Protocols and Video Articles Authored by Conor W. Kelly (Translated to Danish)

Dietary Protein Intake and Blood Pressure: a Meta-analysis of Randomized Controlled Trials American Journal of Epidemiology. Oct, 2012 | Pubmed ID: 23035142 The authors conducted a meta-analysis of randomized controlled trials to evaluate the association of dietary protein intake with blood pressure. To identify articles published before April 2011, the authors searched electronic databases, conducted a manual bibliography review, and consulted experts in the field. Forty trials (including 3,277 participants in total) met the eligibility criteria and were included. Using a standardized form, 2 investigators independently abstracted data on study design, participant characteristics, and treatment outcomes. Net change estimates were pooled across trials using random-effects models. Compared with carbohydrate, dietary protein intake was associated with significant changes in mean systolic and diastolic blood pressure of -1.76 mm Hg (95% confidence interval (CI): -2.33, -1.20) and -1.15 mm Hg (95% CI: -1.59, -0.71), respectively (both Pâ€Š's < 0.001). Both vegetable protein and animal protein were associated with significant blood pressure changes of -2.27 mm Hg (95% CI: -3.36, -1.18) and -2.54 mm Hg (95% CI: -3.55, -1.53), respectively, for systolic blood pressure (both Pâ€Š's < 0.001) and -1.26 mm Hg (95% CI: -2.26, -0.26) and -0.95 mm Hg (95% CI: -1.72, -0.19), respectively, for diastolic blood pressure (both Pâ€Š's = 0.014). Blood pressure reduction was not significantly different when vegetable protein was compared directly with animal protein. These findings indicate that partially replacing dietary carbohydrate with protein may be important for the prevention and treatment of hypertension.

Effects of Low-carbohydrate Diets Versus Low-fat Diets on Metabolic Risk Factors: a Meta-analysis of Randomized Controlled Clinical Trials American Journal of Epidemiology. Oct, 2012 | Pubmed ID: 23035144 The effects of low-carbohydrate diets (â‰¤45% of energy from carbohydrates) versus low-fat diets (â‰¤30% of energy from fat) on metabolic risk factors were compared in a meta-analysis of randomized controlled trials. Twenty-three trials from multiple countries with a total of 2,788 participants met the predetermined eligibility criteria (from January 1, 1966 to June 20, 2011) and were included in the analyses. Data abstraction was conducted in duplicate by independent investigators. Both low-carbohydrate and low-fat diets lowered weight and improved metabolic risk factors. Compared with participants on low-fat diets, persons on low-carbohydrate diets experienced a slightly but statistically significantly lower reduction in total cholesterol (2.7 mg/dL; 95% confidence interval: 0.8, 4.6), and low density lipoprotein cholesterol (3.7 mg/dL; 95% confidence interval: 1.0, 6.4), but a greater increase in high density lipoprotein cholesterol (3.3 mg/dL; 95% confidence interval: 1.9, 4.7) and a greater decrease in triglycerides (-14.0 mg/dL; 95% confidence interval: -19.4, -8.7). Reductions in body weight, waist circumference and other metabolic risk factors were not significantly different between the 2 diets. These findings suggest that low-carbohydrate diets are at least as effective as low-fat diets at reducing weight and improving metabolic risk factors. Low-carbohydrate diets could be recommended to obese persons with abnormal metabolic risk factors for the purpose of weight loss. Studies demonstrating long-term effects of low-carbohydrate diets on cardiovascular events were warranted.

Maternal History of Hypertension and Blood Pressure Response to Potassium Intake: The GenSalt Study American Journal of Epidemiology. Oct, 2012 | Pubmed ID: 23035145 The relation between parental history of hypertension and blood pressure response to potassium intake is unknown. A 7-day high-sodium followed by a 7-day high-sodium plus potassium dietary-feeding study was conducted from 2003 to 2005 among 1,871 Chinese participants. Those with a maternal history of hypertension had larger systolic blood pressure responses to potassium compared with those without: -4.31 (95% confidence interval (CI): -4.99, -3.62) mm Hg versus -3.35 (95% CI: -4.00, -2.70) mm Hg, respectively (P(difference) = 0.002). A consistent trend was observed for diastolic blood pressure responses: -1.80 (95% CI: -2.41, -1.20) mm Hg versus -1.35 (95% CI: -1.95, -0.74) mm Hg, respectively (P = 0.07). Stronger associations between early onset maternal hypertension and blood pressure responses were noted, with systolic blood pressure decreases of -4.80 (95% CI: -5.65, -3.95) mm Hg versus -3.55 (95% CI: -4.17, -2.93) mm Hg and diastolic blood pressure decreases of -2.25 (95% CI: -3.01, -1.50) mm Hg versus -1.42 (95% CI: -1.99, -0.85) mm Hg among those with early onset maternal hypertension versus those without, respectively (P = 0.001 and 0.009, respectively). Odds ratios for high potassium sensitivity were 1.36 (95% CI: 0.96, 1.92) and 1.60 (95% CI: 1.08, 2.36) for those with maternal hypertension and early onset maternal hypertension, respectively (P = 0.08 and 0.02, respectively). Potassium supplementation could help to reduce blood pressure among those with a maternal history of hypertension.

The Role of the Kallikrein-Kinin System Genes in the Salt Sensitivity of Blood Pressure: The GenSalt Study American Journal of Epidemiology. Oct, 2012 | Pubmed ID: 23035147 The current study comprehensively examined the association between common genetic variants of the kallikrein-kinin system (KKS) and blood pressure salt sensitivity. A 7-day low-sodium followed by a 7-day high-sodium dietary intervention was conducted among 1,906 Han Chinese participants recruited from 2003 to 2005. Blood pressure was measured by using a random-zero sphygmomanometer through the study. A total of 205 single nucleotide polymorphisms (SNPs) covering 11 genes of the KKS were selected for the analyses. Genetic variants of the bradykinin receptor B2 gene (BDKRB2) and the endothelin converting enzyme 1 gene (ECE1) showed significant associations with the salt-sensitivity phenotypes even after adjustment for multiple testing. Compared with the major G allele, the BDKRB2 rs11847625 minor C allele was significantly associated with increased systolic blood pressure responses to low-sodium intervention (P = 0.0001). Furthermore, a haplotype containing allele C was associated with an increased systolic blood pressure response to high-sodium intervention (P = 0.0009). Seven highly correlated ECE1 SNPs were shown to increase the diastolic blood pressure response to low-sodium intervention (P values ranged from 0.0003 to 0.002), with 2 haplotypes containing these 7 SNPs also associated with this same phenotype (P values ranged from 0.0004 to 0.002). In summary, genetic variants of the genes involved in the regulation of KKS may contribute to the salt sensitivity of blood pressure.

Reproducibility of Blood Pressure Response to the Cold Pressor Test: The GenSalt Study American Journal of Epidemiology. Oct, 2012 | Pubmed ID: 23035148 An elevated blood pressure (BP) response to the cold pressor test (CPT) is associated with increased risk of hypertension and cardiovascular disease. However, it is still unclear whether BP response to the CPT is a stable and reproducible trait over time. Using the same study protocol, the authors repeated the CPT 4.5 years after initial administration among 568 Han Chinese in rural northern China (2003-2005 and 2008-2009). BP was measured using a standard mercury sphygmomanometer prior to and 0, 1, 2, and 4 minutes after the participants immersed their hand in ice water (3Â°C-5Â°C) for 1 minute. Absolute BP levels and BP responses during the CPT in the initial and repeated administrations were highly correlated. For example, the correlation coefficients were 0.67, 0.73, 0.71, and 0.72 for absolute systolic BP levels at 0, 1, 2, and 4 minutes after ice-water immersion (all P 's < 0.0001). The correlation coefficients for systolic BP response were 0.41 at 0 minutes, 0.37 at 1 minute, 0.42 for maximum response, and 0.39 for the area under the curve during CPT (all P 's < 0.0001). These data indicate that BP response to the CPT is a long-term reproducible and stable characteristic in the general population.

Unique Blood Pressure Characteristics in Mother and Offspring After Early Onset Preeclampsia Hypertension. Nov, 2012 | Pubmed ID: 23045462 Risk of hypertension in mother and offspring after preeclampsia is greater if preeclampsia develops early in pregnancy. We investigated whether those who develop early onset disease have unique adverse blood pressure characteristics. One hundred forty women were studied 6 to 13 years either after a pregnancy complicated by preeclampsia (45 women with early onset preeclampsia before 34 weeks gestation and 45 women with late-onset preeclampsia) or after a normotensive pregnancy (50 women). Forty-seven offspring from these pregnancies also participated. Data on maternal antenatal and postnatal blood pressures were extracted from maternity records and related to peripheral, central, and ambulatory blood pressure measurements in later life. Compared with late-onset preeclampsia, early onset preeclampsia was associated with higher diastolic blood pressure 6 weeks postnatally (86.25Â±13.46 versus 75.00Â±5.00 mm Hg, P

Investigating Drug Repositioning Opportunities in FDA Drug Labels Through Topic Modeling BMC Bioinformatics. Sep, 2012 | Pubmed ID: 23046522 Drug repositioning offers an opportunity to revitalize the slowing drug discovery pipeline by finding new uses for currently existing drugs. Our hypothesis is that drugs sharing similar side effect profiles are likely to be effective for the same disease, and thus repositioning opportunities can be identified by finding drug pairs with similar side effects documented in U.S. Food and Drug Administration (FDA) approved drug labels. The safety information in the drug labels is usually obtained in the clinical trial and augmented with the observations in the post-market use of the drug. Therefore, our drug repositioning approach can take the advantage of more comprehensive safety information comparing with conventional de novo approach.

Lower Mortality in Magnet Hospitals Medical Care. Oct, 2012 | Pubmed ID: 23047129 BACKGROUND:: Although there is evidence that hospitals recognized for nursing excellence-Magnet hospitals-are successful in attracting and retaining nurses, it is uncertain whether Magnet recognition is associated with better patient outcomes than non-Magnets, and if so why. OBJECTIVES:: To determine whether Magnet hospitals have lower risk-adjusted mortality and failure-to-rescue compared with non-Magnet hospitals, and to determine the most likely explanations. METHOD AND STUDY DESIGN:: Analysis of linked patient, nurse, and hospital data on 56 Magnet and 508 non-Magnet hospitals. Logistic regression models were used to estimate differences in the odds of mortality and failure-to-rescue for surgical patients treated in Magnet versus non-Magnet hospitals, and to determine the extent to which differences in outcomes can be explained by nursing after accounting for patient and hospital differences. RESULTS:: Magnet hospitals had significantly better work environments and higher proportions of nurses with bachelor's degrees and specialty certification. These nursing factors explained much of the Magnet hospital effect on patient outcomes. However, patients treated in Magnet hospitals had 14% lower odds of mortality (odds ratio 0.86; 95% confidence interval, 0.76-0.98; P=0.02) and 12% lower odds of failure-to-rescue (odds ratio 0.88; 95% confidence interval, 0.77-1.01; P=0.07) while controlling for nursing factors as well as hospital and patient differences. CONCLUSIONS:: The lower mortality we find in Magnet hospitals is largely attributable to measured nursing characteristics but there is a mortality advantage above and beyond what we could measure. Magnet recognition identifies existing quality and stimulates further positive organizational behavior that improves patient outcomes.

Expression of Key Genes of the Somatotropic Axis in Longissimus Dorsi Muscle of Beef Heifers Phenotypically Divergent for Residual Feed Intake Journal of Animal Science. Oct, 2012 | Pubmed ID: 23048153 This study evaluated the effect of residual feed intake (RFI) on the expression of constituent genes of the somatotropic axis in skeletal muscle across 2 diverse dietary regimes. Beef heifers (n = 86; initial BW = 191.8 kg [SD = 37]) fed a low-forage (LF) total mixed ration comprised of 70:30 concentrate:corn silage (11.0 MJ ME/kg DM) were ranked on RFI. The 10 highest- (high RFI) and 10 lowest- (low RFI) ranking animals were selected for the current study. Biopsies of the M. longissimus dorsi were harvested at the end of LF dietary period and again following a 6-wk period during which heifers were offered a high-forage (HF) grass silage only diet (9.7MJ ME/kg DM). Real-time PCR was used to quantify mRNA transcripts of 11 genes including IGF-1, IGF-2, their receptors (IGF-1R; IGF-2R), 6 IGFBP, and GH receptor (GHR). There was no evidence of a RFI phenotype Ã— diet interaction (P > 0.10) for any of the genes examined. An effect (P = 0.02) of RFI phenotype was evident for the abundance of GHR mRNA, with 2-fold greater expression levels detected in the low-RFI compared with the high-RFI phenotype. Additionally, mRNA expression of IGF-1R was up-regulated (1.7 fold; P = 0.04) for the low-RFI compared to high-RFI heifers. Residual feed intake was negatively associated with IGF-1R (r = -0.41; P < 0.05) and GHR (r = -0.50; P < 0.05) mRNA. Moderate negative correlation coefficients were also observed between feed conversion ratio (F:G) and gene expression levels for IGF-1R (r = -0.61; P < 0.01), as well as for GHR (r = - 0.49; P < 0.05). Moreover, associations were detected between DMI with IGF-1R (r = -0.42; P =0.07) and IGF-2R (r = 0.40; P = 0.07). The IGF-1R mRNA was positively correlated with IGF-1 (r = 0.34; P < 0.05) and IGF-2 (r = 0.71; P < 0.001) mRNA. Associations between IGF-1R and IGF-2R with IGFBP5 and GHR were positive (ranging from, r = 0.32 to 0.49). These data suggest that components of the somatotropic axis expressed within muscle tissue may be involved in the 3 regulation of feed efficiency in beef cattle. This effect is apparently consistent across contrasting dietary regimes.

EXERCISE AND DIET AFFECT QUANTITATIVE TRAIT LOCI FOR BODY WEIGHT AND COMPOSITION TRAITS IN AN ADVANCED INTERCROSS POPULATION OF MICE Physiological Genomics. Oct, 2012 | Pubmed ID: 23048196 Driven by the recent obesity epidemic, there is much interest in understanding the complex genetic and environmental basis of body weight and composition. We investigated this by searching for quantitative trait loci (QTLs) affecting a number of weight and adiposity traits in a G(10) advanced intercross population produced from crosses of mice in inbred strain C57BL/6J with those in a strain selected for high voluntary wheel running. The mice in this population were fed either a high-fat or a control diet throughout the study, and also measured for four exercise traits prior to sacrifice, allowing us to test for pre- and post-exercise QTLs as well as QTL by diet and QTL by exercise interactions. Our genome scan uncovered a number of QTLs, of which 40% replicated QTLs previously found for similar traits in an earlier (G(4)) generation. For those replicated QTL, the confidence intervals were reduced from an average of 19 Mb in the G(4) to 8 Mb in the G(10). Four QTLs on chromosomes 3, 8, 13, and 18 were especially prominent in affecting the percentage of fat in the mice. About 1/3 of all QTLs showed interactions with diet, exercise, or both, their genotypic effects on the traits showing a variety of patterns depending on the diet or level of exercise. It was concluded that the indirect effects of these QTLs provide an underlying genetic basis for the considerable variability in weight or fat loss typically found among individuals on the same diet and/or exercise regimen.

Multiple Pathways Regulate Minisatellite Stability During Stationary Phase in Yeast G3 (Bethesda, Md.). Oct, 2012 | Pubmed ID: 23050229 Alterations in minisatellite DNA repeat tracts in humans have been correlated with a number of serious disorders, including cancer. Despite their importance for human health, the genetic factors that influence minisatellite stability are not well understood. Previously, we identified mutations in the Saccharomyces cerevisiae zinc homeostasis genes ZRT1 and ZAP1 that significantly increase the frequency of minisatellite alteration specifically during stationary phase. In this work, we identified mutants of END3, PKC1, and RAD27 that increase minisatellite instability during stationary phase. Genetic analysis reveals that these genes, along with ZRT1 and ZAP1, comprise multiple pathways regulating minisatellite stability during stationary phase. Minisatellite alterations generated by perturbation of any of these pathways occur via homologous recombination. We present evidence that suggests formation of ssDNA or ssDNA breaks may play a primary role in stationary phase instability. Finally, we examined the roles of these pathways in the stability of a human minisatellite tract associated with the HRAS1 oncogene and found that loss of RAD27, but not END3 or PKC1, destabilizes the HRAS1 minisatellite in stationary phase yeast. This result indicates that the genetic control of stationary phase minisatellite stability is dependent on the sequence composition of the minisatellite itself.

Use of a Drug Eluting Pleural Catheter for Pleurodesis Experimental Lung Research. Nov, 2012 | Pubmed ID: 23050934 ABSTRACT Purpose: Repeated administration of low-dose silver nitrate (SN) has been shown to be effective in creating pleurodesis. This study aimed to determine the effectiveness of a SN-eluting pleural catheter for pleurodesis. Methods: Catheters with a chitosan-SN-hyaluronic acid hydrogel coating designed to release SN over 14Â days, or placebo uncoated catheters, were inserted in rabbit and lamb pleurodesis models. Pleurodesis was assessed at 28Â days according to a 1-8 point scoring system and pleural fibrosis and inflammation assessed histologically on a 0-4 point scale. Results: In the rabbit model, pleurodesis scores were significantly increased in both the 24Â mg and 50Â mg SN catheters versus control animals as well as compared to the contralateral untreated pleural space (median-treated side scores were 5, 8, and 1, respectively, median score for contralateral side was 1 in all groups). In the lamb model, pleurodesis scores were significantly increased in both the 750Â mg and 1000Â mg catheter groups versus control animals as well as compared to the contralateral untreated pleural space (median-treated side scores were 7, 7, and 1, respectively, median score for contralateral pleural space was 1 in all groups). Catheters appeared well tolerated, although higher than expected mortality was seen in the 50Â mg catheter rabbit group. Conclusions: A catheter designed to deliver SN to the pleural space over 14Â days appears to be effective in creating pleurodesis. Further investigations to determine in-vivo catheter pharmacokinetics, toxicity, dose and optimal coating methods are warranted.

