title stringlengths 0 1.13k | abstract stringlengths 1 15.7k | PMID int64 22 36.5M |
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Edema caused by continuous epidural hydromorphone infusion: a case report and review of the literature. | Intraspinal drug delivery (IDD) therapy has been increasingly employed in patients with intractable, nonmalignant pain. Before implantation of permanent intraspinal pump, an intraspinal opioid screening trial is conducted to demonstrate the efficacy. The patient-controlled continuous epidural opioid infusion trail, performed in an outpatient setting, is widely accepted by many interventional pain specialists. To report a case of severe edema observed during the continuous epidural hydromorphone infusion trial. An otherwise healthy 68-year-old lady with a 5-year history of severe low back pain and bilateral leg pain because of failed back surgery syndrome was referred to our clinic for IDD therapy. A tunneled lumbar epidural catheter was placed at L2-L3 with catheter tip advanced to L1 under fluoroscopic guidance. Satisfactory catheter placement was confirmed by epidurogram. The catheter was then tunneled subcutaneously and connected to a Microject patient-controlled epidural analgesia (PCEA) pump (Codman, Raynham, MA). The pump was programmed to deliver hydromorphone (0.1 mg/ml) at basal rate of 0.3 ml/h. The bolus dose was 0.1 ml with a 60-minute lockout interval. The patient was instructed how to operate the infusion pump. During the following infusion trial, she reported satisfactory analgesia (> 70 percent pain reduction) and was able to wean off her other systemic opioids. However, she developed diffuse edema and gained over 16 pounds during the 5-day infusion trial. Her edema finally resolved 3-4 days after termination of the epidural infusion. Edema may occur and persist during epidural hydromorphone infusion. This report represents the first case report, to the best of our knowledge, describing severe edema in a patient on continuous epidural hydromorphone administration during an outpatient epidural infusion trial. | 18,837,206 |
[Early glottic cancer--treatment results]. | Early glottic cancer (stage T1, T2) is connected with very good prognosis as well as organ and function preservation. The aim of the study was the assessment of early glottic treatment results. Between 1999-2005 1007 patients with larynx cancer were treated in Dept. of Otolaryngology Head Neck Oncological Surgery Poznań University of Medical Sciences. The majority constitute the patients with II and III stage of clinical advancement of the disease. Early glottic cancer was diagnosed in 43 patients (4.3%). The diagnose of the larynx cancer was set upon indirect and direct laryngoscopy, histological examination of larynx samples and neck ultrasonography. In all 43 patients CO2 laser surgery in Klein1 sasser microlaryngoscopy set was performed. In all cases, confirmed in histological examination the resection was radical. Follow-up was conducted every month in the first year of observation, then every 2-3 months. The time of follow-up ranged from 40 to 64 month, mean 51 month. In 4 patients (9.3%) treated for early glottic cancer with CO2 laser surgery the local relapse occurred after 10, 15, 19 and 28 month respectively. In two patients total laryngectomy, in one reconstructive partial laryngectomy and in one radiotherapy was performed. The mean time of observation after salvage treatment is 29 months. All patients are alive and free of disease. The laser surgery is an effective and non-invasive treatment of early glottic cancer but the strict follow-up regimen is demanded. | 18,837,217 |
[The analysis of the bacterial and fungal flora in maxillary sinuses in patients operated due to FESS method]. | The aim of this work was to analyse the bacterial and fungal flora in maxillary sinuses in patients operated due to the FESS method. Studies were conducted on 110 patients, including 47 women aged 17-78 and 63 men aged 17-66, who underwent endoscopic surgical procedures due to chronic polypoid maxillary sinusitis between 2006 and 2007. 214 cultures were prepared altogether. During the endoscopic operation on paranasal sinuses, a cannula was introduced along the natural entrance and material for the culture and antibiogram was removed by suction. In the studied material of 214 cultures, 72 (33.6%) cultures obtained positive results, including 2 cases with bacterial and fungal floras present simultaneously (Aspergillus fumigatus and Aspergillus niger) in 38 operated patients. In 25 (34.5%) cultures we noted the presence of Staphylococcus epidermidis, which was sensitive to the following antibiotics: Cotrimoxazole, Rifampicin, Vankomycin, Teicoplanin and Levofloxacin. Staphylococcus epidermidis was isolated in 22 (31.0%) cultures, showing 100% sensitivity to similar antibiotics like the previous one. Another bacteria (Escherichia coli) was cultured in 10 cultures (13.8%), in 70% of the cases every second bacteria was Staphylococcus epidermidis with 100% sensitivity mainly to cephalosporins and aminoglycosides. In 3 cultures (4.17%) we found Klebsiella pneumoniae, with 100% sensitivity to cephalosporins and aminoglycosides and 100% resistance to penicillins. In three cases Pseudomonas fluorescens and Proteus mirabilis (4.17% each) were cultured with their sensitivity and resistance similar to those of Klebsiella pneumoniae. Two cases (2.8% each) in the cultures were noted: Citrobacter freundii, Streptococcus oralis and Hafnia alvei, which were 100% sensitive to some cephalosporins and aminoglycosides whereas their resistance to penicillins and Cefuroxime was as high as 100%. In the operated patients suffering from chronic polypoid maxillary sinuses we found 33.6% of positive results in the bacterial flora. This indicates that the changes were accompanied by an acute inflammatory condition, thus surgical procedures had to be followed by a guided antibiotic. The cultured bacteria demonstrated sensitivity to some cephalosporins and aminoglycosides and resistance to penicillins, which proves the abuse of penicillins in the treatment of acute inflammatory states of upper airways. | 18,837,224 |
[Own experience in stapes revision surgery--analysis of indications]. | Analysis of indications for stapes revision surgery in patients qualified for the secondary procedure at the Otosurgery Dept. Medical University of Lodz. 25 cases of stapes revision surgery out of the 385 total treated surgically otosclerosis cases are discussed. In group A (patients after total stapedectomy) the following indications for the secondary surgical procedure were observed: 12 cases--platinum wire prosthesis displacement with ossicular chain discontinuity; 3 cases--perichondrium or adipose tissue atrophy; 2 cases of incudo-stapedial joint luxation. Group B was composed of 8 patients after stapedotomy (teflon piston operation, 0.6 mm). (1) The most common indication for the stapes revision surgery in patients after total stapedectomy were prosthesis displacement and necrosis of the long crus of the incus. (2) Obliteration of the stapes footplate after small fenestra operation was observed in our material to be the most frequent indication for the secondary stapes procedure. | 18,837,226 |
Comparison of NSAID consumption in Slovakia, Finland and Norway. | Non-steroidal anti-inflammatory drugs (NSAIDs) belong to most frequently used drugs worldwide. NSAIDs belong to the family of drugs that represent the biggest drug risk as to the number of adverse drug reactions (ADRs), as well as to the number of deregistered drugs. We analysed the whole consumption of NSAIDs from ATC class M01 in Slovakia during 1996-2007. Most frequently used NSAIDs in Slovakia were ibuprofen and diclofenac. There was a marked increasing trend in piroxicam, meloxicam, ibuprofen and especially nimesulide medicines. Prescription habits of doctors in Slovakia reflect the drug risk only partially, nevertheless the total consumption of dangerous medicines is decreasing and substances with safer profile remain being more used. In the prescribing process the patients' risk factors together with the differences in drug characteristics should be considered. Nevertheless some of these drugs are OTC, and their consumption is strongly influenced by pharmacists and advertisement (Tab. 2, Fig. 1, Ref. 18). Full Text (Free, PDF) www.bmj.sk. | 18,837,248 |
Early (1 hour) post-operative parathyroid hormone (PTH) measurement predicts hypocalcaemia after thyroidectomy: a prospective case-control single-institution study. | The aim of the study was to evaluate the efficacy of parathyroid hormone 1-hour assay for the early prediction of hypoparathyroidism after thyroidectomy. Candidates for total, subtotal, completion thyroidectomy or lobectomy were entered into the study. Pre- and postoperative calcium and parathyroid hormone (1 hour and postoperative day 1 after thyroidectomy) levels and clinical hypocalcaemia were recorded. Patients were divided into 3 groups and 2 subgroups: 1. patients who underwent lobectomy (control group); 2. patients who underwent total thyroidectomy with postoperative hypocalcaemia (2A: asymptomatic patients, 2B: symptomatic patients); 3. asymptomatic patients with normal calcium levels after total thyroidectomy. Of 119 patients, 109 underwent total thyroidectomy and 10 lobectomy. Of the 109 patients submitted to total thyroidectomy, 35 (32.11%) developed postoperative transient hypocalcaemia. Twenty-one patients (19.27%) were asymptomatic and 14 (12.84%) were symptomatic. Parathyroid hormone levels decreased after 1 hour in group 3 (32.98 pg/dl), 2A (9.84 pg/dl) and 2B (7.46 pg/dl). There was no significant difference in parathyroid hormone levels at 1 hour between group 2A and 2B (p = 0.06), but were significantly lower compared to groups 3 and 1 (p < 0.05). Parathyroid hormone levels at 1 hour after total thyroidectomy is a good predictor of early hypocalcaemia. It might be more useful than serum calcium monitoring for the early identification of patients requiring postoperative calcium supplementation. | 18,837,252 |
Gallstone ileus: a rare cause of colon obstruction. Report of a case. | The colon is a rare site of gallstone ileus. We report the case of a woman with cholelithiasis who underwent a total colectomy and cholecystectomy for colon obstruction due to a gallstone impacted in the sigmoid colon narrowed by diverticulitis. | 18,837,260 |
[Intestinal endometriosis: a case report]. | Endometriosis is seldom of interest to the general surgeon, since it is generally an exclusively gynaecological condition. Atypical locations, however, do fall within the domain of general surgery. Extra-gynaecological endometriosis denotes an ectopic localization of functional endometrial tissue, a finding whose incidence is increasing due to the increasingly widespread use of laparoscopic procedures in chronic abdominal pain and infertility. We report our experience with complete laparoscopic management of deep pelvic endometriosis with isolated bowel involvement. In those patients without a past history of this condition, extragonadal endometriosis is rarely diagnosed preoperatively because the disease may mimic other abdominal pathologies. An accurate diagnosis can be provided by laparoscopy and especially by an intraoperative histopathological examination. Operative laparoscopy is a safe and effective method for treating intestinal endometriosis, significantly improves the patient's quality of life, is followed by resolution of the gynaecological and digestive symptoms and can enhance fertility. | 18,837,264 |
Research on immigrant earnings. | As the first in a trio of pieces devoted to incorporating immigration into policy models, this review of research on immigrant earnings trajectories brings to light several findings. Controlling for demographic and human capital characteristics, immigrants often start their U.S. lives at substantially lower earnings, but experience faster earnings growth than natives with comparable years of education and experience. The extent to which the earnings trajectories of immigrants and natives differ varies by country of origin, with the source-country's level of economic development being a key determinant of the size of the U.S.-born/ foreign-born difference. The earnings profiles of immigrants from economically developed countries such as Japan, Canada, or Western Europe resemble those of U.S. natives who are of the same age and education level. In contrast, the earnings of immigrants from developing nations tend to start well below those of U.S. natives with comparable education levels and experience, but rise more rapidly than their U.S. counterparts. Comparing the earnings profiles of immigrants of similar age, sex, and years of schooling, over time and across groups, a strong inverse relationship emerges between their initial earnings and their subsequent U.S. earnings growth. In other words, the lower (higher) the initial earnings are, the higher (lower) the earnings growth. These and other research results have important implications for the projection of immigrant earnings and emigration in microsimulation models, as discussed in the two articles following this one: (1) "Adding Immigrants to Microsimulation Models" and (2) "Incorporating Immigrant Flows into Microsimulation Models". | 18,837,270 |
Adding immigrants to microsimulation models. | Forecasts of the financial status of Social Security's Old-Age, Survivors, and Disability Insurance (OASDI) programs and forecasts of the effects of various OASDI policy options on Americans would be improved if information about the earnings and labor force behavior of various population subgroups were included in projection models. Focusing on the projection of immigrant earnings, this article proffers a conceptual basis for incorporating immigration into microsimulation models. Key results from research on immigrant earnings, as described in the first article in this trilogy--"Research on Immigrant Earnings"--are linked to methods for forecasting individual earnings in microsimulation models. The research on immigrant earnings also inspires new methods for forecasting earnings in microsimulation models as well as the projection of immigrant emigration. Forecasting immigrant earnings and emigration is discussed in the context of a "closed system"--that is, forecasts are only made for a given population, which is represented in the base sample of the microsimulation model. The third article in our trilogy--"Incorporating Immigrant Flows into Microsimulation Models"--explores how to project immigrant earnings in the context of an "open system," which includes future immigrants. | 18,837,271 |
Reversibility testing in patients with asthma and COPD. | This article examines the difference between chronic obstructive pulmonary disease and asthma, the use of reversibility testing and the various guidelines available to help healthcare professionals diagnose and treat patients with these conditions. | 18,837,279 |
[Biomass structure analysis of Atractylodes lancea in different ecological environments]. | To study the ecological environments of Atractylodes lancea by biomass structural analysis. Through the scientific investigation in Maoshan, the sampling spots were set up, the relation between growth and ecological environments was researched and the ecological environments of A. lancea were divided as following: the vegetation layer, the shrub layer, the shrub-weed layer and the weed layer. The ramet biomass, height, leaves and coverage of A. lancea were studied. The several factors (ramet biomass, height, leaves and coverage) showed the regular change. Among maximum, minimum and average, the shrub layer was the biggest, the shrub and weed layer was the second biggest and the vegetation layer and the weed layer was the least. A. lancea tends to distribute in the shrub layer and the shrub-weed layer. | 18,837,303 |
[Effect of weiganli on level of FL in bone marrow and serum of myelosuppressed anemic mice]. | To study the effect of Weiganli on the level of FL in bone marrow and serum of myelosuppressed anemic mice, and to explore it's function on hematopoietic regulation. Models of myelosuppressed anemic mice were induced by radiation and chemotherapeutic drug, and the mice were randomly divided into normal group, myelosuppressed anemic group, and Weiganli group (high dose 100 g x L(-1), medium dose 50 g x L(-1), low dose 25 g x L(-1)). Effect of Weiganli on the number of the peripheral blood cells and bone marrow nucleated cells (BMC) were evaluated. Effect of Weiganli on the level of FL (Flt3 ligand) was investigated by ELISA technique. High dose of Weiganli could significantly increase granulocytes, erythrocytes, Hb and BMC, while both the medium dose and the low dose had more significant action in increase of platelet. The level of FL in bone marrow and serum were lower in Weiganli group than that in myelosuppressed anemic group, especially in high and medium dose group. The myelosuppresion of mice which induced by radiation and chemotherapeutic drug could be significantly relieved by Weiganli. | 18,837,322 |
