances is considered to be a potential additional treatment for pediatric sdb.","oral appliances may help improve upper airway patency during sleep by enlarging the upper airway and/or by decreasing upper airway collapsibility, thereby enhancing upper airway muscle tone. orthodontic therapy should be encouraged in pediatric osas, and an early approach may permanently modify nasal breathing and respiration, thereby preventing obstruction of the upper airway.",Treatment
does chrysin inhibit foam cell formation through promoting cholesterol efflux from raw264.7 macrophages?,"chrysin, a natural flavonoid, has been shown to possess multiple pharmacological activities including anti-atherosclerosis. the effects of chrysin on foam cell formation and cholesterol flow in raw264.7 macrophages were investigated in this work to explore the potential mechanism underlying its anti-atherogenic activity. the inhibitive effect of chrysin on foam cell formation and cholesterol accumulation induced by oxidized low-density lipoprotein cholesterol (ox-ldl) was assessed by oil red o staining and intracellular total cholesterol and triglyceride quantification in raw264.7 macrophages. the action of chrysin on cholesterol efflux and influx was tested by fluorescent assays. real-time quantitative pcr was used to quantify the relative expression of cholesterol flow-associated genes and luciferase assay was applied to test the transcription activity of peroxisome proliferator-activated receptor gamma (ppar). chrysin dose dependently inhibited the formation of foam cells and prevented the enhanced cholesterol accumulation by ox-ldl. treatment with chrysin (10 m) significantly enhanced cholesterol efflux and substantially inhibited cholesterol influx. simultaneously, chrysin significantly increased the mrna levels of ppar, liver x receptor alpha (lxr), atp-binding cassette, sub-family a1 (abca1), and sub-family g1 (abcg1), decreased scavenger receptor a1 (sr-a1) and sr-a2, and increased the transcriptional activity of ppar.",chrysin is a new inhibitor of foam cell formation that may stimulate cholesterol flow. up-regulation of the classical ppar-lxr-abca1/abcg1 pathway and down-regulation of sr-a1 and sr-a2 may participate in its suppressive effect on intracellular cholesterol accumulation.,Medication
is obstructive sleep apnea associated with fatigue in multiple sclerosis?,"multiple sclerosis (ms) patients often suffer from fatigue. we evaluated the relationship of obstructive sleep apnea (osa) to fatigue and sleepiness in ms patients. ambulatory ms patients without known sleep disorders and healthy controls underwent diagnostic polysomnography and a multiple sleep latency test (objective sleepiness measure). fatigue was measured with the fatigue severity scale (fss) and the multidimensional fatigue inventory (mfi), and subjective sleepiness by epworth sleepiness scale. covariates included age, sex, body mass index, expanded disability status scale (edss), depression, pain, nocturia, restless legs syndrome, and medication. osa (apnea-hypopnea index 15) was found in 36 of 62 ms subjects and 15 of 32 controls. after adjusting for confounders, severe fatigue (fss 5) and mfi-mental fatigue (group median) were associated with osa and respiratory-related arousals in ms, but not control subjects. subjective and objective sleepiness were not related to osa in either group. in a multivariate model, variables independently associated with severe fatigue in ms were severe osa or 17.33, 95 ci 2.53-199.84, edss or 1.88, 95 ci 1.21-3.25, and immunomodulating treatment or 0.14, 95 ci 0.023-0.65.","osa was frequent in ms and was associated with fatigue but not sleepiness, independent of ms-related disability and other covariates.",Symptoms
do human vdelta1 gamma-delta t cells exert potent specific cytotoxicity against primary multiple myeloma cells?,"human gamma-delta () t cells are potent effector lymphocytes of innate immunity involved in anti-tumor immune surveillance. however, the v1 t-cell subset targeting multiple myeloma (mm) has not previously been investigated. v1 t cells were purified from peripheral blood mononuclear cells of healthy donors and patients with mm by immunomagnetic sorting and expanded with phytohemagglutinin (pha) together with interleukin (il)-2 in the presence of allogeneic feeders. v1 t cells were phenotyped by flow cytometry and used in a 4-h flow cytometric cytotoxicity assay. cytokine release and blocking studies were performed. primary myeloma cells were purified from mm patients' bone marrow aspirates. v1 t cells expanded from healthy donors displayed prominent cytotoxicity by specific lysis against patients' cd38 () cd138 () bone marrow-derived plasma cells. v1 t cells isolated from mm patients showed equally significant killing of myeloma cells as v1 t cells from normal donors. v1 t cells showed similarly potent cytotoxicity against myeloma cell lines u266 and rpmi8226 and plasma cell leukemia arh77 in a dose-dependent manner. the interferon (ifn)- secretion and v1 t-cell cytotoxicity against myeloma cells was mediated in part through the t-cell receptor (tcr) in addition to involvement of natural killer-g2d molecule (nkg2d), dnax accessory molecule-1 (dnam-1), intracellular cell adhesion molecule (icam)-1, cd3 and cd2 receptors. in addition, v1 t cells were shown to exert anti-myeloma activity equal to that of v2 t cells.",we have shown for the first time that v1 t cells are highly myeloma-reactive and have therefore established v1 t cells as a potential candidate for a novel tumor immunotherapy.,Medication
is hemangioma associated with atopic disease?,"to determine if atopic disease is associated with infantile hemangioma. case control study. state of utah inpatient and outpatient records obtained from the department of health, intermountain healthcare medical records, and the university of utah health care medical records using the utah population database. patients given an international classification of diseases, ninth revision diagnosis of hemangioma prior to age 5 years, from 1991 to 2009. allergy, asthma, and eczema rates in the hemangioma cohort compared to randomly matched controls using logistic regression analysis. the authors identified 2063 patients in the hemangioma group. the overall odds ratio of atopic disease in patients diagnosed with hemangioma was 1.67 compared to the control group (p .0001). in the hemangioma cohort, the authors found a 36 increased risk of allergies (p .0001), 67 increased risk of asthma (p 4e-12), and 82 increased risk of eczema (p 2e-16).","this study indicates that allergy, asthma, and eczema are positively associated with hemangioma. eczema was most strongly associated with hemangioma, with a nearly 2-fold increased risk. understanding the relationship between atopic disease and infantile hemangioma may elucidate the pathophysiology of each and ultimately lead to better treatment options.",Diagnosis
do recessive mutations in leprel1 underlie a recognizable lens subluxation phenotype?,"to uncover the homozygous recessive gene mutation underlying familial lens subluxation and/or juvenile lens opacities in four sisters from a consanguineous family. prospective family study (clinical phenotyping; homozygosity-analysis-guided candidate gene testing). the proband was a 14-year-old girl with long-standing poor vision, bilateral temporal lens subluxation, lens opacities, and axial high myopia. there were no syndromic findings, and fibrillin-1 sequencing was normal. three sisters, also non-syndromic, had undergone bilateral juvenile lens surgery (two for juvenile cataract, 1 for lens subluxation) within the first two decades of life. both sisters who had cataract surgery developed bilateral post-operative retinal detachments and one had documented lens instability during cataract surgery. genetic analysis revealed the phenotype to segregate with a novel homozygous recessive mutation in leprel1 (c.292delc; p.gly100alafs104). recessive mutations in this gene were recently highlighted as a cause for axial myopia and early-onset cataract in two families for whom some affected members also had ectopia lentis and/or post-operative retinal detachments.","recessive leprel1 mutations should be recognized as part of the differential diagnosis of lens subluxation. the associated phenotype is non-syndromic and distinguishable from other causes of ectopia lentis in the context of its additional features: juvenile lens opacities, axial myopia, and a predisposition to retinal tears/detachment following intraocular surgery.",Treatment
is the killer immunoglobulin-like receptor ( kir ) group a haplotype associated with bronchiolitis obliterans syndrome after lung transplantation?,"the development of bronchiolitis obliterans syndrome (bos) after lung transplantation is associated with viral infections. natural killer (nk) cells are involved in the lysis of viral infected cells, and their activation is largely controlled by activating and inhibitory killer immunoglobulin-like receptors (kirs). we hypothesized that kir ligand incompatibility and recipients' individual kirs could influence the development of bos and the incidence of cytomegalovirus reactivation after lung transplantation. the kir gene contents were determined in 48 patients who received a lung transplant, and human leukocyte antigen (hla)-cw and hla-bw4 typing was performed on their respective donors. bos developed in 7 patients and cytomegalovirus reactivation occurred in 16. bos developed in 5 of 19 patients homozygous for kir haplotype a compared with 2 of 27 patients with kir haplotype ab and b (homozygous; p 0.03; log-rank test). in none of the patients with bos was the activating kir2ds5 gene detected, whereas it was present in 35 of patients without bos (p 0.04; log-rank test). no correlation was found between kir gene content and cytomegalovirus reactivation.",our results suggest that the lack of activating kirs may play an important role in the development of bos but not in the control of cytomegalovirus reactivation after lung transplantation.,Medication
is renal artery stenosis associated with the development of acute renal failure following coronary artery bypass grafting?,"acute renal failure (arf) is a frequent complication of coronary artery bypass grafting (cabg) surgery and is strongly associated with perioperative morbidity and mortality. we hypothesized that renal artery stenosis (ras), causing occult renal ischemia, may be an important factor contributing to development of arf after cabg surgery. preoperative and intraoperative data on 798 consecutive adult patients undergoing cabg surgery with cardiopulmonary bypass from february 1, 1995 to february 1, 1997 (who had also undergone an abdominal aortogram for the evaluation of ras) were recorded and entered into a computerized database. the development of arf was defined as a rise in serum creatinine of 1 mg/dl (88.4 micromol/l) above baseline postoperatively. the association between the presence of renal artery stenosis together with preoperative and intraoperative variables and the development of arf was assessed by multivariate logistic regression. a total of 798 patients underwent isolated coronary bypass grafting, of which 18.7 demonstrated 50 or more ras. arf developed in 82 patients (10.2), of which three (0.3) required dialysis support. the mortality for patients who developed arf was 14 (or 15, p0.0001) compared to 0.2 among those who did not develop arf. the presence of renal artery stenosis of any severity ranging from unilateral 50 ras to bilateral 95 ras was not associated with the subsequent development of arf.",the development of arf following cabg surgery is associated with high mortality. the presence of ras does not appear to increase the risk for developing arf.,Treatment
does sodium ferulate inhibit neointimal hyperplasia in rat balloon injury model?,"neointimal formation after vessel injury is a complex process involving multiple cellular and molecular processes. inhibition of intimal hyperplasia plays an important role in preventing proliferative vascular diseases, such as restenosis. in this study, we intended to identify whether sodium ferulate could inhibit neointimal formation and further explore potential mechanisms involved. cultured vascular smooth muscle cells (vsmcs) isolated from rat thoracic aorta were pre-treated with 200 mol/l sodium ferulate for 1 hour and then stimulated with 1 mol/l angiotensin ii (ang ii) for 1 hour or 10 serum for 48 hours. male sprague-dawley rats subjected to balloon catheter insertion were administrated with 200 mg/kg sodium ferulate (or saline) for 7 days before sacrificed. in presence of sodium ferulate, vsmcs exhibited decreased proliferation and migration, suppressed intracellular reactive oxidative species production and nadph oxidase activity, increased sod activation and down-regulated p38 phosphorylation compared to ang ii-stimulated alone. meanwhile, vsmcs treated with sodium ferulate showed significantly increased protein expression of smooth muscle -actin and smooth muscle myosin heavy chain protein. the components of notch pathway, including nuclear notch-1 protein, jagged-1, hey-1 and hey-2 mrna, as well as total -catenin protein and cyclin d1 mrna of wnt signaling, were all significantly decreased by sodium ferulate in cells under serum stimulation. the levels of serum 8-iso-pgf2 and arterial collagen formation in vessel wall were decreased, while the expression of contractile markers was increased in sodium ferulate treated rats. a decline of neointimal area, as well as lower ratio of intimal to medial area was observed in sodium ferulate group.",sodium ferulate attenuated neointimal hyperplasia through suppressing oxidative stress and phenotypic switching of vsmcs.,Prevention
does insulin attenuate endotoxin-induced acute lung injury in conscious rats?,"to investigate the effects of insulin on the acute lung injury induced by lipopolysaccharide using a conscious rat model. prospective, randomized, controlled animal study. university research laboratory. a total of 190 adult male sprague-dawley rats weighing 250-300 g. endotoxemia was induced by intravenous infusion of lipopolysaccharide. lipopolysaccharide at various doses (0, 1, 5, 10, 20, and 30 mg/kg, n10 for each dose) was administered intravenously in 20 mins. insulin infusion at doses of 0.5, 1, and 5 microu/kg/min was given 5 mins before lipopolysaccharide administration. plasma glucose was clamped at 90-110 mg/dl by infusion of 10-80 glucose solution. insulin and glucose infusion (0.01 ml/min) was started 5 mins before lipopolysaccharide and continued for 120 mins. the rats received a total of 60, 120, and 600 microu/kg insulin as well as 0.12, 0.36, and 0.96 g of glucose in respective groups. the animals were then observed for 4 hrs. the extent of acute lung injury was evaluated by lung weight/body weight ratio, lung weight gain, protein concentration in bronchoalveolar lavage, and exhaled nitric oxide. we also measured plasma nitrate/nitrite and methyl guanidine. in addition, histopathologic changes of the lung were examined. lipopolysaccharide caused systemic hypotension and severe acute lung injury with increases in plasma nitrate/nitrite and methyl guanidine. pretreatment with insulin infusion at doses of 0.5, 1, and 5 microu/kg/min mitigated or prevented systemic hypotension and the development of acute lung injury, depending on the dose. insulin also attenuated the lipopolysaccharide-induced increases in nitrate/nitrite and methyl guanidine.",insulin is effective in reducing or preventing the lipopolysaccharide-induced increases in plasma nitrate/nitrite and methyl guanidine and the occurrence of acute lung injury.,Medication
is loss of ifn gamma receptor an independent prognostic factor in ovarian cancer?,"there is evidence that ifn gamma plays an important role in ovarian cancer development. ifn gamma produces numerous antitumor effects and it may be evasion of these effects which allows tumor progression. we postulate that genetic instability in tumor cells may lead to modulation of expression of the ifn gamma receptor, thus leading to altered tumor biology and patient prognosis. this hypothesis would support the theory of immunoediting in ovarian cancer. using tissue microarray technology of 339 primary ovarian cancers, the expression of ifn gamma receptor was assessed immunohistochemically. coupled to a comprehensive database of clinicopathologic variables, its effect on these factors was studied. tumors expressing high levels of ifn gamma receptor had significantly improved survival (p0.017) compared with tumors expressing low levels of the receptor; this was also seen with complete receptor loss (p0.014). factors shown to predict prognosis independently of each other were the following: age, international federation of gynecologists and obstetricians stage, and the absence of macroscopic disease after surgery. the level of ifn gamma receptor expression and complete receptor loss were independently predictive of prognosis on multivariate analysis. there was no correlation between receptor status and any of the standard clinicopathologic variables.",loss of ifn gamma receptor independently predicts poor prognosis in ovarian cancer. loss of receptor expression may be responsible for the limited success in the therapeutic use of ifn gamma in ovarian cancer trials and highlights a subgroup of high expressing ifn gamma receptor tumors which are more likely to be susceptible to such treatments.,Medication
is regulation of vascular smooth muscle cell expression and function of matrix metalloproteinases mediated by estrogen and progesterone exposure?,"postmenopausal women receiving hormone replacement therapy (hrt) have been reported to have more adverse outcomes after vascular reconstructions, including increased intimal hyperplasia development and bypass graft failure. hrt may be affecting the pathway contributing to intimal hyperplasia. an important component of this pathway involves matrix metalloproteinases (mmps), implicated in vascular remodeling due to their ability to degrade components of the extracellular matrix. we hypothesize that estrogen (est) and progesterone (prog) upregulate the mmp pathway in vascular smooth muscle cells (vsmcs) thereby increasing mmp activity and function. vsmcs were incubated with est (5 ng/ml), prog (50 ng/ml), est prog combination (est/prog), and/or doxycycline (40 microg/ml; doxy). using reverse transcriptase polymerase chain reaction (rt-pcr) analysis we have previously shown membrane type 1-mmp (mt1-mmp) messenger ribonucleic acid (mrna) levels are significantly increased by est. here, western blot analyses indicated mt1-mmp and mmp-2 protein levels, not tissue inhibitor of mmp-2 (timp-2), were increased in response to est and est/prog (p .05 vs control). in-gel zymography revealed that est and est/prog resulted in increased mmp-2 activity (hormone groups, p .05 vs control) with no significant difference among the hormone groups. vsmc migration was increased by 45 /- 14 in response to est (p .05 vs control), as measured using a modified boyden chamber assay. doxycycline significantly inhibited basal and est/prog-stimulated increases in mmp-2 activity (p .05 vs control; p .05 vs hormone groups), and partially blocked basal and hormonally stimulated migration (p .05 vs control and est).","estrogen and progesterone affects the mmp pathway by increasing mmp-2 enzymatic activity, possibly via the upregulation of mt1-mmp expression without a corresponding increase in timp expression. this increased collagenase activity increases vsmc motility and their ability to migrate through a collagen type iv lattice. est/prog upregulation of mt1-mmp may contribute to the adverse effect of hrt on vascular interventions.",Treatment
"are adjacent genes , for col2a1 and the vitamin d receptor , associated with separate features of radiographic osteoarthritis of the knee?","to study the association of the col2a1 genotype, in relation to the vitamin d receptor (vdr) genotype, with features of radiographic osteoarthritis (roa) in a population of elderly men and women. in this cross-sectional study, we analyzed a population-based sample of 851 men and women ages 55-80 years from a large cohort study, the rotterdam study. we determined the prevalence of roa of the knee according to the kellgren/lawrence (k/l) score and features of roa (presence of osteophytes and narrowing of the joint space jsn) without considering clinical parameters of the disease. genotypes were determined at a variable-number tandem repeats marker 1 kb downstream of the col2a1 gene using a newly developed heteroduplexing method. the vdr genotype was previously determined by a direct molecular haplotyping polymerase chain reaction method to establish the phase of alleles at 3 adjacent restriction fragment length polymorphisms for bsm i, apa i, and taq i. we found the col2a1 genotype to be associated with a 2-fold increased risk for jsn, but not with osteophytes or the k/l score. we had previously found the vdr genotype to be associated with osteophytes and the k/l score, but not with jsn. when the col2a1 genotype was analyzed in combination with the vdr genotype, we found evidence suggesting that the presence of haplotypes of the 2 genes was associated with increased risk for roa.","our findings demonstrate that both the col2a1 gene and the vdr gene are involved in roa, but in separate features. the col2a1 genotype is associated with jsn, while the vdr genotype is associated with osteophytes.",Diagnosis
does ketamine alter the neurogenesis of rat cortical neural stem progenitor cells?,"high doses or prolonged exposure to ketamine increase neuronal apoptosis in the developing brain, although effects on neural stem progenitor cells remain unexplored. this study investigated dose- and time-dependent responses to ketamine on cell death and neurogenesis in cultured rat fetal cortical neural stem progenitor cells. laboratory-based study. university research laboratory. sprague-dawley rats. neural stem progenitor cells were isolated from the cortex of sprague-dawley rat fetuses on embryonic day 17. in dose-response experiments, cultured neural stem progenitor cells were exposed to different concentrations of ketamine (0-100 m) for 24 hrs. in time-course experiments, neural stem progenitor cells cultures were exposed to 10 m ketamine for different durations (0-48 hrs). apoptosis and necrosis in neural stem progenitor cells were assessed using activated caspase-3 immunostaining and lactate dehydrogenase assays, respectively. proliferative changes in neural stem progenitor cells were detected using bromo-deoxyuridine incorporation and ki67 immunostaining. neuronal differentiation was assessed using tuj-1 immunostaining. cultured neural stem progenitor cells were resistant to apoptosis and necrosis following all concentrations and durations of ketamine exposure tested. ketamine inhibited proliferation with decreased numbers of bromo-deoxyuridine-positive cells following ketamine exposure to 100 m for 24 hrs (p10 m for 24 hrs (p8 hrs (p.001).",clinically relevant concentrations of ketamine do not induce cell death in neural stem progenitor cells via apoptosis or necrosis. ketamine alters the proliferation and increases the neuronal differentiation of neural stem progenitor cells isolated from the rat neocortex. these studies imply that ketamine exposure during fetal or neonatal life may alter neurogenesis and subsequent brain development.,Medication
"are systemic levels of cotinine and elastase , but not pulmonary function , associated with the progression of small abdominal aortic aneurysms?","to study whether smoking and impaired pulmonary function are associated with the expansion of abdominal aortic aneurysms (aaa). seventy-nine men with small (3-5 cm), screen-detected aaa underwent a simple 5-step smoking history, measurement of the forced first second expiratory volume (fev1), venepuncture and annual ultrasound scan for mean follow-up period of 3.5 years. all but one patient had a significantly reduced fev1 (p0.05, mann-whitney). the fev1/expected fev1 ratio (rfev1) was not related to aaa expansion but was negatively correlated with p-elastase-alpha1-antitrypsin-complexes (p-elastase). p-elastase was positively correlated with smoking and s-cotinine. smoking, s-cotinine, and p-elastase were positively correlated with the mean annual aaa expansion rate but not rfev1.","in general, patients with aaa have impaired pulmonary function. a simple five step smoking classification is as predictive of aaa-expansion as s-cotinine. smoking may cause elastase secretion leading to pulmonary and aortic elastin degradation but the lack of association between aaa-expansion and rfev1 suggest that other mechanisms are important.",Diagnosis
do an update on the relationship between statins and physical activity?,"this review examined studies published within the last 16 months that investigated the relationship between statins and physical activity. these recent studies suggest that statins do not adversely affect cardiorespiratory fitness, muscle strength, athletic performance, or physical activity adherence. one recent study comparing patients with statin-associated myalgia and nonstatin-using controls did report that statins are associated with a slowing of time to peak power output, increased abdominal adiposity, and insulin resistance. statin users also had different muscle gene expression than controls, but conclusions are limited by the design of that study.","previous reports suggest that statin-associated muscle symptoms such as myalgia, cramps, and weakness occur more frequently in physically active individuals, but the recent studies we reviewed do not provide additional support for this possibility. well-designed clinical trials are needed to determine whether different statins or statin doses evoke statin-associated muscle symptoms or muscle damage that may reduce cardiorespiratory fitness and adherence to physical activity.",Medication
does insulin resistance predict steatosis and fibrosis in morbidly obese patients undergoing bariatric surgery?,"influence of adipokines and insulin resistance on liver histology is an unclear area in morbidly obese patients. the aim of our study was to study the influence of insulin resistance and adipokines in the grade of liver steatosis and fibrosis in morbidly obese patients undergoing bariatric surgery. tertiary hospital. a sample of 36 morbidly obese patients undergoing bariatric surgery was analyzed in a cross-sectional study. a liver biopsy was performed. weights, basal glucose, insulin, insulin resistance (homeostasis model assessment for insulin resistance homa-ir), total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, and adipokine blood levels were measured. seventeen patients (47.2) had low-grade steatosis, and 19 patients (52.8) had high-grade steatosis. sixteen patients (44.4) did not have liver fibrosis, and 20 patients (56.6) had liver fibrosis. only insulin levels, homa-ir, and aspartate aminotransferase activity were higher in the patients with high-grade steatosis. insulin levels and homa-ir were higher in patients with fibrosis. in the logistic regression analysis with a dependent dichotomous variable (grades of steatosis: low vs high), the homa-ir remained in the model, with an odds ratio to develop high-grade steatosis of 1.33 (95 confidence interval, 1.09-1.86). in the second logistic regression analysis with a dependent dichotomy variable (grades of fibrosis: present vs absent), the homa-ir remained in the model, with an odds ratio to develop fibrosis of 1.53 (95 confidence interval, 1.13-2.51).",insulin resistance determined with homa-ir model is associated with high-grade steatosis and liver fibrosis in obese patients before bariatric surgery.,Medication
do endogenous antibodies contribute to macrophage-mediated demyelination in a mouse model for cmt1b?,"we could previously identify components of both the innate and the adaptive immune system as disease modifiers in the pathogenesis of models for charcot-marie-tooth (cmt) neuropathies type 1b and 1x. as part of the adaptive immune system, here we investigated the role of antibodies in a model for cmt1b. antibodies were localized and characterized in peripheral nerves of the cmt1b model by immunohistochemistry and western blot analysis. experimental ablation of antibodies was performed by cross breeding the cmt1b models with mutants deficient in b-lymphocytes (jhd-/- mutants). ameliorated demyelination by antibody deficiency was reverted by intravenous injection of mouse igg fractions. histopathological analysis was performed by immunocytochemistry and light and quantitative electron microscopy. we demonstrate that in peripheral nerves of a mouse model for cmt1b, endogenous antibodies strongly decorate endoneurial tubes of peripheral nerves. these antibodies comprise igg and igm subtypes and are preferentially, but not exclusively, associated with nerve fiber aspects nearby the nodes of ranvier. in the absence of antibodies, the early demyelinating phenotype is substantially ameliorated. reverting the neuropathy by reconstitution with murine igg fractions identified accumulating antibodies as potentially pathogenic at this early stage of disease.","our study demonstrates that in a mouse model for cmt1b, endogenous antibodies contribute to early macrophage-mediated demyelination and disease progression. thus, both the innate and adaptive immune system are mutually interconnected in a genetic model for demyelination. since in wallerian degeneration antibodies have also been shown to be involved in myelin phagocytosis, our study supports our view that inherited demyelination and wallerian degeneration share common mechanisms, which are detrimental when activated under nonlesion conditions.",Medication
is aspidosperma species as sources of anti-malarials : uleine the major anti-malarial indole alkaloid from aspidosperma parvifolium ( apocynaceae )?,"several species of the genus aspidosperma (apocynaceae) are used for the treatment of human malaria in brazil and other meso- and south american countries. ethanol extract from aspidosperma parvifolium trunk bark was submitted to acid-base extractions leading to alkaloid and neutral fractions. the alkaloid fraction was chromatographed over a silica gel column. ethanol extract, fractions and uleine were analysed by hplc-dad, uplc-esi-ms/ms and hplc-esi-microtof-ms. the anti-malarial activity was assayed against resistant and sensitive chloroquine plasmodium falciparum strains by microscopic, (3)h-hypoxanthine incorporation and hrpii techniques. cytotoxicity (cc50) was evaluated against vero and hepg2 cell lines by the mtt technique; selectivity indexes (si cc50/ic50) were calculated. the major peak in the hplc-dad chromatograms of the ethanol extract, alkaloid and neutral fractions suggested the presence of uleine that was isolated from the alkaloid fraction by column chromatography and was characterized by spectroscopic methods. a total of 15 alkaloids, besides uleine, were identified in the alkaloid fraction by uplc-dad-esi-ms/ms and hplc-esi-microtof-ms. the ethanol extract from aspidosperma parvifolium and the neutral fraction were moderately active against p. falciparum strains. the alkaloid fraction and uleine disclosed high anti-malarial activity against chloroquine-resistant p. falciparum strain (ic50 300 g/ml). the alkaloid fraction showed moderate cytotoxicity to hepg2 cell line (cc50 74.4 g/ml). high si values (10) were determined for all samples.","ethanol extract from aspidosperma parvifolium trunk bark afforded uleine that is the major constituent of the alkaloid fraction and disclosed a good in vitro anti-malarial activity. moreover, 15 other indole alkaloids have been identified along with uleine.",Treatment
does malocclusion traits and orthodontic treatment need in prematurely born children?,"to evaluate if prematurely born children have higher prevalence of malocclusion traits and greater orthodontic treatment need than matched full-term born controls. seventy-three preterm children were selected from the medical birth register and divided into two subgroups according to their gestational age. one group consisted of 37 very preterm children (vpt), born in gestational week 29-32, and the other of 36 extremely preterm children (ept), born before the 29th gestational week. the subjects were compared with a control group of 41 full-term children, who were matched for sex, age, and nationality. data from clinical examinations, study casts, and panoramic radiographs were used to determine malocclusion traits. the dental health component of the index of orthodontic treatment need (iotn) was used to rank the treatment need. two or more malocclusion traits occurred significantly more often among ept (83.3) and vpt children (73.0), compared with the full-term children (51.2). significantly higher prevalence of deep bites and was found in ept and vpt groups compared with the full-term control group. deep bite was the most common malocclusion trait in the ept and vpt group. higher orthodontic treatment need was found for the preterm children but no differences in prevalence of malocclusion traits and treatment need were found between vpt and ept children.",the clinician should be aware of the potential for a higher number of malocclusion traits and greater orthodontic treatment need in prematurely born children compared with full-term children.,Treatment
does d-2-hydroxyglutaric acid inhibit creatine kinase activity from cardiac and skeletal muscle of young rats?,"tissue accumulation of high amounts of d-2-hydroxyglutaric acid (dga) is the biochemical hallmark of the inherited neurometabolic disorder d-2-hydroxyglutaric aciduria (dhga). patients affected by this disease usually present hypotonia, muscular weakness, hypertrophy and cardiomyopathy, besides severe neurological findings. however, the underlying mechanisms of muscle injury in this disorder are virtually unknown. in the present study we have evaluated the in vitro role of dga, at concentrations ranging from 0.25 to 5.0 mm, on total, cytosolic and mitochondrial creatine kinase activities from skeletal and cardiac muscle of 30-day-old wistar rats. we also tested the effects of various antioxidants on the effects elicited by dga. we first verified that total creatine kinase (ck) activity from homogenates was significantly inhibited by dga (22-24 inhibition) in skeletal and cardiac muscle, and that this activity was approximately threefold higher in skeletal muscle than in cardiac muscle. we also observed that ck activities from mitochondrial (mi-ck) and cytosolic (cy-ck) preparations from skeletal muscle and cardiac muscle were also inhibited (12-35 inhibition) by dga at concentrations as low as 0.25 mm, with the effect being more pronounced in cardiac muscle preparations. finally, we verified that the dga-inhibitory effect was fully prevented by preincubation of the homogenates with reduced glutathione and cysteine, suggesting that this effect is possibly mediated by modification of essential thiol groups of the enzyme. furthermore, alpha-tocopherol, melatonin and the inhibitor of nitric oxide synthase l-name were unable to prevent this effect, indicating that the most common reactive oxygen and nitrogen species were not involved in the inhibition of ck provoked by dga.","considering the importance of creatine kinase activity for cellular energy homeostasis, our results suggest that inhibition of this enzyme by increased levels of dga might be an important mechanism involved in the myopathy and cardiomyopathy of patients affected by dhga.",Medication
does propofol action in both spinal cord and brain blunt electroencephalographic responses to noxious stimulation in goats?,"anesthetics, including propofol, depress the electroencephalogram (eeg) and neuronal activity in the midbrain reticular formation (mrf). because propofol has anesthetic effects in the spinal cord, we hypothesized that it would indirectly depress eeg and mrf neuronal responses to noxious stimulation in part by a spinal cord action. six goats were anesthetized with isoflurane and the jugular veins and carotid arteries were isolated to permit cranial bypass and differential propofol delivery. a noxious mechanical stimulus was applied to the distal forelimb while recording bifrontal eeg and mrf single-unit activities. propofol was separately administered to the cranial (0.08 /- 0.06 mg/kg) and torso circulations (4 mg/kg) and the noxious stimulus applied at 1,5, 10, and 15 min after each injection. n/a. n/a. n/a. noxious stimulation decreased total power (tp) from 96 /- 33, microv2/hz to 38 /- 20microv2/hz, (mean /- sd) and increased spectral edge frequency (sef) from 10 /- 3 hz to 19 /- 5 hz (p0.01). propofol administered to the torso prevented stimulus-evoked changes in tp (121/- 80 microv2/hz, 121 /- 74 microv2/hz, 114 /- 74 microv2/hz at 1,5, and 10 min respectively, p0.01 compared to control evoked response) and sef (11 /- 6hz, 9 /- 2hz, 10 /- 6hz, and 12 /- 5hz at 1, 5, 10 and 15 min, respectively, p0.001 compared to control evoked response). propofol administered to the cranial circulation significantly blunted the eeg and mrf response, while torso-administered propofol had slight effects on mrf responses.",propofol blunted the eeg response to noxious stimulation in part via a subcortical action.,Medication
is intraoperative ultrasound associated with clear lumpectomy margins for palpable infiltrating ductal breast cancer?,"to evaluate the efficacy of intraoperative ultrasound in obtaining adequate surgical margins in women undergoing lumpectomy for palpable breast cancer. adequacy of surgical margins is a subject of debate in the literature for women undergoing breast-conserving therapy. the emerging technology of intraoperative ultrasound-guided surgery lends itself well to a prospective study evaluating surgical accuracy and margin status after lumpectomy. two groups of women undergoing lumpectomy for palpable breast cancer were studied, one group using intraoperative ultrasound (n 27) and the other without (n 24). pathologic specimens were evaluated for size, margins, and accuracy, and patients were questioned about satisfaction with cosmetic results. surgical accuracy was improved with intraoperative ultrasound-guided surgery. margin status was improved, patient satisfaction was equivalent, and cost was not affected using ultrasound technology. intraoperative ultrasound appears especially efficacious for women whose preoperative mammogram shows dense parenchyma surrounding the lesion.",the use of ultrasound-guided surgery optimizes the surgeon's ability to obtain satisfactory margins for breast-conserving techniques in patients with breast cancer. patient satisfaction is excellent and a cost savings is most likely realized.,Diagnosis
is initial cognitive decline associated with cortical thinning in early parkinson disease?,"our aim was to assess cortical thickness in a large multicenter cohort of drug-naive patients with early parkinson disease (pd), with and without mild cognitive impairment (mci), and explore the cognitive correlates of regional cortical thinning. one hundred twenty-three newly diagnosed patients with pd and 56 healthy controls with 3-tesla structural mri scans and complete neuropsychological assessment from the parkinson's progression markers initiative were included. modified movement disorders society task force level ii criteria were applied to diagnose mci in pd. freesurfer image processing and analysis software was used to measure cortical thickness across groups and the association with cognitive domains and tests. in patients with mci, atrophy was found in temporal, parietal, frontal, and occipital areas compared with controls. specific regional thinning in the right inferior temporal cortex was also found in cognitively normal patients. memory, executive, and visuospatial performance was associated with temporoparietal and superior frontal thinning, suggesting a relationship between cognitive impairment and both anterior and posterior cortical atrophy in the whole patient sample.","these findings confirm that mci is associated with widespread cortical atrophy. in addition, they suggest that regional cortical thinning is already present at the time of diagnosis in patients with early, untreated pd who do not meet the criteria for mci. together, the results indicate that cortical thinning can serve as a marker for initial cognitive decline in early pd.",Diagnosis
does interferon- contribute to hla-b27-associated unfolded protein response in spondyloarthropathies?,"hla-b27 positivity strongly influences the susceptibility to and phenotype of spondyloarthropathies (spa). this study was designed to screen factors that activate the promoter of hla-b27 in u937 cells, and to assess whether these promoter-activating factors induce the unfolded protein response (upr) in hla-b27-expressing cells. cytometric bead array, flow cytometry, and real-time polymerase chain reaction were used to detect the expression of cytokines and upr-associated proteins in peripheral blood and synovial fluid of patients with spa. the hla-b27 promotor transfectant was incubated separately with cytokines and toll-like receptor ligands. after interferon- (ifn-) stimulation, expressions of grp78, chop, and xbp-1 were tested in hla-b27-expressing u937 cells and peripheral blood mononuclear cell (pbmc) of patients with ankylosing spondylitis (as). (clinical trial registration no. chictr-occ-11001565) expressions of grp78, chop, and xbp-1 in monocytes/macrophages of spa peripheral blood and synovial fluid were higher than those in healthy controls and patients with osteoarthritis (oa) (p 0.05). tumor necrosis factor- (tnf-) and ifn-, ifn-, and ifn- were found to have activated the hla-b27 promoter in the u937 cell line (p 0.05). following stimulation with ifn-, the expressions of grp78, chop and xbp-1 in hla-b27-transfected u937 cells and pbmc of hla-b27-positive as patients were more intense than those in a2-u937 cells, hla-b27-negative as patients, or healthy controls (p 0.05).","expressions of grp78, chop, and xbp-1 were higher in monocytes/macrophages of patients with spa than those in both oa patients and healthy controls, suggesting that upr may participate in the pathogenesis of spa. tnf- and ifn-, ifn-, and ifn- significantly activated hla-b27 promoter in the u937 cell line, and ifn-, the strongest activating factor, may induce the upr in hla-b27-expressing cells.",Medication
are endothelial lipase concentrations increased in metabolic syndrome and associated with coronary atherosclerosis?,"endothelial lipase (el), a new member of the lipase family, has been shown to modulate high-density lipoprotein (hdl-c) metabolism and atherosclerosis in mouse models. we hypothesized that el concentrations would be associated with decreased hdl-c and increased atherosclerosis in humans. healthy individuals with a family history of premature coronary heart disease (n 858) were recruited as part of the study of the inherited risk of atherosclerosis. blood was drawn in the fasting state before and, in a subgroup (n 510), after administration of a single dose of intravenous heparin. plasma lipids were measured enzymatically, lipoprotein subclasses were assessed by nuclear magnetic resonance, and coronary artery calcification (cac) was quantified by electron beam computed tomography. plasma el mass was measured using a newly developed enzyme-linked immunosorbent assay. median el mass in pre-heparin plasma was 442 (interquartile range 324-617) ng/ml. median post-heparin mass was approximately 3-fold higher, 1,313 (888-1,927) ng/ml. the correlation between pre-heparin el mass and post-heparin el mass was 0.46 (p 0.001). el mass concentrations in both pre- and post-heparin plasma significantly correlated with all ncep atpiii-defined metabolic syndrome factors: waist circumference (r 0.28 and 0.22, respectively, p 0.001 for each), blood pressure (r 0.18 and 0.24, p 0.001 for each), triglycerides (r 0.22, p 0.001; and 0.13, p 0.004), hdl cholesterol (r -0.11, p 0.002; and -0.18, p 0.001), and fasting glucose (r 0.11 and 0.16, p 0.001 for both). el mass in both routine (odds ratio or 1.67, p 0.01) and post-heparin (or 2.42, p 0.003) plasma was associated with cac as determined by ordinal regression after adjustment for age, gender, waist circumference, vasoactive medications, hormone replacement therapy (women), and established cardiovascular risk factors.","we report, to our knowledge for the first time, that human plasma el concentrations, in both post-heparin and routine pre-heparin plasma, are significantly associated with metabolic syndrome features and with subclinical atherosclerosis. el may be a pro-atherogenic factor in humans, especially in overweight individuals and those with metabolic syndrome.",Medication
is why publishing everything more effective than selective publishing of statistically significant results?,"de winter and happee examined whether science based on selective publishing of significant results may be effective in accurate estimation of population effects, and whether this is even more effective than a science in which all results are published (i.e., a science without publication bias). based on their simulation study they concluded that ""selective publishing yields a more accurate meta-analytic estimation of the true effect than publishing everything, (and that) publishing nonreplicable results while placing null results in the file drawer can be beneficial for the scientific collective"" (p.4). using their scenario with a small to medium population effect size, we show that publishing everything is more effective for the scientific collective than selective publishing of significant results. additionally, we examined a scenario with a null effect, which provides a more dramatic illustration of the superiority of publishing everything over selective publishing.",publishing everything is more effective than only reporting significant outcomes.,General
does a short-term long-chain triglycerides infusion have no influence on immune function of adult patients undergoing gastrointestinal surgery?,"parenteral nutrition (pn) support containing long-chain triglycerides (lct) plays a critical supportive role in surgical patients' management. this study aims to investigate the effects of intravenous (iv) lct emulsion on human immune function in adult patients receiving a gastrointestinal surgical procedure. sixty adult patients were randomly assigned either to the lct treatment group (n 32) or to the control group (n 28). after an abdominal operation, the subjects received pn treatment with or without lct for 5 days. neutrophil, peripheral blood mononuclear cell (pbmc), lymphocyte and cd4/cd8, serum immunoglobulin a (iga), igg, igm, complement c3 and c4, interleukin (il)-2, il-4, il-10, il-12, tumor necrosis factor (tnf)-alpha, and interferon (ifn)-gamma were measured and statistically analyzed. the lct and control groups did not differ significantly at entry in terms of general features. except for a significant increase of neutrophil number at 24 hours after the surgery in both groups (p .05, respectively) 24 hours before the operation, and 24 hours and 120 hours after the operation.","the regimens of lct administration may have diverse effects on human immune function in different patient populations. however, lct emulsion at an appropriate dose and infusion speed does not alter human immune function of adult patients undergoing moderate gastrointestinal surgery.",Treatment
is masked hypertension prevalent in children with sickle cell disease : a midwest pediatric nephrology consortium study?,"the prevalence of hypertension and abnormal blood pressure (bp) patterns on 24-h ambulatory bp monitoring (abpm) remains unknown in children with sickle cell disease (scd). thirty-eight asymptomatic children with sickle cell disease (scd) (12 hbss receiving routine care, 13 hbsc, and 13 hbss receiving chronic transfusion therapy) underwent 24-h abpm. average clinic bp, demographic and biochemical characteristics were collected. median age was 13 years (range 11-16), body mass index (bmi) 19.1 kg/m(2) (range 18.2-21.1), and 50 were male. seventeen subjects (43.6) had ambulatory hypertension, while 4 (10.3) were hypertensive based on their clinic bp. mean systolic blood pressure (sbp) and diastolic blood pressure (dbp) dip were 8.3 5.9 and 14.7 7.6 respectively. twenty-three subjects (59) had impaired sbp dipping, 7 (18) had impaired dbp dipping, and 5 (13) had reversed dipping. clinic and abp classification were modestly correlated (rho 0.38, p 0.02).",abnormalities in abp measurements and patterns in children with scd are prevalent and require more attention from heath care providers. abpm is a valuable tool in identifying masked hypertension and abnormalities in circadian bp.,Treatment
is cripto-1 overexpression involved in the tumorigenesis of nasopharyngeal carcinoma?,"human cripto-1, a member of the egf-cfc family, is indispensable for early embryonic development. cripto-1 plays an important oncogenic role during tumorigenesis and is overexpressed in a wide range of epithelial carcinomas, yet little is known about cripto-1 in nasopharyngeal carcinoma (npc). the aim of this study was to analyze the roles of cripto-1 in the progression and clinical characteristics in npc clinical samples and cell lines. the expression of cripto-1 at mrna level was detected by the reverse transcription-polymerase chain reaction (rt-pcr) and real time rt-pcr, and western blot was used to examine the protein expression. cripto-1 expression and its clinical characteristics were investigated by performing immunohistochemical analysis on a total of 37 npc clinical tissue samples. lentiviral vectors were constructed to get an efficient expression of anti-cripto-1 sirna in cne-2 and c666-1 cells, with invalid rnai sequence as control. after the inhibition of the endogenous cripto-1, the growth, cell cycle and invasion of cells were detected by mtt, facs and boyden chamber assay respectively. moreover, in vivo, the proliferation of the tumor cells was evaluated in xenotransplant nude mice model with whole-body visualizing instrument. the results of real-time rt-pcr and western blot showed that the expression level of cripto-1 was markedly higher in npc cell lines than that in the immortalized nasopharyngeal epithelial cell at both mrna and protein levels. rt-pcr of 17 npc tissues showed a high expression rate in 76.5 (13/17) cases. in an immunohistochemical study, cripto-1 was found to express in 54.1 (20/37) cases of npc. in addition, cripto-1 overexpression was significantly associated with n classification (p 0.034), distant metastasis (p 0.036), and clinical stage (p 0.007). inhibition of endogenous cripto-1 by lentivirus-mediated rnai silencing technique suppressed npc cell growth and invasion in vitro. in vivo, the average weight (p 0.026) and volume (p 0.044) of tumor in cne-2/gfp/cripto-1- xenotransplant mice group were significantly lower than those in the control group. the ki67 index was obviously lower in cripto-1 rnai treated tumors (p 0.01).","data of this study suggest that cripto-1 overexpression is connected with the tumorigenesis and progression of npc, lentivector-mediated rnai might be feasible for the inhibition of the growth and invasion of npc.",Treatment
does the nitric oxide donor glyceryl trinitrate increase subchondral bone sclerosis and cartilage degeneration following ovine meniscectomy?,"to examine the effect of glyceryl trinitrate (gtn), a nitric oxide (no) donor compound, on the concurrent progression of cartilage and subchondral bone changes in an ovine meniscectomy model of osteoarthritis (oa). bilateral lateral meniscectomy (mx) was performed on 12 ewes to induce oa. six were treated with topical gtn (0.7mg/kg twice weekly) (mxgtn). six other sheep formed non-operated controls (noc). after sacrifice at six months, the subchondral bone density (bmd) of the lateral and medial femoral condyles (lfc, mfc) and tibial plateau (ltp, mtp) was assessed by dexa. dynamic biomechanical testing was performed across the mtp and ltp. histological sections from each region were scored qualitatively and the thickness of the subchondral bone plate (scb) was determined by image analysis. mxgtn displayed significantly greater scb thickness relative to mx in the lfc (mean increase 88 and 42, respectively) and the mfc. scb bmd was 10-12 greater in mxgtn relative to mx in the lfc, ltp and mtp. mxgtn sheep also showed greater increases in some histopathology variables, greater central erosion of the ltp, and changes in dynamic stiffness (decreased) and phase lag (increased) in the outer zone of the ltp.","treatment with gtn significantly increased subchondral bone thickness and density during subchondral remodelling following meniscectomy. in addition, it slightly but significantly worsened degeneration of cartilage structure and function. these results suggest that clinical use of gtn may accelerate both cartilage degeneration and subchondral bone sclerosis if used in the presence of oa, and demonstrate that no has the potential be an important mediator of the subchondral bone changes seen in oa.",Medication
does intrapericardial ethanol delivery inhibit neointimal proliferation after porcine coronary overstretch?,"previous work has shown that ethanol dampens cell growth signals and inhibits smooth muscle proliferation in a restenosis model. catheter-based approaches to intrapericardial (ipc) delivery of therapeutic agents have been recently demonstrated to be feasible. this study tested the effect of ipc instillation of ethanol on the injury response of overstretched porcine coronary arteries. ethanol, 30, (e, 10 ml, n 6) or saline, 0.9, (c, 10 ml, n 6) was administered ipc after overstretch injury of porcine coronary arteries. animals were sacrificed 28 days after balloon dilation. the neointimal and adventitial area were significantly reduced in the e group (0.36 /- 0.05 mm2; 1.68 /- 0.09 mm2) as compared to the c group (0.61 /- 0.05 mm2; 2.61 /- 0.14 mm2; p 0.001). the maximal intimal and adventitial thicknesses of the treated vessels were also significantly smaller than those of untreated vessels (0.44 /- 0.02, 0.38 /- 0.08 mm vs 0.57 /- 0.03, 0.54 /- 0.03 mm, respectively; p 0.005). the calculated luminal stenosis decreased in the treated group, 16.1, versus the control group, 25.3.",perivascular administration of a single-dose of ethanol significantly reduce neointimal proliferation in the porcine balloon-overstretch model. this data suggests that intrapericardial delivery of therapeutic agents may be useful and feasible in the coronary angioplasty setting for prevention of restenosis.,Treatment
does hospital profitability for a surgeon 's common procedures predict the surgeon 's overall profitability for the hospital?,"to evaluate whether a hospital's profitability for a surgeon's common procedures predicts the surgeon's overall profitability for the hospital. observational study. community and university-affiliated tertiary hospital with 21,903 surgical procedures performed per year. 7,520 patients having surgery performed by one of 46 surgeons. none. financial data were obtained for all patients cared for by all the surgeons who performed at least ten cases of one of the hospital's six most common procedures. a surgeon's overall profitability for the hospital was measured using his or her contribution margin ratio (i.e., total revenue for all of the surgeon's patients divided by total variable cost for the patients). contribution margin was calculated twice: once with all of a surgeon's patients, and second, limiting consideration to those patients who underwent one of the six common procedures. the common procedures accounted for 22 /- 15 of the 46 surgeons' overall caseload, 29 /- 10 of their patients' hospital costs, and 30 /- 12 of the hospital revenue generated by the surgeons. hospital contribution margin ratios ranged from 1.4 to 4.2. contribution margin ratios for common procedures and contribution margin ratios for all patients were correlated (tau 0.58, n 46, p 0.0001).","even though most surgical cases were for uncommon procedures, a surgeon's hospital profitability on common procedures predicted the surgeon's overall financial performance. perioperative incentive programs based on common surgical procedures (clinical pathways) are likely to accurately reflect a surgeon's financial performance on their other surgeries.",Treatment
does propofol modulate phasic and tonic gabaergic currents in spinal ventral horn interneurones?,"surgical interventions like skin incisions trigger withdrawal reflexes which require motor neurones and local circuit interneurones in the spinal ventral horn. this region plays a key role in mediating immobilizing properties of the gabaergic anaesthetic propofol. however, it is unclear how propofol modulates gaba(a) receptors in the spinal ventral horn and whether tonic or phasic inhibition is involved. organotypic spinal cord tissue slices were prepared from mice. whole-cell recordings were performed for quantifying effects of propofol on gaba(a) receptor-mediated phasic transmission and tonic conductance. propofol increased gabaergic phasic transmission by a prolongation of the decay time constant in a concentration-dependent manner. the amount of the charge transferred per inhibitory post-synaptic current, described by the area under the curve, was significantly augmented by 1 m propofol (p0.01). a gaba(a) receptor-mediated tonic current was not induced by 1 m propofol but at a concentration of 5 m (p0.05).","propofol depresses ventral horn interneurones predominantly by phasic rather than by tonic gaba(a) receptor-mediated inhibition. however, the present results suggest that the involvement of a tonic inhibition might contribute to the efficacy of propofol to depress nociceptive reflexes at high concentrations of the anaesthetic.",Medication
is high consumption of pulses associated with lower risk of abnormal glucose metabolism in women in mauritius?,"to investigate if consumption of pulses was associated with a reduced risk of developing abnormal glucose metabolism, increases in body weight and increases in waist circumference in a multi-ethnic cohort in mauritius. population-based surveys were performed in mauritius in 1992 and in 1998. pulse consumption was estimated from a food frequency questionnaire in 1992 and outcomes were measured in 1998. at both time points, anthropometry was undertaken and an oral glucose tolerance test was performed. mauritian women with the highest consumption of pulses (highest tertile) had a reduced risk of developing abnormal glucose metabolism odds ratio 0.52; 95 ci 0.27, 0.99) compared with those with the lowest consumption, and also after multivariable adjustments. in women, a high consumption of pulses was associated with a smaller increase in bmi.",high consumption of pulses was associated with a reduced risk of abnormal glucose metabolism and a smaller increase in bmi in mauritian women. promotion of pulse consumption could be an important dietary intervention for the prevention of type 2 diabetes and obesity in mauritius and should be examined in other populations and in clinical trials.,General
is cytochrome p450 2c9-induced angiogenesis dependent on ephb4?,"cytochrome p450 (cyp) epoxygenase-derived epoxyeicosatrienoic acids (eets) are known to stimulate angiogenesis, but the mechanisms involved are incompletely understood. because ephb4 is involved in vascular development, the aim of this study was to investigate whether, and to what extent, ephb4 is part of the signaling cascade that results in cyp2c9-mediated angiogenesis. cyp2c9 overexpression as well as stimulation with 11,12-eet (up to 48 hours) time-dependently increased ephb4 expression in endothelial cells. this effect and the activation of the ephb4 promoter were mediated by the phosphatidylinositol-3-kinase (p13-k)/akt pathway and sensitive to the p13-k inhibitor ly 294002 as well as to simultaneous transfection with dominant-negative akt. 11,12-eet treatment also increased ephb4 expression in isolated mouse mesenteric arteries as well as in the vessels that developed in 11,12-eet-impregnated matrigel plugs. moreover, the cyp2c9-stimulated formation of capillary-like structures in a modified spheroid assay was markedly attenuated by ephb4 downregulation (antisense oligonucleotides). using a parallel approach in vivo, the inclusion of sirna directed against ephb4 in eet-impregnated matrigel plugs prevented endothelial cell invasion and vascularization.","our data indicate that ephb4 is a critical component of the cyp2c9- and 11,12-eet-activated signaling cascade that promotes angiogenesis in vitro as well as in vivo.",Medication
is long-term therapy with the dual 5alpha-reductase inhibitor dutasteride well tolerated in men with symptomatic benign prostatic hyperplasia?,"to examine the long-term (4-year) safety and tolerability of dutasteride in the treatment of symptomatic benign prostatic hyperplasia (bph). patients who completed the double-blind phase of three dutasteride phase iii studies were eligible to enter a 2-year open-label extension, during which all patients received dutasteride 0.5 mg. safety was assessed, including adverse-event reporting, clinical laboratory assessments, yearly physical examinations, and vital sign assessments. in all, 2340 patients entered the open-label phase, 1188 of whom previously received dutasteride during the double-blind phase of the study. the most common drug-related adverse events (occurring in or 1) were effects on sexual function, which decreased with a longer duration of therapy. gynaecomastia was reported in a small percentage of men throughout the 4-year study period. the incidence of individual sexual functional adverse events that led to withdrawal was or 1 (0.3-1.0) during the 4-year study period. dutasteride had no relevant effects on vital signs or clinical laboratory variables.",these data show that dutasteride is well tolerated during long-term use for the treatment of symptomatic bph.,Treatment
do a comprehensive patents review on cannabinoid 1 receptor antagonists as antiobesity agents?,"obesity is a rapidly expanding worldwide health problem. various targets are investigated presently for the treatment of obesity, but there remains an unmet need for an effective drug therapy with acceptable efficacy levels and reduced side effects. targeting peripherally located cannabinoid 1 (cb1) receptors is an attractive strategy as these receptors play a vital role in energy homeostasis. cb1 receptor antagonists constitute one of the most important categories of compounds of interest for the control of obesity. in this review, the authors focus on recent advances (since 2007) in diverse chemical classes of patented compounds belonging to the category of cb1 receptor antagonists.","safer cb1 receptor antagonists for the treatment of obesity can be discovered by developing such compounds that act peripherally. increasing the polar service area, decreasing the lipophilicity and designing of neutral antagonists and allosteric inhibitors are some interesting strategies that could offer promising results.",Medication
does paretic upper-limb strength best explain arm activity in people with stroke?,"the purpose of this study was to determine the relationship among variables of upper-limb impairment, upper-limb performance in activities of daily living (activity), and engagement in life events and roles (participation) in people with chronic stroke. the subjects were 93 community-dwelling individuals with stroke ( or 1 year). this study, which was conducted in a tertiary rehabilitation center, used a cross-sectional design. the main measures of impairment were the modified ashworth scale, handheld dynamometry, sensory testing (monofilaments), and the brief pain inventory. the main measures of activity were the chedoke arm and hand activity inventory (cahai) and the motor activity log (mal). the main measure of participation was the reintegration to normal living (rnl) index. paretic upper-limb strength (force-generating capacity) (r.89, p.01), grip strength (r.69, p.01), and tone (resistance to passive movement) (r-.80, p.01) were the impairment variables that were most strongly related to activity. tone (r-.23, p.05) and cahai scores (r.22, p.05) had a significant, but weak, relationship to participation. upper-limb strength accounted for 87 of the variance of the cahai scores and 78 of the variance of the mal scores. in the participation models, tone and cahai scores accounted for 5 of the variance of the rnl index scores.","paretic upper-limb strength had the strongest relationship with variables of activity and best explained upper-limb performance in activities of daily living. grip strength, tone, and sensation also were factors of upper-limb performance in activities of daily living. increased tone and upper-limb performance in activities of daily living had a weak relationship with participation.",Treatment
is circulating haptoglobin an independent prognostic factor in the sera of patients with epithelial ovarian cancer?,"this study was conducted to evaluate the prognostic significance of haptoglobin levels in the overall survival of patients presenting with various stages of epithelial ovarian cancer. we employed an in-house sandwich enzyme-linked immunosorbent assay method to determine the concentrations of preoperative haptoglobin and c-reactive protein (crp) in sera samples obtained from 66 malignant tumors, 60 benign tumors, and 10 normal healthy women. levels of serum haptoglobin significantly correlated with tumor type (p .001) and international federation of gynecology and obstetrics stage (p .05). a significant correlation was observed between clinical stage and patient survival (r 5.99, p .026). our data also indicated that elevated serum haptoglobin levels were associated with poor outcome for overall survival using both univariate and multivariate analyses (p .048 and p .036 respectively). using pearson's correlation, we have noted that serum crp concentrations significantly correlated with haptoglobin levels (r(2) 0.22, p .001). immunohistochemical findings and western blot analyses were compatible with sera levels of haptoglobin in which a higher intensity of staining occurred in late-stage epithelial ovarian cancers.",this study provides evidence that preoperative serum levels of haptoglobin could serve as an independent prognostic factor in patients presenting with epithelial ovarian cancer.,Diagnosis
is frameless stereotactic aspiration and thrombolysis of deep intracerebral hemorrhage associated with reduction of hemorrhage volume and neurological improvement?,"this is a phase-2 safety trial to demonstrate the ability of frameless stereotactic aspiration and thrombolysis of ich to safely remove blood. patients with ich in the deep basal ganglia and internal capsule of 5 cc volume were consented to undergo computed tomographic imaging for frameless stereotactic guidance registration. using the frameless stereotactic (ct) guidance, a 4-mm diameter catheter was inserted into the body of the hematoma using a frontal burr hole approach. the catheter was aspirated and then flushed with saline and aspirated to remove unclotted blood. after a confirmatory ct scan to localize the catheter, 1 mg of recombinant tissue plasminogen activator (t-pa) was infused into the clot, permitted to bathe the clot for 30 minutes, and then drained into a closed circuit collection system. t-pa was infused every 8 hours for 48 hours. a follow up ct scan was obtained at 48 hours. 28 patients with ich (mean age 67.1) were admitted and underwent the procedure. mean initial ich volume was 54.6 cc /-6 37.8. mean time from onset to aspiration was 44 hours (range 7-180). mean initial nih stroke scale (nihss) score was 24 (range 15-33). compared with initial ct scan, there was a mean reduction of ich volume by 77 /-6 13 on final ct scan (p 0.0002). compared with initial nihss, the discharge mean nihss (16 /- 6) was significantly improved (p 0.001). there were no infectious, hemodynamic or neurologic complications. there were no episodes of symptomatic hemorrhagic enlargement and one case of asymptomatic bleeding along the catheter tract.","frameless stereotactic aspiration and thrombolysis (fast) of deep spontaneous intracerebral hemorrhage is a safe therapy that is associated with reduction in ich volume, early improvement in nihss and potentially could be used to improve outcome.",Diagnosis
do foxp3 regulatory t cells affect the development and progression of hepatocarcinogenesis?,"tumor-infiltrating lymphocytes represent the host immune response to cancer. cd4cd25foxp3 regulatory t cells (tregs) suppress the immune reaction. the aim of the present study was to investigate the clinicopathologic significance and roles of tregs and cd8 t cells during hepatocarcinogenesis. we examined the infiltration of foxp3 tregs and cd8 t cells in the tumor stroma and nontumorous liver parenchyma using 323 hepatic nodules including precursor lesions, early hepatocellular carcinoma (hcc), and advanced hcc, along with 39 intrahepatic cholangiocarcinomas and 59 metastatic liver adenocarcinomas. we did immunohistochemical comparative studies. the prevalence of tregs was significantly higher in hcc than in the nontumorous liver (p0.001). the patient group with a high prevalence of tregs infiltrating hcc showed a significantly lower survival rate (p0.007). multivariate analysis revealed that the prevalence of tregs infiltrating hcc was an independent prognostic factor. the prevalence of tregs increased in a stepwise manner (p0.001) and that of cd8 t cells decreased during the progression of hepatocarcinogenesis (p0.001). regardless of the presence of hepatitis virus infection or histopathologic evidence of hepatitis, the prevalence of tregs was significantly increased in nontumorous liver bearing primary hepatic tumors.",tregs play a role in controlling the immune response to hcc during the progression of hepatocarcinogenesis. it has been suggested that primary hepatic cancers develop in liver that is immunosuppressed by a marked infiltration of tregs. a high prevalence of tregs infiltrating hcc is thought to be an unfavorable prognostic indicator.,Diagnosis
does arabidopsis thaliana gyrb3 encode a dna gyrase subunit?,"dna topoisomerases are enzymes that control the topology of dna in all cells. dna gyrase is unique among the topoisomerases in that it is the only enzyme that can actively supercoil dna using the free energy of atp hydrolysis. until recently gyrase was thought to be unique to bacteria, but has now been discovered in plants. the genome of the model plant, arabidopsis thaliana, is predicted to encode four gyrase subunits: atgyra, atgyrb1, atgyrb2 and atgyrb3. we found, contrary to previous data, that atgyrb3 is not essential to the survival of a. thaliana. bioinformatic analysis suggests atgyrb3 is considerably shorter than other gyrase b subunits, lacking part of the atpase domain and other key motifs found in all type ii topoisomerases; but it does contain a putative dna-binding domain. partially purified atgyrb3 cannot bind e. coli gyra or support supercoiling. atgyrb3 cannot complement an e. coli gyrb temperature-sensitive strain, whereas atgyrb2 can. yeast two-hybrid analysis suggests that atgyrb3 cannot bind to atgyra or form a dimer.",these data strongly suggest that atgyrb3 is not a gyrase subunit but has another unknown function. one possibility is that it is a nuclear protein with a role in meiosis in pollen.,General
does soluble cd30 predict late acute rejection or safe tapering of immunosuppression in renal transplantation?,"previous reports revealed the potential value of the soluble cd30 level (scd30) as biomarker for the risk of acute rejection and graft failure after renal transplantation, here we examined its use for the prediction of safe tapering of calcineurin inhibitors as well as late acute rejection. in a cohort of renal transplant patients receiving triple immunosuppressive therapy we examined whether scd30 can be used as a marker for safe (rejection-free) discontinuation of tacrolimus at six months after transplantation (tds cohort: 24 rejectors and 44 non-rejecting controls). also, in a second cohort of patients (n22, rejectors n11 and non-rejectors n11), participating in a clinical trial of rituximab as induction therapy after renal transplantation (rits cohort), we examined whether scd30 could predict the occurrence of late (3months post-transplant) acute rejection episodes. scd30 was measured by elisa in serum taken before and at several time points after transplantation. overall, in the tds cohort scd30 decreased after transplantation. no difference in scd30 was observed between rejectors and non-rejecting controls at any of the time points measured. in addition, in the rits cohort, scd30 measured at three months after transplantation were not indicative for the occurrence of late acute rejection.",in two prospectively followed cohorts of renal transplant patients we found no association between scd30 and the occurrence of either late acute rejection or acute rejection after reduction of immunosuppression.,Treatment
is breastfeeding associated with a maternal feeding style low in control from birth?,"the influence of maternal child-feeding style upon child weight and eating style for children over the age of twelve months is well established. however there is little empirical evidence examining maternal child-feeding style during milk feeding despite evidence that mothers who breastfeed exert lower levels of control over later diet. the aim of this paper was to examine variation in maternal child-feeding style during the first six months postpartum and to explore associations with mode of milk feeding and infant weight. the child feeding questionnaire (cfq) is frequently used to measure maternal child-feeding style in preschool children. 390 mothers with an infant aged 0-6 months completed an adapted version of the cfq to measure maternal child-feeding style during milk feeding. participants reported breastfeeding duration, infant weight and perceived size. principle components analysis of questionnaire items produced six factors; encouraging feeding, feeding to a routine, limiting intake, concern for weight, monitoring and perceived responsibility. breastfeeding was associated with lower levels of control compared to formula feeding. infant birth weight was significantly inversely associated with concern for weight, monitoring and encouraging feeding.","formula feeding is associated with greater maternal control of child-feeding from birth whilst a lower birth weight is linked to concerns for infant weight and pressure to eat. as early maternal child-feeding relationships may impact negatively upon longer term child weight and eating style, identifying variations in maternal feeding style and understanding the factors that influence this is pertinent.",Prevention
does amantadine ameliorate dopamine-releasing deficits and behavioral deficits in rats after fluid percussion injury?,"to investigate the role of dopamine in cognitive and motor learning skill deficits after a traumatic brain injury (tbi), we investigated dopamine release and behavioral changes at a series of time points after fluid percussion injury, and explored the potential of amantadine hydrochloride as a chronic treatment to provide behavioral recovery. in this study, we sequentially investigated dopamine release at the striatum and behavioral changes at 1, 2, 4, 6, and 8 weeks after fluid percussion injury. rats subjected to 6-pa cerebral cortical fluid percussion injury were treated by using subcutaneous infusion pumps filled with either saline (sham group) or amantadine hydrochloride, with a releasing rate of 3.6 mg/kg/hour for 8 weeks. the dopamine-releasing conditions and metabolism were analyzed sequentially by fast scan cyclic voltammetry (fscv) and high-pressure liquid chromatography (hplc). novel object recognition (nor) and fixed-speed rotarod (fsrr) behavioral tests were used to determine treatment effects on cognitive and motor deficits after injury. sequential dopamine-release deficits were revealed in 6-pa-fluid-percussion cerebral cortical injured animals. the reuptake rate (tau value) of dopamine in injured animals was prolonged, but the tau value became close to the value for the control group after amantadine therapy. cognitive and motor learning impairments were shown evidenced by the nor and fsrr behavioral tests after injury. chronic amantadine therapy reversed dopamine-release deficits, and behavioral impairment after fluid percussion injuries were ameliorated in the rats treated by using amantadine-pumping infusion.",chronic treatment with amantadine hydrochloride can ameliorate dopamine-release deficits as well as cognitive and motor deficits caused by cerebral fluid-percussion injury.,Treatment
is body fat associated with blood pressure in school-aged girls with low cardiorespiratory fitness : the european youth heart study?,"to examine the association between anthropometric measurements of total and central adiposity and blood pressure in school-aged children, and to study whether these associations are modified by the levels of cardiorespiratory fitness. systolic and diastolic blood pressure, weight, height, skinfold thickness and waist circumference were measured in 873 children aged 9-10 years participating in the estonian and swedish part of the european youth heart study. mean arterial pressure was calculated. body mass index and skinfold thickness were used as markers of total adiposity, whereas waist circumference and waist-height ratio were used as markers of central adiposity. cardiorespiratory fitness was estimated by a maximal ergometer bike test, and dichotomized into low and high levels. markers of total and central adiposity were positively associated with blood pressure. the results from the regression models showed that the markers of total and central adiposity were significantly associated with systolic blood pressure in girls with low levels of cardiorespiratory fitness. similar results were observed when mean arterial pressure was the outcome variable. none of the markers of total and central adiposity were significantly associated with blood pressure in girls with high levels of cardiorespiratory fitness or in boys with low or high levels of cardiorespiratory fitness.","the results show a positive influence of simple anthropometric measurements of total and central adiposity on blood pressure, and suggest that higher cardiorespiratory fitness may attenuate the association between body fat and blood pressure in school-aged children.",Diagnosis
is low hdl-c level associated with the development of intracranial artery stenosis : analysis from the chinese intracranial atherosclerosis ( cicas ) study?,"intracranial atherosclerotic stenosis (icas) is an important cause of ischemic stroke worldwide. the role of high-density lipoprotein cholesterol (hdl-c) or low-density lipoprotein cholesterol (ldl-c) in the development of icas remains to be elucidated. in the current study, we investigated the relationship of hdl-c level and the risk of developing icas in chinese patients with acute ischemic stroke. from october 2007 to june 2009, a total of 1,984 consecutive ischemic stroke patients were evaluated for the presence of symptomatic icas by magnetic resonance angiography (mra). patients were classified into two groups: intracranial steno-occlusion (icas group, n 888) and non-intracranial stenosis (nicas group, n 1096). serum lipid profiles were analyzed and compared between the icas and nicas group. significantly more patients in icas group had low hdl-c level (51.6) than in the nicas group (42.9, p0.001). the observed association remained significant after adjustment for conventional risk factors (adjusted or 1.36; 95ci (1.13-1.63). such predictive value of low level hdl-c persisted even when ldl-c was at very low level(1.8 mmol/l). patients in the lowest serum hdl-c quartile (0.96 mmol/l) had the highest risk of developing icas adjusted or 1.52; 95ci (1.17-1.98) compared to patients in the highest serum hdl-c quartile ( 1.32 mmol/l) after adjustments for the covariates.",low hdl-c level is strongly associated with the development of icas. there was an inverse relationship between the level of hdl-c and the risk of developing icas.,Prevention
do histopathological features predict metastatic potential in locally advanced colon carcinomas?,"metastatic dissemination can exist before a pathologically and clinically detectable manifestation. the structural heterogeneity of colon cancer (cc) in histological sections with respect to the morphology of tumor aggressiveness and composition of the tumor microenvironment raises the question of whether the microscopical tumor architecture enables a discrimination of groups with different metastatic potential. this would result in an assessment of the prognosis and provision of an ancillary tool for the therapeutic management after surgery, beside the estimation of the local tumor extent. in order to identify predictive biomarkers for metastasis of locally advanced cc, which can easily be integrated into the pathologist's daily routine diagnostic activity, we determined tumor budding, peritumoral inflammation, extent of desmoplasia and necrosis, density of macro- and microvascular blood vessels and functional state of lymphatics in the tumor center, invasive margin and tumor-free surrounding tissue in 86 non-metastatic, lymphogenous-metastatic and haematogenous-metastatic, subserosa-invasive cc. features influencing nodal metastasis in the univariate analysis included high tumor budding (p 0.004), high large vessel density in the subserosa (p 0.043), abundant desmoplasia (p 0.049), non-finger-like desmoplastic pattern (p 0.051) and absent lymphocellular intratumoral inflammation (p 0.084). in the multivariate analysis, with the exception of large vessel density, these pathomorphological features were independent risk factors for lymphogenous metastasis (p 0.023, p 0.017, p 0.037, p 0.012, respectively) with a good discrimination ability (auc of 0.853). features associated with distant metastasis in the univariate analysis included high tumor budding (p 0.002), low intratumoral small vessel density (p 0.013), absent lymphocellular intratumoral inflammation (p 0.048) and abundant necrosis (p 0.073). in the multivariate analysis only tumor budding was an independent predictor for haematogenous metastasis (p 0.007) with a good discrimination ability (auc of 0.829).","thus, mainly tumor budding but also the described structural characteristics of the peritumoral tissue appears to reflect the metastatic potential of locally advanced cc and therefore should be stated in pathological reports.",Treatment
does muscle pain differentially modulate short interval intracortical inhibition and intracortical facilitation in primary motor cortex?,"excitability of the motor cortex can be suppressed during muscle pain. yet the mechanisms are largely unknown. short interval intracortical inhibition (sici) and intracortical facilitation (icf) were examined as possible candidate mechanisms to underpin this change. sici and icf were investigated in 11 healthy individuals before, during and after infusion of hypertonic saline into right first dorsal interosseous (fdi). using paired-pulse transcranial magnetic stimulation (tms), interstimulus intervals of 2, 3, and 13 ms were investigated. pain intensity and quality were recorded using a 10-cm visual analogue scale and the mcgill pain questionnaire. resting motor threshold and motor-evoked potentials (meps) to single tms stimuli were recorded before and after pain. electromyographic recordings were made from right fdi and abductor digiti minimi. participants reported an average pain intensity of 5.8 (1.6) cm. mep amplitudes decreased in both muscles. compared with the pre-pain condition, sici was increased following pain, but not during. icf was decreased both during and after pain when compared with the pre-pain condition. these findings suggest that muscle pain differentially modulates sici and icf. although the functional relevance is unknown, we hypothesize decreased facilitation and increased inhibition may contribute to the restriction of movement of a painful body part.",this article provides evidence for decreased intracortical facilitation and increased short interval intracortical inhibition in response to muscle pain. this finding is relevant to clinicians as a mechanism which may underlie restricted movement in acute and chronic pain.,Diagnosis
does treatment with ephrin b2 positively impact the abnormal metabolism of human osteoarthritic chondrocytes?,"members of the ephrin system, the ephrin receptor erythropoietin-producing hepatocellular b4 (ephb4) and its specific ligand, ephrin b2, appear to be involved in the bone remodelling process. we recently showed that their interaction inhibits the resorptive activity of human osteoarthritic (oa) subchondral bone osteoblasts. hence, we further investigated the possible implication of these ephrin members on the catabolic/anabolic activities of human oa chondrocytes. ephb4 receptor and ephrin b2 levels were determined by quantitative pcr and immunohistochemistry, and the effects of ephrin b2 on the expression/production of factors involved in the oa process. ephb4 receptors and ephrin b2 ligands are expressed and produced by human normal and oa chondrocytes. ephrin b2 protein was found at similar levels in both cartilage types, whereas ephb4 receptor expression (p 0.0001) and production (p 0.01) levels were significantly increased in oa chondrocytes/cartilage. ephrin b2 treatment significantly inhibited the interleukin (il)-1beta, il-6, matrix metalloproteinase-1 (mmp-1), mmp-9, mmp-13, and proteinase-activated receptor-2 (par-2) gene expression levels, whereas mmp-2 was unaffected, and significantly increased collagen type ii, a cartilage specific macromolecule. it also inhibited the il-1beta stimulated protein production of il-6, mmp-1 and mmp-13.",our study is the first to provide data on the presence and role of ephrin b2/ephb4 receptors in human chondrocytes/cartilage. data showed that ephrin b2 treatment positively impacts the abnormal metabolism of oa cartilage by inhibiting important catabolic factors involved in this disease at the same time as increasing anabolic activity.,Treatment
is increased risk of non-q wave myocardial infarction after directional atherectomy platelet dependent : evidence from the epic trial . evaluation of c7e3 for the prevention of ischemic complications?,"we sought to determine the effects of platelet glycoprotein iib/iiia receptor blockade on adverse outcomes, especially non-q wave myocardial infarction, in patients undergoing directional atherectomy in the evaluation of c7e3 for the prevention of ischemic complications (epic) trial. randomized trials comparing directional atherectomy with percutaneous transluminal coronary angioplasty (ptca) have demonstrated modest benefits favoring atherectomy but at a cost of increased acute ischemic complications, notably non-q wave myocardial infarction. the mechanism for this excess risk is unknown. of 2,038 high risk patients undergoing coronary intervention in the epic trial, directional atherectomy was performed in 197 (10). patients randomly received the chimeric glycoprotein iib/iiia antibody 7e3 (c7e3), as a bolus or a bolus and 12-h infusion or placebo. study end points included death, myocardial infarction, repeat intervention or bypass surgery. patients undergoing directional atherectomy had a lower baseline risk for acute complications but had a higher incidence of any myocardial infarction (10.7 vs. 6.3, p 0.021) and non-q wave myocardial infarction (9.6 vs. 4.9, p 0.006). bolus and infusion of c7e3 reduced non-q wave myocardial infarctions by 71 after atherectomy (15.4 for placebo vs. 4.5 for bolus and infusion, p 0.046). non-q wave myocardial infarction rates after ptca were not affected by c7e3, although q wave myocardial infarctions were reduced from 2.6 to 0.8 (p 0.017).",the epic trial confirmed the increased risk of non-q wave myocardial infarction with directional atherectomy use compared with ptca. a bolus and 12-h infusion of the glycoprotein iib/iiia receptor inhibitor c7e3 abolished this excess risk. directional atherectomy-related non-q wave myocardial infarction appears to be platelet aggregation dependent.,Prevention
is mapping a prerequisite for elimination of filariasis and effective targeting of filarial 'hot spots '?,"this study was undertaken to determine the prevalence of filarial infection in the districts of madhya pradesh, which were classified as non-endemic by the national program for control of filariasis. these districts showed evidence of clinical symptoms related to filariasis. to confirm the presence of filariasis, night blood surveys and entomological surveys were carried out to detect microfilaria in humans and filarial infection in vectors. for microfilaria surveys, thick blood smears were prepared by taking 60 l of blood between 8.00 and 11.00 pm and examined under a microscope. vectors culex quinquefasciatus were dissected for the filarial infection from the affected villages of four non-endemic districts. prevalence of microfilaria in the four districts ranged from 3.8 in district shivpuri to 11.2 in district bhind (overall mf rate 6.9, 95 ci 6.2-7.7). infection and infectivity rates among vectors were recorded from three districts which varied from 2 to 13 and from 1.3 to 3.6.","the study confirmed the presence of circulating microfilaria in non-endemic population of four districts, which has significant public health implications. to assess filarial endemicity and hot spots, precise filarial risk mapping using new efficient diagnostic tools is needed to reinforce and extend the strategy in other areas to achieve elimination of lymphatic filariasis.",Symptoms
do filomicelles from aromatic diblock copolymers increase paclitaxel-induced tumor cell death and aneuploidy compared with aliphatic copolymers?,"in order to improve the delivery of aromatic drugs by micellar assemblies, and particularly by long and flexible filomicelles, aromatic groups were integrated into the hydrophobic block of a degradable diblock copolymer. aromatic filomicelles were formed by self-directed assembly of amphiphilic diblock copolymer peg-pbcl with suitable block ratios. worm-like filomicelles with an aromatic core were loaded with a common chemotherapeutic, paclitaxel, for tests of release as well as effects on cancer cell lines in vitro and in vivo. aromatic filomicelles loaded more paclitaxel than analogous aliphatic systems. cell death and aneuploidy of surviving cells (which indicates toxicity) were highest for carcinoma lines treated in vitro with the new filomicelles. initial tests in vivo also suggest more potent tumor shrinkage.","flexible filomicelles with an aromatic core form an efficient drug delivery system that leads to higher cell death than previously reported systems, while inducing aneuploidy in surviving cells.",Medication
does polyethylene glycol-superoxide dismutase inhibit lipid peroxidation in hepatic ischemia/reperfusion injury?,"hepatic injury after ischemia/reperfusion is attributed to the development of oxygen free radical (ofr)-mediated lipid peroxidation--a process that can be measured through its byproducts, specifically malondialdehyde. the use of free radical scavengers can offer significant protection against ofr-induced liver injury. we hypothesize that a new potent ofr scavenger, polyethylene glycol-superoxide dismutase (peg-sod), can inhibit ofr-mediated lipid peroxidation in hepatic ischemia/reperfusion injury. twelve male sprague-dawley rats (300-350 g) were subjected to occlusion of the left and middle hepatic arteries and portal veins for 90 min, followed by 120 min reperfusion. peg-sod (5000 units/kg) was given intravenously before vascular occlusion and again immediately upon reperfusion to six rats. normal saline was given to the remaining six rats to be used as a control group. the right hepatic lobe (used as internal control) and left hepatic lobe were harvested separately and tissue malondialdehyde was measured. a marked increase in lipid peroxide was found in the normal saline group after 2 h reperfusion. treatment with peg-sod prevented the rise in tissue malondialdehyde. the mean difference in the malondialdehyde between the left and right hepatic lobes were 13.20 /- 6.35 and 1.70 /- 3.65 nmol/g in the normal saline (control) and peg-sod groups, respectively. this difference was found to be statistically significant (p 0.005) using student's t-test.",peg-sod can effectively attenuate hepatic ischemia/reperfusion injury by inhibiting ofr-mediated lipid peroxidation.,Medication
is colon capsule endoscopy a safe and useful tool to assess disease parameters in patients with ulcerative colitis?,"colon capsule endoscopy (cce) is a new endoscopic technique that is minimally invasive and allows evaluation of the colon mucosa without pain, sedation, and gas insufflation. to date, few studies have investigated the use of cce in patients with ulcerative colitis (uc). this study compares the ability of cce and a conventional colonoscopy to assess mucosal disease activity and the extent of inflammatory mucosa in patients with uc. forty-two patients (27 men, mean age 48.5 years) with known uc and indication for colonoscopy were enrolled in this single-blind, prospective study. all patients underwent cce, followed by a colonoscopy. the activity and extent of the disease was assessed using mayo scores and montreal scores, respectively. there was a good correlation between cce and colonoscopy in disease severity (0.79; 95 confidence interval: 0.62-0.96) and extent of inflammation (0.71; 95 confidence interval: 0.52-0.90) observed. the ability of cce to assess a broad segment of distal ileum led to a change in the diagnosis of uc to ileocolonic crohn's disease in three patients. bowel preparation was considered adequate in 80 of the patients and no serious adverse events related to the cce procedure or bowel preparation were reported.","cce is a safe and useful method for the evaluation of patients with uc. the ability of cce to assess distal ileum provides an advantage to colonoscopy as cce can identify patients who have been incorrectly diagnosed with uc, resulting in a change in their diagnosis to crohn's disease.",Medication
are pathogenic aquaporin-4 reactive t cells sufficient to induce mouse model of neuromyelitis optica?,"neuromyelitis optica (nmo) is an autoimmune disease primarily targeting the spinal cord and optic nerve leading to paralysis and blindness. the discovery of an antibody against the astrocytic water channel, aquaporin-4 (aqp4), in the majority of patients, has led to the presumption that the antibody was necessary for disease pathogenesis. the potential role of t cells in the central nervous system, however, has not been thoroughly examined. we generated an anti-aqp4 antibody seronegative model of nmo using pathogenic aqp4-reactive t cells in mice by immunizing aqp4 null mice with peptides corresponding to the second extracellular loop of aqp4, loop c. when polarized to a th17 phenotype and transferred to wild-type mice, these cells caused tail and limb weakness. histology showed demyelination and t cell infiltration in the spinal cord, optic nerve and brain. animals receiving cells re-stimulated in culture with non-specific proteins resulted in no behavioral disease, indicating that specific targeting of aqp4 is essential for this phenotype.","in summary, we show that aqp4-reactive t cells are sufficient to trigger an nmo-like disease in mice, independent of antibodies, indicating that pathogenic aqp4-reactive t cells may play a similar role in humans.",Medication
does decursin enhance trail-induced apoptosis through oxidative stress mediated- endoplasmic reticulum stress signalling in non-small cell lung cancers?,"the tnf-related apoptosis-inducing ligand (trail) is a promising anticancer agent due to its remarkable ability to selectively kill tumour cells. however, because most tumours exhibit resistance to trail-induced apoptosis, the development of combination therapies to overcome resistance to trail is required for effective cancer therapy. cell viability and possible synergy between the plant pyranocoumarin decursin and trail was measured by mtt assay and calcusyn software. reactive oxygen species (ros) and apoptosis were measured using dichlorodihydrofluorescein and annexin/propidium iodide in cell flow cytometry. changes in protein levels were assessed with western blotting. combining decursin and trail markedly decreased cell viability and increased apoptosis in trail-resistant non-small-cell lung cancer (nsclc) cell lines. decursin induced expression of the death receptor 5 (dr5). inhibition of dr5 attenuated apoptotic cell death in decursin trail treated nsclc cell lines. interestingly, induction of dr5 and ccaat/enhancer-binding protein homologues protein by decursin was mediated through selective induction of the pancreatic endoplasmic reticulum kinase (perk)/activating transcription factor 4 (atf4) branch of the endoplasmic reticulum stress response pathway. furthermore, enhancement of perk/atf4 signalling by decursin was mediated by ros generation in nsclc cell lines, but not in normal human lung cells. decursin also markedly down-regulated expression of survivin and bcl-xl in trail-resistant nsclc cells.","ros generation by decursin selectively activated the perk/atf4 axis of the endoplasmic reticulum stress signalling pathway, leading to enhanced trail sensitivity in trail-resistant nsclc cell lines, partly via up-regulation of dr5.",Treatment
does nap1 strain type predict outcomes from clostridium difficile infection?,"studies are conflicting regarding the importance of the fluoroquinolone-resistant north american pulsed-field gel electrophoresis type 1 (nap1) strain in clostridium difficile infection (cdi) outcome. we describe strain types causing cdi and evaluate their association with patient outcomes. cdi cases were identified from population-based surveillance. multivariate regression models were used to evaluate the associations of strain type with severe disease (ileus, toxic megacolon, or pseudomembranous colitis within 5 days; or white blood cell count 15 000 cells/l within 1 day of positive test), severe outcome (intensive care unit admission after positive test, colectomy for c. difficile infection, or death within 30 days of positive test), and death within 14 days of positive test. strain typing results were available for 2057 cases. severe disease occurred in 363 (17.7) cases, severe outcome in 100 (4.9), and death within 14 days in 56 (2.7). the most common strain types were nap1 (28.4), nap4 (10.2), and nap11 (9.1). in unadjusted analysis, nap1 was associated with greater odds of severe disease than other strains. after controlling for patient risk factors, healthcare exposure, and antibiotic use, nap1 was associated with severe disease (adjusted odds ratio aor, 1.74; 95 confidence interval ci, 1.36-2.22), severe outcome (aor, 1.66; 95 ci, 1.09-2.54), and death within 14 days (aor, 2.12; 95 ci, 1.22-3.68).","nap1 was the most prevalent strain and a predictor of severe disease, severe outcome, and death. strategies to reduce nap1 prevalence, such as antibiotic stewardship to reduce fluoroquinolone use, might reduce cdi morbidity.",Medication
does parental origin of the x-chromosome influence growth hormone treatment effect in turner syndrome?,"the parental origin of the intact x-chromosome has been reported to affect phenotype and response to gh treatment in turner syndrome (ts). our objective was to evaluate the influence of the parental origin of the x-chromosome on body growth and gh treatment effect in ts. we conducted a population-based cohort study of ts patients previously treated with gh. participants included patients with a nonmosaic 45,x karyotype; 556 women were identified as eligible, 233 (49) of whom participated, together with their mothers. data were analyzed for 180 of these patients. we performed fluorescence in situ hybridization analysis to exclude mosaicism and microsatellite analysis of nine polymorphic markers in dna from the patients and their mothers. the influence on growth and effect of gh were analyzed by univariate and multivariate methods. the x-chromosome was of paternal origin (x(pat)) in 52 (29) of 180 and of maternal origin (x(mat)) in 128 (71) of 180 patients. height gain from the start of gh treatment to adult height was similar in x(mat) and x(pat) patients (2.1 0.9 vs. 2.2 0.8 ts sd score, p 0.45). the lack of influence of parental origin of the x-chromosome was confirmed in multivariate analysis. parental origin of the x-chromosome also had no effect on the other growth characteristics studied, including growth velocity during the first year on gh treatment. patient height was correlated with the heights of both parents and was not influenced by the parental origin of the x-chromosome.","in this, the largest such study carried out to date, the parental origin of the x-chromosome did not alter the effect of gh treatment or affect any other features of growth in ts.",Treatment
"is quaking , an rna-binding protein , a critical regulator of vascular smooth muscle cell phenotype?","rna-binding proteins are critical post-transcriptional regulators of rna and can influence pre-mrna splicing, rna localization, and stability. the rna-binding protein quaking (qki) is essential for embryonic blood vessel development. however, the role of qki in the adult vasculature, and in particular in vascular smooth muscle cells (vsmcs), is currently unknown. we sought to determine the role of qki in regulating adult vsmc function and plasticity. we identified that qki is highly expressed by neointimal vsmcs of human coronary restenotic lesions, but not in healthy vessels. in a mouse model of vascular injury, we observed reduced neointima hyperplasia in quaking viable mice, which have decreased qki expression. concordantly, abrogation of qki attenuated fibroproliferative properties of vsmcs, while potently inducing contractile apparatus protein expression, rendering noncontractile vsmcs with the capacity to contract. we identified that qki localizes to the spliceosome, where it interacts with the myocardin pre-mrna and regulates the splicing of alternative exon 2a. this post-transcriptional event impacts the myocdv3/myocdv1 mrna balance and can be modulated by mutating the quaking response element in exon 2a of myocardin. furthermore, we identified that arterial damage triggers myocardin alternative splicing and is tightly coupled with changes in the expression levels of distinct qki isoforms.","we propose that qki is a central regulator of vsmc phenotypic plasticity and that intervention in qki activity can ameliorate pathogenic, fibroproliferative responses to vascular injury.",General
does effect of diltiazem on lid tension during light-flash-induced eye blink in the rabbit?,"the purpose of this study was to examine the effect of the ca blocker diltiazem in combination with the ca chelator egta (ethyleneglycol-bis-ta-amino-ethyl ethern,n'-tetraacetic acid) on eyelid tension generated during the light-induced eyeblink reflex in the adult rabbit. the goal is to develop nontoxic, nonsurgical therapies for blepharospasm. blinks were triggered in the alert rabbit, and tension was measured with a strain gauge attached to the eyelid. strain gauge output was amplified, digitized, and stored on computer for later analysis. experiments consisted of a set of trials in which identical light stimuli were delivered at 0.1 hz for 5 min. in control trials, blink tensions decreased dramatically for the first seven to nine blinks and then levelled off, indicating that with respect to muscle tension output, blinks contained both rapidly habituating and nonhabituating components. after diltiazem and egta were injected in the lid, blinks were reduced 30 to 90 over those in control trials. reductions could not be explained by injection trauma or irritation due to fluid volume, because injections of saline alone did not produce such tension depression.",diltiazem-egta produces a transient reduction in blink tension. a clinical application will depend on developing methods for the sustained release of these drugs in the eyelid.,Medication
does mitochondrial dna 4977bp deletion mutation in peripheral blood reflect atrial remodeling in patients with non-valvular atrial fibrillation?,"recently, mitochondrial dna 4977bp deletion (mtdna4977-mut), a somatic mutation related to oxidative stress, has been shown to be associated with atrial fibrillation (af). we hypothesized that patient age, as well as electroanatomical characteristics of fibrillating left atrial (la), vary depending on the presence of mtdna4977-mut in peripheral blood among patients with non-valvular af. analyzing clinical and electroanatomical characteristics, we investigated the presence of the mtdna4977-mut in peripheral blood of 212 patients (51.113.2 years old, 83.5 male) undergoing catheter ablation for non-valvular af, as well as 212 age-matched control subjects. the overall frequency of peripheral blood mtdna4977-mut in patients with af and controls was not significantly different (24.5 vs. 19.3, p0.197). when the af patient group was stratified according to age, mtdna4977-mut was more common (47.4 vs. 20.0, p0.019) in af patients older than 65 years than their age-matched controls. among af patients, those with mtdna4977-mut were older (58.111.9 years old vs. 48.811.9 years old, p0.001). af patients positive for the mtdna mutation had greater la dimension (p0.014), higher mitral inflow peak velocity (e)/diastolic mitral annular velocity (em) ratio (p0.001), as well as lower endocardial voltage (p0.035), and slower conduction velocity (p0.048) in the posterior la than those without the mutation. in multivariate analysis, e/em ratio was found to be significantly associated with the presence of mtdna4977-mut in peripheral blood.","mtdna4977-mut, an age-related somatic mutation detected in the peripheral blood, is associated with advanced age and electro-anatomical remodeling of the atrium in non-valvular af.",Treatment
is heart transplant systolic and diastolic function impaired by prolonged pretransplant graft ischaemic time and high donor age : an echocardiographic study?,"due to the need for suitable donors for heart transplantation (htx), older grafts and grafts with prolonged graft ischaemic time (git) are accepted. the impact of git and donor age on post-transplant cardiac function has not been examined with either newer echocardiographic techniques (tissue doppler imaging, tdi) or cardiopulmonary exercise testing (cpet). thus, we studied the influence of git and donor age on post-transplant cardiac function and exercise capacity. fifty-two stable recipients underwent echocardiography with colour tdi and cpet at a median of 4 years after htx. left ventricular (lv) systolic (s') and early diastolic (e') mitral annular velocities, right ventricular (rv) s', rve' as well as lv ejection fraction (ef) and vo(2peak) were analysed. htx recipients with git median value (200 min) had significantly lower septal lvs' (15, p 0.005), lvef (9, p 0.015), rvs' (21, p 0.007), septal lve' (22, p 0.001) and rve' velocities (23, p 0.011), and slightly lower vo(2peak) (p 0.098). recipients with grafts from donor median age (37 years) had significantly lower lve' velocities (septal lve' p 0.047 and lateral lve' p 0.010), but not lv systolic or rv parameters.","prolonged git impairs both systolic and diastolic function at the interventricular septum and rv free wall, while increasing donor age impairs lv diastolic function. the duration of graft ischaemia and donor age should be taken into account when evaluating for cardiac dysfunction in htx recipients.",Treatment
does comparison of injuries in sow housed in gestation stalls versus group pens with electronic sow feeders?,"to compare the location and severity of injuries in pregnant sows housed in individual gestation stalls with that in pregnant sows housed in dynamic groups in pens with electronic sow feeders. prospective study. 100 pregnant sows of parity 1 to 3 and various body weights. fifty sows each were randomly allotted to gestation stalls or group pens with electronic sow feeders. injuries were scored on the basis of location, number, and depth of wounds. injury scores for sows in both housing systems were compared during a period of 90 days. the influence of factors such as duration of stay in the housing system, parity, and body weight on sow injuries was also examined. injury scores were higher in group pens with electronic sow feeders. as body weight increased, injury scores decreased for sows housed in group pens with electronic sow feeders and increased for sows housed in gestation stalls. there was a significant negative association between second parity and total injury scores.",modifications in housing system design and management procedures are needed to reduce injuries in pregnant sows.,General
is the apob/apoa-i ratio better than the cholesterol ratios to estimate the balance between plasma proatherogenic and antiatherogenic lipoproteins and to predict coronary risk?,"the apolipoprotein b (apob)/apoa-i ratio represents the balance of proatherogenic and antiatherogenic lipoproteins. the purpose of this study was to determine whether the apob/apoa-i ratio was superior to any of the cholesterol ratios - total cholesterol/high-density lipoprotein cholesterol (tc/hdl-c), low-density lipoprotein cholesterol (ldl-c)/hdl-c and non-hdl-c/hdl-c - in predicting the risk of coronary disease. moreover, we examined whether any lipids, lipoproteins or cholesterol ratios add significant predictive information beyond that provided by the apob/apoa-i ratio. plasma lipids, lipoproteins, apob, and apoa-i were measured in 69,030 men and 57,168 women above 40 years of age. after a mean follow-up of 98 months, 1183 men and 560 women had died from a myocardial infarction in this prospective apolipoprotein-related mortality risk (amoris) study. high apob and a high apob/apoa-i ratio were strongly related to increased coronary risk, while high apoa-i was inversely related to risk. the apob/apoa-i ratio was superior to any of the cholesterol ratios in predicting risk. this advantage was most pronounced in subjects with ldl-c levels 3.6 mmol/l. addition of lipids, lipoproteins or any cholesterol ratio to apob/apoa-i in risk models did not further improve the strong predictive value of apob/apoa-i.","these results indicate that the apob/apoa-i ratio is at present the best single lipoprotein-related variable to quantitate coronary risk. given the additional advantages apolipoproteins possess - fasting samples are not required, apob/apoa-i is a better index of the adequacy of statin therapy than ldl-c, and the measurement of apob and apoa-i are standardized, whereas ldl-c and hdl-c are not - there would appear to be considerable advantage to integrating apolipoproteins into clinical practice.",General
do il-18 and il-12 induce intestinal inflammation and fatty liver in mice in an ifn-gamma dependent manner?,"in murine models of inflammatory bowel disease, colonic inflammation is considered to be caused by an aberrant th1-type immune response. to investigate if systemic administration of interleukin (il)-12 and il-18 to wild-type balb/c mice induces liver injury and intestinal inflammation, and if pathological changes are observed, what cytokines are involved. mice (balb/c-wild-type (wt), mrl-lpr/lpr, balb/c-interferon gamma knock out (ifn-gamma ko), c57bl/6-inducible nitric oxide synthase (inos) ko, and balb/c tumour necrosis factor alpha (tnf-alpha) ko) were injected intraperitoneally each day with il-12 (20 ng/g/mouse) and/or il-18 (200 ng/g/mouse). administration of il-12 and il-18 to balb/c-wt mice induced prominent intestinal mucosal inflammation and fatty liver, leading to piloerection, bloody diarrhoea, and weight loss. il-12 and il-18 induced striking elevations in serum levels of ifn-gamma that caused no production, although increased no had no exacerbating effect on mice. moreover, inos ko mice, or mrl lpr/lpr mice lacking functional fas were equally susceptible to il-12 and il-18. administration of il-12 and il-18 did not induce tnf-alpha production in wild-type mice, and the same treatment to tnf-alpha ko mice induced intestinal mucosal inflammation. furthermore, they had diffuse and dense infiltration of small fat droplets in their hepatocytes associated with an increase in serum levels of liver enzymes. in contrast, the same treatment in ifn-gamma ko balb/c mice and inos ko mice did not induce these changes.","our study strongly indicates that il-18 together with il-12 induces intestinal mucosal inflammation in an ifn-gamma dependent but tnf-alpha, no, and fas ligand independent manner, and fatty liver is dependent on ifn-gamma and no.",Medication
does elevated serum parathyroid hormone predict impaired survival prognosis in a general aged population?,"short-term studies on selected patients have indicated that elevated serum parathyroid hormone (pth) is an independent risk factor of death. however, long-term data on unselected populations are lacking, thus far. in order to evaluate the predictive value of elevated serum pth during the last years of life, random persons of age cohorts of 75, 80 and 85 years were followed for 17 years. a prospective cohort study. subjects (n567) were investigated for calcaemic status including serum intact pth, serum total calcium (cat) and ionized calcium (ca(2)). thorough clinical examinations included an assessment of co-morbidity. mortality data were collected from national census records. up to 93 of the subjects died within the follow-up. in contrast to ca(2) levels, high serum pth ( or 63 ng/l, iv quartile cut point) was associated with significant over-mortality (hr1.56, 95 ci: 1.29-1.88) and a 2.3-year reduction of median life expectancy. after controlling for age, gender, co-morbidity and creatinine, the prognostic impact of elevated serum pth was still significant (hr1.24, 95 ci: 1.01-1.53). the tendency for over-mortality was consistent in both genders, in all age groups as well as in subjects with varying co-morbidity, renal function, body mass index categories and ca(2) levels.","elevated serum pth level is an independent predictor of impaired long-term survival prognosis in unselected aged population. serum ca(2) did not emerge as a significant prognostic indicator. the long-term prognostic impact of vitamin d deficiency, the most common cause of elevated pth levels in the elderly, remains to be investigated.",Diagnosis
is pathological 99mtc-sestamibi myocardial perfusion scintigraphy independently associated with emerging cardiac events in elderly patients with known or suspected coronary artery disease?,"only few data are available regarding the prognostic impact of myocardial perfusion scintigraphy with (99m)tc-sestamibi (mps) regarding emerging cardiac events in elderly patients to evaluate the prognostic value of mps regarding emerging cardiac events in patients aged 70 years with known or suspected coronary artery disease (cad). one hundred and thirty-three patients (74.6 3.7 years) who underwent exercise or pharmacological stress/rest mps were included in this analysis. semi-quantitative visual interpretation of mps images was performed and summed-stress- (sss), summed-difference- (sds), and summed-rest scores (srs) were calculated. multivariate logistic regression analyses were calculated for evaluation of the independent prognostic impact of mps results and several cardiac-related patient characteristics with regard to emerging cardiac events. kaplan-meier survival- and log rank analyses were calculated for assessment of cardiac event-free survival. pathological sss (or: 3.3), angina (or: 2.7) and ischemic ecg (or: 3.0) were independently associated with cardiac events. patients with pathological sss (p0.005) and ischemic ecg (p0.012) had a significantly lower incidence of cardiac event-free survival.",pathological mps is independently associated with emerging cardiac events predicting a significantly lower incidence of cardiac event-free survival in patients aged 70 years.,Diagnosis
does inhibition of calcium-independent phospholipase a impair agonist-induced calcium entry in keratinocytes?,"in many cells, depletion of intracellular calcium (ca2) reservoirs triggers ca2 entry through store-operated ca2 channels in the plasma membrane. however, the mechanisms of agonist-induced calcium entry (ace) in keratinocytes are not fully understood. this study was designed to determine if pharmacological inhibition of calcium-independent phospholipase a (ipla(2)) impairs ace in normal human epidermal keratinocytes. confocal laser scanning microscopy was used to monitor the dynamics of ca2 signalling in keratinocytes loaded with the calcium-sensitive dye fluo-4. cells were stimulated with extracellular nucleotides adenosine triphosphate (atp) or uridine triphosphate (utp) or with lysophosphatidic acid (lpa), a bioactive lipid that regulates keratinocyte proliferation and differentiation. both atp and utp induced ca2 release in primary human keratinocytes. this was not followed by robust ca2 influx when the experiments were performed in low ca2 (70 micromol l(-1)) medium. upon elevation of extracellular ca2 to 1.2 mmol l(-1), however, a biphasic response consisting of an initial ca2 peak followed by an elevated plateau was observed. the plateau phase was inhibited when cells were treated with bromoenol lactone, a specific pharmacological inhibitor of ipla(2). these findings indicate that ipla(2) activity is required for ace in keratinocytes. lpa also evoked ca2 release in keratinocytes but failed to induce sustained ca2 entry even when extracellular ca2 was elevated to 1.2 mmol l(-1).",our results demonstrate for the first time an important role for ipla(2) in regulating ace in primary human keratinocytes.,Medication
is nevus type in dermoscopy related to skin type in white persons?,"dermoscopic classification of acquired melanocytic nevi (amn) is based on the evaluation of 3 main criteria-global pattern, pigment distribution, and color. to determine whether these features are different in amn in white people with different skin types (sts) according to the fitzpatrick classification. digital dermoscopic images of amn were evaluated, and the correlation of the 3 main dermoscopic criteria with patient st was analyzed. consecutive patients were recruited from 7 pigmented lesion clinics between june 1, 2004, and june 30, 2005. patients for each patient, the st (i always burns, never tans to iv rarely burns, tans with ease) was scored, and 1 representative amn (defined as the amn showing a dermoscopic typology that is repeatedly seen in the same patient) was selected and photographed. the distribution of the dermoscopic criteria of amn in patients with different sts was calculated by univariate analysis. differences in prevalence were tested using the chi(2) test. the correlation between dermoscopic criteria and st, adjusted for age, sex, and enrolling center, was evaluated by calculating odds ratios and 95 confidence intervals by logistic regression analysis. of 680 included patients, dermoscopic analysis revealed significant differences in the prevalent nevus pattern in the 4 st groups. light brown amn with central hypopigmentation were associated with st i, and st iv was associated with the so-called black nevus (p.001), typified by reticular pattern, central hyperpigmentation, and dark brown coloration. a significant association was also found between multifocal pattern and st ii and st iii.",the dermoscopic nevus type varies according to different st in white people. this knowledge may have an effect on obtaining for biopsy lesions that exhibit unusual dermoscopic patterns when patient st is considered.,General
is unilateral hearing loss associated with worse speech-language scores in children?,"to determine whether children with unilateral hearing loss (uhl) demonstrate worse language skills than their siblings with normal hearing, and whether children with uhl are more likely to receive extra assistance at school. we conducted a case-control study of 6- to 12-year-old children with uhl compared with sibling controls (74 pairs, n 148). scores on the oral portion of the oral and written language scales (owls) were the primary outcome measure. multivariable analysis was used to determine whether uhl independently predicted owls scores after we controlled for potential confounding variables. children with uhl had worse scores than their siblings on language comprehension (91 vs 98; p .003), oral expression (94 vs 101; p .007), and oral composite (90 vs 99; p .001). uhl independently predicted these owls scores when multivariable regression was used with moderate effect sizes of 0.3 to 0.7. family income and maternal education were also independent predictors of oral expression and oral composite scores. no differences were found between children with right- or left-ear uhl or with varying severity of hearing loss. children with uhl were more likely to have an individualized education plan (odds ratio: 4.4 95 confidence interval: 2.0-9.5) and to have received speech-language therapy (odds ratio: 2.6 95 confidence interval: 1.3-5.4).","school-aged children with uhl demonstrated worse oral language scores than did their siblings with normal hearing. these findings suggest that the common practice of withholding hearing-related accommodations from children with uhl should be reconsidered and studied, and that parents and educators should be informed about the deleterious effects of uhl on oral language skills.",Treatment
do serum igg antibodies to human herpesvirus-6 ( hhv-6 ) predict the progression of hiv disease to aids . italian seroconversion study group?,"to evaluate if different levels of human herpesvirus 6 (hhv-6) antibodies can predict hiv disease progression. longitudinal study of individuals with a documented date of hiv seroconversion. clinical centers located throughout italy. individuals who serconverted for hiv between 1983 and 1995 in italy. sera were tested for igg antibodies to hhv-6 using a commercial enzyme immunoassay. a serum sample with an optical density (od) or 242 (i.e. the mean value of 10 negative controls 4x standard deviation) was considered as hhv-6 positive; the progression of hiv disease was evaluated estimating the relative hazards (rh) of aids (by cox models) for individuals with higher levels vs. lower levels of hhv-6 antibodies or considering levels of antibodies based on 10 increase of the distribution (deciles). rates of cd4 decline fitting linear regression were also estimated. a total of 381 persons were followed for a median time of 4 years (range: 0.15-9 years) following the date of collection of the serum sample. the median od value of hhv-6 antibodies was 306, with an interquartile range of 241-440 and a range of 48-2330. a slight inverse correlation was found between hhv-6 antibody levels and age of the individual at the time of serum collection (spearman rank correlation coefficient, -0.16; p 0.0013). no association was found between hhv-6 and cd4 level or between hhv-6 and cd8 level at the date of serum collection. the unadjusted rh of progression to aids was 0.63 (95 ci: 0.42-0.96) for hhv-6 positive individuals vs. hhv-6 negative; when adjusting for possible confounders (cd4, age, pre-aids hiv-related pathologies at the date of sera collection, and previous anti-herpes treatment), the rh of aids increased to 0.80 (95 ci: 0.51-1.23). no particular association with hiv disease progression was found when using the deciles of the distribution of hhv-6 antibodies. the median cd4 cell loss was 5.0x10(6) cells/l per month among hhv-6 positive individuals and 5.7x10(6) cells/l per month among the others.",the presence of high levels of hhv-6 antibodies does not seem to predict the clinical or immunologic progression of hiv disease.,Treatment
is -tocotrienol reversal of epithelial-to-mesenchymal transition in human breast cancer cells associated with inhibition of canonical wnt signalling?,"frizzled-7 (fzd7) receptor-dependent activation of the canonical wnt/-catenin pathway plays a crucial role in epithelial-to-mesenchymal transition (emt) and breast cancer metastasis. fzd7 and its co-receptor, low-density lipoprotein receptor-related protein 6 (lrp6), are highly expressed in mda-mb-231 and t-47d breast cancer cells, and endogenous ligands for fzd7 include wnt3a and wnt5a/b. -tocotrienol, a natural isoform of vitamin e, inhibits human breast cancer cell proliferation and emt. here, studies have been conducted to investigate the role of the canonical wnt pathway in mediating inhibitory effects of -tocotrienol on emt in human breast cancer cells. mda-mb-231, t-47d and mcf-10a cells were maintained in serum-free defined media containing selected doses of -tocotrienol. cell viability was determined using the mtt colorimetric assay, western blot analysis was used to measure protein expression and the wound-healing assay was employed to study cell mobility and migration. immunohistochemical fluorescence staining visualized expression and localization of emt cell markers. -tocotrienol was found to induce dose-responsive inhibition of mda-mb-231 and t-47d cell growth at doses that had no effect on immortalized normal mcf-10a mammary epithelial cells. these growth inhibitory effects were associated with suppression in canonical wnt signalling, reversal of emt and significant reduction in breast cancer cell motility.",-tocotrienol suppression of metastatic breast cancer cell proliferation and emt was associated with suppression of the canonical wnt/-catenin signalling pathway.,Medication
does 1-methyl-4-phenyl-pyridinium time-dependently alter expressions of oxoguanine glycosylase 1 and xeroderma pigmentosum group f protein in pc12 cells?,"to determine if dna excision repair enzymes oxoguanine glycosylase 1 (ogg1) and xeroderma pigmentosum group f protein (xpf) are involved in the pathogenesis of parkinson's disease (pd) in a cell model. pc12 cells were treated with 1-methyl-4-phenylpyridine ion (mpp()) for various periods of time to induce oxidative dna damage. mtt assay was used to determine cell viability. immunocytochemistry with antibody against 8-hydroxy-2'-deoxyguanosine (8-oxodg) was used to evaluate oxidative dna damage. immunoblotting was used to detect the protein levels of ogg1 and xpf. mpp() treatment (1 mmol/l) for 18 h and 24 h reduced cell viability to 78.6 and 70.3 of the control, respectively, in a time-dependent way. mpp() increased the immunoreactivity of 8-oxodg in the cytoplasm at 3 h and in the nucleus at 24 h of treatment. with the treatment of mpp(), the expression of ogg1 was significantly increased at 1 h, reaching a peak at 3 h, and then it was decreased at 24 h, as compared to that with vehicle treatment. the same effect was exerted on xpf level, except that the xpf level reached a peak at 18 h of mpp() treatment. moreover, the maximally-increased protein level of ogg1 by mpp() was approximately 2-fold higher than that of xpf.","mpp() treatment could time-dependently induce increases in ogg1 and xpf expressions in pc12 cells. also, this study indicates that the base and nucleotide excision repair pathways may be compensatory activated in the early stage of pathogenesis in the cells after mpp() treatment.",Treatment
do cd4 lymphocytes are increased in the sinus mucosa of children with chronic sinusitis?,"to quantitate lymphocyte subtypes in sinus tissues harvested from children with chronic sinusitis and coexisting asthma, allergies, and cystic fibrosis during functional endoscopic sinus surgery and compare them with those in normal adult sphenoid sinus mucosa. immunohistochemical staining of surgical specimens with monoclonal antibodies against cd4 and cd8 surface antigens. tertiary medical center. thirty-two children who underwent functional endoscopic sinus surgery for chronic sinusitis refractory to medical treatment (median age, 8 years; range, 2-13 years) were divided into 3 groups: 10 with asthma, 15 without asthma, and 7 with cystic fibrosis. sphenoid sinus mucosa obtained from 10 adults (median age, 70 years) undergoing transsphenoidal hypophysectomy was used as control tissue. numbers of cd4 and cd8 cells in the lamina propria and epithelium of surgical specimens. significantly more cd4 cells were in the sinus mucosa of patients with chronic sinusitis than in the normal sinus mucosa (p .01), but there was no significant difference in the number of cd8 cells (p 4). patients with chronic sinusitis with asthma, without asthma, and with cystic fibrosis all had increased numbers of cd4 cells compared with sphenoid mucosa, with the difference reaching statistical significance only in the subgroup with chronic sinusitis without asthma (p .001). the numbers of cd4 cells were higher in patients with chronic sinusitis than in the sphenoid mucosa irrespective of allergic status. significantly more cd4 than cd8 cells were in tissues from the patients with chronic sinusitis irrespective of concomitant diseases or allergic status. cd4 and cd8 cells were more numerous in the apical portion of the submucosa (immediately beneath the epithelium) than in the basal portion both in patients with chronic sinusitis and in normal sphenoid tissue.","children with chronic sinusitis have predominance of cd4 cells in the sinus mucosa as compared with normal sphenoid tissue. this contrasts with published results in adults with chromic sinusitis, in whom cd8 cells predominate in nasal polyps and the submucosa, possibly reflecting a difference in the immunologic response of children and adults.",Treatment
are patients with both cyp2c19 loss-of-function allele and peripheral endothelial dysfunction significantly correlated with adverse cardiovascular events following coronary stent implantation?,"there is some controversy regarding the effect of cyp2c19 polymorphism on clinical outcome in patients receiving dual antiplatelet therapy (dapt). peripheral endothelial dysfunction has recently been reported to predict adverse cardiovascular events. we hypothesized that cyp2c19 loss-of-function (lof) allele carriers with peripheral endothelial dysfunction had worse prognosis. the aim of this study was to evaluate an additive effect of peripheral endothelial dysfunction on clinical outcome following percutaneous coronary intervention (pci) in patients with a cyp2c19 variant. we enrolled 434 patients on dapt following pci. cyp2c19 genotype was examined, and we divided patients into two groups: carriers, who had at least one cyp2c19 lof allele, and non-carriers. peripheral endothelial dysfunction was examined using reactive hyperemia-peripheral arterial tonometry index (rhi), and we divided patients into low and high rhi. thus, subjects were divided into four groups, and clinical events were followed up. a total of 55 patients had a cardiovascular event. kaplan-meier analysis demonstrated a significantly higher probability of cardiovascular events in carriers with low rhi (log-rank test: p0.007). multivariate cox proportional hazards analysis identified both cyp2c19 lof allele possession (hazard ratio (hr): 1.94; 95 confidence interval (ci): 1.1-3.69; p0.045) and low rhi (hr: 2.15; 95 ci: 1.22-3.78; p0.008) as independent and significant predictors of future cardiovascular events.",cyp2c19 lof allele carriers with peripheral endothelial dysfunction were significantly correlated with cardiovascular events. the additional evaluation of peripheral endothelial function along with cyp2c19 polymorphism might improve risk stratification after coronary stent implantation.,Symptoms
does postprandial fullness correlate with rapid inflow of gastric content into duodenum but not with chronic gastritis?,"the aim of this study is evaluating the correlation of postprandial fullness with chronic gastritis or rapid inflow of gastric content into duodenum, based on double-contrast barium x-ray imaging. 253 healthy subjects who underwent upper gastrointestinal barium x-ray examination were analyzed. chronic gastritis was judged from mucosal atrophy and hypertrophic thickened folds on barium x-ray images. for the gastric excretion, the tips of barium flow on the single-contrast frontal barium x-ray images of the stomach were classified into four categories; v type (all the barium remained in the stomach), v-h type (some barium had flowed into the duodenum but the tip of barium remained in the proximal half of the duodenal bulb), h-v type (some barium had flowed into the duodenum and the tip of barium was in the distal half of duodenal the bulb, but no barium was observed in the descending part of the duodenum), and h type (some barium had flowed into the descending part of the duodenum). the chi-square test and cochran-mantel-haenzel test were used for evaluation. chronic gastritis was observed in 72 subjects, among which 21 subjects (29.2) presented with postprandial fullness. for the remaining 181 subjects without chronic gastritis, 53 subjects (29.3) complained of postprandial fullness. there is no significant correlation between chronic gastritis and postprandial fullness (p 0.973). for the rapid flow of gastric content into duodenum, all the 253 subjects comprised 136 subjects with v type (in the stomach), 40 subjects with v-h type (in the proximal half of the duodenal bulb), 21 subjects with h-v type (in the distal half of the duodenal bulb), and 56 subjects with h type (in the descending part of the duodenum). postprandial fullness was present in 30 subjects with v type (22.1), 9 subjects with v-h type (22.5), 8 subjects with h-v type (38.1), and 27 subjects with h type (48.2). there is a distinct correlation between postprandial fullness and gastric barium excretion on barium x-ray imaging (p 0.002).","bothersome postprandial fullness correlates with rapid inflow of gastric content into duodenum, but not with chronic gastritis.",Diagnosis
does comparative genomics of the family vibrionaceae reveal the wide distribution of genes encoding virulence-associated proteins?,"species of the family vibrionaceae are ubiquitous in marine environments. several of these species are important pathogens of humans and marine species. evidence indicates that genetic exchange plays an important role in the emergence of new pathogenic strains within this family. data from the sequenced genomes of strains in this family could show how the genes encoded by all these strains, known as the pangenome, are distributed. information about the core, accessory and panproteome of this family can show how, for example, genes encoding virulence-associated proteins are distributed and help us understand how virulence emerges. we deduced the complete set of orthologs for eleven strains from this family. the core proteome consists of 1,882 orthologous groups, which is 28 of the 6,629 orthologous groups in this family. there were 4,411 accessory orthologous groups (i.e., proteins that occurred in from 2 to 10 proteomes) and 5,584 unique proteins (encoded once on only one of the eleven genomes). proteins that have been associated with virulence in v. cholerae were widely distributed across the eleven genomes, but the majority was found only on the genomes of the two v. cholerae strains examined.",the proteomes are reflective of the differing evolutionary trajectories followed by different strains to similar phenotypes. the composition of the proteomes supports the notion that genetic exchange among species of the vibrionaceae is widespread and that this exchange aids these species in adapting to their environments.,General
do effects of uni- and multimodal cueing on handrail grasping and associated gaze behavior in older adults?,"it appears that age-related changes in visual attention may impair ability to acquire the visuospatial information needed to grasp a handrail effectively in response to sudden loss of balance. this, in turn, may increase risk of falling. to counter this problem, we developed a proximity-triggered cueing system that provides a visual cue (flashing lights) and/or verbal cue (""attention use the handrail"") to attract attention to the handrail. this study examined the effect of handrail cueing on grasping of the rail and associated gaze behavior in a large cohort (n160) of independent and ambulatory older adults (age 64-80). the handrail and cueing system was mounted on a large (2 m6 m) motion platform configured to simulate a real-life environment. subjects performed a daily-life task that required walking to the end of the platform, which was triggered to perturb balance by moving suddenly when they were adjacent to the rail. to prevent adaptation, each subject performed only one trial, and a deception was used to ensure that the perturbation was truly unexpected. each subject was assigned to one of four cue conditions: visual, verbal, multimodal (visual-plus-verbal) or no cue. verbal cueing attracted overt visual attention to the handrail and markedly increased proactive grasping (prior to the onset of the balance perturbation) particularly when delivered unimodally. subjects were otherwise much more likely to grasp the rail in reaction to the perturbation. a possible trend for visual cueing to improve the accuracy of these reactions was offset by adverse effects on reaction speed and on frequency of proactive grasping.","the results support the viability of using unimodal verbal cueing to reduce fall risk by increasing proactive handrail use. conversely, they do not strongly support use of visual cueing (either alone or in combination with verbal cueing) and suggest that it may even have adverse effects. further study is needed to evaluate effects of handrail cueing in a wide range of populations and real-life settings.",Medication
are beta-subunits important modulators of the acute response to alcohol in human bk channels?,"the bk channel (a ca2-activated potassium ion channel encoded by the slo gene) has been defined as a target of alcohol action in a number of preparations, possibly serving as primary mediator of intoxication in the caenorhabditis elegans model system. however, we know little of the actions of alcohol on human bk, nor the consequences of bk subunit composition on alcohol action. here, we use human embryonic kidney (hek) cells to express various subunit combinations (hslo alphabeta1 or beta4) of human bk, and examine the acute actions of alcohol on this channel using single channel recording techniques. the human channel is potentiated by alcohol, although the presence of the beta1, and to a lesser extent, beta4-subunit, significantly reduced acute ethanol potentiation. potentiation increased with concentration up to an asymptote, at which point potentiation decreased. the concentration of the asymptote differed according to subunit composition. the mechanism of potentiation was also subunit-dependent, with 25 mm ethanol affecting the mean open time of hslobeta4 channels, whereas channel open time was unaffected by the presence of beta1. the possibility that the known effect of the beta-subunit on calcium sensitivity accounts for its modulation of acute alcohol action is discussed.","our data reinforce the idea that, as in other systems, bk may play a major role in alcohol's actions in humans, and highlight the potential role of channel subunit composition in the response to alcohol.",Diagnosis
"are baseline disease activity , hyperlipidemia , and hypertension predictive factors for ischemic stroke and stroke severity in systemic lupus erythematosus?","to determine factors associated with ischemic stroke and stroke severity in patients with systemic lupus erythematosus. between 1992 and january 2005, 238 consecutive systemic lupus erythematosus patients with no history of stroke were followed-up longitudinally at the maryland lupus clinic. patients were monitored quarterly for a mean of 8 years after their systemic lupus erythematosus diagnosis, and 44 patients (19) developed first-ever ischemic stroke. at the end of study, cox proportional regression analyses were used to determine the effect of baseline clinical variables of systemic lupus erythematosus patients in relation to the subsequent occurrence of ischemic stroke and stroke severity after first-ever ischemic strokes. severe stroke was defined as having a national institute of health stroke scale or 6. severe ischemic strokes occurred in 34 of 44 (77) patients. baseline predictors of ischemic strokes and severe ischemic strokes included disease activity, hyperlipidemia, and hypertension.","severe ischemic strokes in systemic lupus erythematosus are not uncommon. aggressive primary and secondary stroke prevention measures, particularly treatment of hyperlipidemia and hypertension, as well as vigorous treatment of clinical symptoms of active lupus, are needed to prevent serious morbidity and neurological disability.",Diagnosis
does stem cell injection in the hindlimb skeletal muscle enhance neurorepair in mice with spinal cord injury?,"to develop a low-risk, little-invasive stem cell-based method to treat acute spinal cord injuries. methods: adult mice were submitted to an incomplete spinal cord injury, and mesenchymal stem cells injected intramuscularly into both hindlimbs. behavior tests and mri of the spinal cord were periodically performed for up to 6 months, along with immunohistochemical analysis. immunohistochemical and pcr analysis of the muscles were used to detect the grafted cells as well as the soluble factors released. the stem cell-treated mice presented significant improvements in their motor skills 5 months after treatment. spinal cord repair was detected by magnetic resonance and immunohistochemistry. in the hindlimb muscles, the stem cells activated muscle and motor neuron repair mechanisms, due to the secretion of several neurotrophic factors.",bone marrow mesenchymal stem cell injection into hindlimb muscles stimulates spinal cord repair in acute spinal cord lesions.,Medication
does bold signal in memory paradigms in hippocampal region depend on echo time?,"to evaluate the hypothesis that the entire hippocampus might be affected by susceptibility artifacts. previous studies described susceptibility artifacts in the amygdala and the anterior hippocampus. we investigated 20 subjects with a verbal memory paradigm aiming at testing two different tes (45 vs. 64 msec) at 1.5 t for hippocampal blood oxygenation level-dependent (bold) activity. t2 maps were calculated from the normalized mean echo-planar imaging (epi) of the two echo times (tes). within the hippocampal region of interest (roi), the amount of suprathreshold voxels was significantly higher at te 64 msec compared to te 45 msec. when corrected for multiple comparisons (family-wise error fwe in a small volume of interest, p 0.05) we no longer found significant activations at te 45 msec, while a significant number of voxels remained after the small volume correction (p 0.05, fwe) within the roi at te 64 msec.","although a shorter te demonstrates advantages, a te of 45 msec leads to a significant loss of bold signal detection in memory functional magnetic resonance imaging (fmri) studies when compared to 64 msec. we assume that the hippocampal region, even the anterior part, is not strongly affected by susceptibility gradients.",Diagnosis
does hla-drb1 donor-recipient mismatch affect the outcome of hepatitis c disease recurrence after liver transplantation?,"this study extends our previously reported observations that various immunological factors are associated with the occurrence of histologically proven recurrent hepatitis c. the two specific issues investigated were to confirm the associations of mhc alleles and donor/recipient mismatch with the occurrence of recurrent hepatitis c in an independent cohort of newly transplanted patients and to look for immunologic and nonimmunologic variables affecting the severity of the recurrent disease. two separate cohorts of consecutive patients were studied: a look-back cohort (lc) of 120 patients and a cohort for studying the disease progression (csdp) of 190 patients. protocol liver biopsies were obtained at least 1, 3, 5, 7, and 10 years after liver transplantation (lt). a fully mismatched donor/recipient pair at the drb1 locus was confirmed to be associated with both the recurrence of histologic hepatitis in the lc (59 vs 23, p .0002) and its progression beyond stage 3 in the cspd (71.4 vs 39.3, p .0003). relevant immunologic and nonimmunologic variables were included into a multivariate cox proportional model and three variables, namely, donor age, full hla-drb1 donor-recipient mismatch, and hla b14, resulted in independent risk factors for the development of severe fibrosis.",this study provides evidence that drb1 donor-recipient mismatch affects both the occurrence and progression of recurrent hepatitis c disease. this information is clinically relevant as it may help to better allocate organs and to recognize patients at risk for progression so that specific interventions can be implemented.,Treatment
do increases in inflammatory mediators in drg implicate in the pathogenesis of painful neuropathy in type 2 diabetes?,"painful neuropathy is a common, difficult to treat complication of both types 1 and 2 diabetes (t1d and t2d). reports have shown that activation of inflammatory cascades play an important role in the development and persistence of neuropathic pain states, but it is not well established in painful diabetic neuropathy (pdn). previously, studies have shown increased inflammatory cytokines in the serum of the diabetic patients with painful neuropathy. this study focuses on the changes in the levels of inflammatory mediators such as tnf, interleukins, chemokines and cell adhesion molecules with the development of pain in the drg of the zucker diabetic fatty (zdf) rat, an established model for t2d. this study also demonstrates an alteration in the levels of voltage gated sodium channel 1.7 (nav1.7) with the development of pain in drg of the zdf rats. pre-diabetic zdf animals at 8-9 weeks of age showed no thermal and mechanical hyperalgesia compared to their respective lean controls. diabetic-zdf animals tested for pain related behaviors showed significant thermal and mechanical hyperalgesia at 4 and 6 weeks after the onset of diabetes when compared with their age matched lean controls. these zdf animals with pdn also showed changes in a large number of inflammatory mediators in the drg as assessed by western blot as well as by cytokine antibody array compared to their age matched lean controls. further analysis by rat cytokine antibody array of drg of the zdf animals with pdn at 6 weeks after diabetes when compared with zdf animals with no pain revealed an elevation of a significant number of inflammatory mediators including, the pro-inflammatory cytokines such as tnf, interleukin-1, 6, 13 and 17, chemokines such as mip1 and 3, rantes, fractalkine and cell adhesion molecule sicam that are associated with pain phenotype. the zdf animals with pdn also demonstrated an increase in the protein levels of voltage gated sodium channel nav1.7 in drg compared to lean controls with no pain.",the rise in inflammatory markers in the drg of type 2 diabetic animals and increases in voltage gated sodium channel nav1.7 in drg with the onset of pain in pdn suggest that inflammation in the drg may play an important role in the development of pain in this model.,Symptoms
is atp8b1 gene expression driven by a housekeeping-like promoter independent of bile acids and farnesoid x receptor?,"mutations in atp8b1 gene were identified as a cause of low -glutamyltranspeptidase cholestasis with variable phenotype, ranging from progressive familial intrahepatic cholestasis to benign recurrent intrahepatic cholestasis. however, only the coding region of atp8b1 has been described. the aim of this research was to explore the regulatory regions, promoter and 5'untranslated region, of the atp8b1 gene. 5'rapid amplification of cdna ends using human liver and intestinal tissue was performed to identify the presence of 5' untranslated exons. expression levels of atp8b1 transcripts were determined by quantitative reverse-transcription pcr and compared with the non-variable part of atp8b1. three putative promoters were examined in vitro using a reporter gene assay and the main promoter was stimulated with chenodeoxycholic acid. four novel untranslated exons located up to 71 kb upstream of the previously published exon 1 and twelve different splicing variants were found both in the liver and the intestine. multiple transcription start sites were identified within exon -3 and the proximal promoter upstream of this transcription start site cluster was proven to be an essential regulatory element responsible for 70 of total atp8b1 transcriptional activity. in vitro analysis demonstrated that the main promoter drives constitutive atp8b1 gene expression independent of bile acids.",the structure of the atp8b1 gene is complex and the previously published transcription start site is not significant. the basal expression of atp8b1 is driven by a housekeeping-like promoter located 71 kb upstream of the first protein coding exon.,Medication
do serum insulin-like growth factor-1 levels predict outcomes of patients with advanced hepatocellular carcinoma receiving antiangiogenic therapy?,"patients with liver cirrhosis or hepatocellular carcinoma (hcc) have decreased serum insulin-like growth factor (igf)-1 levels. we evaluated whether igf-1 levels were associated with the outcomes of patients with advanced hcc treated with systemic antiangiogenic therapy. the study was based on patients with advanced hcc who were enrolled in two clinical trials evaluating first-line combination antiangiogenic therapy. serum samples were collected before treatment and four to six weeks after the start of treatment. the levels of igf-1, igf-2, and igf-binding protein-3 (igfbp3) were analyzed for their associations with treatment outcomes. a total of 83 patients were included in the study. patients who had high (the median level) baseline igf-1 levels had significantly higher disease control rate (dcr) than patients who had low (the median level) levels (71 vs. 39, p 0.003). the levels of posttreatment igf-1, and pre- or posttreatment igf-2 and igfbp3 were not associated with dcr. patients with high baseline igf-1 levels, compared with patients with low levels, had significantly longer progression-free survival (pfs; median, 4.3 vs. 1.9 months, p 0.014) and overall survival (os; median, 10.7 vs. 3.9 months, p 0.009). the high baseline igf-1 level remains an independent factor associated with favorable pfs and os in multivariate analysis.","high pretreatment igf-1 levels were associated with better dcr, pfs, and os of patients who received antiangiogenic therapy for advanced hcc. this finding warrants validation in large studies.",Treatment
are serum but not cerebrospinal fluid levels of insulin-like growth factor-i ( igf-i ) and igf-binding protein-3 ( igfbp-3 ) increased in alzheimer 's disease?,"although insulin-like growth factor-i (igf-i) is of importance for the adult function of the central nervous system (cns), little is known of the significance of igf-i in cerebrospinal fluid (csf) in relation to alzheimer's disease (ad). a cross-sectional study of 60 consecutive patients under primary evaluation of cognitive impairment and 20 healthy controls. the patients had ad dementia or mild cognitive impairment (mci) diagnosed with ad dementia upon follow-up (n32), stable mci (smci, n13), or other dementias (n15). igf-i, igf-binding protein-3 (igfbp-3), and insulin were measured in serum and csf. serum igf-i level was increased in ad patients and in patients with other dementias compared to healthy controls (p0.01 and p0.05, respectively). serum igfbp-3 concentration was increased in ad and smci patients compared to controls (p0.001 and p0.05, respectively). csf levels of igf-i and igfbp-3 as well as serum and csf levels of insulin were similar in all study groups. in the total study population (n80), serum levels of igf-i and igfbp-3 correlated negatively with csf -amyloid (a) level (r-0.29, p0.01 and r-0.27, p0.02, respectively) and in the ad patients (n32), the increased csf/serum igf-i ratio correlated positively with the csf level of phosphorylated tau protein (p-tau; r0.42, p0.02).","patients with ad as well as other dementias had high levels of igf-i in serum but not in csf. in ad patients, the igf-i system was associated with biomarkers of ad disease status.",Medication
does rigid ring fixation of the mitral annulus impair left ventricular systolic function in the normal canine heart?,"previous studies suggest that rigid fixation of the mitral annulus with an annuloplasty ring may impair left ventricular (lv) systolic performance. we used load-insensitive indexes of global and regional lv contractile mechanics to test the hypothesis that rigid fixation of the mitral annulus alters lv systolic function. global and regional lv systolic mechanics were compared in 10 dogs during two mitral annular conditions: rigidly fixed and freely mobile. carpentier-edwards annuloplasty rings (20-24 mm) were inserted using a special buttressing suture technique that permitted alternate cinching of the ring down onto the annulus and subsequent removal away from the annulus. aortic flow was measured with an electromagnetic flow probe, lv pressure by a micromanometer, and lv wall thickness and three near-orthogonal lv endocardial chamber dimensions using piezoelectric crystals during four sequential ring conditions: 1) down, 2) away, 3) down, and 4) away. the following parameters were analyzed during each ring condition to assess global lv systolic function: end-systolic chamber elastance (end-systolic pressure-volume relation), fiber elastance (end-systolic stress-volume relation), preload recruitable stroke work, and myocardial stress-strain relation. additionally, regional lv systolic performance was assessed using the end-systolic pressure-diameter relation and a regional analog of preload recruitable stroke work. no significant differences in any of these measurements of lv systolic mechanics were observed between the two mitral annular conditions.","rigid fixation of the mitral annulus alters neither global nor regional lv systolic function in anesthetized, open-chest dogs with normal ventricles.",General
does commencing peritoneal dialysis with 1.1 amino acid solution influence biochemical nutritional parameters in incident capd patients?,"to evaluate the influence of 1.1 amino acid dialysis solutions on nutritional parameters in incident continuous ambulatory peritoneal dialysis (capd) patients. the effect of daily use of 1.1 amino acid solution was studied retrospectively in 32 incident capd patients (14 women and 18 men, mean age 54 /- 13 years) who began capd at our tertiary university hospital between july 2005 and february 2009 (amino acid solution (aas) group). serum total protein, albumin, and creatinine were assessed for all patients prior to dialysis and at the end of the study period. thirty-two control patients (12 women and 20 men, mean age 52 /- 14 years) who started peritoneal dialysis with a standard capd program were also investigated and grouped as the dextrose solution (ds) group. baseline serum albumin levels were significantly lower in the aas group compared to the ds group (3.4 /- 0.4 g/dl vs. 3.7 /- 0.5 g/dl, p 0.011). at the end of the 12-month follow-up period, mean serum albumin levels had decreased from 3.4 to 3.3 g/dl in the aas group (p 0.218) and increased from 3.7 to 3.8 g/dl in the ds group (p 0.360). overall, no significant changes were observed in serum total protein, creatinine, or albumin in either group.",amino acid solutions conferred no demonstrable benefit on biochemical parameters in incident capd patients. the effects of aas may be different when added to the capd regimen of patients undergoing prior capd treatment.,Prevention
does in vivo expression of recombinant pregnancy-specific glycoprotein 1a inhibit the symptoms of collagen-induced arthritis?,"the contribution of pregnancy-specific glycoproteins (psg), the major variant of psg released into the circulation during pregnancy, to the pregnancy-dependent improvement of rheumatoid arthritis (ra) has still not been elucidated. collagen-induced arthritis (cia) was used to test the hypothesis that psg1a when released into circulation has a modulatory role on the th1-pathogenic response, thus improving the cia symptoms. in vivo expression of psg1a was induced by injection of the vaccinia (vac)-based expression vector harboring the complete open-reading frame of psg1a cdna. in vivo psg1a expression during the induction of cia ameliorated the clinical symptoms, thereby reducing the arthritis score and incidence. significantly lower levels of il-17, il-6, and ifn-, but higher levels of tgf- and il-10 were secreted by collagen type ii-stimulated spleen mononuclear cells from vac-psg1a-treated mice compared with control mice. moreover, vac-psg1a treatment promoted the increase in splenic cd4cd25foxp3 treg cells.","pre-clinical vac-psg1a treatment suppressed the th1- and th17-type-specific responses, leading to an increase in splenic treg cells as well as il-10- and tgf--secreting cells, with the cia symptoms being ameliorated.",Symptoms