Second Heart Field Cardiac Progenitor Cells in the Early Mouse Embryo Biochimica Et Biophysica Acta. Oct, 2012 | Pubmed ID: 23051926 At the end of the first week of mouse gestation, cardiomyocyte differentiation initiates in the cardiac crescent to give rise to the linear heart tube. The heart tube subsequently elongates by addition of cardiac progenitor cells from adjacent pharyngeal mesoderm to the growing arterial and venous poles. These progenitor cells, termed the second heart field, originate in splanchnic mesoderm medial to cells of the cardiac crescent and are patterned into anterior and posterior domains adjacent to the arterial and venous poles of the heart, respectively. Perturbation of second heart field cell deployment results in a spectrum of congenital heart anomalies including conotruncal and atrial septal defects seen in human patients. Here, we briefly review current knowledge of how the properties of second heart field cells are controlled by a network of transcriptional regulators and intercellular signaling pathways. Focus will be on 1) the regulation of cardiac progenitor cell proliferation in pharyngeal mesoderm, 2) the control of progressive progenitor cell differentiation and 3) the patterning of cardiac progenitor cells in the dorsal pericardial wall. Coordination of these three processes in the early embryo drives progressive heart tube elongation during cardiac morphogenesis. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Cardiac Pathways of Differentiation, Metabolism and Contraction.

Safety and Efficacy of NA-1 in Patients with Iatrogenic Stroke After Endovascular Aneurysm Repair (ENACT): a Phase 2, Randomised, Double-blind, Placebo-controlled Trial Lancet Neurology. Nov, 2012 | Pubmed ID: 23051991 BACKGROUND: Neuroprotection with NA-1 (Tat-NR2B9c), an inhibitor of postsynaptic density-95 protein, has been shown in a primate model of stroke. We assessed whether NA-1 could reduce ischaemic brain damage in human beings. METHODS: For this double-blind, randomised, controlled study, we enrolled patients aged 18 years or older who had a ruptured or unruptured intracranial aneurysm amenable to endovascular repair from 14 hospitals in Canada and the USA. We used a computer-generated randomisation sequence to allocate patients to receive an intravenous infusion of either NA-1 or saline control at the end of their endovascular procedure (1:1; stratified by site, age, and aneurysm status). Both patients and investigators were masked to treatment allocation. The primary outcome was safety and primary clinical outcomes were the number and volume of new ischaemic strokes defined by MRI at 12-95 h after infusion. We used a modified intention-to-treat (mITT) analysis. This trial is registered with ClinicalTrials.gov, number NCT00728182. FINDINGS: Between Sept 16, 2008, and March 30, 2011, we randomly allocated 197 patients to treatment-12 individuals did not receive treatment because they were found to be ineligible after randomisation, so the mITT population consisted of 185 individuals, 92 in the NA-1 group and 93 in the placebo group. Two minor adverse events were adjudged to be associated with NA-1; no serious adverse events were attributable to NA-1. We recorded no difference between groups in the volume of lesions by either diffusion-weighted MRI (adjusted p value=0Â·120) or fluid-attenuated inversion recovery MRI (adjusted p value=0Â·236). Patients in the NA-1 group sustained fewer ischaemic infarcts than did patients in the placebo group, as gauged by diffusion-weighted MRI (adjusted incidence rate ratio 0Â·53, 95% CI 0Â·38-0Â·74) and fluid-attenuated inversion recovery MRI (0Â·59, 0Â·42-0Â·83). INTERPRETATION: Our findings suggest that neuroprotection in human ischaemic stroke is possible and that it should be investigated in larger trials. FUNDING: NoNO Inc and Arbor Vita Corp.

Topical Yunnan Baiyao Administration As an Adjunctive Therapy for Bleeding Complications in Adolescents with Advanced Cancer Supportive Care in Cancer : Official Journal of the Multinational Association of Supportive Care in Cancer. Dec, 2012 | Pubmed ID: 23052909 Yunnan Baiyao (White Medicine from Yunnan, YNB) is a Chinese herbal medicinal powder used to stop bleeding and improve circulation in traumatic injuries. We describe the use of YNB in adolescents with cancer as an adjunct to uncontrolled bleeding in the palliative care setting.

Severe Adhesive Small Bowel Obstruction Frontiers of Medicine. Oct, 2012 | Pubmed ID: 23054502 Adhesive small bowel obstruction is a frequent cause of hospital admission. Water soluble contrast studies may have diagnostic and therapeutic value and avoid challenging demanding surgical operations, but if bowel ischemia is suspected, prompt surgical intervention is mandatory. A 58-year-old patient was operated for extensive adhesive small bowel obstruction after having had two previous laparotomies for colorectal surgery, and had a complex clinical course with multiple operations and several complications. Different strategies of management have been adopted, including non-operative management with the use of hyperosmolar water soluble contrast medium, multiple surgical procedures, total parenteral nutrition (TPN) support, and finally use of anti-adherences icodextrin solution. After 2 years follow-up the patient was doing well without presenting recurrent episodes of adhesive small bowel obstruction. For patients admitted several times for adhesive small bowel obstruction, the relative risk of recurring obstruction increases in relation to the number of prior episodes. Several strategies for non-operative conservative management of adhesive small bowel obstruction have already addressed diagnostic and therapeutic value of hyperosmolar water soluble contrast. According to the most recent evidence-based guidelines, open surgery is the preferred method for surgical treatment of strangulating adhesive small bowel obstruction as well as after failed conservative management. Research interest and clinical evidence are increasing in adhesions prevention. Hyaluronic acid-carboxycellulose membrane and icodextrin may reduce incidence of adhesions.

Using Google Street View to Audit the Built Environment: Inter-rater Reliability Results Annals of Behavioral Medicine : a Publication of the Society of Behavioral Medicine. Oct, 2012 | Pubmed ID: 23054943 BACKGROUND: Observational field audits are recommended for public health research to collect data on built environment characteristics. A reliable, standardized alternative to field audits that uses publicly available information could provide the ability to efficiently compare results across different study sites and time. PURPOSE: This study aimed to assess inter-rater reliability of built environment audits conducted using Google Street View imagery. METHODS: In 2011, street segments from St. Louis and Indianapolis were geographically stratified to ensure representation of neighborhoods with different land use and socioeconomic characteristics in both cities. Inter-rater reliability was assessed using observed agreement and the prevalence-adjusted bias-adjusted kappa statistic (PABAK). RESULTS: The mean PABAK for all items was 0.84. Ninety-five percent of the items had substantial (PABAKâ€‰â‰¥â€‰0.60) or nearly perfect (PABAKâ€‰â‰¥â€‰0.80) agreement. CONCLUSIONS: Using Google Street View imagery to audit the built environment is a reliable method for assessing characteristics of the built environment.

Evolutionary Conserved Role of C-Jun-N-Terminal Kinase in CO(2)-Induced Epithelial Dysfunction PloS One. 2012 | Pubmed ID: 23056407 Elevated CO(2) levels (hypercapnia) occur in patients with respiratory diseases and impair alveolar epithelial integrity, in part, by inhibiting Na,K-ATPase function. Here, we examined the role of c-Jun N-terminal kinase (JNK) in CO(2) signaling in mammalian alveolar epithelial cells as well as in diptera, nematodes and rodent lungs. In alveolar epithelial cells, elevated CO(2) levels rapidly induced activation of JNK leading to downregulation of Na,K-ATPase and alveolar epithelial dysfunction. Hypercapnia-induced activation of JNK required AMP-activated protein kinase (AMPK) and protein kinase C-Î¶ leading to subsequent phosphorylation of JNK at Ser-129. Importantly, elevated CO(2) levels also caused a rapid and prominent activation of JNK in Drosophila S2 cells and in C. elegans. Paralleling the results with mammalian epithelial cells, RNAi against Drosophila JNK fully prevented CO(2)-induced downregulation of Na,K-ATPase in Drosophila S2 cells. The importance and specificity of JNK CO(2) signaling was additionally demonstrated by the ability of mutations in the C. elegans JNK homologs, jnk-1 and kgb-2 to partially rescue the hypercapnia-induced fertility defects but not the pharyngeal pumping defects. Together, these data provide evidence that deleterious effects of hypercapnia are mediated by JNK which plays an evolutionary conserved, specific role in CO(2) signaling in mammals, diptera and nematodes.

Fusion Toxin BLyS-Gelonin Inhibits Growth of Malignant Human B Cell Lines In Vitro and In Vivo PloS One. 2012 | Pubmed ID: 23056634 B lymphocyte stimulator (BLyS) is a member of the TNF superfamily of cytokines. The biological activity of BLyS is mediated by three cell surface receptors: BR3/BAFF-R, TACI and BCMA. The expression of these receptors is highly restricted to B cells, both normal and malignant. A BLyS-gelonin fusion toxin (BLyS-gel) was generated consisting of the recombinant plant-derived toxin gelonin fused to the N-terminus of BLyS and tested against a large and diverse panel of B-NHL cell lines. Interestingly, B-NHL subtypes mantle cell lymphoma (MCL), diffuse large B cell lymphoma (DLBCL) and B cell precursor-acute lymphocytic leukemia (BCP-ALL) were preferentially sensitive to BLyS-gel mediated cytotoxicity, with low picomolar EC(50) values. BLyS receptor expression did not guarantee sensitivity to BLyS-gel, even though the construct was internalized by both sensitive and resistant cells. Resistance to BLyS-gel could be overcome by treatment with the endosomotropic drug chloroquine, suggesting BLyS-gel may become trapped within endosomal/lysosomal compartments in resistant cells. BLyS-gel induced cell death was caspase-independent and shown to be at least partially mediated by the "ribotoxic stress response." This response involves activation of p38 MAPK and JNK/SAPK, and BLyS-gel mediated cytotoxicity was inhibited by the p38/JNK inhibitor SB203580. Finally, BLyS-gel treatment was shown to localize to sites of disease, rapidly reduce tumor burden, and significantly prolong survival in xenograft mouse models of disseminated BCP-ALL, DLBCL, and MCL. Together, these findings suggest BLyS has significant potential as a targeting ligand for the delivery of cytotoxic "payloads" to malignant B cells.

Cosmetic Dermatology Training in Residency: Results of a Survey from the Residents' Perspective Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. Oct, 2012 | Pubmed ID: 23057855 BACKGROUND: Dermatologists are expected to be experts in the evaluation and treatment of their patient's cosmetic concerns. It has been reported that some dermatology residents do not feel adequately trained in this field. OBJECTIVE: To assess how dermatology residents are being trained in cosmetic dermatology. METHODS: A survey was e-mailed to 473 third-year dermatology residents. RESULTS: One hundred eighteen surveys were returned (24.9%), representing 45% of programs. Most residents have assigned reading (70.7%) and lectures (81.4%) in cosmetic dermatology. To learn technical skills, 79.7% participate in formal training sessions, and 73% have an apprenticeship model. Most residents have the opportunity to perform botulinum toxin injections, laser surgery, fillers, chemical peels, and sclerotherapy. More than 58% of programs have an encouraging or somewhat encouraging attitude toward teaching cosmetics, whereas 22% were somewhat discouraging or discouraging. Most residents (75.4%) plan to incorporate cosmetics into their practice. Residents do not feel less prepared (94.9%) or less interested (97.4%) in medical dermatology as a result of their cosmetic training. CONCLUSIONS: Residents are being trained in cosmetic dermatology through a variety of methods. Residency programs should periodically assess and adapt their curricula to ensure adequate training in this field.

HYPERNATREMIA IS ASSOCIATED WITH INCREASED RISK OF MORTALITY IN PAEDIATRIC SEVERE TRAUMATIC BRAIN INJURY Journal of Neurotrauma. Oct, 2012 | Pubmed ID: 23057958 Acquired hypernatremia in hospitalized patients is often associated with poorer outcomes. Our aim was to evaluate the relationship between acquired hypernatremia and outcome in children with severe traumatic brain injury (sTBI). We performed a retrospective cohort study of all severely injured trauma patients (Injury Severity Scoreâ‰¥12) with sTBI (GCSâ‰¤8 and MAISâ‰¥4) admitted to a Paediatric Critical Care Unit (PCCU; 2000-09). Of 165 patients included, 76% had normonatremia [135-150 mmol/L], 18% had hypernatremia [151-160 mmol/L] and 6% had severe hypernatremia [>160 mmol/L]. The groups were similar except for lower GCS (p=0.002) and increased incidence of fixed pupil(s) on admission in both hypernatremia groups (p

Incidence, Clinical Course, and Predictors of Prolonged Recovery Time Following Sport-Related Concussion in High School and College Athletes Journal of the International Neuropsychological Society : JINS. Oct, 2012 | Pubmed ID: 23058235 Sport-related concussion (SRC) is typically followed by clinical recovery within days, but reports of prolonged symptoms are common. We investigated the incidence of prolonged recovery in a large cohort (n = 18,531) of athlete seasons over a 10-year period. A total of 570 athletes with concussion (3.1%) and 166 controls who underwent pre-injury baseline assessments of symptoms, neurocognitive functioning and balance were re-assessed immediately, 3 hr, and 1, 2, 3, 5, 7, and 45 or 90 days after concussion. Concussed athletes were stratified into typical (within 7 days) or prolonged (> 7 days) recovery groups based on symptom recovery time. Ten percent of athletes (n = 57) had a prolonged symptom recovery, which was also associated with lengthier recovery on neurocognitive testing (p < .001). At 45-90 days post-injury, the prolonged recovery group reported elevated symptoms, without deficits on cognitive or balance testing. Prolonged recovery was associated with unconsciousness [odds ratio (OR), 4.15; 95% confidence interval (CI) 2.12-8.15], posttraumatic amnesia (OR, 1.81; 95% CI, 1.00-3.28), and more severe acute symptoms (p < .0001). These results suggest that a small percentage of athletes may experience symptoms and functional impairments beyond the typical window of recovery after SRC, and that prolonged recovery is associated with acute indicators of more severe injury. (JINS, 2012, 18, 1-12).

On the Use of Simulated Field-evaporated Specimen Apex Shapes in Atom Probe Tomography Data Reconstruction Microscopy and Microanalysis : the Official Journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada. Oct, 2012 | Pubmed ID: 23058657 The ability to accurately reconstruct original spatial positions of field-evaporated ions emitted from a surface is fundamental to the success of atom probe tomography. As such, a clear understanding of the evolution of specimen shape and the resultant ions' trajectories during field evaporation plays an important role in improving reconstruction accuracy. To further this understanding, field-evaporation simulations of a bilayer specimen composed of two materials having an evaporation field difference of 20% were performed. The simulated field-evaporation patterns qualitatively compare favorably with experimental data, which provides confidence in the accuracy of specimen shapes predicted by the simulation. Correlations of known original atom positions with detector hit positions as a function of lateral detector position and evaporated depth were derived from the simulation. These correlations are contrasted with the current state-of-the-art reconstruction method thus outlining limitations of the current methodology. A pair of transformations are defined that take into account field-evaporated specimen shapes, and the resulting radial magnifications, to relate recorded ion positions in detector space to reconstructed atomic positions in specimen space. This novel process, when applied to simulated data, results in approximately a factor of 2 improvement in accuracy for reconstructions of interfaces with unequal fields (most general interfaces). This method is not constrained by the fundamental assumption of a hemispherical specimen shape.

Detection of Mycobacterium Avium Subspecies Paratuberculosis in Several Herds of Arctic Caribou (Rangifer Tarandus Ssp.) Journal of Wildlife Diseases. Oct, 2012 | Pubmed ID: 23060493 Mycobacterium avium subspecies paratuberculosis (MAP) is a common pathogen in domestic ruminants that causes granulomatous inflammation of the small intestine leading to emaciation and wasting. Clinical disease (Johne's disease) is also reported for several wild ruminant species. Between 2007 and 2009 we collected 561 fecal samples from caribou (Rangifer tarandus ssp.) representing 10 herds of migratory caribou, two herds of caribou from Greenland, and three populations of boreal woodland caribou. Feces were tested for MAP by bacterial culture and PCR targeting the IS900 insertion sequence. In total, 31 samples from eight different populations representing all three ecotypes were found positive for MAP by PCR, with one sample from the RiviÃ¨re-aux-Feuilles herd also being culture positive for the type II (cattle) strain. The proportion of positive animals was particularly high in the Akia-Maniitsoq herd in Greenland, and RiviÃ¨re-aux-Feuilles and RiviÃ¨ re-George herds in northeastern Canada (23.4, 11.5, and 10.0%, respectively). Our results indicate that MAP is present in several caribou herds of different ecotypes in northern Canada and Greenland and that MAP circulates within wildlife populations that do not have ongoing contact with domestic livestock. The epidemiology, pathogenicity, and effects on the health of caribou in northern ecosystems remain unknown.

The Burden of Illness in Patients with Moderate to Severe Chronic Obstructive Pulmonary Disease in Canada Canadian Respiratory Journal : Journal of the Canadian Thoracic Society. Sep, 2012 | Pubmed ID: 23061077 No recent Canadian studies with physician- and spirometry-confirmed diagnosis of chronic obstructive pulmonary disease (COPD) that assessed the burden of COPD have been published.

Self-reported Hand Symptoms: a Role in Monitoring Health Care Workers for Latex Sensitization? Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology. Nov, 2012 | Pubmed ID: 23062385 The use of powdered natural rubber latex (NRL) gloves increased greatly in the 1980s because of concerns about transmission of blood-borne infections and the subsequent implementation of universal precautions. The most common clinical reactions to glove use are irritant and T-cell-mediated contact dermatitis. However, IgE-mediated immediate reactions to latex have become a serious concern for health care workers (HCWs). The diagnosis of latex allergy requires a comprehensive medical history and diagnostic tests. The skin prick test is the preferred diagnostic method, although it can be time-consuming.