[Absorption of triterpenoid compounds from Indian bread (Poria cocos) across human intestinal epithelial (Caco-2) cells in vitro]. | To study the absorption of 3-epidehydrotumulosic acid (EDHTA), polyporenic acid C (PPAC) and 6alpha-hydroxypolyporenic acid C (HPPA) isolated from the sclerotium of Poria cocos. In human intestinal epithelial. By using Caco-2 (the human colonic adenocarcinoma cell lines) cells monolayer as an intestinal epithelial cell model, the permeability of EDHTA, PPAC and HPPA were studied from apical side (AP side) to basolateral side (BL side) or from BL side to AP side. The three compounds were measured by reversed-phase high performance liquid chromatography (HPLC) coupled with UV detector. Transport parameters and apparent permeability coefficients (P(app)) were then calculated and compared with those of propranolol and atenolol, which are the transcellular transport marker and as a control substance for high and poor permeability, respectively. The P(app) values of EDHTA, PPAC and HPPA were (9.99 +/- 1.08) x 10(-6), (10.06 +/- 0.53) x 10(-6) and (3.32 +/- 0.66) x 10(-6) cm x s(-1) from AP side to BL side, and (17.76 +/- 0.91) x 10(-6), (19.23 +/- 1.16) x 10(-6) and (8.19 +/- 0.57) x 10(-6) cm x s(-1) from BL side to AP side,respectively. Under the condition of this experiment, the P(app) value was 1.45 x 10(-5) cm x s(-1) for propranolol and 4.22 x 0(-7) cm x s(-1) for atenolol. The P(app) values of EDHTA and PPAC were at a nearly same magnitude with those of propranolol, and HPPA lied between those of propranolol and atenolol. On the other hand, the efflux transport of EDHTA, PPAC and HPPA were higher 1.78, 1.91 and 2. 47 times more than its influx transport with 0.56, 0.52 and 0.41 rate of P(app A --> B)/P(app (B --> A). EDHTA, PPAC and HPPA can be absorbed across intestinal epithelial cells, among EDHTA and PPAC will be completely. HPPA will be moderately absorbed compounds. EDHTA, PPAC and HPPA may have been involved in efflux mechanism in Caco-2 cells monolayers model from the basolateral-to-apical direction. | 18,837,324 |
[Effects of guanxin II on cardiac protein expression after acute myocardial ischemia on rats]. | Guanxin II is a famous modern formula of traditional Chinese medicine. Guanxin II after myocardial infarction (MI) has been shown to have beneficial effects on cardiac anatomy and function. The purpose of this study was to examine the effects of Guanxin 1I on cardiac protein expression after MI. Rats were randomized into 3 groups, sham, model and treating groups. Model and treating groups were fed with Guanxin II and sham group was fed with water for 10 days before MI. MI operation is to ligate left coronary artery. 24 hours after MI, myocardial protein expression of junctional zone was assessed with 2D gel electrophoresis and mass spectra analysis. Guanxin II was found to be able to improve myocardial protein expression, especially 11 proteins. These proteins are mainly involved in suppressing changes of cell shape and structure and energy metabolism. Guanxin II after MI affected myocardial protein expression. Further experiments of larger research extent should be done to receive more results. | 18,837,326 |
[Textural research on "Xuelihua" in "Bencao Gangmu Shiyi" (A Supplement to the Compendium of Materia Medica)]. | To investigate the historical origins of folk herbal medicine 'Xuelihua', the origin of 'Xuelihua' was confirmed by textural, botanical characteristics research, investigation of therapeutic effects and field survey. The 'Xuelihua' which was originally recorded in 'Bencao Gangmu Shiyi' (A Supplement to the Compendium of Materia Medica) should be 'Riben Shegencao' (Ophirrhiza japonica) of Rubiaceae family. | 18,837,331 |
[Study of using shattering extraction with solvent to extract ingredient of three kinds of traditional Chinese medicine]. | To prove if it is possible for using the shattering extraction with solvent to extract ingredients of traditional Chinese medicine. The shattering extraction with solvent, the refluxing extraction and the ultrasonic extraction were used to extract paeoniflorin from Radix Paeoniae rubra, and to extract baicalein from Radix Scutellariae, and to extract chlorogenic acid from Flos lonicerae japonicae respectively, using ingredient content and extract yield as the measuring indexes. The content of each every ingredient obviously higher by using shattering extraction with solvent than using refluxing extraction or the ultrasonic extraction. The shattering extraction with solvent is a high efficiency, simple and quick extraction. It may be used to extract the ingredient of three kinds of traditional Chinese medicine. | 18,837,338 |
[Expression and activity analysis of interferonalpha-con and thymosin-alpha1]. | This study aimed to obtain recombinant fusion protein of thymosin alphal(TM-alpha1) and consensus IFNalpha (IFNalpha-con) which have bath TM-alpha1 and IFNalpha-con activities. The DNA sequence for the fusion protein was cloned into expression vector of pET-22b (+) and expressed in BL21 (DE3)-Codon plus-RP-X. The expressed product (TM-alpha1-IFN-con) was soluble, and amounted to more than 20% in total proteins of E. coli. By precipitation of (NH4)2SO4, hydrophobic interaction chromatography (HIC, Phenyl Sepharose 6 Fast Flow), anion-exchange chromatography (Q Sepharose Fast Flow), cation-exchange chromatography (SP Sepharose Fast Flow) and gel filtration (Sephadex G-75), it was purified to more than 96% purity. The activity of fusion protein for antivirus was tested by cytopathic-effect inhibition assay and activity for promoting lymphocyte proliferation was tested by cell proliferative assay. The activity for antivirus was higher than commercial IFNalpha1b and IFNalpha2a and activity for promoting lymphocyte proliferation was similar to commercial TM-alpha1. The fusion protein had better effect for anti-HBV in vitro, its effect was stronger than combination of IFNalpha and TM-alpha1 and cell toxicity was less than combination of IFNalpha and TM-alpha1. The above results show that it has effect bath antivirus of IFNalpha and promoting lymphocyte proliferation of the soluble fusion protein expressed in E. coli. | 18,837,390 |
Umbilical venous volume flow in twin-twin transfusion syndrome. | To examine umbilical venous volume flow (UVF) dynamics by twin status and disease severity in untreated twin-twin transfusion syndrome (TTTS). In 70 cases of untreated TTTS, absolute UVF, UVF corrected for estimated fetal weight (UVF/kg), intertwin difference (DeltaUVF/kg) and recipient to donor ratio (R/D-UVF/kg) were calculated. Parameters for UVF were compared with respect to twin status and disease severity (early, Quintero Stages I and II; advanced, Stages III and IV). UVF/kg was higher in recipients than in donors and decreased with advancing stage in both twins (in recipients, 183.9 mL/kg/min vs. 145.6 mL/kg/min, P = 0.043; in donors, 137.5 mL/kg/min vs. 122.5 mL/kg/min, P = 0.033). Linear regression analysis demonstrated that the overall best correlation coefficient for DeltaUVF/kg was obtained for the Doppler pulsatility index of the umbilical artery (t = - 4.536, P < 0.001). In advanced stage, absolute and weight-corrected UVF were lower overall, while significant differences in intertwin volume flows persisted. The lowest flows were observed in hydropic recipients (median, 67.0 (range, 55.2-122.0) mL/kg/min vs. 180.8 (range, 59.1-565.4) mL/kg/min; P = 0.001). In TTTS, UVF is significantly higher in recipients than in donors. With progression to advanced stage UVF/kg decreases in both twins as the magnitude of UVF that can be accommodated by the recipient declines. Further study of these dynamics in combination with cardiac performance parameters is warranted to refine diagnostic and prognostic assessment. | 18,837,441 |
Micro-computed tomographic analysis of bone healing subsequent to graft placement. | A micro-computed tomographic (muCT) analysis of bone healing subsequent to graft (tri calcium phosphate/TCP) placement in the maxillary sinus prior to dental endosteal implant placement was the focus of the current study. Ten trephined rod shaped human bone cores were obtained three months after the placement of particulate graft material. Using the muCT, samples were evaluated at 6 and 20 mum resolutions. The images exhibited regions of different grey scale (GL) magnitudes for bone and graft allowing a differentiation and quantification of the two sample regions. The GL threshold magnitudes at 20 mum resolution were determined to be less than 235 for organic and fluid, 235-450 for bone, 400-600 for bone and graft, and 600 and above for the graft material. The graft material was integrated with the bone showing the osteoconductivity of the TCP material, the mean bone volume was 25.50 (11.28) ranging from 5.66 to 37.9 and the mean graft volume was 0.42 (0.37) ranging from 0.01 to 1.17. The mean graft to bone volume ratio was 0.015 (0.01) with a range from 0.002 to 0.024. The structural data and observations from two- and three-dimensional images provided a valuable assessment of the graft distribution, its relation to modeling bone and also the anatomy of the healing bone. Thus this study demonstrated the capability to uniquely evaluate the status of healing bone associated with this TCP grafting biomaterial with opportunities for subsequent correlations with histomorphometrical studies and clinical outcomes of these type implant treatments. | 18,837,447 |
Oxidoreductase activities of polyclonal IgGs from the sera of Wistar rats are better activated by combinations of different metal ions. | It was shown that IgGs purified from the sera of healthy Wistar rats contain several different bound Me2+ ions and oxidize 3,3'-diaminobenzidine through a H2O2-dependent peroxidase and H2O2-independent oxidoreductase activity. IgGs have lost these activities after removing the internal metal ions by dialysis against EDTA. External Cu2+ or Fe2+ activated significantly both activities of non-dialysed IgGs containing different internal metals (Fe > or = Pb > or = Zn > or = Cu > or = Al > or = Ca > or = Ni > or = Mn > Co > or = Mg) showing pronounced biphasic dependencies corresponding to approximately 0.1-2 and approximately 2-5 mM of Me2+, while the curves for Mn2+ were nearly linear. Cu2+ alone significantly stimulated both the peroxidase and oxidoreductase activities of dialysed IgGs only at high concentration (> or = 2 mM), while Mn2+ weakly activated peroxidase activity at concentration >3 mM but was active in the oxidoreductase oxidation at a low concentration (<1 mM). Fe2+-dependent peroxidase activity of dialysed IgGs was observed at 0.1-5 mM, but Fe2+ was completely inactive in the oxidoreductase reaction. Mg2+, Ca2+, Zn2+, Al2+ and especially Co2+ and Ni2+ were not able to activate dialysed IgGs, but slightly activated non-dialysed IgGs. The use of the combinations of Cu2+ + Mn2+, Cu2+ + Zn2+, Fe2+ + Mn2+, Fe2+ + Zn2+ led to a conversion of the biphasic curves to hyperbolic ones and in parallel to a significant increase in the activity as compared with Cu2+, Fe2+ or Mn2+ ions taken separately; the rates of the oxidation reactions, catalysed by non-dialysed and dialysed IgGs, became comparable. Mg2+, Co2+ and Ni2+ markedly activated the Cu2+-dependent oxidation reactions catalysed by dialysed IgGs, while Ca2+ inhibited these reactions. A possible role of the second metal in the oxidation reactions is discussed. | 18,837,443 |
Partially polyurethane-covered stent for cerebral aneurysm treatment. | Partially polyurethane-covered stent (PPCS) is proposed for the treatment of cerebral aneurysms. The PPCSs were observed to substantially modify the flow entering the aneurysm in a patient-specific aneurysm phantom (PSAP). These stents can act as flow modulators and the polyurethane (PU) membrane can provide a smooth scaffold for restoring the structural integrity of the diseased vessel. Partial coating of the stent aids in sealing only the entrance to the aneurysm while keeping the perforators around the aneurysm open and patent. Biocompatibility of the PU membrane was monitored using contact angle measurements to show that critical surface tension (CST) values remained in the thromboresistant range of 20-30 mN/m. Stent flexibility, stiffness, and pressure-diameter relationship showed no significant change after asymmetric PU film application. No delamination of the PU membrane from the stent was observed within the working strains of the stent. The flow modulating capability of the PPCS was monitored by intentionally orienting the stent to cover either the proximal or the distal regions along the neck of the PSAP. Time density curves (TDCs) compared the relative metrics of input rate, washout rate, residence time, and influx in the aneurysm before and after the stent placement. | 18,837,459 |
Regulation of beta-catenin and connexin-43 expression: targets for sphingolipids in colon cancer prevention. | Sphingolipid metabolites are generated throughout the intestinal tract after hydrolysis of orally administered complex sphingolipids and significantly suppress colon cancer in carcinogen-treated CF1 mice. In the present study, the mechanisms of tumor suppression by dietary sphingolipids were investigated. Changes in select genes that are critical in early stages of colon cancer were analyzed in the colonic mucosa of dimethylhydrazine-treated CF1 mice fed AIN76A diet with or without 0.05% sphingomyelin (SM). Supplementation with SM did not significantly alter mRNA levels of most of the selected genes. However, a downregulation of beta-catenin (p = 0.007) and increased protein levels of connexin-43 (p = 0.017) and Bcl-2 (p = 0.033) were observed in SM-fed animals. This suggests that sphingolipids may be regulating specific post-transcriptional events to reverse aberrant expression of individual proteins. Since the dysregulation of beta-catenin metabolism and its transcriptional activity in addition to a decreased intercellular communication has been causally linked to the development of colon cancer while a low Bcl-2 expression is associated with a worse prognosis in colon cancer, the reversal of these early changes may be important events in the prevention of colon cancer by orally administered sphingolipids, and may provide specific molecular biomarkers for sphingolipid efficacy in vivo. | 18,837,472 |
Effective diffusion coefficients for methanol in sulfuric acid solutions measured by Raman spectroscopy. | The diffusion of methanol into 0-96.5 wt % sulfuric acid solutions was followed using Raman spectroscopy. Because methanol reacts to form protonated methanol (CH 3OH 2 (+)) and methyl hydrogen sulfate in H 2SO 4 solutions, the reported diffusion coefficients, D, are effective diffusion coefficients that include all of the methyl species diffusing into H 2SO 4. The method was first verified by measuring D for methanol into water. The value obtained here, D = (1.4 +/- 0.6) x 10 (-5) cm (2)/s, agrees well with values found in the literature. The values of D in 39.2-96.5 wt % H 2SO 4 range from (0.11-0.3) x 10 (-5) cm (2)/s, with the maximum value of D occurring for 61.6 wt % H 2SO 4. The effective diffusion coefficients do not vary systematically with the viscosity of the solutions, suggesting that the speciation of both methanol and sulfuric acid may be important in determining these transport coefficients. | 18,837,493 |
Effects of epilactose on calcium absorption and serum lipid metabolism in rats. | Epilactose (4-O-beta-galactopyranosyl-D-mannnose) is a rare disaccharide in cow milk that can be synthesized from lactose by the cellobiose 2-epimerase of Ruminococcus albus. In this study, we examined the biological activities of epilactose using male Wistar-ST rats. The apparent rates of calcium and magnesium absorption of rats fed epilactose and fructooligosaccharide diets were greater than those fed control and lactose diets, accompanied by greater weight gain of the cecal wall and higher levels of short-chain fatty acids and other organic acids. Epilactose also increased the calcium absorption in everted small intestinal sacs. In addition, the levels of plasma total cholesterol and nonhigh-density lipoprotein cholesterol were lower in epilactose-fed rats. These results indicate that epilactose promotes calcium absorption in the small intestine and possibly lowers the risk of arteriosclerosis. Cecal microbes may efficiently utilize epilactose and contribute to these biological activities. | 18,837,503 |