does nitric oxide synthase activity in pregnant rabbit uterus decrease on the last day of pregnancy?,"our purpose was to test a potential role for the endogenous smooth muscle relaxant nitric oxide in the control of gestational uterine activity by quantifying and characterizing its synthetic enzyme, nitric oxide synthase, in uterine tissue at the end of pregnancy. we measured nitric oxide synthase activity through the conversion of tritiated l-arginine to tritiated l-citrulline in subcellular preparations of decidua and myometrium from pregnant rabbits at 27, 30, and 31 days' (term)gestation. nitric oxide synthase was characterized by measuring its relative inhibition by arginine analogs and its calcium-calmodulin requirement. nitric oxide synthase activities were compared by one-way analysis of variance with fisher's post hoc test. nitric oxide synthase activity in decidua was high at 27 days' gestation (6.32 /- 1.10 pmol/mg protein per minute, n 6), less with the approach of labor (30 days 3.16 /- 1.25 pmol/mg per minute, n 4), and lowest at 31 days (1.07 /- 0.29 pmol/mg per minute, n 4, p 0.05). decidual nitric oxide synthase was calcium insensitive, and arginine analogs reduced activity with potencies consistent with their effect on the induced form of nitric oxide synthase.","decidual nitric oxide synthase activity, which has the characteristics of the inducible isoform of the enzyme, is significantly lower on the last day of gestation. this suggests a role for nitric oxide in the control of uterine contractility during pregnancy.",General
does low expression of gnai3 predict poor prognosis in patients with hcc?,"this study was performed with an aim to explain the underlying role of gnai3 on the prognosis of patients with hcc. the expression of gnai3 at protein level was detected with the utilization of immunohistochemistry (ihc). chi-square test was conducted to assay the relationship between gnai3 expression and clinical parameters of hcc patients. the correlation between expression level of gnai3 and survival time after surgeries of hcc patients was evaluated by kaplan-meier method. finally, the cox regression was established to evaluate the relationship between gnai3 expression and the prognosis of patients with hcc. in this study, the negative rate of gnai3 expression in hcc samples was about 76.6, which was significantly higher than that in paired normal specimens (12.5). result showed that there was no correlation between gnai3 expression and age, gender, liver cirrhosis and vein invasion (p0.05), but tight relationship between gnai3 expression and tnm stage and tumor size was found (p0.05). the following kaplan-meier analysis result illustrated that negative expression of gnai3 induced high mortality of hcc patients. cox regression result revealed that gnai3 might be a biomarker for prognosis of patients with hcc (hr: 0.218, p0.016, 95 ci 0.063-0.750).","generally, results of this study demonstrated that expression of gnai3 shared a tight relationship with the prognosis of patients with hcc. therefore, gnai3 could be considered as a novel index for prognosis of patients with hcc.",Diagnosis
does nocturnal oxygen therapy prevent progress of congestive heart failure with central sleep apnea?,"sleep disordered breathing has been reported to be associated with congestive heart failure (chf). nocturnal oxygen has been shown to abolish apnea. the aim of this study is to examine whether nocturnal oxygen reduces sympathetic nerve activity, and prevents progress of chf. 93 patients with left ventricular ejection fractions or 4/h were examined with polysomnography. apnea-hypopnea index (ahi) was calculated as the total number of episodes of apnea and hypopnea per hour of sleep. we started nocturnal oxygen for the patients with ahi or 20. urinary and plasma catecholamines concentrations, serum brain natriuretic peptide, human atrial natriuretic peptide, and endothelial nitric oxide synthase levels were measured before and after starting oxygen. compared among the three groups, chf with central sleep apnea (chf-csa) group had significantly higher 24-h urinary adrenaline (chf-csa: 4.411/-2.940 micromol/day, chf with obstructive sleep apnea (chf-osa): 2.686/-1.084 micromol/day, chf without apnea (chf-n): 3.178/-1.778 micromol/day, p0.05). oxygen therapy significantly decreased ahi and 4 serum bnp levels (from 91.75/-80.35 pg/ml to 52.75/-45.70 pg/ml, mean change33.85 pg/ml, p0.0208). serum enos levels were lower in chf-csa group and chf-osa group than in chf-n group (chf-csa: 15.89/-10.75 pg/ml, chf-osa: 7.46/-3.91 pg/ml, chf-n: 27.33/-14.83 pg/ml, p0.05).",nocturnal oxygen may prevent progress of chf with central sleep apnea.,Prevention
does periarticular injection with corticosteroid have an additional pain management effect in total knee arthroplasty?,"although the analgesic effects of corticosteroids have been well documented, little information is available on periarticular injection (pi) containing corticosteroids for early postoperative pain management after total knee arthroplasty (tka). we performed a prospective double-blind randomized trial to evaluate the efficacy and safety of an intraoperative corticosteroid pi in patients undergoing tka. seventy-six consecutive female patients undergoing bilateral staged tka were randomized to receive steroid or non-steroid pi, with 3 months separating the procedures. the steroid group received pi with a mixture containing triamcinolone acetonide (40 mg). the non-steroid group received the same injection mixture without corticosteroid. during the postoperative period, nighttime pain, functional recovery straight leg raising (slr) ability and maximal flexion, patient satisfaction, and complications were recorded. short-term postoperative clinical scores and patient satisfaction were evaluated at 6 months. the pain level was significantly lower in the pi steroid than the non-steroid group on the night of the operation (vas, 1.2 vs. 2.3; p0.021). rebound pain was observed in both groups at pod1 (vas, 3.2 vs. 3.8; p0.248), but pain remained at a low level thereafter. no significant differences were seen in maximal flexion, frequency of acute rescuer, clinical scores, and patient satisfaction. the steroid group was able to perform slr earlier than the non-steroid group (p0.013). the incidence of complications was similar between the groups.","pi containing a corticosteroid provided an additional pain-relieving effect on the night of the operation. in addition, corticosteroid pi did not increase the perioperative complications of tka.",Medication
does maternal preeclampsia protect preterm infants against severe retinopathy of prematurity?,"to study the influence of maternal preeclampsia on the occurrence of retinopathy of prematurity. a prospective cohort study of 324 preterm neonates with birth weight 1500 g and gestational age 32 weeks. multiple maternal and perinatal factors were analyzed for association and confounding by multiple logistic regression analysis. mean birth weight was 1128 240 g, and mean gestational age 29.7 1.9 weeks. twenty-four newborns (7.4) had severe retinopathy of prematurity; 97 had any stage of retinopathy, and 227 had no retinopathy of prematurity. preeclampsia and complete antenatal steroid treatment course reduced the risk for any stage of retinopathy of prematurity by 60 and 54, respectively. preeclampsia reduced the risk for severe retinopathy of prematurity by 80.",preeclampsia lowered the risk for occurrence of any stage and severe retinopathy of prematurity in very low birth weight infants.,Medication
do cysteinyl leukotrienes regulate tgf- ( 1 ) and collagen production by bronchial fibroblasts obtained from asthmatic subjects?,"cysteinyl leukotrienes (cyslts) play an important role in airway inflammation in asthma but their role in airway remodeling is not completely known. cyslts receptors and procollagen i((1)) mrna were determined by qpcr. procollagen protein production was measured by ria and tgf-(1) expression was determined by elisa. tgf- receptor expression was assessed by western blots. cyslt1r, tgf--r1 and active tgf-(1) are highly expressed in cells from asthmatics compared to normal controls. ltd(4) increased significantly procollagen i((1)) mrna and protein expression in fibroblasts from asthmatics. this increase was blocked by cyslts receptor antagonist. ltd(4) increased significantly mrna expression of tgf-(1) and active form production in fibroblasts from asthmatics. inhibition of tgf-(1) signaling blocked ltd(4)-induced procollagen i((1)) expression.",fibroblasts from asthmatic subjects express high level of cyslt1r. ltd(4) regulates procollagen i((1)) transcription in fibroblasts derived from asthmatic patients by modulating tgf-(1) expression. this suggests that cyslts may play a role in regulating collagen deposition in asthma.,Medication
is candida albicans hom6 a homoserine dehydrogenase involved in protein synthesis and cell adhesion?,"candida albicans is a common fungal pathogen in humans. in healthy individuals, c. albicans represents a harmless commensal organism, but infections can be life threatening in immunocompromised patients. the complete genome sequence of c. albicans is extremely useful for identifying genes that may be potential drug targets and important for pathogenic virulence. however, there are still many uncharacterized genes in the candida genome database. in this study, we investigated c. albicans hom6, the functions of which remain undetermined experimentally. hom6-deleted and hom6-reintegrated mutant strains were constructed. the mutant strains were compared with wild-type in their growth in various media and enzyme activity. effects of hom6 deletion on translation were further investigated by cell susceptibility to hygromycin b or cycloheximide, as well as by polysome profiling, and cell adhesion to polystyrene was also determined. c. albicans hom6 exhibits homoserine dehydrogenase activity and is involved in the biosynthesis of methionine and threonine. hom6 deletion caused translational arrest in cells grown under amino acid starvation conditions. additionally, hom6 protein was found in both cytosolic and cell-wall fractions of cultured cells. furthermore, hom6 deletion reduced c. albicans cell adhesion to polystyrene, which is a common plastic used in many medical devices.","given that there is no hom6 homologue in mammalian cells, our results provided an important foundation for future development of new antifungal drugs.",Medication
does vitamin d improve viral response in hepatitis c genotype 2-3 nave patients?,"to examine whether vitamin d improved viral response and predicted treatment outcome in patients with hepatitis c virus (hcv) genotype 2-3. fifty patients with chronic hcv genotype 2-3 were randomized consecutively into two groups: treatment group 20 subjects, age 48 14 years, body mass index (bmi) 30 6, 65 male, who received 180 g pegylated -interferon-2a plus oral ribavirin 800 mg/d (peg/rbv), together with oral vitamin d3 (vitamidyne d drops; 2000 iu/d, 10 drops/d, normal serum level 32 ng/ml) for 24 wk; and control group (30 subjects, age 45 10 years, bmi 26 3, 60 male), who received identical therapy without vitamin d. hcv rna was assessed by reverse transcription polymerase chain reaction. undetectable hcv rna at 4, 12 and 24 wk after treatment was considered as rapid virological response, complete early virological response, and sustained virological response (svr), respectively. biomarkers of inflammation were measured. the treatment group with vitamin d had higher bmi (30 6 vs. 26 3, p 400,000 iu/ml, 65 vs. 40, p 15 ng/ml, or 2.2, p 30, or 2.6, p 0.01) as independent predictors of viral response. adverse events were mild and typical of peg/rbv.","low vitamin d levels predicts negative treatment outcome, and adding vitamin d to conventional peg/rbv therapy for patients with hcv genotype 2-3 significantly improves viral response.",Treatment
is estrogen induction of smooth muscle differentiation of human prostatic stromal cells mediated by transforming growth factor-beta?,"the differentiation of prostatic fibroblasts into smooth muscle cells is regarded as the key step in the development of periurethral stromal nodules. intraprostatic stromal estrogen and transforming growth factor-beta1 (tgf-beta1) are considered to be involved in this process. we investigated whether estrogen enhances the stromal cell growth and induction of smooth muscle phenotype, and whether this process is mediated by tgf-beta1. prostate specimens obtained from patients undergoing transurethral resection of the prostate were used for primary cell culture. growth of the prostatic stromal cells was assessed with mtt (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) test and cell numbers were determined by hemocytometry. the effect of estradiol on the production of tgf-beta1 protein and expression of smooth muscle markers such as smooth muscle alpha-actin (sma) and desmin were evaluated by western blot and immunohistochemical staining. the mrna levels of tgf-beta1 and its receptors were analyzed by reverse transcriptase-polymerase chain reaction. we also investigated whether the enhanced expression of sma by estradiol was mediated through the tgf-beta1 pathway using tgf-beta1 blocking antibody. estradiol promoted the proliferation of prostatic stromal cells by 10 to 20. estradiol and tgf-beta1 enhanced sma expression. although the levels of mrna expression of tgf-beta1 or its receptors did not change after estradiol treatment, increased production of tgf-beta1 protein was noted. enhanced expression of sma by estradiol was blocked by tgf-beta1 blocking antibody.","these results suggest that estrogen stimulates the growth of prostatic stromal cells and increases smooth muscle cell markers, which may be achieved through a pathway involving tgf-beta1.",Treatment
does the use of the needle-free jet injection system with buffered lidocaine device change intravenous placement success in children in the emergency department?,"the needle-free jet injection system with buffered lidocaine (j tip) has been shown to reduce pain for intravenous (iv) line insertion, but its relationship with successful iv placement has not been well studied. this study aimed to determine if j tip use is associated with improved first-attempt iv placement success in children. this was a retrospective cohort study of children ages 1 to 18 years with need for emergent iv placement. approximately 300 children were selected from each of three separate age groups: 1 to 2, 3 to 6, and 7 to 18 years. the standard treatment group (no device) included children with iv insertions from january 2009 through january 2010 with no j tip. the j tip treatment group (device) included children with iv insertions from december 2010 through december 2011 who received j tips. successful iv placement on first attempt was the primary outcome. a chi-square test was used to compare the proportion of first-attempt success and logistic regression was performed to assess the effect of device use and patient age, sex, and race on first-attempt success. a total of 958 children were identified, 501 in the no-device group and 457 in the device group. the most common diagnoses were vomiting or dehydration (30.3), trauma or burn (20.0), and infection (15.5). overall, first-attempt success was 69.0 and was similar between the no-device (68.7) and device (69.4) groups (p 0.81). no difference in first-attempt success with the use of the device was found in any of the age groups. multivariate analysis found that only age of 1 to 2 years was associated with lower odds of first-attempt success when controlling for patient characteristics and device use.",the use of the j tip did not affect first-attempt success for iv placement in children.,Medication
is tyrosine kinase b protein expression reduced in the cerebellum of patients with bipolar disorder?,"the role of the cerebellum in coordinating mental activity is supported by its connections with cerebral regions involved in cognitive/affective functioning, with decreased activities on functional neuroimaging observed in the cerebellum of schizophrenia patients performing mental tasks. brain-derived neurotrophic factor (bdnf)-induced activation of tyrosine kinase b (trkb) is essential to synaptic plasticity. we hypothesized that alterations in bdnf and trkb expression in the cerebellum were associated with schizophrenia and affective disorders. we employed immunohistochemistry and immunoblotting to quantify protein expression of bdnf and trkb in the cerebellum of patients with schizophrenia, bipolar disorder, and major depression compared to controls (n15 each). while trkb immunoreactivity in each of the molecular and granule-cell layers was reduced in all 3 disease groups (12-34) compared to the control (p0.018 and 0.038, respectively, anova), only the reduction in bipolar disorder remained statistically significant upon tukey-kramer post hoc analyses (p0.019 and 0.021, respectively). apparent decreases in bdnf immunoreactivity in all 3 disease groups (12-30) compared to the control were not statistically significant. trkb immunoreactivity was not significantly associated with any of the demographic, clinical, and postmortem variables. immunoblotting displayed an 85-kda trkb-immunoreactive band, consistent with a truncated isoform, in all 60 cases.","on immunoblotting, apparent decreases in 85-kda-trkb levels in all 3 disease groups compared to the control were not statistically significant.",General
do an analysis of the uncertainty and bias in dce-mri measurements using the spoiled gradient-recalled echo pulse sequence?,"the pharmacokinetic parameters derived from dynamic contrast-enhanced (dce) mri have been used in more than 100 phase i trials and investigator led studies. a comparison of the absolute values of these quantities requires an estimation of their respective probability distribution function (pdf). the statistical variation of the dce-mri measurement is analyzed by considering the fundamental sources of error in the mr signal intensity acquired with the spoiled gradient-echo (spgr) pulse sequence. the variance in the spgr signal intensity arises from quadrature detection and excitation flip angle inconsistency. the noise power was measured in 11 phantoms of contrast agent concentration in the range 0-1 mm (in steps of 0.1 mm) and in onein vivo acquisition of a tumor-bearing mouse. the distribution of the flip angle was determined in a uniform 10 mm cuso4 phantom using the spin echo double angle method. the pdf of a wide range of t1 values measured with the varying flip angle (vfa) technique was estimated through numerical simulations of the spgr equation. the resultant uncertainty in contrast agent concentration was incorporated in the most common model of tracer exchange kinetics and the pdf of the derived pharmacokinetic parameters was studied numerically. the vfa method is an unbiased technique for measuringt1 only in the absence of bias in excitation flip angle. the time-dependent concentration of the contrast agent measured in vivo is within the theoretically predicted uncertainty. the uncertainty in measuring k(trans) with spgr pulse sequences is of the same order, but always higher than, the uncertainty in measuring the pre-injection longitudinal relaxation time (t10). the lowest achievable bias/uncertainty in estimating this parameter is approximately 20-70 higher than the bias/uncertainty in the measurement of the pre-injection t1 map. the fractional volume parameters derived from the extended tofts model were found to be extremely sensitive to the variance in signal intensity. the snr of the pre-injection t1 map indicates the limiting precision with which k(trans) can be calculated.","current small-animal imaging systems and pulse sequences robust to motion artifacts have the capacity for reproducible quantitative acquisitions with dce-mri. in these circumstances, it is feasible to achieve a level of precision limited only by physiologic variability.",Diagnosis
does transient sympathovagal imbalance trigger ischemic '' sudden death in patients undergoing electrocardiographic holter monitoring?,"the aim of this study was to investigate the relation between ""ischemic"" sudden death (arrhythmic death preceded by st segment shift) and autonomic nervous system activity. background. mechanisms precipitating sudden death are poorly known despite the importance of detecting functional factors that may contribute to such a fatal event. we analyzed the tapes of eight patients (seven men and one woman with a mean age of 66 /- 8 years) who had ischemic sudden death during ambulatory electrocardiographic (holter) monitoring. four patients had unstable and four had stable angina; none was taking antiarrhythmic drugs. twenty patients with angina and transient myocardial ischemia during holter monitoring served as control subjects. arrhythmias, st segment changes and heart rate variability were analyzed by a computerized interactive holter system. five patients had ventricular tachyarrhythmias (ventricular fibrillation in three, ventricular tachycardia in two), and three had bradyarrhythmias (atrioventricular block in two, sinus arrest in one) as the terminal event; all eight patients showed st segment shift (maximal change 0.46 /- 0.16 mv; with st elevation in two) that occurred 41 /- 34 min (mean /- sd) before sudden death. the standard deviation of normal rr intervals (sdnn) was 89 /- 33 ms during the 10 /- 6 h of holter monitoring; 5 min before the onset of the fatal st shift, sdnn measurements were significantly lower than during the initial 5-min period (48 /- 10 vs. 29 /- 9 ms; p0.002). in control patients, the sdnn was 102 /- 39 ms during holter monitoring, whereas it measured 56 /- 30 ms 5 min before the most significant episode of st shift (p0.01 vs. 29 /- 9 ms corrected in the group with sudden death).","autonomic dysfunction, as detected by a marked decrease in heart rate variability, is present in the period (5 min) immediately preceding the onset of the st shift precipitating ischemic sudden death. these data suggest that sympathovagal imbalance may trigger fatal arrhythmias during acute myocardial ischemia, thus resulting in sudden death.",Medication
does the combination oral and nutritional treatment of late-onset diabetes mellitus ( control dm ) trial result?,"to examine the effect of short-term improvements in glycaemic control on brachial artery endothelial function as a marker of cardiovascular health. persons with type 2 diabetes who were poorly controlled on oral therapy were randomly assigned to monotherapy with repaglinide or combination therapy with repaglinide plus metformin. brachial artery flow-mediated vasodilation was assessed by ultrasonography at randomization and following 16 weeks of therapy. the primary outcome was change in brachial artery endothelial function from baseline. comparison of randomized groups was a secondary aim. eighty-six participants were randomized, and 83 were followed to study completion. post occlusion brachial artery vasodilation was 3.74 at baseline and 3.82 following 16 weeks of therapy (p 0.77). the treatment effect was 0.08 (95 ci: -0.48, 0.64). no difference was seen between treatment groups (p 0.69). overall, a1c was reduced from 8.3 to 7.0, with a greater reduction in the combination therapy group (from 8.4 to 6.7) than in the monotherapy group (from 8.3 to 7.3, p for difference between groups 0.01). statistically significant reductions were observed in fasting glucose, and plasminogen activator inhibitor-1. statistically significant increases were observed for fasting insulin, uric acid, weight and bmi.",brachial artery endothelial function was not influenced by short-term improvements in glycaemic control. the control dm group was successful in lowering a1c. future research should explore more intensive and longer-lasting improvements in glycaemic control on endothelial function. some data previously published in abstract form (diabetes 2001; 50 (suppl. 2): a217).,Treatment
does behavioral impulsivity predict naturalistic alcohol consumption or treatment outcomes?,"the purpose of this study was to determine if behavioral impulsivity under multiple conditions (baseline, after alcohol consumption or after serotonin depletion) predicted naturalistic alcohol use or treatment outcomes from a moderation-based contingency management intervention. the current data analysis pulls information from three phases of a large study: 1) phase 1 examined baseline and the effects of alcohol use and serotonin depletion on three types of behavioral impulsivity: response initiation (imt task), response inhibition (gostop task), and delay discounting (skip task); 2) phase 2 involved 28 days of naturalistic drinking; and 3) phase 3 involved 3 months of contingency management. during phases 2 and 3 alcohol use was measured objectively using transdermal alcohol monitors. the results of each individual phase has been previously published showing that at a group level the effects of alcohol consumption on impulsivity were dependent on the component of impulsivity being measured and the dose of alcohol consumed but serotonin depletion had no effect on impulsivity, and that a moderation-based contingency management intervention reduced heavy drinking. the current analysis combining data from those who completed all three phases (","contingency management interventions may prove to be an effective intervention for impulsive individuals, however, normal variations in measured impulsivity do not seem to relate to normal variations in drinking pattern or response to moderation-based contingency management.",Treatment
does exposure to air pollution during different gestational phases contribute to risks of low birth weight?,"although there have been growing concerns about the adverse effects of air pollution on birth outcomes, little is known about which specific exposure times of specific pollutants contribute to low birth weight (lbw). we evaluated the relationships between lbw and air pollution exposure levels in seoul, korea. using the air pollution data, we estimated the exposure during each trimester and also during each month of pregnancy on the basis of the gestational age and birth date of each newborn. generalized additive logistic regression analyses were conducted considering infant sex, birth order, maternal age, parental education level, time trend, and gestational age. the monthly analyses suggested that the risks for lbw tended to increase with carbon monoxide (co) exposure between months 2-5 of pregnancy, with exposure to particles 10 micro m (pm(10)) in months 2 and 4, and for sulphur dioxide (so(2)) and nitrogen dioxide (no(2)) exposure between months 3-5.","this study suggests that exposure to co, pm(10,) so(2) and no(2) during early to mid pregnancy contribute to risks for lbw.",Medication
do region of difference 1 antigen-specific cd4 memory t cells correlate with a favorable outcome of tuberculosis?,"interferon (ifn)-gamma response to region of difference (rd) 1 proteins (culture filtrate 10 and early secreted antigenic target 6) or overlapping peptides is a novel diagnostic marker of tuberculosis (tb) infection. because we have recently shown that the response to certain peptides selected from rd1 allows discrimination between active tb (a-tb) and successfully treated tb (t-tb), we analyzed here the effector memory t cell profile and rd1-specific responses under the same clinical conditions. t cell responses to rd1 antigens were analyzed in patients with either severe or mild a-tb (classified on the basis of radiological lesions) and in 2 sets of healthy control subjects--those who had been successfully treated (the t-tb control subjects) and those whose tuberculin skin test (tst) results were negative (the tst-negative control subjects). ifn-gamma -producing cd4 effector t cells were monitored by flow-cytometric analysis and ex vivo enzyme-linked immunospot (elispot) assay, whereas a ""cultured"" elispot assay was used to determine the frequency of memory t cells. in the patients with severe a-tb, both cd4-mediated effector memory and central memory responses to the selected rd1 peptides were almost absent, whereas these responses were found in the majority of the patients with mild a-tb. in contrast, recognition of the selected rd1 peptides was detected in the t-tb control subjects only by expanding the central memory t cell pool.","these data suggest a protective role for rd1 peptide-specific cd4 effector t cells, which undergo clonal expansion during mycobacterium tuberculosis replication and then a contraction phase after disease resolution, culminating in the generation of cd4 memory t cells.",Diagnosis
do opportunities and challenges for tcr mimic antibodies in cancer therapy?,"monoclonal antibodies (mabs) are potent cancer therapeutic agents, but exclusively recognize cell-surface targets whereas most cancer-associated proteins are found intracellularly. hence, potential cancer therapy targets such as over expressed self-proteins, activated oncogenes, mutated tumor suppressors, and translocated gene products are not accessible to traditional mab therapy. an emerging approach to target these epitopes is the use of tcr mimic mabs (tcrm) that recognize epitopes similar to those of t cell receptors (tcr). tcrm antigens are composed of a linear peptide sequence derived from degraded proteins and presented in the context of cell-surface mhc molecules. we discuss how the nature of the tcrm epitopes provides both advantages (absolute tumor specificity and access to a new universe of important targets) and disadvantages (low density, mhc restriction, mhc down-regulation, and cross-reactive linear epitopes) to conventional mab therapy. we will also discuss potential solutions to these obstacles.","tcrm combine the specificity of tcr recognition with the potency, pharmacologic properties, and versatility of mabs. the structure and presentation of a tcrm epitope has important consequences related to the choice of targets, mab design, available peptides and mhc subtype restrictions, possible cross-reactivity, and therapeutic activity.",Treatment
does optical coherence tomography enable imaging of tumor initiation in the tag-rb mouse model of retinoblastoma?,"retinoblastoma is the most common primary intraocular malignancy in children. although significant advances in treatment have decreased mortality in recent years, morbidity continues to be associated with these therapies, and therefore, there is a pressing need for new therapeutic options. transgenic mouse models are popular for testing new therapeutics as well as studying the pathophysiology of retinoblastoma. the t-antigen retinoblastoma (tag-rb) model has close molecular and histological resemblance to human retinoblastoma tumors; these mice inactivate prb by retinal-specific expression of the simian virus 40 t-antigens. here, we evaluated whether optical coherence tomography (oct) imaging could be used to document tumor growth in the tag-rb model from the earliest stages of tumor development. the micron iii rodent imaging system was used to obtain fundus photographs and oct images of both eyes of tag-rb mice weekly from 2 to 12 weeks of age and at 16 and 20 weeks of age to document tumor development. tumor morphology was confirmed with histological analysis. before being visible on funduscopy, hyperreflective masses arising in the inner nuclear layer were evident at 2 weeks of age with oct imaging. after most of these hyperreflective cell clusters disappeared around 4 weeks of age, the first tumors became visible on oct and funduscopy by 6 weeks. the masses grew into discrete, discoid tumors, preferentially in the periphery, that developed more irregular morphology over time, eventually merging and displacing the inner retinal layers into the vitreous.","oct is a non-invasive imaging modality for tracking early tag-rb tumor growth in vivo. using oct, we characterized tag-positive cells as early as 2 weeks, corresponding to the earliest stages at which tumors are histologically evident, and well before they are evident with funduscopy. tracking tumor growth from its earliest stages will allow better analysis of the efficacy of novel therapeutics and genetic factors tested in this powerful mouse model.",Diagnosis
does hepatic ratio of phosphatidylcholine to phosphatidylethanolamine predict survival after partial hepatectomy in mice?,"a major predictor of failed liver resection and transplantation is nonalcoholic fatty liver disease (nafld). nafld is linked to a wide spectrum of diseases including obesity and diabetes that are increasingly prevalent in western populations. thus, it is important to develop therapies aimed at improving posthepatectomy outcomes in patients with nafld, as well as to improve the evaluation of patients slated for hepatic surgery. decreased hepatic phosphatidylcholine (pc) content and decreased ratio of hepatic pc to phosphatidylethanolamine (pe) have previously been linked to nafld. to determine if decreased hepatic pc/pe could predict survival after hepatectomy, we used mouse models lacking key enzymes in pc biosynthesis, namely, phosphatidylethanolamine n-methyltransferase and hepatic-specific ctp:phosphocholine cytidylyltransferase . these mice were fed a high-fat diet to induce nafld. we then performed a 70 partial hepatectomy and monitored postoperative survival. we identified hepatic pc/pe to be inversely correlated with the development of steatosis and inflammation in the progression of nafld. decreased hepatic pc/pe before surgery was also strongly associated with decreased rates of survival after partial hepatectomy. choline supplementation to the diet increased hepatic pc/pe in pemt(-/-) mice with nafld, decreased inflammation, and increased the survival rate after partial hepatectomy.",decreased hepatic pc/pe is a predictor of nafld and survival following partial hepatectomy. choline supplementation may serve as a potential therapy to prevent the progression of nafld and to improve postoperative outcome after liver surgery.,Treatment
are bone geometry and strength adapted to muscle force in children and adolescents perinatally infected with hiv?,"to determine if bone health is compromised in perinatally hiv-infected youth. we assessed bmc at the proximal femur, lumbar spine and total body using dxa in perinatally hiv-infected youth (n31; 9-18y). using pqct, we assessed muscle csa, total and cortical bone area, cortical bmd and thickness and strength strain index at the tibial shaft. thirty and 18 participants returned at 12- and 24-months, respectively. we calculated age- and sex-specific z-scores for the hiv-infected youth using data from a healthy cohort (n883; 9-18y). at baseline, height and mcsa were reduced in hiv-infected youth (-0.79 to -0.23, p0.05). bmc z-scores adjusted for height and lean mass were lower than controls at all sites except the lumbar spine (-0.57 to -0.27, p0.05). bone area and strength z-scores were not different from zero after adjusting for tibial length and mcsa. in contrast, cortical bmd z-scores were greater in hiv-infected youth (0.46, p0.011). z-scores for all bone outcomes showed positive trends over time in hiv-infected youth.","although hiv infection may be associated with bone mass deficits during growth, bone geometry and strength appear adapted to muscle force. further, deficits in bone mass may dissipate over time in this population.",General
is breast cancer-associated gene 3 ( bca3 ) a novel rac1-interacting protein?,"bca3 was identified in a yeast two-hybrid screen as a novel rac1-interacting partner in osteoclasts. bca3 binds directly to rac and, in vivo, binds gtp-rac but not gdp-rac. perinuclear co-localization of bca3 and rac1 is observed in csf-1-treated osteoclasts. overexpression of bca3 attenuates csf-1-induced cell spreading. we conclude that bca3 regulates csf-1-dependent rac activation. rac1, a ubiquitously expressed gtpase, is a mediator of colony-stimulating factor 1 (csf-1)-dependent actin remodeling in osteoclasts. because the role of rac in osteoclasts has not been fully defined, we undertook a yeast two-hybrid screen to identify rac-interacting partners in these cells. a yeast two-hybrid screen was undertaken using a cdna library prepared from osteoclast-like cells as prey and either native rac1 or constitutively active rac1 (q61l) as bait. radiolabeled breast cancer-associated gene 3 (bca3) protein constructs were generated in vitro using rabbit reticulate lysates and used in vitro binding assays with rac1. in vivo binding was assessed using myc-tagged rac1(q61l) and ha-tagged bca3. pbd pull-down assays were used to determine if gtp-loaded rac1 preferentially bound bca3. co-localization of rac1 and bca3 in osteoclasts was assessed using confocal immunofluorescence. the functional significance of the bca3-rac1 interaction was assessed by examining the effect of overexpressing bca3 in raw 264.7 cells on the subsequent spreading response to csf-1. one of three positive clones from the wildtype rac1 screen and all three positive clones from the rac1(q61l) screen encoded the same protein, bca3. bca3 expression in osteoclasts was confirmed by rt-pcr and immunocytochemistry. bca3 bound directly to rac1 in vitro. deletional analysis indicated that amino acids 76-125 in bca3 are important for its ability to bind rac. in vivo association of the two proteins was shown by co-immunoprecipitation of bca3 and rac1. only gtp-bound-rac but not gdp-bound rac could interact with bca3 in vivo. confocal immunocytochemistry showed perinuclear co-localization of bca3 and rac1 in csf-1-treated neonatal rat osteoclasts but not in resting osteoclasts. overexpression of bca3 markedly attenuated the spreading response to csf-1 in raw 264.7 cells.",these data establish that bca3 is a novel rac1-interacting protein and suggest that it may influence the ability of rac1 to remodel the actin cytoskeleton.,Treatment
are the contrasting relationships between betaine and homocysteine in two clinical cohorts associated with plasma lipids and drug treatments?,"urinary betaine excretion positively correlated with plasma homocysteine in outpatients attending a lipid disorders clinic (lipid clinic study). we aimed to confirm this in subjects with established vascular disease. the correlation between betaine excretion and homocysteine was compared in samples collected from subjects 4 months after hospitalization for an acute coronary episode (acs study, 415 urine samples) and from 158 sequential patients visiting a lipid disorders clinic. in contrast to the lipid clinic study, betaine excretion and plasma homocysteine did not correlate in the total acs cohort. differences between the patient groups included age, non-hdl cholesterol and medication. in acs subjects with below median betaine excretion, excretion correlated (using log transformed data) negatively with plasma homocysteine (r -0.17, p 0.019, n 199), with no correlation in the corresponding subset of the lipid clinic subjects. in acs subjects with above median betaine excretion a positive trend (r 0.10) between betaine excretion and homocysteine was not significant; the corresponding correlation in lipid clinic subjects was r 0.42 (p 0.0001). in acs subjects, correlations were stronger when plasma non-hdl cholesterol and betaine excretion were above the median, r 0.20 (p 0.045); in subjects above median non-hdl cholesterol and below median betaine excretion, r -0.26 (p 0.012). acs subjects taking diuretics or proton pump inhibitors had stronger correlations, negative with lower betaine excretion and positive with higher betaine excretion.",betaine excretion correlates with homocysteine in subjects with elevated blood lipids.,Medication
is congestive heart failure a risk factor for venous thromboembolism in bariatric surgery?,"venous thromboembolism (vte) is a major complication of bariatric surgery leading to significant morbidity and mortality. we sought to identify predictive factors that increase the risk of deep venous thrombosis (dvt) and pulmonary embolism (pe) using data from the national surgical quality improvement program (nsqip). patients undergoing bariatric procedures from 2005-2012 were identified in the nsqip database. pretreatment patient characteristics were examined by laparoscopic and open treatment groups using t tests and chi-square regression. independent associations between patient characteristics and dvt and pe were examined using logistic regression. logistic regression was also used to examine whether patients who had postprocedure dvt or pe were more likely than those who did not have these events to have additional morbidity and mortality outcomes. 102,869 patients underwent bariatric surgery (96,085 laparoscopic; 6,784 open) from 2005-2012. preoperative variables associated with increased risk of dvt in laparoscopic bariatric surgery are male gender, higher bmi, congestive heart failure (chf), and hypertension (htn). preoperative variables associated with increased risk of pe in laparoscopic bariatric surgery are male gender, age greater than or equal to 60, higher bmi, african american race, chronic obstructive pulmonary disease (copd) and chf. there are no preoperative variables associated with an increased risk of dvt in open bariatric surgery although there is a trend toward significance with chf. finally, higher bmi and chf is associated with an increased risk of pe in open bariatric surgery.",chf is a significant risk factor for vte in bariatric surgery. surgeons should consider aggressive screening and vte prophylaxis in patients with chf and other known risk factors to decrease postoperative morbidity from vte.,Treatment
is elevated expression of nodal and yap1 associated with poor prognosis of gastric adenocarcinoma?,"to investigate the correlation between nodal and yap1 expression and the clinicopathological characteristics of gastric adenocarcinoma (gac). quantitative real-time rt-pcr, western blot, and immunohistochemistry were performed to measure nodal and yap1 mrna and protein in 20 fresh frozen samples and 220 paraffin-embedded gac tissues with their paired non-tumor mucosa (pntm). the prognostic values of nodal and yap1 were evaluated in 161 gac patients using univariate and multivariate analyses. both mrna and protein expression of nodal and yap1 were significantly increased in gac compared to pntm (p 0.05). immunohistochemistry showed that nodal was more highly expressed in 56.4 gac samples compared to pntm; additionally, nodal expression correlated with depth of tumor invasion, lymph node metastasis, and distant metastasis (all p 0.05). there was no association between nodal and yap1 in gac (p 0.171). kaplan-meier analysis showed that the outcome of nodal-high patients was significantly worse than those with low nodal expression ( (2) 30.452, p 0.001). cox multivariate regression showed that high nodal expression was an independent risk factor affecting the prognosis of gac patients (p 0.000, rr 2.976). furthermore, patients with tumors in which both nodal and yap1 were expressed at high levels had the worst prognosis.",elevated nodal expression is a marker of poor prognosis in gastric cancer. patient outcome is further worsened if nodal and yap1 are both expressed in the same tumor. the datas we present here suggest that the inhibition of nodal signaling may represent a new therapeutic strategy for the treatment of gastric adenocarcinoma.,Diagnosis
do c-myc antisense oligonucleotides sensitize human colorectal cancer cells to chemotherapeutic drugs?,"overexpression of the c-myc oncogene frequently occurs in both colon tumors and colon carcinoma cell lines. we examined the sensitization of human colorectal cancer cells to chemotherapeutic drugs using c-myc antisense (as) phosphorothioate oligonucleotides (sodns). cancer cells were treated with c-myc sodns, taxol, 5-fluorouracil (5-fu), doxorubicin and vinblastine individually and in combination. the antiproliferative effects, type of interaction between c-myc sodns and cytotoxic drugs, cell cycle, apoptosis and expression of cell-cycle- and apoptosis-regulatory genes were evaluated. after treatment with c-myc assodns, the growth of cancer cells was markedly inhibited in a dose- and time-dependent manner and the levels of c-myc mrna and protein were greatly decreased (p 0.0001). the combinations of c-myc assodns and cytotoxic drugs produced greater growth inhibition of human colorectal cancer cells compared to single treatment with either c-myc assodns (p 0.006) or cytotoxic drugs (p 0.0001). these combinations exhibited time- and dose-dependent additive and/or synergistic antiproliferative effects. cancer cells treated with cytotoxic drugs were growth arrested in the s phase. in contrast, cells treated with either c-myc assodns or by the combination of c-myc assodns and cytotoxic drugs were growth arrested in the g(2)/m and s phases. the combination treatments also exhibited a marked apoptotic effect compared to single treatments. c-myc assodn treatment reduced the mrna levels of bcl2, bclxl, cdk2, cyclin e1, cdk1 and cyclin b1, while increasing the mrna levels of p21, p27, bax and caspase-3.",this two-hit approach may be important in the quest to overcome drug resistance in cancer patients whose tumors carry an overexpressed c-myc gene.,Medication
is henoch-schnlein purpura in adults uncommon in elderly patients with an adverse prognosis?,"henoch-schnlein purpura (hsp) is a fairly common disease in children and adolescents. there are only limited data available for adults. a retrospective analysis was conducted to study renal manifestations in patients with hsp treated in our institution between 1982 and 2007. we divided our adult cohort according to age - under or over 60 years - to examine differences in elderly patients. hsp was identified in 2.2 of patients referred to us for kidney biopsy. purpuric lesions and renal involvement were found in all patients. an important triggering factor for the development of hsp in our series was chronic alcohol intake. forty percent of our patients fulfilled the who criteria for alcoholics. renal involvement was particularly prominent in patients over 60 years of age. at disease onset, estimated glomerular filtration rate (egfr) was 63 lower in the elderly. within a median follow-up of 8 years, renal function was significantly better in younger adults than in the elderly. 32 of the elderly have shown modification of diet in renal disease (mdrd) 20 ml/min/1.73 m2 in contrast to only 7 in patients 60 years. furthermore, significantly more elderly patients reached end-stage renal failure.","the data indicate that renal manifestation of hsp in the elderly is severe and its outcome relatively poor, and worsens when compared to patients 60 years.",Diagnosis
is a non-synonymous single-nucleotide polymorphism in the gene encoding toll-like receptor 3 ( tlr3 ) associated with sero-negative rheumatoid arthritis ( ra ) in a danish population?,"it has been suggested that polymorphisms in toll-like receptors (tlrs) are associated with rheumatoid arthritis (ra), but the implicated alleles have differed between studies. the aim of this investigation was to explore whether polymorphisms of tlr genes are associated with ra in a predominantly caucasian population from denmark using a case-control approach. dna samples (3 university hospital outpatient clinics) were obtained from patients with ra (n 704) and healthy controls (n 639) in a danish population. tlr single nucleotide polymorphisms (snps) were selected based on the previously reported associations with chronic autoimmune diseases. genotyping for the tlr snps was performed using sequenom multiplex technology.we identified one snp in tlr3, (rs3775291, p 0.02, or (95 ci) 1.31 (1.1087-1.5493) significantly associated with the whole ra cohort. subgroup analysis according to igm rheumatoid factor (rf) and anti-cyclic citrinullated peptide (ccp) status suggested a significant association of sero-negative ra with the rs3775291 a allele and disease activity in this subset.","these observations on a ra population of danish ancestry suggest that variations in the tlr3 locus may be implicated in the pathogenesis of sero-negative ra. since this tlr3 snp has previously been associated with systemic lupus erythematous (sle), the present findings support the notion that tlr3 genetic variants may represent a common risk factor in different chronic inflammatory conditions, including ra and sle.",Medication
does bim mediate egfr tyrosine kinase inhibitor-induced apoptosis in lung cancers with oncogenic egfr mutations?,"epidermal growth factor receptor (egfr) mutations are present in the majority of patients with non-small cell lung cancer (nsclc) responsive to the egfr tyrosine kinase inhibitors (tkis) gefitinib or erlotinib. these egfr-dependent tumors eventually become tki resistant, and the common secondary t790m mutation accounts for half the tumors with acquired resistance to gefitinib. however, the key proapoptotic proteins involved in tki-induced cell death and other secondary mutations involved in resistance remain unclear. the objective of this study was to identify the mechanism of egfr tki-induced apoptosis and secondary resistant mutations that affect this process. to study tki-induced cell death and mechanisms of resistance, we used lung cancer cell lines (with or without egfr mutations), ba/f3 cells stably transfected with egfr mutation constructs, and tumor samples from a gefitinib-resistant patient. here we show that up-regulation of the bh3-only polypeptide bim (also known as bcl2-like 11) correlated with gefitinib-induced apoptosis in gefitinib-sensitive egfr-mutant lung cancer cells. the t790m mutation blocked gefitinib-induced up-regulation of bim and apoptosis. this blockade was overcome by the irreversible tki cl-387,785. knockdown of bim by small interfering rna was able to attenuate apoptosis induced by egfr tkis. furthermore, from a gefitinib-resistant patient carrying the activating l858r mutation, we identified a novel secondary resistant mutation, l747s in cis to the activating mutation, which attenuated the up-regulation of bim and reduced apoptosis.",our results provide evidence that bim is involved in tki-induced apoptosis in sensitive egfr-mutant cells and that both attenuation of the up-regulation of bim and resistance to gefitinib-induced apoptosis are seen in models that contain the common egfr t790m and the novel l747s secondary resistance mutations. these findings also suggest that induction of bim may have a role in the treatment of tki-resistant tumors.,Medication
does overrides of medication-related clinical decision support alert in outpatients?,"electronic prescribing is increasingly used, in part because of government incentives for its use. many of its benefits come from clinical decision support (cds), but often too many alerts are displayed, resulting in alert fatigue. to characterize the override rates for medication-related cds alerts in the outpatient setting, the reasons cited for overrides at the time of prescribing, and the appropriateness of overrides. we measured cds alert override rates and the coded reasons for overrides cited by providers at the time of prescribing. our primary outcome was the rate of cds alert overrides; our secondary outcomes were the rate of overrides by alert type, reasons cited for overrides at the time of prescribing, and override appropriateness for a subset of 600 alert overrides. through detailed chart reviews of alert override cases, and selective literature review, we developed appropriateness criteria for each alert type, which were modified iteratively as necessary until consensus was reached on all criteria. we reviewed 157,483 cds alerts (7.9 alert rate) on 2,004,069 medication orders during the study period. 82,889 (52.6) of alerts were overridden. the most common alerts were duplicate drug (33.1), patient allergy (16.8), and drug-drug interactions (15.8). the most likely alerts to be overridden were formulary substitutions (85.0), age-based recommendations (79.0), renal recommendations (78.0), and patient allergies (77.4). an average of 53 of overrides were classified as appropriate, and rates of appropriateness varied by alert type (p0.0001) from 12 for renal recommendations to 92 for patient allergies.","about half of cds alerts were overridden by providers and about half of the overrides were classified as appropriate, but the likelihood of overriding an alert varied widely by alert type. refinement of these alerts has the potential to improve the relevance of alerts and reduce alert fatigue.",Medication
is prevalence of plasma small dense ldl increased in obesity in a thai population?,"plasma low density lipoprotein (ldl) particles vary in size, density, electrical charge and chemical composition. an increased presence of small dense ldl (sdldl), along with raised triglyceride concentrations and decreased high density lipoprotein (hdl) cholesterol concentrations is commonly known as the atherogenic triad and has been observed in some cases of obesity, principally in europe and america. this study examines the prevalence of sdldl in the plasma of an obese (bmi25 kg/m2) thai population. plasma from fasted obese (n48) and non-obese (n16) thai participants was subjected to density gradient ultracentrifugation in iodixanol to separate lipoproteins. gradients were unloaded top-to-bottom into 20 fractions which were assayed for cholesterol, triglyceride, apo b and apo a-1 to identify lipoprotein types and subtypes. ldl cholesterol was subfractionated into ldl iii (fractions 3-6, 1.021-1.033 g/ml) which was considered to represent large buoyant ldl (lbldl), ldl iii (fractions 7-9, 1.036-1.039 g/ml) which was considered to represent sdldl, and, ldl iv (fractions 10-12, 1.044-1.051 g/ml) which was considered to represent very sdldl. concentrations of ldl iii and iv were increased by 15-20 in obese participants whilst that of ldl iii was concomitantly decreased by 10. this was accompanied by a 50 increase in plasma triglyceride concentrations and 15 decrease in hdl cholesterol concentrations. only 3/16 (19) non-obese participants had a pattern b ldl cholesterol profile (peak density of 1.033 g/ml), whilst 28/48 (58) obese participants were pattern b. when expressed as a fraction of the ldl concentration, total sdldl (i.e. ldl iiiiv) showed highly significant correlations to plasma triglyceride concentrations and the triglyceride/hdl cholesterol ratio.",the prevalence of sdldl is increased in obesity in a thai population such that they demonstrate a similar atherogenic triad to that previously observed in european and american populations.,Prevention
does implementation of a patient selection protocol for intra-arterial therapy increase treatment rates in patients with acute ischemic stroke?,"strategies for patient selection for intra-arterial therapy (iat) in acute ischemic stroke (ais) are highly variable. the degree of protocol adoption and treatment rates associated with implementation of a service-wide patient selection iat protocol were assessed. all patients with ais prospectively recorded in our stroke database from january 2007 to june 2009 were reviewed. the iat patient selection protocol was implemented in march 2008. patients were defined as likely to benefit (ltb) from iat if they had brain imaging completed within 6 h from last known well time, nih stroke scale score 8, infarct volume 100 ml and evidence of proximal artery occlusion. of 1348 subjects identified, 118 (8.7) met the criteria for ltb and 62 (52) underwent iat. there was a significant increase in rates of iat among ltb patients after protocol implementation (61 vs 40, p0.02). in ltb patients, factors associated with iat were stroke duration (or 0.78, 95 ci 0.6 to 0.9 per hour), arrival within later calendar months during study period (or 1.1, 95 ci 1.02 to 1.2 per month), intravenous tissue plasminogen activator (or 0.6, 95 ci 0.4 to 0.9) and age (or 0.98, 95 ci 0.95 to 1.02 per year). after multivariable adjustment, only stroke duration (or 0.65, 95 ci 0.5 to 0.8 per hour) remained an independent predictor of iat.","most patients with ais did not meet our criteria for ltb and only 52 of those defined as ltb received iat. protocol adoption increased the use of iat over time; however, further exploration of factors associated with the reasons for non-treatment and the impact of iat on outcomes is necessary.",Treatment
is the effect of electrical stimulation on corticospinal excitability dependent on application duration : a same subject pre-post test design?,"in humans, corticospinal excitability is known to increase following motor electrical stimulation (es) designed to mimic a voluntary contraction. however, whether the effect is equivalent with different application durations and whether similar effects are apparent for short and long applications is unknown. the aim of this study was to investigate whether the duration of peripheral motor es influenced its effect on corticospinal excitability. the excitability of the corticomotor pathway to abductor pollicis brevis (apb) was measured in fourteen health subjects using transcranial magnetic stimulation before, immediately after and 10 minutes after three different durations (20-, 40-, 60-min) of motor es (30hz, ramped). this intervention was designed to mimic a voluntary contraction in apb. to control for effects of motor es on the peripheral elements (muscle fibre, membrane, neuromuscular junction), maximum compound muscle actions potentials (m-waves) were also recorded at each time point. results were analysed using a repeated measures analysis of variance. peripheral excitability was reduced following all three motor es interventions. conversely, corticospinal excitability was increased immediately following 20- and 40-min applications of motor es and this increase was maintained at least 20-min following the intervention. a 60-min application of motor es did not alter corticospinal excitability.","a 20-min application of motor es that is designed to mimic voluntary muscle contraction is as effective as that applied for 40-min when the aim of the intervention is to increase corticospinal excitability. longer motor es durations of 60-min do not influence corticospinal excitability, possibly as a result of homeostatic plasticity mechanisms.",Treatment
do 3-polyunsaturated fatty acids suppress lipoprotein-associated phospholipase a2 expression in macrophages and animal models?,"3-polyunsaturated fatty acids (3-pufas) have beneficial effects on cardiovascular function, and lipoprotein-associated phospholipase a2 (lp-pla2 ) is associated with the risk of cardiovascular disease. here, we investigated the effects of 3-pufas on lp-pla2 expression in vitro and in vivo and explored the mechanisms involved. human monocyticcells (thp-1) were induced into macrophages in an in vitro model. 3-pufas suppressed lp-pla2 expression; the suppression induced by docosahexaenoic acid (dha) was related to reduced inflammation. tumor necrosis factor- (tnf-) was employed to stimulate the phosphorylation of p38 mitogen-activated protein kinase (mapk), nuclear factor-b (nf-b) p65 and lp-pla2 expression in macrophages. the stimulation was inhibited by dha and the anti-inflammatory drug sodium salicylate. moreover, the stimulation of lp-pla2 expression by tnf- could be suppressed by nf-b and mapk pathway inhibitors. then, chronic inflammation was induced in an in vivo mouse model, resulting in an increase in lp-pla2 expression in peripheral blood mononuclear cells (pbmcs) and arteries. this increase was suppressed by 3-pufas. inhibition of lp-pla2 transcription in pbmcs was also observed in 3-pufa-enriched swine.",our results demonstrate that the protective effects of 3-pufas against cardiovascular events may be related to the suppression of lp-pla2 levels.,Medication
are homologs of genes expressed in caenorhabditis elegans gabaergic neurons also found in the developing mouse forebrain?,"in an effort to identify genes that specify the mammalian forebrain, we used a comparative approach to identify mouse homologs of transcription factors expressed in developing caenorhabditis elegans gabaergic neurons. a cell-specific microarray profiling study revealed a set of transcription factors that are highly expressed in embryonic c. elegans gabaergic neurons. bioinformatic analyses identified mouse protein homologs of these selected transcripts and their expression pattern was mapped in the mouse embryonic forebrain by in situ hybridization. a review of human homologs indicates several of these genes are potential candidates in neurodevelopmental disorders.",our comparative approach has revealed several novel candidates that may serve as future targets for studies of mammalian forebrain development.,General
does antigen challenge induce a supraglottic but not a subglottic edema in the rat larynx?,"to examine the reaction of mast cells in the larynx of sensitized rats after allergen challenge and determine whether a type i hypersensitivity reaction can elicit a supraglottic and subglottic edema. rats were sensitized with ovalbumin (oa) and challenged 3 weeks later by intravenous injection of either oa or nacl and perfused with glutaraldehyde. the larynges were removed and processed for light and electron microscopy. sections from the epiglottis and subglottic region were examined. in challenged animals, the connective tissue mast cells (ctmc) in the epiglottic submucosa, but not the mucosal mast cells (mmc) in epithelium, were significantly reduced compared with the case of controls, and the connective tissue was edematous. in the subglottic region, the number of both mmc and ctmc was reduced (albeit not significantly), and there was no edema in the lamina propria.",allergen challenge induces a marked edema in the epiglottis but not in the subglottic area.,Medication
is conscious level in children with diabetic ketoacidosis related to severity of acidosis and not to blood glucose concentration?,"to ascertain whether initial depression of conscious level in children with diabetic ketoacidosis (dka) is related to hyperosmolality, acidosis or other factors. in 225 episodes of dka without evidence of cerebral edema, we examined the relationship between conscious level and initial biochemical variables. we contrasted these findings with those in 42 children who later developed cerebral oedema. on admission, 42/225 (19) had mild (ph 7.26-7.35); 96 (44) moderate (ph 7.11-7.25); and 80 (37) severe dka (ph or 7.10). conscious level: alert and oriented (group 1, n123), drowsy but oriented when woken (group 2, n62), semi-conscious or confused/agitated (group 3, n9), comatose (group 4, n4). glasgow coma score (gcs) was available in 65. ph varied significantly with conscious level; group 1, 7.20/- 0.11(mean/- sd); group 2, 7.10/- 0.16; group 3, 6.96/- 0.11; group 4, 6.88/- 0.09 (anova, p0.001). blood glucose (bg) was not different between the groups. gcs was related to ph (r(s) 0.49, p 0.001), but not to bg or electrolyte levels. age, sex, plasma sodium, corrected sodium and osmolality also varied with conscious level in a univariate model. using multivariate analysis comparing groups 1 with groups 2-4, lower ph and younger age were the only independent determinants of impaired conscious level (p0.001, p0.036). conscious level in the children with cerebral edema was also closely related to ph and not to other biochemical variables. ph was lower at each conscious level in the children with later cerebral edema.","in children with dka, initial conscious level is closely related to ph and weakly to age, but not to bg or plasma sodium level. thus cerebral function in dka is related to severity of acidosis even when there is no evidence of cerebral edema.",General
is hpv e6/e7 mrna testing more specific than cytology in post-colposcopy follow-up of women with negative cervical biopsy?,"in norway, women with negative or low-grade cervical biopsies (normal/cin1) are followed up after six months in order to decide on further follow-up or recall for screening at three-year intervals. a high specificity and positive predictive value (ppv) of the triage test is important to avoid unnecessary diagnostic and therapeutic procedures whereas a low risk of high-grade disease among triage negative women assures safety. at the university hospital of north norway, cytology and the hpv mrna test pretect hpv-proofer, detecting e6/e7 mrna from hpv types 16, 18, 31, 33 and 45, are used in post-colposcopy follow-up of women with negative or low-grade biopsy. in this study, women with negative biopsy after high grade cytology (asc-h/hsil) and/or positive hpv mrna test in the period 2005-2009 were included (n 520). histologically confirmed cervical intraepithelial neoplasia of grade 2 or worse (cin2) was used as study endpoint. of 520 women with negative or low-grade biopsy, 124 women (23.8) had cin2 in follow-up biopsy. the sensitivity and specificity of the hpv mrna test were 89.1 (95 ci, 80.1-98.1) and 92.5 (95 ci, 88.2-96.7), respectively. the ratios of sensitivity, specificity and ppv of hpv mrna testing compared to repeat cytology for finding cin2 was 1.05 (95 ci: 0.92-1.21), 1.21 (95 ci: 1.12-1.32), and 1.49 (95 ci: 1.20-1.86), respectively. the ppv of mrna was 77.3 (95 ci, 59.8-94.8) in women aged 40 or older.","women with negative cervical biopsy require follow-up before resumption of routine screening. post-colposcopy hpv mrna testing was as sensitive but more specific than post-colposcopy cytology. in addition, the hpv mrna test showed higher ppv. a positive mrna test post-colposcopy could justify treatment in women above 40 years.",Diagnosis
is skeletal muscle radiodensity prognostic for survival in patients with advanced non-small cell lung cancer?,"recent research indicates that severe muscular depletion (sarcopenia) is frequent in cancer patients and linked to cachexia and poor survival. our aim was to investigate if measures of skeletal muscle hold prognostic information in advanced non-small cell lung cancer (nsclc). we included nsclc patients with disease stage iiib/iv, performance status 0-2, enrolled in three randomised trials of first-line chemotherapy (n 1305). computed tomography (ct) images obtained before start of treatment were used for body composition analyses at the level of the third lumbar vertebra (l3). skeletal muscle mass was assessed by measures of the cross sectional muscle area, from which the skeletal muscle index (smi) was obtained. skeletal muscle radiodensity (smd) was measured as the mean hounsfield unit (hu) of the measured muscle area. a high level of mean hu indicates a high smd. complete data were available for 734 patients, mean age 65 years. both skeletal muscle index (smi) and muscle radiodensity (smd) varied largely. mean smi and smd were 47.7 cm",low smd is associated with poorer survival in advanced nsclc. further research is warranted to establish whether muscle measures should be integrated into routine practice to improve prognostic accuracy.,Diagnosis
does variation in 12 porcine genes involved in the carbohydrate moiety assembly of glycosphingolipids account for differential binding of f4 escherichia coli and their fimbriae?,"glycosphingolipids (gsls) are important membrane components composed of a carbohydrate structure attached to a hydrophobic ceramide. they can serve as specific membrane receptors for microbes and microbial products, such as f4 escherichia coli (f4 etec) and isolated f4 fimbriae. the aim of this study was to investigate the hypothesis that variation in genes involved in the assembly of the f4 binding carbohydrate moiety of gsls (i.e. arsa, b4galt6, gal3st1, galc, gba, gla, glb1, glb1l, neu1, neu2, ugcg, ugt8) could account for differential binding of f4 etec and their fimbriae. rt-pcr could not reveal any differential expression of the 12 genes in the jejunum of f4 receptor-positive (f4r()) and f4 receptor-negative (f4r(-)) pigs. sequencing the complete open reading frame of the 11 expressed genes (neu2 was not expressed) identified 72 mutations. although some of them might have a structural effect, none of them could be associated with a f4r phenotype.",we conclude that no regulatory or structural variation in any of the investigated genes is responsible for the genetic susceptibility of pigs towards f4 etec.,Diagnosis
is estrogen-mediated renoprotection following cardiac arrest and cardiopulmonary resuscitation robust to gpr30 gene deletion?,"acute kidney injury is a serious,sexually dimorphic perioperative complication, primarily attributed to hypoperfusion. we previously found that estradiol is renoprotective after cardiac arrest and cardiopulmonary resuscitation in ovariectomized female mice. additionally, we found that neither estrogen receptor alpha nor beta mediated this effect. we hypothesized that the g protein estrogen receptor (gpr30) mediates the renoprotective effect of estrogen. ovariectomized female and gonadally intact male wild-type and gpr30 gene-deleted mice were treated with either vehicle or 17-estradiol for 7 days, then subjected to cardiac arrest and cardiopulmonary resuscitation. twenty four hours later, serum creatinine and urea nitrogen were measured, and histologic renal injury was evaluated by unbiased stereology. in both males and females, gpr30 gene deletion was associated with reduced serum creatinine regardless of treatment. estrogen treatment of gpr30 gene-deleted males and females was associated with increased preprocedural weight. in ovariectomized female mice, estrogen treatment did not alter resuscitation, but was renoprotective regardless of gpr30 gene deletion. in males, estrogen reduced the time-to-resuscitate and epinephrine required. in wild-type male mice, serum creatinine was reduced, but neither serum urea nitrogen nor histologic outcomes were affected by estrogen treatment. in gpr30 gene-deleted males, estrogen did not alter renal outcomes. similarly, renal injury was not affected by g1 therapy of ovariectomized female wild-type mice.","treatment with 17-estradiol is renoprotective after whole-body ischemia-reperfusion in ovariectomized female mice irrespective of gpr30 gene deletion. treatment with the gpr30 agonist g1 did not alter renal outcome in females. we conclude gpr30 does not mediate the renoprotective effect of estrogen in ovariectomized female mice. in males, estrogen therapy was not renoprotective. estrogen treatment of gpr30 gene-deleted mice was associated with increased preprocedural weight in both sexes. of significance to further investigation, gpr30 gene deletion was associated with reduced serum creatinine, regardless of treatment.",Treatment
is the platelet-sparing effect of paclitaxel related to changes in the pharmacokinetics of carboplatin?,"to determine whether the platelet-sparing effect of paclitaxel is related to changes in pharmacology of carboplatin. a group of 32 patients with epithelial ovarian cancer were treated with intraperitoneal (i.p.) carboplatin-based chemotherapy with carboplatin alone or in combination with cyclophosphamide or paclitaxel, and the relationship between the pharmacology of serum platinum and thrombocytopenia was examined. the target auc of i.p. carboplatin was 6.5 mg min/ml. cyclophosphamide was administered intravenously at 400 mg/m2 after i.p. carboplatin and paclitaxel at 175 mg/m2 was given before i.p. carboplatin. ten patients received i.p. carboplatin alone, 10 received cyclophosphamide and 12 received paclitaxel. the ages of the patients, body surface area, serum creatinine, platelet count before chemotherapy, and the total dose of carboplatin in each patient were similar in all groups. the measured auc, cmax, t 1/2, and mrt were similar in these groups. the nadir platelet counts were significantly higher (p 0.0018) in patients treated with i.p. carboplatin with paclitaxel (12.1 /- 4.3 x 10(4)/mm3) compared with carboplatin alone (5.2 /- 3.3 x 10(4)/mm3) or with cyclophosphamide (5.2 /- 4.8 x 10(4)/mm3). the percentage decrease in platelet counts was significantly lower (62.5 /- 18.2) in patients treated with paclitaxel than in the other two groups (81.5 /- 12.6 carboplatin alone, 88.7 /- 7.9 with cyclophosphamide).",the addition of paclitaxel or cyclophosphamide to i.p. carboplatin did not alter the pharmacology of serum platinum. thrombocytopenia was significantly less in patients treated with carboplatin in combination with paclitaxel. the platelet-sparing effect of paclitaxel is not related to changes in the pharmacology of carboplatin.,Medication
do analysis of the effects of the continuous electrode paste band on precordial leads of the electrocardiogram?,"to determine if the application of a continuous electrode paste band on precordial leads results in alteration of the electrocardiographic tracing as compared with an adequate amount of electrode paste, and if the former condition does not cause uniform morphologies from v1 to v6. the amplitude and morphology of the electrocardiographic waves on the precordial leads in electrocardiographic tracings, which were performed with standard (control group) or excessive (continuous band) application of the electrode paste, were compared. none of the 106 patients studied showed uniformity of the qrs morphology from v1 to v6. the electrocardiographic alterations identified in the tracings performed with a continuous electrode paste band that showed statistical significance in relation to the control group were the following: inversion of the p wave in v1; inversion of the t wave in v1, v2, and v3; appearance of r' waves in v1 and v2; disappearance of s waves in v1; appearance of s waves in v5 and v6; alterations in the amplitude of almost all waves, in all leads.",application of a continuous electrode paste band in the precordial leads may cause significant alterations in the electrocardiographic tracing obtained.,General
is mir-103a targeting piezo1 involved in acute myocardial infarction through regulating endothelium function?,"acute myocardial infarction (ami) is commonly known as the heart attack. the molecular events involved in the development of ami remain unclear. this study was to investigate the expression of mir-103a in patients with high blood pressure (hbp) and ami patients with and without hbp, as well as its effect on endothelial cell functions. mir-103a expression in plasma and peripheral blood mononuclear cells was measured by real-time polymerase chain reaction (pcr). the regulatory effect of mir-103a on piezo1 gene was identified by a luciferase reporter system. the role of mir-103a in endothelial cells was evaluated by the capillary tube formation ability and cell viability of human umbilical vein endothelial cells (huvecs). the plasma mir-103a concentration was significantly elevated in patients with hbp alone, ami alone, and comorbidity of ami and hbp. the mir-103a expression in peripheral blood mononuclear cells (pbmcs) in patients with ami and hbp was significantly higher than the one in healthy controls (p 0.05), however mir-103a expression in pbmcs was not significantly different among patients with hbp alone, patients with ami alone, and healthy controls. mir-103a targeted piezo1 and inhibited piezo1 protein expression, which subsequently reduced capillary tube formation ability and cell viability of huvecs.",mir-103a might be a potential biomarker of myocardium infarction and could be used as an index for the diagnosis of ami. it may be involved in the development of high blood pressure and onset of ami through regulating the piezo1 expression.,General
do emphysema scores predict death from copd and lung cancer?,"our objective was to assess the usefulness of emphysema scores in predicting death from copd and lung cancer. emphysema was assessed with low-dose ct scans performed on 9,047 men and women for whom age and smoking history were documented. each scan was scored according to the presence of emphysema as follows: none, mild, moderate, or marked. follow-up time was calculated from time of ct scan to time of death or december 31, 2007, whichever came first. cox regression analysis was used to calculate the hazard ratio (hr) of emphysema as a predictor of death. median age was 65 years, 4,433 (49) were men, and 4,133 (46) were currently smoking or had quit within 5 years. emphysema was identified in 2,637 (29) and was a significant predictor of death from copd (hr, 9.3; 95 ci, 4.3-20.2; p .0001) and from lung cancer (hr, 1.7; 95 ci, 1.1-2.5; p .013), even when adjusted for age and smoking history.",visual assessment of emphysema on ct scan is a significant predictor of death from copd and lung cancer.,Medication
does bmp-7 inhibit tgf--induced invasion of breast cancer cells through inhibition of integrin ( 3 ) expression?,"the transforming growth factor (tgf)- superfamily comprises cytokines such as tgf- and bone morphogenetic proteins (bmps), which have a critical role in a multitude of biological processes. in breast cancer, high levels of tgf- are associated with poor outcome, whereas inhibition of tgf--signaling reduces metastasis. in contrast, bmp-7 inhibits bone metastasis of breast cancer cells. in this study, we investigated the effect of bmp-7 on tgf--induced invasion in a 3 dimensional invasion assay. bmp-7 inhibited tgf--induced invasion of the metastatic breast cancer cell line mcf10ca1a, but not of its premalignant precursor mcf10at in a spheroid invasion model. the inhibitory effect appears to be specific for bmp-7, as its closest homolog, bmp-6, did not alter the invasion of mcf10ca1a spheroids. to elucidate the mechanism by which bmp-7 inhibits tgf--induced invasion, we analyzed invasion-related genes. bmp-7 inhibited tgf--induced expression of integrin (v)(3) in the spheroids. moreover, targeting of integrins by a chemical inhibitor or knockdown of integrin (3) negatively affected tgf--induced invasion. on the other hand, overexpression of integrin (3) counteracted the inhibitory effect of bmp7 on tgf--induced invasion.","thus, bmp-7 may exert anti-invasive actions by inhibiting tgf--induced expression of integrin (3).",Medication
does recombinant acetylated trypsin demonstrate superior stability and higher activity than commercial products in quantitative proteomics studies?,"trypsin is an important digestive enzyme in peptide sample preparation for proteomics. it digests proteins at the c-terminal of arg or lys residues. the majority of commercial products are obtained from animal sources. in a previous study, we reported the production process for recombinant trypsin (r-trypsin) and acetylated trypsin (r-ac-trypsin). in this paper, we want to evaluate whether the r-trypsin and r-ac-trypsin are suitable for proteomics research. the trypsins used in this research were first normalized to the same concentration and used for further evaluation. the stability and buffer compatibility (2m urea, 0.1 sds and 10 acetonitrile) were compared and visualized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (sds-page). the digestion efficiency and specificity were compared based on a simple protein substrate, human serum albumin (hsa) and a complex proteomic sample, yeast lysate. the acquisition of proteomics data was achieved by ultra-high performance liquid chromatography (uplc) connected to an ltq orbitrap velos mass spectrometer. r-ac-trypsin demonstrated similar tolerance to 2 m urea and 10 acetonitrile but weaker 0.1 sds tolerance than commercial trypsins. based on simple protein sample hsa, the activity and specificity of r-ac-trypsin were similar to that of commercial trypsins. however, it demonstrated superior activity and specificity on complicated samples like yeast lysate. more interestingly, the newly developed r-ac-trypsin was more resistant to autolysis, which enabled more complete digestion of proteomic samples.",the r-ac-trypsin described here is a recombinant product. in addition it showed similar or superior properties such as stability activity and specificity to commercial products. it can be used in peptide sample preparation in proteomics studies.,Diagnosis
is autologous serum skin test for autoantibodies associated with airway hyperresponsiveness in patients with asthma?,"autoimmune diseases have been implicated as a cause of intrinsic asthma; however, there is little data on the role of autoimmunity in the pathogenesis of asthma. the purpose of this study was to investigate circulating functional autoantibodies against the high-affinity ige receptor fcepsilonri or ige in patients with asthma. twenty-eight patients with asthma and 19 control subjects were included. all subjects were skin tested with autologous serum to assess for the potential presence of receptor fcepsilonri or ige autoantibodies. if the serum-induced wheal diameter was 1.5 mm larger than the histamine-induced wheal diameter and that was 3 mm larger than the saline-induced wheal diameter at 30 min, the reaction was defined positive. of the 47 total subjects (both asthma patients and control subjects), 13 (27.7) had a positive autologous serum skin test (asst). of the 28 asthma patients, 8 (28.6) were regarded as having autoimmune origin. autoantibodies against fcepsilonri or ige were found in asthma patients, irrespective of atopic status (atopy 3/13 vs. atopy- 5/15). the wheal diameter related to asst was not related to atopy. asthma patients with asst-positive results as compared with patients with asst-negative results exhibited a significant increased airway hyperresponsiveness (pc(20) methacholine, 2.70 /- 1.27 vs. 9.08 /- 2.35; p 0.026).",our data demonstrate that aberrant autoantibodies against the high-affinity ige receptor fcepsilonri or ige are related to airway hyperresponsiveness in patients with asthma.,Diagnosis
do ccl25/ccr9 interactions regulate the function of inkt cells in oxazolone-induced colitis in mice?,"natural killer t (nkt) cells share phenotypic and functional properties with both conventional natural killer cells and t cells. these cells might have an important role in the pathogenesis of ulcerative colitis (uc). the interaction of chemokine ligand 25 (ccl25) with chemokine receptor 9 (ccr9) is involved in gut-specific migration of leukocytes and induces regulatory t cells (tregs) to migrate to the intestine in chronic ileitis. in uc patients, nkt receptor cd161, ccl25, and ccr9 expression levels were evaluated by qrt-pcr. a murine model of oxazolone-induced colitis was induced in balb/c mice. the mrna levels of nk1.1, ccl25 and ccr9, and pro-inflammatory cytokines in mice were evaluated. the ccr9 expression on type i or invariant nkt (inkt) cells, and the inkt cells chemotaxis are observed according to flow cytometry. nkt receptor cd161, ccl25 and ccr9 expression levels were significantly increased in uc patients. and, the mrna expression levels of nk1.1, ccl25 and ccr9 were increased in oxazolone-induced colitis in mice. the production of pro-inflammatory cytokines was significantly increased, especially interleukin 4 (il-4), il-10 and il-13. we observed significantly increased ccr9 expression on inkt cells. furthermore, we found an increased inkt population and enhanced chemotaxis during oxazolone-induced colitis.",our study suggests that ccl25/ccr9 interactions may promote the induction and function of inkt cells during oxazolone-induced colitis. these findings may have important implications for uc treatment and suggest a role for ccr9 inhibitors.,Medication
does da6034 promote gastric epithelial cell migration and wound-healing through the mtor pathway?,"7-carboxymethyloxy-3',4',5-trimethoxy flavone (da6034), a synthetic derivative of eupatilin, has a protective effect on gastric mucosa against various ulcerogens, and is currently in the phase iii clinical trial in the treatment of peptic ulcer disease. cell migration and/or growth plays a role in the repair process of gastric ulcer, so this study investigated the effect of da6034 on the movement and proliferation of gastric epithelial cells and its associated signaling pathway. the migration of ags or snu484 human gastric epithelial cells was shown by scratch-induced wound healing and transwell assays, and the proliferation of the cells was assessed by facs and proliferation assays. treatment of da6034 promoted the migration of gastric epithelial cells in a concentration-dependent manner. da6034 treatment facilitated the phosphorylation of mtor that led to an increase in the activity of s6k1, indicating its ability to activate mtor and s6k1. rapamycin aborted the wound-healing effect of da6034, which supported the role of mtor activation in the wound-healing process. in addition, da6034 treatment increased pi3k-dependent akt phosphorylation, which was necessary for the enhancement of cell migration. da6034, however, did not stimulate the proliferation of gastric epithelial cells, being consistent with no activation of erk1/2 by the agent.","da6034 has the ability to heal scratch wounds, which may result from an increase in gastric epithelial cell migration as mediated by pi3k-akt-dependent activation of mtor and s6k1. our finding may be of help in understanding the molecular basis of the anti-ulcer effect of da6034.",Treatment
do mutations in the non-structural protein region contribute to intra-genotypic evolution of enterovirus 71?,"clinical manifestations of enterovirus 71 (ev71) range from herpangina, hand-foot-and-mouth disease (hfmd), to severe neurological complications. unlike the situation of switching genotypes seen in ev71 outbreaks during 1998-2008 in taiwan, genotype b5 was responsible for two large outbreaks in 2008 and 2012, respectively. in china, by contrast, ev71 often persists as a single genotype in the population and causes frequent outbreaks. to investigate genetic changes in viral evolution, complete ev71 genome sequences were used to analyze the intra-genotypic evolution pattern in taiwan, china, and the netherlands. genotype b5 was predominant in taiwan's 2008 outbreak and was re-emergent in 2012. ev71 strains from both outbreaks were phylogenetically segregated into two lineages containing fourteen non-synonymous substitutions predominantly in the non-structural protein coding region. in china, genotype c4 was first seen in 1998 and caused the latest large outbreak in 2008. unlike shifting genotypes in taiwan, genotype c4 persisted with progressive drift through time. a majority of non-synonymous mutations occurred in residues located in the non-structural coding region, showing annual increases. interestingly, genotype b1/b2 in the netherlands showed another stepwise evolution with dramatic ev71 activity increase in 1986. phylogeny of the vp1 coding region in 1971-1986 exhibited similar lineage turnover with genotype c4 in china; however, phylogeny of the 3d-encoding region indicated separate lineage appearing after 1983, suggesting that the 3d-encoding region of genotype b2 was derived from an unidentified ancestor that contributed to intra-genotypic evolution in the netherlands.","unlike vp1 coding sequences long used for phylogenetic study of enteroviruses due to expected host immune escape, our study emphasizes a dominant role of non-synonymous mutations in non-structural protein regions that contribute to (re-)emergent genotypes in continuous stepwise evolution. dozens of amino acid substitutions, especially in non-structural proteins, were identified via genetic changes driven through intra-genotypic evolution worldwide. these identified substitutions appeared to increase viral fitness in the population, affording valuable insights not only for viral evolution but also for prevention, control, and vaccine against ev71 infection.",Symptoms
is surgery alone adequate treatment for early stage soft tissue sarcoma of the extremity?,"evolving evidence suggests that, in selected patients with tumour category 1 (t1) extremity soft tissue sarcoma (ests), surgery alone offers satisfactory results without decreasing survival. this study assessed the effect of sarcoma treatments on survival outcomes of t1 ests in a population-based data set. using the surveillance, epidemiology, and end results database, 1618 patients with primary ests underwent limb-sparing surgery. multivariable analysis was used to assess the impact of radiotherapy on overall survival (os) and sarcoma-specific survival (sss), adjusting for co-variables. some 803 patients (49.6 per cent) underwent surgery alone for t1 ests. radiotherapy in patients with low- and high-grade tumours did not result in any significant difference in os or sss. when stratified by grade, multivariable analysis showed that adjuvant radiotherapy was not an independent predictor of sss (hazard ratio (hr) 1.05; p 0.906) or os (hr 0.89; p 0.695) in low-grade tumours. neither was radiotherapy a significant predictor of sss (hr 0.87; p 0.608) or os (hr 0.67; p 0.071) in high-grade tumours.","this population-based appraisal validated previous evidence supporting a role for surgery alone in the treatment of t1 ests. future policies should be tailored to offer patients minimal yet effective therapy, rather than maximum tolerated therapy.",Treatment
does long-term use of vitamin e-coated polysulfone membrane reduce oxidative stress markers in haemodialysis patients?,"asymmetric dimethylarginine (adma) is an endogenous inhibitor of nitric oxide synthase and an independent predictor of overall mortality and cardiovascular outcome in haemodialysis (hd) patients. in the present study, we compared the effects of a vitamin e-coated polysulfone membrane (pse) and a non-vitamin e-coated polysulfone membrane (ps) on oxidative stress markers such as adma. thirty-one hd patients were enrolled to this investigation. they were allocated into two groups: in the pse group (n 16), pse was used for 6 months, followed by ps for an additional 12 months; in the ps group (n 15), ps was used for the entire observation period. plasma adma, oxidized low density lipoprotein (ox-ldl) and malondialdehyde ldl (mda-ldl) levels were measured at baseline, 3, 6, 12 and 18 months. plasma adma in peritoneal dialysis (pd) patients and in healthy individuals was also measured. predialysis concentrations of adma (0.72/- 0.13 nmol/ml) were significantly higher in the hd group than in both pd patients (0.63/-0.10 nmol/ml, p0.01) and healthy individuals (0.44/-0.01 nmol/ml, p0.0001). treatment with pse for 6 months significantly reduced predialysis levels of adma (0.54/-0.09 nmol/ml) compared with baseline (0.74/-0.12 nmol/ml; p0.01). predialysis levels of ox-ldl and mda-ldl after 6 months therapy with pse were also significantly lower than baseline values. treatment with ps subsequent to treatment with pse again increased adma, ox-ldl and mda-ldl back to baseline levels. in the ps group, adma, ox-ldl and mda-ldl levels remained unchanged during the entire treatment period of 18 months.",we confirmed that use of pse reduced adma that had accumulated in hd patients. this finding indicates that pse exerts anti-oxidant activity. a randomized controlled study will be required to determine whether pse prevents cardiovascular diseases and other dialysis-related complications by reducing oxidative stress.,Diagnosis
does weight stigma mediate the association between bmi and self-reported health?,"weight stigma is pervasive in the united states. we tested the hypothesis that stigma may be a mechanism through which obesity negatively affects self-reported health. two studies examined whether perceived weight-based discrimination and concerns over weight stigma mediated the association between bmi and self-reported psychological health (study 1) and physical health (study 2). in 2 online studies, adult community members completed measures of stigma-relevant mediators (perceived weight discrimination, weight stigma concerns) and provided their height and weight. in study 1 (n 171) participants also completed measures of psychological health (depression, self-esteem, quality of life), whereas participants in study 2 (n 194) also completed a measure of self-reported physical health. process modeling was used to simultaneously test for mediation through perceived discrimination and stigma concerns independently as well as for serial mediation through both variables. across both studies, we hypothesized and found support for serial mediation such that bmi was indirectly related to poorer self-reported health through its effect on perceived discrimination and concerns about stigma. additionally, concerns about stigma mediated the association between bmi and health independent of perceived discrimination.","weight stigma is an important mediator of the association between bmi and self-reported health. furthermore, results indicate that concerns about facing stigma in the future mediate the link between perceived past experiences of discrimination and psychological and physical health.",Prevention
are low physical activity level and short sleep duration associated with an increased cardio-metabolic risk profile : a longitudinal study in 8-11 year old danish children?,"as cardio-metabolic risk tracks from childhood to adulthood, a better understanding of the relationship between movement behaviors (physical activity, sedentary behavior and sleep) and cardio-metabolic risk in childhood may aid in preventing metabolic syndrome (mets) in adulthood. to examine independent and combined cross-sectional and longitudinal associations between movement behaviors and the mets score in 8-11 year old danish children. physical activity, sedentary time and sleep duration (seven days and eight nights) were assessed by accelerometer and fat mass index (fat mass/height2) was assessed using dual-energy x-ray absorptiometry. the mets-score was based on z-scores of waist circumference, mean arterial blood pressure, homeostatic model assessment of insulin resistance, triglycerides and high density lipoprotein cholesterol. all measurements were taken at three time points separated by 100 days. average of the three measurements was used as habitual behavior in the cross-sectional analysis and changes from first to third measurement was used in the longitudinal analysis. 723 children were included. in the cross-sectional analysis, physical activity was negatively associated with the mets-score (p0.17). children in the most favorable tertiles of changes in moderate-to-vigorous physical activity, sleep duration and sedentary time during the 200-day follow-up period had an improved mets-score relative to children in the opposite tertiles (p 0.005).","the present findings indicate that physical activity, sedentary time and sleep duration should all be targeted to improve cardio-metabolic risk markers in childhood; this is possibly mediated by adiposity.",Prevention
is renomedullary interstitial cell lipid droplet content increased in spontaneously hypertensive rats and by low salt diet?,"to compare the volumes of renomedullary interstitial cell (rmic) lipid droplets (putative source of vasodepressor substance) in spontaneously hypertensive (shr) and wistar-kyoto (wky) rats on high and low salt diets as an indication of whether the renomedullary vasodepressor system of the shr is defective. ten-week-old male shr and wky rats received a low (0.05 w/w) or high salt (5.0) diet for 21 days. conscious mean arterial pressure (map) was measured and the renal papilla perfusion fixed with a high osmolarity fixative. using electron microscopic stereological techniques, the volume density of lipid in rmic (vvlipid,rmic) and the total volumes of lipid (vlipid) and rmic (vrmic) in papilla were measured. map of shr (high 155 /- 3 mmhg; low 151 /- 3 mmhg) was significantly greater than wky rats (high 126 /- 2 mmhg; low 129 /- 2 mmhg; p 0.001), however salt diet had no significant effect on map. the vlipid of rats on the low salt diet was approximately 2.5 times greater than in rats on the high salt diet (p 0.01). shr had significantly greater vlipid than wky rats irrespective of salt diet (p 0.05; shr-low 0.245 /- 0.031 mm3, shr-high 0.093 /- 0.007 mm3; wky-low 0.126 /- 0.032 mm3, wky-high 0.051 /- 0.020 mm3). similar differences were seen for vvlipid,rmic, however vrmic was not different between rat strains or salt diet groups.","shr and wky rats responded similarly to the altered salt diets, and shr demonstrated greater volumes of stored rmic lipid droplets irrespective of the level of salt intake. these results indicate that shr hypertension is not due to a deficiency in the amount of lipid droplets, the putative source of the renomedullary vasodepressor substance and that the renomedullary vasodepressor system of the shr is capable of responding normally to the physiological stimulus of altered salt intake.",Prevention
is pancreas recovery following cerulein-induced pancreatitis impaired in plasminogen-deficient mice?,"the plasminogen (plg) system participates in tissue repair in several organs, but its role in pancreas repair remains poorly characterized. to understand better the role of plg in pancreas recovery following injury, we examined the course of cerulein-induced pancreatitis in plg-deficient and -sufficient mice. pancreatitis was induced by cerulein administration (50 microg/kg, 7 intraperitoneal injections). mice were killed either at the acute phase (7 hours after the first cerulein injection) or during recovery (at 2, 4, and 7 days). in pancreatic sections, we examined pancreatic morphology, trypsin activation, inflammatory cell infiltration, acinar cell death, cell proliferation, extracellular matrix deposition, activation of stellate cells (pscs), and components of the plg and metalloproteinase systems. in plg-sufficient mice, pancreatic plg levels and plasmin activity increased during the acute phase and remained elevated during recovery. pancreatitis resolved in plg-sufficient mice within 7 days. pancreas recovery involved reorganization of the parenchyma structure, removal of necrotic debris, cell proliferation, transient activation of pscs, and moderate deposition of extracellular matrix proteins. acute pancreatitis (7 hours) was indistinguishable between plg-deficient and -sufficient mice. in contrast, pancreas recovery was impaired in plg-deficient mice. plg deficiency led to disorganized parenchyma, extensive acinar cell loss, poor removal of necrotic debris, reduced cell proliferation, and fibrosis. fibrosis was characterized by deposition of collagens and fibronectin, persistent activation of pscs, and up-regulation of pancreatic transforming growth factor beta1.",plg/plasmin deficiency leads to features similar to those found in chronic pancreatitis such as parenchymal atrophy and fibrosis.,Medication
do hbmp-2 and htgf-1 expressed in implanted bmscs synergistically promote the repairing of segmental bone defects?,"to evaluate the effects of co-expressing hbmp-2 and htgf-1 in bmscs (bone marrow-derived mesenchymal stem cells) on the repairing process of radial segmental defects in rats. bmscs were infected with a high titer recombinant adenovirus carrying htgf-l and/or hbmp-2 genes. expression of exogenous genes in bmscs was confirmed by rt-pcr and elisa assays. in vitro effects of exogenous genes were assessed by mtt and alp activity tests. a left radial defect model was created using 120 sd rats. genetically modified or unmodified bmscs were implanted with collagen sponge scaffolds into the 5-mm radial defect. the bone repair process was systematically monitored and evaluated by x-ray examinations, gross anatomic examinations, histological analyses, and biomechanical tests. expression of hbmp-2 and htgf-1 showed synergistic effects on promoting bmsc proliferation and enhancing alp activity in vitro. bone repair assays showed that hbmp-2 and htgf-1 promoted the production of chondrocytes and osteoblasts. implanted bmscs transfected with both hbmp-2 and htgf-1 led to the best bone repair outcome.",hbmp-2 and htgf-1 can synergistically improve the bone repair process. our results suggest a potential clinical value of combining hbmp-2 and htgf-1 in repairing bone defects.,Treatment
does 48-hour fluid balance predict a successful spontaneous breathing trial?,"both premature and delayed liberation from mechanical ventilation are associated with increased morbidity and mortality, and fluid balance could negatively influence extubation outcomes. we sought to determine the impact of fluid balance in the 48 h before a spontaneous breathing trial (sbt) on weaning outcomes in a mixed icu population. this was a prospective observational study in 2 adult medical-surgical icus. all enrolled subjects met eligibility criteria for weaning from mechanical ventilation. sbt failure was defined as inability to tolerate a t-piece trial for 30-120 min. data on demographics, physiology, fluid balance in the 48 h preceding sbt (fluid input minus output over the 48-h period), lung ultrasound findings, and outcomes were collected. of a total of 250 sbts, sbt failure eventuated in 51 (20.4). twenty-nine subjects (11.6) had copd, and 40 subjects (16) were intubated due to respiratory sepsis. one-hundred eighty-nine subjects (75.6) were extubated on the first attempt. compared with subjects with sbt success, sbt failure subjects were younger (median of 66 vs. 75 y, p .001) and had a higher duration of mechanical ventilation (median of 7 vs. 4 d, p .001) and a higher prevalence of copd (19.6 vs. 9.5, p .04). there were no statistically significant differences in 48-h fluid balance before sbt between groups (sbt failure, 1,201.65 2,801.68 ml; sbt success, 1,324.39 2,915.95 ml). however, in the copd subgroup, we found a significant association between positive fluid balance in the 48 h before sbt and sbt failure (odds ratio of 1.77 1.24-2.53, p .04).","fluid balance should not delay sbt indication because it does not predict greater probability of sbt failure in the medical-surgical critically ill population. notwithstanding, avoiding positive fluid balance in patients with copd might improve weaning outcomes. (clinicaltrials.gov registration nct02022839.).",Treatment
does the ubiquitin proteasome system acutely regulate presynaptic protein turnover and synaptic efficacy?,"the ubiquitin proteasome system (ups) mediates regulated protein degradation and provides a mechanism for closely controlling protein abundance in spatially restricted domains within cells. we hypothesized that the ups may acutely determine the local concentration of key regulatory proteins at neuronal synapses as a means for locally modulating synaptic efficacy and the strength of neurotransmission communication. we investigated this hypothesis at the drosophila neuromuscular synapse by using an array of genetic and pharmacological tools. this study demonstrates that ups components are present in presynaptic boutons and that the ups functions locally in the presynaptic compartment to rapidly eliminate a conditional transgenic reporter of proteasome activity. we assayed a panel of synaptic proteins to determine whether the ups acutely regulates the local abundance of native synaptic targets. both acute pharmacological inhibition of the proteasome (1 hr) and targeted genetic perturbation of proteasome function in the presynaptic neuron cause the specific accumulation of the essential synaptic vesicle-priming protein dunc-13. most importantly, acute pharmacological inhibition of the proteasome (1 hr) causes a rapid strengthening of neurotransmission (an approximately 50 increase in evoked amplitude) because of increased presynaptic efficacy. the proteasome-dependent regulation of presynaptic protein abundance, both of the exogenous reporter and native dunc-13, and the modulation of presynaptic neurotransmitter release occur on an intermediate, rapid (tens of minutes) timescale.","taken together, these studies demonstrate that the ups functions locally within synaptic boutons to acutely control levels of presynaptic protein and that the rate of ups-dependent protein degradation is a primary determinant of neurotransmission strength.",Medication
does saliva from obese individuals suppress the release of aroma compounds from wine?,"recent evidence suggests that a lower extent of the retronasal aroma release correspond to a higher amount of ad libitum food intake. this has been regarded as one of the bases of behavioral choices towards food consumption in obese people. in this pilot study we investigated the hypothesis that saliva from obese individuals could be responsible for an alteration of the retro-nasal aroma release. we tested this hypothesis in vitro, by comparing the release of volatiles from a liquid food matrix (wine) after its interaction with saliva from 28 obese (o) and 28 normal-weight (n) individuals. amplicon sequencing of the 16s rrna v4 region indicated that firmicutes and actinobacteria were more abundant in o, while proteobacteria and fusobacteria dominated in n. streptococcaceae were significantly more abundant in the o subjects and constituted 34 and 19 on average of the saliva microbiota of o and n subjects, respectively. the total antioxidant capacity was higher in o vs n saliva samples. a model mouth system was used to test whether the in-mouth wine aroma release differs after the interaction with o or n saliva. in o samples, a 18 to 60 significant decrease in the mean concentration of wine volatiles was detected as a result of interaction with saliva, compared with n. this suppression was linked to biochemical differences in o and n saliva composition, which include protein content.",microbiological and biochemical differences were found in o vs n saliva samples. an impaired retronasal aroma release from white wine was detected in vitro and linked to compositional differences between saliva from obese and normal-weight subjects. additional in vivo investigations on diverse food matrices could contribute to understanding whether a lower olfactory stimulation due to saliva composition can be a co-factor in the development/maintenance of obesity.,General
do relative extended haplotype homozygosity signals across breeds reveal dairy and beef specific signatures of selection?,"a number of methods are available to scan a genome for selection signatures by evaluating patterns of diversity within and between breeds. among these, ""extended haplotype homozygosity"" (ehh) is a reliable approach to detect genome regions under recent selective pressure. the objective of this study was to use this approach to identify regions that are under recent positive selection and shared by the most representative italian dairy and beef cattle breeds. a total of 3220 animals from italian holstein (2179), italian brown (775), simmental (493), marchigiana (485) and piedmontese (379) breeds were genotyped with the illumina bovinesnp50 beadchip v.1. after standard quality control procedures, genotypes were phased and core haplotypes were identified. the decay of linkage disequilibrium (ld) for each core haplotype was assessed by measuring the ehh. since accurate estimates of local recombination rates were not available, relative ehh (rehh) was calculated for each core haplotype. genomic regions that carry frequent core haplotypes and with significant rehh values were considered as candidates for recent positive selection. candidate regions were aligned across to identify signals shared by dairy or beef cattle breeds. overall, 82 and 87 common regions were detected among dairy and beef cattle breeds, respectively. bioinformatic analysis identified 244 and 232 genes in these common genomic regions. gene annotation and pathway analysis showed that these genes are involved in molecular functions that are biologically related to milk or meat production.",our results suggest that a multi-breed approach can lead to the identification of genomic signatures in breeds of cattle that are selected for the same production goal and thus to the localisation of genomic regions of interest in dairy and beef production.,Treatment
does pretreatment with angiotensin-converting enzyme inhibitor improve doxorubicin-induced cardiomyopathy via preservation of mitochondrial function?,"doxorubicin is a widely used chemotherapy drug, but its application is associated with cardiotoxicity. free radical generation and mitochondrial dysfunction are thought to contribute to doxorubicin-induced cardiac failure. angiotensin-converting enzyme inhibitors are commonly used as cardioprotective agents and have recently been shown in clinical studies to be efficacious in the prevention of anthracycline-induced heart failure. this study evaluated a mechanism for these protective effects by testing the ability of the angiotensin-converting enzyme inhibitor enalapril to preserve mitochondrial function in a model of chronic doxorubicin treatment in rats. sprague dawley rats were divided into 3 groups and followed for a total of 10 weeks: (1) control-untreated, (2) doxorubicin treated, and (3) doxorubicin enalapril treated. doxorubicin was administered via intraperitoneal injection at weekly intervals from weeks 2 to 7. enalapril was administered in the drinking water of the doxorubicin enalapril group for the study duration. doxorubicin treatment produced a significant loss in left ventricular contractility (p .05), decrease in mitochondrial function via impairment of state-3 respiration, decrease in the cytosolic fraction of adenosine triphosphate, and up-regulation of free radical production. enalapril significantly attenuated the decrease in percent fractional shortening (p .05) and prevented the doxorubicin-associated reduction in respiratory efficiency and cytosolic adenosine triphosphate content (p .05). enalapril also abolished the robust doxorubicin-induced increase in free radical formation.",administration of enalapril attenuates doxorubicin-induced cardiac dysfunction via preservation of mitochondrial respiratory efficiency and reduction in doxorubicin-associated free radical generation.,Medication
does use of acute hospital beds increase as the population ages : results from a seven year cohort study in germany?,"(1) to compare the number of hospital days used by survivors with those by persons in their last, second last, and third last year of life in relation to age; (2) to analyse lifelong hospital utilisation in relation to life expectancy. cohort study using a 10 sample (stratified by age and sex) of persons insured by one sickness fund. germany, 1989-1995. 69,847 survivors (with a minimum of three more years to live), 1385 persons in last, 1368 in second last, and 1333 in third last year of life. the number of days spent in hospital in the last year of life was lowest for the young (24.2 days under age 25) and the old (23.2 days at age 85) and was greatest at ages 55-64 (40.6 days). the ratio of days to survivors was highest at age 35-44 (31.0) and fell continuously thereafter to 4.3 at age 85. similar patterns were seen for hospital days in the second and third year before death, except that peaks were at 35-44 years (22.5 and 13.7 days respectively). calculated lifelong number of hospital days increased with age from 54.8 (death at age 20) to 201.0 (age 90). numbers of hospital days per year of life, averaged over the entire lifespan, were stable at 2.0-2.2 for deaths between age 50 and 90 (and up to 2.7 at age 20).",lifelong hospital utilisation for persons who die at 50 or later is directly proportional to the number of years lived. these data contradict results from cross sectional studies that suggest an exponential rise in health care costs as longevity increases. they have important implications for projections of future health care expenditure.,General
is a tumor promoter-resistant subpopulation of progenitor cells larger in limbal epithelium than in corneal epithelium?,"in the epidermis, proliferative basal cells can be divided into two subpopulations according to their response to phorbol ester tumor promoters. the tumor promoter-sensitive subpopulation ceases mitosis and initiates terminal differentiation and, thus, represents more differentiated transient amplifying cells. in contrast, the tumor promoter-resistant subpopulation that continues to proliferate may be the target of neoplastic transformation by chemical carcinogens and may contain stem cells. based on this concept, we examined the differential response of stem cell-containing limbal epithelium and transient amplifying cell-containing corneal epithelium to phorbol 12-myristate 13-acetate (pma) treatment. a reported serum-free clonal growth assay was used. the mitogenic response was measured by colony-forming efficiency (cfe), colony size, bromodeoxyuridine (brdu) labeling index; the differentiation was assessed by colony morphology, ae-5 monoclonal antibody staining. the addition of pma dose dependently inhibited the clonal proliferation of both limbal and corneal epithelial cultures with respect to cfe, colony size, and brdu labeling index, suggesting that both cultures contain pma-sensitive subpopulations. nevertheless, the magnitudes of a decrease in cfe and colony size in peripheral corneal cultures were significantly greater than those in limbal cultures, indicating that the size of the pma-resistant subpopulation is larger in the limbal epithelium. the inhibitory effect of pma on clonal proliferation was partially reversible upon its early withdrawal, indicating that its inhibitory effect is continuous and coupled with progressive differentiation of progenitor cells in this culture system.","these results further suggest that the cell cycle length of progenitor cells correlates with the mitogenic pathway mediated via calcium- and phospholipid-dependent protein kinase c, the receptor inhibited by prolonged treatment of phorbol ester tumor promoters.",Medication
does tribbles homologue 3 stimulate canonical tgf- signalling to regulate fibroblast activation and tissue fibrosis?,"tribbles homologue 3 (trb3) is a pseudokinase that modifies the activation of various intracellular signalling pathways to control fundamental processes extending from mitosis and cell activation to apoptosis and modulation of gene expression. here, we aimed to analyse the role of trb3 in fibroblast activation in systemic sclerosis (ssc). the expression of trb3 was quantified by quantitative pcr, western blot and immunohistochemistry. the role of trb3 was analysed in cultured fibroblasts and in experimental fibrosis using small interfering rna (sirna)-mediated knockdown and overexpression of trb3. trb3 expression was increased in fibroblasts of patients with ssc and in murine models of ssc in a transforming growth factor- (tgf-)/smad-dependent manner. overexpression of trb3 stimulated canonical tgf- signalling and induced an activated phenotype in resting fibroblasts. in contrast, knockdown of trb3 reduced the profibrotic effects of tgf- and decreased the collagen synthesis. moreover, sirna-mediated knockdown of trb3 exerted potent antifibrotic effects and ameliorated bleomycin as well as constitutively active tgf- receptor i-induced fibrosis with reduced dermal thickening, decreased hydroxyproline content and impaired myofibroblast differentiation.","the present study characterises trb3 as a novel profibrotic mediator in ssc. tgf- induces trb3, which in turn activates canonical tgf-/smad signalling and stimulates the release of collagen, thereby inducing a positive feedback loop that may contribute to aberrant tgf- signalling in ssc.",Medication
does overexpression of mir-200c induce chemoresistance in esophageal cancers mediated through activation of the akt signaling pathway?,"to determine the relationship between resistance to chemotherapy and microrna (mirna) expression in esophageal cancer, we focused on mirnas known to be associated with maintenance of stem cell function. using 98 formalin-fixed, paraffin-embedded samples obtained from patients with esophageal cancer who had received preoperative chemotherapy followed by surgery, we measured expression levels of several mirnas that are considered to be involved in the regulation of stem cell function (e.g., let-7a, let-7g, mir-21, mir-134, mir-145, mir-155, mir-200c, mir-203, and mir-296) by real-time reverse transcriptase pcr. then, we examined the relationship between mirna expression and prognosis or response to chemotherapy. to investigate the mechanism of mirna-induced chemoresistance, in vitro assays were carried out using esophageal cancer cells. analyses of the 9 mirnas expression showed that overexpression of mir-200c (p 0.037), underexpression of mir-145 (p 0.023), and overexpression of mir-21 (p 0.048) correlated significantly with shortened overall duration of survival. in particular, mir-200c expression correlated significantly with response to chemotherapy (p 0.009 for clinical response; p 0.007 for pathologic response). in vitro assay showed significantly increased mir-200c expression in cisplatin-resistant cells compared with their parent cells (1.7-fold). in anti-mir-200c-transfected cells, chemosensitivity to cisplatin and apoptosis after exposure to cisplatin was found to increase as compared with the negative control. western blotting showed that knockdown of mir-200c expression was associated with increased expression of ppp2r1b, a subunit of protein phosphatase 2a, which resulted in reduced expression of phospho-akt.",results of this study emphasized the involvement of mir-200c in resistance to chemotherapy among esophageal cancers and that this effect was mediated through the akt pathway.,Medication
does mineralocorticoid receptor suppress cancer progression and the warburg effect by modulating the mir-338-3p-pklr axis in hepatocellular carcinoma?,"hormones and their corresponding receptors are vital in controlling metabolism under normal physiologic and pathologic conditions, but less is known about their roles in the metabolism of cancer. using a small interfering rna screening approach, we examined the effects of silencing 20 well-known hormone receptors on the warburg effect, specifically by measuring the production of lactate in four established hepatocellular carcinoma (hcc) cell lines. we found that silencing a variety of hormone receptors had effects on the production of this metabolite. unexpectedly silencing of mineralocorticoid receptor (mr) significantly increased lactate production in all these hcc cell lines. subsequent in vitro and in vivo studies showed that gain- and loss-of-function of mr significantly influenced hcc cellular proliferation, cell cycle distribution, and apoptosis. furthermore, mechanistic studies revealed that mr as a transcriptional factor directly regulated the expression of mir-338-3p, suppressing the warburg effects of hcc cells by targeting a key enzyme of glycolysis: pyruvate kinase, liver and red blood cells. moreover, mr expression was significantly down-regulated in 81 of hcc patient tissues, caused by both chromosome deletion and histone deacetylation. low expression of mr in tumor tissues was associated with poor patient prognosis. the expression level of mir-338-3p was found to positively correlate with the expression of mr in hcc tissues and to inversely correlate with expression of the enzyme pyruvate kinase, liver and red blood cells.","mr affects hcc development by modulating the mir-338-3p/pyruvate kinase, liver and red blood cells axis with an ability to suppress the warburg effect.",Medication
are circulating levels of persistent organic pollutants related to retrospective assessment of life-time weight change?,"persistent organic pollutants (pops) have been suggested to be linked to obesity. we have previously shown that less-chlorinated pcbs were positively related to fat mass, while highly-chlorinated pcbs were inversely related to obesity. the aim of the present evaluation is to investigate the relationship between retrospective assessed life-time change in body weight (20-70 years) with circulating pop levels measured at age 70 years. 1016 subjects aged 70 years were investigated in the prospective investigation of the vasculature in uppsala seniors (pivuss) study. 16 pcbs and 3 oc pesticides were analyzed using hrgc/hrms. current body weight was measured and participants self-reported their weight at age 20. the average estimated weight change over 50 years was 14.4 kg. both the sum of oc pesticide concentrations (4.3 kg more weight gain in quintile 5 vs. quintile 1, p0.0001) and the sum of the less-chlorinated pcbs were positively related to the estimated weight change (3.7 kg more weight gain in quintile 2 vs. quintile 1, non-linear relationship p0.0015). in contrast, the sum of concentrations of highly-chlorinated pcbs were inversely related to estimated weight change (8.4 kg less weight gain in quintile 5 vs. quintile 1, p0.0001).","high levels of oc pesticides and the less-chlorinated pcbs at age 70 were associated with a pronounced estimated weight change over the previous 50 years. however, the opposite was seen for highly-chlorinated pcbs. differences in mode of action, toxicokinetics, non-linear relationships and reverse causation might explain these discrepancies.",Prevention
do training of cochlear implant users to improve pitch perception in the presence of competing place cues?,"perception of musical pitch in cochlear implant (ci) systems is relatively poor compared with normal hearing and can be adversely affected by changes in spectral timbre coded by stimulation place. in this study, we evaluated whether the perception of musical pitch could be improved through specific training designed to teach listeners to attend to fundamental frequency (f0) exclusively for judgment of pitch and to spectral envelope exclusively for discrimination of spectral timbre. a computer-based training program to improve musical pitch perception was developed that required listeners to match acoustic patterns of pitch and spectral timbre to visual patterns. ten adult ci recipients participated: five used the training program and five acted as controls. before training, f0 and center frequency discrimination for band-limited complex harmonic stimuli presented in the sound field were measured in all subjects using their standard clinical device(s). the f0 tests were conducted with and without spectral variations. the trainees subsequently used the training program at home for a period of 4 months, during which they were asked to train for approximately 30 min per day. the training schedule comprised two successive phases, each lasting 2 months. in the first phase, training employed a single cue (i.e., f0 for pitch or center frequency for spectral timbre) in the absence of other cue variations. in the second phase, training incorporated more complex sounds in which multiple cues were varied. discrimination thresholds were remeasured in all subjects after each phase and again with trainees 3 months after training had ceased. trainees obtained significant improvements in f0 and center frequency discrimination as compared with control subjects for tests conducted at 2 months. the improvements in f0 discrimination were observed both in the absence and presence of small variations in place. however, the effect of training diminished for large variations in place or for higher f0s. neither group showed further improvement in tests after additional training in the second phase. tests conducted with trainees after training had ceased showed that f0 discrimination improvements were retained.","the results showed that performance on pitch and timbre discrimination can be improved by training with single cues (f0 and center frequency) in the absence of other cue variations. although results indicated that training with single cues can improve f0 discrimination within more complex sounds in which multiple cues vary, little improvement was seen when large variations in place were present, which suggests a diminishing effect of the training with increased influence of place-pitch. these data imply that although such training techniques may help listeners to follow melody in music, changes in instrument are likely to affect perception of melody. results of subsequent training with complex sounds in which multiple cues varied were less conclusive and showed no further improvement. follow-up evaluations with trainees conducted well after training had ceased verified the robustness of the training effect on f0 but not center frequency discrimination. further studies are needed, however, to determine whether and to what degree subject motivation may be an important factor in these outcomes.",General
does self-microemulsifying drug delivery system improve curcumin dissolution and bioavailability?,"curcumin has a wide spectrum of biological and pharmacological activities, but it has not yet been approved as a therapeutic agent because of its low solubility and stability in aqueous solution, and the relatively low bioavailability in vivo. to overcome these limitations, self-microemulsifying drug delivery system (smedds) of curcumin was developed. various oils, surfactants, and cosurfactants were selected to optimize the formulation. pseudoternary phase diagrams were constructed and orthogonal design was used to compare the oil-in-water (o/w) microemulsion-forming capacity of different oils/surfactants/cosurfactants. the solubility of curcumin in various oils and cosurfactants was determined to find suitable ingredients with a good solubilizing capacity. droplet size was measured to obtain the concentration of oil, surfactant, and cosurfactant for forming stable microemulsion. furthermore, its quality and bioavailability in mice were assessed. pseudoternary phase diagrams and solubility test showed that the formulation of smedds composed of 20 ethanol, 60 cremophor rh40, and 20 isopropyl myristate, in which the concentration of curcumin reached 50 mg/ml. curcumin was released completely from smedds at 10 minutes. the developed smedds formulation improved the oral bioavailability of curcumin significantly, and the relative oral bioavailability of smedds compared with curcumin suspension was 1213.",the smedds can significantly increase curcumin dissolution in vitro and bioavailability in vivo.,Medication
is collagen production at the edge of ruptured rotator cuff tendon correlated with postoperative cuff integrity?,"the purpose was to evaluate the correlation between messenger rna (mrna) expression of collagen at the edge of the ruptured rotator cuff tendon and postoperative cuff integrity. the edge of the ruptured tendon was sampled during open rotator cuff surgery in 12 patients with full-thickness rotator cuff tears (mean age, 58.2 years). the mean period from symptom onset was 9.3 months (range, 1 to 36 months), and the mean tear size was 4.1 cm. as controls, rotator cuff tendons with no gross rupture were taken from 5 fresh cadavers. production of type i and type iii collagen was examined by real-time reverse transcription polymerase chain reaction. by use of magnetic resonance imaging, postoperative cuff integrity was evaluated based on the classification of sugaya et al. and then scored, ranging from 5 points for type i to 1 point for type v. looking at the mrna of type i and type iii collagen in tendons, we found that the expression of mrna for both collagen types in ruptured tendons was significantly greater than in control tendons (p .0462 for type i collagen and p .0306 for type iii collagen). correlating the mrna of type i and type iii collagen with repaired cuff integrity on postoperative magnetic resonance imaging, we found a close relation between expression of mrna for both collagen types and postoperative rotator cuff integrity (r 0.63 p .038 for type i collagen and r 0.626 p .03 for type iii collagen). furthermore, expression of type i collagen mrna showed a significant inverse correlation with the period from symptom onset (r -0.845, p .0005).",this study showed that expression of mrna for type i and type iii collagen at the edge of the ruptured rotator cuff tendon was significantly correlated with postoperative cuff integrity and that mrna expression for type i collagen was significantly associated with the period from symptom onset. these results may suggest that conservative treatment should not be prolonged if patients do not respond within a certain period.,Treatment
do circulating tnf alpha receptor levels identify older adults who fail to regain weight after acute weight loss?,"some healthy older adults have difficulty regaining weight after acute weight loss, and the reason for this failure to regain weight is unknown. the objective of this study was to determine if elevated leptin or pro-inflammatory cytokine levels are associated with failure to regain weight over two years after an acute weight loss intervention. two year prospective study after an acute weight loss intervention. university of washington medical center from 2001-2006. nineteen older ( 70 years old) men and women. body weights, health status questionnaire, body composition data, serum leptin, glucose, insulin, c- reactive protein and pro-inflammatory cytokine levels were measured every six months for two years. five subjects out of 19 failed to regain weight after two years. the subjects who failed to regain weight after 2 years had higher circulating levels of tumor necrosis factor receptor particle 55 (tnfrp55) at baseline and at 6, 12, 18 and 24 months of follow up compared to subjects who regained weight after 2 years (p 0.02 ).","five out of 19 older subjects had difficulty regaining weight for up to 2 years following an acute weight loss intervention, and their tnfrp55 levels were persistently higher than in subjects who regained weight. greater tnf action, as reflected by higher circulating levels of tnfrp55, could be contributing towards inability of some older persons to regain weight after acute weight loss.",Medication
are cardiac magnetic resonance imaging findings useful for differentiating between hypertrophic obstructive cardiomyopathy and aortic valve stenosis in elderly patients?,"the objective of this study was to assess whether cardiac magnetic resonance (mr) imaging is useful for differentiating between hypertrophic obstructive cardiomyopathy (hocm) and aortic valve stenosis (as) in 21 elderly patients (75 years old). cine and delayed contrast-enhanced cardiac mr imaging was performed and used to assess the regional wall thickness, myocardial mass, mitral valve motion, and myocardial hyperenhancement in elderly patients with hocm and as. the basal anterior septal and midventricular inferior septal walls were significantly thicker, the ejection fraction was higher, and the ratio between the basal and midventricular inferior wall thicknesses was lower in patients with hocm than those in patients with as. apical wall thinning and abnormal mitral valve motion were detected in patients with hocm.","structural and functional parameters that are characteristic of hocm can be assessed in cardiac mr imaging, and these parameters may be useful for differentiating between hocm and as in elderly patients.",Diagnosis
is loss of kcnq1 expression in stage ii and stage iii colon cancer a strong prognostic factor for disease recurrence?,"colorectal cancer (crc) is the third most common cancer worldwide. accurately identifying stage ii crc patients at risk for recurrence is an unmet clinical need. kcnq1 was previously identified as a tumour suppressor gene and loss of expression was associated with poor survival in patients with crc liver metastases. in this study the prognostic value of kcnq1 in stage ii and stage iii colon cancer patients was examined. kcnq1 mrna expression was assessed in 90 stage ii colon cancer patients (amc-ajccii-90) using microarray gene expression data. subsequently, kcnq1 protein expression was evaluated in an independent cohort of 386 stage ii and stage iii colon cancer patients by immunohistochemistry of tissue microarrays. low kcnq1 mrna expression in stage ii microsatellite stable (mss) colon cancers was associated with poor disease-free survival (dfs) (p0.025). loss of kcnq1 protein expression from epithelial cells was strongly associated with poor dfs in stage ii mss (p0.0001), stage iii mss (p0.0001) and stage iii microsatellite instable colon cancers (p0.041). kcnq1 seemed an independent prognostic value in addition to other high-risk parameters like angio-invasion, nodal stage and microsatellite instability-status.",we conclude that kcnq1 is a promising biomarker for prediction of disease recurrence and may aid stratification of patients with stage ii mss colon cancer for adjuvant chemotherapy.,Diagnosis
does intravenous basic fibroblast growth factor protect the lung but not mediastinal organs against radiation-induced apoptosis in vivo?,"we evaluated the therapeutic potential of intravenously injected basic fibroblast growth factor against the lethal syndromes associated with irradiation of intrathoracic organs and assessed whether such protection might be associated with inhibition of programmed cell death (apoptosis) in the exposed tissues. c3h/hej and c3h/scid mice received either whole-chest, mediastinal, or bilateral lung irradiation. human recombinant basic fibroblast growth factor was injected intravenously at doses of 400 ng immediately before and after irradiation, and then at 1 hour and 2 hours later. time-adjusted survival was calculated from the date of irradiation by the product-limit kaplan-meier method. detection of apoptotic changes in paraffin sections was performed by the dna terminal transferase nick-end translation method. basic fibroblast growth factor protected the lungs but not other intrathoracic organs against radiation-induced damage. when radiation was restricted to the lungs, the ld50/180 from radiation pneumonitis was 20.75 gy and increased to 23.0 gy in basic fibroblast growth factor-treated mice. when the whole thorax was irradiated, basic fibroblast growth factor partially protected against pneumonitis at the low range of radiation doses ( or ld50/180), but failed to confer protection at higher doses, nor did it protect against lethal radiation esophagitis. staining for the presence of apoptotic nuclei revealed time- and radiation dose-dependent development of apoptosis in endothelial cells of the pulmonary capillary network, endocardium, and mesothelial cells of the pleura and pericardium. although basic fibroblast growth factor inhibited apoptosis in the microvascular endothelium and the endocardium, it had no effect on apoptosis in the serosal mesothelium of the pleura and pericardium.",intravenous basic fibroblast growth factor protects against the apoptotic microvascular component of early-phase radiation pneumonitis but may have no effect on other elements of the primary damage produced by radiation in the lungs and other intrathoracic organs. understanding the patterns and temporal evolution of radiation-induced apoptosis and basic fibroblast growth factor-mediated antiapoptotic effects in thoracic organs and tumors may offer opportunities for pharmacologic intervention in the radiotherapeutic management of primary and metastatic lung tumors.,Medication
do craniofacial and cutaneous findings expand the phenotype of hereditary neuralgic amyotrophy?,"hereditary neuralgic amyotrophy (hna) is an autosomal-dominant disorder associated with recurrent, episodic, painful, brachial neuropathy. the gene for hna has been mapped to chromosome 17q25. characteristic features including hypotelorism, short stature, and cleft palate occur in some patients. to further characterize the clinical, neurologic, and craniofacial features in 27 patients from seven families with hna. medical history, physical examination, and facial measurements were obtained. facial measurements were also made on 60 healthy controls. twenty-five patients had an average of three attacks of brachial neuritis. the right arm was involved more frequently. cleft palate was present in four individuals. facial measurements showed significant hypotelorism in hna patients versus controls. unusual skin folds and creases were observed on the necks of several individuals as well as on the scalp of one man: cutis verticis gyrata. in three families, deep skin creases were present on the limbs of infants and toddlers who were subsequently affected with hna.",the phenotypic consequences of the mutant hereditary neuralgic atrophy gene may include a wider spectrum than previously appreciated and involve nonneural tissue.,Symptoms
do thyroglobulin antibody levels predict disease status in papillary thyroid cancer?,"thyroglobulin antibodies (tgab) are present in approximately 20 of patients with papillary thyroid cancer (ptc) and invalidate the serum thyroglobulin (tg) level as a tumour marker. we examined whether trends in the tgab level could serve as a surrogate marker of disease status in the surveillance of patients with ptc. all patients found to have a least one positive postoperative tgab level (determined by the beckman-coulter access assay) after undergoing initial surgery for ptc from 2000 to 2010 at a single institution were included. log-log transformation and linear regression were applied to longitudinal tgab levels, yielding patient-specific regression coefficients that categorized as follows: highly negative, moderately negative and positive/no trend. the recurrence rate in each category was then assessed. ninety-three of 967 patients with ptc were included. recurrent disease was detected in 19 patients (20) after a mean follow-up time of 51 months. regression coefficients in the highly negative and moderately negative groups were not different, and hence these groups were pooled. the proportion of recurrent cases in the negative trend group was similar to that in the positive/no trend group (19.7 vs 21.9, ns). the mean regression coefficients were similar for recurrent and nonrecurrent cases within both the negative trend group (-0.89 vs -0.80, ns) and the positive/no trend group (0.08 vs 0.33, ns).","trends in the tgab level do not predict disease status in ptc in our experience. in the context of most commercially available tgab assays, surveillance of tgab-positive patients will hinge on high-quality imaging until a valid alternative serum marker to tg is identified.",Treatment
does mutation of tbck cause a rare recessive developmental disorder?,"to characterize the underlying genetic defect in a family with 3 siblings affected by a severe, yet viable, congenital disorder. extensive genetic and metabolic investigations were performed, and the affected children were imaged at different ages. whole-genome genotyping and whole-exome sequencing were undertaken. a single large region (8 mb) of homozygosity in chromosome 4 (chr4:100,268,553-108,609,628) was identified that was shared only in affected siblings. inspection of genetic variability within this region led to the identification of a novel mutation. sanger sequencing confirmed segregation of the mutation with disease. all affected siblings share homozygosity for a novel 4-bp deletion in the gene tbck (nm033115:c.614617del:p.205206del).",this finding provides the genetic cause of a severe inherited disease in a family and extends the number of mutations and phenotypes associated with this recently identified disease gene.,General
do two genome-wide association studies of aggressive prostate cancer implicate putative prostate tumor suppressor gene dab2ip?,"the consistent finding of a genetic susceptibility to prostate cancer suggests that there are germline sequence variants predisposing individuals to this disease. these variants could be useful in screening and treatment. we performed an exploratory genome-wide association scan in 498 men with aggressive prostate cancer and 494 control subjects selected from a population-based case-control study in sweden. we combined the results of this scan with those for aggressive prostate cancer from the publicly available cancer genetic markers of susceptibility (cgems) study. single-nucleotide polymorphisms (snps) that showed statistically significant associations with the risk of aggressive prostate cancer based on two-sided allele tests were tested for their association with aggressive prostate cancer in two independent study populations composed of individuals of european or african american descent using one-sided tests and the genetic model (dominant or additive) associated with the lowest value in the exploratory study. among the approximately 60,000 snps that were common to our study and cgems, we identified seven that had a similar (positive or negative) and statistically significant (p.01) association with the risk of aggressive prostate cancer in both studies. analysis of the distribution of these snps among 1032 prostate cancer patients and 571 control subjects of european descent indicated that one, rs1571801, located in the dab2ip gene, which encodes a novel ras gtpase-activating protein and putative prostate tumor suppressor, was associated with aggressive prostate cancer (one-sided p value .004). the association was also statistically significant in an african american study population that included 210 prostate cancer patients and 346 control subjects (one-sided p value .02).",a genetic variant in dab2ip may be associated with the risk of aggressive prostate cancer and should be evaluated further.,Diagnosis
do higher methylation levels in gastric mucosae significantly correlate with higher risk of gastric cancers?,"helicobacter pylori infection potently induces methylation of cpg islands in gastric mucosae, which is considered to decrease to a certain level after active h. pylori infection discontinues. noncancerous gastric mucosae of h. pylori-negative cases with a gastric cancer had higher methylation levels than those of h. pylori-negative healthy individuals. here, using cases with multiple gastric cancers, we analyzed whether the higher methylation levels correlated with the higher risk of gastric cancers. twenty-six healthy volunteers (hv), 30 cases with a single well-differentiated gastric cancer (s cases), and 32 cases with multiple well-differentiated gastric cancers (m cases) were recruited. h. pylori infection status was analyzed by the culture method. methylation levels were quantified by real-time methylation-specific pcr of seven cpg islands. in h. pylori-negative individuals, significant increasing trends were present in the order of hv, s cases, and m cases for flnc and hand1 methylation levels (p 0.01, spearman's rank-order test). furthermore, the flnc methylation level of m cases was significantly higher than that of s cases (p 0.01, t test). even adjusted by the extent of gastric atrophy, the flnc methylation level retained a significant increasing trend (p 0.03). in contrast, methylation levels in h. pylori-positive individuals were increased to various degrees in all the three groups.","in h. pylori-negative individuals, methylation levels in gastric mucosae significantly increased in cases with a single gastric cancer and more in cases with multiple gastric cancers. quantitative analysis of methylation levels is a promising risk marker for gastric cancers.",General
does vascular smooth muscle cell peroxisome proliferator-activated receptor- mediate pioglitazone-reduced vascular lesion formation?,"peroxisome proliferator-activated receptor- (ppar) has been reported to decrease vascular lesion formation. however, the critical role of vascular smooth muscle cell (vsmc) ppar in vascular lesion formation following transplantation is not well understood. in this study, we investigated the role of vsmc ppar-mediated signaling in transplantation-associated vascular lesion formation. carotid arteries from smooth muscle cell-selective ppar knockout (smpg ko) and wild-type mice were transplanted to cba/caj recipient mice. the recipient mice received a control diet or pioglitazone-containing diet. pioglitazone reduced vascular lesion formation in transplanted wild-type, but not in smpg ko carotid arteries. histological analysis suggested that ppar attenuates vascular lesion formation through antiinflammatory signaling, as evidenced by the increase of intimal inflammatory cells and tumor necrosis factor- expression in smpg ko allografts. intravital microscopy revealed increased inflammatory cell rolling and attachment to endothelial cells in small blood vessels of smpg ko mice following cytokine stimulation. smpg ko mice, as shown by western blotting, have elevated vascular cell adhesion molecule-1 (vcam-1) expression. furthermore, immunohistochemistry demonstrated smpg ko allografts have increased vcam-1.",loss of ppar in vsmc promotes transplantation-associated vascular lesion formation through increased vcam-1 expression. vsmc ppar also mediates pioglitazone-reduced vascular lesion formation.,Medication
does diabetes mellitus affect response to neoadjuvant chemoradiotherapy in the management of rectal cancer?,"although diabetic patients with rectal cancer have poorer outcomes than their nondiabetic counterparts, few studies have looked at diabetics' response to therapy as an explanation for this disparity. this study compares the neoadjuvant chemoradiotherapy (crt) response in diabetic and nondiabetic patients with locally advanced rectal cancers. this is a single-institution, retrospective review of rectal cancer patients who received crt followed by resection from 1995 to 2006. pretreatment tumor-node-metastasis (tnm) staging was determined using endorectal ultrasound, computed tomography (ct) scan, and magnetic resonance imaging (mri); post-treatment staging was determined by pathological review. 110 patients were included; seventeen had diabetes and 93 were nondiabetics. pretreatment staging was similar in both groups. sixteen of the diabetics (94) completed crt compared to 92 (86/93) of the nondiabetics. tumor downstaging rates were similar in the two groups (53 in diabetics, 52 in nondiabetics). nondiabetic patients had a higher rate of nodal downstaging although not statistically significant (67 versus 27, p 0.80). while none of the diabetics patients achieved a pathologic complete response (pcr), 23 (21/93) of the nondiabetics did (p 0.039). local progression rates were higher in the diabetic group (24 versus 5, p 0.046).","our study shows that neoadjuvant chemoradiotherapy in rectal cancer is less effective in diabetic patients than in nondiabetics. while minimal differences are found in the rate of downstaging, the rate of achieving a complete pathologic response was significantly higher in nondiabetic patients, and in fact was not seen in any of our diabetic patients. this may explain the poorer outcomes seen in diabetic patients with rectal cancer.",Treatment
does 17-estradiol attenuate hypoxic pulmonary hypertension via estrogen receptor-mediated effects?,"17-estradiol (e2) attenuates hypoxic pulmonary vasoconstriction and hypoxic pulmonary hypertension (hph) through an unknown mechanism that may involve estrogen receptors (er) or e2 conversion to catecholestradiols and methoxyestradiols with previously unrecognized effects on cardiopulmonary vascular remodeling. to determine the mechanism by which e2 exerts protective effects in hph. male rats were exposed to hypobaric hypoxia while treated with e2 (75 g/kg/d) or vehicle. subgroups were cotreated with pharmacologic er-antagonist or with inhibitors of e2-metabolite conversion. complementary studies were performed in rats cotreated with selective er- or er-antagonist. hemodynamic and pulmonary artery (pa) and right ventricular (rv) remodeling parameters, including cell proliferation, cell cycle, and autophagy, were measured in vivo and in cultured primary rat pa endothelial cells. e2 significantly attenuated hph endpoints. hypoxia increased er but not er lung vascular expression. co-treatment with nonselective er inhibitor or er-specific antagonist rendered hypoxic animals resistant to the beneficial effects of e2 on cardiopulmonary hemodynamics, whereas er- and er-specific antagonists opposed the remodeling effects of e2. in contrast, inhibition of e2-metabolite conversion did not abolish e2 protection. e2-treated hypoxic animals exhibited reduced erk1/2 activation and increased expression of cell-cycle inhibitor p27(kip1) in lungs and rv, with up-regulation of lung autophagy. e2-induced signaling was recapitulated in hypoxic but not normoxic endothelial cells, and was associated with decreased vascular endothelial growth factor secretion and cell proliferation.","e2 attenuates hemodynamic and remodeling parameters in hph in an er-dependent manner, through direct antiproliferative mechanisms on vascular cells, which may provide novel nonhormonal therapeutic targets for hph.",Medication
does 130-nm albumin-bound paclitaxel enhance tumor radiocurability and therapeutic gain?,"130-nm albumin-bound paclitaxel (nab-paclitaxel) is a novel solvent-free albumin-bound paclitaxel, designed to avoid solvent-related toxicity. nab-paclitaxel has been successfully introduced into the clinic but its radiation-enhancing potential has not yet been evaluated. we conducted a preclinical evaluation of the radiation-modulating effects of nab-paclitaxel in tumor and normal tissues. mice bearing syngeneic ovarian or mammary carcinomas were treated with nab-paclitaxel, radiation, or combination of both. nab-paclitaxel was administered at 90 mg/kg, 1.5 times the maximum tolerated dose for solvent-based paclitaxel. end points were antitumor efficacy (growth delay, radiocurability, and cellular effects) and normal tissue toxicity (gut and skin). nab-paclitaxel showed single-agent antitumor efficacy against both tumor types and acted as a radiosensitizer. combined with radiation, nab-paclitaxel produced supra-additive effects when given before radiation. nab-paclitaxel significantly increased radiocurability by reducing the dose yielding 50 tumor cure (tcd(50)) from 54.3 to 35.2 gy. tumor histology following nab-paclitaxel treatment was characterized by pronounced necrotic and apoptotic cell death and mitotic arrest. nab-paclitaxel did not increase normal tissue radioresponse.",nab-paclitaxel exhibited strong antitumor efficacy against both tumors as a single agent and it improved radiotherapy in a supra-additive manner. these improved effects were achieved without increased normal tissue toxicity to either rapidly or slowly proliferating normal tissues although the drug dose was 1.5 times higher than the maximum tolerated dose of solvent-based paclitaxel. these preclinical findings show that combining nab-paclitaxel with radiotherapy would improve the outcome of taxane-based chemoradiotherapy. this novel taxane is thus a good candidate for testing in clinical chemoradiotherapy trials.,Treatment
does use of radiotracer for sentinel lymph node mapping in breast cancer optimize staging independent of site of administration?,"in an effort to optimize sentinel lymph node (sln) mapping for breast cancer, sites of mapping agent administration and types of mapping agents used continue to be evaluated. this study compares sln mapping using peritumoral (pt) or subareolar (sa) injection of radiolabeled colloid and examines the relative contributions of radiotracer and blue dye to sln identification. a retrospective review was performed of 456 patients with breast cancer and clinically negative axillae who underwent sln mapping. sequential groups of patients were injected with filtered tc-99m sc, 326 peritumorally (group 1) and 130 subareolarly (group 2). all patients had intraoperative sa injection of 1 isosulfan blue dye. the sln identification and isotope success rates were 97 and 96 in group 1 and 98 and 98 in group 2, respectively. eighty-one patients (25) in group 1 and 44 patients (34) in group 2 had positive slns. of these patients, 15 from group 1 and 14 from group 2 had only positive nodes detected by radiotracer, and 9 of these patients (6 from group 1 and 3 from group 2) had other nodes identified by both radiotracer and blue dye that were negative for metastases. six percent of patients with positive slns were upstaged because of use of radiotracer.","pt and sa injection of radiotracer have comparable success rates for axillary sln identification. given that 15 of patients in group 1 and 14 in group 2 had only positive slns detected by radiotracer, independent of site of administration, radiotracer remains essential for optimizing breast sln mapping.",Medication
does endotoxin fail to stimulate inositol triphosphate production in macrophages?,"inositol triphosphate (ip3) production is an early cell signaling event which leads to mobilization of intracellular calcium (ca). we examined whether bacterial endotoxin (lipopolysaccharide, lps) stimulates ip3 production in macrophages pretreated with lps (tolerant) or not. raw 264.7 macrophages were cultured at 5 x 10(6) cells in rpmi supplemented with 10 fcs. lps tolerance was induced by pretreating macrophages (tol) for 19 h with 10 ng/ml of lps. non-tolerant (non-tol) macrophages received no lps pretreatment. macrophages were next washed, repleted with fresh media, and stimulated with 100 ng/ml lps. paired cultures were stimulated with 1 microm platelet activating factor (paf), a known stimulant of ip3 production. following 1, 10, and 15-min stimulation intervals, ip3 was extracted with trichloroacetic acid and measured by receptor displacement assay. lps did not stimulate ip3 production in either non-tol or tol macrophages. in contrast, paf stimulated significant increases in ip3 levels within 1 min in both non-tol (9.5 /- 3.0 pmol/ml) and tol (9.5 /- 2.4 pmol/ml) macrophages. non-tol ip3 levels returned to baseline by 10 min, while tol ip3 levels remained significantly elevated (8.2 /- 1.7 pmol/ml).","unlike paf, bacterial lps fails to stimulate ip3 production in macrophages. furthermore, ip3 production could not be elicited in cultured macrophages repetitively stimulated with lps.",Medication
is limited resection followed by intraoperative seed implantation comparable to stereotactic body radiotherapy for solitary lung cancer?,"the objective of this study was to compare the outcomes of patients who underwent wedge resection plus intraoperative brachytherapy versus patients who received stereotactic body radiotherapy (sbrt) for single malignant lung nodules. a retrospective chart review included 55 patients who were treated for single lung nodules, and 47 of those patients who had adequate information were chosen for the current analysis. twenty-five patients with single malignant lung nodules received sbrt. twenty-two patients underwent limited surgical resection plus radioactive seed implantation for solitary malignant lung nodules. univariate statistical analysis demonstrated a significance difference only for age in the 2 groups: the mean age in the radioactive seed group (66.6 years) was statistically significantly different from the mean of the age in the sbrt group (75.9 years; 2-sided p.04). no significant differences were observed between the 2 groups in terms of local control, distant metastasis, survival, or toxicity.",the current results demonstrated comparable efficacy in outcome and toxicity between surgical resection with radioactive seed implantation and sbrt for the treatment of single malignant lung nodules in patients who were not candidates for lobectomy/pneumonectomy.,Treatment
do trigeminal nasal-specific neurons respond to nerve growth factor with substance-p biosynthesis?,"nerve growth factor (ngf) has been found to induce substance-p biosynthesis in large-diameter a-fibres vagal airway neurons. however, the effect of ngf on trigeminal neurons innervating the nasal mucosa of the mouse has not been investigated so far. ngf has been implicated in allergic diseases by modulating sensory nerves. therefore, the present study investigated the effect of ngf on neuropeptides expression such as substance-p and glutamate in nasal trigeminal neurons. using neuronal tracing in combination with double labelling immunohistochemistry the expression of substance-p, glutamate and neurofilament protein 68-kda expression was examined in nasal-specific trigeminal neurons of balb/c-mice. the numbers of fast blue-labelled trigeminal neurons expressing substance-p were significantly increased after ngf exposure (ngf-treated ganglia: 16.4 /- 0.6 vs. control: 7.0 /- 0.4, por0.001). ngf treatment-induced substance-p biosynthesis in neurofilament-positive (ngf-treated ganglia: 8.6 /- 0.2 vs. control: 1.1 /- 0.2, por0.001) as well as neurofilament-negative (ngf-treated ganglia: 7.8 /- 0.6 vs. control: 5.9 /- 0.4, p0.05) and non-glutamatergic neurons (ngf-treated ganglia: 11.8 /- 1.9 vs. control 1.1 /- 1.0, por0.001) 24 h after ngf exposure.","under normal conditions, substance-p was expressed in nasal-specific neurofilament-negative, glutamatergic and c-fibre neurons. nasal-specific trigeminal neurons respond to ngf treatment with substance-p biosynthesis in non-glutamatergic, neurofilament-positive as well as -negative neurons. these findings suggest that nasal-specific trigeminal neurons are composed of heterogenous subpopulations in relation to their peptide profiles and therefore may have different functions in neurogenic airway inflammation.",Treatment
is ace inhibitor or angiotensin ii receptor blocker use a risk factor for contrast-induced nephropathy?,"the aim of the present study was to assess the influence of angiotensin-converting enzyme inhibitor (acei) or angiotensin ii receptor blocker (arb) use on the incidence of contrast-induced nephropathy (cin) in patients undergoing coronary angiography. a retrospective case control study was conducted on a total of 201 patients divided into 2 groups (cin group and control group). cin was defined as an increase in serum creatinine by more than 25 from baseline within 48 hours of radiocontrast exposure. the cin group had 96 patients, and the control group had 105 patients. the 2 groups were matched for variables such as age, sex, weight, baseline serum creatinine, diabetes, dye load, use of diuretics, statins and preprocedure prophylactic measures for cin. the incidence of cin was found to be 4.55. the cin group had 96 patients out of which 56 patients (58.3) were on chronic acei or arb, while the control group had 105 patients, but only 36 of patients (34.3) were on acei or arb (p0.001).the odds ratio for development of cin with respect to acei or arb use was 2.68 (95 confidence interval, 1.51-4.76).","use of acei or arb is an independent risk factor for developing cin. it is reasonable to discontinue their use 48 hours prior to exposure to radiocontrast agents, especially in patients with multiple risk factors.",Medication
