title stringlengths 0 1.13k | abstract stringlengths 1 15.7k | PMID int64 22 36.5M |
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Gene expression and isoform variation analysis using Affymetrix Exon Arrays. | Alternative splicing and isoform level expression profiling is an emerging field of interest within genomics. Splicing sensitive microarrays, with probes targeted to individual exons or exon-junctions, are becoming increasingly popular as a tool capable of both expression profiling and finer scale isoform detection. Despite their intuitive appeal, relatively little is known about the performance of such tools, particularly in comparison with more traditional 3' targeted microarrays. Here, we use the well studied Microarray Quality Control (MAQC) dataset to benchmark the Affymetrix Exon Array, and compare it to two other popular platforms: Illumina, and Affymetrix U133. We show that at the gene expression level, the Exon Array performs comparably with the two 3' targeted platforms. However, the interplatform correlation of the results is slightly lower than between the two 3' arrays. We show that some of the discrepancies stem from the RNA amplification protocols, e.g. the Exon Array is able to detect expression of non-polyadenylated transcripts. More importantly, we show that many other differences result from the ability of the Exon Array to monitor more detailed isoform-level changes; several examples illustrate that changes detected by the 3' platforms are actually isoform variations, and that the nature of these variations can be resolved using Exon Array data. Finally, we show how the Exon Array can be used to detect alternative isoform differences, such as alternative splicing, transcript termination, and alternative promoter usage. We discuss the possible pitfalls and false positives resulting from isoform-level analysis. The Exon Array is a valuable tool that can be used to profile gene expression while providing important additional information regarding the types of gene isoforms that are expressed and variable. However, analysis of alternative splicing requires much more hands on effort and visualization of results in order to correctly interpret the data, and generally results in considerably higher false positive rates than expression analysis. One of the main sources of error in the MAQC dataset is variation in amplification efficiency across transcripts, most likely caused by joint effects of elevated GC content in the 5' ends of genes and reduced likelihood of random-primed first strand synthesis in the 3' ends of genes. These effects are currently not adequately corrected using existing statistical methods. We outline approaches to reduce such errors by filtering out potentially problematic data. | 18,990,248 |
Review on solving the inverse problem in EEG source analysis. | In this primer, we give a review of the inverse problem for EEG source localization. This is intended for the researchers new in the field to get insight in the state-of-the-art techniques used to find approximate solutions of the brain sources giving rise to a scalp potential recording. Furthermore, a review of the performance results of the different techniques is provided to compare these different inverse solutions. The authors also include the results of a Monte-Carlo analysis which they performed to compare four non parametric algorithms and hence contribute to what is presently recorded in the literature. An extensive list of references to the work of other researchers is also provided. This paper starts off with a mathematical description of the inverse problem and proceeds to discuss the two main categories of methods which were developed to solve the EEG inverse problem, mainly the non parametric and parametric methods. The main difference between the two is to whether a fixed number of dipoles is assumed a priori or not. Various techniques falling within these categories are described including minimum norm estimates and their generalizations, LORETA, sLORETA, VARETA, S-MAP, ST-MAP, Backus-Gilbert, LAURA, Shrinking LORETA FOCUSS (SLF), SSLOFO and ALF for non parametric methods and beamforming techniques, BESA, subspace techniques such as MUSIC and methods derived from it, FINES, simulated annealing and computational intelligence algorithms for parametric methods. From a review of the performance of these techniques as documented in the literature, one could conclude that in most cases the LORETA solution gives satisfactory results. In situations involving clusters of dipoles, higher resolution algorithms such as MUSIC or FINES are however preferred. Imposing reliable biophysical and psychological constraints, as done by LAURA has given superior results. The Monte-Carlo analysis performed, comparing WMN, LORETA, sLORETA and SLF, for different noise levels and different simulated source depths has shown that for single source localization, regularized sLORETA gives the best solution in terms of both localization error and ghost sources. Furthermore the computationally intensive solution given by SLF was not found to give any additional benefits under such simulated conditions. | 18,990,257 |
Patients' attitude towards the use of a chaperone in breast examination. | The aim of this study was to assess the attitude and the preferences of patients towards the use of a chaperone during breast examination. A two-part questionnaire was circulated among 204 consecutive new patients, attending both symptomatic breast and screened assessment clinics. A total of 200 questionnaires were fully completed and returned. Although 104 (52%) patients felt that they did not need a chaperone during breast examination, 65 (33%) preferred to have one. Amongst these 65 patients, the majority (52%) wanted a chaperone in the presence of both a male and female doctor whereas 19 (29%) wanted a chaperone in the presence of a male doctor. When patients were asked which person would be the best chaperone for them, 63 patients (32%) preferred their spouse to act as a chaperone, whereas 57 (29%) preferred a clinic nurse. However, the majority of teenagers and young adults (10-30 years) preferred their parents to act as a chaperone. On asking the reason for preferring a chaperone during breast examination, 69% felt a chaperone helped them to feel more at ease, 28% felt they get more support, 23% get less embarrassed and 10% felt safer. The majority (54%) preferred the nurse to offer a chaperone instead of the doctor (22%). Patients generally said they were comfortable in asking for a chaperone (68%). Overall, 68% of patients considered the offer of a chaperone as a sign of respect and the majority felt the attitude (32%) and gender (20%) of the clinician are the two most important factors influencing the chaperone use. Most patients were of the opinion that the presence of a chaperone does not have a negative effect on the doctor-patient relationship (75%), patient confidentiality (74%) and do not cause embarrassment (68%). Following their assessment in clinic, the patients' views on the use of a chaperone were not significantly changed. There is a wide variety of opinion among patients about the desirability of a chaperone during breast examination. However, the majority consider the offer of a chaperone as a sign of respect and many patients commented that the presence of a chaperone is important for medicolegal protection of both patient and clinician. In recent years, there has been an increasing call from medicolegal societies and medical insurance companies for greater use of chaperones during intimate examinations. We feel that recommendations regarding the use of a chaperone should now be incorporated into the British Association of Surgical Oncology guidelines. | 18,990,268 |
Urgent cholecystectomy for acute cholecystitis in a district general hospital - is it feasible? | Laparoscopic cholecystectomy has become the gold standard for treatment of symptomatic gall stone disease. However, its place remains controversial in the management of acute cholecystitis due to a high reported incidence of bile leaks and conversion rate. Tertiary referral centres have reported good results. We present a series of cases after the introduction of an urgent cholecystectomy pathway in a district general hospital. A practice of urgent cholecystectomy for acute cholecystitis was introduced by three consultant general surgeons. All prospective patients having an urgent laparoscopic cholecystectomy for acute cholecystitis, over an 8-month period were entered into a database. A dedicated ultrasound service was instituted to provide prompt diagnosis in these patients. Their demographic details, operative findings, laboratory results were recorded in a prospective database. Timing of ERCP, postoperative complications and conversion rate and hospital stay were also noted. There were 64 patients in the study with a median age of 51 years (range, 21-84 years). There were 21 males and 43 females. All patients underwent laparoscopic cholecystectomy during the index admission. Eleven patients had pre-operative ERCP and 12 patients had on-table cholangiogram. There were no conversions. Postoperative ERCP was required in six patients. The median time interval between admission and operation was 3 days (range, 2-7 days). There were two bile leaks but no common bile duct injury. There were two cases of superficial wound infection. One patient required re-operation for small bowel obstruction secondary to a port site hernia. Urgent laparoscopic cholecystectomy for acute cholecystitis is a feasible treatment option in a district general hospital. A safe practice can be ensured by adherence to a care pathway and a multidisciplinary, consultant-delivered service. Urgent cholecystectomy service can be provided safely in a district general hospital with outcomes comparable to previously published literature. | 18,990,272 |
Total hip arthroplasty in Klippel-Trenaunay syndrome. | Klippel-Trenaunay syndrome patients often suffer degenerative joint disease at an early age. Performing arthroplasty in these patients is particularly difficult for a number of reasons. In this case report, we describe the second reported case of total hip replacement in Klippel-Trenaunay syndrome, using novel techniques to surmount the problems faced in this challenging condition. | 18,990,275 |
Spinal muscular atrophy: advances in research and consensus on care of patients. | Spinal muscular atrophy (SMA) is an autosomal recessive disease characterized by degeneration of spinal cord motor neurons and muscular atrophy. Advances in recent research have led to understanding of the molecular genetics of SMA. Therapeutic strategies have been developed according to the unique genomic structure of the SMN genes. Three groups of compounds have been identified as therapeutic candidates. One group was identified before the molecular genetics of SMA was understood, chosen on the basis of their effectiveness in similar neurologic disorders. The second group was identified based on their ability to modify SMN2 gene expression. Several of these agents are currently in clinical trials. A third group, identified by large-scale drug screening, is still under preclinical investigation. In addition, other advances in medical technology have led to the publication of a consensus statement regarding the care of SMA patients. | 18,990,310 |
Dehydroepiandrosterone replacement therapy in hypoadrenal women: protein anabolism and skeletal muscle function. | To determine whether dehydroepiandrosterone (DHEA) replacement therapy in hypoadrenal women improves performance, muscle protein accretion, and mitochondrial functions. Thirty-three hypoadrenal women were enrolled in the study from May 1, 2002, through May 31, 2003. Twenty-eight completed a 12-week, prospective, randomized, placebo-controlled, crossover study with either daily placebo or 50 mg of DHEA with a 2-week washout period and then crossed over to the other treatment. Body composition, physical performance, whole-body and muscle protein metabolism, and mitochondrial functions were determined. Administration of DHEA significantly increased plasma levels of DHEA sulfate, testosterone, and androstenedione but did not change body composition, muscle strength, peak aerobic capacity, and whole-body protein turnover or synthesis rates of mitochondrial, sarcoplasmic, or mixed muscle proteins. Muscle mitochondrial oxidative enzymes and messenger RNA (mRNA) levels of genes encoding mitochondrial proteins and nuclear transcription factors did not change after DHEA administration. However, mRNA levels of muscle myosin heavy chain 1 (P=.004), which determines muscle fiber type, and those of insulinlike growth factor binding proteins 4 and 5 significantly decreased (P=.02 and P=.03, respectively). Three months of DHEA administration increased DHEA sulfate and androgen levels but had no effect on physical performance, body composition, protein metabolism, or muscle mitochondrial biogenesis in hypoadrenal women. However, lowering of mRNA levels of binding proteins of insulinlike growth factor 1 and myosin heavy chain 1 suggests potential effects of longterm treatment with DHEA on muscle fiber type. | 18,990,320 |
[Combination and transformation of toxin and blood stasis in etiopathogenesis of thrombotic cerebro-cardiovascular diseases]. | According to the basic theory of traditional Chinese medicine (TCM), the pathogenetic factors such as platelet activation, adhesion, congregation and thrombosis fall into the category of blood stasis, while the pathological changes such as tissue necrosis, oxidative stress injury and inflammation, etc, are far beyond the etiological category of blood stasis. The toxin or the combination and transformation of toxin and blood stasis of TCM are involved in the pathogenesis of thrombotic cerebro-cardiovascular diseases. It is significant to recognize and stress the combination and transformation of toxin and stasis in pathogenicity so as to enrich TCM etiology and improve TCM clinical efficacy in the treatment of cerebro-cardiovascular and thrombotic diseases. | 18,990,334 |
Possible role of GABAA-benzodiazepine receptor in anticonvulsant effects of Pasipay in rats. | To investigate the anticonvulsant effects of Pasipay, a commercially available preparation of hydro-alcoholic extract of Passiflora incarnata in rats. The anticonvulsant effects of hydro-alcoholic extract of P. incarnata, Pasipay, were observed by intracerebroventricular injection of 0.125, 0.25, 0.55 and 1.5 microg Pasipay. Pasipay could dose-dependently affected minimal clonic seizures and generalized tonic-clonic seizures induced by pentylenetetrazole, through increment in seizure onset significantly. Additionally, pretreatment with 5 nmol/L flumazenil could abolish the anticonvulsant effects of Pasipay on the onset of both seizures. The results indicate that Pasipay has anticonvulsant effects in the brain, possibly through positive allosteric modulation of the GABAA receptor complex via interaction at the benzodiazepine site. | 18,990,344 |
Genetic variability in residual feed intake in rainbow trout clones and testing of indirect selection criteria (Open Access publication). | Little is known about the genetic basis of residual feed intake (RFI) variation in fish, since this trait is highly sensitive to environmental influences, and feed intake of individuals is difficult to measure accurately. The purpose of this work was (i) to assess the genetic variability of RFI estimated by an X-ray technique and (ii) to develop predictive criteria for RFI. Two predictive criteria were tested: loss of body weight during feed deprivation and compensatory growth during re-feeding. Ten heterozygous rainbow trout clones were used. Individual intake and body weight were measured three times at three week intervals. Then, individual body weight was recorded after two cycles of a three-week feed deprivation followed by a three-week re-feeding. The ratio of the genetic variance to the phenotypic variance was found high to moderate for growth, feed intake, and RFI (VG/VP = 0.63+/-0.11, 0.29 +/-0.11, 0.29 +/-0.09, respectively). The index that integrates performances achieved during deprivation and re-feeding periods explained 59% of RFI variations. These results provide a basis for further studies on the origin of RFI differences and show that indirect criteria are good candidates for future selective breeding programs. | 18,990,354 |
T lymphocyte activation and cytokine expression in periapical granulomas and radicular cysts. | Radicular cysts (RCs) are periapical lesions resulting in jaw bone destruction. The inflammatory dental periapical granuloma (PG) is considered to be the origin of RC formation; however the mechanism of RC development remains unclear. Cell suspension from the surgically extirpated tissue of 27 RCs and 25 PGs was obtained. Bacteriological analysis of the PG tissue samples was performed in order to define two major groups of PG according to the prevailing causative bacterial infection: the streptococcal PG (PG-S, n=10) and the anaerobe PG (PG-A, n=9) group. The inflammatory response of tissue infiltrating lymphocytes was assessed by following T lymphocyte activation (HLA-DR expression) as well as interferon gamma (IFN-gamma) and interleukin 4 (IL-4) production which were evaluated by the flow cytometry. In comparison to RC both types of PG contained a higher proportion of activated T cells (HLA-DR) and lower proportion of IL-4 producing cells. PG-A tissue contained increased percentage of CD3 cells and increased percentage of T helper 1 (Th1) cells in comparison with PG-S. In RC the IFN-gamma production is higher than in streptococcal PG-S but similar as in PG-A. Tissue infiltration by Th2 cells and IL-4 production is likely to play an etiopathogenic role in RC formation. | 18,990,362 |