A 200-antibody microarray biochip for environmental monitoring: searching for universal microbial biomarkers through immunoprofiling. | Environmental biomonitoring approaches require the measurement of either unequivocal biomarkers or specific biological profiles. Antibody microarrays constitute new tools for fast and reliable analysis of up to hundreds of biomarkers simultaneously. Herein we report 150 new polyclonal antibodies against microbial strains and environmental extracts, as well as the construction and validation of an antibody microarray (EMCHIP200, for "Environmental Monitoring Chip") containing 200 different antibodies. Each antibody was tested against its antigen for its specificity and cross-reactivity by a sandwich microarray immunoassay. The limit of detection was 0.2 ng mL (-1) for some proteins and 10 (4)-10 (5) cells mL (-1) for bacterial cells and spores. Partial biochemical characterization allowed identification of polymeric compounds (proteins and polysaccharides) as some of the targets recognized by the antibodies. We have successfully used the EMCHIP200 for the detection of biological polymers in samples from extreme environments around the world (e.g., a deep South African mine, Antarctica's dry valleys, Yellowstone National Park, Iceland, and Rio Tinto surface and subsurface). Clustering analysis permitted us to associate similar immunoprofiles or patterns to samples from apparently very different environments, indicating that they indeed share similar universal biomarkers. Our EMCHIP200 constitutes a new generation of immunosensors for biomarker detection and profiling, for either environmental, industrial, biotechnological, or astrobiological applications. | 18,837,515 |
Pt/glassy carbon model catalysts prepared from PS-b-P2VP micellar templates. | Poly(styrene)-block-poly(2-vinylpyridine) (PS-b-P2VP) diblock copolymer was used as a micellar template to fabricate arrays of Pt nanoparticles on mica and glassy carbon (GC) supports. Polymer micellar deposition yields Pt nanoparticles with tunable particle size and surface number density on both mica and GC. After deposition of precursor-loaded micelles onto GC, oxygen plasma etching removes the polymer shell, followed by thermal treatment with H2 gas to reduce the Pt. Etching conditions were optimized to maximize removal of the polymer while minimizing damage to the GC. Arrays of Pt nanoparticles with controlled size and surface number density can be prepared on mica (for particle size characterization) and GC to make Pt/GC model catalysts. These model catalysts were characterized by tapping mode atomic force microscopy, X-ray photoelectron spectroscopy, and cyclic voltammetry to measure activity for oxidation of carbon monoxide or methanol. Cyclic voltammetry results demonstrate the existence of a correlation between Pt particle size and electrocatalytic properties including onset potential, tolerance of carbonaceous adsorbates, and intrinsic activity (based on active Pt area from CO stripping voltammetry). Results obtained with Pt/GC model catalysts duplicate prior results obtained with Pt/porous carbon catalysts therefore validating the synthesis approach and offering a new, tunable platform to study catalyst structure and other effects such as aging on proton exchange membrane fuel cell (PEMFC) reactions. | 18,837,528 |
Copper-catalyzed intramolecular N-vinylation of sulfonamides: general and efficient synthesis of heterocyclic enamines and macrolactams. | With the catalysis of CuI/N,N'-dimethylethylenediamine, intramolecular C-N coupling between sulfonamides and vinyl halides was successfully implemented, leading to the efficient synthesis of 5-, 6-, 7-, and even 8-membered heterocyclic enamines in both exo and endo modes. The bicyclic enamines thus formed provided a convenient entry to the corresponding 9- to 12-membered lactams by oxidative C=C bond cleavage. | 18,837,542 |
Qualitative mapping of structurally different dipeptide nanotubes. | Biological self-assembled structures are receiving increasing focus within micro- and nanotechnology, for example, as sensing devices, due to the fact that they are cheap to produce and easy to functionalize. Therefore, methods for the characterization of these structures are much needed. In this paper, electrostatic force microscopy (EFM) was used to distinguish between hollow nanotubes formed by self-assembly by a simple aromatic dipeptide, L-phenylalanine, silver-filled peptide-based nanotubes, and silver wires placed on prefabricated SiO2 surfaces with a backgate. The investigation shows that it is possible to distinguish between these three types of structures using this method. Further, an agreement between the detected signal and the structure of the hollow peptide was demonstrated; however only qualitative agreement with the mathematical expressing of the tubes is shown. | 18,837,544 |
Studies of carbon incorporation on the diamond [100] surface during chemical vapor deposition using density functional theory. | Accurate potential energy surface calculations are presented for many of the key steps involved in diamond chemical vapor deposition on the [100] surface (in its 2 x 1 reconstructed and hydrogenated form). The growing diamond surface was described by using a large (approximately 1500 atoms) cluster model, with the key atoms involved in chemical steps being described by using a quantum mechanical (QM, density functional theory, DFT) method and the bulk of the atoms being described by molecular mechanics (MM). The resulting hybrid QM/MM calculations are more systematic and/or at a higher level of theory than previous work on this growth process. The dominant process for carbon addition, in the form of methyl radicals, is predicted to be addition to a surface radical site, opening of the adjacent C-C dimer bond, insertion, and ultimate ring closure. Other steps such as insertion across the trough between rows of dimer bonds or addition to a neighboring dimer leading to formation of a reconstruction on the next layer may also contribute. Etching of carbon can also occur; the most likely mechanism involves loss of a two-carbon moiety in the form of ethene. The present higher-level calculations confirm that migration of inserted carbon along both dimer rows and chains should be relatively facile, with barriers of approximately 150 kJ mol (-1) when starting from suitable diradical species, and that this step should play an important role in establishing growth of smooth surfaces. | 18,837,545 |
Open bridge-structured gold nanoparticle array for label-free DNA detection. | We focused on changes in the electrical property of the open bridge-structured gold nanoparticles array consisting of 46-nm parent and 12-nm son gold nanoparticles by hybridization and applied it for a simple electrical DNA detection. Since a target DNA of a 24-mer oligonucleotide was added to the probe DNA modified 12-nm Au nanoparticles, which was arranged on the gap between the 46-nm Au particles, the response was read by an electrical readout system. Even in a simple measuring method, we obtained a rapid response to the cDNA with a high S/N ratio of 30 over a wide concentration range and a detection limit of 5.0 fmol. Moreover, the array discriminated 1-base mismatches, regardless of their location in the DNA sequence, which enabled us to detect single-nucleotide polymorphism, which is one of the important diagnoses, without any polymerase chain reaction amplification, sophisticated instrumentation, or fluorescent labeling through an easy-to-handle electrical readout system. | 18,837,561 |
A new mermithid nematode in imagos of Cladopelma collator (Townes) (Diptera: Chironomidae) eclosing from waterways in northern Minnesota. | Octomyomermis connellyi n. sp. (Nematoda: Mermithidae) is described from the hemocoel of male and female imagos of Cladopelma collator (Townes) eclosing from Lake Ozawindib and from Gulsvig Landing in the upper Mississippi River in northern Minnesota. The species is distinguished from the other species in the genus. Included is a list of the other 9 adequately described members of the genus Octomyomermis that have been reported from the United States (California and Minnesota), Argentina, Russia, and Zambia. Bionomics and anomalies of the new species are addressed. | 18,837,568 |
Does precontemplation represent a homogeneous stage category? A latent class analysis on German smokers. | The authors examined the subtype structure of smokers classified in the precontemplation stage of change within the transtheoretical model. From a general practice-based sample of 1,499 daily smoking patients from Germany (participation rate 80%), they used a subgroup of 929 smokers who were classified in the precontemplation stage and applied latent class analysis, using the pros and cons of nonsmoking and smoking cessation self-efficacy as the defining variables. Cross-sectional validation of the emerging classes was based on smoking behavior and processes of change variables. For longitudinal validation, generalized estimation equation analyses were used on motivational and abstinence criteria from 6-, 12-, 18-, and 24-month follow-ups. A 4-class model best represented the data. Three subtypes (labeled progressive, immotive, and disengaged pessimistic) were similar to clusters identified in U.S. studies. The 4th (disengaged optimistic), by contrast, was reminiscent of a type that had previously only emerged in a Dutch study. Cross-sectional and longitudinal validation results confirmed the distinctiveness and predictive power of the classes. The findings highlight the importance of tailoring interventions for smoking behavior change to the needs of different subgroups of precontemplating smokers. | 18,837,601 |
Cognitive-behavioral therapy for intermittent explosive disorder: a pilot randomized clinical trial. | No randomized clinical trials have evaluated the efficacy of psychotherapy for intermittent explosive disorder (IED). In the present study, the authors tested the efficacy of 12-week group and individual cognitive-behavioral therapies (adapted from J. L. Deffenbacher & M. McKay, 2000) by comparing them with a wait-list control in a randomized clinical trial among adults with IED (N = 45). Aggression, anger, and associated symptoms were assessed at baseline, midtreatment, posttreatment, and 3-month follow-up. Group and individual cognitive-behavioral therapy tended not to differ, with each reducing aggression, anger, hostile thinking, and depressive symptoms, while improving anger control relative to wait-list participants. Posttreatment effect sizes were large. These effects were maintained at 3-month follow-up. Findings provide initial support for the use of multicomponent cognitive-behavioral therapy in the treatment of IED. | 18,837,604 |
Teacher key opinion leaders and mental health consultation in low-income urban schools. | Diffusion theory posits that information is disseminated throughout a social network by the persuasion of key opinion leaders (KOLs). This study examined the relative and combined influence of peer-identified KOL teachers (n = 12) and mental health providers (n = 21) on classroom teachers' (n = 61) self-reported use of commonly recommended classroom practices for children with attention-deficit/hyperactivity disorder in 6 low-income urban African American communities, relative to teachers (n = 54) at 4 matched schools who received mental health provider consultation only. Mixed-effects regression models showed that KOLs in collaboration with mental health providers promoted higher rates of teachers' self-reported use of recommended strategies than mental health providers alone, and that these effects were mediated by KOL support but not by mental health provider support. The results suggest an expanded role for KOL teachers as indigenous and natural supports for the dissemination and implementation of school-based mental health programs. | 18,837,608 |
Interpretation bias in social anxiety as detected by event-related brain potentials. | Little is known about psychophysiological correlates of interpretation bias in social anxiety. To address this issue, the authors measured event-related brain potentials (ERPs) in high and low socially anxious individuals during a task wherein ambiguous scenarios were resolved with either a positive or negative ending. Specifically, the authors examined modulations of the P600, an ERP that peaks approximately 600 ms following stimulus onset and indexes violations of expectancy. Low-anxious individuals were characterized by an increased P600 to negative in comparison with positive sentence endings, suggesting a positive interpretation bias. In contrast, the high-anxious group evidenced equivalent P600 magnitude for negative and positive sentence endings, suggesting a lack of positive interpretation bias. Similar, but less reliable results emerged in earlier time windows, that is, 200-500 ms poststimulus. Reaction time, occurring around 900 ms poststimulus, failed to show a reliable interpretation bias. Results suggest that ERPs can detect interpretation biases in social anxiety before the emission of behavioral responses. | 18,837,619 |
Ezetimibe 5 and 10 mg for lowering LDL-C: potential billion-dollar savings with improved tolerability. | To compare the clinical efficacy of ezetimibe 5 mg (prescribed as a 10-mg tablet split in half) with a whole 10-mg tablet. From January 2003 through July 2005, all Bronx Veterans Administration ezetimibe prescriptions were for 10 mg. In August 2005, it was mandated that all new ezetimibe prescriptions be 5 mg, prescribed as a 10-mg tablet split in half. The impact of the 2 ezetimibe dosing strategies on percent lowering of low-density lipoprotein cholesterol (LDL-C) and achievement of National Cholesterol Education Program Adult Treatment Panel III (ATP III) goals was assessed in all patients prescribed ezetimibe 5 or 10 mg. A total of 272 patients were prescribed ezetimibe; 86 received 5 mg and 186 received 10 mg. Of those 272 patients, 197 had evaluable baseline and posttreatment LDL-C (55 taking the 5-mg dose and 142 taking the 10-mg dose). The effects of ezetimibe 5 and 10 mg on all lipid parameters were similar. Ezetimibe 10 mg reduced LDL-C by 26.1%, whereas 5 mg reduced LDL-C by 25.8%. The percentages of patients achieving goal LDL-C were similar: 61.8% (5 mg) and 60.5% (10 mg). These data strongly suggest that ezetimibe 5 mg and ezetimibe 10 mg are clinically equivalent with respect to LDL-C reduction and achievement of ATP III LDL-C goals. Widespread adoption of this low-dose strategy could result in a potential cost savings of more than a billion dollars annually, with a potential reduction in hepatotoxicity. | 18,837,641 |
Connected culture of murine hepatocytes and HUVEC in a multicompartmental bioreactor. | A multicompartmental bioreactor was conceived and designed to mimic cross talk between cells in different culture chambers connected only by flow, such that cell-cell interaction is mediated by soluble ligands as occurs in the body. The system was tested with a connected culture of murine hepatocytes and human umbilical vein endothelial cells. Metabolites such as albumin, urea, lactate and viability were monitored during the course of the experiments and compared with monoculture conditions in the bioreactor. When the two cell types are placed in connected culture, there is an increase in endothelial cell viability and hepatic glucose synthesis as well as albumin and urea production, while overall lactate production in the system is downregulated. The results show that the multicompartmental bioreactor enhances cell function, effectively combining both heterotypic interactions with increased nutrient availability. | 18,837,649 |
Anti-oxidized low-density lipoprotein antibody levels are associated with the development of type 2 diabetes mellitus. | Anti-oxidized low-density lipoprotein (LDL) antibodies are associated with the oxidative capacity of plasma, but whether they protect or promote diabetes is unknown. We undertook a prospective study to determine the predictive capacity of anti-oxidized LDL antibodies for the onset of type 2 diabetes mellitus (T2DM). We selected 391 non-diabetic women aged 18-65 years. The subjects were classified as being normal (oral glucose test tolerance normal, OGTT-N), or having impaired glucose tolerance (IGT), impaired fasting glucose (IFG) or T2DM according to their baseline glucose levels and after an OGTT. The same subjects were studied six years later. The levels of anti-oxidized LDL antibodies were classified as above or below the 50th percentile. Of the women who were OGTT-N at the start of the study and who had anti-oxidized LDL antibody levels below the 50th percentile, only 65.1% were still OGTT-N after 6 years versus 79.5% of those who had anti-oxidized LDL antibody levels above the 50th percentile (P = 0.015). Women who had IGT or IFG at the start of the study whose anti-oxidized LDL antibody levels were below the 50th percentile had a relative risk of 9.79 (95% confidence interval, 1.40-68.45) of developing diabetes (P < 0.001). Logistic regression analysis showed that the variables predicting the development of a carbohydrate metabolism disorder in the women after 6 years were body mass index (P < 0.001) and the levels of anti-oxidized LDL antibodies (P = 0.042). Levels of anti-oxidized LDL antibodies are independent predictors for the development of T2DM in women. | 18,837,736 |