"is hddd2 a familial frontotemporal lobar degeneration with ubiquitin-positive , tau-negative inclusions caused by a missense mutation in the signal peptide of progranulin?","familial autosomal dominant frontotemporal dementia with ubiquitin-positive, tau-negative inclusions in the brain linked to 17q21-22 recently has been reported to carry null mutations in the progranulin gene (pgrn). hereditary dysphasic disinhibition dementia (hddd) is a frontotemporal dementia with prominent changes in behavior and language deficits. a previous study found significant linkage to chromosome 17 in a hddd family (hddd2), but no mutation in the mapt gene. longitudinal follow-up has enabled us to identify new cases and to further characterize the dementia in this family. the goals of this study were to develop research criteria to classify the different clinical expressions of dementia observed in this large kindred, to identify the causal mutation in affected individuals and correlate this with phenotypic characteristics in this pedigree, and to assess the neuropathological characteristics using immunohistochemical techniques. in this study we describe a detailed clinical, pathological and mutation analysis of the hddd2 kindred. neuropathologically, hddd2 represents a familial frontotemporal lobar degeneration with ubiquitin-positive, tau-negative inclusions (ftld-u). we developed research classification criteria and identified three distinct diagnostic thresholds, which helped localize the disease locus. the chromosomal region with the strongest evidence of linkage lies within the minimum critical region for ftld-u. sequencing of each exon of the pgrn gene led to the identification of a novel missense mutation, ala-9 asp, within the signal peptide.","hddd2 is an ftld-u caused by a missense mutation in the pgrn gene that cosegregates with the disease and with the disease haplotype in at-risk individuals. this mutation is the first reported pathogenic missense mutation in the signal peptide of the pgrn gene causing ftld-u. in light of the previous reports of null mutations and its position in the gene, two possible pathological mechanisms are proposed: (1) the protein may accumulate within the endoplasmic reticulum due to inefficient secretion; and (2) mutant rna may have a lower expression because of degradation via nonsense-mediated decay.",Diagnosis
do clinical and entomological factors influence the outcome of sting challenge studies?,"the reported frequency of systemic reactions to challenge sting varies greatly. to evaluate the interaction of clinical and entomological factors that determine the outcome of a challenge sting. patients allergic to yellow jacket were stung and monitored for systemic reaction. the frequency and severity of sting reactions were analyzed in relation to the species of insect used and patient characteristics. objective systemic reactions occurred in 21 of 69 patients (30) stung with vespula maculifrons and in 8 of 71 patients (11) with vespula germanica (p.005). systemic reactions were more frequent in patients with a severe history (9/30; 30) than in those with a mild or moderate history (21/145; 14; p.04). in only 1 of 111 patients (0.9) was the reaction to sting challenge more severe than previous reactions. the reaction rate was higher when venom skin tests were positive at 1.0 microg/ml (17/7523) than when sensitivity was milder (9/1009; p.012). we compared sting outcome and venom-induced histamine release in relation to insects collected in july or in october, and found no difference.","allergic reactions to sting challenge are determined by the species of yellow jacket used, the severity of previous sting reactions, and the degree of skin test sensitivity, but not by the time of year. these factors are important to clinicians when they evaluate the chance of reaction to a future sting and to researchers when they design and report sting challenge studies.",Diagnosis
does oral administration of surfactant protein-a reduce pathology in an experimental model of necrotizing enterocolitis?,"necrotizing enterocolitis (nec) frequently results in significant morbidity and mortality in premature infants. others reported that mice deficient in pulmonary surfactant protein-a (sp-a) born and raised in a nonhygienic environment succumb to significant gastrointestinal tract pathology, and enteral administration of purified sp-a significantly reduced mortality. we hypothesized that oral administration of purified sp-a can ameliorate pathology in an experimental model of neonatal nec. experimental nec was induced in newborn sprague-dawley rat pups by daily formula gavage and intermittent exposure to hypoxia. purified human sp-a (5 g/day) was administered by oral gavage. after 4 days, surviving pups were sacrificed, and intestinal pathology was assessed by histological examination of distal terminal ileal sections. intestinal levels of inflammatory cytokines (il-1, ifn-, and tnf-) were assessed by enzyme-linked immunosorbent assay and levels of toll-like receptor 4 (tlr4) by western analysis. sixty-one percent of the gavaged rat pups that survived to day 4 met the criteria for experimental nec after hypoxia, whereas treatment with sp-a significantly reduced mortality and assessment of nec. intestinal levels of proinflammatory cytokines were significantly increased in pups exposed to hypoxia. administration of sp-a to pups exposed to hypoxia significantly reduced il-1 and tnf- levels, but had little effect on elevated levels of ifn-. sp-a treatment of hypoxia-exposed pups significantly reduced expression of intestinal tlr4, key in nec pathogenesis.","in a rat model of experimental neonatal nec, oral administration of sp-a reduces intestinal levels of proinflammatory cytokines and tlr4 protein and ameliorates adverse outcomes associated with gastrointestinal pathologies.",Medication
does immersion of bovine eyeballs after 1 hour in seawater result in elevation of postmortem vitreous humor sodium and chloride levels?,"elevations in postmortem vitreous sodium chloride (pmvsc) levels may help in differentiating saltwater/seawater drowning (swd) deaths from immersion deaths not related to drowning (dnrd). it is unclear whether the elevation is related to blood/plasma electrolyte changes after inhalation of seawater as hypothesized in swds or possibly caused by electrolyte diffusion and/or osmosis across the outer coats of the eyeball during immersion. to investigate the changes in bovine pmvsc levels at different time points while immersed in seawater. bovine eyeballs were obtained from an abattoir and randomized into 2 groups: a) submerged in seawater (""wet"" group) or b) placed in an impermeable plastic bag that was immersed in seawater (""dry"" group). the pmvsc levels from 6 eyeballs were measured from each group (without replacement) at 30 minutes, 1 hour, 6 hours, and 12 hours. there was no significant difference in mean pmvsc levels between the 2 groups at 30-minute and 1-hour intervals. a significant difference was noted from 6 hours onward.","there is no statistically significant elevation in bovine pmvsc levels when immersed in seawater for up to 1 hour. assuming similar physical properties in humans, any elevations in pmvsc levels in bodies immersed in seawater for less than 1 hour should not be caused by immersion.",General
do changes in bp induced by passive leg raising predict response to fluid loading in critically ill patients?,"to test the hypothesis that passive leg raising (plr) induces changes in arterial pulse pressure that can help to predict the response to rapid fluid loading (rfl) in patients with acute circulatory failure who are receiving mechanical ventilation. prospective clinical study. two medical icus in university hospitals. thirty-nine patients with acute circulatory failure who were receiving mechanical ventilation and had a pulmonary artery catheter in place. plr for 4 min and a subsequent 300-ml rfl for 20 min. radial artery pulse pressure (pprad), heart rate, right atrial pressure, pulmonary artery occlusion pressure (paop), and cardiac output were measured invasively in a population of 15 patients at each phase of the study procedure (i.e., before and during plr, and then before and after rfl). pprad, paop, and stroke volume (sv) significantly increased in patients performing plr. these changes were rapidly reversible when the patients' legs were lowered. changes in pprad during plr were significantly correlated with changes in sv during plr (r 0.77; p 0.001). changes in sv induced by plr and by rfl were significantly correlated (r 0.89; p 0.001). finally, plr-induced changes in pprad were significantly correlated to rfl-induced changes in sv (r 0.84; p 0.001). in a second population of 24 patients, we found the same relationship between plr-induced changes in pprad and rfl-induced changes in sv (r 0.73; p 0.001).",the response to rfl could be predicted noninvasively by a simple observation of changes in pulse pressure during plr in patients with acute circulatory failure who were receiving mechanical ventilation.,Treatment
is sublingual microcirculation impaired in post-cardiac arrest patients?,"we hypothesized that microcirculatory dysfunction, similar to that seen in sepsis, occurs in post-cardiac arrest patients and that better microcirculatory flow will be associated with improved outcome. we also assessed the association between microcirculatory dysfunction and inflammatory markers in the post-cardiac arrest state. we prospectively evaluated the sublingual microcirculation in post-cardiac arrest patients, severe sepsis/septic shock patients, and healthy control patients using sidestream darkfield microscopy. microcirculatory flow was assessed using the microcirculation flow index (mfi) at 6 and 24h in the cardiac arrest patients, and within 6h of emergency department admission in the sepsis and control patients. we evaluated 30 post-cardiac arrest patients, 16 severe sepsis/septic shock patients, and 9 healthy control patients. sublingual microcirculatory blood flow was significantly impaired in post-cardiac arrest patients at 6h (mfi 2.6 iqr: 2-2.9) and 24h (2.7 iqr: 2.3-2.9) compared to controls (3.0 iqr: 2.9-3.0; p0.01 and 0.02, respectively). after adjustment for initial apache ii score, post-cardiac arrest patients had significantly lower mfi at 6-h compared to sepsis patients (p0.03). in the post-cardiac arrest group, patients with good neurologic outcome had better microcirculatory blood flow as compared to patients with poor neurologic outcome (2.9 iqr: 2.4-3.0 vs. 2.6 iqr: 1.9-2.8; p0.03). there was a trend toward higher median mfi at 24h in survivors vs. non-survivors (2.8 iqr: 2.4-3.0 vs. 2.6 iqr: 2.1-2.8 respectively; p0.09). we found a negative correlation between mfi-6 and vascular endothelial growth factor (vegf) (r-0.49, p0.038). however, after bonferroni adjustment for multiple comparisons, this correlation was statistically non-significant.",microcirculatory dysfunction occurs early in post-cardiac arrest patients. better microcirculatory function at 24h may be associated with good neurologic outcome.,Diagnosis
does fetal growth restriction result in remodeled and less efficient hearts in children?,"fetal growth restriction (fgr) affects 5 to 10 of newborns and is associated with increased cardiovascular mortality in adulthood. the most commonly accepted hypothesis is that fetal metabolic programming leads secondarily to diseases associated with cardiovascular disease, such as obesity, diabetes mellitus, and hypertension. our main objective was to evaluate the alternative hypothesis that fgr induces primary cardiac changes that persist into childhood. within a cohort of fetuses with growth restriction identified in fetal life and followed up into childhood, we randomly selected 80 subjects with fgr and compared them with 120 normally grown fetuses, matched for gender, birth date, and gestational age at birth. cardiovascular assessment was performed in childhood (mean age of 5 years). compared with control subjects, children with fgr had a different cardiac shape, with increased transversal diameters and more globular cardiac ventricles. although left ejection fraction was similar among the study groups, stroke volume was reduced significantly, which was compensated for by an increased heart rate to maintain output in severe fgr. this was associated with subclinical longitudinal systolic dysfunction (decreased myocardial peak velocities) and diastolic changes (increased e/e' ratio and e deceleration time). children with fgr also had higher blood pressure and increased intima-media thickness. for all parameters evaluated, there was a linear increase with the severity of growth restriction.","these findings suggest that fgr induces primary cardiac and vascular changes that could explain the increased predisposition to cardiovascular disease in adult life. if these results are confirmed, the impact of strategies with beneficial effects on cardiac remodeling should be explored in children with fgr.",Prevention
"are improved blood pressure , nitric oxide and asymmetric dimethylarginine independent after bariatric surgery?","obesity is associated with hypertension, but the exact mechanism is not fully understood. bariatric surgery significantly decreases weight and blood pressure (bp). low plasma nitric oxide (no) and raised asymmetric dimethylarginine (adma), an endogenous inhibitor of no, concentrations are associated with both obesity and hypertension. correlations between the changes in these parameters were studied after bariatric surgery. weight, bp, plasma adma and no were measured in 29 obese patients (24 female, 5 male) before and six weeks after bariatric surgery. patients were 39.2 1.2 (mean sem) years old and weighed 126 3 kg. six weeks after the surgery, patients had lost 10 0.7 kg (p 0.0001) and mean arterial pressure (map) decreased by 11 1.0 mmhg (p 0.0001). the plasma adma concentration decreased by 24 2 from 5 0.4 to 4.0 0.3 mol/l (p 0.0001). the plasma total nitrite concentration increased by 15 1 from 51.4 2.6 to 60 3 mol/l (p 0.0001). the correlation between the decrease of adma and increase of no subsequent to weight loss was significant (p 0.0001). however, map was not correlated to the changes in adma or no.","after bariatric surgery, beneficial changes in bp, no and adma occur, but our findings suggest that these bp changes are independent of changes in the no-adma axis. other causes for the changes in bp should therefore be considered.",Treatment
are plasma phosphorylated tdp-43 levels elevated in patients with frontotemporal dementia carrying a c9orf72 repeat expansion or a grn mutation?,"about a half of patients with frontotemporal dementia (ftd) has deposition of phosphorylated tdp-43 protein (ptdp-43) in the brain. we studied ptdp-43 and total tdp-43 levels in plasma and cerebrospinal fluid (csf) in healthy controls and patients with ftd, including those carrying a repeat expansion in the c9orf72 gene or a mutation in grn. we included 88 plasma samples of 10 c9orf72 expansion carriers, 5 grn mutation carriers, 51 patients with ftd without a known mutation and 22 healthy controls. we also obtained csf samples from 25 patients with ftd (2 with c9orf72 expansion and 3 with a grn mutation) and 22 healthy controls. we measured ptdp-43 and total tdp-43 levels using sandwich elisa. patients carrying the c9orf72 repeat expansion or a grn mutation had significantly higher plasma and csf levels of ptdp-43 than the remaining patients with ftd (p0.05). in addition, plasma ptdp-43 levels were higher in patients with ftd carrying a c9orf72 expansion or grn mutations than in healthy controls (p0.05).",our study shows that plasma ptdp-43 levels may be increased in some genetic forms of ftd known to be associated with tdp-43 proteinopathies.,General
is peripheral vascular disease associated with reduced glycosuria in newly diagnosed type 2 diabetic patients?,"we examined whether the finding of glycosuria and its level in themselves give information of clinical relevance, apart from being an unreliable indicator of glycemic control. subjects were a population-based sample of 1,284 newly diagnosed type 2 diabetic patients. median age was 65.2 years. urinary glucose concentration (ugc) was determined quantitatively in a freshly voided morning urine specimen. the over-all prevalence of peripheral vascular disease (pvd) was 16.5. bivariately, high values of ugc were associated with low prevalence of pvd (p0.001, chi2-test). the predictive value of pvd--together with hba1c, glomerular filtration rate (gfr) and 10 other possible predictors--was confirmed in a logistic regression analysis with glycosuria (y/n) as outcome variable (p0.0004).","surprisingly, type 2 diabetic patients with pvd tend not to have glycosuria as compared to patients without pvd. pvd may be indicative of generalized atherosclerotic lesions in the major vessels, including the renal arteries. this could lead to a lowering of gfr and thereby of the amount of glucose filtered. assuming no, or only a minor direct effect of pvd on tubular function, this would lead to an increased renal threshold for glucose in patients with pvd.",Diagnosis
do braf and nras locus specific variants have different outcomes on survival to colorectal cancer?,"somatic mutation status at kras, braf and nras is associated with prognosis in patients with advanced colorectal cancer (acrc); however, it remains unclear whether there are intra-locus, variant-specific differences in survival and other clinicopathological parameters. we profiled 2,157 acrcs for somatic mutations in kras, braf and nras and determined microsatellite instability status. we sought inter- and intra-locus correlations between mutations, and variant-specific associations with survival and clinicopathology. kras mutations were rarely found together and those in codons 12 and 13 conferred poor prognosis (hr 1.44, 95 ci 1.28-1.61, p6.4e-10 and hr 1.53, 95 ci 1.26-1.86, p1.5e-05, respectively). for braf, more c.1781ag (p.d594g) crcs carried ras mutations (14 3/21) compared to c.1799ta (p.v600e) crcs (1 2/178, p9.0e-03). c.1799ta (p.v600e) was associated with poor prognosis (hr 2.60, 95 ci 2.06-3.28, p1.0e-15), whereas c.1781ag (p.d594g) was not (hr 1.30, 95 ci 0.73-2.31, p0.37); this intra-locus difference was significant (p0.04). more c.1799ta (p.v600e) crcs were found in the right colon (47 47/100), compared to c.1781ag (p.d594g) crcs (7 1/15, p3.7e-03). for nras, 5 (3/60) of codon 61 mutant crcs had kras mutations compared to 44 (10/23) of codons 12 and 13 mutant crcs (p7.9e-05). codon 61 mutations conferred poor prognosis (hr 1.47, 95 ci 1.09-1.99, p0.01), whereas codons 12 and 13 mutations did not (hr 1.29, 95 ci 0.64-2.58, p0.48).",our data show considerable intra-locus variation in the outcomes of mutations in braf and nras. these data need to be considered in patient management and personalised cancer therapy.,Diagnosis
is high-dose vasopressin superior to norepinephrine in septic shock?,"we examined the effects of arginine vasopressin, when substituted for norepinephrine as a vasopressor in septic shock, on global and hepatosplanchnic hemodynamic and oxygen transport variables. experimental study. intensive care unit. twelve septic shock patients. norepinephrine was replaced by vasopressin in a dose sufficient to keep mean arterial blood pressure constant. blood flow, oxygen delivery, and oxygen consumption of the hepatosplanchnic region (calculated by a hepatic venous catheter technique using the fick principle during continuous infusion of indocyanine green), global hemodynamics (by thermodilution), and gastric regional pco2 gap (by air tonometry) were calculated during infusion of norepinephrine (mean, 0.56 microg.kg-1.min-1; range, 0.18-1.1 microg.kg-1.min-1) and again 2 hrs after replacement by vasopressin (mean, 0.47 iu/min; range, 0.06-1.8 iu/min). cardiac index decreased significantly from 3.8 /- 1.3 to 3.0 /- 1.1 l.min-1.m-2, heart rate decreased from 96 /- 14 to 80 /- 16 min-1 (p .01), and global oxygen uptake decreased from 248 /- 67 to 218 /- 75 ml/min (p .05). absolute splanchnic blood flow tended to increase, although not significantly, whereas fractional splanchnic blood flow increased from 10.8 /- 7.6 to 25.9 /- 16.6 of cardiac output (p .05). gastric regional pco2 gap increased from 17.5 /- 26.6 to 36.5 /- 26.6 mm hg (p .01).","vasopressin, in doses sufficient to replace the vasopressor norepinephrine, had mixed effects in septic shock patients. hepatosplanchnic blood flow was preserved during substantial reduction in cardiac output. an increased gastric pco2 gap suggests that the gut blood flow could have been redistributed to the disadvantage of the mucosa. based on these limited data, it does not appear beneficial to directly replace norepinephrine with vasopressin in septic shock.",Medication
does microrna-150 protect the mouse heart from ischaemic injury by regulating cell death?,"cardiac injury is accompanied by dynamic changes in the expression of micrornas (mirs). for example, mir-150 is down-regulated in patients with acute myocardial infarction, atrial fibrillation, dilated and ischaemic cardiomyopathy as well as in various mouse heart failure (hf) models. circulating mir-150 has been recently proposed as a better biomarker of hf than traditional clinical markers such as brain natriuretic peptide. we recently showed using the -arrestin-biased -blocker, carvedilol that -arrestin1-biased 1-adrenergic receptor cardioprotective signalling stimulates the processing of mir-150 in the heart. however, the potential role of mir-150 in ischaemic injury and hf is unknown. here, we show that genetic deletion of mir-150 in mice causes abnormalities in cardiac structural and functional remodelling after mi. the cardioprotective roles of mir-150 during ischaemic injury were in part attributed to direct repression of the pro-apoptotic genes egr2 (zinc-binding transcription factor induced by ischaemia) and p2x7r (pro-inflammatory atp receptor) in cardiomyocytes.",these findings reveal a pivotal role for mir-150 as a regulator of cardiomyocyte survival during cardiac injury.,Diagnosis
does clinical outcome after radiofrequency catheter ablation of focal atrial fibrillation trigger?,"ablative therapy for atrial fibrillation (af) by targeting initiating triggers, usually in or around the pulmonary veins, has been reported by several centers. evidence for an overall improvement in quality of life (qol) and amelioration of symptoms is lacking. seventy-one patients undergoing attempted ablation of focal af were followed for 60/-33 weeks. qol and symptom questionnaires were completed 1 month before and 6 months after electrophysiologic study. twenty-three patients (32) underwent electrophysiologic mapping but no ablation because of either insufficient or multifocal ectopy; the other 48 patients (68) underwent attempted ablation. sixteen of 48 patients (33) undergoing ablation, or 16 (23) of 71 on an intention-to-treat basis, were found at last follow-up to have persistent sinus rhythm without antiarrhythmic drugs. patients who underwent mapping without ablation reported no improvements in any qol or symptom score, whereas patients who had long-term successful ablation had significant improvements in all six qol measures. interestingly, patients who developed af recurrence after ablation still reported significant improvements in 4 of 6 qol measures. four of 48 patients (8.3) undergoing ablation developed pulmonary vein stenosis.","paroxysmal af can be treated successfully in some patients by ablating initiating triggers in the pulmonary veins; however, in our experience the recurrence rate (32/48 68) and risk of pulmonary vein stenosis (8) after ablation are high. patients with recurrent af after ablation of focal af triggers have significant improvement in qol and symptoms compared with before ablation. patients and their physicians should carefully balance the risks and benefits before considering ablation.",Treatment
does vitamin d deficiency be prevalent in morbidly obese adolescents prior to bariatric surgery?,obese adults are frequently vitamin d deficient before bariatric surgery; whether similar abnormalities exist in morbidly obese adolescents is unknown. to determine the prevalence of vitamin d deficiency in morbidly obese adolescents. cross-sectional study of preoperative laboratory measures from 236 adolescents evaluated for bariatric surgery. the group (,"most adolescents presenting for bariatric surgery have suboptimal vitamin d levels, with african americans and those with higher bmis at greatest risk for vitamin d deficiency. all morbidly obese adolescents should be screened for vitamin d deficiency before bariatric procedures.",Treatment
is the carcinoembryonic antigen ( cea ) family ( cd66 ) expressed in melanocytic naevi expressed in blue naevuscell naevi in dendritic type?,"although sporadic reports have regarded the expression of the carcinoembryonic antigen (cea) family in melanoma, there has been no information about the expression in precursor lesions of melanoma such as melanocytic naevi and blue naevi. the expression was immunohistochemically studied in frozen biopsy specimens of 45 acquired and 16 congenital melanocytic naevi and 20 blue naevi, using a panel of monoclonal and polyclonal antibodies that recognize different epitopes of cea and related molecules. members of the cea glycoprotein family were strongly expressed in all of the subtypes of melanocytic naevus. a reduced expression of the cea glycoproteins with increased dermal depth or acquisition of a spindled morphology of naevus cells was apparent. the expression was not seen in the present blue naevi and normal epidermal melanocytes.","although the significance of the expression was not clarified, this report has clearly demonstrated that the cea family is strongly expressed in melanocytic naevi and immunoreactivity is divergent between melanocytic naevi and blue naevi and between dermal naevus cell types, suggesting that the expression may be altered with architectural changes in the melanocyte-lineage cells.",Diagnosis
are caregiver food behaviours associated with dietary intakes of children outside the child-care setting?,"to evaluate whether food behaviours of parents are associated with childrens dietary intakes outside the child-care setting, and to compare childrens dietary intakes at home with foods and beverages consumed when they are at child-care centres. in 20052006, a survey was completed by parents of at least one child between 3 and 5 years old who attended group child-care centres. surveys about nutrition practices were completed by centre directors. research assistants observed foods and beverages consumed by children at lunchtime at the centres. sixteen licensed group child-care centres in three underserved new york city communities (south bronx, east/central harlem, central brooklyn) and the lower east side of manhattan. two hundred parents. children were more likely to consume healthful foods including fruits or vegetables if parents reported purchasing food from produce stands/farmers markets, shopped for frozen or canned fruits frequently and ate family meals or meals prepared at home daily. children were more likely to consume less healthful foods such as french fries, or fruit drinks, more frequently if parents reported eating meals from fast-food or other restaurants at least once weekly, or if children ate while watching television. types of foods and beverages offered to children at home (e.g. higher-fat milk, soft drinks and desserts) were less healthful than those offered at child-care centres.",childrens dietary intakes at home need to be improved. parents need to understand the importance of providing home environments that support healthful food behaviours in children.,Prevention
does robot-assisted gastrojejunal anastomosis improve the results of the laparoscopic roux-en-y gastric bypass?,"traditional laparoscopic surgery presents some difficulties for morbidly obese patients due to limited motion of instruments related to a thick abdominal wall, intraabdominal fat, and a large hepatic left lobe, with consequent loss of dexterity and greater musculoskeletal discomfort. robotic technique could potentially overcome these limitations. this study aimed to evaluate robot-assisted laparoscopic roux-en-y gastric bypass in morbidly obese patients and to compare the results of robotic assistance with those of traditional laparoscopic technique. between september 2006 and june 2009, 110 morbidly obese patients underwent laparoscopic roux-en-y gastric bypass with robot-assisted hand-sewn gastrojejunal anastomosis using the da vinci surgical system. the data for these patients was compared with the data for 423 consecutive patients treated in a standard laparoscopic manner during the same period. the patients had a mean preoperative age of 42.6 years, a mean weight of 127.5 kg, and a mean body mass index (bmi) of 46.7 kg/m2. the total mean operative time was 247.5 min. the robotic setup time was 10.1 min, and the robotic operative time was 54.5 min. the conversion rate was nil. the intraoperative complication rate was 4.5. the early and late major postoperative complication rates were 3.6 and 6.4 respectively. the cost per patient was 5777.76 . for the standard laparoscopy, the operative time was significantly shorter (187 min; p0.001), and the costs per patient were significantly lower (4658.28 ; p0.001), whereas no differences were found in terms of the intra- or postoperative complication rates, revisional surgery, or hospital length of stay.","although safe and intuitive, the robotic approach was burdened by a longer operative time and higher equipment costs. moreover, it did not seem to provide a real advantage over standard laparoscopy in terms of hospital length of stay and complications rates.",Treatment
does methylphenidate improve visual-spatial memory in children with attention-deficit/hyperactivity disorder?,"to investigate the effect of methylphenidate (mph) on visual-spatial memory, as measured by subtests of the cambridge neuropsychological testing automated battery (cantab), in children with attention-deficit/hyperactivity disorder (adhd). visual-spatial memory is a core component of working memory that has been shown to be impaired in adhd, irrespective of comorbid reading and/or language problems. a clinic-referred sample of school-age children with a confirmed dsm-iv diagnosis of adhd (n 26) completed tests of visual-spatial memory, planning ability, and recognition memory in an acute, randomized, placebo-controlled, crossover trial with three single fixed doses of mph. mph effects on right-handed and left-handed motor control were also assessed. mph significantly improved performance on a self-ordered, updating visual-spatial working memory task and on maintenance of visual-spatial information but had no effects on measures of visual-spatial planning ability or recognition memory. also, mph significantly improved left-handed motor control.",beneficial effects of mph on visual-spatial processing in adhd are selective and restricted to visual-spatial memory.,Medication
does bottom-up driven involuntary attention modulate auditory signal in noise processing?,"auditory evoked responses can be modulated by both the sequencing and the signal-to-noise ratio of auditory stimuli. constant sequencing as well as intense masking sounds basically lead to n1m response amplitude reduction. however, the interaction between these two factors has not been investigated so far. here, we presented subjects tone stimuli of different frequencies, which were either concatenated in blocks of constant frequency or in blocks of randomly changing frequencies. the tones were presented either in silence or together with broad-band noises of varying levels. in silence, tones presented with random sequencing elicited a larger n1m response than tones presented with constant sequencing. with increasing noise level, this difference decreased and even vanished in the condition where noise intensity exceeded the tone intensity by 10 db. furthermore, under noisy conditions, the n1m latency was shorter in the constant sequencing condition compared to the random sequencing condition.","besides the well-known neural habituation mechanisms, bottom-up driven attention plays an important role during auditory processing in noisy environments. this bottom-up driven attention would allow us to track a certain auditory signal in noisy situations without voluntarily paying attention to the auditory modality.",General
does nitric oxide modulate expression of matrix metalloproteinase in asthmatic rats ?,"to observe the effect of nitric oxide on expression of matrix metalloproteinase and tissue inhibitor of metalloproteinase in asthmatic rats. thirty healthy male wistar rats were randomly divided into control (n 10), asthmatic (n 10) and l-arginine (n 10) groups. lung tissues were sliced and stained with he. the following morphometric parameters were measured by image analysis system: airway wall basement membrane perimeter (pbm), total bronchial wall area (wat), the inner wall area (wai) and the area of smooth muscle (wam). levels of nitrites/nitrates and nos activity in the lungs were measured by commercial no and nos kits. transcriptional levels of mmp-2 and timp-1 mrna in the lungs were assessed by semiquantitative reverse transcription-polymerase chain reaction (rt-pcr). (1) wat/pbm, wai/pbm and wam/pbm in the l-arginine group were (35.1 /- 2.6) microm(2)/microm, (25.3 /- 2.0) microm(2)/microm, and (8.7 /- 1.5) microm(2)/microm, respectively. wat/pbm, wai/pbm and wam/pbm in the asthmatic group were (25.3 /- 2.1) microm(2)/microm, (20.4 /- 2.3) microm(2)/microm, and (4.2 /- 2.0) microm(2)/microm, respectively. wat/pbm, wai/pbm and wam/pbm in the control group were (20.8 /- 1.3) microm(2)/microm, (15.3 /- 2.1) microm(2)/microm, and (3.1 /- 1.1) microm(2)/microm, respectively. the differences among three groups were statistically significant. (2) levels of nitrites/nitrates in the l-arginine group (11.8 /- 1.7) nmol/mg and the asthmatic group (7.2 /- 2.1) nmol/mg were significantly higher than that in the control group (3.1 /- 1.2) nmol/mg. nos activity in the lungs was (16.5 /- 1.3) u/mg l-arginine group, (10.8 /- 1.4) u/mg asthmatic group, and (1.46 /- 0.98) u/mg control group, respectively, the differences being statistically significant between groups. (3) mmp-2 and timp-1 mrna levels in the l-arginine group and the asthmatic group were significantly higher than that in the control group l-arginine group (0.82 /- 0.11), (0.51 /- 0.12); asthmatic group (0.68 /- 0.14), (0.56 /- 0.10); control group (0.14 /- 0.03), (0.11 /- 0.05), respectively. the difference in the mmp-2 mrna levels was significant between the l-arginine group and the asthmatic group (p 0.05). (4) a significant positive correlation was found between the mmp-2 mrna levels and nitrites/nitrates levels in l-arginine group and asthmatic group (r(s) 0.65, 0.68, p 0.05).",nitric oxide may contribute to airway inflammation and remodeling by influencing the balance between matrix metalloproteinases and tissue inhibitors of metalloproteinases.,Medication
is s100a4 expression an early event of papillary carcinoma of the thyroid?,"s100a4 is a calcium-binding protein related to the metastatic potential of carcinoma. in order to elucidate its contribution to the progression of thyroid carcinoma, we investigated s100a4 expression in various thyroid neoplasms. we immunohistochemically examined s100a4 expression in 195 cases of thyroid neoplasms. although s100a4 was absent in normal follicular cells and follicular adenoma, s100a4 was positive in all 115 cases of papillary carcinoma examined, including 58 microcarcinomas. however, a significant relationship could not be established between s100a4 expression and clinicopathological features of papillary carcinoma. in follicular carcinoma, the widely invasive type expressed s100a4 more frequently than the minimally invasive type (p 0.0028). in anaplastic carcinoma, s100a4 was expressed in 61.9 of cases, but the incidence was significantly lower (p 0.0001) than that in papillary carcinoma.",these findings suggest that (1) s100a4 plays a constitutive role in papillary carcinoma and (2) s100a4 may be a useful marker for early the detection of this carcinoma.,General
does extracellular matrix of current biological scaffolds promote the differentiation potential of mesenchymal stem cells?,"the purpose of this study was to quantitatively assess the ability of bone marrow-derived mesenchymal stem cells (bmsc) to differentiate toward bone, fat, cartilage, and tendon lineages when grown on commercially available scaffolds compared with control and native tendon tissue. bmscs were cultured and analyzed by fluorescent automated cells sorting for surface markers cd73, -90, and -105. bmscs were grown on rotator cuff tendon (rct), decellularized human dermis patch (ddp), bilayer collagen matrix, and fibrin matrix (fm) to test their differentiation potential using quantitative polymerase chain reaction and establish markers for osteogenic, adipogenic, chondrogenic, and tenogenic lineages. immunocytochemical testing was used to determine the specific proteins present on the scaffolds. alkaline phosphatase and osteocalcin gene expression was significantly higher on rct (p .001) and collagen scaffold (cs) (p .001) compared with ddp and fm scaffolds (p .001, p .001). when differentiated toward a cartilage lineage, bmscs grown on cs had significantly more type ii collagen and aggrecan compared with ddp (p .001, p .001), fm (p .001, p .001), and rct (p .001, p .001). differentiated bmscs grown on the cs had a significant increase in ppar and fabp4 gene expression compared with bmscs grown on all other scaffolds (all p .001). the differentiation of bmscs into tendon on css had significantly more tenacin c, decorin, and type iii collagen gene expression when compared with rct, ddp, and fm (all p .001). decorin gene expression in the control undifferentiated cs was also significantly increased, suggesting that the matrix alone may promote a tenogenic lineage (p .637).","differences in the extracellular matrix composition of scaffolds significantly impact their potential to promote differentiation of bmscs. comparing the native rct to the tested scaffolds showed that a high content of type i and iii collagen significantly increased the potential of bmscs to differentiate toward bone, tendon, fat, and cartilage lineages.",Diagnosis
is obesity associated with increased health care charges in patients undergoing outpatient plastic surgery?,"obesity is associated with greater rates of surgical complications. to address these complications after outpatient plastic surgery, obese patients may seek care in the emergency department and potentially require admission to the hospital, which could result in greater health care charges. the purpose of this study was to determine the relationship of obesity, postdischarge hospital-based acute care, and hospital charges within 30 days of outpatient plastic surgery. from state ambulatory surgery center databases in four states, all discharges for adult patients who underwent liposuction, abdominoplasty, breast reduction, and blepharoplasty were identified. patients were grouped by the presence or absence of obesity. multivariable regression models were used to compare the frequency of hospital-based acute care, serious adverse events, and hospital charges within 30 days between groups while controlling for confounding variables. the final sample included 47,741 discharges, with 2052 of these discharges (4.3 percent) being obese. obese patients more frequently had a hospital-based acute care encounter 7.3 percent versus 3.9 percent; adjusted or, 1.35 (95 ci,1.13 to 1.61) or serious adverse event 3.2 percent versus 0.9 percent; adjusted or, 1.73 (95 ci, 1.30 to 2.29) within 30 days of surgery. obese patients had adjusted hospital charges that were, on average, 3917, 7412, and 7059 greater (p 0.01) than those of nonobese patients after liposuction, abdominoplasty, and breast reduction, respectively.","obese patients who undergo common outpatient plastic surgery procedures incur substantially greater health care charges, in part attributable to more frequent adverse events and hospital-based health care within 30 days of surgery.",Treatment
do impact of the 2nd story peer respite program on use of inpatient and emergency services?,"by providing a safe and supportive space for individuals experiencing or at risk of experiencing a mental health crisis, a peer respite may reduce the need for traditional crisis interventions. this study examined the relationship between peer respite and use of inpatient and emergency services among adults receiving publicly funded behavioral health services. this analysis used propensity score matching to create matched pairs of 139 users of peer respite and 139 nonusers of respite with similar histories of behavioral health service use and clinical and demographic characteristics. a two-stage regression model first predicted the likelihood of inpatient or emergency service use after peer respite start date and then predicted hours of inpatient and emergency service use among 89 individuals who used any inpatient or emergency services. after the authors controlled for relevant covariates, the odds of using any inpatient or emergency services after the program start date were approximately 70 lower among respite users than nonrespite users, although the odds increased with each additional respite day. among individuals who used any inpatient or emergency services, a longer stay in respite was associated with fewer hours of inpatient and emergency service use. however, the association was one of diminishing returns, with negligible decreases predicted beyond 14 respite days.","by reducing the need for inpatient and emergency services for some individuals, peer respites may increase meaningful choices for recovery and decrease the behavioral health system's reliance on costly, coercive, and less person-centered modes of service delivery.",Treatment
is self-medication with anti-malarials a common practice in rural communities of kilosa district in tanzania despite the reported decline of malaria?,"self-medication has been widely practiced worldwide particularly in developing countries including tanzania. in sub-saharan africa high incidences of malaria have contributed to self-medication with anti-malarial drugs. in recent years, there has been a gain in malaria control, which has led to decreased malaria transmission, morbidity and mortality. therefore, understanding the patterns of self-medication during this period when most instances of fever are presumed to be due to non-malaria febrile illnesses is important. in this study, self-medication practice was assessed among community members and information on the habit of self-medication was gathered from health workers. twelve focus group discussions (fgd) with members of communities and 14 in-depth interviews (idi) with health workers were conducted in kilosa district, tanzania. the transcripts were coded into different categories by maxqda software and then analysed through thematic content analysis. the study revealed that self-medication was a common practice among fgd participants. anti-malarial drugs including sulphadoxine-pyrimethamine and quinine were frequently used by the participants for treatment of fever. study participants reported that they visited health facilities following failure of self-medication or if there was no significant improvement after self-medication. the common reported reasons for self-medication were shortages of drugs at health facilities, long waiting time at health facilities, long distance to health facilities, inability to pay for health care charges and the freedom to choose the preferred drugs.","this study demonstrated that self-medication practice is common among rural communities in the study area. the need for community awareness is emphasized for correct and comprehensive information about drawbacks associated with self-medication practices. deliberate efforts by the government and other stakeholders to improve health care services, particularly at primary health care facilities will help to reduce self-medication practices.",Medication
is tension-free hernia repair associated with an increase in inflammatory response markers against the mesh?,"the purpose of this study was to evaluate the involvement of inflammatory mediators in patients undergoing lichtenstein tension-free hernioplasty (lh) using polypropylene prosthetic materials or conventional bassini hernia repair (bh). thirty patients male with unilateral inguinal hernia without complications or recurrence were included in this study. randomly, patients underwent lh or bh. peripheral venous bloods samples were collected 24 hours prior to surgery and then 6, 24, 48 and 168 hours postoperatively. we present evidences that lh patients showed a higher increased serum level of fibrinogen, c-reactive protein, alpha-1-antitrypsin, and interleukin-6 than bh patients. postoperative visual analogue scales for pain were reduced on mobilization for patients undergoing lh compared with bh. neutrophils were significantly increased only in lh compared with baseline. ceruloplasmin, transferrin, and albumin levels were unmodified after bh or lh.","in conclusion our data show that although lh induces less pain and more rapid postoperative recovery, it is associated with an higher inflammatory response compared with bh, likely due to polypropylene mesh.",Treatment
do vitamin d3 influence the th1/th2 ratio in c57bl/6 induced model of experimental autoimmune encephalomyelitis?,"multiple sclerosis (ms) is known as a progressive inflammatory cns disease. cytokines belong to th1 or th2 family and inflammatory cells, play significant role in pathophysiology of ms. thus, any treatment supposed to influence the relation between th1 to th2 cytokines expression. although vitamin d has been prescribed as a therapeutic supplement of ms for a long time, it is not clear how much it may affect the th1/th2 ratio. to answer this question the present research was designed. thirty c57bl/6 adult female mice were used. the animals were randomly divided into trial and control groups. experimental autoimmune encephalomyelitis (eae) modeling for ms and clinical scoring as cited by others was used. based on scoring and step of the disease vitamin d3 prescription (5 mg/kg) started and continued for three weeks. by using elisa and rt-pcr the brain level of tnf-, il-10, il-4 and il-12 determined. significant decrease of clinical symptoms in trial group which received vitamin d was seen comparing to control animals (p0.05). the level of tnf- but not il-10 significantly decreased following vitamin d3 administration. by comparing the level of th1 and th2 interleukins and counting the ratio of them we found that in treated animals the ratio was significantly less than non-treated (p0.01).","according to the results, vitamin d3 may be able to suppress the inflammatory ways that lead to progression of ms. whether this ability is clinically valuable in human subjects is not clear and needs more clinical research.",Medication
does whole-genome optical mapping reveal a mis-assembly between two rrna operons of corynebacterium pseudotuberculosis strain 1002?,"studies have detected mis-assemblies in genomes of the species corynebacterium pseudotuberculosis. these new discover have been possible due to the evolution of the next-generation sequencing platforms, which have provided sequencing with accuracy and reduced costs. in addition, the improving of techniques for construction of high accuracy genomic maps, for example, whole-genome mapping (wgm) (opgen inc), have allow high-resolution assembly that can detect large rearrangements. in this work, we present the resequencing of corynebacterium pseudotuberculosis strain 1002 (cp1002). cp1002 was the first strain of this species sequenced in brazil, and its genome has been used as model for several studies in silico of caseous lymphadenitis disease. the sequencing was performed using the platform ion pgm and fragment library (200 bp kit). a restriction map was constructed, using the technique of wgm with the enzyme kpni. after the new assembly process, using wgm as scaffolder, we detected a large inversion with size bigger than one-half of genome. a specific analysis using blast and nr database shows that the inversion occurs between two homology rna ribosomal regions.","in conclusion, the results showed by wgm could be used to detect mismatches in assemblies, providing genomic maps with high resolution and allow assemblies with more accuracy and completeness. the new assembly of c. pseudotuberculosis was deposited in genbank under the accession no. cp012837.",Diagnosis
does health-related quality of life predict mortality in idiopathic pulmonary fibrosis?,"although health-related quality of life (hrql) has recently been considered to be an important outcome in clinical trials of idiopathic pulmonary fibrosis (ipf), its relationship with survival is unknown. to determine the prognostic significance of hrql scores in ipf assessed with the sgrq. eighty-seven consecutive patients with ipf, who had undergone evaluations and completed the st. george's respiratory questionnaire (sgrq) at diagnosis were included in this study, as is the general practice. cox proportional hazards analyses were performed to examine the relationship between hrql scores and survival. the mean observation period was 44.2 /- 29.6 mo, in the course of which 54 patients (62.0) died. univariate analysis revealed that the activity scores in the sgrq(hr: 1.016, 95 ci: 1.004-1.029, p 0.01) were significantly predictive of survival, although the symptoms, impacts, and total scores were not significantly related to mortality from all causes. however, multivariate analysis revealed that only the forced vital capacity percent predicted was a significant predictor of survival, and that the activity score in the sgrqwas not significantly related to mortality.",there was no significant relationship between hrql evaluated with the sgrq and the subsequent mortality in ipf. the present negative result might suggest that hrql is measuring an aspect other than one from physiological and functional impairment or disability.,Diagnosis
is egr-2 required for in vivo cd4 t cell mediated immune responses?,"the zinc finger transcription factor egr-2 has been shown to play an important role in the induction of t cell anergy and the regulation of peripheral t cell tolerance. in vitro, a prior study has show that t cells deficient in egr-2 are hyperproliferative to il-2 and produce elevated levels of the effector cytokine ifn-. egr-2 deficient mice have increased levels of cd44(high) t cells in peripheral lymphoid organs, and with age, develop autoimmune-like features. here we show that despite increased numbers of cells bearing an activated cd44(high)cd62l(low) phenotype, t cells from young healthy egr-2 deficient mice have normal proliferative and cytokine responses, and the mice themselves mount normal immune responses against minor histocompatibility antigens, and the pathogens toxoplasma gondii and lymphocytic choriomeningitis virus.","our results indicate that egr-2 is not required to mount normal acute in vivo immune responses against foreign antigens, and suggest instead that it may serve to regulate the response to chronic antigenic exposure, such as that which occurs to autoantigens.",General
does correction for tissue optical properties enable quantitative skin fluorescence measurements using multi-diameter single fiber reflectance spectroscopy?,"fluorescence measurements in the skin are very much affected by absorption and scattering but existing methods to correct for this are not applicable to superficial skin measurements. the first use of multiple-diameter single fiber reflectance (mdsfr) and single fiber fluorescence (sff) spectroscopy in human skin was investigated. mdsfr spectroscopy allows a quantification of the full optical properties in superficial skin (a, s' and ), which can next be used to retrieve the corrected - intrinsic - fluorescence of a fluorophore qa,x(f). our goal was to investigate the importance of such correction for individual patients. we studied this in 22 patients undergoing photodynamic therapy (pdt) for actinic keratosis. the magnitude of correction of fluorescence was around 4 (for both autofluorescence and protoporphyrin ix). moreover, it was variable between patients, but also within patients over the course of fractionated aminolevulinic acid pdt (range 2.7-7.5). patients also varied in the amount of protoporphyrin ix synthesis, photobleaching percentages and resynthesis (100 difference between the lowest and highest ppix synthesis). the autofluorescence was lower in actinic keratosis than contralateral normal skin (0.0032 versus 0.0052; p0.0005).","our results clearly demonstrate the importance of correcting the measured fluorescence for optical properties, because these vary considerably between individual patients and also during pdt. protoporphyrin ix synthesis and photobleaching kinetics allow monitoring clinical pdt which facilitates individual-based pdt dosing and improvement of clinical treatment protocols. furthermore, the skin autofluorescence can be relevant for diagnostic use in the skin, but it may also be interesting because of its association with several internal diseases.",Treatment
does considering scores between unrelated proteins in the search database improve profile comparison?,"profile-based comparison of multiple sequence alignments is a powerful methodology for the detection remote protein sequence similarity, which is essential for the inference and analysis of protein structure, function, and evolution. accurate estimation of statistical significance of detected profile similarities is essential for further development of this methodology. here we analyze a novel approach to estimate the statistical significance of profile similarity: the explicit consideration of background score distributions for each database template (subject). using a simple scheme to combine and analytically approximate query- and subject-based distributions, we show that (i) inclusion of background distributions for the subjects increases the quality of homology detection; (ii) this increase is higher when the distributions are based on the scores to all known non-homologs of the subject rather than a small calibration subset of the database representatives; and (iii) these all known non-homolog distributions of scores for the subject make the dominant contribution to the improved performance: adding the calibration distribution of the query has a negligible additional effect.","the construction of distributions based on the complete sets of non-homologs for each subject is particularly relevant in the setting of structure prediction where the database consists of proteins with solved 3d structure (pdb, scop, cath, etc.) and therefore structural relationships between proteins are known. these results point to a potential new direction in the development of more powerful methods for remote homology detection.",General
do central pituitary adenylate cyclase 1 receptors modulate nociceptive behaviors in both inflammatory and neuropathic pain states?,"the pituitary adenylate cyclase-activating polypeptide type 1 receptor (pac(1)-r) is a member of the 7-transmembrane domain, group 2 g-protein coupled receptor family. pac(1)-rs modulate neurotransmission and neurotrophic actions and have been implicated in both pronociception and antinociception. to better understand the role of pac(1)-rs in pain, pacap 6-38, a pac(1)-r antagonist, was evaluated in several inflammatory and neuropathic pain models after intrathecal (i.t.) administration. pacap 6-38 potently reduced mechanical allodynia in a neuropathic spinal nerve ligation model (77 /- 15 maximal effect at 12 nmol, p .01) and was also effective in reducing thermal hyperalgesia in the carrageenan model of inflammatory pain (89 /- 17 maximal effect at 12 nmol, p .01). although nociceptive responses were also attenuated with pacap 6-38 in a dose-dependent manner in models of chronic inflammatory and persistent pain, no effects on motor performance were observed at analgesic doses. taken together, these data demonstrate that blockade of the pac(1)-r/pacap complex by pacap 6-38 can effectively attenuate thermal hyperalgesia and mechanical allodynia associated with inflammatory and neuropathic pain states. these results further emphasize that at the level of the spinal cord, pac(1)-r activation is pronociceptive.","this article presents the analgesic profile generated by the blockade, at the spinal cord level, of the pac-1 receptor by a potent peptide antagonist. this comprehensive data set demonstrates that if small molecule pac-1 receptor antagonists could be identified, they would potentially produce broad-spectrum analgesia in both inflammatory and neuropathic pain states.",Medication
does cabazitaxel cause a dose-dependent central nervous system toxicity in rats?,"chemotherapeutic agents may lead to serious neurological side effects, which in turn can deteriorate the quality of life and cause dose limiting. direct toxic effect or metabolic derangement of chemotherapeutic agents may cause these complications. cabazitaxel is a next generation semi-synthetic taxane derivative, which is effective in both preclinical models of human tumors sensitive or resistant to chemotherapy and in patients with progressive prostate cancer despite docetaxel treatment. the primary aim of this study was to investigate the central nervous system toxicity of cabazitaxel. secondary aim was to investigate the safety dose of cabazitaxel for the central nervous system. a total of 24 adult male wistar-albino rats were equally and randomly divided into four groups as follows: group 1 (controls), group 2 (cabazitaxel 0.5mg/kg), group 3 (cabazitaxel 1.0mg/kg) and group 4 (cabazitaxel 1.5mg/kg). cabazitaxel (jevtana, sanofi-aventis usa) was intraperitoneally administered to groups 2, 3 and 4 at 0.5, 1.0 and 1.5mg/kg (body-weight/week) doses, respectively for four consecutive weeks. beside this, group 1 received only i.p. saline at the same volume and time. at the end of the study, animals were sacrificed and bilateral brain hemispheres were removed for biochemical, histopathological and immunohistochemical examinations. intraperitoneal administration of cabazitaxel has exerted neurotoxic effect on rat brain. we have observed that biochemical and immunohistochemical results became worse in a dose dependent manner.",our findings have suggested that cabazitaxel may be a neurotoxic agent and can trigger apoptosis in neuron cells especially at high doses.,Medication
do cytochrome p450 2e1 and 3a activities differ between mexicans and european americans?,"population differences in the activity of various cytochrome p450 (cyp) enzymes have been demonstrated on the basis of either genetic or environmental determinants. hispanics are a large demographic group both worldwide and within the united states; hence the possibility of differences in metabolism between one such group-mexicans-and a european-derived population was determined with respect to cyp2e1 and cyp3a. young healthy mexican immigrants living in los angeles, calif, who had maintained a traditional diet were compared with previously and identically studied groups of age-, sex-, and weight-matched european americans who resided in middle tennessee and ate a ""western"" diet (15 men and 15 women). in one study carried out in 15 women, the disposition of chlorzoxazone after an oral dose (250 mg) was compared. in the other investigation, all of the 15 subjects were men and received intravenous (15)n(3)-labeled midazolam (1 mg) and oral midazolam (2 mg) simultaneously to characterize the disposition of benzodiazepine in the two populations. plasma concentration-time profiles of chlorzoxazone and its 6-hydroxy metabolite and the 0- to 24-hour urinary recovery of the latter were not different between mexicans and european americans. this indicates that cyp2e1 activity is similar in the two populations. similarly, no significant intergroup differences were noted in the plasma concentration-time profiles of midazolam after either intravenous or oral administration. accordingly, cyp3a does not appear to be different between mexicans and european americans.","similarity in the metabolism of chlorzoxazone between mexicans and european americans suggests that the risk associated with cyp2e1-mediated activation of procarcinogens is not different between these two populations. likewise, the absence of any difference in the disposition of midazolam indicates that, from a pharmacokinetic standpoint, dosages of drugs metabolized by cyp3a need not be different between mexicans and european americans.",Medication
is post-operative survival following metastasectomy for patients receiving braf inhibitor therapy associated with duration of pre-operative treatment and elective indication?,"metastasectomy can provide durable disease control for selected patients with metastatic melanoma. vemurafenib is a braf kinase inhibitor which has demonstrated significant improvement in disease-specific survival in patients with metastatic melanoma with a braf gene mutation. this study examined the efficacy and safety of metastasectomy during treatment with vemurafenib. a retrospective review was performed of all patients receiving vemurafenib at peter maccallum cancer centre. patient records were reviewed to identify patients undergoing surgery within 30 days of vemurafenib therapy. descriptive statistics and survival analysis were performed. nineteen patients underwent 21 metastasectomies including craniotomy (57), spinal decompression (14), small bowel resection (14), lung resection (9.5) and neck dissection (4.5). indications for surgery were: an isolated residual focus of disease (n 2); isolated progressive disease in the setting of stability elsewhere (n 9); and symptomatic disease (n 8). grade 2 or higher surgical complications occurred in 19 of cases and there was one peri-operative death. median post-operative survival was seven months. there was a trend toward improved post-operative survival for patients with longer duration of vemurafenib therapy (p 0.04) and for those undergoing elective surgery (p 0.07).",resection of oligometastatic disease during braf-targeted therapy is safe. selected patients have durable post-operative disease control.,Treatment
does alleviation of renal mitochondrial dysfunction and apoptosis underlie the protective effect of sitagliptin in gentamicin-induced nephrotoxicity?,"this study aimed to investigate the potential protective effect of sitagliptin on gentamicin-induced nephrotoxicity and to elucidate the underlying mechanism. wistar rats were allocated as follows: gentamicin group: received gentamicin intraperitoneally (100 mg/kg/day); gentamicin plus sitagliptin group: received simultaneous gentamicin and sitagliptin (30 mg/kg/day orally); sitagliptin group: received only sitagliptin; and received saline. blood urea nitrogen (bun), serum creatinine, urine protein levels and histopathology of kidney tissues were evaluated. the activity of mitochondrial enzyme complexes reflects the mitochondrial function. oxidative stress biomarkers and immunohistochemical studies for apoptotic markers caspase-3 and bax were evaluated. gentamicin causes significant elevation of bun, serum creatinine and urine proteins. oxidative stress was revealed by decreased superoxide dismutase activity and catalase activity, glutathione depletion and increased malondialdehyde. significant decrease in mitochondrial nadh dehydrogenase, succinate dehydrogenase, cytochrome c oxidase and mitochondrial redox activity indicates mitochondrial dysfunction, along with significant elevation in renal caspase-3 and bax. the aforementioned markers and the histological injury in renal tubules were significantly reversed upon sitagliptin treatment.","these findings suggest that sitagliptin treatment attenuates renal dysfunction and structural damage through the reduction of oxidative stress, mitochondrial dysfunction and apoptosis in the kidney.",Symptoms
"is rpa , an extracellular protease similar to the metalloprotease of serralysin family , required for pathogenicity of ralstonia pickettii?","to investigate the biochemical and functional properties of an extracellular protease, rpa, in ralstonia pickettii wp1 isolated from water supply systems. an extracellular protease was identified and characterized from r. pickettii wp1. a mutant strain wp1m2 was created from strain wp1 by mini-tn5 transposition. the culture filtrates from wp1m2 had a lower cytotoxic effect than the parental wp1 on several mammalian cell lines. cloning and sequence analysis revealed the tn5 transposon inserted at a protease gene (rpa) which is 81 homologous to prta and aprx genes of pseudomonas fluorescens. the rpa gene encodes a 482-residue protein showing sequence similarity to metalloproteases of the serralysin family. the rpa protein was expressed in escherichia coli using a pet expression vector and purified as a 55 kda molecular weight protein. furthermore, the protease activity of rpa was inhibited by protease inhibitor and heat treatment.",the in vitro cytotoxic activity of r. pickettii culture filtrates was attributed to rpa protease.,Medication
does sequence specificity incompletely define the genome-wide occupancy of myc?,"the myc-max heterodimer is a transcription factor that regulates expression of a large number of genes. genome occupancy of myc-max is thought to be driven by enhancer box (e-box) dna elements, cacgtg or variants, to which the heterodimer binds in vitro. by analyzing chip-seq datasets, we demonstrate that the positions occupied by myc-max across the human genome correlate with the rna polymerase ii, pol ii, transcription machinery significantly better than with e-boxes. metagene analyses show that in promoter regions, myc is uniformly positioned about 100 bp upstream of essentially all promoter proximal paused polymerases with max about 15 bp upstream of myc. we re-evaluate the dna binding properties of full length myc-max proteins. electrophoretic mobility shift assay results demonstrate myc-max heterodimers display significant sequence preference, but have high affinity for any dna. quantification of the relative affinities of myc-max for all possible 8-mers using universal protein-binding microarray assays shows that sequences surrounding core 6-mers significantly affect binding. compared to the in vitro sequence preferences,myc-max genomic occupancy measured by chip-seq is largely, although not completely, independent of sequence specificity.",we quantified the affinity of myc-max to all possible 8-mers and compared this with the sites of myc binding across the human genome. our results indicate that the genomic occupancy of myc cannot be explained by its intrinsic dna specificity and suggest that the transcription machinery and associated promoter accessibility play a predominant role in myc recruitment.,Diagnosis
does aldosterone promote fibronectin synthesis in rat mesangial cells via erk1/2-stimulated na-h exchanger isoform 1?,"aldosterone plays an important role in fibrosis. recent studies showed that na()-h() exchanger isoform 1 (nhe1) is involved in mineralocorticoid-induced organ fibrosis. in this study, we examined the role of nhe1 in aldosterone-induced fibronectin accumulation in rat mesangial cells and the signaling pathway involved. we detected the expression of mineralocorticoid receptor and 11beta-hydroxysteroid dehydrogenase 2 in rat glomeruli by immunochemistry and western blot. then the eukaryotic vectors of shrna with insert targeting on nhe1 were successfully constructed and transfected into rat mesangial cells. the mrna was quantified by real-time pcr. we measured the protein abundance of nhe1, erk1/2 and phosphor-erk1/2 by western blot and the level of fibronectin by elisa. first we demonstrated the local action of aldosterone on rat glomeruli in vivo. then, after exposure to aldosterone, the nhe1 protein abundance was found increased in rat mesangial cells. aldosterone treatment markedly increased the fibronectin level, which can be reduced by pd98059, spironolactone and shrna-nhe1. pd98059 substantially reduced the aldosterone-induced nhe1 expression, while the knocking down of nhe1 did not alter aldosterone-stimulated phospho-erk1/2 stimulation.",the present study suggests that nhe1 may play an important role in aldosterone-mediated fibronectin accumulation in rat mesangial cells via the erk1/2 pathway.,Medication
are adhesive functions of both chains of vla-integrins fully conserved across the human-porcine species barrier : implications for xenotransplantation?,"a possible solution to the shortage of organs for transplantation would be the use of swine as source animals. as current immunosuppressive protocols cannot prevent rejection of these organs, super-selective immunosuppression or the induction of donor-specific central tolerance represent two promising approaches. central tolerance induction involves bone marrow transplantation, and depends on intrathymic deletion of donor reactive host cells by donor antigen-presenting cells. in super-selective immunosuppression, the aim would be to block specific adhesive interactions on one species side only, leaving the other species side unaffected. as both processes depend on the interaction of adhesion molecules with their ligands, we investigated whether the beta1-integrins, which play roles in hematopoiesis as well as in rejection, can successfully interact across the swine-to-human species barrier. we employed static cell-to-extracellular protein and cell-to-cell adhesion assays, using different cell types and monoclonal antibody as well as peptide-fragments to analyze conservation of cross-species adhesive interactions. we found that porcine and human cells interact differently with their cross-species ligands than their own and that the adhesive function of the beta1-chain does not seem to be fully conserved across the species barrier.","integrin functions are not fully conserved across the pig-to-human species barrier. while the development of multi-transgenic pigs, whose integrins interact with human ligands in a more ''human-like'' manner may be necessary to facilitate tolerance induction, these facts give rise to new possibilities concerning super-selective immunosuppression.",Prevention
do circulating microrna profiles reflect the presence of breast tumours but not the profiles of micrornas within the tumours?,"extra-cellular micrornas have been identified within blood and their profiles reflect various pathologies; therefore they have potential as disease biomarkers. our aim was to investigate how circulating microrna profiles change during cancer treatment. our hypothesis was that tumour-related profiles are lost after tumour resection and therefore that comparison of profiles before and after surgery would allow identification of biomarker micrornas. we aimed to examine whether these micrornas were directly derived from tumours, and whether longitudinal expression monitoring could provide recurrence diagnoses. plasma was obtained from ten breast cancer patients before and at two time-points after resection. tumour tissue was also obtained. quantitative pcr were used to determine levels of 367 mirnas. relative expressions were determined after normalisation to mir-16, as is typical in the field, or to the mean microrna level. 210 micrornas were detected in at least one plasma sample. using mir-16 normalisation, we found few consistent changes in circulating micrornas after resection, and statistical analyses indicated that this normalisation was not justifiable. however, using data normalised to mean microrna expression we found a significant bias for levels of individual circulating micrornas to be reduced after resection. potential biomarker micrornas were identified, including let-7b, let-7g and mir-18b, with higher levels associated with tumours. these micrornas were over-represented within the more highly expressed micrornas in matched tumours, suggesting that circulating populations are tumour-derived in part. longitudinal monitoring did not allow early recurrence detection.",we concluded that specific circulating micrornas may act as breast cancer biomarkers but methodological issues are critical.,Treatment
is platelet dysfunction an early marker for traumatic brain injury-induced coagulopathy?,"the goal of this study is to determine the presence of platelet dysfunction in patients with traumatic brain injury (tbi). the mechanisms underlying the coagulopathy associated with tbi remain elusive. the question of platelet dysfunction in tbi is unclear. this was a prospective observational study conducted at memorial hospital of south bend, in, and denver health medical center, co. a total of 50 patients sustaining tbi, and not under treatment with anticoagulants or platelet inhibitors, were analyzed utilizing modified thromboelastography (teg) with platelet mapping (teg/pm), along with standard coagulation tests. compared to normal controls, patients with severe tbi had a significantly increased percentage of platelet adp and arachidonic acid (aa) receptor inhibition. furthermore, the percentage of adp inhibition distinguished between survivors and non-survivors in patients with tbi (mann-whitney test, p 0.035). adp inhibition correlates strongly with severity of tbi (mann-whitney test, p 0.014), while aa inhibition did not.","these data indicate that early platelet dysfunction is prevalent after severe tbi, can be measured in a point-of-care setting using teg/pm, and correlates with mortality. the mechanism responsible for this platelet dysfunction and associated implications for tbi management remains to be defined.",Symptoms
does hyperbaric oxygen therapy improve the effects of standardized treatment in a severe attack of ulcerative colitis : a prospective randomized study?,"complementary therapy options are needed in the treatment of active ulcerative colitis (uc). hyperbaric oxygen therapy (hbot) has been shown to have positive effects in experimental models of colitis and perianal crohn's disease. in the present prospective randomized open-label study, hbot in addition to conventional medical treatment was compared with conventional treatment alone. the primary objective in this study was improved clinical outcome evaluated by mayo score, laboratory tests and fecal weight. the secondary objectives were improvement in health-related quality of life, avoidance of colectomy and evaluation of hbot safety. the authors found no statistically significant differences between the treatment groups in any of the assessed variables.",the study results do not support the use of hbot as a treatment option in a severe attack of uc.,Treatment
does helicobacter pylori induce apoptosis in human epithelial gastric cells by stress activated protein kinase pathway?,"the pathway by which helicobacter pylori induces apoptosis in gastric epithelial cells is not known. the aim of this study was to determine whether h. pylori-induced apoptosis is associated with sapk/jnk activity in human gastric cancer kato iii cells. h. pylori vaca toxin positive strain was incubated with kato iii cells for 0.5, 1, 2 or 24 hours. the sapk/jnk protein was harvested from the kato iii cell lysate by precipitation with a c-jun fusion protein and its activity was measured by c-jun phosphorylation utilizing transblotting and phosphoserine antibody. cellular apoptosis was demonstrated by dna fragmentation. in addition, cell growth in coculture with h. pylori was determined over 72 hours. h. pylori significantly stimulated sapk/jnk activity in kato iii cells with a peak at the 0.5 hour time point (3.6-fold vs. control, p .05), but a return to basal levels by 2 hours. in addition, significant dna fragmentation was observed after 24 hours in these cells but not in the control kato iii cells. cell growth was inhibited in a dose dependent fashion in coculture with h. pylori.",these results show that h. pylori triggers an increase in apoptosis in kato iii cells as reflected by dna fragmentation. this effect was preceded and correlated with an increase in sapk/jnk activity suggesting that the h. pylori-induced apoptosis in human gastric epithelial cells may be mediated by the sapk/jnk pathway.,Medication
do context-specific gene regulatory networks subdivide intrinsic subtypes of breast cancer?,"breast cancer is a highly heterogeneous disease with respect to molecular alterations and cellular composition making therapeutic and clinical outcome unpredictable. this diversity creates a significant challenge in developing tumor classifications that are clinically reliable with respect to prognosis prediction. this paper describes an unsupervised context analysis to infer context-specific gene regulatory networks from 1,614 samples obtained from publicly available gene expression data, an extension of a previously published methodology. we use the context-specific gene regulatory networks to classify the tumors into clinically relevant subgroups, and provide candidates for a finer sub-grouping of the previously known intrinsic tumors with a focus on basal-like tumors. our analysis of pathway enrichment in the key contexts provides an insight into the biological mechanism underlying the identified subtypes of breast cancer.",the use of context-specific gene regulatory networks to identify biological contexts from heterogenous breast cancer data set was able to identify genomic drivers for subgroups within the previously reported intrinsic subtypes. these subgroups (contexts) uphold the clinical relevant features for the intrinsic subtypes and were associated with increased survival differences compared to the intrinsic subtypes. we believe our computational approach led to the generation of novel rationalized hypotheses to explain mechanisms of disease progression within sub-contexts of breast cancer that could be therapeutically exploited once validated.,Treatment
does arc contribute to the inhibitory effect of preconditioning on cardiomyocyte apoptosis?,"inhibition of cardiomyocyte apoptosis plays a key role in preconditioning-triggered cardioprotection. however, the molecular mechanism(s) by which preconditioning inhibits apoptosis is not fully understood. apoptosis repressor with caspase recruitment domain (arc) possesses the ability to block hypoxia-induced cardiomyocyte apoptosis. we tested whether arc contributes to the inhibitory effect of preconditioning on cardiomyocyte apoptosis. cardiomyocytes from 1-day-old male sprague-dawley rats were preconditioned by exposing to 10 min of hypoxia, followed by 30 min of reoxygenation. then, the preconditioned and non-preconditioned cardiomyocytes were exposed to 90 min of hypoxia followed by 120 min of reoxygenation. the results showed that preconditioning inhibited cell death induced by hypoxia and reoxygenation. hypoxia and reoxygenation could induce a decrease of arc protein levels. intriguingly, preconditioning could maintain arc protein levels. inhibition of endogenous arc expression by arc antisense oligonucleotides reduced the inhibitory effect of preconditioning on apoptosis. furthermore, preconditioning-induced suppression of the release of mitochondrial cytochrome c to cytosol and caspase-3 activation could be abolished by the inhibition of endogenous arc expression using arc antisense oligonucleotides.",these data indicate that arc participates in preconditioning-triggered cardioprotection by interfering with cytochrome c release and caspase-3 activation.,Medication
is peri-operative bowel perforation in early stage colon cancer associated with an adverse oncological outcome?,"the presence of an inflammatory response resulting from bowel perforation or anastomotic leakage has been suggested to enhance recurrence rates in colorectal cancer patients. currently, it is unknown if bowel perforation or anastomotic leakage has prognostic significance in early stage colon cancer patients. in this study, the impact of peri-operative bowel perforation including anastomotic leakage on disease-free survival of stage i/ii colon cancer patients was investigated. prospective follow up data of 448 patients with stages i/ii colon cancer that underwent resection were included. patients who died within 3 months after initial surgery were excluded. median follow up was 56.0 months. patients with peri-operative bowel perforation (n 25) had a higher recurrence rate compared to patients without perforation (n 423), 36.0 vs. 16.1 (p 0.01). disease-free survival was significantly worse for the perforation group compared to patients without perforation (p 0.004). multivariate analysis including t-stage, histological grade, and adjuvant chemotherapy showed peri-operative bowel perforation to be an independent factor significantly associated with disease recurrence (odds ratio, 2.7; 95 ci, 1.1-6.7).",peri-operative bowel perforation is associated with increased recurrence rates and impaired disease-free survival in early-stage colon cancer patients.,Treatment
do murine amniotic fluid stem cells contribute mesenchymal but not epithelial components to reconstituted mammary ducts?,"amniotic fluid harbors cells indicative of all three germ layers, and pluripotent fetal amniotic fluid stem cells (afss) are considered potentially valuable for applications in cellular therapy and tissue engineering. we investigated whether it is possible to direct the cell fate of afss in vivo by transplantation experiments into a particular microenvironment, the mammary fat pad. this microenvironment provides the prerequisites to study stem cell function and the communication between mesenchymal and epithelial cells. on clearance of the endogenous epithelium, the ductal tree can be reconstituted by the transfer of exogenously provided mammary stem cells. analogously, exogenously provided stem cells from other tissues can be investigated for their potential to contribute to mammary gland regeneration. we derived pluripotent murine afss, measured the expression of stem cell markers, and confirmed their in vitro differentiation potential. afss were transplanted into cleared and non cleared fat pads of immunocompromised mice to evaluate their ability to assume particular cell fates under the instructive conditions of the fat-pad microenvironment and the hormonal stimulation during pregnancy. transplantation of afss into cleared fat pads alone or in the presence of exogenous mammary epithelial cells caused their differentiation into stroma and adipocytes and replaced endogenous mesenchymal components surrounding the ducts in co-transplantation experiments. similarly, transplantation of afss into fat pads that had not been previously cleared led to afs-derived stromal cells surrounding the elongating endogenous ducts. afss expressed the marker protein -sma, but did not integrate into the myoepithelial cell layer of the ducts in virgin mice. with pregnancy, a small number of afs-derived cells were present in acinar structures.","our data demonstrate that the microenvironmental cues of the mammary fat pad cause afss to participate in mammary gland regeneration by providing mesenchymal components to emerging glandular structures, but do not incorporate or differentiate into ductal epithelial cells.",Treatment
do ex vivo-expanded human regulatory t cells prevent the rejection of skin allografts in a humanized mouse model?,"composite tissue transplantation effectively reconstructs the most complex defects, but its use is limited because of harmful immunosuppression and the high susceptibility of skin to rejection. development of tolerance is an ideal solution, and protocols using regulatory t cells (tregs) to achieve this have been promising in experimental animal models. the aim of this study was to investigate the ability of human tregs to regulate immune responses to a human skin allograft in vivo. we isolated and expanded naturally occurring cd127locd25cd4 human tregs from peripheral blood mononuclear cells (pbmcs) and examined their phenotype and suppressive activity in vitro. using a clinically relevant chimeric humanized mouse system, we transplanted mice with human skin grafts followed by allogeneic populations of pbmcs with or without tregs derived from the same pbmc donor. ex vivo-expanded tregs maintain the appropriate treg markers and retain suppressive activity against allostimulated and polyclonally stimulated autologous pbmcs in vitro. mice receiving allogeneic pbmcs alone consistently reject human skin grafts, whereas those also receiving tregs display stable long-term human skin transplant survival along with a reduction in the cd8 human cellular graft infiltrate.","we show for the first time the unique ability of human tregs to prevent the rejection of a skin allograft in vivo, highlighting the therapeutic potential of these cells clinically.",Prevention
does intramuscular injection of islet neogenesis-associated protein peptide stimulate pancreatic islet neogenesis in healthy dogs?,"diabetes is a serious health problem. it has been proposed that islet neogenesis from pancreatic progenitor cells may restore insulin secretion in diabetic mammals. islet neogenesis- associated protein (ingap) stimulates islet neogenesis; therefore, we hypothesized that it would stimulate islet neogenesis in dogs. forty nondiabetic beagle dogs were randomly divided into 4 groups. group 1 received daily intramuscular injections of vehicle, whereas the other 3 groups received daily ingap injections of 0.5, 1.5, or 10 mg/kg. after 30 days, pancreatic tissues were collected, and rna and histological sections were analyzed. in dogs treated with 1.5 mg/kg ingap, there was a significant (p 0.001) increase in the percentage of insulin-positive cells (p 0.001) and insulin gene expression. there was a trend to increased insulin-positive cells and gene expression with treatments of 0.5 and 10 mg/kg peptide. protein gene product 9.5-positive cells were increased with treatment.",these results indicate that ingap stimulates cells in the pancreatic duct epithelium of healthy dogs (putative islet progenitor cells) to develop along a neuroendocrine pathway and form new islets in response to ingap peptide. the ingap might be an effective therapy for diabetes.,Medication
does metformin suppress sonic hedgehog expression in pancreatic cancer cells?,"metformin use has previously been associated with decreased cancer risk. the hedgehog signaling pathway is a well-characterized early and late mediator of pancreatic cancer oncogenesis. the aim of the present study was to clarify the effect of metformin on factors involved in hedgehog signaling. bxpc3 human pancreatic cancer cells were treated with metformin, and sonic hedgehog (shh) mrna and protein levels were examined by real time reverse transcription-polymerase chain reaction, immunohistochemistry and immunoblotting, respectively. the effect of metformin on shh levels was also examined in three other cancer cell lines. shh protein and mrna expression was suppressed by metformin in bxpc3 cells. this phenomenon was further confirmed in three other cancer cell lines. shh mrna expression was inhibited by metformin in a concentration-dependent manner in two cancer cell lines.",metformin reduces the expression of shh in several cancer cell lines including pancreatic cancer cell.,Medication
are low ercc1 mrna and protein expression associated with worse survival in cervical cancer patients treated with radiation alone?,"to evaluate the association of excision repair cross-complementation group 1 (ercc1) expression, using both mrna and protein expression analysis, with clinical outcome in cervical cancer patients treated with radical radiation therapy (rt). patients (n186) with locally advanced cervical cancer, treated with radical rt alone from a single institution were evaluated. pre-treatment ffpe biopsy specimens were retrieved from 112 patients. ercc1 mrna level was determined by real-time pcr, and ercc1 protein expression (fl297, 8f1) was measured using quantitative immunohistochemistry (aqua). the association of ercc1 status with local response, 10-year disease-free (dfs) and overall survival (os) was analyzed. ercc1 protein expression levels using both fl297 and 8f1 antibodies were determined for 112 patients; mrna analysis was additionally performed in 32 patients. clinical and outcome factors were comparable between the training and validation sets. low ercc1 mrna expression status was associated with worse os (17.9 vs 50.1, p0.046). ercc1 protein expression using the fl297 antibody, but not the 8f1 antibody, was significantly associated with both os (p0.002) and dfs (p0.010). after adjusting for pre-treatment hemoglobin in a multivariate analysis, ercc1 fl297 expression status remained statistically significant for os hr 1.9 (1.1-3.3), p0.031.","pre-treatment tumoral ercc1 mrna and protein expression, using the fl297 antibody, are predictive factors for survival in cervical cancer patients treated with rt, with ercc1 fl297 expression independently associated with survival. these results identify a subset of patients who may derive the greatest benefit from the addition of cisplatin chemotherapy.",Treatment
does aspirin suppress the growth and metastasis of osteosarcoma through the nf-b pathway?,"aspirin has recently been reported to reduce both the incidence and the risk of metastasis in colon cancer. however, there is no evidence at the cellular levels or in the animal models for such an effect of aspirin on cancer metastasis. mtt assay, colony formation assay, and apoptosis assay were employed to analyze the effects of aspirin on the osteosarcoma cell viability in vitro. the nf-b activity was measured by the nf-b p65 luciferase reporter. western blotting was used to analyze the proteins in cells. the migration and invasion abilities of osteosarcoma cells in vitro were measured by the transwell assay. xenograft-bearing mice were used to assess the roles of aspirin in both tumor growth and metastasis of osteosarcoma in vivo (n 5-8 mice/group). an unpaired student t test or anova with the bonferroni post hoc test were used for the statistical comparisons. aspirin reduced cell viability in a dose- and time-dependent manner in osteosarcoma cell lines, and aspirin synergistically sensitized osteosarcoma cells to cisplatin (ddp) in vitro and in vivo (p 0.001). moreover, aspirin markedly repressed the migration and invasion of osteosarcoma cells in vitro (p 0.001), and dramatically diminished the occurrence of osteosarcoma xenograft metastases to the lungs in vivo (p 0.001). mechanistically, aspirin diminishes osteosarcoma migration, invasion, and metastasis through the nf-b pathway.",aspirin suppresses both the growth and metastasis of osteosarcoma through the nf-b pathway at the cellular level and in the animal models.,Medication
does tgf-1 reduce mir-29a expression to promote tumorigenicity and metastasis of cholangiocarcinoma by targeting hdac4?,"transforming growth factor 1 (tgf-1) and mirnas play important roles in cholangiocarcinoma progression. in this study, mir-29a level was found significantly decreased in both cholangiocarcinoma tissues and tumor cell lines. tgf-1 reduced mir-29a expression in tumor cell lines. furthermore, anti-mir-29a reduced the proliferation and metastasis capacity of cholangiocarcinoma cell lines in vitro, overexpression of mir-29a counteracted tgf-1-mediated cell growth and metastasis. subsequent investigation identified hdac4 is a direct target of mir-29a. in addition, restoration of hdac4 attenuated mir-29a-mediated inhibition of cell proliferation and metastasis.",tgf-1/mir-29a/hdac4 pathway contributes to the pathogenesis of cholangiocarcinoma and our data provide new therapeutic targets for cholangiocarcinoma.,General
is self-rated health among women with coronary disease : depression as important as recent cardiovascular events?,"prior studies have shown an association between depression and self-rated health among patients with coronary disease. however, the magnitude of the effect of depression on self-rated health compared with that of major clinical events is unknown. our main objective was to clarify the association between depression and self-rated health using longitudinal data. we performed a prospective cohort study of 2675 postmenopausal women with coronary disease. the primary predictor variable was a 4-state categorical depression variable based on the burnam depression screen assessed at sequential visits. the outcome variable was self-rated overall health (excellent, very good, or good vs fair or poor). after adjustment for age, comorbidities, prior self-rated health, and interim events, women with depression at both current and prior annual visits had a 5-fold increased odds of fair/poor self-rated health (odds ratio or 5.1, 95 ci 3.8-6.8). new depression was associated with a 2-fold increased odds of fair/poor self-rated health (or 2.6, 95 ci 2.0-3.4). having a history of depression at the preceding annual visit but not at the current visit was associated with a slight increased odds of fair/poor self-rated health (or 1.3, 95 ci 1.0-1.7). the magnitude of the impact of persistent or new depression was comparable to that of recent angina, myocardial infarction, angioplasty, heart failure, or bypass surgery.",women with persistent or new depression are more likely to report fair/poor self-rated health. the magnitude of the impact of persistent or new depression is comparable to that of major cardiac events.,Treatment
does inflammation induce tau pathology in inclusion body myositis model via glycogen synthase kinase-3beta?,"inclusion body myositis (ibm) is an inflammatory muscle disease, although the role of inflammation remains to be elucidated. here, we address the mechanisms by which inflammation modulates abeta and tau, two hallmark features of this disease. a transgenic mouse model of ibm was utilized in which acute and chronic inflammation was induced via lipopolysaccharide. the effects of inflammation were assessed by analyzing the myopathological and the behavioral phenotype. human ibm skeletal muscle biopsies were investigated to determine concordance with data from the animal model. both acute and chronic lipopolysaccharide exposure augmented infiltration by cd8() cytotoxic t cells and increased amyloid precursor protein steady-state levels in skeletal muscle, whereas increased abeta generation was observed only in chronically treated mice. both acute and chronic inflammation enhanced tau phosphorylation in skeletal muscle. the mechanism underlying this effect was mediated by the tau kinase, glycogen synthase kinase-3beta (gsk-3beta). suppression of gsk-3beta activity using either a specific inhibitor or lithium chloride significantly reduced tau phosphorylation and partially rescued motor impairment. in human ibm muscle, gsk-3beta and phospho-tau were colocalized, further supporting the pathogenic role of gsk-3beta in this disease. using c2c12 myoblast cultures, we found that gsk-3beta was activated by proinflammatory cytokines (interleukin-1beta, interleukin-6, tumor necrosis factor-alpha), leading to enhanced tau phosphorylation.",our results identify a molecular mechanism by which proinflammatory stimuli affect tau pathology via the gsk-3beta signaling pathway in skeletal muscle.,Medication
are clinical assessment of sacroiliitis and hla-b27 poor predictors of sacroiliitis diagnosed by magnetic resonance imaging in psoriatic arthritis?,"to determine the frequency and clinical predictors of sacroiliitis diagnosed by magnetic resonance imaging (mri) in a psoriatic arthritis (psa) population. the studied comprised 103 patients with psa. a careful clinical assessment for sacroiliitis was made from history and examination, and hla-b27 testing was performed. sixty-eight patients underwent tilted coronal fat-saturated t1-weighted and stir mri of the sacroiliac joints. clinical features of moderate or severe sacroiliitis were found in 24/68 (35) patients. mri features of sacroiliitis were found in 26/68 (38) patients. clinical features of sacroiliitis were present in 14/42 (33) with normal mri scans and 10/26 (38) with abnormal scans (normal vs abnormal scans, p 0.7). the presence of sacroiliitis on mri was associated with restricted spinal movements (p 0.004) and the duration of psa (p 0.04). there was no correlation between hla-b27 and sacroiliitis diagnosed by mri.",sacroiliitis diagnosed by mri occurs commonly in psa but is difficult to detect clinically.,Diagnosis
does impairment of aerobic glycolysis by inhibitors of lactic dehydrogenase hinder the growth of human hepatocellular carcinoma cell lines?,"by reducing the number of atp molecules produced via aerobic glycolysis, the inhibition of lactic dehydrogenase (ldh) should hinder the growth of neoplastic cells without damaging the normal cells which do not rely on this metabolic pathway for their energetic needs. here, we studied the effect of oxamic and tartronic acids, 2 inhibitors of ldh, on aerobic glycolysis and cell replication of hepg2 and plc/prf/5 cells, 2 lines from human hepatocellular carcinomas. aerobic glycolysis was measured by calculating the amounts of lactic acid formed. the effect on replication was assessed by culturing the cells in both standard conditions and glucose-deprived medium, which was used to shut down aerobic glycolysis. the oxamic and tartronic acids inhibited aerobic glycolysis, impaired the growth of both cell lines and also induced an increased expression of p53-upregulated modulator of apoptosis, a signal of cell death. a strong impairment of cell replication by oxamic acid was only found when the cells were cultured in the presence of glucose, indicating that it was for the most part owing to inhibition of aerobic glycolysis.","inhibition of aerobic glycolysis achieved by blocking ldh could be useful in the treatment of human hepatocellular carcinomas. without interfering with glucose metabolism in normal cells, it could hinder cell growth by itself and could also enhance the chemotherapeutic index of associated anticancer agents by decreasing the levels of atp selectively in neoplastic cells.",Medication
does self-management and supervisory feedback improve trainer implementation of communication rehabilitation programmes?,"this study investigated the differential effects of self-management and supervisory feedback on the acquisition and maintenance of accurate use of response prompts by five trainers who provided communication training to individuals with severe intellectual disability. a counterbalanced design was used. for three trainers the self-management condition was first in effect followed by the supervisory feedback condition. for the two other trainers this order was reversed. results revealed that for three trainers there was a statistically significant difference between the two conditions, favouring supervisory feedback. for the other two trainers, self-management and supervisory feedback were equally effective in establishing accurate use of response prompts. acceptability ratings from trainers suggest a preference for self-management over supervisory feedback.",for three out of five trainers supervisory feedback was more effective in improving implementation of the communication intervention (i.e. response prompting) than self-management.,Treatment
is acute onset human atrial fibrillation associated with local cardiac platelet activation and endothelial dysfunction?,"the purpose of this study was to determine whether acute onset atrial fibrillation (af), independent of other risk factors, predisposes to an early prothrombotic state. several risk factors predispose to the hypercoagulable state in human af, but whether acute onset af alone is prothrombotic remains unclear. patients with paroxysmal af (n 22) underwent radiofrequency catheter ablation. all patients presented in sinus rhythm. baseline blood samples were obtained simultaneously from the femoral vein (systemic sample) and the coronary sinus (local cardiac sample). the af was induced by burst atrial pacing in 14 patients (af group). a control group (n 8) underwent atrial pacing at 120 beats/min. blood samples were recollected after 15 min. platelet p-selectin expression (cd62) was measured using flow cytometry. markers of thrombin generation (thrombin antithrombin complex, prothrombin fragment 1.2), inflammation (c-reactive protein, interleukin-6), and nitric oxide were measured using enzyme-linked immunosorbent assays. neither local nor systemic platelet activation changed in the control group. in the af group, local cardiac platelet activation (percent p-selectin platelets) increased significantly (2.2 /- 0.6 to 2.8 /- 1.0, p 0.007); however, systemic platelet activation did not change. the af group had increased local thrombin generation (thrombin antithrombin complex: 8.5 /- 7.6 ng/ml to 33.2 /- 17.4 ng/ml, p 0.003; prothrombin fragment 1.2: 95.6 /- 45.6 micromol/l to 243.8 /- 120.1 micromol/l, p 0.003), decreased nitric oxide production (25.2 /- 10.8 micromol/l to 22.3 /- 10.0 micromol/l, p 0.02), and no change in inflammatory markers.","human af causes local cardiac platelet activation within minutes of onset. the results demonstrate how af alone, independent of other risk factors, may contribute to the hypercoagulable state.",Symptoms
does farnesyltransferase inhibitor fti-277 prevent autocrine growth stimulation of neuroblastoma by bdnf?,"autocrine growth stimulation by igf-ii and bdnf is frequently observed in neuroblastoma. the signals of the receptors of these growth factors are transduced to the nucleus via the ras-map-kinase pathway where they induce proliferation. inactivation of ras-proteins by farnesyltransferase inhibitors such as fti-277 disrupts growth stimulation of ras-transformed cells. we investigated whether fti-277 is also active against tumor cells with constitutively activated growth factor receptors but lacking ras-mutations. we analyzed eight different neuroblastoma cell lines for the expression of bdnf and its receptor trkb. two of these cell lines with a complete autocrine bdnf loop were treated with fti-277, and the effects of ras-inactivation on the signal transduction of bdnf were analyzed. treatment of neuroblastoma cells with 10 microm fti-277 for 4 days reduced the amount of membrane-bound ras-protein to almost 50. activation of map-kinase, induction of n-myc expression, and proliferation were clearly reduced in the treated cells. in addition, we observed some cytotoxic effects of fti-277 accompanied by morphological changes of the neuroblastoma cells and a delayed induction of apoptosis.",farnesyltransferase inhibitors are active against neuroblastoma cells but the mechanism of action is not limited to inactivation of ras. further investigations on the targets of fti-277 are recommended.,Prevention
are increased expression of cyclooxygenase-2 and ki-67 associated with malignant transformation of pleomorphic adenoma?,"in the present study, we attempted to identify cyclooxygenase-2 (cox-2) expression and ki-67 index in carcinoma ex-pleomorphic adenoma (ca ex-pa) using quantitative immunohistochemical analysis and to compare the benign component of the neoplasia. we also aimed to relate the overexpression of cox-2 with the pathways of malignant transformation of ca ex-pa as evidenced by distinct morphological features. forty ca ex-pa from patients treated at department of otolaryngology, yokohama city university medical center, yokohama, japan, from 1999 to 2005, were selected. all ca ex-pa showed only one malignant histological component: adenocarcinoma (23 cases), adenoid-cystic carcinoma (10), epithelial-myoepithelial carcinoma (7). the tissues were stained with monoclonal antibodies to cox-2 and ki-67. the results were analyzed using quantitative immunohistochemical analysis. we also analyzed the association of the histological classification of the carcinomatous component. in the immunohistochemical analysis of cox-2 and ki-67 index, significant increase was observed in ca ex-pa, especially with adenocarcinoma, compared to pleomorphic adenoma and sialadenitis. quantitative assessment is more sensitive as a measure of cellular protein content as compared to standard optical density measurement.",the data support the hypothesis that increased cox-2 expression is associated with early events in malignant transformation of pleomorphic adenoma.,Treatment
does methylnaltrexone potentiate body weight and fat reduction with leptin?,"leptin increases energy expenditure by enhancing systemic and brown adipose metabolism. in a neonatal rat model, retroperitoneal fat pad weight decreased significantly in leptin-treated animals, which reduced body weight. as opioids increase feeding, opioid antagonists may decrease food intake and body weight. however, interactions between leptin and the activity of peripheral opioids on body weight and fat accumulation have not been investigated. in this study, the authors evaluated the effects of naloxone (a nonselective opioid antagonist) and methylnaltrexone (a peripherally acting opioid antagonist) on the action of leptin in neonatal rats. compared with control, the weight gain of pups given a single daily intraperitoneal injection of leptin 0.5 mg/kg, leptin 0.5 mg/kg plus naloxone 0.3 mg/kg, or leptin 0.5 mg/kg plus methylnaltrexone 3.0 mg/kg for 8 consecutive days was significantly reduced (all p 0.01). naloxone or methylnaltrexone significantly potentiated leptin's effect on body weight (p 0.05 or p 0.01, respectively). after coadministration of leptin plus naloxone or leptin plus methylnaltrexone, weight reduction in the right retroperitoneal fat pads was also significant compared with the reduction after leptin alone (p 0.05 or p 0.01, respectively).",the data suggest the existence of a peripheral opioid-related mechanism in leptin-active modulation of body weight.,Medication
is smoking a risk factor for sporadic amyotrophic lateral sclerosis in an australian population?,"controversy persists as to whether smoking is a risk factor for sporadic amyotrophic lateral sclerosis (sals), the most common form of sporadic motor neuron disease (smnd). we therefore undertook a large case-control study of smoking and sals in australia. cases and controls were recruited australia-wide over a 10-year period. sals and the other subgroups of smnd were categorised on the basis of neurologists' reports. controls were partners or friends of smnd patients or community volunteers. individuals filled in a questionnaire regarding smoking habits. a total of 809 patients with smnd (631 with sals) and 779 controls were included in the study. sals males and females were analysed separately. no differences between sals patients and control groups were found with regard to (1) the odds ratios of ever-smokers, ex-smokers or current smokers compared to never-smokers, (2) the means of numbers of cigarettes per day, years of smoking, pack years or age smoking began or (3) the proportions of their parents who had ever smoked. the proportion of ever-smokers and mean pack years did not differ between the clinical subgroups of smnd or between different sites of sals onset. partner smoking did not increase the risk of smnd.",this australian case-control study does not support a link between cigarette smoking and any form of smnd.,Prevention
are lactobacillus acidophilus and bifidobacterium bifidum stored at ambient temperature effective in the treatment of acute diarrhoea?,"probiotics have demonstrated potential to reduce duration of diarrhoea and frequency of watery stools. probiotics such as lactobacillus acidophilus and bifidobacterium bifidum (infloran()) are usually maintained at a storage temperature of 4c which is generally not feasible in tropical or sub-tropical countries. the efficacy of infloran() for treatment of acute diarrhoea when stored at 28-32c (room temperature) was evaluated. this was a double-blind, randomised study of infants and children aged 2 months to 7 years with acute diarrhoea. patients were randomly assigned to receive infloran() stored at 4c, at room temperature, or to a placebo group. duration of diarrhoea was a primary outcome, while the number of stools, hospital stay and requirement for rehydration fluid were secondary outcomes. probiotics shortened duration of diarrhoea (34.1 and 34.8 hrs when stored either at 4c or at room temperature, respectively, and 58 hrs with placebo, p0.01) and reduced the number of stools (7.3 and 8 vs 15.9 with placebo, p0.01).",administration of probiotics is beneficial as additional treatment of acute diarrhoea and efficacy is not affected by storage temperature.,Treatment
is smoothelin-a essential for functional intestinal smooth muscle contractility in mice?,"in patients with chronic intestinal pseudo-obstruction, intestinal motility is disturbed by either nervous or myogenic aberrations. the cause of the myogenic form is unknown, but it is likely to originate in the contractile apparatus of the smooth muscle cells. smoothelins are actin-binding proteins that are expressed abundantly in visceral (smoothelin-a) and vascular (smoothelin-b) smooth muscle. experimental data indicate a role for smoothelins in smooth muscle contraction. a smoothelin-deficient mouse model may help to establish the role of smoothelin-a in intestinal contraction and provide a model for myogenic chronic intestinal pseudo-obstruction. we used gene targeting to investigate the function of smoothelin-a in intestinal tissues. by deletion of exons 18, 19, and 20 from the smoothelin gene, the expression of both smoothelin isoforms was disrupted. the effects of the deficiency were evaluated by pathologic and physiologic analyses. in smoothelin-a/b knockout mice, the intestine was fragile and less flexible compared with wild-type littermates. the circular and longitudinal muscle layers of the intestine were hypertrophic. deficiency of smoothelin-a led to irregular slow wave patterns and impaired contraction of intestinal smooth muscle, leading to hampered transport in vivo. this caused obstructions that provoked intestinal diverticulosis and occasionally intestinal rupture.","smoothelin-a is essential for functional contractility of intestinal smooth muscle. hampered intestinal transit in smoothelin-a/b knockout mice causes obstruction, starvation, and, ultimately, premature death. the pathology of mice lacking smoothelin-a is reminiscent of that seen in patients with chronic intestinal pseudo-obstruction.",General
does characteristics of united states emergency department visit for traumatic amputations in the elderly adult from 2010 to 2013?,"elderly adults (65 years of age and older) are of particular concern for traumatic amputations due to age-related changes in vision and coordination, making them more susceptible to injury. the objective of this study is to describe the epidemiology of traumatic amputations in the elderly adults treated in united states emergency departments (ed). a retrospective analysis using data from the national electronic injury surveillance system from 2010 to 2013. people aged 65 years and older treated in u.s. hospital eds for traumatic amputations from 2010 to 2013. there were 15,611 elderly patients treated for amputations from 2010 to 2013, averaging 3,902 amputations per year in the united states. the frequency of amputations declined with increasing age. the mean age was 74 years old. males represented 84 of the cohort. the majority of the injuries that were recorded took place at home (71). the most common associated consumer products were saws, lawnmowers, and doors. saws accounted for approximately 45 of amputations. in females, doors were the most common consumer product associated with amputations. approximately 45 of amputations were complete amputations. the most common digit to be amputated was the thumb (24). approximately 72 of the cases in the cohort were treated and released from the ed.",traumatic amputations in elderly adults were frequently due to saws and lawnmowers. an increase in injury prevention efforts in this patient population is warranted.,Prevention
does an obesity drug sibutramine reduce brain natriuretic peptide ( bnp ) levels in severely obese patients?,"sibutramine is a selective inhibitor of the reuptake of monoamines. plasma levels of brain natriuretic peptide (bnp) appear to be inversely associated with body mass index (bmi) in subjects with and without heart failure for reasons that remain unexplained. the aim of this study was to investigate the possible influence of sibutramine treatment on bnp levels in severely obese patients. fifty-two severely obese female patients with bmi 40 kg/m(2) were included to this study. the women were recommended to follow a weight-reducing daily diet of 25 kcal/kg of ideal body weight. during the treatment period, all patients were to receive 15 mg of sibutramine once a day. blood chemistry tests were performed before the onset of the medication and after 12 weeks of treatment. none of the subjects was withdrawn from the study because of the adverse effects of sibutramine. body weight (108.8 /- 13.3 kg vs. 101.7 /- 15.6 kg, p 0.001), bmi (44.6 /- 4.6 kg/m(2) vs. 41.8 /- 5.7 kg/m(2), p 0.001) and bnp 8.6 (0.5-49.5) ng/l vs. 3.1 (0.2-28.6) ng/l, p 0.018 levels were significantly decreased after 12 weeks of sibutramine treatment. total cholesterol (5.19 /- 0.90 mmol/l vs. 4.82 /- 1.05 mmol/l respectively; p 0.001), low-density lipoprotein-cholesterol (3.26 /- 0.86 mmol/l vs. 2.99 /- 0.40 mmol/l respectively; p 0.008), levels were significantly decreased; however, there was no significant alteration in high-density lipoprotein-cholesterol and triglyceride levels.",this study has shown a decrease in bnp levels which may lead to improvement in cardiac outcome after sibutramine treatment. further randomised studies are needed to be conducted to clarify the relationship between sibutramine and bnp.,Medication
do oral administration of leaf extracts of momordica charantia affect reproductive hormones of adult female wistar rats?,"to determine the effect of graded doses of aqueous leaf extracts of momordica charantia on fertility hormones of female albino rats. twenty adult, healthy, female wistar rats were divided into four groups: low dose (ld), moderate dose (md) and high dose (hd) groups which received 12.5 g, 25.0 g, 50.0 g of the leaf extract respectively and control group that was given with water ad libatum. estrogen levels reduced by 6.40 nmol/l, 10.80 nmol/l and 28.00 nmol/l in the ld, md and hd groups respectively while plasma progesterone of rats in the ld, md and hd groups reduced by 24.20 nmol/l, 40.8 nmol/l and 59.20 nmol/l respectively.","our study has shown that the antifertility effect of momordica charantia is achieved in a dose dependent manner. hence, cautious use of such medication should be advocated especially when managing couples for infertility.",Medication
do vasoactive peptides with angiogenesis-regulating activity predict cancer risk in males?,"tumor development requires angiogenesis, and antiangiogenesis has been introduced in the treatment of cancer patients; however, how the cardiovascular phenotype correlates with cancer risk remains ill-defined. here, we hypothesized that vasoactive peptides previously implicated in angiogenesis regulation predict long-term cancer risk. we measured midregional proatrial natriuretic peptide (mr-proanp), proadrenomedullin (mr-proadm), and c-terminal preprovasopressin (copeptin) in fasting plasma from participants of the malm diet and cancer study that were free from cancer prior to the baseline exam in 1991 to 1994 (1,768 males and 2,293 females). we used cox proportional hazards models to determine the time to first cancer event in relation to baseline levels of vasoactive peptides during a median follow-up of 15 years. first cancer events occurred in 366 males and in 368 females. in males, one sd increase of mr-proanp, copeptin, and mr-proadm was independently related to incident cancer hr (95 ci) by 0.85 (0.74-0.96), p 0.012; 1.17 (1.04-1.32), p 0.009; and 1.12 (0.99-1.26), p 0.065, respectively, and a summed biomarker score identified an almost 2-fold difference in cancer risk between the top and bottom quartile (p 0.001). in younger males, the biomarker score identified a more than 3-fold increase in risk between the top and bottom quartile (p 0.001). among females, we found no relationship between biomarkers and cancer incidence.","our data suggest that vasoactive peptide biomarkers predict cancer risk in males, particularly in younger males.",Prevention
is the upregulation of transglutaminase-2 by cyclosporin a in human gingival fibroblasts augmented by oxidative stress?,"transglutaminase-2 (tgm-2) has been implicated in several fibrotic disorders and can be induced by reactive oxygen species (ros). hence, the authors hypothesize that cyclosporin a (csa) may regulate tgm-2 via ros, and this regulation may have a role in the pathogenesis of csa-induced gingival overgrowth. cytotoxicity, 2',7'-dichlorodihydrofluorescein diacetate assay, and western blot were used to investigate the effects of csa in human gingival fibroblasts (hgfs). in addition, extracellular signal-regulated kinase (erk) inhibitor pd98059, phosphatidylinositol 3-kinase inhibitor ly294002, glutathione precursor n-acetyl-l-cysteine (nac), curcumin, epigallocatechin-3 gallate (egcg), and p38 inhibitor sb203580 were added to find the possible regulatory mechanisms. concentrations of csa 500 ng/ml demonstrated cytotoxicity to hgfs (p 200 ng/ml (p 0.05). tgm-2 protein induced by csa was found in hgfs in a dose- and time-dependent manner (p 0.05). the addition of pd98059, ly294002, nac, curcumin, egcg, and sb203580 markedly inhibited tgm-2 expression induced by csa (p 0.05).","these results demonstrate that csa significantly upregulates intracellular ros generation and elevates tgm-2 expression in hgfs. in addition, tgm-2 induced by csa is downregulated by pd98059, ly294002, nac, curcumin, egcg, and sb203580.",Medication
does neuregulin 1 sustain the gene regulatory network in both trabecular and nontrabecular myocardium?,"the cardiac gene regulatory network (grn) is controlled by transcription factors and signaling inputs, but network logic in development and it unraveling in disease is poorly understood. in development, the membrane-tethered signaling ligand neuregulin (nrg)1, expressed in endocardium, is essential for ventricular morphogenesis. in adults, nrg1 protects against heart failure and can induce cardiomyocytes to divide. to understand the role of nrg1 in heart development through analysis of null and hypomorphic nrg1 mutant mice. chamber domains were correctly specified in nrg1 mutants, although chamber-restricted genes hand1 and cited1 failed to be activated. the chamber grn subsequently decayed with individual genes exhibiting decay patterns unrelated to known patterning boundaries. both trabecular and nontrabecular myocardium were affected. network demise was spatiotemporally dynamic, the most sensitive region being the central part of the left ventricle, in which the grn underwent complete collapse. other regions were partially affected with graded sensitivity. in vitro, nrg1 promoted phospho-erk1/2-dependent transcription factor expression, cardiomyocyte maturation and cell cycle inhibition. we monitored cardiac perk1/2 in embryos and found that expression was nrg1-dependent and levels correlated with cardiac grn sensitivity in mutants.","the chamber grn is fundamentally labile and dependent on signaling from extracardiac sources. nrg1-erbb1/4-erk1/2 signaling critically sustains elements of the grn in trabecular and nontrabecular myocardium, challenging our understanding of nrg1 function. transcriptional decay patterns induced by reduced nrg1 suggest a novel mechanism for cardiac transcriptional regulation and dysfunction in disease, potentially linking biomechanical feedback to molecular pathways for growth and differentiation.",Diagnosis
is postabsorptive plasma citrulline concentration a marker of absorptive enterocyte mass and intestinal failure in humans?,"no blood marker assessing the functional absorptive bowel length has been identified. plasma citrulline, a nonprotein amino acid produced by intestinal mucosa, is one candidate. we tested this hypothesis in adult patients with the short-bowel syndrome, whose condition can lead to intestinal failure. in 57 patients, after a minimal follow-up of 2 years subsequent to final digestive circuit modification, postabsorptive citrulline concentration was measured and parenteral nutrition dependence was used to define permanent (n 37) and transient (n 20) intestinal failure. absorptive function, studied over a 3-day period, was evaluated by net digestive absorption for protein and fat (n 51). relations between quantitative values were assessed by linear regression analysis and cutoff citrulline threshold, for a diagnosis of intestinal failure by linear discriminant analysis. cox model was used to compare citrulline threshold and anatomic variables of the short bowel as indicators of transient as opposed to permanent intestinal failure. in patients with short-bowel syndrome, citrulline levels were lower than in controls (n 51): 20 /- 13 vs. 40 /- 10 micromol/l (mean /- sd), respectively (p 0.001). after multivariate analysis, citrullinemia was correlated to small bowel length (p 0.0001, r 0.86) and to net digestive absorption of fat, but to neither body mass index nor creatinine clearance. a 20-micromol/l threshold citrullinemia, (1) classified short bowel patients with permanent intestinal failure with high sensitivity (92), specificity (90), positive predictive value (95), and negative value (86); and (2) was a more reliable indicator (odds ratio, 20.0; 95 confidence interval, 1.9-206.1) than anatomic variables (odds ratio, 2.9; 95 confidence interval, 0. 5-15.8) to separate transient as opposed to permanent intestinal failure.","in patients with short-bowel syndrome, postabsorptive plasma citrulline concentration is a marker of functional absorptive bowel length and, past the 2-year adaptive period, a powerful independent indicator allowing distinction of transient from permanent intestinal failure.",Diagnosis
does low-intensity and moderate exercise training improve autonomic nervous system activity imbalanced by postnatal early overfeeding in rats?,"postnatal early overfeeding and physical inactivity are serious risk factors for obesity. physical activity enhances energy expenditure and consumes fat stocks, thereby decreasing body weight (bw). this study aimed to examine whether low-intensity and moderate exercise training in different post-weaning stages of life is capable of modulating the autonomic nervous system (ans) activity and inhibiting perinatal overfeeding-induced obesity in rats. the obesity-promoting regimen was begun two days after birth when the litter size was adjusted to 3 pups (small litter, sl) or to 9 pups (normal litter, nl). the rats were organized into exercised groups as follows: from weaning until 90-day-old, from weaning until 50-day-old, or from 60- until 90-days-old. all experimental procedures were performed just one day after the exercise training protocol. the sl-no-exercised (sl-n-exe) group exhibited excess weight and increased fat accumulation. we also observed fasting hyperglycemia and glucose intolerance in these rats. in addition, the sl-n-exe group exhibited an increase in the vagus nerve firing rate, whereas the firing of the greater splanchnic nerve was not altered. independent of the timing of exercise and the age of the rats, exercise training was able to significantly blocks obesity onset in the sl rats; even sl animals whose exercise training was stopped at the end of puberty, exhibited resistance to obesity progression. fasting glycemia was maintained normal in all sl rats that underwent the exercise training, independent of the period. these results demonstrate that moderate exercise, regardless of the time of onset, is capable on improve the vagus nerves imbalanced tonus and blocks the onset of early overfeeding-induced obesity.","low-intensity and moderate exercise training can promote the maintenance of glucose homeostasis, reduces the large fat pad stores associated to improvement of the ans activity in adult rats that were obesity-programmed by early overfeeding.",Prevention
is the positive effect of posterolateral lumbar spinal fusion preserved at long-term follow-up : a rct with 11-13 year follow-up?,"few studies have investigated the long-term effect of posterolateral lumbar spinal fusion on functional outcome. to investigate the long-term result after posterolateral lumbar spinal fusion with and without pedicle screw instrumentation. questionnaire survey of 129 patients originally randomised to posterolateral lumbar spinal fusion with or without pedicle screw instrumentation. follow-up included dallas pain questionnaire (dpq), oswestry disability index (odi), sf-36 and a question regarding willingness to undergo the procedure again knowing the result as global outcome parameter. follow-up was 83 of the original study population (107 patients). average follow-up time was 12 years (range 11-13 years). dpq-scores were significantly lower than preoperatively in both groups (p 0.005) and no drift towards the preoperative level was seen. no difference between the two groups were observed (instrumented vs. non-instrumented): dpq daily activity mean 37.0 versus 32.0, odi mean 33.4 versus 30.6, sf-36 pcs mean 38.8 versus 39.8, sf-36 mcs mean 49.0 versus 53.3. about 71 in both groups were answered positively to the global outcome question. patients who had retired due to low back pain had poorer outcome than patients retired for other reasons, best outcome was seen in patients still at work (p 0.01 or less in all questionnaires, except sf-36 mcs p 0.08).",improvement in functional outcome is preserved for 10 or more years after posterolateral lumbar spinal fusion. no difference between instrumented fusion and non-instrumented fusion was observed. patients who have to retired due to low back pain have the smallest improvement.,Treatment
is blood-brain barrier dysfunction developed during normal aging associated with inflammation and loss of tight junctions but not with leukocyte recruitment?,"functional loss of blood-brain barrier (bbb) is suggested to be pivotal to pathogenesis and pathology of vascular-based neurodegenerative disorders such as alzheimer's disease. we recently reported in wild-type mice maintained on standard diets, progressive deterioration of capillary function with aging concomitant with heightened neuroinflammation. however, the mice used in this study were relatively young (12 months of age) and potential mechanisms for loss of capillary integrity were not investigated per se. the current study therefore extended the previous finding to investigate the effect of aging on bbb integrity in aged mice at 24 months and its potential underlying molecular mechanisms. immunomicroscopy analyses confirmed significantly increased capillary permeability with heightened neuroinflammation in naturally aged 24-month old mice compared to young control at 3 months of age. aged mice showed significant attenuation in the expression of bbb tight junction proteins, occludin-1 and to lesser extent zo-1 compared to young mice. in addition, tnf- in cerebral endothelial cells of aged mice was significantly elevated compared to controls and this was associated with heightened peripheral inflammation. the expression of icam-1 and vcam-1 remained unelevated, and no sign of leukocyte recruitment was observed in aged mice.",the bbb breakdown that occurs during ordinary aging is associated with inflammation and disruption of tight junction complex assembly but not through leukocyte trafficking.,Symptoms
do primitive mesodermal cells with a neural crest stem cell phenotype predominate proliferating infantile haemangioma?,"infantile haemangioma is a tumour of the microvasculature characterised by aggressive angiogenesis during infancy and spontaneously gradual involution, often leaving a fibro-fatty residuum. the segmental distribution of a subgroup of infantile haemangioma, especially those associated with midline structural anomalies that constitute posterior fossa malformations-hemangiomas-arterial anomalies-cardiac defects-eye abnormalities-sternal cleft and supraumbilical raphe syndrome (phaces), led us to investigate whether neural crest cells might be involved in the aetiology of this tumour. immunohistochemical staining on paraffin embedded infantile haemangioma sections and immunocytochemical staining on cells derived from proliferating haemangioma cultures were performed. the endothelium of proliferating infantile haemangioma contains abundant cells that express the neurotrophin receptor (p75), a cell surface marker that identifies neural crest cells, and also for brachyury, a transcription factor expressed in cells of the primitive mesoderm. the endothelium is also immunoreactive for the haematopoietic stem cell marker, cd133; the endothelial-haematopoietic stem/progenitor marker, cd34; the endothelial cell markers, cd31 and vegfr-2; and the mesenchymal stem cell markers, cd29 and vimentin. additionally, immunoreactivity for the transcription factors, sox 9 and sox 10, that are expressed by prospective neural crest cells was also observed. cells from microvessel-like structures were isolated from in vitro cultured haemangioma tissue explants embedded in a fibrin matrix. immunostaining of these cells showed that they retained expression of the same lineage-specific markers that are detected on the paraffin embedded tissue sections.","these data infer that infantile haemangioma is derived from primitive mesoderm and that the cells within the lesion have a neural crest stem cell phenotype, and they express proteins associated with haematopoietic, endothelial, neural crest and mesenchymal lineages. the authors propose a model to account for the natural progression of infantile haemangioma based upon the multipotent expression profile of the primitive mesoderm and their neural crest stem cell phenotype to form all the cell lineages detected during infantile haemangioma proliferation and involution.",Medication
does regular egg consumption increase the risk of stroke and cardiovascular diseases?,"we performed this study to examine the association between egg consumption and risk of cardiovascular diseases and mortality in a nationally representative cohort of 9734 adults aged 25 to 74 years. egg consumption was categorized into no or less than 1 egg, 1 to 6 eggs, or greater than 6 eggs per week. cox proportional hazards analysis was used to identify the relative risk (rr) of incident stroke, ischemic stroke, coronary artery disease and mortality over a 20-year follow-up in all participants and subsequently in diabetic participants. after adjusting for differences in age, gender, race, serum cholesterol level, body mass index, diabetes mellitus, systolic blood pressure, educational status and cigarette smoking, no significant difference was observed between persons who consumed greater than 6 eggs per week compared to those who consume none or less than 1 egg per week in regards to any stroke (rr, 0.9; 95 confidence interval (ci), 0.7 to 1.1), ischemic stroke (rr, 0.9; 95 ci, 0.7 to 1.1), or coronary artery disease (rr, 1.1; 95 ci, 0.9 to 1.3). in subgroup analysis among diabetics, consumption of greater than 6 eggs per week was associated with an increased risk of coronary artery disease (rr 2.0, 95 ci 1.0-3.8).",consumption of greater than 6 eggs per week (average of 1 egg or greater per day) does not increase the risk of stroke and ischemic stroke. the increased risk of coronary artery disease associated with higher egg consumption among diabetics warrants further investigations.,General
do surgical risk factors and maxillary nerve function after le fort i osteotomy?,"data on intraoperative risk factors for long-term postoperative complications after le fort i osteotomy (lfo) are limited. the aim of this study was to describe prospectively the overall postoperative changes in maxillary nerve function after lfo, and to correlate these changes with a number of possible intraoperative risk factors. twelve men and 13 women (mean /- standard deviation: aged 25/-10 years) participated in 4 sessions: 1 before lfo (baseline), and the rest at 3, 6, and 12 months after lfo. at each session, somatosensory sensitivity was assessed for the skin, oral mucosa, and teeth, using quantitative sensory tests at either 1 cutaneous point or on a 5 x 5 point matrix reproduced on the skin. in addition, all patients were asked to report their perceived differences in somatosensory sensitivity and their overall satisfaction with the lfo. the thresholds of tactile stimuli on the gingiva and palate were increased 12 months after lfo (p .001). significant increases in 2-point discrimination detection thresholds (p .01) and increased sensitivity to heat (p .01) and cold (p .001) in the infraorbital region were also recorded 12 months after lfo. correspondingly, self-reported complaints of changed sensation under the eyes (p .01), upper lip (p .01), gingiva (p .001), palate (p .01), and teeth (p .01) were reported during the entire postoperative period. intraoperative risk factors were identified and correlated with postoperative changes in somatosensory sensitivity. segmentation of the maxilla was associated with an increase in tactile thresholds at the palate and gingiva (p .05), as were self-reported complaints involving the palate and gingiva (p .001), whereas maxillary impaction was related to lower-tooth pulp pain thresholds when compared with maxillary lowering (p .01). all patients expressed satisfaction with lfo, despite signs of somatosensory disturbances in up to 64 of patients.","numerous changes in postoperative somatosensory function are to be expected after lfo. in most patients, these changes are minor, and some are dependent on intraoperative procedures. nonetheless, all patients reported satisfaction with the surgical results, and would recommend the procedure to others.",Prevention
is fas and fas ligand expression elevated in prostatic intraepithelial neoplasia and prostatic adenocarcinoma?,"fas is a type i membrane receptor of the tumor necrosis factor/nerve growth factor family. on binding to fas ligand, a type ii transmembrane protein, the fas/fas ligand complex, induces apoptosis in target cells. dysregulation of fas and fas ligand expression has been found in some malignant neoplasms. using immunohistochemical analysis, the authors studied the expression of fas and fas ligand in prostatic adenocarcinoma, high-grade prostatic intraepithelial neoplasia (pin), and adjacent benign prostate tissue from 95 radical prostatectomy specimens. the percentage of cells that stained positively with fas in benign prostate tissue (mean, 2) was statistically significantly lower compared with that in prostatic intraepithelial neoplasia (mean, 13; p 0.0014) and prostatic adenocarcinoma (mean, 31; p 0.0001). the staining intensity of fas was significantly less in benign prostate tissue compared with the staining intensity in pin and prostatic adenocarcinoma. the percentage of cells that stained positively with fas ligand in benign prostate tissue (mean, 13) was statistically significantly lower compared with that in pin (mean, 47; p 0.0001) and in prostatic adenocarcinoma (mean, 53; p 0.0001). the staining intensity of fas ligand was significantly less in benign prostate tissue compared with that in pin and prostatic adenocarcinoma.","data from the current study indicate that fas/fas ligand is elevated in prostatic malignancy, suggesting that fas-mediated apoptosis may be a potential target for therapeutic intervention.",Medication
does the microglial activation state regulate migration and roles of matrix-dissolving enzymes for invasion?,"microglial cells are highly mobile under many circumstances and, after central nervous system (cns) damage, they must contend with the dense extracellular matrix (ecm) in order to reach their target sites. in response to damage or disease, microglia undergo complex activation processes that can be modulated by environmental cues and culminate in either detrimental or beneficial outcomes. thus, there is considerable interest in comparing their pro-inflammatory ('classical' activation) and resolving 'alternative' activation states. almost nothing is known about how these activation states affect the ability of microglia to migrate and degrade ecm, or the enzymes used for substrate degradation. this is the subject of the present study. primary cultured rat microglial cells were exposed to lipopolysaccharide (lps) to evoke classical activation or il4 to evoke alternative activation. high-resolution microscopy was used to monitor changes in cell morphology and aspects of the cytoskeleton. we quantified migration in a scratch-wound assay and through open filter holes, and invasion through matrigel. a panel of inhibitors was used to analyze contributions of different matrix-degrading enzymes to migration and invasion, and quantitative real-time reverse transcriptase pcr (qrt-pcr) was used to assess changes in their expression. vinculin- and f-actin-rich lamellae were prominent in untreated and il4-treated microglia (but not after lps). il4 increased the migratory capacity of microglia but eliminated the preferential anterior nuclear-centrosomal axis polarity and location of the microtubule organizing center (mtoc). microglia degraded fibronectin, regardless of treatment, but lps-treated cells were relatively immobile and il4-treated cells invaded much more effectively through matrigel. for invasion, untreated microglia primarily used cysteine proteases, but il4-treated cells used a wider range of enzymes (cysteine proteases, cathepsin s and k, heparanase, and matrix metalloproteases). untreated microglia expressed mmp2, mmp12, heparanase, and four cathepsins (b, k, l1, and s). each activation stimulus upregulated a different subset of enzymes. il4 increased mmp2 and cathepsins s and k; whereas lps increased mmp9, mmp12, mmp14 (mt1-mmp), heparanase, and cathepsin l1.","microglial cells migrate during cns development and after cns damage or disease. thus, there are broad implications of the finding that classically and alternatively activated microglia differ in morphology, cytoskeleton, migratory and invasive capacity, and in the usage of ecm-degrading enzymes.",Medication
does vascular invasion discriminate between pancreatic tuberculosis and pancreatic malignancy : a case series?,"pancreatic tuberculosis is very rare and most commonly involves the head and uncinate process of the pancreas. it closely mimics pancreatic malignancy and is often diagnosed after pancreatico-duodenectomy. vascular invasion is believed to be a hallmark of malignant lesions and described as a point of differentiating benign lesions from malignant lesions. we herein retrospectively evaluated the patients with pancreatic tuberculosis seen at our unit over the last 4 years for features of vascular invasion. we retrospectively analyzed the collected database of all patients diagnosed with pancreatic tuberculosis at our unit over the last four years and identified patients who had evidence of local vascular invasion and their clinical and imaging findings were retrieved. over the last four years, 16 patients (12 males) with pancreatic tuberculosis were seen and five of these 16 patients had imaging features of vascular invasion by the pancreatic head mass. of these five patients, four were males and the mean age was 32.05.47 years. of these five patients, three had involvement of portal vein and superior mesenteric vein and two had involvement of hepatic artery.","presence of vascular invasion does not distinguish pancreatic tuberculosis and malignancy, and, therefore, cytopathological confirmation is mandatory to differentiate between the two.",Diagnosis
are anatomical landmarks and skin markers reliable for accurate labeling of thoracic vertebrae on mri?,"numbering of the thoracic spine on mri can be tedious if c2 and l5s1 are not included and may lead to errors in lesion level. to determine whether anatomic landmarks or external markers are reliable as an aid for accurate numbering of thoracic vertebrae on mri. sixty-seven thoracic spine mr studies of 67 patients (30 males, 37 females, age range 1883 years) were studied, composed of 52 consecutive mr studies and an additional 15 mri in which vitamin e markers were placed over the skin. in the 52 thoracic mr examinations potential numbering aids such as the level of the sternal apex, pulmonary artery, aortic arch, and osseous or disc abnormalities were numbered on both cervical localizer (standard of reference) and thoracic sagittal images. the additional 15 examinations in which vitamin e markers were placed over the skin were evaluated for consistency in the level of the markers on different sequences in the same exam. the sternal apex level ranged from t2 to t5 t3 in 28/51 patients (55), t2 in 10/51 (20). the aortic arch level ranged from t2 to t4 t4 in 18/48 (38) and t3 in 17 (35). pulmonary artery level ranged from t4 to t67 disc t5 in 20/52 patients (38) and t6 in 14/52 (27). in 3 of 12 patients who had abnormalities in a vertebral body or disc as definite point reference, the non-localizer image mislabeled the level. in 11/15 (73) patients with vitamin e markers that were placed over the upper thoracic spine, the results showed consistency in the level of the markers in relation to the reference points or consistent inter-marker gap between the sequences.","there are only two reliable ways to accurately define the levels if no landmarking feature is available on the magnet. the first is by including c2 in the thoracic sequence of a diagnostic quality, and the second is by using an abnormality in the discs or vertebral bodies as a point of reference.",Diagnosis
do cancer stem-like sphere cells induced from de-differentiated hepatocellular carcinoma-derived cell lines possess the resistance to anti-cancer drugs?,"cancer stem cells (cscs) are thought to play important roles in therapy-resistance. in this study, we induced cancer stem-like cells from hepatocellular carcinoma (hcc) cell lines using a unique medium, and examined their potential for resistance to anti-cancer drugs. the human hcc cell lines sk-hep-1 (sk), hle, hep 3b, and huh-7 were used to induce cancer stem-like cells with our sphere induction medium supplemented with neural survival factor-1. nanog and lin28a were examined as stemness markers. several surface markers for csc such as cd24, cd44, cd44 variant, and cd90 were analyzed by flow-cytometry. to assess the resistance to anti-cancer drugs, the mts assay, cell cycle analysis, and reactive oxygen species (ros) activity assay were performed. poorly differentiated hcc derived sk and undifferentiated hcc derived hle cell lines efficiently formed spheres of cells (sk-sphere and hle-sphere), but well-differentiated hcc-derived huh-7 and hep 3b cells did not. sk-spheres showed increased nanog, lin28a, and aldh1a1 mrna levels compared to parental cells. we observed more cd44 variant-positive cells in sk-spheres than in parental cells. the cell viability of sk-spheres was significantly higher than that of sk cells in the presence of several anti-cancer drugs except sorafenib (1.7- to 7.3-fold, each p 0.05). the cell cycle of sk-spheres was arrested at the g0/g1 phase compared to sk cells. sk-spheres showed higher abcg2 and hif1a mrna expression and lower ros production compared to parental cells.","our novel method successfully induced cancer stem-like cells, which possessed chemoresistance that was related to the cell cycle, drug efflux, and ros.",Medication
is chronic tamoxifen use associated with a decreased risk of intestinal metaplasia in human gastric epithelium?,"intestinal metaplasia (im), a premalignant lesion, is associated with an increased risk of gastric cancer. although estrogen exposure, including tamoxifen, has been studied in correlation with gastric cancer, little has been investigated about its effects on im. therefore, we investigated whether chronic tamoxifen use was associated with the risk of im in human stomach. we evaluated 512 gastric biopsies from 433 female breast cancer patients that underwent endoscopic gastroduodenoscopy (egd) 6 months after breast surgery. histopathological findings were scored according to the updated sydney classification. demographic and clinical characteristics were also included to identify predictive factors for im. in a multivariate logistic regression analysis, age at egd (odds ratio or, 1.04; p 0.002), biopsies from antrum (or 2.08; p 0.001), and helicobacter pylori positivity (or 1.68; p 0.016) were significantly associated with an increased risk of im, whereas chronic tamoxifen use (3 months) was associated with a decreased risk of im (or 0.59; p 0.025). after stratifying by biopsy site, association between tamoxifen use and im persisted for corpus (or 0.42; p 0.026) but not for antrum (or 0.74; p 0.327). in analysis limited to patients with follow-up egd, chronic tamoxifen use also correlated with improved im score compared to no tamoxifen use (improved, 77.8 vs. 22.2; no change, 65.4 vs. 34.6; worsened, 30.0 vs. 70.0; p 0.019).",this study suggests that chronic tamoxifen use can decrease the risk of im in human stomach. the effect of tamoxifen is predominantly observed in the corpus.,Treatment
is tlr4 involved in hepatic ischemia/reperfusion injury in mice ?,"to explore the role of tlr4 in the mechanism of hepatic ischemia/reperfusion (i/r) injury in mice. wild-type (c3h/heouj) mice and tlr4 deficient mice (c3h/hej) were used to prepare the models of liver i/r injury. partial hepatic ischemia was produced by inflow causing occlusion in the median and left lobes for 45 minutes. blood was drawn to kill the mice at 1 hours and 3 hours after reperfusion. the blood was used to analyze aspartate aminotransferase (ast) and tumor necrosis factor-alpha (tnfalpha). tnf-alpha mrna expression and myeloperoxidase (mpo) level in ischemic lobes was examined by northern blot and myeloperoxidase assay, respectively. ast levels were significantly lower in tlr4 deficient mice, compared with those in wild-type mice at both time points (661.83u/l/-106.09u/l vs. 1215.5u/l/- 174.03u/l, t-6.65, p0.01; 1145.17u/l/-132.42u/l vs. 2958.17u/l/-186.81u/l, t-5.57, p0.01). serum tnf-alpha level was lower in tlr4 deficient mice at 3 hours after reperfusion compared with that in wild-type mice (152.39pg/ml/-43.3 pg/ml vs. 249.12pg/ml/-51.89pg/ml, t-3.13, p0.05). this difference appeared to be mediated at the gene level, since tnf-alpha mrna expression had decreased in tlr4 deficient mice at 1 hours after reperfusion, compared with that in wild type mice (80.3/-28.8 vs. 189.4/-24.6, t-3.25, p0.05). mpo level in ischemic lobes in tlr4 deficient mice at 3 hours after reperfusion was significantly lower than that in wild type mice (f33.49, p0.01).",i/r hepatic injury in tlr4 deficient mice is less than that in wild-type mice. tnf-alpha expression down-regulated at the mrna level appears critical. these suggest that tlr4 be involved in the mechanism of hepatic ischemia/reperfusion injury in mice.,General
does es-62 protect against collagen-induced arthritis by resetting interleukin-22 toward resolution of inflammation in the joints?,"the parasitic worm-derived immunomodulator es-62 protects against disease in the mouse collagen-induced arthritis (cia) model of rheumatoid arthritis (ra) by suppressing pathogenic interleukin-17 (il-17) responses. the th17-associated cytokine il-22 also appears to have a pathogenic role in autoimmune arthritis, particularly in promoting proinflammatory responses by synovial fibroblasts and osteoclastogenesis. the present study was undertaken to investigate whether the protection against joint damage afforded by es-62 also reflects suppression of il-22. the role(s) of il-22 was assessed by investigating the effects of neutralizing anti-il-22 antibodies and recombinant il-22 (ril-22) on proinflammatory cytokine production, synovial fibroblast responses, and joint damage in mice with cia in the presence or absence of es-62. neutralization of il-22 during the initiation phase abrogated cia, while administration of ril-22 enhanced synovial fibroblast responses and exacerbated joint pathology. in contrast, after disease onset anti-il-22 did not suppress progression, whereas administration of ril-22 promoted resolution of inflammation. consistent with these late antiinflammatory effects, the protection afforded by es-62 was associated with elevated levels of il-22 in the serum and joints that reflected a desensitization of the synovial fibroblast responses. moreover, neutralization of il-22 during the late effector stage of disease prevented es-62-mediated desensitization of synovial fibroblast responses and protection against cia.","il-22 plays a dual role in cia, being pathogenic during the initiation phase while acting to resolve inflammation and joint damage during established disease. harnessing of the tissue repair properties of il-22 by es-62 highlights the potential for joint-targeted therapeutic modulation of synovial fibroblast responses and consequent protection against bone damage in ra.",Prevention
does platelet-rich plasma releasate inhibit inflammatory processes in osteoarthritic chondrocytes?,"platelet-rich plasma (prp) has recently been postulated as a treatment for osteoarthritis (oa). although anabolic effects of prp on chondrocytes are well documented, no reports are known addressing effects on cartilage degeneration. since oa is characterized by a catabolic and inflammatory joint environment, the authors investigated whether prp was able to counteract the effects of such an environment on human osteoarthritic chondrocytes. platelet-rich plasma inhibits inflammatory effects of interleukin-1 (il-1) beta on human osteoarthritic chondrocytes. controlled laboratory study. human osteoarthritic chondrocytes were cultured in the presence of il-1 beta to mimic an osteoarthritic environment. medium was supplemented with 0, 1, or 10 prp releasate (prpr, the active releasate of prp). after 48 hours, gene expression of collagen type ii alpha 1 (col2a1), aggrecan (acan), a disintegrin and metalloproteinase with thrombospondin motifs (adamts)4, adamts5, matrix metalloproteinase (mmp)13, and prostaglandin-endoperoxide synthase (ptgs)2 was analyzed. additionally, glycosaminoglycan (gag) content, nitric oxide (no) production, and nuclear factor kappa b (nfb) activation were studied. platelet-rich plasma releasate diminished il-1 beta-induced inhibition of col2a1 and acan gene expression. the prpr also reduced il-1 beta-induced increase of adamts4 and ptgs2 gene expression. adamts5 gene expression and gag content were not influenced by il-1 beta or additional prpr. matrix metalloproteinase 13 gene expression and no production were upregulated by il-1 beta but not affected by added prpr. finally, prpr reduced il-1 beta-induced nfb activation to control levels containing no il-1 beta.","platelet-rich plasma releasate diminished multiple inflammatory il-1 beta-mediated effects on human osteoarthritic chondrocytes, including inhibition of nfb activation.",Medication
"are serum hiv-1 p24 antibody , hiv-1 rna copy number and cd4 lymphocyte percentage independently associated with risk of mortality in hiv-1-infected children . national institute of child health and human development intravenous immunoglobulin clinical trial study group?","the role of hiv-1 antibody in modulating disease progression must be assessed in the context of other immune and viral load markers. we evaluated the association between hiv-1 p24 antibody, hiv-1 rna, immune complex-dissociated (icd) p24 antigen, cd4 cell percentage, and mortality in a cohort of 218 hiv-infected children enrolled in a trial of intravenous immunoglobulin prophylaxis of bacterial infections. cd4 cell percentage was measured and sera collected and stored at baseline and every 3 months on study (1988-1991). stored sera were assayed for hiv-1 p24 antibody, hiv-1 rna, and icd p24 antigen. mortality was recorded during the trial and updated through 1996 (mean total follow-up, 6.3 years). eighty-one (37) children died; probability of mortality for children with baseline hiv-1 p24 antibody concentrations of undetectable ( or 125 reciprocal titer units (rtu) was 61, 50, 24, and 10, respectively. a 3.5-fold increase in the relative risk (rr) of death 95 confidence interval (ci), 2.2-5.5 was observed among children with baseline hiv-1 p24 antibody concentration or 5 rtu. in multivariate analyses, p24 antibody, hiv-1 rna, and cd4 cell percentage but not icd p24 antigen were independently associated with mortality; the rr of death increased by 1.7 (95 ci, 1.3-2.1) for each log10 decrement in baseline hiv-1 p24 antibody.","hiv-1 p24 antibody, hiv-1 rna and cd4 cell percentage independently predict mortality amongst infected children. whereas cd4 cell percentage provides an estimate of the general degree of immune suppression, hiv-1 p24 antibody could provide an easily obtained, inexpensive assessment of cd4 cell function and could augment prognostic information provided by cd4 cell count and viral load for clinical management of infected children.",Medication
do parental depression and family environment predict distress in children before stem cell transplantation?,"to examine parental symptoms of depression, family environment, and interaction of these parent and family factors in explaining severity of distress in children scheduled to undergo stem cell or bone marrow transplantation. a self-report measure of illness-related distress, adjusted to reflect the experience of medical diagnosis and associated stressors was completed by 146 youth scheduled to undergo stem cell or bone marrow transplantation. measures of parental depressive symptoms and family environment (cohesion, expressiveness, and conflict) were completed by the resident parent. parental symptoms of depression, family cohesion, and family expressiveness emerged as significant predictors of child-reported distress. additionally, significant parental depression x family cohesion and parental depression x family expressiveness interactions emerged as predictors of the intensity of the child's distress. when parental depressive symptomatology was high, child distress was high regardless of family environment. however, when parental depressive symptomatology was low, family cohesion and expression served as protective factors against child distress.","parental depressive symptomatology and family functioning relate to child distress in an interactive manner. these findings inform future directions for research, including interventions for parents aimed at promoting child adjustment during the pediatric cancer experience.",Treatment
"is umbelliprenin potentially toxic against the ht29 , ct26 , mcf-7 , 4t1 , a172 , and gl26 cell lines , potentially harmful against bone marrow-derived stem cells , and non-toxic against peripheral blood mononuclear cells?","resistance to chemotherapy is a growing concern, thus natural anticancer agents are drawing the attention of many scientists and clinicians. one natural anticancer agent, umbelliprenin, is a coumarin produced by many species of we aimed to examine the inhibitory effect of umbelliprenin on human and mouse bone marrow-derived stem cells (bmdscs), peripheral blood mononuclear cells (pbmcs), and different cancer cell lines. in this in vitro experimental study, the ht29, ct26, mcf-7, 4t1, a172, and gl26 cancer cells and human and mouse bmdscs and pbmcs were cultured in rpmi-1640 medium supplemented with 10 fetal bovine serum (fbs), incubated at 37c for 24 hours in a 5 co umbelliprenin inhibited the cancer cells in a concentration-dependent (p 0.05). the most sensitive and resistant cell lines at the 24-hour incubation time were 4t1 (ic","our findings indicate that umbelliprenin exhibits concentration-dependent inhibitory effects on various cell types; it is potentially toxic against the ht29, ct26, mcf-7, 4t1, a172, and gl26 cell lines, potentially harmful against bmdscs, and non-toxic against pbmcs. therefore, if our results are approved in the future, umbelliprenin can be an appropriate candidate for developing treatments against different cancers.",Medication
does dysfunction of the liver affect the sense of smell?,"cirrhosis of the liver (cl) has been reported to be accompanied by olfactory loss. the aim of the present study was to re-investigate previous work with a special focus on differential olfactory function, the relation between cl etiology and olfactory function, and the correlations between laboratory/psychological parameters and olfactory function. a total of 45 cl patients participated. olfactory function was tested using the ""sniffin' sticks"" technique, which provides measures for butanol odor thresholds, odor discrimination and odor identification. serum levels of zinc and bilirubin were obtained. psychometric measurements included the trailmaking test. the study provided the following major results: (1) olfactory function was compromised in 76 of cl patients; in addition, the patient's ability to identify odors, but not odor thresholds or odor discrimination, was related to the degree of cl. this pattern may be an expression of a stronger effect of cl on the central- nervous processing of odors than on the periphery of the system. (2) neither etiology of the cl (e.g., alcoholism) nor serum levels of bilirubin and zinc were correlated with olfactory function. however, (3) there was a relation between the results from psychometric function tests and the ability to identify odors.","although the reason for olfactory dysfunction in cl is far from clear, future investigations should focus on the hypothesis that endogenous intoxication may lead to a stronger deficit in the central-nervous processing of olfactory information than to peripheral lesions in the olfactory system. in addition, while more specific research is needed, olfactory dysfunction may serve as a subclinical indicator of hepatic encephalopathy.",Symptoms