Central Diabetes Insipidus in the Setting of Acute Myelogenous Leukemia American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. Dec, 2012 | Pubmed ID: 23062886 We present 2 patients with central diabetes insipidus in the setting of acute myelogenous leukemia (AML). Both patients had months of polyuria and polydipsia compensated by increased fluid intake. Decreased oral intake in the setting of acute illness with continued polyuria led to the development of hypernatremia and the recognition of the underlying diabetes insipidus. Both patients responded well to treatment with desmopressin. Hematologic abnormalities in patients with a diagnosis of central diabetes insipidus should prompt clinicians to consider the possibility of a new AML diagnosis or a relapse in patients with known AML in remission.

A Resource for Manipulating Gene Expression and Analyzing Cis-Regulatory Modules in the Drosophila CNS Cell Reports. Oct, 2012 | Pubmed ID: 23063363 Here, we describe the embryonic central nervous system expression of 5,000 GAL4 lines made using molecularly defined cis-regulatory DNA inserted into a single attP genomic location. We document and annotate the patterns in early embryos when neurogenesis is at its peak, and in older embryos where there is maximal neuronal diversity and the first neural circuits are established. We note expression in other tissues, such as the lateral body wall (muscle, sensory neurons, and trachea) and viscera. Companion papers report on the adult brain and larval imaginal discs, and the integrated data setsÂ are available online (http://www.janelia.org/gal4-gen1). This collection of embryonically expressed GAL4 lines will be valuable for determining neuronal morphology and function. The 1,862 lines expressed in small subsets of neurons (

Obesity Results in Progressive Atrial Structural and Electrical Remodeling: Implications for Atrial Fibrillation Heart Rhythm : the Official Journal of the Heart Rhythm Society. Sep, 2012 | Pubmed ID: 23063864 BACKGROUND: Obesity is associated with atrial fibrillation (AF); however, the mechanisms by which it induces AF are unknown. OBJECTIVE: To examine the effect of progressive weight gain on the substrate for AF. METHODS: Thirty sheep were studied at baseline, 4 months, and 8 months, following a high-calorie diet. Ten sheep were sampled at each time point for cardiac magnetic resonance imaging and hemodynamic studies. High-density multisite biatrial epicardial mapping was used to quantify effective refractory period, conduction velocity, and conduction heterogeneity index at 4 pacing cycle lengths and AF inducibility. Histology was performed for atrial fibrosis, inflammation, and intramyocardial lipidosis, and molecular analysis was performed for endothelin-A and -B receptors, endothelin-1 peptide, platelet-derived growth factor, transforming growth factor Î²1, and connective tissue growth factor. RESULTS: Increasing weight was associated with increasing left atrial volume (P = .01), fibrosis (P = .02), inflammatory infiltrates (P = .01), and lipidosis (P = .02). While there was no change in the effective refractory period (P = .2), there was a decrease in conduction velocity (P

Pipeline Embolization Device in Aneurysmal Subarachnoid Hemorrhage AJNR. American Journal of Neuroradiology. Oct, 2012 | Pubmed ID: 23064594 BACKGROUND AND PURPOSE:The PED is an FDS designed for the treatment of intracranial aneurysms. Data regarding the use of this device in acute or subacute aSAH is limited to a few case reports or small series. We aimed to demonstrate the feasibility of using an FDS, the PED, for the treatment of ruptured intracranial aneurysms with challenging morphologies.MATERIALS AND METHODS:We conducted a retrospective review of all known patients treated with the PED for aSAH at 4 institutions between June 2008 and January 2012. Pertinent clinical and radiologic information was submitted by individual centers for central collation. The decision to treat with the PED was made on a case-by-case basis by a multidisciplinary team under compassionate use.RESULTS:Twenty patients (15 women; median age, 54.5 years; IQR, 8.0 years) were found. There were 8 blister, 8 dissecting or dysplastic, 2 saccular, and 2 giant aneurysms. Median time to treatment was 4 days (range, 1-90 days; IQR, 12.75 days) from rupture. Three patients had previous failed treatment. Procedure-related symptomatic morbidity and mortality were 15%, with 1 (5%) procedure-related death. Two patients died relative to medical complications, and 1 patient was lost to follow-up. Sixteen patients were available for follow-up, 81% had a GOS of 5, and 13% had a GOS of 4 attributed to a poorer initial clinical presentation. One patient died of urosepsis at 4 months. Occlusion rates were 75% and 94% at 6 months and 12 months, respectively. There were 3 delayed complications (1 silent perforator infarct, 2 moderate asymptomatic in-stent stenoses). No symptomatic delayed complications or rehemorrhages occurred.CONCLUSIONS:The FDS may be a feasible treatment option in the acute or subacute setting of selected ruptured aneurysms, especially blister aneurysms. Ruptured giant aneurysms remain challenging for both surgical and endovascular techniques; at this stage, FDSs should be used with caution in this aneurysm subtype.

A Prospective Multicenter Study of Legg-CalvÃ©-Perthes Disease: Functional and Radiographic Outcomes of Nonoperative Treatment at a Mean Follow-up of Twenty Years The Journal of Bone and Joint Surgery. American Volume. Apr, 2012 | Pubmed ID: 23064653 Long-term studies have indicated good outcomes for most patients with Legg-CalvÃ©-Perthes disease. However, clinical experience suggests that less favorable outcomes are common. We sought to prospectively document pain and function in a cohort of adults who had previously been treated nonoperatively for Legg-CalvÃ©-Perthes disease.

Pregnant Women's Knowledge, Practices, and Needs Related to Food Safety and Listeriosis: A Study in British Columbia Canadian Family Physician MÃ©decin De Famille Canadien. Oct, 2012 | Pubmed ID: 23064922 To understand the knowledge, attitudes, practices, and needs of pregnant women regarding food safety, including the risk of listeriosis, in order to develop targeted messages and educational resources in British Columbia (BC).

Hemostasis Management During Completely Endoscopic Removal of a Highly Vascular Intraparenchymal Brain Tumor: Technique Assessment Journal of Neurological Surgery. Part A, Central European Neurosurgery. Oct, 2012 | Pubmed ID: 23065778 Backgroundâ€ƒRecently, stereotactic-guided removal of intraparenchymal lesions using endoscopic visualization through a brain port has been successfully reported. Although endoneurosurgical tumor resection uses the same principles as those used in microneurosurgery, the ability to control bleeding through the port requires an adapted technique.Material and Methodsâ€ƒWe present a patient that underwent a completely endoscopic resection of a vascular brain tumor through a brain port and describe the hemostatic technique.Resultsâ€ƒA 68 year-old female presented with progressive gait difficulties. She had been previously treated for a breast cancer. Magnetic resonance imaging (MRI) showed a right subcortical solitary cerebellar lesion that homogeneously enhanced. The patient underwent an endoscopic brain port removal of a supposed brain metastasis. After port cannulation, the tumor partly delivered itself into the port. Following initial tumor biopsy, active bleeding occurred. Irrigation and application of Surgifoam allowed to control the bleeding. Coagulation with an adapted bipolar and removal of coagulated tissue with the side-cutting aspiration device were sequentially repeated. Once the tumor was resected, the suction served as counter-traction elongating the vessels whereas the bipolar cauterized them over a long segment. Hemostasis was performed circumferentially along the cavity's walls from deep to superficial, benefiting from the endoscope's dynamic properties and magnification. Pathology confirmed intraoperative suspicion of hemangioblastoma.Conclusionâ€ƒRemoval of vascular tumors is feasible through the brain port, despite a relatively narrow corridor of 11.5 mm. However, specific hemostasis techniques are required and adapted instruments are needed to ensure hemostasis through these small corridors.

Day-case Laparoscopic Nissen Fundoplication: a Default Pathway or is Selection the Key? Journal of Laparoendoscopic & Advanced Surgical Techniques. Part A. Nov, 2012 | Pubmed ID: 23067070 Abstract Background: In recent years, day-case laparoscopic Nissen fundoplication (LNF) has became popular. Our study aims to evaluate the effect of patient factors and severity of gastroesophageal reflux disease measured by DeMeester score on the success of day-case LNF. Subjects and Methods: We conducted a retrospective case series review of patient demographics (age, gender, body mass index [BMI], and smoking status) and DeMeester score over a 5-year period. Between 2005 and 2010, 112 patients had day-case LNF. Same-day discharge was achieved in 80.3%. Twenty-two patients (19.7%) required postoperative admission ("failed day-case surgery"), with a resultant mean length of stay of 1.41 days. Univariate analysis showed that female gender had a significantly higher incidence of postsurgical admission (30.76% females versus 13.69% males, P=.03 by Mann-Whitney U test). Compared with the same-day discharge group, the failed day-case group has a higher mean DeMeester score (50.89 versus 36.03, P=.021 by t test) and BMI (28.71Â±0.778â€‰kg/m(2) versus 26.79Â±0.3737â€‰kg/m(2), P=.023). Age and smoking status were not significant determining factors in postoperative admission rates. Using multivariable analysis and logistical regression, we derived a model based on gender, BMI, and DeMeester score to predict the probability of admission following day-case LNF. Conclusions: We conclude that day-case LNF is a safe, feasible procedure in the appropriately selected patient population. Our novel finding of higher admission rates in females, high DeMeester score, and high BMI should be used in planning perioperative hospitalization in this cohort.

Prenatal HIV Testing: The Compartmentalization of Women's Sexual Risk Exposure and the Return of the Maternal Fetal Conflict Women & Health. Oct, 2012 | Pubmed ID: 23067153 The purpose of the researchers in this study was to investigate how women who were being tested for HIV during their pregnancies were evaluating, conceptualizing, and negotiating their risk of infection. The study included two focus groups and 20 in-depth interviews with 30 patients, ages 17-38 years, from diverse ethnic/racial, social, and economic backgrounds. Qualitative analyses of the interview transcripts revealed support for the idea that pregnant women have a responsibility to minimize risks to their fetus, with all interviewees describing actions to minimize those risks while pregnant. Two sub-themes emerged that were related to the presence of differences in how interviewees conceptualized risk depending on the type of risk being discussed. In the case of diet and lifestyle influences, interviewees framed their health and the health of the fetus as connected. In contrast, when the issue of HIV risk and testing was raised, the interviewees described the risk of HIV to themselves and their fetuses as separate concerns and, with few exceptions, reported no effort to reduce the risk of becoming infected while pregnant (beyond consenting to HIV screening while receiving prenatal care). Findings suggest the importance of developing HIV prevention messages that counter the compartmentalization of risk during pregnancy.

Salt Metathesis for the Synthesis of M-Al and M-H-Al Bonds Dalton Transactions (Cambridge, England : 2003). Oct, 2012 | Pubmed ID: 23069776 Salt metathesis has been exploited in the synthesis of M-Al bonds, stabilized by a variety of chelating N-donor substituents at aluminium and including the first examples of such systems featuring ancillary guanidinato frameworks. Importantly, this synthetic approach can be extended to the synthesis of Ïƒ-alane complexes through the use of hydride-containing transition metal nucleophiles. Cp'Mn(CO)(2)-[H(Cl)Al{(N(i)Pr)(2)CPh}] synthesized via this route features an alane ligand bound in a more 'side-on' fashion than other alane complexes, although DFT calculations imply that the potential energy surface associated with variation in the Mn-H-Al angle is a very soft one.

PloS One. 2012 | Pubmed ID: 23071743

Modelling and Simulation of the Coefficient of Restitution of the Sliotar in Hurling Sports Biomechanics / International Society of Biomechanics in Sports. Sep, 2012 | Pubmed ID: 23072045 The coefficient of restitution (COR) is one of the most important standards in all bat-and-ball sports to study the ball suitability and bouncing characteristics. Currently, a demand exists for an improved analytical model for computing the COR, particularly when a new material is introduced. A viscoelastic ball known as a sliotar is taken from the Irish bat-and-ball sport of hurling and used in this paper as a case study. For the theoretical approach, a modified Maxwell's viscoelastic model was used to derive an analytical formula to predict the COR. The developed formula confirms that the damping ratio and the dependency of the COR on the impact speed are the most dominant factors. A 3-dimensional finite element (FE) model was developed to simulate the sliotar impact test to estimate the COR, and to provide a simple tool for further studies on the sliotar. A high-speed camera was used to film the impact event to validate the models' behavior. The close correlation of 9% and 5% between the experimental and the developed analytical and FE models, respectively, indicates that the developed models can successfully identify the COR of the ball in the game of hurling and similar bat-and-ball sports.

Should We Rethink How We Teach Cultural Competency in Physician Assistant Education? The Journal of Physician Assistant Education : the Official Journal of the Physician Assistant Education Association. 2012 | Pubmed ID: 23072070 Cultural competency training has traditionally been viewed as addressing race and ethnicity and its influence on health care disparity. There are many aspects of culture or diversity that have been overshadowed in physician assistant education but are equally as important. These cultural elements include socioeconomic status, religion, sexual orientation, and disability. This article will briefly discuss the importance of these elements and how each can affect the medical care of patients in these diverse populations.

Nitric Oxide Generated by the Rice Blast Fungus Magnaporthe Oryzae Drives Plant Infection The New Phytologist. Oct, 2012 | Pubmed ID: 23072575 Plant-derived nitric oxide (NO) triggers defence, priming the onset of the hypersensitive response and restricting pathogen ingress during incompatibility. However, little is known about the role of pathogen-produced NO during pre-infection development and infection. We sought evidence for NO production by the rice blast fungus during early infection. NO production was measured using fluorescence of DAR-4M and the role of NO assessed using NO scavengers. The synthesis of NO was investigated by targeted knockout of genes potentially involved in NO synthesis, including nitric oxide synthase-like genes (NOL2 and NOL3) and nitrate (NIA1) and nitrite reductase (NII1), generating single and double Î”nia1Î”nii1, Î”nia1Î”nol3, and Î”nol2Î”nol3 mutants. We demonstrate that Magnaporthe oryzae generates NO during germination and in early development. Removal of NO delays germling development and reduces disease lesion numbers. NO is not generated by the candidate proteins tested, nor by other arginine-dependent NO systems, by polyamine oxidase activity or non-enzymatically by low pH. Furthermore, we show that, while NIA1 and NII1 are essential for nitrate assimilation, NIA1, NII1, NOL2 and NOL3 are all dispensable for pathogenicity. Development of M.Â oryzae and initiation of infection are critically dependent on fungal NO synthesis, but its mode of generation remains obscure.

Angular Amplitude Matters: Exploring the Functional Relationship of Geometric Cue Use by Clark's Nutcrackers (Nucifraga Columbiana) Behavioural Processes. Oct, 2012 | Pubmed ID: 23073501 Four groups of Clark's nutcrackers (Nucifraga columbiana) learned to search for food hidden at one of two geometrically identical corners of a parallelogram-shaped enclosure. The corners of the enclosure projected either 40Â° and 140Â° angles or 60Â° and 120Â° angles. Tests using both rhomboid and rectangular enclosures examined whether birds had encoded angular amplitude and the length of walls, respectively. Cue conflict tests using a mirror-image of the training parallelogram reversed the relationship between wall length and corner angle, allowing for the examination of cue weighing. Furthermore, cue conflict tests which manipulated the angular amplitude allowed for the investigation of whether the encoding of angular information was similar among the training groups. Our results showed that nutcrackers encoded both angular amplitude and wall length. During cue conflict tests that maintained the training angular amplitudes, birds did not show a strong weighing of angular cues at a population-level but rather considerable individual differences were found. Finally, manipulating angular amplitude in the direction towards the unrewarded angle resulted in reduced weighing of angular cues whereas manipulating angular amplitude in the direction away from the unrewarded angle resulted in greater weighing of angular cues. In summary, our results support the importance of using multiple exemplars during training and testing to better understand the functional relationship between geometric cues during a spatial search task. This article is part of a Special Issue entitled: Special Issue Co3 2012 (Tony Wright).

Tolerance to Effects of High-Dose Oral {Delta}9-Tetrahydrocannabinol and Plasma Cannabinoid Concentrations in Male Daily Cannabis Smokers Journal of Analytical Toxicology. Oct, 2012 | Pubmed ID: 23074216 Oral cannabinoids are taken for medicinal or recreational purposes, yet little is known about tolerance to their effects after high-dose extended exposure. The development of tolerance to effects of around-the-clock oral synthetic Î”9-tetrahydrocannabinol (THC) (20 mg every 3.5-6 h) was evaluated in 13 healthy male daily cannabis smokers residing on a secure research unit: 40 mg on Day 1; 100 mg on Days 2-4; 120 mg on Days 5-6. Systolic and diastolic blood pressure (BP), heart rate, and symptoms of subjective intoxication (100 mm visual-analogue scales, VAS) were assessed the morning of Day 1 (before any oral THC), and on Days 2, 4 and 6, every 30 min for 3 h after the first morning THC dose. Morning subjective intoxication ratings increased from Days 1 to 2, and then declined on Days 4 and 6. The morning THC dose increased intoxication ratings on Day 2, but had less effect on Days 4 and 6, a pattern consistent with tolerance. THC lowered BP and increased heart rate over the six days. Plasma THC and 11-OH-THC concentrations increased significantly over the first five days of dosing. Six days of around-the-clock, oral THC produced tolerance to subjective intoxication, but not to cardiovascular effects.

Collaboration Between Local Health and Local Government Agencies for Health Improvement Cochrane Database of Systematic Reviews (Online). 2012 | Pubmed ID: 23076937 In many countries, national, regional and local inter- and intra-agency collaborations have been introduced to improve health outcomes. Evidence is needed on the effectiveness of locally developed partnerships which target changes in health outcomes and behaviours.