Patterns in dental enamel hypoplasia by sex and age at death in two archaeological populations. | Levels of enamel hypoplasia in past populations are frequently used to study health. However, few studies have looked at patterning in the occurrence of different types of hypoplasia. In this pilot study, skeletal remains from an Iron Age tomb at Pella in Jordan were analysed for the presence of linear and pit enamel hypoplasia, to investigate enamel hypoplasia aetiology by comparison of the results obtained for adults and juveniles, and females and males. The proportion of individuals with enamel hypoplasia was determined for males and females and for adults and juveniles using the F.D.I. Developmental Defects of Enamel (DDE) Index. Although males and females had a similar percentage of individuals affected, females had a higher prevalence of enamel hypoplasia per tooth than males. Adults had a higher prevalence of enamel hypoplasia than juveniles. In particular, adults had a higher prevalence of linear enamel hypoplasias and pit enamel hypoplasia arrays, but a similar prevalence of single pit enamel hypoplasia when both the permanent and deciduous dentitions were considered. These differences were largely due to different patterns and frequencies of enamel hypoplasia in deciduous teeth compared to permanent teeth. The different patterns of occurrence of the various forms of hypoplasia observed in this study imply that single pits may have a different aetiology to linear enamel hypoplasias and pit arrays. By investigating similar patterns in other archaeological populations, we may develop a better understanding of the specific causes of particular types of enamel hypoplasia, and may be able to more meaningfully interpret enamel hypoplasia data from past populations. | 18,990,363 |
Mental imagery as an emotional amplifier: application to bipolar disorder. | Cognitions in the form of mental images have a more powerful impact on emotion than their verbal counterparts. This review synthesizes the cognitive science of imagery and emotion with transdiagnostic clinical research, yielding novel predictions for the basis of emotional volatility in bipolar disorder. Anxiety is extremely common in patients with bipolar disorder and is associated with increased dysfunction and suicidality, yet it is poorly understood and rarely treated. Mental imagery is a neglected aspect of bipolar anxiety although in anxiety disorders such as posttraumatic stress disorder and social phobia focusing on imagery has been crucial for the development of cognitive behavior therapy (CBT). In this review we present a cognitive model of imagery and emotion applied to bipolar disorder. Within this model mental imagery amplifies emotion, drawing on Clark's cyclical panic model [(1986). A cognitive approach to panic. Behaviour Research and Therapy, 24, 461-470]. We (1) emphasise imagery's amplification of anxiety (cycle one); (2) suggest that imagery amplifies the defining (hypo-) mania of bipolar disorder (cycle two), whereby the overly positive misinterpretation of triggers leads to mood elevation (escalated by imagery), increasing associated beliefs, goals, and action likelihood (all strengthened by imagery). Imagery suggests a unifying explanation for key unexplained features of bipolar disorder: ubiquitous anxiety, mood instability and creativity. Introducing imagery has novel implications for bipolar treatment innovation--an area where CBT improvements are much-needed. | 18,990,364 |
Pilot study evaluating a progesterone vaginal ring for luteal-phase replacement in donor oocyte recipients. | To evaluate the proportions of women demonstrating adequate endometrial transformation during a mock cycle and the 8-week clinical pregnancy rate in a donor oocyte cycle using a P vaginal ring or P vaginal gel. Prospective, controlled, randomized trial. Donor egg program at an academic center. Women who are candidates for donor oocytes. Subjects were analyzed for adequate endometrial transformation after suppression and pretreatment with E(2). Subjects were treated with 18 days of E(2) coupled with a weekly P vaginal ring or 90 mg 8% vaginal gel twice daily. Endometrial biopsies were performed on cycle day 25 or 26. Nine subjects successfully completing the mock cycle participated in an ET cycle using the same randomly assigned study medication. Adequate endometrial transformation, pregnancy, safety, and tolerability of the vaginal ring. Twenty women randomized 1:1 to either the P vaginal ring or vaginal gel completed the mock cycle. Endometrial histology was "in phase" for 8 of 10 (80%) in the vaginal ring group and 10 of 10 (100%) in the gel group. For the women who participated in the ET cycle, clinical pregnancies and live births were observed in 4 of 5 (80%) in the vaginal ring group and 1 of 4 (25%) in the vaginal gel group. In women requiring luteal-phase replacement, the P vaginal ring was able to adequately transform the endometrium and was comparable to the P vaginal gel in efficacy and safety, while offering the advantage of weekly rather than multiple daily doses. | 18,990,373 |
Laparoscopic management of ureteral endometriosis in case of moderate-severe hydroureteronephrosis. | To evaluate prospectively the efficacy of laparoscopic ureterolysis versus ureteroureterostomy in women with ureteral endometriosis. Prospective study. Department of Obstetrics and Gynecology, Ospedale Sacro Cuore of Negrar, Verona, Italy, a tertiary care endometriosis referral center. Endometriotic patients with moderate-severe ureter dilatation. All women underwent laparoscopic endometriosis excision and concomitant laparoscopic ureterolysis, ureteroureterostomy, nephrectomy, or laparotomic ureterocystoneostomy. Clinical outcomes were evaluated. Fifty-six patients with preoperative or intraoperative evidence of moderate-severe ureter dilatation were enrolled. Dysmenorrhea (91%) and dyspareunia (68%) were the symptoms more frequently reported; only two patients had typical obstructive uropathy pain. In 35 cases, laparoscopic ureterolysis, in 17 laparoscopic ureteroureterostomy, in 2 laparotomic ureterocystoneostomy, and in 2 laparoscopic nephrectomy was performed. 11 out of 35 (31.4%) major complications occurred in the ureterolysis group, and 2 out of 17 (11.7%) in the ureteroureterostomy group. Median follow-up time was 21 months. Ureteral endometriosis recurrence was surgically detected in three patients who underwent conservative ureteral surgery. Preoperative planning should be rigorous, and complete surgical excision of ureteral endometriosis should be ensured by a team of experts familiar with endometriosis, its multiple manifestations, and its management. | 18,990,377 |
Cost analysis model of outpatient management of ovarian hyperstimulation syndrome with paracentesis: "tap early and often" versus hospitalization. | To compare the cost of two treatment regimens for moderate to severe ovarian hyperstimulation syndrome (OHSS): conservative inpatient versus outpatient management with paracentesis. A decision-tree mathematical model comparing conservative inpatient versus outpatient management of moderate to severe OHSS was created. The common final pathway of either management was resolution of OHSS. Sensitivity analyses were performed over the range of variables. Total management cost of OHSS. The cost of conservative therapy including first-tier complications was $10,099 (range $9,655-$15,044). The cost of outpatient management with paracentesis was $1954 (range $788-$12,041). This resulted in an estimated cost savings of $8145 with outpatient management with paracentesis. One-way sensitivity analyses were performed. Varying the probability of admission after outpatient treatment still indicated that outpatient treatment was the most cost-effective (probability = 1.0, cost = $6110). Varying the duration of hospitalization with primary inpatient treatment was equal to outpatient treatment costs only at a stay of 0.71 days or shorter. Our model suggests early outpatient paracentesis for moderate to severe OHSS is the most cost-effective management plan when compared with traditional conservative inpatient therapy. The cost savings for outpatient management persisted throughout a variety of outcome probabilities. | 18,990,389 |
Effect of phosphate complexation on Cd2+ sorption by manganese dioxide (beta-MnO2). | Sorption of metal ions on oxide/hydroxide surfaces mediates the fate and transport of these ions in many natural systems. These metallic ions often exist in bulk in the aqueous phase as complexes with inorganic and organic ligands. In the present study, we investigated the sorption properties of manganese dioxide in the presence of phosphate which is thought to be one of the most important complex forming species. The surface area, point of zero charge and structural morphology of the solid manganese dioxide were determined. Cd(2+) sorption studies were carried out on manganese dioxide as a function of pH, temperature and phosphate concentration. Cd(2+) sorption increased with increasing pH, temperature and phosphate concentration. It was found that phosphate formed both outer and inner sphere complexes via metal and ligand-like adsorption. The Langmuir equation was applied to describe the data and from the constants of this equation different thermodynamic parameters such as DeltaH(0), DeltaS(0) and DeltaG(0) were evaluated. | 18,990,403 |
Serum cholesterol, apolipoprotein E genotype and depressive symptoms in elderly European men: the FINE study. | Cohort and case-control studies found that lower serum total cholesterol is associated with depression. It is, however, unclear whether low cholesterol or its lipoprotein fractions are causally related to depression. Using a Mendelian randomization design, the potential association between apolipoprotein E (APOE) genotype (affecting lifetime cholesterol levels) and depressive symptoms was studied. In the longitudinal Finland, Italy, the Netherlands Elderly (FINE) Study 1089 men were included in 1985. The 435 men from Finland, 418 men from The Netherlands, and 236 men from Italy (aged 65-84 years) were free of myocardial infarction, stroke, diabetes mellitus and cancer at all time points. They were prospectively studied around 1985 (n=658), 1990 (n=668), 1995 (n=327), and 2000 (n=82). Associations between serum cholesterol, lipoprotein fractions and APOE genotype, with depressive symptoms (by Zung self-rating depression scale [SDS]) were analyzed using multilevel regression models. Serum total cholesterol was inversely associated with the Zung SDS (-0.61 points per 1 mmol/L increase in cholesterol; 95% confidence interval: -1.05 to -0.17; P=0.007), after adjustment for country, age, body mass index, smoking, and alcohol intake. However, none of the cholesterol lipoprotein fractions were associated with the Zung SDS. The APOE genotypes epsilon4/4, epsilon4/3; epsilon3/3; epsilon4/2, and epsilon3/2 or epsilon2/2 were associated with decreasing levels of serum total and LDL cholesterol (Ps<0.001), but not with increasing depressive symptoms (P=0.67). APOE genotype was assessed through protein isoforms and not actual DNA-based typing. There was a modest inverse relationship between depression scores and serum total cholesterol in elderly men, but no associations with lipoprotein fractions or with the APOE genotype. | 18,990,452 |
Antenatal depression and male gender preference in Asian women in the UK. | to identify the prevalence of antenatal depression among Asian women living in the UK in one antenatal clinic, and to investigate the possible association with a desire for a male child and other risk factors. cross-sectional questionnaire-based study. general antenatal clinic in a hospital in Birmingham. 300 Asian women, irrespective of place of birth. consecutive Asian women attending routine antenatal appointments during the study period self-completed a questionnaire. The first part investigated socio-demographic, cultural and other possible risk factors, including gender preference. The second part comprised the Edinburgh Postnatal Depression Scale (EPDS). EPDS score greater than or equal to 12 indicating probable depression. the prevalence of depression was 30.7% (92/300, 95% confidence interval 25.4-35.9%). Maternal male gender preference was not common and was not associated with antenatal depression. Family male gender preference, unplanned pregnancy, a history of depression and feeling anxious in pregnancy were independently associated with an increased likelihood of depression, whilst support from family and friends, being satisfied with pregnancy and being multiparous were associated with a reduced likelihood of depression. rates of antenatal depression were very high in Asian women with some associated risk factors. However, male gender preference was not associated with antenatal depression. given the high prevalence, screening Asian women for depression may be indicated to allow treatment. | 18,990,472 |
Cardiopulmonary resuscitation: knowledge and opinions among the U.S. general public. State of the science-fiction. | Cardiopulmonary resuscitation is undertaken more than 250,000 times annually in the United States. This study was undertaken to determine knowledge and opinions of the general public regarding cardiopulmonary resuscitation. Validated multisite community-based cross-sectional survey. Knowledge and opinions about resuscitative practices and outcomes, using hypothetical clinical scenarios and other social, spiritual, and environmental considerations. Among 1831 participants representing 38 states, markedly inaccurate perceptions of cardiac arrest were reported. Participants' mean estimate of predicted survival rate after cardiac arrest was 54% (median 50%, IQR 35-75%), and mean estimated duration of resuscitative efforts in the ED was 28min (median 15min; IQR 10-30). Projected age and health status were independent predictors of resuscitation preferences in a series of 4 hypothetical scenarios. Participants indicated that physicians should consider patient and family wishes as the most important factors when making resuscitation decisions. Participants considered advanced technology and physician communication to be the most important actions during attempted resuscitation. Inaccurate perceptions regarding resuscitation and survival rates exist among the lay public. Participants indicated strong preferences regarding resuscitation and advance directives. | 18,990,479 |
Occurrence of pharmaceutically active compounds during 1-year period in wastewaters from four wastewater treatment plants in Seville (Spain). | Several pharmaceutically active compounds have been monitored during 1-year period in influent and effluent wastewater from wastewater treatment plants (WWTPs) to evaluate their temporal evolution and removal from wastewater and to know which variables have influence in their removal rates. Pharmaceutical compounds monitored were four antiinflammatory drugs (diclofenac, ibuprofen, ketoprofen and naproxen), an antiepileptic drug (carbamazepine) and a nervous stimulant (caffeine). All of the pharmaceutically active compounds monitored, except diclofenac, were detected in influent and effluent wastewater. Mean concentrations measured in influent wastewater were 6.17, 0.48, 93.6, 1.83 and 5.41 microg/L for caffeine, carbamazepine, ibuprofen, ketoprofen and naproxen, respectively. Mean concentrations measured in effluent wastewater were 2.02, 0.56, 8.20, 0.84 and 2.10 microg/L for caffeine, carbamazepine, ibuprofen, ketoprofen and naproxen, respectively. Mean removal rates of the pharmaceuticals varied from 8.1% (carbamazepine) to 87.5% (ibuprofen). The existence of relationships between the concentrations of the pharmaceutical compounds, their removal rates, the characterization parameters of influent wastewaters and the WWTP control design parameters has been studied by means of statistical analysis (correlation and principal component analysis). With both statistical analyses, high correlations were obtained between the concentration of the pharmaceutical compounds and the characterization parameters of influent wastewaters; and between the removal rates of the pharmaceutical compounds, the removal rates of the characterization parameters of influent wastewaters and the WWTP hydraulic retention times. Principal component analysis showed the existence of two main components accounting for 76% of the total variability. | 18,990,491 |
[Allergy to betalactams: myth and realities]. | Allergic reactions to penicillins have been reported since the 1950s, shortly after their introduction as therapeutic agents. An increasing number of reported anaphylactic reactions and other adverse effects proved this to be a serious public health problem. Fifty years later, betalactam-induced hypersensitivity is the most frequent cause of drug reaction and has been the source of a great number of publications. Clinically, betalactam-induced allergic reactions may be immediate or non-immediate according to the time interval between drug intake and the occurrence of symptoms. The diagnosis of betalactam hypersensitivity is based on skin tests methods, in vitro tests and drug provocation test. There are three classical methods for skin testing: prick, intradermal, and patch. These tests are still the most sensitive techniques. In vitro tests, mainly based on the quantification of IgE antibodies to betalactams by immunoassay (Fluorescent Enzyme Immunoassay [FEIA]), may sometimes yield useful complementary information. Drug provocation tests must be performed with the required caution and the adequate indication. Algorithms are available for both immediate and non-immediate reactions to provide a practical approach for patient evaluation. They are based on the following data: clinical history, skin tests, FEIA, and drug provocation tests. Finally, cross reactivity between betalactams has been reported, especially between penicillins and cephalosporins. Their frequency was long over-estimated, but recent evidence, indicates that cross reactivity between betalactams has become rare. Administration of cephalosporins in patients with a history of penicillin allergy requires performing skin testing with penicillin, the probably allergenic drug, and the cephalosporin to be prescribed. | 18,990,520 |
Microbial genome count in cerebrospinal fluid compared with clinical characteristics in pneumococcal and Haemophilus influenzae type b meningitis in children. | Cerebrospinal fluid genome counts were determined by quantitative real-time polymerase chain reaction from 121 children: 36 with Streptococcus pneumoniae and 85 with Haemophilus influenzae meningitis. To examine the interactions of genome count and to determine its prognostic importance, we projected the results against findings on admission and different outcomes. The genome count varied vastly in both meningitides ranging from 0 to 9,250,000/microL. The genome quantity was weakly associated with only some of the patient findings on admission. High counts predicted neurologic (odds ratio [OR]=1.36; 95% confidence interval [CI], 1.09-1.69; P=0.006 for 1 log increase) but not audiologic sequelae. They also predicted death in S .pneumoniae (OR=2.05; 95% CI, 1.08-3.87; P=0.03) but not in H. influenzae meningitis. | 18,990,528 |