A novel antagonist of prostaglandin D2 blocks the locomotion of eosinophils and basophils. | Chemoattractant receptor homologous molecule of Th2 cells (CRTH2) has been shown to mediate the chemotaxis of eosinophils, basophils and Th2-type T lymphocytes. The major mast cell product prostaglandin (PG) D(2) is considered to be the principal ligand of CRTH2. We developed a novel CRTH2 antagonist, AZ11665362 [2,5-dimethyl-3-(8-methylquinolin-4-yl)-1H-indole-1-yl]acetic acid, and characterized its efficacy in binding assay in HEK293 cells, eosinophil and basophil shape change assay and migration assay, platelet aggregation and eosinophil release from guinea pig bone marrow. The effects were compared with ramatroban, the sole CRTH2 antagonist clinically available to date. AZ11665362 bound with high affinity to human and guinea pig CRTH2 expressed in HEK293 cells and antagonized eosinophil and basophil shape change responses to PGD(2). AZ11665362 was without effect on the PGD(2)-induced inhibition of platelet aggregation. In contrast, AZ11665362 effectively inhibited the in vitro migration of human eosinophils and basophils towards PGD(2). The release of eosinophils from the isolated perfused hind limb of the guinea pig was potently stimulated by PGD(2), and this effect was prevented by AZ11665362. In all assays tested, AZ11665362 was at least 10 times more potent than ramatroban. AZ11665362 is a potent CRTH2 antagonist that is capable of blocking the migration of eosinophils and basophils, and the rapid mobilization of eosinophils from bone marrow. AZ11665362 might hence be useful for the treatment of allergic diseases. | 18,837,743 |
Low-molecular-weight heparin for routine hemodialysis. | Unfractionated heparin (UFH) is a series of molecules, and as such has variable pharmacodynamics. Low-molecular-weight heparins were developed to improve both drug pharmacokinetics and dynamics, so as to provide a reliable clinical effect. These are potent agents, but have an increased half-life compared with UFH in dialysis patients, and also require special laboratory monitoring. We switched our chronic hemodialysis patients from unfractionated to low-molecular-weight heparins. Low-molecular-weight heparins proved to be effective in preventing extracorporeal circuit clotting, and safe with fewer bleeding episodes and heparin-induced thrombocytopenia than standard UFH. Indeed, we stopped routine laboratory monitoring because of the lack of side effects, and simply dosed by clinical inspection of the extracorporeal circuit for thrombus, and the time for fistula needle sites to stop bleeding. These agents have become the anticoagulants of choice in Europe for routine outpatient hemodialysis sessions, not only due to reduced drug costs but also due to the reliability of their clinical effect and ease of administration. | 18,837,768 |
Orally administrated Juzen-taiho-to/TJ-48 ameliorates erythropoietin (rHuEPO)-resistant anemia in patients on hemodialysis. | Maintenance of the red blood cell volume is a fundamental aspect of ensuring oxygen supply to the tissue. Recombinant human erythropoietin (rHuEPO) was approved for marketing in Japan in 1990 for the treatment of anemia in patients on dialysis. Recombinant human erythropoietin caused a significant increase in hemoglobin (Hb) levels in patients on dialysis. However, not all have a good response to rHuEPO therapy; the causes of rHuEPO failure include iron deficiency, infection, uremia, and interaction of some drugs. Juzen-taiho-to (TJ-48), a mixture of extracts from 10 medicinal herbs, has been used traditionally to treat patients with anemia, anorexia, or fatigue. To clarify the effect of TJ-48 on erythropoietin-resistant anemia, we studied the effect of TJ-48 in patients on hemodialysis with erythropoietin-resistant anemia. We divided 42 end-stage renal disease patients on hemodialysis with erythropoietin-resistant anemia (Hb<10.0 g/dL with rHuEPO 9000 U/wk or 15 U/kg/wk treatment) into 2 groups as follows: a TJ-48-treated group (TJ-48 group, 7.5 g/d, n=22) and a TJ-48 nontreated (control group, n=20). At the beginning of this study, there was no significant difference between the groups in age, sex, serum creatinine, blood urea nitrogen, serum iron, and ferritin. After 12 weeks of treatment, the Hb level had significantly increased from 8.4 +/- 1.1 to 9.5 +/- 1.3 g/dL (P=0.0272) in the TJ-48 group. C-reactive protein (CRP) had significantly decreased from 1.4 +/- 1.7 to 0.6 +/- 0.8 mg/dL (P=0.0438). There was a significant negative correlation between Hb and CRP in the TJ-48 group (r(2)=0.121, P=0.0066). In contrast, in the control group, Hb and CRP showed no significant changes throughout this study. Nor was there a significant correlation between Hb and CRP in the control group. In conclusion, TJ-48 was effective in improving erythropoietin-resistant anemia in end-stage renal disease patients. This effect was, at least in part, due to the anti-inflammatory effect of TJ-48 in patients on hemodialysis. | 18,837,771 |
Protective CD8 T cells against Plasmodium liver stages: immunobiology of an 'unnatural' immune response. | Immunization with high doses of irradiated sporozoites delivered by the bites of infected mosquitoes has been shown to induce protective responses against malaria, mediated in part by CD8(+) T cells. In contrast, natural transmission involving low exposure to live sporozoite antigen fails to elicit strong immunity. In this review, we examine how irradiated sporozoite immunization breaks the natural host-parasite interaction and induces protective CD8(+) T cells. Upon biting, the malaria-infected mosquitoes deposit parasites in the skin, many of which eventually exit to the bloodstream and infect hepatocytes. However, certain antigens, including the circumsporozoite (CS) protein, remain in the skin and are presented in the draining lymph node. These antigens prime specific CD8(+) T cells, which migrate to the liver where they eliminate parasitized hepatocytes. We discuss the relevance of the different tissue compartments involved in the induction and effector phases of this response, as well as the cellular requirements for priming and memory development of CD8(+) T cells, which include a complete dependence on dendritic cells and a near absolute need for CD4(+) T-cell help. Finally, we discuss the impact of the immunodominant CS protein on this protection and the implications of these findings for vaccine design. | 18,837,788 |
Effect of weight loss on markers of triglyceride-rich lipoprotein metabolism in the metabolic syndrome. | Hypertriglyceridaemia, a consistent feature of dyslipidaemia in the metabolic syndrome (MetS), is related to the extent of abdominal fat mass and altered adipocytokine secretion. We determined the effect of weight loss by dietary restriction on markers of triglyceride-rich lipoprotein (TRL) metabolism and plasma adipocytokines. Thirty-five men with MetS participated in a 16 week randomized controlled dietary intervention study. Apolipoprotein (apo) C-III, apoB-48, remnant-like particle (RLP)-cholesterol, total adiponectin, high-molecular weight (HMW) adiponectin, and retinol-binding protein-4 (RBP-4) concentrations were measured using immunoassays. Compared with weight maintenance (n = 15), weight loss (n = 20) significantly decreased body weight, plasma insulin, triglycerides, total cholesterol, low-density lipoprotein (LDL)-cholesterol and lathosterol (P < 0.05). Weight loss also decreased plasma concentrations of apoC-III (-33%), apoB-48 (-37%), very low-density lipoprotein (VLDL)-apoB (-43%), RLP-cholesterol (-48%), and RBP-4 (-20%), and significantly increased plasma total (+20%) and HMW-adiponectin (+19%) concentrations. In the weight loss group, reduction in plasma apoC-III was associated (P < 0.05) with reduction in plasma apoB-48, VLDL-apoB, RLP-cholesterol and triglycerides. Increase in total adiponectin was associated (P < 0.05) with the reduction in plasma VLDL-apoB and triglycerides. The changes in HMW-adiponectin and RBP-4 were not associated with changes in plasma apoB-48, apoC-III, VLDL-apoB, RLP-cholesterol or triglycerides. In multiple regression analysis including changes in visceral fat, insulin and total adiponectin concentrations, the fall in plasma apoC-III concentration was an independent predictor of the reductions in plasma apoB-48, VLDL-apoB, RLP-cholesterol and triglycerides concentrations. In men with MetS, weight loss decreases the plasma concentrations of apoB-48, VLDL-apoB, RLP-cholesterol and triglycerides. This effect could partly relate to concomitant changes in plasma apoC-III and adiponectin concentrations that accelerate the catabolism of TRLs. | 18,837,799 |
Apoptotic effect of Helicobacter pylori on oesophageal squamous-cell carcinoma cells in vitro. | The relationship between Helicobacter pylori (Hp) infection and oesophageal squamous-cell carcinoma (ESCC) risk is still inconclusive. Our previous study found an inverse association between the two, but its mechanism is still unknown. Thus, we conducted in vitro studies to clarify the issue. One ESCC (CE 81T/VGH) cell line was co-cultured with Hp, using one gastric adenocarcinoma (AGS) cell line as the control. Hp-induced cell apoptosis was determined by flow cytometry, terminal transferase-mediated dUTP nick end labelling (TUNEL) assay and staining; caspase-3 protein expressions in cell lysates were detected by Western immunoblot. Increased apoptosis was found in CE 81T/VGH, but not in AGS cells, by flow cytometry and TUNEL assay after being co-cultured with Hp at the multiplicity of infection of 1/100 (but not at 1/400) for 36 h. The amount of activated caspase-3 (17/19 kDa) also increased in CE 81T/VGH, but not in AGS cells, after co-culturing with Hp at MOI of 1/100 for 36 h. The results were confirmed by triplicate experiments in which the different apoptotic assays remained consistent. Our study provides indirect evidence of the inverse association between Hp infection and ESCC risk, which is possibly due to Hp-induced apoptosis in ESCC cells. A further in vivo study is necessary to confirm our findings. | 18,837,801 |
Has the time come to control hepatitis A globally? Matching prevention to the changing epidemiology. | For the first time a global meeting on hepatitis A virus (HAV) infection as vaccine preventable disease was organized at the end of 2007. More than 200 experts from 46 countries gathered to investigate the changing global HAV epidemiology reflecting the increasing numbers of persons at risk for severe clinical disease and mortality from HAV infection. The benefits of childhood and adult hepatitis A (HepA) vaccination strategies and the data needed by individual countries and international health organizations to assess current HepA prevention strategies were discussed. New approaches in preventing HAV infection including universal HepA vaccination were considered. This introductory paper summarizes the major findings of the meeting and describes the changing epidemiology of HAV infections and the impact of HepA vaccination strategies in various countries. Implementation of HepA vaccination strategies should take into account the level of endemicity, the level of the socio-economic development and sanitation, and the risk of outbreaks. A stepwise strategy for introduction of HepA universal immunisation of children was recommended. This strategy should be based on accurate surveillance of cases and qualitative documentation of outbreaks and their control, secure political support on the basis of high-quality results, and comprehensive cost-effectiveness studies. The recognition of the need for increased global attention towards HepA prevention is an important outcome of this meeting. | 18,837,827 |
Acute amiodarone-induced pulmonary toxicity: an association of risk factors in a child operated by arterial switch operation. | Amiodarone is an antiarrhythmic benzoflurane drug with an imposing adverse effect profile. Amiodarone pulmonary toxicity is the major complication. It is well described in adults, whereas it is extremely rare in pediatric patients. This is a case of a child with supraventricular tachycardia post repair of transposition of the great vessels who developed amiodarone toxicity. | 18,837,818 |
Changing epidemiology of hepatitis A in Brazil: reassessing immunization policy. | Recent studies have shown that the prevalence of antibody to hepatitis A virus (HAV) is decreasing in several Latin American countries. Brazil is a very large and heterogeneous country, showing striking regional differences. With regard to sanitary facilities, 81.7% of the districts in the south-eastern region have sewage systems, compared with only 5.8% in the northern region. Results of sero-epidemiological studies and reported hepatitis A outbreaks indicate a change in the epidemiological pattern of hepatitis A in the country. Individuals, especially those under the age of 10, are mostly unprotected from HAV infection, regardless of their socioeconomic status. During 2000-2005, approximately 14 000-21 000 cases of hepatitis A were reported annually in Brazil, a rate of 7.5-11 cases per 100 000 population. Nationwide, hepatitis A mortality rates declined progressively from 1980 to 2002. As fatal cases constitute a small, but predictable, portion of all acute hepatitis A cases, which are in turn part of the total number of HAV infections, these data suggest that there has been a decline in HAV circulation in all Brazilian regions over the last two decades. Taken together these facts point out that the epidemiological pattern of hepatitis A is changing in Brazil. Besides improvements in sanitary conditions in the poorest Brazilian regions, the introduction of hepatitis A vaccination of young children could be a strategy for controlling HAV infection in the country. | 18,837,829 |
Hypersensitivity myocarditis presenting as atrioventricular block and wide complex tachycardia in a toddler. | A 13-month-old boy presented with acute onset of complete atrioventricular block and wide complex tachycardia but normal hemodynamics. Endomyocardial biopsy disclosed active myocarditis with eosinophils, suggesting a hypersensitivity reaction. With no treatment, the rhythm disturbance resolved within days of onset. Our patient's presentation and self-limited illness is unique. To our knowledge, this is only the second reported case of eosinophilic myocarditis in a young child or infant. | 18,837,817 |
Hepatitis A acute liver failure: follow-up of paediatric patients in southern Brazil. | We retrospectively analysed 33 children and adolescents who had been hospitalized in a liver transplant unit within the previous 10 years for acute liver failure (ALF). The patients' age varied between 2 months and 15 years of age (median 6.2 +/- 5.3), and 21 (63%) were male. Thirteen patients (39%) were immunoglobulin-M anti-hepatitis A virus (HAV) sero-positive. Eleven cases (33%) had an undetermined aetiology. The 13 children with HAV ALF were between 17 months and 15.6 years of age (median 5.8 +/- 4.6) and eight were male (61.5%). All were on a list for urgent liver transplant. Of these, five (38%) died while waiting for a liver. Only one patient recovered spontaneously. Seven patients received a liver transplant; three died in the immediate postoperative period and one died 45 days after transplant. Three children are alive 1, 2 and 5 years after transplant. We conclude that HAV was the most frequent cause of ALF, which had high mortality even when a liver transplant was possible. The results support universal HAV vaccination in this area. | 18,837,838 |
Male sex and pre-existing diabetes are independent risk factors for stillbirth. | To determine whether the risk of stillbirth is associated with male fetal sex, fetal growth and maternal factors in an Australian population. A retrospective secondary data analysis of 16 445 singleton births was performed using a tertiary referral centre obstetric database (1995-1999). Univariate and multiple logistic regression analyses were performed. Stillbirth complicated 1% of the pregnancies in the study population, and 59% of stillbirths were associated with a male fetus. Significant characteristics associated with stillbirth were intrauterine growth restriction (IUGR), birth defects, gestational age, Aboriginal ethnicity, previous stillbirth, parity greater than three and placental abruption. Male stillbirths were more likely to occur at a later gestation (median gestation 30.5 weeks, range 20-43 weeks) compared to females (median 25 weeks, range 20-40 weeks), P = 0.01. Sixty per cent of IUGR fetuses were female (P < 0.001). Male sex (odds ratio (OR) 1.5, confidence interval (CI) 1.01, 2.17, P = 0.04) and maternal type 1 diabetes (OR 4.7, CI 1.58, 14.19, P = 0.006) were independently associated with stillbirth. Male fetal sex and pre-existing diabetes are independent risk factors for stillbirth. Diabetes remains a significant risk for stillbirth even with contemporary monitoring and clinical management. Those diabetic pregnancies where the fetus is male require appropriate monitoring and timely interventions to achieve an optimal outcome. | 18,837,843 |