Influenza and Other Respiratory Viruses. Oct, 2012 | Pubmed ID: 23078073

Systematic Review of Clinical Research on Biomarkers for Pediatric Traumatic Brain Injury Journal of Neurotrauma. Oct, 2012 | Pubmed ID: 23078348 The objective was to systematically review the medical literature and comprehensively summarize clinical research done on biomarkers for pediatric traumatic brain injury (TBI) and to summarize the studies that have assessed serum biomarkers acutely in determining intracranial lesions on CT in children with TBI. The search strategy included a literature search of PubMedÂ®, MEDLINEÂ® and the Cochrane Database from 1966 to August 2011, as well as a review of reference lists of identified studies. Search terms used included pediatrics, children, traumatic brain injury, and biomarkers. Any article with biomarkers of traumatic brain injury as a primary focus and containing a pediatric population was included. The search initially identified 167 articles. Of these, 49 met inclusion and exclusion criteria and were critically reviewed. The median sample size was 58 [IQR 31-101]. The majority of the articles exclusively studied children 36 (74%) and 13 (26%) were studies that included both children and adults in different proportions. There were 99 different biomarkers measured in these 49 studies and the five most frequently examined biomarkers were S100B (27 studies), NSE (15 studies), IL-6 (7 studies), MBP (6 studies), and IL-8 (6 studies). There were 6 studies that assessed the relationship between serum markers and CT lesions. Two studies found that NSE levels â‰¥ 15 ng/ml within 24 hours of TBI was associated with intracranial lesions. Four studies using serum S100B were conflicting: 2 studies found no association with intracranial lesions and 2 studies found a weak association. The flurry of research in the area over the last decade is encouraging but is limited by small sample sizes, variable practices in sample collection, inconsistent biomarker-related data elements and disparate outcome measures. Future studies of biomarkers for pediatric TBI will require rigorous and more uniform research methodology, common data elements, and consistent performance measures.

Punjabi Sikh Patients' Perceived Barriers to Engaging in Physical Exercise Following Myocardial Infarction Public Health Nursing (Boston, Mass.). Nov, 2012 | Pubmed ID: 23078424 The aim of this research was to describe Punjabi Sikh patients' perceived barriers to engaging in physical exercise following myocardial infarction (MI).

Variation in Radiotherapy Target Volume Definition, Dose to Organs at Risk and Clinical Target Volumes Using Anatomic (Computed Tomography) Versus Combined Anatomic and Molecular Imaging (Positron Emission Tomography/Computed Tomography): Intensity-modulated Radiotherapy Delivered Using a Tomotherapy Hi Art Machine: Final Results of the VortigERN Study Clinical Oncology (Royal College of Radiologists (Great Britain)). Dec, 2012 | Pubmed ID: 23079100 Contrast-enhanced computed tomography (CECT) is the current standard for delineating tumours of the head and neck for radiotherapy. Although metabolic imaging with positron emission tomography (PET) has been used in recent years, the studies were non-confirmatory in establishing its routine role in radiotherapy planning in the modern era. This study explored the difference in gross tumour volume and clinical target volume definitions for the primary and nodal volumes when FDG PET/CT was used as compared with CECT in oropharyngeal cancer cases.

Evaluating the Feasibility of Measuring Travel to School Using a Wearable Camera American Journal of Preventive Medicine. Nov, 2012 | Pubmed ID: 23079179 The school journey is often studied in relation to health outcomes in children and adolescents. Self-report is the most common measurement tool.

Concept Mapping: Priority Community Strategies to Create Changes to Support Active Living American Journal of Preventive Medicine. Nov, 2012 | Pubmed ID: 23079266 From 2003 to 2008, a total of 25 cross-sector, multidisciplinary community partnerships funded through the Active Living by Design (ALbD) national program designed, planned, and implemented policy and environmental changes, with complementary programs and promotions.

Adverse Ophthalmic Reaction in Poppers Users: Case Series of 'poppers Maculopathy' Eye (London, England). Nov, 2012 | Pubmed ID: 23079752 BackgroundPoppers are a recreational substance of abuse belonging to the alkyl nitrite family of compounds. In the United Kingdom, where they are legal to purchase but illegal to sell for human consumption, 10% of the general population have tried them. They are considered low risk to physical and mental health. Two recent case series from France demonstrated foveal pathology in individuals associated with poppers use.MethodA case series of seven patients presenting to four hospitals in the United Kingdom with visual impairment and maculopathy associated with inhalation of poppers.ResultsAll patients experienced visual symptoms associated with poppers use. The majority had impaired visual acuity, central scotomata, distortion, or phosphenes. Clinical signs on fundoscopy ranged from normal foveal appearance to yellow, dome-shaped lesions at the foveola. Spectral domain optical coherence tomography (SD-OCT) showed varying degrees of disruption of the presumed inner segment/outer segment (IS/OS) junction.DiscussionAlthough poppers have been in use for several decades, in 2007, following legislative changes, there was a change in the most commonly used compound from isobutyl nitrite to isopropyl nitrite. There were no reports of 'poppers maculopathy' before this. Poppers maculopathy may be missed if patients are not directly questioned about their use. The disruption or loss of the presumed IS/OS junction on SD-OCT are a characteristic feature. Further study of maculopathy in poppers users is now needed. Raising public awareness of the ocular risks associated with their use may be necessary.

Equine Cellular Therapy-from Stall to Bench to Bedside? Cytometry. Part A : the Journal of the International Society for Analytical Cytology. Oct, 2012 | Pubmed ID: 23081833 Pioneering clinical stem cell research is being performed in the horse, a recipient of cutting edge veterinary medicine as well as a unique animal model, paving the way for human medical applications. Although demonstrable progress has been made on the clinical front, in vitro characterization of equine stem cells is still in comparatively early stages. To translate the promising results of clinical stem cell therapy in the horse, advances must be made in the characterization of equine stem cells. Aiming to improve communication between veterinarians and other natural scientists, this review gives an overview of veterinary "bedside" achievements, focusing on stem cell therapies in equine orthopedics as well as the current state of in vitro characterization of equine multipotent mesenchymal stromal cells (MSCs) and equine embryonic stem cells (ESCs). Â© 2012 International Society for Advancement of Cytometry.

Assessing Water Filtration and Safe Storage in Households with Young Children of HIV-Positive Mothers: A Randomized, Controlled Trial in Zambia PloS One. 2012 | Pubmed ID: 23082124 Unsafe drinking water presents a particular threat to people living with HIV/AIDS (PLHIV) due to the increased risk of opportunistic infections, diarrhea-associated malabsorption of essential nutrients, and increased exposure to untreated water for children of HIV-positive mothers who use replacement feeding to reduce the risk of HIV transmission. This population may particularly benefit from an intervention to improve water quality in the home.

Allogeneic Hematopoietic Stem Cell Transplantation for a BCR-FGFR1 Myeloproliferative Neoplasm Presenting As Acute Lymphoblastic Leukemia Case Reports in Hematology. 2012 | Pubmed ID: 23082258 Hematopoietic myeloproliferative neoplasms (MPNS) with rearrangements of the receptor tyrosine kinase FGFR1 gene, located on chromosome 8p11, are uncommon and associated with diverse presentations such as atypical chronic myeloid leukemia, acute myeloid leukemia, or an acute T- or B-lymphoblastic leukemia, reflecting the hematopoietic stem cell origin of the disease. A review of MPN patients with the t(8;22) translocation that results in a chimeric BCR-FGFR1 fusion gene reveals that this disease either presents or rapidly transforms into an acute leukemia that is generally unresponsive to currently available chemotherapeutic regimens including tyrosine kinase inhibitors (TKIS). The first case of a rare BCR-FGFR1 MPN presenting in a B-acute lymphoblastic phase who underwent allogeneic hematopoietic stem cell transplantation (HSCT) with a subsequent sustained complete molecular remission is described. Allogeneic HSCT is currently the only available therapy capable of achieving long-term remission in BCR-FGFR1 MPN patients.

This is How We Do It The Practising Midwife. Sep, 2012 | Pubmed ID: 23082403 The purpose of this article is to explore students' experiences of variations in practice and how this impacts on their learning. This is particularly pertinent in terms of reconfiguration of services instigated by the Department of Health's (DH) Making it better agenda (DH 2007), meaning that many qualified staff are moving hospitals and also experiencing changes in practice. Students are thus being mentored by a range of mentors in a variety of settings, which can often mean that practice can be perceived as inconsistent and even idiosyncratic (Jones et al 2005). This writing is unique in that the midwifery lecturer facilitated the students' development of the work in a truly collaborative piece, developed through a writing and journal club. All details of the practice placements and the student comments have been anonymised.

Cutaneous Metastases from Head and Neck Squamous Cell Carcinoma The Medical Journal of Malaysia. Aug, 2012 | Pubmed ID: 23082459 The presence of cutaneous metastases in squamous cell carcinomas of the head and neck (SCCHN) is rare and associated with a dismal prognosis. It is vital to distinguish these lesions from direct invasion of the skin by SCCHN or primary cutaneous malignancies as the prognosis is vastly different and so is the management. In this case report, we present four cases of cutaneous metastases and also briefly review the literature pertaining to this phenomenon.

Use and Perceptions of Sexual and Reproductive Health Services Among Northern Thai Adolescents The Southeast Asian Journal of Tropical Medicine and Public Health. Mar, 2012 | Pubmed ID: 23082599 This study sheds light on obstacles to safe sexual health for young Thais and their need for appropriate sexual and reproductive health services. The study population was 1,745 unmarried adolescents aged 17-20 who resided or worked in Chiang Mai, the major city in northern Thailand. The study used quantitative and qualitative methods to explore the vulnerability of sexually active adolescents as well as the lack of support and care for them from parents and health providers. We found that young Thais still prefer pharmacies for self-medication and use government health care facilities as a last resort. Current health services are not suitable for adolescents in northern Thailand because they lack privacy and impose judgemental attitudes, especially towards sexually active adolescent females. Current programs for adolescent sexual and reproductive health focus on education and counselling and do not provide appropriate privacy or clinical care. There is a pressing need for advocacy, and policy support for the development of youth-friendly sexual and reproductive health services in Thailand.

The Association Between Labour Force Participation and Being in Income Poverty Amongst Those with Mental Health Problems Aging & Mental Health. Oct, 2012 | Pubmed ID: 23082972 Objectives: Mental health conditions are associated with lower standards of living. This study quantifies the relationship between employment, depression and other mental health conditions and being in income poverty. Methods: Cross-sectional analysis was undertaken using the 2003 Survey of Disability, Ageing and Carers data for Australians aged 45-64 years. Results: Those not in the labour force due to depression and other mental health conditions are significantly more likely (odds ratio (OR) 12.53, 95% CI: 12.20-12.86, pâ€‰

The Composition of Engineered Cartilage at the Time of Implantation Determines the Likelihood of Regenerating Tissue with a Normal Collagen Architecture Tissue Engineering. Part A. Oct, 2012 | Pubmed ID: 23082998 The biomechanical functionality of articular cartilage is derived from both its biochemical composition and the architecture of the collagen network. Failure to replicate this normal "Benninghoff" architecture in regenerating articular cartilage may in turn predispose the tissue to failure. In this paper, the influence of the maturity (or functionality) of a tissue engineered construct at the time of implantation into a tibial chondral defect on the likelihood of recapitulating a normal Benninghoff architecture was investigated using a computational model featuring a collagen remodelling algorithm. Such a normal tissue architecture was predicted to form in the intact tibial plateau due to the interplay between the depth-dependent extracellular matrix properties, foremost swelling pressures, and external mechanical loading. In the presence of even small empty defects in the articular surface the collagen architecture in the surrounding cartilage was predicted to deviate significantly from the native state, indicating a possible predisposition for osteoarthritic changes. These negative alterations were alleviated by the implantation of tissue engineered cartilage, where a mature implant was predicted to result in the formation of a more native-like collagen architecture than immature implants. The results of this study highlight the importance of cartilage graft functionality to maintain and/or re-establish joint function and suggest that engineering a tissue with a native depth-dependent composition may facilitate the establishment of a normal Benninghoff architecture following implantation into load bearing defects.

At What Age Should Children Engage in Agricultural Tasks? The Journal of Rural Health : Official Journal of the American Rural Health Association and the National Rural Health Care Association. Sep, 2012 | Pubmed ID: 23083083 Purpose: We compared parents' perceived-as-appropriate ages with actual-performance ages for their children engaging in selected agricultural tasks or practices, and we examined the factors associated with age discrepancy. Methods: We analyzed data from the Keokuk County Rural Health Study collected among parents of children age 17 or younger. Parents were interviewed separately regarding the age of their children's involvement in 14 selected agricultural tasks and their opinions about appropriate age of involvement. Findings: Of the 264 families included, 86.5% with a son and 69.8% with a daughter reported having children involved in at least 1 of 14 selected agricultural tasks. The average actual-performance ages for children to be involved in any of the tasks were younger than those that parents perceived appropriate. Furthermore, in 6 of the 9 North American Guidelines for Children's Agricultural Tasks (NAGCAT) that we assessed, parents' perceived-as-appropriate ages were younger than minimum ages recommended by the NAGCAT. Driving an all-terrain vehicle (ATV) was the most common task with actual-performance age younger than the NAGCAT-recommended age; 53.0% of boys (n = 106) and 36.1% of girls (n = 61) did so under the recommended age. Boys and children who live on a farm, or whose parents have been or are farmers, were significantly more likely to perform agricultural tasks at earlier ages. Conclusions: Our results suggest farm parents and other rural stakeholders need to be better educated and encouraged to follow the NAGCAT guidelines, and that multilevel interventions need to be developed to ensure protection of children from agricultural injury and death.

Assessment of Self-reported Negative Affect in the NIH Toolbox Psychiatry Research. Oct, 2012 | Pubmed ID: 23083918 We report on the selection of self-report measures for inclusion in the NIH Toolbox that are suitable for assessing the full range of negative affect including sadness, fear, and anger. The Toolbox is intended to serve as a "core battery" of assessment tools for cognition, sensation, motor function, and emotional health that will help to overcome the lack of consistency in measures used across epidemiological, observational, and intervention studies. A secondary goal of the NIH Toolbox is the identification of measures that are flexible, efficient, and precise, an agenda best fulfilled by the use of item banks calibrated with models from item response theory (IRT) and suitable for adaptive testing. Results from a sample of 1763 respondents supported use of the adult and pediatric item banks for emotional distress from the Patient-Reported Outcomes Measurement Information System (PROMIS(Â®)) as a starting point for capturing the full range of negative affect in healthy individuals. Content coverage for the adult Toolbox was also enhanced by the development of a scale for somatic arousal using items from the Mood and Anxiety Symptom Questionnaire (MASQ) and scales for hostility and physical aggression using items from the Buss-Perry Aggression Questionnaire (BPAQ).

Nondietary Therapies for Celiac Disease Gastrointestinal Endoscopy Clinics of North America. Oct, 2012 | Pubmed ID: 23083995 Currently, the only available therapy for celiac disease is strict lifelong adherence to a gluten-free diet (GFD). Although safe and effective, the GFD is not ideal. It is frequently expensive, of limited nutritional value, and not readily available in many countries. Consequently, a need exists for novel, nondietary therapies for celiac disease. Based on the current understanding of celiac disease pathogenesis, several potential targets of therapeutic intervention exist. These novel strategies provide promise of alternative, adjunctive treatment options but also raise important questions regarding safety, efficacy, and monitoring of long-term treatment effect.

Angiodysplasia (vascular Malformations) of the Colon Presenting As an Acute Abdomen Journal of Pediatric Surgery. Oct, 2012 | Pubmed ID: 23084229 Angiodysplasia (vascular malformations) of the colon is extremely rare in children, and, as in adults, present with lower gastrointestinal hemorrhage. Here we report an unusual pediatric case of angiodysplasia of the terminal ileum and cecum presenting as an acute abdomen with radiological features suggestive of lymphoma.

Targeting Angiogenesis As a Promising Modality for the Treatment of Prostate Cancer The Urologic Clinics of North America. Nov, 2012 | Pubmed ID: 23084530 Antiangiogenic therapy has been successful for the treatment of solid tumors. Several strategies have been used to target angiogenesis in prostate cancer. These strategies include blocking proangiogenic factors via monoclonal antibodies or small molecule inhibitors targeting downstream signaling effector pathways, or using agents with immune-modulatory effects. This review examines the general concepts of tumor angiogenesis and the key clinical trials that have used these agents and other novel biologics in prostate cancer. Targeting angiogenesis is still a promising treatment strategy in prostate cancer with a rational trial design and combination approach.

Multicenter Study on Season of Birth and Celiac Disease: Evidence ForÂ aÂ New Theoretical Model of Pathogenesis The Journal of Pediatrics. Oct, 2012 | Pubmed ID: 23084709 OBJECTIVE: To investigate whether season of birth is associated with celiac disease (CD). STUDY DESIGN: We performed a medical record review of 1964 patients with biopsy-proven CD at 3 teaching hospitals (2 pediatric centers and 1 adult center) between 2000 and 2010. The first positive small intestinal biopsy result defined age of diagnosis. The observed proportions of births in each season (spring [March-May], summer [June-August], fall [September-November], and winter [December-February]) were compared with the expected proportions using binomial probability tests. RESULTS: The mean age at diagnosis was 9.8Â Â±Â 5.0 years in the 2 pediatric centers and 43.6Â Â±Â 15.8 years in the adult center. The cohort was predominately female (69%). Overall, more patients were born in spring (27%) than in any other season: summer (25%), fall (25%), and winter (23%). In patients diagnosed before age 15 years, the spring birth excess was present in boys (33%; PÂ =Â .0005), but not in girls (26%; PÂ =Â .43). The sex difference in season of birth was less striking in patients with CD diagnosed at age â‰¥15 years. CONCLUSION: Season of birth is an environmental risk factor for CD, particularly in boys diagnosed before age 15Â years. The results are consistent with a new theoretical model that integrates potential environmental factors (eg, gluten introduction, ultraviolet-B exposure, vitamin D status) and acute viral gastrointestinal infections in early childhood.