does ikk/chuk regulate extracellular matrix remodeling independent of its kinase activity to facilitate articular chondrocyte differentiation?,"the non-canonical nf-b activating kinase ikk, encoded by chuk (conserved-helix-loop-helix-ubiquitous-kinase), has been reported to modulate pro- or anti- inflammatory responses, cellular survival and cellular differentiation. here, we have investigated the mechanism of action of ikk as a novel effector of human and murine chondrocyte extracellular matrix (ecm) homeostasis and differentiation towards hypertrophy. ikk expression was ablated in primary human osteoarthritic (oa) chondrocytes and in immature murine articular chondrocytes (imacs) derived from ikk(f/f):creert2 mice by retroviral-mediated stable shrna transduction and cre recombinase-dependent lox p site recombination, respectively. mmp-10 was identified as a major target of ikk in chondrocytes by mrna profiling, quantitative rt-pcr analysis, immunohistochemistry and immunoblotting. ecm integrity, as assessed by type ii collagen (col2) deposition and the lack of mmp-dependent col2 degradation products, was enhanced by ikk ablation in mice. mmp-13 and total collagenase activities were significantly reduced, while timp-3 (tissue inhibitor of metalloproteinase-3) protein levels were enhanced in ikk-deficient chondrocytes. ikk deficiency suppressed chondrocyte differentiation, as shown by the quantitative inhibition of.alizarin red staining and the reduced expression of multiple chondrocyte differentiation effectors, including runx2, col10a1 and vegfa,. importantly, the differentiation of ikk-deficient chondrocytes was rescued by a kinase-dead ikk protein mutant.","ikk acts independent of its kinase activity to help drive chondrocyte differentiation towards a hypertrophic-like state. ikk positively modulates ecm remodeling via multiple downstream targets (including mmp-10 and timp-3 at the mrna and post-transcriptional levels, respectively) to maintain maximal mmp-13 activity, which is required for ecm remodeling leading to chondrocyte differentiation. chondrocytes are the unique cell component in articular cartilage, which are quiescent and maintain ecm integrity during tissue homeostasis. in oa, chondrocytes reacquire the capacity to proliferate and differentiate and their activation results in pronounced cartilage degeneration. , our findings are also of potential relevance for defining the onset and/or progression of oa disease.",Medication
is impaired pressure natriuresis associated with interstitial inflammation in salt-sensitive hypertension?,"impairment of the pressure natriuresis relationship is a central event in the pathogenesis of hypertension. renal tubulointerstitial inflammation results in salt-sensitive hypertension and, until recently, the changes in pressure natriuresis induced by renal inflammation received little attention. oxidative stress and increased intrarenal angiotensin ii activity, in association with rarefaction and loss of peritubular vascular network, may be involved in the inflammation-induced blunting of the natriuresis resulting from increments in renal perfusion pressure.","here, we review the mechanisms for the impairment in pressure natriuresis resulting from renal tubulointerstitial inflammation in reference to the normal physiologic mechanisms involved in this response.",General
does central administration of melanin-concentrating hormone increase alcohol and sucrose/quinine intake in rats?,"alcohol is a caloric compound that can contribute to energy intake. therefore, peptides that regulate energy balance likely modify the motivation to consume alcohol. melanin-concentrating hormone (mch) regulates energy homeostasis and has been implicated in other behaviors that impact alcohol consumption (i.e., anxiety, fluid balance, and reward). we tested the hypothesis that mch would decrease the motivation to consume alcohol secondarily to reducing anxiety. rats were trained to drink 10 ethanol or an isocaloric concentration of sucrose with use of a sucrose-fading technique. mch (1, 5, or 10 microg) or its saline vehicle was administered into the third cerebral ventricle (i3vt), and intake of ethanol or sucrose and chow was assessed for 2 hr. alcohol-nave rats were evaluated in an elevated plus maze after i3vt mch (10 microg), neuropeptide y, or saline administration. contrary to the hypothesis, mch dose-dependently increased alcohol intake: saline 0.7 /- 0.1 g/kg, 1 microg mch 1.0 /- 0.1 g/kg, 5 microg mch 1.2 /- 0.1 g/kg, and 10 microg mch 1.8 /- 0.3 g/kg (p 0.01), and this was true whether water was simultaneously available or not. mch also significantly increased sucrose intake (saline 1.0 /- 0.3 g/kg, 10 mug mch 1.4 /- 0.5 g/kg; p 0.05). mch had no effect on time spent in the open arms (54.3 /- 11.5 sec) relative to saline (58.2 /- 23.8 sec), whereas neuropeptide y, a known anxiolytic, increased time spent on the open arms (119.2 /- 22 sec, p 0.05).","we conclude that mch nonspecifically increases ingestive behavior. furthermore, mch had no apparent effect on anxiety. the ability of mch to increase alcohol and/or sucrose intake may be explained by the effect of mch on energy balance and/or reward processes.",Medication
does oral clonidine change ventilatory response to carbon dioxide in sevoflurane-anesthetized children?,"clonidine is a useful premedicant for pediatric anesthesia. the drug has potential for ventilatory depression. the aim of the current study was to determine the effects of clonidine premedication on the ventilatory response to hypercapnia during sevoflurane anesthesia using the carbon dioxide (co(2)) steady state method. sixty children (3-13 yr) were assigned to receive clonidine 4 microg x kg(-1) or placebo. anesthesia was maintained with spontaneous breathing and 2 sevoflurane. minute ventilation (ve), respiratory rate (rr), endtidal co(2) pressure (p(eco(2)), and arterial hemoglobin oxygen saturation (spo2) were measured with a facemask tightly fitted before and during 7 co(2) inhalation. compared with placebo, oral clonidine failed to reduce ve volume before co(2) loading under general anesthesia with 2 sevoflurane. inhalation of co(2) increased ve. oral clonidine did not attenuate the increase in ve induced by hypercapnic challenge under sevoflurane anesthesia. there were no differences in rr, p(eco(2), or spo2 between the placebo and clonidine groups before and during co(2) loading.",these data suggest that oral clonidine is a suitable premedication for sevoflurane anesthesia under spontaneous breathing conditions in children.,Medication
does prevalence and correlate of 12-month prescription drug misuse in alberta?,"we examined the prevalence and correlates of prescription drug misuse (pdm) in a population-based sample of adults from alberta. data were collected from 3511 adults in alberta aged 18 years and older in 2002 using a computer-aided telephone survey; the survey response rate was 57.4. the prevalence of 12-month pdm in alberta was 8.2 in 2002. opiates were the most frequently misused drug class, followed by sedatives, stimulants, and tranquilizers. current disability was particularly associated with pdm. odds of pdm were also elevated among adult students and adults with a high school diploma relative to adults with a post-secondary degree. past-year problem gambling, illicit drug use, and alcohol use and dependence were each associated with pdm, while past-year binge drinking and daily smoking were not.",findings suggest pdm was an important public health concern in alberta in 2002. estimates suggest prescription use and misuse have increased substantially in canada since that time. there is an urgent need for an ongoing assessment of this evolving problem so that effective prevention and therapeutic strategies can be developed.,Medication
does helicobacter pylori colonization ameliorate glucose homeostasis in mice through a ppar -dependent mechanism?,"there is an inverse secular trend between the incidence of obesity and gastric colonization with helicobacter pylori, a bacterium that can affect the secretion of gastric hormones that relate to energy homeostasis. h. pylori strains that carry the cag pathogenicity island (pai) interact more intimately with gastric epithelial cells and trigger more extensive host responses than cag(-) strains. we hypothesized that gastric colonization with h. pylori strains differing in cag pai status exert distinct effects on metabolic and inflammatory phenotypes. to test this hypothesis, we examined metabolic and inflammatory markers in db/db mice and mice with diet-induced obesity experimentally infected with isogenic forms of h. pylori strain 26695: the cag pai wild-type and its cag pai mutant strain 99-305. h. pylori colonization decreased fasting blood glucose levels, increased levels of leptin, improved glucose tolerance, and suppressed weight gain. a response found in both wild-type and mutant h. pylori strain-infected mice included decreased white adipose tissue macrophages (atm) and increased adipose tissue regulatory t cells (treg) cells. gene expression analyses demonstrated upregulation of gastric ppar -responsive genes (i.e., cd36 and fabp4) in h. pylori-infected mice. the loss of ppar in immune and epithelial cells in mice impaired the ability of h. pylori to favorably modulate glucose homeostasis and atm infiltration during high fat feeding.",gastric infection with some commensal strains of h. pylori ameliorates glucose homeostasis in mice through a ppar -dependent mechanism and modulates macrophage and treg cell infiltration into the abdominal white adipose tissue.,Prevention
does loss of pten attenuate the development of pathological hypertrophy and heart failure in response to biomechanical stress?,"the maladaptive response to biomechanical stress is a fundamental response in heart disease. loss of the 3'-lipid phosphatase, phosphatase and tensin homolog deleted on chromosome ten (pten), is associated with increased phosphorylation of akt/protein kinase b and glycogen synthase kinase-beta. we hypothesize that these key changes will halt the development of pathological hypertrophy and the progression to heart failure in response to pressure overload. in mice, muscle-specific knockout of pten, mckcre-pten(flox/flox) (pten ko), resulted in basal hypertrophy and mild reduction in left ventricular (lv) systolic function. male mice were subjected to aortic banding (ab) or sham operation. in contrast to mckcre-pten(/) control mice, pressure overload in pten ko mice resulted in reduced pathological hypertrophy, less interstitial fibrosis, and reduced apoptosis with a marked preservation of lv function. western blot analysis of mitogen-activated protein kinase (mapk) signalling showed equivalent phosphorylation of extracellular signal-regulated kinase (erk)1 and erk2 with markedly reduced phosphorylation of jun n-terminal kinase (jnk)1 and jnk2, and p38 in pten ko mice subjected to ab. loss of pten was associated with increased expression of the proangiogenic factors, vascular endothelial growth factor-a and angiopoietin-2, with preservation of the myocardial capillary density in response to pressure overload. moreover, banded pten ko mice maintained the expression of several key metabolic genes that are known to be dysregulated in heart failure. in contrast, a subpressor dose of the g protein-coupled receptor (gpcr) agonist angiotensin ii (ang ii) leads to increased pathological hypertrophy and mapk activation in pten ko mice.","loss of pten prevents the development of maladaptive ventricular remodelling with preservation of angiogenesis and metabolic gene expression in response to pressure overload but not in response to the gpcr agonist, ang ii. inhibition of pten signalling in the heart may represent a novel approach to slow the progression of heart failure in response to pathological biomechanical stress.",Medication
does automated identification and susceptibility determination directly from blood cultures facilitate early targeted antibiotic therapy?,"the increasing prevalence of antibiotic resistance is challenging established empirical treatments, making early identification and susceptibility determination more important. to avoid time-consuming overnight cultures, a previously published method for the rapid identification and susceptibility testing of blood cultures was instituted at molde hospital. the time saved compared to the standard method, and how often the results could have led to a change in the empirical antibiotic treatment compared to gram stain from cultures, were evaluated. all positive blood cultures with gram-negative bacilli obtained between march and december 2010 were included in the study (n 69). accuracy and turn-around times were compared to those of the standard methods. the empirical antibiotic treatment was recorded when consulting the clinician about the results. correct identification was obtained in 66/69 (95.7) of the isolates. correct susceptibility determination was obtained in 758/759 (99.9) of the tests. oral reports to the clinician were given on average 11 h 22 min earlier for identification, and 10 h 51 min earlier for susceptibility determination, compared to the standard methods. with optimal handling we could have managed 17 h 26 min and 16 h 14 min, respectively. in 14/69 cases the empirical treatment included no effective or appropriate antibiotics. 7 of these 14 would not have been changed to working antibiotic treatment based on gram stain alone.",the rapid method was found to be accurate and showed the potential for the initiation of effective antibiotic treatment more than 16 h earlier for 10 of the patients in this small sample.,Treatment
does disposition of cefepime in the central nervous system of patients with external ventricular drain?,"to assess central nervous system (cns) penetration of cefepime in adults with external ventricular drains and to compare the achieved cerebrospinal fluid (csf) concentrations with the usual minimum inhibitory concentrations (mics) of common pathogens. open-label, prospective study. university-affiliated medical center. seven patients with external ventricular drains and normal renal function (documented creatinine clearance 60 ml/min) who received cefepime 2 g intravenously every 12 hours for treatment of nosocomial pneumonia. serial serum and csf samples were obtained concurrently after the fourth dose during one dosing interval. the concentration-time profiles in serum and csf were comodeled by using a two-compartment model with zero-order infusion to the central compartment. the csf concentration-time profiles of the individual patients were compared with published mic90 of common pathogens isolated in nosocomial meningitis. our model reasonably characterized the disposition of cefepime in serum and csf. penetration into the cns was 4-34 based on area under the curve and was 5-58 based on minimum concentration.",penetration of cefepime into the cns was variable among the patients (4-34) but appeared similar to that reported for other cephalosporins given to treat meningitis. the concentrations attained by most patients in this study were above the mic90 of many common nosocomial organisms.,Medication
does absence of t cells confer increased pulmonary arterial hypertension and vascular remodeling?,"severe pulmonary arterial hypertension (sph) is a frequently lethal condition characterized by pulmonary vascular remodeling and right heart strain or failure. sph is also often associated with autoimmune and collagen vascular disorders. to study the effects of t cells on the development of experimental sph. athymic nude rats lacking t cells were treated with a single subcutaneous injection of vascular endothelial growth factor (vegf) receptor blocker su5416 (20 mg/kg) to induce pulmonary vascular endothelial cell apoptosis. immunohistochemical analysis and il-4 levels of the lung tissue were performed. cell death and proliferation were assessed by western blot and immunohistochemistry. in contrast to su5416-treated euthymic rats that develop sph only in combination with chronic hypoxia, athymic nude rats developed sph and vascular remodeling (similar to clinical sph) at normoxic conditions as demonstrated by measurements of pulmonary artery pressure and right ventricle hypertrophy. pulmonary arterioles became occluded with proliferating endothelial cells and were surrounded by mast cells, b cells, and macrophages. il-4, proliferating cell nuclear antigen, and collagen type i levels were markedly increased in su5416-treated athymic rat lungs. antibody deposition was noted along the vascular endothelium in rats with sph. finally, protection from sph was conferred by immune challenge with spleen cells from euthymic nude rats.","these studies demonstrate the importance of a complete, intact immune system in protecting against pulmonary angioproliferation in this new model of sph as well as the importance of intact vegf receptor signaling for lung endothelial cell homeostasis.",Medication
does urethral plate grafting improve the results of tubularized incised plate urethroplasty in primary hypospadias?,"we conducted a competitive efficacy trial in order to examine whether grafting the raw area of the urethral plate (up) with inner preputial skin in children with primary hypospadias (ph) during tubularized incised plate urethroplasty (tip) improves the results of the operation. fifty consecutive patients with pathology ranging from glanular to proximal penile ph were randomized into two groups, comparable for age and pathology, to be operated on either with tip or a grafted tip (g-tip) procedure. three patients failed the re-examination protocol, so the tip group comprised 23 children aged 9.0 months-9.6 years (mean age 3.4 years) and the g-tip group comprised 24 children, aged 10.0 months-9.4 years (mean 3.5 years). the patients were followed up for a period of 2-5 years (mean 3.2 years). within the tip group, we observed the development of fistula with concomitant neourethral stenosis in two cases (8.7), stenosis without fistula in four (17.4), and glans dehiscence in one case (4.35). within the g-tip group there was one case of fistula without stenosis (4.16), no case of neourethral stenosis, and one case of glans dehiscence (4.16). two cases of non-slit-like meatus were observed in the tip group. the results show that the complications of neourethral stenosis are significantly reduced (p 0.05) in the g-tip group, as is the total number of complications and unsatisfactory results. the duration of the tip operation was 72-110 (mean 92) min, and for the g-tip 100-136 (mean 115) min. no postoperative symptoms were observed that could be attributed to prolonged anesthesia time.","up grafting with inner preputial skin, when added to the tip procedure in the treatment of ph, results in a significantly smaller number of unsatisfactory results, and particularly fewer cases of neourethral stenosis. g-tip can be used as the procedure of choice in ph patients.",Treatment
are t1 and t2 relaxation times associated with progression of hip osteoarthritis?,"to evaluate whether baseline t1 and t2 relaxation times of hip cartilage are associated with magnetic resonance imaging (mri) based progression of hip osteoarthritis (oa) at 18 months. 3t mri studies of the hip were obtained at baseline and 18-month follow-up for 54 subjects without evidence of severe oa at baseline kellgren-lawrence (kl) score of 0-3. 2d fast spin-echo sequences were used for semi-quantitative morphological scoring of cartilage lesions and a combined t1/t2 sequence was used to quantitatively assess cartilage composition. progression of hip oa was defined based on incident or progression of morphological semi-quantitative grade at 18 months. baseline t1 and t2 relaxation times were compared between progressors and non-progressors using one-way analysis of variance and mann-whitney u tests and used to predict progression with binary logistic regression after adjusting for age, gender, body mass index, and kl score. additionally, a novel voxel-based relaxometry technique was used to compare the spatial distribution of baseline t1 and t2 between progressors and non-progressors. significantly higher baseline t1 and t2 values were observed in hip oa progressors compared to non-progressors, particularly in the posterosuperior and anterior aspects of the femoral cartilage. logistic regression showed that higher baseline t1 or t2 values in the femoral cartilage were significantly associated with progression of femoral cartilage lesions at 18 months.",t1 and t2 relaxation parameters are associated with morphological cartilage degeneration at 18 months and may serve as potential imaging biomarkers for progression of cartilage lesions in hip oa.,Diagnosis
does apolipoprotein 4 polymorphism modify the association between body mass index and high-density lipoprotein cholesterol : a cross-sectional cohort study?,"we sought to examine whether 4 carrier status modifies the relation between body mass index (bmi) and hdl. the national heart, lung, and blood institute family heart study included 657 families with high family risk scores for coronary heart disease and 588 randomly selected families of probands in the framingham, atherosclerosis risk in communities, and utah family health tree studies. we selected 1402 subjects who had 4 carrier status available. we used generalized estimating equations to examine the interaction between bmi and 4 allele carrier status on hdl after adjusting for age, gender, smoking, alcohol intake, mono- and poly-unsaturated fat intake, exercise, comorbidities, ldl, and family cluster. the mean (standard deviation) age of included subjects was 56.4(11.0) years and 47 were male. adjusted means of hdl for normal, overweight, and obese bmi categories were 51.2( 0.97), 45.0( 0.75), and 41.6( 0.93), respectively, among 397 4 carriers (p for trend 0.0001) and 53.6( 0.62), 51.3( 0.49), and 45.0( 0.62), respectively, among 1005 non-carriers of the 4 allele (p-value for trend 0.0001). there was no evidence for an interaction between bmi and 4 status on hdl(p-value 0.39).",our findings do not support an interaction between 4 allele status and bmi on hdl.,Prevention
does switching types of drug-eluting stents prevent repeated in-stent restenosis in patients with coronary drug-eluting stent restenosis?,"we treated patients experiencing drug-eluting stent (des) restenosis with plain old balloon angioplasty (poba), implantation of the same type of des homogeneous drug-eluting stent (homo-des), or implantation of a different type of des heterogeneous drug-eluting stent (hetero-des), and compared the efficacy and safety of these procedures for the prevention of repeated in-stent restenosis (isr). in patients with de-novo coronary lesions, des implantation is associated with a markedly reduced restenosis rate as compared with that associated with a bare metal stent and poba. however, the optimal management strategy for patients with des isr remains unknown. we identified 191 consecutive des isr lesions from 183 patients who required clinically driven revascularization and divided them into three groups according to the treatment: 38 lesions were treated with poba, 38 with homo-des, and 115 with hetero-des. the incidence of target lesion revascularization (tlr) was 42.1 (16/38), 15.8 (6/38), and 16.5 (19/115) in the poba, homo-des, and hetero-des groups (poba vs. homo, hetero-des; p0.002, respectively). multivariate analysis indicated that diabetes odds ratio (or), 3.4, hemodialysis (or, 7.74), nonfocal isr patterns (or, 3.35), previous myocardial infarction (or, 3.26), and poba (or, 8.84) were independent predictors of tlr.","a strategy involving repeated des implantation was superior to poba for preventing recurrent restenosis. treatment with a different type or generation of des does not appear to reduce the incidence of tlr. moreover, we identified certain useful factors for facilitating appropriate and early triage in the patients with repeated des isr.",Prevention
do metabolite profiles in the anterior cingulate cortex of depressed patients differentiate those taking n-acetyl-cysteine versus placebo?,"increased oxidative stress is thought to contribute to the pathophysiology of major depressive disorder (mdd), which is in part due to diminished levels of glutathione, the primary anti-oxidant of the brain. oral administration of n-acetyl-cysteine (nac) replenishes glutathione and has therefore been shown to reduce depressive symptoms. proton magnetic spectroscopy ((1)h-mrs) that allows quantification of brain metabolites pertinent to both mdd and oxidative biology may provide some novel insights into the neurobiological effects of nac, and in particular metabolite concentrations within the anterior cingulate cortex (acc) are likely to be important given the key role of this region in the regulation of affect. the aim of this study was to determine whether the metabolite profile of the acc in mdd patients predicts treatment with adjunctive nac versus placebo. this study was nested within a multicentre, randomized, double-blind, placebo-controlled study of mdd participants treated with adjunctive nac. participants (n 76) from one site completed the spectroscopy component at the end of treatment (12 weeks). spectra from a single-voxel in the acc were acquired and absolute concentrations of glutamate (glu), glutamate-glutamine (glx), n-acetyl-aspartate (naa) and myo-inositol (mi) were obtained. binary logistic regression analysis was performed to determine whether metabolite profiles could predict nac versus placebo group membership. when predicting group outcome (nac or placebo), glx, naa and mi were a significant model, and had 75 accuracy, while controlling for depression severity and sex. however, the glu, naa and mi profile was only predictive at a trend level, with 68.3 accuracy. for both models, the log of the odds of a participant being in the nac group was positively related to naa, glx and glu levels and negatively related to mi levels.",the finding of higher glx and naa levels being predictive of the nac group provides preliminary support for the putative anti-oxidative role of nac in mdd.,Treatment
"is kava-kava extract li 150 as effective as opipramol and buspirone in generalised anxiety disorder -- an 8-week randomized , double-blind multi-centre clinical trial in 129 out-patients?","an 8-week randomized, reference-controlled, double-blind, multi-centre clinical trial investigated kava-kava li 150 in generalized anxiety disorder (gad; icd-10: f41.1). 129 out-patients received either 400 mg kava li 150, 10 mg buspirone or 100 mg opipramol daily for 8 weeks. at week 9, subjects were seen to check for symptoms of withdrawal or relapse. primary outcome measures comprised the hama scale and the proportion of responders at week 8. secondary measures were the boerner anxiety scale (boeas), sas, cgi, a self-rating scale for well-being (bf-s), a sleep questionnaire (sf-b), a quality-of-life questionnaire (al) and global judgements by investigator and patients. in 127 patients (itt) no significant differences could be observed regarding all efficacy and safety measures. about 75 of patients were classified as responders (50 reduction of hama score) in each treatment group, about 60 achieved full remission.",kava-kava li150 is well tolerated and as effective as buspirone and opipramol in the acute treatment of out-patients suffering from gad.,Treatment
do interstitial cells of cajal mediate enteric inhibitory neurotransmission in the lower esophageal and pyloric sphincters?,"previous studies have suggested that a specific class of interstitial cells of cajal (icc) act as mediators in nitrergic inhibitory neurotransmission. the aim of this investigation was to examine the role of intramuscular icc (ic-im) in neurotransmission in the murine lower esophageal (les) and pyloric sphincters (ps). immunohistochemistry and electrophysiology were used to study the distribution and role of ic-im. the les and ps contain spindle-shaped ic-im, which form close relationships with nitric oxide synthase-containing nerve fibers. the ps contains icc within the myenteric plexus and c-kit immunopositive cells along the submucosal surface of the circular muscle. ic-im were absent in the les and ps of c-kit (w/wv) mutant mice. using these mutants, we tested whether ic-im mediate neural inputs in the les and ps. although the distribution of inhibitory nerves was normal in w/wv animals, no-dependent inhibitory neurotransmission was reduced. hyperpolarizations to sodium nitroprusside were also attenuated in w/wv animals.",the data suggest that ic-im play an important role in no-dependent neurotransmission in the les and ps. ic-im may be the effectors that transduce no signals into hyperpolarizing responses. loss of ic-im may interfere with relaxations and normal motility in these sphincters.,Medication
is antiretroviral therapy associated with reduced herpes simplex virus shedding in hiv coinfected adults : an observational cohort study?,"herpes simplex virus types 1 and 2 (hsv-1/2) may have adverse consequences on hiv type 1 infection. we quantified the frequency of hsv reactivations in highly active antiretroviral therapy (haart)-treated adults with hiv, and compared it with that in haart-nave patients. 2 academic hospital sites in toronto, canada. asymptomatic haart-naive (n44) or treated (with hiv rna 50 copies/ml, n41) adults with hsv-1 and/or 2, hiv coinfection. hsv-1 and hsv-2 shedding as measured by pcr on oral, genital and anal swabs self-collected daily for 28 days. of the 85 participants, 88, 67 and 53 were coinfected with hsv-1, hsv-2 and both hsv types, respectively. median (iqr) cd4 count was 516 (382, 655) cells/mm(3). hsv (type 1 and/or 2) shedding occurred on a median (iqr) of 7.1 (0, 17.9) of days in haart users and 3.6 (0, 10.7) of days in non-haart users. no significant relationship was observed between haart and hsv-1/2 shedding in univariable (or1.55, 95 ci 0.83 to 2.87) or multivariable negative binomial models adjusted for sex, baseline cd4 count, recent immigrant status and time since hiv diagnosis (adjusted or, aor1.05, 95 ci 0.43 to 2.58). similar null results were observed for hsv-2 shedding in hsv-2 seropositive participants (aor1.16, 95 ci 0.40 to 3.36) and hsv-1 shedding in hsv-1 seropositive participants (aor0.70, 95 ci 0.14 to 3.47).",hsv reactivations persist despite suppressive haart among adults coinfected with hsv and hiv. clinical trials of suppressive anti-hsv therapy are warranted in this population.,Treatment
is maternal and fetal outcomes if gestational impaired glucose tolerance treated?,"to evaluate whether there is increased maternal or neonatal morbidity in connection with impaired glucose tolerance (igt) during pregnancy when the condition is not treated. during the study period of 1997-2001, in a defined geographical area in sweden, the diagnostic criteria for gestational diabetes mellitus (gdm) were limited to the criteria for diabetes. prospectively, 213 women who were identified with igt during pregnancy were undiagnosed and untreated. data on maternal and fetal outcome was collected from records. for each case subject, four control subjects were taken from the same delivery department. the proportion of women who underwent cesarean section was significantly higher in the case subjects than in the control subjects and was independently associated with igt. the adjusted odds ratio (or) was 1.9 (95 ci 1.2-2.9). the proportion of infants who were large for gestational age (lga), defined as birth weight 2 sds greater than the mean for gestation and sex, was independently significantly associated with untreated igt during pregnancy (or 7.3, 95 ci 4.1-12.7). admission to a neonatal intensive care unit (nicu) for 2 days or longer was more common (adjusted or 2.0, 95 ci 1.1-3.8). however, 71.3 of the children in the igt group and 87.3 of the control subjects had no neonatal complications.","there is increased independent association between cesarean section rate, prematurity, lga, and macrosomic infants born to mothers with untreated igt. most of the children were healthy, but there is still increased morbidity. therefore, to evaluate the effects of treatment, there is a need for a randomized study.",Treatment
is transanal endoscopic microsurgery feasible for adenomas throughout the entire rectum : a prospective study?,"transanal endoscopic microsurgery for rectal adenomas is safe and has low recurrence rates. however, the feasibility of the procedure for all rectal adenomas is unclear. this issue was investigated prospectively. from 1996 to 2007, 353 consecutive rectal adenomas were evaluated according to a standard protocol. transanal endoscopic microsurgery was intended in all rectal adenomas. the median diameter was 3 cm and median distance was 8 cm. the peritoneum was opened peroperatively without any adverse effects in 8.7 percent. the conversion rate was 9.6 percent, with an alternative local procedure performed in 4.2 percent and a transabdominal procedure performed in 5.4 percent. conversion rate correlated with the distance of the tumor (p 0.007) and the operating surgeon's level of experience (p 0.004). the median operation time was 45 minutes. operation time correlated with specimen area, experience, and operating surgeon (all p 0.001). all rectal adenomas were excised in one piece. complete margins were observed in 85 percent. rectal adenomas with incomplete margins were larger (p 0.001) and were located more proximally (p 0.001). morbidity was 7.8 percent and mortality 0.6 percent. the median hospital stay was four days. the median follow-up was 27 months. the recurrence rate at three years was 9.1 percent. the median time from operation to recurrence was 12 (range, 4-54) months. resection margin status was a predictor of recurrence, with 6.1 percent recurrence in cases of complete margins and 25.2 percent in cases of incomplete margins (p 0.001).","for nearly all rectal adenomas, transanal endoscopic microsurgery is safe, feasible, and has excellent results.",Treatment
does immunoprofiling of glial tumours of the neurohypophysis suggest a common pituicytic origin of neoplastic cells?,"to analyse the antigen expression profiles of 27 cases of pituicytoma, spindle cell oncocytoma, and granular cell tumour of the sellar region concerning a common pituicytic origin of neoplastic cells. material from 12 female and 15 male patients (13 granular cell tumours of the sellar region, 10 pituicytomas, four spindle cell oncocytomas) collected in the german registry of pituitary tumours between 1993 and 2015 was re-evaluated according to the current who classification of tumours of the central nervous system and supplementary immunohistochemistry including s100-protein, cd56, cd68, thyroid transcription factor-1 (ttf-1), and ki-67 was performed. s100-protein was detected in all 27 tumours and ttf-1 in all 16 tumours that were assessed. vimentin was expressed in all 13 cases investigated whereas broad spectrum cytokeratin was not detected in any of 14 evaluated cases. gfap was observed in nine out of 21 cases. 15 out of 17 investigated lesions showed some cd68 expression and five out of 14 cases were labelled with cd56 antibodies. proliferative activity did not differ significantly between the three tumour subgroups although one primary and one recurrent pituicytoma showed exceptionally high ki-67-proliferation indices of 15.3 and 12.7 , respectively (means: granular cell tumour of the sellar region 2.0 , pituicytoma 2.8 , spindle cell oncocytoma 2.7 ).",the study confirms and expands earlier data and is in line with the notion that the three tumour types are variants of pituicytoma.,Medication
do anti-alpha-glucose-based glycan igm antibodies predict relapse activity in multiple sclerosis after the first neurological event?,"there is no specific serum-based biomarker for the diagnosis or prognosis of relapsing-remitting multiple sclerosis (rrms). we investigated whether levels of igm antibodies to glc(alpha1,4)glc(alpha) (gaga4) or to a panel of four glucose-based glycans could differentiate ms from other neurological diseases (ond) or predict risk of early relapse following first presentation (fp) of rrms. retrospective analysis of 440 sera samples of three cohorts: a) fp-rrms (n 44), ond (n 44); b) fp-rrms (n 167), ond (n 85); and c) fp (n 100). anti-gaga4 igm levels were measured by enzyme immunoassay in cohort-a and cohort-b. cohort-c igm antibodies to glucose-based glycan panel were measured by immunofluorescence. fp-rrms had higher levels of anti-gaga4 igm than ond patients (cohort-a, p 0.01; cohort-b, p 0.0001). sensitivity and specificity were 27 and 97 for cohort-a; and 26 and 90 for cohort-b, respectively. in cohort-c, 58 patients experienced early relapse ( or 24 months), and 11 did not experience second attack during follow-up. kaplan-meier curves demonstrated decrease in time to next relapse for patients positive for the antibody panel (p 0.02, log rank).",serum anti-gaga4 igm discerns fp-rrms patients from ond patients. higher levels of serum anti-alpha-glucose igm in fp patients predict imminent early relapse.,Diagnosis
is alleviation of insulin resistance and liver damage by oral administration of imm124-e mediated by increased tregs and associated with increased serum glp-1 and adiponectin : results of a phase i/ii clinical trial in nash?,"nonalcoholic steatohepatitis (nash) is considered to be part of the nonalcoholic fatty liver disorders and its incidence is increasing. imm124-e (immuron ltd, melbourne, australia), containing hyperimmune bovine colostrum, has been shown to exert an immunomodulatory effect and to alleviate target organ damage in animal models of nash. the aim of our study was to determine the safety and efficacy of oral administration of imm124-e to patients with insulin resistance and nash. in an open-label trial, ten patients with biopsy-proven nash and insulin resistance were orally treated with imm124-e for 30 days. oral administration of imm124-e was safe, and no side effects were noted. alleviation of insulin resistance was reflected by significantly improved hemoglobin a(1c) (hba(1c)) values in all ten treated patients. for between five and eight responders, the following effects were noted: a decrease in fasting glucose levels; improved oral glucose tolerance test (oggt) and homeostatic model assessment insulin resistance (homa) scores; and alleviation in lipid profile. these effects were accompanied by increased serum levels of glucagon-like peptide 1 (glp-1), adiponectin and t regulatory cells.",hyperimmune colostrum alleviates nash.,Medication
does hypoproteinemia alter plasma volume expansion in response to a 0.9 saline bolus in awake sheep?,to test the hypothesis that hypoproteinemia reduces plasma volume expansion produced by a bolus of crystalloid solution given to awake sheep. prospective and observational. laboratory. five female merino sheep (n 5) weighing 37 3 kg were anesthetized. each animal was subjected to a 5-day test period: day 1: 50 ml/min 0.9 saline infusion over 20 mins. days 2-4: daily plasmapheresis and replacement of the shed plasma with 6 l of 0.9 saline were performed in increments. fractional plasma volume expansion after rapid infusion of saline on days 1 and 5 was calculated from changes in hemoglobin concentration. there was a significant reduction in total plasma protein concentration after plasmapheresis (p .05). colloid osmotic pressures were also significantly lowered (p .05). a crystalloid infusion of 0.9 saline did not alter any of these values compared with baseline. the hemodynamic measurements did not show significant differences between the experiments. the plasma volume expansion reached approximately 20 at the end of infusion and stayed at 10-15 during the experiments. no difference was found in plasma volume expansion produced by a bolus of 50 ml/min of 0.9 in the hypoproteinemic state when compared with the euproteinemic state (p .61). no difference in cumulative urinary output was found between the two states.,"in contrast to our hypothesis, severe acute hypoproteinemia does not reduce plasma volume expansion in response to 50 ml/min 0.9 saline infusion in nonspleenectomized sheep when compared with the resultant plasma volume expansion after a 50 ml/min of 0.9 infusion in the euproteinemic state.",Medication
do hephaestin and ceruloplasmin play distinct but interrelated roles in iron homeostasis in mouse brain?,"iron accumulation in the central nervous system (cns) is a common feature of many neurodegenerative diseases. multicopper ferroxidases (mcfs) play an important role in cellular iron metabolism. however, the role of mcfs in the cns in health and disease remains poorly characterized. the aim was to study the role of hephaestin (heph) and ceruloplasmin (cp) in cns iron metabolism and homeostasis. iron concentrations and l-ferritin protein levels of selected brain regions were determined in global hephaestin knockout (heph ko), global ceruloplasmin knockout (cp ko), and wild-type (wt) male mice at 6-7 mo of age. gene expression of divalent metal transporter 1 (dmt1), ferroportin 1 (fpn1), heph, cp, and transferrin receptor 1 (tfrc) and heph protein level was quantitated in the same brain regions. iron and l-ferritin protein levels were significantly increased in heph ko mouse brain cortex (iron: 30, p 0.05; l-ferritin: 200, p 0.05), hippocampus (iron: 80, p 0.05; l-ferritin: 300, p 0.05), brainstem (iron: 20, p 0.05; l-ferritin: 150, p 0.05), and cerebellum (iron: 20, p 0.05; l-ferritin: 100, p 0.05) regions than in wt and cp ko mouse brain regions at 6 mo of age. expression of the heph gene was significantly increased in the cp ko mouse cortex (100; p 0.01), hippocampus (350; p 0.001), brainstem (30; p 0.01), and cerebellum (150; p 0.001) than in wt controls, and cp gene expression was significantly decreased in the heph ko mouse hippocampus (20; p 0.05) than in wt control mice at 6 mo of age.",ablation of heph or cp results in disordered brain iron homeostasis in mice. heph ko may provide a novel model for neurodegenerative disorders.,Medication
is overexpression of lcmr1 significantly associated with clinical stage in human nsclc?,"lung cancer is one of the most common human cancers and the leading cause of cancer death worldwide. the identification of lung cancer associated genes is essential for lung cancer diagnosis and treatment. differential display-pcr technique was used to achieve the novel cdna, which were then verified by real-time pcr. northern blot was utilized to observe the expression of lcmr1 in different human tissues. 84 cases human nsclc tissues and normal counterparts were analyzed for the expression of lcmr1 by immunohistochemistry. a novel 778-bp cdna fragment from human large cell lung carcinoma cell lines 95c and 95d was obtained, and named lcmr1 (lung cancer metastasis related protein 1). lcmr1 was differentially expressed in different human tissues. lcmr1 was strongly overexpressed in nsclc and its expression was significantly associated with clinical stage.","our data indicated that lcmr1, strongly overexpressed in nsclc, might have applications in the clinical diagnosis and treatment of lung cancer.",Diagnosis
do adverse reactions and other factors that impact subsequent blood donation visits?,"the importance of adverse reactions in terms of donor safety recently has received significant attention, but their role in subsequent donation behavior has not been thoroughly investigated. six reds-ii blood centers provided data for this analysis. summary minor and major adverse reaction categories were created. the influence of adverse reactions on donation was examined in two ways: kaplan-meier curves were generated to determine the cumulative pattern of first return, and adjusted odds ratios (aors) for demographic and other factors positively and negatively associated with return were estimated using multivariable logistic regression. donors who had major reactions had longer times to return than donors with minor or no reactions. the aor of returning for donors with major reactions was 0.32 (95 confidence interval ci, 0.28-0.37) and with minor reactions 0.59 (95 ci, 0.56-0.62) when compared to donors who did not have reactions. conversely, the most important factors positively associated with return were the number of donations in the previous year and increasing age. subsequent return, whether a major, minor, or no reaction occurred, varied by blood center. factors that are associated with the risk of having adverse reactions were not substantial influences on the return after adverse reactions.",having an adverse reaction leads to significantly lower odds of subsequent donation irrespective of previous donation history. factors that have been associated with a greater risk of adverse reactions were not important positive or negative predictors of return after a reaction.,General
are 5f sphincterotomes and 4f sphincterotomes equivalent for the selective cannulation of the common bile duct?,"cannulation of the common bile duct (cbd) is the first step in endoscopic retrograde cholangiopancreatography (ercp). cannulation difficulty is a known risk factor for post-ercp complications and may be minimized by the use of a smaller caliber sphincterotome. to compare the efficacy of cbd cannulation with a 4 f versus a 5 f sphincterotome. a randomized controlled trial, with concealed allocation and double-blinding. adult patients undergoing their first ercp at a tertiary referral center. patients were randomized to undergo cbd cannulation with either a 4 f or 5 f sphincterotome. successful deep cannulation in 15 attempts was the primary outcome. secondary outcomes included number of attempts/time to cannulation, incidence of complications within 24 hours, and overall cannulation success (including patients before and after crossover). analysis was intention to treat and included standard descriptive and inferential methods. a total of 107 patients were randomized: 51 (4 f) versus 56 (5 f). the majority were female (71) and white (92). baseline demographics, presenting symptoms, and laboratory values were similar between groups. similar success in initial cannulation was observed: 84.3 (4 f) and 83.9 (5 f). no differences were noted in time to cannulation (5.12 min sd, 4.8 for 4 f vs 4.46 min sd, 4.13 for 5 f; p ns), number of attempts to cannulation (6.2 sd, 5.2 for 4 f vs 5.7 sd, 4.9 for 5 f; p ns), or complications. the overall cannulation success was 92.2 (4 f) and 92.9 (5 f).",premature termination of the trial resulted in decreased power.,Prevention
is exercise-induced nrf2-signaling impaired in aging?,"the transcription factor nuclear erythroid-2 like factor-2 (nrf2) is the master regulator of antioxidant defense. data from animal studies suggest exercise elicits significant increases in nrf2 signaling, and that signaling is impaired with aging resulting in decreased induction of phase ii detoxifying enzymes and greater susceptibility to oxidative damage. we have previously shown that older adults have lower resistance to an oxidative challenge as compared to young, and that this response is modified with physical fitness and phytonutrient intervention. we hypothesized that a single bout of submaximal exercise would elicit increased nuclear accumulation of nrf2, and that this response to exercise would be attenuated with aging. nrf2 signaling in response to 30-min cycling at 70 vo2max was compared in young (231y, n10) and older (631, n10) men. blood was collected at six time points; pre-exercise, and 10min, 30min, 1h, 4h, and 24h post-exercise. nrf2 signaling was determined in peripheral blood mononuclear cells by measuring protein expression by western blot of nrf2 in whole cell and nuclear fractions, and whole cell sod1, and hmox, as well as gene expression (rt-pcr) of downstream nrf2-are antioxidants sod1, hmox, and nqo1. baseline differences in protein expression did not differ between groups. the exercise trial elicited significant increase in whole cell nrf2 (p0.003) for both young and older groups. nuclear nrf2 levels were increased significantly in the young but not older group (p0.031). exercise elicited significant increases in gene expression of hmox1 and nqo1 in the young (p0.006, and p0.055, respectively) whereas gene expression in the older adults was repressed. there were no significant differences in sod1 or hmox1 protein expression.","these findings indicate a single session of submaximal aerobic exercise is sufficient to activate nrf2 at the whole cell level in both young and older adults, but that nuclear import is impaired with aging. additionally we have shown repressed gene expression of downstream antioxidant targets of nrf2 in older adults. together these translational data demonstrate for the first time the attenuation of nrf2 activity in response to exercise in older adults.",Prevention
"are low borderline plasma levels of antithrombin , protein c and protein s risk factors for venous thromboembolism?","inherited deficiencies of antithrombin (at), protein c (pc) and protein s (ps) are risk factors for venous thromboembolism (vte). they are usually defined by laboratory cut-offs (in our setting 81, 70 and 63 iu dl(-1), respectively), which give only a rough idea of the vte risk associated with plasma levels of these proteins. we investigated whether the risk of vte associated with the plasma deficiencies of at, pc or ps has a dose-response effect, and whether low borderline levels of these proteins are associated with an increased risk of vte, both in the whole study population and separately in carriers of either factor v leiden or g20210a prothrombin gene mutation. a case-control study of 1401 patients with a first objectively-documented vte and 1847 healthy controls has been carried out. a dose-response effect on the vte risk was observed for all the three anticoagulant proteins. compared with individuals with at, pc or ps levels 100 iu/dl, the adjusted odds ratio (95 ci) of vte was 2.00 (1.44-2.78) for at levels between 76 and 85 iudl(-1) , 2.21 (1.54-3.18) and 1.84 (1.31-2.59) for pc and ps levels between 61 and 75 iudl(-1) . the risk of unprovoked vte in factor v leiden or prothrombin g20210a carriers appears 2 to 3-fold increased when levels of at or ps are low borderline.","low borderline plasma levels of at, pc and ps are associated with a 2-fold increased risk of vte and should be considered in the assessment of the individual vte risk.",Medication
do inflammatory cytokines epigenetically regulate rheumatoid arthritis fibroblast-like synoviocyte activation by suppressing hdac5 expression?,"epigenetic modifications play an important role in the regulation of gene transcription and cellular function. here, we examined if pro-inflammatory factors present in the inflamed joint of patients with rheumatoid arthritis (ra) could regulate histone deacetylase (hdac) expression and function in fibroblast-like synoviocytes (fls). protein acetylation in synovial tissue was assessed by immunohistochemistry. the mrna levels of hdac family members and inflammatory mediators in the synovial tissue and the changes in hdac expression in ra fls were measured by quantitative (q) pcr. fls were either transfected with hdac5 sirna or transduced with adenoviral vector encoding wild-type hdac5 and the effects of hdac5 manipulation were examined by qpcr arrays, elisa and elisa-based assays. synovial class i hdac expression was associated with local expression of tumour necrosis factor (tnf) and matrix metalloproteinase-1, while class iia hdac5 expression was inversely associated with parameters of disease activity (erythrocyte sedimentation rate, c-reactive protein, disease activity score in 28 joints). interleukin (il)-1 or tnf stimulation selectively suppressed hdac5 expression in ra fls, which was sufficient and required for optimal ifnb, cxcl9, cxcl10 and cxcl11 induction by il-1, associated with increased nuclear accumulation of the transcription factor, interferon regulatory factor 1(irf1).","inflammatory cytokines suppress ra fls hdac5 expression, promoting nuclear localisation of irf1 and transcription of a subset of type i interferon response genes. our results identify hdac5 as a novel inflammatory mediator in ra, and suggest that strategies rescuing hdac5 expression in vivo, or the development of hdac inhibitors not affecting hdac5 activity, may have therapeutic applications in ra treatment.",General
do evaluation of the implant sites of palatal implants using cone beam computed tomography ?,"to investigate the vertical bone height and the bone density of the palate for implants placement using cone beam ct(cbct) and to provide references to the safe and stable placement of palatal implants. three-dimensional reformatting images were reconstructed with the selected cbct scanning data of 34 patients aged 18 to 35 yeras, by means of ez implant software. the vertical bone height was measured at 20 interesting sites of palate. bone density was measured at 10 sites that could support 3.0 mm long implants. the data of the vertical bone height and bone density were analyzed by k-means cluster analysis. according to the cluster analysis results, the 10 sites were classified into 3 clusters. there were statistical differences among these three clusters in bone height and bone density (p 0.05). the lsd result showed that the greatest mean value of vertical bone height was obtained in cluster 2, followed by cluster 1 and cluster 3; the highest bone density was founded in cluster 3, followed by cluster 1 and cluster 2.",evaluation of the sites for palatal implant placement with cone beam ct would be helpful in safe and stable implantation.,Treatment
"is standard diagnostic laparoscopy superior to notes approaches : results of a blinded , randomized controlled porcine study?","the use of transluminal endoscopic access via the stomach or colon for flexible diagnostic peritoneoscopy has been proposed, although the diagnostic value of the technique has not yet been fully clarified. in this animal trial, the two main natural orifice transluminal endoscopic surgery (notes) approaches - transgastric (tg) and transcolonic (tc) - were compared with standard transabdominal access using both rigid (tar) and flexible instruments (taf) for diagnostic laparoscopy. a total of 48 peritoneoscopies were performed using two randomly assigned approaches in 24 anesthetized pigs. the ability of the examinations to detect 576 electrocautery markings simulating intraperitoneal metastases, to achieve complete organ visualization, and to simulate organ biopsies was analyzed. sensitivities for the detection of lesions were 78.5 , 59.7 , 48.6 , and 38.9 for tar, taf, tc, and tg, respectively; standard laparoscopy was superior to all other approaches (p 0.01). among the notes approaches, tc was superior for examining the upper abdomen (p 0.03). complete organ visualization was better with the transabdominal approach (visual analogue scale tar 7.15, taf 6.71) than with the notes access routes (tc 5.07, tg 4.35); standard rigid laparoscopy was superior to both notes approaches (p 0.01). organ biopsy simulation was possible in 87 , 85 , 72 , and 65 of cases with tar, taf, tc, and tg, respectively. standard rigid laparoscopy was again superior to both notes approaches (tar vs. tc, p 0.03; tar vs. tg, p 0.01).","in this experimental trial, rigid standard laparoscopy provided better organ visualization, better lesion detection, and better biopsy capability than the transgastric and transcolonic notes approaches. in its current form, notes appears to be unsuitable for diagnostic laparoscopy.",Diagnosis
is sucrose non-fermenting related kinase enzyme mediated rho-associated kinase signaling responsible for cardiac function?,"-cardiac metabolism is critical for the functioning of the heart, and disturbance in this homeostasis is likely to influence cardiac disorders or cardiomyopathy. our lab has previously shown that sucrose non-fermenting related kinase (snrk) enzyme, which belongs to the amp-activated kinase (ampk) family, was essential for cardiac metabolism in mammals. snrk global homozygous knockout (ko) mice die at postnatal day 0, and conditional deletion of snrk in cardiomyocytes (snrk cmcko) leads to cardiac failure, and death by 8-10 months. -we performed additional cardiac functional studies using echocardiography (echo), and identified further cardiac functional deficits in snrk cmcko mice. nmr-based metabolomics analysis identified key metabolic pathway deficits in snrk knockdown cardiomyocytes (cms) in vitro specifically, metabolites involved in lipid metabolism and oxidative phosphorylation are altered and perturbations in these pathways can result in cardiac function deficits and heart failure. a phosphopeptide-based proteomic screen identified rho-associated kinase (rock) as a putative substrate for snrk and mass spec-based fragment analysis confirmed key amino acid residues on rock that are phosphorylated by snrk. western blot analysis on heart lysates from snrk cmcko adult mice and snrk knockdown cms showed increased rock activity. in addition, in vivo inhibition of rock partially rescued the in vivo snrk cmcko cardiac function deficits.","-collectively, our data suggests that snrk in cms is responsible for maintaining cardiac metabolic homeostasis, which is mediated in part by rock and alteration of this homeostasis influences cardiac function in the adult heart.",Diagnosis
does n-acetyl-cysteine exhibit potent anti-mycobacterial activity in addition to its known anti-oxidative functions?,"mycobacterium tuberculosis infection is thought to induce oxidative stress. n-acetyl-cysteine (nac) is widely used in patients with chronic pulmonary diseases including tuberculosis due to its mucolytic and anti-oxidant activities. here, we tested whether nac exerts a direct antibiotic activity against mycobacteria. oxidative stress status in plasma was compared between pulmonary tb (ptb) patients and those with latent m. tuberculosis infection (ltbi) or healthy uninfected individuals. lipid peroxidation, dna oxidation and cell death, as well as accumulation of reactive oxygen species (ros) were measured in cultures of primary human monocyte-derived macrophages infected with m. tuberculosis and treated or not with nac. m. tuberculosis, m. avium and m. bovis bcg cultures were also exposed to different doses of nac with or without medium ph adjustment to control for acidity. the anti-mycobacterial effect of nac was assessed in m. tuberculosis infected human thp-1 cells and bone marrow-derived macrophages from mice lacking a fully functional nadph oxidase system. the capacity of nac to control m. tuberculosis infection was further tested in vivo in a mouse (c57bl/6) model. ptb patients exhibited elevated levels of oxidation products and a reduction of anti-oxidants compared with ltbi cases or uninfected controls. nac treatment in m. tuberculosis-infected human macrophages resulted in a decrease of oxidative stress and cell death evoked by mycobacteria. importantly, we observed a dose-dependent reduction in metabolic activity and in vitro growth of nac treated m. tuberculosis, m. avium and m. bovis bcg. furthermore, anti-mycobacterial activity in infected macrophages was shown to be independent of the effects of nac on the host nadph oxidase system in vitro. short-term nac treatment of m. tuberculosis infected mice in vivo resulted in a significant reduction of mycobacterial loads in the lungs.",nac exhibits potent anti-mycobacterial effects and may limit m. tuberculosis infection and disease both through suppression of the host oxidative response and through direct antimicrobial activity.,Medication
does lipopolysaccharide promote lipid accumulation in human adventitial fibroblasts via tlr4-nf-b pathway?,"atherosclerosis is a chronic degenerative disease of the arteries and is thought to be one of the most common causes of death globally. in recent years, the functions of adventitial fibroblasts in the development of atherosclerosis and tissue repair have gained increased interests. lps can increase the morbidity and mortality of atherosclerosis-associated cardiovascular disease. although lps increases neointimal via tlr4 activation has been reported, how lps augments atherogenesis through acting on adventitial fibroblasts is still unknown. here we explored lipid deposition within adventitial fibroblasts mediated by lipopolysaccharide (lps) to imitate inflammatory conditions. in our study, lps enhanced lipid deposition by the up-regulated expression of adipose differentiation-related protein (adrp) as the silencing of adrp abrogated lipid deposition in lps-activated adventitial fibroblasts. in addition, pre-treatment with anti-toll-like receptor 4 (tlr4) antibody diminished the lps-induced lipid deposition and adrp expression. moreover, lps induced translocation of nuclear factor-b (nf-b), which could markedly up-regulate lipid deposition as pre-treatment with the nf-b inhibitor, pdtc, significantly reduced lipid droplets. in addition, the lowering lipid accumulation was accompanied with the decreased adrp expression. furthermore, lps-induced adventitial fibroblasts secreted more monocyte chemoattractant protein (mcp-1), compared with transforming growth factor-1 (tgf-1).","taken together, these results suggest that lps promotes lipid accumulation via the up-regulation of adrp expression through tlr4 activated downstream of nf-b in adventitial fibroblasts. increased levels of mcp-1 released from lps-activated adventitial fibroblasts and lipid accumulation may accelerate monocytes recruitment and lipid-laden macrophage foam cells formation. here, our study provides a new explanation as to how bacterial infection contributes to the pathological process of atherosclerosis.",Medication
is polymorphism of nos2a promoter -969 ( g c ) associated with portal hypertension of liver cirrhosis ?,"to determine whether polymorphism of nos2a promoter -969gc is associated with the portal hypertension of liver cirrhosis. a case control study covering 106 patients with liver cirrhosis due to hepatitis b virus(hbv) in comparison with 108 controls was performed using pcr-restriction fragment length polymorphism. the nos2a mrna and protein expression in liver cirrhosis tissues were detected by reverse transcription-pcr and western blot. the recombinant plasmids of nos2a promoter luciferase reporter gene were constructed and were transfected transiently into hepg2 cells for analyzing the functional activity of the promoter. the frequencies of the c allele and gc genotype at nos2a promoter -969gc were significantly higher in portal hypertension group (16.9, 33.8) than in control group(8.8, 17.6)(p0.05). the expressions of nos2a mrna and protein in liver cirrhosis tissues were more increased in c allele carriers with liver cirrhosis than in g allele carriers with liver cirrhosis, which led to higher functional activity of the promoter. multivariate logistic regression analysis revealed that nos2a polymorphism at promoter -969gc is an independent novel risk factor for the occurrence of portal hypertension in patients with liver cirrhosis.","the polymorphism of nos2a promoter -969(gc) is associated with portal hypertension of liver cirrhosis, which results in functional activity increase of nos2a promoter and is an independent risk factor for portal hypertension.",Prevention
"is the expression of p16 ( ink4a ) , the product of a tumor suppressor gene for melanoma , upregulated in human melanocytes by uvb irradiation?","the genetic locus cdkn2a has been linked to familial melanoma, and mutations or deletions in its coding sequence are seen in some cases of sporadic and familial melanomas. the protein encoded by cdkn2a, p16(ink4a), functions as a negative regulator of cell cycle progression and as a tumor suppressor, but the regulatory mechanisms involved in controlling its expression remain poorly defined. this study tested the hypothesis that uvb irradiation, which transiently inhibits the growth of human melanocytes, is one of the regulators of p16(ink4a) expression. cultured human melanocytes were irradiated with uvb over a sublethal dosage range, and p16(ink4a) protein and mrna levels were quantified at varying times thereafter by quantitative immunostaining and by western and northern blotting. levels of p16(ink4a) protein in melanocytes increased significantly after sublethal uvb irradiation as compared with nonirradiated cells. northern analysis indicated that p16(ink4a) messenger rna coordinately increased in a dose-dependent manner more than 2-fold in irradiated cells at the tested doses.","uvb irradiation transcriptionally activates the expression of p16(ink4a) in cultured human melanocytes. therefore the growth arrest that occurs with irradiation of melanocytes could be mediated, in part, by upregulation of p16(ink4a). this transient arrest may allow repair of uvb-induced dna damage before cell division. conversely, hereditary or acquired defects in cdk4a that give rise to functional insufficiency of p16(ink4a) could permit the premature propagation of melanocytes harboring potentially carcinogenic dna damage.",Medication
does blockade of cxcl12/cxcr4 signaling inhibit intrahepatic cholangiocarcinoma progression and metastasis via inactivation of canonical wnt pathway?,"intrahepatic cholangiocarcinoma (ihcc) is the second most frequent primary malignant liver tumor following hepatocellular carcinoma. it is a highly fatal disease and has few therapeutics. the cxc chemokine ligand-12 (cxcl12)/cxc chemokine receptor type 4 (cxcr4) axis has been shown to be involved in tumorgenesis, proliferation, and angiogenesis in a variety of cancers including ihcc. however, its prognostic significance in ihcc is unclear. the purpose of this study was to examine the functional role of cxcr4 in the progression and metastasis of ihcc and explore the underlying mechanism. the cxcr4 expression, overall survival, and the clinical characteristics including age, sex, differentiation degree, tumor size, vascular invasion, lymph node metastasis, tnm stage, and t stage were analyzed for 122 ihcc patients. short hairpin rna (shrna) against cxcr4 was used to disrupt the cxcl12/cxcr4 signal transduction pathways in ihcc cell lines. in vitro assays, including cck-8 assay, flow cytometry, and colony formation assay, and in vivo tumor formation assay were utilized to detect the cell phenotype of cxcr4 knockdown cells. transwell and wound healing assays were used to examine the ihcc cell invasion and migration ability. the wnt pathway was assessed by western blot and -catenin/tcf transcription reporter assay. we demonstrated that cxcr4 expression was closely correlated with ihcc progression and metastasis characteristics. the overall survival of patients with high cxcr4 expression was significantly lower than that of patients with low cxcr4 expression. furthermore, we showed that the abrogation of cxcr4 had significantly negative influence on the ihcc cell phenotype, including in vitro cell proliferation, cell cycle, colony formation, cell invasion, and in vivo tumorigenicity. in addition, cxcr4 knockdown downregulated wnt target genes and mesenchymal markers such as vimentin and slug.","in conclusion, our result shows that high cxcr4 expression is associated with ihcc progression and metastasis via the canonical wnt pathway, suggesting that cxcr4 may serve as a promising therapeutic target for ihcc.",Diagnosis
do evaluation of the so2 and nox offset ratio method to account for secondary pm2.5 formation?,"the u.s. environmental protection agency (epa), state and local agencies have focused their efforts in assessing secondary fine particulate matter (aerodynamic diameter or 2.5 microm; pm2.5) formation in prevention of significant deterioration (psd) air dispersion modeling. the national association of clean air agencies (nacaa) developed a method to account for secondary pm2.5 formation by using sulfur dioxide (so2) and nitrogen oxides (nox) offset ratios. these ratios are used to estimate the secondary formation of sulfate and nitrate pm2.5. these ratios were first introduced by the epa for nonattainment areas in the implementation of the new source review (nsr) program for particulate matter less than 2.5 micrometers (pm2.5), 73 fr 28321, to offset emission increases of direct pm2.5 emissions with reductions of pm2.5 precursors and vice versa. some regulatory agencies such as the minnesota pollution control agency (mpca) have developed area-specific offset ratios for so2 and nox based on comprehensive air quality model with extensions (camx) evaluations for air dispersion modeling analyses. the current study evaluates the effect on american meteorological society/environmental protection agency regulatory model (aermod) predicted concentrations from the use of epa and mpca developed ratios. the study assesses the effect of these ratios on an electric generating utility (egu), taconite mine, food processing plant, and a pulp and paper mill. the inputs used for these four scenarios are based on common stack parameters and emissions based on available data. the effect of background concentrations also evaluates these scenarios by presenting results based on uniform annual pm2.5 background values. this evaluation study helps assess the viability of the offset ratio method developed by nacaa in estimating primary and secondary pm2.5 concentrations. an alternative tier 2 approach to combine modeled and monitored concentrations is also presented.","on january 4, 2012, the epa committed to engage in rulemaking to evaluate updates to the guideline on air quality models (appendix w of 40 cfr 51) and, as appropriate, incorporate new analytical techniques or models for secondary pm2.5. as a result, the national association of clean air agencies (nacaa) developed a screening method involving offset ratios to account for secondary pm2.5 formation. the use of this method is promising to evaluate total (direct and indirect) pm2.5 impacts for permitting purposes. therefore, the evaluation of this method is important to determine its viability for widespread use.",Prevention
is medication use a better predictor of length of hospital stay in total hip arthroplasty than the american society of anesthetists ( asa ) score?,"length of hospital stay (los) greatly influences costs of total hip arthroplasty (tha). los is, among others, dependent on patient comorbidity. american society of anesthetists (asa) scores are traditionally used as comorbidity measure, but simple medication-based measures may suffice. therefore, the objective of the study is to determine if medication-based measures (count of medication and the medication-based index chronic disease score cds) have a surplus value compared to a diagnosis-based measure for comorbidity (asa score) to predict los in tha. a retrospective cohort study. tha patients from 3 hospitals were included for 2009-2013, and demographic data, comorbidity (asa score), and medication use (count of medication and cds) were collected. a binomial regression model was used to compare the predictive ability of the medication-based and diagnosis-based measures. a total of 2,282 tha patients were included. number of medications proved a statistical significant predictor of los. los increased 6 (incidence rate ratios: 10.06 confidence interval: 1.03-1.09) with each medication. neither the cds nor the asa score had a statistically significant relation to los.","the medication-based measure count of medication is a better predictor for los in tha than the cds and asa score. this simple measure also appears to have more clinical relevance, as it has a higher range in scores than diagnosis-based indexes and is easily applicable.",Medication
does ultrasonic tissue characterization predict myocardial viability in early stage of reperfused acute myocardial infarction?,"the aim of the present study was to characterize temporal changes in cyclic variation of ultrasonic integrated backscatter (ibs), which reflects intrinsic contractile performance, in patients with reperfused acute myocardial infarction (ami) and to elucidate the clinical value of tissue characterization in predicting myocardial viability. we recorded short-axis ibs images before and 3, 7, and 21 days after reperfusion in 26 patients with ami and obtained the cyclic variation of ibs in the normal and infarct zones. when cyclic variation showed synchrony and asynchrony, we expressed its magnitude as positive and negative values, respectively, called the phase-corrected magnitude. we also measured average wall motion score (dyskinesis, 4; normal, 0) of the infarct segments. the phase-corrected magnitude was lower in the infarct zone than in the normal zone before reperfusion (0.3/-2.5 versus 5.2/-1.7 db, p or 2.0 db at day 3 showed significantly lower wall motion score at day 21 than did the other patients (1.7/-0.6 versus 2.4/-0.5, p.01).","in patients with ami, cyclic variation of ibs is blunted during ischemia but recovers much faster after reperfusion than the improvement in wall motion. the greater phase-corrected magnitude at day 3 may be a predictor of better functional improvement.",General
does occurrence and correlate of overweight and obesity among island puerto rican youth?,"objective and main outcome measures: this article provides 2005-2008 population-based prevalence data on obesity and overweight among youth residing in puerto rico. data for this report are from the asthma, depression, and anxiety in puerto rican youth (ada) study. measures included height and weight level data on youth in puerto rico aged 10 to 19 years with and without asthma as well as body mass index data on their caregivers. a total of 436 youth-caregiver dyads were selected and weighted to represent the general population of youth in puerto rico using 2008 us census data. household surveys demonstrated that 40 of youth aged 10 to 19 were overweight or obese. twenty-five percent met moderate-to-vigorous-intensity physical activity guidelines, however, physical activity was not associated with overweight or obesity in this sample. in multivariate analyses, females were 50 less likely than males to be overweight or obese. older youth were 73 less likely to be overweight or obese than younger youth. youth whose parents were obese were more than two times more likely to be overweight or obese than those whose parents were at a desirable weight.",youth in puerto rico have higher rates of overweight and obesity and lower compliance to moderate-to-vigorous-intensity physical activity guidelines than rates reported for youth on the mainland. more population-based research is needed to understand the epidemiology of obesity and overweight among island puerto rican youth and the contribution of physical activity to the phenomenon.,Prevention
does specific telomere dysfunction induced by grn163l increase radiation sensitivity in breast cancer cells?,"telomerase is expressed in 80-90 of tumor cells, but is absent in most somatic cells. the absence of telomerase activity results in progressive telomere shortening, leading to cellular senescence or death through deoxyribonucleic acid (dna) damage signals. in addition, a role for telomerase in dna damage repair has also been suggested. a specific telomerase inhibitor, grn163l that is complementary to the template region of the telomerase ribonucleic acid component (htr). we hypothesized that exposure to grn163l, either through immediate inhibition of telomerase activity or through eventual telomere shortening and dysfunction, may enhance radiation sensitivity. our goal was to test whether the treatment with grn163l enhances sensitivity to irradiation (ir) in mda-mb-231 breast cancer cells. the mda-mb-231 breast cancer cells were treated with or without grn163l for 2-42 days. inhibition of telomerase activity and shortening of telomeres were confirmed. cells were then irradiated and clonogenic assays were performed to show cell survival differences. in vivo studies using mda-mb-231 xenografts were performed to corroborate the in vitro results. we show that cells with shortened telomeres due to grn163l enhance the effect on ir reducing survival by an additional 30 (p 0.01). these results are confirmed in vivo, with a significant decrease in tumor growth in mice exposed to grn163l.",we found that grn163l is a promising adjuvant treatment in combination with radiation therapy that may improve the therapeutic index by enhancing the radiation sensitivity. these studies prompt further investigation as to whether this combination can be applied to other cancers and the clinic.,Treatment
does tumor plasma flow determined by dynamic contrast-enhanced mri predict response to induction chemotherapy in head and neck cancer?,"non-response to induction chemotherapy (ic) occurs in 30 of head and neck squamous cell carcinoma (hnscc) and has been predicted by tumor plasma flow (fp) derived by perfusion computed tomography. the present study was designed to test whether baseline tumor fp determined by dynamic contrast-enhanced magnetic resonance imaging (dce-mri) would predict ic response. a prospective open study powered to test the relationship between tumor fp and response to ic (docetaxel, cisplatin, 5-fluorouracil) enrolled 50 patients with stage iv hnscc. response after two ic cycles was measured by mri using response evaluation criteria in solid tumors in 37 patients. tumor fp (primary end point) and multiple parameters in tumors and lymph nodes (secondary end points) were generated at baseline. differences in baseline dce-mri parameters according to ic response were assessed by the mann-whitney u test, and predictive value by receiver operating characteristic (roc) analysis. median baseline tumor fp was 53.2ml/100ml/min in 25 responders and 23.9 in 12 non-responders (u 82; p0.027; area under roc curve (auc) 0.73). median baseline fp in lymph nodes was 25.8ml/100ml/min for 37 nodes in 25 responders and 17.1 for 15 nodes in 12 non-responders (u 186, p0.066; auc 0.67). frequency of ic response in 37 patients was 68 overall, 83 for tumor fp above the median (40.6ml/100ml/min) and 45 below the median. other dce-mri parameters were not associated with ic response.",pre-treatment tumor fp determined by dce-mri predicts ic response in hnscc.,Medication
does neural response telemetry result with the nucleus 24 contour in a perimodiolar position?,"the purpose of the study was to analyze changes in neural response telemetry using the cochlear nucleus 24 contour before and after stylet removal in a human model. prospective study. tertiary referral center. twelve patients (23-72 years old) undergoing cochlear implantation, using the nucleus 24 contour implant, secondary to congenital and age-related hearing loss. cochlear implantation with cochlear nucleus 24 contour implant. neural response telemetry thresholds were recorded initially with the stylet in and then with the stylet out during the implant procedure. stimulus levels to obtain neural response telemetry threshold after stylet removal were statistically lower after the stylet was removed.","the nucleus 24 contour achieves a perimodiolar position once the stylet is removed, and this leads to reduction in the current required to elicit a threshold neural response telemetry response.",Treatment
does pin size influence sagittal alignment in percutaneously pinned pediatric supracondylar humerus fractures?,"no study examining pin constructs has adequately addressed pin size and its role in fracture fixation. our goal was to review our experience with wilkins-modified gartland type-iii pediatric supracondylar humerus fractures treated with closed reduction and percutaneous pinning to evaluate the effects of pin size within 2 different pin constructs on maintenance of reduction and on the risk of surgical complications. we retrospectively reviewed the medical records of pediatric patients with wilkins-modified gartland type-iii supracondylar humerus fractures that were closed reduced and percutaneously pinned at our institution from march 1999 through december 2008. we grouped those 159 patients by fracture stabilization method (lateral-entry-pin or crossed-pin constructs), by pin size ratio (ie, ratio of pin diameter to the humeral midshaft cortical thickness: small 0.9; large 0.9), and then by 4 combinations of pin construct and pin size ratio. for each group, we evaluated radiographs for immediate postoperative reduction (coronal and sagittal alignment), maintenance of reduction at last follow-up, and the number of surgical complications. we used the student t test, test, mann-whitney u test, and wilcoxon signed rank test to examine for significance, which was set at p0.05. although we found no significant differences between the groups immediately after surgery, final follow-up sagittal alignment was significantly more likely to be maintained in the large pin size ratio group than in the small pin size ratio group. for 2 types of surgical complications, infection and nerve palsy, we found no statistically significant differences in these complications between the pin construct or pin size ratio groups.",large pin sizes improved radiographic sagittal alignment at final follow-up without an increased rate of infection or ulnar nerve palsy.,Treatment
do swedish fathers contemplate the difficulties they face in parenthood?,"the aim was to explore what concerns swedish fathers had about parenting difficulties at two months after the birth of their baby. self-report questionnaires were used and data were analyzed with mixed methods. thirty percent of the 827 fathers reported concerns about the difficulties of parenthood. the theme 'managing the demands of being a father' emerged and was based on concerns about how to raise the baby, having enough money, health issues, lack of time and finding balance in the new family pattern. financial worries, feeling less positive about expecting a baby, and self-reported poor emotional health were related to fathers who perceived parenthood as difficult.","experienced fathers as well as new fathers expressed similar concerns about parenthood. preparation classes for reassurance and skills coaching about child raising may provide important support for fathers. this is especially important for fathers who may have poor emotional health or who may not be feeling positive about expecting a baby. policy-makers and health care providers should recognize that offering support for all fathers benefits not only men, but also their children, and their partners and can help encourage egalitarian practices at home and work.",General
is intrauterine neutrophil activation associated with pulmonary haemorrhage in preterm infants?,"clinical and experimental studies showing lung damage associated with biologically active neutrophil derivatives suggests the possibility that intrauterine neutrophil activation may predispose to the development of pulmonary haemorrhage in extremely low birthweight infants early after birth. to assess neutrophil functional activity in cord blood from extremely low birthweight infants who subsequently developed severe pulmonary haemorrhage. neutrophil functional activity was evaluated in the cord blood of preterm neonates (gestational age 28 weeks and weight 800 g) who developed pulmonary haemorrhage (n 6) and in controls who did not (n 6). infants with congenital abnormalities and noteworthy maternal complications such as diabetes, pre-eclampsia, haemorrhagic disorders, and connective tissue disease were excluded. neutrophils isolated from cord blood immediately after delivery were tested to evaluate neutrophil chemotaxis, random motility, and chemiluminescence. standard methodology was used. chemotaxis and chemiluminescence of neutrophils from cord blood of infants with pulmonary haemorrhage was higher than in the controls (34.8 (2.0) v 28.6 (0.8) microm, p0.001, and 95.8 (8.5) v 73.2 (3.6) cpm x10(3), p0.001 respectively). random motility of cord blood neutrophils was comparable in the two groups (28.6 (1.2) v 25.3 (1.2) microm, p0.09).",intrauterine induction of chemotactic activity and metabolic oxygenation of neutrophils may predispose to the development of pulmonary haemorrhage in extremely low birthweight infants with respiratory distress early after birth.,General
does mir-101 inhibit the g1-to-s phase transition of cervical cancer cells by targeting fos?,"the chief objective of this study was to identify the mirnas targeting fos, a well-recognized proto-oncogene that is commonly overexpressed in cervical cancer, and its biological significance on the cellular behaviors of hela, a cervical cancer cell. we initially analyzed the 3'untranslated region (3'utr) of fos and screened the potential mirnas targeting fos using 3 bioinformatical web sites. luciferase reporter assay, real-time polymerase chain reaction, and western blotting were used to validate the binding of chosen mirna (mir-101) on the 3'utr of fos and the downstream regulation on its mrna and protein levels. furthermore, flow cytometry along with the fos rescue strategy was applied to analyze the modulation of cell cycle of hela cells by mir-101. among these predicted candidate mirnas, mir-101 was the mirnas preferred by all the 3 used web sites. the results of luciferase reporter assay, real-time polymerase chain reaction, and western blotting demonstrated that mir-101 directly targeted on the 3'utr of fos and down-regulated the expression of fos at mrna and protein levels. furthermore, cell cycle analysis showed that mir-101 arrests g1-to-s phase transition of hela cells, at least partially by targeting fos.","we concluded that by targeting the proto-oncogene fos, mir-101 is involved in g1-to-s phase transition in cervical cancer cells in vitro and might provide a new approach for the pharmacological interference node in cervical cancer treatment.",Diagnosis
does mometasone furoate nasal spray reduce the ocular symptoms of seasonal allergic rhinitis?,"mometasone furoate nasal spray (mfns), a potent intranasal corticosteroid with proved efficacy in relieving nasal allergic rhinitis symptoms, has demonstrated effectiveness in improving ocular symptoms associated with seasonal allergic rhinitis (sar) in retrospective analyses. we sought to evaluate prospectively the efficacy of mfns in reducing total ocular symptom scores (tosss) and individual ocular symptoms in subjects with sar. subjects 12 years or older (n 429) with moderate-to-severe baseline symptoms were randomized to mfns, 200 microg once daily, or placebo in this 15-day, double-blind, parallel-group study. subjects evaluated morning instantaneous tosss and daily reflective tosss, total nasal symptom scores (tnsss; both instantaneous tnsss and reflective tnsss, respectively), and individual ocular and nasal symptoms. mean changes from baseline averaged over days 2 to 15 (instantaneous) and days 1 to 15 (reflective) were calculated. quality of life was assessed by using the rhinoconjunctivitis quality of life questionnaire. mfns treatment yielded significant reductions from baseline versus placebo in instantaneous tosss (-0.34, p .026, coprimary end point), instantaneous tnsss (-0.88, p .001, coprimary end point), reflective tosss (-0.44, p .005), and reflective tnsss (-1.06, p .001). significant decreases in all individual reflective ocular symptoms and instantaneous eye itching/burning and eye watering/tearing were observed for mfns versus placebo (p .05). numeric improvements in instantaneous eye redness were seen but did not reach statistical significance. improvements in rhinoconjunctivitis quality of life questionnaire total scores and individual symptom domains were achieved with mfns treatment versus placebo (p .001). mfns was well tolerated.",this prospective study demonstrates that mfns significantly reduces ocular symptoms in subjects with sar.,Symptoms
is down-regulation of the microrna processing enzyme dicer a prognostic factor in human colorectal cancer?,"microrna deregulation is a key feature of cancer; however, the molecular mechanisms underlying deregulation are unknown. dicer is a central enzyme in microrna processing essential for production of mature micrornas which, in turn, regulate gene expression post-transcription. the aim was to investigate whether dicer expression in colorectal cancer correlates with conventional clinicopathological parameters and patient survival. immunohistochemical staining for dicer was performed on tissue microarrays of 331 samples from patients with primary colorectal carcinoma. a subset (19.6) of colorectal carcinomas was negative for dicer. dicer protein expression was associated significantly and inversely with disease (who) stage (p 0.029), tumour grade (p 0.001), tumour stage (p 0.022) and nodal metastasis (p 0.004). negative expression of dicer correlated significantly with shortened overall survival (p 0.007) and was independent of other prognostic factors in multivariate analysis (cox regression: p 0.035, hazard ratio1.6; 95 confidence interval 1.034-2.513). additionally, in univariate analysis, an association of dicer expression with survival was observed in subsets of patients without metastasis (p 0.026), older patients (p 0.005) and patients with advanced tumour stage (p 0.022).",dicer deregulation is linked significantly to adverse disease state and decreased overall survival in colorectal cancer. our data suggest that reduced dicer expression might contribute to tumour progression in colorectal cancer.,Diagnosis
is the imbalanced mixed lymphocyte reaction between maternal and fetal lymphocytes as well as between the lymphocytes of adult children and their parents mediated by activated cd8 t cells?,"the mixed lymphocyte reaction (mlr) between maternal and fetal lymphocytes as well as between adult children and their parents is imbalanced in bidirectional mixed lymphocyte cultures. the present investigation was aimed at examining which type of t cells has primary responsibility for this phenomenon. two-way mixed lymphocyte cultures between lymphocytes of five female and five male adults and five male and five female newborns against lymphocytes of their parents were performed. unrelated adults served as the controls. before and after 72 hr incubation the mixed leukocytes cultures (mlcs) were sorted by flow cytometry according to the surface markers cd4 and cd69 or cd8 and cd69. the single cell populations within the four resulting fractions were discriminated by fluoresence in situ hybridization (fish) using xy-dna probes. before incubation the share of cd8() cd69() cells in the mlcs between mothers and their newborn infants was significantly shifted toward the newborn cells (p 0.01). after 72 hr incubation the cd8() cd69() ratio in the mlcs between mother and newborn cells and between adult children (male as well female) and their parents showed a significant shift of the cd8() cd69() cells toward the children's direction. all other mlcs showed a balanced cell population for all investigated cell types, both before and after incubation.",the imbalanced mlr between maternal and fetal lymphocytes and lymphocytes of adult children against their parents is mediated by a specific imbalance of the activation of cd8() but not of cd4() t cells.,Diagnosis
does mri dwi/adc signal predict shrinkage of lumbar disc herniation after o2-o3 discolysis?,"evaluate the discal morpho-structural changes as a predictive sign in the clinical outcome after ozone therapy in lumbar disc herniation using the t2-shine through effect in diffusion-weighted imaging (dwi). one hundred and fifty-four patients suffering from lumbosciatica (89 men and 65 women; age range, 23-62 years) were included, previous mr study performed with fse-t2 and t2-fat, se-t1 and dwi sequences, and were randomly assigned to two groups. seventy-seven patients (control group) underwent conservative treatment with intraforaminal injection of steroid and anaesthetic. the remaining 77 patients (study group) underwent the same treatment with the addition of oxygen-ozone (o2-o3). during the following six months, a mri follow-up with the same sequences was performed. an intervertebral disc volumetric analysis (idva), dwi signal score and post treatment clinical outcome evaluation were performed for an assessment of hernia reduction. test, student's t test and analysis of covariance were used for comparison of variables. in the study group, 58 of 77 patients had a successful outcome (responders). in the responders group, dwi t2-shine through effect was present during mri follow-up and in particular in 53 of 77 patients in six months of follow-up (p 0.05). moreover, in the same group a statistically significant disc shrinkage was shown by idva in sixth months of follow-up (p 0.05).",t2-shine through effect in dwi is present before morphological disc reduction and moreover could be considered as a predictive sign of response to oxygen-ozone treatment.,Diagnosis
does new testing approach in hla genotyping help overcome barriers in effective clinical practice?,"severe and potentially fatal hypersensitivity reactions to drugs, particularly antiepileptics, are clinically unpredictable. recent evidence has revealed a strong and specific association between the implicated drug, the type of adverse reaction, and the particular hla genotype. an urgent need exists for rapid diagnosis of hla status to guide drug prescription; however, traditional hla genotyping has a long turnaround time, is expensive, and is available only in specialized centers. we tested the feasibility of the loop-mediated isothermal amplification (lamp)-based approach to detect a specific hla genotype. as an example, we used b1502, an hla allele strongly associated with carbamazepine-induced stevens-johnson syndrome/toxic epidermal necrolysis, and validated the assay's application as a simple, accurate, rapid, and low-cost blood test for use in both clinical and bedside settings. we evaluated b1502 status with the new lamp method and compared the results with those obtained by sequence-based typing (sbt) (n 250) and by sequence-specific primer pcr (ssp-pcr) (n 200) for 450 samples of dna (n 50) and blood (n 400) from a hematology laboratory. lamp results showed 100 concordance with both sbt and ssp-pcr results, confirming that lamp detection of a specific hla genotype (b1502 in this case) is an accurate method. all results were available within 1 h.","our study confirmed that the new lamp method for detecting a specific hla genotype is simple, inexpensive, accurate, and rapid, and may be of help in overcoming barriers in effective clinical practice.",Medication
is trocar site recurrence unlikely to result from aerosolization of tumor cells?,"this study was undertaken to investigate the ability of a high-pressure co2 environment to aerosolize tumor cells in both in vitro and in vivo models. (an aerosol is defined as a stable gaseous suspension of insoluble particles). also, this study was designed to determine if rapid desufflation is capable of transporting fluid laden with tumor cells. the four in vitro aerosol experiments were performed in an 18.9-1 plastic vessel fitted with two 7-mm ports and a compliant latex balloon affixed to the top. after co2 insufflation, the vessel was desufflated through a sterile soluset containing 25 ml of culture media that was subsequently emptied into a culture dish, incubated for two weeks, and periodically assessed for growth. at the bottom of the vessel, one of the following was placed: study 1 and 2, a suspension of b16 melanoma or colon 26 tumor cells in liquid culture media; study 3, colon 26 cells in saline solution; study 4, several pieces of solid colon 26 tumor. in studies 1 to 3, cell preparations were subjected to the following high-pressure co2 conditions (pneumo): 1) static pneumo of 15 and 30 mmhg (10 minute dwell); 2) a continuous flow (cf) of co2 (1o l) while maintaining a pressure of 15 or 30 mmhg in the vessel. in study 4, only the 30 mmhg static and cf conditions were tested. between 6 and 12 determinations were performed for each condition and cell preparation. in vivo aerosol experiments consisted of spraque dawley rats that received intraperitoneal injections of 10-5 b16 cells in 0.1 ml of liquid media. two laparoscopic ports were placed in the abdomen, one each for insufflation and desufflation. study groups were: 1, static co2 pneumo of 15 mmhg; 2 and 3, continuous co2 flow (10 l) at a stable pneumo pressure of 5 and 10 mmhg. desufflation was performed via the same collecting device and handled in an identical manner to the in vitro experiments described above. the in vitro balloon experiment was designed to investigate the ability of desufflation to transport fluid-containing tumor cells; latex balloon model was used. to prevent complete loss of volume on desufflation, a wire coil was placed inside the balloon. twenty ml of media containing 20 x 10(-6) b16 cells was placed in the bottom of the balloon. the balloon was insufflated with 1 to 2 l of gas. there were three study groups that differed in the degree to which the cell suspension was agitated before desufflation. study conditions were as follows: 1) no agitation; 2) moderate agitation to coat the lower walls and coil; 3) maximum agitation to coat the entire balloon. to verify the viability of tumor cells, at the end of each in vitro and in vivo study, a sample of tumor cells or peritoneal washing was incubated in sterile media. these samples served as positive controls. in vitro aerosol studies consisted of the following. at the end of two weeks of incubation, no tumor growth was noted in any of the 124 test dishes. the 14 control samples all demonstrated tumor growth. in vivo aerosol studies consisted of the following. zero of 18 experimental dishes grew tumor. all three peritoneal washing samples demonstrated growth. in vitro balloon studies consisted of the following. zero of 12 test dishes in groups 1 and 2 demonstrated growth, whereas five of six dishes did so in group 3 (maximally agitated before desufflation). again, positive controls all grew tumor cells.","we were unable to demonstrate aerosol formation in any of the in vitro and in vivo studies performed. in the balloon experiment, desufflation-related transport of tumor cells was demonstrated but only when the entire balloon surface was coated with the tumor cell suspension before desufflation.",Medication
do serum matrix metalloproteinase-3 and fibrin degradation product levels correlate with clinical disease activity in rheumatoid arthritis?,"plasmin and matrix metalloproteinase-3 (mmp-3) have been linked to articular destruction in rheumatoid arthritis (ra). we compared circulating levels of plasmin-mediated fibrin degradation product (fdp d-dimer) and mmp-3 with traditional parameters of disease activity in ra to determine their clinical utility. serum levels of mmp-3 and d-dimer were determined by enzyme-linked immunoassays in 60 patients with ra. twenty healthy females and 21 patients with systemic lupus erythematosus (sle) served as controls. mmp-3 (436.8 /- 474.2 ng/ml) and d-dimer levels (351.2 /- 296.3 ng/ml) were markedly elevated in the sera from ra patients as compared with healthy controls (43.9 /- 15.2 ng/ml and 63.0 /- 64.1 ng/ml, p 0.0001, respectively). both levels strongly correlated with each other (r 0.627, p 0.0001) and were closely associated with various clinical parameters for the disease activity of ra, including the erythrocyte sedimentation rate (esr) and the lansbury's activity index (p 0.0001). mmp-3 levels were more highly correlated with articular parameters such as the swollen and painful joint counts (r 0.454, p 0.0002), whereas d-dimer levels correlated well with c-reactive protein (crp) levels (r 0.581, p 0.0001). in sle patients, mmp-3 (239.1 /- 199.6 ng/ml, p 0.0001) and d-dimer levels (86.9 /- 85.2 ng/ml, p 0.0278) were also higher than in healthy controls. both levels correlated with each other (r 0.612, p 0.0025), and were associated with esr and crp levels, as was observed in ra patients, but not with most of the other clinical indicators for sle.","serum levels of mmp-3 and d-dimer are clinically useful indicators for disease activity in ra. our results further support the hypothesis that mmp-3 and plasmin may interact in the inflammatory synovial tissues, and thus augment the articular destruction seen in ra. in sle patients, however, mmp-3 producing cells could be different from in ra patients, and further studies will be required to clarify the pathogenetic mechanism underlying the raised serum levels of mmp-3 and/or d-dimer.",Medication
is symptom awareness affected by the subjects ' expectations during insulin-induced hypoglycemia?,"to assess how expectations and symptom beliefs based on a previous episode of insulin-induced hypoglycemia influence symptom awareness after a second insulin injection in healthy subjects. after a first episode of insulin-induced hypoglycemia in session 1, half of 40 healthy male subjects were told at the beginning of session 2 that they would receive human insulin (0.05 iu/kg), the other half saline. according to a 2 x 2 balanced placebo design, only half of each group received the announced substance, whereas the other half received the substance contrary to their expectations. data collection at 10-15 min intervals included a symptom checklist, blood pressure, heart rate, plasma glucose, and counterregulatory hormone levels. the expectation of a repeated hypoglycemia clearly influenced the subjects' psychophysiological responses. without knowledge about the actual treatment, there was only an average maximum confidence of 65 of having received insulin. expecting the insulin injection led to an increased sum score of neuroglycopenic symptoms but not of autonomic symptoms. subjects expecting the insulin injection reported more weakness, blurred vision, and inner restlessness than those subjects expecting the saline injection. those subjects correctly informed about receiving insulin experienced the most drowsiness, dizziness, and headaches. the expectations of the insulin injection increased the norepinephrine levels and the heart rate. the told insulin/given insulin group showed the highest glucagon levels.",the results support the hypothesis that the subjects' expectations influence their perceived symptoms.,Symptoms
does the nuclear autoantigen cenp-b display cytokine-like activities toward vascular smooth muscle cells?,"a growing number of intracellular autoantigenic polypeptides have been found to play a second biologic role when they are present in the extracellular medium. we undertook this study to determine whether the cenp-b nuclear autoantigen could be added to this set of bifunctional molecules. purified cenp-b or cenp-b released from apoptotic cells was tested for surface binding to a number of human cell types by cell-based enzyme-linked immunosorbent assay, flow cytometry, and indirect immunofluorescence. the biologic effects of cenp-b on the migration, interleukin secretion, and signaling pathways of its specific target cells were evaluated. cenp-b was found to bind specifically to the surface of human pulmonary artery smooth muscle cells (smcs) and not to fibroblasts or endothelial cells (ecs). furthermore, cenp-b bound preferentially to smcs of the contractile type rather than to smcs of the synthetic type. binding of cenp-b to smcs stimulated their migration during in vitro wound healing assays, as well as their secretion of interleukins 6 and 8. the mechanism by which cenp-b mediated these effects involved the focal adhesion kinase, src, erk-1/2, and p38 mapk pathways. finally, cenp-b released from apoptotic ecs was found to bind to smcs, thus indicating a plausible in vivo source of extracellular cenp-b.",these novel biologic roles of the nuclear autoantigen cenp-b open up a new perspective for studying the pathogenic role of anti-cenp-b autoantibodies.,General
does s. typhimurium ssej gene decrease the s. typhi cytotoxicity toward cultured epithelial cells?,"salmonella enterica serovar typhi and typhimurium are closely related serovars as indicated by 96 dna sequence identity between shared genes. nevertheless, s. typhi is a strictly human-specific pathogen causing a systemic disease, typhoid fever. in contrast, s. typhimurium is a broad host range pathogen causing only a self-limited gastroenteritis in immunocompetent humans. we hypothesize that these differences have arisen because some genes are unique to each serovar either gained by horizontal gene transfer or by the loss of gene activity due to mutation, such as pseudogenes. s. typhi has 5 of genes as pseudogenes, much more than s. typhimurium which contains 1. as a consequence, s. typhi lacks several protein effectors implicated in invasion, proliferation and/or translocation by the type iii secretion system that are fully functional proteins in s. typhimurium. ssej, one of these effectors, corresponds to an acyltransferase/lipase that participates in scv biogenesis in human epithelial cell lines and is needed for full virulence of s. typhimurium. in s. typhi, ssej is a pseudogene. therefore, we suggest that ssej inactivation in s. typhi has an important role in the development of the systemic infection. we investigated whether the s. typhi trans-complemented with the functional ssej gene from s. typhimurium (stm) affects the cytotoxicity toward cultured cell lines. it was found that s. typhi harbouring ssejstm presents a similar cytotoxicity level and intracellular retention/proliferation of cultured epithelial cells (ht-29 or hep-2) as wild type s. typhimurium. these phenotypes are significantly different from wild type s. typhi","based on our results we conclude that the mutation that inactivate the ssej gene in s. typhi resulted in evident changes in the behaviour of bacteria in contact with eukaryotic cells, plausibly contributing to the s. typhi adaptation to the systemic infection in humans.",Symptoms
does angiotensin-converting enzyme-2 overexpression attenuate inflammation in rat model of chronic obstructive pulmonary disease?,"to investigate the anti-inflammatory effects of angiotensin-converting enzyme 2 (ace2) overexpression on rat model of chronic obstructive pulmonary disease (copd), and explore underlying mechanism. the rat copd model was established by cigarette smoking using a total body exposure method. a total of 64 male wistar rats were randomly divided into four groups: normal, copd, ad-ace2 and ad-egfp groups. the copd model rats (including copd, ad-ace2 and ad-egfp groups) received an intratracheal injection of normal saline, ad-ace2 and ad-egfp, respectively. the normal group underwent the same procedure but received an intratracheal injection of normal saline only. pulmonary function tests, lung histopathology analysis, malondialdehyde (mda) and reactive oxygen species (ros) level, ace2 mrna and protein expression level, inflammatory cytokines and related signaling pathway proteins were measured. copd rats showed impairment of lung function as evidenced by decreased ratio of forced expiratory volume at 0.3 s and forced vital capacity (fev0.3/fvc) and dynamic lung compliance (cldyn), increased resistance inspiration (ri) and resistance expiration (re) as compared with the normal group, accompanying with reduced ace2 mrna expression, elevated ros and mda, elevated inflammatory cytokines levels (tumor necrosis factor , tnf-; interleukin-8, il-8; il-2 and il-1) and activation of nuclear factor-b (nf-b) and p38 mapk (mitogen activated protein kinases) pathway in lung tissues. ace2 overexpression through ad-ace2 infusion significantly attenuated the inflammatory response in lung tissues of copd model rats.",ace2 could attenuate copd inflammatory process induced by cigarette smoke through reduction of oxidative stress and inhibition of nf-b and p38 mapk pathway activation.,Medication
does high-salt diet increase glomerular ace/ace2 ratio leading to oxidative stress and kidney damage?,"angiotensin ii (angii) contributes to salt-driven kidney damage. in this study, we aimed at investigating whether and how the renal damage associated with a high-salt diet could result from changes in the ratio between angiotensin-converting enzyme (ace) and angiotensin-converting enzyme 2 (ace2). forty-eight rats randomly allocated to three different dietary contents of salt were studied for 4 weeks after undergoing a left uninephrectomy. we focussed on kidney functional, structural and molecular changes. at the same time, we studied kidney molecular changes in 20 weeks old ace2-knockout mice (ace2ko), with and without ace inhibition. a high salt content diet significantly increased the glomerular ace/ace2 ratio. this was associated with increased oxidative stress. to assess whether these events were related, we measured renal oxidative stress in ace2ko, and found that the absence of ace2 promoted oxidative stress, which could be prevented by ace inhibition.","one of the mechanisms by which a high-salt diet leads to renal damage seems to be the modulation of the ace/ace2 ratio which in turn is critical for the cause of oxidative stress, through angii.",Prevention
is there no increased risk for colorectal cancer and adenomas in patients with diverticulitis : a retrospective longitudinal study?,this study was designed to assess the relationship between diverticulitis and the development of colorectal cancer (crc) and colonic adenomas. a retrospective study was longitudinally conducted. patients who had been admitted to the hospital between 1990 and 2000 with diverticulitis were retrieved and the incidence of crc and prevalence of colonic adenomas in these patients was determined. data were collected from the electronic clinical and pathology records. the incidence of crc and prevalence of adenomas in this patient cohort was compared with the general population. the patients were followed until 2008. a total of 288 patients with diverticulitis were included (167 of whom were female patients 58). the mean age of patients at admittance for diverticulitis was 66 years (range: 27-92). crc was detected in five patients (1.7) (95 ci 0.8-3.5) with a mean age of 77 years; colonic adenomas were found in 18 patients (6.3) (95 ci 4.3-9.0) with a mean age of 62 years. the lifetime risks of developing crc and adenomas were presumed to be 4 and 20 respectively. expected rates for crc and adenomas in our patients were calculated as 17 (95 ci 4.0-8.6) and 69 patients (95 ci 20.1-28.3) respectively.,this study showed a lower prevalence of crc and colonic adenomas in patients with diverticulitis compared with the lifetime risk which means that diverticulitis is not a risk factor for development of crc and adenomas. long-term colonic screening after a negative colonoscopy for diverticulitis (generally performed several weeks after recovery) does not seem to be justified.,General
does presence of spink-1 variant alter the course of chronic pancreatitis?,"there is growing evidence that genetic mutations/variants increase susceptibility to the development and progression of chronic pancreatitis (cp). several mutations have been identified that have a direct and indirect role in events leading to cp. mutations in the serine protease inhibitor, kazal type-1 (spink-1) gene have been reported to lower the threshold for pancreatitis in the presence of other genetic or environmental factors. the prevalence and impact of spink-1 mutations on the clinical course and outcomes of cp remains unclear. this study was conducted to assess the prevalence of the spink-1/n34s variant in patients with cp, and to understand the impact of the spink-1 mutation on the natural history of cp. a retrospective-prospective analysis of 239 patients with cp was performed. a detailed history, including duration of symptoms, type of pain (intermittent flares or chronic continuous pain), number of flares requiring hospital admission, alcohol and smoking history, and family history was obtained. the baseline morphological stage of cp was categorized by cambridge classification. clinical outcome variables included frequency and severity of pain episodes, presence of exocrine failure (defined by presence of steatorrhea and/or fecal elastase 200 ug/g), and diabetes. the genetic tests included the cationic trypsinogen gene-1 mutation, cystic fibrosis gene mutations (genzyme assay), and the spink-1/n34s mutation. of the 239 patients with cp, 13 (5.4) were positive for the spink-1/n34s mutation. there were 35 (14.6) patients with idiopathic pancreatitis (ip) in this cohort. most of the patients who were positive for the spink-1/n34s mutation had ip and were caucasian (69.2). the patients with the spink-1/n34s mutation had a younger age of onset (32.9 10.2 vs 40.1 13.6 years; p 0.108) than those with ip and no mutation. over a median follow up of 9.6 years, the patients with the spink-1/n34s mutation had a significantly greater number of acute flares each year, as compared to those without the mutation (11.8 1.5 vs 4 0.98; p 0.0001).","the prevalence of the spink-1/n34s mutation in patients with cp is 5.4, and is approximately 37.1 in patients with ip. these mutations are more prevalent in caucasian patients with cp. the spink-1/n34s mutation predisposes to early onset ip and more frequent acute flares of pancreatitis that might ultimately lead to pancreatic insufficiency. the patients with ip and borderline alcohol history should be considered for testing for genetic analysis, including spink-1 mutations, initially restricted to clinical trials.",Symptoms
is neuronal nitric oxide synthase involved in the induction of nerve growth factor-induced neck muscle nociception?,"neck muscle nociception mediated by nitric oxide may play a role in the pathophysiology of tension-type headache. the present study addresses the involvement of neuronal nitric oxide synthase (nnos) in the facilitation of neck muscle nociception after local application of nerve growth factor (ngf). after administration of ngf into semispinal neck muscles, the impact of neck muscle noxious input on brainstem processing was monitored by the jaw-opening reflex in anesthetized mice. the modulatory effect of preceding and subsequent administration of an inhibitor of neuronal nitric oxide synthase on central facilitation was addressed in a controlled study. with preceding i.p. application of saline or 0.096 mg/kg of the specific nnos inhibitor n-propyl-l-arginine (npla), ngf induced a sustained reflex facilitation within 60 minutes. preceding injection of 0.96 mg/kg or 1.92 mg/kg npla completely prevented the potentially facilitatory effect of ngf. subsequent administration of 0.96 mg/kg npla did not affect established ngf-evoked reflex facilitation. thus, npla prevents facilitation of brainstem processing by noxious myofascial input from neck muscles in a dose-dependent manner.",these findings suggest that nnos is involved in the induction but not the maintenance of ngf-evoked facilitation of nociception in the brainstem. these results from an experimental animal model may support the idea of nos and nnos as potential targets for pharmacological treatment of tension-type headache.,Medication
are osteopontin expression of circulating t cells and plasma osteopontin levels increased in relation to severity of heart failure?,"t cells in peripheral blood reflect the systemic inflammatory response in patients with heart failure (hf). in a rat model of hf, osteopontin is dramatically increased in the left ventricular myocardium, so the association between osteopontin and hf was examined in the present study. peripheral blood was collected from 93 patients with heart disease and 38 controls. left ventricular ejection fraction (lvef) was calculated using a modified simpson's rule. the 93 patients were classified into 3 classes according to the new york heart association (nyha) functional classification. osteopontin-expressing cd4 t cells were quantified by flow cytometry. plasma osteopontin levels (ng/ml) and the frequencies of osteopontin-expressing cd4 t cells () were higher in patients with hf than in controls (800/-554, 575/-229, p0.016 and 27.3/-12.2, 16.7/-10.0, p0.001). furthermore, the plasma osteopontin levels and the frequencies of osteopontin-expressing cd4 t cells increased in proportion to the severity of the nyha functional class. the frequencies of osteopontin-expressing cd4 t cells were significantly correlated with lvef (r-0.336, p0.0048) and log plasma brain natriuretic peptide levels (r0.305, p0.0025).",osteopontin expression of circulating cd4 t cells and plasma osteopontin levels reflect the severity of hf. osteopontin could be a new target in the assessment of hf.,General
is abducens nerve present in patients with type 2 duane 's retraction syndrome?,"to determine whether the abducens nerve is present in patients with type 2 duane's retraction syndrome (drs). retrospective, observational case series. twelve consecutive patients diagnosed with type 2 drs. a retrospective review of medical records of ophthalmologic examination and thin-sectioned magnetic resonance imaging (mri) at the brainstem level and the orbit was performed on 12 patients who showed the typical signs of type 2 drs, including adduction deficit; globe retraction; narrowing of fissure on adduction; and upshoot, downshoot, or both. presence of the abducens nerve and any other extraocular muscle abnormalities discovered by mri scan. magnetic resonance imaging revealed the presence of the abducens nerve in all the affected eyes (n 13) of 12 patients with type 2 drs.",the abducens nerve is present on the affected side in type 2 duane's retraction syndrome.,Diagnosis
is n-butyl cyanoacrylate very effective for massive haemorrhage during the perinatal period?,"the liquid embolic agent n-butyl cyanoacrylate (nbca) is a tissue adhesive used as an immediate and permanent embolic agent when mixed with oil-based contrast medium. in this study, the preservation of fertility with tae using nbca for massive haemorrhage during pregnancy or the peripartum period and the utility of this therapy were investigated. cases from january 2005 to october 2010 in which tae was performed for massive haemorrhage in pregnant women, particularly during the peripartum period, were investigated. tae was performed in 27 pregnant women. the embolic agent used was gs only in five cases, nbca only in 19 cases, and additional embolization with nbca when the effect with gs was insufficient in three cases, one each of abruptio placentae, cervical pregnancy, and uterine atony.a comparison of mean blood loss when each embolic agent was used for haemostasis showed a significant difference between cases in which gs only was used and cases in which nbca only was used. in a comparison of mean transfusion volume, a significant difference was seen between cases in which both gs and nbca were used and cases in which nbca only was used. in a postoperative follow-up survey, menses resumed in eight patients, including four patients who later became pregnant and three who delivered.","tae with nbca, which has an embolic effect unrelated to clotting dysfunction for massive haemorrhage during the peripartum period, is a minimally invasive and very effective treatment method for patients with severe dic.",Treatment
do estrogens affect endothelin-1 mrna expression in lncap human prostate carcinoma cells?,"to study effects of estrogens on endothelin-1 (et-1) mrna expression in the androgen-sensitive lncap-fgc cell line and its androgen-resistant derivative lncap-r. further, if effects of estrone sulfate (e1s) are mediated via conversion to estradiol-17beta (e2). estrogens have been shown to down-regulate et-1, a mediator of the osteoblastic response of bone to metastatic prostate cancer. cells were grown in steroid-depleted medium and incubated for 2-4 and 48 hours with 0, 1, 10, and 100 nm of either e1s or e2. mrna levels were measured with an rt-pcr technique. estrogen metabolism by lncap-fgc cells was studied by incubation with estrone (e1) and e1s at the same conditions, followed by determination of e1 and e2. et-1 mrna expression in lncap-fgc cells was significantly suppressed by e2 and e1s following incubation for 2-4h but after 48 h only by e2 at 1 and 10nm and in lncap-r cells only by e2 at 100 nm following 2-4h of incubation. et-1 mrna expression was significantly higher in untreated lncap-r than in untreated lncap-fgc cells. e1 was efficiently transformed into e2 by lncap-fgc cells but very little to e1 and no e2 was formed from e1s.","et-1 mrna expression in lncap-fgc can be inhibited by e2, but also by its prehormone e1s. the lack of formation of e2 from e1s suggests a mode of action not related to classical steroid receptors. the higher level of et-1 mrna expression found in lncap-r cells may reflect the capability of a hormone refractory tumor to maintain activity on its own, independently of known regulatory mechanisms such as sex steroids.",Medication
is higher serum concentrations of betaine rather than choline associated with better profiles of dxa-derived body fat and fat distribution in chinese adults?,"animal studies have suggested that betaine, but not choline, may improve body composition, but little evidence is available in humans. we examined the association of serum concentrations of choline and betaine with body composition and fat distribution in adults. this community-based study recruited 1996 adults (women/men: 1380/616) aged 40-75 years in urban guangzhou, china. general information and anthropometric measurements were taken, and serum choline and betaine levels were assessed by high-performance liquid chromatography-tandem mass spectrometry between july 2008 and june 2010. after 3.2 years, 1623 of the 1996 participants were measured for fat mass (fm and fm) over the total body (tb), trunk, limbs, android (a) and gynoid (g) regions. the fm ratios of the a/g regions and the trunk and limbs were determined by dual energy x-ray absorptiometry. univariate analyses showed that higher serum betaine levels were significantly associated with lower values of adiposity indices (all p-trends0.05), except in the case of the fm at the gynoid area. after adjusting for potential covariates, similar associations were observed. the mean percentage differences between quartiles 4 and 1 of the serum betaine levels were -4.9 (weight), -4.7 (body mass index, bmi), -2.5 (waist circumference), -7.9 (tb fm) and -3.4 (tb fm). the mean differences in the fm and fm were much more pronounced at the trunk (-10.0 and -4.5) or android areas (-10.7 and -4.7) than those at the limbs (-0.8 and -2.3) or gynoid areas (-0.6 and -1.4). such favorable associations were stronger in men than in women. no significant associations between serum choline and the adiposity indices were observed, except in the cases of body weight and bmi.","greater circulating betaine, but not choline, was dose-dependently associated with better body composition and fat distribution due to a lower fm in the trunk regions in this population.",Diagnosis
is suppression of hath1 gene expression directly regulated by hes1 via notch signaling associated with goblet cell depletion in ulcerative colitis?,"the transcription factor atoh1/hath1 plays crucial roles in the differentiation program of human intestinal epithelium cells (iecs). although previous studies have indicated that the notch signal suppresses the differentiation program of iec, the mechanism by which it does so remains unknown. this study shows that the undifferentiated state is maintained by the suppression of the hath1 gene in human intestine. to assess the effect of notch signaling, doxycycline-induced expression of notch intracellular domain (nicd) and hes1 cells were generated in ls174t. hath1 gene expression was analyzed by quantitative reverse-transcription polymerase chain reaction (rt-pcr). hath1 promoter region targeted by hes1 was determined by both reporter analysis and chip assay. expression of hath1 protein in ulcerative colitis (uc) was examined by immunohistochemistry. hath1 mrna expression was increased by notch signal inhibition. however, hath1 expression was suppressed by ectopic hes1 expression alone even under notch signal inhibition. suppression of the hath1 gene by hes1, which binds to the 5' promoter region of hath1, resulted in suppression of the phenotypic gene expression for goblet cells. in uc, the cooperation of aberrant expression of hes1 and the disappearance of caudal type homeobox 2 (cdx2) caused hath1 suppression, resulting in goblet cell depletion.","the present study suggests that hes1 is essential for hath1 gene suppression via notch signaling. moreover, the suppression of hath1 is associated with goblet cell depletion in uc. understanding the regulation of goblet cell depletion may lead to the development of new therapy for uc.",General
does formation of hematopoietic territories and bone by transplanted human bone marrow stromal cells require a critical cell density?,"bone marrow stromal cells (bmscs) include multipotent cells with the ability to form mature bone organs upon in vivo transplantation. hematopoiesis in these bone organs has been ascribed to the action of skeletal stem cells, which are capable of differentiating towards bone and hematopoiesis-supporting stroma. yet, the creation of hematopoietic territories may be in part a natural consequence of the formation of a sufficiently mature and large bone microenvironment. here, we describe, for the first time, a relationship between bmsc numbers and the extent of bone/hematopoiesis formation in heterotopic transplants. human bmscs were transplanted along with hydroxyapatite/tricalcium phosphate, utilizing a spectrum of dosages, into immunotolerant mice; the transplants were followed for up to 29 months. the extent of bone and hematopoiesis formation increased with increasing bmsc numbers; however, the relationship was sigmoid in character, and a threshold number of bmscs was necessary for extensive bone formation or any hematopoiesis. hematopoiesis only occurred in conjunction with extensive bone formation, and no hematopoiesis occurred where bone formation was poor. consistent with our earlier studies of long-term bmsc transplantation, the transplants underwent a change in bone morphology but not bone content after 8 weeks.",our results have provided evidence that the formation of both hematopoiesis and a mature bone organ is as much a consequence of a sufficiently high local density of bone marrow stromal cells as it is the product of skeletal stem cell action.,Treatment
does a vegan or vegetarian diet substantially alter the human colonic faecal microbiota?,"consisting of 10(14) microbial cells, the intestinal microbiota represents the largest and the most complex microbial community inhabiting the human body. however, the influence of regular diets on the microbiota is widely unknown. we examined faecal samples of vegetarians (n144), vegans (n105) and an equal number of control subjects consuming ordinary omnivorous diet who were matched for age and gender. we used classical bacteriological isolation, identification and enumeration of the main anaerobic and aerobic bacterial genera and computed absolute and relative numbers that were compared between groups. total counts of bacteroides spp., bifidobacterium spp., escherichia coli and enterobacteriaceae spp. were significantly lower (p0.001, p0.002, p0.006 and p0.008, respectively) in vegan samples than in controls, whereas others (e. coli biovars, klebsiella spp., enterobacter spp., other enterobacteriaceae, enterococcus spp., lactobacillus spp., citrobacter spp. and clostridium spp.) were not. subjects on a vegetarian diet ranked between vegans and controls. the total microbial count did not differ between the groups. in addition, subjects on a vegan or vegetarian diet showed significantly (p0.0001) lower stool ph than did controls, and stool ph and counts of e. coli and enterobacteriaceae were significantly correlated across all subgroups.",maintaining a strict vegan or vegetarian diet results in a significant shift in the microbiota while total cell numbers remain unaltered.,Prevention
"is intra-articular injection of hyaluronic acid superior to saline solution injection for ankle arthritis : a randomized , double-blind , placebo-controlled study?","intra-articular injections of hyaluronic acid are potentially useful to treat ankle osteoarthritis, yet their effectiveness has not been proven. both single and multiple-dose treatments for ankle arthritis with use of various hyaluronic acid products have been recommended, but few high-quality studies have been published. the aim of this study was to compare the effectiveness of a single intra-articular injection of hyaluronic acid with a single intra-articular injection of normal saline solution (placebo) for osteoarthritis of the ankle. sixty-four patients with ankle osteoarthritis who met all study criteria were randomly assigned to a single intra-articular injection of 2.5 ml of low-molecular-weight, non-cross-linked hyaluronic acid or a single intra-articular injection of 2.5 ml of normal saline solution. the primary outcome measure was the change from baseline in the american orthopaedic foot ankle society (aofas) clinical rating score at the six-week and twelve-week follow-up examination. secondary outcome measures included the ankle osteoarthritis scale score and patient-reported pain with use of a visual analog pain scale. of the sixty-four patients randomized and treated, eight patients withdrew, leaving fifty-six patients who completed the entire study. there was one mild adverse event (1.6) among the sixty-four patients. at six weeks and twelve weeks, the mean aofas scores in the hyaluronic acid group had improved from baseline by 4.9 and 4.9 points, respectively, whereas the mean aofas scores in the placebo group initially worsened by 0.4 point at six weeks and then improved by 5.4 points at twelve weeks. while the change at twelve weeks from baseline was substantial for both groups, the between-group differences were not significant.","we found that a single intra-articular injection of low-molecular-weight, non-cross-linked hyaluronic acid is not demonstrably superior to a single intra-articular injection of saline solution for the treatment of osteoarthritis of the ankle.",Medication
does placenta growth factor in eyes with neovascular glaucoma be decreased after intravitreal ranibizumab injection?,"to evaluate changes in the concentrations of placental growth factor (plgf) and vascular endothelial growth factor-a (vegf-a) in aqueous humor of patients with neovascular glaucoma (nvg) before and after an intravitreal injection of ranibizumab (ivr) and to determine the underlying correlation between the levels. the prospective interventional comparative study involved 20 eyes of 20 patients with surgery-required advanced nvg and 20 control subjects from january 2013 to november 2013. the nvg eyes received the ivr treatment before glaucoma surgery. aqueous humor was collected at the time of the ivr injection (pre- ivr) and at the time of antiglaucomatous surgery (post-ivr). aqueous humor was also collected at the time of cataract surgery in normal control. aqueous humor and plasma vegf-a and plgf levels were measured with an enzyme-linked immunosorbent assay methods, respectively. the mean aqueous humor plgf and vegf-a concentrations in the pre-ivr eyes were significantly higher than in those of the control subjects (p0.001), whereas the plasma levels showed no significant difference. there was a statistically significant correlation between the aqueous humor plgf and the vegf-a concentration (r 0.612, p 0.003). the mean aqueous humor plgf in the post-ivr eyes dramatically decreased from 1078.36 755.83 to 177.64 151.73 pg/ml (p0.001). the vegf-a level showed a similar trend from 3697.64 2104.47 pg/ml to 183.54 130.35 pg/ml (p0.001).","aqueous humor concentrations of vegf-a and plgf were significantly elevated in the eyes with nvg, and there was a positive correlation between the levels. after an ivr treatment, vegf-a and plgf were significantly decreased in nvg eyes.",Medication
does autocrine stimulation by insulin-like growth factor 1 and insulin-like growth factor 2 mediate chondrocyte survival in vitro?,"to determine the role of autocrine stimulation by insulin-like growth factor 1 (igf-1) and igf-2 in mediating chondrocyte survival and to determine whether chondrocytes from older individuals are more susceptible to cell death when igf action is blocked. survival was assessed in human and monkey chondrocytes cultured in suspension in alginate under serum-free conditions. the role of igfs in mediating survival was determined by treating cultures with neutralizing antibodies to igf-1 and igf-2, an antibody that blocks the type 1 igf receptor, and antisense oligonucleotides to inhibit igf-1 production. survival was measured in chondrocyte cultures from young and old adult monkeys in the presence and absence of the igf receptor blocking antibody and ceramide to induce cell death. cell survival of 90 was noted when chondrocytes were cultured for as long as 107 days in alginate in a supplemented serum-free medium. compared with controls, survival was significantly reduced by treatment with neutralizing antibodies to igf-1 (25 cell death), neutralizing antibodies to igf-2 (18 cell death), antibody to the igf receptor (45 cell death), and igf-1 antisense oligonucleotides (28 cell death). cell death from inhibition of the type 1 igf receptor was associated with an increase in caspase 3 activity and with positive dna fragmentation, consistent with apoptotic cell death. chondrocytes from old adult monkeys were more susceptible to cell death than were those from young adult monkeys when the igf receptor was blocked and cell death was further stimulated by ceramide.","autocrine production of igfs helps to maintain chondrocyte survival in vitro and could play a similar role in vivo. with aging, chondrocytes may become more susceptible to factors that induce cell death.",Medication
do amniotic membrane transplantation to reconstruct the conjunctival surface in cases of chemical burn?,"to evaluate the efficiency of preserved human amniotic membrane transplantation for conjunctival surface reconstruction in cases of chemical burn. preserved amniotic membrane transplantation was performed in 6 patients (6 eyes) having symblepharon and fornix insufficiency due to chemical burn. amniotic membrane was sutured to the intact conjunctiva after the fibrotic tissue was excised. the fornix was reconstructed in cases having fornix insufficiency. these cases were followed up for 4-24 months. during the mean follow-up period (10/-7.37 months) adequate bulbar conjunctiva and fornix depth was achieved in 5 patients without recurrence and with mild fibrosis. in 1 patient who did not have a healthy conjunctiva preoperatively, conjunctival fibrosis and symblepharon recurred.",preserved human amniotic membrane transplantation is a good alternative treatment method for conjunctival surface reconstruction in those cases with some healthy peripheral conjunctival tissue.,Treatment
do experimental investigation of battery-induced esophageal burn injury in rabbits?,"in recent years, small high-performance batteries have become very popular. with this increasing miniaturization of batteries, clinicians have noted an increasing frequency rate of esophageal injury due to battery ingestion by infants. the situation is associated with severe injury to the esophagus due to the electrical current produced, particularly in the case of high-performance batteries producing high currents. the pathophysiologic features and complications of esophageal battery burns have not been thoroughly investigated. our study intended to investigate the pathophysiologic features and complications of esophageal battery burn. open, randomized, controlled study. experimental animal laboratory in a university hospital. male adult mixed-breed rabbits, 22 wks old and weighing 3 to 3.5 kg. the experimental rabbit model of esophageal injury due to battery ingestion described herein was designed to study not only the direct influence of contact with the battery but also damage to neighboring tissues and the biochemical and pathologic mechanisms of injury. we investigated the relationship between the direction of the inserted battery and the mechanism underlying these complications. esophageal burn injury was created by placing a 3-v battery into the esophagus for 9 hrs. the cathode side of the esophagus became increasingly alkaline, while the anode side was acidic. low-voltage battery burns are likely to be due to secondary chemical reactions caused by the electric current because of acid generated at the anode and alkali at the cathode using a micro ph meter. injury was significantly more severe on the alkaline side when a battery was placed with its cathode directed toward the trachea. alkaline complications affecting neighboring tissues were more severe than acid complications. these results indicate that as well as the esophageal mucosa itself being injured, deleterious effects are exerted on surrounding tissues, the severity of which vary depending on the orientation and duration of the battery being lodged in the esophagus.","the direction of the battery cathode, which produces alkali, is important in determining the severity of complications. based on our investigation of the underlying mechanisms of these complications, we advocate the establishment of treatment guidelines for battery swallowing accidents.",General
are statin and aspirin therapy associated with decreased rates of choroidal neovascularization among patients with age-related macular degeneration?,"to investigate the relationship between statin and aspirin use and the risk of choroidal neovascularization (cnv) in patients with age-related macular degeneration (amd). retrospective consecutive case series. all patients 60 years and older with amd who were seen between january 1, 1990, and march 1, 2003, at the san francisco veterans affairs hospital eye clinic with fundus photographs were included. patients with other diagnoses predisposing to cnv or incomplete medical records were excluded. the main outcome measure was angiographically evident cnv. diagnosis was based on review of fundus photographs and fluorescein angiograms in masked fashion; medical records were reviewed for variables possibly predisposing to cnv or statin use. for patients with cnv, age of onset was recorded; those without cnv were treated as censored. age-related macular degeneration disease status and time of onset of cnv was compared between patients treated or not treated with statins for at least 6 months. of 326 patients with amd, 104 had cnv, 204 had dry amd, and 18 had geographic atrophy (ga). of cnv subjects, 21 (20) used statins, compared with 77 (38) of dry amd subjects without ga and 6 (33) of controls with ga (hazard ratio 0.51, 95 confidence interval (ci) 0.31-0.86, p .01). aspirin use was also significantly associated with decreased rates of cnv; 62 cnv subjects (60) used aspirin, compared with 154 (75) dry amd subjects without ga or 12 (67) with ga (hazard ratio 0.63, 95 ci 0.40-0.98, p .04).",therapy with statins or aspirin is associated with decreased rates of cnv among amd patients. additional study with a prospective and/or randomized trial of statin and aspirin use in amd patients is warranted.,Medication
do women with polycystic ovary syndrome have intrinsic insulin resistance on euglycaemic-hyperinsulaemic clamp?,what is the prevalence of insulin resistance (ir) and the contributions of intrinsic and extrinsic ir in women diagnosed with polycystic ovary syndrome (pcos) according to the rotterdam criteria?,"we report novel clamp data in rotterdam diagnosed pcos women, using world health organization criteria for ir showing that women with pcos have a high prevalence of ir, strengthening the evidence for an aetiological role of ir in both national institutes of health (nih) and rotterdam diagnosed pcos in lean and overweight women.",Medication
does exposure to waterpipe smoke induce renal functional and oxidative biomarkers variations in mice?,"waterpipe smoking (wps) has been known for over 400 years. it has been spread widely especially between youth because of the addition of pleasant flavor and because it was misconsidered to be less harmful than cigarette. in this study, we investigated the effect of waterpipe smoking on renal oxidative and functional parameters and compared that at acute and chronic exposure time in mice. mice were divided into three groups, namely acute, chronic and fresh air control. acute group was exposed to waterpipe smoke for one hour daily for six days using whole-body exposure system, while chronic group was exposed to waterpipe smoke for one hour daily for 30 days using whole-body exposure system. exposure to waterpipe smoke has shown significant changes on the mice kidney functional parameters such as creatinine and blood urea nitrogen. both exposures (acute and chronic) has shown a significant reduction in superoxide dismutase (sod) activity (p 0.05), whereas the activity of other antioxidant enzymes (catalase and gpx) reduced only with chronic exposure to waterpipe smoke (p 0.05). additionally, the level of thiobarbituric acid reactive substances (tbars) in mice kidney homogenates has shown a significant elevation following chronic exposure to waterpipe smoke (p 0.05).","in conclusion, chronic waterpipe smoke affects the kidney parameter and antioxidant markers, therefore affecting its functionality of detoxifying and removal of poisonous material from the body.",Diagnosis
does ginsenoside metabolite compound k attenuate inflammatory responses of adjuvant-induced arthritis rats?,"to investigate the effects of ginsenoside metabolite compound k (ck) on adjuvant-induced arthritis (aa) rats and the partial mechanisms focused on the function of immunocyte (b cell and macrophage) and effectors' cell (fibroblast-like synoviocyte, fls). animals were divided randomly into nine groups including control, aa, ck (5, 10, 20, 40, 80, and 160 mg/kg, i.g.), and mtx (0.5 mg/kg, i.g.). the effects of ck on aa rats are evaluated by swelling of the paw, histopathology of joint, and inflammatory cytokine production in serum. to further investigate the effects of ck on the function of b cell, peritoneal macrophage, and fls from aa rats, we examined the proliferation of b cell and fls by 3h thymidine incorporation, and the phagocytic function of peritoneal macrophage was measured by neutral red uptake. cytokines and antibodies in serum and the supernatant from peritoneal macrophage and fls were measured by elisa kit. ck suppressed the severity of aa rats by attenuating the paw swelling and histopathology of joint. ck can inhibit the proliferation of b cell and autoantibody levels, and suppressed the phagocytic function of peritoneal macrophage and secreted pro-inflammatory cytokines tnf-, ifn-, and il-17 and up-regulated the level of protective cytokines il-10. ck attenuated the proliferation of fls, and balanced the ratio of rankl to opg in aa rats.","our results suggest that ck may attenuate the severity of aa rats, partially by influencing the function of immunocyte (b cell and macrophage) and effectors' cells (fls) in aa.",Symptoms
"are low-density lipoprotein subfraction , carotid artery intima-media thickness , nitric oxide , and tumor necrosis factor alpha associated with newly diagnosed ischemic stroke?","small dense (sd) low-density lipoprotein (ldl), tumor necrosis factor (tnf) alpha (), and nitric oxide (no) have recently emerged as important stroke risk factors. the aim of the study was to investigate the effects of increased levels of small ldl particle size, tnf- and no on the developed ischemic stroke and increased carotid artery intima-media thickness (cimt). a total of 29 women and 25 men (a total of 54 ischemic stroke patients) and a similar age group of 50 controls (29 females and 21 males) were included in the study. cimt, c-reactive protein (crp), tnf-, no, and lipid subfraction test of the two groups were measured. the mean ldl particle size was smaller in patients with stroke than in the controls (26.8 0.31 nm vs. 27.0 0.31 nm, p 0.003). sd-ldl, tnf-, no, crp, right cimt, and left cimt were higher in patients with stroke than in the controls (respectively; 8.2 7.8 mg/dl vs. 3.3 3.5 mg/dl, p 0.001;75.6 25.0 pg/ml vs. 65.4 9.1 pg/ml, p 0.009;76.4 53.3 mmol/l vs. 41.5 27.0 mmol/l, p 0.001;1.9 2.6 mm vs. 0.4 0.3 mm p 0.001;0.97 0.38 mm vs. 0.83 0.15 mm, p 0.007;1.04 0.44 mm vs. 0.87 0.19 mm, p 0.010).","these results show that sd-ldl is independently associated with the incidence of stroke and may be a risk factor in the development of stroke. in addition, tnf-, no, right cimt, and left cimt may be a risk factor in the development of ischemic stroke.",Diagnosis
does antisense-mediated post-transcriptional silencing of scn1b gene modulate sodium channel functional expression?,"voltage-dependent sodium channels are membrane proteins essential for cell excitability. they are composed by a pore-forming -subunit and one or more subunits. nine subunit and five subunit isoforms have been identified in mammals: 1, its splice variant 1b, 2, 3 and 4. although they do not form the ion channel pore, subunits modulate both function as well as expression of sodium channels on cell membrane. to investigate the role of 1 subunit on the modulation of sodium channel expression, we silenced this auxiliary subunit with specific antisense oligonucleotides (asons) in two rat cell lines, the gh3 and the h9c2, from neuro-ectoderm and cardiac myocyte origin, respectively. treatment of cells with asons determined a reduction of about 50 of 1 subunit mrna and protein expression in both cell lines. we found that this level of 1 subunit silencing resulted in an overall decrease of subunit mrna, protein expression and a decrease of sodium current density, without altering significantly the voltage-dependent and kinetic properties of the currents. in gh3 cells, the 1 subunit silencing reduced the expression of nav1.1, nav1.3 and nav1.6 isoforms, whereas the nav 1.2 isoform expression remained unaltered. the expression of the only subunit present in h9c2 cells, the nav1.5, was also reduced by 1 subunit silencing.",these results indicate that the 1 subunit may exert an isoform-specific fine-tuned modulation of sodium channel expression.,Treatment
is preoperative b-type natriuretic peptide as independent predictor of ventricular dysfunction and mortality after primary coronary artery bypass grafting?,"elevated b-type natriuretic peptide is associated with increased morbidity and mortality in ambulatory patients with congestive heart failure or acute coronary syndromes. its utility in predicting adverse cardiac surgical outcomes is less certain. we hypothesized that preoperative plasma b-type natriuretic peptide would independently predict in-hospital postoperative ventricular dysfunction, hospital stay, and up to 5-year mortality after primary coronary artery bypass grafting. this is a prospective, longitudinal study of 1023 patients at two institutions undergoing primary coronary artery bypass grafting with cardiopulmonary bypass. ventricular dysfunction was defined as requirement for at least two inotropes or new intra-aortic balloon pump or ventricular assist device support after coronary artery bypass grafting. multivariable analyses assessed independent roles of preoperative b-type natriuretic peptide in predicting postoperative ventricular dysfunction, hospital stay, and 5-year all-cause mortality. preoperative plasma b-type natriuretic peptide concentration predicted ventricular dysfunction, hospital stay, and mortality in univariate and multivariable analyses. logistic regression demonstrated preoperative b-type natriuretic peptide to independently predict ventricular dysfunction (odds ratio 1.92, 95 confidence interval 1.12-3.29, p .018), after adjustment for preoperative left ventricular ejection fraction, congestive heart failure severity, and other clinical predictors. multivariable cox proportional hazards models showed preoperative b-type natriuretic peptide to independently predict hospital stay (hazard ratio 1.42, 95 confidence interval 1.18-1.72, p .0002) and mortality (hazard ratio 1.89, 95 confidence interval 1.08-3.33, p .026).","preoperative plasma b-type natriuretic peptide independently predicted in-hospital ventricular dysfunction, hospital stay, and up to 5-year all-cause mortality after primary coronary artery bypass grafting.",Symptoms
does cyclic tensile strain suppress catabolic effects of interleukin-1beta in fibrochondrocytes from the temporomandibular joint?,"to discern the effects of continuous passive motion on inflamed temporomandibular joints (tmj). the effects of continuous passive motion on tmj were simulated by exposing primary cultures of rabbit tmj fibrochondrocyte monolayers to cyclic tensile strain (cts) in the presence of recombinant human interleukin-1beta (rhuil-1beta) in vitro. the messenger rna (mrna) induction of rhuil-1beta response elements was examined by semiquantitative reverse transcriptase-polymerase chain reaction. the synthesis of nitric oxide was examined by griess reaction, and the synthesis of prostaglandin e2 (pge2) was examined by radioimmunoassay. the synthesis of proteins was examined by western blot analysis of the cell extracts, and synthesis of proteoglycans via incorporation of 35s-sodium sulfate in the culture medium. exposure of tmj fibrochondrocytes to rhuil-1beta resulted in the induction of inducible nitric oxide synthase (inos) and cyclooxygenase 2 (cox-2), which were paralleled by no and pge2 production. additionally, il-1beta induced significant levels of collagenase (matrix metalloproteinase 1 mmp-1) within 4 hours, and this was sustained over a period of 48 hours. concomitant application of cts abrogated the catabolic effects of il-1beta on tmj chondrocytes by inhibiting inos, cox-2, and mmp-1 mrna production and no, pge2, and mmp-1 synthesis. cts also counteracted cartilage degradation by augmenting expression of mrna for tissue inhibitor of metalloproteinases 2 that is inhibited by rhuil-1beta. in parallel, cts also counteracted rhuil-1beta-induced suppression of proteoglycan synthesis. nevertheless, the presence of an inflammatory signal was a prerequisite for the observed cts actions, because fibrochondrocytes, when exposed to cts alone, did not exhibit any of the effects described above.","cts acts as an effective antagonist of rhuil-1beta by potentially diminishing its catabolic actions on tmj fibrochondrocytes. furthermore, cts actions appear to involve disruption/regulation of signal transduction cascade of rhuil-1beta upstream of mrna transcription.",Medication
does sex affect myocardial blood flow and fatty acid substrate metabolism in humans with nonischemic heart failure?,"in animal models of heart failure (hf), myocardial metabolism shifts from high-energy fatty acid (fa) metabolism toward glucose. however, fa (vs glucose) metabolism generates more atp/mole; thus, fa metabolism may be especially advantageous in hf. sex modulates myocardial blood flow (mbf) and substrate metabolism in normal humans. whether sex affects mbf and metabolism in patients with hf is unknown. we studied 19 well-matched men and women with nonischemic hf (ef 35). mbf and myocardial substrate metabolism were quantified using positron emission tomography. women had higher mbf (ml/g/minute), fa uptake (ml/g/minute), and fa utilization (nmol/g/minute) (p 0.005, p 0.005, p 0.05, respectively) and trended toward having higher fa oxidation than men (p 0.09). these findings were independent of age, obesity, and insulin resistance. there were no sex-related differences in fasting myocardial glucose uptake or metabolism. higher mbf was related to improved event-free survival (hr 0.31, p 0.02).","in nonischemic hf, women have higher mbf and fa uptake and metabolism than men, irrespective of age, obesity, or insulin resistance. moreover, higher mbf portends a better prognosis. these sex-related differences should be taken into account in the development and targeting of novel agents aimed at modulating mbf and metabolism in hf.",Medication
are intact hla not beta2m-free heavy chain-specific hla class i antibodies predictive of graft failure?,"we investigated the effects of intact and beta2m-free heavy chain (hc)-specific human leukocyte antigen (hla) class i antibodies on long-term graft survival. hla class i mixed antigen beads were used to detect intact and beta2m-free hc-specific antibodies, whereas elution buffer-treated beads were used to detect antibodies against beta2m-free hc. donor-specific antibodies (dsas) were identified using single-antigen beads. complement-dependent cytotoxicity assays were performed to determine the cytotoxicity of dsa. three hundred seventy-nine of 994 of patients (38) had antibodies against intact hla and beta2m-free hc. there was no survival rate difference between antibody-positive and -negative groups. when the 379 antibody-positive patients were further tested with beta2m-free hc-coated beads, 179 of them with antibodies only against intact form of antigens had a 4-year graft survival rate of 76, which is significantly lower than that of 200 patients with antibodies against beta2m-free hc of hla antigens (88, p0.0056). patients with intact antigen specific dsas had a significantly lower graft survival rate as compared with those with no dsas (70 vs. 89, p0.0073). more patients with strong donor-specific cytotoxic antibodies lost allografts than those with weak-cytotoxic or noncytotoxic antibodies. however, cytotoxic activity of dsa was not correlated to antibody level.","we concluded that intact antigen-specific antibodies, especially dsas, are predictive of graft failure. dsas were not always cytotoxic. strong cytotoxic activity of dsa was associated with a higher rate of graft loss but not correlated to the antibody level. antibodies against beta2m-free hc negatively interfere with the predictive value of intact antigen-specific antibodies.",Treatment
is pre-transplant portal vein thrombosis an independent risk factor for graft loss due to hepatic artery thrombosis in liver transplant recipients?,"hepatic artery thrombosis is an uncommon but catastrophic complication following liver transplantation. we hypothesize that recipients with portal vein thrombosis are at increased risk. data on all liver transplants in the u.s. during the meld era through september 2014 were obtained from unos. status one, multivisceral, living donor, re-transplants, pediatric recipients and donation after cardiac death were excluded. logistic regression models were constructed for hepatic artery thrombosis with resultant graft loss within 90 days of transplantation. 63,182 recipients underwent transplantation; 662 (1.1) recipients had early hepatic artery thrombosis; of those, 91 (13.8) had pre-transplant portal vein thrombosis, versus 7.5 with portal vein thrombosis but no hepatic artery thrombosis (p 0.0001). portal vein thrombosis was associated with an increased independent risk of hepatic artery thrombosis (or 2.17, 95 ci 1.71-2.76, p 0.001) as was donor risk index (or 2.02, 95 ci 1.65-2.48, p 0.001). heparin use at cross clamp, inr, and male donors were all significantly associated with lower risk.",pre-transplant portal vein thrombosis is associated with post-transplant hepatic artery thrombosis independent of other factors. recipients with portal vein thrombosis might benefit from aggressive coagulation management and careful donor selection. more research is needed to determine causal mechanism.,Treatment
are smaller feedback ern amplitudes during the bart associated with a greater family history density of alcohol problems in treatment-nave alcoholics?,"alcoholism is characterized by impaired decision-making (i.e., choosing intoxication in the face of mounting negative consequences). this impairment may involve a reduced brain response to the negative consequences of behavior, which supports an inclination to engage in risky behaviors. the feedback error-related negativity (f-ern) is hypothesized to reflect the valence attached to the negative consequences of behavior. performance on the balloon analogue risk task (bart) measures risk-taking propensity. we recorded f-erns during the bart and during a bart simulation, where individuals observed the rewards and consequences of (someone else's) bart performance. eegs were recorded on 22 actively drinking, treatment-nave alcoholics during the bart and bart simulation. f-erns were measured and their association with psychological and alcohol use measures was examined. f-erns over fronto-central electrode sites were observed to balloon pops in the bart and bart simulation. f-erns during the bart were more than twice the amplitude of f-erns during the bart simulation. smaller f-ern amplitudes from the bart (but not the bart simulation) were associated with a greater family history density of alcohol problems.",the results suggest a possible link between the genetic vulnerability toward developing alcoholism and the brain's response to the negative consequences of behavior.,Treatment
does lipoic acid inhibit leptin secretion and sp1 activity in adipocytes?,"lipoic acid (la) is an antioxidant with therapeutic potential on several diseases such as diabetes and obesity. hyperleptinemia and oxidative stress play a major role in the development of obesity-linked diseases. the aim of this study was to examine in vivo and in vitro the effects of la on leptin production, as well as to elucidate the mechanisms and signalling pathways involved in la actions. dietary supplementation with la decreased both circulating leptin, and adipose tissue leptin mrna in rats. treatment of 3t3-l1 adipocytes with la caused a concentration-dependent inhibition of leptin secretion and gene expression. moreover, la stimulated the anaerobic utilization of glucose to lactate, which negatively correlated with leptin secretion. furthermore, la enhanced phosphorylation of sp1 and inhibited sp1 transcriptional activity in 3t3-l1 adipocytes. moreover, la inhibited akt phosphorylation, a downstream target of phosphatidylinositol 3-kinase (pi3k). treatment with the pi3k inhibitor ly294002 mimicked la actions, dramatically inhibiting both leptin secretion and gene expression and stimulating sp1 phosphorylation.","all of these data suggest that the phosphorylation of sp1 and the accompanying reduced dna-binding activity are likely to be involved in the inhibition of leptin induced by la, which could be mediated in part by the abrogation of the pi3k/akt pathway.",Medication