Negative events and their potential risk of precipitating pathological forms of dental anxiety. | The purpose of the present study was to assess which types of experiences are most closely associated with pathological forms of dental anxiety. Data came from a sample of dental patients (n=1462). Pathological dental anxiety was operationalized in two ways: (1) a score of > or =36 on the Short form of the Dental Anxiety Inventory (S-DAI; high dental anxiety, HDA), or (2) fulfilling the screening criteria of specific phobia (DSM-IV-TR; dental phobia, DP). A wide variety of dental experiences appeared to be significantly related with both HDA and DP, while general traumatic experiences were not. No differences were found between women and men. Retrospective accounts of dental experiences involving helplessness were most strongly associated with having HDA [OR=8.2] and positive screens of DP [OR=16.2]. The results suggest that disruptive emotional and interoceptive reactions during dental treatment (particularly helplessness) have the greatest potential risk of precipitating pathological forms of dental anxiety. | 18,990,543 |
Production of the Auger emitter 119Sb for targeted radionuclide therapy using a small PET-cyclotron. | The use of Auger electrons in radionuclide therapy of cancer is a promising tool for specific tumor cell killing of micrometastases and small tumors. The radioisotope (119)Sb has recently been identified as a potent Auger-emitter for therapy. We here present a method for producing this isotope using a low-energy cyclotron. With this method, it will be possible to produce clinically relevant amounts of (119)Sb radioactivity with high chemical and radionuclidic purity for cancer therapy. | 18,990,581 |
Renal insufficiency and anticancer drugs in elderly cancer patients: a subgroup analysis of the IRMA study. | The Renal Insufficiency and Anticancer Medications (IRMA) study is a French national, observational study which demonstrated the high prevalence of abnormal renal function in a population of 4684 solid tumor patients. Among them, 50-60% had decreased renal function, and 80% were treated with anticancer drugs that either necessitated dosage adjustment in case of renal insufficiency (RI) or were potentially nephrotoxic drugs. Since elderly patients are well-known to have reduced renal function, either due to physiological aging or their disease/medication history, a subgroup analysis of this particular population of patients was performed. In 1553 IRMA patients whose age was > or =65 years, the prevalence of RI was very high in spite of normal serum creatinine values in most cases. Anticancer drugs used may be nephrotoxic or need dosage adjustment in a high number of cases. | 18,990,585 |
Vascular training and endovascular practice in Europe. | To evaluate the influence of the status of vascular surgery (VS) training paradigms on the actual practice of endovascular therapy among the European countries. An email-based survey concerning vascular surgery training models and endovascular practices of different clinical specialties was distributed to a VS educator within 14 European countries. European Vascular and Endovascular Monitor (EVEM) data also were processed to correlate endovascular practice with training models. Fourteen questionnaires were gathered. Vascular training in Europe appears in 3 models: 1. Mono-specialty (independence): 7 countries, 2. Subspecialty: 5 countries, 3. An existing specialty within general surgery: 2 countries. Independent compared to non-independent certification shortens overall training length (5.9 vs 7.9 years, p=0.006), while increasing overall training devoted specifically to VS (3.9 vs 2.7 years, p=0.008). Among countries with independent certification an average of 76% of aortic and 50% of peripheral endovascular procedures are performed by vascular surgeons, while the corresponding values, for countries with a non-independent certification, are 69% and 36% respectively. Countries with independent vascular certification, despite their lower average endovascular index (procedures per 100,000 population), reported a higher growth rate of aortic endovascular procedures (VS independent 132% vs VS non-independent 87%), within a four-year period (2003-2007). Peripheral endovascular procedures, though, have similar growth rates in both country groups (VS independent 62% vs VS non-independent 60%). In European countries with VS as an independent specialty, vascular surgeons have a shorter total training period but spend more time in VS training, although they may not undertake a greater proportion of the endovascular procedures their countries appear to have adopted endovascular technologies more rapidly compared to the ones with non-independent VS curricula. Whether such differences influence patient outcomes requires investigation in future studies. | 18,990,591 |
Antiepileptic drugs to treat pain in rheumatic conditions. Recommendations based on evidence-based review of the literature and expert opinion. | Neuropathic pain is commonly encountered in rheumatology practice, often associated with nociceptive mechanisms. It is caused by nervous system lesions, and the usual treatments with analgesics and anti-inflammatory drugs are mostly ineffective. Antiepileptic drugs (AED) have proved effective in relieving neuropathic pain. AED are recently used by rheumatologists since the role of neuropathic pain in rheumatological conditions has only recently been documented. Nevertheless, the tendency seems to be reversed when these drugs are used inappropriately. The CEDR (Cercle d'Etude de la Douleur en Rhumatologie), a specific interest group of the French Society of Rheumatology that focuses on pain in rheumatology, undertook to develop recommendations for the use of AED in Rheumatology. A list of questions concerning the prescription of AED in painful rheumatic conditions was validated by a working group of 7 experts from the CEDR. The list of questions was used to draw up the recommendations. A literature review was performed using electronic databases (Medline, Embase and Cochrane library between 1980 and 2007) without limitations on the type of publication: case reports, clinical trials, literature review and guidelines about therapeutic management of neuropathic pain. Selected studies were scored for quality. Based on the literature and clinical experience, recommendations were developed using the Delphi method. We identified 29 studies concerning the use of AED in painful rheumatic conditions and 16 studies were considered valid and scored for quality. These few studies, the guidelines published for neuropathic pain treatment and the clinical experience of each expert, were used to develop 11 recommendations for the use of AED in painful rheumatic conditions. These recommendations can be used as guidelines to help prescribers to use AED for the management of pain in rheumatic conditions until further scientific evidence becomes available. | 18,990,602 |
Automatic real-time ECG coding methodology guaranteeing signal interpretation quality. | This paper introduces a new methodology for compressing ECG signals in an automatic way guaranteeing signal interpretation quality. The approach is based on noise estimation in the ECG signal that is used as a compression threshold in the coding stage. The Set Partitioning in Hierarchical Trees algorithm is used to code the signal in the wavelet domain. Forty different ECG records from two different ECG databases commonly used in ECG compression have been considered to validate the approach. Three cardiologists have participated in the clinical trial using mean opinion score tests in order to rate the signals quality. Results showed that the approach not only achieves very good ECG reconstruction quality but also enhances the visual quality of the ECG signal. | 18,990,621 |
Vestibulo-ocular responses evoked via bilateral electrical stimulation of the lateral semicircular canals. | We investigated the vestibulo-ocular responses (VORs) evoked by bilateral electrical stimulation of the nerves innervating horizontal semicircular canals in squirrel monkeys and compared these responses to those evoked by unilateral stimulation. In response to sinusoidal modulation of the electrical pulse rate, the VOR for bilateral stimulation roughly equals the addition of the responses evoked by unilateral right ear and unilateral left ear stimulation; the VOR time constants were about the same for bilateral and unilateral stimulation and both were much shorter than for normal animals. In response to individual pulse stimulation, the VOR evoked by bilateral stimulation closely matches the point-by-point addition of responses evoked by unilateral right ear and unilateral left ear stimulation. We conclude that, to first order, the VOR responses evoked by bilateral stimulation are the summation of the responses evoked by unilateral stimulation. These findings suggest that--from a physiologic viewpoint--unilateral and bilateral vestibular prostheses are about equally viable. Given these findings, one possible advantage of a bilateral prosthesis is higher gain. However, at least for short-term stimulation such as that studied herein, no inherent advantage in terms of the response time constant ("velocity storage") was found. | 18,990,631 |
Space-time adaptive decision feedback neural receivers with data selection for high-data-rate users in DS-CDMA systems. | A space-time adaptive decision feedback (DF) receiver using recurrent neural networks (RNNs) is proposed for joint equalization and interference suppression in direct-sequence code-division multiple-access (DS-CDMA) systems equipped with antenna arrays. The proposed receiver structure employs dynamically driven RNNs in the feedforward section for equalization and multiaccess interference (MAI) suppression and a finite impulse response (FIR) linear filter in the feedback section for performing interference cancellation. A data selective gradient algorithm, based upon the set-membership (SM) design framework, is proposed for the estimation of the coefficients of RNN structures and is applied to the estimation of the parameters of the proposed neural receiver structure. Simulation results show that the proposed techniques achieve significant performance gains over existing schemes. | 18,990,643 |
Robust stability analysis for interval cohen-grossberg neural networks with unknown time-varying delays. | In this paper, robust stability problems for interval Cohen-Grossberg neural networks with unknown time-varying delays are investigated. Using linear matrix inequality, M -matrix theory, and Halanay inequality techniques, new sufficient conditions independent of time-varying delays are derived to guarantee the uniqueness and the global robust stability of the equilibrium point of interval Cohen-Grossberg neural networks with time-varying delays. All these results have no restriction on the rate of change of the time-varying delays. Compared to some existing results, these new criteria are less conservative and are more convenient to check. Two numerical examples are used to show the effectiveness of the present results. | 18,990,645 |
Brain activity-based image classification from rapid serial visual presentation. | We report the design and performance of a brain-computer interface (BCI) system for real-time single-trial binary classification of viewed images based on participant-specific dynamic brain response signatures in high-density (128-channel) electroencephalographic (EEG) data acquired during a rapid serial visual presentation (RSVP) task. Image clips were selected from a broad area image and presented in rapid succession (12/s) in 4.1-s bursts. Participants indicated by subsequent button press whether or not each burst of images included a target airplane feature. Image clip creation and search path selection were designed to maximize user comfort and maintain user awareness of spatial context. Independent component analysis (ICA) was used to extract a set of independent source time-courses and their minimally-redundant low-dimensional informative features in the time and time-frequency amplitude domains from 128-channel EEG data recorded during clip burst presentations in a training session. The naive Bayes fusion of two Fisher discriminant classifiers, computed from the 100 most discriminative time and time-frequency features, respectively, was used to estimate the likelihood that each clip contained a target feature. This estimator was applied online in a subsequent test session. Across eight training/test session pairs from seven participants, median area under the receiver operator characteristic curve, by tenfold cross validation, was 0.97 for within-session and 0.87 for between-session estimates, and was nearly as high (0.83) for targets presented in bursts that participants mistakenly reported to include no target features. | 18,990,647 |
An experimental study of the decay of turbulent puffs in pipe flow. | As reported in a number of recent studies, turbulence in pipe flow is transient for Re<2000 and the flow eventually always returns to the laminar state. Generally, the lifetime of turbulence has been observed to increase rapidly with Reynolds number but there is currently no accord on the exact scaling behaviour. In particular, it is not clear whether a critical point exists where turbulence becomes sustained or if it remains transient. We here aim to clarify if these conflicting results may have been caused by the different experimental and numerical protocols used to trigger turbulence in these studies. | 18,990,664 |
Critical threshold in pipe flow transition. | This study provides a numerical characterization of the basin of attraction of the laminar Hagen-Poiseuille flow by measuring the minimal amplitude of a perturbation required to trigger transition. For pressure-driven pipe flow, the analysis presented here covers autonomous and impulsive scenarios where either the flow is perturbed with an initial disturbance with a well-defined norm or perturbed by means of local impulsive forcing that mimics injections through the pipe wall. In both the cases, the exploration is carried out for a wide range of Reynolds numbers by means of a computational method that numerically resolves the transitional dynamics. For , the present work provides critical amplitudes that decay as Re(-3/2) and Re(-1) for the autonomous and impulsive scenarios, respectively. For Re=2875, accurate threshold amplitudes are found for constant mass-flux pipe by means of a shooting method that provides critical trajectories that never relaminarize or trigger transition. These transient states are used as initial guesses in a damped Newton-Krylov method formulated to find periodic travelling wave solutions that either travel downstream or exhibit a helicoidal advection. | 18,990,665 |
Levosimendan enhances force generation of diaphragm muscle from patients with chronic obstructive pulmonary disease. | Levosimendan is clinically used to improve myocardial contractility by enhancing calcium sensitivity of force generation. The effects of levosimendan on skeletal muscle contractility are unknown. Patients with chronic obstructive pulmonary disease (COPD) suffer from diaphragm weakness, which is associated with decreased calcium sensitivity. To investigate the effects of levosimendan on contractility of diaphragm fibers from patients with COPD. Muscle fibers were isolated from diaphragm biopsies obtained from thoracotomized patients with and without COPD (both groups n = 5, 10 fibers per patient). Diaphragm fibers were skinned and activated with solutions containing incremental calcium concentrations and 10 microM levosimendan or vehicle (0.02% dimethyl sulfoxide). Developed force was measured at each step and force versus calcium concentration relationships were derived. Results were grouped per myosin heavy chain isoform, which was determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). At sub-maximal activation levosimendan improved force generation of COPD and non-COPD diaphragm fibers by approximately 25%, both in slow and fast fibers. Levosimendan increased calcium sensitivity of force generation (P < 0.01) in both slow and fast diaphragm fibers from patients with and without COPD, without affecting maximal force generation. Levosimendan enhances force generating capacity of diaphragm fibers from patients with and without COPD patients by increasing calcium sensitivity of force generation. These results provide a strong rationale for testing the effect of calcium sensitizers on respiratory muscle dysfunction in patients with COPD. | 18,990,676 |
Severe exacerbations and decline in lung function in asthma. | To evaluate the association between asthma exacerbations and the decline in lung function, as well as the potential effects of an inhaled corticosteroid, budesonide, on exacerbation-related decline in patients with asthma. To determine whether severe asthma exacerbations are associated with a persistent decline in lung function. The START (inhaled steroid treatment as regular therapy in early asthma) study was a 3-year, randomized, double-blind study of 7,165 patients (5-66 yr) with persistent asthma for less than 2 years, to determine whether early intervention with low-dose inhaled budesonide prevents severe asthma-related events (exacerbations requiring hospitalization or emergency treatment) and decline in lung function. There were 315 patients who experienced at least one severe asthma exacerbation, of which 305 were analyzable, 190 in the placebo group and 115 in the budesonide group. In the placebo group, the change in post-bronchodilator FEV(1) % predicted from baseline to the end of the study, in patients who did or did not experience a severe exacerbation was -6.44% and -2.43%, respectively (P < 0.001). A significant difference was seen in both children and in adults, but not in adolescents. In the budesonide group, the change in the post-bronchodilator FEV(1) % predicted in patients who did or did not experience a severe exacerbation was -2.48% and -1.72%, respectively (P = 0.57). The difference in magnitude of reduction afforded by budesonide, in patients who experienced at least one severe asthma-related event compared with those who did not, was statistically significant (P = 0.042). Severe asthma exacerbations are associated with a more rapid decline in lung function. Treatment with low doses of inhaled corticosteroid is associated with an attenuation of the decline. | 18,990,678 |