Through the Lens of Culture: Quality of Life Among Latina Breast Cancer Survivors Breast Cancer Research and Treatment. Nov, 2012 | Pubmed ID: 23085764 Latinas have lower quality of life than Caucasian cancer survivors but we know little about factors associated with quality of life in this growing population. Bilingual staff conducted interviews with a national cross-sectional sample of 264 Latina breast cancer survivors. Quality of life was measured using the Functional Assessment of Cancer Therapy-Breast (FACT-B). Regression models evaluated associations between culture, social and medical context and overall quality of life and its subdomains. Latina survivors were 1-5Â years post-diagnosis and reported a lower mean quality of life score compared to other published reports of non-Latina survivors (MÂ =Â 105; SDÂ =Â 19.4 on the FACT-B). Culturally based feelings of breast cancer-related stigma and shame were consistently related to lower overall quality of life and lower well-being in each quality of life domain. Social and medical contextual factors were independently related to quality of life; together cultural, social and medical context factors uniquely accounted for 62Â % of the explained model variance of overall quality of life (Adjusted R (2)Â =Â 0.53, PÂ

Dispensable, Redundant, Complementary and Cooperative Roles of Dopamine, Octopamine and Serotonin in Drosophila Melanogaster Genetics. Oct, 2012 | Pubmed ID: 23086220 To investigate the regulation of Drosophila melanogaster behavior by biogenic amines, we have exploited the broad requirement of the vesicular monoamine transporter (VMAT) for the vesicular storage and exocytotic release of all monoamine neurotransmitters. We used the Drosophila VMAT (dVMAT) null mutant to globally ablate exocytotic amine release, and then restored DVMAT activity in either individual or multiple aminergic systems using transgenic rescue techniques. We find that larval survival, larval locomotion, and female fertility rely predominantly on octopaminergic circuits with little apparent input from the vesicular release of serotonin or dopamine. In contrast, male courtship and fertility can be rescued by expressing DVMAT in octopaminergic or dopaminergic neurons, suggesting potentially redundant circuits. Rescue of major aspects of adult locomotion and startle behavior required octopamine, but a complementary role was observed for serotonin. Interestingly, adult circadian behavior could not be rescued by expression of DVMAT in a single subtype of aminergic neurons, but required at least two systems, suggesting the possibility of unexpected cooperative interactions. Further experiments using this model will help determine how multiple aminergic systems may contribute to the regulation of other behaviors. Our data also highlight potential differences between behaviors regulated by standard exocytotic release versus other mechanisms.

HLA-DR3-DQ2 Mice Do Not Develop Ataxia in the Presence of High Titre Anti-gliadin Antibodies Cerebellum (London, England). Oct, 2012 | Pubmed ID: 23086706 Recently, it has been suggested that anti-gliadin antibodies (Î±GAb) may produce "gluten ataxia", even in the absence of celiac disease enteropathy. Î±GAb are reportedly present in 12-50Â % of patients with sporadic ataxia, but also in 12Â % of the general population, such that the importance of Î±GAb as a cause of sporadic ataxia is not conclusively settled. We aimed to determine whether mice transgenic for HLA-DR3-DQ2 and immunised with gliadin to achieve high titres of Î±GAb would develop ataxia and/or cerebellar damage. From 6Â weeks of age, HLA-DR3-DQ2 transgenic mice were immunised fortnightly with gliadin (nâ€‰=â€‰10) or a saline control (nâ€‰=â€‰6) in adjuvant. Serum titres were measured by Î±GAb enzyme-linked immunosorbent assay. At 24Â weeks of age, mice were tested for locomotor function using the accelerating rotarod, ledged beam, ink-paw gait, and several neurological severity score subtests. Brains were then collected and processed for immunohistochemistry. Sections were analysed for lymphocytic infiltration, changes in morphology and Purkinje cell (PC) dendritic volume and the number of PCs counted via unbiased stereology. Gliadin-immunised mice developed high Î±GAb titres while controls did not. There was no statistically significant difference between the gliadin and sham-immunised HLA-DR3-DQ2 mice on any of the tests of motor coordination, in lymphocytic infiltration, PC number or in dendritic volume. High levels of Î±GAb are not sufficient to produce ataxia or cerebellar damage in HLA-DR3-DQ2 transgenic mice.

The NKI-Rockland Sample: A Model for Accelerating the Pace of Discovery Science in Psychiatry Frontiers in Neuroscience. 2012 | Pubmed ID: 23087608 The National Institute of Mental Health strategic plan for advancing psychiatric neuroscience calls for an acceleration of discovery and the delineation of developmental trajectories for risk and resilience across the lifespan. To attain these objectives, sufficiently powered datasets with broad and deep phenotypic characterization, state-of-the-art neuroimaging, and genetic samples must be generated and made openly available to the scientific community. The enhanced Nathan Kline Institute-Rockland Sample (NKI-RS) is a response to this need. NKI-RS is an ongoing, institutionally centered endeavor aimed at creating a large-scale (Nâ€‰>â€‰1000), deeply phenotyped, community-ascertained, lifespan sample (ages 6-85â€‰years old) with advanced neuroimaging and genetics. These data will be publically shared, openly, and prospectively (i.e., on a weekly basis). Herein, we describe the conceptual basis of the NKI-RS, including study design, sampling considerations, and steps to synchronize phenotypic and neuroimaging assessment. Additionally, we describe our process for sharing the data with the scientific community while protecting participant confidentiality, maintaining an adequate database, and certifying data integrity. The pilot phase of the NKI-RS, including challenges in recruiting, characterizing, imaging, and sharing data, is discussed while also explaining how this experience informed the final design of the enhanced NKI-RS. It is our hope that familiarity with the conceptual underpinnings of the enhanced NKI-RS will facilitate harmonization with future data collection efforts aimed at advancing psychiatric neuroscience and nosology.

Comment on "Feather Meal: A Previously Unrecognized Route for Reentry into the Food Supply of Multiple Pharmaceuticals and Personal Care Products (PPCPs)" Environmental Science & Technology. Nov, 2012 | Pubmed ID: 23088604

Fitness Profiling of Elite Level Adolescent Gaelic Football Players Journal of Strength and Conditioning Research / National Strength & Conditioning Association. Oct, 2012 | Pubmed ID: 23090319 ABSTRACT: The purpose of this study was to evaluate the anthropometric characteristics and fitness levels of elite level under 18 (U-18) Gaelic football players in order to establish normative centile scores for selected fitness parameters, and to compare the physical and fitness characteristics relative to each playing position. A total of 265 male U-18 Gaelic football players (age: 16.96 Â± 0.7 yr.; height: 178.11 Â± 6.27 cm; weight: 72.07 Â± 8.68 kg) participated in the study. According to positional roles, players were categorized as goalkeepers (n=13), defenders (n=113), midfielders (n=30) and forwards (n=109). Height, and weight were measured, and skinfolds were taken before participants sequentially performed a sit and reach test (S&R), countermovement jump (CMJ), standing long jump (SLJ), 5 m and 20 m speed test and the Yo-Yo Intermittent Recovery Test Level 1 (YYIRT1). The percentage body fat was higher (p < 0.01) in goalkeepers than each of the other playing positions. Goalkeepers had a higher BMI than defenders (p < 0.05) and forward players (p < 0.01). Midfield players and goalkeepers were taller (p < 0.01) and heavier (p < 0.01) than defenders and forward players. The total distance covered in the YYIRT1 was significantly lower (p < 0.01) in goalkeepers than the other playing positions. There was no significant positional difference in the performance scores in the S&R test, CMJ, SLJ and 5 m and 20 m running speed. The study findings indicate minimal differences in the anthropometric and physiological characteristics between playing positions in elite youth level Gaelic football players. The norm-referenced percentile scores will enable conditioning coaches to benchmark elite performance and design training programmes.

Introduction to the Special Issue: Subgroup Analysis in Prevention and Intervention Research Prevention Science : the Official Journal of the Society for Prevention Research. Oct, 2012 | Pubmed ID: 23090721

Autophagy As a Target for Cancer Therapy: New Developments Cancer Management and Research. 2012 | Pubmed ID: 23091399 Autophagy is an evolutionarily conserved lysosomal degradation pathway that eliminates cytosolic proteins, macromolecules, organelles, and protein aggregates. Activation of autophagy may function as a tumor suppressor by degrading defective organelles and other cellular components. However, this pathway may also be exploited by cancer cells to generate nutrients and energy during periods of starvation, hypoxia, and stress induced by chemotherapy. Therefore, induction of autophagy has emerged as a drug resistance mechanism that promotes cancer cell survival via self-digestion. Numerous preclinical studies have demonstrated that inhibition of autophagy enhances the activity of a broad array of anticancer agents. Thus, targeting autophagy may be a global anticancer strategy that may improve the efficacy of many standard of care agents. These results have led to multiple clinical trials to evaluate autophagy inhibition in combination with conventional chemotherapy. In this review, we summarize the anticancer agents that have been reported to modulate autophagy and discuss new developments in autophagy inhibition as an anticancer strategy.

The Personal and National Costs of Early Retirement Because of Spinal Disorders: Impacts on Income, Taxes, and Government Support Payments The Spine Journal : Official Journal of the North American Spine Society. Oct, 2012 | Pubmed ID: 23092718 BACKGROUND CONTEXT: Spinal disorders can reduce an individual's ability to participate in the labor force, and this can lead to considerable impacts on both the individual and the state. PURPOSE: This study was aimed to quantify the personal cost of lost income and the cost to the state from lost income taxation, increased benefits payments, and lost gross domestic product (GDP) as a result of early retirement because of spinal disorders in Australians aged 45 to 64 years inÂ 2009. METHODS: This was done using cross-sectional analysis of the base population of Health&WealthMOD, a microsimulation model built on data from the Australian Bureau of Statistics' Survey of Disability, Ageing and Carers, and STINMOD, an income and savings microsimulation model. Linear regression models were used to examine the relationship between spinal disorders, labor force participation, income, taxation, and government support payments. RESULTS: It was found that individuals aged 45 to 64 years who have retired early because of spinal disorders have significantly lower income (79% less; 95% confidence interval [CI], -84.7, -71.1; p

Use of a Fenestrated Instrument Tray Intraoperatively Allows Assessment of Plantar Contact Areas and Percutaneous Fixation Without Losing Deformity Correction Foot and Ankle Surgery : Official Journal of the European Society of Foot and Ankle Surgeons. Dec, 2012 | Pubmed ID: 23093128

Ethical Challenges of Caring for VIPs in the Rehabilitation Setting: Part II PM & R : the Journal of Injury, Function, and Rehabilitation. Oct, 2012 | Pubmed ID: 23093219

Counseling Customers: Emerging Roles for Genetic Counselors in the Direct-to-Consumer Genetic Testing Market Journal of Genetic Counseling. Oct, 2012 | Pubmed ID: 23093333 Individuals now have access to an increasing number of internet resources offering personal genomics services. As the direct-to-consumer genetic testing (DTC GT) industry expands, critics have called for pre- and post-test genetic counseling to be included with the product. Several genetic testing companies offer genetic counseling. There has been no examination to date of this service provision, whether it meets critics' concerns and implications it may have for the genetic counseling profession. Considering the increasing relevance of genetics in healthcare, the complexity of genetic information provided by DTC GT, the mediating role of the internet in counseling, and potential conflicts of interest, this is a topic which deserves further attention. In this paper we offer a discourse analysis of ways in which genetic counseling is represented on DTC GT websites, blogs and other online material. This analysis identified four types of genetic counseling represented on the websites: the integrated counseling product; discretionary counseling; independent counseling; and product advice. Genetic counselors are represented as having the following roles: genetics educator; mediator; lifestyle advisor; risk interpreter; and entrepreneur. We conclude that genetic counseling as represented on DTC GT websites demonstrates shifting professional roles and forms of expertise in genetic counseling. Genetic counselors are also playing an important part in how the genetic testing market is taking shape. Our analysis offers important and timely insights into recent developments in the genetic counseling profession, which have relevance for practitioners, researchers and policy makers concerned with the evolving field of personal genomics.

Optic Neuropathy in McCune-Albright Syndrome: Effects of Early Diagnosis and Treatment of Growth Hormone Excess The Journal of Clinical Endocrinology and Metabolism. Oct, 2012 | Pubmed ID: 23093488 Context:GH excess is a serious complication of McCune-Albright syndrome (MAS) and has been associated with craniofacial morbidity.Objective:The aim of the study was to determine whether early diagnosis and treatment of MAS-associated GH excess prevents optic neuropathy and hearing impairment, the major morbidities associated with GH excess.Design and Setting:A retrospective cross-sectional analysis was conducted at a clinical research center.Patients:Twenty-two subjects with MAS-associated GH excess and 21 control MAS subjects without GH excess were included in the study.Intervention:Biochemical testing included random GH, nadir GH after glucose load, nadir GH on frequent sampling, and IGF-I Z-score. Subjects underwent imaging, ophthalmological, audiological, and otolaryngological assessment. Treatment included octreotide, pegvisomant, transphenoidal surgery, and/or radiotherapy as indicated.Main Outcome Measure:Association of optic neuropathy and hearing impairment to age at GH excess diagnosis/treatment was measured.Results:Of 129 MAS subjects, 26 (20%) were diagnosed with GH excess based on elevation of two measures of GH function. Of these, 22 subjects were candidates for pharmacological intervention. Optic neuropathy was significantly correlated with intervention status, with no cases in the early intervention group (diagnosed/treated before age 18) or the control group, and four of seven (57%) in the late intervention group (diagnosed/treated after age 18) (Fisher's exact test; odds ratio, 0.027; P = 0.0058). Early diagnosis/intervention was not associated with reduction in hearing deficits (odds ratio, 1.25; P = 1.00). Mean head circumference sd score was significantly higher in the late (6.08; range, 2.70 to 22.56) than the early intervention (2.67; range, -0.65 to 6.72) or control groups (2.13; range, -2.06 to 7.79) (P = 0.003).Conclusions:Early diagnosis/treatment of GH excess in MAS is important to prevent optic neuropathy and craniofacial expansion. The relationship between hearing deficits and GH excess remains less clear and requires further study.

Treatment Burden Among People with Chronic Illness: What Are Consumer Health Organizations Saying? Chronic Illness. Oct, 2012 | Pubmed ID: 23093542 OBJECTIVES: To explore the perspectives of consumer health organizations about the burden of chronic illness and multiple treatment regimens experienced by the consumers they represent. METHODS: In-depth interviews (n = 15) were conducted with senior representatives from peak Australian consumer health organizations representing diabetes, asthma, cardiovascular disease, cancer, musculoskeletal illness and mental health. RESULTS: Medication burden, which included aspects such as multiple medications, side effects, stigma and adverse events resulting from medication use, emerged as the most significant and prevalent theme. Carer burden and the negative impact of financial burden was widely discussed, particularly for low-income earners with claims that these consumers were forced to prioritise medications according to how effective they perceived them to be. Time taken to learn about treatment, administer, and monitor or travel to obtain treatment also emerged as being burdensome, however, difficulty accessing treatment was considered to be particularly burdensome. The disjointed nature of care among healthcare services was thought to create a sense of confusion and distress. DISCUSSION: Many of the issues discussed by participants corroborated existing research, underscoring the complementary provider, and advocacy role of these organisations in mitigating treatment burden for people with chronic illness.

Fibroblast Growth Factor 10 Gene Regulation in the Second Heart Field by Tbx1, Nkx2-5, and Islet1 Reveals a Genetic Switch for Down-regulation in the Myocardium Proceedings of the National Academy of Sciences of the United States of America. Nov, 2012 | Pubmed ID: 23093675 During cardiogenesis, Fibroblast Growth Factor (Fgf10) is expressed in the anterior second heart field. Together with Fibroblast growth factor 8 (Fgf8), Fgf10 promotes the proliferation of these cardiac progenitor cells that form the arterial pole of the heart. We have identified a 1.7-kb region in the first intron of Fgf10 that is necessary and sufficient to direct transgene expression in this cardiac context. The 1.7-kb sequence is directly controlled by T-box transcription factor 1 (Tbx1) in anterior second heart field cells that contribute to the outflow tract. It also responds to both NK2 transcription factor related, locus 5 (Nkx2-5) and ISL1 transcription factor, LIM/homeodomain (Islet1), acting through overlapping sites. Mutation of these sites reduces transgene expression in the anterior second heart field where the Fgf10 regulatory element is activated by Islet1 via direct binding in vivo. Analysis of the response to Nkx2-5 loss- and Isl1 gain-of-function genetic backgrounds indicates that the observed up-regulation of its activity in Nkx2-5 mutant hearts, reflecting that of Fgf10, is due to the absence of Nkx2-5 repression and to up-regulation of Isl1, normally repressed in the myocardium by Nkx2-5. ChIP experiments show strong binding of Nkx2-5 in differentiated myocardium. Molecular and genetic analysis of the Fgf10 cardiac element therefore reveals how key cardiac transcription factors orchestrate gene expression in the anterior second heart field and how genes, such as Fgf10, normally expressed in the progenitor cell population, are repressed when these cells enter the heart and differentiate into myocardium. Our findings provide a paradigm for transcriptional mechanisms that underlie the changes in regulatory networks during the transition from progenitor state to that of the differentiated tissue.

Vemurafenib for the Treatment of Melanoma Expert Opinion on Pharmacotherapy. Dec, 2012 | Pubmed ID: 23094782 Introduction: Metastatic melanoma is an aggressive disease resistant to chemotherapy. Recent clinical trials have reported improved survival for two novel agents; ipilimumab, a humanized, IgG1 monoclonal antibody that blocks cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and vemurafenib , a BRAF (v-raf murine sarcoma viral oncogene homolog B1) inhibitor targeting an activating mutation in the serine-threonine-protein kinase BRAF gene. Areas covered: The authors reviewed preclinical and clinical data examining the safety of vemurafenib in melanoma. MEDLINE and EMBASE were searched using the medical subject heading 'vemurafenib' and the following text terms: melanoma, BRAF inhibition, vemurafenib. This review provides the reader with an overview of current data examining the efficacy and safety of vemurafenib in metastatic melanoma. Expert opinion: Vemurafenib is an oral agent licensed for patients with BRAF V600E mutation-positive inoperable and metastatic melanoma. The most common adverse effects observed in Phase III clinical trials were dermatological events, arthralgia and fatigue. Specific dermatological toxicities included development of cutaneous squamous cell cancers and keratoacanthomas. Prolongation of the QT interval was also reported. Regular dermatological assessments and electrocardiograms are recommended. Ongoing trials are examining vemurafenib in both the adjuvant setting and metastatic setting in combination with ipilimumab and MEK inhibitors (mitogen-activated protein kinase/extracellular signal-regulated kinase). Understanding and overcoming mechanisms of resistance to BRAF inhibitors is the focus of ongoing research.