are humoral responses after influenza vaccination severely reduced in patients with rheumatoid arthritis treated with rituximab?,"for patients with rheumatoid arthritis (ra), yearly influenza vaccination is recommended. however, its efficacy in patients treated with rituximab is unknown. the objectives of this study were to investigate the efficacy of influenza vaccination in ra patients treated with rituximab and to investigate the duration of the possible suppression of the humoral immune response following rituximab treatment. we also undertook to assess the safety of influenza vaccination and the effects of previous influenza vaccination. trivalent influenza subunit vaccine was administered to 23 ra patients who had received rituximab (4-8 weeks after rituximab for 11 patients the early rituximab subgroup and 6-10 months after rituximab for 12 patients the late rituximab subgroup), 20 ra patients receiving methotrexate (mtx), and 29 healthy controls. levels of antibodies against the 3 vaccine strains were measured before and 28 days after vaccination using hemagglutination inhibition assay. the disease activity score in 28 joints (das28) was used to assess ra activity. following vaccination, geometric mean titers (gmts) of antiinfluenza antibodies significantly increased for all influenza strains in the mtx-treated group and in healthy controls, but for no strains in the rituximab-treated group. however, in the late rituximab subgroup, a rise in gmt for the a/h3n2 and a/h1n1 strains was demonstrated, in the absence of a repopulation of cd19 cells at the time of vaccination. seroconversion and seroprotection occurred less often in the rituximab-treated group than in the mtx-treated group for the a/h3n2 and a/h1n1 strains, while seroprotection occurred less often in the rituximab-treated group than in the healthy controls for the a/h1n1 strain. compared with unvaccinated patients in the rituximab-treated group, previously vaccinated patients in the rituximab-treated group had higher pre- and postvaccination gmts for the a/h1n1 strain. the das28 did not change after vaccination.","rituximab reduces humoral responses following influenza vaccination in ra patients, with a modestly restored response 6-10 months after rituximab administration. previous influenza vaccination in rituximab-treated patients increases pre- and postvaccination titers. ra activity was not influenced.",Medication
does impact of contamination and pre-treatment on stable carbon and nitrogen isotopic composition of charred plant remain?,"stable isotope analysis of archaeological charred plants has become a useful tool for interpreting past agricultural practices and refining ancient dietary reconstruction. charred material that lay buried in soil for millennia, however, is susceptible to various kinds of contamination, whose impact on the grain/seed isotopic composition is poorly understood. pre-treatment protocols have been adapted in distinct forms from radiocarbon dating, but insufficient research has been carried out on evaluating their effectiveness and necessity for stable carbon and nitrogen isotope analysis. the effects of previously used pre-treatment protocols on the isotopic composition of archaeological and modern sets of samples were investigated. an archaeological sample was also artificially contaminated with carbonates, nitrates and humic acid and subjected to treatment aimed at removing the introduced contamination. the presence and removal of the contamination were investigated using fourier transform infrared spectroscopy (ftir) and (13)c and (15)n values. the results show a ca 1 decrease in the (15)n values of archaeological charred plant material caused by harsh acid treatments and ultra-sonication. this change is interpreted as being caused by mechanical distortion of the grains/seeds rather than by the removal of contamination. furthermore, specific infrared peaks have been identified that can be used to detect the three types of contaminants studied. we argue that it is not necessary to try to remove humic acid contamination for stable isotope analysis. the advantages and disadvantages of crushing the grains/seeds before pre-treatment are discussed.",we recommend the use of an acid-only procedure (0.5 m hcl for 30 min at 80 c followed by three rinses in distilled water) for cleaning charred plant remains. this study fills an important gap in plant stable isotope research that will enable future researchers to evaluate potential sources of isotopic change and pre-treat their samples with methods that have been demonstrated to be effective.,Treatment
"is livestock-associated methicillin and multidrug resistant staphylococcus aureus present among industrial , not antibiotic-free livestock operation workers in north carolina?","administration of antibiotics to food animals may select for drug-resistant pathogens of clinical significance, such as methicillin-resistant staphylococcus aureus (mrsa). in the united states, studies have examined prevalence of mrsa carriage among individuals exposed to livestock, but prevalence of multidrug-resistant s. aureus (mdrsa) carriage and the association with livestock raised with versus without antibiotic selective pressure remains unclear. we aimed to examine prevalence, antibiotic susceptibility, and molecular characteristics of s. aureus among industrial livestock operation (ilo) and antibiotic-free livestock operation (aflo) workers and household members in north carolina. participants in this cross-sectional study were interviewed and provided a nasal swab for s. aureus analysis. resulting s. aureus isolates were assessed for antibiotic susceptibility, multi-locus sequence type, and absence of the scn gene (a marker of livestock association). among 99 ilo and 105 aflo participants, s. aureus nasal carriage prevalence was 41 and 40, respectively. among ilo and aflo s. aureus carriers, mrsa was detected in 7 (3/41) and 7 (3/42), respectively. thirty seven percent of 41 ilo versus 19 of 42 aflo s. aureus-positive participants carried mdrsa. s. aureus clonal complex (cc) 398 was observed only among workers and predominated among ilo (13/34) compared with aflo (1/35) s. aureus-positive workers. only ilo workers carried scn-negative mrsa cc398 (2/34) and scn-negative mdrsa cc398 (6/34), and all of these isolates were tetracycline resistant.","despite similar s. aureus and mrsa prevalence among ilo and aflo-exposed individuals, livestock-associated mrsa and mdrsa (tetracycline-resistant, cc398, scn-negative) were only present among ilo-exposed individuals. these findings support growing concern about antibiotics use and confinement in livestock production, raising questions about the potential for occupational exposure to an opportunistic and drug-resistant pathogen, which in other settings including hospitals and the community is of broad public health importance.",Medication
is elevation of serum levels of urokinase-type plasminogen activator and its receptor associated with disease progression and prognosis in patients with prostate cancer?,"several investigators have revealed that urokinase-type plasminogen activator (upa) and its receptor (upar) are overexpressed in serum as well as in tumor tissues in patients with various types of cancer. in this study, we examined whether the serum levels of upa and upar could be used as predictors of the progression and prognosis of prostate cancer. serum levels of upa and upar in 54 healthy controls, 62 patients with benign prostatic hypertrophy (bph), and 72 patients with prostate cancer were measured by a sandwich enzyme immunoassay. the mean serum levels of upa and upar in patients with prostate cancer were significantly higher than those in healthy controls and patients with bph. furthermore, the serum upa and upar levels in prostate cancer patients with metastasis were significantly elevated compared with those in patients without metastasis. among patients who underwent radical prostatectomy, the serum levels of upa and upar in patients with pathologically organ-confined disease were significantly lower than in those with advanced disease. the overall survival rate of prostate cancer patients with elevated serum levels of either upa or upar, or of both, was significantly lower than that of patients with normal serum levels of upa and upar.","the results of this study indicate that the elevation of serum levels of either upa or upar, or of both, could be used as new predictors of progression and prognosis in patients with prostate cancer.",Medication
does external beam irradiation inhibit neointimal hyperplasia after injury-induced arterial smooth muscle cell proliferation?,"restenosis after catheter-based revascularization has been demonstrated to be primarily caused by smooth muscle cell proliferation. this study examines the effects of external beam irradiation on neointimal proliferation after external injury to the central artery of the rabbit ear. thirty male new zealand white rabbits were used in this study. crush lesions were performed on each ear under general anesthesia and bilateral auricular nerve blockade. a single dose of 1200 cgy (n 10), 1600 cgy (n 10), or 2000 cgy (n 10) gamma radiation was delivered to the left or right central artery of the ear 24 hours after injury; the contralateral central artery served as control. all rabbits were sacrificed after 21 days and the central arteries of both ears were fixed for morphometric measurements. mean (/-sd) neointimal area was 0.062 /- 0.005 mm2 (1200 cgy), 0.022 /- 0.005 mm2 (1600 cgy), and 0.028 /- 0.006 mm2 in irradiated arteries compared with 0.081 /- 0.009 mm2 in the control group. mean (/-sd) luminal area was 0.049 /- 0.004 mm2 (1200 cgy), 0.059 /- 0.002 mm2 (1600 cgy), and 0.072 /- 0.006 mm2 (2000 cgy) in irradiated arteries compared with 0.043 /- 0.008 mm2 in the control group. the differences in neointimal and luminal area between control and irradiated arteries were significant (p 0.05) for the 1600 and 2000 cgy group only.","we conclude that in this model, external beam x-ray irradiation was successful in reducing neointimal proliferation after injury of the central artery of the rabbit ear. marked reductions in neointimal proliferation were demonstrated in vessels subject to 1600 and 2000 cgy radiation; a less prominent effect was noted for 1200 cgy. whether this approach can be used successfully to inhibit restenosis in the clinical setting requires further investigation.",Medication
do morules in endometrioid proliferations of the uterus and ovary consistently express the intestinal transcription factor cdx2?,"to undertake an immunohistochemical analysis of squamous elements in endometrioid proliferations of the uterus and ovary and to compare the immunophenotype of typical squamous elements and so-called squamous morules. cases of uterine or ovarian endometrioid glandular lesions with squamous elements were stained with cdx2, beta-catenin, oestrogen receptor (er), cd10, p63 and high-molecular-weight cytokeratin lp34. thirteen cases had typical squamous elements and 18 cases morules. morules typically exhibited diffuse nuclear cdx2 and beta-catenin immunoreactivity and were positive for cd10 and lp34. they were usually er- and p63-. in contrast, typical squamous elements were usually positive for er, cd10, p63 and lp34. they were usually cdx2- or focally positive and exhibited no nuclear immunoreactivity for beta-catenin. ten endometrioid carcinomas not exhibiting squamous differentiation were immunoreactive for cdx2; one was focally positive. electron microscopy in two ovarian endometrioid adenocarcinomas with extensive morular differentiation showed that the morules exhibited epithelial features, but no overt evidence of squamous differentiation.","typical squamous elements and morules have an overlapping but differing immunophenotype. morules exhibit no firm immunohistochemical or ultrastructural evidence of squamous differentiation, although immature squamous differentiation cannot be excluded. nuclear beta-catenin positivity is in keeping with the observation that endometrioid glandular lesions with morules are often associated with beta-catenin gene mutation. the explanation for diffuse nuclear positivity with the intestinal transcription factor cdx2 in morules is not clear, but may be a result of overexpression of nuclear beta-catenin. we suggest that the term morular metaplasia is used instead of squamous morules.",Medication
does hospitalist intervention for appropriate use of telemetry reduce length of stay and cost?,"telemetry monitoring is a widely used, labor-intensive, and often-limited resource. little is known of the effectiveness of methods to guide appropriate use. our intervention for appropriate use included: (1) a hospitalist-led, daily review of bed utilization, (2) hospitalist-driven education module for trainees, (3) quarterly feedback of telemetry usage, and (4) financial incentives. hospitalists were encouraged to discuss daily telemetry utilization on rounds. a module on appropriate telemetry usage was taught by hospitalists during the intervention period (january 2013-august 2013) on medicine wards. pre- and post-evaluations measured changes regarding telemetry use. we compared hospital bed-use data between the baseline period (january 2012-december 2012), intervention period, and extension period (september 2014-march 2015). during the intervention period, hospital bed-use data were sent to the hospitalist group quarterly. financial incentives were provided after a decrease in hospitalist telemetry utilization. stanford hospital, a 444-bed, academic medical center in stanford, california. hospitalists saw reductions for both length of stay (los) (2.75 vs 2.13 days, p 0.005) and total cost (22.5 reduction) for telemetry bed utilization in the intervention period. nonhospitalists telemetry bed utilization remained unchanged. we saw significant improvements in trainee knowledge of the most cost-saving action (p 0.002) and the least cost-saving action (p 0.003) in the pre- and post-evaluation analyses. results were sustained in the hospitalist group, with telemetry los of 1.93 days in the extension period.","a multipronged, hospitalist-driven intervention to improve appropriate use of telemetry reduces los and cost, and increases knowledge of cost-saving actions among trainees.",Treatment
is osteoprotegerin associated with hip fracture incidence : the tromso study?,"osteoprotegerin (opg) is a cytokine essential for the regulation of bone resorption, but large longitudinal studies on its relationship to fracture risk in humans are lacking. in this population-based study of 2740 men and 2857 post-menopausal women, it was examined whether serum opg was associated with hip fracture incidence. the participants were followed for 15 years. baseline measurements included height, weight and serum opg, and information about lifestyle, prevalent diseases and use of medication. men with opg in the highest quartile were 2.79-fold 95 confidence interval (ci) 1.34-5.82 more likely to have a hip fracture during follow-up, compared with those with opg in the lowest quartile (p-trend over opg quartiles 0.001, after adjustments for age and other confounders). in women not using post-menopausal hormone therapy (ht), the risk of hip fracture was 1.64-fold higher (95 ci 0.94-2.86) in the highest quartile compared with the lowest opg quartile (p-trend over opg quartiles 0.05). no relationship was found in post-menopausal women using ht (p-trend over opg quartiles 0.23).","in men, opg was positively associated with the incidence of hip fracture. in post-menopausal women not using ht a similar, but weaker, relationship was found.",Medication
does tension cost correlate with mechanical and biochemical parameters in different myocardial contractility conditions?,"tension cost, the ratio of myosin atpase activity to tension, reflects the economy of tension development in the myocardium. to evaluate the mechanical advantage represented by the tension cost, we studied papillary muscle contractility and the activity of myosin atpase in the left ventricles in normal and pathophysiological conditions. experimental protocols were performed using rat left ventricles from: (1) streptozotocin-induced diabetic and control wistar rats; (2) n-nitro-l-arginine methyl ester (l-name) hypertensive and untreated wistar rats; (3) deoxycorticosterone acetate (doca) salt-treated, nephrectomized and salt- and doca-treated rats; (4) spontaneous hypertensive rats (shr) and wistar kyoto (wky) rats; (5) rats with myocardial infarction and shamoperated rats. the isometric force, tetanic tension, and the activity of myosin atpase were measured. the results obtained from infarcted, diabetic, and deoxycorticosterone acetate-salt-treated rats showed reductions in twitch and tetanic tension compared to the control and sham-operated groups. twitch and tetanic tension increased in the n-nitro-l-arginine methyl ester-treated rats compared with the wistar rats. myosin atpase activity was depressed in the infarcted, diabetic, and deoxycorticosterone acetate salt-treated rats compared with control and sham-operated rats and was increased in n-nitro-l-arginine methyl ester-treated rats. these parameters did not differ between shr and wky rats. in the studied conditions (e.g., post-myocardial infarction, deoxycorticosterone acetate salt-induced hypertension, chronic n-nitro-l-arginine methyl ester treatment, and streptozotocin-induced diabetes), a positive correlation between force or plateau tetanic tension and myosin atpase activity was observed.",our results suggest that the myocardium adapts to force generation by increasing or reducing the tension cost to maintain myocardial contractility with a better mechanical advantage.,Treatment
does contemporary result with ampullectomy for 29 benign '' neoplasms of the ampulla?,"ampullectomy may be an appropriate oncologic procedure in selected patients. sparse data exist on procedure-related complications and the relationship between histologic analysis and outcomes. we retrospectively reviewed our experience with ampullectomy in 29 patients with a preoperative benign histologic diagnosis over 15 years (1991 to 2006). presenting signs, symptoms, and preoperative diagnostic studies were reviewed. postoperative complications and followup for recurrence were recorded. the abilities of preoperative histologic biopsy, intraoperative frozen section, and final histologic analysis to guide management and predict outcomes were determined. median age was 63 years. jaundice was present in 30 of patients. median length of hospital stay was 9 days. forty-five percent of patients had a complication, and there was one postoperative mortality (3). ampullary adenomatous neoplasms were present in 89 of patients. preoperative biopsy had complete concordance with final pathology in 76 of patients. preoperative biopsy and intraoperative frozen section failed to identify carcinoma in four patients. pancreaticoduodenectomy was performed within 7 days in the postoperative period in three of these patients. after ampullectomy (median followup16 months), recurrences were identified in two patients (8) with benign tumors. no patients with high-grade dysplasia (n4) have had recurrence.","preoperative biopsy and intraoperative frozen section analysis have limitations in the management of patients undergoing ampullectomy. high-grade dysplasia on preoperative biopsy is not an absolute contraindication to ampullectomy. morbidity of ampullectomy is significant, but longterm outcomes of this procedure, in patients without invasive malignancy, are acceptable.",Treatment
does quantitative magnetic resonance imaging detect changes in meniscal volume in vivo after partial meniscectomy?,"quantifying changes in meniscal volume in vivo before and after partial meniscectomy (pm) could help elucidate the mechanisms involved in osteoarthritis development after meniscal injury and its surgical treatment. purpose/ to determine whether quantitative magnetic resonance imaging (qmri) can detect the immediate reduction in meniscal volume created by pm, while ruling out changes in unresected structures. we hypothesized that qmri would be reliable for determining meniscal volume within the repeated images of unresected menisci. additionally, we expected no significant difference in volume between the uninjured menisci of the injured knees and the same menisci of the uninjured knees. cohort study (diagnosis); level of evidence, 2. ten subjects with meniscal tears were evaluated with 3-t mri before and after arthroscopic pm. manual segmentation was used to create models of the menisci and to determine the preoperative and postoperative meniscal volumes for each subject. the responsiveness and reliability of qmri for determining meniscal volume in vivo were evaluated using these measurements. we expected a decrease in volume of the resected menisci, but not in the uninjured menisci, after surgery. the mean preoperative volume of the injured menisci was significantly greater than the mean postoperative volume (2896 /- 277 vs 2480 /- 277 mm(3); p .000). there was no significant difference between the mean preoperative and postoperative volumes of the uninjured menisci (2687 /- 256 vs 2694 /- 256 mm(3); p 1.000).","manual segmentation demonstrated a significant reduction in the volume of the surgically resected menisci after pm, but no significant change in the volume of unresected meniscal tissue, indicating that the manual segmentation method is responsive.",Diagnosis
does genome-wide dna methylome reveal the dysfunction of intronic micrornas in major psychosis?,"dna methylation is thought to be extensively involved in the pathogenesis of many diseases, including major psychosis. however, most studies focus on dna methylation alteration at promoters of protein-coding genes, despite the poor correlation between dna methylation and gene expression. we analyzed differentially methylated regions and differentially expressed genes in patients with schizophrenia and bipolar disorder and normal subjects. gene expression and dna methylation were analyzed with rna-seq and medip-seq of post-mortem brain tissue (brain region ba9) cohort in five schizophrenia, seven bipolar disorder cases and six controls, respectively. here, we performed a large-scale integrative analysis using medip-seq, coupled with rna-seq, on brain samples from major psychotic and normal subjects and observed obvious discrepancy between dna methylation and gene expression. we found that differentially methylated regions (dmrs) were distributed across different types of genomic elements, especially introns. these intronic dmrs were significantly enriched for diverse regulatory elements, such as enhancers and binding sites of certain transcriptional factors (e.g., pol3). notably, we found that parts of intronic dmrs overlapped with some intragenic mirnas, such as hsa-mir-7-3. these intronic dmr-related mirnas were found to target many differentially expressed genes. moreover, functional analysis demonstrated that differential target genes of intronic dmr-related mirnas were sufficient to capture many important biological processes in major psychosis, such as neurogenesis, suggesting that mirnas may function as important linkers mediating the relationships between dna methylation alteration and gene expression changes.","collectively, our study indicated that dna methylation alteration could induce expression changes indirectly by affecting mirnas and the exploration of dmr-related mirnas and their targets enhanced understanding of the molecular mechanisms underlying major psychosis.",Symptoms
is mta1-upregulated epcam associated with metastatic behaviors and poor prognosis in lung cancer?,"overexpression of metastasis-associated protein 1 (mta1) in various cancer cells promotes tumor invasion and migration and predicts cancer patients' poor prognosis. the pilot rna-seq data from our laboratory indicated that epithelial cell adhesion molecule (epcam) was statistically reduced in mta1-silencing cells. epcam has been recognized as more than a mere cell adhesion molecule and recent findings have revealed its causal role in mediating migratory and invasive capacity. thus, this study was aimed to explore whether mta1 was able to upregulate epcam expression and, consequently, modulate its effects on invasion and migration of the lung cancer cells as well as patients' prognosis. we checked the epcam expression by overexpressing or silencing mta1 in lung cancer cells. furthermore, these lung cancer cells with stably overexpressed or silenced mta1 were transfected with siepcam or epcam-expressing plasmids and then subjected to western blot, invasion and migration assays. in addition, patients (n 118) with early-stage lung cancer were enrolled in this study to confirm the correlations between mta1 and epcam and pathoclinical parameters by using immunohistochemistry (ihc). all statistical analyses were performed with spss 20.0 statistical software. mta1 upregulated epcam expression in lung cancer cell lines, and epcam overexpression rescued the inhibitory effects by silencing mta1 on cell invasion and migration in vitro. what's more, both mta1 and epcam, correlated to each other, were overexpressed in lung cancer tissues and significantly correlated with their clinical stages, tumor diameters, lymph node metastasis. multivariate analysis indicated that local advancement (p 0.03), mta1 overexpression (p 0.001) and epcam overexpression (p 0.045) of the lung cancer tissues remained significant in predicting unfavorable overall survival.","we revealed a new molecular mechanism of mta1-mediated invasion and metastasis in lung cancer through downstream target epcam, and interfering with epcam function may be a novel therapeutic strategy for treatment of mta1-overexpressing lung carcinoma.",Diagnosis
do human immunodeficiency virus type 1 vpu and cellular task proteins suppress transcription of unintegrated hiv-1 dna?,"unintegrated hiv-1 dna serves as transcriptionally active templates in hiv-infected cells. several host factors including nf- enhance hiv-1 transcription. hiv-1 induced nf- activation can be suppressed by viral protein u (vpu). interestingly hiv-1 vpu shares amino acid homology with cellular twik-related acid sensitive k (task) channel 1 and the proteins physically interact in cultured cells and aids lymphoid tissue. furthermore, the first transmembrane domain of task-1 is functionally interchangeable with vpu and like vpu enhances hiv-1 release. here we further characterize the role of task channels and vpu in hiv-1 replication. we demonstrate that both task channels and vpu can preferentially inhibit transcription of unintegrated hiv-1 dna. interestingly, task-1 ion channel function is not required and suppression of hiv-1 transcription by task-1 and vpu was reversed by overexpression of rela (nf- p65).",task proteins and vpu suppress transcription of unintegrated hiv-1 dna through an nf--dependent mechanism. taken together these findings support a possible physiological role for hiv-1 vpu and task proteins as modulators of transcription of unintegrated hiv-1 dna genomes.,General
does supplementation of highly concentrated -cryptoxanthin in a satsuma mandarin beverage improve adipocytokine profiles in obese japanese women?,"serum -cryptoxanthin levels are lower in overweight subjects than in normal subjects. abnormalities of adipocytokine profiles in obesity subjects have been reported. there are several reports that serum -cryptoxanthin levels in them were relatively lower than normal subjects. we hypothesize that supplementation of highly concentrated -cryptoxanthin improves serum adipocytokine profiles in obese subjects. this study tested the association between -cryptoxanthin intake and serum adipocytokine levels. an intervention study consisted of a 3-week long before-and-after controlled trial, where -cryptoxanthin (4.7 mg/day) was given to 17 moderately obese postmenopausal women. the results indicated no significant changes in body weight or body mass index (bmi). serum -cryptoxanthin levels increased significantly by 4-fold. serum high molecular weight (hmw)-adiponectin levels increased significantly, while serum plasminogen activator inhibitor (pai)-1 levels decreased.",we concluded that increasing the intake of -cryptoxanthin to approximately 4 mg per day for 3 weeks may have beneficial effects on the serum adipocytokine status and consequently alleviate progression of metabolic syndrome.,Medication
does cigarette smoking predict differential benefit from naltrexone for alcohol dependence?,"identifying factors that modify responsiveness to pharmacotherapies for alcohol dependence is important for treatment planning. cigarette smoking predicts more severe alcohol dependence and poorer treatment response in general. nevertheless, there is limited research on cigarette smoking as a potential predictor of differential response to pharmacological treatment of alcoholism. we examined the association between cigarette smoking and drinking outcomes in the combine (combined pharmacotherapies and behavioral interventions for alcohol dependence) study, a randomized, double-blind placebo-controlled 16-week trial comparing combinations of medications (i.e., acamprosate and naltrexone) and behavioral interventions (i.e., medical management, combined behavioral therapy) in 1383 alcohol-dependent individuals. smokers (i.e., more than one half the sample) significantly differed from nonsmokers on several demographic and drinking-related variables at baseline and generally had poorer treatment outcomes than nonsmokers. however, smokers who received naltrexone had better drinking outcomes than smokers who received placebo, whereas alcohol use among nonsmokers did not vary by naltrexone assignment. this pattern of findings occurred independent of whether patients received combined behavioral intervention or medical management and remained after controlling for alcoholism typology and baseline demographic differences. approximately 9 of smokers quit smoking, and an additional 10 reduced their cigarette intake during treatment. reductions in smoking did not vary by treatment assignment.",these results suggest that naltrexone might be particularly beneficial for improving alcohol use outcomes in alcohol-dependent smokers.,Treatment
does 17beta-estradiol stimulate flow-induced vasodilatation in isolated small mesenteric arteries from prepubertal femal rats?,"flow-induced vasodilatation may contribute to lowering of peripheral resistance to pregnancy. this study investigated modulation of flow responses by 17beta-estradiol. small mesenteric arteries from prepubertal female wistar rats were pretreated for 3 hours with 17beta-estradiol (10(-7) mol/l) with 17alpha-estradiol (10(-7) mol/l) or vehicle (0.1 dimethylsulfoxide). responses to intraluminal flow were evaluated with use of a pressure arteriograph. after pretreatment with 17beta-estradiol arteries relaxed to flow, whereas those treated with vehicle or 17alpha-estradiol did not (percent change in diameter at maximum flow rate after 17beta-estradiol 38.7 /- 5.7, n 10, vs 1.1 /- 4.3, n 10 after vehicle; p 0.01). endothelium removal or pretreatment with either a nitric oxide synthase inhibitor or a novel soluble guanylyl cyclase inhibitor diminished the response to 17beta-estradiol.",17beta-estradiol stimulated nitric oxide-mediated flow-induced relaxation. through this pathway 17beta-estradiol could play an important role in the control of vascular tone.,Medication
does injury induce localized airway increases in pro-inflammatory cytokines in humans and mice?,"secretory immunoglobulin a (siga) increases in the airways of humans and mice after injury to protect against infection. the pro-inflammatory cytokines tumor necrosis factor (tnf)-, interleukin (il)-1, and il-6 are linked molecularly to siga production and secretion and are required for siga increases in the airway after injury in a mouse model. we investigated the injury effect on airway and serum concentrations to determine the source of the cytokines involved in the airway iga response. in the first experiment, tnf-, il-1, and il-6 concentrations in bronchoalveolar lavage (bal) fluid and serum obtained from 11 ventilated trauma patients within 30 h of admission were compared with those in eight elective surgical patients. in the second experiment, male icr mice received no injury (n 7) or injury with sham celiotomy and neck incisions (n 8) with sacrifice of all animals at 8 h for bal fluid and serum cytokine measurements by enzyme-linked immunosorbent assay. injured patients had significantly higher bal fluid and serum tnf-, il-1, and il-6 concentrations, with greater increases in the bal fluid than in the serum. injured mice had significantly increased bal fluid concentrations of tnf-, il-1, and il-6 without significant changes in serum tnf- or il-1. serum il-6 increased significantly.","injury significantly increases human and mouse airway tnf-, il-1, and il-6. increases are greater in the airway than in serum, implying a local rather than a systemic stress response to injury.",Treatment
does apolipoprotein e4 association with metabolic syndrome depend on body fatness?,"the human apolipoprotein e (apoe) gene is polymorphic. the apoe4 allele is a risk factor for cardiovascular disease and could contribute to the development of the metabolic syndrome (mets) as it may affect all mets components. we hypothesize that the common apoe4 polymorphism differentially regulates mets risk and that this association might be modulated by body fatness. we used body mass index (bmi) as surrogate of fatness and cross-sectionally studied the prevalence of mets in 4408 middle-aged men of the aragon workers health study (awhs). our analysis revealed i) a gene dose-dependent association between apoe4 allele and increased risk for mets, ii) this association primarily derived from the overweight subjects. for these individuals, the mets risk was higher in apoe4 carriers than in non-carriers (odds ratio 1.31; 95 ci, 1.03-1.67). additionally, we examined 3908 healthy young individuals from the coronary artery risk development in young adults (cardia) cohort, followed-up for 25 years. compared with apoe4 non-carriers, apoe4 presence significantly increased the risk of developing mets (hazard ratio, 1.12; 95 ci, 1.00-1.26). again, an interplay between apoe4 and the longitudinal development of fatness towards the onset of mets occurred throughout the study. for individuals with bmi gain below the median, the cumulative onset rate of mets was significantly higher in apoe4 carriers than in the non-carriers (hr, 1.29; 95 ci, 1.07-1.55).","carrying apoe4 alleles increases mets in a dose-dependent manner, characterizing individual's apoe genotype might help identify at-risk subjects for preventive intervention.",Medication
does a review found that the autoreply e-mail function avoids problems of subject allocation concealment?,using the autoreply e-mail function to avoid problems of subject allocation concealment. a narrative review discussing technologic and methodologic issues in using autoreply e-mail to securely conceal subject allocation in randomized control trials. autoreply e-mail can be successfully used to securely conceal subjects in a variety of randomized control trials.,the allocation of subjects to intervention groups in randomized controlled trials should be achieved using methods that avoid both systematic bias and subject allocation transparency. the use of computer-generated tables and the automatic e-mail reply system are suggested as a solution to ensuring subject allocation concealment.,Prevention
does expression of peg10 be associated with poor survival and tumor recurrence in hepatocellular carcinoma?,"paternally expressed gene 10 (peg10), first identified as an imprinted gene, is paternally expressed and maternally silenced. in hepatocellular carcinoma (hcc), peg10 has been identified as a potential target gene located within the amplified 7q21 locus. the purpose of this study was to investigate the expression of peg10 protein in hcc and evaluate its prognostic significance. peg10 protein expression was examined by immunohistochemistry in tumor tissues from 218 hcc patients undergoing curative resection. furthermore, the relationships between peg10 expression and clinicopathologic features or postoperative survival of hcc patients were evaluated. the median follow-up period was 119.8 months for survivors. peg10 expression was observed in 148 of the 218 hccs (67.9) and was significantly correlated with younger age, female, higher edmondson grade, microvascular invasion, intrahepatic metastasis, higher american joint committee on cancer t-stage, and higher -fetoprotein level. peg10 expression was an independent predictor of early recurrence (p0.013), and it showed an unfavorable influence on recurrence-free survival (p 0.001). a subgroup analysis showed that among patients with -fetoprotein 20 ng/ml (80 patients), the peg10-positive group also showed an unfavorable influence on recurrence-free survival (p0.002). moreover, a multivariate survival analysis identified peg10 as an independent predictor of shorter recurrence-free survival (p0.005). peg10 expression showed an unfavorable influence on overall survival (p0.007) but was not an independent predictor of shorter overall survival (p0.128).","peg10 protein could be a potential biomarker predicting early recurrence and recurrence-free survival in hcc patients after curative resection, even in those with normal serum -fetoprotein levels.",Treatment
does simvastatin treatment improve liver sinusoidal endothelial dysfunction in ccl4 cirrhotic rats?,"sinusoidal endothelial dysfunction with decreased nitric oxide (no) production contributes to increased hepatic resistance in cirrhosis. statins improve endothelial dysfunction in peripheral vasculature. this study was designed to characterize the hemodynamic and molecular effects of statins in cirrhotic rats. systemic and splanchnic hemodynamics were evaluated in ccl(4) ascitic cirrhotic rats treated with placebo or simvastatin (25 mg/kg/day, for 3 days), at baseline and after volume expansion. vascular responses of liver vasculature were evaluated after isolation and perfusion of the liver. there were no differences in baseline hemodynamics in rats treated with simvastatin or placebo. however, in rats treated with simvastatin the increase in portal pressure induced by volume expansion was significantly attenuated. in isolated and perfused cirrhotic livers simvastatin pre-treatment significantly attenuated the pressure response to methoxamine, and significantly improved paradoxical vasoconstriction induced by acetylcholine. these effects were not observed in the presence of a nitric oxide synthase inhibitor. simvastatin increased enos expression, akt-dependent enos phosphorylation and cgmp liver content.","the administration of simvastatin might constitute a new way to selectively increase no availability in the cirrhotic liver circulation and, therefore improve the vascular disturbances that contribute to portal hypertension.",Treatment
does comparative proteomics reveal that central metabolism changes are associated with resistance against sporisorium scitamineum in sugarcane?,"sugarcane smut, which is caused by sporisorium scitamineum, has been threatening global sugarcane production. breeding smut resistant sugarcane varieties has been proven to be the most effective method of controlling this particular disease. however, a lack of genome information of sugarcane has hindered the development of genome-assisted resistance breeding programs. furthermore, the molecular basis of sugarcane response to s. scitamineum infection at the proteome level was incomplete and combining proteomic and transcriptional analysis has not yet been conducted. we identified 273 and 341 differentially expressed proteins in sugarcane smut-resistant (yacheng05-179) and susceptible (roc22) genotypes at 48 h after inoculation with s. scitamineum by employing an isobaric tag for relative and absolute quantification (itraq). the proteome quantitative data were then validated by multiple reaction monitoring (mrm). the integrative analysis showed that the correlations between the quantitative proteins and the corresponding genes that was obtained in our previous transcriptome study were poor, which were 0.1502 and 0.2466 in yacheng05-179 and roc22, respectively, thereby revealing a post-transcriptional event during yacheng05-179-s. scitamineum incompatible interaction and roc22-s. scitamineum compatible interaction. most differentially expressed proteins were closely related to sugarcane smut resistance such as beta-1,3-glucanase, peroxidase, pathogenesis-related protein 1 (pr1), endo-1,4-beta-xylanase, heat shock protein, and lectin. ethylene and gibberellic acid pathways, phenylpropanoid metabolism and prs, such as pr1, pr2, pr5 and pr14, were more active in yacheng05-179, which suggested of their possible roles in sugarcane smut resistance. however, calcium signaling, reactive oxygen species, nitric oxide, and abscisic acid pathways in yacheng05-179 were repressed by s. scitamineum and might not be crucial for defense against this particular pathogen.","these results indicated complex resistance-related events in sugarcane-s. scitamineum interaction, and provided novel insights into the molecular mechanism underlying the response of sugarcane to s. scitamineum infection.",Diagnosis
are helicobacter pylori strains harboring baba2 from indian sub population associated with increased virulence in ex vivo study?,"the baba2 gene along with the caga and vaca of helicobacter pylori has been considered as a risk factor for the disease outcome in certain populations. this study was aimed to understand the role of baba2 of h. pylori with the background of caga and vaca in disease manifestations in indian sub population. a total of 114 h. pylori strains isolated from duodenal ulcer (du) (n 53) and non-ulcer dyspepsia (nud) patients (n 61) were screened for the prevalence of these virulence markers by pcr. the comparative study of il-8 production and apoptosis were done by co-culturing the ags cell line with h. pylori strains with different genotypes. adherence assay was performed with baba2 positive and negative strains. two isogenic mutants of baba2 were constructed and the aforesaid comparative studies were carried out. pcr results indicated that 90.6 (48/53), 82 (50/61) and 73.6 (39/53) strains from du patients were positive for caga, vaca, and baba2, respectively. whereas the prevalence of these genes in nud subjects were 70.5 (43/61); 69.8 (37/53), and 65.6 (39/61), respectively. although adherence to ags cells was comparable among strains with baba2 positive and negative genotypes, but the triple positive strains could induce highest degree of il-8 production and apoptosis, followed by the caga (-)/vaca (-)/baba2 () strains and triple negative strains, respectively. the wild type strains showed significantly higher il-8 induction as well as apoptosis in ex vivo than its isogenic mutant of baba2.",pcr study demonstrated that there was no significant association between the distribution of baba2 genotype or of triple positive strains and disease outcome in this sub population. the adherence assay showed that there was no significant difference in the extent of adherence to ags cells among baba2 positive and negative strains. but the ex vivo study indicated that the triple positive or even the baba2 only positive strains are involved in increased virulence. the wild type strains also exhibited increased virulence compared to the baba2 mutant strains. this inconsistency demonstrated that bacterial genotype along with host genetic polymorphisms or other factors play important role in determining the clinical manifestation of h. pylori infections.,Diagnosis
does swietenia macrophylla extract promote the ability of caenorhabditis elegans to survive pseudomonas aeruginosa infection?,"swietenia macrophylla or commonly known as big leaf mahogany, has been traditionally used as an antibacterial and antifungal agent. the unwanted problem of antibiotic resistance in many bacterial species advocates the need for the discovery of the new anti-infective drugs. here, we investigated the anti-infective properties of swietenia macrophylla with an assay involving lethal infection of caenorhabditis elegans with the opportunistic human pathogen pseudomonas aeruginosa. using a slow killing assay, caenorhabditis elegans was challenged with an infective strain of pseudomonas aeruginosa (pa14). the ability of swietenia macrophylla seed ethyl acetate extract to promote the survival of infected worms was assessed by comparing the percentage of survival between extract treated and non-treated worm populations. the effect of swietenia macrophylla towards pa14 growth, caenorhabditis elegans feeding rate and degree of pa14 colonization in the worm gut was also evaluated. lastly, using a fluorescent transgenic caenorhabditis elegans strain and real time pcr, the effect of swietenia macrophylla on the expression of lys-7, an immune response gene was also investigated. our results demonstrate the ability of swietenia macrophylla seed ethyl acetate extract in rescuing caenorhabditis elegans from fatal pa14 infection. consequently, we showed that the extract promotes the survival without exhibiting any bactericidal effect or perturbation of caenorhabditis elegans feeding rate. we also showed that swietenia macrophylla was able to restore the initially repressed lys-7 level in pa14 infected caenorhabditis elegans.","swietenia macrophylla extract is able to enhance the ability of caenorhabditis elegans to survive pa14 infection without directly killing the pathogen. we further showed that the extract boosted the expression of a gene pivotal for innate immunity in caenorhabditis elegans. collectively, these findings strongly suggest the presence of compounds within swietenia macrophylla seed that either reduces pseudomonas aeruginosa virulence and/or enhance host resistance.",Medication
does telmisartan ameliorate oxidative stress and subarachnoid haemorrhage-induced cerebral vasospasm?,"growing evidence suggests that oxidative stress is one of the factors contributing to subarachnoid haemorrhage (sah)-induced cerebral vasospasm. sah-induced cerebral vasospam alters thioredoxin (trx) cycle enzymes and thioredoxin-interacting protein (txnip) as an important endogenous antioxidant system. in this study, we have explored the effects of telmisartan on the vascular morphological changes, endothelial apoptosis, tissue oxidative stress status and the level of trx cycle enzymes/ txnip in a rabbit sah model. forty male new zealand rabbits were randomly divided into five groups of eight rabbits each: control group, sham group, sah group, sah vehicle group and sah telmisartan group. sah was created by a single cisterna magna blood injection. sah telmisartan group received telmisartan treatment (5 mg/kg intraperitoneal, once daily) for 72 h. the brainstem tissue trx1, trx2, trx reductase (trxr), trxr1and txnip levels were investigated. total oxidant status (tos), total antioxidant status (tas), malondialdehyde (mda) levels and tumour necrosis factor alpha (tnf alpha) levels were investigated. basilar artery segments were investigated for cross-sectional area, wall thickness measurements and endothelial apoptosis. telmisartan treatment restored the lowered level of trx1, trxr, tas and the expression of trxr1 seen in sah. telmisartan treatment also decreased txnip expression, tos, mda and tnf alpha levels. morphological changes of cerebral vasospasm were attenuated after treatment. endothelial apoptosis significantly reduced.",treatment with telmisartan ameliorates oxidative stress and sah-induced cerebral vasospasm in rabbits. these effects of telmisartan may be associated with downregulation of txnip and upregulation of trx/trxr.,Medication
does inactivation of smad4 lead to impaired ocular development and cataract formation?,"signaling by members of the tgf superfamily of molecules is essential for embryonic development and homeostasis. smad4, a key intracellular mediator in tgf signaling, forms transcriptional activator complexes with activin-, bmp-, and tgf-restricted smad proteins. however, the functional role of smad4 in controlling different visual system compartments has not been fully investigated. using the pax6 promoter-driven cre transgenic, smad4 was conditionally inactivated in the lens, cornea and ectoderm of the eyelids. standard histological and molecular analytical approaches were employed to reveal morphological and cellular changes. inactivation of smad4 in the lens led to microphthalmia and cataract formation in addition to the persistent adhesion of the retina to the lens and the iris to the cornea. inactivation of smad4 from the ectoderm of the eyelid and cornea caused disruption to eyelid fusion and proper development of the corneal epithelium and corneal stroma.","smad4 is required for the development and maintenance of the lens in addition to the proper development of the cornea, eyelids, and retina.",General
does variability of the be revealed ionization enhancement by bile acid in mouse plasma?,"elevated is response was observed in 22 out of 157 mouse plasma samples in a 3-month toxicity study. this initiated a root cause investigation. mass spectra revealed that taurocholic acid (tca) was present in the samples, partially eluted overlapping the analyte peak. an enhanced is response ( twofold) was reproduced by injecting tca together with the is. tests with five other drug compounds showed compound dependent matrix effects on esi; enhancement as well as suppression. the matrix effects did not affect the integrity of study results, most likely due to the use of a 13c-labeled is.","the variability of tca levels in plasma as well as the observed instability of the chromatographic retention complicates the evaluation of tca-induced matrix effects during method development. thus, monitoring the is response in incurred samples is a useful tool to evaluate the performance of a validated method.",Medication
does single living predict a higher mortality in both women and men with chronic heart failure?,"we examined the impact of single living on all-cause mortality in patients with chronic heart failure and determined if this association was modified by gender. this historical cohort study included 637 patients who were admitted to the department of cardiology, herlev hospital, denmark, between 1 july 2005 and 30 june 2007. baseline clinical data were obtained from patient records. data on survival rates were obtained from the danish civil registration system. cox proportional hazard analysis was used to compute the hazard ratio (hr) of all-cause mortality, controlling for confounding factors. the median follow-up time was 2.8 years. a total of 323 (50.7) patients died during the follow-up period. after adjustment for confounding factors, risk of death was associated with being single (hr 1.53 (95 confidence interval: 1.19-1.96)). in a gender-stratified analysis, the risk of death did not differ among single-living women and men.",single living is a prognostic determinant of all-cause mortality in men and women with chronic heart failure.,General
does intestinal alkaline phosphatase have beneficial effects in mouse models of chronic colitis?,"the brush border enzyme intestinal alkaline phosphatase (iap) functions as a gut mucosal defense factor and is protective against dextran sulfate sodium (dss)-induced acute injury in rats. the present study evaluated the potential therapeutic role for orally administered calf iap (ciap) in two independent mouse models of chronic colitis: 1) dss-induced chronic colitis, and 2) chronic spontaneous colitis in wiskott-aldrich syndrome protein (wasp)-deficient (knockout) mice that is accelerated by irradiation. the wildtype (wt) and iap knockout (iap-ko) mice received four cycles of 2 dss ad libitum for 7 days. each cycle was followed by a 7-day dss-free interval during which mice received either ciap or vehicle in the drinking water. the wasp-ko mice received either vehicle or ciap for 6 weeks beginning on the day of irradiation. microscopic colitis scores of dss-treated iap-ko mice were higher than dss-treated wt mice (523.8 versus 28.86.6, respectively, p0.0001). ciap treatment attenuated the disease in both groups (ko30.76.01, wt18.75.0, p0.05). in irradiated wasp-ko mice ciap also attenuated colitis compared to control groups (3.30.52 versus 6.20.34, respectively, p0.001). tissue myeloperoxidase activity and proinflammatory cytokines were significantly decreased by ciap treatment.",endogenous iap appears to play a role in protecting the host against chronic colitis. orally administered ciap exerts a protective effect in two independent mouse models of chronic colitis and may represent a novel therapy for human ibd.,Treatment
are three single nucleotide variants of the hdac gene associated with type 2 diabetes mellitus in a chinese population : a community-based case-control study?,"there are no data regarding the possible role of the single nucleotide polymorphism (snp) of class i histone deacetylases (hdacs) in type 2 diabetes mellitus (dm). we designed this study to examine whether polymorphisms of hdacs can be implicated in that disease. a community-based, case-control study was conducted, with a total of 568 subjects (284 patients and 284 controls) enrolled. four polymorphisms of hdac1 (rs1741981) and hdac3 (rs11741808, rs2547547, rs2530223) were examined by the use of taqman technology. we found a significant association with risk of type 2 dm for three snps of hdac3, including rs11741808 odds ratio (or)0.53, 95 confidence interval (ci): 0.35-0.81, rs2547547 or1.72, 95 ci: 1.13-2.64, and rs2530223 or1.39; 95 ci: 1.01-1.91. subgroup analysis showed that bmi23kg/m(2), high triglyceride and high blood pressure, together with the rs11741808ag genotype, were associated with a significantly decreased risk for type 2 dm, with ors of 0.50 (95 ci: 0.27-0.91), 0.38 (95 ci: 0.20-0.71) and 0.43 (95 ci: 0.24-0.76) compared with the aa genotype, respectively. in a population with normal total cholesterol, the ag genotype yielded a significantly decreased risk of type 2 dm risk, with an or of 0.42 (95 ci: 0.25-0.70) when compared with the persons of the aa genotype. for rs2547547, in a population with normal total cholesterol and triglyceride, the ag genotype was associated with a significantly increased risk of type 2 dm, with ors of 1.92 (95 ci: 1.17-3.15) and 2.24 (95 ci: 1.28-3.94) when compared with the population carrying the aa genotype.",the results suggest that variants of hdac3 contribute to an increased prevalence of type 2 dm in the chinese han population.,General
is dihydrofolate reductase transcript level suitable for methotrexate-resistance prediction in choriocarcinoma cell line?,"to assess whether dihydrofolate reductase (dhfr) expression is correlated with the concentration of methotrexate (mtx) exposure and the resistance index during the establishment of mtx-resistant human choriocarcinoma jeg-3 cell line. two series of different mtx-resistant jeg-3 sublines were established by intermittent- and consecutive-inducing methods. quantitative real-time reverse transcription polymerase chain reaction was used to measure dhfr messenger rna expression in the sublines during different concentrations of mtx exposure. beta-human chorionic gonadotropin (beta-hcg) secretion in these cell lines were detected by using chemoluminescence method. in the 2 series of mtx-resistant cell lines, the same dynamic profiling of beta-hcg secretion and dhfr transcript level were found: at a certain range of concentration, the upward beta-hcg secretion and the messenger rna level of dhfr were correlated with the dose of mtx exposing. however, once the concentration of mtx exceeded this range, the expression would not increase but decrease sharply. according to the concentration of mtx exposure from low to high, the multiples of beta-hcg increases were 1.86-, 5.15-, 8.38-, 64.17-, 2.6-, and 0.78-fold for intermittent induction and 22.05-, 6.12-, 5.80-, and 1.77-fold for continuous induction; the multiples of dhfr gene expression increases were 12.84-, 99.02-, 129.01-, 177.63-, 420.78-, and 86.09-fold for intermittent induction and 9.59-, 20.56-, 96.05-, and 58.72-fold for continuous induction.",the transcript level of dhfr gene only correlated with mtx drug resistance at a certain phase. it would be of limited use as a biomarker for the mtx-based chemoresistance prediction.,Medication
does low-volume muscle endurance training prevent decrease in muscle oxidative and endurance function during 21-day forearm immobilization?,"to examine the effects of low-volume muscle endurance training on muscle oxidative capacity, endurance and strength of the forearm muscle during 21-day forearm immobilization (imm-21d). the non-dominant arm (n 15) was immobilized for 21 days with a cast and assigned to an immobilization-only group (imm-group; n 7) or an immobilization with training group (immtr-group; n 8). training comprised dynamic handgrip exercise at 30 of pre-intervention maximal voluntary contraction (mvc) at 1 hz until exhaustion, twice a week during the immobilization period. the duration of each exercise session was 51.7 /- 3.4 s (mean /- se). muscle oxidative capacity was evaluated by the time constant for phosphocreatine recovery (tau(off)pcr) after a submaximal handgrip exercise using (31)phosphorus-magnetic resonance spectroscopy. an endurance test was performed at 30 of pre-intervention mvc, at 1 hz, until exhaustion. tau(off)pcr was significantly prolonged in the imm-group after 21 days (42.0 /- 2.8 and 64.2 /- 5.1 s, pre- and post-intervention respectively; p 0.01) but did not change for the immtr-group (50.3 /- 3.0 and 48.8 /- 5.0 s, ns). endurance decreased significantly for the imm-group (55.1 /- 5.1 and 44.7 /- 4.6 s, p 0.05) but did not change for the immtr-group (47.9 /- 3.0 and 51.7 /- 4.0 s, ns). mvc decreased similarly in both groups (p 0.01).","twice-weekly muscle endurance training sessions, each lasting approx. 50 s, effectively prevented a decrease in muscle oxidative capacity and endurance; however, there was no effect on mvc decline with imm-21d.",Prevention
is obesity associated with impaired ventricular protein kinase c-map kinase signaling and altered anp mrna expression in the heart of adult zucker rats?,"in the obesity model of the zucker rat, myocardial protein kinase c (pkc) activation by phorbol ester is impaired. the influence of obesity on myocardial cell signaling was investigated by studying the activation of pkc isozymes and map kinases (mapk) p38 and p42/44 as well as the induction of anp mrna. isolated hearts obtained from 17-week-old lean and obese zucker rats were perfused with 200 nm phorbol 12-myristate 13-acetate (pma) at different time periods. immunodetectable pkc isozymes, phosphorylated-mapk, and anp mrna were determined by western and northern blots, respectively. pma promoted a marked transient translocation of ventricular pkcalpha from the cytosol to the membranes within 10 minutes in lean rats, whereas it had a much weaker effect in obese rats. moreover, pma induced a significant activation of pkcdelta in lean but not in obese rat hearts. after pkc activation, increases in phosphorylation levels of myocardial p38 and p42 mapk were approximately 3-fold higher in lean rats than in obese animals. concerning the induction of anp, pma transiently tripled anp mrna within 60 minutes in lean but not in obese rats.","in the genetically obese zucker rat, the myocardial signal transduction cascade pkc-mapk-anp mrna seems to be markedly impaired. it can be speculated that this abnormal cardiac cell signaling in obese rats reflects an early phase in the cardiac pathogenesis accompanying obesity.",Prevention
does long-term detraining increase the risk of metabolic syndrome in japanese men?,"the aim of the present study was to examine the effect of long-term detraining on metabolic syndrome (mets). 1109 japanese men were categorized by their exercise habits. clinical data, number of mets risk factors, and differences in lifestyle-related behaviors of the non-training group (n 233) and the detraining group (n 483) were compared with those of the training group (n 87). waist circumference and body mass index were significantly higher in the non-training group and the detraining group than in the training group, and also higher in the detraining group than in the non-training group. high-density lipoprotein cholesterol (hdl-c) was lower and low-density lipoprotein cholesterol (ldl-c) was higher in the non-training group and the detraining group than in the training group. both the non-training group and the detraining group had more mets risk factors than the training group. the odds ratio for smoking was higher in the detraining group than in the training group.","detraining results in similar degrees of obesity, low hdl-c, high ldl-c, and high mets risk as non-training. to prevent lifestyle-related diseases, it is particularly important not only to encourage adults to become physically active, but also discourage active young people from discontinuing physical exercise.",Prevention
does insulin treatment improve microalbuminuria and other cardiovascular risk factors in patients with type 2 diabetes mellitus?,"insulin treatment of patients with type 2 diabetes causes hyperinsulinaemia and improves glycaemic control. we have studied how this affects risk factors for cardiovascular disease. patients with secondary failure to oral hypoglycaemic agents were studied whilst still taking oral agents and after insulin treatment for 8 weeks in an open study. department of internal medicine, university hospital, linkping. ten consecutive patients with type 2 diabetes and secondary failure to oral hypoglycaemic agents. switching oral treatment to insulin treatment. effect on several cardiovascular risk factors. fasting and postprandial plasma insulin concentrations were increased by insulin treatment whereas c-peptide concentrations were lowered. hba1c was reduced from 8.9 /- 0.3 (mean /- sem) to 6.3 /- 0.2 after 8 weeks. there was a weight gain of 2.8 /- 0.7 kg. plasma concentrations of total- and very-low-density-lipoprotein (vldl) cholesterol, vldl-, low density lipoprotein and high-density-lipoprotein triglycerides were all reduced. the plasma concentration of apolipoprotein b was also lowered. tissue plasminogen activator antigen measured after venous occlusion showed a significant reduction whilst plasminogen activator inhibitor 1 activity was 26.0 /- 9.8 iu ml-1 on oral treatment and 18.2 /- 4.7 iu ml-1 on insulin treatment (ns). albumin excretion in the urine was reduced and the percentage reduction correlated with the percentage lowering of the tissue plasminogen activator antigen concentration after venous occlusion but not with the percentage change of basal tissue plasminogen activator antigen concentration.",insulin treatment of patients with type 2 diabetes and secondary failure to oral hypoglycaemic agents causes hyperinsulinaemia and improves or has no unfavourable effect on several cardiovascular risk factors.,Medication
is pramipexole a possible effective treatment for primary orthostatic tremor ( shaky leg syndrome )?,"to report the successful treatment of primary orthostatic tremor in a 76-year-old man. primary orthostatic tremor is a rare condition, with few reports describing therapies. established therapies had previously failed in our patient. using an evidence-based evaluation of treatments via medline's grateful med search engine, a therapeutic option was determined during the first consultation with the patient, and pramipexole therapy was initiated. the therapy proved effective, and the patient had relief from his symptoms for the first time in 6 years.",pramipexole is a potential therapy for primary orthostatic tremor. arch neurol. 2000;57:1519-1520,Treatment
does pathology analysis reveal that dysplastic pancreatic ductal lesions are frequent in patients with hereditary pancreatitis?,"hereditary pancreatitis (hp) is a risk factor for pancreatic adenocarcinoma. we performed a retrospective, multicenter study to characterize and evaluate the frequency of pancreatic intraepithelial neoplasia (panin) and to describe the characteristics of fibrosis in pancreatic surgical specimens from patients with hp. samples from partial pancreatectomies (n 13) of patients with hp complications (n 12; 7 males; mean age, 24 y; 1 patient underwent 2 surgeries over 16 years) were analyzed by histologic and immunohistologic analyses; patients with suspected or proven pancreatic adenocarcinoma were excluded. hp diagnosis was confirmed by analysis of prss1 mutations. dysplastic lesions were described according to the panin classification. eleven patients were found to have the r122h mutation in prss1 and 1 patient was found to have the n29i mutation in prss1. fifty-one panin lesions were observed in 10 specimens (77): panin lesions 1a, 1b, 2, and 3 were observed in 8, 5, 8, and 5 specimens, respectively. the median number of panin lesions was 3.5 for each specimen. the density of the lesions was 2.6 per 10 cm(2). the size of lesions was greater than 0.5 mm in 55 of the samples. two patients with panin-3 developed pancreatic cancer, 18 months and 44 years after surgery.","panin lesions are frequent, severe, and occur early in the course of hp. among patients with panins, 50 had panin-3 lesions. pancreatectomy could be considered as a prophylactic against pancreatic cancer in patients with high-grade dysplasia.",Treatment
does the culture site of the gallbladder affect recovery of bacteria in symptomatic cholelithiasis?,"traditional methods for bile culturing may miss a large number of underlying bacterial infections that could lead to acute or chronic cholecystitis. to evaluate possible differences regarding the site of material collection and thus to detect the most suitable sample site for gallbladder culture. a cohort of 137 patients with symptomatic cholelithiasis was enrolled. after surgical excision of the gallbladder, bile cultures were separately performed from fundus, body and neck. identification of bacteria as well as computation of mean bacterial concentrations were performed with standard microbiological techniques. wilcoxon's paired and chi-square tests were used for comparison between continuous and discrete parameters, respectively. thirty-one patients (22.6) demonstrated at least one positive culture sample. positivity was 31/31 (100.0) in neck samples, 20/31 (64.5) in body and 13/31 (41.9) in fundus samples (p0.001). the microorganisms identified were escherichia coli (14 cases) and enterococcus faecalis (10 cases), followed by staphylococcus aureus (3 cases), pseudomonas aeruginosa, enterococcus faecium, enterobacter aerogenes and enterobacter cloacae (1 case each). mean bacterial concentrations in positive samples derived from the neck (272.2 /- 187.5) were higher (p0.01) when compared to those derived from both the body (38.2 /- 28.7) and the fundus (12.5 /- 11.3). mean bacterial concentrations in positive samples derived from the body were higher (p0.01) than those derived from the fundus.","the neck of the gallbladder hosts the biggest bacterial load in comparison with the body and the fundus. this difference might be attributed to the presence of rokitansky-aschoff sinuses, which is the main histological characteristic of the region.",Symptoms
is current smoking associated with incident ankylosing spondylitis -- the hunt population-based norwegian health study?,"smoking contributes to progression of ankylosing spondylitis (as). because smoking is also a risk factor for incident rheumatoid arthritis (ra) and psoriatic arthritis, our aim was to test whether smoking habits are associated with incident as. using data from the hunt health study of the entire adult population of nord-trndelag, norway, participants in hunt2 (1995-1997) and hunt3 (2006-2008) were identified who reported a diagnosis of as in hunt3 but not in hunt2 (n 107). incident as cases were compared with as-unaffected individuals (n 35,278) in a case-control design. participants with ra were excluded. present smoking was significantly associated with incident self-reported as in logistic regression adjusted for potential confounders (or 1.99, 95 ci 1.28-3.11, p 0.002). previous smoking (or 1.15, 95 ci 0.66-2.02, p 0.62) or total pack-years at hunt2 (or 1.01, 95 ci 0.99-1.04, p 0.21) were not significant. the association with present smoking remained significant in various sensitivity analyses: including only cases with high probability of true as diagnosis (or 1.82, 95 ci 1.03-3.19, p 0.04); including only cases with as reported more than 3-5 years after hunt2 (or 2.34, 95 ci 1.09-5.03, p 0.029), or including only participants genotyped for hla-b27 (94 cases and 859 controls) adjusting for genotype (or 1.79, 95 ci 1.04-2.85, p 0.033). hypertension was also significantly associated with incident as (or from 1.65 to 2.81).","in the hunt population-based study, incident as was associated with current smoking and hypertension. if verified in further studies, this suggests that smoking should be discouraged in those at a higher as risk, e.g., with a family history or carrying hla-b27.",Diagnosis
is cofactor-activated phosphorylation required for inhibition of cortical neuron differentiation by groucho/tle1?,"transcriptional co-repressors of the groucho/transducin-like enhancer of split (gro/tle) family regulate the expression of a variety of genes and are involved in numerous developmental processes in both invertebrate and vertebrate species. more specifically, gro/tle1 participates in mechanisms that inhibit/delay the differentiation of cerebral cortex neural progenitor cells into neurons during mammalian forebrain development. the anti-neurogenic function of gro/tle1 depends on the formation of protein complexes with specific dna-binding transcription factors that engage gro/tle1 through wrp(w/y) sequences. interaction with those transcription partners results in gro/tle1 recruitment to selected dna sites and causes increased gro/tle1 phosphorylation. the physiological significance of the latter event, termed ""cofactor-activated phosphorylation,"" had not been determined. therefore, this study aimed at clarifying the role of cofactor-activated phosphorylation in the anti-neurogenic function of gro/tle1. a combination of site-directed mutagenesis, mass spectrometry, biochemistry, primary cell culture, and immunocytochemical assays was utilized to characterize point mutations of ser-286, a residue that is phosphorylated in vivo and is located within the serine/proline-rich (sp) domain of gro/tle1. mutation of ser-286 to alanine or glutamic acid does not perturb the interaction of gro/tle1 with dna-binding partners, including the basic helix-loop-helix transcription factor hes1, a prototypical anti-neurogenic wrp(w/y) motif protein. ser-286 mutations do not prevent the recruitment of gro/tle1 to dna, but they impair cofactor-activated phosphorylation and weaken the interaction of gro/tle1 with chromatin. these effects are correlated with an impairment of the anti-neurogenic activity of gro/tle1. similar results were obtained when mutations of ser-289 and ser-298, which are also located within the sp domain of gro/tle1, were analyzed.","based on the positive correlation between gro/tle1 cofactor-activated phosphorylation and ability to inhibit cortical neuron differentiation, we propose that hyperphosphorylation induced by cofactor binding plays a positive role in the regulation of gro/tle1 anti-neurogenic activity.",Prevention
do lysyl oxidase and the lysyl oxidase-like protein modulate odontoblastic differentiation of human dental pulp cells?,"the lysyl oxidase (lox) family is an emerging family of amine oxidases responsible for the formation of collagen fibrils in the extracellular matrix. to date, 5 lox family genes have been identified in humans, encoding lox and lox-like proteins (loxl, loxl2, loxl3, and loxl4). the goal of this study was to evaluate the expression and function of the lox family genes in odontoblastic differentiation of human dental pulp (hdp) cells. expression of the lox family genes was assessed by reverse transcriptase polymerase chain reaction analysis, and the amine oxidase activity of hdp cells was evaluated by peroxidase-coupled fluorometric assays. mineral nodule formation and expression of odontoblastic marker genes were assessed in the presence and absence of specific small interfering rnas (sirnas) of the lox family genes. among the lox family genes, only lox and loxl showed prominent expression during odontoblastic differentiation of hdp cells. suppression of lox and loxl expression by sirna-induced interference substantially decreased the amine oxidase activity of the differentiating hdp cells. furthermore, interference of lox and loxl expression inhibited mineral nodule formation and expression of odontoblastic marker genes during odontoblastic differentiation of hdp cells.",these findings show for the first time that the lox- and loxl-mediated organization of collagen fibrils in extracellular matrices of hdp cells might be an important regulator for odontoblastic differentiation of hdp cells.,Diagnosis
does human growth hormone induce system b transport in short bowel syndrome?,"after massive enterectomy, remnant intestine undergoes compensatory adaptation. a combination of human growth hormone (hgh) and a glutamine-enriched modified diet induces further adaptation in patients with short bowel syndrome (sbs) on long-term total parenteral nutrition. the specific actions of each component, however, are not well-defined. new zealand white rabbits were randomized to control, sham operation, or sbs (70 midjejunoileal resection) groups and treated with either hgh or saline. sodium-dependent uptake of glucose, glutamine, alanine, leucine, and arginine into brush border membrane vesicles was quantitated. serum insulin-like growth factor-i (igf-i) levels were determined by immunoradiometric assay. mucosal mrna expression of igf-i and igf binding protein 4 (igfbp-4) was evaluated by northern blot analysis using rat cdna probes. glutamine and leucine transports were 33 and 39 greater, respectively, in the hgh-treated versus saline-treated sbs group (p 0.05), supporting induction of system b amino acid transport. this upregulation was due, in part, to an 88 increase in glutamine carrier capacity (vmax) with no change in carrier affinity (km). both hgh treatment and sbs increased serum igf-i levels without direct correlation with increased nutrient transport. igfbp-4 mrna expression in small bowel mucosa of saline-treated sbs animals was significantly greater than saline-treated unoperated control values. mucosal igfbp-4 mrna was not significantly altered from control in the other study groups. igf-i mrna expression was not detected in mucosa, but weak hybridization was noted in rabbit liver.","human growth hormone accelerates early adaptation in sbs by upregulation of system b carrier capacity. serum igf-i levels and mucosal igf-i and igfbp-4 mrna expression did not directly correlate with this enhanced nutrient transport, suggesting that hgh might exert its adaptive effects by mechanisms that are independent from the igf system in this model.",Treatment
does peripheral corneal contour measured by topography influence soft toric contact lens fitting success?,"empirical fitting success is important to expanding the soft toric contact lens market. previous study has lead to the hypothesis that lens flexure may alter expected fitting relationships and back vertex power (bvp) in situ. in this study, baseline topographic features as potential variables in predicting soft toric fitting success were analyzed. one-hundred forty-nine eyes were empirically fit with back surface toric soft lenses after placido-based videokeratography was performed. measurements recorded from baseline instantaneous maps included: flat simulated keratometry (sim-k) value (in diopters) and axis, steep sim-k value (in diopters) and axis, eccentricity of the flat meridian, and the form of corneal astigmatism. astigmatism was classified as types i-v based upon differences between central and peripheral corneal toricity. ninety-three of 149 (62.4) eyes were successfully fit empirically with the first trial lens. one-hundred thirty-five of 149 (90.6) eyes were ultimately successful after unsuccessful trial lenses were adjusted and reordered. there were no differences between the empirically fit success and failure groups in instrument reported eccentricity, sim-k values, or sim-k axes (p0.05). of 115 eyes classified for form of corneal astigmatism, 76 (66) were classified with high or irregular peripheral astigmatism (types iv and v). there was a significant association between fitting success and the form of corneal toricity (p0.0327). thirty-nine of 115 (34) eyes were classified as corneal types i-iii (spherical or minimally toric corneal periphery) and were associated with empirical fitting success (p0.0092).","empirical soft toric fitting success can be anticipated in spherical corneas, central astigmatism, or corneas with peripheral toricity which matches the central toricity. however, high and irregular peripheral corneal toricity occurs in the majority of astigmatic patients. corneal topography is a valuable tool to assess peripheral astigmatism which may be one factor influencing unexpected lens performance.",General
do evolutionary pattern of 5'-utr of enteroviruses and primer update for the detection of enteroviral rna in environmental samples?,"to study the recombination events among enterovirus strains and the development of specific primers for the detection of enteroviruses in environmental samples. nucleotide sequence analysis of enteroviruses deposited in the international database genbank (www.ncbi.nlm.nih.gov/genbank) was conducted to develop specific primers for the detection of these viruses. the specificity and sensitivity of the method were tested using coxackievirus b3 strain nancy, environmental isolate of human hepatitis a virus and human rotavirus strain wa. seventy sewage samples were analyzed. enterovirus genome was detected in all positive samples. the genome of enterovirus was not detected in negative samples. the level of detection of these viruses was 10(2) tcid(50)/ml.",the development of new primers is an important issue for the detection of enteroviruses in the environment and the assessment of risk factors to human health.,Diagnosis
does ifi16 induction by glucose restriction in human fibroblasts contribute to autophagy through activation of the atm/ampk/p53 pathway?,"glucose restriction in cells increases the amp/atp ratio (energetic stress), which activates the ampk/p53 pathway. depending upon the energetic stress levels, cells undergo either autophagy or cell death. given that the activated p53 induces the expression of ifi16 protein, we investigated the potential role of the ifi16 protein in glucose restriction-induced responses. we found that glucose restriction or treatment of human diploid fibroblasts (hdfs) with the activators of the ampk/p53 pathway induced the expression of ifi16 protein. the induced levels of ifi16 protein were associated with the induction of autophagy and reduced cell survival. moreover, the increase in the ifi16 protein levels was dependent upon the expression of the functional atm protein kinase. importantly, the knockdown of the ifi16 expression in hdfs inhibited the activation of the atm/ampk/p53 pathway in response to glucose restriction and also increased the survival of hdfs.","our observations demonstrate a role for the ifi16 protein in the energetic stress-induced regulation of autophagy and cell survival. additionally, our findings also indicate that the loss of ifi16 expression, as found in certain cancers, may provide a survival advantage to cancer cells in microenvironments with low glucose levels.",Treatment
does high skp2 expression characterize high-risk neuroblastomas independent of mycn status?,"amplified mycn oncogene defines a subgroup of neuroblastomas with poor outcome. however, a substantial number of mycn single-copy neuroblastomas exhibits an aggressive phenotype similar to that of mycn-amplified neuroblastomas even in the absence of high mycn mrna and/or protein levels. to identify shared molecular mechanisms that mediate the aggressive phenotype in mycn-amplified and single-copy high-risk neuroblastomas, we defined genetic programs evoked by ectopically expressed mycn in vitro and analyzed them in high-risk versus low-risk neuroblastoma tumors (n 49) using cdna microarrays. candidate gene expression was validated in a separate cohort of 117 patients using quantitative pcr, and protein expression was analyzed in neuroblastoma tumors by immunoblotting and immunohistochemistry. we identified a genetic signature characterized by a subset of mycn/myc and e2f targets, including skp2, encoding the f-box protein of the scf(skp2) e3-ligase, to be highly expressed in high-risk neuroblastomas independent of amplified mycn. we validated the findings for skp2 and analyzed its expression in relation to mycn and e2f-1 expression in a separate cohort (n 117) using quantitative pcr. high skp2 expression proved to be a highly significant marker of dire prognosis independent of both mycn status and disease stage, on the basis of multivariate analysis of event-free survival (hazard ratio, 3.54; 95 confidence interval, 1.56-8.00; p 0.002). skp2 protein expression was inversely correlated with expression of p27, the primary target of the scf(skp2) e3-ligase, in neuroblastoma tumors.",skp2 may have a key role in the progression of neuroblastomas and should make an attractive target for therapeutic approaches.,Diagnosis
does simulation-based training improve applied clinical placement of ultrasound-guided piccs?,"skilled placement of peripherally inserted central catheters (picc) has a profound impact on patient well-being and costs of care. the use of ultrasound-guided methods and prescribed training for cannulation skills are evidence-based practice recommendations. the purpose of this study was to compare two methods of picc instruction on the acquisition of applied skills. residents were randomly assigned to one of two groups (n 16/16) of this blind-rater study and were trained to perform ultrasound-guided picc cannulation using either simulation or apprenticeship methods. all residents were assessed placing a picc in applied clinical patient care. residents who completed simulation training had significantly better transfer of skills to applied clinical practice than residents who received apprenticeship training, having better performance ratings on eight of nine procedure-specific task measures (p 0.05) and higher success rates in endpoint picc placement.","these results support the use of prescribed simulation-based training for the acquisition of requisite skills associated with picc placement and expand on similar studies that suggest the advantages of simulation-based training for central line placement. additionally, the data suggest that training using a single simulation model may support the acquisition of both central venous catheterization and picc skills.",Diagnosis
is the functional variant of the inhibitory fcgamma receptor iib ( cd32b ) associated with the rate of radiologic joint damage and dendritic cell function in rheumatoid arthritis?,"fcgamma receptors (fcgammars) recognize immune complexes (ics) and coordinate the immune response by modulating the functions of dendritic cells (dcs). the purpose of this study was to unravel the role of the inhibitory fcgammariib in rheumatoid arthritis (ra) by studying the effect of the fcgr2b 695tc polymorphism on susceptibility to ra, severity of the disease, and dc function. genotyping was performed in ra patients (n 246) and healthy blood donors (n 269). the patients' demographic data, disease severity, and disease progression were assessed over a followup of 6 years. dcs were cultured for flow cytometry to determine the expression of fcgammars. for detection of fcgammariib (cd32b), a unique anti-fcgammariib antibody (2b6-fluorescein isothiocyanate fitc) was used. the capacity for antigen uptake by dcs was studied by assessing the uptake of fitc-labeled ics. levels of cytokine production by dcs were measured during lipopolysaccharide-mediated cell activation in the presence and absence of ics. although no role of the fcgr2b variant in ra susceptibility was demonstrated, this variant was associated with a nearly doubled rate of radiologic joint damage during the first 6 years of ra. multiple regression analysis showed that fcgr2b was by far the strongest predictor of joint damage identified to date. dcs from patients carrying this variant failed to display the inhibitory phenotype normally observed upon ic-mediated triggering of inflammation and displayed diminished fcgammarii-mediated antigen uptake compared with wild-type dcs. however, the levels of fcgammars were not affected, suggesting that the fcgr2b variant alters the function rather than regulation of proteins.","this study is the first to show that a single genetic variant, the fcgr2b 695tc polymorphism, is a critical determinant of disease severity in ra and radically changes dc behavior. our results underscore the key role of dcs in the progression of ra and reveal fcgammariib as an important potential therapeutic target in ra and other autoimmune conditions.",Medication
is worsening lipid profile associated with progression of carotid artery stenosis?,"to determine if uncontrolled hypercholesterolaemia predisposes to progression of carotid artery stenosis. fasting blood samples were collected from 76 patients referred for carotid duplex ultrasound for investigation of transient ischaemic attacks or recent stroke. patients were grouped depending on the severity of the stenosis found. patients on lipid lowering agents were excluded. the data were analysed using one way analysis of variance and the c2 test as appropriate. there were more men in the 70-99 group (15 vs 6, c2 10.6, p 0.001, table i). the total cholesterol was raised in all three groups. patients with carotid stenosis of 70-99 had significantly elevated triglycerides (2.4 mmol vs 1.47 mmol and 1.37 mmol, p 0.003), low hdl (1.14 mmol vs 1.45 mmol and 1.18 mmol, p 0.003) and a higher cholesterol/hdl ratio (5.56 vs 4.29 and 4.71, p 0.014) compared with the other two groups. there was no difference in lipoprotein(a) in the three groups.",increased triglycerides and low hdl cholesterol seen in the 70-99 group suggest that a worsening lipid profile is associated with progression of carotid artery stenosis.,Diagnosis
do ccl2 and ccl5 are novel therapeutic targets for estrogen-dependent breast cancer?,"novel therapeutic targets of estrogen receptor (er)-positive breast cancers are urgently needed because current antiestrogen therapy causes severe adverse effects, nearly 50 of patients are intrinsically resistant, and the majority of recurrences have maintained er expression. we investigated the role of estrogen-dependent chemokine expression and subsequent cancer growth in human tissues and experimental breast cancer models. for in vivo sampling of human chemokines, microdialysis was used in breast cancers of women or normal human breast tissue before and after tamoxifen therapy. estrogen exposure and targeted therapies were assessed in immune competent pymt murine breast cancer, orthotopic human breast cancers in nude mice, cell culture of cancer cells, and freshly isolated human macrophages. cancer cell dissemination was investigated using zebrafish. er() cancers in women produced high levels of extracellular ccl2 and ccl5 in vivo, which was associated with infiltration of tumor-associated macrophages. in experimental breast cancer, estradiol enhanced macrophage influx and angiogenesis through increased release of ccl2, ccl5, and vascular endothelial growth factor. these effects were inhibited by anti-ccl2 or anti-ccl5 therapy, which resulted in potent inhibition of cancer growth. in addition, estradiol induced a protumorigenic activation of the macrophages. in a zebrafish model, macrophages increased cancer cell dissemination via ccl2 and ccl5 in the presence of estradiol, which was inhibited with anti-ccl2 and anti-ccl5 treatment.",our findings shed new light on the mechanisms underlying the progression of er() breast cancer and indicate the potential of novel therapies targeting ccl2 and ccl5 pathways.,Treatment
does learning need analysis -- developing a new tool for general practice training?,"general practice registrars are a diverse group of doctors, each with a unique set of learning needs. this diversity sets training providers the challenge of identifying the learning needs of individual registrars early and then tailoring their educational programs to meet those needs. this article describes the development of a multicomponent learning needs analysis tool designed to better identify registrars' learning needs in both knowledge content and attitudinal areas.",the accurate identification of registrars' individual and common learning needs allows the creation of more appropriate learning plans and the tailoring of shared educational activities to suit both individuals and the group.,General
is the apolipoprotein e epsilon 4 allele associated with increased neuritic plaques and cerebral amyloid angiopathy in alzheimer 's disease and lewy body variant?,"to determine the relationship between apolipoprotein e (apoe) genotype and neuropathologic lesions in alzheimer's disease (ad) and lewy body variant (lbv). retrospective genetic-neuropathologic study of ad and lbv cases. the main neuropathologic outcome measures were modeled as a function of apoe genotype, neuropathologic diagnosis, and gender. age at death and duration of symptom effects were controlled for by ancova. one hundred twenty-seven cases with neuropathologically diagnosed ad (n 84) or lbv (n 43). quantitative scores of neuritic plaques (nps), neurofibrillary tangles (nfts), cerebral amyloid angiopathy (caa) severity, and caa prevalence were averaged across four brain regions: midfrontal, inferior parietal, superior temporal, and hippocampal. the apoe epsilon 4 allele was associated with increased nps within both ad and lbv. the epsilon 4 allele was associated with an increased frequency of caa in the ad and lbv groups combined groups combined and in and in lbv alone. while caa severity and nets were increased in the epsilon 4/4 homozygous case when ad and lbv were combined, there were no significant effects within ad or lbv alone.","the apoe epsilon 4 allele is strongly associated with increased nps, but not neocortical nfts, in both ad and lbv.",Diagnosis
do the nestin-expressing and non-expressing neurons in rat basal forebrain display different electrophysiological properties and project to hippocampus?,"nestin-immunoreactive (nestin-ir) neurons have been identified in the medial septal/diagonal band complex (ms/dbb) of adult rat and human, but the significance of nestin expression in functional neurons is not clear. this study investigated electrophysiological properties and neurochemical phenotypes of nestin-expressing (nestin) neurons using whole-cell recording combined with single-cell rt-pcr to explore the significance of nestin expression in functional ms/dbb neurons. the retrograde labelling and immunofluorescence were used to investigate the nestin neuron related circuit in the septo-hippocampal pathway. the results of single-cell rt-pcr showed that 87.5 (35/40) of nestin cells expressed choline acetyltransferase mrna (chat), only 44.3 (35/79) of chat cells expressed nestin mrna. furthermore, none of the nestin cells expressed glutamic acid decarboxylases 67 (gad(67)) or vesicular glutamate transporters (vglut) mrna. all of the recorded nestin cells were excitable and demonstrated slow-firing properties, which were distinctive from those of gad(67) or vglut mrna-positive neurons. these results show that the ms/dbb cholinergic neurons could be divided into nestin-expressing cholinergic neurons (nechs) and nestin non-expressing cholinergic neurons (nnchs). interestingly, nechs had higher excitability and received stronger spontaneous excitatory synaptic inputs than nnchs. retrograde labelling combined with choline acetyltransferase and nestin immunofluorescence showed that both of the nechs and nnchs projected to hippocampus.",these results suggest that there are two parallel cholinergic septo-hippocampal pathways that may have different functions. the significance of nestin expressing in functional neurons has been discussed.,General
does hepatitis b virus cause mixed cryoglobulinaemia by driving clonal expansion of innate b-cells producing a vh1-69-encoded antibody?,"to investigate the expression of a vh1-69-encoded idiotype, and the phenotypic and functional features of monoclonal b-cells from patients with type ii mixed cryoglobulinaemia (mc) secondary to chronic hepatitis b virus (hbv) infection. b-cell immunophenotype and expression of a vh1-69-encoded idiotype were investigated by flow cytometry. b-cell proliferative responses to stimuli were investigated by the cfse dilution assay. two out of five patients with chronic hbv studied had massive monoclonal expansion of vh1-69-expressing b-cells. these cells had the peculiar cd21(low) phenotype and low responsiveness to stimuli typical of the vh1-69-expressing b-cells commonly expanded in mc secondary to hepatitis c virus (hcv) infection. in both patients, anti-hbv therapy led to the regression of mc and of vh1-69 b-cell expansion.","vh1-69-encoded antibodies are known to preferentially recognise a variety of viral proteins including hcv e2, influenza a virus haemagglutinin and hiv gp41/gp120, and may serve as innate first line antiviral defense. thus, like hcv, hbv may cause mc by protracted antigenic stimulation of vh1-69-expressing b-cells.",Treatment
does transgenic up-regulation of alpha-camkii in forebrain lead to increased anxiety-like behaviors and aggression?,"previous studies have demonstrated essential roles for alpha-calcium/calmodulin-dependent protein kinase ii (alpha-camkii) in learning, memory and long-term potentiation (ltp). however, previous studies have also shown that alpha-camkii (/-) heterozygous knockout mice display a dramatic decrease in anxiety-like and fearful behaviors, and an increase in defensive aggression. these findings indicated that alpha-camkii is important not only for learning and memory but also for emotional behaviors. in this study, to understand the roles of alpha-camkii in emotional behavior, we generated transgenic mice overexpressing alpha-camkii in the forebrain and analyzed their behavioral phenotypes. we generated transgenic mice overexpressing alpha-camkii in the forebrain under the control of the alpha-camkii promoter. in contrast to alpha-camkii (/-) heterozygous knockout mice, alpha-camkii overexpressing mice display an increase in anxiety-like behaviors in open field, elevated zero maze, light-dark transition and social interaction tests, and a decrease in locomotor activity in their home cages and novel environments; these phenotypes were the opposite to those observed in alpha-camkii (/-) heterozygous knockout mice. in addition, similarly with alpha-camkii (/-) heterozygous knockout mice, alpha-camkii overexpressing mice display an increase in aggression. however, in contrast to the increase in defensive aggression observed in alpha-camkii (/-) heterozygous knockout mice, alpha-camkii overexpressing mice display an increase in offensive aggression.","up-regulation of alpha-camkii expression in the forebrain leads to an increase in anxiety-like behaviors and offensive aggression. from the comparisons with previous findings, we suggest that the expression levels of alpha-camkii are associated with the state of emotion; the expression level of alpha-camkii positively correlates with the anxiety state and strongly affects aggressive behavior.",General
do clinical criteria replenish high-sensitive troponin and inflammatory markers in the stratification of patients with suspected acute coronary syndrome?,"in patients with suspected acute coronary syndrome (acs), rapid triage is essential. the aim of this study was to establish a tool for risk prediction of 30-day cardiac events (ce) on admission. 30-day cardiac events (ce) were defined as early coronary revascularization, subsequent myocardial infarction, or cardiovascular death within 30 days. this single-centre, prospective cohort study included 377 consecutive patients presenting to the emergency department with suspected acs and for whom troponin t measurements were requested on clinical grounds. fifteen biomarkers were analyzed in the admission sample, and clinical parameters were assessed by the timi risk score for unstable angina/non-st myocardial infarction and the grace risk score. sixty-nine (18) patients presented with and 308 (82) without st-elevations, respectively. coronary angiography was performed in 165 (44) patients with subsequent percutaneous coronary intervention--accounting for the majority of ce--in 123 (33) patients, respectively. eleven out of 15 biomarkers were elevated in patients with ce compared to those without. high-sensitive troponin t (hs-ctnt) was the best univariate biomarker to predict ce in non-st-elevation patients (auc 0.80), but did not yield incremental information above clinical timi risk score (auc 0.80 vs 0.82, p 0.69). equivalence testing of aucs of risk models and non-inferiority testing demonstrated that the clinical timi risk score alone was non-inferior to its combination with hs-ctnt in predicting ce.","in patients presenting without st-elevations, identification of those prone to ce is best based on clinical assessment based on timi risk score criteria and hs-ctnt.",Diagnosis
does laparoscopic heller myotomy relieve dysphagia in achalasia when the esophagus is dilated?,"it has been said that a heller myotomy cannot improve dysphagia in achalasia when the esophagus is markedly dilated or sigmoid shaped. those who hold this belief recommend esophagectomy as the primary treatment in such cases. this study aimed to compare the results of laparoscopic heller myotomy combined with dor fundoplication in 66 patients with and without esophageal dilatation, all of whom had achalasia. on the basis of the maximal diameter of the esophageal lumen and the shape of the esophagus, the patients were placed into four groups: group a (esophageal diameter 6.0 cm and straight esophageal axis; 12 patients), and group c2 (diameter 6.0 cm and sigmoid-shaped esophagus; 7 patients). all patients underwent a laparoscopic heller myotomy and dor fundoplication. the duration of the operation and the length of hospital stay were similar among the four groups. excellent or good results were obtained in 88 of group a, 100 of group b, 83 of group c1, and 100 of group c2. no patient in this consecutive series ultimately required an esophagectomy.","in patients with achalasia who have esophageal dilation, a laparoscopic heller myotomy and dor fundoplication (a) took no longer and was no more difficult, (b) was associated with no more postoperative complications, and (c) gave just as good relief of dysphagia. we conclude that esophageal dilation by itself should rarely serve as an indication for esophagectomy rather than myotomy as the initial surgical treatment.",Treatment
is tonsil surface epithelium ideal for monitoring ki-67 immunohistochemical staining?,"to identify an easily obtainable non-neoplastic tissue that can be used as control material for monitoring optimal ki-67 immunohistochemical staining. various tissues, including tonsil (60), uterine cervix (31), breast skin (26), oesophagus (15), stomach (15), small intestine (15) and colon (16), were studied in the search for ideal control tissue. tonsil surface epithelium is superior to other tissues because it displayed an easily recognized ki-67 staining pattern including high positive (parabasal layer), low positive (intermediate layer) and negative (basal and superficial layers) zones. moderate to weak staining of the majority of the intermediate cells could serve as a threshold for positive staining. of the variables potentially affecting staining results that were tested, the pretreatment solution for antigen retrieval had the greatest impact, of which ph 9 edta was far better than ph 6 citrate solution.",tonsil surface epithelium is a useful control for monitoring ki-67 staining. achieving optimal staining results could minimize variations in ki-67 index due to differences in the staining methods used by different laboratories.,General
do fluorescence-expressing viruses allow rapid identification and separation of rare tumor cells in spiked samples of human whole blood?,"finding and isolating rare tumor cells in blood allows for diagnosis of disseminated cancer and for molecular profiling to direct the choice of biologic therapy. we explored whether the candidate gene therapy virus nv1066-designed to specifically infect cancer cells and express green fluorescence protein (gfp)-can be used for rapid infection, identification, and isolation of rare circulating tumor cells (ctc) in human whole blood. mixtures of human cancer cell lines and human whole blood were exposed to nv1066 or heat-inactivated virus, incubated, and then examined for gfp expression by fluorescence microscopy and flow cytometry. fluorescence-assisted cell sorting (facs) was used to determine the efficiency of virally assisted tumor cell isolation. sorted cells were subsequently stained for carcinoembryonic antigen (cea) to determine if cells isolated in this way would maintain sufficient cellular integrity for molecular characterization. in our study, there was 100 specificity for detection of cancer cells. detection was consistent even at the highest dilution tested (10 cancer cells in 10 ml whole blood). the processing involved simple incubation without the technical demands of immunohistochemistry. facs allowed for rapid isolation of gfp-expressing cells. cells isolated by this method can subsequently undergo molecular characterization.","oncolytic herpes simplex virus mediated green fluorescence in combination with facs is a novel technique for the identification and isolation of cancer cells in an experimental model of blood-borne metastases. this procedure is a promising method for improving our diagnosis, staging, and molecular profiling of cancer.",Diagnosis
is management of extensively drug-resistant tuberculosis in peru : cure possible?,"to describe the incidence of extensive drug-resistant tuberculosis (xdr-tb) reported in the peruvian national multidrug-resistant tuberculosis (mdr-tb) registry over a period of more than ten years and present the treatment outcomes for a cohort of these patients. from the peruvian mdr-tb registry we extracted all entries that were approved for second-line anti-tb treatment between january 1997 and june of 2007 and that had drug susceptibility test (dst) results indicating resistance to both rifampicin and isoniazid (i.e. mdr-tb) in addition to results for at least one fluoroquinolone and one second-line injectable (amikacin, capreomycin and kanamycin). of 1,989 confirmed mdr-tb cases with second-line dsts, 119(6.0) xdr-tb cases were detected between january 1997 and june of 2007. lima and its metropolitan area account for 91 of cases, a distribution statistically similar to that of mdr-tb. a total of 43 xdr-tb cases were included in the cohort analysis, 37 of them received itr. of these, 17(46) were cured, 8(22) died and 11(30) either failed or defaulted treatment. of the 14 xdr-tb patients diagnosed as such before itr treatment initiation, 10 (71) were cured and the median conversion time was 2 months.","in the peruvian context, with long experience in treating mdr-tb and low hiv burden, although the overall cure rate was poor, a large proportion of xdr-tb patients can be cured if dst to second-line drugs is performed early and treatment is delivered according to the who guidelines.",Treatment
does a fast track recovery program significantly reduce hospital length of stay following uncomplicated pancreaticoduodenectomy?,"factors affecting length of hospital stay after uncomplicated pancreaticoduodenectomy have not been reported. we hypothesized that patients undergoing uncomplicated pancreaticoduodenectomy treated by fast track recovery program would have a shorter length of hospital stay compared to those managed by a standard program. patients without surgical or medical complications following pancreaticoduodenectomy managed by fast track or standard protocols, between 2005 and 2011, were identified and prognostic predictors for length of hospital stay determined. forty-one patients treated by pancreaticoduodenectomy had no medical or surgical complications during this period. of these patients, 20 underwent fast track recovery program compared to 21 who underwent standard care. patients in the standard group were more likely to have a feeding jejunostomy tube (plt;0.001), pylorus preserving procedure (p0.001) and a nasogastric tube in place longer than 24 hours postoperatively (plt;0.001). the median postoperative length of stay was shorter in the fast track recovery program group (8 days, range: 7-16 days) versus 14 days, range: 8-29 days; plt;0.001). there were three readmissions in the fast track recovery program related to abdominal pain and none in the standard group. the overall length of stay, accounting for readmissions, still remained significantly shorter in the fast track recovery program group (median 9 days, range: 7-17 days versus median14 days, range: 8-29 days ; plt;0.001). there were no significant differences in discharge destination between groups. on multivariate analysis, the only factor independently associated with postoperative discharge by day 8 was fast track recovery program (or: 37.1, 95 ci: 4.08-338; plt;0.001).",fast track recovery program achieved significantly shorter length of stay following uncomplicated pancreaticoduodenectomy.,Treatment
does diacylglycerol kinase inhibit ventricular tachyarrhythmias in a mouse model of heart failure?,"diacylglycerol kinase (dgk) inhibited atrial tachyarrhythmias in a mouse model of heart failure (hf) in our study. however, whether dgk prevents the hf-induced ventricular tachyarrhythmia (vt) is unknown. effects of dgk on vt using transgenic mice with transient cardiac expression of activated g protein (q) (g(q)-tg; model of hf) were elucidated and double transgenic mice with cardiac-specific overexpression of both dgk and the activated g(q) (g(q)/dgk-tg) were used. premature ventricular contraction (pvc) and/or vt were frequently observed in g(q)-tg mice but not in g(q)/dgk-tg and wild-type (wt) mice (p0.01). protein expressions of canonical transient receptor potential (trpc) channels 3 and 6 increased in g(q)-tg hearts compared with wt and g(q)/dgk-tg hearts. skf96365, a trpc channel blocker, decreased the number of pvc and prevented vt in anesthetized g(q)-tg mice (p0.05). 1-oleoyl-2-acyl-sn-glycerol (oag), a diacylglycerol analogue, increased the number of pvc in isolated g(q)-tg hearts compared with wt hearts and induced vt in g(q)-tg hearts (p0.01). skf96365 decreased the number of pvc and prevented vt in isolated g(q)-tg hearts (p0.01) even in the presence of oag. early afterdepolarization (ead)-induced triggered activity was frequently observed in single g(q)-tg ventricular myocytes. moreover, skf96365 prevented the ead.",these results demonstrated that dgk inhibited vt in a mouse model of hf and suggest that trpc channels participate in vt induction in failing hearts.,Medication
does identification of pigment epithelium-derived factor protein form with distinct activities on tumor cell lines?,"pigment epithelium-derived factor (pedf) is a multifunctional serpin. the purpose of this study is to identify pedf protein forms and investigate their biological activities on tumor cell lines. recombinant human pedf proteins were purified by cation- and anion-exchange column chromatography. they were subjected to sds-page, ief, deglycosylation, heparin affinity chromatography, and limited proteolysis. cell viability, real-time electrical impedance of cells, and wound healing assays were performed using bladder and breast cancer cell lines, rat retinal r28, and human arpe-19 cells. two pedf protein peaks were identified after anion-exchange column chromatography: pedf-1 eluting with lower ionic strength than pedf-2. pedf-1 had higher pi value and lower apparent molecular weight than pedf-2. both pedf forms were glycosylated, bound to heparin, and had identical patterns by limited proteolysis. however, pedf-2 emerged as being highly potent in lowering cell viability in all tumor cell lines tested, and in inhibiting tumor and arpe-19 cell migration. in contrast, pedf-1 minimally affected tumor cell viability and cell migration but protected r28 cells against death caused by serum starvation.",two distinct biochemical forms of pedf varying in overall charge have distinct biological effects on tumor cell viability and migration. the existence of pedf forms may explain the multifunctional modality of pedf.,Medication
does chronic ischemia induce regional axonal damage in experimental primate optic neuropathy?,"to evaluate the effects of chronic optic nerve ischemia in a nonhuman primate model and to evaluate the regional variability of axonal loss. unilateral ischemic optic neuropathy was induced by administration of endothelin-1 to the retrobulbar space via osmotic pumps in 12 primates for 6 to 12 months. the transversely cut sections were stained and divided into 16 regions. average axonal density in each region was quantified and compared with the untreated contralateral control eyes. mean axonal density was 208 310/mm(2) and 220 661/mm(2) in treated and control eyes, respectively (p .03, 1-tailed paired t test), for the entire group. two-way analysis of variance showed a significant effect of endothelin-1 on overall axonal density for the experimental group (p.001). among the nerves with significant axonal loss, the mean axonal loss was 11.6 (4-21). regional mapping of the damage showed the axonal loss varied in the damaged nerves; the damaged regions often clustered within specific quadrants.","chronic ischemia induced by local administration of endothelin-1 causes significant loss of optic nerve axons with varying regional susceptibility. clinical relevance localized damage occurs in other types of optic neuropathy, such as glaucoma, and may result from regional differences in anatomy, metabolism, or vasculature of the primate optic nerve.",Treatment
does scar burden by myocardial perfusion imaging predict echocardiographic response to cardiac resynchronization therapy in ischemic cardiomyopathy?,"about 30 of patients with heart failure do not respond to cardiac resynchronization therapy (crt). we hypothesized that scar burden can predict poor response to crt in patients with ischemic cardiomyopathy (icm). fifty patients (age, 68.5 /- 9.2 years; 84 men; mean left ventricular ejection fraction (lvef), 19.7 /- 5.2) with icm who underwent crt-defibrillator implantation and 201tl single photon emission computed tomography myocardial perfusion imaging were included. myocardial perfusion imaging studies were read quantitatively, generating a summed perfusion score (sps). left ventricular (lv) lead position was determined by chest radiography. echocardiograms were performed before and after (median, 11.0 months) crt. echocardiographic response, defined as or 15 relative increase in lvef, was documented in 28 (56) patients. the mean sps (18.8 /- 11.3 vs 33.7 /- 11.1; p .000025) and the average scar density in the segments immediately adjacent to the lv lead (0.70 /- 0.91 vs 1.64 /- 0.82; p .0004) were significantly lower in responders versus nonresponders. global scar burden (r -0.53; p .00007), scar burden near the lv lead (r -0.49; p .0003), and the number of segments with a score of 4 (r -0.53; p .0007) inversely correlated with increase in lvef after crt. the hazard ratio for nonresponse increased with increasing tertiles of global sps, scar density in the vicinity of the lv lead, and number of segments with transmural scar (ie, perfusion score 4).","higher overall scar burden, a larger number of severely scarred segments, and greater scar density near the lv lead tip portend an unfavorable response to crt in icm patients. prospective confirmation of these findings is warranted.",Diagnosis
is increase in maternal adiposity and poor lipid profile associated with oxidative stress markers during pregnancy?,"this study aimed to evaluate changes in maternal adiposity and lipid profile and to correlate these parameters with deoxyribonucleic acid (dna) damage and total antioxidant capacity (tac) levels among pregnant women. this was a longitudinal study which took place in kelantan state, malaysia. fasting blood samples of 159 healthy pregnant women were collected in second and third trimesters from april 2010 until october 2011. maternal total body fat was assessed using bioimpedance analysis method. when compared to data in second trimester, pregnant women in third trimester showed significantly higher levels of total body fat (p0.001), total cholesterol (p0.001), triglyceride (p0.001), ldl-c (p0.001), dna damage (p0.001) and tac (p0.001) but a lower level of hdl-c (p0.001). maternal adiposity and lipid profile were positively and consistently correlated with dna damage in second and third trimesters. significant and positive correlations of triglyceride with tac levels were noted in both periods indicating compensatory action against increased oxidative stress.","normal pregnancy is associated with marked changes in lipid metabolism, prooxidant and antioxidant status. dyslipidemia-associated oxidative stress was demonstrated with advancing gestational age. appropriate preventive and compensatory measures should be practiced to minimize the effect of oxidative stress throughout pregnancy.",Diagnosis
"is congenital cholesteatoma predominantly found in the posterior-superior quadrant in the asian population : systematic review and meta-analysis , including our clinical experience?","the study compares the clinical features of patients with congenital cholesteatoma seen in our institution over the most recent 10 years versus those seen in the previous decade. furthermore, this study includes a systematic review and meta-analysis investigating whether differences in site predilection of congenital cholesteatoma exist between patients from asian and western countries. the retrospective review consisted of 31 cases encountered from 2001 to 2011 as compared with 40 cases previously described. for systematic review, data were retrieved from pubmed, embase, and the japan medical abstracts society database (january 1995 through may 2012). articles addressing site predilection of congenital cholesteatoma were selected with no language preference. the database was searched using the keywords ""congenital cholesteatoma."" after critical review of 408 studies, 27 studies were eligible for quantitative synthesis. a retrospective analysis of our departmental cases showed that more than 70 (8/11) of the potsic's stage i or ii cases had a predilection for the anterior-superior quadrant (asq). none of the stage iii (17) or iv (3) cases had a similar site predilection. consistent with our previous chart review, stage iii was the most common, comprising more than 60 of cases. meta-analysis of the 27 eligible studies provided sufficient information regarding locations of congenital cholesteatoma, and asian studies showed less frequent asq involvement (overall estimate, 0.54; 95 confident interval ci, 0.49-0.59) when compared with western studies (overall estimate, 0.76; 95 ci, 0.73-0.80). moreover, the involvement of posterior-superior quadrant (psq) in asian studies was estimated as 0.69 (95 ci, 0.64-0.73), which was higher than that associated with involvement of asq.","in contrast to western studies, psq was more frequently involved than asq in asian studies of congenital cholesteatoma. the posteriorly located lesions might have a completely distinct pathophysiologic origin when compared with lesions originating from the asq.",General
does inhibition of wnt signaling pathway decrease chemotherapy-resistant side-population colon cancer cells?,"the prognosis of advanced or recurrent colorectal cancer is still poor. dye-effluxing side population (sp) colon cancer cells are reportedly resistant to chemotherapeutic agents. most sporadic colorectal cancers involve constitutive activation of the wnt signaling pathway. in this study, we examined the effect of the wnt signaling on sp cells and the possibility that inhibition of wnt signaling may decrease the resistance to chemotherapeutic drugs in the human colon cancer cells. drug resistance of sp cells to 5-fluorouracil (5-fu) and irinotecan, decrease of sp cells by the wnt signaling inhibition and activation of the wnt signaling of the sorted sp cells were examined using the sw480 colon cancer cell line. mrna expressions of atp-binding cassette (abc) transporters when wnt signaling was inhibited were evaluated with real-time pcr using colon cancer cell lines (sw480, dld-1, hct116, ht29 and lovo). the sensitivity to irinotecan and paclitaxel when the wnt signaling was inhibited was investigated using sw480. inhibition of wnt signaling was performed by sirna of beta-catenin. sp cells showed more resistance to 5-fu and irinotecan, and higher activation of the wnt signaling pathway, than non-sp cells. silencing of beta-catenin decreased significantly more sp cells than non-sp cells. expression of abc transporter genes, such as abcb1 and abcg2, was significantly higher in sp cells than non-sp cells. silencing of beta-catenin decreased transcription of these abc transporter genes; beta-catenin-silenced cells became relatively sensitive to paclitaxel and irinotecan.","these results indicate that inhibiting the wnt signaling pathway may be a fruitful strategy for targeting chemotherapy-resistant colon cancer cells, including sp cells.",Medication
do macrophages contribute to cellular but not humoral mechanisms of acute rejection in rat renal allografts?,"cells of the monocyte/macrophage lineage have been implicated as effectors in acute allograft rejection based on short-term depletion studies. however, the therapeutic potential of targeting monocyte/macrophages in acute rejection is unknown. we investigated the potential of a c-fms kinase inhibitor (fms-i) in acute renal allograft rejection. lewis rats underwent bilateral nephrectomy and received an orthotopic dark agouti renal allograft. recipients received fms-i or vehicle from the time of transplantation until being killed on day 5. vehicle-treated rats developed severe allograft rejection with massive macrophage and t-cell infiltration. in contrast, fms-i substantially inhibited renal allograft dysfunction and structural damage with abrogation of macrophage and dendritic cell infiltration but had only a minor effect on the t-cell infiltrate. however, fms-i suppressed t-cell activation within the allograft, whereas systemic t- and b-cell activation was not affected. in a longer-term study to assess therapeutic potential, fms-i-treated rats developed severe antibody-mediated rejection on day 8 after transplantation. these transplants exhibited features of antibody-mediated rejection including capillaritis with thrombosis, acute tubular injury, igg and c4d deposition, and neutrophil infiltration and activation. interestingly, t-cell activation within these rejecting allografts remained suppressed, indicating separation of t-cell and antibody-mediated rejection.","this study demonstrates the ability of c-fms kinase blockade to selectively deplete monocyte/macrophages in acute allograft rejection, although this did not result in significant prolongation of allograft survival. furthermore, we identify contrasting roles for macrophages in cellular and humoral mechanisms of acute renal allograft rejection.",Treatment
do urat1 gene polymorphisms influence uricosuric action of losartan in hypertensive patients with hyperuricemia?,"to explore the effect of urate transporter 1 (urat1) polymorphisms on the hypertensive patients with hyperuricemia and the uricosuric action of losartan therapy among hypertensive patients with hyperuricemia. 101 hypertensive patients with hyperuricemia were detected the genotypes of urat1 rs1529909 and rs3825016 and undergo a 2-weeks following losartan treatment. before and after treatment, serum uric acid (sua) and other clinical data were compared between different genotypes of urat1 patients. the frequency of rs3825016 (c/t) ct genotype was significant higher in the hypertensive patients with hyperuricemia than that in the healthy controls (32.7 vs 18.8; p 0.02). after lorsatan treatment, the patients with the rs3825016 (c/t) or rs1529909 (t/c) mutant genotypes had lower decreased value (dv) of sua compared with the patients who are wild-type of the variant (p 0.001 and p 0.001, respectively). combined the two variants together, the dv of sua in two variants both wild-type patients higher than that in the two variants mutant patients (p 0.0001).",these results suggest that urat1 rs3825016 and rs1529909 polymorphisms influence the uricosuric action of losartan. original submitted 20 august 2014; revision submitted 15 april 2015.,Treatment
are simple tone discriminations disrupted following experimental frontal traumatic brain injury in rats?,"to assess cognitive deficits in a rat model of brain injury. cognitive deficits are some of the most pervasive and enduring symptoms of frontal traumatic brain injury (tbi) in human patients. in animal models, the assessment of cognitive deficits from tbi has primarily been limited to tests of spatial learning. recently, simple discrimination performance has been shown to be sensitive to frontal brain damage. the current study provides a detailed characterization of deficits in a two-choice tone discrimination following a bilateral frontal controlled cortical impact injury. rats were trained on a two-tone discrimination task in a standard operant chamber, then either a frontal brain injury was delivered or sham procedures performed. following recovery, they were re-tested on the discrimination task and then tested on a reversal of the discrimination. frontal injury caused substantial deficits in responding and discrimination accuracy as well as an increase in side bias.","based on the outcomes seen in this study, discrimination and other operant tasks may provide a sensitive tool to assess the effect of therapeutic agents on cognitive deficits in animal models, which could lead to improved characterization of deficits and yield an improved assessment tool to aid in drug discovery.",Treatment
does vigilin involve in regulation of imprinting gene igf2 and h19 in human hepatocellular carcinoma cell ?,"to explore possible relationship among expression of human high density lipoprotein binding protein(vigilin), h19 and the insulin-like growth factor 2 (igf2) mrna in hepg2 cell cycle and investigate the role of vigilin in controlling imprinting genes of h19 and igf2 mrna expression. we investigated time course cell cycle distribution of hepg2 cells by facs, analyzed vigilin, h19 and igf2 mrna expression at the indicated times using rt-pcr, rnai and real-time pcr. cell-cycle of hepg2 cells was approximately 20 h. 0 h-9 h and 20 h-28 h, 9 h-20 h and 28 h-39 h were s-phase and g2/m-g1-phase, respectively. firstly, cells were synchronized by serum-starvation for 24 h. as expected, vigilin transcription was up-regulated with expression peaks at 20 h and 60 h after serum stimulating by the addition of 10 fetal calf serum. in parallel, h19 mrna had a high expression level at 6 h and 43 h, and igf2 mrna was also increasing with cell-cycle. the expression profiles of human vigilin, h19, and igf2 mrna were ascending with cell-cycle. in addition, the knock-down of vigilin expression by transfecting hepg2 cells with shrna expression plasmid psiren-vig inhibited the expression of human vigilin, which led to the expression of h19 mrna decrease by 12.08, and igf2 mrna increase by 30.13.",the expression of vigilin and h19 mrna was the cell-cycle dependent and had something to do with each other. the results clearly shed light on the roles of vigilin in controlling expression of the imprinted h19 and igf2 genes.,Medication
does use of laboratory test result in patient management by clinicians in malawi?,"malawi has a high burden of infectious disease. the expansion of programmes targeting these diseases requires a strong laboratory infrastructure to support both diagnosis and treatment. to assess the use of laboratory test results in patient management and to determine the requirements for improving laboratory services. a cross-sectional study was conducted in 2012 to survey practising clinicians. two hospitals were purposively selected for observations of clinicians ordering laboratory tests. twelve management-level key informants were interviewed. descriptive statistics were conducted. a total of 242 clinicians were identified and 216 (89) were interviewed. of these, 189 (87) reported doubting laboratory test results at some point. clinicians most often doubted the quality of haematology (67), followed by malaria (53) and cd4 (22) test results. a total of 151 (70) clinicians reported using laboratory tests results in patient management. use of laboratory test results at all times in patient management varied by the type of health facility (","gaps in the public laboratory system were evident. key recommendations to enhance the use of laboratory test results in patient management were to strengthen the supply chain, reduce turn-around times, improve the test menu and improve the laboratory infrastructure.",Treatment
do total phenytoin concentrations accurately predict free phenytoin concentrations in critically ill children?,"to determine the relationship between estimated free, measured free, and measured total phenytoin levels in critically ill pediatric patients, assess the utility of the sheiner-tozer equation in predicting free phenytoin levels, and identify comedications that may influence phenytoin binding or confound attempts to maintain therapeutic concentrations. retrospective chart review. twenty-four-bed medical-surgical pediatric intensive care unit. sixty critically ill pediatric patients receiving phenytoin for treatment of seizures in a large multidisciplinary intensive care unit. the linear correlation between free and total phenytoin concentrations was moderate (r .795), but the mean difference between actual free concentrations and those estimated from total concentrations using the sheiner-tozer equation was -0.31 /- 0.5 microg/ml (95 confidence interval, -1.3 to 0.7). this difference was of concern, as 10 of patients had toxic free levels (2 microg/ml) when simultaneously measured total levels were therapeutic (20 microg/ml). the mean free/total phenytoin ratio was 0.13 /- 0.07 (range, 0.06-0.42) and varied considerably among patients. free fractions were particularly elevated in children whose serum albumin concentrations were 2.5 g/dl (0.22, p .001). however, the relationship between free phenytoin and serum albumin concentration appeared to be nonlinear. coadministration of valproic acid and cefazolin also increased free fraction (p .001).","measured total phenytoin concentrations are unreliable for directing therapy in critically ill children. in part, this is because phenytoin binding shows greater variability in this population than has been reported in adults. this phenomenon is exacerbated by coadministration of other highly protein-bound drugs. instead, free phenytoin concentrations should be routinely measured in critically ill children to prevent possible intoxications and ensure therapeutic dosing. corrections using the sheiner-tozer equation were unreliable.",Treatment
does motor/prefrontal transcranial direct current stimulation ( tdcs ) following lumbar surgery reduce postoperative analgesia use?,"randomized, controlled pilot trial. the present study is the first randomized, double-blind, sham-controlled pilot clinical trial of transcranial direct current stimulation (tdcs) for pain and patient-controlled analgesia (pca) opioid usage among patients receiving spine surgery. lumbar spinal surgeries are common, and while pain is often a complaint that precedes surgical intervention, the procedures themselves are associated with considerable postoperative pain lasting days to weeks. adequate postoperative pain control is an important factor in determining recovery and new analgesic strategies are needed that can be used adjunctively to existing strategies potentially to reduce reliance on opioid analgesia. several novel brain stimulation technologies including tdcs are beginning to demonstrate promise as treatments for a variety of pain conditions. twenty-seven patients undergoing lumbar spine procedures at medical university of south carolina were randomly assigned to receive four 20-minute sessions of real or sham tdcs during their postsurgical hospital stay. patient-administered hydromorphone usage was tracked along with numeric rating scale pain ratings. the effect of tdcs on the slope of the cumulative pca curve was significant (p 0.001) and tdcs was associated with a 23 reduction in pca usage. in the real tdcs group a 31 reduction was observed in pain-at-its-least ratings from admission to discharge (p 0.027), but no other changes in numeric rating scale pain ratings were significant in either group.","the present pilot trial is the first study to demonstrate an opioid sparing effect of tdcs after spine surgical procedures. although this was a small pilot trial in a heterogeneous sample of spinal surgery patients, a moderate effect-size was observed for tdcs, suggesting that future work in this area is warranted.",Treatment
does surgical time of day affect outcome following hip fracture fixation?,"due to the need for medical optimization and congested operating room schedules, surgical repair is often performed at night. studies have shown that work done at night increases complications. the primary aim of our study is to compare the rates of complications and 30-day mortality between 2 surgical times of day, daytime group (dtg, 07:00-15:59) and nighttime group (ntg, 16:00-06:59). retrospective chart review from 2005 through 2010. level 1 trauma center. 1443 patients with hip fracture, age 50 years with isolated injury and surgical treatment of the fracture. thirty-day mortality and complications: myocardial infarction, cardiac event, stroke, central nervous system event, pneumonia, urinary tract infection, postoperative wound infection, and bleeding requiring transfusion of 3 or more red blood cell units. a total of 859 patients met the inclusion criteria; 668 patients in the dtg and 191 patients in the ntg. the 30-day mortality was 7.8. the complication rate was 28. no difference was found in 30-day mortality or complication rate based on the time of day the surgery was performed (p 1.0 and p .92, respectively). this remained unchanged when controlling for health status and surgical complexity. age (odds ratio 1.03/year), charlson comorbidity index (cci; odds ratio 1.21), and american society of anesthesiologists (asa; odds ratio 1.85) score were predictive of adverse outcomes.","surgical time of day did not affect 30-day mortality or total number of complications. age, asa score, and cci were associated with adverse outcomes.",Treatment
does s100a4 silencing block invasive ability of esophageal squamous cell carcinoma cells?,"to investigate a potential role of s100a4 in esophagus squamous cell carcinoma metastasis (esccs). expression of s100a4 and e-cadherin were analyzed in frozen sections from esccs (metastasis, n 28; non-metastasis, n 20) by reverse transcription-polymerase chain reaction, quantitative polymerase chain reaction and immunohistochemistry. to explore the influence of s100a4 on esophageal cancer invasion and metastasis, s100a4 was overexpressed or silenced by s100a4 sirna in te-13 or eca-109 cells in vitro and in vivo. we found the mrna and protein levels of s100a4 expression in esccs was significantly upregulated, and more importantly, that expression of s100a4 and e cadherin are strongly negatively correlated in patients who had metastasis. it was indicated that overexpression of s100a4 in te-13 and eca-109 cells downregulates the expression of e-cadherin, leading to increased cell migration in vitro, whereas knockdown of s100a4 inhibited cell migration and upregulation of e-cadherin expression. moreover, the loss of cell metastatic potential was rescued by overexpression of e-cadherin completely. in addition, nude mice inoculated with s100a4 sirna-transfected cells exhibited a significantly decreased invasion ability in vivo.","s100a4 may be involved in escc progression by regulate e-cadherin expression, vector-based rna interference targeting s100a4 is a potential therapeutic method for human escc.",General
do resistance of rumen bacteria murein to bovine gastric lysozyme?,"lysozymes, enzymes mostly associated with defence against bacterial infections, are mureinolytic. ruminants have evolved a gastric c type lysozyme as a digestive enzyme, and profit from digestion of foregut bacteria, after most dietary components, including protein, have been fermented in the rumen. in this work we characterized the biological activities of bovine gastric secretions against membranes, purified murein and bacteria. bovine gastric extract (bge) was active against both g and g- bacteria, but the effect against gram- bacteria was not due to the lysozyme, since purified bgl had only activity against gram bacteria. we were unable to find small pore forming peptides in the bge, and found that the inhibition of gram negative bacteria by bge was due to an artefact caused by acetate. we report for first time the activity of bovine gastric lysozyme (bg lysozyme) against pure bacterial cultures, and the specific resistance of some rumen gram positive strains to bgl.",some gram rumen bacteria showed resistance to abomasum lysozyme. we discuss the implications of this finding in the light of possible practical applications of such a stable antimicrobial peptide.,Prevention
is increased visfatin in hemodialysis patients associated with decreased demands for recombinant human erythropoietin?,"studies detected an association between visfatin and markers of iron metabolism in patients with insulin resistance. in this study, such a relation was evaluated in hemodialysis (hd) patients. also relations between visfatin and hepcidin, demands for recombinant human erythropoietin (rhuepo), inflammation, and situations characterized by insulin resistance were evaluated. after a four-week washout period from iron treatment, 33 hd patients and 20 healthy volunteers enrolled in the study. serum visfatin, hepcidin, and interleukin-6 (il-6) were assessed by means of enzyme-linked immunosorbent assay. hemoglobin, serum iron, ferritin, and transferrin saturation (tsat) were also measured. visfatin was markedly increased in hd patients. visfatin levels did not differ between diabetics and non-diabetics. no relation was detected between visfatin and body mass index or il-6 in hd patients. from the markers of iron metabolism, the hepcidin included, visfatin was related only to tsat. a strong positive relation was revealed between visfatin and hemoglobin, whereas visfatin was inversely related to rhuepo dose. resistance to rhuepo index was inversely and independently of tsat related to visfatin.",visfatin is increased in hd patients and it is associated with decreased demands for rhuepo.,Medication
does peroral cholangioscopy facilitate targeted tissue acquisition in patients with suspected cholangiocarcinoma?,"biliary strictures that are suspicious for cholangiocarcinoma (cca) are commonly encountered in clinical practice in patients with and without primary sclerosing cholangitis (psc). a definitive histologic diagnosis of cca via endoscopic retrograde cholangiography (ercp) is often not obtainable with standard biliary brush cytology. peroral cholangioscopy is an additional tool to help provide a diagnosis of cca in patients with suspicious biliary strictures. aim of the study was to assess the use of peroral cholangioscopy in patients with and without psc and indeterminate biliary strictures. retrospective study. 25 patients were included in the study. all patients underwent ercp with peroral cholangioscopy. tissue samples obtained included routine cytology, fluorescent in-situ hybridization, and cholangioscopic-directed forceps biopsies. the operating characteristics of cholangioscopy to detect malignancy in 18 psc patients with suspected cholangiocarcinoma were a sensitivity of 75, specificity of 55, and a positive predictive value (ppv) of 23, and a negative predictive value of 92. in 7 non-psc patients with suspected cholangiocarcinoma these values sensitivity100, 25, 50, and npv100, respectively. the overall operating characteristics of cholangioscopy to detect malignancy in all 25 patients with suspected cholangiocarcinoma were: sensitivity of 86, specificity of 50, ppv of 32, and npv of 93.",cholangioscopy helps identify sites for tissue acquisition in psc and non-psc patients with biliary strictures suspicious for malignancy.,Diagnosis
does calcitonin gene-related peptide trigger migraine-like attacks in patients with migraine with aura?,"calcitonin gene-related peptide (cgrp) is a key molecule in migraine pathogenesis. intravenous cgrp infusion triggers delayed migraine-like attacks in patients with migraine without aura (mo). in contrast to patients with mo, in prior studies patients with familial hemiplegic migraine (fhm) did not report more migraine-like attacks compared to controls. whether cgrp triggers migraine in patients with typical (non-hemiplegic) migraine with aura is (ma) unknown. in the present study we examined the migraine inducing effect of cgrp infusion in patients suffering from ma and healthy controls. fourteen patients suffering exclusively from migraine with typical aura (ma) and 11 healthy volunteers received a continuous intravenous infusion of 1.5 g/min cgrp over 20 minutes. headache and other migraine symptoms were scored every 10 minutes for one hour and self recorded hourly thereafter and until 13 hours post-infusion. cgrp infusion induced significantly more delayed headaches in ma patients (12 out of 14) than in controls (2 out of 11) (p 0.001). furthermore, significantly more ma patients (57; 8 out of 14) fulfilled criteria for an experimentally induced migraine attack after cgrp than controls (0; 0 out of 11) (p 0.003). four patients (28) reported aura symptoms after cgrp infusion.","cgrp triggered migraine-like attacks without aura in patients suffering exclusively from ma. it also triggered a typical aura in 28 of the patients. these data indicate similar neurobiological pathways responsible for triggering migraine headache in ma and mo patients, and suggest differences between ma/mo and fhm.",Medication
are common heterozygous hemochromatosis gene mutations risk factors for inflammation and fibrosis in chronic hepatitis c?,"chronic hepatitis c is frequently associated with increased hepatic iron stores. it remains controversial whether heterozygous mutations of hemochromatosis genes affect fibrosis progression. therefore our aim was to assess associations between hfe mutations and hepatic inflammation and stage of fibrosis in german hepatitis c patients. liver biopsies from 166 patients were scored for inflammatory activity (a0-4) and hepatic fibrosis (f0-4). gene mutations were determined by lightcycler, restriction fragment length polymorphism analysis, or direct sequencing. the frequencies of common hfe mutations c282y and h63d are 4.2 and 21.3, whereas the recently described s65c substitution and the y250x mutation in the transferrin receptor 2 gene are very rare. in regression analysis, heterozygous carriers of c282y or h63d mutations display significantly (p 0.05) higher inflammatory activities and more advanced fibrosis than patients without mutations. for c282y heterozygous patients, the odds ratios for marked inflammatory activity (a2-4) and advanced liver fibrosis or cirrhosis (f2-4) are 4.9 and 4.6, respectively, compared with patients carrying homozygous wild-type alleles. c282y mutations are associated with significantly (p 0.05) increased serum iron and aminotransferase levels, whereas h63d heterozygotes display higher transferrin saturation, serum iron, and ferritin concentrations compared to wild-type (p 0.01).",common heterozygous hemochromatosis mutations are associated with higher grades of inflammation and more severe hepatic fibrosis. our findings support a role of hfe mutations as primary risk factors for fibrogenesis and disease progression in chronic hepatitis c.,Prevention
do gut microbiota drive the development of neuroinflammatory response in cirrhosis in mice?,"the mechanisms behind the development of hepatic encephalopathy (he) are unclear, although hyperammonemia and systemic inflammation through gut dysbiosis have been proposed. the aim of this work was to define the individual contribution of hyperammonemia and systemic inflammation on neuroinflammation in cirrhosis using germ-free (gf) and conventional mice. gf and conventional c57bl/6 mice were made cirrhotic using ccl4 gavage. these were compared to their noncirrhotic counterparts. intestinal microbiota, systemic and neuroinflammation (including microglial and glial activation), serum ammonia, intestinal glutaminase activity, and cecal glutamine content were compared between groups. gf cirrhotic mice developed similar cirrhotic changes to conventional mice after 4 extra weeks (16 vs. 12 weeks) of ccl4 gavage. gf cirrhotic mice exhibited higher ammonia, compared to gf controls, but this was not associated with systemic or neuroinflammation. ammonia was generated through increased small intestinal glutaminase activity with concomitantly reduced intestinal glutamine levels. however, conventional cirrhotic mice had intestinal dysbiosis as well as systemic inflammation, associated with increased serum ammonia, compared to conventional controls. this was associated with neuroinflammation and glial/microglial activation. correlation network analysis in conventional mice showed significant linkages between systemic/neuroinflammation, intestinal microbiota, and ammonia. specifically beneficial, autochthonous taxa were negatively linked with brain and systemic inflammation, ammonia, and with staphylococcaceae, lactobacillaceae, and streptococcaceae. enterobacteriaceae were positively linked with serum inflammatory cytokines.",gut microbiota changes drive development of neuroinflammatory and systemic inflammatory responses in cirrhotic animals. (hepatology 2016;64:1232-1248).,General
does gamma-aminobutyric acid inhibit synergistic interleukin-6 release but not transcriptional activation in astrocytoma cells?,"a decline in the inhibitory neurotransmitter gamma-aminobutyric acid (gaba) may enhance cytokine release in alzheimer's disease (ad) resulting in neuroinflammation. we investigated the gaba-mediated suppression of the synergistic release of interleukin (il)-6 due to interleukin 1-beta (il-1 beta) and tumor necrosis factor-alpha (tnf-alpha). rat c6 astrocytoma cells were treated with il-1 beta and tnf-alpha in the absence and presence of gaba. activation of p38, degradation of i kappab-alpha and total cellular il-6 were determined by western blot analysis. il-6 release and gene expression were measured by elisa and rt-pcr, respectively. although p38 and nuclear factor (nf)-kappab are essential for the synergistic release of il-6, gaba did not affect either p38 phosphorylation or i kappab-alpha degradation. additionally, gaba suppressed il-6 release but did not alter cytokine-driven synergistic increases in il-6 gene expression. western blot analysis revealed that co-treatments with il-1 beta and tnf-alpha resulted in an increase in intracellular il-6 that was prevented by gaba.",gaba-induced inhibition of il-6 release appears to coincide with a reduction in cellular il-6. the gaba-induced suppression of il-6 release may include inhibition of il-6 gene translation.,Medication
does morning or evening activity improve neuropsychological performance and subjective sleep quality in older adults?,"sleep disturbances and decline in neuropsychological performance are common in older adults. reduced social and physical activity is likely a contributing factor for these age-related changes in sleep and cognition. we previously demonstrated that a program of structured social and physical activity, with 2 daily activity sessions, 1 in the morning and 1 in the evening for a relatively short period of 2 weeks, improved sleep and neuropsychological performance in community-dwelling older adults. the goals of this pilot study were to determine whether a single daily morning or evening activity session for 2 weeks would also improve sleep and neuropsychological function and whether these effects were dependent on the timing of the activity sessions. we compared the effect of morning or evening structured activity sessions in a repeated-measures crossover design. subjective mood, neuropsychological performance tasks, and subjective and objective measures of sleep were assessed at baseline and after the intervention. all procedures took place in the participant's residence. twelve older men and women (74.6 /- 5.5 years of age). subjects participated in 14 days of structured activity sessions in the morning (9:00-10:30 am) or evening (7:00-8:30 pm). sessions consisted of stretching, low-impact aerobics, and game playing. exposure to either morning or evening activity significantly improved performance on a neuropsychological test battery. morning activity sessions increased throughput on 4 of 8 performance tasks, while evening activity sessions improved throughput on 7 of the 8 performance tasks. subjective sleep-quality ratings, measured by the pittsburg sleep quality index, improved following activity sessions in either the morning or the evening. objective measures of sleep did not improve when measured by actigraphy or polysomnography.",these results suggest that short-term exposure to either morning or evening social and physical activity improves objective measures of neuropsychological performance and subjective sleep quality in the elderly. increasing exposure to social and physical activity may be a useful intervention to improve sleep quality and daytime function in older adults.,Treatment
does beclin 1 enhance proteasome inhibition-mediated cytotoxicity of thyroid cancer cells in macroautophagy-independent manner?,"the ubiquitin-proteasome system and macroautophagy are two major pathways for intracellular protein degradation. emerging lines of evidence have shown that blockade of ubiquitin-proteasome system by proteasome inhibitors activates macroautophagy. the purpose of this study was to determine the involvement of autophagy essential gene beclin 1 in cytotoxicity of thyroid cancer cells mediated by proteasome inhibitors. autophagy was measured by acidic-trophic dye staining and egf-lc3 distribution using fluorescence microscopy, as well as lc3-ii transition using western blot. to ascertain the effect of beclin 1, cells were transfected with beclin 1 plasmid or shrna against beclin 1. cell viability and apoptotic cells were measured using mtt assay and flow cytometry, respectively. proteasome inhibitors decreased beclin 1 expression. in addition, treatment with pi3k inhibitors 3-ma or wortmannin, as well as knockdown of beclin 1 expression, was unable to affect autophagic responses mediated by proteasome inhibitors. overexpression of beclin 1 enhanced proteasome inhibitor-mediated cytotoxicity of thyroid cancer cells via suppression of survivin.",proteasome inhibitors cause beclin 1-independent macroautophagic responses of thyroid cancer cells in a beclin 1-independent manner. beclin 1 possesses autophagy-independent antitumoral effects upon exposure of thyroid cancer cells to proteasome inhibitors.,Medication
does cadherin-11 overexpression induce extracellular matrix remodeling and calcification in mature aortic valves?,"calcific aortic valve (aov) disease is a significant clinical problem for which the regulatory mechanisms are poorly understood. enhanced cell-cell adhesion is a common mechanism of cellular aggregation, but its role in calcific lesion formation is not known. cadherin-11 (cad-11) has been associated with lesion formation in vitro, but its function during adult valve homeostasis and pathogenesis is not known. this study aims to elucidate the specific functions of cad-11 and its downstream targets, rhoa and sox9, in extracellular matrix remodeling and aov calcification. we conditionally overexpressed cad-11 in murine heart valves using a novel double-transgenic nfatc1(cre);r26-cad11(tgltg) mouse model. these mice developed hemodynamically significant aortic stenosis with prominent calcific lesions in the aov leaflets. cad-11 overexpression upregulated downstream targets, rhoa and sox9, in the valve interstitial cells, causing calcification and extensive pathogenic extracellular matrix remodeling. aov interstitial cells overexpressing cad-11 in an osteogenic environment in vitro rapidly form calcific nodules analogous to in vivo lesions. molecular analyses revealed upregulation of osteoblastic and myofibroblastic markers. treatment with a rho-associated protein kinase inhibitor attenuated nodule formation, further supporting that cad-11-driven calcification acts through the small gtpase rhoa/rho-associated protein kinase signaling pathway.",this study identifies one of the underlying molecular mechanisms of heart valve calcification and demonstrates that overexpression of cad-11 upregulates rhoa and sox9 to induce calcification and extracellular matrix remodeling in adult aov pathogenesis. the findings provide a potential molecular target for clinical treatment.,Medication
are prospective evaluation of dietary treatment in childhood constipation : high dietary fiber and wheat bran intake associated with constipation amelioration?,"the aim of the study was to evaluate, over 24 months, the intake of dietary fiber (df) and the bowel habit (bh) of constipated children advised a df-rich diet containing wheat bran. bh and dietary data of 28 children with functional constipation defined by the ""boston criteria"" were obtained at visit 1 (v1, n 28) and at 4 follow-up visits (v2-v5, n 80). at each visit the bh was rated bad (worse/unaltered; improved but still complications) or recovery (rec) (improved, no complications; asymptomatic), and a food intake questionnaire was applied. df intake was calculated according to age (year) 5 to 10 g/day and bran intake according to international tables. nonparametric statistics were used. median age (range) was 7.25 years (0.25-15.6 years); 21 children underwent bowel washout (most before v1/v2), and 14 had the last visit at v3/v4. df intake, bran intake, and the bh rate significantly increased at v2 and remained higher than at v1 through v2 to v5. at v1, median df intake was 29.9 below the minimum recommended and at the last visit 49.9 above it. twenty-four children accepted bran at 60 visits, at which median bran intake was 20 g/day and median proportion of df due to bran 26.9. children had significantly higher df and higher bran intake at v2 to v5 at which they had rec than at those at which they presented bad bh. df intake age 10 g/day was associated with bran acceptance and rec. at the last visit 21 children presented rec (75); 20 of them were asymptomatic and 18 were off washout/laxatives.",high df and bran intake are feasible in constipated children and contribute to amelioration of constipation.,Prevention
does ecgonine methyl ester protect against cocaine lethality in mice?,"plasma cholinesterase (pche) metabolizes cocaine to ecgonine methyl ester (eme). limited data demonstrate that eme is a mild vasodilator. exogenous pche protects against cocaine-induced seizures and lethality. it is unclear whether this protective effect results from enhanced degradation of cocaine, the loss of active metabolites (benzoylecgonine, norcocaine), or the production of a beneficial metabolite (eme). this study was designed to further investigate the pharmacologic effects of eme. all experiments used female icr swiss albino mice weighing 20-30 grams. mice were acclimated to 12 h alternating light-dark cycles and given food and water ad libitum. using a randomized, blinded protocol, 80 mice were then pretreated with either ip eme (50 mg/kg) in a 0.9 sodium chloride solution or an equal volume of 0.9 sodium chloride solution as control. five minutes later, all animals received 126 mg/kg of cocaine ip and were observed for seizures and death. fatality was compared using a fisher's exact test, and the time to seizures and death were compared using a mann-whitney u statistic. pretreatment with eme increased survival following cocaine (9/40 vs. 2/40, for eme vs. control, respectively, p0.05), and 4.5 vs. 4.6 min (p0.05) (eme vs. control for seizures and death, respectively).","in this animal model, eme is protective against cocaine lethality. this effect is consistent with the previously described vasodilatory effects of eme. further studies are indicated to determine whether the increase in eme produced by exogenous pche administration contributes to the benefits that occur when pche is given to cocaine-poisoned animals.",Diagnosis
is bisphenol a exposure associated with in vivo estrogenic gene expression in adults?,"bisphenol a (bpa) is a synthetic estrogen commonly used in polycarbonate plastic and resin-lined food and beverage containers. exposure of animal and cell models to doses of bpa below the recommended tolerable daily intake (tdi) of 50 g/kg/day have been shown to alter specific estrogen-responsive gene expression, but this has not previously been shown in humans. we investigated associations between bpa exposure and in vivo estrogenic gene expression in humans. we studied 96 adult men from the inchianti population study and examined in vivo expression of six estrogen receptor, estrogen-related receptor, and androgen receptor genes in peripheral blood leukocytes. the geometric mean urinary bpa concentration was 3.65 ng/ml 95 confidence interval (ci): 3.13, 4.28, giving an estimated mean excretion of 5.84 g/day (95 ci: 5.00, 6.85), significantly below the current tdi. in age-adjusted models, there were positive associations between higher bpa concentrations and higher esr2 estrogen receptor 2 (er beta) expression (unstandardized linear regression coefficient 0.1804; 95 ci: 0.0388, 0.3221; p 0.013) and esrra (estrogen related receptor alpha) expression (coefficient 0.1718; 95 ci: 0.0213, 0.3223; p 0.026): these associations were little changed after adjusting for potential confounders, including obesity, serum lipid concentrations, and white cell subtype percentages. upper-tertile bpa excretors (urinary bpa 4.6 ng/ml) had 65 higher mean esr2 expression than did lower-tertile bpa excretors (0-2.4 ng/ml).","because activation of nuclear-receptor-mediated pathways by bpa is consistently found in laboratory studies, such activation in humans provides evidence that bpa is likely to function as a xenoestrogen in this sample of adults.",Medication
does automated curation of gene name normalization result using the konstanz information miner?,"gene name recognition and normalization is, together with detection of other named entities, a crucial step in biomedical text mining and the underlying basis for development of more advanced techniques like extraction of complex events. while the current state of the art solutions achieve highly promising results on average, performance can drop significantly for specific genes with highly ambiguous synonyms. depending on the topic of interest, this can cause the need for extensive manual curation of such text mining results. our goal was to enhance this curation step based on tools widely used in pharmaceutical industry utilizing the text processing and classification capabilities of the konstanz information miner (knime) along with publicly available sources. f-score achieved on gene specific test corpora for highly ambiguous genes could be improved from values close to zero, due to very low precision, to values 0.9 for several cases. interestingly the presented approach even resulted in an increased f-score for genes showing already good results in initial gene name normalization. for most test cases, we could significantly improve precision, while retaining a high recall.",we could show that knime can be used to assist in manual curation of text mining results containing high numbers of false positive hits. our results also indicate that it could be beneficial for future development in the field of gene name normalization to create gene specific training corpora based on incorrectly identified genes common to current state of the art algorithms.,General