Characterization of the complement inhibitory function of rhesus rhadinovirus complement control protein (RCP). | Rhesus rhadinovirus (RRV) is currently the closest known, fully sequenced homolog of human Kaposi sarcoma-associated herpesvirus. Both these viruses encode complement inhibitors as follows: Kaposi sarcoma-associated herpesvirus-complement control protein (KCP) and RRV-complement control protein (RCP). Previously we characterized in detail the functional properties of KCP as a complement inhibitor. Here, we performed comparative analyses for two variants of RCP protein, encoded by RRV strains H26-95 and 17577. Both RCP variants and KCP inhibited human and rhesus complement when tested in hemolytic assays measuring all steps of activation via the classical and the alternative pathway. RCP variants from both RRV strains supported C3b and C4b degradation by factor I and decay acceleration of the classical C3 convertase, similar to KCP. Additionally, the 17577 RCP variant accelerated decay of the alternative C3 convertase, which was not seen for KCP. In contrast to KCP, RCP showed no affinity to heparin and is the first described complement inhibitor in which the binding site for C3b/C4b does not interact with heparin. Molecular modeling shows a structural disruption in the region of RCP that corresponds to the KCP-heparin-binding site. This makes RRV a superior model for future in vivo investigations of complement evasion, as RCP does not play a supportive role in viral attachment as KCP does. | 18,990,693 |
Ca2+ entry via TRPC channels is necessary for thrombin-induced NF-kappaB activation in endothelial cells through AMP-activated protein kinase and protein kinase Cdelta. | The transient receptor potential canonical (TRPC) family channels are proposed to be essential for store-operated Ca2+ entry in endothelial cells. Ca2+ signaling is involved in NF-kappaB activation, but the role of store-operated Ca2+ entry is unclear. Here we show that thrombin-induced Ca2+ entry and the resultant AMP-activated protein kinase (AMPK) activation targets the Ca2+-independent protein kinase Cdelta (PKCdelta) to mediate NF-kappaB activation in endothelial cells. We observed that thrombin-induced p65/RelA, AMPK, and PKCdelta activation were markedly reduced by knockdown of the TRPC isoform TRPC1 expressed in human endothelial cells and in endothelial cells obtained from Trpc4 knock-out mice. Inhibition of Ca2+/calmodulin-dependent protein kinase kinase beta downstream of the Ca2+ influx or knockdown of the downstream Ca2+/calmodulin-dependent protein kinase kinase beta target kinase, AMPK, also prevented NF-kappaB activation. Further, we observed that AMPK interacted with PKCdelta and phosphorylated Thr505 in the activation loop of PKCdelta in thrombin-stimulated endothelial cells. Expression of a PKCdelta-T505A mutant suppressed the thrombin-induced but not the TNF-alpha-induced NF-kappaB activation. These findings demonstrate a novel mechanism for TRPC channels to mediate NF-kappaB activation in endothelial cells that involves the convergence of the TRPC-regulated signaling at AMPK and PKCdelta and that may be a target of interference of the inappropriate activation of NF-kappaB associated with thrombosis. | 18,990,707 |
Puffing style and human exposure minimally altered by switching to a carbon-filtered cigarette. | Potential Reduced Exposure tobacco Products (PREP) are intended to lower human exposure to toxic constituents of tobacco smoke, but rigorous clinical evaluations are required to assess such claims. The present study assessed human smoking behavior and short-term exposure to a new carbon-filtered PREP, Marlboro UltraSmooth (MUS). Two MUS prototypes with filter carbon loads of 120 and 180 mg were compared with low and ultralow-yield conventional cigarettes. After a 48-hour baseline period, 32 adult Marlboro Lights smokers were switched in a counterbalanced order, to MUS and Marlboro Ultra Lights for 48 hours each. Measures of smoking topography, subjective response, change in cardiac response, and carbon monoxide boost were obtained under supervised test conditions on separate days. After each test, topography measures were obtained via a 48-hour free smoking phase for each brand. Salivary cotinine was measured at the end of each 48-hour period. Although MUS was generally smoked in a style similar to conventional cigarettes, compensatory smoking was observed with 1 MUS prototype (P = 0.003). Carbon monoxide boost was lower for MUS compared with Marlboro Lights, but salivary cotinine and cardiac function measures after smoking of MUS did not vary from conventional brands. Smoking MUS produced few differences in smoking topography and exposure compared with conventional low and ultralow-yield cigarettes. Results suggest that the manner in which MUS is smoked by humans is unlikely in the short term to reduce exposure among smokers who switch from a conventional brand. | 18,990,741 |
Self-report versus medical records for assessing cancer-preventive services delivery. | Accurate measurement of cancer-preventive behaviors is important for quality improvement, research studies, and public health surveillance. Findings differ, however, depending on whether patient self-report or medical records are used as the data source. We evaluated concordance between patient self-report and medical records on risk factors, cancer screening, and behavioral counseling among primary care patients. Data from patient surveys and medical records were compared from 742 patients in 25 New Jersey primary care practices participating at baseline in SCOPE (supporting colorectal cancer outcomes through participatory enhancements), an intervention trial to improve colorectal cancer screening in primary care offices. Sensitivity, specificity, and rates of agreement describe concordance between self-report and medical records for risk factors (personal or family history of cancer, smoking), cancer screening (breast, cervical, colorectal, prostate), and counseling (cancer screening recommendations, diet or weight loss, exercise, smoking cessation). Rates of agreement ranged from 41% (smoking cessation counseling) to 96% (personal history of cancer). Cancer screening agreement ranged from 61% (Pap and prostate-specific antigen) to 83% (colorectal endoscopy) with self-report rates greater than medical record rates. Counseling was also reported more frequently by self-report (83% by patient self-report versus 34% by medical record for smoking cessation counseling). Deciding which data source to use will depend on the outcome of interest, whether the data is used for clinical decision making, performance tracking, or population surveillance; the availability of resources; and whether a false positive or a false negative is of more concern. | 18,990,740 |
N2-ethyldeoxyguanosine as a potential biomarker for assessing effects of alcohol consumption on DNA. | Head and neck cancers are causally related to alcohol consumption, but the underlying mechanisms are unclear. Ethanol is metabolized to acetaldehyde, an experimental carcinogen. Quantitation of the major DNA adduct of acetaldehyde, N2-ethylidenedeoxyguanosine, in human tissues could help to elucidate the mechanism of alcohol carcinogenicity. We applied a quantitative method for the analysis of this adduct, measured as the NaBH3CN reduction product N2-ethyldeoxyguanosine (N2-ethyl-dGuo) by liquid chromatography-electrospray ionization-tandem mass spectrometry-selected reaction monitoring, on DNA (0.04 +/- 0.03 mg) isolated from blood collected from control subjects recruited from two studies conducted in different areas of Europe between 1999 and 2005. The group selected from the first study (n = 127) included alcohol drinkers and abstainers while the group from the second study (n = 50) included only heavy drinkers. N2-ethyl-dGuo was detected in all DNA samples. After adjusting for potential confounders, in the first study, drinkers showed a higher level of N2-ethyl-dGuo (5,270 +/- 8,770 fmol/micromol dGuo) compared with nondrinkers (2,690 +/- 3040 fmol/micromol dGuo; P = 0.04). A significant trend according to dose was observed in both studies (P = 0.02 and 0.04, respectively). Taking into account the amount of alcohol consumption, adduct levels were higher in younger compared with older subjects (P = 0.01), whereas no differences were observed comparing men with women. These results show the feasibility of quantifying N2-ethyl-dGuo in small-volume blood samples and are consistent with the hypothesis that ethanol contributes to carcinogenesis through DNA adducts formation. | 18,990,745 |
Red meat intake, doneness, polymorphisms in genes that encode carcinogen-metabolizing enzymes, and colorectal cancer risk. | Colorectal cancer literature regarding the interaction between polymorphisms in carcinogen-metabolizing enzymes and red meat intake/doneness is inconsistent. A case-control study was conducted to evaluate the interaction between red meat consumption, doneness, and polymorphisms in carcinogen-metabolizing enzymes. Colorectal cancer cases diagnosed 1997 to 2000, ages 20 to 74 years, were identified through the population-based Ontario Cancer Registry and recruited by the Ontario Family Colorectal Cancer Registry. Controls were sex-matched and age group-matched random sample of Ontario population. Epidemiologic and food questionnaires were completed by 1,095 cases and 1,890 controls; blood was provided by 842 and 1,251, respectively. Multivariate logistic regression was used to obtain adjusted odds ratio (OR) estimates. Increased red meat intake was associated with increased colorectal cancer risk [OR (> 5 versus < or = 2 servings/wk), 1.67 (1.36-2.05)]. Colorectal cancer risk also increased significantly with well-done meat intake [OR (> 2 servings/wk well-done versus < or = 2 servings/wk rare-regular), 1.57 (1.27-1.93)]. We evaluated interactions between genetic variants in 15 enzymes involved in the metabolism of carcinogens in overcooked meat (cytochrome P450, glutathione S-transferase, UDP-glucuronosyltransferases, SULT, NAT, mEH, and AHR). CYP2C9 and NAT2 variants were associated with colorectal cancer risk. Red meat intake was associated with increased colorectal cancer risk regardless of genotypes; however, CYP1B1 combined variant and SULT1A1-638G>A variant significantly modified the association between red meat doneness intake and colorectal cancer risk. In conclusion, well-done red meat intake was associated with an increased risk of colorectal cancer regardless of carcinogen-metabolizing genotype, although our data suggest that persons with CYP1B1 and SULT1A1 variants had the highest colorectal cancer risk. | 18,990,750 |
Frequent alterations of p16INK4a and p14ARF in oral proliferative verrucous leukoplakia. | Proliferative verrucous leukoplakia (PVL) represents a rare but highly aggressive form of oral leukoplakia with > 70% progressing to malignancy. Yet, PVL remains biologically and genetically poorly understood. This study evaluated the cell cycle regulatory genes, p16INK4a and p14ARF, for homozygous deletion, loss of heterozygosity, and mutation events in 20 PVL cases. Deletion of exon 1beta, 1alpha, or 2 was detected in 40%, 35%, and 0% of patients, respectively. Deletions of exons 1alpha and 1beta markedly exceed levels reported in non-PVL dysplasias and approximate or exceed levels reported in oral squamous cell carcinomas. Allelic imbalance was assessed for markers reported to be highly polymorphic in squamous cell carcinomas and in oral dysplasias. Loss of heterozygosity was detected in 35.3%, 26.3%, and 45.5% of PVLs for the markers IFNalpha, D9S1748, and D9S171, respectively. INK4a and ARF sequence alterations were detected in 20% and 10% of PVL lesions, accordingly. These data show, for the first time, that both p16INK4a and p14ARF aberrations are common in oral verrucous leukoplakia; however, the mode and incidence of inactivation events differ considerably from those reported in non-PVL oral premalignancy. Specifically, concomitant loss of p16INK4a and p14ARF occurred in 45% of PVL patients greatly exceeding loss reported in non-PVL dysplastic oral epithelium (15%). In addition, p14ARF exon 1beta deletions were highly elevated in PVLs compared with non-PVL dysplasias. These data illustrate that molecular alterations, even within a specific genetic region, are associated with distinct histologic types of oral premalignancy, which may affect disease progression, treatment strategies, and ultimately patient prognosis. | 18,990,760 |
What's new with the FHA's Section 242? | FHA hospital mortgage insurance, also called the Section 242 program, acts as a credit enhancement that allows borrowers to issue bonds up to the equivalent of an "AAA" rating, with the benefits of lower interest rates. Although the program has operated in relative obscurity over its 40 years of existence, the FHA has undertaken a new marketing campaign to raise its profile. Federal backing may make the program an attractive option amid today's financial turmoil in the capital markets. | 18,990,841 |
The relationship of educational preparation, autonomy, and critical thinking to nursing job satisfaction. | This descriptive correlational study explored factors influencing job satisfaction in nursing. Relationships between educational preparation, autonomy, and critical thinking and job satisfaction were examined. A convenience sample of 140 registered nurses was drawn from medical-surgical, management, and home health nursing specialties. The nurses were asked to complete the Watson-Glaser Critical Thinking Appraisal and Minnesota Satisfaction Questionnaire. Relationships between variables were analyzed to determine which explained the most variance in job satisfaction. Results indicated significant positive correlations between total job satisfaction and perceived autonomy, critical thinking, educational preparation, and job satisfiers. Significant negative correlations between job dissatisfiers and total job satisfaction were also found. Understanding nursing job satisfaction through critical thinking, educational level, and autonomy is the key to staff retention. Further research focusing on increasing these satisfiers is needed. | 18,990,891 |
Promoting critical appraisal of the research literature: a workshop for school nurses. | To promote healthy lifestyles and prevent youth obesity, school nurses collaborate with teachers and other professionals to implement effective health promotion activities (e.g., physical fitness initiatives and nutrition education). Critical appraisal of relevant, published literature is an essential competency for school nurses engaged in health promotion within their schools. A 1-day continuing education workshop was conducted to enhance literature appraisal skills needed for evidence-based practice among school nurses employed within one urban school district. Forty-six school nurses, students, and other professionals attended this workshop and participated in appraisals of selected research articles. Although the attendees rated the faculty and content highly, their intent to apply the findings to practice was limited. Applying a critical appraisal approach to the literature focused on youth obesity prevention and health promotion was innovative for educating school nurses in this process while helping them choose whether and how existing literature may be applied to their practice. Nurse educators and faculty may replicate this process with school nurses or other nursing specialties. | 18,990,892 |
Loss of confidence in diabetes management. | Using current treatment approaches, many patients with type 2 diabetes do not achieve glycemic goals--and do experience macrovascular complications that contribute to morbidity and mortality. It's time to consider other options. Aggressive therapeutic interventions aimed at insulin resistance and cell dysfunction may alter outcomes. Managed care organizations may need to modify the way they look at diabetes and should consider changing their focus from drug costs to wellness. Value-based insurance design may provide opportunities to optimize diabetes management, resulting in improved outcomes for patients and economic benefits for managed care organizations. | 18,990,924 |
Out of Africa: traveller malaria in paediatric patients presenting to Our Lady of Lourdes Hospital Drogheda. | Malaria is one of the world's most important parasitic infections and is endemic in over 100 countries. The number of cases of malaria in Ireland has increased significantly over the last 10 years. The aim of this study was to retrospectively examine cases of paediatric malaria presenting to Our Lady of Lourdes Hospital Drogheda over a one year period to identify the reason for travel to endemic areas, to establish if prophylaxis was received on travelling and to determine the clinical course and post-treatment follow up. Five children presented during the study period, all children were infected with the Plasmodium falciparum, two had evidence of cerebral involvement, all were children travelling to visit family and none of the children received adequate prophylaxis. This study highlights the importance of parental education on the risks associated with non-compliance with malaria prophylaxis and the complications associated with malaria infection in children. | 18,990,954 |