Antenatal topographical assessment of placenta accreta with ultrasound. | The major risk of placenta accreta is severe haemorrhage when the placenta is separated at delivery. A case series of placenta accreta with antenatal sonographic topographical assessment of myometrial involvement is presented. The extent of myometrial involvement and the vascularity could be assessed by the observation of the extent of placental-uterine wall interface disruption and the vessels crossing the interface disruption sites. Such assessment results in strategic planning of management of the placenta at delivery with favourable pregnancy outcomes. | 18,837,849 |
Regional brain changes in bipolar I depression: a functional magnetic resonance imaging study. | To investigate neural activity in prefrontal cortex and amygdala during bipolar depression. Eleven bipolar I depressed and 17 normal subjects underwent functional magnetic resonance imaging (fMRI) while performing a task known to activate prefrontal cortex and amygdala. Whole brain activation patterns were determined using statistical parametric mapping (SPM) when subjects matched faces displaying neutral or negative affect (match condition) or matched a geometric form (control condition). Contrasts for each group for the match versus control conditions were used in a second-level random effects analysis. Random effects between-group analysis revealed significant attenuation in right and left orbitofrontal cortex (BA47) and right dorsolateral prefrontal cortex (DLPFC) (BA9) in bipolar depressed subjects. Additionally, random effects analysis showed a significantly increased activation in left lateral orbitofrontal cortex (BA10) in the bipolar depressed versus control subjects. Within-group contrasts demonstrated significant amygdala activation in the controls and no significant amygdala activation in the bipolar depressed subjects. The amygdala between-group difference, however, was not significant. Bipolar depression is associated with attenuated bilateral orbitofrontal (BA47) activation, attenuated right DLPFC (BA9) activation and heightened left orbitofrontal (BA10) activation. BA47 attenuation has also been reported in mania and may thus represent a trait feature of the disorder. Increased left prefrontal (BA10) activation may be a state marker to bipolar depression. Our findings suggest dissociation between mood-dependent and disease-dependent functional brain abnormalities in bipolar disorder. | 18,837,865 |
Role of Tc99m MIBI SPECT in the assessment of treatment response in pharyngeal carcinoma. | The purpose of this study was to compare Tc(99m) MIBI SPECT imaging with computed tomography (CT) for assessment of post-radiotherapy treatment response in pharyngeal carcinoma. Twenty-two subjects took part in this study, which included six patients with nasopharyngeal carcinoma (Group I), three patients with oropharyngeal carcinoma and eight patients with hypopharyngeal carcinoma (Group II), and five control patients (Group III). All scans were analyzed qualitatively and quantitatively and correlated with findings on local examination and biopsy. Various indices such as ratios of nasopharynx, oropharynx, and hypopharynx to scalp (NSR, OSR, HSR), to nuchal muscles (NNR, ONR, HNR), and parotid glands (NPR, OPR, HPR) were calculated. The mean values of these above mentioned ratios calculated in the control group (Group III) were used as cutoff values to determine the presence or absence of tumor tissue in the patient groups (Groups I and II). The cutoff values calculated were 2.89 (NSR), 1.39 (NNR), 0.57(NPR), 3.83 (OSR), 1.81 (ONR), 0.83 (OPR), 2.86 (HSR), 1.73 (HNR), and 0.59 (HPR). The results revealed 100% sensitivity for primary nasopharyngeal tumors but less sensitivity for primary oropharyngeal and hypopharyngeal tumors (63.6%). Based on a relative decrease in tracer uptake, Tc(99m) MIBI SPECT scan was able to predict partial remission, complete remission, and no response on post-therapy scans. There were three false-negative results of disease progression in addition to evidence of disease eradication on CT scan. Thus Tc(99m) MIBI SPECT imaging has shown promising results in the detection of primary tumors and evaluation of treatment response much earlier than CT scan, which needs further exploration and large-scale studies. | 18,837,883 |
Selective surgical management of well-differentiated thyroid cancer. | There has been a rapid rise in the incidence of thyroid cancer in the United States, along with more incidentalomas of the thyroid. Treatment of thyroid cancer revolves around appropriate surgical intervention, minimizing complications, and the use of adjuvant therapy in select circumstances. Prognostic features and risk-group analysis are crucial in determining the appropriate treatment. Thyroid cancers are divided into low-, intermediate-, and high-risk groups. Surgical treatment should adhere to the risk-group analysis. The prognostic features in thyroid cancer are age, gender, size and grade of the tumor, extrathyroidal extension, and completeness of resection. The patient presenting with extrathyroidal extension needs extra attention in the operating room to remove all gross tumor during the initial surgical procedure to avoid future recurrences. Nodal metastasis generally has minimal implications; however, in older patients and those with poorly differentiated histology, it has major implications. Grading of the tumor is important, especially for understanding the poorly differentiated varieties of thyroid cancer, such as tall cell and insular. These patients do not respond well to RAI and are best followed with a PET scan. Overall survival in patients with well-differentiated thyroid cancer exceeds 95%. | 18,837,884 |
Cancer pain and analgesia. | Pain ranges in prevalence from 14-100% among cancer patients and occurs in 50-70% of those in active treatment. Cancer pain may result from direct invasion of tumor into nerves, bones, soft tissue, ligaments, and fascia, and may induce visceral pain through distension and obstruction. Cancer pain is multifaceted. Clinicians may describe cancer pain as acute, chronic, nociceptive (somatic), visceral, or neuropathic. Despite implementation of the WHO guidelines, reports of undertreatment of cancer pain persist in various clinical settings and in spite of decades of work to reduce unnecessary discomfort. Substantial obstacles to adequate pain relief with opioids include specific concerns of patients themselves, their family members, physicians, nurses, and the healthcare system. The WHO analgesic ladder serves as the mainstay of treatment for the relief of cancer pain in concert with tumoricidal, surgical, interventional, radiotherapeutic, psychological, and rehabilitative modalities. This multidimensional approach offers the greatest potential for maximizing analgesia and minimizing adverse effects. Primary therapies are directed at the source of the cancer pain and may enhance a patient's function, longevity, and comfort. Adjuvant therapies include nonopioids that confer analgesic effects in certain medical conditions but primarily treat conditions that do not involve pain. Nonopioid medications (over-the-counter agents) are useful in the management of mild to moderate pain, and their continuation through step 3 of the WHO ladder is an option after weighing a drug's risks and benefits in individual patients. Symptomatic treatment of severe cancer pain should begin with an opioid, regardless of the mechanism of the pain. They are very effective analgesics, titrate easily, and offer a favorable risk/benefit ratio. Cancer pain remains inadequately controlled despite the diagnostic and therapeutic means of ensuring that patients feel comfortable during their illness. Therefore, all practitioners need to make control of cancer pain a professional duty, even if they can only use the most basic and least expensive analgesic medications, such as morphine, codeine, and acetaminophen, to reduce human suffering. | 18,837,907 |
Metabolic DNA as the origin of spontaneously released DNA? | A DNA fraction is spontaneously released from living, but not dead or dying, human, other mammalian, avian, amphibian, plant, and prokaryote cells. The spontaneously released DNA fraction has been shown to be (a) present in both actively dividing and nondividing, differentiated cell populations; (b) labile; (c) associated with DNA-dependent RNA or DNA polymerase; (d) associated with an RNA fraction; and to have (e) a lower molecular weight than the typical genetic DNA fraction; and (f) Alu repeat sequences in increased proportions compared to a unique gene in plasma/serum. On the other hand, early autoradiographic and biochemical and quantitative cytochemical and cytophysical studies on DNA permitted the identification of a DNA fraction which was (1) present in both actively dividing and nondividing, differentiated cell populations; (2) labile; and (3) had a lower molecular weight than the typical genetic DNA fraction. This DNA fraction was termed metabolic DNA (m-DNA) and was proposed as possibly forming extra gene copies for the rapid production of m-RNA, to be destroyed subsequently. Therefore, we suggest that the metabolic DNA fraction might represent the precursor to the formation of the spontaneously released DNA fraction. | 18,837,918 |
Circulating nucleic acids in the assessment of endogenous growth hormone production. | There is growing concern about the use of recombinant human growth hormone (rhGH) by individuals taking part in competitive sports. Although rhGH is banned by the international organizations, the detection of GH doping is difficult. We postulated that rhGH will suppress endogenous GH production, which can be assessed by the measurement of mRNA for GH and growth hormone-releasing hormone (GHRH). In order to prove this concept, we undertook a pilot study to examine whether circulating nucleic acids are useful in the detection of endogenous GH production. Blood samples were collected into PAXgene tubes from 37 healthy controls and 12 acromegalic patients. RNA was extracted from the samples, cDNA was obtained, and the quantities of mRNA for GH and GHRH were measured using real-time PCR. In acromegalic patients, median mRNA concentration for GHRH (corrected for beta-actin mRNA) was 30.7 times lower than in controls (median delta C(T)) value of -0.128 versus 3.927, P < 0.001). There was a significant correlation between serum IGF-1 SD score and mRNA for GHRH (r= 0.407). In acromegalic patients, mRNA for GH was significantly higher than in controls (median values of -4.694 versus -0.044, P < 0.05). As GH production is known to decline with age, we also examined mRNA for GH and GHRH according to age subgroups. Both markers were significantly lower in the older age group (>50 years) compared to the younger age group (<34 years). These results show that mRNA for GH and GHRH can be detected in the peripheral circulation and raises the possibility of using these markers in the detection of exogenously administered GH. | 18,837,926 |
Point-of-admission hypothermia among high-risk Nigerian newborns. | Facilities which manage high-risk babies should frequently assess the burden of hypothermia and strive to reduce the incidence. To determine the incidence and outcome of point-of-admission hypothermia among hospitalized babies. The axillary temperatures of consecutive admissions into a Nigerian Newborn Unit were recorded. Temperature <36.5 degrees C defined hypothermia. The biodata and outcome of these babies were studied. Of 150 babies aged 0 to 648 hours, 93 had hypothermia with an incidence of 62%. Mild and moderate hypothermia accounted for 47.3% and 52.7% respectively. The incidence of hypothermia was highest (72.4%) among babies aged less than 24 hours. It was also higher among out-born babies compared to in-born babies (64.4% vs 58.3%). Preterm babies had significantly higher incidence of hypothermia (82.5%) compared with 54.5% of term babies (RR = 1.51; CI = 1.21 - 1.89). The incidence of hypothermia was also highest (93.3%) among very-low-birth-weight babies. The Case-Fatality-Rate was significantly higher among hypothermic babies (37.6% vs 16.7%; RR = 2.26, CI = 1.14 - 4.48) and among out-born hypothermic babies (50% vs 17.1%; RR = 0.34, CI = 0.16 - 0.74). CFR was highest among hypothermic babies with severe respiratory distress, sepsis, preterm birth and asphyxia. The high incidence and poor outcome of hypothermia among high-risk babies is important. The use of the 'warm chain' and skin-to-skin contact between mother and her infant into routine delivery services in health facilities and at home may be useful. | 18,837,973 |
The role of positive selection in determining the molecular cause of species differences in disease. | Related species, such as humans and chimpanzees, often experience the same disease with varying degrees of pathology, as seen in the cases of Alzheimer's disease, or differing symptomatology as in AIDS. Furthermore, certain diseases such as schizophrenia, epithelial cancers and autoimmune disorders are far more frequent in humans than in other species for reasons not associated with lifestyle. Genes that have undergone positive selection during species evolution are indicative of functional adaptations that drive species differences. Thus we investigate whether biomedical disease differences between species can be attributed to positively selected genes. We identified genes that putatively underwent positive selection during the evolution of humans and four mammals which are often used to model human diseases (mouse, rat, chimpanzee and dog). We show that genes predicted to have been subject to positive selection pressure during human evolution are implicated in diseases such as epithelial cancers, schizophrenia, autoimmune diseases and Alzheimer's disease, all of which differ in prevalence and symptomatology between humans and their mammalian relatives. In agreement with previous studies, the chimpanzee lineage was found to have more genes under positive selection than any of the other lineages. In addition, we found new evidence to support the hypothesis that genes that have undergone positive selection tend to interact with each other. This is the first such evidence to be detected widely among mammalian genes and may be important in identifying molecular pathways causative of species differences. Our dataset of genes predicted to have been subject to positive selection in five species serves as an informative resource that can be consulted prior to selecting appropriate animal models during drug target validation. We conclude that studying the evolution of functional and biomedical disease differences between species is an important way to gain insight into their molecular causes and may provide a method to predict when animal models do not mirror human biology. | 18,837,980 |
Pica and refractory iron deficiency anaemia: a case report. | Iron deficiency is the most common cause of anaemia worldwide. Pica, the ingestion of substances that are inappropriate for consumption, is associated with iron deficiency and may be under-diagnosed. A 34-year-old woman presented with iron deficiency anaemia refractory to treatment for more than a decade. The clinical presentation, endoscopic findings and laboratory investigations were consistent with pica. Subsequent geophysical analysis confirmed that the ingested material was kaolin, a negatively charged silicate. Prolonged unexplained iron deficiency anaemia should prompt clinicians to remember and inquire about pica. In our patient, this would have averted numerous unnecessary investigations and prevented a decade-long suffering. | 18,838,005 |