is esophageal dilation for endosonographic evaluation of malignant esophageal strictures safe and effective?,"endoscopic ultrasound (eus) is accepted as the most accurate modality for t- and n-staging of esophageal cancer, but some malignant strictures prevent passage of the echoendoscope beyond the level of the tumor. this incomplete evaluation may decrease staging accuracy. previous studies have yielded conflicting results regarding the safety and efficacy of esophageal dilation for eus. we prospectively evaluated 267 consecutive patients undergoing eus for esophageal carcinoma staging at our institution over a 66-month period to determine the number of patients requiring dilation for eus examination, the success of dilation, safety of dilation, and clinical importance. among 267 endosonographic examinations of the esophagus, 81 (30.3) required dilation to advance the echoendoscope beyond the level of the stricture. after dilation was performed, the echoendoscope could be passed through the stricture in 69 patients (85.2), and in 63 of 67 of the patients dilated to or 14 mm (94.0). no complications have occurred secondary to the dilations performed to permit completion of the endosonographic examination. tumor staging by eus after dilation was t2 (14.8), t3 (56.8), and t4 (21.0), nodal staging n0 (14.6) and n1 (75.3); and m1 (9.9).","we conclude that incremental, stepwise dilation of malignant strictures to 14 mm is safe and effective in permitting echoendoscope passage beyond the stenosis. the presence of a malignant stricture does not seem to diminish the utility of eus staging of esophageal cancer.",Diagnosis
do glucocorticoids inhibit osteocalcin transcription in osteoblasts by suppressing egr2/krox20-binding enhancer?,"glucocorticoids are widely used for the management of rheumatoid arthritis. osteoporosis is a major side effect of glucocorticoid therapy and is attributable to inhibition of bone formation. we developed an osteoblast culture system in which glucocorticoids strongly inhibit development of the osteoblast phenotype, including expression of the bone-specific osteocalcin (oc) gene. using this gene as a model, the goal of this study was to discover glucocorticoid-sensitive transcriptional mechanisms in osteoblasts. dexamethasone (dex; 1 microm) was administered to murine mc3t3-e1 osteoblastic cultures under conditions that inhibit mineralized extracellular matrix formation and oc messenger rna levels by 10-fold. because standard (short-term) transient transfection assays with oc promoter-reporter constructs did not recapitulate the strong dex-mediated repression, mapping of oc negative glucocorticoid response elements (gres) was performed initially by stable transfection and then with long-term transient transfection assays. transcription factor binding to the oc negative gre was studied by electrophoretic mobility shift assays. several-fold repression of oc-luciferase constructs was recapitulated in stable and long-term transient transfection assays, in which the transfected cells were allowed to progress to a sufficiently advanced developmental stage. analysis of a 5' promoter deletion series mapped an oc negative gre to a 15-bp g/c-rich motif (-161/-147) located just upstream of the binding site for the osteoblast master transcription factor runx2. oligonucleotides encompassing this element and mc3t3-e1 cell extracts formed a protein-dna complex that contained an egr/krox family member(s). complex formation was competed by either an oligonucleotide containing 2 consensus egr motifs or by anti-egr2/krox20 antibodies. three copies of this krox-binding element conferred 20-fold transcriptional activation on the 147-bp basal oc promoter in osteoblasts, and the enhancer activity was inhibited by dex. enhancer activity was not observed in 10t1/2 fibroblasts unless these cells were cotransfected with runx2.","an egr2/krox20-binding site located immediately upstream of the runx2 site of the mouse oc promoter was identified as an enhancer in osteoblasts, whose activity is repressed by glucocorticoids. sequence similarity suggests that such a mechanism is likely operative in both murine and human cells. because glucocorticoids inhibit egr2/krox20 expression in osteoblasts, and because trabecular bone formation is arrested in egr2/krox20-knockout mice, the inhibition of egr2/krox20 activity likely contributes to glucocorticoid-induced osteoporosis.",Medication
do low concentrations of 17beta-estradiol protect single cardiac cells against metabolic stress-induced ca2 loading?,"the main objective of the present study was to determine whether low physiological levels of estrogen directly protect cardiac cells against metabolic stress. the beneficial effect of estrogens on the cardiovascular system has been traditionally ascribed to decrease in peripheral vascular resistance and to an antiatherogenic action. whether physiological concentrations of 17beta-estradiol (e2) are also able to protect cardiomyocytes against metabolic insult directly is unknown. isolated ventricular cardiomyocytes were loaded with the ca2-sensitive fluorescent dye fluo-3 and imaged by a digital epifluorescence imaging system. in cardiac cells preincubated with hormones and/or drugs for 8 h, metabolic stress was induced by addition and removal of 2,4-dinitrophenol (dnp). in cardiomyocytes, a 3-min-long exposure to chemical hypoxia, followed by reoxygenation, produced intracellular ca2 loading independently of gender (female: 729 /- 88 nmol/liter; male: 778 /- 97 nmol/liter). pretreatment with e2 (10 nmol/liter) significantly reduced the magnitude of hypoxia/reoxygenation-induced ca2 loading in female (e2-treated: 298 /- 39 nmol/liter; untreated: 729 /- 88 nmol/liter), but not in male (e2-treated: 1029 /- 177 nmol/liter; untreated: 778 /- 97 nmol/liter) cardiac cells. the protective action of e2 was not mimicked by the inactive estrogen stereoisomer, 10 nmol/liter 17alpha estradiol (17alpha estradiol-treated: 886 /- 122 nmol/liter; untreated: 729 /- 88 nmol/liter), and was abolished by tamoxifen (1 micromol/liter), which acts as an antagonist of e2 on estrogen receptors (e2 plus tamoxifen-treated: 702 /- 98 nmol/liter; untreated: 729 /- 88 nmol/liter).","in a gender-dependent manner, e2 directly protects cardiac cells against hypoxia-reoxygenation injury through an estrogen receptor-mediated mechanism. such property of e2 may contribute to cardioprotection in the female gender.",Medication
does microrna-138 regulate chemoresistance in human non-small cell lung cancer via epithelial mesenchymal transition?,"down-regulation of mir-138 is observed in a variety of cancers, which suggests that mir-138 may be involved in cancer pathogenesis. our current work aimed to evaluate the effects of mir-138 in adriamycin (adm)-resistant human nsclc cells. cell proliferation was determined by mtt assay. real-time pcr and western blot were performed to detect the mrna and protein expression levels. the target of mir-138 was validated by luciferase activity assay. compared with the chemosensitive parental cells, mir-138 was remarkably decreased in a549/adm and nci-h23/adm cells. ectopic expression of mir-138 sensitized chemoresistant tumor cells to adm administration. in addition, the epithelial-mesenchymal transition (emt) related markers e-cadherin or vimentin was up-regulated or down-regulated upon the overexpression of mir-138 in nsclc cells. further studies identified zinc finger e-box-binding homeobox 2 (zeb2) as the target of mir-138 and up-regulation of mir-138 suppressed the mrna and protein expression of zeb2. notably, luciferase reporter assay confirmed that zeb2 was a direct target of mir-138.","our study demonstrates that mir-138 sensitizes nsclc cells to adm via emt, suggesting that mir-138 might be a potential therapeutic target for drug-resistant nsclc patients.",Diagnosis
is bladder volume at onset of vesicoureteral reflux an independent risk factor for breakthrough febrile urinary tract infection?,"improved identification of children with vesicoureteral reflux at risk for recurrent febrile urinary tract infection may impact management decisions. we hypothesized that reflux occurring earlier during bladder filling increases the duration of exposure of the kidneys to bacteria, and, therefore, increases the risk of pyelonephritis. children with vesicoureteral reflux and detailed voiding cystourethrogram data were identified. bladder volume at onset of reflux was normalized for age. demographics, reflux grade, laterality, presence/absence of bladder-bowel dysfunction and breakthrough febrile urinary tract infections were assessed. median followup was 24 months (iqr 12 to 52). a total of 208 girls and 47 boys were analyzed with a mean sd age at diagnosis of 3.1 2.6 years. on univariate analysis history of febrile urinary tract infection (hr 2.17, 95 ci 1.33-2.85, p 0.01), dilating vesicoureteral reflux (hr 1.6, 95 ci 1.05-2.42, p 0.03) and bladder-bowel dysfunction (hr 1.66, 95 ci 0.99-2.75, p 0.05) were associated with an increased risk of breakthrough febrile urinary tract infection. median bladder volume at onset of reflux in children with breakthrough febrile urinary tract infection was significantly less (33.1) than in those without infection (49.5, p 0.003). reflux onset at 35 predicted bladder capacity or less was associated with a significantly increased risk of breakthrough febrile urinary tract infection on multivariate analysis (hr 1.58, 95 ci 1.05-2.38, p 0.03).","children with early filling vesicoureteral reflux are at increased risk for breakthrough febrile urinary tract infection independent of reflux grade. bladder volume at onset of reflux should be recorded during cystograms since it provides additional prognostic information about the risk of pyelonephritis and resolution, and may assist with counseling and clinical decision making.",Prevention
are plasma micrornas associated with atrial fibrillation and change after catheter ablation ( the mirhythm study )?,"micrornas (mirnas) are associated with cardiovascular disease and control gene expression and are detectable in the circulation. the purpose of this study was to test the hypothesis that circulating mirnas may be associated with atrial fibrillation (af). using a prospective study design powered to detect subtle differences in mirnas, we quantified plasma expression of 86 mirnas by high-throughput quantitative reverse transcriptase-polymerase chain reaction in 112 participants with af and 99 without af. to examine parallels between cardiac and plasma mirna profiles, we quantified atrial tissue and plasma mirna expression using quantitative reverse transcriptase-polymerase chain reaction in 31 participants undergoing surgery. we also explored the hypothesis that lower af burden after ablation would be reflected in the circulating blood pool by examining change in plasma mirnas after af ablation (n 47). mean age of the cohort was 59 years; 58 of participants were men. plasma mirs-21 and 150 were 2-fold lower in participants with af than in those without af after adjustment (p .0006). plasma levels of mirs-21 and 150 also were lower in participants with paroxysmal af than in those with persistent af (p .05). expression of mir-21, but not of mir-150, was lower in atrial tissue from patients with af than in those without af (p .05). plasma levels of mirs-21 and 150 increased 3-fold after af ablation (p .0006).","cardiac mirs-21 and 150 are known to regulate genes implicated in atrial remodeling. our findings show associations between plasma mirs-21 and 150 and af, suggesting that circulating mirnas can provide insights into cardiac gene regulation.",Treatment
does more than one in two venous thromboembolism treated in french hospitals occur during the hospital stays?,"the objective was to describe the prevalence of venous thromboembolism, pulmonary embolism, and deep vein thrombosis among hospitalized patients and the percentages of those occurring during the hospital stays. french drg gave now the opportunity to investigate the frequency of venous thromboembolism occurring during the hospital stay. statistics are issued from the national pmsi mco databases encoded using the cim10. since 2010-2011 it is possible to differentiate the reason for hospital admission from the pathologies which secondly occurred. any stay with the icd-10 codes selected was considered as a hospital-occurred thrombosis unless it was the principal diagnosis of the first medical unit summary. to eliminate outpatient consultations or in day care, stays of 48 h were excluded. the results pertain to the 78,838,983 hospitalizations in france from 2005 to 2011 and on the 18,683,603 hospital stays in 2010-2011. the incidence of hospital stays came to 860,343 (1.09) for venous thromboembolism, with 428,261 (0.543) for deep vein thrombosis without pulmonary embolism and 432,082 (0.548) for pulmonary embolism. it corresponds to an incidence of 189 per 100,000 inhabitants. out of 100 hospital stays involving venous thromboembolism, for 40.3 venous thromboembolism was the cause of hospitalization whereas 59.7 can be considered to have occurred during hospital stay. these distributions are of 25.6 and 74.4 for deep vein thrombosis, respectively, 53.8 and 46.2 for pulmonary embolism.",the high proportion of hospital-occurred venous thromboembolism is an alarming situation that should question the quality of prevention and/or its effectiveness.,Treatment
does hepatic organic anion transporting polypeptide transporter and thyroid hormone receptor interplay determine cholesterol and glucose homeostasis?,"the role of organic anion transporting polypeptides (oatps), particularly the members of oatp1b subfamily, in hepatocellular handling of endogenous and exogenous compounds is an important and emerging area of research. using a mouse model lacking slco1b2, the murine ortholog of the oatp1b subfamily, we have demonstrated previously that genetic ablation causes reduced hepatic clearance capacity for substrates. in this study, we focused on the physiological function of the hepatic oatp1b transporters. first, we studied the influence of the oatp1b2 deletion on bile acid (ba) metabolism, showing that lack of the transporter results in a significantly reduced expression of cyp7a1, the key enzyme of ba synthesis, resulting in elevated cholesterol levels after high dietary fat challenge. furthermore, slco1b2-/- mice exhibited delayed clearance after oral glucose challenge resulting from reduced hepatic glucose uptake. in addition to increased hepatic glycogen content, slco1b2-/- mice exhibited reduced glucose output after pyruvate challenge. this is in accordance with reduced hepatic expression of phosphoenolpyruvate carboxykinase (pepck) in knockout mice. we show that this phenotype is due to the loss of liver-specific oatp1b2-mediated hepatocellular thyroid hormone entry, which then leads to reduced transcriptional activation of target genes of hepatic thyroid hormone receptor (tr), including cyp7a1 and pepck but also dio1 and glut2. importantly, we assessed human relevance using a cohort of archived human livers in which oatp1b1 expression was noted to be highly associated with tr target genes, especially for glucose facilitating transporter 2 (glut2). furthermore, glut2 expression was significantly decreased in livers harboring a common genetic polymorphism in slco1b1.",our findings reveal that oatp1b-mediated hepatic thyroid hormone entry is a key determinant of cholesterol and glucose homeostasis.,Medication
"is bulky disease an adverse prognostic factor in patients treated with chemotherapy comprised of cyclophosphamide , doxorubicin , vincristine , and prednisone with or without radiotherapy for aggressive lymphoma?","in the current study, the authors analyzed prognostic factors in patients with aggressive lymphoma treated with a chemotherapy regimen comprised of cyclophosphamide, doxorubicin, vincristine, and prednisone (chop) with or without radiotherapy. between september 1988 and december 1996, 294 patients with newly diagnosed, clinical ann arbor stage i-iv, aggressive lymphoma were enrolled on 2 protocols at the university of texas m. d. anderson cancer center. patients on these studies had a relatively favorable prognosis; 100 had m. d. anderson tumor scores 1 extranodal site of disease (p or 7 cm) (p 0.005), and an at least 10 elevation in the serum lactate dehydrogenase (ldh) level (p 0.007). patient age 60 years (p 0.001), bulky disease (p 0.016), and an at least 10 elevation in the serum ldh level (p 0.040) also were found to be independent prognostic factors for overall survival.",the independent prognostic factors in the current study suggest that either the m. d. anderson tumor score system or the ipi can be used to select which aggressive lymphoma patients are at high risk for disease recurrence based on their having more than two adverse factors and who consequently are candidates for more intensive frontline therapy. involved-field radiotherapy should be considered in those patients with bulky lymphomas.,Treatment
does platelet-riched plasma promote potential mineralizing capacity of human dental pulp cells in vivo ?,"to investigate the biocompatibility of human platelet-rich plasma (prp) and human dental pulp cells (dpcs), and the effect of human platelet-rich plasma on the mineralization of human dental pulp cells in vivo. dpcs were isolated from healthy dental pulp, and identified by immunostaining of vimentin and cytokeratin. prp was obtained from healthy volunteer donors by traditional two-step centrifugation. the forth passage of dpcs and prp were mixed well and activated, and then transplanted subcutaneously in 5-week female nude mice. the groups which were implanted with prp alone or dpcs alone were used as controls. the animals were sacrificed after 4 weeks and 8 weeks post-transplantation, and the histological and immunohistostaining examinations were used to evaluate the effect of prp on the mineralization of dpcs. immunostaining showed that dpcs were positive for vimentin and negative for cytokeratin. in vivo assay showed that the newly formed mineralized tissues were only found in prp combined with dpcs group after 4 weeks and 8 weeks, while newly formed tissues were not observed in prp alone or dpcs alone groups. he staining showed the mineralized tissues were found in prpdpcs samples. immunohistochemistry staining showed these mineralized tissues were positive for osteopontin(opn), osteocalcin(oc) and collagen i (coli).","prp had good biocompatibility with dpcs, and could induce the mineralization of dpcs. the study suggests that platelet-rich plasma can be used as a scaffold for pulp capping.",Treatment
does calcium supplementation and increase in bone mineral density in children?,"increased dietary intake of calcium during childhood, usually as calcium in milk, is associated with increased bone mass in adulthood; the increase in mass is important in modifying the later risk of fracture. whether the increase is due to the calcium content of milk, however, is not certain. we conducted a three-year, double-blind, placebo-controlled trial of the effect of calcium supplementation (1000 mg of calcium citrate malate per day) on bone mineral density in 70 pairs of identical twins (mean /- sd age, 10 /- 2 years; range, 6 to 14). in each pair, one twin served as a control for the other; 45 pairs completed the study. bone mineral density was measured by photon absorptiometry at two sites in the radius (at base line, six months, and one, two, and three years) and at three sites in the hip and in the spine (at base line and three years). the mean daily calcium intake of the twins given placebo was 908 mg, and that of the twins given calcium supplements was 1612 mg (894 mg from the diet and 718 mg from the supplement). among the 22 twin pairs who were prepubertal throughout the study, the twins given supplements had significantly greater increases in bone mineral density at both radial sites (mean difference in the increase in bone mineral density: midshaft radius, 5.1 percent 95 percent confidence interval, 1.5 to 8.7 percent; distal radius, 3.8 percent 95 percent confidence interval, 1.4 to 6.2 percent) and in the lumbar spine (increase, 2.8 percent 95 percent confidence interval, 1.1 to 4.5 percent) after three years; the differences in the increases at two of three femoral sites approached significance (ward's triangle in the femoral neck, 2.9 percent; greater trochanter, 3.5 percent). among the 23 pairs who went through puberty or were postpubertal, the twins given supplements received no benefit.","in prepubertal children whose average dietary intake of calcium approximated the recommended dietary allowance, calcium supplementation increased the rate of increase in bone mineral density. if the gain persists, peak bone density should be increased and the risk of fracture reduced.",Medication
are histologic atherosclerotic plaque characteristics associated with restenosis rates after endarterectomy of the common and superficial femoral arteries?,"this study assessed the predictive value of histologic plaque characteristics for the occurrence of restenosis after femoral artery endarterectomy. it would be advantageous if patients at increased risk for restenosis after arterial endarterectomy could be identified by histologic characteristics of the dissected plaque. differences in atherosclerotic plaque composition of the carotid artery have been associated with restenosis rates after surgical endarterectomy. however, whether atherosclerotic plaque characteristics are also predictive for restenosis in other vascular territories is unknown. atherosclerotic plaques of 217 patients who underwent a common femoral artery endarterectomy (cfae; n 124) or remote superficial femoral artery endarterectomy (rsfae; n 93) were examined and scored microscopically for the presence of collagen, macrophages, smooth muscle cells, lipid core, intraplaque hemorrhage, and calcifications. the 12-month restenosis rate was assessed using duplex ultrasound imaging (peak systolic velocity psv ratio or2.5). the 1-year restenosis rate was 66 (61 of 93) after rsfae compared to 21 (26 of 124) after cfae. plaque with characteristics of high collagen and smooth muscle cell content were positively associated with the occurrence of restenosis, with odds ratios (ors) of 2.90 (95 confidence interval ci, 1.82-4.68) and 2.20 (1.50-3.20) for superficial femoral artery (sfa) and common femoral artery (cfa), respectively. sfa plaques showed significantly heavier staining for collagen (69 vs 31 for cfa; p .001) and smooth muscle cells (64 vs 36 for cfa; p .001). after multivariate analysis, the operation type (cfae or rsfae), gender, and the presence of collagen were independent predictive variables for restenosis after endarterectomy of the cfa and sfa.","plaque composition of the cfa and sfa differs. furthermore, the dissection of a fibrous collagen-rich plaque is an independent predictive variable for restenosis after endarterectomy of the cfa and sfa.",Treatment
does hypertonic saline attenuate end-organ damage in an experimental model of acute pancreatitis?,"hypertonic saline (hts) has been noted previously to reduce neutrophil activation. the aim of this study was to elucidate the effect of hypertonic resuscitation on the development of end-organ damage in an animal model of pancreatitis. pancreatitis was induced in sprague-dawley rats by intraperitoneal injection of 20 per cent l-arginine. animals were randomized into four groups (each n 8): controls; pancreatitis without intervention; pancreatitis plus intravenous resuscitation with normal saline (0.9 per cent sodium chloride 2 ml/kg) at 24 and 48 h; or hts (7.5 per cent sodium chloride 2 ml/kg) at these time points. pulmonary endothelial leakage was assessed by measurement of lung wet : dry ratios, bronchoalveolar lavage protein and myeloperoxidase activity. animals that received hts showed less pancreatic damage than those resuscitated with normal saline (1.0 versus 3.0; p 0.04). lung injury scores were also significantly diminished in the hts group (1.0 versus 3.5; p 0.03). pulmonary neutrophil sequestration (myeloperoxidase activity 1.80 units/g) and increased endothelial permeability (bronchoalveolar lavage protein content 1287 microgram/ml) were evident in animals resuscitated with normal saline compared with hts (1.22 units/g and 277 microgram/ml respectively; p 0.02).",hts resuscitation results in a significant attenuation of end-organ injury following a systemic inflammatory response to severe pancreatitis.,Medication
does resveratrol inhibit hyperxia-induced cell apoptosis through up-regulating sirt1 expression in hpaecs ?,"to investigate the protection effect of sirtuin 1 (sirt1) agonist resveratrol (res) against the apoptosis of human pulmonary alveolar epithelial cells (hpaecs) induced by hyperxia. the hpaecs in vitro were randomly divided into three groups: control group, hyperxia group, res group. after 24-hour culture, the expressions of caspase-9, x-linked inhibitor of apoptosis protein (xiap), sirt1 proteins were measured by sp immunohistochemistry. the changes of reactive oxygen species (ros) marked with mitosox(tm) and membrane potential marked with jc-1 in mitochondrion were detected by laser scanning confocal microscopy. the expression of sirt1 protein was determined by western blotting, and the change of cell apoptosis rate was analyzed by flow cytometry combined with annexin v-fitc/pi staining. compared with the control group, the expression of caspase-9, the generation of ros in mitochondrion of hpaecs and the cell apoptosis rate increased obviously. the expressions of both xiap and sirt1 and membrane potential decreased evidently in the hyperxia group. compared with the hyperxia group, the expression of caspase-9, the generation of ros in mitochondrion of hpaecs and the cell apoptosis rate went down obviously. the expressions of xiap and sirt1, and the membrane potential went up evidently in the res group.","by up-regulating the expression of sirt1 in of hpaecs and depressing the generation of ros, res inhibits the apoptosis of hpaecs and maintains the cell membrane potential, thus effectively alleviating hyperxia-induced lung injury.",Medication
does interferon-gamma induce caspase-8 in neuroblastomas without affecting methylation of caspase-8 promoter?,"the expression of caspase-8, a cysteine protease that is crucial for the apoptotic cascade, is absent in a high percentage of neuroblastomas, the most frequent extracranial solid tumor of infants and children. resistance of neuroblastomas to death-receptor (eg, tumor necrosis factor alpha (tnf-alpha) receptor)--mediated apoptosis is thought to be caused by loss of caspase-8 expression. gene silencing by hypermethylation of caspase-8 promoter has been proposed for the loss of caspase-8 expression in neuroblastoma cells. to further evaluate the role of caspase-8 in neuroblastoma, we assessed the induction of caspase-8 expression in neuroblastoma cells by treating the cells with a physiologic agent such as interferon-gamma. the authors found that interferon-gamma induces caspase-8 expression in neuroblastoma cells irrespective of the gene silenced by hypermethylation of caspase-8 promoter. the authors show that interferon-gamma also regulates other apoptosis related gene expression. moreover, they show that interferon-gamma treatment in combination with tnf-alpha decreases neuroblastoma cell proliferation.","interferon-gamma induces procaspase-8 expression in neuroblastoma cells, and this induction is not dependent on demethylation of the caspase-8 promoter. therapies aimed at inducing caspase-8 expression by adjunctive treatment, such as interferon-gamma, may increase the effectiveness of current chemotherapeutic regimens.",Medication
does combination of isoliquiritigenin and tumor necrosis factor-related apoptosis-inducing ligand induce apoptosis in colon cancer ht29 cells?,"isoliquiritigenin is a chalcone derivative with potential in cancer chemoprevention. although tumor necrosis factor-related apoptosis-inducing ligand (trail) is a promising anti-cancer agent, some cancer cells are resistant to trail treatment. current studies have tried to overcome trail-resistant cancer cells. here, we show for the first time that isoliquiritigenin overcomes trail resistance in colon cancer ht29 cells. ht29 cells were treated with isoliquiritigenin and/or trail, and apoptosis induction was detected by flow cytometry and fluorescence microscopy. protein expression relating to the trail pathway was analyzed by western blotting. a single treatment with isoliquiritigenin scarcely induced apoptosis in ht29 cells. combined treatment with suboptimal concentrations of isoliquiritigenin and trail markedly induced apoptosis, however. the effect was blocked by a pan-caspase inhibitor and a caspase-3, 8, 9, or 10 inhibitor, suggesting that the combination facilitates caspase-dependent apoptosis. furthermore, the apoptosis induced by isoliquiritigenin and trail was blocked by a dominant negative form of the trail receptor. this result indicates that the combined effect is caused by specific interaction between trail and its receptors. isoliquiritigenin increased the amount of dr5 protein among trail receptors. isoliquiritigenin did not significantly increase levels of the bcl-2 family proteins bcl-2, bcl-xl, and bax.",our results suggest that isoliquiritigenin has the potential to overcome resistance to trail in cancer cells and its chemopreventive effects may depend on trail function.,Medication
does paeonolum protect against mpp ( ) -induced neurotoxicity in zebrafish and pc12 cells?,"parkinson's disease (pd) is the second most common neurodegenerative disease, affecting 2 of the population aged over 65 years old. mitochondrial defects and oxidative stress actively participate in degeneration of dopaminergic (da) neurons in pd. paeonolum, a main component isolated from moutan cortex, has potent antioxidant ability. here, we have examined the effects of paeonolum against mpp()-induced neurotoxicity in zebrafish and pc12 cells. the overall viability and neurodegeneration of da neurons was assessed in etvmat2:green fluorescent protein (gfp) transgenic zebrafish, in which most monoaminergic neurons are labeled by gfp. damage to pc12 cells was measured using a cell viability assay and assessment of nuclear morphology. intracellular reactive oxygen species (ros) and the level of total gsh were assessed. the mitochondrial cell death pathway including mitochondrial membrane potential, cytochrome c release and caspase-3 activity were also examined in pc12 cells. paeonolum protected against mpp()-induced da neurodegeneration and locomotor dysfunction in zebrafish in a concentration-dependent manner. similar neuroprotection was replicated in the pc12 cellular model of mpp() toxicity. paeonolum attenuated mpp()-induced intracellular ros accumulation and restored the level of total gsh in pc12 cells. furthermore, paeonolum significantly inhibited the mitochondrial cell death pathway induced by mpp().","collectively, the present study demonstrates that paeonolum protects zebrafish and pc12 cells against mpp()-induced neurotoxicity.",Medication
is c-reactive protein associated with obstructive sleep apnea independent of visceral obesity?,"obstructive sleep apnea (osa) is associated with adverse cardiovascular outcomes. c-reactive protein (crp) predicts atherosclerotic complications. our study evaluates whether osa is associated with an elevated crp level, after elimination of known confounders including visceral obesity. men without significant chronic medical illness, regular medications, or illness in the preceding 4 weeks were enrolled. subjects with morbid obesity, newly detected high bp, or fasting glucose were excluded. they underwent polysomnography and mri of abdomen to quantify visceral fat volume. high-sensitivity crp levels were measured. 111 men with mean body mass index (bmi) 26.3 /- 3.8 kg/m(2) were evaluated. after adjustment for age, smoking, bmi, waist circumference, and sleep efficiency, crp correlated positively with the apnea-hypopnea index (ahi) r 0.35, p or 15 events/h) in mri visceral fat volume. crp was higher in subjects with moderate-to-severe osa (median, 1.32; 0.45 to 2.34 mg/l) when compared to subjects with no or mild osa (median, 0.54; 0.25 to 0.89 mg/l; p 0.001).","in healthy middle-aged men, elevated crp level is associated with osa independent of visceral obesity.",Prevention
do purple corn anthocyanins retard diabetes-associated glomerulosclerosis in mesangial cells and db/db mice?,"diabetic glomerulosclerosis is the hardening of the renal glomeruli that can lead to kidney failure. in the early stage of glomerulosclerosis occur renal mesangial expansion and renal filtration dysfunction. purple corn has been classified as a functional food and is rich in anthocyanins exerting potential disease-preventive activities. the in vitro study using human renal mesangial cells examined that anthocyanin-rich purple corn butanol fraction (pcb) can attenuate high glucose (hg)-promoted mesangial cell proliferation and matrix accumulation. cells were cultured for 3 days in media containing 33 mm glucose in the presence of 1-20 g/ml pcb. in the in vivo animal study, db/db mice were treated with 10 mg/kg anthocyanin-rich polyphenolic extracts of purple corn (pce) for 8 weeks. hg enhanced mesangial production of the fibrosis biomarkers of collagen iv and connective tissue growth factor (ctgf), which was markedly attenuated by adding pcb. such mesangial fibrosis entailed interleukin-8 activation via eliciting tyk2-stat signaling pathway. pcb dampened hg-promoted mesangial hyperplasia that appeared to be attributed to increased expression of platelet-derived growth factor. the 8-week administration of pce lowered plasma glucose level of db/db mice and ameliorated severe albuminuria. moreover, pce lessened collagen fiber accumulation in kidney glomeruli and ctgf expression via retarding tgf- signaling. protein expressions of nephrin and podocin, key proteins for filtration barrier function of the glomerular capillary wall, were repressed by treating mice with pce.",purple corn may be a potent therapeutic agent for the treatment for diabetes-associated glomerulosclerosis accompanying proteinuria and kidney filtration dysfunction.,Prevention
does a dual tyrosine kinase inhibitor lapatinib suppress overexpression of matrix metallopeptidase 1 ( mmp1 ) in endometrial cancer?,"endometrial cancers have been recently molecularly characterized; amplifications of human epidermal growth factor receptor 2 (her2) were seen in 25 of the serous-like tumors, and mutations in the pi(3)k/akt pathways were seen in 93 of endometrioid tumors. these new findings about endometrial cancer suggest a potential for targeted therapy with lapatinib, a dual inhibitor of epidermal growth factor receptor and her2 tyrosine kinases. however, the clinical efficacy of lapatinib in phase ii clinical trials for the treatment of endometrial cancers was only minimal. in this study, we investigated the signaling changes induced by lapatinib in endometrial cancer, which may improve its therapeutic efficacy in molecularly selected patient groups. we identified one of the final molecular targets of lapatinib to be interstitial collagenase, matrix metallopeptidase 1 (mmp1). lapatinib suppresses mmp1 through egfr and her2, and their downstream erk and akt signaling pathways. we also found that the activating protein-1 binding site of mmp1 promoter is required for its transcriptional activation, which may be unique for endometrial cancers. our results also showed that forced expression of active erk or active akt mutants rescued mmp1 expression from lapatinib suppression, further suggesting the importance of molecular selection to find appropriate patients with endometrial cancer for future clinical trials with any targeted therapies.",mmp1 expression was high in tissues and sera in patients with endometrial cancer. lapatinib inhibited mmp1 via both her2 and egfr signaling pathways. both akt and erk need to be inhibited for efficient mmp1 suppression by lapatinib. activating protein-1 (ap-1) binding site of mmp1 promoter is uniquely required for mmp1 activation in endometrial cancer. suppression of both c-fos and c-jun bound to ap1 binding site is required for lapatinib inhibition.,Medication
does hazelnut-enriched diet improve cardiovascular risk biomarkers beyond a lipid-lowering effect in hypercholesterolemic subjects?,"tree nuts, particularly almonds, walnuts, and pistachios, have been shown to possess cardioprotective effects. however, there is little information on the effects of hazelnut consumption on cardiovascular risk markers. the antiatherogenic effect of hazelnut before and after consumption in hypercholesterolemic subjects was investigated. twenty-one hypercholesterolemic volunteers (18 men and 3 women) were recruited in a double control sandwich model intervention study with a single group and three isoenergetic diet periods. these were control diet i (4 weeks), hazelnut-enriched diet (4 weeks; hazelnut contributing 18-20 of the total daily energy intake), and control diet period ii (4 weeks). the cardiovascular risk biomarkers such as endothelial function, using flow-mediated dilation (fmd) technique, low-density lipoprotein (ldl) oxidation products and inflammatory markers such as high-sensitivity c-reactive protein (hs-crp), soluble intercellular adhesion molecule-1, and soluble vascular cell adhesion molecule-1 (svcam-1) as well as lipids and lipoprotein levels were monitored. consumption of a hazelnut-enriched diet significantly improved fmd (56.6), total cholesterol (-7.8), triacylglycerol (-7.3), ldl-cholesterol (-6.17), and high-density lipoprotein cholesterol (6.07) compared with the control diet i. oxidized-ldl, hs-crp, and svcam-1 levels were significantly lower in the group ingesting a hazelnut-enriched diet compared with the control diets i and ii. modest correlations between svcam-1 and fmd and between svcam-1 and hs-crp were observed (r -0.49, p .025; r 0.66, p .001, respectively).","hazelnut-enriched diets may exert antiatherogenic effect by improving endothelial function, preventing ldl oxidation, and inflammatory markers, in addition to their lipid and lipoprotein-lowering effects. these beneficial effects appeared to be reversible after 4 weeks on a hazelnut-free diet. therefore, hazelnut may be incorporated into daily diet without change in total caloric intake for sustained health benefit.",Diagnosis
do proton pump inhibitors increase risk for clostridium difficile infection in the intensive care unit?,"patients in the intensive care unit (icu) frequently receive proton pump inhibitors (ppis) and have high rates of clostridium difficile infection (cdi). ppis have been associated with cdi in hospitalized patients, but icu patients differ fundamentally from non-icu patients and few studies have focused on ppi use exclusively in the critical care setting. we performed a retrospective cohort study to determine the associations between ppis and health-care facility-onset cdi in the icu. we analyzed data from all adult icu patients at three affiliated hospitals (14 icus) between 2010 and 2013. patients were excluded if they had recent cdi or an icu stay of 3 days. we parsed electronic medical records for icu exposures, focusing on ppis and other potentially modifiable exposures that occurred during icu stays. health-care facility-onset cdi in the icu was defined as a newly positive pcr for the c. difficile toxin b gene from an unformed stool, with subsequent receipt of anti-cdi therapy. we analyzed ppis and other exposures as time-varying covariates and used cox proportional hazards models to adjust for demographics, comorbidities, and other clinical factors. of 18,134 patients who met the criteria for inclusion, 271 (1.5) developed health-care facility-onset cdi in the icu. receipt of antibiotics was the strongest risk factor for cdi (adjusted hr (ahr) 2.79; 95 confidence interval (ci), 1.50-5.19). there was no significant increase in risk for cdi associated with ppis in those who did not receive antibiotics (ahr 1.56; 95 ci, 0.72-3.35), and ppis were actually associated with a decreased risk for cdi in those who received antibiotics (ahr 0.64; 95 ci, 0.48-0.83). there was also no evidence of increased risk for cdi in those who received higher doses of ppis.",exposure to antibiotics was the most important risk factor for health-care facility-onset cdi in the icu. ppis did not increase risk for cdi in the icu regardless of use of antibiotics.,Medication
is autosomal recessive hypophosphataemic rickets with hypercalciuria caused by mutations in the type ii renal sodium/phosphate cotransporter gene?,at present the genetic defect for autosomal recessive and autosomal dominant hypophosphataemic rickets with hypercalciuria (hhrh) is unknown. type ii sodium/phosphate cotransporter (npt2) gene is a serious candidate for being the causative gene in either or both autosomal recessive and autosomal dominant hhrh. in the present study we tested this hypothesis in one autosomal recessive family. the gene structure of human npt2 is known. we tested the complete open reading frame in the affected siblings by polymerase chain reaction in combination with automatic dna sequencing for the presence of mutations. we did not observe disease-causing mutations in the npt2 gene of the affected siblings. a t855c polymorphism resulting in a histidine to arginine transition was present in the open reading frame of npt2. the polymorphism was present in both affected as well as unaffected family members.,the hypothesis that a defect in the npt2 gene could be an underlying cause for autosomal recessive hhrh could not be sustained in our study.,General
are vein resections 3 cm during pancreatectomy associated with poor 1-year patency rates?,"resection of the superior mesenteric vein (smv) and portal vein (pv) involved in pancreatic neoplasms improves the chances of complete tumor removal. no consensus exists, however, on the optimal reconstructive approach, and postoperative venous stenosis in the first 6 months to 1 year can cause patient morbidity. we investigated medium-term patency after direct, end-to-end venous anastomosis and evaluate predictive factors for stenosis or occlusion. we analyzed retrospectively the records of 810 patients who underwent pancreatectomy at our institution from january 2000 through april 2014, and 197 patients who underwent concurrent smv/pv resection were selected. the venous anastomosis was assessed every 4 or 6 months postoperatively by the use of portography with computed tomography. preoperative and intraoperative variables were evaluated for their possible association with the development of severe anastomotic stenosis (70 occlusion). among patients whose cancer did not recur during the 1-year follow-up period, 18 developed severe stenosis. univariate analyses showed that operation time 520 minutes and length of smv/pv resection 31 mm were associated with the development of severe anastomotic stenosis. multivariate analysis showed that length of smv/pv resection 31 mm was among independent predictors of medium-term, severe anastomotic stenosis (hazard ratio, 5.96; 95 confidence interval 1.79-22.69; p .003).","direct end-to-end anastomosis of the pv system is safe and offers patients with periampullary neoplasia improved chances of complete tumor excision. when tension-free anastomosis cannot be guaranteed, generally in cases requiring 31 mm of smv/pv resection, venous autografting may decrease the likelihood of anastomotic stenosis.",Treatment
is the concentration of cyclosporine metabolites significantly lower in kidney transplant recipients with diabetes mellitus?,"diabetes mellitus is prevalent among kidney transplant recipients. the activity of drug metabolizing enzymes or transporters may be altered by diabetes leading to changes in the concentration of parent drug or metabolites. this study was aimed to characterize the effect of diabetes on the concentration of cyclosporine (csa) and metabolites. concentration-time profiles of csa and metabolites (am1, am9, am4n, am1c, am19, and am1c9) were characterized over a 12-hour dosing interval in 10 nondiabetic and 7 diabetic stable kidney transplant recipients. all patients were male, had nonfunctional cyp3a53 genotype, and were on combination therapy with ketoconazole. the average daily dose (sd) of csa was 65 21 and 68 35 mg in nondiabetic and diabetic subjects, respectively (p 0.550). cyclosporine metabolites that involved amino acid 1 (am1, am19, am1c) exhibited significantly lower dose-normalized values of area under the concentration-time curve in patients with diabetes. moreover, during the postabsorption phase (3 hours after dose), metabolite-parent concentration ratios for all metabolites, except am4n, was significantly lower in diabetic patients. the pharmacokinetic parameters of ketoconazole were similar between the 2 groups thus excluding inconsistent ketoconazole exposure as a source of altered csa metabolism.","this study indicates that diabetes mellitus significantly affects the concentration of csa metabolites. because csa is eliminated as metabolites via the biliary route, the decrease in the blood concentration of csa metabolites during postabsorption phase would probably reflect lower hepatic cytochrome p450 3a4 enzyme activity. however, other mechanisms including altered expression of transporters may also play a role. results of cyclosporine therapeutic drug monitoring in diabetic patients must be interpreted with caution when nonspecific assays are used.",Treatment
does a study of medication review to identify drug-related problems of polypharmacy patients in the dutch nursing home setting?,"little is known about the extent of drug-related problems of polypharmacy patients in dutch nursing homes. we investigated the feasibility of teams of hospital pharmacists and nursing home physicians carrying out medication reviews. we aimed to identify the number and nature of drug-related problems of nursing home patients receiving more than nine drugs (polypharmacy). the study was carried out in five dutch nursing homes (n 742 beds) between october 2005 and may 2006. ninety-one polypharmacy patients, (average age 80 years) were included. a medication review was carried out by teams consisting of one hospital pharmacist and the patient's nursing home physician with a follow-up meeting of the same team 6 weeks later. a total of 323 drug-related problems were identified (mean of 3.5 problems per patient). sixty-two per cent of problems, in 87 of patients, were classified as 'unclear or not confirmed indication or need for review' of the prescribed drug. by the time of the follow-up, a mean of 1.7 (n 159) problems per patient had been solved and the number of drugs per patient had decreased significantly from 13.5 to 12.7 (p 0.0001).","the majority of patients had at least one drug prescribed for which the indication was unknown. the intervention was accompanied by a significant decrease in the number of drugs per patient, but half of the drug-related problems remained unsolved.",Medication
does functional mri predict memory performance after right mesiotemporal epilepsy surgery?,"anterior temporal lobe resection (atr) is a treatment option in drug-resistant epilepsy. an important risk of atr is loss of memory because mesiotemporal structures contribute substantially to memory function. we investigated whether memory-activated functional mri (fmri) can predict postoperative memory loss after anterior temporal lobectomy in right-sided medial temporal lobe epilepsy (mtle). we included 16 patients (10 women) aged 16-54 years. the mean age at epilepsy onset was 12.5 years (range, 1-26 years). the patients' mean wechsler iq score was 95.2 (range, 62-125). the activation condition of fmri consisted of retrieval from long-term memory induced by self-paced performance of an imaginative walk. all but one patient had left-sided speech dominance according to speech-activated fmri. outside the scanner, we evaluated the pre- and postoperative visual memory retention by using rey visual design learning test. we found a correlation between the preoperative asymmetry index of memory-fmri and the change between pre- and postsurgical measures of memory retention. reduced activation of the mesiotemporal region ipsilateral to the epileptogenic region correlated with a favorable memory outcome after right-sided atr.","in light of the postoperative results, the theoretical implication of our study is that fmri based on a simple introspective retrieval task measures memory functions. the main clinical implication of our study is that memory-fmri might replace the invasive wada test in mtle by using a simple fmri paradigm. predictive power, however, will be studied in larger patient samples. other studies are required for left-sided mtle and neocortical epilepsies to assess the clinical usefulness of memory-fmri.",Treatment
are idh1 mutations in grade ii astrocytomas associated with unfavorable progression-free survival and prolonged postrecurrence survival?,"the favorable prognostic impact of mutations in the idh1 gene is well documented for malignant gliomas; its influence on world health organization (who) grade ii astrocytomas, however, is still under debate. a previously published database of 127 predominantly surgically treated patients harboring who grade ii astrocytomas was revisited. patients were screened for tp53 mutations (sequencing analysis), idh1 mutations (pyrosequencing), and mgmt promoter methylation (methylation-specific polymerase chain reaction and bisulfite sequencing). endpoints were overall survival, progression-free survival (pfs), time to malignant transformation, and postrecurrence survival. radiotherapy was usually withheld until tumor progression/malignant transformation occurred. idh1 mutations, tp53 mutations, and methylated mgmt promoters were seen in 78.1, 51.2, and 80.0 of the analyzed tumors, respectively. idh1 mutations, which were significantly associated with tp53 mutations and/or mgmt promoter methylation (p .001), resulted in shortened pfs (median, 47 vs 84 months; p .004); postrecurrence survival, however, was significantly increased in those patients undergoing malignant transformation (median, 49 vs 13.5 months; p .006). overall survival was not affected by idh1. a similar pattern of influence was seen for mgmt promoter methylation. methylated tumors did significantly worse (better) in terms of pfs (postrecurrence survival); a low number of unmethylated tumors, however, limited the power of this analysis. conversely, tp53 mutations were stringently associated with a worse prognosis throughout the course of the disease.",idh1 mutations are associated with a janus headlike phenomenon; unfavorable prognostic influence on pfs turns into favorable impact on postrecurrence survival. a similar pattern of influence might exist for mgmt methylation.,Treatment
do nanohybrids of silver particles on clay platelets delaminate pseudomonas biofilms?,"to evaluate the effectiveness of novel nanohybrids, composed of silver nanoparticles and nanoscale silicate platelets, to clear pseudomonas aeruginosa biofilms. the nanohybrids were manufactured from an in situ reduction of silver salts in the silicate platelet dispersion, and then applied to biofilms in vitro and in vivo. in reference to the biocidal effects of gentamycin, the nanohybrids mitigated the spreading of the biofilms, and initiated robust cell death and exfoliation from the superficial layers of the biofilms in vitro. in vivo, the nanohybrids exhibited significant therapeutic effects by eliminating established biofilms from infected corneas and promoting the recovery of corneal integrity.",all of the evaluations indicate the high potency of the newly developed silver nanoparticle/nanoscale silicate platelet nanohybrids for eliminating biofilms.,Treatment
is synthesis of sphingosine essential for oxidative stress-induced apoptosis of photoreceptors?,"oxidative stress is involved in inducing apoptosis of photoreceptors in many retinal neurodegenerative diseases. it has been shown that oxidative stress increases in photoreceptors the synthesis of ceramide, a sphingolipid precursor that then activates apoptosis. in several cell types, ceramide is converted by ceramidases to sphingosine (sph), another apoptosis mediator; hence, this study was undertaken to determine whether sph participates in triggering photoreceptor apoptosis. rat retina neurons were incubated with (3)hpalmitic acid and treated with the oxidant paraquat (pq) to evaluate sph synthesis. sph was added to cultures with or without docosahexaenoic acid (dha), the major retina polyunsaturated fatty acid and a photoreceptor survival factor, to evaluate apoptosis. synthesis of sph and sphingosine-1-phosphate (s1p), a prosurvival signal, were inhibited with alkaline ceramidase or sphingosine kinase inhibitors, respectively, before adding pq, c(2)-ceramide, or sph. apoptosis, mitochondrial membrane polarization, cytochrome c localization, and reactive oxygen species (ros) production were determined. pq increased (3)hsph synthesis in photoreceptors and blocking this synthesis by inhibiting alkaline ceramidase decreased pq-induced apoptosis. addition of sph induced photoreceptor apoptosis, increased ros production, and promoted cytochrome c release from mitochondria. although dha prevented this apoptosis, inhibiting sph conversion to s1p blocked dha protection.","these results suggest that oxidative stress enhances formation of ceramide and its subsequent breakdown to sph; ceramide and/or sph would then trigger photoreceptor apoptosis. preventing sph synthesis or promoting its phosphorylation to s1p rescued photoreceptors, suggesting that sph is a mediator of their apoptosis and modulation of sph metabolism may be crucial for promoting photoreceptor survival.",Medication
is intratumoral expression of macrophage migration inhibitory factor correlated with serum c-reactive protein and interleukin-6 in patients with non-small cell lung cancer?,"to investigate if macrophage migration inhibitory factor (mif) affects systemic inflammatory response in patients with non-small cell lung cancer (nsclc), we studied the relationship between intratumoral mif expression and serum levels of c-reactive protein (crp) and interleukin-6 (il-6). mrnas for mif and beta-actin, and 18s ribosomal rna derived from tumor-bearing and nontumor-bearing tissues were quantified by a quantitative reverse transcription-polymerase chain reaction in 35 patients with nsclc. spearman's test was used to examine the correlation between the quantities of rnas and the preoperative serum levels of crp and il-6 in the corresponding patients. the intratumoral level of mif mrna was significantly correlated with the serum levels of crp (rho 0.542, p 0.0016) and il-6 (rho 0.532, p 0.0173). the level of mif mrna in the non-tumor-bearing lung also showed a positive, but relatively weak correlation with the serum crp level (rho 0.418, p 0.0148).",macrophage migration inhibitory factor expression in the tumor site may affect the systemic inflammatory response in patients with nsclc.,Medication
does nadph oxidase 4 protect against development of endothelial dysfunction and atherosclerosis in ldl receptor deficient mice?,"endothelial dysfunction is an early step in the development of atherosclerosis. increased formation of superoxide anions by nadph oxidase nox1, 2, and 5 reduces nitric oxide availability and can promote endothelial dysfunction. in contrast, recent evidence supports a vasoprotective role of h2o2 produced by main endothelial isoform nox4. therefore, we analysed the impact of genetic deletion of nox4 on endothelial dysfunction and atherosclerosis in the low-density lipoprotein receptor (ldlr) knockout model. ex vivo analysis of endothelial function by mulvany myograph showed impaired endothelial function in thoracic aorta of nox4(-/-)/ldlr(-/-) mice. further progression of endothelial dysfunction due to high-fat diet increased atherosclerotic plaque burden and galectin-3 staining in nox4(-/-)/ldlr(-/-) mice compared with ldlr(-/-) mice. under physiological conditions, loss of nox4 does not influence aortic vascular function. in this setting, loss of nox4-derived h2o2 production could be partially compensated for by nnos upregulation. using an innovative optical coherence tomography approach, we were able to analyse endothelial function by flow-mediated vasodilation in the murine saphenous artery in vivo. this new approach revealed an altered flow-mediated dilation in nox4(-/-) mice, indicating a role for nox4 under physiological conditions in peripheral arteries in vivo.","nox4 plays an important role in maintaining endothelial function under physiological and pathological conditions. loss of nox4-derived h2o2 could be partially compensated for by nnos upregulation, but severe endothelial dysfunction is not reversible. this leads to increased atherosclerosis under atherosclerotic prone conditions.",Medication
do the apolipoprotein b/ai ratio and the metabolic syndrome independently predict risk for myocardial infarction in middle-aged men?,"both the metabolic syndrome and an increased apolipoprotein b/ai (apob/ai) ratio are powerful risk factors for cardiovascular events. we hypothesized that the apob/ai ratio well-characterizes the dyslipidemia associated with insulin resistance and the metabolic syndrome and investigated those relations and if the apob/ai ratio and the metabolic syndrome independently predicted subsequent myocardial infarction (mi). a community-based sample of 1826 men aged 50 was investigated at baseline and again at age 70. apob/ai ratio and the metabolic syndrome (national cholesterol education program definition) were evaluated, and the incidence of fatal and nonfatal mi was followed for a median of 26.8 years from the age 50 baseline. apob/ai ratio was significantly higher in men with versus without the metabolic syndrome (p or 0.9 (hazard ratio hr, 1.48; 95 confidence interval ci, 1.15 to 1.91) and presence of the metabolic syndrome (hr, 1.69; 95 ci, 1.30 to 2.21) at baseline were independent predictors for mi, adjusting for low-density lipoprotein cholesterol and smoking.","the apob/ai ratio was related to the metabolic syndrome, as well as to a direct measurement of insulin resistance. despite this, the apob/ai ratio and the metabolic syndrome were both independent long-term predictors of mi in a community-based sample of middle-aged men.",Medication
does male sex predispose the newborn surgical patient to parenteral nutrition-associated cholestasis and to sepsis?,"sepsis is an epiphenomenon of parenteral nutrition-associated cholestasis (pnac) and not a causative factor, and the incidence of sepsis is not affected by the presence or absence of pnac. observational cohort study. pediatric surgery department in a tertiary referral children's hospital. newborns receiving pn for at least 7 days following intestinal surgery. the criteria for pnac were as follows: pn for at least 14 consecutive days, conjugated bilirubin level greater than 1.5 mg/dl (26 micromol/l), conjugated bilirubin fraction greater than 50, and absence of another identifiable cause of cholestasis. the identification of septic events was based on centers for disease control and prevention criteria. the patients (26 with pnac and 72 without pnac) were well comparable for underlying disease, gestational age, birth weight, and age at the start of pn. time receiving pn and length of hospital stay were significantly (p.001) longer in patients with pnac. parenteral nutrition-associated cholestasis was associated with male sex (p .03; odds ratio, 2.8; 95 confidence interval, 1.1-7.1). the overall sepsis incidence was low (9 per 1000 hospital days). the sepsis incidence tended to be higher in patients with pnac than in patients without pnac (11.8 vs 7.1 per 1000 days; p .08), but was significantly higher in male than in female patients (12.2 vs 5.6 per 1000 days; p .01). most septic events were caused by coagulase-negative staphylococci.","sepsis is an epiphenomenon of pnac rather than a causative factor. moreover, male sex predisposes the newborn surgical patient to pnac and to sepsis.",Prevention
does obesity have no effect on outcomes following unicompartmental knee arthroplasty?,"although obesity has historically been described as a contraindication to uka, improved outcomes with modern uka implant designs have challenged this perception. the purpose of this study was to assess the influence of obesity on the outcomes of uka with a robotic-assisted system at a minimum follow-up of 24 months with the hypothesis that obesity has no effect on robotic-assisted uka outcomes. there were 746 medial robotic-assisted ukas (672 patients) with a mean age of 64 years (sd 11) and a mean follow-up time of 34.6 months (sd 7.8). mean overall body mass index (bmi) was 32.1 kg/m patient bmi did not influence the rate of revision surgery to tka (5.8 ) or conversion from inlay to onlay design (1.7 , n.s.). mean postoperative oxford knee score was 37 (sd 11) without correlation with bmi (n.s.). the type of prosthesis (inlay/onlay) regardless of bmi had no influence on revision rate (n.s.). bmi did not influence 90-day readmissions (4.4 , n.s.), but showed significant correlation with higher opioid medication requirements and a higher number of physical therapy session needed to reach discharge goals (p 0.031).",these findings suggest that bmi does not influence clinical outcomes and readmission rates of robotic-assisted uka at mid-term. the classic contraindication of bmi 30 kg/m,Prevention
are the inflammatory properties of electronegative low-density lipoprotein from type 1 diabetic patients related to increased platelet-activating factor acetylhydrolase activity?,"chemical and biological characteristics of ldl(-) from type 1 diabetic subjects were analysed. the diabetic patients were studied during poor and optimised glycaemic control. total ldl was subfractionated into electropositive ldl() and electronegative ldl(-) by anion exchange chromatography and the lipid and protein composition of the two determined. ldl(-) differed from ldl() in that it had higher triglyceride, non-esterified fatty acids, apoe, apoc-iii and platelet-activating factor acetylhydrolase (paf-ah), as well as lower apob relative content. no evidence of increased oxidation was observed in ldl(-). ldl(-) increased two-fold the release of interleukin 8 (il-8) and monocyte chemotactic protein 1 (mcp-1) in endothelial cells, suggesting an inflammatory role. optimisation of glycaemic control after insulin therapy decreased the proportion of ldl(-), but did not modify the composition of ldl subfractions, except for a decrease in paf-ah activity in ldl(-). the possibility that ldl(-) could be generated by non-enzymatic glycosylation was studied. fructosamine and glycated ldl content in ldl subfractions from type 1 diabetic patients was greater than in ldl subfractions isolated from normoglycaemic subjects, and decreased after glycaemic optimisation in both subfractions. however, no difference was observed between ldl() and ldl(-) before and after insulin therapy.","these results provide evidence that ldl(-) is not produced by glycosylation. nevertheless, ldl(-) from diabetic patients displays inflammatory potential reflected by the induction of chemokine release in endothelial cells. this proatherogenic effect could be related to the high paf-ah activity in ldl(-).",Medication
do effect of 12-week isokinetic training on muscle strength in adult with healed thermal burn?,"severe burns result in marked and prolonged skeletal muscle catabolism and weakness, which persist despite 'standard"" rehabilitation programmes of occupational and physical therapy. therefore, the objectives of this study were of twofold: to quantify the long-term effects of burns on leg muscle strength and to assess whether adults with thermal burn would benefit from the isokinetic training programme. burned adult patients, with 35-55 total body surface area (tbsa) burned, were assessed at 6 months after burn in respect to leg muscle strength at 150 s(-1), using isokinetic dynamometry. non-burned adults were assessed similarly, and served as controls. the burned adults participated in the resistance training programme 3 times weekly. the isokinetic exercise programme was begun with 60 of the average peak torque. intensity of isokinetic exercise was increased from one set to five sets during the first through fifth sessions and remained at six sets for the remaining 6th to 24th sessions. finally, a dose of 10 sets was applied for the 25th to the 36th sessions. each set consisted of five repetitions of concentric contraction in angular velocities of 150 s(-1) for knee extensors, and flexors. all exercise sessions were preceded by a 5-min warm-up period on the treadmill. subjects with burns more than 35 of tbsa produced significantly less torque, work, and power in the quadriceps and hamstring than control subjects (20.5, 15.2, p0.05). three months after isokinetic programme, muscle strength further increased by 17.910.1 compared to the baseline measurement for burned patients but continued to be below the concurrent age-matched, non-burned adult.","we found that adults with severe burns, relative to non-burned adults, had significantly lower peak torque as well as total work performance using the extensors and flexors muscles of the thigh. participation in isokinetic training resulted in a greater improvement in extensor and flexor muscle strength in adults with held thermal burn compared to base line values.",Treatment
is p73 g4c14 to a4t14 polymorphism associated with colorectal cancer risk and survival?,"to analyze the association between the p73 g4c14-to-a4t14 polymorphism (a.k.a., the gc/at variation) and colorectal cancer risk and survival in the korean population, and to evaluate the relationships between p73 polymorphism and the p73 protein expression or clinicopathological characteristics of colorectal cancer. three hundred and eighty-three histologically confirmed cases and 469 healthy controls, recruited at one teaching hospital in pusan, korea from 2001 and 2007, were genotyped for p73 g4c14-to-a4t14 by pcr with confronting two-pair primers (pcr-ctpp) and the expression profile of p73 in cancer tissues (n 383) was analyzed by immunohistochemistry. odds ratios (ors) and 95 confidence intervals (cis) were calculated by unconditional logistic regression model adjusted for age and gender. compared with the gc/gc genotypes, the gc/at and at/at genotypes were significantly associated with colorectal cancer risk (gc/at vs gc/gc: or 1.46, 95 ci: 1.10-1.94; at/at vs gc/gc: 1.72, 0.98-3.03; p(trend) 0.01). when stratified by age and gender, the association was restricted to those less than 60 years of age (gc/at or at/at vs gc/gc: 2.22, 1.39-3.55) and male (gc/at or at/at vs gc/gc: 1.91, 1.31-2.77). the expression of p73 was associated with invasion depth (p 0.003) and advanced duke's stage (p 0.06) of colorectal cancer. the patients with the gc/gc genotype were associated with worse survival compared with those with the other genotypes (p 0.02). however, no significant relationship was observed between the p73 g4c14-to-a4t14 polymorphism and p73 protein expression in cancer tissues.",our results suggest that the p73 gc/at polymorphism is associated with an increased colorectal cancer risk and survival in the korean population.,General
does functional response of bladder strips from streptozotocin diabetic rats depend on bladder mass?,"we investigated the relationship of bladder mass to responses to electrical field stimulation and adrenergic agonists in diabetic rat bladders. longitudinal strips were removed from the ventral and dorsal detrusor of age matched control, 2-month diabetic and sucrose drinking rats. contractile responses to electrical field stimulation, kcl and phenylephrine, and relaxation in response to norepinephrine and isoproterenol were measured. bladders from sucrose drinking and diabetic rats weighed significantly more than those of controls. diabetic rats were divided into 2 groups with the bladder weighing less than or greater than 265 mg. strips from small diabetic bladders were generally more responsive to field stimulation and norepinephrine than those from control or sucrose drinking rats. conversely decreased function was especially apparent in dorsal strips from large diabetic bladders. ventral strips were significantly more sensitive to the relaxant actions of norepinephrine and isoproterenol than dorsal strips.","our results suggest that the responsiveness of diabetic rat bladder to electrical field stimulation and adrenergic agonists is related to bladder mass, analogous to observations after partial outlet obstruction. decreased function was particularly apparent in dorsal strips from diabetic rats with a large bladder.",Medication
do event-related potentials indicate motivational relevance of cocaine cues in abstinent cocaine addicts?,"motivational drive and its underlying affect-related states are the core mechanisms that precede the seeking and taking of drugs in substance dependence. the present study aimed to investigate the motivational relevance of cocaine cues and whether or not an appetitive emotional system is involved employing event-related potential (erp) measurements. cocaine-addicted subjects and healthy controls were exposed to neutral and cocaine-related pictures whilst erps were recorded simultaneously over frontal, parietal and midline sites. patients exhibited erp amplitude discrepancies between neutral and cocaine-related pictures for n300, late slow positive wave (lspw) and sustained slow positive wave (sspw), whilst this effect was absent in control subjects. differences in neutral and cocaine cue-evoked erp waves were also found at left frontal sites for lspw and sspw in the patient group only. no group-specific cue-evoked erp amplitudes were observed at parietal and midline sites.",the findings confirm the assumption that cocaine cues induce motivational relevance in cocaine-dependent individuals. it is possible that exposure to cocaine cues triggers an appetitive emotional system since left frontal sites are assumed to be involved in processing positive emotional-laden stimuli. the present study provides evidence that the sensitivity of erp correlates for cocaine cues may be an indicator of motivational and emotional processes in drug-dependent individuals.,Medication
is onset of mechanical ventilation associated with rapid activation of circulating phagocytes in preterm infants?,"in preterm infants with respiratory distress syndrome (rds), circulating neutrophils are activated. kinetics and effects of surfactant therapy on this activation are unknown. therefore, we studied activation of circulating neutrophils and monocytes in newborn preterm infants with and without rds. preterm infants with rds who were mechanically ventilated and received surfactant (""ventilated infants"": n 38; mean gestational age /- sd: 28.3 /- 2.2 weeks; mean birth weight /- sd: 1086 /- 353 g) and preterm infants who received nasal continuous positive airway pressure (n 8) or no ventilatory support (n 17) (""control infants"": mean gestational age /- sd: 32.1 /- 1.2 weeks; mean birth weight /- sd: 1787 /- 457 g) were recruited. blood samples were taken from ventilated infants at birth, before surfactant treatment, at 1 and 2 hours after surfactant, and at 12 to 24 hours of age. blood samples were taken from control infants at birth, at 2 to 6 hours, and at 12 to 24 hours of age. phagocyte cd11b expression was analyzed by flow cytometry. in ventilated infants, phagocyte cd11b expression increased from birth to the first postnatal samples. it increased further by 12 to 24 hours of age. control infants with or without nasal continuous positive airway pressure showed no significant increase after birth. at 12 to 24 hours of age, phagocyte cd11b expression was higher in ventilated infants than in control infants. in ventilated infants, neutrophil cd11b expression at 1 and 2 hours after surfactant correlated positively with gestational age.","in preterm infants with rds, significant activation of circulating phagocytes occurs within 1 to 3 hours of the onset of mechanical ventilation, independent of surfactant administration, which indicates that mechanical ventilation may be the inducer of this systemic inflammatory response.",Treatment
does a novel zinc finger protein zfp277 mediate transcriptional repression of the ink4a/arf locus through polycomb repressive complex 1?,"polycomb group (pcg) proteins play a crucial role in cellular senescence as key transcriptional regulators of the ink4a/arf tumor suppressor gene locus. however, how pcg complexes target and contribute to stable gene silencing of the ink4a/arf locus remains little understood. we examined the function of zinc finger domain-containing protein 277 (zfp277), a novel zinc finger protein that interacts with the pcg protein bmi1. zfp277 binds to the ink4a/arf locus in a bmi1-independent manner and interacts with polycomb repressor complex (prc) 1 through direct interaction with bmi1. loss of zfp277 in mouse embryonic fibroblasts (mefs) caused dissociation of pcg proteins from the ink4a/arf locus, resulting in premature senescence associated with derepressed p16(ink4a) and p19(arf) expression. levels of both zfp277 and pcg proteins inversely correlated with those of reactive oxygen species (ros) in senescing mefs, but the treatment of zfp277(-/-) mefs with an antioxidant restored the binding of prc2 but not prc1 to the ink4a/arf locus. notably, forced expression of bmi1 in zfp277(-/-) mefs did not restore the binding of bmi1 to the ink4a/arf locus and failed to bypass cellular senescence. a zfp277 mutant that could not bind bmi1 did not rescue zfp277(-/-) mefs from premature senescence.",our findings implicate zfp277 in the transcriptional regulation of the ink4a/arf locus and suggest that the interaction of zfp277 with bmi1 is essential for the recruitment of prc1 to the ink4a/arf locus. our findings also highlight dynamic regulation of both zfp277 and pcg proteins by the oxidative stress pathways.,Treatment
are complete blood counts frequently abnormal 1 year after dosimetry-guided radioactive iodine therapy for metastatic thyroid cancer?,"radioactive iodine (rai) has been associated with hematologic abnormalities. previous research has shown that even a single dose of rai can cause changes in the peripheral complete blood count (cbc). it is unclear if the use of dosimetry guidance would prevent the effects of high doses of rai on bone marrow suppression. cbc at baseline was compared to a cbc obtained 1 year after the last rai treatment in 50 thyroid cancer patients that received 250 mci rai during the course of their disease. cumulative dose, number of treatments, patients' age, and the use of external beam radiation therapy (ebrt) were considered in the analysis. we observed a small but statistically significant decrease in hemoglobin (hb), hematocrit (hct), and platelet (plt) counts at 1 year in 50 patients who had received 250 mci rai. we did not find a significant change in white blood cell count (wbc). approximately 60 of patients who developed anemia had concomitant wbc and plt abnormalities. rai dose, number of treatments, and age at diagnosis did not confer a higher risk of bone marrow suppression.","high cumulative activities of rai administered under dosimetric guidance are associated with a small but statistically significant decreases in hb, hct, and plt counts. the clinical implications of these changes, if any, are unclear. the benefits obtained with high doses of rai, when indicated, are likely to outweigh the minimal hematologic risks observed in the present study.",Treatment
is chronic mucosal inflammation of the gastric cardia in gastroesophageal reflux disease regulated by foxp3-expressing t cells?,"chronic inflammation at the cardia occurs in gastroesophageal reflux disease (gerd), as well as in the presence of helicobacter pylori. regulatory t cells have been demonstrated for h. pylori-induced gastritis, whereas their role has not been studied in gerd. we prospectively analyzed the expression of foxp3, a marker of various regulatory t cells, as well as the mucosal transcript levels of tgf-beta1 and il-10. rna and protein levels have been determined in cardiac biopsies of 70 patients stratified according to gerd (n 22), controls (n 17), and h. pylori (n 31). gerd presented with chronic inflammation and reduced foxp3-mrna in the cardiac mucosa (-84), whereas h. pylori-positive patients revealed a 25.1-fold increase of foxp3 gene expression. these results were verified by the regulatory cytokines il-10 and tgf-beta1, and by the immunohistochemical detection of intramucosal foxp3-expressing t cells.","chronic inflammation at the cardia associated with either gerd or h. pylori differs concerning the presence of foxp3-expressing t cells. in contrast to h. pylori, foxp3-expressing t cells are not associated with gerd-associated carditis.",Diagnosis
are serum and plasma fragments of c-telopeptides of type i collagen ( ctx ) stable during storage at low temperatures for 3 years?,"control of pre-analytical variables is essential for successful application of biological markers, including bone resorption markers, in clinical trials and routine use. the effect of storage temperature on stability of bone resorption markers have not been subject of systematically investigation, and therefore the present study was set out to determine the stability of c-telopeptides of type i collagen (ctx) in serum and plasma samples stored frozen for 3 years. the serum and plasma levels of ctx were determined in samples aliquoted and stored frozen for up to 3 years. no significant decrease could be detected in neither serum nor plasma samples after 3 years of storage at -20, -80 or -150 degrees c. however, at elevated temperature, i.e. 4 and 37 degrees c, improved stability of ctx was observed in edta plasma samples compared to serum.",ctx is stable in frozen serum and plasma samples for up to 3 years. edta plasma might be the preferred matrix due to improved stability at elevated temperatures.,Medication
is participation in community-originated interventions associated with positive changes in weight status and health behaviors in youth?,"to assess changes in children's health behaviors and weight status after participation in community-originated interventions. prospective cohort study following body mass index (bmi) z-score trajectory over time. schools and community settings in 19 locations in north carolina. a total of 1144 children, with an average age of 9.5 years, participating in community-originated physical activity and nutrition interventions, such as active recess and healthy cafeteria offerings, and environment and policy changes designed to prevent and reduce the prevalence of childhood obesity. retention from baseline to final collection was 54. measures . self-reported physical activity and eating behaviors; measured height and weight were collected at baseline and after interventions (average of 20 months). z-score was compared with expected growth without intervention. descriptive statistics, (2) tests and t-tests, and anova analyses of variance to assess changes in health behaviors and weight status. more than 11 of children improved their weight status, and 86 of children who began at a healthy weight remained there. the average bmi for children who were overweight at enrollment was significantly lower after intervention (1.1 kg/m(2) lower for boys and 0.88 kg/m(2) lower for girls). overweight and obese children who made improvements in key health behaviors showed greater decreases in bmi z-score than those who did not improve those behaviors (increased fruit -.2207 vs. -.0793 and vegetable -.2215 vs. -.0855 intake, and drinking less soda -.1985 vs. -.0912). there were no significant increases in physical activity, and changes in physical activity were not related to decreases in bmi z-score in this study.",community-originated interventions to raise awareness about food choices and to change policies and environments may improve bmi z-scores.,Prevention
does stromal integrin 111 affect rm11 prostate and 4t1 breast xenograft tumors differently?,"it has been implied that the collagen binding integrin 111 plays a role in carcinogenesis. as still relatively little is known about how the stromal integrin 111 affects different aspects of tumor development, we wanted to examine the direct effects on primary tumor growth, fibrosis, tumor interstitial fluid pressure (pif) and metastasis in murine 4t1 mammary and rm11 prostate tumors, using an in vivo scid integrin 11-deficient mouse model. tumor growth was measured using a caliper, pif by the wick-in-needle technique, activated fibroblasts by -sma immunofluorescence staining and fibrosis by transmission electron microscopy and picrosirius-red staining. metastases were evaluated using hematoxylin and eosin stained sections. rm11 tumor growth was significantly reduced in the scid integrin 11-deficient (11-ko) compared to in scid integrin 11 wild type (wt) mice, whereas there was no similar effect in the 4t1 tumor model. the 4t1 model demonstrated an alteration in collagen fibril diameter in the integrin 11-ko mice compared to wt, which was not found in the rm11 model. there were no significant differences in the amount of activated fibroblasts, total collagen content, collagen organization or pif in the tumors in integrin 11-deficient mice compared to wt mice. there was also no difference in lung metastases between the two groups.","deficiency of stromal integrin 111 showed different effects on tumor growth and collagen fibril diameter depending on tumor type, but no effect on tumor pif or development of lung metastasis.",General
is increase on the initial soluble heme levels in acidic conditions an important mechanism for spontaneous heme crystallization in vitro?,"hemozoin (hz) is a heme crystal that represents a vital pathway for heme disposal in several blood-feeding organisms. recent evidence demonstrated that -hematin (h) (the synthetic counterpart of hz) formation occurs under physiological conditions near synthetic or biological hydrophilic-hydrophobic interfaces. this seems to require a heme dimer acting as a precursor of hz crystals that would be formed spontaneously in the absence of the competing water molecules bound to the heme iron. here, we aimed to investigate the role of medium polarity on spontaneous h formation in vitro. we assessed the effect of water content on spontaneous h formation by using the aprotic solvent dimethylsulfoxide (dmso) and a series of polyethyleneglycols (pegs). we observed that both dmso and pegs (3.350, 6.000, 8.000, and 22.000) increased the levels of soluble heme under acidic conditions. these compounds were able to stimulate the production of h crystals in the absence of any biological sample. interestingly, the effects of dmso and pegs on h formation were positively correlated with their capacity to promote previous heme solubilization in acidic conditions. curiously, a short chain polyethyleneglycol (peg 300) caused a significant reduction in both soluble heme levels and h formation. finally, both heme solubilization and h formation strongly correlated with reduced medium water activity provided by increased dmso concentrations.","the data presented here support the notion that reduction of the water activity is an important mechanism to support spontaneous heme crystallization, which depends on the previous increase of soluble heme levels.",General
does tnf- suppression by glutathione preconditioning attenuate hepatic ischemia reperfusion injury in young and aged rats?,"hepatic ischemia reperfusion (i/r) stimulates kupffer cells and initiates injury through tumor necrosis factor- (tnf-) upregulation. aim of this study was to compare the variable effects of reduced glutathione (gsh) pre-treatment on i/r liver injury in young and aged rats. wistar male rats were sorted into young (groups i-iii) and aged (groups iv-vi). all groups except sham (groups i and iv) were subjected to 90-min ischemia and 2-h reperfusion. the treatment groups received 200 mg/kg bwt (groups iii and vi) of gsh, 30 min prior to i/r. variable effects of gsh were studied by transaminase activities, thiobarbituric acid-reactive substances (tbars), gsh level, gsh/oxidized gsh (gssg) ratio, tnf- level, apoptotic markers and confirmed by histopathological observations. our findings revealed that i/r inflicted more liver damage in aged rats than young rats. the gsh treatment prior to surgery significantly lowered the serum transaminase activities, hepatic tbars level and effectively restored the gsh/gssg ratio in both young and aged rats more remarkably in the mitochondria. western analysis depicted that the gsh treatment effectively suppressed tnf- expression and apoptotic markers in both young and aged rats. these findings were further confirmed by terminal deoxynucleotide transferase dutp nick end labeling assay and histopathological observations of liver sections of young and aged rats.","restoration of gsh/gssg ratio through gsh pre-conditioning inhibits tnf- and apoptosis in hepatic i/r injury. hence, gsh pre-conditioning may be utilized in both young and aged individuals during liver transplantation/surgery for better post-operative outcomes.",Treatment
does erdosteine ameliorate neurological outcome and oxidative stress due to ischemia/reperfusion injury in rabbit spinal cord?,"oxygen-derived free radicals have been suggested as important in degeneration after spinal cord ischemia. the aim of this study was to investigate whether erdosteine has a protective effect against spinal cord ischemia during aortic cross clamping. new zealand white rabbits (n21) were divided into three groups. in the ischemia/reperfusion group (i/r) (n8), the infrarenal aorta of rabbits was cross clamped for 21 min and then reperfused. in erdosteine group, the administration of erdosteine solution (50 mg/kg) was started two days before aortic cross-clamping and rabbits (n8) were subjected to ischemia and reperfusion. animals in control group (n5) underwent a surgical procedure similar to the other groups but the aorta was not clamped. the animals were sacrificed at 72 h and histopathological, and biochemical analyses were carried out on the lumbar spinal cords. erdosteine treatment was associated with improved neurological function in the postoperative period. histopathological examination of spinal cord tissues in erdosteine group revealed changes consistent with mild ischemic injury, but rabbits in i/r group with paraplegia had total destruction of the motor neurons. biochemical analyses of spinal cord tissues, in the i/r group, revealed a significant increase in the superoxide dismutase, xanthine oxidase, adenosine deaminase and myeloperoxidase activities, and a significant depletion in glutathione peroxidase activity when compared to that of control rabbits. erdosteine treatment prevented the increase of all these enzymes except adenosine deaminase. ischemia/reperfusion produced a significant increase in the tissue malondialdehyde levels. ischemia/reperfusion-induced increments in malondialdehyde content of the spinal cord were significantly prevented by erdosteine treatment.","the present study demonstrated that erdosteine treatment before aortic cross clamping ameliorates neurological outcome, neuronal injury and oxidative stress in the rabbit spinal cord.",Treatment
does west nile virus methyltransferase domain interact with protein kinase g?,"the flaviviral nonstructural protein 5 (ns5) is a phosphoprotein, though the precise identities and roles of many specific phosphorylations remain unknown. protein kinase g (pkg), a cgmp-dependent protein kinase, has previously been shown to phosphorylate dengue virus ns5. we used mass spectrometry to specifically identify ns5 phosphosites. co-immunoprecipitation assays were used to study protein-protein interactions. effects on viral replication were measured via replicon system and plaque assay titering. we identified multiple sites in west nile virus (wnv) ns5 that are phosphorylated during a wnv infection, and showed that the n-terminal methyltransferase domain of wnv ns5 can be specifically phosphorylated by pkg in vitro. expressing pkg in cell culture led to an enhancement of wnv viral production. we hypothesized this effect on replication could be caused by factors beyond the specific phosphorylations of ns5. here we show for the first time that pkg is also able to stably interact with a viral substrate, wnv ns5, in cell culture and in vitro. while the mosquito-borne wnv ns5 interacted with pkg, tick-borne langat virus ns5 did not. the methyltransferase domain of ns5 is able to mediate the interaction between ns5 and pkg, and mutating positive residues in the e region of the methyltransferase interrupts the interaction. these same mutations completely inhibited wnv replication.","pkg is not required for wnv replication, but does make a stable interaction with ns5. while the consequence of the ns5:pkg interaction when it occurs is unclear, mutational data demonstrates that this interaction occurs in a region of ns5 that is otherwise necessary for replication. overall, the results identify an interaction between virus and a cellular kinase and suggest a role for a host kinase in enhancing flaviviral replication.",General
does il-5 deficiency abolish aspects of airway remodelling in a murine model of lung inflammation?,"lung remodelling is a recognized feature of chronic asthma. in the present study, we have used il-5-deficient mice to evaluate the role of this cytokine and eosinophilic inflammation in the initial stages of the structural changes occurring in the lung after antigen challenge. ovalbumin-sensitized wild type and il-5-deficient mice were daily challenged for 5 consecutive days and killed 3 or 7 days after the last challenge to study the inflammatory and remodelling events, respectively. wild type mice challenged with ovalbumin exhibited an accumulation of eosinophils in the bronchoalveolar lavage (bal) fluid, associated with a production of bal cellular fibronectin. histological analysis also revealed an antigen-specific increase in epithelial and alveolar cell proliferation together with an increase in mucus producing epithelial cells. eosinophilic infiltration and the associated lung remodelling were totally abrogated in il-5-deficient mice. in wild type mice, treated intranasally with 1 microg of murine il-5 for 5 consecutive days, no bal eosinophilia and structural changes of the lungs could be observed.","our results demonstrate that eosinophil accumulation, but not il-5 alone, plays a central role in the initial stages of the lung remodelling process and suggests that therapies directed at inhibiting eosinophilic inflammation may be beneficial in treating chronic asthma.",Treatment
is myocardial perfusion imaging ( mpi ) superior to the demonstration of distal collaterals in predicting cardiac events in chronic total occlusion ( cto )?,"in chronic total occlusion (cto), the evidence for revascularization is less robust than for stable angina. a medical therapy strategy is common and often based on distal collateralization, regardless of the presence of ischemia. the aim of this study was to examine the correlation between distal collateralization, myocardial perfusion imaging (mpi), and hard cardiac events (hce) in cto. retrospective analysis of consecutive patients undergoing coronary angiography revealed 21 non-revascularized patients with cto and mpi, over a 24-month period. blinded review of patient charts, mpi, and angiography was undertaken. hce of death, myocardial infarct, and unstable angina were assessed. mean follow up was 23 months. summed difference scores were calculated on a 17-segment model and collaterals graded on the rentrop scale. 43 of patients had hce, and 62 had collaterals. ischemia on mpi accurately predicted hce in cto (60 vs 0, p .01). distal collateralization failed to predict freedom from ischemia on mpi (31 vs 25, p .53) or hce (31 vs 62, p .15).",mpi in patients with cto accurately predicted hce. this allows for accurate triage of patients by mpi for consideration of revascularization. patients without ischemia can be safely managed with optimal medical therapy. the presence of collateralization did not predict either ischemia or hce.,Diagnosis
does a psycho-educational video used in the emergency department provide effective treatment for whiplash injuries?,"randomized control trial conducted between june 2000 and september 2002. to determine whether a short psycho-educational video shown in the emergency department shortly after the injury would produce follow-up pain reductions and reduced medical utilization. chronic pain following a whiplash injury is one example of the massive medical/legal problem of chronic muscular pain. approaches using local pain sources (trigger points) have shown promise as treatment models for this type of pain. 1) setting: emergency departments (ed) and urgent care (uc) facilities. 2) patients: 126 patients entering eds or ucs. 3) intervention: patients assigned to 12-minute video or care as usual. 4) main outcome measures: short form musculoskelatal function assessment (smfa), phone questionnaires assessing: narcotics use, er use, uc use, surgical consultations, etc.","patients viewing the video had dramatically lower pain ratings at a 1-month follow (6.09 10.6 vs. 21.23 17.4, p 0.001) and this pattern held for the 3- and 6-month follow-up period. similarly, for 17 of 21 items asked at follow-up, the video group showed superior outcomes (chi2 ranged from 5 to 35, p 0.05, all). for example, 4 of video patients were using narcotics at 6 month post ed visit compared with 36 of controls. the brief psycho-educational video had a profound effect on subsequent pain and medical utilization.",Treatment
"are growth , phenotype , and function of human intestinal mast cells tightly regulated by transforming growth factor beta1?","transforming growth factor beta1 (tgf-beta1) is expressed in the healthy human intestine and controls mucosal immune responses and inflammation by regulating the function of lymphocytes, macrophages, dendritic cells, and eosinophils. here, we asked whether human intestinal mast cells (mc) might also be subject to immunoregulation by tgf-beta1. mc were isolated from the intestinal mucosa, purified, and cultured in vitro in the presence of stem cell factor (scf) with or without tgf-beta1. growth characteristics, phenotype, and immunological mediator release of mc were analysed by reverse transcription-polymerase chain reaction, flow cytometry, immunocytochemistry, western blot, and different immunoassays, respectively. tgf-beta1 dose dependently (ed50 approximately 0.1 ng/ml) inhibited scf dependent growth of human intestinal mc by both enhancing apoptosis and decreasing proliferation. in parallel, tgf-beta1 increased the percentage of connective tissue-type mc expressing tryptase and chymase while downregulating expression of the receptors for ige and scf. furthermore, tgf-beta1 dramatically changed the profile of mediators released by mc following ige receptor crosslinking. release of histamine, cysteinyl-leukotrienes, and tumour necrosis factor alpha was strongly reduced whereas prostaglandin d2 generation and cyclooxygenase 1 and 2 expression were upregulated by tgf-beta1.","our data indicate that tgf-beta1 acts as a novel potent inhibitor and modulator of human intestinal mc effector functions. the change in mc mediator release profile and protease expression induced by tgf-beta1 might be of relevance for the control of mc associated disorders of the intestine such as allergic reactions, crohn's disease, irritable bowel syndrome, and parasitic infection.",Medication
are normal levels of adamts13 and factor h present in the pharmaceutically licensed plasma for transfusion ( octaplas ) and in the universally applicable plasma ( uniplas ) in development?,"the pathomechanism of thrombotic thrombocytopenic purpura (ttp) and atypical haemolytic uraemic syndrome (ahus) is associated with a severe deficiency of adamts13 and factor h. the aim of this study was to quantify the levels of adamts13 and factor h in the pharmaceutically licensed plasma for transfusion, octaplas, and the universally applicable plasma, uniplas (development product, working title). furthermore, octaplas batches of blood groups a, b, o, ab, and plasmas derived from different sources were compared. twenty-four octaplas and three uniplas batches were selected for the study. adamts13 activities were measured by fluorescence resonance energy transfer assay, adamts13 antigen levels were quantified using enzyme-linked immunosorbent assay test kit, while factor h antigen levels were detected using radial immunodiffusion (rid) methods. in addition, von willebrand factor (vwf) multimeric analyses were performed. both octaplas, produced from us and european plasma of different blood groups, and uniplas contain adamts13 antigen and activity levels as well as factor h concentrations at normal levels without significant differences. in addition, octaplas and uniplas show a vwf multimeric pattern comparable to normal plasma.","the study revealed that octaplas and uniplas contain normal levels of adamts13 at low batch-to-batch variations. therefore, both products can substitute the missing or neutralized protease activity in ttp patients and thereby limit vwf-dependent (platelet-related) thrombosis. in addition, both plasma products contain factor h at a physiological level, and, thus can be used efficiently in the treatment of ahus patients, which have been shown to benefit from plasma administration.",Treatment
does haplotype-based analysis of ulcerative colitis risk loci identify both il2 and il21 as susceptibility genes in han chinese?,"the incidence of ulcerative colitis (uc) varies between western and eastern ethnicities. a distinct genetic background may play a role in the differences. until now, very little was known of the uc genetics in asian populations. here we performed a haplotype-based analysis of six known uc susceptibility loci in han chinese patients. in all, 245 uc patients and 300 healthy controls of han chinese descent were genotyped for 27 single nucleotide polymorphisms (snps), which cover the major haplotypes of the chromosome regions containing il10, il2/il21, myo9b, ecm1, mst1, and il23r in han chinese. in contrast to the tight linkage disequilibrium (ld) block of the il2/il21 region in caucasians, il2 and il21 reside in two independent ld blocks in han chinese. the il2 snp rs2069762 (p 7.0 10(-4) , odds ratio or 1.54, 95 confidence interval ci 1.20-1.99) and the il21 snp rs2055979 (p 1.2 10(-4) , or 1.50, 95 ci 1.17-1.92) were independently associated with uc. we identified one risk haplotype in il2 and another independent risk haplotype in il21. in addition to the il2/il21 locus, we observed association of the tt genotype of snp rs1545620 in myo9b with uc (p 0.0169; or 0.29, 95 ci 0.11-0.78) and association of rs17375018 in il23r with pancolitis in chinese uc patients (p 0.002; or 2.38, 95 ci 1.41-4.02).","our study confirmed the association of the il2/il21 region with uc in han chinese patients, and further implied both il2 and il21 as genetic risk factors for uc. han chinese uc patients share part of their genetic susceptibility with caucasian patients.",General
does sam68 mediate leptin-stimulated growth by modulating leptin receptor signaling in human trophoblastic jeg-3 cells?,"sam68, a member of the signal transduction and activation of rna metabolism (star) family of rna-binding proteins, has been previously implicated as an adaptor molecule in different signaling systems, including leptin receptor (lepr) signaling. lepr activation is known to stimulate jak-stat, mapk and pi3k signaling pathways, thus mediating the biological effects of leptin in different cell types, including trophoblastic cells. we have recently found that leptin stimulation also promotes the overexpression and tyrosine phosphorylation of sam68 in human trophoblastic jeg-3 cells, suggesting a role for sam68 in leptin signaling and action in these cells. in the present work, we have studied the participation of sam68 in the main signaling pathways activated by lepr to increase growth and proliferation in trophoblastic jeg-3 cells. we used an antisense strategy to down-regulate sam68 expression in these cells, and we studied lepr signaling by immunoprecipitation and poly-u affinity precipitation and by analyzing phosphorylation levels of signaling proteins by immunoblot. the effect of leptin on protein synthesis and proliferation was studied by h-leucine and h-thymidine incorporation. sam68 knockdown impaired leptin activation of jak-stat, pi3k and mapk signaling pathways in jeg-3 cells. we have also found that leptin-stimulated sam68 tyrosine phosphorylation is dependent on jak-2 activity, since the pharmacological inhibitor ag490 prevents the phosphorylation of sam68 in jeg-3 cells. finally, the trophic and proliferative effect of leptin in trophoblastic cells is dependent on sam68 expression, since its down-regulation impaired the leptin-stimulated dna and protein synthesis.",these data demonstrate that sam68 participates in the main signaling pathways of lepr to mediate the trophic and proliferative effect of leptin in human trophoblastic cells.,Medication
are nerves more abundant than blood vessels in the degenerate human intervertebral disc?,"chronic low back pain (lbp) is the most common cause of disability worldwide. new ideas surrounding lbp are emerging that are based on interactions between mechanical, biological and chemical influences on the human ivd. the degenerate ivd is proposed to be innervated by sensory nerve fibres and vascularised by blood vessels, and it is speculated to contribute to pain sensation. however, the incidence of nerve and blood vessel ingrowth, as well as whether these features are always associated, is unknown. we investigated the presence of nerves and blood vessels in the nucleus pulposus (np) of the ivd in a large population of human discs. immunohistochemistry was performed with 61 human ivd samples, to identify and localise nerves (neurofilament 200 nf200/protein gene product 9.5) and blood vessels (cd31) within different regions of the ivd. immunopositivity for nf200 was identified within all regions of the ivd within post-mortem tissues. nerves were seen to protrude across lamellar ridges and through matrix towards np cells. nerves were identified deep within the np and were in many cases, but not always, seen in close proximity to fissures or in areas where decreased matrix was seen. fifteen percent of samples were degenerate and negative for nerves and blood vessels, whilst 16 of all samples were degenerate with nerves and blood vessels. we identified 52 of samples that were degenerate with nerves but no blood vessels. interestingly, only 4 of all samples were degenerate with no nerves but positive for blood vessels. of the 85 samples investigated, only 6 of samples were non-degenerate without nerves and blood vessels and 7 had nerves but no blood vessels.",this study addresses the controversial topic of nerve and blood vessel ingrowth into the ivd in a large number of human samples. our findings demonstrate that nerves are present within a large proportion of np samples from degenerate ivds. this study shows a possible link between nerve ingrowth and degeneration of the ivd and suggests that nerves can migrate in the absence of blood vessels.,Symptoms
does information collected during the residency match process predict clinical performance?,"to determine whether information collected during the national resident matching program (nrmp) predicts clinical performance during residency. ten faculty members rated the overall quality of 69 pediatric house officers as clinicians. after rating by the faculty, folders were reviewed for absolute rank on the nrmp match list; relative ranking (where they ranked in their postgraduate year 1 pgy-1 group); scores on part i of the national board of medical examiners (nbme) examination; grades during medical school pediatrics and internal medicine rotations; membership in the alpha omega alpha medical honor society; scores of faculty interviews during intern application; scores on the pediatric in-service examination during pgy-1; and scores on the american board of pediatrics certification examination. there was substantial agreement among faculty raters as to the overall quality of the residents (agreement rate, 0.60; kappa 0.50; p .001). there was little correlation between faculty ratings and absolute (r 0.19; p .11) or relative (r 0.20; p .09) ranking on the nrmp match list. individuals ranked in the top 10 of the match list had higher faculty ratings than did their peers (mean /- sd, 3.66/-1.22 vs. 3.0/-1.27; p .03), as did individuals ranked highest in their pgy-1 group (mean /- sd, 3.88/-1.45 vs. 3.04/-1.24; p .03). there was no correlation between faculty ratings and scores on part i of the nbme examination (r 0.10; p .49) or scores on the american board of pediatrics certification examination (r 0.22; p . 11). there were weak correlations between faculty ratings and scores of faculty interviews during the intern application process (r 0.27; p .02) and scores on the pediatric in-service examination during pgy-1 (r 0.28; p .02). there was no difference in faculty ratings of residents who were elected to alpha omega alpha during medical school (mean /- sd, 3.32/-1.21) as compared with those who were not (mean /- sd, 3.08/-1.34) (p .25).","there is significant agreement among faculty raters about the clinical competence of pediatric residents. medical school grades, performance on standardized examinations, interviews during the intern application process, and match-list ranking are not predictors of clinical performance during residency.",General
does prophylactic im small-dose phenylephrine blunt spinal anesthesia-induced hypotensive response during surgical repair of hip fracture in the elderly?,"in a double-blinded, placebo-controlled, randomized study, we evaluated the effect of prophylactic im phenylephrine at doses of 1.5 and 3 mg on hyperbaric tetracaine spinal anesthesia-induced hypotension in 90 normotensive and hypertensive patients aged 65 yr undergoing surgery for hip fracture. thirty normotensive patients received 1.5 or 3 mg of phenylephrine im (n/p-1.5 and n/p-3.0 groups; n 15 in each), whereas controls received saline (n/c group; n 15), and 45 hypertensive patients were treated in a similar manner (h/p-1.5, h/p-3.0, and h/c groups; n 15 in each). all groups had a peak sensory block height of t9, with a range of t8 to t10. the incidence of hypotension (25 decrease in mean arterial blood pressure map from baseline) was significantly lower in the patients who received phenylephrine 1.5 or 3 mg than in the controls, both in the normotensive and hypertensive groups (p 20 increase from baseline) after medication occurred in the n/p-3.0 and h/p-3.0 groups, but not in the n/p-1.5 and h/p-1.5 groups. we conclude that prophylactic im injection of 1.5 mg of phenylephrine is a safe (defined as the inhibition of bradycardia and hypertension) and effective means of reducing the incidence of hypotension associated with spinal anesthesia in normotensive and hypertensive elderly patients.",we evaluated the efficacy and safety of small-dose im phenylephrine for prophylaxis against spinal anesthesia-induced hypotension in normotensive and hypertensive elderly patients. phenylephrine 1.5 mg im was effective for reducing the incidence of hypotension and avoided adverse effects.,Medication
is prucalopride no more effective than placebo for children with functional constipation?,"prucalopride is a selective, high-affinity agonist of the 5-hydroxytryptamine (serotonin) receptor 4 that enhances motility in the gastrointestinal tract. we performed a multicenter, randomized, placebo-controlled, double-blind, phase 3 trial to evaluate the efficacy and safety of prucalopride in children (6 months to 18 years old) with functional constipation. children with functional constipation, based on the rome iii criteria, were given prucalopride (children 50 kg were given a 0.04 mg/kg oral solution; children 50 kg were given a 2-mg tablet) or placebo once daily for 8 weeks. the primary efficacy end point was the proportion of children with toileting skills who had a mean of 3 spontaneous bowel movements/week and 1 episode of fecal incontinence/2 weeks, from study weeks 5-8 (responders). adverse events, clinical laboratory values, and electrocardiograms were monitored. efficacy and safety were assessed in 213 children (106 prucalopride, 107 placebo). twenty-five percent were younger than 4 years old, 50 were 4-11 years old, and 25 were 12-18 years old; 55.4 were girls. at screening, 62.3 of patients in the prucalopride group and 55.1 in the placebo group had a history of fecal incontinence; 60.4 and 55.1 in the prucalopride and placebo groups, respectively, had a mean of 1 spontaneous bowel movements/week. the proportion of responders was similar between groups (prucalopride, 17.0 and placebo, 17.8). there were no statistically significant differences in the primary efficacy end point when patients were stratified by sex, age group, or country. the incidence of treatment-emergent adverse events was similar in the prucalopride (69.8) and placebo (60.7) groups.","prucalopride, although generally well tolerated, was not more effective than placebo in children with functional constipation. clinicaltrials.gov number: nct01330381.",Medication
does endothelin-3 at low concentrations attenuate inflammatory responses via the endothelin b2 receptor?,"the aim of this study was to clarify a role of endothelins (ets: et-1, -2, and -3) and their receptors (eta, etb1, and etb2) in inflammatory responses. male wistar rats (180-220 g) were used. the effects of ets in the absence or presence of the eta antagonist bq-123/the selective etb2 antagonist bq-788, and the effect of the selective etb1 agonist irl-1620 and the nonselective etb agonist bq-3020, on rat hind paw oedema induced by several proinflammatory substances were examined. the involvement of nitric oxide (no) in the effects of ets on the paw oedema was investigated using the no synthase inhibitor ng-nitro-l-arginine methyl ester (l-name). et-3, which acts mainly on etb, at low concentrations specifically inhibited platelet-activating factor (paf)-induced paw oedema, whereas neither et-1 nor et-2, both of which act on eta and etb, showed inhibitory activity. the inhibition by et-1 and et-3 (each 0.5 pmol/paw) in the presence of bq-123 (66.4 6.7 and 65.4 22.6 , respectively), was comparable to that by et-3 (0.5 pmol/paw) alone (65.4 10.9 ), whereas neither et-1 nor et-3 in the presence of bq-788 showed inhibitory activity. bq-3020 (0.5 pmol/paw) inhibited the oedema by 50.9 6.0 , whereas irl-1620 showed almost no activity. additionally, l-name markedly attenuated the inhibitory effects of et-3 on paf-induced paw oedema. these results indicate that etb2 may mediate no production and attenuation of paf-induced inflammatory responses. moreover, et-3 (0.5 pmol/paw) inhibited the oedema induced by et-1 at higher dose and zymosan by 76.6 11.0 and 85.4 13.6 , respectively, indicating that et-3 at lower concentrations inhibits the paw oedema induced by various inflammatory substances.",et-3 at low concentrations may attenuate inflammatory responses via etb2 activation and no production.,Medication
do cantilever fpds have lower success rates than end abutted fpds after 10-years of follow-up?,"studies were located using a medline search strategy for english-language articles published from 1966 to 2004. a systematic review of 13 studies of cohort design (no randomized control trials were available) with the majority being retrospective. seven hundred subjects with an age range of 26 to 84-years with a total of 816 fpds with cantilever extensions were selected. the mean number of cantilever extensions varied from 1 to 6. prostheses were of mixed design with 72 gold/acrylic structures. there are no data on the number of abutments compared with pontics or the overall length of the prostheses in this analysis longitudinal follow-up of cantilever fpds to failure or complication. all studies were required to have a mean minimum follow-up time of 5 years. time to survival of the restorations, with secondary outcome measures of proportion of restoration successful at 10 years (success was defined as survival with no biological or mechanical complications) and time to biological (caries, loss of vitality and periodontal disease) and technical (loss of retention, abutment fracture, superstructure fracture) complication. the estimated aggregate proportion of cantilever fpds surviving at 10 years was 81.8 (95 ci: 78.2-84.9), with an annualized failure rate of 2 per 100 fpds (95 ci: 1.63-2.46). failure was not influenced by the number of cantilevered pontics or the material used for bridge construction in these data. the estimated aggregate proportion of cantilever fpds successful (free of all complications) at 10 years was 63 (95 ci: 54.7-70.2). the estimated aggregate proportion with caries at one or more abutment teeth at 10 years was 9.1 (95 ci: 6.3-13). the estimated aggregate proportion with loss of vitality of one or more abutment teeth at 10 years was 32.6 (95 ci: 13.9-64.9). rates of loss of vitality were much higher in the studies using extensive (12-unit fpds supported by 2 cuspids) mandibular prostheses than those with shorter extensions. the estimated aggregate proportion with progression of periodontal disease leading to loss of the fpd at 10 years was 1 (95 ci: 0.3-3).the estimated aggregate proportion with loss of retention of the fpd at 10 years was 16.1 (95 ci: 8.8-28.4). rates of loss of retention were much higher in the studies using extensive (12-unit fpds supported by 2 cuspids) mandibular prostheses than those with shorter extensions. the estimated aggregate proportion with fracture of abutment teeth at 10 years was 2.4 (95 ci: 0.6-9.8). the estimated aggregate proportion with framework, veneer, or core fractures at 10 years was 5.9 (95 ci: 3.3-10.4).",estimated survival and success rates of cantilever fpds were lower than previously reported rates for typical end-abutement supported fpds; a 10-year failure rate of 18.2 had previously been reported for end-abutment supported fpds for comparison.,General
does pholcodine exposure raise serum ige in patients with previous anaphylaxis to neuromuscular blocking agents?,"neuromuscular blocking agents (nmbas) can cause anaphylaxis through immunoglobulin e (ige) antibodies that bind quaternary ammonium ion epitopes. these epitopes are present in numerous common chemicals and drugs, exposure to which, theoretically, could be of importance in the development and maintenance of the ige sensitization promoting allergic reactions. pholcodine is one such drug, which in a recent pilot study was shown to induce a remarkable increase in serum ige levels in two ige-sensitized individuals. the present study explores the effect of pholcodine exposure on ige in a population with previously diagnosed ige-mediated anaphylaxis towards nmbas. seventeen patients were randomized to 1 week's exposure with cough syrup containing either pholcodine or guaifenesin. the primary variables serum ige and ige antibodies towards pholcodine, morphine and suxamethonium were measured before and 4 and 8 weeks after start of exposure. patients exposed to pholcodine had a sharp rise in levels of ige antibodies towards pholcodine, morphine and suxamethonium, the median proportional increases 4 weeks after exposure reaching 39.0, 38.6 and 93.0 times that of the base levels respectively. median proportional increase of ige was 19.0. no changes were observed in the guaifenesin group.",serum levels of ige antibodies associated with allergy towards nmbas increase significantly in sensitized patients after exposure to cough syrup containing pholcodine. availability of pholcodine should be restricted by medical authorities because of the potential risk of future allergic reactions to muscle relaxants.,Medication
"is overhead tank the potential breeding habitat of anopheles stephensi in an urban transmission setting of chennai , india?","wells and overhead tanks (oht) are the major breeding sources of the local malaria vector, anopheles stephensi in the indian city of chennai; they play a significant role in vector breeding, and transmission of urban malaria. many other man-made breeding habitats, such as cemented cisterns/containers, barrels or drums, sumps or underground tanks, and plastic pots/containers are maintained to supplement water needs, temporarily resulting in enhanced mosquito/vector breeding. correlating breeding habitats with immature vector abundance is important in effective planning to strengthen operational execution of vector control measures. a year-long, weekly study was conducted in chennai to inspect available clear/clean water mosquito breeding habitats. different breeding features, such as instar-wise, immature density and co-inhabitation with other mosquito species, were analysed. the characteristics of breeding habitats, i.e., type of habitat, water temperature and presence of aquatic organisms, organic matter and green algal remnants on the water surface at the time of inspection, were also studied. immature density of vector was correlated with presence of other mosquito species, malaria prevalence, habitat characteristics and monthly/seasonal fluctuations. all the data collected from field observations were analysed using standard statistical tools. when the immature density of breeding habitats was analysed, using one-way anova, it was observed that the density did not change in a significant way either across seasons or months. ohts contributed significantly to the immature population when compared to wells and other breeding habitats of the study site. the habitat positivity of wells and ohts was significantly associated with the presence of aquatic organisms, organic matter and algal remnants. significant correlations of malaria prevalence with monthly immature density, as well as number of breeding habitats with immature vector mosquitoes, were also observed.","the findings that ohts showed fairly high and consistent immature density of an. stephensi irrespective of seasons indicates the potentiality of the breeding habitat in contributing to vector density. the correlation between vector breeding habitats, immature density and malaria prevalence indicates the proximity of these habitats to malaria cases, proving its role in vector abundance and local malaria transmission. the preference of an. stephensi to breed in ohts calls for intensified, appropriate and sustained intervention measures to curtail vector breeding and propagation to shrink malaria to pre-elimination level and beyond.",Medication
does adjuvant therapy with the monoclonal antibody edrecolomab plus fluorouracil-based therapy improve overall survival of patients with stage iii colon cancer?,"edrecolomab (ed) is a murine monoclonal antibody targeting the epcam antigen. this phase iii randomized multicenter trial investigated the benefit of adding ed to fluorouracil (fu) based therapy in patients with stage iii colorectal cancer. patients with stage iii colon cancer were randomly assigned to one of two treatments after curative surgery. patients in arm 1 received five infusions of ed together with fu-based chemotherapy; patients in arm 2 received fu-based chemotherapy alone. the primary end point was overall survival (os). one thousand eight hundred thirty-nine patients were randomly assigned; results were analyzed on an intent-to-treat basis. patient characteristics were well-balanced across treatment arms. five-year follow-up has been completed. patients randomly assigned to ed plus fu-based therapy showed a 5-year survival rate of 69.6 while for patients receiving fu-based therapy, the rate was 68.2. the hazard ratio for death with ed plus fu-based therapy compared to fu-based therapy was 0.896 (95 ci, 0.752 to 1.068), which was not statistically significant (p .220). the adverse effect profiles of the two treatment arms were similar, with the main adverse effects being diarrhea, abdominal pain, and nausea. anaphylaxis occurred in fewer than 1 of patients receiving ed.","for patients with stage iii colon cancer, the addition of ed to fu-based therapy had no statistically significant effect on os.",Treatment
does fresh frozen plasma increase adhesion molecule expression on human pulmonary endothelial cells?,"current blood banking practices allow fresh frozen plasma (ffp) to be thawed and then stored for 5 d between 1 and 6 c. we hypothesized that aged plasma (d 5 ffp) would be pro-inflammatory to the endothelium compared with fresh plasma (d 0 ffp). human pulmonary endothelial cells (pecs) were treated with (1) media, (2) media lipopolysaccharide (lps), (3) lactated ringer's (lr), (4) lr lps, (5) d 0 ffp, (6) d 0 ffp lps, (7) d 5 ffp, and (8) d 5 ffp lps. after a 24 h incubation, the pecs were stained with antibodies for i-cam, v-cam, p-selectin, and e-selectin. the cells were subsequently analyzed by flow cytometry. in both pec groups treated with ffp and stimulated with lps, i-cam, v-cam, p-selectin, and e-selectin were significantly up-regulated compared with lr when stimulated by lps.",ffp at both ages significantly increased expression of four different adhesion molecules compared with lr in pecs. this may represent a possible mechanism for increased leukocyte binding on the endothelium as a result of ffp transfusion.,Treatment
does candesartan reduce urinary fatty acid-binding protein excretion in patients with autosomal dominant polycystic kidney disease?,"free fatty acids (ffas) bound to albumin are overloaded in renal proximal tubules and exacerbate tubulointerstitial damage. liver-type fatty acid-binding protein (l-fabp) is an intracellular carrier protein of ffas that is expressed in renal proximal tubules in humans. urinary l-fabp reflects the clinical prognosis of chronic glomerulonephritis. the aim of the present study was to determine whether urinary l-fabp excretion is altered in patients with autosomal dominant polycystic kidney disease (adpkd) and whether candesartan cilexetil, an angiotensin ii receptor antagonist, affects these levels. subjects comprised 20 normotensive adpkd patients (8 men and 12 women, mean age 42.6 years) and 20 age-matched healthy volunteers (8 men and 12 women, mean age 44.0 years). the 20 adpkd patients participated in a randomized double-blind placebo-controlled study of candesartan cilexetil for 6 months. urinary l-fabp levels were measured by a newly established elisa method. urinary l-fabp levels were significantly higher in adpkd patients (154.5 /- 110.6 microg/g cr) than in healthy subjects (5.5 /- 3.8 microg/g cr) (p 0.001). candesartan cilexetil reduced urinary l-fabp levels from 168.5 /- 104.5 microg/g cr to 98.5 /- 68.5 microg/g cr after 3 months (p 0.01) and to 44.6 /- 30.8 microg/g cr after 6 months (p 0.001). placebo had no effect on l-fabp levels (before, 140.5 /- 100.5 microg/g cr; at 3 months, 148.5 /- 108.5 microg/g cr; at 6 months, 150.5 /- 110.8 microg/g cr). during the 6 months, serum creatinine, blood urea nitrogen, 24-hour creatinine clearance and blood pressure showed little change in either group.","increased urinary l-fabp levels may be associated with the development of adpkd, and candesartan cilexetil has a beneficial effect on reducing these levels.",Medication
does chronic transcutaneous electrical stimulation of calf muscles improve functional capacity without inducing systemic inflammation in claudicants?,"to assess whether electrical stimulation of ischaemic calf muscles in claudicants causes a systemic inflammatory response and to evaluate effects of its chronic application on muscle function and walking ability. prospective randomised controlled trial of calf muscle stimulation. stable claudicants were randomised to receive either active chronic low frequency (6 hz) motor stimulation (n15) or, as a control treatment, submotor transcutaneous electrical nerve (tens) stimulation (n15) of calf muscles in one leg, 3 x 20 min per day for four weeks. leucocyte activation was quantified by changes in cell morphology, vascular permeability by urinary albumin:creatinine ratio (acr), calf muscle function by isometric twitch contractions and walking ability by treadmill performance pre- and post-intervention. acute active muscle stimulation activated leucocytes less (28 increase) than a standard treadmill test (81 increase) and did not increase acr. chronic calf muscle stimulation significantly increased pain-free walking distance by 35 m (95 ci 17, 52, p0.001) and maximum walking distance by 39 m (95 ci 7, 70, p0.05) while control treatment had no effect. active stimulation prevented fatigue of calf muscles during isometric electrically evoked contractions by abolishing the slowing of relaxation that was responsible for loss of force.","chronic electrical muscle stimulation is an effective treatment for alleviating intermittent claudication which, by targeted activation of a small muscle mass, does not engender a significant systemic inflammatory response.",Treatment
does anti-cdc25b autoantibody predict poor prognosis in patients with advanced esophageal squamous cell carcinoma?,"the oncogene cdc25b phosphatase plays an important role in cancer cell growth. we have recently reported that patients with esophageal squamous cell carcinoma (escc) have significantly higher serum levels of cdc25b autoantibodies (cdc25b-abs) than both healthy individuals and patients with other types of cancer; however, the potential diagnostic or prognostic significance of cdc25b-abs is not clear. the aim of this study is to evaluate the clinical significance of serum cdc25b-abs in patients with escc. cdc25b autoantibodies were measured in sera from both 134 patients with primary escc and 134 healthy controls using a reverse capture enzyme-linked immunosorbent assay (elisa) in which anti-cdc25b antibodies bound cdc25b antigen purified from eca-109 escc tumor cells. the clinicopathologic significance of cdc25b serum autoantibodies was compared to that of the tumor markers carcinoembryonic antigen (cea), squamous cell carcinoma antigen (scc-ag) and cytokeratin 19 fragment antigen 21-1(cyfra21-1). higher levels of cdc25b autoantibodies were present in sera from patients with escc (a450 0.917, sd 0.473) than in sera from healthy control subjects (a450 0.378, sd 0.262, p 0.001). the area under the receiver operating characteristic (roc) curve for cdc25b-abs was 0.870 (95 ci: 0.835-0.920). the sensitivity and specificity of cdc25b-abs for detection of escc were 56.7 and 91.0, respectively, when cdc25-abs-positive samples were defined as those with an a450 greater than the cut-off value of 0.725. relatively few patients tested positive for the tumor markers cea, scc-ag and cyfra21-1 (13.4, 17.2, and 32.1, respectively). a significantly higher number of patients with escc tested positive for a combination of cea, scc, cyfra21-1 and cdc25b-abs (64.2) than for a combination of cea, scc-ag and cyfra21-1 (41.0, p 0.001). the concentration of cdc25b autoantibodies in serum was significantly correlated with tumor stage (p 0.001). although examination of the total patient pool showed no obvious relationship between cdc25b autoantibodies and overall survival, in the subgroup of patients with stage iii-iv tumors, the cumulative five-year survival rate of cdc25b-seropositive patients was 6.7, while that of cdc25b-seronegative patients was 43.4 (p 0.001, log-rank). in the n1 subgroup, the cumulative five-year survival rate of cdc25b-seropositive patients was 13.6, while that of cdc25b-seronegative patients was 54.5 (p 0.040, log-rank).","detection of serum cdc25b-abs is superior to detection of the tumor markers cea, scc-ag and cyfra21-1 for diagnosis of escc, and cdc25b-abs are a potential prognostic serological marker for advanced escc.",Diagnosis
does arginine vasopressin alter mucosal tissue oxygen tension and oxygen supply in an acute endotoxemic pig model?,"to determine the effects of increasing dosages of continuously infused arginine-vasopressin (avp) on mucosal tissue oxygen tension and oxygen supply in an auto-perfused, innervated jejunal segment in an acute endotoxic porcine model. prospective, randomized, experimental study. university hospital animal research laboratory. jejunal mucosal tissue po2 was measured employing two clark-type surface oxygen electrodes. oxygen saturation of jejunal microvascular hemoglobin was determined by tissue reflectance spectrophotometry. systemic hemodynamic variables, mesenteric-venous and systemic acid base and blood gas variables and lactate measurements were recorded. measurements were performed at baseline, after e. coli lipopolysaccharide (lps) administration and at 20 min intervals during incremental avp infusion (n8; 0.014, 0.029, 0.057, 0.114 and 0.229 iu kg(-1) h(-1), respectively) or infusion of saline (n 8). lps infusion leads to a significant (p0.05) decrease of mucosal tissue oxygen tension (po2muc, 24/-3 to 12/-2 mmhg) and microvascular hemoglobin oxygen saturation (hbo2, 38/-4 to 21/-4). mesenteric venous lactate level increased (2.4/-0.3 to 4.7/-1.7 mmol l(-1)), while mesenteric venous ph decreased (7.38/-0.02 to 7.26/-0.12), indicating tissue hypoxia. avp significantly increased mean arterial pressure (map, 81/-15 to 97/-17 at 0.057 iu kg(-1) h(-1)). no differences in jejunal mucosal oxygenation occurred between study groups at any dosage during the experimental protocol.",avp administration did not further compromise mucosal tissue oxygen tension and oxygen supply in the acute phase of endotoxic pigs.,Medication
do women with voiding dysfunction secondary to bladder outlet dyssynergia in the setting of multiple sclerosis demonstrate significantly elevated intravesical pressures?,"elevated intravesical pressures secondary to detrusor sphincter dyssynergia result in an increased risk of renal deterioration in patients with cervical and thoracic spinal cord injury, although the risk is less clear in patients with multiple sclerosis (ms). the purpose of this study was to study the impact of a closed bladder outlet on intravesical pressures in patients with ms. the data from all patients with ms referred for urologic evaluation were prospectively entered into a urodynamic database. patients were advised to undergo full multichannel urodynamic studies. among the patients with detrusor overactivity, the detrusor pressures were compared between the patients with and without bladder outlet dyssynergia (bod). of the 143 patients referred for evaluation and entered into the database, 127 were women. of the 127 women, 108 completed the urodynamic studies. overall, 62 (57) of the 108 women had detrusor overactivity, 30 of whom had coexisting bod. the detrusor pressures during bladder contractions were greater in patients with bod, although not significantly. for example, the maximal detrusor pressure (49.9 /- 19.5 cm h2o versus 43.7 /- 23.0 cm h2o, p 0.25) and detrusor pressure at maximal flow (37.9 /- 15.7 cm h2o versus 33.5 /- 16.3 cm h2o, p 0.93) were both only slightly greater in patients with bod.","nonsignificant elevations in detrusor pressures were noted in patients with ms and bod. the lack of significant elevations in detrusor pressure among the patients with ms, detrusor overactivity, and bod could account for the relatively low incidence of upper tract damage in women with ms.",Symptoms
does switching to a 10-day mediterranean-style diet improve mood and cardiovascular function in a controlled crossover study?,"even short-term adherence to a mediterranean-style diet may benefit aspects of psychological functioning. the aim of the present study was to assess the effects of switching to a 10-d mediterranean-style diet on mood, cognition, and cardiovascular measures. using a crossover design, 24 women were randomly assigned to either the diet change (where they switched to a mediterranean-style diet) or no diet change (normal diet) condition for 10 days before switching to the other condition for the same duration. mood, cognition, and cardiovascular measures of blood pressure, blood flow velocity, and arterial stiffness were assessed at baseline and at the completion of the two diets (days 11 and 22). independent of whether the mediterranean-style diet was undertaken before or after the crossover, it was associated with significantly elevated contentment and alertness, and significantly reduced confusion. additionally, aspects of cognition, such as memory recall, improved significantly as a result of switching to the mediterranean-style diet. regarding cardiovascular measures, there was a significant reduction in augmentation pressure associated with the mediterranean-style diet intervention, but blood flow velocity through the common carotid artery did not change.","this mediterranean-style diet has the potential to enhance aspects of mood, cognition, and cardiovascular function in a young, healthy adult sample.",Prevention
does resveratrol stimulate mitochondrial bioenergetics to protect retinal pigment epithelial cells from oxidative damage?,"resveratrol (rsv) alleviates oxidative damage in human adult retinal pigment epithelial (arpe) cells. mitochondrial bioenergetics is associated with oxidative stress. the purpose of this study was to examine the role of mitochondrial bioenergetics in the cytoprotective effect of rsv. its role in protection against the adverse effects of cigarette smoke (cs) in experimental choroidal neovascularization (cnv) was also examined. cultured arpe-19 cells were treated with acrolein alone or acrolein with added rsv. temporal changes in cell viability, expression of the antioxidant protein, and mitochondrial bioenergetics were evaluated. in an animal study, cnv lesions were created in brown norway rats by laser-induced photocoagulation. effects of cs alone or with additional rsv treatment on cnv lesions were quantified by fundus fluorescein angiography. in arpe-19 cells, rsv rescued acrolein-induced cell death, alongside reversal of acrolein-induced superoxide dismutase expression. resveratrol increased the mitochondrial bioenergetics, including basal respiratory rate, adenosine triphosphate synthesis via oxidative phosphorylation, and maximal mitochondrial capacity. in animal experiments, cs induced a significant increase in cnv following laser injury, and this increase in cnv was appreciably prevented following peripheral infusion of rsv.","our results indicate that rsv, a major polyphenol found in red wine, exerts protection against acrolein-induced cytotoxicity in human arpe-19 cells via increases in the mitochondrial bioenergetics. in addition, the antioxidant effect of rsv may contribute to protection against laser-induced cnv in animals exposed to cs. therefore, rsv might be beneficial for treatment of acrolein-induced or cs-evoked rpe degeneration.",Medication
do specific fracture configurations predict sexual and excretory dysfunction in men and women 1 year after pelvic fracture?,"we determined the prevalence and predictors of sexual and excretory dysfunction in patients 1 year after pelvic fracture. the multicenter pennsylvania trauma outcomes study enrolled 1,238 patients and contacted them 1 year after injury. sexual limitations and excretory dysfunction (bladder/bowel incontinence) were defined based on responses from the functional capacity index. health related quality of life was determined using sf-36. the relationship between specific fracture patterns and dysfunction along with the effect of dysfunction on quality of life in patients with pelvic fracture were evaluated by multivariate analysis. of 1,160 eligible patients 292 (26) had pelvic fractures. sexual dysfunction was reported in 21 vs 14 of those with vs without pelvic fractures and bowel or bladder incontinence was reported in 8 vs 4. on multivariate analysis men with sacroiliac fractures were at higher risk for sexual (rr 4.0, 95 ci 2.3 to 6.8) and excretory (rr 4.3, 95 ci 1.4 to 13.5) dysfunction. in women symphyseal diastasis was associated with sexual (rr 4.8, 95 ci 2.0 to 11.2) and excretory (rr 12.5, 95 ci 1.9 to 80.2) dysfunction. of patients with pelvic fractures men with sexual dysfunction and women with excretory dysfunction had significantly worse quality of life than those without dysfunction.",one year after trauma men with sacroiliac fractures and women with symphyseal diastasis were at increased risk for sexual and excretory dysfunction independent of overt pelvic organ injury. in patients with pelvic fracture male sexual dysfunction and female excretory dysfunction were associated with decreased quality of life. our data highlight the need for further study of dysfunction following pelvic trauma and interventions to decrease the risk of long-term disability.,Symptoms
does in vivo confocal microscopy demonstrate bilateral loss of endothelial cells in unilateral herpes simplex keratitis?,"to report bilateral corneal endothelial cell density (ecd), as well as its correlation with subbasal nerve changes, in patients with unilateral herpes simplex keratitis (hsk). thirty-six eyes of 36 patients with corneal scarring caused by hsk, as well as their respective contralateral clinically unaffected eyes, were prospectively studied and compared with 26 eyes of 26 healthy volunteers. in vivo confocal microscopy and corneal sensation of the central cornea were performed bilaterally in all patients and in one random eye of controls. the ecd and subbasal corneal nerve density, including the lengths of total nerves, main trunks, and branches were evaluated and correlated to central corneal sensation. the ecd was significantly lower in eyes affected with hsk than in controls (2304 578 vs. 2940 370 cells/mm(2), p 0.0001). surprisingly, lower ecd was also detected in contralateral clinically unaffected eyes (2548 423), compared to controls (p 0.02). both affected and contralateral eyes showed decrease in total nerve length, compared to controls (10.0 6.3 vs. 17.6 6.3 vs. 21.9 4.3 mm/mm2, respectively; p 0.05 for all). the ecd correlated positively with total nerve length (r 0.39, p 0.0009) and with corneal sensation (r 0.31, p 0.009).","in vivo confocal microscopy findings demonstrated alterations in corneal ecd in both affected and clinically unaffected contralateral eyes of patients with unilateral hsk. moreover, the positive significant correlation between the ecd and the subbasal nerve density may suggest a potential link between corneal innervation and corneal endothelial cell homeostasis.",General
is little rock a rock1 pseudogene expressed in human smooth muscle cells?,"sequencing of the human genome has identified numerous chromosome copy number additions and subtractions that include stable partial gene duplications and pseudogenes that when not properly annotated can interfere with genetic analysis. as an example of this problem, an evolutionary chromosome event in the primate ancestral chromosome 18 produced a partial duplication and inversion of rho-associated protein kinase 1 (rock1 -18q11.1, 33 exons) in the subtelomeric region of the p arm of chromosome 18 detectable only in humans. rock1 and the partial gene copy, which the gene databases also currently call rock1, include non-unique single nucleotide polymorphisms (snps). here, we characterize this partial gene copy of the human rock1, termed little rock, located at 18p11.32. little rock includes five exons, four of which share 99 identity with the terminal four exons of rock1 and one of which is unique to little rock. in human while rock1 is expressed in many organs, little rock expression is restricted to vascular smooth muscle cell (vsmc) lines and organs rich in smooth muscle. the single nucleotide polymorphism database (dbsnp) lists multiple variants contained in the region shared by rock1 and little rock. using gene and cdna sequence analysis we clarified the origins of two non-synonymous snps annotated in the genome to actually be fixed differences between the rock1 and the little rock gene sequences. two additional coding snps were valid polymorphisms selectively within little rock. little rock-green fluorescent fusion proteins were highly unstable and degraded by the ubiquitin-proteasome system in vitro.","in this report we have characterized little rock (rock1p1), a human expressed pseudogene derived from partial duplication of rock1. the large number of pseudogenes in the human genome creates significant genetic diversity. our findings emphasize the importance of taking into consideration pseudogenes in all candidate gene and genome-wide association studies, as well as the need for complete annotation of human pseudogenome.",General
does helicobacter pylori eradication treatment benefit patients with nonulcer dyspepsia?,"the aim of this study was to assess the still controversial role of treatment of helicobacter pylori (h. pylori) infection in patients with nonulcer dyspepsia. we conducted a double-blind, randomized, placebo-controlled, multicenter trial comparing the efficacy of 7 days of eradication treatment (lansoprazole 15 mg b.i.d., amoxicillin i g b.i.d., and clarithromycin 500 mg b.i.d.) with a control treatment (lansoprazole 15 mg b.i.d. and placebo) in h. pylori-infected patients with nonulcer dyspepsia. 13c breath tests were performed at baseline and during follow-up. we assessed patient symptoms, health status (based on the sf-12 questionnaire), patient satisfaction, drug consumption, health care consultation behavior, and absenteeism related to dyspepsia over a 1-yr period. a total of 74 patients randomized to eradication treatment and 70 patients randomized to placebo were compared. the rate of eradication of h. pylori infection was 75 in the active treatment group and 4 in the placebo group (p 0.005). the symptom score improved to a similar extent in the group receiving active treatment (-4.0; 95 ci -5.0 to -3.0) and placebo (-3.6; 95 ci -4.5 to -2.7). treatment response was not related to the severity or duration of initial symptoms or to the severity of gastritis on histology. quality of life scores were comparable at 12 months. there was no significant difference in dyspepsia-related absenteeism or satisfaction with management of nud. patients receiving active treatment were more likely not to have had to use any dyspepsia treatment over the 12 months (60.8 vs 44.3; p 0.047).",this study did not demonstrate any substantial benefit of curing h. pylori infection in patients with nonulcer dyspepsia. the study adds further evidence that h. pylori is not the main pathogenetic or therapeutic target in these patients.,Treatment
does over-expression of cysteine leucine rich protein be related to sag resistance in clinical isolates of leishmania donovani?,"resistance emergence against antileishmanial drugs, particularly sodium antimony gluconate (sag) has severely hampered the therapeutic strategy against visceral leishmaniasis, the mechanism of resistance being indistinguishable. cysteine leucine rich protein (clrp), was recognized as one of the overexpressed proteins in resistant isolates, as observed in differential proteomics between sensitive and resistant isolates of l. donovani. the present study deals with the characterization of clrp and for its possible connection with sag resistance. in pursuance of deciphering the role of clrp in sag resistance, gene was cloned, over-expressed in e. coli system and thereafter antibody was raised. the expression profile of clrp and was found to be over-expressed in sag resistant clinical isolates of l. donovani as compared to sag sensitive ones when investigated by real-time pcr and western blotting. clrp has been characterized through bioinformatics, immunoblotting and immunolocalization analysis, which reveals its post-translational modification along with its dual existence in the nucleus as well as in the membrane of the parasite. further investigation using a chip assay confirmed its dna binding potential. over-expression of clrp in sensitive isolate of l. donovani significantly decreased its responsiveness to sag (sbv and sbiii) and a shift towards the resistant mode was observed. further, a significant increase in its infectivity in murine macrophages has been observed.","the study reports the differential expression of clrp in sag sensitive and resistant isolates of l. donovani. functional intricacy of clrp increases with dual localization, glycosylation and dna binding potential of the protein. further over-expressing clrp in sensitive isolate of l. donovani shows significantly decreased sensitivity towards sag and increased infectivity as well, thus assisting the parasite in securing a safe niche. results indicates the possible contribution of clrp to antimonial resistance in l. donovani by assisting the parasite growth in the macrophages.",Medication
does zyxin antagonize the ferm protein expanded to couple f-actin and yorkie-dependent organ growth?,"coordinated multicellular growth during development is achieved by the sensing of spatial and nutritional boundaries. the conserved hippo (hpo) signaling pathway has been proposed to restrict tissue growth by perceiving mechanical constraints through actin cytoskeleton networks. the actin-associated lim proteins zyxin (zyx) and ajuba (jub) have been linked to the control of tissue growth via regulation of hpo signaling, but the study of zyx has been hampered by a lack of genetic tools. we generated a zyx mutant in drosophila using talen endonucleases and used this to show that zyx antagonizes the ferm-domain protein expanded (ex) to control tissue growth, eye differentiation, and f-actin accumulation. zyx membrane targeting promotes the interaction between the transcriptional co-activator yorkie (yki) and the transcription factor scalloped (sd), leading to activation of yki target gene expression and promoting tissue growth. finally, we show that zyx's growth-promoting function is dependent on its interaction with the actin-associated protein enabled (ena) via a conserved lpppp motif and is antagonized by capping protein (cp).",our results show that zyx is a functional antagonist of ex in growth control and establish a link between actin filament polymerization and yki activity.,Prevention
do follicular cell implantation for induce hair follicle growth in nude mice ?,"to establish a convenient and reliable method for inducing hair regeneration by follicular cell implantation for the treatment of alopecia. the human hair follicle stem cells were separated and purified by micromanipulation and magnetic cell sorting, and human scalp dermal papilla cells were isolated by enzyme digestion. the two cells were mixed and implanted subcutaneously in nude mice to observe the regeneration of the hair follicles. formation of intact hair follicle-like structures was observed in the skin sections of the recipient nude mice.","follicular cell implantation can induce hair follicle-like structures in nude mice, which provides a means for efficient hair regeneration for treatment of hair loss.",Treatment
is transmural dispersion of refractoriness and conduction velocity associated with heterogeneously reduced connexin43 in a rabbit model of heart failure?,"heterogeneity of repolarization and conduction is a potential source of arrhythmogenesis. in heart failure (hf), intercellular coupling is reduced and heterogeneities may become evident because of reduced intercellular coupling. this study sought to investigate connexin43 (cx43) expression, conduction velocity (cv), refractoriness and inducibility of arrhythmias at multiple sites of the left ventricle during hf. hf was induced by pressure-volume overload in rabbits. epicardial and intramural mapping was performed in isolated perfused hearts following programmed stimulation. myocytes were enzymatically dissociated and studied using d-4-anepps fluorescence. western blotting and immunohistochemistry was performed to quantify heterogeneity of cx43 expression. cx43 was heterogeneously reduced in the midmyocardial, but not in the sub epicardium layer of the left ventricular free wall in hf compared to control rabbits. in hf, subepicardial and midmyocardial refractory periods (rps) were increased compared to control rabbits (148 /- 3 ms and 143 /- 3 versus 131 /- 2 and 129 /- 2 ms, respectively, both p 0.001). also, transmural dispersion of rps was larger in hf (30 /- 4 ms) than in control rabbits (24 /- 3 ms, p 0.05). intrinsic dispersion of action potential duration in isolated myocytes was similar in hf and control rabbits. transmural cv was heterogeneous, although the mean cv was not different between groups. arrhythmias were more easily inducible in hf, especially from midmyocardium.","in hf, midmyocardial cx43 expression is heterogeneously reduced. this is associated with increased transmural dispersion in refractoriness and conduction, and with increased arrhythmia inducibility.",General
do serum cortisol concentration with exploratory cut-off values predict the effects of hydrocortisone administration in children with low cardiac output after cardiac surgery?,"low cardiac output syndrome is common after paediatric cardiac surgery. previous studies suggested that hydrocortisone administration may improve haemodynamic stability in case of resistant low cardiac output syndrome in critically ill children. this study was set up to test the hypothesis that the effects of hydrocortisone on haemodynamics in children with low cardiac output syndrome depend on the presence of (relative) adrenal insufficiency. a retrospective study was done on paediatric patients who received hydrocortisone when diagnosed with resistant low cardiac output syndrome after paediatric cardiac surgery in the period from 1 november 2005 to 31 december 2008. we studied the difference in effects of treatment with hydrocortisone administration between patients with adrenal insufficiency defined as an exploratory cut-off value of total cortisol of 100 nmol/l and patients with a serum total cortisol of 100 nmol/l. a total of 62 of patients were enrolled, meeting the inclusion criteria for low cardiac output syndrome. thirty-two patients were assigned to group 1 (100 nmol/l) and 30 were assigned to group 2 ( 100 nmol/l). haemodynamics improved after hydrocortisone administration, with an increase in blood pressure, a decrease in administered vasopressors and inotropic drugs, an increase in urine production and a decrease in plasma lactate concentrations.",the effects of treatment with hydrocortisone in children with low cardiac output after cardiac surgery was similar in patients with a low baseline serum cortisol concentration and those with normal baseline cortisol levels. a cortisol value using an exploratory cut-off value of 100 nmol/l for adrenal insufficiency should not be used as a criterion to treat these patients with hydrocortisone.,Treatment
does a multilocus candidate approach identify ace and hif1a as susceptibility genes for cellulite?,"cellulite is a common complex cosmetic problem for many post-adolescent women characterised by relief alterations of the skin surface, which give the skin an orange-peel appearance. although genetic factors have been suggested to play a role in the development of cellulite, the genetic background of this condition remains unclear. we therefore conducted a multi-locus genetic study examining the potential associations of candidate gene variants in oestrogen receptors, endothelial function/adipose tissue hypoxia, lipid metabolism, extracellular matrix homeostasis, inflammation and adipose tissue biology, with the risk of cellulite. using a case-control study of 200 lean women with cellulite and 200 age- and bmi-matched controls (grade 0 according to nurnberger-muller scale), we examined the association of cellulite with 25 polymorphisms in 15 candidate genes. two of the 25 polymorphisms were significantly associated with cellulite at the p 0.01 level. after allowance for age, body mass index, the prevalence of contraceptive use and smoking in logistic regression analysis, the multivariable-adjusted odds ratios for cellulite were 1.19 (95 ci: 1.10-1.51; p 0.01) for ace rs1799752 and 0.61 (95 ci: 0.45-0.88, p 0.01) for hif1a rs11549465.","this study, which demonstrates an independent role of ace and hif1a in predisposing to cellulite, may provide novel information on the pathophysiology of this common cosmetic problem, and offer a topic for research for novel beautification interventions.",Medication
is niacin extended-release therapy in phase iii clinical trials associated with relatively low rates of drug discontinuation due to flushing and treatment-related adverse events : a pooled analysis?,"niacin is a highly effective agent for increasing low high-density lipoprotein cholesterol (hdl-c) levels. it also has beneficial effects on key pro-atherogenic lipoprotein parameters. however, the side effect of flushing can challenge patient adherence to treatment. in this study, we pooled safety data from available trials of at least 16 weeks' duration to evaluate the impact of flushing on patient adherence to niacin extended-release (ner) therapy. data were pooled from eight ner studies (administered as ner with a maximum dosage of 1000, 1500, and 2000 mg/day, either as monotherapy or in combination with simvastatin 20 or 40 mg/day ner/s, or lovastatin 20 or 40 mg/day ner/l) to evaluate rates of study discontinuation due to flushing or any treatment-related adverse events. while 66.6 of patients experienced flushing, only 5.2 of patients discontinued treatment due to flushing. of the total number of patients treated with ner (n 307), ner/s (n 912), or ner/l (n 928), 34 (11), 105 (11), and 127 (14) patients discontinued due to any treatment-related adverse event, respectively, while 14 (5), 43 (5), and 55 (6) discontinued due to flushing. discontinuation for flushing did not differ with regard to maximum dose, or to the presence or type of statin combined with ner.","although flushing was common with ner treatment, discontinuation due to flushing occurred in only 5-6 of patients in this pooled analysis. this could be due to several factors, including the fact that all patients in the ner trials were educated about flushing and its management. translation of methodology employed in these trials into clinical practice may improve long-term adherence to ner therapy, which would enhance the therapeutic benefit of ner for reducing cardiovascular risk.",Medication
is cadherin-11 expressed in detrusor smooth muscle cells and myofibroblasts of normal human bladder?,"it has recently been found that detrusor smooth muscle cells and myofibroblasts are coupled via gap junctions. however, gap junctions cannot account for strong physical interaction between cells, which has prompted the search for intercellular adhesion molecules. cadherin-11 is a candidate for such a molecule, since it mediates the interaction of dermal myofibroblasts in contractile wound granulation tissue. we therefore hypothesised that the physical adhesion between detrusor smooth muscle cells and myofibroblasts is mediated by cadherin-11. the aim of this study was to test this hypothesis. bladder biopsies from eight radical cystectomy specimens were snap-frozen, sectioned, and stained for e-cadherin; cadherin-11; alpha-catenin; beta-catenin; gamma-catenin; and smooth muscle cell/myofibroblast markers connexin-43, vimentin, desmin, smooth muscle actin, and smoothelin. specimens were analysed by using binocular epifluorescent and confocal laser-scanning microscopy. specific positive membranous expression of all adhesion complex molecules except e-cadherin was detected in detrusor suburothelial tissue. all biopsies showed a similar punctate pattern of expression for cadherin-11 within bundles of smooth muscle cells and a suburothelial layer of cells. cadherin-11 was specifically located at the cell membrane, in distinct linear domains.",to our knowledge this is the first time evidence has been provided for cadherin-mediated smooth muscle and suburothelial myofibroblast cell-cell interaction in the human bladder. cadherin-11 most probably plays an important role in the intercellular physical coupling of detrusor smooth muscle cells and also of myofibroblasts.,Diagnosis
does atp stimulate chemokine production via a store-operated calcium entry pathway in c6 glioma cells?,"glioma present as one of the most challenging cancers to treat, however, understanding of tumor cell biology is not well understood. extracellular adenosine triphosphate (atp) could serve as a critical signaling molecule regulating tumor development. this study has examined pharmacological modulation of calcium (ca2) entry through store-operated channels (soc) on cellular expression and production of immune-cell mobilizing chemokines in atp-stimulated c6 glioma cells. calcium spectrofluorometry was carried out to measure mobilization of intracellular ca2 ca2i following atp stimulation of rat c6 glioma cells. pretreatment with two inhibitors of soc, skf96365 or gadolinium, was used to examine for effects on ca2i. rt-pcr was performed to determine effects of purinergic stimulation on c6 cell expression of metabotropic p2y receptors (p2yr) and the chemokines, monocyte chemoattractant protein-1 (mcp-1) and interleukin-8 (il-8). elisa was carried out to measure production of mcp-1 and il-8 with atp stimulation of glioma cells. application of atp (at 100 microm) to c6 glioma induced an increase in ca2i with the response exhibiting two components of decay. in the presence of the soc inhibitors, skf96365 or gadolinium, or with ca2-free solution, atp responses lacked a slow phase suggesting the secondary component was due to soc-mediated influx of ca2. rt-pcr confirmed expression of purinergic p2y-subtype receptors in c6 cells which would serve as a precursor to activation of soc. in addition, atp-stimulated c6 cells showed enhanced expression of the chemokines, mcp-1 and il-8, with skf96365 or gadolinium effective in reducing chemokine expression. gadolinium treatment of atp-stimulated c6 cells was also found to inhibit the production of mcp-1 and il-8.","these results suggest atp-induced ca2 entry, mediated by activation of soc in c6 glioma, as a mechanism leading to increased cellular expression and release of chemokines. elevated levels of mcp-1 and il-8 are predicted to enhance the mobility of tumor cells and promote recruitment of microglia into developing tumors thereby supporting tumor growth.",Medication