Skeletal dysplasias: 38 prenatal cases. | To assess the prenatal diagnosis of skeletal dysplasias in a single center over a ten-years period. All antenatal detected skeletal dysplasias during the period January 1st 1996 until December 31 2005 (10 years) were retrieved from the genetic database. This database includes all skeletal dysplasias where invasive prenatal diagnosis (chorionic villus sampling/amniocentesis) was performed. The final diagnosis was sought on the basis of fetopathological examination, radiographic studies and if possible molecular testing. A total of 46 antenatal skeletal dysplasias were diagnosed during this period. Follow-up was only available in 38 cases. The other 8 cases involved prenatally presumed lethal skeletal dysplasias that were interrupted in the referral hospital with no further information sent to us. The mean gestational age at diagnosis was 23 weeks (range 12-33 weeks). A diagnosis < or = 24 weeks was made in 25 cases (65.8%). Eleven skeletal dysplasias were diagnosed > 30 weeks (29%) and these included all achondroplasias (n = 6), hypophosphatasia (n = 1), Jeune syndrome (n = 1), osteogenesis imperfecta type II (n = l), type I (n = 1) and type III (n = 1). In 27 cases a lethal skeletal dysplasia was present (71%) and these were all correctly predicted. Of the lethal skeletal dysplasias 5 cases were diagnosed only after 24 weeks of pregnancy (19%) and 3 were only referred after 30 weeks (11.5%). A final diagnosis was obtained in 36 cases by fetopathological examination and radiographic studies and molecular testing as deemed necessary. Specific diagnoses included: achondroplasia (n = 6), achondrogenesis (n = 2), osteogenesis imperfecta type II (n = 9), osteogenesis imperfecta type I (n = 1), osteogenesis imperfecta type III (n = 1), thanatophoric dysplasia (n = 7), hypophosphatasia (n = 1), Majewski syndrome (n = 11), Mohr-Majewski syndrome (n = 11), Jeune syndrome (n = 2), Ellis-van Creveld syndrome (n = 2), Roberts syndrome (n = 1), campomelic dysplasia (n = 2). In two cases postnatal investigation revealed no certain diagnosis and these included one patient with symmetrical tetraphocomelia with aspects of Roberts and Femur-fibula-Ulna syndrome and one patient at 15 weeks with a lethal skeletal dysplasia with rhizomelic limb shortening, a narrow thorax, platyspondyly, normocephaly, a normal pelvis, and a posterior cleft palate. A correct antenatal diagnosis was made in 25 cases (65.8%) including osteogenesis imperfecta type II (n = 9), thanatophoric dysplasia (n = 7), achondroplasia (n = 6), achondrogenesis (n = 2) and Roberts syndrome (n = 1). The antenatal prediction of lethality in this series of prenatal diagnosed skeletal dysplasias was correct. A correct antenatal diagnosis of the type of skeletal dysplasia was difficult, with 25 of 38 cases correctly diagnosed. | 18,990,981 |
Scoliosis, blindness and arachnodactyly in a large Turkish family: is it a new syndrome? | In this report we have described an affected sib in a large Turkish family who appears to have a new distinct dominantly-inherited blindness, scoliosis and arachnodactyly syndrome. The combination of clinical abnormalities in these patients did not initially suggest Marfan syndrome or other connective tissue disorders associated with ectopia lentis. The proband was a 16-year-old boy who was referred to our clinics for scoliosis. He had arachnodactyly of both fingers and toes. He had been suffering from progressive visual loss and strabismus since he was eight-years-old. His 20-year-old brother had severe kyphoscoliosis, and arachnodactyly of fingers and toes. He was 130 cm tall and was bilaterally blind. His 23-year-old sister had only eye findings but no arachnodactyly or scoliosis. His 60-year-old father had mild scoliosis, blindness and arachnodactyly and mother was normal. We performed routine mutation analyses in the genes FBN1, TGFBR1 and TGFBR2, but no mutation has been detected. Our Turkish patients are most likely affected by a hitherto unrecorded condition which is caused by an autosomal dominant gene defect with variable expression but we can not exclude multigenic inheritance. Further studies are needed to assess the contribution of sex influence to the syndrome because the female relative is less affected. | 18,990,988 |
Functional prefrontal reorganization accompanies learning-associated refinements in surgery: a manifold embedding approach. | The prefrontal cortex (PFC) is known to be vital for acquisition of visuomotor skills, but its role in the attainment of complex technical skills which comprise both perceptual and motor components, such as those associated with surgery, remains poorly understood. We hypothesized that the prefrontal response to a surgical knot-tying task would be highly dependent on technical expertise, and that activation would wane in the context of learning success following extended practice. The present series of experiments investigated this issue, using functional Near Infrared Spectroscopy (fNIRS) and dexterity analysis to compare the PFC responses and technical skill of expert and novice surgeons performing a surgical knot-tying task in a block design experiment. Applying a data-embedding technique known as Isomap and Earth Mover's Distance (EMD) analysis, marked differences in cortical hemodynamic responses between expert and novice surgeons have been found. To determine whether refinement in technical skill was associated with reduced PFC demands, a second experiment assessed the impact of pre- and post-training on the PFC responses in novices. Significant improvements (p < 0.01) were observed in all performance parameters following training. Smaller EMD distances were observed between expert surgeons and novices following training, suggesting an evolving pattern of cortical responses. A random effect model demonstrated a statistically significant decrease in relative changes of total hemoglobin (Delta HbT) [coefficient = -3.825, standard error (s.e.) = 0.8353, z = -4.58, p < 0.001] and oxygenated hemoglobin (Delta HbO(2)) [coefficient = -4.6815, s.e = 0.6781, z = -6.90, p < 0.001] and a significant increase in deoxygenated hemoglobin (Delta HHb) [coefficient = 0.8192, s.e = 0.3034, z = 2.66, p < 0.01] across training. The results indicate that learning-related refinements in technical performance are mediated by temporal reductions in prefrontal activation. | 18,991,082 |
Revisiting the molecular structure of collagen. | The triple helix is a specialized protein motif found in all collagens. Although X-ray diffraction studies of collagen began in the 1920s, the very small amount of data available from fiber diffraction of native collagen caused the determination of its molecular conformation to take a very long time. In the early 1950s, two plausible fiber periods of about 20 and 30 A were proposed, together with corresponding single-strand models having 7/2- and 10/3-helical symmetry, respectively. The first framework of the triple helix was proposed by Ramachandran and Kartha in 1955. In the same year, Rich and Crick proposed another structure with the same framework that avoided some of the steric problems of the first model. Their framework, which involved a triple-helical structure with a fiber period of 28.6 A and 10/3-helical symmetry, was exactly the same as one of two single-strand models for collagen proposed at that time, except for the number of strands. At that time, however, nobody considered the triple-strand model with the other framework, with a fiber period of 20 A and 7/2-helical symmetry, until Okuyama et al. detected this structure in the single crystal of (Pro-Pro-Gly)(10) in 1972. Although they proposed this structure as a new structural model for collagen in 1977, it has not been acknowledged as such, but instead has been regarded only as a model for a collagen-like peptide. In 2006, it was shown that both 7/2- and 10/3-helical models could explain X-ray diffraction data from native collagen quantitatively. Furthermore, during the past decade, many single crystals of collagen-model peptides have been analyzed at high resolution. The helical symmetries observed in these model peptides are very close to the ideal 7/2-helical symmetry, whereas no supporting data were found for the 10/3-helical model. This evidence strongly suggests that an average molecular structure of native collagen is the 7/2-helical model rather than the prevailing Rich and Crick (10/3-helical) model. Knowing the correct molecular structure, the driving force for the formation of a quarter-staggered structure in collagen fibrils will be elucidated in the near future by analysis incorporating the molecular structure of collagen and its amino acid sequence. | 18,991,083 |
Uniform partial dissolution of bone mineral by using fluoride and phosphate ions combination. | Mineral content is one of the main predictors of the mechanical properties of bone tissue. The contribution of the bone mineral phase to the mechanical properties of bone has been investigated by reducing the mineral content of bone with different in vitro treatment techniques such as hydrochloric acid (HCl), ethylenedinitrilo tetraacetic acid (EDTA), and fluoride ion treatment. In this study, we propose a new treatment technique which combines fluoride and phosphate ions. Bovine femur specimens were used to determine the mechanical properties of cortical bone after different fluoride phosphate ion combination treatments. The treatment solutions, which contain different fluoride and phosphate ion concentrations, dissolved part of the bone mineral in a uniform manner throughout the bone samples. Dissolution by products, which precipitated in the bone tissue, contained calcium fluoride with phosphate ions (CaF(2)/P) and fluorapatite/fluorhydroxyapatite-type material (FAp/FHAp) and acted as filler. Depending on the fluoride and phosphate concentration in a treatment solution, the precipitated material's ratio of FAp/FHAp to total fluoride containing phase (FAp/FHAp + CaF(2)/P) in bone tissue also changed. High fluoride ion content in treatment solutions generated more CaF(2)/P type of precipitate, and low fluoride ion concentration generated more FAp/FHAp type precipitates as compared to high fluoride concentration treatments. These experiments show that phosphate ions are another important parameter of a treatment solution, in addition to ionic strength, pH, and the duration of treatment. In vitro, phosphate fluoride combinations partially dissolve bone mineral content in a wider range than fluoride treatment alone in a uniform manner. With this new technique one can control more precisely the partial dissolution of the bone mineral and mineral phase's contribution to mechanical properties of bone tissue. | 18,991,086 |
Endothelin-1 does not change the function of monocyte-derived dendritic cells grown from patients with systemic sclerosis. | Systemic sclerosis (SSc) is characterized by both vasculopathy and autoimmunity. The interplay between these pathogenetic links requires further exploration. The aim was to assess the interrelationship of endothelin-1 (ET-1), a vasoconstrictor peptide, whose levels are usually elevated in the plasma of the patients with SSc and the function of monocyte-derived dendritic cells (MDDCs), which serve as organizers of the immune response. MDDCs were grown from 5 patients with SSc and severe Raynaud's phenomenon and 5 healthy volunteers. The cells were further stimulated by synthetic ET-1, lipopolysaccharide (LPS) or both. The production of endogenous ET-1, TNFalpha and IL-12 was assessed by RT-PCR and/or ELISA. The plasma levels of ET-1 were significantly higher in patients with SSc compared to healthy controls (p = 0.0005). The production of ET-1 by MDDCs was negligible in all examined conditions, while the release of TNFalpha and IL-12 was stimulated by LPS but not by ET-1. The in vitro concentration of the exogenous ET-1, where added, was comparable to the plasma levels of ET-1 in patients with SSc. High plasma levels of ET-1 are characteristic for the patients with SSc and severe Raynaud's phenomenon. An in vitro model with concentrations of ET-1 comparable to those in the plasma of SSc patients has been elaborated. The examined function of MDDCs from SSc patients and healthy volunteers did not differ under these conditions and was not dependent on the presence of ET-1. | 18,991,099 |
Thymulin, a thymic peptide, prevents the overproduction of pro-inflammatory cytokines and heat shock protein Hsp70 in inflammation-bearing mice. | The effects of synthetic analogue of peptide hormone thymulin, which is normally produced by thymic epithelial cells, on immune cells activity and blood cytokine profile had been studied in male NMRI mice with acute inflammation induced by injection of lipopolysaccharide from gram-negative bacteria (LPS, 250 microg/100 g of body weight). Inflammation induced by LPS resulted in accumulation of several plasma pro-inflammatory cytokines, IL-1 beta, IL-2, IL-6, TNF-alpha, interferon-gamma, and also IL-10, anti-inflammatory cytokine. Thymulin previously injected in dose of 15 microg/100 g body weight, prevented the accumulation of proinflammatory cytokines in plasma. Thymulin also prevented LPS-induced up-regulation of production of several cytokines by spleen lymphocytes and peritoneal macrophages. Added in vitro, thymulin decreased the peak of TNF-alpha production in macrophages cultivated with LPS. In addition, thymulin lowered the peak of Hsp70 production induced by LPS treatment. The results indicate that thymulin having significant anti-inflammatory effect may be promising in clinical application. | 18,991,101 |
A comparison of doubly hierarchical discriminant analyses for multiple class longitudinal data from EEG experiments. | This paper proposes a general and simple procedure that can be applied to establish classification rules for application to multiple-class longitudinal data. The procedure is applied to preclinical pharmaco-electroencephalogram (EEG) studies aiming at characterizing psychotropic drug effects on the basis of spectral EEG analysis. It is a flexible hierarchical supervised learning tool that takes into account the specific nature of the multiple drug classes, as well as the longitudinal aspect of the data. Several variations of this procedure are applied to the EEG data, generally producing comparable results, in particular similar association between the sleeping stages and the psychotropic drug classes. | 18,991,112 |
A threshold regression mixture model for assessing treatment efficacy in a multiple myeloma clinical trial. | A first-hitting-time (FHT) survival model postulates a health status process for a patient that gradually declines until the patient dies when the level first reaches a critical threshold. Threshold regression (TR) is a new regression methodology that incorporates the effects of covariates on the threshold and process parameters of this FHT model. In this study, we use TR to analyze data from a randomized clinical trial of treatment for multiple myeloma. The trial compares VELCADE and high-dose dexamethasone, the former a new therapy and the latter an established therapy for this disease. Patients are switched between the two drugs based on patient response. The novel contribution of this work is the modeling of this clinical trial design using a mixture of TR models. Specifically, we propose a mixture FHT model to fit the survival distribution. The model includes a composite time scale that differentiates the rate of disease progression before and after switching. The analysis shows significant benefit from initial treatment by VELCADE. A comparison is made with a Cox proportional hazards regression analysis of the same data. | 18,991,113 |
Maternal sadness and adolescents' responses to stress in offspring of mothers with and without a history of depression. | This study examined maternal sadness and adolescents' responses to stress in the offspring (n = 72) of mothers with and without a history of depression. Mothers with a history of depression reported higher levels of current depressive symptoms and exhibited greater sadness during interactions with their adolescent children (ages 11-14) than mothers without a history of depression. Similarly, adolescent children of mothers with a history of depression experienced higher rates of internalizing and externalizing symptoms than adolescents of mothers without a history of depression. Regression analyses indicated that adolescents' use of secondary control coping mediated the relationship between observed maternal sadness and adolescents' internalizing and externalizing symptoms, in that higher levels of secondary control coping (e.g., cognitive reframing) were related to fewer symptoms. | 18,991,125 |
Own and friends' smoking attitudes and social preference as early predictors of adolescent smoking. | This study examined the role of friends' attitudes in adolescent smoking (N = 203). Growth mixture modeling was used to identify three trajectories of smoking behavior from ages 12 to 14 years: a low-rate group, an increasing-rate group, and a high-rate group. Adolescents' own and their friends' attitudes at age 11 years were not significantly related to smoking. However, in the increasing-rate group (compared with the low-rate group), friends' attitudes interacted with both adolescents' own and friends' social preference (i.e., likeability). The link between friends' attitudes and membership in the increasing-rate group was stronger for early adolescents with low social preference scores and for early adolescents with friends who had low social preference scores. Other than for the high-rate group, for which causal factors of smoking may be located early in childhood (e.g., family and personality or temperamental characteristics), the combination of low social preference and friends who hold a positive attitude toward smoking is associated with escalating cigarette use among young adolescents. | 18,991,131 |
Rosiglitazone prevents nutritional fibrosis and steatohepatitis in mice. | Currently, no agent has been confirmed as preventing the fibrosing progression of non-alcoholic steatohepatitis (NASH). In this study, rosiglitazone was used in the clinical treatment of insulin resistance in patients with type 2 diabetes mellitus. However, its protective effect on non-alcoholic fibrosing steatohepatitis is not clear. The study aimed to elucidate the effect and the mechanism of rosiglitazone in inhibiting nutrition-related fibrosis in mice. C57BL6/J mice were fed a high fat, methionine-choline deficient (MCD) diet for 8 weeks to induce hepatic fibrosis, and rosiglitazone was given in the treated group. The effect of rosiglitazone was assessed by comparing the severity of hepatic fibrosis in liver sections, the activation of hepatic stellate cells (HSCs) and the expression of TGF-beta1 and connective tissue growth factor (CTGF). At week 8, MCD-diet-induced fibrosing NASH models showed increased serum ALT and AST levels, severe hepatic steatosis, and infiltration of inflammation and fibrosis which, associated with down-regulated PPAR gamma mRNA and protein expression, up-regulated alpha-SMA protein expression and enhanced TGF-beta1, CTGF mRNA and protein expression. Rosiglitazone significantly lowered serum ALT and AST and it reduced MCD-induced fibrosis by repressing levels of alpha-SMA protein expression and pro-fibrosis factors TGF-beta1 and CTGF. It also restored expression of PPAR gamma. The present study provides clear morphological and molecular biological evidence of the protective role of rosiglitazone in ameliorating nutritional fibrosing steatohepatitis. Rosiglitazone may ameliorate hepatic fibrosis by activating PPAR gamma, which can inhibit HSC activation and suppress TGF-beta1 and CTGF expression. | 18,991,162 |