The effect of coaching on the simulated malingering of memory impairment. | Detecting malingering or exaggeration of impairments in brain function after traumatic brain injury is of increasing importance in neuropsychological assessment. Lawyers involved in brain injury litigation cases routinely coach their clients how to approach neuropsychological testing to their advantage. Thus, it is important to know how robust assessment methods are with respect to symptom malingering or exaggeration. The influence of different coaching methods on the simulated malingering of memory impairments is investigated in neurologically healthy participants using the Short-Term-Memory Test from the Bremer Symptom-Validierung (STM-BSV). Cut-offs were derived from patients with mild to severe traumatic brain injury. For comparison purposes, the German adaptation of the Rey Auditory Verbal Learning Test (AVLT), and the Rey 15 Items Test (FIT) were additionally administered. Four groups of neurologically healthy subjects were instructed to (1) perform as best as they can, (2) simulate brain injury, (3) simulate brain injury and received additional information about the sequelae of head trauma, (4) simulate brain injury and received additional information on how to avoid detection. Furthermore, a group of patients with mild to severe closed head injury performed the tests with best effort. The naïve simulator and the symptom coached groups were the easiest to detect, whereas the symptom plus test coached group was the hardest to detect. The AVLT and the FIT were not suited to detect simulators (sensitivities from 0% to 50.8% at 75% specificity) whereas the STM-BSV detected simulators with 67% - 88% sensitivity at a specificity of 73%. However, the STM-BSV was not robust to coaching. The present investigation shows that symptom validity testing as implemented in the BSV-STM is one clinically useful element in the detection of memory malingering. However, clinicians have to be aware that coaching influences performance in the test. | 18,838,010 |
Multi-jurisdictional investigation of interactive fountain-associated cryptosporidiosis and salmonellosis outbreaks. | Interactive water fountains are established sources of gastrointestinal infections yet most health codes fail to regulate their design and operation. This report describes multi-agency, concurrent interactive fountain-associated cryptosporidiosis and salmonellosis outbreak investigations and highlights the need for the adoption of appropriate regulations for interactive fountains. | 18,838,018 |
Creation of an intraatrial tunnel to produce a total cavo-pulmonary connection in a patient with dominant right ventricle, totally anomalous pulmonary venous connection, and pulmonary atresia with non-confluent pulmonary arteries. | The surgical strategy for patients having a functionally single ventricle associated with totally anomalous pulmonary venous connection and pulmonary atresia with non-confluent pulmonary artery has yet to be agreed. We created an intraatrial tunnel to produce a total cavo-pulmonary connection in such a patient, also creating a confluence for the pulmonary arteries. By minimizing the use of the GoreTex patch, the patient was able to discontinue the use of warfarin. | 18,838,024 |
Food patterns and Mediterranean diet in western and eastern Mediterranean islands. | To assess current Mediterranean dietary patterns (MDP) in the western and eastern Mediterranean, i.e. in Balearic islanders (BI) and Greek islanders (GI). Dietary patterns were assessed using FFQ on a representative sample (n 1200) of the BI and GI (n 1324) adult population. A Mediterranean Diet Score (MDS) was calculated according to the consumption of nine MDP components: (i) with a beneficial effect on health, i.e. vegetables, fruits and nuts, cereals, legumes, fish and shellfish, MUFA:SFA ratio, and moderate alcohol consumption; and (ii) with a detrimental effect on health, i.e. meat and meat products, and milk and dairy products. Persons with consumption of beneficial components below the median (GI plus BI) received a value of 0 and those with consumption above the median a value of 1. Persons with below-median consumption of detrimental components received a value of 1 and above-median consumption a value of 0. For alcohol, a value of 1 was given to consumptions of 10-50 g/d (men) and 5-25 g/d (women). The range of the MDS was 0-9, with higher scores indicating greater adherence to the MDP. GI showed higher adherence (mean MDS 5.12 (sd 1.42)) to the MDP than BI (mean MDS 3.32 (sd 1.23)). BI diet was characterized by a high intake of legumes, nuts, seed oils, sugar and confectionery, and non-alcoholic beverages compared with GI, whereas GI diet was richer in fruit, vegetables, potatoes, olive oil, animal products and alcoholic beverages. The GI diet seems closer to the traditional MDP than the BI diet. | 18,838,026 |
From emotion resonance to empathic understanding: a social developmental neuroscience account. | The psychological construct of empathy refers to an intersubjective induction process by which positive and negative emotions are shared, without losing sight of whose feelings belong to whom. Empathy can lead to personal distress or to empathic concern (sympathy). The goal of this paper is to address the underlying cognitive processes and their neural underpinnings that constitute empathy within a developmental neuroscience perspective. In addition, we focus on how these processes go awry in developmental disorders marked by impairments in social cognition, such as autism spectrum disorder, and conduct disorder. We argue that empathy involves both bottom-up and top-down information processing, underpinned by specific and interacting neural systems. We discuss data from developmental psychology as well as cognitive neuroscience in support of such a model, and highlight the impact of neural dysfunctions on social cognitive developmental behavior. Altogether, bridging developmental science and cognitive neuroscience helps approach a more complete understanding of social cognition. Synthesizing these two domains also contributes to a better characterization of developmental psychopathologies that impacts the development of effective treatment strategies. | 18,838,031 |
Developmental disruptions in neural connectivity in the pathophysiology of schizophrenia. | Schizophrenia has been thought of as a disorder of reduced functional and structural connectivity. Recent advances in neuroimaging techniques such as functional magnetic resonance imaging, structural magnetic resonance imaging, diffusion tensor imaging, and small animal imaging have advanced our ability to investigate this hypothesis. Moreover, the power of longitudinal designs possible with these noninvasive techniques enable the study of not just how connectivity is disrupted in schizophrenia, but when this disruption emerges during development. This article reviews genetic and neurodevelopmental influences on structural and functional connectivity in human populations with or at risk for schizophrenia and in animal models of the disorder. We conclude that the weight of evidence across these diverse lines of inquiry points to a developmental disruption of neural connectivity in schizophrenia and that this disrupted connectivity likely involves susceptibility genes that affect processes involved in establishing intra- and interregional connectivity. | 18,838,043 |
Attrition and related trends in scientific rigor: a score card for ART adherence intervention research and recommendations for future directions. | Scientific rigor in intervention trials is frequently used in systems that identify effective interventions for dissemination. In these systems, and in work that synthesizes bodies of research, percent attrition is often considered a fatal threat to validity. However, differential attrition, versus percent total, is of primary concern. Key methodologic, design, and analytic issues pertaining to scientific rigor in longitudinal designs were identified, and the current literature on antiretroviral therapy adherence interventions (k = 51) was evaluated in relation to these. Although results suggest that this body of literature has progressed in rigor, improvements are needed in transparency of reporting participant flow, retention strategies, handling of missing data, and characterization of retained and lost cohorts. Attrition averaged 30% total, and differential by study arm was estimated at 9%. Differential attrition continues to be underreported and is not well represented by the more frequently used, though arguably less appropriate, metric of overall percent attrition. | 18,838,057 |
The information-motivation-behavioral skills model of antiretroviral adherence and its applications. | Suboptimal adherence to highly active antiretroviral therapy (HAART) may have serious consequences for HIV patients, and for public health overall. The Information-Motivation-Behavioral Skills (IMB) model of HAART adherence can be used to understand the dynamics of HAART adherence and to intervene with patients to promote more optimal levels of adherence. This article reviews the core hypotheses of the IMB model of HAART adherence and describes available correlational and experimental evaluations of the model, outcomes of adherence intervention trials that applied the model, and IMB model-based interventions that are currently under evaluation. It then explores one potential promising application of the model that uses a protocol originally developed and demonstrated as a structured patient-centered, provider-delivered risk reduction intervention to deliver information, motivation, and behavioral skills-based adherence-promotion strategies. This protocol could be incorporated into clinical practice as a valuable tool in working with patients individually. | 18,838,059 |
Withaferin A inhibits iNOS expression and nitric oxide production by Akt inactivation and down-regulating LPS-induced activity of NF-kappaB in RAW 264.7 cells. | Induction of inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production is thought to have beneficial immunomodulatory effects in acute and chronic inflammatory disorders. In Raw 264.7 cells stimulated with lipopolysaccharide (LPS) to mimic inflammation, withaferin A inhibited LPS-induced expression of both iNOS protein and mRNA in a dose-dependent manner. To investigate the mechanism by which withaferin A inhibits iNOS gene expression, we examined activation of mitogen-activated protein kinases (MAPKs) and Akt in Raw 264.7 cells. We did not observe any significant changes in the phosphorylation of p38 MAPK in cells treated with LPS alone or LPS plus withaferin A. However, LPS-induced Akt phosphorylation was markedly inhibited by withaferin A, while the phosphorylation of p42/p44 extracellular signal-regulated kinases (ERKs) was slightly inhibited by withaferin A treatment. Withaferin A prevented IkappaB phosphorylation, blocking the subsequent nuclear translocation of nuclear factor-kappaB (NF-kappaB) and inhibiting its DNA binding activity. LPS-induced p65 phosphorylation, which is mediated by extracellular signal-regulated kinase (ERK) and Akt pathways, was attenuated by withaferin A treatment. Moreover, LPS-induced NO production and NF-kappaB activation were inhibited by SH-6, a specific inhibitor of Akt. Taken together, these results suggest that withaferin A inhibits inflammation through inhibition of NO production and iNOS expression, at least in part, by blocking Akt and subsequently down-regulating NF-kappaB activity. | 18,838,070 |
Lidocaine affects the redox environment and the antioxidant enzymatic system causing oxidative stress in the hippocampus and amygdala of adult rats. | Our objective was to investigate if oxidative stress is involved in the neural damage caused by lidocaine. Male Wistar rats were used. The control group received 0.9% saline ip and the treated group received a single 60 mg/kg lidocaine dose ip. On days 1, 2, 5, and 10 after dosing, ten rats were sacrificed and their brains were quickly removed. The amygdala and hippocampus were dissected. Five samples were used to determine lipid peroxidation, reactive oxygen species (ROS), reduced glutathione (GSH), and oxidized glutathione (GSSG). Another five were used to measure antioxidant activities of glutathione peroxidase (GPX), catalase, Cu-Zn SOD (superoxide dismutase), Mn SOD, and total SOD. Ten days after injection of lidocaine, lipid peroxidation increases in the hippocampus because the ROS are enhanced from day 5, whereas in the amygdala lipid peroxidation and the ROS were enhanced only on the first day postinjection. Lidocaine causes an increased concentration of GSH and GSSG in the hippocampus from the first day. In the amygdala the GSH and GSSG content were increased at day 10. In the hippocampus the catalase activity was enhanced, whereas the total SOD and Cu-Zn SOD activities were decreased. In the amygdala the lidocaine enhances the activities of catalase and GPX, but no SOD isoenzymes were modified. In this research we demonstrated that lidocaine affects the redox environment and promotes increases of the oxidative markers both in the hippocampus and amygdala but in a different pattern. | 18,838,081 |
Chitosan derivatives obtained by chemical modifications for biomedical and environmental applications. | Chitosan is a natural based polymer, obtained by alkaline deacetylation of chitin, which presents excellent biological properties such as biodegradability and immunological, antibacterial and wound-healing activity. Recently, there has been a growing interest in the chemical modification of chitosan in order to improve its solubility and widen its applications. The main chemical modifications of chitosan that have been proposed in the literature are reviewed in this paper. Moreover, these chemical modifications lead to a wide range of derivatives with a broad range of applications. Recent and relevant examples of the distinct applications, with particular emphasis on tissue engineering, drug delivery and environmental applications, are presented. | 18,838,086 |
Identification of a novel DPA1 allele, DPA1*010602, in an East African population. | We report here a novel DPA1 allele, DPA1*010602, which was identified from an East African population during sequence-based human leukocyte antigen DPA1 typing. Through cloning and sequencing of multiple clones we confirmed that the new allele is identical to DPA1*010301 at exon 2 with the exception of two nucleotide substitutions (ATG to CAG) at codon 31. The substitutions changed the amino acid at codon 31 from methionine to glutamine. The World Health Organization nomenclature committee named the new allele DPA1*010602. | 18,838,095 |
Neuroprotective effects of berberine on stroke models in vitro and in vivo. | Berberine is an alkaloid derived from herb medicine Coptidis Rhizom. Although there are increasing evidences that berberine exhibits neuroprotective effects against ischemic brain damage, little is known about the mechanism. In this study, we investigated the effect of berberine on ischemic injury in a middle cerebral artery occlusion (MCAO) model. We found that berberine improved neurological outcome and reduced ischemia/reperfusion (I/R)-induced cerebral infarction 48h after MCAO. The protective effect of berberine was confirmed in in vitro study. Berberine protected PC12 cells against oxygen-glucose deprivation (OGD)-induced injury. The results showed that berberine inhibited reactive oxygen species (ROS) generation, and subsequent release of pro-apoptotic factor cytochrome c and apoptosis-inducing factors (AIFs) evoked by OGD. Findings of this study suggest that berberine protects against ischemic brain injury by decreasing the intracellular ROS level and subsequently inhibiting mitochondrial apoptotic pathway. | 18,838,103 |
NaCl preference and water intake effects of food availability in median eminence polydipsia. | Lesions in the median eminence (ME) produce a well-known neurological model of polydipsia and polyuria in rats. The effect of food availability (ad lib/deprivation) on the polydipsic/polyuric behaviour of animals was tested. As expected, all lesioned rats developed strong polyuria and polydipsia during the first postoperative 24h. This effect was maintained during day 2 when food was available ad lib (experiment A), but both polyuria and polydipsia were abolished when animals were deprived of food during the next 24h (day 3). Animals deprived of food from the first post-operative day (experiment B) showed a significant reduction in the initial polyuria and polydipsia (day 1) on day 2, but these effects were again observed on day 3 when food was available ad lib. Finally, when food-deprived animals were able to choose between a 1.5% sodium chloride solution and water (experiment C), they preferentially chose (82% of total liquid consumed) the hypertonic saline solution (day 1); during the next 24h (day 2), when only water was available, the polyuric/polydipsic effect was abolished but returned when food became available ad lib on day 3. Hence, the polyuria/polydipsia effect produced by ME lesions appears to be consistent during the first 24h but might later be related to the availability of standard food and is completely abolished under food deprivation conditions. Preference for the hypertonic solution supports the volemic component of this syndrome and demonstrates the need for appropriate amounts of hypertonic nutrients to be consumed during the first 24h. | 18,838,106 |