is tumour budding a reproducible index for risk stratification of patients with stage ii colon cancer?,"high-risk patients with stage ii colon cancer may benefit from adjuvant chemotherapy, but it is difficult to identify such a patient group. a robust and reproducible index would be helpful to select the subset of stage ii colon cancer patients at high risk. this study investigated the potential prognostic significance of tumour budding in stage ii colon cancer. in all, 135 stage ii colon cancer patients with known outcome were identified. the degree of tumour budding was assessed by two individual observers and was classified, according to the number of tumour buds in the area with the greatest budding intensity on haematoxylin and eosin slides, as high-grade budding (10 or more tumour buds) and low-grade budding (0-9 buds). inter-observer agreement for two observers was assessed by using the kappa test. progression-free and cancer-specific survivals were analysed using the kaplan-meier method and cox regression. the 5-year progression-free survival rates for patients with high-grade tumour budding (n 36) and those with low-grade budding (n 99) were 57.6 and 89.0 (p 0.001). the 5-year cancer-specific survival rates were 66.7 vs 92.0 (p 0.001). cox regression analyses demonstrated tumour budding as an independent predictor of disease progression (hazard ratio 4.982, p 0.001) and cancer-related death (hazard ratio 4.142, p 0.003). the two observers agreed on the classification of tumour budding in 118 cases (87.4) and the inter-observer agreement was good ( 0.692).","tumour budding is a strong and reproducible prognostic factor for adverse outcome in stage ii colon cancer, which may serve as a prognostic marker to identify patients with a high risk of recurrence who may benefit from adjuvant therapy.",Medication
are fluctuating transglutaminase autoantibodies related to histologic features of celiac disease?,"asymptomatic children at risk for celiac disease (cd) and seropositive for immunoglobulin a anti-tg autoantibodies (tgaa) may lack small intestinal mucosal changes characteristic of cd. we have followed a group of children with serial testing for tgaa. subjects were a group of at-risk children comprised of infants expressing hla-dr3 on newborn screening, those with type 1a diabetes, or a first-degree relative of someone with type 1 diabetes. all children participating in the prospective study for development of cd underwent serial testing for tgaa. data from clinical evaluation and small intestinal biopsy were compared to the tgaa levels followed over time. in 42 children, serial tgaa determinations while on a gluten-containing diet showed levels fluctuating 10-100-fold over 3-12 months. a tgaa index more than 0.5 had a positive predictive value (ppv) for histologic confirmation of cd of 96 (22/23). a tgaa index above the usual cutoff for positivity (0.05) had a ppv of only 76 (28/37).","in children with tgaa seropositivity, the tgaa level varied over time and a higher titer predicted an abnormal biopsy characteristic of cd. a threshold for biopsy for diagnosis of cd could be set higher for screening-identified cases than for clinically identified cases to decrease the frequency of performing ""normal"" biopsies.",Diagnosis
are genetic variations of muc17 associated with endometriosis development and related infertility?,"genetic alterations of mucin genes, such as muc2 and muc4, were previously identified to be associated with endometriosis and related infertility. additionally, gene expression profiling has confirmed muc17 to be overexpressed in mucinous ovarian carcinoma; however, its associated risk for endometriosis remains unclear. this study was focused on the potential impact of genetic variations in muc17 on endometriosis development and associated clinical features. the study subjects included 189 female taiwanese patients with pathology-proven endometriosis and 191 healthy taiwanese women as controls. five single-nucleotide polymorphisms (rs4729645, rs10953316, rs74974199, rs4729655, and rs4729656) within the muc17 gene were selected and genotyped using the taqman genotyping assay to examine the allele frequency and genotype distributions of muc17 polymorphisms. genotyping revealed that the a allele at rs10953316 in muc17 was a protective genetic factor in endometriosis development (p 0.008; or 0.53; 95 ci: 0.36-0.79). genetic variation of rs4729655 protected patients against endometriosis-induced infertility, but was associated with a higher cancer antigen 125 (ca125) level. base-pairing analysis, called maxexpect, predicted an additional loop in the mrna structure caused by rs10953316 polymorphism, possibly influencing ribosome sliding and translation efficiency. such predictions were confirmed by immunohistochemistry that patients with aa genotype at rs10953316 showed low muc17 levels in their endometrium, patients with ga genotype showed moderate levels, and strong staining could be found in patients with gg genotype.",muc17 polymorphisms are involved in endometriosis development and the associated infertility in the taiwanese population.,General
does active hip and spine rom differ when comparing unconstrained motion with voluntary segmental constraint?,"active range of motion trials are frequently used as a baseline for normalizing other data. however, previous research has not focused on methods utilized to achieve maximum active range of motion. twenty-seven males (age 20-38 years) participated in this study. active hip extension in upright standing was compared to active lumbar extension with regards to degrees of total hip and spine extension obtained. similarly, active spine rotation whereby participants attempted to constrain associated pelvis and hip rotation was compared to rotation trials in which the pelvis and hips were free to rotate concurrently. an infra-red motion capture system and associated software were used to capture movement and determine joint angles. results indicate that average degrees of hip extension did not differ between the two methods (p 0.138), nor did either method result more frequently in the highest measurement. spine extension values were significantly greater in the active spine extension manoeuvre compared to the associated back extension that occurred when participants were asked to actively extend their hip (p 0.001). average degrees of spine rotation were greater in the unconstrained trials: when concurrent hip and pelvis rotation were allowed to take place (p 0.001). of the 27 participants, 23 obtained maximum rotation during the unconstrained trials.","to obtain maximum active hip joint extension, both hip and back extension trials should be collected. maximum spine rotation is more likely to occur when the pelvis and hips are unconstrained.",General
are osteoprotegerin levels associated with liver fat and liver markers in dysmetabolic adults?,"this study aimed to determine the association between visceral adipose tissue (vat), liver fat (lf) content, and other markers of the metabolic syndrome (mets) and osteoprotegerin (opg) in dysmetabolic adults. subjects from the numevox cohort were included if they fulfilled at least one mets criterion. they then underwent a thorough metabolic and cardiovascular evaluation, including arterial stiffness, atherosclerotic plaques, homoeostasis model assessment for insulin resistance (homa-ir) indices and opg. vat and lf content were measured by magnetic resonance imaging (mri). ultrasound examination of arteries and arterial stiffness were recorded, and age- and gender-adjusted paired correlations calculated. body mass index, waist circumference and mri-derived vat correlated with opg, whereas abdominal subcutaneous fat did not. opg levels were strongly correlated with lf content (r0.25, p0.003), liver markers such as alanine aminotransferase (r0.39, p0.001) and homa-ir index (r0.39, p0.0001). plasma opg also correlated with arterial stiffness and the number of atherosclerotic sites.","plasma opg levels are positively associated with both liver markers and increased lf content, but not with subcutaneous fat in dysmetabolic men. these findings suggest that elevated opg levels may play a role in the link between fatty liver disease and enhanced cardiovascular risk.",Diagnosis
are common variants in the regulative regions of gria1 and gria3 receptor genes associated with migraine susceptibility?,"glutamate is the principal excitatory neurotransmitter in the central nervous system which acts by the activation of either ionotropic (ampa, nmda and kainate receptors) or g-protein coupled metabotropic receptors. glutamate is widely accepted to play a major role in the path physiology of migraine as implicated by data from animal and human studies. genes involved in synthesis, metabolism and regulation of both glutamate and its receptors could be, therefore, considered as potential candidates for causing/predisposing to migraine when mutated. the association of polymorphic variants of gria1-gria4 genes which encode for the four subunits (glur1-glur4) of the alpha-amino-3- hydroxy-5-methyl-4-isoxazole-propionic acid (ampa) receptor for glutamate was tested in migraineurs with and without aura (ma and mo) and healthy controls. two variants in the regulative regions of gria1 (rs2195450) and gria3 (rs3761555) genes resulted strongly associated with ma (p 0.00002 and p 0.0001, respectively), but not associated with mo, suggesting their role in cortical spreading depression. whereas the rs548294 variant in gria1 gene showed association primarily with mo phenotype, supporting the hypothesis that ma and mo phenotypes could be genetically related. these variants modify binding sites for transcription factors altering the expression of gria1 and gria3 genes in different conditions.",this study represents the first genetic evidence of a link between glutamate receptors and migraine.,Medication
is a subset of the diverse cog0523 family of putative metal chaperones linked to zinc homeostasis in all kingdoms of life?,"cog0523 proteins are, like the nickel chaperones of the ureg family, part of the g3e family of gtpases linking them to metallocenter biosynthesis. even though the first cog0523-encoding gene, cobw, was identified almost 20 years ago, little is known concerning the function of other members belonging to this ubiquitous family. based on a combination of comparative genomics, literature and phylogenetic analyses and experimental validations, the cog0523 family can be separated into at least fifteen subgroups. the cobw subgroup involved in cobalamin synthesis represents only one small sub-fraction of the family. another, larger subgroup, is suggested to play a predominant role in the response to zinc limitation based on the presence of the corresponding cog0523-encoding genes downstream from putative zur binding sites in many bacterial genomes. zur binding sites in these genomes are also associated with candidate zinc-independent paralogs of zinc-dependent enzymes. finally, the potential role of cog0523 in zinc homeostasis is not limited to bacteria. we have predicted a link between cog0523 and regulation by zinc in archaea and show that two cog0523 genes are induced upon zinc depletion in a eukaryotic reference organism, chlamydomonas reinhardtii.","this work lays the foundation for the pursuit by experimental methods of the specific role of cog0523 members in metal trafficking. based on phylogeny and comparative genomics, both the metal specificity and the protein target(s) might vary from one cog0523 subgroup to another. additionally, zur-dependent expression of cog0523 and putative paralogs of zinc-dependent proteins may represent a mechanism for hierarchal zinc distribution and zinc sparing in the face of inadequate zinc nutrition.",General
is 6-minute walk testing more sensitive than maximal incremental cycle testing for detecting oxygen desaturation in patients with copd?,"some respiratory patients exhibit oxygen desaturation during rehabilitative walking but not during maximal cardiopulmonary exercise testing (cpet). we evaluated exercise-induced desaturation during 6-min walk testing (6mwt) in comparison with cpet in patients with copd and determined the reproducibility of the phenomenon. we tested 80 consecutive patients with copd (fev(1), 62.4 /- 2 predicted) and 10 patients with supplementary copd (fev(1), 59.1 /- 5 predicted) mean /- sem to determine the reproducibility. first, patients with copd performed cycle cpet (first cpet cpet-1). three days later, they performed two 6mwts (first 6mwt 6mwt-1 and second 6mwt 6mwt-2). pulse oximetric saturation (spo(2)) was recorded every minute in both tests. three groups emerged: desaturation at 6mwt not observed at cpet (dnd) n 23, desaturation in both tests (n 16), and no desaturation in either test (n 41). second, to evaluate reproducibility, 10 additional subjects with copd who exhibited desaturation during two successive 6mwts but not in cpet performed a second cpet (cpet-2) and a single-bout 6mwt (6mwt-3) in a supplementary trial. when two cpets were performed, lack of o(2) desaturation was noted in both. o(2) desaturation was confirmed in 6mwt-2 and 6mwt-3 (7.4 /- 1 and 7.4 /- 1.5, respectively).","twenty-eight percent of patients with copd presented dnd. the phenomenon was reproducible and not protocol dependent, emphasizing the clinical interest of the 6mwt.",Medication
"is tranexamic acid effective in decreasing postoperative bleeding and transfusions in primary coronary artery bypass operations : a double-blind , randomized , placebo-controlled trial?","we evaluated the effects of tranexamic acid (ta) administered before and after cardiopulmonary bypass (cpb) in a prospective, randomized, placebo-controlled, double-blind study of adult patients undergoing primary coronary artery bypass grafting surgery. patients received placebo (n 30) or ta 15 mg/kg before cpb, followed by a ta infusion of 1 mg x kg(-1) x h(-1) for 5 h (n 30) or ta 15 mg/kg after cpb, followed by a ta infusion of 1 mg x kg(-1) x h(-1) for 5 h (n 30). demographic, medical, surgical, laboratory, mediastinal chest tube drainage (mctd), hemoglobin loss, transfusion, and outcome data were collected. allogenic blood product administration was tightly controlled. the demographic, medical, and surgical characteristics were similar in all three groups. the median postoperative mctd and hemoglobin loss in the pre-cpb ta group (710 ml, 8.6 g) was significantly less (p 0.001) compared with the control (1202 ml, 44.2 g) and post-cpb ta groups (1020 ml, 23.4 g). the percentage of patients who received no allogenic blood products was 27 for the pre-cpb ta group and 33 for the post-cpb ta group (not significant). these percentages were significantly lower than those in the placebo group (66, p 0.001). the median number of allogenic blood products administered to the pre-cpb ta group (0 units) was significantly less compared with the control group (4.5 units). the thromboelastogram and fibrinogen split product levels in the pre-cpb ta group indicated better platelet function and less activation of the fibrinolytic system compared with the other two groups (p 0.05). there were no intergroup differences in reoperation, myocardial infarction, stroke, infections, or death. these data support the use of pre-cpb ta to decrease patient exposure to postcardiopulmonary bypass allogenic blood products.","in this randomized, placebo-controlled trial, we investigated the efficacy of tranexamic acid to decrease bleeding and blood transfusions after open-heart operations. tranexamic acid administered before and during the operation was effective in decreasing both bleeding and transfusions. when tranexamic acid was administered immediately after the operation, it had a minor beneficial effect.",Treatment
do antagonists of the tmem16a calcium-activated chloride channel modulate airway smooth muscle tone and intracellular calcium?,"perioperative bronchospasm refractory to agonists continues to challenge anesthesiologists and intensivists. the tmem16a calcium-activated chloride channel modulates airway smooth muscle (asm) contraction. the authors hypothesized that tmem16a antagonists would relax asm contraction by modulating membrane potential and calcium flux. human asm, guinea pig tracheal rings, or mouse peripheral airways were contracted with acetylcholine or leukotriene d4 and then treated with the tmem16a antagonists: benzbromarone, t16ainh-a01, n-((4-methoxy)-2-naphthyl)-5-nitroanthranilic acid, or b25. in separate studies, guinea pig tracheal rings were contracted with acetylcholine and then exposed to increasing concentrations of isoproterenol (0.01 nm to 10 m) benzbromarone. plasma membrane potential and intracellular calcium concentrations were measured in human asm cells. benzbromarone was the most potent tmem16a antagonist tested for relaxing an acetylcholine -induced contraction in guinea pig tracheal rings (n 6). further studies were carried out to investigate the clinical utility of benzbromarone. in human asm, benzbromarone relaxed either an acetylcholine- or a leukotriene d4-induced contraction (n 8). benzbromarone was also effective in relaxing peripheral airways (n 9) and potentiating relaxation by agonists (n 5 to 10). in cellular mechanistic studies, benzbromarone hyperpolarized human asm cells (n 9 to 12) and attenuated intracellular calcium flux from both the plasma membrane and the sarcoplasmic reticulum (n 6 to 12).",tmem16a antagonists work synergistically with agonists and through a novel pathway of interrupting ion flux at both the plasma membrane and sarcoplasmic reticulum to acutely relax human asm.,Medication
do effects of arginine enriched enteral nutrition on nutritional status and cellular immunity in burn patients ?,"to investigate the effects of arginine enriched enteral nutrition (en) on nutritional status and cellular immunity of severely burned patients. randomized, single blind, parallel and positive control investigation was employed in the study. thirty severely burned patients were divided into enteral immune nutrition (ein) group and en group. sixteen patients in ein group received enteral nutrition enriched with arginine, while the other 14 patients in en group received standard enteral nutrition. nutritional support was continued for 14 days. gastrointestinal reaction of patients in 2 groups was observed. fasting venous blood was drawn from patients of both groups before receiving nutrition treatment and on the morning of 7th, 14th day of treatment. level of serum protein, hepatic function parameters, renal function parameters, fasting-blood glucose, and subpopulations of t lymphocytes in peripheral blood were determined. (1) incidence of gastrointestinal side effect in ein group (25.0) was close to that of en group (21.4 , p 0.05). (2) compared with pre-treatment days, levels of prealbumin and transferrin in serum of patients in 2 groups on 7th and 14th post-treatment days were significantly increased (p 0.05). (4) the ratio of cd4(), cd8() on 14th day of treatment in ein group was close to that of pretreatment level. in en group, cell percentage of cd4() significantly decreased, while that of cd8() significantly increased (p 0.05), and cd4() was significantly higher (56 /- 8) in ein group than that in en group (55 /- 12), p 0.05. in both groups, cell percentage of cd3() was significantly higher than that in pre-treatment days (p 0.05), while there was no obvious change in cd4()/cd8().",arginine enriched enteral nutrition can effectively improve nutritional status and cellular immune function of burn patients.,Prevention
"are increased plasma levels of beta2-microglobulin , cystatin c and beta-trace protein in term pregnancy due to utero-placental production?","to study concentration gradients of the low molecular mass proteins, beta2-microglobulin, cystatin c and beta-trace protein, between the uterine and ante-cubital veins, the umbilical artery and vein and in the amniotic fluid compartment. the study comprised 27 healthy women with uncomplicated pregnancies undergoing caesarean section at term. samples were collected simultaneously and paired t-tests were used to compare mean plasma concentrations. there was no significant concentration gradient in the plasma levels of beta2-microglobulin, cystatin c or beta-trace protein between the uterine and antecubital veins. there were no correlations between the protein levels in the compartments.","the utero-placental unit does not contribute significantly to the maternal levels of beta2-microglobulin, cystatin c and beta-trace protein in normal pregnancy, and the proteins are not likely to be transferred across the placental barrier.",Medication
does increases in medicare prescription drug plan cost attributable to psychotropic medications?,"older patients may regard some medications, particularly psychotropic medications, as discretionary compared with what they perceive as more ""essential "" nonpsychiatric medications. patients' concerns about psychotropic medication costs under medicare part d may reinforce these impressions. the authors examined which medicare prescription drug plans (pdps) would be least expensive for beneficiaries considering the costs of 1) all medications; and 2) only nonpsychiatric medications. the authors collected data from the pdp online comparison tool provided by the centers for medicare and medicaid services (cms). hypothetical medicare beneficiaries. the authors examined four clinical scenarios from older outpatients with both chronic medical and psychiatric conditions (including psychosis, bipolar disorder, depression, and dementia with behavioral disturbances). the authors examined data from all 160 plans available in cms pdp regions in may 2007. there were frequent discrepancies in the least expensive pdps within region, depending on considering the costs of all medications, or just nonpsychiatric medications. in the clinical scenarios, patients selecting a pdp based on nonpsychiatric medications alone would pick an unnecessarily more expensive plan 74-100 of the time (when they took any brand name medication), suggesting that excluding psychiatric medications from pdp choices may be excessively costly. however, brand name psychotropic medications significantly increased the costs of the least expensive plans. the latter finding might persuade patients to avoid taking needed psychiatric medication due to cost.",this research highlights the complexity that patients with psychiatric and cognitive disorders face when choosing a medicare pdp. policymakers and clinicians should be aware of the tradeoffs that beneficiaries with psychiatric disorders face when making pdp plan choices.,Medication
is age-related accrual of methylomic variability linked to fundamental ageing mechanisms?,"epigenetic change is a hallmark of ageing but its link to ageing mechanisms in humans remains poorly understood. while dna methylation at many cpg sites closely tracks chronological age, dna methylation changes relevant to biological age are expected to gradually dissociate from chronological age, mirroring the increased heterogeneity in health status at older ages. here, we report on the large-scale identification of 6366 age-related variably methylated positions (avmps) identified in 3295 whole blood dna methylation profiles, 2044 of which have a matching rna-seq gene expression profile. avmps are enriched at polycomb repressed regions and, accordingly, methylation at those positions is associated with the expression of genes encoding components of polycomb repressive complex 2 (prc2) in trans. further analysis revealed trans-associations for 1816 avmps with an additional 854 genes. these trans-associated avmps are characterized by either an age-related gain of methylation at cpg islands marked by prc2 or a loss of methylation at enhancers. this distinct pattern extends to other tissues and multiple cancer types. finally, genes associated with avmps in trans whose expression is variably upregulated with age (733 genes) play a key role in dna repair and apoptosis, whereas downregulated avmp-associated genes (121 genes) are mapped to defined pathways in cellular metabolism.",our results link age-related changes in dna methylation to fundamental mechanisms that are thought to drive human ageing.,Treatment
does psychological resilience provide no independent protection from suicidal risk?,"little is known about the role of resilience in the likelihood of suicidal ideation (si) over time. we examined the association between resilience and si in a young-adult cohort over 4 years. our objectives were to determine whether resilience was associated with si at follow-up or, conversely, whether si was associated with lowered resilience at follow-up. participants were selected from the personality and total health (path) through life project from canberra and queanbeyan, australia, aged 28-32 years at the first time point and 32-36 at the second. multinomial, linear, and binary regression analyses explored the association between resilience and si over two time points. models were adjusted for suicidality risk factors. while unadjusted analyses identified associations between resilience and si, these effects were fully explained by the inclusion of other suicidality risk factors.","despite strong cross-sectional associations, resilience and si appear to be unrelated in a longitudinal context, once risk/resilience factors are controlled for. as independent indicators of psychological well-being, suicidality and resilience are essential if current status is to be captured. however, the addition of other factors (e.g., support, mastery) makes this association tenuous. consequently, resilience per se may not be protective of si.",Prevention
does down-regulation of mir-186 contribute to podocytes apoptosis in membranous nephropathy?,"podocytes apoptosis is the key process in the development of membranous nephropathy and mir-186 is reported to be related with cell apoptosis. here we investigated the expression of mir-186 in membranous nephropathy (mgn) patients and the mechanism underlying the podocytes apoptosis. thirty patients with mgn and 30 healthy people were included in this study. the expression of mir-186 was detected in renal tissue and podocyte cells exposed to angii by real-time pcr. caspase-3 activity was used to evaluate podocytes apoptosis. tlr4 and p27 protein expression was quantified by western blotting. mir-186 inhibitor and mir-186 mimic were transfected into cells to investigate the mechanism underlying mir-186 in podocytes apoptosis. in mgn patients, the level of mir-186 was significantly down-regulated as well as the protein expression of tlr4 and p27 was up-regulated in renal tissue. in vitro experiments, tlr4 sirna increased the expression of mir-186 and mir-186 inhibitor elevated the mrna and protein expression of p27 in podocytes exposed to angii. in addition, the level of cleaved-caspase-3 was up-regulated by mir-186 inhibitor. the tunel-positive cells and caspase-3 activity of podocytes induced by angii were down-regulated by mir-186 mimic.","we revealed that tlr4 is involved in the regulation of mir-186 expression, and the anti-apoptotic effect of mir-186 on podocytes is correlated with p27 regulation.",Medication
is increased oxidative stress related to disease severity in the als motor cortex : a pet study?,"to investigate cerebral oxidative stress based on an over-reductive state caused by mitochondrial dysfunction and its relationship to disease severity in patients with amyotrophic lateral sclerosis (als) using pet with (62)cudiacetyl-bis(n(4)-methylthiosemicarbazone) ((62)cu-atsm). twelve patients with als and 9 age-matched healthy controls underwent a 20-minute dynamic brain pet scan after (62)cu-atsm injection. the standardized uptake value (suv) images obtained from the last 10 minutes of frames were normalized by the global mean (nsuv). regional (62)cu-atsm retention in the nsuv images was compared between groups using statistical parametric mapping (spm) and region of interest (roi) analysis. secondary analyses evaluated the correlations between regional nsuvs and the clinical characteristics of the participants. in spm mapping, patients with als showed a significantly greater accumulation of (62)cu-atsm compared to controls in the bilateral cortices around the central sulcus, including the motor cortex, and the right superior parietal lobule. roi analysis also revealed significantly greater nsuvs in patients than controls in these regions. increases in nsuv for these regions were associated with decreases in the revised als functional rating scale score, suggesting a good correlation with the severity of als. in controls, age was correlated with nsuv for the bilateral cortices around the central sulcus, although this correlation was not observed in patients with als.","(62)cu-atsm pet imaging demonstrated increased oxidative stress based on an over-reductive state, primarily in the motor cortex, in patients with als. the magnitude of oxidative stress correlated well with clinical severity, indicating that it may be associated with neurodegenerative changes in als.",Medication
does continuous inhalation of allergen induce immunotolerance in a mouse asthma model ?,"to investigate the mechanism of immunotolerance caused by allergen immunotherapy in allergen-induced asthmatic airway inflammation. sixty ovalbumin (ova)-sensitized balb/c mice were randomly divided into two groups, 50 in the experimental group and 10 in the control group. the mice in the experimental group were treated with 3 injections of ovalbumin intraperitoneally (1 mg for each separated for two weeks) and challenged by ovalbumin inhalation 1 h/day for 10 successive days. then the mice were divided further into group a, group b, group c, group d and e with 10 mice in each group. the mice in group a were sacrificed after 10 day challenge. the mice in group b and d were continuously exposed to inhaled ova for 4 and 8 weeks (1 h/day, 5 days a week), respectively, then to inhaled ova 1 h/day for 10 successive days. the inhalation was interrupted for 4 weeks in group c after initial challenge and restarted for another 10 days (1 h/day) afterwards. the mice in group e were exposed continuously to inhaled ova for 4 weeks (1 h/day, 5 days a week) after initial challenge, which was interrupted for 4 weeks, and restarted for 10 days (1 h/day). bronchoalveolar lavage (bal) was performed, and total cells, eosinophils, lymphocytes were assessed; cd4, cd8, cd4 il-10 cells were determined using flow cytometry, and il-4, ifn-gamma and il-10 in the bal fluid were measured by elisa. serum ovalbumin-specific ige, il-4, ifn-gamma and il-10 were also determined. pathologic manifestation of the lung was analyzed. the percentage of eos, b lymphocytes, cd4 il-10 cells in bal were 0.010 /- 0.000, 2.1 /- 1.9 and 4.9 /- 1.5, respectively in the control group; 0.480 /- 0.110, 5.1 /- 2.6 and 5.1 /- 2.3, respectively, in group a; 0.120 /- 0.020, 8.9 /- 3.6, and 10.4 /- 3.6, respective, in group b; 0.560 /- 0.050, 4.7 /- 1.7 and 6.3 /- 3.1, respectively, in group c; 0.070 /- 0.030, 10.1 /- 2.9 and 12.7 /- 4.5, respectively, in group d; 0.680 /- 0.030, 5.6 /- 3.2 and 6.1 /- 3.4, respectively, in group e. the difference was significant among different groups (f 36.46, 31.89, 167.89 respectively; all p 0.01). the percentage of cd4 il-10 cells in bal was increased in group b and group d, which were significantly higher than those in group a (q 5.8, 6.4, p 0.05). the levels of il-4 and il-10 in bal fluid were (21 /- 3) pg/ml and (44 /- 12) pg/ml, respectively, in the control group; (128 /- 23) pg/ml and (68 /- 18) pg/ml, respectively, in group a; (54 /- 12) pg/ml and (127 /- 27) pg/ml, respectively, in group b; (133 /- 21) pg/ml and (78 /- 17) pg/ml, respectively, in group c; (8 /- 18) pg/ml and (135 /- 34) pg/ml, respectively, in group d; (143 /- 26) pg/ml and (76 /- 15) pg/ml, respectively, in group e. the difference was statistically significant among different groups (f 37.20, 143.78 respectively; all p 0.01). the levels of il-10 in bal fluid were increased in group b and group d, which were significantly higher than that in group a (q 7.8, 9.6, all p 0.05).","the results show that continuous allergen inhalation suppresses allergen-induced airway inflammation and produces immunotolerance, in which il-10 may play an important role.",Medication
are interleukin-1 gene variants associated with qtc interval prolongation following cardiac surgery : a prospective observational study?,"we characterized cardiac surgery-induced dynamic changes of the corrected qt (qtc) interval and tested the hypothesis that genetic factors are associated with perioperative qtc prolongation independent of clinical and procedural factors. all study subjects were ascertained from a prospective study of patients who underwent elective cardiac surgery during august 1999 to april 2002. we defined a prolonged qtc interval as 440 msec, measured from 24-hr pre- and postoperative 12-lead electrocardiograms. the association of 37 single nucleotide polymorphisms (snps) in 21 candidate genes -involved in modulating arrhythmia susceptibility pathways with postoperative qtc changes- was investigated in a two-stage design with a stage i cohort (n 497) nested within a stage ii cohort (n 957). empirical p values (pemp) were obtained by permutation tests with 10,000 repeats. after adjusting for clinical and procedural risk factors, we selected four snps (p value range, 0.03-0.1) in stage i, which we then tested in the stage ii cohort. two functional snps in the pro-inflammatory cytokine interleukin-1 (il1), rs1143633 (odds ratio or, 0.71; 95 confidence interval ci, 0.53 to 0.95; pemp 0.02) and rs16944 (or, 1.31; 95 ci, 1.01 to 1.70; pemp 0.04), remained independent predictors of postoperative qtc prolongation. the ability of a clinico-genetic model incorporating the two il1b polymorphisms to classify patients at risk for developing prolonged postoperative qtc was superior to a clinical model alone, with a net reclassification improvement of 0.308 (p 0.0003) and an integrated discrimination improvement of 0.02 (p 0.000024).",the results suggest a contribution of il1 in modulating susceptibility to postoperative qtc prolongation after cardiac surgery.,Treatment
is coronary distensibility index measured by computed tomography associated with the severity of coronary artery disease?,"atherosclerotic changes within the coronary artery wall can affect vessel distensibility. this study evaluated the relationship between the coronary distensibility index (cdi) and the severity of coronary artery disease (cad) measured by computed tomographic angiography (cta). one hundred thirteen subjects, age 63 /- 10 years, 32 women, who underwent coronary artery calcium (cac) scanning and cta, were studied. early diastolic and mid diastolic (md) cross-section area (csa) of the left anterior descending (lad) artery were measured 5 mm distal to the left main bifurcation. cdi was defined as deltalumen csa/lumen csa in md x estimated central pulse pressure (ecpp) x 10(3) ecpp 0.77 x peripheral pulse pressure. lad diameter measured by cta and quantitative coronary angiography (qca) was compared in 19 subjects without cad. cad was defined as normal (no stenosis and cac 0), mild (stenosis or 70) on cta. excellent correlation was observed between cta and qca measured by cdi (r(2) 0.96, p 0.0001). cdi decreased from normal coronaries (6.75 /- 1.43) to arteries with mild (5.78 /- 1.45), moderate (3.96 /- 1.06), and severe (3.31 /- 1.06) disease (p 0.004). the risk factor adjusted odds ratio of lowest versus 2 upper tertiles of cdi was 1.28 for mild, 8.47 for moderate, and 10.59 for severe cad compared with the normal cohort. the area under the roc curve to predict obstructive cad (stenosis or 50) increased significantly from 0.71 to 0.84 by addition of cdi to cac (p 0.05).","cta-measured cdi is inversely related to the severity of cad independent of age, sex, cardiovascular risk factors, and cac.",Prevention
is increased frequency and compromised function of t regulatory cells in systemic sclerosis ( ssc ) related to a diminished cd69 and tgfbeta expression?,"regulatory t cells (tregs) are essential in the control of tolerance. evidence implicates tregs in human autoimmune conditions. here we investigated their role in systemic sclerosis (ssc). patients were subdivided as having limited cutaneous ssc (lcssc, n 20) or diffuse cutaneous ssc (dcssc, n 48). further subdivision was made between early dcssc (n 24) and late dcssc (n 24) based upon the duration of disease. 26 controls were studied for comparison. cd3 cells were isolated using facs and subsequently studied for the expression of cd4, cd8, cd25, foxp3, cd127, cd62l, gitr, cd69 using flow cytometry. t cell suppression assays were performed using sorted cd4cd25(high)cd127(-) and cd4cd25(low)cd127(high) and cd3() cells. suppressive function was correlated with cd69 surface expression and tgfbeta secretion/expression. the frequency of cd4()cd25() and cd25(high)foxp3(high)cd127(neg) t cells was highly increased in all ssc subgroups. although the expression of cd25 and gitr was comparable between groups, expression of cd62l and cd69 was dramatically lower in ssc patients, which correlated with a diminished suppressive function. co-incubation of tregs from healthy donors with plasma from ssc patients fully abrogated suppressive activity. activation of tregs from healthy donors or ssc patients with pha significantly up regulated cd69 expression that could be inhibited by ssc plasma.",these results indicate that soluble factors in ssc plasma inhibit treg function specifically that is associated with altered treg cd69 and tgfbeta expression. these data suggest that a defective treg function may underlie the immune dysfunction in systemic sclerosis.,General
does hyperleptinemia be a risk factor for the development of central arterial stiffness in kidney transplant patients?,"arterial stiffness could cause adverse outcomes in kidney transplant (kt) patients. leptin has a role in influencing vascular smooth muscle that may contribute to atherosclerosis. the aim of this study was to evaluate the relationship between fasting serum leptin concentration and carotid-femoral pulse wave velocity (cfpwv) in kt patients. fasting blood samples were obtained from 55 kt patients and 65 subjects from the outpatient department were enrolled as the control group. the cfpwv values of 10 m/s were used to define as the high arterial stiffness group and 10 m/s as the low arterial stiffness group. the predictive ability of leptin for arterial stiffness of kt was assessed using receiver operating characteristic (roc) curve and multivariate logistic regression analyses. kidney transplant patients had lower hemoglobin, but higher blood urea nitrogen, creatinine, total cholesterol, diastolic blood pressure, intact parathyroid hormone levels, and leptin levels than controls. although cfpwv levels were higher in kt patients, there is no difference of cfpwv levels between kt patients and control (p .595). fifteen kt patients (27.3) were defined in the high arterial stiffness group, and serum leptin level was higher in the high arterial stiffness group compared with the low arterial stiffness group in kt patients (p .001). multivariate logistic regression analysis showed that leptin (odds ratio: 1.044, 95 confidence interval ci: 1.016-1.072, p .002) was an independent predictor of arterial stiffness in kt patients. the sensitivity, specificity, positive predictive value, negative predictive value, and area under the roc curve predicting arterial stiffness in kt patients were 73.33, 87.5, 68.7, 89.7, and 0.828 (95 ci: 0.703-0.917, p .001), and the leptin cut-off value was 74.14 ng/ml.",serum fasting leptin level could predict the development of central arterial stiffness of kt patients.,Treatment
does the mitochondria-targeted anti-oxidant mitoquinone decrease liver damage in a phase ii study of hepatitis c patients?,"increased oxidative stress and subsequent mitochondrial damage are important pathways for liver damage in chronic hepatitis c virus (hcv) infection; consequently, therapies that decrease mitochondrial oxidative damage may improve outcome. the mitochondria-targeted anti-oxidant mitoquinone combines a potent anti-oxidant with a lipophilic cation that causes it to accumulate several-hundred fold within mitochondria in vivo. in this phase ii study, we investigated the effect of oral mitoquinone on serum aminotransferases and hcv rna levels in hcv-infected patients. thirty hcv patients who were either non-responders or unsuitable candidates for standard-of-care (pegylated interferon plus ribavirin) were randomized to receive mitoquinone (40 or 80 mg) or placebo once daily for 28 days, and serum aminotransferases and hcv rna levels were measured. both treatment groups showed significant decreases in absolute and percentage changes in serum alanine transaminase (alt) from baseline to treatment day 28 (p0.05). there was no change in hcv load on mitoquinone treatment.","administration of the mitochondria-targeted anti-oxidant mitoquinone significantly decreased plasma alt and aspartate aminotransferase in patients with chronic hcv infection, and this suggests that mitoquinone may decrease necroinflammation in the liver in these patients. as mitochondrial oxidative damage contributes to many other chronic liver diseases, such as steatohepatitis, further studies using mitochondria-targeted anti-oxidants in hcv and other liver diseases are warranted.",Treatment
does tangeretin regulate platelet function through inhibition of phosphoinositide 3-kinase and cyclic nucleotide signaling?,"dietary flavonoids have long been appreciated in reducing cardiovascular disease risk factors, but their mechanisms of action are complex in nature. in this study, the effects of tangeretin, a dietary flavonoid, were explored on platelet function, signaling, and hemostasis. tangeretin inhibited agonist-induced human platelet activation in a concentration-dependent manner. it inhibited agonist-induced integrin iib3 inside-out and outside-in signaling, intracellular calcium mobilization, and granule secretion. tangeretin also inhibited human platelet adhesion and subsequent thrombus formation on collagen-coated surfaces under arterial flow conditions in vitro and reduced hemostasis in mice. further characterization to explore the mechanism by which tangeretin inhibits platelet function revealed distinctive effects of platelet signaling. tangeretin was found to inhibit phosphoinositide 3-kinase-mediated signaling and increase cgmp levels in platelets, although phosphodiesterase activity was unaffected. consistent with increased cgmp levels, tangeretin increased the phosphorylation of vasodilator-stimulated phosphoprotein at s239.","this study provides support for the ability and mechanisms of action of dietary flavonoids to modulate platelet signaling and function, which may affect the risk of thrombotic disease.",Prevention
does serum amyloid a induce toll-like receptor 2-dependent inflammatory cytokine expression and atrophy in c2c12 skeletal muscle myotubes?,"skeletal muscle wasting is an important comorbidity of chronic obstructive pulmonary disease (copd) and is strongly correlated with morbidity and mortality. patients who experience frequent acute exacerbations of copd (aecopd) have more severe muscle wasting and reduced recovery of muscle mass and function after each exacerbation. serum levels of the pro-inflammatory acute phase protein serum amyloid a (saa) can rise more than 1000-fold in aecopd and are predictively correlated with exacerbation severity. the direct effects of saa on skeletal muscle are poorly understood. here we have examined saa effects on pro-inflammatory cachectic cytokine expression (il-6 and tnf) and atrophy in c2c12 myotubes. saa increased il-6 (31-fold) and tnf (6.5-fold) mrna levels compared to control untreated cells after 3h of saa treatment, and increased secreted il-6 protein at 24h. oxpapc, a dual tlr2 and tlr4 inhibitor, reduced the response to saa by approximately 84 compared to saa alone, and the tlr2 neutralising antibody t2.5 abolished saa-induced expression of il-6, indicating that saa signalling in c2c12 myotubes is primarily via tlr2. saa also reduced myotube width by 10-13 and induced a 2.5-fold increase in the expression of the muscle atrophy gene atrogin-1, suggesting direct effects of saa on muscle wasting. blocking of tlr2 inhibited the saa-induced decrease in myotube width and atrogin-1 gene expression, indicating that saa induces atrophy through tlr2.","these data demonstrate that saa stimulates a robust pro-inflammatory response in skeletal muscle myotubes via the tlr2-dependent release of il-6 and tnf. furthermore, the observed atrophy effects indicate that saa could also be directly contributing to the wasting and poor recovery of muscle mass. therapeutic strategies targeting this saa-tlr2 axis may therefore ameliorate muscle wasting in aecopd and a range of other inflammatory conditions associated with loss of muscle mass.",Medication
is infarct healing a dynamic process following acute myocardial infarction?,"the role of infarct size on left ventricular (lv) remodeling in heart failure after an acute st-segment elevation myocardial infarction (stemi) is well recognized. infarct size, as determined by cardiovascular magnetic resonance (cmr), decreases over time. the amount, rate, and duration of infarct healing are unknown. a total of 66 patients were prospectively enrolled after reperfusion for an acute stemi. patients underwent a cmr evaluation within 1 week, 4 months, and 14 months after stemi. mean infarct sizes for the 66 patients at baseline (acute necrosis), early follow-up (early scar), and late follow-up (late scar) were 25 17 g, 17 12 g, and 15 11 g, respectively. patients were stratified in tertiles, based on infarct size, with the largest infarcts having the greatest absolute decrease in mass at early and late scar. the percent reduction of infarct mass was independent of initial infarct size. there was an 8 g or 32 decrease in infarct mass between acute necrosis and early scar (p 0.01) with a 2 g or 12 additional decrease in infarct mass between early and late scar (p 0.01).","infarct healing is a continuous process after reperfusion for stemi, with greatest reduction in infarct size in the first few months. the dynamic nature of infarct healing through the first year after stemi indicates that decisions based on infarct size, and interventions to reduce infarct size, must take into consideration the time frame of measurement.",General
does acute moderate-intensity exercise induce vasodilation through an increase in nitric oxide bioavailiability in humans?,"long-term moderate-intensity exercise augments endothelium-dependent vasodilation through an increase in nitric oxide (no) production. the purpose of this study was to determine the effects of different intensities of acute exercise on hemodynamics in humans. we evaluated forearm blood flow (fbf) responses to different intensities of exercise (mild, 25 maximum oxygen consumption vo2max; moderate, 50 vo2max; and high, 75 vo2max; bicycle ergometer, for 30 min) in eight healthy young men. the fbf was measured by using a strain-gauge plethysmography. after exercise began, moderate-intensity exercise, but not mild-intensity exercise, promptly increased fbf from 2.8/-1.1 ml/min/100 ml to a plateau at 5.4/-1.6 ml/min/100 ml at 5 min (p.01) and increased mean arterial pressure from 84.7/-11.8 mm hg to a plateau at 125.7/-14.3 mm hg at 5 min (p.01). moderate-intensity exercise decreased forearm vascular resistance (fvr) from 29.2/-5.4 to 16.8/-3.2 mm hg/ml/min/100 ml tissue (p.01). the administration of ng-monomethyl-l-arginine, an no synthase inhibitor, abolished moderate exercise-induced augmentation of vasodilation. although we were not able to measure fbf during high-intensity exercise because of large body motion, high-intensity exercise markedly increased mean arterial pressure from 82.6/-12.2 to 146.8/-19.8 mm hg. high-intensity exercise, but not mild-intensity or moderate-intensity exercise, increased plasma concentration of 8-isoprostane, an index of oxidative stress, from 24.1/-10.8 to 40.2/-16.7 pg/ml (p.05) at 10 min after the end of exercise.",these findings suggest that acute moderate-intensity exercise induces vasodilation through an increase in no bioavailability in humans and that high-intensity exercise increases oxidative stress.,Prevention
is four-week prehabilitation program sufficient to modify exercise behaviors and improve preoperative functional walking capacity in patients with colorectal cancer?,"high complication rates following colorectal surgery render many patients unable to fully regain functional capacity, thus seriously compromising quality of life. the aim of this study was to assess whether a 4-week trimodal prehabilitation program (exercise, nutritional supplementation, and counseling on relaxation techniques), implemented during the preoperative period, is sufficient to modify exercise behaviors and improve functional capacity of elderly patients scheduled for colorectal cancer surgery. patients were assigned to either a prehabilitation (prehab; n 57) or matched time control group (ctrl; n 59). over the 4-week period prior to surgery, patients in prehab participated in a trimodal prehabilitation program. patients in ctrl received the same program but only postoperatively. the community healthy activities model program for seniors (champs) questionnaire was used to measure physical activity levels, while the 6-min walk test (6mwt) was used for assessment of functional walking capacity. measurements were collected at baseline and at the time of surgery. over the preoperative period, patients in prehab significantly increased the amount of moderate- and vigorous-intensity physical activities that they performed. prehab patients also demonstrated a greater improvement in 6mwt compared to ctrl. at the time of surgery, a greater proportion of patients in prehab met current physical activity guidelines, as compared to ctrl.",these findings highlight the positive effects of a trimodal prehabilitation program on patients' physical activity levels and functional walking capacity and demonstrate that modifying exercise behaviors and improving physical function within the 4-week preoperative period are an achievable goal.,Prevention
do chemokine ( c-c motif ) receptor 2-positive monocytes aggravate the early phase of acetaminophen-induced acute liver injury?,"acetaminophen (apap, paracetamol) poisoning is a leading cause of acute liver failure (alf) in humans and induces hepatocyte necrosis, followed by activation of the innate immune system, further aggravating liver injury. the role of infiltrating monocytes during the early phase of alf is still ambiguous. upon experimental apap overdose in mice, monocyte-derived macrophages (momfs) massively accumulated in injured liver within 12-24 hours, whereas the number of tissue-resident macrophages (kupffer cells) decreased. influx of momfs is dependent on the chemokine receptor, chemokine (c-c motif) receptor 2 (ccr2), given that ccr2","infiltrating monocyte-derived macrophages aggravate apap hepatotoxicity, and the pharmacological inhibition of either ccl2 or ccr2 might bear therapeutic potential by reducing the inflammatory reaction during the early phase of aili. (hepatology 2016;64:1667-1682).",Medication
does the use of cell-sheet technique eliminate arrhythmogenicity of skeletal myoblast-based therapy to the heart with enhanced therapeutic effects?,"clinical application of skeletal myoblast transplantation has been curtailed due to arrhythmogenicity and inconsistent therapeutic benefits observed in previous studies. however, these issues may be solved by the use of a new cell-delivery mode. it is now possible to generate ""cell-sheets"" using temperature-responsive dishes without artificial scaffolds. this study aimed to validate the safety and efficacy of epicardial placement of myoblast-sheets (myoblast-sheet therapy) in treating heart failure. after coronary artery ligation in rats, the same numbers of syngeneic myoblasts were transplanted by intramyocardial injection or cell-sheet placement. continuous radio-telemetry monitoring detected increased ventricular arrhythmias, including ventricular tachycardia, after intramyocardial injection compared to the sham-control, while these were abolished in myoblast-sheet therapy. this effect was conjunct with avoidance of islet-like cell-cluster formation that disrupts electrical conduction, and with prevention of increased arrhythmogenic substrates due to exaggerated inflammation. persistent ectopic donor cells were found in the lung only after intramyocardial injection, strengthening the improved safety of myoblast-sheet therapy. in addition, myoblast-sheet therapy enhanced cardiac function, corresponding to a 9.2-fold increase in donor cell survival, compared to intramyocardial injection. both methods achieved reduced infarct size, decreased fibrosis, attenuated cardiomyocyte hypertrophy, and increased neovascular formation, in association with myocardial upregulation of a group of relevant molecules. the pattern of these beneficial changes was similar between two methods, but the degree was more substantial after myoblast-sheet therapy.","the cell-sheet technique enhanced safety and therapeutic efficacy of myoblast-based therapy, compared to the current method, thereby paving the way for clinical application.",Treatment
is apolipoprotein e polymorphism a predictor for repeated coronary artery bypass surgery?,"factors leading to the occlusion of coronary grafts are diverse and may at least partially be inherited. we aimed to study the possible genetic predisposition and especially the role of apoe epsilon4 allele as a risk factor for repeated coronary artery bypass grafting (cabg) in a case-control setting. all patients (n184) who underwent repeated cabg between 1990 and 1998 were identified in the computed registry of the department of cardiothoracic surgery in tampere university hospital. age, sex and operation date matched controls with first time cabg were selected from the same registry. dna samples were collected by sample stick sent via the mail for buccal smear. the final analysis included 137 surviving matched pairs. in patients 62 years of age (median age), family history emerged as the only significant (or3.4; 95 ci1.5-7.8, p0.004) predictor for repeated surgery. among older patients, repeated cabg was no longer predicted by family history but by hypercholesterolemia (or2.1; 95 ci1.1-4.0, p0.027), modified by apoe genotype.","our results suggest that medium-term survivors after redo cabg have a strong genetic predisposition unrelated to hypercholesterolemia or apoe genotype, leading to more severe coronary artery disease at earlier age. in the older age group, redo coronary artery bypass surgery is associated with hypercholesterolemia, which, although modified by apoe genotype, may mainly be due to other genetic or acquired factors.",Treatment
do agonists of toll-like receptors 2 and 4 activate airway smooth muscle via mononuclear leukocytes?,"toll-like receptors 2 and 4 (tlr2, tlr4) enable cellular responses to bacterial lipoproteins, lps, and endogenous mediators of cell damage. they have an established role in the activation of leukocytes, endothelial cells, and some smooth muscle cell types, but their roles in airway smooth muscle are uncertain. to determine the roles of tlrs in activation of airway smooth muscle. airway smooth muscle cells were cultured with tlr agonists, in the presence or absence of mononuclear leukocytes. we observed expression of tlr2 and tlr4 mrnas, which could be upregulated by treatment with proinflammatory cytokines in primary human airway smooth muscle, but no important functional responses to agonists of these tlrs were seen. coincubation of airway smooth muscle with peripheral blood mononuclear cells, at concentrations as low as 250 mononuclear cells/ml, resulted in a marked cooperative response to tlr stimuli, and synergistic production of cytokines, including chemokines (interleukin il--8) and il-6. this cooperative response was greater when monocytes were enriched and was transferable using supernatants from lps-stimulated peripheral blood mononuclear cells. activation of cocultures required il-1 generation from mononuclear cells, and was blocked by il-1 receptor antagonist, though il-1 generation alone was not sufficient to account for the magnitude of mononuclear cell-dependent coculture activation.","these data indicate that potent amplification of inflammation induced by tlr agonists, such as lps, may be achieved by cooperativity between airway smooth muscle and leukocytes involved in immune surveillance or inflammation.",Medication
is scn5a variation associated with electrocardiographic traits in the jackson heart study?,"understanding variation in the normal electric activity of the heart, assessed by the ecg, may provide a starting point for studies of susceptibility to serious arrhythmias such as sudden cardiac death during myocardial infarction or drug therapy. recent genetic association studies of one ecg trait, the qt interval, have identified common variation in european-descent populations, but little is known about the genetic determinants of ecg traits in populations of african descent. to identify genetic risk factors, we have undertaken a candidate gene study of ecg traits in collaboration with the jackson heart study, a longitudinal study of 5301 blacks ascertained from the jackson, mississippi, area. nine quantitative ecg traits were evaluated: p, pr, qrs, qt, and qtc durations, heart rate, and p, qrs, and t axes. we genotyped 72 variations in the predominant sodium channel gene expressed in heart, scn5a, encoding the na(v)1.5 voltage-gated sodium channel in 4558 subjects. both rare and common variants in this gene have previously been associated with inherited arrhythmia syndromes and variable conduction. adjusting for age, sex, and european ancestry, we performed tests of association in 3054 unrelated participants and identified 14 significant associations (p1.010(-4)), of which 13 are independent, based on linkage disequilibrium. these variants explain up to 2 of the variation in ecg traits in the jackson heart study.","these results suggest that scn5a variation contributes to ecg trait distributions in blacks, and these same variations may be risk or protective factors associated with susceptibility to arrhythmias.",Medication
does intensive weight loss program improve physical function in older obese adults with knee osteoarthritis?,"physical function and body composition in older obese adults with knee osteoarthritis (oa) were examined after intensive weight loss. older obese adults (n 87; or 60 years; bmi or 30.0 kg/m2) with symptomatic knee oa and difficulty with daily activities were recruited for a 6-month trial. participants were randomized into either a weight stable (ws) or weight loss (wl) program. participants in wl (10 weight loss goal) were prescribed a 1000 kcal/d energy deficit diet with exercise 3 d/wk. ws participants attended health information sessions. body composition and physical function (western ontario and mcmaster university osteoarthritis index, 6-minute walking distance, and stair climb time) were assessed at baseline and 6 months. statistical analysis included univariate analysis of covariance on 6-month measurements using baseline values as covariates. associations between physical function and body composition were performed. body weight decreased 8.7 /- 0.8 in wl and 0.0 /- 0.7 in ws. body fat and fat-free mass were lower for wl than ws at 6 months (estimated means: fat 38.1 /- 0.4 vs. 40.9 /- 0.4, respectively; fat-free mass 56.7 /- 0.4 vs. 58.8 /- 0.4 kg, respectively). wl had better function than ws, with lower western ontario and mcmaster university osteoarthritis index scores, greater 6-minute walk distance, and faster stair climb time (p 0.05). changes in function were associated with weight loss in the entire cohort.",an intensive weight loss intervention incorporating energy deficit diet and exercise training improves physical function in older obese adults with knee oa. greater improvements in function were observed in those with the most weight loss.,Prevention
does apo a2 -265t/c polymorphism is associate with increased inflammatory responses in patients with type 2 diabetes mellitus?,"apolipoprotein a2 (apo a2) is the second most abundant structural apolipoprotein in high density lipoprotein. several studies have examined the possible effect of apo a2 on atherosclerosis incidence. due to the role of inflammation in atherosclerosis, we aimed to determine the relationship between apo a2 -265t/c polymorphism and inflammation as a risk factor in type 2 diabetes mellitus (t2dm) patients. in total, 180 t2dm patients, with known apo a2 -265t/c polymorphism, were recruited for this comparative study and were grouped equally based on their genotypes. dietary intakes, anthropometric parameters, lipid profile, and inflammatory markers (i.e., pentraxin 3 ptx3, high-sensitivity c-reactive protein hs-crp, and interleukin 18) were measured. the data were analyzed using an independent t-test, a chi-square test, and the analysis of covariance. after adjusting for confounding factors, in the entire study population and in the patients with or without obesity, the patients with the cc genotype showed higher hs-crp (p0.001, p0.008, and p0.01, respectively) and lower ptx3 (p0.01, p0.03, and p0.04, respectively) in comparison with the t allele carriers. in the patients with the cc genotype, no significant differences were observed in the inflammatory markers between the obese or non-obese patients. however, regarding the t allele carriers, the plasma hs-crp level was significantly higher in the obese patients compared to the non-obese patients (p0.01).","in the t2dm patients, the cc genotype could be considered as a risk factor and the t allele as a protective agent against inflammation, which the latter effect might be impaired by obesity. our results confirmed the anti-atherogenic effect of apo a2, though more studies are required to establish this effect.",Prevention
"is attenuation of the stimulant response to ethanol associated with enhanced ataxia for a gaba , but not a gaba , receptor agonist?","the gamma-aminobutyric acid (gaba) system is implicated in the neurobiological actions of ethanol, and pharmacological agents that increase the activity of this system have been proposed as potential treatments for alcohol use disorders. as ethanol has its own gaba mimetic properties, it is critical to determine the mechanism by which gabaergic drugs may reduce the response to ethanol (i.e., via an inhibition or an accentuation of the neurobiological effects of ethanol). in this study, we examined the ability of 3 different types of gabaergic compounds, the gaba reuptake inhibitor no-711, the gaba(a) receptor agonist muscimol, and the gaba(b) receptor agonist baclofen, to attenuate the locomotor stimulant response to ethanol in fast mice, which were selectively bred for extreme sensitivity to ethanol-induced locomotor stimulation. to determine whether these compounds produced a specific reduction in stimulation, their effects on ethanol-induced motor incoordination were also examined. no-711, muscimol, and baclofen were all found to potently attenuate the locomotor stimulant response to ethanol in fast mice. however, both no-711 and muscimol markedly increased ethanol-induced ataxia, whereas baclofen did not accentuate this response.","these results suggest that pharmacological agents that increase extracellular concentrations of gaba and gaba(a) receptor activity may attenuate the stimulant effects of ethanol by accentuating its intoxicating and sedative properties. however, selective activation of the gaba(b) receptor appears to produce a specific attenuation of ethanol-induced stimulation, suggesting that gaba(b) receptor agonists may hold greater promise as potential pharmacotherapies for alcohol use disorders.",Medication
do dendritic cell-based vaccines suppress metastatic liver tumor via activation of local innate and acquired immunity?,"dendritic cell (dc)-based vaccines have been applied clinically in the setting of cancer, but tumor-associated antigens (taas) have not yet been enough identified in various cancers. in this study, we investigated whether preventive vaccination with unpulsed dcs or peptide-pulsed dcs could offer anti-tumor effects against mc38 or bl6 liver tumors. mice were subcutaneously (s.c.) immunized with unpulsed dcs or the recently defined taa epha2 derived peptide-pulsed dendritic cells (eph-dcs) to treat epha2-positive mc38 and epha2-negative bl6 liver tumors. liver mononuclear cells (lmncs) from treated mice were subjected to (51)cr release assays against yac-1 target cells. in some experiments, mice were injected with anti-cd8, anti-cd4 or anti-asialo gm1 antibody to deplete each lymphocyte subsets. immunization with unpulsed dcs displayed comparable efficacy against both mc38 and bl6 liver tumors when compared with eph-dcs. both dc-based vaccines significantly augmented the cytotoxicity of lmncs against yac-1 cells. in vivo antibody depletion studies revealed that nk cells, as well as, cd4 and cd8 t cells play critical roles in the anti-tumor efficacy associated with either dc-based modality. tumor-specific cytotoxic t lymphocyte (ctl) activity was generally higher if mice had received eph-dcs versus unpulsed dcs. importantly, the mice that had been protected from mc38 liver tumor by either unpulsed dcs or eph-dcs became resistant to s.c. mc38 rechallenge, but not to bl6 rechallenge.","these results demonstrate that unpulsed dc vaccines might serve as an effective therapy for treating metastatic liver tumor, for which taa has not yet been identified.",Medication
is up-regulation of alpha-catenin associated with increased lymph node involvement in colorectal cancer?,"to investigate the changing pattern of alpha-catenin expression and its relationship to clinical and pathological features of colorectal cancer (crc) patients. archival tumor samples were analyzed using immunohistochemistry (ihc) for alpha-catenin in 91 patients with advanced crc. the values of alpha-catenin membrane index (mi) and cytoplasmic index (ci) were significantly related to the depth of tumor invasion (p 0.027, p 0.020, respectively), high indices being associated with increased depth of the primary tumor invasion (t3 and t4). similarly, patients with high alpha-catenin expression had a significantly increased risk of lymph node metastasis (32/39 vs 37/52 for mi and 37/45 vs 32/46 for ci) (p 0.001, p 0.0001, respectively, for lnn status). an altered expression (i.e., cytoplasmic pattern) was also related (p 0.047) to the response to chemotherapy; patients with low ci were more responsive (cr: 7/46) than patients with high ci values (cr: 0/45). there was a marginal effect on survival in patients time with metastases (swm) (p 0.087); patients with low ci showing slightly longer swm, but no such effect on disease free survival (dfs) or disease specific survival (dss). as to co-expression with another member of the adhesion complex (beta-catenin), high alpha-catenin/beta-catenin mi index was of marginal significance in predicting longer dss (p 0.063, log-rank).","the results implicate that high alpha-catenin expression is intimately involved in the key regulatory mechanisms leading to invasive phenotype, lymph node metastases, and progressive disease in crc.",Medication
is overweight associated with impaired beta-cell function during pregnancy : a longitudinal study of 553 normal pregnancies?,"to monitor beta-cell function and insulin sensitivity longitudinally in a large cohort of pregnant women to elucidate mechanisms that influence glycemic control in pregnancy. five hundred and fifty-three pregnant scandinavian women underwent 75 g oral glucose tolerance test (ogtt) at weeks 14-16 and 30-32. insulin sensitivity (matsuda index) and beta-cell function (ratio of auc(insulin) to auc(glucose), auc(ins/glc)) were calculated from 520 complete tests, and subsequently beta-cell function was adjusted for insulin sensitivity, rendering an oral disposition index (di(o)). eleven women (2.1) had gestational diabetes mellitus (gdm1) at weeks 14-16, and 49 (9.4) at weeks 30-32 (gdm2), which is higher than that previously reported in this region. in the subdivision of ogtt, more overweight (body mass index25) was found in glucose-intolerant groups (glucose-tolerant women (normal glucose tolerance, ngt) 38 versus gdm2 women 58 and gdm1 women 82, p0.005). in early pregnancy, insulin sensitivity was lowest in gdm1, intermediate in gdm2, and highest in ngt. in late pregnancy, insulin sensitivity decreased in all groups, most in gestational diabetes. beta-cell function demonstrated minor shifts during pregnancy, but when adjusted for decreasing insulin sensitivity, di(o) levels fell by 40 (p0.001). di(o) was significantly attenuated relative to glucose intolerance (gdm1 25 and gdm2 53) during pregnancy. in overweight women, di(o) levels were lower throughout pregnancy (p0.001 versus normal weight women), this reduction was significant (p0.01) in both ngt (21-25) and gdm2 subjects (26-49).",beta-cell function adjusted for insulin sensitivity (di(o)) deteriorated during pregnancy in both glucose-tolerant and glucose-intolerant women. the failure to compensate the decrease in insulin sensitivity was accentuated in overweight women.,Medication
does resilience mediate the longitudinal relationships between social support and mental health outcomes in multiple sclerosis?,"to investigate the longitudinal relationships between social support and subsequent mental health outcomes in individuals with multiple sclerosis (ms); and to examine resilience as a mediator between social support and subsequent mental health outcomes in this population. observational, longitudinal cohort study. participants were assessed at four time points over 12 months in the context of a previously-reported randomized controlled trial. telephone-based measures administered to community-based participants across the united states. one hundred sixty-three individuals with ms and one or more of the following symptoms: depression, fatigue, and/or pain. not applicable. mental health outcomes included: depressive symptomatology, assessed using the patient health questionnaire - 9; anxious symptomatology, assessed using the short form of the emotional distress - anxiety scale from the patient-reported outcomes measurement information system; and general mental health status, assessed using the mental component summary score from the short form - 8 health survey. at any given time, social support from significant others, family member, and friends was significantly associated with subsequent mental health outcomes for all three measures assessed (all ps .05). resilience measured concomitantly with social support significantly mediated the relationships between social support and subsequent mental health outcomes. after controlling for resilience, most of the direct relationships between social support and mental health outcomes were no longer significant.","there are significant longitudinal relationships between social support, resilience, and mental health outcomes for people with ms. given the mediating role of resilience in supporting better mental health outcomes, future clinical research and practice may benefit from an emphasis on resilience-focused psychological interventions.",Symptoms
"are genetic polymorphisms of the serotonin transporter , but not the 2a receptor or nitric oxide synthetase , associated with pulmonary hypertension in chronic obstructive pulmonary disease?","pulmonary hypertension (ph) is prognosti- cally important in chronic obstructive pulmonary disease (copd). since ph only weakly correlates with hypoxemia, other factors must play a role. to investigate whether polymorphisms of the serotonin transporter (5htt), serotonin-2a receptor (5htr2a) and endothelial nitric oxide synthetase (enos) are related to ph in copd. in 59 copd patients who underwent right heart catheterization, 6-min walking distance, nyha functional class, pulmonary function tests, blood gases and 5htt, 5htr2a and enos (4ab and t298c) polymorphisms were determined. forty-nine copd patients in nyha functional class iii-iv were included. ten were excluded due to comorbid causes of ph (mainly chronic thromboembolic). ph (mpap or 25 mm hg) was present in 55 and usually mild, but out of proportion (mpap or 40 mm hg) in 12. patients with ph had significantly higher frequencies of the 5htt-l-allele (52) compared to individuals without ph (36), and ll homozygote patients had more severe ph. in patients with out-of-proportion ph, the l-allelic frequency was even 75. we found no association of 5htr2a and enos polymorphism with ph in copd.","in this copd cohort we confirm that ph is frequent and usually mild, but out of proportion in a subgroup. we found a significant association of the l-allelic variant of 5htt with ph overall and especially in out-of-proportion ph. these findings may point towards a role of the serotonin system in copd-ph and warrant further studies.",Medication
does electrotransfer of human il-1ra into skeletal muscles reduce the incidence of murine collagen-induced arthritis?,"it has previously been demonstrated that high levels of gene expression in skeletal muscles can be achieved after direct in vivo electrotransfer of naked plasmid dna. the purpose of this study is to examine the potential of in vivo electroporation of plasmid dna encoding human il-1ra for the prevention of murine collagen-induced arthritis (cia). dba/1 mice were injected in gastrocnemius muscles with plasmid dna followed by in vivo electroporation. to uncover the optimum conditions of gene transfer, various electric field strengths and different amounts of plasmid dna were applied. calf muscles around the injected areas were investigated with histological methods for damage to muscle tissue. the levels of human il-1ra expression in the injected area and also in the serum were determined with elisa for human il-1ra. based on these data, the effects of electrotransfer of plasmid dna were tested using the murine cia model. dba/1 mice were immunized with bovine collagen type ii at the base of the tail. on day 21, mice were given a booster injection with the same antigen. mice were divided into two groups on day 26. one group of mice received plasmid containing the il-1ra cdna sequence, while control mice were given plasmid lacking the il-1ra coding sequence. the incidence of arthritis was evaluated by macroscopic analysis, histological analysis, and the levels of inflammatory cytokines. il-1ra expression increased as a function of the electrical field strength and the amount of dna. 200 v/cm (eight pulses; 20 ms per pulse; 1 hz) and 15 microg of plasmid dna per mouse were found to be optimum for gene transfer. after in vivo electroporation, gene expression in both muscle and serum increased gradually, reaching a peak value on day 10. significant levels of human il-1ra expression were maintained for 20 days. macroscopic analysis showed that the onset of cia was significantly inhibited by direct electrotransfer of plasmid dna encoding human il-1ra. histological analysis of knee joints showed that the incidence of arthritis in knee joints was also prevented. the levels of mouse il-1beta and il-12 in paws were significantly lower in the group treated with il-1ra than those in the control group.",these results demonstrate that direct electrotransfer of plasmid containing the human il-1ra cdna sequence to skeletal muscle can reduce the incidence of cia in mice.,Medication
is atopy a risk factor for non-steroidal anti-inflammatory drug sensitivity?,"there is scarce information in the literature about a possible association between atopy and certain clinical manifestations of nsaid sensitivity. (1) to evaluate the prevalence of atopy in patients proved to be sensitive to cyclooxygenase inhibitors. (2) to assess cross-reactivity to two alternative nsaids, paracetamol (acetaminophen) and nimesulide. nsaid-sensitive patients attending an allergy clinic and unselected controls were prick tested with inhalant allergens. oral challenges with nsaids were carried out by the single-blinded (sboc) method. clinical data about personal and family history of allergic and atopic diseases were obtained by a careful review of the medical records and by direct questioning by experienced allergists. fifty patients had positive sbocs to the suspected nsaid and only these were studied. a personal history of atopic diseases was present in 41 patients (82) and 7 controls (14.5), and a family history in 24 patients (48) and 6 controls (12.5). prick skin tests with aeroallergens were positive in 39 of 45 patients tested (86.6) and in 14 of 48 controls (29.1), (p .0001). skin test positivity rates were higher in patients with cutaneous challenge reactions who responded to only one nsaid (single reactors) in comparison to cross-reactors (p .04). the most frequent clinical manifestations of nsaid sensitivity were (1) cutaneous (angioedema, urticaria) in 34 patients, (2) blended (cutaneous plus respiratory) in 12, (3) respiratory in 3, and (4) anaphylactoid in 1. aspirin, pyrazolone, paracetamol, and ibuprofen were the drugs more frequently implicated in these reactions. cross-sensitivity with paracetamol and nimesulide were 32 and 25, respectively.","the prevalence of atopy is increased in challenge-proven nsaid-intolerant patients. the atopic condition may represent an important risk factor for developing reactions to these drugs. paracetamol and nimesulide are relatively safe alternative choices in those patients, although their use still carries some risk of unwanted reactions.",Medication
is elevated serum adiponectin related to elevated serum ferritin and interleukin-6 in -thalassaemia major children?,"there is evidence that iron affects lipid metabolism and adipocyte biology. given the effects of iron on adiponectin, the role of iron in lipid oxidation, and the potential additive effects of oxidative stress from excess iron and lipid metabolism. we aimed to investigate serum adiponectin in relation to clinical and laboratory parameters including the inflammation markers c-reacitve protein (crp) and interleukin-6 (il-6) in -thalassaemia major children. we investigated 58 -thalassaemia major children under scheduled blood transfusion and 30 controls. routine clinical evaluation, laboratory investigations including serum ferritin as well as crp measured by immunoturbidimetry, il-6 and serum adiponectin measured by elisa are performed. crp, il-6 and serum adiponectin levels were higher in patients than controls (p0.001, p0.04 and p0.001, respectively). patients received desferoxamine showed significantly lower levels of adiponectin than those did not receive it (meansd4.503.37 vs. 9.969.68, p0.006). serum adiponectin was significantly negatively correlated with hemoglobin (hb) concentration (r-0.36, p0.005). it was significantly positively correlated with platelets count, serum ferritin, crp and il-6 (r0.27, r0.26, r0.30, r0.35, respectively and p0.04, p0.04, p0.01, p0.008, respectively). serum ferritin and il-6 were the significant predictors of serum adiponectin level (p0.001 and p0.003, respectively).",serum adiponectin was increased in -thalassaemia major as were pro-inflammatory markers (crp and il-6). its level is directly associated with ferritin and il-6 levels.,Treatment
is genetic polymorphism of urokinase-type plasminogen activator interacting with plasminogen activator inhibitor-1 to raise risk of cervical neoplasia?,"to evaluate the impact of plasminogen activator (pa) system genes, including urokinase plasminogen activator (upa), upa receptor (upar), and plasminogen activator inhibitor-1 (pai-1) gene polymorphisms in patients with the cervical neoplasia. in total, 336 blood samples were collected from healthy women and 136 patients with cervical neoplasia to analyze the gene polymorphisms of representative pa system genes. there was no significant association between cervical neoplasia cases and gene polymorphisms of upa, upar and pai-1 genes as well as to the carcinogenesis of cervical if the cervical neoplasia cases were stratified to hsils and invasive cancer cases. however, we found a mutual interaction between upa/pai-1 genes, which women carrying the upa/pai-1 cc/4g4g allele had a 1.70-fold higher risk (or 1.70; 95 ci 1.04-2.79) of cervical neoplasia compared with those carrying the cc/4g5g allele.",individuals with upa/pai-1 cc/4g5g allele were in high susceptibility for cervical neoplasia. the combined polymorphism of upa/pai-1 might diminish the ability of pai-1 to inhibiting cervical cancer carcinogenesis when pai-1 alone as the role of inhibitor.,Medication
does choice of intravenous antibiotic prophylaxis for colorectal surgery do matter?,"the surgical care improvement program endorses mandatory compliance with approved intravenous prophylactic antibiotics; however, oral antibiotics are optional. we hypothesized that surgical site infection (ssi) rates may vary depending on the choice of antibiotic prophylaxis. a retrospective cohort study of elective colorectal procedures using veterans affairs surgical quality improvement program (vasqip) and ssi outcomes data was linked to the office of informatics and analytics (oia) and pharmacy benefits management (pbm) antibiotic data from 2005 to 2009. surgical site infection rates by type of iv antibiotic agent alone (iv) or in combination with oral antibiotic (iv oa) were determined. generalized estimating equations were used to examine the association between type of antibiotic prophylaxis and ssi for the entire cohort and stratified by use of oral antibiotics. after 5,750 elective colorectal procedures, 709 ssis (12.3) developed within 30 days. oral antibiotic iv (n 2,426) had a lower ssi rate than iv alone (n 3,324) (6.3 vs 16.7, p 0.0001). there was a significant difference in the ssi rate based on type of preoperative iv antibiotic given (p 0.0001). generalized estimating equations adjusting for significant covariates of age, body mass index, procedure work relative value units, and operation duration demonstrated an independent protective effect of oral antibiotics (odds ratio or 0.37, 95 ci 0.29 to 0.46), as well as increased rates of ssi associated with ampicillin/sulbactam (or 2.21, 95 ci 1.37 to 3.56) and second generation cephalosporins (cefoxitin, or 2.50, 95 ci 1.83 to 3.42; cefotetan, or 2.70, 95 ci 1.72 to 4.22) when compared with first generation cephalosporin/metronidazole.","the choice of iv antibiotic was related to the ssi rate; however, oral antibiotics were associated with reduced ssi rate for every antibiotic class.",Medication
is efavirenz associated with higher bone mass in south african children with hiv?,"we investigate if switching from a ritonavir-boosted lopinavir (lpv/r)-based to an efavirenz-based antiretroviral therapy (art) regimen is associated with beneficial bone development. the changes bone study follows hiv-infected children who participated in a noninferiority randomized trial in johannesburg, south africa evaluating the safety and efficacy of preemptive switching to efavirenz (n 106) compared with remaining on lpv/r (n 113). hiv-uninfected children were also recruited. whole-body and lumbar spine bone mineral content (bmc) were assessed by dual-energy x-ray absorptiometry at a cross-sectional visit. bmc z-scores adjusted for sex, age, and height were generated. physical activity and dietary intake were assessed. cd4 percentage and viral load were measured. we compared bone indices of hiv-infected with hiv-uninfected children and lpv/r with efavirenz by intent-to-treat. the 219 hiv-infected (52 boys) and 219 hiv-uninfected (55 boys) children were 6.4 and 7.0 years of age, respectively. mean art duration for hiv-infected children was 5.7 years. whole-body bmc z-score was 0.17 lower for hiv-infected children compared with hiv-uninfected children after adjustment for physical activity, dietary vitamin d and calcium (p 0.03). whole-body bmc z-score was 0.55 higher for hiv-infected children switched to efavirenz compared with those remaining on lpv/r after adjustment for physical activity, dietary vitamin d and calcium, cd4 percentage, and viral load (p 0.0001).","south african hiv-infected children receiving art have lower bone mass compared with hiv-uninfected controls. accrued bone mass is positively associated with switching to efavirenz-based art compared with remaining on lpv/r, providing additional rationale for limiting lpv/r exposure once viral suppression has been achieved.",Prevention
does il-17a promote pulmonary inflammation in rats with pulmonary fibrosis induced by bleomycin ?,"to investigate the role of il-17a in the development of pulmonary fibrosis in rats. twenty female wistar rats were randomly divided into normal saline (ns) group and bleomycin (blm) group. the blm group was intratracheally instilled with blm, while the ns group was treated with saline instead. half of the rats in each group were sacrificed respectively on day 7 and 28 after intratracheal instillation. he and masson stainings were performed to show the pathological changes of lung tissues. the expression of il-17a in lung tissues was detected by the immunohistochemistry. the bronchoalveolar lavage fluid (balf) was harvested; one part of it was used for cell counting and classification, and for the detection of the concentration of il-17a in balf using elisa; the other part of it was used for determining the concentration of il-17a in the culture supernatant of the purified alveolar macrophage (am) using elisa and reverse transcription pcr (rt-pcr). compared with the ns group, the blm group presented a great deal of inflammatory cells in the alveoli, the increased total number of cells, decreased am level and increased neutrophil number in balf on day 7; on day 28, the blm group had milder alveolitis and more serious fibrosis. the expression of il-17a protein in lung tissues was obviously higher on day 7 and 28 in the blm group than in the ns group (p0.05), and it was higher on day 7 than on day 28. the increased total number of balf cells in blm group returned to the normal level on day 28. the level of il-17a in balf increased significantly on day 7 and 28 in blm group, however, compared with that on day 7, it decreased on day 28. compared to the ns group, the expression of il-17a protein in the culture supernatant of the blm group was remarkably higher at 12th, 24th and 48th hours (p0.05). rt-pcr showed that compared with the ns group, the expression of il-17a mrna increased significantly in blm group on day 7 and 28 (p0.05).","il-17a promotes the development of pulmonary inflammation, indicating that it may be involved in the progress of pulmonary fibrosis.",Treatment
do both happy and sad melodies modulate tonic human heat pain?,"the mechanism of music effects on pain perception remains to be elucidated. to determine which component (mood or valence) of music is more important in music-induced hypoalgesia, we compared the effects of 2 melodies with different moods (happy vs sad) but with the same degree of valence (pleasant vs unpleasant) to an affective neutral lecture and a control (baseline) on the objective and subjective responses to tonic heat pain. our hypothesis was that if mood was the key component, the happy melody would reduce pain, whereas the sad one would exacerbate pain; and if valence is the key component, the 2 melodies would both alleviate pain. twenty females participated in this study which consisted of 4 conditions (baseline, happy melody, sad melody, and lecture). pain tolerance time (ptt), pain intensity, and distress dynamics and the characteristics of pain were measured. a newly devised multiple affective rating scale (mars) was employed to assess the subjective experience of auditory perception. both happy and sad melodies of equal valence resulted in significant lower pain ratings during the pain test and were in contrast to the mood prediction. these results indicate that the valence of music, rather than the mood it induced, appears to be the most likely mediator of the hypoalgesic effect of the different music.",this article provides new evidence that the valence of music is more crucial than mood in affective pain modulation. this finding gives impetus for health professionals to manage pain more effectively in patients with proper music.,Symptoms
does comparative performance information play no role in the referral behaviour of gps?,"comparative performance information (cpi) about the quality of hospital care is information used to identify high-quality hospitals and providers. as the gatekeeper to secondary care, the general practitioner (gp) can use cpi to reflect on the pros and cons of the available options with the patient and choose a provider best fitted to the patient's needs. we investigated how gps view their role in using cpi to choose providers and support patients. we used a mixed-method, sequential, exploratory design to conduct explorative interviews with 15 gps about their referral routines, methods of referral consideration, patient involvement, and the role of cpi. then we quantified the qualitative results by sending a survey questionnaire to 81 gps affiliated with a representative national research network. seventy gps (86 response rate) filled out the questionnaire. most gps did not know where to find cpi (87) and had never searched for it (94). the gps reported that they were not motivated to use cpi due to doubts about its role as support information, uncertainty about the effect of using cpi, lack of faith in better outcomes, and uncertainty about cpi content and validity. nonetheless, most gps believed that patients would like to be informed about quality-of-care differences (62), and about half the gps discussed quality-of-care differences with their patients (46), though these discussions were not based on cpi.","decisions about referrals to hospital care are not based on cpi exchanges during gp consultations. as a gatekeeper, the gp is in a good position to guide patients through the enormous amount of quality information that is available. nevertheless, it is unclear how and whether the gp's role in using information about quality of care in the referral process can grow, as patients hardly ever initiate a discussion based on cpi, though they seem to be increasingly more critical about differences in quality of care. future research should address the conditions needed to support gps' ability and willingness to use cpi to guide their patients in the referral process.",General
does galectin-9 prolong the survival of septic mice by expanding tim-3-expressing natural killer t cells and pdca-1 cd11c macrophages?,"galectin-9 ameliorates various inflammatory conditions including autoimmune diseases by regulating t cell and macrophage/dendritic cell (dc) functions. however, the effect of galectin-9 on polymicrobial sepsis has not been assessed. we induced polymicrobial sepsis by cecal ligation and puncture (clp) in mice. the survival rate was compared between galectin-9- and pbs-treated clp mice. an elisa was used to compare the levels of various cytokines in the plasma and culture supernatants. fluorescence-activated cell sorting analysis was further performed to compare the frequencies of subpopulations of spleen cells. galectin-9 exhibited a protective effect in polymicrobial sepsis as demonstrated in galetin-9 transgenic mice and therapeutic galectin-9 administration. in contrast, such effect was not observed in nude mice, indicating the involvement of t cells in galectin-9-mediated survival prolongation. galectin-9 decreased tnf, il-6, il-10 and, high mobility group box 1 (hmgb1) and increased il-15 and il-17 plasma and spleen levels. galectin-9 increased the frequencies of natural killer t (nkt) cells and pdca-1 cd11c macrophages (pdc-like macrophages) but did not change the frequency of cd4 or cd8 t cells, t cells or conventional dc. as expected, galectin-9 decreased the frequency of tim-3 cd4 t cells, most likely th1 and th17 cells. intriguingly, many spleen nk1.1 nkt cells and pdc-like macrophages expressed tim-3. galectin-9 increased the frequency of tim-3-expressing nk1.1 nkt cells and pdc-like macrophages. galectin-9 further increased il-17 nk1.1 nkt cells.","these data suggest that galectin-9 exerts therapeutic effects on polymicrobial sepsis, possibly by expanding nkt cells and pdc-like macrophages and by modulating the production of early and late proinflammatory cytokines.",Treatment
are apoptosis and expression of bcl-2 protein inverse factors influencing tumour cell turnover in primary carcinoid tumours of the lung?,"this study evaluates potential regulating factors in primary pulmonary carcinoid tumours, 16 typical and four atypical samples, with special emphasis on apoptosis and the bcl-2 gene family. furthermore, p53-related oncogenes were analysed in a search for associated biological parameters. the in-situ end-labelling technique (isel) was used to determine apoptotic cells, in addition to immunohistochemical methods, which were used to investigate the expression of the ki67 antigen (avidinbiotin complex (abc) method) and bcl-2, bcl-x, p53, p21/waf1, p27 and mdm-2 proteins (catalysed reporter deposition (card) technique). the incidence of apoptotic tumour cells was significantly enhanced in typical carcinoids. the bcl-2 protein was expressed to a higher degree in atypical carcinoids, which displayed a higher proliferative capacity as well. in contrast, bcl-x was observed predominantly in so-called typical carcinoids. the tumour cell turnover index was the most distinguishing parameter between both entities. all carcinoid tumours failed to show a staining for p53, p21/waf. p27 and mdm-2 proteins.",the different biological behaviour of the carcinoid tumours under study seems to be influenced by the bcl-2 gene family preventing programmed cell death. we speculate that this results in a more aggressive course in atypical carcinoid tumours.,General
does ghrelin alleviate spinal cord injury in rats via its anti-inflammatory effects?,"spinal cord injury (sci) leads to an inflammatory response that generates substantial secondary damage within the tissue besides the primary damage. ghrelin, 28 amino-acid peptide, has been shown to modulate the release of proinflammatory cytokines and exert antiinflammatory effects. the aim of the current study was to investigate the anti-inflammatory effects of ghrelin, in a rat model of sci. wistar albino rats were divided as control, sci, and ghrelin-treated (10 g/kg/day, ip) sci groups. in order to induce sci, a standard weight-drop method that induced a moderately severe injury (100 g/cm force) at t10, was used. injured animals were given either ghrelin or saline 15 min post-injury. in plasma samples, neuron-specific enolase (nse) and s-100 protein levels were evaluated. spinal cord samples were taken for histological examination or determination of myeloperoxidase (mpo) activity and dna fragmentation. sci caused significant increases in plasma nse and s-100 levels and tissue mpo activity and dna damage. on the other hand, ghrelin treatment improved histological findings as well as biochemical parameters while it failed to improve the impairment of the neurological functions due to sci.",the present study suggests that ghrelin could reduce sci-induced oxidative stress and exert anti-inflammatory effects in the spinal cord following trauma.,Treatment
is mobilization of endothelial progenitor cells from bone marrow impaired in a piglet model of acute respiratory distress syndrome?,"to characterize the endothelial progenitor cell mobilization in the models of moderate and severe lung injury, we hypothesized that there were differences in endothelial progenitor cell levels and mobilizing cytokines between moderate and severe lung injury. prospective, randomized, and controlled experimental study. university research laboratory center. fifteen healthy piglets. piglets were randomly allocated to control, moderate lung injury (acute lung injury), and severe lung injury (acute respiratory distress syndrome) groups. lung injury was established by intravenous infusion of oleic acid. animals were mechanically ventilated for 24-48 hours, and then animals were weaned from ventilation and cared for until day 7. endothelial progenitor cells were quantified by flow cytometry. after 24 hours, the number of endothelial progenitor cells in peripheral blood increased in the acute lung injury group but was not altered in the acute respiratory distress syndrome group compared to the control group. the number of cd34kdr, kdrcd133, and cd34kdrcd133 cells was higher in the acute lung injury group than in the acute respiratory distress syndrome group. in bone marrow, the number of cd34kdr and kdrcd133 cells was greater in acute respiratory distress syndrome animals but not altered in acute lung injury animals at 24 hours. furthermore, plasma stromal cell-derived factor-1 and vascular endothelial growth factor concentrations were higher in acute lung injury than in acute respiratory distress syndrome at 24 hours. matrix metalloproteinase-9 and soluble kit ligand levels in bone marrow were reduced in acute respiratory distress syndrome compared with acute lung injury. lung cd34, kdr, and lung stromal cell-derived factor-1 messenger rna expression were higher in the acute lung injury group than in the acute respiratory distress syndrome group. furthermore, the expression of cd34, kdr, and cd133 messenger rna in lung tissue was correlated with stromal cell-derived factor-1 in the lung.","there was a rapid release of endothelial progenitor cells from bone marrow into circulation in moderate acute lung injury, and endothelial progenitor cell mobilization was impaired in acute respiratory distress syndrome.",Medication
do tetrahydrobiopterin deficiency and nitric oxide synthase uncoupling contribute to atherosclerosis induced by disturbed flow?,"tetrahydrobiopterin (bh(4)) is a critical cofactor for nitric oxide (no) synthesis by no synthase (nos). recently, we demonstrated that disturbed flow produced by partial carotid ligation decreases bh(4) levels in vivo. we therefore aimed to determine whether atherosclerosis induced by disturbed flow is due to bh(4) deficiency and nos uncoupling and whether increasing bh(4) would prevent endothelial dysfunction, plaque inflammation, and atherosclerosis. we produced a region of disturbed flow in apolipoprotein e(-/-) mice using partial carotid ligation and fed these animals a high-fat diet. this caused endothelial nos uncoupling as characterized by increased vascular superoxide production, altered vascular reactivity, and a change in endothelial nos migration on low-temperature gel. these perturbations were accompanied by severe atherosclerosis, infiltration of t cells and macrophages, and an increase in cytokine production. treatment with bh(4) recoupled nos, decreased superoxide production, improved endothelium-dependent vasodilatation, and virtually eliminated atherosclerosis. bh(4) treatment also markedly reduced vascular inflammation and improved the cytokine milieu induced by disturbed flow.",our results highlight a key role of bh(4) deficiency and nos uncoupling in atherosclerosis induced by disturbed flow and provide insight into the effect of modulating vascular bh(4) levels on atherosclerosis and inflammation at these sites of the circulation.,Prevention
is menstrual cycle-related sialidase activity of the female cervical mucus associated with exosome-like vesicles?,"to study endogenous sialidase activity in genital tract secretions of pregnant and nonpregnant women. laboratory study. department of evolutionary biology and department of obstetrics and reproductive medicine, university of siena, siena, italy. vaginal and cervical mucus samples were obtained from pregnant and nonpregnant women in different phases of the menstrual cycle and in different weeks of pregnancy. sialidase activity was assessed by fluorimetric assay and localized by transmission electron microscopy and differential centrifugation. sialidase activity in cervical mucus of healthy women reaches a maximum in the ovulatory phase. cervical mucus from pregnant and nonpregnant women had significant sialidase activity that was associated with membranous vesicles having an exosome-like structure.",female cervical mucus contains an endogenous menstrual cycle-related sialidase that could be involved in modifying the rheologic properties of mucus to favor sperm progression at fertilization. its association with exosome-like vesicles also suggests a role in intercellular communication before and after fertilization.,Diagnosis
does timothy grass pollen major allergen phl p 1 activate respiratory epithelial cells by a non-protease mechanism?,"group 1 allergens from grass pollen (e.g. phl p 1, the major allergen of timothy grass phleum pratense) cause ige reactivity in about 95 of allergic subjects and exist in all grass species. the respiratory epithelium represents a first line of contact of the immune system with airborne allergens, functions as physical barrier and is an important immunological regulation system. the aim of this study was to investigate the interaction of phl p 1 with human respiratory epithelium to elucidate the contribution of epithelial cells to the development of allergic reactions. purified phl p 1 was used to stimulate a549 cells and transient transfected hek293 cells. mrna level of different mediators were investigated by real-time pcr, release of the mediators was determined by elisa. the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (mtt) test and an ex vivo model of the murine trachea were used to investigate a potential proteolytic activity of phl p 1. phl p 1 activates respiratory epithelial cells as measured by induction of il-6, il-8 and tgf-beta mrna and release. phl p 1, in contrast to der p 1 from the house dust mite, does not exert proteolytic activity, as investigated by microscopic observation and mtt test. in an ex vivo model of the murine trachea we were able to show that der p 1, in contrast to phl p 1, enhances the transportation velocity of particles by the trachea, presumably by atp released from the injured epithelium.",we conclude that under physiological conditions phl p 1 affects tracheal epithelial cells through a non-proteolytic activity. enhancement of tgf-beta expression induced by phl p 1 together with the increased release of il-6 and il-8 might provide an indirect mechanism through which the allergen may cross the epithelial barrier and attracts immunocompetent cells.,General
does tlr-3 receptor activation protect the very immature brain from ischemic injury?,"we have shown that preconditioning by lipopolysaccharide (lps) will result in 90 reduction in ischemic brain damage in p7 rats. this robust lps neuroprotection was not observed in p3 or p5 pups (corresponding to human premature infant). lps is a known toll-like receptor 4 (tlr-4) ligand. we hypothesized that tlrs other than tlr-4 may mediate preconditioning against cerebral ischemic injury in the developing brain. tlr-2, tlr-3, tlr-4, and tlr-9 expression was detected in brain sections from p3, p5, and p7 rats by immuno-staining. in subsequent experiments, p5 rats were randomly assigned to tlr-3 specific agonist, poly i:c, or saline treated group. at 48 h after the injections, hypoxic-ischemic (hi) injury was induced by unilateral carotid artery ligation followed by hypoxia for 65 min. brains were removed 1 week after hi injury and infarct volumes were compared in he stained sections between the two groups. tlr-2 and tlr-3 were highly expressed in brains of p3 and p5 but not in p7 rats. the number of tlr-4 positive cells was lower in p3 and p5 compared to p7 brains (p 0.05). tlr-3 was predominately expressed in p5 pups (p 0.05). there was no significant difference in tlr-9 expression in the three age groups. there was a significant reduction in infarct volume (p0.01) in poly i:c compared to saline pre-treated p5 pups. pre-treatment with poly i:c downregulated nf-b and upregulated irf3 expression in p5 rat ischemic brains. pre-treatment with poly i:c did not offer neuroprotection in p7 rat brains.",tlrs expression and function is developmentally determined. poly i:c-induced preconditioning against ischemic injury may be mediated by modulation of tlr-3 signaling pathways. this is the first study to show that tlr-3 is expressed in the immature brain and mediates preconditioning against ischemic injury.,Medication
does grp78 overproduction in pancreatic beta cells protect against high-fat-diet-induced diabetes in mice?,"endoplasmic reticulum (er) stress has been detected in pancreatic beta cells and in insulin-sensitive tissues, such as adipose and liver, in obesity-linked rodent models of type 2 diabetes. the contribution of er stress to pancreatic beta cell dysfunction in type 2 diabetes is unclear. we hypothesised that increased chaperone capacity protects beta cells from er stress and dysfunction caused by obesity and improves overall glucose homeostasis. we generated a mouse model that overproduces the resident er chaperone grp78 (glucose-regulated protein 78 kda) in pancreatic beta cells under the control of a rat insulin promoter. these mice were subjected to high-fat diet (hfd) feeding for 20 weeks and metabolic variables and markers of er stress in islets were measured. as expected, control mice on the hfd developed obesity, glucose intolerance and insulin resistance. in contrast, grp78 transgenic mice tended to be leaner than their non-transgenic littermates and were protected against development of glucose intolerance, insulin resistance and er stress in islets. furthermore, islets from transgenic mice had a normal insulin content and normal levels of cell-surface glut2 (glucose transporter 2) and the transgenic mice were less hyperinsulinaemic than control mice on the hfd.","these data show that increased chaperone capacity in beta cells provides protection against the pathogenesis of obesity-induced type 2 diabetes by maintaining pancreatic beta cell function, which ultimately improves whole-body glucose homeostasis.",Prevention
does malnutrition assessed by phase angle determine outcomes in low-risk cardiac surgery patients?,"phase angle (pa), which is obtained from bioelectrical impedance analysis (bia), is a non-invasive method for measuring altered electrical properties of biological tissues. it has been recognised as an objective prognostic marker of disease severity and frailty. the aim of this study is to determine whether pa is a marker of malnutrition and postoperative morbidity in low operative risk patients undergoing cardiac surgery. a prospective study was conducted in a tertiary hospital. the nutritional state of the cardiac surgery patients was evaluated using bia the day before the scheduled surgery. after applying selection criteria, 342 low operative risk patients were selected and classified into two groups in accordance with the pa value: a low pa group and a normal pa group. the correlation between low pa and low fat-free mass index (ffmi), a marker of malnutrition, was assessed. associations between low pa and adverse postoperative outcomes, defined by the society of thoracic surgeons postoperative risk evaluation model, were analysed. the impact of low pa on length of stay in an icu and hospital was evaluated. low pa was detected in 61 (17.8) patients in the selected group, which consisted of low operative risk patients with a median euroscore ii value of 1.46 (iqr: 0.97-2.03) and was associated with ffmi with pearson's r of 0.515 (p 14 days) rate (31 50.8 vs. 105 37.8, p 0.063) in the group with low pa.","a low preoperative pa is an indicator of malnutrition and determines adverse outcomes after cardiac surgery. further research is needed to evaluate clinical applications of the pa, such as a more accurate identification of malnourished cardiac surgery patients.",Treatment
do the relationship between initial implant stability quotient values and bone-to-implant contact ratio in the rabbit tibia?,"implant stability quotient (isq) values have been supposed to predict implant stability. however, the relationship between isq values and bone-to-implant contact ratio (bic) which is one of the predictors of implant stability is still unclear. the aim of the present study was to evaluate initial isq values in relation to bic using rabbit model. four new zealand white rabbits received a total of 16 implants in their tibia. immediately after implant placement isq values were assessed. the measurements were repeated at the time of sacrifice of the rabbits after 4 weeks. peri-implant bone regeneration was assessed histomorphometrically by measuring bic and bone volume to total volume values (bone volume ). the relationships between isq values and the histomorphometric output were assessed, and then, the osseointegration prediction model via the initial isq values was processed. initial isq values showed significant correlation with the bic. the bone volume did not show any significant association with the isq values.","in the limitation of this study, resonance frequency analysis is a useful clinical method to predict the bic values and examine the implant stability.",General
is office-based ureteral stent placement under local anesthesia for obstructing stones safe and efficacious?,"to evaluate the outcomes of urgent ureteral stent placement under local anesthesia (la) with those placed under general anesthesia (ga) for obstructing stones. after institutional review board approval, ureteral stents placed from january 2007 to july 2011 at our institution were reviewed. only primary stent placement for obstructing renal or ureteral calculi was included in the present analysis. data were evaluated for 2 groups: ga and la. the primary outcomes were demographics, interval from presentation to stent insertion, interval from stent insertion to stone removal, success and complication rates, and secondary outcomes were costs per encounter. a total of 119 primary stent insertion procedures in 110 unique patients were assessed; 73 (ga) and 46 (la). no differences were found in the mean age or sex between the 2 groups. both ga and la groups were stented within 12 hours of presentation, at 58 and 54, respectively (p .69); and the interval from stent insertion to stone removal was similar in both groups (mean 33 days and 35 days in the ga and la groups, respectively, p .79). no significant differences were found in the failure to place the stent between the ga and la groups (1.3 vs 8.7, respectively, p .07). no complications related to stent placement occurred in either group. the average cost per encounter was nearly 4 times greater in the ga group.","urgent ureteral stent placement for obstructing stones can be safely and effectively performed under la in the office. although avoiding ga and reducing costs, this approach did not prolong the interval to definitive stone management.",Medication
do non-steroidal anti-inflammatory drugs inhibit helicobacter pylori-induced human neutrophil reactive oxygen metabolite production in vitro?,"helicobacter pylori infection is associated with increased production of gastric mucosal reactive oxygen metabolites which have been implicated in mucosal damage and carcinogenesis. in vitro, neutrophils produce reactive oxygen metabolites following activation by h. pylori. non-steroidal anti-inflammatory drugs (nsaids) inhibit neutrophil activation by several factors, e.g. n-formyl-methionyl-leucyl-phenyalanine (f-mlp). to examine the effect of nsaids on h. pylori-induced reactive oxygen metabolite production by human peripheral blood neutrophils. neutrophils were stimulated by h. pylori (nctc 11637) water extract or f-mlp in the presence or absence of nsaids. reactive oxygen metabolite activity was measured by luminol-enhanced chemiluminescence. h. pylori water extract stimulated a sevenfold increase in chemiluminescence which was inhibited dose-dependently by diclofenac. all six nsaids studied (at 10-4 m) significantly inhibited h. pylori-and f-mlp-stimulated neutrophil reactive oxygen metabolite production. meclofenamic acid and diclofenac had the greatest inhibitory effects on both h. pylori and f-mlp-stimulated neutrophil reactive oxygen metabolite production. the inhibitory effects of other nsaids varied with the activation stimulus. nsaids did not quench reactive oxygen metabolites generated in a cell-free xanthine:xanthine oxidase assay.",several nsaids attenuate h. pylori-induced neutrophil reactive oxygen metabolites production in vitro. this may be relevant to a potential chemopreventative role in gastric cancer and to a possible lack of synergy between h. pylori and nsaid use regarding peptic ulceration.,Medication
do the impact of suboptimal bowel preparation on adenoma miss rates and the factors associated with early repeat colonoscopy?,"there are no guidelines for the recommended interval to the next examination after colonoscopy with suboptimal bowel preparation. to identify factors associated with early repeat colonoscopy after initial examinations with suboptimal preparations and to measure adenoma miss rates in this context. retrospective study. hospital-based endoscopy unit. bowel preparation quality was recorded in 12,787 patients. of 12,787 colonoscopies, preparation quality was suboptimal (poor or fair) in 3047 patients (24). among these 3047 patients, repeat examination was performed in 3 years in 505 (17). factors associated with early repeat colonoscopy included lack of cecal intubation (odds ratio or 3.62, 95 confidence interval ci, 2.50-5.24) and finding a polyp (or 1.55, 95 ci, 1.17-2.07). among 216 repeat colonoscopies with optimal preparation, 198 adenomas were identified, of which 83 were seen only on the second examination, an adenoma miss rate of 42 (95 ci, 35-49). the advanced adenoma miss rate was 27 (95 ci, 17-41). for colonoscopies repeated in 1 year, the adenoma and advanced adenoma miss rates were 35 and 36, respectively.","single-center, retrospective study.",General
is the maternal plasma soluble vascular endothelial growth factor receptor-1 concentration elevated in sga and the magnitude of the increase relates to doppler abnormalities in the maternal and fetal circulation?,"the soluble form of vascular endothelial growth factor receptor-1 (svegfr-1), an antagonist to vascular endothelial growth factor and placental growth factor, has been implicated in the pathophysiology of preeclampsia. preeclampsia and pregnancy complicated with small for gestational age (sga) fetuses share some pathophysiologic derangements, such as failure of physiologic transformation of the spiral arteries, endothelial cell dysfunction, and leukocyte activation. the objectives of this study were to: (1) determine whether plasma concentrations of svegfr-1 in mothers with sga fetuses without preeclampsia at the time of diagnosis are different from those in patients with preeclampsia or normal pregnant women, and (2) examine the relationship between plasma concentrations of svegfr-1 and doppler velocimetry in uterine and umbilical arteries in patients with preeclampsia and those with sga. a cross-sectional study was conducted to determine the concentrations of the soluble form of vegfr-1 in plasma obtained from normal pregnant women (n 135), women with sga fetuses (n 53), and patients with preeclampsia (n 112). patients with sga fetuses and those with preeclampsia were sub-classified according to the results of uterine and umbilical artery doppler velocimetry examinations. plasma concentrations of svegfr-1 were determined by an elisa. since these concentrations change with gestational age, differences among various subgroups were statistically estimated with the delta value, defined as the difference between the observed and expected plasma svegfr-1 concentration. the expected values were derived from regression analysis of plasma svegfr-1 concentrations in normal pregnancy. regression analysis and univariate and multivariate analysis were employed. (1) mothers with sga fetuses had a mean plasma concentration of svegfr-1 higher than normal pregnant women (p 0.001), but lower than patients with preeclampsia (p 0.001). (2) among patients with sga fetuses, only those with abnormal uterine artery doppler velocimetry had a mean plasma svegfr-1 concentration significantly higher than normal pregnant women (p 0.001). (3) among mothers with sga fetuses in whom doppler velocimetry was performed (n 41), those with abnormalities in both the uterine and umbilical artery velocimetry had the highest mean delta of svegfr-1 plasma concentration (mean /- standard deviation (sd): 0.69 /- 0.29). conversely, patients who had normal doppler velocimetry in both uterine and umbilical arteries had the lowest mean delta (mean /- sd: 0.09 /- 0.29) of svegfr-1 plasma concentrations (anova; p 0.001). (4) among patients with preeclampsia in whom doppler velocimetry was performed (n 69), those with abnormalities in both the uterine and umbilical artery velocimetry had the highest mean delta svegfr-1 plasma concentration (mean /- sd: 1.01 /- 0.22) among all groups classified (anova; p 0.001). (5) among patients with sga and those with preeclampsia, there was a relationship (chi-square for trend p 0.001 for both) between the severity of doppler velocimetry abnormalities and the proportion of patients who had high delta svegfr-1 plasma concentrations (defined as a concentration two standard deviations (2sd) above the mean delta of normal pregnant women). (6) multiple regression analysis suggested that the diagnostic category (e.g., sga or preeclampsia), doppler abnormalities, and gestational age at blood sampling were associated with an increase in plasma svegfr-1 concentrations (p 0.001).","these observations provide support for the participation of the soluble receptor of vascular endothelial growth factor in the pathophysiology of sga with abnormal uterine artery doppler velocimetry and preeclampsia. an excess of svegfr-1 is released into the maternal circulation of patients with preeclampsia and those with sga fetuses, as abnormalities of impedance to blood flow involve uterine and umbilical circulation.",Medication
is the neutrophil to lymphocyte ratio associated with severity of rheumatic mitral valve stenosis?,"rheumatic heart disease (rhd) is a serious health concern in developing countries. rheumatic mitral stenosis (rms) is the most long-term sequel in rhd. the neutrophil to lymphocyte ratio (nlr) is a novel marker, and a higher nlr has been associated with poor clinical outcomes in various cardiovascular disorders. we evaluated the availability of nlr to predict severity of mitral stenosis (ms) in patients with rhd. we analyzed 300 consecutive patients with rms. the patients were divided into tertiles according to nlr: 0.85 nlr 1.85 (n100, tertile 1), 1.86 nlr 2.46 (n100, tertile 2), and 2.47 nlr 7.08 (n100, tertile 3). patients with rms were divided into three groups based on the degree of ms as mild, moderate, and severe ms. after the initial evaluation, 187 patients with moderate-to-severe rms (group 1) and 113 patients with mild rms (group 2) were reassessed. the patients with severe rms had significantly elevated nlr, mean platelet volume, and pulmonary artery systolic pressure values compared to patients with moderate and mild ms (p0.001, p0.001, p0.001 respectively). multivariate binary logistic regression analysis revealed that high levels of nlr was an independent predictor of severe rms (odds ratio 0.68, p0.008). moderate-to-severe rms incidence was significantly higher among patients in the tertile 3 (odds ratio 2.8, p0.001).","nlr is a new inflammatory marker and a simple, rapid, and easily accessible prognostic parameter that can be associated with severity of rms in patients with rhd.",Diagnosis
does transcript and protein analysis reveal better survival skills of monocyte-derived dendritic cells compared to monocytes during oxidative stress?,"dendritic cells (dcs), professional antigen-presenting cells with the unique ability to initiate primary t-cell responses, are present in atherosclerotic lesions where they are exposed to oxidative stress that generates cytotoxic reactive oxygen species (ros). a large body of evidence indicates that cell death is a major modulating factor of atherogenesis. we examined antioxidant defence systems of human monocyte-derived (mo)dcs and monocytes in response to oxidative stress. oxidative stress was induced by addition of tertiary-butylhydroperoxide (tert-bhp, 30 min). cellular responses were evaluated using flow cytometry and confocal live cell imaging (both using 5-(and-6)-chloromethyl-2,7-dichlorodihydrofluorescein diacetate, cm-h(2)dcfda). viability was assessed by the neutral red assay. total rna was extracted for a pcr profiler array. five genes were selected for confirmation by taqman gene expression assays, and by immunoblotting or immunohistochemistry for protein levels. tert-bhp increased cm-h(2)dcfda fluorescence and caused cell death. interestingly, all processes occurred more slowly in modcs than in monocytes. the mrna profiler array showed more than 2-fold differential expression of 32 oxidative stress-related genes in unstimulated modcs, including peroxiredoxin-2 (prdx2), an enzyme reducing hydrogen peroxide and lipid peroxides. prdx2 upregulation was confirmed by taqman assays, immunoblotting and immunohistochemistry. silencing prdx2 in modcs by means of sirna significantly increased cm-dcf fluorescence and cell death upon tert-bhp-stimulation.","our results indicate that modcs exhibit higher intracellular antioxidant capacities, making them better equipped to resist oxidative stress than monocytes. upregulation of prdx2 is involved in the neutralization of ros in modcs. taken together, this points to better survival skills of dcs in oxidative stress environments, such as atherosclerotic plaques.",Diagnosis
does even short-time storage in physiological saline solution impair endothelial vascular function of saphenous vein grafts?,"a faultless endothelial layer is decisive for vascular function and therewith graft's patency. functional impairment of the endothelium increases risk of graft thrombosis, intimal hyperplasia, and consecutive accelerated graft atherosclerosis. storage solutions for intra-operatively harvested saphenous vein segments (svs) might have significant impact on endothelial function. we investigated the impact of short-time storage in physiological saline solution (pss) and a potassium-chloride- and n-acetylhistidine-enriched storage solution on venous endothelial function. intra-operatively isolated svss (n19) were stored in different storage solutions for 90 min. they were then immediately studied in tissue bath at 36c with continuous oxygen insufflation. following preconstriction with norepinephrine, dose-response relaxation curves of bradykinine (brad) and sodium nitroprusside (snp) were determined. we compared developed maximum wall tension, vessel constriction kinetics, endothelial cell- and smooth muscle cell (smc)-dependent vasodilatory function. maximum vessel wall tension was reduced significantly in pss-stored vessels (10.1 9.8 mn mm(-1) vs 3.5 3.4 mn mm(-1); p0.0372). endothelium-derived vasodilatory function was likewise significantly reduced after short-time storage (20.6 34.4 vs 35.0 27.0; p0.0437). snp-mediated smc-vasodilatory function was maintained equally well in both groups (88.2 21.8 vs 83.0 30.6 in pss; pn.s.).","even short-time storage in pss significantly impairs endothelial vascular function. concerning the essential role of a faultless endothelial layer, the quite common use of pss as a storage solution for svss in cabg surgery has to be discussed critically.",Medication
does a novel locus for an autosomal recessive hereditary spastic paraplegia ( spg35 ) map to 16q21-q23?,"the hereditary spastic paraplegias (hsps) are a group of clinically and genetically heterogeneous neurodegenerative disorders in which the cardinal pathologic feature is upper motor neuron degeneration leading to progressive spasticity and weakness of the lower limbs. to date, 14 autosomal recessive hsp loci have been mapped. we have identified a large consanguineous omani family in which an autosomal recessive form of hsp is segregating. the age at onset varied from 6 to 11 years and the course of the disease is progressive with intellectual disability and is associated with seizures in two individuals. to map the chromosomal location of the causative gene we undertook 250k gene chip snp analyses of all affected individuals assuming that a founder mutation was responsible. all affected individuals shared a 20.4 mb (3.25 cm) region of homozygosity located on chromosome 16q21-q23.1, defined by snp markers rs149428 and rs9929635 (peak multipoint lod score of 4.86). two candidate genes, dynein, cytoplasmic 1, light intermediate chain 2 (dync1li2) and vacuolar protein sorting 4 homolog a (vps4a), were sequenced but no disease causing mutations were identified.",we have mapped the chromosomal location of a novel gene responsible for a form of hereditary spastic paraplegia (hsp) (spg35) and defined its clinical presentation.,Diagnosis
does long term highly saturated fat diet induce nash in wistar rats?,"understanding of nonalcoholic steatohepatitis (nash) is hampered by the lack of a suitable model. our aim was to investigate whether long term high saturated-fat feeding would induce nash in rats. 21 day-old rats fed high fat diets for 14 weeks, with either coconut oil or butter, and were compared with rats feeding a standard diet or a methionine choline-deficient (mcd) diet, a non physiological model of nash. mcdd fed rats rapidly lost weight and showed nash features. rats fed coconut (86 of saturated fatty acid) or butter (51 of saturated fatty acid) had an increased caloric intake (143 and 30). at the end of the study period, total lipid ingestion in term of percentage of energy intake was higher in both coconut (45) and butter (42) groups than in the standard (7) diet group. no change in body mass was observed as compared with standard rats at the end of the experiment. however, high fat fed rats were fattier with enlarged white and brown adipose tissue (bat) depots, but they showed no liver steatosis and no difference in triglyceride content in hepatocytes, as compared with standard rats. absence of hepatic lipid accumulation with high fat diets was not related to a higher lipid oxidation by isolated hepatocytes (unchanged ketogenesis and oxygen consumption) or hepatic mitochondrial respiration but was rather associated with a rise in bat uncoupling protein ucp1 (25-28 vs standard).","long term high saturated fat feeding led to increased ""peripheral"" fat storage and bat thermogenesis but did not induce hepatic steatosis and nash.",Prevention
does vitamin d counteract fibrogenic tgf- signalling in human hepatic stellate cells both receptor-dependently and independently?,"non-alcoholic fatty liver disease (nafld) is closely linked to obesity and constitutes part of the metabolic syndrome, which have been associated with low serum vitamin d (vd). due to known crosstalk between vd and transforming growth factor (tgf)- signalling, vd has been proposed as an antifibrotic treatment. we evaluated the association between vd, the vitamin d receptor (vdr) and liver fibrosis in primary human hepatic stellate cells (phhsc) and 106 morbidly obese patients with nafld. treating phhsc with vd ameliorated tgf--induced fibrogenesis via both vdr-dependent and vdr-independent mechanisms. reduction of fibrogenic response was abolished in cells homozygous for gg at the a1012g single nucleotide polymorphisms within the vdr gene. compared with healthy livers, nafld livers expressed higher levels of vdr mrna and vdr fragments. vdr mrna was lower in patients homozygous for gg at a1012g and expression of pro-fibrogenic genes was higher in patients carrying the g allele.",vd may be an antifibrotic treatment option early in the onset of fibrosis in specific genotypes for vdr. known polymorphisms of the vdr may influence the response to vd treatment.,Medication
is topotecan and cytarabine an active combination regimen in myelodysplastic syndromes and chronic myelomonocytic leukemia?,"to evaluate the efficacy and safety of the combination of topotecan and cytarabine in patients with myelodysplastic syndromes (mdss) and chronic myelomonocytic leukemia (cmml). fifty-nine patients with mdss and 27 with cmml were enrolled. they were either previously untreated (66) or had received only biologic agents (14) or chemotherapy with or without biologic agents (20). treatment consisted of topotecan 1.25 mg/m(2) by continuous intravenous infusion daily for 5 days and cytarabine 1. 0 g/m(2) by infusion over 2 hours daily for 5 days. prophylaxis included antibacterial, antifungal, and antiviral agents. at a median follow-up of 7 months, all 86 patients were assessable for response and toxicity. complete remission (cr) was observed in 48 patients (56; 61 with mdss, 44 with cmml; p .15). similar cr rates were observed for patients with good-risk and poor-risk mds (70 and 56, respectively). the treatment effectively induced cr in patients with a poor-prognosis karyotype involving chromosomes 5 and 7 (cr, 71) and secondary mdss (cr, 72). fifty-four patients received one induction course, 25 patients received two, and the rest received more than two. the median number of continuation courses was two. the median overall duration of cr was 34 weeks (50 weeks for mdss and 33 weeks for cmml). the median survival was 60 weeks for mds and 44 weeks for cmml patients. cr and survival durations were longer in patients with refractory anemia with excess blasts (raeb). grade 3 or 4 mucositis or diarrhea was observed in three patients each. fever was observed in 63, and infections in 49 of patients. six patients (7) died during induction therapy.","topotecan and cytarabine induced high cr rates in unselected patients with mdss and cmml, particularly among patients with poor-prognosis cytogenetics and secondary mdss. topotecan-cytarabine is an active induction regimen in mds and cmml patients, is well tolerated, and is associated with a low mortality rate.",Medication
is cartilage matrix formation by bovine mesenchymal stem cells in three-dimensional culture age-dependent?,"cartilage degeneration is common in the aged, and aged chondrocytes are inferior to juvenile chondrocytes in producing cartilage-specific extracellular matrix. mesenchymal stem cells (mscs) are an alternative cell type that can differentiate toward the chondrocyte phenotype. aging may influence msc chondrogenesis but remains less well studied, particularly in the bovine system. the objectives of this study were (1) to confirm age-related changes in bovine articular cartilage, establish how age affects chondrogenesis in cultured pellets for (2) chondrocytes and (3) mscs, and (4) determine age-related changes in the biochemical and biomechanical development of clinically relevant msc-seeded hydrogels. native bovine articular cartilage from fetal (n 3 donors), juvenile (n 3 donors), and adult (n 3 donors) animals was analyzed for mechanical and biochemical properties (n 3-5 per donor). chondrocyte and msc pellets (n 3 donors per age) were cultured for 6 weeks before analysis of biochemical content (n 3 per donor). bone marrow-derived mscs of each age were also cultured within hyaluronic acid hydrogels for 3 weeks and analyzed for matrix deposition and mechanical properties (n 4 per age). articular cartilage mechanical properties and collagen content increased with age. we observed robust matrix accumulation in three-dimensional pellet culture by fetal chondrocytes with diminished collagen-forming capacity in adult chondrocytes. chondrogenic induction of mscs was greater in fetal and juvenile cell pellets. likewise, fetal and juvenile mscs in hydrogels imparted greater matrix and mechanical properties.",donor age and biochemical microenvironment were major determinants of both bovine chondrocyte and msc functional capacity.,General
does decoy oligodeoxynucleotide against activator protein-1 reduce neointimal proliferation after coronary angioplasty in hypercholesterolemic minipigs?,"we sought to demonstrate, in an appropriate animal model, that co-medication with a transcription factor-blocking agent limits restenosis after percutaneous transluminal coronary angioplasty (ptca). enhanced synthesis in the vessel wall of endothelin-1 (et-1), a powerful co-mitogen for vascular smooth muscle cells, appears to be one mechanism that promotes restenosis after ptca. deformation-induced expression of prepro-et-1 is governed by the transcription factor, activator protein-1 (ap-1). an anti-ap-1 decoy oligodeoxynucleotide (dodn) strategy was devised in which the dodn-containing solution (20 nmol) was administered locally through a dispatch catheter into the coronary arteries of hypercholesterolemic minipigs at the time of ptca (ave-gfx stent). treatment with an ap-1 dodn, mimicking the consensus binding site of the transcription factor, significantly reduced neointimal formation in the coronary arteries of hypercholesterolemic minipigs (n 10 to 12), compared with vehicle-treated coronary arteries, after four weeks of follow-up (neointimal area 2.64 /- 0.33 vs. 4.81 /- 1.04 mm(2) mean /- sem; p 0.05). this effect was maintained after eight weeks (neointimal area 2.04 /- 0.22 mm(2); n 3) and correlated with a reduction in both nuclear translocation of ap-1 and et-1 synthesis in the vessel wall 48 h after ptca (n 4). in contrast, an ap-1 mutant dodn, to which the transcription factor does not bind, showed no effect on neointimal formation at either time point (n 3 to 7). moreover, a consensus dodn directed against ccaat/enhancer binding protein (c/ebp), another deformation-sensitive transcription factor, did not significantly affect neointimal formation after four weeks (n 3).","these findings demonstrate the feasibility, efficacy and specificity of the anti-ap-1 dodn approach to the treatment of restenosis, which principally but not exclusively targets deformation-induced et-1 synthesis in the vessel wall. provided that these findings can be extrapolated to the situation of patients with coronary artery disease, the observed extent of the inhibitory effect of the ap-1 dodn treatment suggests that this co-medication may greatly reduce the incidence of in-stent restenosis.",Medication
is the combination of monthly carboplatin and weekly paclitaxel highly active for the treatment of recurrent ovarian cancer?,"to evaluate the response rate and toxicity of a regimen comprised of monthly carboplatin and weekly paclitaxel for recurrent ovarian cancer. we performed a retrospective chart review of patients with recurrent ovarian cancer treated between 2001 and 2006 at a single institution with carboplatin auc 5 (day 1), and paclitaxel 80 mg/m(2) (days 1, 8, 15) of a 28-day cycle. primary endpoints were response rate, progression-free survival and overall survival. twenty patients were treated with this regimen from 2001 to 2006. stage ranged from stages ic to iv. all received intravenous platinum and taxane as their initial therapy. histologic subtypes included papillary serous (17), carcinosarcoma (1), and clear cell (2). the median number of prior regimens was 1 (range 1-3). the overall response rate was 85.0 (15 complete responses, 2 partial responses). patients with tumors categorized as platinum sensitive had a response rate of 93.3 (14/15) and those with tumors deemed platinum resistant had a response rate of 60.0 (3/5). the median survival has not yet been reached after a median follow-up of 28 months. neutropenia was the only grade 3/4 toxicity, occurring in 7 patients (35.0). platinum hypersensitivity reactions occurred in 5 patients (25.0) who all successfully continued treatment using a carboplatin desensitization protocol.","a monthly carboplatin and weekly paclitaxel regimen is highly active for women with recurrent platinum-sensitive and platinum-resistant epithelial ovarian cancer. the regimen is well tolerated. this pilot series demonstrates the potential for this regimen as treatment of choice among doublet first salvage regimens for patients with recurrent epithelial ovarian cancer, thus warranting multi-institutional study.",Treatment
does high phosphate diet increase arterial blood pressure via a parathyroid hormone mediated increase of renin?,"there is growing evidence suggesting that phosphate intake is associated with blood pressure levels. however, data from epidemiological studies show inconsistent results. the present study was designed to evaluate the effect of high circulating phosphorus on arterial blood pressure of healthy rats and to elucidate the potential mechanism that stands behind this effect. animals fed a high phosphate diet for 4 weeks showed an increase in blood pressure, which returned to normal values after the addition of a phosphate binder (lanthanum carbonate) to the diet. the expression of renin in the kidney was higher, alongside an increase in plasma renin activity, angiotensin ii (ang ii) levels and left ventricular hypertrophy. the addition of the phosphate binder blunted the increase in renin and ang ii levels. the levels of parathyroid hormone (pth) were also higher in animals fed a high phosphate diet, and decreased when the phosphate binder was present in the diet. however, blood p levels remained elevated. a second group of rats underwent parathyroidectomy and received a continuous infusion of physiological levels of pth through an implanted mini-osmotic pump. animals fed a high phosphate diet with continuous infusion of pth did not show an increase in blood pressure, although blood p levels were elevated. finally, unlike with verapamil, the addition of losartan to the drinking water reverted the increase in blood pressure in rats fed a high phosphate diet.",the results of this study suggest that a high phosphate diet increases arterial blood pressure through an increase in renin mediated by pth.,Prevention
does dna methylation fingerprint of neuroblastoma reveal new biological and clinical insights?,"to define the dna methylation landscape of neuroblastoma and its clinicopathological impact. microarray dna methylation data were analyzed and associated with functional/regulatory genome annotation data, transcriptional profiles and clinicobiological parameters. dna methylation changes in neuroblastoma affect not only promoters but also intragenic and intergenic regions at cytosine-phosphate-guanine (cpg) and non-cpg sites, and target functional chromatin domains of development and cancer-related genes such as ccnd1. tumors with diverse clinical risk showed differences affecting cpg and, remarkably, non-cpg sites. non-cpg methylation observed essentially in clinically favorable cases was associated with the differentiation status of neuroblastoma and expression of key genes such as alk.",this epigenetic fingerprint of neuroblastoma provides new insights into the pathogenesis and clinical behavior of this pediatric tumor.,General
do protocol for oral implant rehabilitation in a hemophilic hiv-positive patient with type c hepatitis?,"a 46-year-old man with severe hemophilia a, stage a2 hiv infection and chronic hepatitis c genotype 1a, for whom the treatment plan included implant-supported prostheses in 2 mandibular edentulous sections. the protocol followed included factor viii replacement concentrate and oral antifibrinolytic therapy. the right mandibular section was fitted with 3 straumann implants ( 4.1 mm, length 10 mm), and the left mandibular section received 2 implants of the same characteristics. the patient showed no postoperative complications. after implant placement, the patient attended scheduled review appointments. after a 3-month period of osseointegration, the prosthesis was fitted.","although, in this case, the treatment proved successful 2 years postrehabilitation and the protocol used seems safe and effective, long-term prospective studies are needed to evaluate the implant success rate in these patients.",Treatment
does alcohol consumption appear to protect against non-alcoholic fatty liver disease?,"moderate alcohol consumption may have certain beneficial effects against non-alcoholic fatty liver disease, which is associated with metabolic syndrome. to determine the association between drinking pattern and fatty liver in japanese men and women. a cross-sectional study was performed with health checkup data including information concerning alcohol consumption and ultrasonographic assessment of fatty liver. we analysed 4957 men and 2155 women without reported liver diseases (median age, 49 years). in men, 40 of nondrinkers and 28 of drinkers had fatty liver. alcohol consumption was inversely associated with fatty liver (adjusted odds ratio, 0.54; 95 confidence interval, 0.46-0.63). the prevalence of fatty liver in each category of drinking frequency was 38 (1-3 days/week), 29 (4-6 days/week), and 24 (daily drinking); there was a significant inverse correlation between drinking frequency and the prevalence of fatty liver (p 0.001). in women, 16 of nondrinkers and 10 of drinkers had fatty liver. drinking less than 20 g on 1-3 days/week was associated with low prevalence of fatty liver (adjusted odds ratio, 0.47; 95 confidence interval, 0.23-0.96).",alcohol consumption appears to protect against non-alcoholic fatty liver disease.,General
is adequately diversified dietary intake and iron and folic acid supplementation during pregnancy associated with reduced occurrence of symptoms suggestive of pre-eclampsia or eclampsia in indian women?,"pre-eclampsia or eclampsia (pe or e) accounts for 25 of cases of maternal mortality worldwide. there is some evidence of a link to dietary factors, but few studies have explored this association in developing countries, where the majority of the burden falls. we examined the association between adequately diversified dietary intake, iron and folic acid supplementation during pregnancy and symptoms suggestive of pe or e in indian women. cross-sectional data from india's third national family health survey (nfhs-3, 2005-06) was used for this study. self-reported symptoms suggestive of pe or e during pregnancy were obtained from 39,657 women aged 15-49 years who had had a live birth in the five years preceding the survey. multivariable logistic regression analysis was used to estimate the association between adequately diversified dietary intake, iron and folic acid supplementation during pregnancy and symptoms suggestive of pe or e after adjusting for maternal, health and lifestyle factors, and socio-demographic characteristics of the mother. in their most recent pregnancy, 1.2 (n456) of the study sample experienced symptoms suggestive of pe or e. mothers who consumed an adequately diversified diet were 34 less likely (or: 0.66; 95 ci: 0.51-0.87) to report pe or e symptoms than mothers with inadequately diversified dietary intake. the likelihood of reporting pe or e symptoms was also 36 lower (or: 0.64; 95 ci: 0.47-0.88) among those mothers who consumed iron and folic acid supplementation for at least 90 days during their last pregnancy. as a sensitivity analysis, we stratified our models sequentially by education, wealth, antenatal care visits, birth interval, and parity. our results remained largely unchanged: both adequately diversified dietary intake and iron and folic acid supplementation during pregnancy were associated with a reduced occurrence of pe or e symptoms.",having a adequately diversified dietary intake and iron and folic acid supplementation in pregnancy was associated with a reduced occurrence of symptoms suggestive of pe or e in indian women.,Prevention
does the vibrio core group induce yellow band disease in caribbean and indo-pacific reef-building corals?,"to determine the relationship between yellow band disease (ybd)-associated pathogenic bacteria found in both caribbean and indo-pacific reefs, and the virulence of these pathogens. ybd is one of the most significant coral diseases of the tropics. the consortium of four vibrio species was isolated from ybd tissue on indo-pacific corals: vibrio rotiferianus, vibrio harveyi, vibrio alginolyticus and vibrio proteolyticus. this consortium affects symbiodinium (zooxanthellae) in hospite causing symbiotic algal cell dysfunction and disorganization of algal thylakoid membrane-bound compartment from corals in both field and laboratory. infected corals have decreased zooxanthella cell division compared with the healthy corals. vibrios isolated from diseased diploastrea heliopora, fungia spp. and herpolitha spp. of reef-building corals display pale yellow lesions, which are similar to those found on caribbean montastraea spp. with ybd.","the vibrio consortium found in ybd-infected corals in the caribbean are close genetic relatives to those in the indo-pacific. the consortium directly attacks symbiodinium spp. (zooxanthellae) within gastrodermal tissues, causing degenerated and deformed organelles, and depleted photosynthetic pigments in vitro and in situ. infected fungia spp. have decreased cell division compared with the healthy zooxanthellae: 4.9vs 1.9, (p or 0.0024), and in d. heliopora from 4.7 to 0.7 (p or 0.002).",Symptoms
does overexpression of heat-shock protein 20 in rat heart myogenic cells confer protection against simulated ischemia/reperfusion injury?,"to explore whether overexpression of the small heat shock protein hsp20 in rat cardiomyocytes protects against simulated ischemia/reperfusion (si/r) injury. recombinant adenovirus expressing hsp20 was used to infect rat h9c2 cardiomyocytes at high efficiency, as assessed by green fluorescent protein. h9c2 cells were subjected to si/r stress; survival was estimated through assessment of lactate dehydrogenase and cell apoptosis through caspase-3 activity. overexpression of hsp20 decreased lactate dehydrogenase release by 21.5 and caspase-3 activity by 58.8. pretreatment with the protein kinase c inhibitor ro-31-8220 (0.1 micromol/l) for 30 min before si/r canceled the protective effect of hsp20. the selective mitochondrial katp channel inhibitor 5-hydroxydecanoate (100 micromol/l) had a similar effect. however, the non-selective katp channel inhibitor glibenclamide (100 micromol/l) had no significant effect.","these data indicate that the protective effect of hsp20 in vitro is primarily due to reduced necrotic and apoptotic death of cardiomyocytes, possibly via the protein kinase c/mitochondrial katp pathway.",Medication
is loss of phenotypic expression related to tumour progression in early gastric differentiated adenocarcinoma?,"to evaluate the relationship between phenotypic expression and tumour progression as represented by macroscopic features, submucosal invasion and lymph node metastasis in early differentiated gastric adenocarcinoma. one hundred and fifty-five cases of early gastric differentiated adenocarcinoma without any poorly differentiated components were studied. the mucosal and submucosal components of carcinomas and lymph node metastatic lesions were classified into four categories, gastric type (g-type), incomplete intestinal type (i-type), complete intestinal type (c-type) and unclassified type (u-type), based on the combination of the phenotypic expression of hgm (gastric foveolar epithelium), muc 6 (gastric pyloric glands), muc 2 (intestinal goblet cells) and cd 10 (small intestinal brush border). in addition, a new classification representing a phenotypic shift from mucosa to submucosa or from primary lesion to lymph node metastasis was established with the categories of preserved group (p-group), loss group (l-group) and acquired group (a-group). (1) in submucosal carcinoma, u-type was more common in the submucosa (39) than in the mucosa (9). (2) u-type was more common in the metastatic lesions (42) than in the primary lesions (5). (3) the submucosal component and lymph node metastatic lesions were classified as p-group in 48 and 43 of cases, respectively, and as l-group in 50 and 52 of cases, respectively. (4) lymph node metastatic lesions comprising undifferentiated carcinoma were classified as l-group in 100 of cases.","during the course of tumour progression, early differentiated adenocarcinoma at first tends to lose its phenotypic expression despite preserving its morphology, but subsequently morphological dedifferentiation occurs.",General
do hla-g1 molecule expressed by ecv304 cells inhibit cytotoxic activity of allogeneic nk cells ?,"to study the effect of hla-g1 molecule expressed by an endothelial cell line (ecv304) on the cytotoxic activity of allogeneic nk cells. ecv304 cells were transfected with recombinant plasmid pcdna3-hla-g1 by the liposome transfection, and the expressed hla-g1 on the cell surface was detected by indirect immunofluorescent assay and flow cytometry. the cytotoxic activity of allogeneic nk cells against ecv304 cells was analyzed by the mtt method. hla-g1 was expressed on the surface of the transfected ecv304 cells. the specific lysis of nk cells against plasmid pcdna3 transfected ecv304 was (50.6/-18.1), while the specific lysis against pcdna3-hla-g1 transfected ecv304 was (29.7/-11.4), which was significantly lower than the former (p0.001).",hla-g1 expressed by the ecv304 cells can inhibit cytotoxicity of allogeneic nk cells.,General
are genetic variants in scn5a promoter associated with arrhythmia phenotype severity in patients with heterozygous loss-of-function mutation?,"heterozygous scn5a mutations have been associated with varied arrhythmia phenotypes; phenotype severity may range from asymptomatic electrocardiographic changes (mild phenotype) to symptomatic arrhythmias resulting in syncope, cardiac arrest, and sudden cardiac death (severe phenotype) even among family members carrying the same mutation. risk-stratification schemes for scn5a mutation carriers remain uncertain. to determine the role of scn5a promoter variants and dna methylation by using a family-based approach in predicting phenotype severity in a kindred with loss-of-function scn5a mutation. in a large kindred with a heterozygous scn5a loss-of-function mutation (1936delc, q646rfsx5; 22 mutation carriers), we sought scn5a promoter variants. in addition, we assessed scn5a and genome-wide dna methylation profiles on genomic dna derived from blood (illumina human methylation27 beadchip). during systematic survey of the 2.8-kb scn5a promoter region, we identified 2 single nucleotide polymorphisms in complete linkage disequilibrium (rs41310749 and rs41310239). these promoter variants were significantly associated with disease severity (mild vs severe phenotype) (p .0007), as all 3 patients with severe phenotype carried the 2-snp variant on both mutant and wild-type alleles. analysis did not support a role for the methylation of scn5a-related genes.",these family-based genetic findings suggest that the presence of specific promoter variants increase the risk of a severe phenotype in heterozygous carriers of an scn5a loss-of-function mutation.,Symptoms
is increase of theta frequency associated with reduction in regional cerebral blood flow only in subjects with mild cognitive impairment with higher upper alpha/low alpha eeg frequency power ratio?,"several biomarkers have been proposed for detecting alzheimer's disease (ad) in its earliest stages, that is, in the predementia stage. in an attempt to find noninvasive biomarkers, researchers have investigated the feasibility of neuroimaging tools, such as mri, spect as well as neurophysiological measurements using eeg. moreover, the increase of eeg alpha3/alpha2 frequency power ratio has been associated with ad-converters subjects with mild cognitive impairment (mci). to study the association of alpha3/alpha2 frequency power ratio with regional cerebral blood flow (rcbf) changes in subjects with mci. twenty-seven adult subjects with mci underwent eeg recording and perfusion single-photon emission computed tomography (spect) evaluation. the alpha3/alpha2 frequency power ratio was computed for each subject. two groups were obtained according to the median values of alpha3/alpha2, at a cut-off of 1.17. correlation between brain perfusion and eeg markers were detected. subjects with higher alpha3/alpha2 frequency power ratio showed a constant trend to a lower perfusion than low alpha3/alpha2 group. the two groups were significantly different as about the hippocampal volume and correlation with the theta frequency activity.","there is a complex interplay between cerebral blood flow, theta frequency activity, and hippocampal volume in mci patients with prodromal alzheimer's disease, characterized by higher eeg alpha3/alpha2 frequency power ratio.",Diagnosis
do automated reminders increase adherence to guidelines for administration of prophylaxis for postoperative nausea and vomiting?,"correct identification of patients at high risk for postoperative nausea and vomiting (ponv), prescription of ponv prophylaxis and correct administration of medication are all important for effective ponv prophylaxis. this has been acknowledged by development of guidelines throughout the world. we studied the effect of introducing patient-specific automated reminders on timely administration of ponv prophylaxis medication during general anaesthesia. during the visit to the preoperative screening clinic, patients at high risk for ponv were identified and ponv prophylaxis was prescribed. to study the effect of patient-specific decision support a pop-up window reminding the (nurse) anaesthetist that ponv prophylaxis had been prescribed for this particular patient on the timely administration of ponv medication, we queried our database to extract data on all patients for three consecutive periods: 6 weeks before decision support (control), 12 weeks during decision support and 6 weeks after discontinuation of decision support (postdecision support) and studied how often ponv prophylaxis was administered correctly. between november 2005 and may 2006, 1727, 2594 and 1331 patients presented for elective surgery in the control, decision support and postdecision support periods, respectively. in the control period, 236 patients receiving general anaesthesia were scheduled to receive ponv prophylaxis. of these, 93 (39) received both dexamethasone and granisetron in the correct timeframe. this increased to 464 (79) out of 591 patients in the decision support period and decreased back to 99 (41) out of 243 patients in the postdecision support period (p 0.001).","decision support is effective in improving administration and timing of ponv prophylaxis medication. after withdrawal of decision support, adherence decreased to predecision support levels.",Treatment
"is intermuscular adipose tissue associated with monocyte chemoattractant protein-1 , independent of visceral adipose tissue?","emerging evidence suggests that intermuscular adipose tissue is a risk factor for insulin resistance, but the underlying mechanism still remains unclear. we investigated whether the levels of leptin, adiponectin, and monocyte chemoattractant protein-1 are associated with intermuscular adipose tissue in obese subjects. a cross-sectional study was performed on 77 obese korean women. areas of visceral adipose tissue, subcutaneous adipose tissue, and intermuscular adipose tissue were measured by computed tomography scan, and serum concentrations of adipokines were measured by enzyme-linked immunosorbent assays. correlation between the levels of adipokines and the fat areas was assessed using pearson correlation and covariate-adjusted multivariable regression. leptin was positively correlated with subcutaneous adipose tissue (r0.452, p0.001), fasting insulin (r0.403, p0.001), and homeostasis model assessment of insulin resistance (r0.360, p0.001), whereas monocyte chemoattractant protein-1 was positively correlated with intermuscular adipose tissue (r0.483, p0.001). after adjustment for age, height, and other body composition metrics, leptin was still related to subcutaneous adipose tissue (0.390, p0.001). monocyte chemoattractant protein-1 was associated with intermuscular adipose tissue (0.433, p0.001) after adjustment for visceral adipose tissue.","intermuscular adipose tissue was correlated with monocyte chemoattractant protein-1, suggesting its role in the development of insulin resistance.",Medication
is thymic stromal lymphopoietin activation of basophils in patients with allergic asthma il-3 dependent?,"thymic stromal lymphopoietin (tslp) released after antigenic stimulation of allergic asthmatic airways is a key initiator of type 2 inflammation. basophils are important effectors of allergic inflammation in the airways. murine basophils have been shown to respond to tslp independently of il-3 by increasing functional thymic stromal lymphopoietin receptor (tslpr) expression. the purpose of this study was to investigate the effect of tslp stimulation on human basophil function. ten patients with mild allergic asthma underwent diluent and allergen inhalation challenges. peripheral blood and sputum samples were collected at baseline and 7 and 24 hours after challenge, and bone marrow samples were collected at baseline and 24 hours after challenge to measure basophil tslpr expression. in vitro experiments were conducted on purified human basophils to measure the effect of tslp on degranulation, expression of activation markers and th2 cytokines, and eotaxin-induced shape change. allergen inhalation increased basophil numbers in the airways and significantly upregulated the expression of activation markers, th2 intracellular cytokines, and receptors for tslp, il-3, and eotaxin in blood, bone marrow, and sputum basophils. in vitro stimulation with tslp primed basophil migration to eotaxin and induced rapid and sustained basophil activation mediated directly through tslpr and indirectly through an il-3-mediated basophil autocrine loop. basophils responded to tslp at a similar magnitude and potency as the well-described basophil-activating stimuli il-3 and anti-ige.",our findings indicate that basophil activation during early- and late-phase responses to inhaled allergen might be driven at least in part by tslp.,Medication