Paralysis of the first dorsal interosseous muscle after external fixation of a distal radial fracture treated by transfer of the extensor indicis proprius tendon. | We describe a patient in whom the motor branch to the first dorsal interosseous muscle was injured by the pins of an fixator used to treat an unstable fracture of the distal radius. She was successfully treated by extensor indicis proprius transfer to the base of the proximal phalanx of the index finger. | 18,991,180 |
Sustained improvement of vascular endothelial function during anti-TNFalpha treatment in rheumatoid arthritis patients. | Vascular endothelial function and common carotid artery intima-medial thickness (CCA-IMT) are well-established surrogate markers for early atherosclerotic disease, which accounts for 30-40% of excess mortality in rheumatoid arthritis (RA) patients. Our aim was to investigate whether long-term treatment with anti-tumour necrosis factor (TNF)alpha agents can modulate endothelial function and CCA-IMT. Twelve patients with RA (mean age 54.8+/-15 years) on anti-TNFalpha treatment (seven adalimumab, five infliximab) due to uncontrolled disease activity, with mean Disease Activity Score (DAS28) 5.7 (range 4.6-6.9) despite disease-modifying anti-rheumatic drugs (DMARDs), were studied prospectively. Patients were assessed at baseline and after 3 and 18 months for endothelial-dependent vasodilatation, assessed by flow-mediated vasodilatation (FMD), endothelial-independent vasodilatation and CCA-IMT. RA disease activity and response to therapy were assessed by the DAS28 index. After 18 months of treatment, 67% of the patients were responders according to European League Against Rheumatism (EULAR) response criteria. Anti-TNFalpha treatment improved FMD (from 7+/-4.3% to 11.1+/-3.8%, p = 0.026) whereas CCA-IMT did not change significantly [from 0.67 (0.4-1) to 0.68 (0.39-1.2) mm; mean change 0.01 (-0.06 to 0.08) mm]. Endothelial-independent vasodilatation remained stable (20.4+/-7.3% to 22.9+/-6.5%, p = 0.4). In this small cohort of patients with RA and no clinically overt cardiovascular disease (CVD), after 18 months of treatment with anti-TNFalpha agents, endothelial function improved significantly while CCA-IMT remained stable. Longitudinal studies using more patients are needed to determine the clinical significance of these findings in relation to the risk of atherosclerosis. | 18,991,190 |
Language organisation in left perinatal stroke. | Right-hemispheric organisation of language has been observed following early left-sided brain lesions. The role of the site of damage is still controversial, as other aspects influence the pattern of speech organisation including timing of the lesion and the presence of epilepsy. We studied a group of 10 term-born children homogeneous for timing/type of lesion and clinical picture. All subjects had left perinatal arterial stroke, right hemiplegia, normal cognitive functions and no or easily controlled epileptic seizures. In half the patients, the lesion clearly involved Broca's area, in the other half it was remote from it. Language lateralization was explored by an fMRI covert rhyme generation task. Eight of 10 subjects showed a right lateralisation of language, including all five patients with a damaged left Broca and 3/5 of those without it. Group analysis in patients with right hemispheric organisation showed brain activations homotopic to those found in the left hemisphere of a matched control group. Our findings confirm that, at the end of gestation, the human brain exhibits extraordinary (re-)organisational capabilities. Language organisation in the right hemisphere is favoured by the presence of destructive lesions of the left Broca's area at birth, and occurs in brain regions homotopic to those usually involved in language processing. | 18,991,195 |
Factors influencing the prevalence of pulmonary nodules in lung cancer screening trials: re-evaluation of a CT study. | Numerous false positive findings are a problem in computed tomography based lung cancer screening trials. The potential patient-related variables that could predict the existence of such lung nodules were studied. 526 construction workers (age 38-81 yrs.) previously screened with spiral computed tomography were evaluated. Background features (age, body mass index, stature, sex, C-reactive protein, erythrocyte sedimentation rate, asbestos exposure and smoking history), reported symptoms (general condition, cough, mucous production, dyspnoea, chest pain) and findings in high resolution CT were related to the existence of nodules with logistic regression. There were 107 patients with one or more nodules recorded at least by two of the three observers. Advancing age (OR = 1.042/year, 95% CI = 1.000-1.085, p = 0.048) and dyspnoea symptom (p = 0.014) were positively associated with the existence of nodules, while smoking, asbestos exposure history and other studied parameters were not. Nodules < or = 5 mm (50 patients) were inversely associated with the maximal thickness of pleural plaques (OR = 0.384, 95% CI = 0.169-0.873, p = 0.022). No variables helpful to sample subjects for lung cancer screening studies to reduce the number of false positive findings were found. Poor inspiration or associated pathology such as thick pleura may hamper nodule detection. Further studies should focus especially on the possible effect of computer tomography technology on finding nodules. | 18,991,240 |
Biochemical effects of consumption of eggs containing omega-3 polyunsaturated fatty acids. | Today, eggs with an increased content of -3 fatty acids are available but there are few publications on the effects of consumption of such eggs on the lipoproteins and acute phase markers in humans. The aim of the present study was to evaluate the effects of consumption of standard eggs and -3 enriched eggs on lipoproteins, glucose and inflammation markers. Nineteen healthy volunteers consumed one extra egg per day of either standard eggs or omega-3 enriched eggs in a double-blind, cross-over study. The duration of each period was 1 month. The effects of the different egg diets on apolipoprotein A1 and B (Apo A1 and B), lipoprotein (a), creatinine, cystatin C, C-reactive protein, serum amyloid protein A, interleukin 6, triglycerides, glucose, total-, high-density lipoprotein and low-density lipo-protein cholesterol concentrations were analyzed. Addition of one regular egg per day to the normal diet had no negative impact on blood lipids or inflammation markers. Consumption of omega-3 enriched eggs resulted in higher levels of ApoA1, lower ApoB/ApoA1 ratio and lower plasma glucose. These effects have been associated in previous studies with a reduced risk for cardiovascular mortality and diabetes. | 18,991,244 |
Pregnancy-associated myocardial infarction: a report of two cases and review of the literature. | Myocardial infarction in pregnancy carries high morbidity. Spontaneous coronary artery dissection is one etiology of infarction, and up to one third of cases may arise in the third trimester of pregnancy or within three months postpartum. We report two cases of spontaneous coronary artery dissection, one at 34 weeks gestation and one postpartum. Both patients were diagnosed with angiography and treated medically and one required percutaneous coronary intervention, with good obstetric outcome and return of cardiac function. Myocardial infarction, and particularly spontaneous coronary artery dissection, should be in the differential diagnosis of pregnant women presenting with cardiac-type symptoms, despite perceived lack of risk factors. Angiography will aid in diagnosis, and multiple therapeutic modalities exist. | 18,991,245 |
Model for the reconfiguration of specialized vascular services. | This article built on previous work to develop an algorithm for elective abdominal aortic aneurysm (AAA) repair and carotid endarterectomy (CEA), with the aim of improving patient survival by regionalization of services. Vascular procedures were used as an example of specialized surgical services. A model was generated based on a national data set that incorporated the statistical demonstration of procedural safety, hospital annual surgical case volume, and travel distance and time. Elective AAA repair was used to construct a hub-and-spoke model that was tested against CEA. The impact of the model was quantified in terms of mortality rates, and travel distance and time. Only 48 vascular hubs were required to provide adequate coverage in England, with the majority of patients travelling for less than 1 h to access inpatient vascular surgery. The model predicted a reduction in the number of deaths from elective surgery for AAA (P < 0.001) and CEA (P = 0.016). Adoption of this strategic model may lead to improved outcome after AAA and CEA. It could be used as a model for the regionalization of specialized surgery. The model does not take into account the complexity of providing a comprehensive vascular service in every locality. | 18,991,256 |
Selecting variables in non-parametric regression models for binary response. An application to the computerized detection of breast cancer. | In many biomedical applications, interest lies in being able to distinguish between two possible states of a given response variable, depending on the values of certain continuous predictors. If the number of predictors, p, is high, or if there is redundancy among them, it then becomes important to decide on the selection of the best subset of predictors that will be able to obtain the models with greatest discrimination capacity. With this aim in mind, logistic generalized additive models were considered and receiver operating characteristic (ROC) curves were applied in order to determine and compare the discriminatory capacity of such models. This study sought to develop bootstrap-based tests that allow for the following to be ascertained: (a) the optimal number q < or = p of predictors; and (b) the model or models including q predictors, which display the largest AUC (area under the ROC curve). A simulation study was conducted to verify the behaviour of these tests. Finally, the proposed method was applied to a computer-aided diagnostic system dedicated to early detection of breast cancer. | 18,991,258 |
TCR-beta chains derived from peripheral gammadelta T cells can take part in alphabeta T-cell development. | Between 10 and 20% of the peripheral gammadelta T cells express cytoplasmic TCR-beta proteins, but whether such TCR-beta chains can partake in alphabeta T-cell development has never been systematically investigated. Therefore, we reconstituted the T-cell compartment of CD3epsilon-deficient mice with Pax5-TCR-beta deficient proB cells expressing, via a retroviral vector, TCR-beta chains from either peripheral gammadelta or alphabeta T cells. Recipient thymi reconstituted with proB cells containing empty vector were small (<15x10(6) cells), contained few gammadelta T but no alphabeta T cells. In contrast, thymi from mice receiving proB cells containing gammadelta or alphabeta T-cell-derived TCR-beta chains contained 80-130x10(6) cells, and showed a normal CD4, CD8 and alphabeta TCR expression pattern. However, regardless of the source of TCR-beta chain, reconstituted mice rapidly showed signs of autoimmunity dying 5-15 wk following reconstitution. Autoimmune disease induction could be prevented by co-transfer of Treg cells thereby allowing the functionality of the generated T cells to be assessed. Results obtained show that TCR-beta chains from gammadelta T cells can efficiently take part in alphabeta T-cell development. The implications of these findings for gammadelta T-cell development will be discussed. | 18,991,270 |
Vibrational Raman optical activity of pi-conjugated helical systems: hexahelicene and heterohelicenes. | Helicenes constitute a special class of molecules combining helical conformation with pi-electron delocalization. These confer to helicenes specific chirooptical properties. In this article, we investigate the vibrational signatures thanks to the simulation of vibrational Raman optical activity (VROA) spectra. For that, four representative helicenes: hexahelicene, tetrathia-[7]-helicene, and its pyrrole and furan analogs have been simulated and interpreted using a recently implemented analytical scheme. Helicenes show intense VROA peaks attributed to their pi-conjugated structure and associated with collective vibrational modes. In hexahelicene, the dominant VROA features are due to vibrational modes involving motions of the carbon skeleton and H-wagging, but the intensity finds its source almost exclusively in the former. In the case of the three heterohelicenes, the previous statement is also verified, and on changing the heteroatoms, similar modes presenting comparable atomic contribution patterns have been highlighted, though the vibrational and electronic properties are modified. Some fingerprints could therefore be associated with the helicity of the system. In particular, in forward spectra, most of the VROA bands are positive for left-handed helicenes. Nevertheless, the spectral patterns are quite complex, and no easy rule-of-thumb could distinguish between the different heterohelicenes. Then, considering the fact that most of the contributions originate from the C atoms (group coupling matrices decomposition), it can be concluded that the major role of the heteroatom is restricted to modifying the geometry and the normal modes. At last, the small impact of the gauge-origin on the calculated spectra using a relatively modest basis set (rDPS:3-21G) is demonstrated here in the case of the tetrathia-[7]-helicene molecule presenting a C(2) symmetry. This further demonstrates the adequacy of this basis set for VROA calculations. | 18,991,298 |
Comparison of several testing strategies for combination drug efficacy trials based on the closure principle. | The author discusses three multiple testing procedures for identifying the minimum efficacious doses in a balanced factorial combination drug trial. All of these procedures utilize the closed testing principle, and hence strongly control the overall error rate and satisfy the coherence property, that is, if a hypothesis is retained then any hypothesis implied by it is also retained. While coherence is an essential requirement for any multiple testing procedure, consonance is a highly desirable characteristic. In the considered settings if a testing procedure is consonant then it always provides a set of all minimum efficacious combinations as a result, otherwise, it may lead to ambiguity. Although the coherence property is satisfied for any closed testing procedure and thus, does not depend on the test used for an individual hypothesis, whether the considered procedures satisfy the consonance property depends entirely on the nature of the test statistic. The author identifies the consonant and non-consonant procedures among the presented procedures and discusses possible drawbacks of non-consonant procedures with respect to combination drug efficacy trials. Additional properties of these procedures are assessed by simulations. | 18,991,315 |
Structural determination of atricins A and B, new triterpenes from Perovskia atriplicifolia, by 1D and 2D NMR spectroscopy. | Atricins A (1) and B (2), two new oleanane-type triterpenes have been isolated from the chloroform-soluble fractions of Perovskia atriplicifolia and their structures assigned from (1)H and (13)C-NMR spectra, Distortion Enhancement by Polarization Trasfer (DEPT) and by 2D-COSY, HMQC, Nuclear Overhauser Enhancement Spectroscopy (NOESY) and Hetronuclear mutiple-bond correlation (HMBC) experiments. | 18,991,320 |
Determination of heteronuclear coupling constants from 3D HSQC-TOCSY experiment with optimized random sampling of evolution time space. | An application of 3D version of HSQC-TOCSY experiment for the measurement of heteronuclear coupling constants of organic compounds yielding complex spectra is proposed. The approach presented here is based on the optimized random sampling of the evolution time space followed by Multidimensional Fourier Transform (MFT). In this study, we show that the interpretation of omega(3)-(13)C coupled (1)H-(13)C 3D HSQC-TOCSY spectra with E.COSY-type multiplets allows one to evaluate heteronuclear coupling constants of strychnine with high accuracy, whereas the employment of 2D methods is associated with signal overlap and use of conventionally recorded 3D NMR spectra cannot provide accurate results in an overnight experiment. | 18,991,321 |
Expression patterns of microRNAs in the chorioamniotic membranes: a role for microRNAs in human pregnancy and parturition. | MicroRNAs (miRNAs) are involved in the post-transcriptional regulation of gene expression during development. This study was performed to determine gestational age-dependent changes in miRNA expression in the chorioamniotic membranes and to assess the significance of miRNAs in human pregnancy and parturition. The expression profile of 455 miRNAs was compared between patients at term without labour (TNL: n = 10), in labour (TL: n = 10), and preterm labour (PTL: n = 10) using microarrays. A total of 39 miRNAs were differentially expressed between term and preterm cases, of which 31 (79.5%) were down-regulated at term. Expression of ten miRNAs, including miR-338, differentially expressed between PTL and TL groups was decreased at term. Computational analyses using miRBase Targets have identified PLA2G4B, a phospholipase implicated in parturition, as a putative target of miR-338. Inhibition of endogenous miR-338 with anti-miR-338 increased the mRNA and protein expression of PLA2G4B in decidual cells. Luciferase assay with reporter constructs confirmed that the suppression of PLA2G4B occurs through binding of miR-338 to the 3UTR of PLA2G4B. Interestingly, the expression of Dicer, a key miRNA-processing enzyme, was markedly decreased at term, particularly with labour in the chorioamniotic membranes. Collectively, the novel findings reported herein strongly suggest that post-transcriptional regulation of genes by miRNAs, coupled with the changes of miRNA processing machinery in the chorioamniotic membranes, plays a role in pregnancy and parturition. Furthermore, the expression level of Dicer in the chorioamniotic membranes dichotomizes pathological preterm labour and physiological spontaneous labour at term. | 18,991,333 |