Distribution of two-pore-domain potassium channels in the adult rat vestibular periphery. | Constitutively active background or "leak" two-pore-domain potassium (K(+)) channels (Kcnk family), as defined by lack of voltage and time dependency are central to electrical excitability of cells by controlling resting membrane potential and membrane resistance. Inhibition of these channels by several neurotransmitters, e.g. glutamate, or acetylcholine, induces membrane depolarization and subsequent action potential firing as well as increases membrane resistance amplifying responses to synaptic inputs. In contrast, their opening contributes to hyperpolarization. Because of their central role in determining cellular excitability and response to synaptic stimulation, these channels likely play a role in the differential effects of vestibular efferent neurons on afferent discharge. Microarray data from previous experiments showed Kcnk 1, 2, 3, 6, 12 and 1 5 mRNA in Scarpa's ganglia. Real-time RT-PCR showed Kcnk 1, 2, 3, 6, 12 and 15 mRNA expression in Scarpa's ganglia and Kcnk 1, 2, 3, 6, 12 but not 15 mRNA expression in the crista ampullaris. We studied the distribution of two-pore-domain potassium channels K(2P)1.1, 2.1, 3.1 and 6.1 like immunoreactivity (corresponding to Kcnk genes 1, 2, 3 and 6) in the vestibular periphery. K(2P)1.1 (TWIK 1) immunoreactivity was detected along nerve terminals, supporting cells and blood vessels of the crista ampullaris and in the cytoplasm of neurons of the Scarpa's ganglia. K(2P)2.1 (TREK 1) immunoreactivity was detected in nerve terminals and transitional cells of the crista ampullaris, in the vestibular dark cells and in neuronal fibers and somata of neurons of Scarpa's ganglia. K(2P)3.1 (TASK 1) immunoreactivity was detected in supporting cells and transitional cells of the crista ampullaris, in vestibular dark cells and in neuron cytoplasm within Scarpa's ganglia. K(2P)6.1 (TWIK 2) immunoreactivity was detected in nerve terminals, blood vessels hair cells and transitional cells of the crista ampullaris and in the somata and neuron fibers of Scarpa's ganglia. | 18,838,117 |
The good work--a Swedish trade union vision in the shadow of lean production. | "The Good Work" (Det goda arbetet) was established as a highly praised and established concept in the Swedish working life debate in the middle of the 1980s. In this paper, we are going to discuss the concept in relation to the massive introduction of lean production in Swedish industry. The aim of this paper is to restore the theory of the good work into the industrial society of today. We will search for a model for 'good work' in balance between the demands from production and good conditions for a learning environment. The theoretical base for this paper will be found in both organisational research and research on production technology systems. We identify three strong trends in Swedish industrial companies giving both pitfalls and possibilities for the good work; the learning focus as a way to increase productivity and improve working conditions; Lean Production in most cases imply narrow short-cyclic work tasks; and the global market that reduces national discretion. As a result, we formulate a new set of criteria for "the good work". | 18,838,130 |
Different kinetics of cholesterol delivery to components of the cholesterol homeostatic machinery: implications for cholesterol trafficking to the endoplasmic reticulum. | Previously, using an oxysterol to induce cholesterol trafficking to the Endoplasmic Reticulum (ER), we reported a dissociation between cholesterol transport to two important cholesterol regulatory components in the ER: the cholesterol esterifying enzyme ACAT (Acyl CoA:Cholesterol Acyltransferase) and the membrane-bound transcription factor SREBP (Sterol Regulatory Element Binding Protein) (X. Du, Y.H. Pham and A.J. Brown, Effects of 25-hydroxycholesterol on cholesterol esterification and SREBP processing are dissociable: implications for cholesterol movement to the regulatory pool in the endoplasmic reticulum, J. Biol Chem. 279 (2004) 47010-47016). Here, we employed low-density lipoprotein (LDL) as a more physiologically-relevant mode of cholesterol delivery, and compared cholesterol transport to ACAT (determined by esterification) and SREBP (assessed by processing) in mutant Chinese Hamster Ovary cells that have cholesterol-trafficking defects (including Niemann-Pick type C). We showed clear differences in kinetics between the two, with impaired cholesterol trafficking to SREBP being resolved more rapidly than to ACAT. This is unlikely to be due to a reduced threshold of cholesterol sensed by the SREBP system relative to ACAT, since both responded to LDL-derived cholesterol within 2 h whereas the divergence observed between the two was prolonged (>20 h). Furthermore, ACAT inhibition did not expand the ER regulatory pool of cholesterol as judged by unaltered sensitivity of SREBP processing to LDL. Collectively, our data favor the contention that there are different cholesterol pools and/or transport pathways which feed ACAT and SREBP within the ER. | 18,838,129 |
Enantioselective chromatography-a powerful tool for the discrimination of biotic and abiotic transformation processes of chiral environmental pollutants. | On the basis of the general principles of chirality the characteristics of chromatograms obtained by enantioselective GC and HPLC are explained, followed by a description of different enantioselective chromatographic methods (HPLC, high-resolution GC, multidimensional GC, CE, supercritical fluid chromatography) thus far applied. The potential of enantioselective chromatography is highlighted by examples of studies on microbial, enzymatic and photochemical transformation processes, on air/sea exchange and long-range transport processes, enantioselective toxic effects as well as on the fate of emerging environmental chiral pollutants such as pharmaceuticals, personal care products and the flame retardant 1,2,5,6,9,10-hexabromocyclododecane. | 18,838,139 |
Analysis of minor flavonoids in Piper hostmannianum var. berbicense using liquid chromatography coupled with atmospheric pressure chemical ionization mass spectrometry. | The fragmentations of hydroxylated flavanones, chalcones and dihydrochalcones were investigated by direct loop injection using an ion trap mass spectrometry equipped with atmospheric pressure chemical ionization (APCI) probe. Some of them have been isolated from the leaves of Piper hostmannianum var. berbicense and standards were used to confirm their fragmentation behaviour. In negative ion mode, fragmentations of these three types of flavonoids revealed specific diagnostic ions which allowed us to identify aglycones in a crude plant extract. The major fragment ion obtained in MS/MS experiment for methoxylated chalcones is the neutral loss of a methyl radical whereas a H(2)O molecule is lost in the case of methoxylated dihydrochalcones. Methoxylated chalcones and flavanones isomers could be differentiated by the relative intensity ratio of [M-H-CH(3)]*(-) and [M-H-C(2)H(2)O](-) ions. Based on UV and MS data, a decision tree that includes UV lambda(max) absorptions and MS/MS diagnostic ions was built in order to obtain structural information of unknown compounds present in the extract. This tree was used to identify flavonoids in the ethyl acetate extract of P. hostmannianum var. berbicense leaves after analysis by high-performance liquid chromatography-diode array detection-atmospheric pressure chemical ionization ion trap multistage mass spectrometry. A total of 11 flavonoids were tentatively characterized based on the MS fragmentations pattern observed in MS(n) experiments. | 18,838,145 |
Cardiac parasympathetic dysfunction concurrent with cardiac sympathetic denervation in Parkinson's disease. | We aimed to characterize the relationship between cardiac sympathetic and parasympathetic dysfunction employing cardiac (123)I-meta-iodobenzylguanidine (MIBG) uptake and other autonomic function parameters in Parkinson's disease (PD). 79 PD patients were studied. We performed (123)I-MIBG myocardial scintigraphy to assess the extent of cardiac sympathetic denervation. Electrocardiogram readings at rest and postural change in blood pressure were also examined. Coefficient variation of RR intervals (CVR-R) was used as an index for cardiac parasympathetic activity. Cardiac (123)I-MIBG uptake did not vary significantly among the Hoehn-Yahr (H-Y) stages. There was a significant correlation between cardiac (123)I-MIBG uptake and CVR-R (early, r=0.457, p<0.001; late, r=0.442, p<0.001). While the correlation was present among the patients who had had the disease less than two years (early, r=0.558, p<0.001; late, r=0.530, p<0.001), the patients with the disease duration longer than two years did not have such a significant correlation. Age, disease duration, corrected QT interval, or postural blood pressure change did not correlate with cardiac (123)I-MIBG uptake. Orthostatic hypotension was observed in 13 out of 72 subjects, and reduced CVR-R was a major determinant for the development of orthostatic hypotension. We conclude that cardiac parasympathetic dysfunction occurs concurrent with sympathetic denervation as revealed by (123)I-MIBG myocardial scintigraphy in PD and contributes to the development of orthostatic hypotension. | 18,838,148 |
The effect of a low dose of transforming growth factor beta1 (TGF-beta1) on the early bone-healing around oral implants inserted in trabecular bone. | Transforming growth factor beta1 (TGF-beta1) has been shown to stimulate bone healing in several animal models and may influence bone response directly after implant installation. Aim of the present study is to investigate the effect of a low dose of TGF-beta1, on the early bone-healing around oral implants placed in trabecular bone (femoral condyle of goats). Twenty-four cylindrical screw type implants were used and TGF-beta1 in two different concentrations were applied on sixteen of them. Each animal received three implants: one Ti (control), one Ti loaded with 0.5 microg TGF-beta1 (Ti-TGF(0.5)), and one Ti loaded with 1.0 microg TGF-beta1 (Ti-TGF(1.0)). The eight animals were euthanized at 6 weeks after implantation and implants with surrounding tissue were retrieved for histological preparation and histomorphometrical evaluation. Light microscopical analysis showed the occurrence of an intervening fibrous tissue layer around about half of the TGF-beta1 loaded implants. Further, the histomorphometrical measurements revealed that the Ti implants demonstrated the highest percentage of bone-implant contact (65+/-4%), while Ti-TGF(1.0) implants showed the lowest amount (45+/-12%). The difference between these two groups was statistically significant. On basis of the results, it is concluded that a low dose of TGF-beta1 has a negative effect on the integration of oral implants in trabecular bone during the early post-implantation healing phase. | 18,838,161 |
The antimicrobial properties of light-activated polymers containing methylene blue and gold nanoparticles. | We report the formation of polysiloxane polymers containing embedded methylene blue and gold nanoparticles incorporated by a swell-encapsulation-shrink method. These polymers show significant antimicrobial activity against methicillin-resistant Staphylococcus aureus and Escherichia coli with up to a 3.5 log(10) reduction in the viable count when exposed for 5 min to light from a low power 660 nm laser. The bacterial kill is due to the light-induced production of singlet oxygen and other reactive oxygen species by the methylene blue. Interestingly, the presence of 2 nm gold nanoparticles significantly enhanced the ability of the methylene blue to kill bacteria. | 18,838,166 |
Disruption of T cell suppression in chronic lymphocytic leukemia by CD200 blockade. | CD200 plays a key role in regulating the immune system and has been shown to be upregulated on the surface of different tumors including chronic lymphocytic leukemia. In this study we addressed the effects of CD200 over-expression in CLL cells on autologous T cells in a mixed lymphocyte reaction system. We used native and CD40 ligand (CD40L)-stimulated CLL cells as antigen-presenting cells (APCs) to expand autologous T cells of 14 patients. T cell proliferation over 3 weeks of in vitro culture was significantly enhanced compared to control cells when using CD40L-stimulated APCs and the anti-CD200 antibody 1B9 (p=0.0004). CD200 blockade was further shown to stimulate antigen-specific T cell responses towards the CLL-associated antigen fibromodulin (p=0.04). Finally, the number of CD4+/CD25high/FOXP3+ T cells (T(reg)) was significantly decreased adding anti-CD200 antibody (p=0.04). In summary, CD200 blockade may provide therapeutic benefits in CLL by augmenting an antigen-specific T cell response with suppression of regulatory T cells. | 18,838,168 |
Conformational changes involved in G-protein-coupled-receptor activation. | Little is known about the nature of the conformational changes that convert G-protein-coupled receptors (GPCRs), which bind diffusible ligands, from their resting into their active states. To gain structural insight into this process, various laboratories have used disulfide cross-linking strategies involving cysteine-substituted mutant GPCRs. Several recent disulfide cross-linking studies using the M(3) muscarinic acetylcholine receptor as a model system have led to novel insights into the conformational changes associated with the activation of this prototypical class I GPCR. These structural changes are predicted to involve multiple receptor regions, primarily distinct segments of transmembrane helices III, VI and VII and helix 8. Given the high degree of structural homology found among most GPCRs, it is likely that these findings will be of considerable general relevance. A better understanding of the molecular mechanisms underlying GPCR activation might lead to novel strategies aimed at modulating GPCR function for therapeutic purposes. | 18,838,178 |
Activated carbon/iron oxide composites for the removal of atrazine from aqueous medium. | The adsorption features of activated carbon and the oxidation properties of iron oxides were combined in a composite to produce new materials for atrazine removal from aqueous medium. Activated carbon/iron oxide composites were prepared at 1/1 and 5/1 mass ratios and characterized with powder X-ray diffractometry (XRD), infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and nitrogen adsorption measurements. The adsorption and oxidation processes were evaluated in batch experiments, in order to monitor the atrazine removal capacity of these composites. The main iron oxide actually present in the composites was goethite (alpha-FeOOH). Impregnation with iron oxide reduced the surface area by its deposition in the activated carbon pores. However, a higher iron concentration promoted a higher oxidation rate, indicating that the efficiency of the oxidation reaction is related with the iron content and not with the pre-concentration of the contaminant on the carbon surface through adsorption process. | 18,838,216 |
The determination of hexavalent chromium (Cr6+) in electronic and electrical components and products to comply with RoHS regulations. | Toxicity of hexavalent chromium (Cr(6+)) was focused on with a publication of EU RoHS directive, a novel method to determine hexavalent chromium is developed. It is a combination of energy dispersion X-ray fluorescence spectrometry (EDXRF), spot test, alkali digestion and UV-vis spectrophotometric analysis. First, by EDXRF screening, the presence or absence of element Cr was established. Spot test was followed to identify the valent state of chromium because Cr(6+) and Cr(3+) normally coexist. After alkali digestion, Cr(VI) was separated without an undersired Cr(VI)-Cr(III) interconversions. With a color reagent (DPC) to chelated with Cr(VI), the solution was finally detected by a UV-vis spectrophotometer at a wavelength of 540 nm which is the basis of analyzing Cr(VI) quantitatively. Some parameters affecting analyses were studied. It was found that when pH in the final solution was 2.0, the extraction time was 60 min, the extraction temperature was 90 degrees C, pH during the extraction process was 7.5-8.5, and a mixed buffer solution (0.5M K(2)HPO(4)/0.5M KH(2)PO(4)) was added up to 1 ml, colorimetric reagent was added to 2 ml, it is optimal for extraction. Under this condition, interferences from Fe(3+), Pb(2+), Ag(+), etc., were overcome. It was also found that the curves are rectilinear in the range of 0-500 microg l(-1), the correlation coefficient is up to 0.999924, and the recovery rates are more than 85%, the Cr(III)-DPCO complex can be kept stable for 24h with a relative humidity (RH) range of 60-90%, and a temperature range of 5-40 degrees C. So it can be concluded that the proposed method has a good sensitivity and high precision. It is a more convincing and reliable method due to its relative standard deviation (R.S.D.) <1% after six replicate determinations of Cr(VI) in an Fe-Ni alloy sample. | 18,838,223 |