do patient-related factors influence stiffness of the soft tissue complex during intraoperative gap balancing in cruciate-retaining total knee arthroplasty?,"how much force is needed to pre-tension the ligaments during total knee arthroplasty? the goal of this study was to determine this force for extension and flexion, and for both compartments, and to identify predicting patient-related factors. eighty patients 55 females, mean age 71 (sd 9.7) were recruited and had a navigated cruciate-retaining total knee arthroplasty. distraction of the medial and lateral compartments of the extension and flexion gap (90) with an instrumented bi-compartmental double-spring tensioner took place after finishing the bone cuts. applied forces and resulting gap distances were recorded by the navigation system, resulting in a force-elongation curve. lines were fitted with the intersection defined as the stiffness transition point. the slopes (n/mm) represented the stiffness of the ligamentous complex. linear multiple regression analysis was performed to identify predicting factors. the amount of force at the stiffness transition point was on average 52.3 (ci","the amount of force at the stiffness transition point varies between 48 and 59 n, depending on flexion/extension and compartment. patient-related factors influence the stiffness transition point and can help predict the stiffness transition point. when forces higher than 60 n are used for gap distraction, the ligamentous sleeve of the knee might be over-tensioned.",General
is increased disease activity associated with altered sleep architecture in an experimental model of systemic lupus erythematosus?,"the aim of this study was to evaluate sleep patterns during the course of the disease in (nzb/nzw)f1 mice, an experimental model of systemic lupus erythematosus (sle). female mice were implanted with electrodes for chronic recording of sleep-wake cycles during the entire experimental phase (9, 19, and 29 weeks of age). the disease course was also assessed. at each time-point, blood samples were collected from the orbital plexus to evaluate serum antinuclear antibodies (ana), which are important serologic parameters of disease evolution. pain perception was also evaluated. during the dark phase, (nzb/nzw)f, mice aged 19 weeks spent more time in sleep, and, as a consequence, the total waking time was lower when compared with earlier periods. an augmented number of sleep-stage transitions and microarousals were observed at the 29th week of life in both light and dark phases. at this same time-point, the mice showed lower pain thresholds than they had at 9 weeks of life. the disease status was confirmed; the entire group of mice at 29 weeks of life showed positive ana with high titer levels.","the sleep-recording data showed that, during the progress and severe phases of the disease (19 and 29 wks of age, respectively), sleep architecture is altered. according to these results, increased sleep fragmentation, disease activity, and pain sensitivity are features observed in these mice, similar to symptoms of sle.",Symptoms
does cerebral state monitoring in beagle dog sedated with medetomidine?,"to provide experience of monitoring the level of hypnosis with the cerebral state monitor (csm), a device extracting a single numerical variable between 0 and 100 from the electroencephalogram in dogs sedated with medetomidine during dental scale removal. prospective observational study. animals nine female beagle dogs weighing 13.3 /- 1.3 kg. cerebral state index (csi) and burst suppression ratio (bsr) were recorded from sub-dermal needle electrodes in dogs sedated after subcutaneous injection of 114 /- 11 microg kg(-1) medetomidine. ten minutes after injection csi monitoring began, and after 5 minutes, dental scale removal with an ultrasonic probe was started. after approximately 30 minutes, the effects of medetomidine were antagonized with atipamezole. the csi had a median value of 43 (range 40-56) in undisturbed sedated dogs. during dental scale removal, csi increased to a median value of 99 (range 92-100). the bsr in undisturbed sedated dogs ranged from 2 to 15, but fell to zero during dental scale removal.",stimulation during dental scale removal might be expected to reduce the level of sedation and hypnosis in dogs to which medetomidine had been administered. the concurrent increase in csi and decrease in bsr suggested that a higher csi was associated with arousal from sedation and a reduction in the depth of hypnosis. more studies are needed to validate csi in order to better understand the functioning of this monitor.,Medication
does systemic immunosuppression fail to suppress cardiac cytokine induction in pressure overload hypertrophy in rats?,"activation of cytokines such as interleukin-6 (il-6) has been implicated in the pathogenesis of left ventricular dysfunction and hypertrophy since they have been shown to mediate cell proliferation, negative inotropic effects and myocardial hypertrophy. however, the effects of immunosuppressive therapy on cytokines in the treatment of heart failure and hypertrophy are unclear. to test the hypothesis that systemic immunosuppresion may influence serum and myocardial il-6 and, thereby, may affect progression of myocardial hypertrophy. we studied the effects of chronic treatment with methotrexate (mtx) and with the ace inhibitor ramipril on il-6 in rats with pressure overload left ventricular hypertrophy (lvh) due to aortic banding. animals were treated with either vehicle (n 6) or methotrexate (mtx 1: 0.3 mg/kg bw/week; mtx 2: 0.9 mg/kg bw/week; i.p.; n 6 each group) once a week during weeks 4-12 after aortic banding; sham-operated rats served as controls (ctrl; n 8). during the development of lvh, serum il-6 was determined by rat-specific elisa and 12 weeks after aortic banding myocardial il-6 was measured using a tissue superfusion technique or determining of protein concentration. aortic banding significantly lowered blood pressure, increased left ventricular weight and resulted in elevated serum il-6 levels (27.6 /- 5.1 vs 19.1 /- 2.3 pg/ml, p 0.05) compared to ctrl. mtx treatment normalised the initially elevated serum il-6 levels after 8 weeks of treatment. the significant increase in il-6 concentration in the superfusate of all aortic banding groups compared to ctrl ( 30, p 0.05) was not altered by prior mtx therapy. accordingly, both doses of mtx failed to prevent lvh progression (1.67 /- 0.23 g vs. 2.32 /- 0.31 g, p 0.05). in contrast, chronic inhibition of the raas not only prevents lvh but also reduces myocardial il-6 concentration (6898 /- 355 vs. 3073 /- 366 pg/mg protein, p 0.05).","pressure overload lvh in rats is characterized by an increase in serum levels of il-6 as well as myocardial il-6. chronic immunosuppressive therapy normalized systemic il-6 levels, but failed to reduce cardiac il-6 expression and the progression of lvh, while ace inhibition is sufficient to modify lvh and thereby normalises myocardial il-6 expression.",Medication
do integrated metabolite and gene expression profiles identify lipid biomarkers associated with progression of hepatocellular carcinoma and patient outcomes?,"we combined gene expression and metabolic profiling analyses to identify factors associated with outcomes of patients with hepatocellular carcinoma (hcc). we compared metabolic and gene expression patterns between paired tumor and nontumor tissues from 30 patients with hcc, and validated the results using samples from 356 patients with hcc. a total of 469 metabolites were measured using liquid chromatography/mass spectrometry and gas chromatography/mass spectrometry. metabolic and genomic data were integrated, and kaplan-meier and cox proportional hazards analyses were used to associate specific patterns with patient outcomes. associated factors were evaluated for their effects on cancer cells in vitro and tumor formation in nude mice. we identified 28 metabolites and 169 genes associated with aggressive hcc. lipid metabolites of stearoyl-coa-desaturase (scd) activity were associated with aberrant palmitate signaling in aggressive hcc samples. expression of gene products associated with these metabolites, including scd, were associated independently with survival times and tumor recurrence in the test and validation sets. combined expression of scd and -fetoprotein were associated with outcomes of patients with early-stage hcc. levels of monounsaturated palmitic acid, the product of scd activity, were increased in aggressive hccs; monounsaturated palmitic acid increased migration and invasion of cultured hcc cells and colony formation by hcc cells. hcc cells that expressed small interfering rna against scd had decreased cell migration and colony formation in culture and reduced tumorigenicity in mice.","by using a combination of gene expression and metabolic profile analysis, we identified a lipogenic network that involves scd and palmitate signaling and was associated with hcc progression and patient outcomes. the microarray platform and data have been submitted to the gene expression omnibus public database at ncbi following miame guidelines. accession numbers: gpl4700 (platform), and gse6857 (samples).",Diagnosis
does dissection of the candida albicans cdc4 protein reveal the involvement of domains in morphogenesis and cell flocculation?,"cdc4, which encodes an f-box protein that is a member of the skp1-cdc53/cul1-f-box (scf) ubiquitin e3 ligase, was initially identified in the budding yeast saccharomyces cerevisiae as an essential gene for progression through g1-s transition of the cell cycle. although candida albicans cdc4 (cacdc4) can release the mitotic defect caused by the loss of cdc4 in s. cerevisiae, cacdc4 is nonessential and suppresses filamentation. to further elucidate the function of cacdc4, a c. albicans strain, with one cacdc4 allele deleted and the other under the repressible c. albicans met3 promoter (camet3p) control, was made before introducing cassettes capable of doxycycline (dox)-induced expression of various c. albicans cdc4 (cacdc4) domains. cells from each strain could express a specific cacdc4 domain under dox-induced, but camet3-cacdc4 repressed conditions. cells expressing domains without either the f-box or wd40-repeat exhibited filamentation and flocculation similarly to those lacking cacdc4 expression, indicating the functional essentiality of the f-box and wd40-repeat. notably, cells expressing the n-terminal 85-amino acid truncated cacdc4 partially reverse the filament-to-yeast and weaken the ability to flocculate compared to those expressing the full-length cacdc4, suggesting that n-terminal 85-amino acid of cacdc4 regulates both morphogenesis and flocculation.","the f-box and the wd40-repeat of cacdc4 are essential in inhibiting yeast-to-filament transition and flocculation. the n-terminal region (1-85) of cacdc4 also has a positive role for its function, lost of which impairs both the ability to flocculate and to reverse filamentous growth in c. albicans.",General
do evaluation of retrospective multisector and half scan ecg-gated multidetector cardiac ct protocols with moving phantoms?,"we evaluated independently retrospective half scan and multisector mode manufacturer's protocols and compared them with modified acquisition protocols to determine optimal imaging parameters for cardiac scanning. data were acquired using two fabricated gated moving phantoms. in half scan mode, the manufacturer's recommended pitch values were compared with adjacent values at different motion rates. in multisector mode, the manufacturer's protocols were compared with ones with different gantry speeds and pitch values at the same motion rates. weighted ct dose indexes (ctdi) were obtained for all protocols. gated and reformatted reconstructed images of the moving phantoms were evaluated. in half scan mode, slightly better image quality was observed by lowering the pitch value, but with an increase of 6.3 of the weighted ctdi. better results were obtained in multisector mode by lowering the pitch value up to 0.2, but with an increase of 14.3 of the weighted ctdi. optimal images were obtained with the lowest temporal resolution.",gated moving phantom studies offer the advantage of testing acquisition protocols of complex motions and of helping to establish appropriate protocols.,Diagnosis
is elevated erythrocyte carbonic anhydrase activity a novel clinical marker in hyperventilation syndrome?,"the aim of this study was to evaluate the erythrocyte carbonic anhydrase (ca) activity in patients with hyperventilation syndrome. a total of 71 patients with hyperventilation syndrome and 60 controls were recruited in this study for measurement of the erythrocyte ca activity. ca activity was analyzed from erythrocyte using ca esterase activity analysis. the erythrocyte ca activity was significantly elevated in the patients with hyperventilation syndrome compared to controls (31.07/-1.37 u/g hb vs. 24.67/-0.99 u/g hb, p0.003). the standardized beta value and significant r(2) value of total ca activity for prediction of hyperventilation was 0.155 (p0.016) and 0.024, respectively. moreover, a significant negative correlation was found between total ca activity and partial pressure of carbon dioxide (paco(2)) (r-0.185, p0.03, n131). furthermore, the adjusted odds ratios for patients with hyperventilation were 11.6 (95 ci: 4.8-27.9) and 51.0 (95 ci: 5.8-445.2) for individuals with either paco(2)or29.71 u/g hemoglobin (hb), and for individuals with both paco(2)or29.71 u/g hb, respectively, compared to individuals with both paco(2)28.1 mm hg and ca activity 29.71 u/g hb.",erythrocyte ca activity was significantly elevated in patients with hyperventilation. detection of erythrocyte ca activity may provide a potential explanatory parameter for the prediction of hyperventilation syndrome.,Diagnosis
is fracture history of healthy premenopausal women associated with a reduction of cortical microstructural components at the distal radius?,"the objective of this study is to determine in healthy premenopausal women with a history of fracture which bone structural components of the distal radius are the most closely associated with a risk of fracture. the method was as follows: measurement of radial areal bone mineral density (abmd) by dxa, microstructural components by high-resolution quantitative peripheral computerized tomography (hr-pqct) and strength variables by micro finite element analysis (fea) in 196 healthy premenopausal women aged 45.9 3.7 ( sd) years with (fx, n 96) and without (no-fx, n 100) a history of fracture. we evaluated differences in t-scores between fx and no-fx and risk of fracture by odds ratios (or with 95 confidence intervals, ci) per one sd decrease, using logistic regression analysis after adjustment for age, height, weight, menarcheal age, calcium and protein intakes, and physical activity. in the whole group the mean radial metaphysis abmd t-score was not significantly different from zero. in the fx as compared to the no-fx group, the differences in t-scores were as follows: for radial metaphysis: abmd, -0.24 (p 0.005); for distal radius microstructure components: cortical volumetric bmd, -0.38 (p 0.0009); cortical thickness, -0.37 (p 0.0001); cross-sectional area (csa), 0.24 (p0.034); and endosteal perimeter, 0.28 (p 0.032); and for strength estimates: stiffness, -0.15 (p 0.030); failure load, -0.14 (p 0.044); and apparent modulus, -0.28 (p 0.006). t-scores of trabecular volumetric bmd and thickness did not significantly differ between the fx and the no-fx group. accordingly, the risk of fracture (or, 95 ci) for 1 sd decrease in radius bone parameters was as follows: radial metaphysis abmd: 1.70 (1.18-2.44), p 0.004; cortical volumetric bmd: 1.86 (1.28-2.71), p 0.001; and cortical thickness: 2.36 (1.53-3.63), p 0.0001. the corresponding fracture risk for the strength estimates was as follows: stiffness: 1.66 (1.06-2.61), p 0.028; failure load: 1.59 (1.02-2.47), p 0.041; and apparent modulus: 1.76 (1.17-2.64), p 0.006.","in healthy premenopausal women, a history of fracture is associated with reduced t-scores in the distal radius, with the cortical components showing the greatest deficit. a reduction of one sd in cortical thickness is associated with a nearly three-fold increased risk of fracture. this finding strengthens the notion that, in healthy women, a certain degree of bone structural fragility contributes to fractures before the menopause and therefore should be taken into consideration in the individual prevention strategy of postmenopausal osteoporosis.",Prevention
does gastrostomy positively affect nutritional status and diminishes hospital days in patients with inborn errors of metabolism ?,"the nutrition management of patients with inborn errors of metabolism (iem) requires the permanent use of elemental medical formulas whose organoleptic characteristics sometimes impede oral acceptance. in addition, these patients may have gastrointestinal disorders and require constant use of drugs, that often complicate treatment adherence, thereby committing their nutritional status and disease control. gastrostomy is an alternative to facilitate feeding and treatment, but its use is controversial. to compare nutrition status and length of hospitalizations before and after gastrostomy surgery in a group of iem patients. retrospective analysis of anthropometric data, number of hospitalizations due to metabolic decompensation and length in pediatric patients with iem before and after gastrostomy. 16 children were analyzed, 40 with propionate disorders, 25 with abnormal urea cycle and 35 other iem. after gastrostomy, the number of eutrophic patients increased from 6-56, and malnutrition decreased from 94 to 44. after gastrostomy inpatient hospital days significantly decrease from 425 to 131 (p 0.011), admission numbers pre-gastrostomy decreased from 33 to 17, however this difference was not statistically significant.","in this sample, gastrostomy improved nutritional status in 56 of eim patients and significantly reduced hospital days caused by metabolic decompensation.",Prevention
does successful weight maintenance preserve lower levels of oxidized ldl achieved by weight reduction in obese men?,"we studied the association between weight maintenance, oxidized low-density lipoprotein (ox-ldl) and other lipoproteins in obese men. a 2-month weight reduction phase (wrp) with a very-low-energy diet was followed by a 6-month weight maintenance period and an unsupervised 2-year follow-up. ninety men entered and 68 (76) completed the study. subjects were analyzed as one group and after division into two subgroups: 20 most successful men in maintaining the lost weight (subgroup 1) and the remaining (n48) men (subgroup 2). ox-ldl was measured by quantifying the amount of conjugated dienes in ldl particles. the mean (/-s.d.) weight reduction at the end of the wrp (n68) was 14 (confidence interval (ci) 12.9-14.7, 14.5/-4.2 kg, p0.001). ox-ldl decreased by 22 (ci 16.9-28.1, 12.3/-15.4 micromol/l, p0.001). at the end of the 2-year follow-up, the regain in weight from the end of the wrp was 11 (ci 9.0-12.4, 9.6/-6.2 kg, p0.001). the regain in ox-ldl was 30 (ci 18.7-41.2, 8.2/-15.4 micromol/l, p0.001). in subgroup 1 vs 2, the respective regains were 3 (ci 0.9-4.2, 2.2/-3.0 kg, p0.006) vs 14 (ci 12.7-15.6, 12.9/-4.0 kg, p0.001) regarding weight and 9 (2.0/-6.9 micromol/l, pns) vs 39 (ci 23.7-53.9, 11.2/-17.2 micromol/l, p/0.001) in ox-ldl.","the favorable changes seen in ox-ldl particles and serum lipids during weight reduction could be maintained by keeping the weight reduced, which may indicate decreased risk of atherosclerosis. but weight regain causes a resurge of ox-ldl.",Prevention
is participation in a clinical trial for a child with cancer burdensome for a minority of children?,"this study explored how parents who had lost a child to cancer felt about them taking part in a clinical trial. a retrospective questionnaire was sent to parents who had lost a child to cancer. they were asked whether their child took part in a clinical trial during their palliative phase, their motives for their child's participation, how they perceived their child's burden and whether they would, hypothetically speaking, enrol again. the 24 parents of 16 deceased children who had participated in a clinical trial explained their motives for their child's participation. the most common answers, with multiple responses, were treatment for future patients (n 16), hope for a cure (n 9) and prolonging their child's life (n 6). eight parents said that participating was not burdensome for their child and four said it was very burdensome, with others answering in between. none of the parents would decline participation if they would be in the same situation again.","performing clinical trials, even in a vulnerable population, such as children with cancer at the end of life, may not always lead to increased burden. none of the parents would in future, given the same circumstances, decline participation in a clinical trial.",Treatment
do aldosterone and tgf- synergistically increase pai-1 expression in hepatic stellate cells of rats?,"aldosterone is related to the fibrosis of several organs, but the specific mechanism underlying the aldosterone induced hepatic fibrosis is still unclear. separation, culture and identification of primary hepatic stellate cells (hscs): the fluids and digestives used in the present study were able to completely remove blood cells, digest hepatocytes and matrix, and effectively separate hscs. the in situ perfusion was performed at 2 steps: in situ perfusion with pre-perfusion fluid and ex vivo perfusion with enzyme-containing perfusion fluid. influence of ald on pai-1 and smad expressions in hscs: cells were divided into control group, ald group (10(-6) m), spironolactone (spi) group and aldspi group, and the mrna and protein expressions of pai-1 and smad were detected. ald induced type i collagen expression in hscs: immunohistochemistry was performed to detect type i collagen expression in the supernatant of control group, ald group (10(-6) m), tgf-1 group, and aldtgf-1 group. influence of ald and tgf-1 on pai-1 expression in hscs: cells were divided into control group, ald group (10(-6) m), tgf-1 group, and aldtgf-1 group, and the mrna and protein expressions of pai-1 were determined by rt-pcr and western blot assay, respectively. synergistic effect of ald and tgf-1 on pai-1 expression in hscs: cells were divided into control group, ald group (10(-6)), tgf-1 group, ald (10(-6) m)tgf-1 group, ald (10(-7) m)tgf-1 group and ald (10(-8) m)tgf-1 group, and the mrna and protein expressions of pai-1 were detected by rt-pcr and western blot assay, respectively. the survival rate, purity, markers and activation of hscs were determined after separation. influence of ald on pai-1 expression in hscs: pai-1 expression increased in hscs of ald group, spi group and aldapi group, and the pai-1 expression in ald group and aldspi group was significantly higher than in control group (p0.05).","aldosterone is able to activate hscs and increase pai-1 expression during hepatic fibrosis, which may be inhibited by spironolactone. aldosterone and tgf-1 may synergistically act on hscs to increase pai-1 expression as compared to treatment with aldosterone or tgf-1 alone. aldosterone or tgf-1 alone may slightly increase pai-1 expression in hscs, which can be inhibited by spironolactone.",Diagnosis
"are endogenous functional compounds in korean native chicken meat dependent on sex , thermal processing and meat cut?","in this study the effects of sex, meat cut and thermal processing on the carnosine, anserine, creatine, betaine and carnitine contents of korean native chicken (knc) meat were determined. forty 1-day-old chicks (20 chicks of each sex) from a commercial knc strain (woorimatdag) were reared under similar standard commercial conditions with similar diets, and ten birds of each sex were randomly selected and slaughtered at 14 weeks of age. raw and cooked meat samples were prepared from both breast and leg meats and analyzed for the aforementioned functional compounds. female kncs had significantly higher betaine and creatine contents. the breast meat showed significantly higher carnosine and anserine contents, whereas the leg meat had a higher betaine and carnitine content. the content of all functional compounds was significantly depleted by thermal processing.","this study confirms that knc meat is a good source of the above-mentioned functional compounds, which can be considered attractive nutritional quality factors. however, their concentrations were significantly affected by thermal processing conditions, meat cut and sex. further experiments are needed to select the best thermal processing method to preserve these functional compounds.",Prevention
does hyperventilation accelerate the rise of arterial blood concentrations of desflurane in gynecologic patients?,"under a constant inspired concentration, the uptake of a volatile anesthetic into the arterial blood should mainly be governed by alveolar ventilation, according to the assumption that the patient's cardiac output remains stable during anesthesia. we investigated whether ventilation volume affects the rate of desflurane uptake by examining arterial blood concentrations. thirty female patients were randomly allocated into the following three groups: hyperventilation, normal ventilation and hypoventilation. hemodynamic variables were measured using a finometer, inspiratory and end-tidal concentrations of desflurane were measured by infrared analysis, and the desflurane concentration in the arterial blood (ades) was analyzed by gas chromatography. during the first 10 minutes after the administration of desflurane, the ades was highest in the hyperventilation group, and this value was significantly different from those obtained for the normal and hypoventilation groups. in addition, hyperventilation significantly increased the slope of ades-over-time during the first 5 minutes compared with patients experiencing normal ventilation and hypoventilation, but there were no differences in these slopes during the periods from 5-10, 10-20 and 20-40 minutes after the administration of desflurane. this finding indicates that there were no differences in desflurane uptake between the three groups after the first 5 minutes within desflurane administration.","hyperventilation accelerated the rate of the rise in ades following desflurane administration, which was time-dependent with respect to different alveolar ventilations levels.",Medication
does glycemia determine the effect of type 2 diabetes risk genes on insulin secretion?,"several single nucleotide polymorphisms (snps) in diabetes risk genes reduce glucose- and/or incretin-induced insulin secretion. here, we investigated interactions between glycemia and such diabetes risk polymorphisms. insulin secretion was assessed by insulinogenic index and areas under the curve of c-peptide/glucose in 1,576 subjects using an oral glucose tolerance test (ogtt). participants were genotyped for 10 diabetes risk snps associated with -cell dysfunction: rs5215 (kcnj11), rs13266634 (slc30a8), rs7754840 (cdkal1), rs10811661 (cdkn2a/2b), rs10830963 (mtnr1b), rs7903146 (tcf7l2), rs10010131 (wfs1), rs7923837 (hhex), rs151290 (kcnq1), and rs4402960 (igf2bp2). furthermore, the impact of the interaction between genetic variation in tcf7l2 and glycemia on changes in insulin secretion was tested in 315 individuals taking part in a lifestyle intervention study. for the snps in tcf7l2 and wfs1, we found a significant interaction between glucose control and insulin secretion (all p 0.0018 for glucose genotype). when plotting insulin secretion against glucose at 120 min ogtt, the compromising snp effects on insulin secretion are most apparent under high glucose. in the longitudinal study, rs7903146 in tcf7l2 showed a significant interaction with baseline glucose tolerance upon change in insulin secretion (p 0.0027). increased glucose levels at baseline predicted an increase in insulin secretion upon improvement of glycemia by lifestyle intervention only in carriers of the risk alleles.","for the diabetes risk genes tcf7l2 and wfs1, which are associated with impaired incretin signaling, the level of glycemia determines snp effects on insulin secretion. this indicates the increasing relevance of these snps during the progression of prediabetes stages toward clinically overt type 2 diabetes.",Medication
does speech auditory alert promote memory for alerted events in a video-simulated self-driving car ride?,"auditory displays could be essential to helping drivers maintain situation awareness in autonomous vehicles, but to date, few or no studies have examined the effectiveness of different types of auditory displays for this application scenario. recent advances in the development of autonomous vehicles (i.e., self-driving cars) have suggested that widespread automation of driving may be tenable in the near future. drivers may be required to monitor the status of automation programs and vehicle conditions as they engage in secondary leisure or work tasks (entertainment, communication, etc.) in autonomous vehicles. an experiment compared memory for alerted events-a component of level 1 situation awareness-using speech alerts, auditory icons, and a visual control condition during a video-simulated self-driving car ride with a visual secondary task. the alerts gave information about the vehicle's operating status and the driving scenario. speech alerts resulted in better memory for alerted events. both auditory display types resulted in less perceived effort devoted toward the study tasks but also greater perceived annoyance with the alerts.","speech auditory displays promoted level 1 situation awareness during a simulation of a ride in a self-driving vehicle under routine conditions, but annoyance remains a concern with auditory displays.",General
is the impact of prenatal alcohol exposure on hippocampal-dependent outcome measures influenced by prenatal and early-life rearing conditions?,"the clinical course of individuals exposed to alcohol in utero is influenced by multiple factors, including the social environments of the gravid female and offspring. in the present studies we focused on the effects of prenatal alcohol exposure (pae) and the prenatal and early-life social environments on the hippocampal formation, as impaired development and functioning of this brain region have been implicated in several of the adverse cognitive outcomes associated with pae. we combined our pae mouse model with 2 conditions of housing pregnant dams and their preweanling offspring: the standard nest (sn), in which a dam is individually housed prior to parturition and then remains isolated with her offspring, and the communal nest (cn), in which multiple dams are housed together prior to parturition and then following delivery the moms and their litters share a nest. mouse dams consumed either 10 (w/v) ethanol in 0.066 (w/v) saccharin (sac) or 0.066 (w/v) sac alone using a limited (4-hour) access, drinking-in-the-dark paradigm. immunoblotting techniques were used to measure levels of the glucocorticoid receptor (gr), 11--hydroxysteroid dehydrogenase 1, the fk506-binding proteins 51 and 52, and corticotropin-releasing hormone receptor type 1 in the hippocampal formation isolated from male adolescent offspring. we also determined the effect of pae and rearing conditions on context discrimination, a hippocampal-dependent learning/memory task. sn pae offspring displayed impaired context discrimination and neurochemical changes in the hippocampal formation consistent with increased gr nuclear localization. these effects of pae were, in general, ameliorated in mice reared in a cn. the cn also altered neurochemical measures and improved learning/memory in sac control animals.","these studies demonstrate a complex interplay between the effects of pae and social environments. the findings have important translational implications, as well as highlight the importance of considering rearing conditions in the interpretation of research findings on pae.",Medication
do growth and nutritional indexes in early life predict pulmonary function in cystic fibrosis?,"to determine the relation of growth and nutritional status to pulmonary function in young children with cystic fibrosis (cf). the relation of weight-for-age (wfa), height-for-age (hfa), percent ideal body weight (ibw), and signs of lung disease at age 3 years with pulmonary function at age 6 years was assessed in 931 patients with cf. associations of changes in wfa from age 3 to 6 on pulmonary function were also assessed. wfa, hfa, and ibw were poorly associated with lung disease at age 3 years, but all were strongly associated with pulmonary function at age 6 years. those with wfa below the 5th percentile at age 3 had lower pulmonary function at age 6 compared with those above the 75th percentile (fev(1): 86 /- 20 sd versus 102 /- 18 predicted, respectively). pulmonary function was highest in those whose wfa remained 10th percentile from age 3 to 6 (fev(1): 100 /- 19 predicted) and lowest in those who remained 10th percentile (84 /- 21 predicted). patients with signs and symptoms of lung disease at age 3 years had lower pulmonary function at age 6 years.",aggressive intervention early in life aimed at growth and nutrition and/or lung disease may affect pulmonary function.,Prevention
"is normalization of leaky gut in chronic fatigue syndrome ( cfs ) accompanied by a clinical improvement : effects of age , duration of illness and the translocation of lps from gram-negative bacteria?","there is now evidence that an increased translocation of lps from gram negative bacteria with subsequent gut-derived inflammation, i.e. induction of systemic inflammation and oxidative nitrosative stress (ions), is a new pathway in chronic fatigue syndrome (cfs). the present study examines the serum concentrations of iga and igm to lps of gram-negative enterobacteria, i.e. hafnia alvei; pseudomonas aeruginosa, morganella morganii, pseudomonas putida, citrobacter koseri, and klebsielle pneumoniae in cfs patients both before and after intake of natural anti-inflammatory and anti-oxidative substances (naioss), such as glutamine, n-acetyl cysteine and zinc, in conjunction with a leaky gut diet during 10-14 months. we measured the above immune variables as well as the fibromyalgia and chronic fatigue syndrome rating scale in 41 patients with cfs before and 10-14 months after intake of naioss. subchronic intake of those naioss significantly attenuates the initially increased iga and igm responses to lps of gram negative bacteria. up to 24 patients showed a significant clinical improvement or remission 10-14 months after intake of naioss. a good clinical response is significantly predicted by attenuated iga and igm responses to lps, the younger age of the patients, and a shorter duration of illness ( 5 years).","the results show that normalization of the iga and igm responses to translocated lps may predict clinical outcome in cfs. the results support the view that a weakened tight junction barrier with subsequent gut-derived inflammation is a novel pathway in cfs and that it is a new target for drug development in cfs. meanwhile, cfs patients with leaky gut can be treated with specific naioss and a leaky gut diet.",Symptoms
are poor asthma education and medication compliance associated with increased emergency department visits by asthmatic children?,"acute exacerbations of bronchial asthma remain a major cause of frequent emergency department (ed) visits by pediatric patients. however, other factors including psychosocial, behavioural and educational, are also reportedly associated with repetitive ed visits. therefore, it is necessary to determine whether such visits are justifiable. the objective of this cross-sectional study was to identify risk factors associated with visits to ed by asthmatic children. asthmatic children (n 297) between 1-17 years old were recruited and information collected at the time of visiting an ed facility at two major hospitals. asthmatic patients visited the ed 3.9 3.2 times-per-year, on average. inadequately controlled asthma was perceived in 60.3 of patients. the majority of patients (56.4) reported not receiving education about asthma. patients reflected misconceptions about the ed department, including the belief that more effective treatments are available (40.9), or that the ed staff is better qualified (27.8). about half of patients (48.2) visited the ed because of the convenience of being open 24 hours, or because they are received immediately (38.4). uncontrolled asthma was associated with poor education about asthma and/or medication use. patients educated about asthma, were less likely to stop corticosteroid therapy when their symptoms get better (or:0.55; 95 ci:0.3-0.9; p 0.04).","this study reports that most patients had poor knowledge about asthma and were using medications improperly, thus suggesting inefficient application of management action plan. unnecessary and frequent visits to the ed for asthma care was associated with poor education about asthma and medication use. potential deficiencies of the health system at directing patients to the proper medical facility were uncovered and underline the necessity to improve education about the disease and medication compliance of patients and their parents/guardians.",Medication
do anti-carbamylated protein ( anti-carp ) antibodies precede the onset of rheumatoid arthritis?,"the presence of anti-citrullinated protein antibodies (acpa) and igm-rheumatoid factor (igm-rf) years before the clinical diagnosis of rheumatoid arthritis (ra) suggests they are possibly involved in the pathogenic process underlying ra. in this study, we analysed whether anti-carbamylated protein (anti-carp) antibodies, a novel autoantibody system against carbamylated proteins, can also be detected in healthy individuals before they developed ra. multiple sera from asymptomatic blood donors prior to the onset of their ra symptoms and sera from age-matched and sex-matched controls were tested for the presence of antibodies directed against carbamylated-fetal calf serum (ca-fcs), carbamylated-fibrinogen (ca-fib), cyclic citrullinated-peptide 2 and igm-rf. anti-ca-fcs and anti-ca-fib antibodies were each present in 27 and 38 of the last serum samples of blood donors prior to the diagnosis of ra. both anti-ca-fcs and anti-ca-fib antibodies could be detected many years before the onset of ra. anti-carp antibodies as well as acpa are, on average, detected earlier than igm-rf.","in addition to acpa and igm-rf, also the newly identified anti-carp antibodies appear many years before the diagnosis of ra.",Diagnosis
does daily weight-bearing activity increase the risk of diabetic foot ulcers?,"this study had two purposes: to identify characteristics associated with participants' usual weight-bearing activity, and to determine whether weight-bearing activity increased the risk of foot ulcer among persons with diabetes and prior foot ulcer. we conducted a prospective cohort study of 400 participants with diabetes and a prior history of foot ulcer. participants were from the veterans affairs puget sound health care system and group health cooperative in seattle, wa, and were originally assembled for a randomized controlled trial of footwear. feet were examined and demographic and health history information was collected at enrollment. daily weight-bearing activity was reported at enrollment and every 17 wk thereafter for 2 yr. all incident foot lesions were recorded. weight-bearing activity was significantly higher among women. activity was lower among participants who were older, unmarried, or who had a history of congestive heart failure, respiratory disease, stroke, or depression. activity decreased significantly over the study period but remained similar in those with or without insensate feet. after adjustment for foot-related and health-status characteristics, moderately active participants (4.5-7.4 weight-bearing h.d-1) were at substantially but nonsignificantly reduced risk of foot ulcer compared with ""least active"" participants (or7.5 weight-bearing h.d-1) were at significantly reduced risk (or 0.20, 95 ci 0.04-0.87). weight-bearing activity exerted similar effects on foot ulcer risk in participants with insensate versus sensate feet .",increased weight-bearing activity did not increase the risk of foot re-ulceration. further studies are needed to explore weight-bearing activities that are safe for those with diabetes and insensate feet.,General
is expression of fas ligand ( cd95l ) in primary malignant melanoma and melanoma metastases associated with overall survival?,"there is increasing evidence that the fas/fas ligand (fasl) system is involved in tumor-mediated immune suppression. the purpose of this study was to investigate the effect of fas (cd95) as well as fasl (cd95l) expression in primary malignant melanoma and melanoma metastases on overall survival (os). 19 patients with metastatic malignant melanoma who were treated with different dacarbazine (dtic)-based chemotherapy regimens were included in this study. from each patient, primary melanoma biopsies and biopsies from metastases were histologically evaluated. immunohistology was performed with antibodies to fas/cd95 and fasl/cd95l. differences in os were plotted using the kaplan-meier method and compared by the log rank test. fas/cd95 and fasl/cd95l expression was detected in 73.7 and 63.2 of primary melanomas, respectively. in metastases, expression of both fas/cd95 (63.2) and fasl/cd95l (47.4) was markedly decreased. presence of fasl/ cd95l expression in primary melanoma resulted in significantly (p 0.024) prolonged os compared with fasl/cd95l-negative high-risk primary melanomas. in contrast, loss of fasl/cd95l expression in melanoma metastases resected before chemotherapy was associated with significantly prolonged median survival (p 0.0139).",presence of fasl/cd95l expression in primary malignant melanoma and the loss of fasl/ cd95l expression in metastases seem to be positive prognostic factors.,Medication
do olfaction and color vision identify impending neurodegeneration in rapid eye movement sleep behavior disorder?,"for development of neuroprotective therapy, neurodegenerative disease must be identified as early as possible. however, current means of identifying ""preclinical"" neurodegeneration are limited. patients with idiopathic rapid eye movement (rem) sleep behavior disorder (rbd) are at 50 risk of synuclein-mediated neurodegenerative disease--this provides a unique opportunity to directly observe preclinical synucleinopathy and to test potential markers of preclinical disease. patients with rbd without neurodegenerative disease were enrolled in a prospective cohort starting in 2004. olfaction and color vision were tested at baseline, then annually for 5 years. test results were compared between patients who developed neurodegenerative disease and those who remained disease-free. out of 64 patients, 62 (97) participated in annual follow-up. during follow-up, 21 developed disease, and 41 remained disease-free. out of 21, 16 developed a combination of parkinsonism and dementia, 4 developed isolated parkinsonism (all with tremor), and 1 developed isolated dementia. compared to those remaining disease-free, patients destined to develop disease had worse baseline olfaction (university of pennsylvania smell identification test upsit 58.3 27.0 age/sex-adjusted normal vs 80.2 26.3; p 0.003) and color vision (farnsworth-munsell 100-hue color test fm-100 errors 153.0 82.2 normal vs 120.2 26.5; p 0.022). kaplan-meier 5-year-disease-free survival in those with normal olfaction was 86.0, vs 35.4 with impaired olfaction (p 0.029). disease-free survival with normal color vision was 70.3, vs 26.0 with impaired vision (p 0.009). both olfaction and color vision were reduced as much as 5 years before disease diagnosis, with only slight decline in preclinical stages.","olfaction and color vision identify early-stage synuclein-mediated neurodegenerative diseases. in most cases, abnormalities are measurable at least 5 years before disease onset, and progress slowly in the preclinical stages.",Diagnosis
does myocyte dedifferentiation drive extraocular muscle regeneration in adult zebrafish?,"the purpose of this study was to characterize the injury response of extraocular muscles (eoms) in adult zebrafish. adult zebrafish underwent lateral rectus (lr) muscle myectomy surgery to remove 50 of the muscle, followed by molecular and cellular characterization of the tissue response to the injury. following myectomy, the lr muscle regenerated an anatomically correct and functional muscle within 7 to 10 days post injury (dpi). following injury, the residual muscle stump was replaced by a mesenchymal cell population that lost cell polarity and expressed mesenchymal markers. next, a robust proliferative burst repopulated the area of the regenerating muscle. regenerating cells expressed myod, identifying them as myoblasts. however, both immunofluorescence and electron microscopy failed to identify classic pax7-positive satellite cells in control or injured eoms. instead, some proliferating nuclei were noted to express mef2c at the very earliest point in the proliferative burst, suggesting myonuclear reprogramming and dedifferentiation. bromodeoxyuridine (brdu) labeling of regenerating cells followed by a second myectomy without repeat labeling resulted in a twice-regenerated muscle broadly populated by brdu-labeled nuclei with minimal apparent dilution of the brdu signal. a double-pulse experiment using brdu and 5-ethynyl-2'-deoxyuridine (edu) identified double-labeled nuclei, confirming the shared progenitor lineage. rapid regeneration occurred despite a cell cycle length of 19.1 hours, whereas 72 of the regenerating muscle nuclei entered the cell cycle by 48 hours post injury (hpi). dextran lineage tracing revealed that residual myocytes were responsible for muscle regeneration.",eom regeneration in adult zebrafish occurs by dedifferentiation of residual myocytes involving a muscle-to-mesenchyme transition. a mechanistic understanding of myocyte reprogramming may facilitate novel approaches to the development of molecular tools for targeted therapeutic regeneration in skeletal muscle disorders and beyond.,Treatment
do gene expression data reveal common pathways that characterize the unifocal nature of ovarian cancer?,"the objective of the study was to evaluate the biological validity of ovarian cancer (ovca) screening and early detection efforts and to characterize signaling pathways associated with human cancer metastasis and patient survival. using genome-wide expression profiling and deoxyribonucleic acid sequencing, we compared pelvic and matched extrapelvic implants from 30 patients with advanced-stage ovca for expression of molecular signaling pathways and p53 gene mutations. differentially expressed pathways were further evaluated in a series of primary or early-stage vs metastatic or recurrent cancer samples from 389 ovarian, prostate, and oral cancer patients. metastasis pathways were also evaluated for associations with survival in 9 independent clinicogenomic datasets from 1691 ovarian, breast, colon, brain, and lung cancer and leukemia patients. the inhibitory effects of 1 pathway (transforming growth factor tgf-wnt) on in vitro ovca cell migration were studied. pelvic and extrapelvic ovca implants demonstrated similar patterns of signaling pathway expression and identical p53 mutations. however, we identified 3 molecular pathways/cellular processes that were differentially expressed between pelvic and extrapelvic ovca samples and between primary/early-stage and metastatic/advanced or recurrent ovarian, oral, and prostate cancers. furthermore, their expression was associated with overall survival from ovarian cancer (p .006), colon cancer (1 pathway at p .005), and leukemia (p .05). artesunate-induced tgf-wnt pathway inhibition impaired ovca cell migration.",advanced-stage ovca has a unifocal origin in the pelvis. molecular pathways associated with extrapelvic ovca spread are also associated with metastasis from other human cancers and with overall patient survival. such pathways represent appealing therapeutic targets for patients with metastatic disease.,Diagnosis
do human serum antibodies against ebv latent membrane protein 1 cross-react with -synuclein?,"to identify the epitope on -synuclein (-syn) to which antibodies against the epstein-barr virus (ebv) latent membrane protein 1 (lmp1) bind and to determine whether antibodies targeting this mimicry domain are present in human sera. reactivity of the -syn-cross-reacting anti-lmp1 monoclonal antibody cs1-4 to a synthetic peptide containing the putative mimicry domain was compared to those in which this domain was mutated and to murine and rat -syn (which differ from human -syn at this site) in western blots. using elisa, sera from ebv (n 4) and ebv- (n 12) donors as well as those with infectious mononucleosis (im; n 120), and hodgkin disease (hd; n 33) were interrogated for antibody reactivity to synthetic peptides corresponding to regions of -syn and lmp1 containing the mimicry domain. cs1-4 showed strong reactivity to wild-type human -syn, but not to the mutant peptides or rodent -syn. control ebv- and ebv sera showed no reactivity to -syn or lmp1 peptides. however, a significant proportion of im and hd sera contained immunoglobulin m (igm) (59 and 70, in im and hd, respectively), immunoglobulin g (igg) (40 and 48), and immunoglobulin a (iga) (28 and 36) antibodies to both peptides, as well as a significant correlation in the titers of igm ( 0.606 and 0.664, for im and hd, respectively), igg (0.526 and 0.836), and iga (0.569 and 0.728) antibodies targeting lmp1 and -syn peptides.",anti-ebv-lmp1 antibodies cross-reacting with a defined epitope in -syn are present in human patients. these findings may have implications for the pathogenesis of synucleinopathies.,General
does maternal high-fat hypercaloric diet during pregnancy result in persistent metabolic and respiratory abnormalities in offspring?,"we have shown in a previous population-based study significant correlation between childhood asthma and early abnormalities of lipid and glucose metabolism. this study's specific aim was to determine whether maternal nutrition in pregnancy affects postnatal metabolic and respiratory outcomes in the offspring. on gestation day 1, dams were switched from standard chow to either high-fat hypercaloric diet or control diet. terminal experiments were performed on newborn and weanling offspring of dams fed the study diet during gestation and lactation, and on adult offspring maintained on the same diet as their mother. pups born from high-fat hypercaloric diet (hfd) dams developed metabolic abnormalities persistent throughout development. cytokine expression analysis of lung tissues from newborns born to hfd dams revealed a strong proinflammatory pattern. gene expression of neurotrophic factors and receptors was upregulated in lungs of weanlings born to hfd dams, and this was associated to higher respiratory system resistance and lower compliance at baseline, as well as hyperreactivity to aerosolized methacholine. furthermore, hfd dams delivered pups prone to develop more severe disease after respiratory syncytial virus (rsv) infection.",maternal nutrition in pregnancy is a critical determinant of airway inflammation and hyperreactivity in offspring and also increases risk for bronchiolitis independent from prepregnancy nutrition.,Prevention
does acute hyperglycemia impair microvascular reactivity and endothelial function during hyperinsulinemic isoglycemic and hyperglycemic clamp in type 1 diabetic patients?,"the aim of this study was to evaluate the effect of acute glycemia increase on microvasculature and endothelium in type 1 diabetes during hyperinsulinemic clamp. sixteen patients (51 7 yrs) without complications were examined during iso- and hyperglycemic clamp (glucose increase 5.5 mmoll(-1)). insulin, lipid parameters, cell adhesion molecules and fibrinogen were analyzed. microvascular reactivity (mvr) was measured by laser doppler flowmetry. maximum perfusion and the velocity of perfusion increase during porh were higher in hyperglycemia compared to baseline (47 16 versus 40 16 pu, p 0.01, and 10.4 16.5 versus 2.6 1.5 pus(-1), p 0.05, resp.). time to the maximum perfusion during th was shorter and velocity of perfusion increase during th higher at hyperglycemia compared to isoglycemic phase (69 15 versus 77 16 s, p 0.05, and 1.4 0.8 versus 1.2 0.7 pus(-1), p 0.05, resp.). an inverse relationship was found between insulinemia and the time to maximum perfusion during porh (r -0.70, p 0.007).",acute glycemia did not impair microvascular reactivity in this clamp study in type 1 diabetic patients. our results suggest that insulin may play a significant role in the regulation of microvascular perfusion in patients with type 1 diabetes through its vasodilation effect and can counteract the effect of acute glucose fluctuations.,Medication
does planning estimate for the provision of core mental health services in queensland 2007 to 2017?,"to derive planning estimates for the provision of public mental health services in queensland 2007-2017. we used a five-step approach that involved: (i) estimating the prevalence and severity of mental disorders in queensland, and the number of people at each level of severity treated by health services; (ii) benchmarking the level and mix of specialised mental health services in queensland against national data; (iii) examining 5-year trends in queensland public sector mental health service utilisation; (iv) reviewing australian and international planning benchmarks; and (v) setting resource targets based on the results of the preceding four steps. best available evidence was used where possible, supplemented by value judgements as required. recommended resource targets for inpatient service were: 20 acute beds per 100,000 population, consistent with national average service provision but 13 above queensland provision in 2005; and 10 non-acute beds per 100,000, 65 below queensland levels in 2005. growth in service provision was recommended for all other components. adult residential rehabilitation service targets were 10 clinical 24-hour staffed beds per 100,000, and 18 non-clinical beds per 100,000. supported accommodation targets were 35 beds per 100,000 in supervised hostels and 35 places per 100,000 in supported public housing. a direct care clinical workforce of 70 fte per 100,000 for ambulatory care services was recommended. fifteen per cent of total mental health funding was recommended for community support services provided by non-government organisations.","the recommended targets pointed to specific areas for priority in queensland, notably the need for additional acute inpatient services for older persons and expansion of clinical ambulatory care, residential rehabilitation and supported accommodation services. the development of nationally agreed planning targets for public mental health services and the mental health community support sector were identified as priorities.",Treatment
does radiation-induced mir-208a increase the proliferation and radioresistance by targeting p21 in human lung cancer cells?,"lung cancer has long been the most dangerous malignant tumor among males in both well developed and poorly developed countries. radiotherapy plays a critical role in the curative management of inoperable non-small cell lung cancer (nsclc) and is also used as a post-surgical treatment in lung cancer patients. radioresistance is an important factor that limits the efficacy of radiotherapy for nsclc patients. increasing evidence suggests that micrornas (mirnas) possess diverse cellular regulatory roles in radiation responses. in this study, we used mirna microarray technology to identify serum mirnas that were differentially expressed before and after radiotherapy in lung cancer patients. we further examined the biological function of mir-208a on cell viability, apoptotic death and cell cycle distribution in human lung cancer cells and explored the probable mechanism. nine mirnas, including mir-29b-3p, mir-200a-3p, and mir-126-3p were significantly down-regulated, whereas mir-208a was the only mirna that was up-regulated in the serum of the patients after radiation treatment (p 0.05). the expression of mir-208a could be induced by x-ray irradiation in lung cancer cells. forced expression of mir-208a promoted cell proliferation and induced radioresistance via targeting p21 with a corresponding activation of the akt/mtor pathway in lung cancer cells, whereas down-regulation of mir-208a resulted in the opposite effects. in addition, down-regulation of mir-208a increased the percentage of cells undergoing apoptosis and inhibited the g1 phase arrest in nsclc cells. moreover, mir-208a from the serum exosome fraction of lung cancer patients could shuttle to a549 cells in a time-dependent manner, which was likely to contribute to the subsequent biological effects.","the present study provides evidence that mir-208a can affect the proliferation and radiosensitivity of human lung cancer cells by targeting p21 and can be transported by exosomes. thus, mir-208a may serve as a potential therapeutic target for lung cancer patients.",Treatment
"is n-terminal brain natriuretic peptide , but not anemia , a powerful predictor of mortality in advanced heart failure?","anemia is prevalent in patients with chronic heart failure, the proportion of which increases with deteriorating new york heart association functional class. anemia is also associated with increased symptoms, more frequent hospitalizations, and, in some studies, with an increased mortality rate. we have demonstrated that n-terminal brain natriuretic peptide (nt-probnp) is a powerful predictor of death in advanced heart failure and is superior to the traditional markers of chronic heart failure (chf) severity. however, to date, there are no published data that compare the prognostic ability of nt-probnp with that of hemoglobin and hematocrit in patients with advanced heart failure who are referred for consideration of cardiac transplantation at a time when erythropoietin is under investigation as a treatment option in such a population. we prospectively studied 182 consecutive patients with advanced chf who had been referred for consideration of cardiac transplantation. blood samples were taken at recruitment for routine investigation and for nt-probnp analysis; the patients' condition was followed for a median of 554 days. the primary end point of all-cause death was reached in 30 patients, and the secondary end point of all-cause death or urgent cardiac transplantation was reached in 34 patients. the mean hemoglobin level was 13.9 /- 2.2 g/dl, and the median concentration of nt-probnp was 1505 pg/ml (interquartile range, 517-4015). the only multivariate predictor of all-cause death (chi 2 14.2; p .001) or the secondary end point of all-cause death or urgent transplantation (chi 2 21.8; p .001) was an nt-probnp concentration above the median value.",a single measurement of nt-probnp in patients with advanced chf can help to identify patients who are at a higher risk of death and is a better prognostic marker than anemia.,Treatment
is gastrin-releasing peptide a growth factor for human neuroblastomas?,"to evaluate whether gastrin-releasing peptide (grp) and grp receptor (grp-r) expression correlate with tumor behavior and to examine the mitogenic actions of grp on neuroblastomas. neuroblastoma is the most common solid tumor of infants and children. despite recent advances in multimodality treatment regimens, the survival for advanced-stage tumors remains dismal. neuroblastomas are known to produce grp; however, the proliferative effects of grp on neuroblastomas have not been elucidated. sections of paraffin-embedded neuroblastomas from 33 patients were analyzed for grp and grp-r protein expression by immunohistochemistry. functional binding of grp-r to the ca2 signaling pathway was examined. in addition, the proliferative effect of grp on neuroblastoma cells (sk-n-sh, imr-32, sh-sy5y, lan-1) was determined. immunohistochemical analysis showed grp and grp-r protein expression in neuroblastomas; an increased expression of grp-r was noted in a higher percentage of undifferentiated tumors compared with tumors that were benign. grp-r mrna was confirmed in neuroblastoma cell lines. grp treatment resulted in intracellular calcium ca2i mobilization in two cell lines (sk-n-sh, lan-1). grp treatment stimulated growth of all four neuroblastoma cell lines; this effect was inhibited in sk-n-sh cells by pretreatment with grp antibody.","these findings show increased grp-r expression in the more aggressive and undifferentiated neuroblastomas. the synchronous expression of grp and its receptor, grp-r, suggests a role for these proteins in tumor growth. moreover, these findings show enhanced proliferation of neuroblastoma cells in vitro after grp treatment, suggesting that grp may act as an autocrine and/or paracrine growth factor for neuroblastomas. treatment with specific grp-r antagonists may provide novel adjuvant therapy for neuroblastomas in children.",Medication
does measurement of cell-bound complement activation products enhance diagnostic performance in systemic lupus erythematosus?,"to determine the value of cell-bound complement activation products in combination with antinuclear antibody (ana), anti-double-stranded dna antibody (anti-dsdna), and anti-mutated citrullinated vimentin antibody (anti-mcv) for the diagnosis of systemic lupus erythematosus (sle). this was a multicenter cross-sectional study in which 593 subjects were enrolled (210 sle patients, 178 patients with other rheumatic diseases, and 205 healthy subjects). complement receptor 1 levels on erythrocytes (ecr1) together with complement c4d levels on erythrocytes (ec4d), platelets (pc4d), and b cells (bc4d) were determined using fluorescence-activated cell sorting. serologic markers were measured by enzyme-linked immunosorbent assay. statistical analyses were performed using area under the curve (auc), logistic regression, and calculations of diagnostic sensitivity and specificity. anti-dsdna was an insensitive (30) but specific (95) marker for sle. levels of ec4d, bc4d, and pc4d were several times higher, and levels of ecr1 lower, in sle patients compared to patients with other rheumatic diseases and healthy subjects. among 523 anti-dsdna-negative subjects, multivariate logistic regression analysis revealed that sle was associated with ana positivity (20 units), anti-mcv negativity (70 units), and elevated levels of both ec4d and bc4d (auc 0.918, p 90. the combination of anti-dsdna and index score positivity yielded 80 sensitivity for sle and 87 specificity against other rheumatic diseases.","an assay panel combining anti-dsdna, ana, anti-mcv, ec4d, and bc4d is sensitive and specific for the diagnosis of sle.",Diagnosis
does topical glucocorticoid reduce the topical decongestant-induced histologic changes in an animal model nasal mucosa?,"to investigate the histologic consequences of simultaneous nasal glucocorticosteroid and xylometazoline hcl administration in the rabbit nasal mucosa. prospective randomized study. twenty new zealand male rabbits were randomly placed into three groups: group i, control (n 6); group ii, xylometazoline hcl (n 8); or group iii, xylometazoline hcl-fluticasone furoate (n 6). group i received no treatment. groups ii and iii received two intranasal puffs of xylometazoline hcl 0.5 mg/ml twice daily or two puffs of xylometazoline hcl 0.5 mg/ml twice daily plus one puff of 27.5 g fluticasone furoate twice daily to each nostril (110 g), respectively. at the end of 3 weeks, the rabbits were sacrificed. the mucosa of the nasal cavities was excised. specimen sections (5 m) were stained with hematoxylin and eosin, mucicarmine, and gomori one-step trichrome and were examined under a light microscope. the presence of edema, congestion, inflammatory cell infiltration, nasociliary loss, epithelial and nerve-ending degeneration, and goblet cell increase were evaluated semiquantitatively (grades 0-3). statistically significant differences were detected between groups ii and iii in terms of edema, congestion, inflammatory cell infiltration, nasociliary loss, and epithelial degeneration (p .006, p .049, p .015, p .014, and p .049, respectively). nerve-ending degeneration, goblet cell increase, and quantitative goblet and neutrophil cell counts did not yield statistically significant differences between groups ii and iii (p .137, p .580, p .770, and p .616, respectively).","the combined simultaneous intranasal administration of xylometazoline hcl and fluticasone furoate appears to be beneficial in minimizing the long-term usage-associated congestion, edema, inflammatory cell infiltration, epithelial degeneration, and nasociliary loss in the rabbit model nasal mucosa.",Medication
does combination of droperidol and ondansetron reduce ponv after pediatric strabismus surgery more than single drug therapy?,"pediatric strabismus surgery is associated with a very high incidence of postoperative nausea and vomiting (ponv) 44-88. droperidol (10-75 microg kg(-1)) and ondansetron (50-150 microg kg(-1)) have shown variable success in reducing the incidence and severity of ponv. combination of these two drugs has shown promising results. this randomized, double-blind, placebo-controlled clinical trial was conducted to evaluate the efficacy and safety of the combination of these two drugs in reducing the incidence and severity of ponv in pediatric strabismus surgery. after institutional approval and parental informed consent, 240 children of asa physical status i and ii of either sex, aged 1-15 years were included in this study. none of the children received any premedication and a standardized anesthesia technique was used for all the children. they were prospectively randomized to one of the four treatment groups. group pp received normal saline placebo intravenously after induction and at the end of the procedure. group dp received droperidol 25 microg kg(-1) after induction and normal saline at the end. group op received ondansetron 150 microg kg(-1) after induction and saline at the end. group do received droperidol 15 microg kg(-1) after induction and ondansetron 100 microg kg(-1) at the end. combination prophylaxis resulted in a lower incidence of ponv (13) as compared to placebo (62.5, p0.001), ondansetron (37, p0.001), or droperidol (32, p0.01).","droperidol 15 microg kg(-1) in combination with ondansetron 100 microg kg(-1), administered at the induction and end of the operative procedure respectively, is more effective than either drug given individually in reducing the incidence of ponv after strabismus surgery.",Treatment
is neointima formed by arterial smooth muscle cells expressing versican variant v3 resistant to lipid and macrophage accumulation?,"extracellular matrix (ecm) of neointima formed following angioplasty contains elevated levels of versican, loosely arranged collagen, and fragmented deposits of elastin, features associated with lipid and macrophage accumulation. ecm with a low versican content, compact structure, and increased elastic fiber content can be achieved by expression of versican variant v3, which lacks chondroitin sulfate glycosaminoglycans. we hypothesized that v3-expressing arterial smooth muscle cells (asmc) can be used to form a neointima resistant to lipid and macrophage accumulation associated with hypercholesterolemia. asmc transduced with v3 cdna were seeded into ballooned rabbit carotid arteries, and animals were fed a chow diet for 4 weeks, followed by a cholesterol-enriched diet for 4 weeks, achieving plasma cholesterol levels of 20 to 25 mmol/l. v3 neointimae at 8 weeks were compact, multilayered, and elastin enriched. they were significantly thinner (57) than control neointimae; contained significantly more elastin (118), less collagen (22), and less lipid (76); and showed significantly reduced macrophage infiltration (85). mechanistic studies demonstrated that oxidized low-density lipoprotein stimulated the formation of a monocyte-binding ecm, which was inhibited in the presence of v3 expressing asmc.",these results demonstrate that expression of v3 in vessel wall creates an elastin-rich neointimal matrix that in the presence of hyperlipidemia is resistant to lipid deposition and macrophage accumulation.,Prevention
do genetic variations in regulator of g-protein signaling ( rgs ) confer risk of bladder cancer?,"alterations in the regulator of g-protein signaling (rgs) pathway have been implicated in several cancers; therefore, the authors investigated the role of such alterations in overall bladder cancer risk, recurrence, progression, and survival. in this case-control series, 803 patients with bladder cancer were frequency-matched with a control cohort of 803 healthy individuals. ninety-five single-nucleotide polymorphisms (snps) in 17 rgs genes were investigated for an association with overall bladder cancer risk, recurrence, and progression in patients who had nonmuscle-invasive bladder cancer (nmibc) and for an association with death in patients who had muscle-invasive bladder cancer (mibc). cumulative effects and classification and regression tree analyses were performed for snps that were associated with overall bladder cancer risk. kaplan-meier plots were created to evaluate differences in the survival of patients with mibc. reference snp 10759 (rs10759) on the rgs4 gene demonstrated the greatest association with overall bladder cancer risk, conferring a 0.77-fold reduced risk with an increasing number of variant alleles (p .001). a cumulative effects analysis that included all 5 significant snps demonstrated an increasing risk with the number of unfavorable genotypes (odds ratio, 4.13; 95 confidence interval, 2.14-7.98). in patients with nmibc, 11 snps were identified that had an association with disease recurrence, and 13 snps were associated with disease progression. of the 10 snps that were associated with death in patients with mibc, rs2344673 in an additive model was the most significant and was associated with a decreased median survival of 13.3 months compared with 81.9 months in individuals without a variant allele.","genetic variations in the rgs pathway were associated with the overall risk of bladder cancer, recurrence, and progression in patients with nmibc and with the risk of death in patients with mibc.",General
is blood alcohol the best indicator of hazardous alcohol drinking in young adults and working-age patients with trauma?,"to determine the most effective marker of hazardous alcohol drinking in trauma patients. a prospective study of 349 trauma patients aged 16-49 years admitted into a general hospital trauma centre. information on the amount and pattern of alcohol drinking was obtained by interview. blood or breath alcohol concentration (bac), serum gammaglutamyl transferase (ggt), aspartate aminotransferase (ast), carbohydrate-deficient transferrin (cdt) and the mean corpuscular volume (mcv) of erythrocytes were measured as markers of alcohol consumption. in this series, 8 of all trauma patients were found to be dependent drinkers, while 61 were frequent binge drinkers, 17 infrequent binge drinkers, 8 light-to-moderate drinkers and 6 nondrinkers. on admission, the bac test was positive in 68 of the hazardous drinkers (i.e. dependent drinkers or frequent binge drinkers). using a cut-off level of 0 mg/dl, the sensitivity and specificity of the bac test for identifying hazardous drinking were 68 (95 confidence intervals ci, 61-73) and 94 (95 ci, 87-97), respectively, and the positive predictive value was 96 (95 ci, 92-98). ggt, mcv, cdt and ast were less accurate indicators of hazardous drinking. bac was the least expensive marker.","two-thirds of trauma patients were hazardous drinkers, and blood alcohol on admission was an accurate indicator of this. bac should be systematically used in trauma centres if patients are to be selected for an alcohol intervention.",Diagnosis
are antibodies to high-density lipoprotein and beta2-glycoprotein i inversely correlated with paraoxonase activity in systemic lupus erythematosus and primary antiphospholipid syndrome?,"to determine the prevalence of anti-high-density lipoprotein (anti-hdl) antibodies and to establish a possible relationship between anti-hdl, anticardiolipin antibodies (acl), anti-beta(2)-glycoprotein i (anti-beta(2)gpi), and paraoxonase (pon) activity in patients with systemic lupus erythematosus (sle) and primary antiphospholipid syndrome (aps). thirty-two patients with sle and 36 with primary aps were enrolled in a cross-sectional study. twenty age- and sex-matched healthy subjects were used as controls. serum levels of igg and igm acl, anti-beta(2)gpi, and antiprothrombin antibodies and igg anti-hdl were measured by enzyme-linked immunosorbent assay. total cholesterol, hdl cholesterol, hdl(2), and hdl(3) were determined by standard enzymatic techniques. pon activity was assessed by quantification of nitrophenol formation, and total antioxidant capacity (tac) by chemiluminescence. levels of total hdl, hdl(2), and hdl(3) were reduced in patients with sle compared with controls (mean /- sd 0.51 /- 0.3, 0.37 /- 0.3, and 0.14 /- 0.1 mmoles/liter, respectively, versus 1.42 /- 0.9, 1.01 /- 0.7, and 0.40 /- 0.2). patients with sle and primary aps had higher titers of anti-hdl antibodies and lower pon activity than controls. in the sle population, pon activity was inversely correlated with igg anti-hdl titers (r -0.48, p 0.005) whereas in the primary aps population, igg anti-beta(2)gpi was the only independent predictor of pon activity (r -0.483, p 0.003). in the sle group, anti-hdl was inversely correlated with tac (r -0.40, p 0.02), and pon activity was positively correlated with tac (r 0.43, p 0.02).","igg anti-hdl and igg anti-beta(2)gpi antibodies are associated with reduced pon activity in patients with sle and primary aps. since the physiologic role of pon is to prevent low-density lipoprotein oxidation with its attendant atherogenic effects, the reported interactions may be relevant to the development of atherosclerosis in sle and primary aps.",Medication
is sialosyl tn antigen expression associated with the prognosis of patients with advanced gastric cancer?,"several studies have revealed a correlation between sialosyl tn antigen (stn) and certain clinicopathologic features of various cancers, and that stn is an independent prognostic factor. however, the clinical significance of the expression of stn in gastric cancer has not been reported. thus, the purpose of this study was to evaluate immunohistochemically the clinical significance of expression of stn in gastric cancer. the expression of stn in surgically resected specimens of human gastric cancer was evaluated immunohistochemically using a monoclonal antibody (tkh-2), in 60 patients whose serum stn levels were measured and in 54 patients with advanced cancer who had been followed for more than 5 years after gastrectomy. the correlations between the level of stn expression and clinicopathologic factors were analyzed. the staining intensity was graded as follows: (-), less than 5 of the cancer cells expressed stn; (), 5-50; (), more than 50. sialosyl tn antigen staining was detected mainly on the cell membrane, in the cytoplasm, and in the luminal contents, and 57.2 of the 60 specimens expressed stn, whereas the corresponding value for positive serum levels was 15. a higher percentage of advanced tumors expressed stn than did the early cases, but the difference was not statistically significant. all cases with strong staining, the () cases, were advanced cases either with lymph node metastases or with cancer invading in or beyond the muscle layer proper. the expression of stn appeared to be related to the clinical stage, the extent of cancer invasion, and the presence of lymph node metastases. sialosyl tn antigen was detected in the serum in less than 6 of the patients whose tumors were (-) or () for stn expression, and in 86.7 of the patients whose tumors expressed high levels of stn (). the estimated 5-year survival in advanced cases (stage iii) was significantly better in those with negative stn expression than in those with positive stn expression (p 0.01).",these results suggest that stn may be a useful marker associated with the prognosis of patients with advanced gastric cancer.,Diagnosis
does tamoxifen therapy convey increased risk of developing a macular hole?,"to determine etiological factors in the development of, as well as anatomic success rate and visual outcome of a large consecutive series of macular hole surgeries. retrospective analysis of 300 consecutive cases of macular hole surgery by a single surgeon (rdb) between 1999 and 2003. patients' medical and surgical histories were recorded and analysed for factors involved in aetiology and visual outcome. there were 8 (4.12) women, on tamoxifen in the study, two of these women had bilateral macular holes. when this study prevalence of tamoxifen therapy (4.12) was compared to the estimated percentage of women in the same age group in the australian population on tamoxifen (0.82), a statistically significant difference (p value 0.0001) was found. analysis of the number of bilateral holes in the tamoxifen group compared to the non-tamoxifen group was suggestive of an increased incidence of bilateral holes but not to a significantly significant degree.","whilst no published reports link tamoxifen and macular holes, this may be due to the low incidence of the condition. our study demonstrates a strong link between tamoxifen use and macular holes. patients being commenced on tamoxifen should be advised of possible ocular complications and receive prompt ophthalmic review if symptoms develop.",Treatment
is renal afferent signaling diuretic response impaired in streptozotocin-induced diabetic rats?,"renal afferent signaling diuretic response is impaired in streptozotocin-induced diabetic rats. renal insufficiency develops in diabetes and shows structural and functional abnormalities. renal afferents, including chemoreceptors and mechanoreceptors located in the vascular and ureteropelvic portions of the kidney, may reflect changes in the environment and trigger an afferent nerve-mediated regulatory function that is known as the renorenal reflex. in this study, the involvement of these renal sensory receptors during the early diabetic state is defined. diabetes was induced in rats after a tail vein injection of streptozotocin (stz; 60 mg/kg intravenously). four groups of rats, control (c), diabetic (dm), diabetic with acute insulin treatment (dmai, 9 u/rat, subcutaneously, on the experimental day), and chronic insulin treatment (dmci, 9 u/rat, subcutaneously, daily) were studied. spontaneous firing type 2-renal chemoreceptor (cr2), arterial mechanoreceptor (mra), ureteropelvic mechanoreceptor (mru), and venous mechanoreceptor (mrv) were identified by single-unit analysis of renal afferent nervous activity. the receptor activities were confirmed by their response patterns to stimuli elicited by renal arterial occlusion (rao), backflow of urine, increasing arterial pressure, increasing ureteropelvic pressure (up), or renal venous occlusion (rvo). the response of these afferent receptors to a challenge of volume expansion and their functional activities on renorenal reflexes were also examined. immunostaining with pgp 9.5 was applied for examination of the nerve distribution in the diabetic kidney. the tissue level of histamine in the renal pelvis was determined. we explored the effect of histamine on renal receptor activity in these animals to address the possible role of histamine in mru receptor activity. in early diabetics, signaling activities in mra and mrv were maintained; however, activity in cr2 and mru was depressed. for cr2, the reduced basal discharge and the repressed responses to rao, backflow of urine, and volume expansion found in dm rats were recovered by acute insulin treatment to restore glucose levels to near normal. for mru, the depressed response to increasing up and volume expansion was not restored by acute correction of hyperglycemia in dmai rats. however, antihistamine treatment or chronic insulin treatment recovered the mru response to mechanical stimuli in dm rats. because of the desensitized cr2 and mru activity, renorenal reflexes elicited by backflow of urine and increasing up were depressed in dm rats.","despite a lack of structural changes, the operating system, signaling ability, and renorenal reflex regulatory function of two renal afferent nerve receptors, cr2 and mru, are altered in the early diabetic state.",Medication
do the effect of magnesium-incorporated hydroxyapatite coating on titanium implant fixation in ovariectomized rats?,"this study compared the effect of magnesium-incorporated hydroxyapatite (mgha) coating with that of ha coating on implant fixation in ovariectomized (ovx) rats. coatings of ha and mgha (10 mol ca replaced by mg) were prepared on the surface of titanium substrates using the sol-gel dip-coating method, and powders of ha and mgha were produced by the same method. the two kinds of materials were then characterized by scanning electron microscopy and x-ray diffraction. twelve weeks after bilateral ovariectomy, 18 ovx rats received implants in the distal femora; half of the implants were ha-coated and the other half were mgha-coated. after 12 weeks of healing, rats were selected randomly for histomorphometry, microcomputed tomography evaluation, and biomechanical testing. surface characterization analysis demonstrated that the addition of mg did not dramatically change the surface topography or apatite patterns of the coating. histomorphometry revealed higher bone-to-implant contact and bone area ratio for mgha-coated implants than for ha-coated implants. microcomputed tomographic evaluation revealed improved trabecular parameters and increased osseointegration for mgha-coated implants. biomechanical testing revealed that the mgha coating increased the maximum push-out force and interfacial shear strength compared to the ha coating.",mg incorporated into an ha coating on titanium implants could improve the biologic fixation of implants in osteoporotic bone.,Diagnosis
are plasma endothelin levels increased during septic shock?,"to study whether serially measured plasma concentrations of endothelin (a novel, potent, endogenous vasoconstrictor derived from endothelium and macrophages) relate to the pathophysiology and severity of human septic shock. prospective analysis. medical icu of a university hospital. six patients with septic shock, studied for 8 days after icu admission. the initial plasma endothelin concentration was increased (14.2 /- 5.2 sd vs. normal 4.2 /- 0.7 pg/ml, p less than .05) and correlated with the acute physiology and chronic health evaluation ii score (r2 .79, p less than .05). for pooled data, endothelin levels correlated poorly with leukocyte counts (r2 .13), mean arterial pressure (map) (r2 .16), and administered doses of dopamine (r2 .26). in multiple regression analyses, plasma endothelin concentrations were predicted by dopamine doses and not by map. plasma endothelin concentrations predicted the decrease in creatinine clearance, independently from map. the pooled value for correlations between endothelin levels and creatinine clearance, during the course of disease in individual patients, was statistically significant (r2 .31).","during septic shock, the release or production of endothelin may increase as a consequence of endothelial injury by activated leukocytes and the infusion of catecholamines, and this mechanism may relate to renal vasoconstriction and to the severity of disease.",Medication
does intrathecal sufentanil for labor analgesia cause a sympathectomy?,"intrathecal sufentanil (its) is frequently used to provide analgesia during labor. decreases in blood pressure and sensory changes in this circumstance suggest that its may have a local anesthetic effect and thus cause a sympathectomy. to determine whether its given to laboring women causes a sympathectomy, the authors evaluated central and lower extremity temperature changes after its administration. these findings were compared with those in a control group of women having spinal anesthesia with bupivacaine for elective cesarean section in whom an extensive sympathectomy was expected. twenty parturients classified as american society of anesthesiologists' physical status 1 or 2 had temperatures measured centrally, at the calf, and at the great toe at frequent intervals after receiving 10 microg its for labor analgesia (sufentanil group, n 10), or hyperbaric bupivacaine 12 mg in their spinal anesthetic for cesarean section (bupivacaine group, n 10). calf-to-toe temperature indices (c-t) were calculated by subtracting toe temperature from calf temperature. a decrease in this index means that the toe had warmed compared with the calf and is an indication of vasodilation and a sympathectomy. there was no significant change in the c-t indices or central temperature in the sufentanil group, but the c-t indices and central temperature decreased significantly in the bupivacaine group.","the decreases in the c-t index and central temperature in the bupivacaine group indicate the presence of a sympathectomy. the lack of change in the c-t indices and central temperature in the sufentanil group indicates that no significant vasodilation occurred. therefore, the decrease in blood pressure seen after its administration for labor analgesia is unlikely to be the result of a sympathectomy.",Medication
is topoisomerase i but not thymidylate synthase associated with improved outcome in patients with resected colorectal cancer treated with irinotecan containing adjuvant chemotherapy?,"thymidylate synthase (ts) and topoisomerase i (topo i) are significant biomarkers in colorectal cancer (crc). we aimed to study the expression of ts and topo i in patients with resected crc who received adjuvant chemotherapy and correlated it with clinical outcome. all patients diagnosed with crc between 1989 and 2007 and treated with adjuvant chemotherapy within hellenic cooperative oncology group's (hecog) protocols, were identified. archival paraffin-embedded tumor tissues were used for immunohistochemical detection of ts and topo i. immunohistochemistry was performed on tissue microarray slides using monoclonal antibodies against ts and topo i. the results were correlated with survival (os) and disease free survival (dfs). a cohort of 498 patients with a median age of 61 years and dukes' stage b (49) and c (51) fulfilled the criteria of the study. all patients received adjuvant 5-fu-based chemotherapy, 38 irinotecan-containing. positive ts and topo i expression was found in 43 and 48 of cases, respectively. five-year os was 74 and dfs was 68. in univariate analysis no association of ts and topo i expression with os and dfs was identified. in multivariate analysis however, topo i expression was associated with a reduced risk of death (hr 0.61, 95 ci 0.42-0.88, p 0.009). in the irinotecan-treated subgroup, those patients who expressed topo i had a better os (hr 0.47, 95 ci 0.23-0.94, p 0.033).",patients with resected crc expressing topo i seem to benefit from irinotecan-containing adjuvant chemotherapy. however randomised prospective trials are needed to confirm these results.,Medication
is steroid use in lyme disease-associated facial palsy associated with worse long-term outcomes?,"the purpose of this study was to determine whether differences in long-term facial function outcomes following acute lyme disease-associated facial palsy (ldfp) exist between patients who received antibiotic monotherapy (mt); dual therapy (dt) with antibiotics and corticosteroids; and triple therapy (tt) with antibiotics, corticosteroids, and antivirals. retrospective cohort. all patients with a prior diagnosis of unilateral ldfp who presented to our center between 2002 and 2015 were retrospectively assessed for inclusion. two blinded experts graded static, dynamic, and synkinesis parameters of facial functions using standardized video documentation of facial function. fifty-one patients were included. the mean time of assessment following ldfp onset was 15.1 months (range 0.3-84 months). significantly worse facial outcomes were seen among those who received dt and tt as compared to those who received mt, most pronounced among those assessed 12 months or later following onset of ldfp (dynamic-p 0.031, post hoc mt vs. tt: mean difference md, 15.83; 95 confidence interval ci, 1.54-30.13; p 0.030. synkinesis-p 0.026, post hoc mt vs. dt: md, 21.50; 95 ci, 0.68-42.32; p 0.043, post hoc mt vs. tt: md, 19.22; 95 ci, 2.23-36.22; p 0.027).","an association between corticosteroid use in acute ldfp and worse long-term facial function outcomes has been demonstrated. care should be taken in differentiating viral or idiopathic facial palsy (e.g., bell palsy) from ldfp.",Medication
does effect of preserved and preservative-free timolol eye drop on tear film stability in healthy africans?,"preserved versus nonpreserved formulations for ophthalmic use have been well described in the literature although not specifically in the african population where beta blockers are frequently used as the first-line therapy due to economic and availability issues. this study sought to determine the effect of preserved and preservative-free timolol eye drops on tear film stability in healthy black africans. sixty healthy nondry eye subjects aged 19-25 years were randomly assigned into four groups (n 15) and differently treated with eye drops of phosphate buffered saline (pbs), preservative-free timolol (pft), benzalkonium chloride (bak) only, and bak-preserved timolol (bpt). noninvasive tear break-up time (nitbut) was measured using the keratometer at baseline and 30, 60, and 90 min after drop application. no significant decline in nitbut was observed following treatment with pft and pbs. however, bak treatment showed a positive time-dependent significant decline in nitbut (p 0.001) while a significant decline in the bpt-treated group was only found at 90 min (-3.52 s; p 0.001). in comparison to the pft-treated group, treatment with bak and bpt showed significantly lower nitbut (p 0.001).",bpt is associated with a significant decline in tear film stability in black africans. this finding has implications in the management of glaucoma in patients with high-risk of dry eyes in this population.,Treatment
does receptor interacting protein 2 ( rip2 ) be dispensable for ova-induced airway inflammation in mice?,"asthma is a pulmonary chronic inflammatory disease characterized by airway obstruction and hyperresponsiveness. pattern recognition receptors are known to play a key role in the development of allergic diseases as well as host defenses against microbial infection. receptor interacting protein 2 (rip2), a serine/threonine kinase, is an adaptor molecule of nod1 and nod2, and genetic variation in this receptor is known to be associated with the severity of allergic asthma in children. in this study, we examined the role of rip2 in the development of allergic airway inflammation in a mouse model. airway inflammation was induced in mice through intranasal administration of ovalbumin (ova) after 2 intraperitoneal immunizations with ova. lung inflammation and mucus hypersecretion were examined histologically and total cell infiltration in bronchoalveolar (bal) fluids was determined. levels of the th2-related cytokines, il-5 and il-13, in lung extracts were measured by elisa. serum antigen-specific ige and igg1 levels were also assessed. ova-induced lung inflammation and mucus hypersecretion were not different between wt and rip2-deficient mice. the il-5 and il-13 levels in the bronchoalveolar (bal) fluids were also not impaired in rip2-deficient mice compared to wt mice. moreover, rip2 deficiency did not affect serum ova-specific igg1 and ige levels.",our results suggest that rip2 is not associated with the development of allergic airway inflammation.,Medication
does restoration of fgf receptor type 2 enhance radiosensitivity of hormone-refractory human prostate carcinoma pc-3 cells?,"this study was undertaken to investigate the radiosensitizing effects of fibroblast growth factor receptor 2iiib (fgfr2iiib) in androgen-independent human prostate carcinoma pc-3 cells devoid of normally resident epithelial cell fgfr2iiib. a clonal line of pc-3 cells expressing fgfr2iiib was established by stable transfection. clonogenic cell survival, apoptosis and cell cycle distribution with and without gamma-irradiation were then compared between fgfr2iiib-expressing pc-3 cells and control cells mock-transfected with vector alone. gamma-irradiation resulted in an increase of clonogenic cell death concurrent with enhanced apoptosis and cell cycle arrest in the g2/m-phase in both transfected and untransfected cells. a quantitative analysis of all three parameters indicated that cells expressing fgfr2iiib were significantly more sensitive to irradiation than control cells.",these results indicate that restoration of fgfr2iiib to pc-3 cells enhances their sensitivity to irradiation through acceleration of apoptosis and cell cycle arrest.,Medication
does calcium spark in the intact gerbil spiral modiolar artery?,"calcium sparks are ryanodine receptor mediated transient calcium signals that have been shown to hyperpolarize the membrane potential by activating large conductance calcium activated potassium (bk) channels in vascular smooth muscle cells. along with voltage-dependent calcium channels, they form a signaling unit that has a vasodilatory influence on vascular diameter and regulation of myogenic tone. the existence and role of calcium sparks has hitherto been unexplored in the spiral modiolar artery, the end artery that controls blood flow to the cochlea. the goal of the present study was to determine the presence and properties of calcium sparks in the intact gerbil spiral modiolar artery. calcium sparks were recorded from smooth muscle cells of intact arteries loaded with fluo-4 am. calcium sparks occurred with a frequency of 2.6 hz, a rise time of 17 ms and a time to half-decay of 20 ms. ryanodine reduced spark frequency within 3 min from 2.6 to 0.6 hz. caffeine (1 mm) increased spark frequency from 2.3 to 3.3 hz and prolonged rise and half-decay times from 17 to 19 ms and from 20 to 23 ms, respectively. elevation of potassium (3.6 to 37.5 mm), presumably via depolarization, increased spark frequency from 2.4 to 3.2 hz. neither ryanodine nor depolarization changed rise or decay times.",this is the first characterization of calcium sparks in smooth muscle cells of the spiral modiolar artery. the results suggest that calcium sparks may regulate the diameter of the spiral modiolar artery and cochlear blood flow.,Medication
does effect of home bleaching on the mechanical properties of resin luting cement using hertzian indentation test?,"the aim of the present study was to determine the effects of immersion time and 10 carbamide peroxide treatment using a hertzian indentation test after placing resin-based cements into 37c distilled water, with and without 10 carbamide peroxide. disc-shaped specimens (10-mm diameter 1-mm thick), were prepared from five resin-based cements; set pp, maxcem elite, relyx unicem, panavia f, and g-cem. the specimens of each material were randomly divided into three groups of six. the study groups were bleached with 10 carbamide peroxide on one surface for 21 days for 2 h per day. two control groups were kept in distilled water for either 24 h or 21 days. a load was applied to the center of the disc using a hard, steel ball. the load at the first crack was recorded. significant differences were observed between the cements. set pp showed the highest strength, and g-cem the lowest. differences between the treatment and control groups were statistically significant for all cements, except panavia f.","the effect of 10 carbamide peroxide treatment reduces cement strength, which could be important for patients undergoing bleaching who have crowns.",Treatment
does adenovirus-mediated gene transfer of fibroblast growth factor-2 increase brdu-positive cells after forebrain ischemia in gerbils?,"progenitor cells continue to generate neurons in the adult mammalian brain, and cerebral ischemia induces neurogenesis. we examined the efficacy of the intraventricular injection of a recombinant adenovirus-expressing fibroblast growth factor-2 (fgf-2) (axcamassbfgf) on neurogenesis in both normal and ischemic brains. we used a gerbil model of transient global ischemia and counted the number of brdu-positive cells after injection of axcamassbfgf into the brain with or without ischemia. intraventricular axcamassbfgf produced robust fgf-2 protein increases in diverse regions of the brain and markedly increased fgf-2 concentrations in cerebrospinal fluid 2 days after administration and evoked significant proliferation of brdu-positive cells not only in the subventricular zone and dentate gyrus of the hippocampus but also in the cerebral cortex, and some brdu-positive cells differentiated into neurons. continuous intraventricular infusion of fgf-2 protein increased fgf-2 concentration in cerebrospinal fluid but not in brain tissues and produced brdu-positive cell proliferation only in the subventricular zone of the lateral ventricle.",adenovirally mediated transfer of the fgf-2 gene promoted progenitor cell proliferation more efficiently in widespread regions of the brain after transient global ischemia than continuous intraventricular infusion of fgf-2 protein.,Medication
does ppar agonist pioglitazone reverse memory impairment and biochemical changes in a mouse model of type 2 diabetes mellitus?,"pioglitazone, known as a peroxisome proliferator-activated receptor (ppar) agonist, is used to treat type 2 diabetes mellitus (t2dm). t2dm has been associated with reduced performance on numerous domains of cognitive function. here, we investigated the effects of pioglitazone on memory impairment in a mouse model with defects in insulin sensitivity and secretion, namely high-fat diet (hfd) streptozotocin (stz)-induced diabetic mice. icr mice were fed with hfd for 4 weeks and then injected with a single low dose of stz followed by continued hfd feeding for an additional 4 weeks. pioglitazone (18 mg/kg, 9 mg/kg body weight) was orally administered for 6 weeks once daily. y-maze test and morris water maze test (mwm) were employed for testing learning and memory. serum glucose, serum insulin, serum triglyceride, brain -amyloid peptide (a), brain -site amyloid precursor protein cleaving enzyme (bace1), brain nuclear factor b (nf-b), and brain receptor for advanced glycation end products (rage) were also tested. the stz/hfd diabetic mice, characterized by hyperglycemia, hyperlipemia and hypoinsulinemia, performed poorly on y-maze and mwm hence reflecting impairment of learning and memory behavior with increases of a40/a42, bace1, nf-b, and rage in brain. treatment of ppar agonist, pioglitazone (18 or 9 mg/kg body weight), significantly reversed diabetes-induced impairment of learning and memory behavior, which is involved in decreases of a40/a42 via inhibition of nf-b, bace1 and rage in brain as well as attenuation of hyperglycemia, hyperlipemia, and hypoinsulinemia.",it is concluded that ppar agonist pioglitazone may be considered as potential pharmacological agents for the management of cognitive dysfunction in t2dm.,Medication
does ptov1 expression predict prostate cancer in men with isolated high-grade prostatic intraepithelial neoplasia in needle biopsy?,"to analyze the expression of ptov1 in high-grade prostatic intraepithelial neoplasia (hg-pin) and to explore its usefulness to predict prostate cancer in patients with isolated hg-pin in needle biopsy (prostate needle biopsy). ptov1 expression in hg-pin lesions from 140 patients was analyzed by immunohistochemistry in a semiquantitative manner (histo-score). hg-pin derived from 79 radical prostatectomies for prostate cancer and from 11 cistoprostatectomies for bladder cancer without prostate cancer were used as positive and negative controls, respectively. fifty patients with hg-pin without concomitant cancer at their first prostate needle biopsy were chosen as the study group. patients were followed by a mean of 2.5 repeated prostate needle biopsies (1-5), during a mean period of 12.4 months (1-39). ptov1 expression in hg-pin from radical prostatectomies showed a significantly higher histo-score (162.6) compared with specimens from cistoprostatectomies (67.0). in the study group, ptov1 expression was significantly higher in samples with cancer in the follow-up (11 patients, 22) compared with samples in which cancer was not detected (151.4 versus 94.6). ptov1 expression was the only independent predictor of cancer in the multivariate analysis and the area under the curve was 0.803 (95 confidence interval, 0.728-0.878). a threshold of 100 for ptov1 expression provided 90.9 sensitivity, 51.3 specificity, 34.5 positive predictive value, and 95.2 negative predictive value.",ptov1 is overexpressed in hg-pin associated with cancer and is a potential marker for studying the carcinogenesis and progression of prostate cancer. prostate needle biopsy with ptov1 expression in hg-pin above a threshold of 100 should be repeated immediately for the likely presence of undiagnosed cancer.,Diagnosis
"are cirrhosis , liver transplantation and hiv infection risk factors associated with hepatitis e virus infection?","acute and chronic hepatitis e have been associated with high mortality and development of cirrhosis, particularly in solid-organ recipients and patients infected by human immunodeficiency virus. however, data regarding the epidemiology of hepatitis e in special populations is still limited. investigate seroprevalence and possible factors associated with hev infection in a large cohort of immunosuppressed patients. cross-sectional study testing igg anti-hev in serum samples from 1373 consecutive individuals: 332 liver-transplant, 296 kidney-transplant, 6 dual organ recipients, 301 non-transplanted patients with chronic liver disease, 238 hiv-infected patients and 200 healthy controls. igg anti-hev was detected in 3.5 controls, 3.7 kidney recipients, 7.4 liver transplant without cirrhosis and 32.1 patients who developed post-transplant cirrhosis (p0.01). in patients with chronic liver disease, igg anti-hev was also statistically higher in those with liver cirrhosis (2 vs 17.5, p0.01). hiv-infected patients showed an igg anti-hev rate of 9.2, higher than those patients without hiv infection (p0.03). multivariate analysis showed that the factors independently associated with anti-hev detection were liver cirrhosis, liver transplantation and hiv infection (or: 7.6, 3.1 and 2.4). hcv infection was a protective factor for hev infection (or: 0.4).","hev seroprevalence was high in liver transplant recipients, particularly those with liver cirrhosis. the difference in anti-hev prevalence between liver and kidney transplanted cases suggests an association with advanced liver disease. further research is needed to ascertain whether cirrhosis is a predisposing factor for hev infection or whether hev infection may play a role in the pathogeneses of cirrhosis.",Prevention
is purkinje cell dendritic atrophy induced by prenatal stress mitigated by early environmental enrichment?,"prenatal stress (ps) in experimental animals causes long-lasting changes in purkinje cell dendritic morphology. furthermore, these structural changes are associated with an increase in anxiogenic behaviors in the elevated plus maze (epm) and open-field (of) test. as environmental enrichment (ee) has significant restorative effects on brain neurons and behavior, the aim of this study was to evaluate if postweaning ee mitigates the decrease in purkinje cell dendritic expansion and exploratory behavior induced by ps in mice. restraint stress was induced from gestational day 14 (g14) to g21. approximately 50 of the ps animals were submitted to the ee paradigm between postnatal days 22 (p22) and p52. at p52 and p82, male animals were behaviorally evaluated, and then the morphology of the cerebellar vermal purkinje cells was analyzed. we found that ee significantly ameliorates the purkinje cell dendritic atrophy and anxiety-like behavior in the epm.",our data show that long-lasting purkinje cell dendritic impairments and anxiety-like behavior can be mitigated by postweaning ee.,General
do treatment expectations influence the outcome of multidisciplinary rehabilitation treatment in patients with cfs?,"to improve the effectiveness of treatment in patients with chronic fatigue syndrome it is worthwhile studying factors influencing outcomes. the aims of this study were (1) to assess the association of expectancy and credibility on treatment outcomes, and (2) to identify baseline variables associated with treatment expectancy and credibility. 122 patients were included in a randomized controlled trial of whom 60 received cognitive behavioural therapy (cbt) and 62 multidisciplinary rehabilitation treatment (mrt). expectancy and credibility were measured with the credibility and expectancy questionnaire. outcomes of treatment, fatigue, and quality of life (qol), were measured at baseline and post-treatment. multiple linear regressions were performed to analyse associations. in explaining fatigue and the physical component of the qol, the effect of expectancy was significant for mrt, whereas in cbt no such associations were found. the main effect of expectancy on the mental component of qol was not significant. for credibility, the overall effect on fatigue and the physical component of qol was not significant. in explaining the mental component of qol, the interaction between treatment and credibility was significant. however, the effects within each group were not significant. in the regression model with expectancy as dependent variable, only treatment centre appeared significantly associated. in explaining credibility, treatment centre, treatment allocation and depression contributed significantly.","for clinical practice it seems important to check the expectations of the patient, since expectations influence the outcome after mrt.",Treatment
does joint inhibitory effects research on microcystis aeruginosa and chlorella pyrenoidosa of phenolic acids ?,"to investigate the inhibitory effects of single and compound phenolic acids on mixed algae. salicylic acid, cinnamic acid and pyrogallic acid were chosen individually or in pairs to act on mixed algae of microcystis aeruginosa and chlorella pyrenoidosa. three phenolic acids that singled or paired showed certain inhibitory effects on the mixed algae, of which were pyrogallic acid salicylic acid cinnamic acid in single phenolic acid, the ec50s of the three phenolic acids on the mixture of microcystis aeruginosa and chlorella pyrenoidosa were 7.87, 64.90 and 89.34 mg/l at the day 6; and inhibition of the paired phenolic acid group was pyrogallic acid salicylic acid group pyrogallic acid cinnamic acid group salicylic acid cinnamic acid, the first 2 groups had synergistic algal inhibitory effects and the last paired group showed additive action.","some specifically combined phenolic acids can lead to synergistic inhibiting effects on algae, which has better environmental safety for application due to the use of single phenolic acid was massively decreased.",Medication
does preoperative chemoradiation reduce the risk of pancreatic fistula after distal pancreatectomy for pancreatic adenocarcinoma?,"pancreatic fistula (pf) is a common complication after pancreatectomy. previous reports indicate that preoperative irradiation decreases the risk of pf after pancreatoduodenectomy. in this context, the impact of preoperative chemoradiation therapy (crt) on pf formation after distal pancreatectomy is of interest. fifty-eight patients with pancreatic adenocarcinoma who underwent distal pancreatectomy, including 28 patients with preoperative gemcitabine-based crt and 30 patients without preoperative treatment, were assessed in this study. the incidence and severity of postoperative pf, assessed according to the definition of the international study group on pancreatic fistula, were compared between the 2 groups. in the crt group, 86 of patients did not develop pf, whereas grades a and b pf were observed in 1 and 3 patients, respectively. in the non-crt group, 33 of patients did not develop a pf, whereas grades a and b pf were observed in 9 and 11 patients, respectively. the incidence of clinically significant pf, defined as either grade b or grade c pf, was less in the crt group (p .031). the amylase activities in the draining fluid on postoperative days 1 and 3 were both less in the crt group (p .003 and p .006, respectively).","preoperative crt significantly decreases the incidence of pf after distal pancreatectomy, which potentially provides another benefit to patients in addition to its original advantages (ie, locoregional effect and patient selection effect), allowing more opportunities for the immediate initiation of postoperative adjuvant treatment.",Treatment
are self-rated health and a healthy lifestyle the most important predictors of survival in elderly women?,"to test the hypothesis that morbidity and health related behavioural factors are stronger than social factors as predictors of death among older women. we used data from 12,422 participants in the australian longitudinal study on women's health who were aged 70-75 in 1996. proportional hazards models of survival up to 31 october 2005 were fitted separately for the whole cohort and those women who were initially in 'good health'. among the whole cohort, 18.7 died during the followup period. the strongest predictor of death was 'poor' or 'fair' self-rated health (with 52.3 and 28.0, respectively, of women in these categories dying). among the women in 'good health' at baseline 11.5 died, with current cigarette smoking (hazard ratio hr 2.19, 95 confidence interval (1.71, 2.81), physical inactivity (hr 1.45 (1.17, 1.81)), and age (hr 1.10 (1.04, 1.16) per year) as statistically significant predictors of death.","among older women, current health and health related behaviours are stronger predictors than social factors of relatively early mortality. adopting a healthier lifestyle, by doing more exercise and not smoking, is beneficial even in old age.",Prevention
does time to initial operative treatment following open fracture impact development of deep infection : a prospective cohort study of 736 subjects?,"to evaluate the association between time to surgery, antibiotic administration, gustilo grade, fracture location, and development of deep infection in open fractures. prospective cohort between 2001 and 2009. three level 1 canadian trauma centers. a total of 736 (791 fractures) subjects were enrolled and 686 subjects (93; 737 fractures) provided adequate follow-up data (1-year interview and/or clinical follow-up 90 days). demographics, injury information, time to surgery, and antibiotics were recorded. subjects were evaluated using standardized data forms until the fracture(s) healed. phone interviews were undertaken 1 year after the fracture. infection requiring unplanned surgical debridement and/or sustained antibiotic therapy. tibia/fibula fractures were most common (n 413, 52), followed by upper extremity (ue) (n 285, 36), and femoral (n 93, 12) fractures. infection developed in 46 fractures (6). the median time to surgery was 9 hours 4 minutes (interquartile range, 6 hours 39 minutes to 12 hours 33 minutes) and 7 hours 39 minutes (interquartile range, 6 hours 10 minutes to 9 hours 54 minutes) for those without and with infection, respectively (p 0.04). gustilo grade 3b/3c fractures accounted for 17 of 46 infections (37) (p 0.001). four ue (1.5), 7 femoral (8), and 35 tibia/fibula (9) fractures developed infections (p 0.001). multivariate regression found no association between infection and time to surgery odds ratio (or), 0.97; 95 confidence interval (95 ci), 0.90-1.06 or antibiotics (or, 1.0; 95 ci, 0.90-1.05). grades 3a (or, 6.37; 95 ci, 1.37-29.56) and 3b/3c (or, 12.87; 95 ci, 2.72-60.95) relative to grade 1 injuries and tibia/fibula (or, 3.91; 95 ci, 1.33-11.53) relative to ue fractures were significantly associated with infection.",infection after open fracture was associated with increasing gustilo grade or tibia/fibula fractures but not time to surgery or antibiotics.,Treatment
is significant tricuspid regurgitation a marker for adverse outcome in patients undergoing percutaneous balloon mitral valvuloplasty?,"this study examined the association between the presence of tricuspid regurgitation and immediate and late adverse outcomes in patients undergoing balloon mitral valvuloplasty. significant tricuspid regurgitation has an adverse impact on morbidity and mortality in patients undergoing mitral valve surgery for mitral stenosis. we studied 318 consecutive patients (mean /- sd age 54 /- 15 years) who underwent balloon mitral valvuloplasty and had color doppler echocardiographic studies before the procedure. patients were classified into three groups: 221 with no or mild (69), 60 with moderate (19) and 37 with severe (12) tricuspid regurgitation. clinical follow-up ranged from 6 to 62 months. before mitral valvuloplasty, increasing degrees of tricuspid regurgitation were associated with a smaller initial mitral valve area (p 0.05), higher echocardiographic score (p 0.05), lower cardiac output (p 0.01) and higher pulmonary vascular resistance (p 0.01). although the initial success rate did not differ significantly between groups, patients with a higher degree of tricuspid regurgitation had less optimal results, as reflected by a smaller absolute increase in mitral valve area (1.02 vs. 0.9 vs. 0.7 cm2, p 0.01). the estimated 4-year event-free survival rate (freedom from death, mitral valve surgery, repeat valvuloplasty and heart failure) was lower for the group with severe tricuspid regurgitation (68 vs. 58 vs. 35, p 0.0001). at 4 years, 94 of patients with mild tricuspid regurgitation were alive compared with 90 and 69, respectively, of patients with moderate or severe tricuspid regurgitation (p 0.0001). cox proportional analysis identified tricuspid regurgitation as an independent predictor of late outcome (p 0.001).","patients with mitral stenosis and severe tricuspid regurgitation undergoing mitral valvuloplasty have advanced mitral valve and pulmonary vascular disease, suboptimal immediate results and poor late outcome.",Diagnosis
does portosystemic shunt prevent apoptosis in rat intestinal mucosa caused by total hepatic ischemia?,"prolonged splanchnic congestion due to total hepatic ischemia (thi) has been shown to induce damage to the intestinal mucosa. the present study was conducted to examine whether the protective effect of portosystemic shunt (pss) can be seen on apoptosis of intestinal mucosa in a rat model of thi. adult male wistar rats were divided into the following 3 groups: control group; the thi group underwent thi for 30 min, and the pss group was subjected to thi for 30 min with pss. rats were killed after 1, 2, and 6 h of reperfusion. for each time point, levels of serum liver enzymes, intestinal morphology, malondialdehyde (mda) contents and dna fragmentation in intestinal tissue were determined. in addition, the 7-day survival rate was measured. the 7-day survival rate of thi group remained at 50, whereas that of pss group was significantly higher at 90 (p 0.01). serum ast and alt levels of the thi and pss groups rapidly increased after reperfusion, reaching peak values at 2 h. mda levels after 1 and 2 h of reperfusion in the thi group were significantly increased as compared with the control group (p 0.001). increases in the percentage of fragmented dna peaked 1 h after reperfusion in the thi group. pss resulted in the reduction of dna fragmentation and preserved the macroscopic and microscopic appearance of the intestinal mucosa.",splanchnic congestion due to portal occlusion increased apoptosis in the rat intestinal mucosa. pss is very effective in counteracting the principal negative effects of total hepatic ischemia.,Prevention
do high-mobility group box-1 protein serum levels reflect monocytic function in patients with sepsis-induced immunosuppression?,"high-mobility group box-1 (hmgb-1) protein is released during ""late sepsis"" by activated monocytes. we investigated whether systemic hmgb-1 levels are associated with indices of monocytic activation/function in patients with sepsis-induced immunosuppression. 36 patients (31 male, 64 /- 14 years) with severe sepsis/septic shock and monocytic deactivation (reduced mhla-dr expression and tnf-alpha release) were assessed in a subanalysis of a placebo-controlled immunostimulatory trial using gm-csf. hmgb-1 levels were assessed over a 9-day treatment interval. data were compared to standardized biomarkers of monocytic immunity (mhla-dr expression, tnf-alpha release). hmgb-1 levels were enhanced in sepsis but did not differ between treatment and placebo groups at baseline (14.6 /- 13.5 versus 12.5 /- 11.5 ng/ml, p .62). when compared to controls, hmgb-1 level increased transiently in treated patients at day 5 (27.8 /- 21.7 versus 11.0 /- 14.9, p .01). between group differences were not noted at any other point of assessment. hmgb-1 levels were not associated with markers of monocytic function or clinical disease severity.",gm-csf treatment for sepsis-induced immunosuppression induces a moderate but only transient increase in systemic hmgb-1 levels. hmgb-1 levels should not be used for monitoring of monocytic function in immunostimulatory trials as they do not adequately portray contemporary changes in monocytic immunity.,Medication
does lestaurtinib inhibit histone phosphorylation and androgen-dependent gene expression in prostate cancer cells?,"epigenetics is defined as heritable changes in gene expression that are not based on changes in the dna sequence. posttranslational modification of histone proteins is a major mechanism of epigenetic regulation. the kinase prk1 (protein kinase c related kinase 1, also known as pkn1) phosphorylates histone h3 at threonine 11 and is involved in the regulation of androgen receptor signalling. thus, it has been identified as a novel drug target but little is known about prk1 inhibitors and consequences of its inhibition. using a focused library screening approach, we identified the clinical candidate lestaurtinib (also known as cep-701) as a new inhibitor of prk1. based on a generated 3d model of the prk1 kinase using the homolog pkc-theta (protein kinase c theta) protein as a template, the key interaction of lestaurtinib with prk1 was analyzed by means of molecular docking studies. furthermore, the effects on histone h3 threonine phosphorylation and androgen-dependent gene expression was evaluated in prostate cancer cells.","lestaurtinib inhibits prk1 very potently in vitro and in vivo. applied to cell culture it inhibits histone h3 threonine phosphorylation and androgen-dependent gene expression, a feature that has not been known yet. thus our findings have implication both for understanding of the clinical activity of lestaurtinib as well as for future prk1 inhibitors.",Medication
are polymorphisms of udp-glucuronosyltransferase 1a7 involved in pancreatic diseases?,"xenobiotic mediated cellular injury is thought to play a major role in the pathogenesis of pancreatic diseases. genetic variations that reduce the expression or activity of detoxifying phase ii biotransformation enzymes such as the udp-glucuronosyltransferases might be important in this respect. recently, a ugt1a7 low detoxification activity allele, ugt1a73, has been linked to pancreatic cancer and alcoholic chronic pancreatitis. to investigate whether ugt1a7 polymorphisms contribute to the risk of pancreatitis and pancreatic cancer. genetic polymorphisms in the ugt1a7 gene were assessed in a large cohort of patients with different types of pancreatitis and pancreatic cancer originating from the czech republic (n 93), germany (n 638), netherlands (n 136), and switzerland (n 106), and in healthy (n 1409) and alcoholic (n 123) controls from the same populations. polymorphisms were determined by melting curve analysis using fluorescence resonance energy transfer probes. in addition, 229 dutch subjects were analysed by restriction fragment length polymorphism. the frequencies of ugt1a7 genotypes did not differ between patients with acute or chronic pancreatitis or pancreatic adenocarcinoma and alcoholic and healthy controls.","the data suggest that, in contrast to earlier studies, ugt1a7 polymorphisms do not predispose patients to the development of pancreatic cancer and pancreatitis.",General
are de novo missense variants in hecw2 associated with neurodevelopmental delay and hypotonia?,"the causes of intellectual disability (id) are diverse and de novo mutations are increasingly recognised to account for a significant proportion of id. in this study, we performed whole exome sequencing on a large cohort of patients with id or neurodevelopmental delay and identified four novel de novo predicted deleterious missense variants in hecw2 in six probands with id/developmental delay and hypotonia. other common features include seizures, strabismus, nystagmus, cortical visual impairment and dysmorphic facial features. hecw2 is an ubiquitin ligase that stabilises p73, a crucial mediator of neurodevelopment and neurogenesis.",this study implicates pathogenic genetic variants in hecw2 as potential causes of neurodevelopmental disorders in humans.,General
is entecavir monotherapy effective in suppressing hepatitis b virus after liver transplantation?,"we investigated the efficacy of entecavir, a cyclopentyl guanosine nucleoside analogue, as monoprophylaxis in patients with chronic hepatitis b who received a liver transplant. we studied data from 80 consecutive patients who received a liver transplant (47 from living donors and 33 from deceased donors) for hepatitis b-related disease and entecavir monotherapy as prophylaxis. none of the patients received hepatitis b immunoglobulin. indications for transplant included decompensation from cirrhosis (27.5), acute-on-chronic hepatitis b (47.5), and hepatocellular carcinoma (25). the median follow-up time was 26 months (range, 5-40 months). before transplant, 33 patients were not on antiviral therapy and 47 were on oral therapy (18 had received less than 3 months of treatment). at the time of transplant, the median log hbv dna level was 3.5 copies/ml (range, 1.54-8.81); 21 patients (26) had undetectable levels of hbv dna. the cumulative rate of hepatitis b surface antigen (hbsag) loss was 86 and 91 after 1 and 2 years, respectively. ten patients had reappearance of hbsag. eighteen patients (22.5) were hbsag positive at the time of their last examination; 17 of these had undetectable levels of hbv dna, and the remaining patient had a low level of hbv dna (217 copies/ml). there was no evidence of mutations at sites that confer resistance to entecavir among patients who were hbsag positive.","although only 26 of patients had complete viral suppression at the time of transplant, 91 lost hbsag, with 98.8 achieving undetectable levels of hbv dna. a hepatitis b immunoglobulin-free regimen of entecavir monotherapy is effective after liver transplantation for chronic hepatitis b.",Treatment
does smokeless tobacco extract affect biological properties of the pre-osteoblast cell line mc3t3-e1 ?,"to investigate the effects of smokeless tobacco extract (ste) on biological properties of osteoblast, and to identify possible pathological mechanisms of osseointegration. mc3t3-e1 sub-clone 14 cells were cultured in the presence of ste at 0 (control group),0. 01,0. 1,1,5,10 g/l. the cell proliferation was measured by mtt assay 1 d, 3 d, 5 d, and 7 d after exposure. the f-actin cytoskeleton of mc3t3 was stained with rhodamine and dapi, and then examined under a confocal laser scanning microscope 24 h after exposure to ste. the mrna expressions of interleukin-6 (il-6) and core-binding factor l(cbfl) were quantified by real- time pcr (rt-qpcr) 48 h after exposure to ste. the mtt assay showed that 0. 01-10 g/l ste inhibited mc3t3 proliferation (p0. 05). prolonged time enabled 5-10 g/l ste to inhibit mc3t3 proliferation (p0. 05). network structure in f-actin cytoskeleton was demonstrated in the controls. in the cells exposed to ste, f-actin cytoskeleton started to change with disruptive structures. as the concentration of ste increased, the changes became more significant. ste increased the mrna expression of il-6 at the concentration of 5 g/l and 10 g/l (p0.05), decreased the mrna expression of cbf1 at the concentration of 0. 1-10 g/l (po0. 05).","tobacco may inhibit osteoblast proliferation, destroy f-actin cytoskeleton structure, increase the mrna expression of il-6 and decrease the mrna expression of cbf1, and inhibit cell differentiation and adhesion accordingly. smoking is a disadvantage to osseointegration.",General
do association of low serum total cholesterol with major depression and suicide?,"it has been suggested that low serum total cholesterol is associated with an increased risk of suicide. to study the association between serum total cholesterol, depression and suicide using versatile, prospective data. a total of 29,133 men aged 50-69 years were followed up for 5-8 years. baseline blood samples were analysed for serum total and high-density lipoprotein cholesterol concentrations. self-reported depression was recorded, data on hospital treatments due to depressive disorders were derived from the national hospital discharge register and deaths from suicide were identified from death certificates. low serum total cholesterol was associated with low mood and subsequently a heightened risk of hospital treatment due to major depressive disorder and of death from suicide.",our results suggest that low serum total cholesterol appears to be associated with low mood and thus to predict its serious consequences.,Treatment
do bmps induce endochondral ossification in rats when implanted ectopically within a carrier made of fibrous glass membrane?,"bone morphogenetic proteins (bmps) replicate the process of embryonic bone formation when implanted in ectopic sites. our previous studies have indicated that bmps can induce intramembranous ossification, i.e., direct bone formation without preexisting cartilage when implanted in rats subcutaneously by using the fibrous collagen membrane (fcm) as a carrier for implanting bmps (sasano et al. 1993. anat. rec., 236:373-380). the present study was designed to investigate how the physicochemical property of the carrier material influences the process of bone formation induced by bmps, using a carrier made of fibrous glass membrane (fgm). bmps, partially purified from bovine metatarsal bones, were added to an fgm carrier and implanted subcutaneously in rats. the implants were analyzed at weekly intervals, and the osteogenic process induced by bmps was examined by histology and immunohistochemistry for cartilage and bone formation. neither cartilage nor bone were observed after week 1. cartilage formation occurred within the carrier after week 2, although no bone formation was seen. the cartilage matrix showed immunoreactivity for types ii, x, and i collagen. bone was induced on the previously formed cartilage after week 3. the bone matrix stained with anti-osteocalcin antibody and with anti-type i collagen antibody. the cartilage was replaced by bone and bone marrow after week 10.",bmps cause endochondral ossification when administered with an fgm carrier. the physicochemical property of the carrier may be involved in the bmp-induced phenotype expression of bone and cartilage.,General
"is tdrd6 required for spermiogenesis , chromatoid body architecture , and regulation of mirna expression?","chromatoid bodies (cbs) are characteristic spermatid organelles, which were suggested to function in rna storage and small rna processing but whose functions remain largely unknown. cb components include mili, miwi, and tudor domain proteins such as tdrd6, whose contribution to cb structure and function is elusive. we determined gametogenesis stage- and male-specific expression and localization of tdrd6, identified a c-terminally truncated form as predominant after meiosis i, and demonstrated direct physical interaction of tdrd6 with the cb components mili and miwi. development from round into elongated spermatids is abrogated in tdrd6(-/-) mice. their round spermatids bear ""ghost"" cbs, whose architecture is greatly disrupted. mael, miwi, and mvh do not localize to the tdrd6-deficient cbs, but retrotransposons are not significantly activated. however, more than 50 mirnas are more abundant in tdrd6(-/-) testes, as are exemplary pre- and pri-mirnas.","we conclude that tdrd6 is essential for spermiogenesis, for cb structure, and for proper mature and precursor mirna expression.",General
are anti-cyclic citrullinated peptide antibodies associated with familial mediterranean fever?,"this study investigated the presence of anti-cyclic citrullinated peptide (anti-ccp) antibodies in familial mediterranean fever (fmf) patients and controls. forty-nine patients with fmf were enrolled (23 had a history of arthritis during attacks and 26 had no such history). two control groups were enrolled: 20 patients with rheumatoid arthritis (ra) and 30 healthy individuals. clinical and laboratory assessments of the fmf patients were performed during attack-free periods. erythrocyte sedimentation rate (esr), serum c-reactive protein (crp), rheumatoid factor (rf), and anti-ccp antibody levels were measured. in ra patients' esr and crp levels, frequency of rf, and anti-ccp antibody levels were significantly higher than in both fmf patients and healthy controls (p 0.001). moreover, anti-ccp was negative in all healthy controls as well as in all fmf patients.",our results show that anti-ccp antibodies are not associated with fmf.,Symptoms
is corneal power change predictive of myopia progression in orthokeratology?,"this study aims to investigate the relationship between corneal refractive power change along three axes (nasal, temporal, and inferior) after orthokeratology (ok) treatment and 2-year axial growth in children. thirty-two chinese children aged from 9 to 14 were fitted with ok. when corneal reshaping process following ok treatment was completed and stabilized, the 3-month topographic outputs were taken as the post-ok data. corneal refractive powers along the nasal, temporal, and inferior axes were collected over an 8-mm-diameter ring in 1-mm steps using the sagittal power map. the maximum power change along each axis was selected and divided into two subcategories, level 1 and level 2, depending on whether the value was below or above the average. axial length (al) was measured every 6 months during a 24-month period. the relationship between the maximum power changes and 2-year axial elongation were analyzed. twenty-seven subjects completed the 24-month study. after ok treatment, statistically significant steepening (p 0.05) was observed at the nasal 2 mm and 3 mm; temporal 3 mm; and inferior 2 mm, 3 mm, and 4 mm locations compared with the apical center. al increased significantly throughout the 24-month observation period (p 0.001). changes in corneal refractive power significantly affected axial elongation (nasal, p 0.001; temporal, p 0.011; inferior, p 0.001). two-year axial elongation in patients with larger corneal power changes (level 2) was reduced by 54 to 69 compared with those with smaller corneal power changes (level 1). maximum power changes along the three axes were negatively correlated (p 0.05) with 2-year axial growth.",subjects with larger magnitude of corneal relative peripheral power change along specific axes after ok treatment experienced slower axial elongation by the end of 24 months. this effect might be mediated by the induction of greater amount of relative myopic defocus on the peripheral retina. our study lends weight to potential ok lens designs for myopia control in children.,Treatment
does an amelogenin mutation lead to disruption of the odontogenic apparatus and aberrant expression of notch1?,"amelogenins are highly conserved proteins secreted by ameloblasts in the dental organ of developing teeth. these proteins regulate dental enamel thickness and structure in humans and mice. mice that express an amelogenin transgene with a p70t mutation (tgp70t) develop abnormal epithelial proliferation in an amelogenin null (ko) background. some of these cellular masses have the appearance of proliferating stratum intermedium, which is the layer adjacent to the ameloblasts in unerupted teeth. as notch proteins are thought to constitute the developmental switch that separates ameloblasts from stratum intermedium, these signaling proteins were evaluated in normal and proliferating tissues. mandibles were dissected for histology and immunohistochemistry using notch1 antibodies. molar teeth were dissected for western blotting and rt-pcr for evaluation of notch levels through imaging and statistical analyses. notch1 was immunolocalized to ameloblasts of tgp70tko mice, ko ameloblasts stained, but less strongly, and wild-type teeth had minimal staining. cells within the proliferating epithelial cell masses were positive for notch1 and had an appearance reminiscent of calcifying epithelial odontogenic tumor with amyloid-like deposits. notch1 protein and mrna were elevated in molar teeth from tgp70tko mice.","expression of tgp70t leads to abnormal structures in mandibles and maxillae of mice with the ko genetic background and these mice have elevated levels of notch 1 in developing molars. as cells within the masses also express transgenic amelogenins, development of the abnormal proliferations suggests communication between amelogenin producing cells and the proliferating cells, dependent on the presence of the mutated amelogenin protein.",Diagnosis
do estradiol-treated mesenchymal stem cells improve myocardial recovery after ischemia?,"stem cell therapy is a promising treatment modality for injured cardiac tissue. a novel mechanism for this cardioprotection may include paracrine actions. our lab has recently shown that gender differences exist in mesenchymal stem cell (msc) paracrine function. estrogen is implicated in the cardioprotection found in females. it remains unknown whether 17beta-estradiol (e2) affects msc paracrine function and whether e2-treated mscs may better protect injured cardiac tissue. we hypothesize that e2-exposed mscs infused into hearts prior to ischemia may demonstrate increased vascular endothelial growth factor (vegf) production and greater protection of myocardial function compared to untreated mscs. untreated and e2-treated mscs were isolated, cultured, and plated and supernatants were harvested for vegf assay (enzyme-linked immunosorbent assay). adult male sprague-dawley rat hearts (n 13) were isolated and perfused via langendorff model and subjected to 15 min equilibration, 25 min warm global ischemia, and 40 min reperfusion. hearts were randomly assigned to perfusate vehicle, untreated male msc, or e2-treated male msc. transcoronary delivery of 1 million mscs was performed immediately prior to ischemia in experimental hearts. e2-treated mscs provoked significantly more vegf production than untreated mscs (933.2 /- 64.9 versus 595.8 /- 10.7 pg/ml). postischemic recovery of left ventricular developed pressure was significantly greater in hearts infused with e2-treated mscs (66.9 /- 3.3) than untreated mscs (48.7 /- 3.7) and vehicle (28.9 /- 4.6) at end reperfusion. there was also greater recovery of the end diastolic pressure with e2-treated mscs than untreated mscs and vehicle.","preischemic infusion of mscs protects myocardial function and viability. e2-treated mscs may enhance this paracrine protection, which suggests that ex vivo modification of mscs may improve therapeutic outcome.",Treatment
does total number of resected lymph nodes predict survival in esophageal cancer?,"several population-based studies have shown that the total number of surgically removed lymph nodes is independently associated with overall and disease-free survival in a variety of gastrointestinal cancers. in this retrospective study, the impact of total nodal count on overall survival in esophageal cancer was examined using a single institution surgical database. we conducted a retrospective review of 264 patients with esophageal cancer treated by esophagectomy without neoadjuvant therapy between january 1988 and december 2006. the association between overall survival (the primary endpoint) and the total number of dissected lymph nodes was evaluated using multivariable cox regression models. when the total number of resected nodes was examined as a categorical variable based on quartiles (category 1: 40) there was a reduced hazard of death with increasing number of examined nodes. compared with those in category 1, the death hazard was reduced by 34 (p 0.08), 48 (p 0.001), and 49 (p 0.001), respectively, for patients in categories 2, 3, and 4. for node negative patients a significantly reduced hazard was present only when more than 40 nodes were resected (hr 0.23, p 0.01). for node positive patients the death hazard was significantly reduced for those in all higher categories compared with those in category 1 (hr 0.53, 0.39, 0.49; p 0.03, 0.001, 0.02, respectively).","these data support the findings from population based studies in esophageal cancer and other gastrointestinal tumors, suggesting that a higher nodal count favorably influences survival.",Treatment
is hand-assisted laparoscopic splenectomy a better choice for patients with supramassive splenomegaly due to liver cirrhosis?,"the current laparoscopic splenectomy (ls) procedure used for cirrhotic patients still has limitations. the aim of our study was to determine a standard according to the splenic size for hand-assisted ls (hals) in patients with splenomegaly and hypersplenism due to cirrhosis. we conducted a retrospectively review of cirrhotic patients who underwent splenectomy between 2008 and 2011. all patients were divided into two groups: group a (19 patients), in which patients' operations were conducted by hals, and group b (20 patients), in which patients were treated with ls. then the patients in group a were classified on the basis of the spleen size: massive splenomegaly (group a1) and supramassive splenomegaly (group a2). likewise, so were patients in group b: massive splenomegaly (group b1) and supramassive splenomegaly (group b2). perioperative outcomes of these patients were compared. the comparison of hals and ls based on spleen size demonstrated that in the massive splenomegaly groups, group a1 and group b1 had similar estimated blood loss and morbidity, and no transfusion was required in these patients. in the supramassive splenomegaly groups, compared with group a2, group b2 had longer operative time, more estimated blood loss, more patients requiring transfusion, and more complications that needed surgical intervention. however, no significant differences were observed in the requirement of analgesia, time of returning to oral intake, and length of hospitalization in these paired groups.","in cirrhotic patients with supramassive splenomegaly, hals should be considered because of its safety, feasibility, and effectiveness.",Treatment
do nitric oxide and pro-inflammatory cytokines correlate with pain intensity in chronic pain patients?,"inflammatory cytokines as well as nitric oxide (no) play a key role in the pathogenesis of persistent and exaggerated pain states. to document this, we investigated whether a range of cytokines and no were detectable in the plasma of chronic pain patients and whether cytokine and no levels correlated with pain severity. plasma samples of 94 chronic pain patients and 6 healthy volunteers were obtained. average pain intensity during the last 24 h was assessed on a 11-point numeric rating scale and patients were distributed to three groups: light, moderate and severe pain. the concentrations of tnf-alpha, gm-csf, interleukin (il)-1beta, il-6, il-8, interferon (ifn)-gamma, il-2, il-4, il-5, il-10 and nitrate/nitrite were determined. patients with light pain demonstrated significantly increased levels of il-6 compared to controls. in the severe pain group il-6 and nitrate/nitrite were significantly increased. serum concentrations of il-1beta, tnf-alpha, il-2 and il-4 were increased but as we adjusted the level of significance at p 0.0045, most cytokine plasma levels failed to reach statistical significance.","pro-inflammatory cytokines (il-1beta, il-2, il-6, ifn-gamma, tnf-alpha) in the plasma correlate with increasing pain intensity. chronic pain patients show a significant increase in plasma levels of no in comparison to healthy controls.",Symptoms
is primary cilium required for the stimulating effect of icaritin on osteogenic differentiation and mineralization of osteoblasts in vitro?,"icaritin, one effective metabolite of herba epimedii-derived flavonoid icariin, has a strong osteogenic activity. however, its action mechanism remains unclear. since primary cilia have been shown to play a pivotal role in regulating the osteogenesis, we hypothesized primary cilia are indispensable in mediating icaritin osteogenic effect. primary rat calvarial osteoblasts were transfected with sirna1 targeting intraflagellar transport protein 88 (ift88), a protein required for ciliogenesis, to prevent formation of primary cilium and were treated with 10 alkaline phosphatase (alp) activity was significantly increased after 3 days in cells transfected with scrambled sirna control and treated by icaritin (sci group) compared to cells transfected with scrambled sirna control only (sc group). alp activity after ift88 sirna1 transfection and icaritin treatment (sirna1i group) was significantly lower than that of sci group. formation of alp positively stained colonies after 6 days, osteocalcin secretion after 9 days and formation of calcified nodules after 12 days displayed a similar tendency among the three groups. mrna expression of osteogenesis-related genes alp, bmp-2, col1, runx-2 and osx after 24 h was significantly increased in sci group, but was not different with sc group in sirna1i group. protein levels of bmp-2, col1, runx-2 and osx after 48 h showed the similar tendency with gene expression.",primary cilia are important in mediating icaritin-stimulated osteogenic differentiation and may be a novel target for pharmacological therapies for bone loss.,Prevention
do tone recognition ability for post-lingually deafened cochlear implant users using pitch information ?,"the present study was aimed to assess the ability of tone recognition performance for postlingually deafed cochlear implanted adults using no-duration tone test materials. sixteen cochlear implanted users have used their devices at least six months. ten monosyllabic syllables were selected, and combined with four lexical tones which were made up of 40 tone tokens. then, these original words were recorded using one adult male and one adult female native beijing mandarin speaker. the speakers were asked to record these 40 monosyllabic words multiple times, and the 80 tokens in which the durations of four tones in each monosyllabic word were within 5 ms precision were chosen as the original tone tokens. the subjects were asked to perform a four alternative forced-choice study and select the tone they had heard. the mean score of lexical tone perception tasks for 16 cochlear implanted users is (70.7 22.0), and tone 4 was the easiest to perceive, while tone 2 was the hardest for cochlear implanted subjects to perceive. tone 1 was more often misperceived as tone 2 relative to other tones. tone 2 was more often misperceived as tone 1 and 3. tone 3 was more often misperceived as tone 2. the tone perception performance was positively correlated with duration of hearing aid use.","duration cues may impact on the ability of tone recognition performance for cochlear implant subjects, especially for tone 3. due to the limited ability for cochlear implant subjects on pitch perception, tone l and tone 2, and tone 2 and tone 3 are most often confused with each other without duration cues. the experience of hearing aid use may benefit for postlingual deafness cochlear implant recipients on tone perception performance.",General
do pediatric hospitalists collaborate to improve timeliness of discharge communication?,"the transition of care from hospital to primary care provider (pcp) at discharge carries the potential for significant information loss. there is evidence that the timeliness and content of discharge communication are often unreliable during this handoff. suboptimal transitions of care at discharge have been associated with adverse outcomes, and efficient solutions are required to transform the current state. our specific aim was the achievement 90 documentation of hospitalist-pcp communication within 2 days of hospital discharge in 16 weeks of continuous data required for inclusion. the mean rate of documentation of timely discharge communication across the collaborative increased from 57 to 85 over the study period. for the 7 hospitals that were able to collect 16 weeks of data before july 2010, the mean rate of communication was 90. participants reported that the context of the collaborative contributed to their success.",timely hospitalist-pcp communication was inconsistent at the beginning of the study. this low-resource quality improvement collaborative was able to achieve rapid improvement and resulted in improved perceptions of quality improvement knowledge among participants.,General
"is anorectal physiology changed following transanal haemorrhoidal dearterialization for haemorrhoidal disease : clinical , manometric and endosonographic features?","the effect of transanal haemorrhoidal dearterialization (thd) on continence and anorectal physiology has not yet been demonstrated. twenty patients suffering from 3rd degree haemorrhoids were enrolled and underwent thd, including both dearterialization and mucopexy. clinical assessment, anorectal manometry, rectal volumetry and endoanal ultrasound were performed preoperatively and at 6 months postoperatively. postoperatively two and six patients had transient rectal pain and tenesmus, respectively. no patient reported faecal urgency or minor or major incontinence. all patients remained able to discriminate gas from faeces. no significant variation of the mean values of anal manometric and rectal volumetric parameters was recorded at 6 months of follow-up compared with preoperative values. at 6 months both internal and external sphincters were endosonographically intact.",thd does not cause trauma to the anal canal and rectum.,Treatment
does radiation dose predict for biochemical control in intermediate-risk prostate cancer patients treated with low-dose-rate brachytherapy?,"to evaluate the influence of patient- and treatment-related factors on freedom from biochemical failure (ffbf) in patients with intermediate-risk prostate cancer. from a prospectively collected database of 2250 men treated at mount sinai hospital from 1990 to 2004 with low-dose-rate brachytherapy for prostate cancer, 558 men with either one or more intermediate-risk features (prostate-specific antigen psa level 10-20 ng/ml, gleason score 7, or stage t2b) were identified who had a minimum follow-up of 24 months and postimplant ct-based dosimetric analysis. biologically effective dose (bed) values were calculated to compare doses from different isotopes and treatment regimens. patients were treated with brachytherapy with or without hormone therapy and/or external-beam radiotherapy. patient- and treatment-related factors were analyzed with respect to ffbf. the median follow-up was 60 months (range, 24-167 months). biochemical failure was defined according to the phoenix definition. univariate analyses were used to determine whether any variable was predictive of ffbf. a two-sided p value of or150 gy(2)) was the only significant predictor of ffbf (p 0.001). none of the other variables (psa, external-beam radiotherapy, gleason score, treatment type, hormones, stage, and number of risk factors) was found to be a statistically significant predictor of 10-year ffbf.",radiation dose is an important predictor of ffbf in intermediate-risk prostate cancer. treatment should continue to be individualized according to presenting disease characteristics until results from radiation therapy oncology group trial 0232 become available.,Treatment
does fibroblast-derived mt1-mmp promote tumor progression in vitro and in vivo?,"identification of fibroblast derived factors in tumor progression has the potential to provide novel molecular targets for modulating tumor cell growth and metastasis. multiple matrix metalloproteases (mmps) are expressed by both mesenchymal and epithelial cells within head and neck squamous cell carcinomas (hnsccs), but the relative importance of these enzymes and the cell source is the subject of controversy. the invasive potential of hnscc tumor cells were assessed in vitro atop type i collagen gels in coculture with wild-type (wt), mmp-2 null, mmp-9 null or mt1-mmp null fibroblasts. a floor of mouth mouse model of hnscc was used to assess in vivo growth after co-injection of fadu tumor cells with mmp null fibroblasts. here we report changes in tumor phenotype when fadu hnsccs cells are cocultured with wt, mmp-2 null, mmp-9 null or mt1-mmp null fibroblasts in vitro and in vivo. wt, mmp-2 null and mmp-9 null fibroblasts, but not mt1-mmp null fibroblasts, spontaneously invaded into type i collagen gels. wt fibroblasts stimulated fadu tumor cell invasion in coculture. this invasive phenotype was unaffected by combination with mmp-9 null fibroblasts, reduced with mmp-2 null fibroblasts (50) and abrogated in mt1-mmp null fibroblasts. co-injection of fadu tumor cells with fibroblasts in an orthotopic oral cavity scid mouse model demonstrated a reduction of tumor volume using mmp-9 and mmp-2 null fibroblasts (48 and 49, respectively) compared to wt fibroblasts. consistent with in vitro studies, mt1-mmp null fibroblasts when co-injected with fadu cells resulted in a 90 reduction in tumor volume compared to fadu cells injected with wt fibroblasts.",these data suggest a role for fibroblast-derived mmp-2 and mt1-mmp in hnscc tumor invasion in vitro and tumor growth in vivo.,Medication
does ginkgo biloba protect against intermittent hypoxia-induced memory deficits and hippocampal dna damage in rats?,"the aim of the present study was to explore the potential protective effect of ginkgo biloba extract (egb 761) on intermittent hypoxia (ih)-induced memory deficits and oxidative stress in rats. the passive avoidance reflex (par) test was employed to assess the effect of concurrent egb 761 treatment in different dose levels on the memory deficits that were induced by concurrent long-term exposure to ih (21 days). the levels of hippocampal malondialdehyde (mda), nitric oxide (no), and intracellular glutathione (gsh) and the activity of glutathione peroxidase (gsh-px) were estimated. in addition, serum and hippocampal 8-hydroxy-2'-deoxyguanosine (8-ohdg) levels were assessed to study the effect of egb 761 on hippocampal oxidative dna damage induced by ih. exposure to long-term ih in rats induced marked memory impairment that was indicated by a significant decrease in the retention latency in the par test. this effect was accompanied by a significant increase in hippocampal oxidative stress and dna damage. egb 761 that was administered in either 50- or 100-mg/kg doses per day reversed ih-induced memory deficits, an effect that was accompanied by a significant decrease in hippocampal mda and no levels. the antioxidant defence (gsh and gsh-px) that was depressed by ih was significantly reactivated by egb 761. furthermore, serum and hippocampal levels of 8-ohdg that were elevated by ih were significantly reduced.","egb 761 can protect against ih-induced memory impairment, oxidative stress and neuronal dna damage, possibly through multiple mechanisms involving its potential anti-oxidative effect.",Medication
does marine cyanobacteria-derived serotonin receptor 2c active fraction induce psychoactive behavioral effects in mice?,"marine cyanobacteria offer a robust resource for natural products drug discovery due to the secondary metabolites they produce. to identify novel cyanobacterial compounds that exhibit cns psychoactive effects. cyanobacteria were collected from las perlas archipelago, panama and subjected to dichloromethane/methanol extraction and fractionation by column chromatography before being screened for affinity against a panel of cns targets. a 50:50 ethyl acetate:methanol fraction of one cyanobacterial extract (2064h) was subjected to hplc and the major peak was isolated (2064h3). at a dose of 20 g per animal, 2064h and 2064h3 were tested in mice using behavioral assays that included the forced swim, open field and formalin tests. 2064h was shown to bind to the serotonin 2c (5-ht","overall, manipulating the 5-ht",Medication
are low levels of vitamin d associated with multimorbidity : results from the lifelines cohort study?,"the prevalence of multimorbidity ( 1 disease within an individual) is rapidly increasing. so far, studies on the relationship between vitamin d and morbidity are mainly focusing on effects on single disease domains only, while vitamin d biology is associated with several diseases throughout the human body. we studied 8,726 participants from the lifelines cohort study (a cross-sectional, population-based cohort study) and used the self-developed composite morbidity score to study the association between vitamin d levels and multimorbidity. study participants (mean age 45 13 years, 73 females) had a mean plasma vitamin d level of 59 22 nmol/l. in participants aged between 50 and 60 years, 58 had 2 affected disease domains, while morbidity score increased with age (70-80 years: 82 morbidity score 1; 80 years: 89 morbidity score 1). each incremental reduction by 1 standard deviation (sd) of vitamin d level was associated with an 8 higher morbidity score (full model or 0.92, 95 ci 0.88-0.97, p 0.001). participants with vitamin d levels 80 nmol/l, or 1.34, 95 ci 1.07-1.67, p 0.01).","low levels of vitamin d are associated with higher prevalence of multimorbidity, especially in participants with vitamin d levels 25 nmol/l. collectively, our results favor a general, rather than an organ-specific, approach when assessing the impact of vitamin d deficiency.",General
is the mini-mental state exam ( mmse ) sensitive to cognitive impairment in bariatric surgery candidates?,"cognitive dysfunction is common among bariatric surgery candidates and associated with poorer weight loss outcomes. identification of a brief screening measure to detect cognitive impairment in this population is needed, because comprehensive neuropsychological evaluations may not be available in all clinical settings. the present study examined the utility of the mini-mental state examination (mmse) for detecting cognitive impairment in 30 bariatric surgery candidates by comparing impairment on the mmse (at varying cutoffs) to impairment on a comprehensive neuropsychological test battery. results indicated that the mmse showed low sensitivity and specificity in identifying impairment, even at the more stringent mmse cutoffs of 27 and 28.",these findings suggest that the mmse is a poor screener for cognitive impairment in bariatric surgery candidates. future research is needed to identify or develop cognitive screeners for use in this population.,Treatment
do distinct phenotypes distinguish the molecular classes of angelman syndrome?,"angelman syndrome (as) is a severe neurobehavioural disorder caused by defects in the maternally derived imprinted domain located on 15q11-q13. most patients acquire as by one of five mechanisms: (1) a large interstitial deletion of 15q11-q13; (2) paternal uniparental disomy (upd) of chromosome 15; (3) an imprinting defect (id); (4) a mutation in the e3 ubiquitin protein ligase gene (ube3a); or (5) unidentified mechanism(s). all classical patients from these classes exhibit four cardinal features, including severe developmental delay and/or mental retardation, profound speech impairment, a movement and balance disorder, and as specific behaviour typified by an easily excitable personality with an inappropriately happy affect. in addition, patients can display other characteristics, including microcephaly, hypopigmentation, and seizures. we restricted the present study to 104 patients (93 families) with a classical as phenotype. all of our patients were evaluated for 22 clinical variables including growth parameters, acquisition of motor skills, and history of seizures. in addition, molecular and cytogenetic analyses were used to assign a molecular class (i-v) to each patient for genotype-phenotype correlations. in our patient repository, 22 of our families had normal dna methylation analyses along 15q11-q13. of these, 44 of sporadic patients had mutations within ube3a, the largest percentage found to date. our data indicate that the five molecular classes can be divided into four phenotypic groups: deletions, upd and id patients, ube3a mutation patients, and subjects with unknown aetiology. deletion patients are the most severely affected, while upd and id patients are the least. differences in body mass index, head circumference, and seizure activity are the most pronounced among the classes.","clinically, we were unable to distinguish between upd and id patients, suggesting that 15q11-q13 contains the only significant maternally expressed imprinted genes on chromosome 15.",General