Low-level laser irradiation promotes cell proliferation and mRNA expression of type I collagen and decorin in porcine Achilles tendon fibroblasts in vitro. | Achilles tendon problems are commonly encountered in sports medicine and low-level laser therapy (LLLT) is widely used in rehabilitative applications to decrease pain, reduce inflammatory processes, and promote tissue healing. This study examined the effects on the proliferation of porcine Achilles tendon fibroblasts and gene expression, using different doses of low-level laser irradiation (LLLI). Four groups of identically cultured fibroblasts were exposed to LLLI and harvested after 24 h. The control group (Group 1) was subjected to no LLLI. Other groups received 1 J/cm2 (Group 2), 2 J/cm2 (Group 3), and 3 J/cm2 (Group 4), respectively. Cell proliferation and mRNA expressions of type I collagen and decorin were then measured. When compared to the control group, the cell proliferation of irradiated Achilles tendon fibroblasts in the other three groups increased significantly by 13% +/- 0.8% (Group 2), 30% +/- 0.4% (Group 3), and 12% +/- 0.6% (Group 4) respectively. But progressively higher laser intensity did not achieve a correspondingly higher cell proliferation effect in Achilles tendon fibroblasts. The mRNA expressions of decorin and type I collagen in fibroblasts with LLLI were significantly higher (p < 0.05). Therefore, suitable dosages of LLLI may result in more effective tissue healing by promoting type I collagen and decorin synthesis. However, these positive effects of LLLI on the repair of the Achilles tendon in humans should be further investigated in clinic. | 18,991,342 |
Rheological characterization of the nucleus pulposus and dense collagen scaffolds intended for functional replacement. | Lumbar discectomy is an effective therapy for neurological decompression in patients suffering from sciatica due to a herniated nucleus pulposus (NP). However, high numbers of patients suffering from persisting postoperative low back pain have resulted in many strategies targeting the regeneration of the NP. For successful regeneration, the stiffness of scaffolds is increasingly recognized as a potent mechanical cue for the differentiation and biosynthetic response of (stem) cells. The aim of the current study is to characterize the viscoelastic properties of the NP and to develop dense collagen scaffolds with similar properties. The scaffolds consisted of highly dense (0.5%-12%) type I collagen matrices, prepared by plastic compression. The complex modulus of the NP was 22 kPa (at 10 rad s(-1)), which should agree with a scaffold with a collagen concentration of 23%. The loss tangent, indicative of energy dissipation, is higher for the NP (0.28) than for the scaffolds (0.12) and was not dependent of the collagen density. Gamma sterilization of the scaffolds increased the shear moduli but also resulted in more brittle behavior and a reduced swelling capacity. In conclusion, by tuning the collagen density, we can approach the stiffness of the NP. Therefore, dense collagen is a promising candidate for tissue engineering of the NP that deserves further study, such as the addition of other proteins. | 18,991,343 |
Sedative and anticonvulsant drugs suppress postnatal neurogenesis. | Sedative and anticonvulsant drugs, which inhibit N-methyl-D-aspartate receptor-mediated excitation or enhance GABA-mediated action, may cause apoptotic neurodegeneration in the developing mammalian brain. Here we explored whether such agents influence early postnatal neurogenesis. The N-methyl-D-aspartate antagonist MK801 and the GABA subtype A agonists phenobarbital and diazepam were administered to infant rats, and cell proliferation and neurogenesis were studied in the brain using 5-bromo-2'-deoxyuridine and doublecortin immunohistochemistry and stereology. Using confocal microscopy, we quantified neurogenesis in the dentate gyrus on postnatal day 15 (P15) after treatment with MK801 or phenobarbital on P6 to P10. Learning and memory were assessed at the age of 6 months after early postnatal treatment with phenobarbital. MK801, phenobarbital, and diazepam reduced numbers of newly born cells in the brain. We found no evidence that these agents caused apoptosis of 5-bromo-2'-deoxyuridine-positive cells. In the dentate gyrus, many of the newly formed cells differentiated toward a neuronal phenotype. Phenobarbital and MK801 reduced numbers of newly formed neurons in the dentate gyrus. At the age of 6 months, phenobarbital-treated rats had fewer neurons in the dentate gyrus and performed worse than saline-treated littermates in water maze learning and memory task. These findings show that blockade of N-methyl-D-aspartate receptor-mediated excitation and enhancement of GABA subtype A receptor activation impair cell proliferation and inhibit neurogenesis in the immature rat brain. Because many sedative and antiepileptic drugs used in pediatric medicine act via these mechanisms, our findings raise concerns about their potential impact on human brain development. | 18,991,352 |
Paradoxical dysregulation of the neural stem cell pathway sonic hedgehog-Gli1 in autoimmune encephalomyelitis and multiple sclerosis. | Neurovascular niches have been proposed as critical components of the neural stem cell (NSC) response to acute central nervous system injury; however, it is unclear whether these potential reparative niches remain functional during chronic injury. Here, we asked how central nervous system inflammatory injury regulates the intrinsic properties of NSCs and their niches. We investigated the sonic hedgehog (Shh)-Gli1 pathway, an important signaling pathway for NSCs, in experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis (MS), and its regulation by inflammatory cytokines. We show that Shh is markedly upregulated by reactive and perivascular astroglia in areas of injury in MS lesions and during EAE. Astroglia outside the subventricular zone niche can support NSC differentiation toward neurons and oligodendrocytes, and Shh is a critical mediator of this effect. Shh induces differential upregulation of the transcription factor Gli1, which mediates Shh-induced NSC differentiation. However, despite the increase in Shh and the fact that Gli1 was initially increased during early inflammation of EAE and active lesions of MS, Gli1 was significantly decreased in spinal cord oligodendrocyte precursor cells after onset of EAE, and in chronic active and inactive lesions from MS brain. The Th1 cytokine interferon-gamma was unique in inducing Shh expression in astroglia and NSCs, while paradoxically suppressing Gli1 expression in NSCs and inhibiting Shh-mediated NSC differentiation. Our data suggest that endogenous repair potential during chronic injury appears to be limited by inflammation-induced alterations in intrinsic NSC molecular pathways such as Gli1. | 18,991,353 |
Quantum dot-carrier peptide conjugates suitable for imaging and delivery applications. | We developed multifunctional fluorescent nanoparticles suitable for the nonviral delivery of negatively charged molecules like RNA. Therefore, we incorporated the recently developed branched hCT-derived carrier peptide hCT(18-32)-k7 on the surface of luminescent quantum dots (QDs). Besides detailed characterization of our QD-peptide conjugates concerning stability, toxicity, and uptake mechanism. we used them for efficient RNA delivery into different cell lines. The results of our studies indicate the involvement of more than one endocytotic uptake pathway in the internalization process. Furthermore, we could show that the QD-peptide bioconjugates exhibit no effect on cell viability and possess high stability inside living cells. The efficacy of our newly designed constructs for oligonucleotide drug delivery is highlighted by the successful intracellular transport of Cy-3 labeled RNA. Moreover, by using the chemotherapeutic chloroquine the efficient release of the assemblies out of endosomes was demonstrated. These results prove that our multifunctional platforms are versatile tools for diagnostic and therapeutic imaging purposes applicable for biologically active siRNA or aptamer sequences. | 18,991,369 |
Synthesis of conformationally locked versions of puromycin analogues. | Conformationally locked North and South versions of puromycin analogues built on a bicyclo[3.1.0]hexane pseudosugar template were synthesized. The final assembly of the products was accomplished by the Staudinger-Vilarrasa coupling of the corresponding North (2 and 3) and South (6 and 7) 3'-azidopurine carbanucleosides with the Fmoc-protected 1-hydroxybenzotriazole ester of 4-methoxy-L-tyrosine. North azides 2 and 3 were reported earlier. The 3'-azido intermediates 6 and 7 that are necessary for the synthesis of the South puromycin analogues are described herein for the first time. | 18,991,379 |
Structural changes of Salinibacter sensory rhodopsin I upon formation of the K and M photointermediates. | Sensory rhodopsin I (SRI) is one of the most interesting photosensory receptors in nature because of its ability to mediate opposite signals depending on light color by photochromic one-photon and two-photon reactions. Recently, we characterized SRI from eubacterium Salinibacter ruber (SrSRI). This protein allows more detailed information about the structure and structural changes of SRI during its action to be obtained. In this paper, Fourier transform infrared (FTIR) spectroscopy is applied to SrSRI, and the spectral changes upon formation of the K and M intermediates are compared with those of other archaeal rhodopsins, SRI from Halobacterium salinarum (HsSRI), sensory rhodopsin II (SRII), bacteriorhodopsin (BR), and halorhodopsin (HR). Spectral comparison of the hydrogen out-of-plane (HOOP) vibrations of the retinal chromophore in the K intermediates shows that extended choromophore distortion takes place in SrSRI and HsSRI, as well as in SRII, whereas the distortion is localized in the Schiff base region in BR and HR. It appears that sensor and pump functions are distinguishable from the spectral feature of HOOP modes. The HOOP band at 864 cm(-1) in SRII, important for negative phototaxis, is absent in SrSRI, suggesting differences in signal transfer mechanism between SRI and SRII. The strongly hydrogen-bound water molecule, important for proton pumps, is observed at 2172 cm(-1) in SrSRI, as well as in BR and SRII. The formation of the M intermediate accompanies the appearance of peaks at 1753 (+) and 1743 (-) cm(-1), which can be interpreted as the protonation signal of the counterion (Asp72) and the proton release signal from an unidentified carboxylic acid, respectively. The structure and structural changes of SrSRI are discussed on the basis of the present infrared spectral comparisons with other rhodopsins. | 18,991,393 |
Methionine uptake in Corynebacterium glutamicum by MetQNI and by MetPS, a novel methionine and alanine importer of the NSS neurotransmitter transporter family. | The soil bacterium Corynebacterium glutamicum is a model organism in amino acid biotechnology. Here we present the identification of two different L-methionine uptake systems including the first characterization of a bacterial secondary methionine carrier. The primary carrier MetQNI is a high affinity ABC-type transporter specific for l-methionine. Its expression is under the control of the transcription factor McbR, the global regulator of sulfur metabolism in C. glutamicum. Besides MetQNI, a novel secondary methionine uptake system of the NSS (neurotransmitter:sodium symporter) family was identified and named MetP. The MetP system is characterized by a lower affinity for methionine and uses Na(+) ions for energetic coupling. It is also the main alanine transporter in C. glutamicum and is expressed constitutively. These observations are consistent with models of methionine, alanine, and leucine bound to MetP, derived from the X-ray crystal structure of the LeuT transporter from Aquifex aeolicus. Complementation studies show that MetP consists of two components, a large subunit with 12 predicted transmembrane segments and, surprisingly, an additional subunit with one predicted transmembrane segment only. Thus, this new member of the NSS transporter family adds a novel feature to this class of carriers, namely, the functional dependence on an additional small subunit. | 18,991,398 |
Behavior of thin films of poly(oxyethylene)-poly(oxybutylene) copolymers studied by brewster angle microscopy and atomic force microscopy. | Surface films of two copolymers of ethylene oxide (E) and butylene oxide (B), namely E23B8 and E87B18, have been examined by Brewster angle microscopy (BAM) and atomic force microscopy (AFM). Isotherms taken on unsupported films of these copolymers at the air-water interface showed a clear gas to liquid phase transition for E57B18 and a barely discernible phase transition for E23B8. The BAM studies showed a gradual brightening of the films as the surface pressure was increased, which was associated with a film thickening and/or a film densification. Several bright spots were also observed within the films, with the number of spots increasing gradually as the film surface pressure was increased. AFM studies of these films did not show any localized ordering, which fits in with the results from our previous X-ray study of these copolymers [Hodges, C. S.; Neville, F.; Konovalov, O.; Gidalevitz, D.; Hamley, I. W.; Langmuir 2006, 22 (21), 8821-8825], where no long-range ordering was observed. AFM imaging showed two sizes of particulates that were irregularly spaced across the film. The larger particulates were associated with silica contaminants from the copolymer synthesis, whereas the smaller particulates were assumed to be aggregated copolymer. An analysis of the semidilute region of the isotherm showed that while both copolymers had intermixed ethylene oxide and butylene oxide units, the lower molecular weight E23B8 copolymer manifested significantly more intermixing than E87B18. | 18,991,421 |
Effect of fluorescently labeling protein probes on kinetics of protein-ligand reactions. | We studied the effect of fluorescently labeling proteins on protein-ligand reactions. Unlabeled ligands (streptavidin-binding peptides and rabbit immunoglobulin G (IgG) as antigen targets) are immobilized on epoxy-functionalized glass slides. Unlabeled and Cy3-labeled protein probes from the same batch (streptavidin and goat antibodies) subsequently react with the surface-immobilized targets. By monitoring in situ the surface mass density change using an oblique-incidence reflectivity difference scanning microscope (a label-free detector), we measured k(on) and k(off) for streptavidin-peptide reactions and antibody-antigen reaction. We found that (1) equilibrium dissociation constants, defined as K(D) = k(off)/k(on), for streptavidin-peptide reactions increases by a factor of 3-4 when the solution-phase streptavidin is labeled with Cy3 dye and (2) K(D) for reactions of solution-phase goat anti-rabbit antibodies with rabbit IgG targets also change significantly when the goat antibodies are labeled with Cy3 dye. | 18,991,423 |
Computational study of the reaction of CH2(X3B1) with CH3OH. | The reaction of triplet methylene with methanol is a key process in alcohol combustion but surprisingly this reaction has never been studied. The reaction mechanism is investigated by using various high-level ab initio methods, including the complete basis set extrapolation (CBS-QB3 and CBS-APNO), the latest Gaussian-n composite method (G4), and the Weizmann-1 method (W1U). A total of five product channels and six transition states are found. The dominant mechanism is direct hydrogen abstraction, and the major product channel is CH(3) + CH(3)O, involving a weak prereactive complex and a 7.4 kcal/mol barrier. The other hydrogen abstraction channel, CH(3) + CH(2)OH, is less important even though it is more exothermic and involves a similar barrier height. The rate coefficients are predicted in the temperature range 200-3000 K. The tunneling effect and the hindered internal rotational freedoms play a key role in the reaction. Moreover, the reaction shows significant kinetic isotope effect. | 18,991,430 |
Metal ion-dependent fluorescent dynamics of photoexcited zinc-porphyrin and zinc-myoglobin modified with ethylenediaminetetraacetic acid. | The reconstituted zinc-myoglobin (ZnMb) dyads, ZnMb-[M(II)(edta)], have been prepared by incorporating a zinc-porphyrin (ZnP) cofactor modified with ethylenediaminetetraacetic acid (H(4)edta) into apo-Mb. In case of the monomeric ZnP(edta) cofactor coordinated by one pyridine molecule, ZnP(py)(edta), a spontaneous 1:1 complex with a transient metal ion was formed in an aqueous solvent, and the photoexcited singlet state of ZnP, (1)(ZnP)*, was quenched by the [Cu(II)(edta)] moiety through intramolecular photoinduced electron-transfer (ET) reaction. The rate constant for the intramolecular quenching ET (k(q)) at 25 degrees C was successfully obtained as k(q) = 5.1 x 10(9) s(-1). In the case of Co(2+), Ni(2+), and Mn(2+), intersystem crossing by paramagnetic effect was mainly considered between (1)(ZnP)* and the [M(II)(edta)] complex. For the ZnMb-[M(II)(edta)] systems, the intramolecular ET reaction between the excited singlet state of (1)(ZnMb)* and the [Cu(II)(edta)] moieties provided the slower quenching rate constant, k(q) = 2.1 x 10(8) s(-1), compared with that of the ZnP(py)(edta) one. Kinetic studies also presented the efficient fluorescence quenching of the (1)(ZnMb)*-[Co(II)(edta)] dyad. Our study clearly demonstrates that wrapping of the ZnP cofactor by the apoprotein matrix and synthetic manipulation at the Mb surface ensure metal ion-sensitive fluorescent dynamics of ZnMb and provides valuable information to elucidate the complicated mechanism of the biological photoinduced ET reactions of hemoproteins. | 18,991,435 |