Facilitating Medical Withdrawal from Opiates in Rural Ontario Rural and Remote Health. Oct, 2012 | Pubmed ID: 23094953 The abuse of oxycodone in Northwestern Ontario, Canada, has escalated at alarming rates raising concerns that opiate use has reached epidemic proportions, particularly among the First Nations communities. The authors were involved in establishing Ontario's first rural inpatient medical withdrawal unit to serve patients seeking abstinence.

An Evaluation of an Online Postgraduate Dementia Studies Program Gerontology & Geriatrics Education. Oct, 2012 | Pubmed ID: 23095221 Education is key to addressing the challenges of providing high-quality care to the ever growing number of people with dementia. Although dementia education is required for multiple professions and disciplines working with people with dementia and their families and friends, there is a gap in knowledge of students' views about university-level online dementia education. This article reports on an evaluation, via an online questionnaire, of student views of the delivery modes and learning impact for the first online postgraduate program in Dementia Studies worldwide. The majority of our respondents (65%) reported their participation in the Dementia Studies program as broadening their thinking, with 61% reporting that it broadened their practice. Students also reported on the utility of initial face-to-face teaching and the extent to which they are able to apply their learning to practice. The article concludes by suggesting that a blended learning approach, comprising online and face-to-face teaching with an emphasis on reflexivity has the potential to meet the global demand for skilled dementia care practitioners and to create leaders in the dementia care field.

Recent Developments in Home Sleep-monitoring Devices ISRN Neurology. 2012 | Pubmed ID: 23097718 Improving our understanding of sleep physiology and pathophysiology is an important goal for both medical and general wellness reasons. Although the gold standard for assessing sleep remains the laboratory polysomnogram, there is an increasing interest in portable monitoring devices that provide the opportunity for assessing sleep in real-world environments such as the home. Portable devices allow repeated measurements, evaluation of temporal patterns, and self-experimentation. We review recent developments in devices designed to monitor sleep-wake activity, as well as monitors designed for other purposes that could in principle be applied in the field of sleep (such as cardiac or respiratory sensing). As the body of supporting validation data grows, these devices hold promise for a variety of health and wellness goals. From a clinical and research standpoint, the capacity to obtain longitudinal sleep-wake data may improve disease phenotyping, individualized treatment decisions, and individualized health optimization. From a wellness standpoint, commercially available devices may allow individuals to track their own sleep with the goal of finding patterns and correlations with modifiable behaviors such as exercise, diet, and sleep aids.

Developing a Research Agenda for Promoting Physical Activity in Brazil Through Environmental and Policy Change Revista Panamericana De Salud PÃºblica = Pan American Journal of Public Health. Aug, 2012 | Pubmed ID: 23099869 To identify the highest priorities for research on environmental and policy changes for promoting physical activity (PA) in Brazil; to uncover any gaps between researchers' and practitioners' priorities; and to consider which tools, methods, collaborative strategies, and actions could be useful to moving a research agenda forward.

Building a Life Sciences Innovation Ecosystem Science Translational Medicine. Oct, 2012 | Pubmed ID: 23100622 Universities should support research with commercial potential, provide a supportive environment for start-ups, and partner enthusiastically with the private sector.

Clinical Simulation in Health Care--contemporary Learning for Safety and Practice Collegian (Royal College of Nursing, Australia). 2012 | Pubmed ID: 23101344

Providing Simulation Experiences for Large Cohorts of 1st Year Nursing Students: Evaluating Quality and Impact Collegian (Royal College of Nursing, Australia). 2012 | Pubmed ID: 23101345 To provide each student within a large cohort the opportunity to participate in a small group simulation that meets recognised quality indicators is a challenge for Bachelor of Nursing programmes in Australia. This paper, as part of a larger longitudinal study, describes one approach used to manage a simulation for 375 1st year nursing students and to report on the quality of the experience from the student's perspective. To ensure quality was maintained within the large cohort, aspects of the simulation were assessed against the following indicators: alignment with curriculum pedagogy and goals; preparation of students and staff; fidelity; and debriefing. Data obtained from a student focus group were analysed in the context of the quality indicators. The following themes emerged from the data: knowing what to expect; assuming roles for the simulation; authenticity and thinking on your feet; feeling the RN role; and, preparation for clinical practice. This paper demonstrates it is possible to provide students in large cohorts with active participatory roles in simulations whilst maintaining quality indicators.

Clinical Simulation in Australia and New Zealand: Through the Lens of an Advisory Group Collegian (Royal College of Nursing, Australia). 2012 | Pubmed ID: 23101352 Across Australia, innovations in simulation to enhance learning in nursing have been occurring for three decades and nursing is, and needs to be, a leading player in simulation knowledge diffusion. However, expertise is unevenly distributed across health services and education providers. Rather than build on the expertise and achievements of others, there is a tendency for resource duplication and for trial and error problem solving, in part related to a failure to communicate achievements for the benefits of the professional collective. For nursing to become a Leader in the use of simulation and drive ongoing development, as well as conducting high quality research and evaluation, academics need to collaborate, aggregate best practice in simulation learning, and disseminate that knowledge to educators working in health services and higher education sectors across the whole of Australia and New Zealand. To achieve this strategic intent, capacity development principles and committed action are necessary. In mid 2010 the opportunity to bring together nurse educators with simulation learning expertise within Australia and New Zealand became a reality. The Council of Deans of Nursing and Midwifery (CDNM) Australia and New Zealand decided to establish an expert reference group to reflect on the state of Australian nursing simulation, to pool expertise and to plan ways to share best practice knowledge on simulation more widely. This paper reflects on the achievements of the first 18 months since the group's establishment and considers future directions for the enhancement of simulation learning practice, research and development in Australian nursing.

Atypical Pulvinar-cortical Pathways During Sustained Attention Performance in Children with Attention-deficit/hyperactivity Disorder Journal of the American Academy of Child and Adolescent Psychiatry. Nov, 2012 | Pubmed ID: 23101745 The neurobiological basis of inattentiveness, a core feature of attention-deficit/hyperactivity disorder (ADHD), is not yet well understood. Structural abnormalities in thalamus, especially the pulvinar nuclei, have recently been reported in ADHD. Pulvinar nuclei maintain reciprocal connections with cortical/subcortical areas, and play a central coordinating role during visual attention processing. The objective of this study was to test the hypothesis that children and young adolescents with ADHD would show atypical pulvinar-cortical functional pathways during sustained attention performance, and that these functional abnormalities would be associated with the inattentive symptoms of the disorder.

Anatomic Changes in the Inguinal Region After Hip Arthroscopy: Implications for Femoral Nerve Block Journal of Clinical Anesthesia. Nov, 2012 | Pubmed ID: 23101776 Patients may experience significant pain after hip arthroscopy. Two patients who experienced severe pain after arthroscopic hip surgery, despite receiving multimodal pharmacologic therapy, are presented. In both cases, ultrasound-guided femoral nerve block provided excellent analgesia. However, during ultrasound, significant anatomic changes were noted in the inguinal region. In this report, we describe anatomic changes in the inguinal region that are visible with ultrasound after hip arthroscopy.

Measurement of Direct Photons in Au+Au Collisions at Sqrt[s_{NN}]=200â€‰â€‰GeV Physical Review Letters. Oct, 2012 | Pubmed ID: 23102300 We report the measurement of direct photons at midrapidity in Au+Au collisions at sqrt[s_{NN}]=200â€‰â€‰GeV. The direct photon signal was extracted for the transverse momentum range of 4â€‰â€‰GeV/c

Retrieval Analysis of Nonmodular Constrained Tibial Inserts After Primary Total Knee Replacement The Orthopedic Clinics of North America. Nov, 2012 | Pubmed ID: 23102420 Large angular deformities can be a challenge when performing primary total knee replacement. Some investigators have advocated the use of increased component constraint in these settings. The goal of this study was to determine the location and extent of damage to a consecutive series of retrieved constrained tibial inserts used in primary arthroplasty. There was significant post and articular damage in retrieved implants. Reliance on the polyethylene post for implant stability was associated with post and articular surface damage and may be a potential source of failure. Attempts to achieve implant stability using soft tissue techniques seem justified.

Regulation of Sheep Oocyte Maturation Using CAMP Modulators Theriogenology. Oct, 2012 | Pubmed ID: 23102843 Physical removal of mammalian cumulus-oocyte complexes (COCs) from ovarian follicles results in spontaneous resumption of meiosis, largely because of a decrease in cAMP concentrations, causing asynchrony between cytoplasmic and nuclear maturation and decreased oocyte developmental competence. The aim of this study was to modulate cAMP concentrations within ovine COCs to delay spontaneous nuclear maturation and improve developmental competence. Abattoir-derived sheep COCs were cultured for 2 hours (pre-IVM) in 100 Î¼M forskolin (FSK) plus 500 Î¼M 3-isobutyl-1-methylxanthine (IBMX). Pre-IVM (100 Î¼M FSK and 500 Î¼M IBMX) culture increased COC cAMP concentrations 10-fold compared with controls (P < 0.05). With regard to nuclear maturation, with FSK and IBMX and/or with FSH and cilostamide delayed completion of meiosis (metaphase II) by 3 to 4 hours compared with standard IVM (FSH-stimulated induction of meiosis). In this study, pre-IVM (with FSK and IBMX) followed by IVM (with FSH and cilostamide), increased ovine COC cAMP concentrations and delayed, but did not inhibit, completion of nuclear maturation. This did not affect embryo development rates, but increased total cell number of blastocysts compared with IVM with FSH alone (103 Â± 6 vs. 66 Â± 4 cells, respectively; mean Â± SEM; P < 0.05). We inferred that regulation of ovine oocyte cAMP concentrations during IVM improved embryo quality compared with embryos produced by standard IVM methods.

Family Violence Assessment Practices of Pediatric ED Nurses and Physicians Journal of Emergency Nursing: JEN : Official Publication of the Emergency Department Nurses Association. Oct, 2012 | Pubmed ID: 23102934 BACKGROUND: Recommendations by the ENA and other professional organizations have not resulted in widespread adoption of routine assessment for family violence such as child abuse and intimate partner violence. The aim of this qualitative study was to use a theory-driven approach to explore the salient beliefs and attitudes of nurses and physicians related to routine assessment of child abuse and intimate partner violence in the pediatric emergency department. METHODS: Nurse and physician participants from a large Midwestern pediatric trauma center responded to a series of open-ended questions designed to identify positive or negative attitudes toward family violence assessment, approving or disapproving beliefs about family violence assessment, and the perception of ease or difficulty in performing family violence assessment. RESULTS: Respondents valued early identification and the associated health benefits of keeping pediatric patients safe, as well as linking at-risk families to community resources. They believe that victims, health care organizations, and some providers approve of routine family violence assessment but also believe that some providers and families who value privacy disapprove. Previously identified barriers and facilitators to family violence assessment were confirmed by participants. A finding unique to this study was that participants expressed the belief that routine family violence assessment offers more complete health care to children. DISCUSSION: Participants viewed child abuse and intimate partner violence as an event in a child's life that affects the child's health. Participants valued the benefits of routine family violence assessment; however, translating these value beliefs into practice remains elusive. A theoretical framework may provide insight into yet unidentified aspects of known barriers and facilitators.

A Supramodal Accumulation-to-bound Signal That Determines Perceptual Decisions in Humans Nature Neuroscience. Oct, 2012 | Pubmed ID: 23103963 In theoretical accounts of perceptual decision-making, a decision variable integrates noisy sensory evidence and determines action through a boundary-crossing criterion. Signals bearing these very properties have been characterized in single neurons in monkeys, but have yet to be directly identified in humans. Using a gradual target detection task, we isolated a freely evolving decision variable signal in human subjects that exhibited every aspect of the dynamics observed in its single-neuron counterparts. This signal could be continuously tracked in parallel with fully dissociable sensory encoding and motor preparation signals, and could be systematically perturbed mid-flight during decision formation. Furthermore, we found that the signal was completely domain general: it exhibited the same decision-predictive dynamics regardless of sensory modality and stimulus features and tracked cumulative evidence even in the absence of overt action. These findings provide a uniquely clear view on the neural determinants of simple perceptual decisions in humans.

A Case of Hepatopulmonary Syndrome Solved by Mycophenolate Mofetil (An Inhibitor Of Angiogenesis and Nitric Oxid Production) Journal of Hepatology. Oct, 2012 | Pubmed ID: 23104163 BACKGROUND: The autoimmune lymphoproliferative syndrome (ALPS) is a rare, multi-systemic disease, caused by an inherited defect in the Fas apoptotic pathway, characterized by a chronic non-malignant lymphoid accumulation, and autoimmune manifestations. Lung, kidney, liver, and gut infiltration is described in severe, multi-systemic cases; so far there is no description of hepatopulmonary syndrome (HPS), for which orthotopic liver transplantation (OLT) is currently the only known effective treatment. CASE REPORT: A Teenage boy, diagnosed with ALPS at 4 years old (lymph nodes enlargement, splenomegaly, immune cytopenias), was stable until 13 years old when he developed insidiously hypoxemia (PaO2 = 46.7 mmHg). He was diagnosed with HPS on the basis of hypoxemia, non-cirrhotic liver disease with portal hypertension, and pulmonary vascular dilatation (intra-pulmonary shunt = 45%). He was treated with oxygen (maximum 6 liters/minute), prednisolone and sirolimus. There was significant regression of all manifestations of ALPS, except the pulmonary symptoms, so, after evaluation in referral centers in England, OLT was proposed. Since he was to be submitted to major surgery, sirolimus, which has wound healing problems, was switched for mycophenolate mofetil (MMF). Following this change, we observed an enormous improvement of the pulmonary symptoms and reduction of oxygen needs. The intra-pulmonary shunt decreased from 45% to 0% in less than a year, and remains so until today (18 months after complete normalization), on continued treatment with MMF. Indication for OLT was suspended. In the last year lymphoid proliferation increased again, with huge splenomegaly, but no recurrence of HPS. The addition of sirolimus to MMF produced again a rapid resolution of lymphoid proliferation. CONCLUSION: The dramatic and unexpected regression of HPS may have been due to inhibition of angiogenesis and nitric oxide (NO) production by MMF (both important pathways/mediators in the HPS pathogenesis). Therefore, we propose the conduct of clinical trials with MMF, and/or other angiogenesis and NO inhibitors, in a long-term treatment basis, to confirm their potential as a valid alternative for medical treatment of HPS.

Identification of Phosphorylation Sites in the COOH-terminal Tail of the Î¼-opioid Receptor Journal of Neurochemistry. Oct, 2012 | Pubmed ID: 23106126 Phosphorylation is considered a key event in the signalling and regulation of the Î¼ opioid receptor (MOPr). Here we used mass spectroscopy to determine the phosphorylation status of the C-terminal tail of the rat MOPr expressed in HEK-293 cells. Under basal conditions, MOPr is phosphorylated on Ser(363) and Thr(370) , while in the presence of morphine or [D-Ala2, NMe-Phe4, Gly-ol5]-enkephalin (DAMGO), the COOH-terminus is phosphorylated at three additional residues, Ser(356) , Thr(357) , and Ser(375) . Using N-terminal Glutathione S Transferase (GST) fusion proteins of the cytoplasmic, C-terminal tail of MOPr and point mutations of the same, we show that, in vitro, purified G protein-coupled receptor kinase 2 (GRK2) phosphorylates Ser(375) , PKC phosphorylates Ser(363) whilst CaMKII phosphorylates Thr(370) . Phosphorylation of the GST fusion protein of the C-terminal tail of MOPr enhanced its ability to bind arrestin-2 and -3. Hence, our study identifies both the basal and agonist-stimulated phospho-acceptor sites in the C-terminal tail of MOPr, and suggests that the receptor is subject to phosphorylation and hence regulation by multiple protein kinases. Â© 2012 International Society for Neurochemistry, J. Neurochem. (2012) 10.1111/jnc.12071.

Reconstructing the Evolutionary History of an Endangered Subspecies Across the Changing Landscape of the Great Central Valley of California Molecular Ecology. Oct, 2012 | Pubmed ID: 23106496 Identifying historic patterns of population genetic diversity and connectivity is a primary challenge in efforts to re-establish the processes that have generated and maintained genetic variation across natural landscapes. The challenge of reconstructing pattern and process is even greater in highly altered landscapes where population extinctions and dramatic demographic fluctuations in remnant populations may have substantially altered, if not eliminated, historic patterns. Here, we seek to reconstruct historic patterns of diversity and connectivity in an endangered subspecies of woodrat that now occupies only 1-2 remnant locations within the highly altered landscape of the Great Central Valley of California. We examine patterns of diversity and connectivity using 14 microsatellite loci and sequence data from a mitochondrial locus and a nuclear intron. We reconstruct temporal change in habitat availability to establish several historical scenarios that could have led to contemporary patterns of diversity, and use an approximate Bayesian computation approach to test which of these scenarios is most consistent with our observed data. We find that the Central Valley populations harbour unique genetic variation coupled with a history of admixture between two well-differentiated species of woodrats that are currently restricted to the woodlands flanking the Valley. Our simulations also show that certain commonly used analytical approaches may fail to recover a history of admixture when populations experience severe bottlenecks subsequent to hybridization. Overall our study shows the strength of combining empirical and simulation analyses to recover the history of populations occupying highly altered landscapes.