Effects of obesity on neuroendocrine, cardiovascular, and immune cell responses to acute psychosocial stress in premenopausal women. | To analyze the neuroendocrine and immune cell responses to acute psychosocial stress in obese compared to non-obese premenopausal women. N=15 obese (BMI> or =30) and N=24 (BMI<30) non-obese premenopausal women underwent public speaking stress. State anxiety, ACTH, cortisol, and the redistribution of immune cells were measured before, during, and 10 and 45min after public speaking. Serum hsCRP and serum IL-6 levels were analyzed before, and IL-6 additionally 45min after stress. In response to public speaking stress, both groups showed significant but comparable increases in state anxiety, plasma ACTH, and blood pressure (all p<0.01; time effects). The cortisol stress response was significantly enhanced in obese women (p<0.05; interaction effect). In addition, heart rate and diastolic blood pressure were significantly higher in obese women 10min following stress (p<0.05, t-tests). Public speaking stress led to a significant increase in IL-6 concentrations (p<0.001; time effect), and obese women displayed higher IL-6 levels both pre- and post-stress (p<0.05; group effect; between-group t-tests: pre-stress p<0.05; post-stress p<0.01). Baseline numbers of circulating leukocytes, granulocytes, CD3+ cells and hsCRP concentration were significantly higher in obese women (between-group t-tests: all p<0.05, but the groups did not differ in the stress-induced redistribution of circulating leukocyte subpopulations. Our data reveal a strong association of obesity with chronic low-grade inflammation in premenopausal women. This pro-inflammatory state, together with altered neuroendocrine and cardiovascular stress responsiveness, may conceivably constitute one of the mechanisms linking psychological stress and the long-term health risks associated with obesity. | 18,838,227 |
Analysis of retinal cellular infiltrate in experimental autoimmune uveoretinitis reveals multiple regulatory cell populations. | Experimental autoimmune uveoretinitis (EAU) is an animal model for human intraocular inflammatory disease. EAU is induced in B10.RIII mice by immunization with RBP-3 161-180 peptide and intraperitoneal pertussis toxin and is mediated by CD4(+) T cells that generate a clinically monophasic disease peaking approximately 2 weeks post-immunization. Collagenase digestion of retinal tissue allowed the quantification and characterization of leukocytes in the inflamed retina during disease progression. Using this method we identified three stages of disease. Initially there is a prodromal phase where we found significant changes in the number of leukocytes in the eye as early as 5 days post-immunization. This effect was, in part, non-antigen specific as a small increase in retinal leukocytes was also observed following immunization with OVA peptide. Following the prodrome there is a primary peak of infiltration including both CD4(+) T cells and CD11b(+) cells. This coincides with an early influx of neutrophils and is associated with a peak in IL-17-producing T cells. The neutrophils in the eye are CD11b(+) and Gr1(+) but can be distinguished from other myeloid cells by their high expression of Ly6G. The remaining CD11b(+)Gr1(+) cells can suppress proliferation and are analogous to myeloid derived suppressor cells which are found in tumors. The inflamed eye also contains a considerable proportion of FoxP3(+) regulatory cells. Following peak disease, the retina does not return to its pre-disease phenotype. Instead, fluctuations in infiltrating leukocyte numbers and changes to their relative composition continue, indicating that clinical recovery does not equate to the restoration of a normal retinal leukocyte population. | 18,838,247 |
The autoimmunologist: geoepidemiology, a new center of gravity, and prime time for autoimmunity. | There are currently over 100 human diseases that are considered to be autoimmune or chronic inflammatory affecting 5-10% of the world population and spanning through all medical specialties. As a result, health care costs are enormous and the clinical management is often challenging, particularly considering the comorbidity rates and the multi-organ involvement of each condition. We herein propose the creation of a new specialist, coined the autoimmunologist, to overcome the current limitations in the diagnostic process and clinical follow-up of patients with autoimmune diseases. More importantly, we also propose the creation of regional centers of excellence in autoimmunity where clinical research and management, as well as basic research may be united and interact in ideal synergy to ultimately create real translational research and provide better health care. | 18,838,248 |
Glandular stem cells are a promising source for much more than beta-cell replacement. | Glandular stem cells (GSCs) can be obtained from exocrine glands such as pancreas or salivary glands using well-established cell culturing methods. The resulting cell populations are characterized by a high proliferative capacity and an unusually high plasticity. Cells from pancreas have been demonstrated to differentiate into a multitude of cell types and even into oocyte-like cells. It has been found that the preparation method for GSCs can be applied to many vertebrates, including fishes and birds. Since the cells are excellently cryopreservable, this finding has been utilized to establish a new stem cell bank for preserving living cells of rare and wild animals. Apart from these advances, this mini-review also points out that GSCs from pancreas must not be confused with beta-cell progenitors but constitute a distinct cell type. | 18,838,258 |
Bactericidal/permeability-increasing protein (BPI) and BPI homologs at mucosal sites. | At mucosal surfaces, we must co-exist with a high density of diverse microorganisms; therefore, protection against these occurs on multiple levels. Leukocyte- and epithelial derived-antimicrobial peptides and proteins (AMPs) comprise an essential component of immune defense. These molecules possess antibacterial, antifungal and signalling properties and probably contribute to defence and maintenance of homeostasis between the host and commensal microorganisms. Among these AMPs is bactericidal/permeability-increasing protein (BPI), an antimicrobial protein with potent endotoxin-neutralising activity, and several homologs. This review explores the roles of BPI and and its homologs at the mucosal interface. Congeners of BPI are under biopharmaceutical development as novel anti-infective agents, highlighting the potential therapeutic relevance of this protein family. | 18,838,299 |
Validated high performance liquid chromatography-UV detection method for the determination of daptomycin in human plasma. | Daptomycin is the first approved member of the new class cyclic lipopeptide antibiotic drugs, effective against a broad spectrum of Gram-positive bacteria. Here we present an HPLC method with UV detection capable to obtain pharmacokinetic data of daptomycin in human plasma, exemplarily shown in a critically ill patient with acute renal failure undergoing extended daily dialysis. Sample preparation consists only of protein precipitation with methanol. Chromatographic separation was achieved on a Zorbax Eclipse XDB-C8 column and daptomycin was detected at 224 nm. The calibration function was linear over the range from 3.5 to 350 microg/ml. The relative standard deviations were <2% in the intra-day and <6% in the inter-day measurements. The accuracy was always better than 7%. Daptomycin was stable in aqueous solutions for 2 months frozen at-20 degrees C. However, in plasma frozen at -20 degrees C a loss of 25% in 1 month was observed. | 18,838,314 |
Supercritical fluid chromatography comparison of the poly(trans-1,2-cyclohexanediyl-bis acrylamide) (P-CAP) column with several derivatized polysaccharide-based stationary phases. | The poly(trans-1,2-cyclohexanediyl-bis acrylamide) (P-CAP) column has so far been primarily used with normal phase and polar organic mobile phase chromatography. Its use in supercritical fluid chromatography (SFC) was investigated via the analysis of 40 commercial and 100 proprietary compounds using a 12-min gradient with methanol as a modifier. Results were then compared against those obtained from the popular derivatized polysaccharide-based chiral stationary phases (CSPs) such as Chiralpak AD-H and Chiralpak AS-H as well as Chiralcel OD-H and Chiralcel OJ-H columns. P-CAP demonstrated separation of 25% of the 140 total compounds, while each of the derivatized polysaccharide-based CSPs separated at least 46%. A study that compared the loading of 1,1'-bi-2-naphthol with P-CAP and Chiralpak AS columns indicated a similar trend in resolution vs. amount injected, though AS appeared capable of allowing a greater loading of material. The P-CAP column was found to be beneficial in the separation of a complex mixture of enantiomers and achiral impurities, where the derivatized polysaccharide-based columns did not show as desirable of a separation. A key advantage of this type of chiral stationary phase is the fact that it is available in both enantiomeric forms, allowing manipulation of elution order of enantiomers, which is especially helpful for preparative applications. P-CAP also demonstrated that it could resolve an achiral impurity from the desired compound in a different mixture, while the same impurity co-eluted on the Chiralpak AD-H column. Overall, the synthetic polymer-based P-CAP showed less chiral discrimination power compared to the derivatized polysaccharide-based CSPs under the conditions explored in this study. | 18,838,315 |
Selective elimination of autoreactive T cells in vivo by the regulatory T cells. | How regulatory T cells (Treg) control autoreactive T cells has not been analyzed in animals with a normal T cell repertoire. Using endogenous viral superantigens (VSAg) as the primary self antigens and mice with the Scurfy mutation of FoxP3, we show here that the Treg defect causes preferential accumulation of autoreactive T cells. Interestingly, in the Scurfy mice, the proliferation of VSAg-reactive T cells was no more vigorous than that of non-VSAg-reactive T cells, which indicated that the preferential accumulation is not due to preferential proliferation. In contrast, VSAg-reactive T cells disappears in WT host despite their preferential proliferation. Importantly, when adoptively transferred into the newborn Scurfy mice, the Treg selectively kill autoreactive T cells without affecting their proliferation. The selective elimination is due to increased susceptibility of autoreactive T cells to Treg-mediated killing. | 18,838,339 |
Biomechanical evaluation and comparison of polyetheretherketone rod system to traditional titanium rod fixation. | Polyetheretherketone (PEEK) has been increasingly used as a biomaterial for spinal implants. PEEK lumbar fusion rods have recently become available for use in posterior lumbar fusion procedures. To compare Polyetheretherketone Rod System to traditional titanium rod fixation in a cadaveric model and provide mechanical test data for the PEEK system. Biomechanical testing. Cadaveric biomechanical testing was conducted to compare Expedium 5.5 mm PEEK rods to titanium rods of equivalent diameter. Biomaterials testing was performed to determine static and dynamic performance of Expedium 5.5 mm PEEK rods with 6% BaSo4 in compressive bending and torsion. Cadaveric testing demonstrated that PEEK rods can significantly reduce the range of motion of a destabilized segment. The testing showed no significant difference in the stability provided by PEEK and titanium rods in posterolateral fusion (PLF) or posterior lumbar interbody fusion (PLIF) constructs. PEEK static compressive bending tests showed 67 degrees displacement without fracture of the rod. Torsion testing showed 30 degrees of rotation without yield or plastic deformation. Dynamic compression testing revealed two fatigue runouts at 23 degrees. PEEK rods provide comparable stability to titanium rods of equivalent diameter in cadaveric testing. Mechanical testing suggests PEEK rods can withstand far beyond the angular displacements suggested by cadaveric testing and that of normal physiologic range of motion. Potential advantages to PEEK rods include better anterior column load sharing, reduced stress at bone-to-screw interface, and reduced computed tomography and magnetic resonance imaging scatter and artifact. | 18,838,341 |
Exploring time series retrieved from cardiac implantable devices for optimizing patient follow-up. | Current cardiac implantable devices (IDs) are equipped with a set of sensors that can provide useful information to improve patient follow-up and prevent health deterioration in the postoperative period. In this paper, data obtained from an ID with two such sensors (a transthoracic impedance sensor and an accelerometer) are analyzed in order to evaluate their potential application for the follow-up of patients treated with a cardiac resynchronization therapy (CRT). A methodology combining spatiotemporal fuzzy coding and multiple correspondence analysis (MCA) is applied in order to: 1) reduce the dimensionality of the data and provide new synthetic indexes based on the "factorial axes" obtained from MCA; 2) interpret these factorial axes in physiological terms; and 3) analyze the evolution of the patient's status by projecting the acquired data into the plane formed by the first two factorial axes named "factorial plane." In order to classify the different evolution patterns, a new similarity measure is proposed and validated on the simulated datasets, and then, used to cluster observed data from 41 CRT patients. The obtained clusters are compared with the annotations on each patient's medical record. Two areas on the factorial plane are identified, one being correlated with a health degradation of patients and the other with a stable clinical state. | 18,838,359 |
The Berlin Brain--Computer Interface: accurate performance from first-session in BCI-naïve subjects. | The Berlin Brain--Computer Interface (BBCI) project develops a noninvasive BCI system whose key features are: 1) the use of well-established motor competences as control paradigms; 2) high-dimensional features from multichannel EEG; and 3) advanced machine-learning techniques. Spatio-spectral changes of sensorimotor rhythms are used to discriminate imagined movements (left hand, right hand, and foot). A previous feedback study [M. Krauledat, K.-R. MUller, and G. Curio. (2007) The non-invasive Berlin brain--computer Interface: Fast acquisition of effective performance in untrained subjects. NeuroImage. [Online]. 37(2), pp. 539--550. Available: http://dx.doi.org/10.1016/j.neuroimage.2007.01.051] with ten subjects provided preliminary evidence that the BBCI system can be operated at high accuracy for subjects with less than five prior BCI exposures. Here, we demonstrate in a group of 14 fully BCI-naIve subjects that 8 out of 14 BCI novices can perform at >84% accuracy in their very first BCI session, and a further four subjects at >70%. Thus, 12 out of 14 BCI-novices had significant above-chance level performances without any subject training even in the first session, as based on an optimized EEG analysis by advanced machine-learning algorithms. | 18,838,371 |
The Burroughs Wellcome Career Award in the Biomedical Sciences: challenges to and prospects for estimating the causal effects of career development programs. | The Career Award in Biomedical Sciences (CABS) was launched by the Burroughs Wellcome Fund to assist talented scientists to cross the "bridge" that connects postdoctoral training with independent investigator status. This study examines the causal effects of CABS, using both conventional methods and a newer method (propensity score analysis) in attempting to account for selection biases (e.g., selecting the "best and the brightest") in estimating the award's impact. The results indicated that grantees outperformed unsuccessful applicants in obtaining a faculty position, competing for an R01 grant, and publishing in prestigious journals. However, it was nearly impossible to remove all the effects of selection bias from estimates of program effects. Because selection bias is a pervasive problem in assessing these programs, recommendations for improving evaluations of similar merit-based programs are offered. | 18,838,396 |
The nephrotic syndrome: an unusual case of multiple embolic events. | The nephrotic syndrome is an unusual cause of the hypercoaguable state and thromboembolic complications. Here we report the case of a 42-year-old woman with nephrotic syndrome who presented with a pulseless lower extremity and a midpole renal infarct requiring urgent embolectomy of the leg. During her embolic evaluation, she was found to have an intracardiac thrombus. Over the course of her hospitalization, she developed a pulseless upper extremity and required an embolectomy of her arm. We believe that this represents the first case report of a patient with nephrotic syndrome, intracardiac thrombus, and evidence of embolization to 3 sites: kidney, arm, and leg. | 18,838,397 |
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