Pyrazine in supercritical xenon: local number density defined by experiment and calculation. | Toward our goal of using supercritical fluids to study solvent effects in physical and chemical phenomena, we develop a method to spatially define the solvent local number density at the solute in the highly compressible regime of a supercritical fluid. Experimentally, the red shift of the pyrazine n-pi* electronic transition was measured at high dilution in supercritical xenon as a function of pressure from 0 to approximately 24 MPa at two temperatures: one (293.2 K) close to the critical temperature and the other (333.2 K) remote. Computationally, several representative stationary points were located on the potential surfaces for pyrazine and 1, 2, 3, and 4 xenons at the MP2/6-311++G(d,p)/aug-cc-pVTZ-PP level. The vertical n-pi* ((1)B(3u)) transition energies were computed for these geometries using a TDDFT/B3LYP/DGDZVP method. The combination of experiment and quantum chemical computation allows prediction of supercritical xenon bulk densities at which the pyrazine primary solvation shell contains an average of 1, 2, 3, and 4 xenon molecules. These density predictions were achieved by graphical superposition of calculated shifts on the experimental shift versus density curves for 293.2 and 333.2 K. Predicted bulk densities are 0.50, 0.91, 1.85, and 2.50 g cm(-3) for average pyrazine primary solvation shell occupancy by 1, 2, 3, and 4 xenons at 293.2 K. Predicted bulk densities are 0.65, 1.20, 1.85, and 2.50 g cm(-3) for average pyrazine primary solvation shell occupancy by 1, 2, 3, and 4 xenons at 333.2 K. These predictions were evaluated with classical Lennard-Jones molecular dynamics simulations designed to replicate experimental conditions at the two temperatures. The average xenon number within 5.0 A of the pyrazine center-of-mass at the predicted densities is 1.3, 2.1, 3.0, and 4.0 at both simulation temperatures. Our three-component method-absorbance measurement, quantum chemical prediction, and evaluation of prediction with classical molecular dynamics simulation-therefore has a high degree of internal consistency for a system in which the intermolecular interactions are dominated by dispersion forces. | 18,991,436 |
Lewis acid catalyzed ring-opening intramolecular Friedel-Crafts alkylation of methylenecyclopropane 1,1-diesters. | The first Friedel-Crafts reaction initiated by the direct generation of a carbocation at the C3 position of MCP 1,1-diesters through distal-bond cleavage was presented. The described method supplied a new synthetic strategy to prepare indene and hydronaphthalene derivatives in moderate to excellent yields under mild conditions. | 18,991,443 |
Low-fouling, biofunctionalized, and biodegradable click capsules. | We report the synthesis of covalently stabilized hollow capsules from biodegradable materials using a combination of click chemistry and layer-by-layer (LbL) assembly. The biodegradable polymers poly(L-lysine) (PLL) and poly(L-glutamic acid) (PGA) were modified with alkyne and azide moieties. Linear film buildup was observed for both materials on planar surfaces and colloidal silica templates. A variation of the assembly conditions, such as an increase in the salt concentration and variations in pH, was shown to increase the individual layer thickness by almost 200%. The biodegradable click capsules were analyzed with optical microscopy, scanning electron microscopy (SEM), and atomic force microscopy (AFM). Capsules were uniform in size and had a regular, spherical shape. They were found to be stable between pH 2 and 11 and showed reversible, pH-responsive shrinking/swelling behavior. We also show that covalently stabilized PLL films can be postfunctionalized by depositing a monolayer of heterobifunctional poly(ethylene glycol) (PEG), which provides low-fouling properties and simultaneously enhances specific protein binding. The responsive, biodegradable click films reported herein are promising for a range of applications in the biomedical field. | 18,991,459 |
Yoga for veterans with chronic low-back pain. | Chronic back pain affects a large proportion of both the general population and of military veterans. Although numerous therapies exist for treating chronic back pain, they can be costly and tend to have limited effectiveness. Thus, demonstrating the efficacy and cost-effectiveness of additional treatment alternatives is important. The purpose of our study was to examine the benefits of a yoga intervention for Veterans Administration (VA) patients. SUBJECTS/INTERVENTION: VA patients with chronic back pain were referred by their primary care providers to a yoga program as part of clinical care. Before starting yoga, a VA physician trained in yoga evaluated each patient to ensure that they could participate safely. The research study consisted of completing a short battery of questionnaires at baseline and again 10 weeks later. Questionnaires included measures of pain, depression, energy/fatigue, health-related quality of life, and program satisfaction. Paired t-tests were used to compare baseline scores to those at the 10-week follow-up for the single group, pre-post design. Correlations were used to examine whether yoga attendance and home practice were associated with better outcomes. Baseline and follow-up data were available for 33 participants. Participants were VA patients with a mean age of 55 years. They were 21% female, 70% white, 52% married, 68% college graduates, and 44% were retired. Significant improvements were found for pain, depression, energy/fatigue, and the Short Form-12 Mental Health Scale. The number of yoga sessions attended and the frequency of home practice were associated with improved outcomes. Participants appeared highly satisfied with the yoga instructor and moderately satisfied with the ease of participation and health benefits of the yoga program. Preliminary data suggest that a yoga intervention for VA patients with chronic back pain may improve the health of veterans. However, the limitations of a pre-post study design make conclusions tentative. A larger randomized, controlled trial of the yoga program is planned. | 18,991,515 |
Assessment of prescribed herbal medicine on liver function in Korea: a prospective observational study. | The aim of this study was to investigate the influence of herbal medicine (HM) prescribed by doctors of Korean medicine (KMD) on liver function in Korea. For this multicenter, prospective, observational study, we enrolled patients who wished to take HM prescribed by KMD for various medical purposes in Korea. One hundred and twenty-two (122) patients took HM for an average of 20.6 +/- 8.4 (mean +/- standard deviation) days, and completed questionnaires. Liver function tests (LFTs) were performed before (first test) and after each HM treatment (second test). For LFT, aspartate aminotransferase, alanine aminotransferase, total bilirubin (t-Bil), direct bilirubin, alkaline phosphatase, and gamma-glutamyl transferase were measured. There were no significant changes in LFT data between the first and second tests, except in the t-Bil level. However, all data of total bilirubin level in second test were within normal range, except only one patient. Multivariate analysis did not identify any herb that significantly increased t-Bil; hence no hepatotoxic herb was found. Twenty-one (21) of the 122 patients were abnormal on first testing, and 10 at the second testing. Of the patients taking herbs, 4 changed from normal to abnormal and 15 from abnormal to normal (p = 0.019). The current study showed that ingestion of HM prescribed by KMD did not increase the frequency of abnormal LFTs, at least in the short term. | 18,991,516 |
Epidemiology, management, and prognosis of secondary non-postoperative peritonitis: a French prospective observational multicenter study. | Despite improvements in treatment, secondary peritonitis still is associated with high morbidity and mortality rates. Better knowledge of real-life clinical practice might improve management. Prospective, observational study (January-June 2005) of 841 patients with non-postoperative secondary peritonitis. Peritonitis originated in the colon (32% of patients), appendix (31%), stomach/duodenum (18%), small bowel (13%), or biliary tract (6%). Most patients (78%) presented with generalized peritonitis and 26% with severe peritonitis (Simplified Acute Physiology Score [SAPS] II score>38). Among the 841 patients, 27.3% underwent laparoscopy alone; 11% underwent repeat surgery, percutaneous drainage, or both. A SAPS II score>38 and the presence of Enterococcus spp. were predictive of abdominal and non-surgical infections (odds ratio [OR]=1.84; p=0.013 and OR=2.93; p<0.0001, respectively). A SAPS II score>38 also was predictive of death (OR=10.5; p<0.0001). The overall mortality rate was high (15%). Patients receiving inappropriate initial antimicrobial therapy had significantly higher morbidity and mortality rates than patients receiving appropriate therapy (44 vs. 30%; p=0.004 and 23% vs. 14%; p=0.015, respectively). The SAPS II score and rates of severe peritonitis, morbidity, and mortality were significantly lower in patients with appendiceal peritonitis. Patients with non-postoperative peritonitis should be considered high risk and should receive appropriate initial therapy. The presence of Enterococcus spp. in peritoneal cultures significantly increased morbidity but not the mortality rate. Appendiceal peritonitis that was less severe and had a better prognosis than peritonitis originating in other sites should be considered a special case in future studies. | 18,991,521 |
Combinatorial properties of graphs and groups of physico-chemical interest. | Combinatorial properties of graphs and groups of physico-chemical interest are described. A type of mathematical modeling is applied which involves "translating" algebraic expressions into graphs. The idea is applied to both graph theory and group theory. The former topic includes objects of importance in physics and chemistry such as trees, polyomino graphs, king boards, etc. Our study along these lines emphasizes nonadjacency relations, graph-generation, quasicrystals, continued fractions, fractals, and general ordering schemes of graphs. The second part of the paper considers certain colored graphs as models of several group-theoretical concepts including coset representations of groups, subduction of groups, character tables, and mark tables which are essential to the understanding of recent developments of combinatorial enumeration in chemistry. | 18,991,574 |
Solution stability--plasma, gastrointestinal, bioassay. | Solution stability of drug candidates in plasma, gastrointestinal fluids and bioassays is important in order to achieve low clearance, good oral bioavailability and have robust SAR. Screening of solution stability early in drug discovery can avoid pursuing hits with high risk of instability, prioritize chemical series, guide structural modification, and enhance the chance of project success. The conditions of solution stability methods are critical in generating relevant data and include: test compound concentration, enzyme source and preparation, limits of solubility, cosolvent, plasma protein binding effect, detection techniques (LC-UV vs. LC-MS), and what to detect (disappearance of parent vs. formation of degradants). Details of methodologies, applications, structure-stability relationships and case studies are discussed. | 18,991,582 |
Permeability--in vitro assays for assessing drug transporter activity. | The accumulating evidence has revealed that drug transporters have essential roles in the delivery and excretory processes of drugs and their metabolites. Inhibition or induction of drug transporters can affect pharmacokinetic properties and therapeutic efficacy of a drug. Thus, the characterization of drug-transporter interactions becomes important for the selection of compounds to avoid transporter associated absorption, distribution, metabolism, excretion and toxicity (ADME/Tox) issues. Additionally, the potential use of absorptive transporters for drug delivery has been recognized for drug design. In vitro and in vivo approaches have been developed for studying the transporter activities. In vitro assays can rapidly provide the information for identifying interaction of a compound and a particular transporter and have proved to be amenable to high throughput approaches. Therefore, the studies are conducted in early drug discovery. In this article, in vitro methods are reviewed, including cell free and cell-based assays. Their applications, limitations and impact on drug discovery are discussed. | 18,991,588 |
Insights into the regulation of renal hemodynamic function in diabetic mellitus. | Diabetes mellitus (DM) is characterized by renal hemodynamic changes which have been purported to contribute to the development of nephropathy. In this review we have focused on the major renal hemodynamic factors that may be associated with glomerular hyperfiltration. Recent animal and human studies have demonstrated that renal hemodynamic alterations occur very early in the natural history of DM. Most of the literature related to renal hemodynamic functional changes in type 1 DM has focused on major neurohormonal influences, such as the renin angiotensin system, cyclooxygenase-related pathways, the nitric oxide system, the autonomic nervous system and hyperglycemia. In addition, gender may have important modulatory effects on some of these putative pathways that have been implicated in the development of alterations in renal hemodynamic function related to DM. | 18,991,597 |
Environmental chemicals and breast cancer risk--a structural chemistry perspective. | In modern industrialized societies, people are exposed to thousands of naturally occurring and synthetic chemicals throughout their lifetime. Although certain occupational chemicals are known to be carcinogenic in humans, it has been difficult to definitively determine the adverse health effects of many environmental pollutants due to their tremendous chemical diversity and absence of a consistent structural motif. Many environmental chemicals are metabolized in the body to reactive intermediates that readily react with DNA to form modified bases known as adducts, while other compounds mimic the biological function of estrogen. Because environmental chemicals tend to accumulate in human tissues and have carcinogenic and/or estrogenic properties, there is heightened interest in determining whether environmental chemicals increase risk for endocrine-related cancers, including breast cancer. Breast cancer is the most common cancer in women worldwide, but established risk factors account for a relatively small proportion of cases and causative factors remain ambiguous and poorly defined. In this review, we outline the structural chemistry of environmental contaminants, describe mechanisms of carcinogenesis and molecular pathways through which these chemicals may exert detrimental health effects, review current knowledge of relationships between chemicals and breast cancer risk, and highlight future directions for research on environmental contributions to breast cancer. Improved understanding of the relationship between environmental chemicals and breast cancer will help to educate the general public about real and perceived dangers of these pollutants in our environment and has the potential to reduce individual risk by changing corporate practices and improving public health policies. | 18,991,630 |
Chemistry and biology of thyrotropin-releasing hormone (TRH) and its analogs. | Thyrotropin-releasing hormone (TRH), a hypothalamic orally active neuropeptide, has been manifested in a wide range of biological responses. Besides its central role in regulating the pituitary-thyroid axis by simulating the release of thyrotropin, TRH has considerable influence on the activity of a number of neurobiological systems. Due to the therapeutic potential of TRH to treat several CNS maladies, the development of CNS-selective and metabolically stable TRH analogs is an area of interest. TRH is known to elicit its biological response through two G-protein coupled receptors for TRH (namely, TRH-R1 and TRH-R2). The distinct distribution of TRH receptors in tissues has provided opportunity to discover receptor subtype-specific analogs, which would demonstrate high CNS activities, and are completely free of hormonal activities. In this review, an in-depth analysis of the chemistry and biology of TRH and its analogs is provided. Recent discoveries of TRH-R2 selective analogs, TRH super agonists, metabolically stable TRH analogs, and targeted delivery of TRH analogs have been also discussed. | 18,991,632 |
Steroid biosynthesis inhibitors in the therapy of hypercortisolism: theory and practice. | Cushing's syndrome is a rare disease with significant morbidity and mortality. Surgical intervention represents the most effective treatment option in both adrenocorticotropin-dependent and -independent forms of hypercortisolism. It is not uncommon, however, that surgery fails to cure or control the disease. Pharmacotherapy with drugs inhibiting steroid biosynthesis can be effectively used in these cases in order to alleviate symptoms or even to induce chemical adrenalectomy. A few drugs inhibiting single or multiple steps in adrenal steroid biosynthesis can be used in clinical practice. Drugs predominantly inhibiting single enzymatic steps include the 11beta-hydroxylase inhibitor metyrapone and the 3beta-hydroxysteroid dehydrogenase inhibitor trilostane, whereas mitotane, aminoglutethimide, ketoconazole and etomidate block multiple enzymatic reactions. Etomidate is the only agent available for parenteral administration that renders it as a treatment of choice in critically ill patients requiring a rapid control of hypercortisolemia. Ketoconazole, metyrapone and aminoglutethimide can be used alone or in combination for the treatment of hypercortisolism caused by benign adrenocorticotropin- or cortisol-secreting tumors. The clinical utility of trilostane is variable. Besides blocking multiple steps in adrenal steroid biosynthesis, the DDT (insecticide) analogue mitotane also has adrenolytic properties by inducing mitochondrial degeneration that renders it superior to other drugs in the treatment of adrenocortical cancer. Severe side effects may develop during therapy with each aforementioned drug that include hepatic, endocrine and neurological toxicity. After summarizing the chemical and biological properties of steroid biosynthetic inhibitors, the authors describe their possible clinical applications and limitations. | 18,991,633 |
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