The Effects of Altered Intrathoracic Pressure on Resting Cerebral Blood Flow and Its Response to Visual Stimulation NeuroImage. Oct, 2012 | Pubmed ID: 23108273 Investigating how intrathoracic pressure changes affect cerebral blood flow (CBF) is important for a clear interpretation of neuroimaging data in patients with abnormal respiratory physiology, intensive care patients receiving mechanical ventilation and in research paradigms that manipulate intrathoracic pressure. Here, we investigated the effect of experimentally increased and decreased intrathoracic pressures upon CBF and the stimulus-evoked CBF response to visual stimulation. Twenty healthy volunteers received intermittent inspiratory and expiratory loads (plus or minus 9cmH(2)O for 270s) and viewed an intermittent 2Hz flashing checkerboard, while maintaining stable end-tidal CO(2). CBF was recorded with transcranial Doppler sonography (TCD) and whole-brain pseudo-continuous arterial spin labeling magnetic resonance imaging (PCASL MRI). Application of inspiratory loading (negative intrathoracic pressure) showed an increase in TCD-measured CBF of 4% and a PCASL-measured increase in grey matter CBF of 5%, but did not alter mean arterial pressure (MAP). Expiratory loading (positive intrathoracic pressure) did not alter CBF, while MAP increased by 3%. Neither loading condition altered the perfusion response to visual stimulation in the primary visual cortex. In both loading conditions localized CBF increases were observed in the somatosensory and motor cortices, and in the cerebellum. Altered intrathoracic pressures, whether induced experimentally, therapeutically or through a disease process, have possible significant effects on CBF and should be considered as a potential systematic confound in the interpretation of perfusion-based neuroimaging data.

NAD+ Biosynthesis Ameliorates a Zebrafish Model of Muscular Dystrophy PLoS Biology. Oct, 2012 | Pubmed ID: 23109907 Muscular dystrophies are common, currently incurable diseases. A subset of dystrophies result from genetic disruptions in complexes that attach muscle fibers to their surrounding extracellular matrix microenvironment. Cell-matrix adhesions are exquisite sensors of physiological conditions and mediate responses that allow cells to adapt to changing conditions. Thus, one approach towards finding targets for future therapeutic applications is to identify cell adhesion pathways that mediate these dynamic, adaptive responses in vivo. We find that nicotinamide riboside kinase 2b-mediated NAD+ biosynthesis, which functions as a small molecule agonist of muscle fiber-extracellular matrix adhesion, corrects dystrophic phenotypes in zebrafish lacking either a primary component of the dystrophin-glycoprotein complex or integrin alpha7. Exogenous NAD+ or a vitamin precursor to NAD+ reduces muscle fiber degeneration and results in significantly faster escape responses in dystrophic embryos. Overexpression of paxillin, a cell adhesion protein downstream of NAD+ in this novel cell adhesion pathway, reduces muscle degeneration in zebrafish with intact integrin receptors but does not improve motility. Activation of this pathway significantly increases organization of laminin, a major component of the extracellular matrix basement membrane. Our results indicate that the primary protective effects of NAD+ result from changes to the basement membrane, as a wild-type basement membrane is sufficient to increase resilience of dystrophic muscle fibers to damage. The surprising result that NAD+ supplementation ameliorates dystrophy in dystrophin-glycoprotein complex- or integrin alpha7-deficient zebrafish suggests the existence of an additional laminin receptor complex that anchors muscle fibers to the basement membrane. We find that integrin alpha6 participates in this pathway, but either integrin alpha7 or the dystrophin-glycoprotein complex is required in conjunction with integrin alpha6 to reduce muscle degeneration. Taken together, these results define a novel cell adhesion pathway that may have future therapeutic relevance for a broad spectrum of muscular dystrophies.

Age-Dependent Changes in the Sphingolipid Composition of Mouse CD4(+) T Cell Membranes and Immune Synapses Implicate Glucosylceramides in Age-Related T Cell Dysfunction PloS One. 2012 | Pubmed ID: 23110086 To determine whether changes in sphingolipid composition are associated with age-related immune dysfunction, we analyzed the core sphingolipidome (i.e., all of the metabolites through the first headgroup additions) of young and aged CD4(+) T cells. Since sphingolipids influence the biophysical properties of membranes, we evaluated the compositions of immune synapse (IS) and non-IS fractions prepared by magnetic immuno-isolation. Broadly, increased amounts of sphingomyelins, dihydrosphingomyelins and ceramides were found in aged CD4(+) T cells. After normalizing for total sphingolipid content, a statistically significant decrease in the molar fraction of glucosylceramides was evident in both the non-IS and IS fractions of aged T cells. This change was balanced by less dramatic increases in the molar fractions of sphingomyelins and dihydrosphingomyelins in aged CD4(+) T cells. In vitro, the direct or enzymatic enhancement of ceramide levels decreased CD4(+) T cell proliferation without regard for the age of the responding T cells. In contrast, the in vitro inhibition of glucosylceramidase preferentially increased the proliferation of aged CD4(+) T cells. These results suggest that reductions in glucosylceramide abundance contribute to age-related impairments in CD4(+) T cell function.

Social Support and Age Influence Distress Outcomes Differentially Across Urban, Regional and Remote Australia: an Exploratory Study BMC Public Health. Oct, 2012 | Pubmed ID: 23110446 ABSTRACT: BACKGROUND: The variation of determinants of mental health with remoteness has rarely been directly examined. The current research aims to examine whether the association of psychosocial factors with psychological distress outcomes varies with increasing remoteness. METHODS: Participants were persons aged 55 and over from two community cohorts sampling from across rural and urban New South Wales (N = 4219; mean age = 69.00 years; 46.1% male). Measures of social support from these studies were calibrated to facilitate comparison across the sample. Remoteness was assessed using a continuous measure, the Accessibility/Remoteness Index of Australia. The association between demographic characteristics, social support, remoteness, and their interactions with remoteness in the prediction of high psychological distress (cut-off > 21 on the Kessler 10) were examined using logistic regression. RESULTS: Not being in a married or defacto relationship (OR 0.69; 99% CI 0.51-0.94), lower education (OR 0.52; 99% CI 0.38-0.71) and decreased social support (OR 0.36; 99% CI 0.31-0.42) significantly predicted psychological distress. There was a significant interaction of age and remoteness (OR 0.84; 99% CI 0.67-1.00), indicating that as remoteness increases, older persons are less likely to be highly distressed, as well as a significant interaction of social support and remoteness (OR 1.22; 99% CI 1.04-1.44), indicating that as remoteness decreases, persons with low levels of social support are more likely to be highly distressed. CONCLUSIONS: Remoteness may moderate the influence of social support and age on psychological distress outcomes.

What Are You Doing Creatively These Days? Academic Medicine : Journal of the Association of American Medical Colleges. Nov, 2012 | Pubmed ID: 23111265

Comparison of Autoantibody Specificities Between Traditional and Bead-based Assays in a Large, Diverse Collection of Patients with Systemic Lupus Erythematosus and Family Members Arthritis and Rheumatism. Nov, 2012 | Pubmed ID: 23112091 Replacement of standard immunofluorescence methods with bead-based assays for antinuclear antibody (ANA) testing is a new clinical option. The aim of this study was to evaluate a large, multiethnic cohort of patients with systemic lupus erytematosus (SLE), blood relatives, and unaffected control individuals for familial aggregation and subset clustering of autoantibodies by high-throughput serum screening technology and traditional methods.

Colorectal Cancer in Alaska Native People, 2005-2009 Gastrointestinal Cancer Research : GCR. Sep, 2012 | Pubmed ID: 23112882 Colorectal cancer (CRC) is the most frequently diagnosed cancer among Alaska Native (AN) people, and the second leading cause of cancer death. The incidence rate for the combined years 1999 through 2003 was 30% higher than the rate among U.S. whites (USWs) for the same period. Current incidence rates may serve to monitor the impact of screening programs in reducing CRC in the AN population.

The Impact of Infection Control Upon Hospital-acquired Influenza and Respiratory Syncytial Virus Scandinavian Journal of Infectious Diseases. Oct, 2012 | Pubmed ID: 23113868 Background: Respiratory syncytial virus (RSV) and influenza are important pediatric community-acquired (CA) and hospital-acquired (HA) pathogens. The occurrence of pandemic (H1N1) 2009 influenza resulted in additional efforts to intensify infection control (IC) strategies. We detail the impact of IC strategies between 2003 and 2010 on influenza and RSV. Methods: We assessed the rates of CA infections per 100 admissions and HA infections per 1000 patient-days for both RSV and influenza at Children's Memorial Hospital during the winter seasons (September through May) 2003-2010. The season of 2009, however, was extended through June due to ongoing admissions as a result of pandemic (H1N1) 2009 influenza. IC strategies implemented in response to pandemic (H1N1) 2009 influenza are described. The transmission ratio (HA cases/CA cases) was determined and correlated with IC efforts. Results: Substantial season- to-season variability exists for CA RSV and CA influenza rates. The rates of HA RSV and HA influenza and the transmission ratios for these viruses remained unchanged in 2009-10 in comparison to the prior year (at 0.02 and 0.01, respectively) despite implementation of multiple IC strategies. In contrast, since 2005 an inverse association was noted between hand hygiene compliance and the transmission ratio of both RSV and influenza, with Spearman correlation coefficients of -0.84 (p = 0.051) and -0.89 (p = 0.008), respectively. Conclusions: We observed that improvements in hand hygiene compliance correlated with less transmission of RSV and influenza in the hospital. The important role of hand hygiene in preventing transmission of RSV and influenza to hospitalized children should be emphasized.

Of Mast and Mean: Differential-temperature Cue Makes Mast Seeding Insensitive to Climate Change Ecology Letters. Nov, 2012 | Pubmed ID: 23113938 Mast-seeding plants often produce high seed crops the year after a warm spring or summer, but the warm-temperature model has inconsistent predictive ability. Here, we show for 26 long-term data sets from five plant families that the temperature difference between the two previous summers (Î”T) better predicts seed crops. This discovery explains how masting species tailor their flowering patterns to sites across altitudinal temperature gradients; predicts that masting will be unaffected by increasing mean temperatures under climate change; improves prediction of impacts on seed consumers; demonstrates that strongly masting species are hypersensitive to climate; explains the rarity of consecutive high-seed years without invoking resource constraints; and generates hypotheses about physiological mechanisms in plants and insect seed predators. For plants, Î”T has many attributes of an ideal cue. This temperature-difference model clarifies our understanding of mast seeding under environmental change, and could also be applied to other cues, such as rainfall.

Effects of a Competitive Wrestling Season on Body Composition, Endocrine Markers, and Anaerobic Exercise Performance in NCAA Collegiate Wrestlers European Journal of Applied Physiology. Oct, 2012 | Pubmed ID: 23114663 Few data exist examining the body composition, endocrine, and anaerobic exercise performance changes over a competitive wrestling season. Eighteen NCAA wrestlers were tested for endocrine markers, body composition, hydration, grip strength, and power on four occasions: prior to pre-season training (T1); after pre-season training 3Â days prior to the first seasonal meet (T2); mid-season one day prior to a meet (T3); and at the end of the season 2-3Â days following the last meet (T4). Body mass, percent body fat (BFÂ %), and fat mass were significantly lower (PÂ â‰¤Â 0.05) at T2 and T3 compared to T1 but were not different between T1 and T4. Lean body mass was significantly reduced at T2 only. Urine specific gravity was significantly elevated at T3 compared to T1, T2, and T4. Resting cortisol concentrations did not change but resting testosterone concentrations were significantly reduced at T2, T3, and T4. Maximal grip strength was significantly reduced at T2. Vertical jump peak power was significantly reduced at T2, T3, and T4. Wingate peak power was significantly reduced at T2 and T3. However, Wingate average power and total work did not significantly change. Fatigue rate during the Wingate test was significantly improved at T2, T3, and T4 compared to T1. In conclusion, body mass, BFÂ %, and measures of peak force and power were reduced for most of the competitive wrestling season. Competitive wrestling reduces resting total testosterone concentrations throughout the entire season.

Bloodstream Infection Among Children Presenting to a General Hospital Outpatient Clinic in Urban Nepal PloS One. 2012 | Pubmed ID: 23115652 There are limited data on the etiology and characteristics of bloodstream infections in children presenting in hospital outpatient settings in South Asia. Previous studies in Nepal have highlighted the importance of murine typhus as a cause of febrile illness in adults and enteric fever as a leading bacterial cause of fever among children admitted to hospital.

Highly Stable Porous Silicon-Carbon Composites As Label-Free Optical Biosensors ACS Nano. Nov, 2012 | Pubmed ID: 23116211 A stable, label-free optical biosensor based on a porous silicon-carbon (pSi-C) composite is demonstrated. The material is prepared by electrochemical anodization of crystalline Si in an HF-containing electrolyte to generate a porous Si template, followed by infiltration of poly(furfuryl) alcohol (PFA) and subsequent carbonization to generate the pSi-C composite as an optically smooth thin film. The pSi-C sensor is significantly more stable toward aqueous buffer solutions (pH 7.4 or 12) compared to thermally oxidized (in air, 800 Â°C), hydrosilylated (with undecylenic acid), or hydrocarbonized (with acetylene, 700 Â°C) porous Si samples prepared and tested under similar conditions. Aqueous stability of the pSi-C sensor is comparable to related optical biosensors based on porous TiO(2) or porous Al(2)O(3). Label-free optical interferometric biosensing with the pSi-C composite is demonstrated by detection of rabbit IgG on a protein-A-modified chip and confirmed with control experiments using chicken IgG (which shows no affinity for protein A). The pSi-C sensor binds significantly more of the protein A capture probe than porous TiO(2) or porous Al(2)O(3), and the sensitivity of the protein-A-modified pSi-C sensor to rabbit IgG is found to be âˆ¼2Ã— greater than label-free optical biosensors constructed from these other two materials.

Synthesis of Soluble Graphite and Graphene Accounts of Chemical Research. Nov, 2012 | Pubmed ID: 23116420 Because of graphene's anticipated applications in electronics and its thermal, mechanical, and optical properties, many scientists and engineers are interested in this material. Graphene is an isolated layer of the Ï€-stacked hexagonal allotrope of carbon known as graphite. The interlayer cohesive energy of graphite, or exfoliation energy, that results from van der Waals attractions over the interlayer spacing distance of 3.34 Ã… (61 meV/C atom) is many times weaker than the intralayer covalent bonding. Since graphene itself does not occur naturally, scientists and engineers are still learning how to isolate and manipulate individual layers of graphene. Some researchers have relied on the physical separation of the sheets, a process that can sometimes be as simple as peeling of sheets from crystalline graphite using Scotch tape. Other researchers have taken an ensemble approach, where they exploit the chemical conversion of graphite to the individual layers. The typical intermediary state is graphite oxide, which is often produced using strong oxidants under acidic conditions. Structurally, researchers hypothesize that acidic functional groups functionalize the oxidized material at the edges and a network of epoxy groups cover the sp(2)-bonded carbon network. The exfoliated material formed under these conditions can be used to form dispersions that are usually unstable. However, more importantly, irreversible defects form in the basal plane during oxidation and remain even after reduction of graphite oxide back to graphene-like material. As part of our interest in the dissolution of carbon nanomaterials, we have explored the derivatization of graphite following the same procedures that preserve the sp(2) bonding and the associated unique physical and electronic properties in the chemical processing of single-walled carbon nanotubes. In this Account, we describe efficient routes to exfoliate graphite either into graphitic nanoparticles or into graphene without resorting to oxidation. Our exfoliation process involves the intercalation of lithium into bulk graphite to yield graphene sheets reduced by the lithium. We can alkylate the resulting graphite salt reductively using solubilizing dodecyl groups. By probe microscopy, we show that these groups are attached covalently only at the graphitic edges.

Intravaginal Practices and Microbicide Acceptability in Papua New Guinea: Implications for HIV Prevention in a Moderate-prevalence Setting BMC Research Notes. Nov, 2012 | Pubmed ID: 23116431 ABSTRACT: BACKGROUND: The acceptability of female-controlled biomedical prevention technologies has not been established in Papua New Guinea, the only country in the Pacific region experiencing a generalised, moderate-prevalence HIV epidemic. Socio-cultural factors likely to impact on future product uptake and effectiveness, such as women's ability to negotiate safer sexual choices, and intravaginal hygiene and menstrual practices (IVP), remain unclear in this setting. METHODS: A mixed-method qualitative study was conducted among women and men attending a sexual health clinic in Port Moresby. During in-depth interviews, participants used copies of a hand-drawn template to indicate how they wash/clean the vulva and/or vagina. Interviewers pre-filled commercially available vaginal applicators with 2-3mL KY Jelly(R) to create a surrogate vaginal microbicide product, which was demonstrated to study participants. RESULTS: A total of 28 IDIs were conducted (women=16; men=12). A diverse range of IVP were reported. The majority of women described washing the vulva only with soap and water as part of their daily routine; in preparation for sex; and following sexual intercourse. Several women described cleaning inside the vagina using fingers and soap at these same times. Others reported cleaning inside the vagina using a hose connected to a tap; using vaginal inserts, such as crushed garlic; customary menstrual 'steaming' practices; and the use of material fragments, cloth and newspaper to absorb menstrual blood. Unprotected sex during menstruation was common. The majority of both women and men said that they would use a vaginal microbicide gel for HIV/STI protection, should a safe and effective product become available. Microbicide use was considered most appropriate in 'high-risk' situations, such as sex with non-regular, transactional or commercial partners. Most women felt confident that they would be able to negotiate vaginal microbicide use with male sexual partners but if necessary would be prepared to use product covertly. CONCLUSIONS: Notional acceptability of a vaginal microbicide gel for HIV/STI prevention was high among both women and men. IVP were diverse in nature, socio-cultural dimensions and motivators. These factors are likely to impact on the future acceptability and uptake of vaginal microbicides and other biomedical HIV prevention technologies in this setting.

Health-related Quality of Life in Chronic Myeloid Leukemia Leukemia Research. Oct, 2012 | Pubmed ID: 23116602 The increased survival associated with treatments for CML emphasize the importance of understanding the HRQOL of newly diagnosed and previously treated CML patients with all phases of disease. Functional Assessment of Cancer Therapy-Leukemia results from a phase 3 and a phase 2 trial are reported for over 900 1st, 2nd, 3rd line CP, AP, and BP patients. Physical Well-being and Leukemia symptoms were worse for patients in later lines of therapy. Individuals with AP and BP CML had poorer HRQOL than individuals with CP CML. HRQOL of CML patients was predominantly consistent with the longitudinal clinical trajectory of the disease.

Phosphorylated Neurofilament Heavy Subunit (pNF-H) in Peripheral Blood and CSF As a Potential Prognostic Biomarker in Amyotrophic Lateral Sclerosis Journal of Neurology, Neurosurgery, and Psychiatry. Oct, 2012 | Pubmed ID: 23117489 BACKGROUND: The phosphorylated neurofilament heavy subunit (pNF-H), a major structural component of motor axons, is a promising putative biomarker in amyotrophic lateral sclerosis (ALS) but has been studied mainly in CSF. We examined pNF-H concentrations in plasma, serum and CSF as a potential biomarker for disease progression and survival in ALS. METHODOLOGY: We measured pNF-H concentration by monoclonal sandwich ELISA in plasma (n=43), serum and CSF (n=20) in ALS patients collected at the Mayo Clinic Florida and Emory University. We included plasma from an ALS cohort (n=20) from an earlier pilot study in order to evaluate baseline pNF-H levels in relation to disease progression using the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), survival and anatomical region of ALS onset. RESULTS: Higher pNF-H levels in plasma, serum and CSF showed evidence of association with faster decline in ALSFRS-R. There was evidence for a relationship of higher serum and plasma pNF-H levels with shorter survival, although evidence was weaker for CSF. pNF-H concentration in plasma (n=62) may be higher in patients with bulbar onset than in patients with spinal onset. CONCLUSIONS: In ALS, increased pNF-H concentration in plasma, serum and CSF appears to be associated with faster disease progression. Factors affecting pNF-H levels or their detection in serum and plasma in relation to disease course may differ from those in CSF. Data raising the possibility that site of ALS onset (bulbar vs spinal) may influence pNF-H levels in peripheral blood seems noteworthy but requires confirmation. These data support further study of pNF-H in CSF, serum and plasma as a potential ALS biomarker.

Validation of LC-TOF-MS Screening for Drugs, Metabolites, and Collateral Compounds in Forensic Toxicology Specimens Journal of Analytical Toxicology. Nov, 2012 | Pubmed ID: 23118149 Liquid chromatography time-of-flight mass spectrometry (LC-TOF-MS) analysis provides an expansive technique for identifying many known and unknown analytes. This study developed a screening method that utilizes automated solid-phase extraction to purify a wide array of analytes involving stimulants, benzodiazepines, opiates, muscle relaxants, hypnotics, antihistamines, antidepressants and newer synthetic "Spice/K2" cannabinoids and cathinone "bath salt" designer drugs. The extract was applied to LC-TOF-MS analysis, implementing a 13 min chromatography gradient with mobile phases of ammonium formate and methanol using positive mode electrospray. Several common drugs and metabolites can share the same mass and chemical formula among unrelated compounds, but they are structurally different. In this method, the LC-TOF-MS was able to resolve many isobaric compounds by accurate mass correlation within 15 ppm mass units and a narrow retention time interval of less than 10 s of separation. Drug recovery yields varied among spiked compounds, but resulted in overall robust area counts to deliver an average match score of 86 when compared to the retention time and mass of authentic standards. In summary, this method represents a rapid, enhanced screen for blood and urine specimens in postmortem, driving under the influence, and drug facilitated sexual assault forensic toxicology casework.

Pegloticase and the Patient with Treatment-failure Gout Expert Review of Clinical Pharmacology. Sep, 2012 | Pubmed ID: 23121270 Gout is an inflammatory arthritis characterized by sudden, painful inflammation. Gout can affect any joint in an asymmetric distribution. Gouty attacks may be isolated or can be followed by years of recurrent flares. Over time, elevated serum urate levels and tophaceous deposits can lead to deformity and disability from underlying bony erosion. The concept of 'treatment-failure gout' describes a unique population that has been either unable to tolerate allopurinol or who have not experienced normalization of serum urate levels on allopurinol. It is estimated that approximately 1-1.5% of the estimated 3-8 million people with gout in the USA have treatment-failure gout. Pegloticase is an US FDA-approved intravenous medication that is a mammalian recombinant uricase conjugated to monomethoxy polyethylene glycol. Two recent Phase III trials have found pegloticase to be effective in the management of treatment-failure gout. These studies also highlight safety concerns regarding the drug's immunogenicity.

Wanted - New Book Reviewers Sociology of Health & Illness. Nov, 2012 | Pubmed ID: 23121413

The Living with Dysarthria Group: Implementation and Feasibility of a Group Intervention for People with Dysarthria Following Stroke and Family Members International Journal of Language & Communication Disorders / Royal College of Speech & Language Therapists. Nov, 2012 | Pubmed ID: 23121529 Background: The broad life implications of acquired dysarthria are recognized, but they have received little attention in stroke management. Reports of group therapy, which may be a suitable approach to intervention, are not available for stroke-related dysarthria. Aims: To examine the operational feasibility of and response to a new eight-session weekly group intervention programme, Living with Dysarthria, designed for people with chronic dysarthria following stroke and their main communication partners. Methods & Procedures: The target participation was for programme completion by two groups of eight people with dysarthria (PWD) and available family members (FMs) or carers. An active recruitment strategy was undertaken from the speech and language therapy case records for the previous 6 years in two hospitals with combined annual stroke admissions of over 500 people. Twelve PWD and seven FMs were recruited (group 1: seven PWD and four FMs; group 2: five PWD and three FMs). Speech intelligibility, communication effectiveness, general well-being, quality of communication life, and knowledge of stroke and dysarthria were assessed pre- and post-programme. Each PWD and FM also set an individual goal and rated their achievement of this on a 0-10 scale. Outcomes & Results: Recruitment to the programme was lower than anticipated and below target. The 12 PWD were recruited from 62 initial contacts, which was the total number who according to available information met the criteria. The programme was viable: it ran to plan, with only minor content alterations, in community accommodation, and with good participant engagement. Group median score changes were in a positive direction for all measures and effect sizes ranged from 0.17 (quality of communication life) to 0.46 (intelligibility). Significant post-programme changes were present for intelligibility and knowledge of stroke and dysarthria (p= 0.05). Participants' ratings of goal achievements ranged from 6 (some change) to 10 (a lot of change). Conclusions & Implications: The recruitment experience revealed a take-up rate of around 20% from PWD following stroke, informing future planning. The participant engagement and performance results from the piloting of the programme indicate that the Living with Dysarthria programme is viable and has potential for effecting positive change. Further testing is justified.

Can We Identify Patients at High Risk of Recurrent Clostridium Difficile Infection? Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. Dec, 2012 | Pubmed ID: 23121551 Although most patients with Clostridium difficile infection (CDI) can be managed effectively with discontinuation of prescribed antibiotics and additional treatment with oral metronidazole or vancomycin, up to 25% experience disease recurrence, usually within 30Â days of treatment. Failure to mount a systemic anti-toxin antibody response differentiates patients with CDI and recurrent CDI from symptomless carriers of toxinogenic C.Â difficile. The immunological senescence that accompanies ageing may lead to impaired immune responses to C.Â difficile and contribute to the significant association between advancing age and increased risk of CDI recurrence. Inadequate immunity may also explain why previous episodes of recurrence constitute a significant risk factor for further CDI recurrences. Other risk factors for recurrent CDI include concurrent use of antibiotics for non-C.Â difficile infections (which perpetuate the loss of colonization resistance), proton-pump inhibitors, and other gastric acid anti-secretory medications, prolonged hospitalization, and severe underlying illness (as reflected by a high Horn index score). Prominent risk factors have been examined to develop and validate a clinical prediction tool for recurrent CDI, with three factors (age >65Â years, severe underlying disease (by the Horn index score), and continued use of antibiotics for non-CDI infections) being highly predictive of CDI recurrence. Such simple clinical prediction rules have the potential to identify patients at high risk of recurrent CDI, and can alert the treating physician to the need for prompt recognition, confirmatory diagnosis and treatment with regimens ideally designed to mitigate the risk of subsequent recurrences.

Does the Internet Function Like Magazines? An Exploration of Image-focused Media, Eating Pathology, and Body Dissatisfaction Eating Behaviors. Dec, 2012 | Pubmed ID: 23121797 Research has identified a relation between exposure to thin-ideal magazine and television media images and eating disorder pathology. However, few studies have examined the potential influence of Internet media on eating disorder behaviors and attitudes. This study investigated associations among image-focused media exposure, body dissatisfaction, eating pathology and thin-ideal internalization in a sample of 421 female undergraduates. Undergraduate women spent significantly more time viewing online appearance-oriented media, rather than reading image-focused magazines. Appearance-oriented Internet and television use were associated with eating pathology. Moreover, the association between image-focused Internet use and BD was mediated by thin-ideal internalization. These findings are consistent with those of previous research, and highlight the vulnerability individuals high in thin-ideal internalization might have to media exposure. They also suggest that Internet media use is an important topic to attend to in eating disorders prevention and treatment.

Eating Disorder Examination Questionnaire (EDE-Q): Norms for Black Women Eating Behaviors. Dec, 2012 | Pubmed ID: 23121804 The current study provides Eating Disorder Examination Questionnaire (EDE-Q) norms for Black undergraduate women (N=395). EDE-Q subscale scores, clinical cutoffs, and disordered eating behavior were compared with previously published norms for primarily White undergraduate and community samples. The current sample endorsed mean EDE-Q scores similar to those of White females recruited from the community. Regarding clinical cutoffs, Black women in the current sample were most similar to White college women. Despite similar EDE-Q scores, the current sample endorsed significantly less binge eating and compensatory behaviors than White undergraduate or community women. Outcomes suggest that increased eating- and weight-related concerns among Black undergraduate women might not be associated with disordered eating behavior. Similarly, results suggest that the validity of EDE-Q cutoffs is lower in samples of Black women compared with samples of White women. Additional research is needed to enhance understanding of eating disorder risk factors for Black college women.

Emerging Adults' Treatment Outcomes in Relation to 12-step Mutual-help Attendance and Active Involvement Drug and Alcohol Dependence. Oct, 2012 | Pubmed ID: 23122600 BACKGROUND: Participation in Alcoholics Anonymous (AA) and Narcotics Anonymous (NA) during and following treatment has been found to confer recovery-related benefit among adults and adolescents, but little is known about emerging adults (18-24years). This transitional life-stage is distinctive for greater distress, higher density of psychopathology, and poorer treatment and continuing care compliance. Greater knowledge would inform the utility of treatment referrals to 12-step organizations for this age-group. METHODS: Emerging adults (N=303; 18-24years; 26% female; 95% White; 51% comorbid [SCID-derived] axis I disorders) enrolled in a naturalistic study of residential treatment effectiveness assessed at intake, 3, 6, and 12 months on 12-step attendance and involvement and treatment outcomes (percent days abstinent [PDA]; percent days heavy drinking [PDHD]). Lagged hierarchical linear models (HLMs) tested whether attendance and involvement conferred recovery benefits, controlling for a variety of confounds. RESULTS: The percentage attending 12-step meetings prior to treatment (36%) rose sharply at 3 months (89%), was maintained at 6 months (82%), but declined at 12 months (76%). Average attendance peaked at about 3 times per week at 3 months dropping to just over once per week at 12 months. Initially high, but similarly diminishing, levels of active 12-step involvement were also observed. Lagged HLMs found beneficial effects for attendance, but stronger effects, which increased over time, for active involvement. Several active 12-step involvement indices were associated individually with outcome benefits. CONCLUSIONS: Ubiquitous 12-step organizations may provide a supportive recovery context for this high-risk population at a developmental stage where non-using/sober peers are at a premium.

Tissue Proteomics in Pancreatic Cancer Study: Discovery, Emerging Technologies and Challenges Proteomics. Nov, 2012 | Pubmed ID: 23125171 Pancreatic cancer is a highly lethal disease that is difficult to diagnose and treat. The advances of proteomics technology, especially quantitative proteomics, have stimulated a great interest to apply this technology for pancreatic cancer study. A variety of tissue proteomics approaches have been applied to investigate pancreatic cancer and the associated diseases. These studies were carried out with various goals, aiming to better understand the molecular mechanisms underlying pancreatic tumorigenesis, to improve therapeutic treatment and to identify cancer associated protein signatures, signaling events as well as interactions between cancer cells and tumor microenvironment. Here, we provide an overview on the tissue proteomics studies of pancreatic cancer reported in the past few years in light of discovery and technology development.

A Quantitative Assessment of the Prion Risk Associated with Wastewater from Carcase-Handling Facilities Risk Analysis : an Official Publication of the Society for Risk Analysis. Nov, 2012 | Pubmed ID: 23126436 Wastewater from facilities processing livestock that may harbor transmissible spongiform encephalopathies (TSEs) infectivity is permitted under license for application to land where susceptible livestock may have access. Several previous risk assessments have investigated the risk of bovine spongiform encephalopathy (BSE) associated with wastewater effluents; however, the risk of exposure to classical scrapie and atypical scrapie has not been assessed. With the prevalence of certain TSEs (BSE in cattle and classical scrapie in sheep) steadily in decline, and with considerable changes in the structure of carcase-processing industries in Great Britain, a reappraisal of the TSE risk posed by wastewater is required. Our results indicate that the predicted number of new TSE infections arising from the spreading of wastewater on pasture over one year would be low, with a mean of one infection every 1,000 years for BSE in cattle (769, 555,556), and one infection every 30 years (16, 2,500), and 33 years (16, 3,333) for classical and atypical scrapie, respectively. It is assumed that the values and assumptions used in this risk assessment remain constant. For BSE in cattle the main contributors are abattoir and rendering effluent, contributing 35% and 22% of the total number of new BSE infections. For TSEs in sheep, effluent from small incinerators and rendering plants are the major contributors (on average 32% and 31% of the total number of new classical scrapie and atypical scrapie infections). This is a reflection of the volume of carcase material and Category 1 material flow through such facilities.

Atomic Force Microscopy Characterization of Collagen 'nanostraws' in Human Costal Cartilage Micron (Oxford, England : 1993). Oct, 2012 | Pubmed ID: 23127510 Costal cartilage, a type of hyaline cartilage that bridges the bony ribs and sternum, is relatively understudied compared to the load bearing cartilages. Deformities of costal cartilage can result in deformation of the chest wall, where the sternum is largely pushed toward or away from the spine, pectus excavatum and pectus carinatum, respectively, with each condition having significant clinical impact. In the absence of extensive literature describing morphological features of costal cartilage, we characterized a sample from the costal margin immunohistologically and through atomic force microscopy. We had previously observed the presence of collagen 'nanostraws' running the length of costal cartilage. Hypothesizing that these structures may be responsible for fluid flow within this thick, avascular tissue, and prior to microfluidic analysis, we estimated the diameters and measured Young's modulus of elasticity of the collagen nanostraws. We found significant differences in results between treatment type and fixation. Significant differences in nanostraw elasticity and diameter obviously affect nano-fluidic transport calculations, and therefore, we consider these results of importance to the scientific community relying upon measurements in the nanoscale.

Hydrogen Shuttling: Synthesis and Reactivity of a 14-electron Iridium Complex Featuring a Bis(alkyl) Tethered N-heterocyclic Carbene Ligand Chemical Communications (Cambridge, England). Nov, 2012 | Pubmed ID: 23128505 Solvent dependent double C-H activation in an Ir(NHC)(2) system generates an agostically stabilized 14-electron complex featuring a face-capping bis(alkyl) tethered NHC ligand [NHC = N-heterocyclic carbene]. These activation processes are reversible, and the resulting ligand-derived hydrogen shuttle can be applied to the dehydrogenation of BN-containing substrates.

15-Year Follow-Up of Recurrent "Hypoglycemia" in Preterm Infants Pediatrics. Nov, 2012 | Pubmed ID: 23129080 BACKGROUND:Observational study of 543 infants who weighed

Nurses for Patient-centered Medical Homes Health Affairs (Project Hope). Nov, 2012 | Pubmed ID: 23129693

Fire on an Intensive Care Unit Caused by an Oxygen Cylinder Anaesthesia. Nov, 2012 | Pubmed ID: 23130822

Reconstruction of the Pelvis and Perineum with a Free Latissimus Dorsi Myocutaneous Flap: a Case Report Annals of the Royal College of Surgeons of England. Nov, 2012 | Pubmed ID: 23131218 Reconstruction of the perineum and pelvic cavity in continuity is an uncommon and difficult challenge. This case describes a 66-year-old man who presented following recurrence of a Dukes' B rectosigmoid adenocarcinoma that had been treated nine years previously by anterior resection, 5-fluorouracil and radiotherapy. His recurrent disease was treated with radical pelvic exenteration with formation of an end colostomy and urinary ileal conduit. A post-operative pelvic collection necessitated incisional drainage via the perineum. This resulted in a perineal defect in continuity with the pelvic cavity, neither of which healed in spite of alternate day packing with antiseptic dressings. The perineum and cavity were reconstructed successfully with a microvascular transfer of the latissimus dorsi using the primary gracilis pedicle as recipient donor vessels.

Editorial Current Opinion in Gastroenterology. Nov, 2012 | Pubmed ID: 23132212

Cohort Profile: The Caerphilly Health and Social Needs Electronic Cohort Study (E-CATALyST) International Journal of Epidemiology. Nov, 2012 | Pubmed ID: 23132614 The Caerphilly Health and Social Needs study was established to inform and support collaborative multiagency working on reducing inequalities in health and to investigate neighbourhood influences on mental health. Initially, we collated a robust small-area multiagency dataset of contextual health determinants and outcomes from routine sources and sharing of data between the National Health Service and Caerphilly county borough council. These data were widely used in local joint planning to improve health and reduce health inequalities. Secondly, we carried out a baseline population questionnaire survey, collecting data from 10 892 (60.6%) respondents aged 18-74 years on a wide range of socio-economic, lifestyle, health and housing factors and perceptions of the local neighbourhood, including access to services, social cohesion and neighbourhood quality. We carried out wave 2 of the survey after 7 years with responses from 4558 (50.2%) participants to the same range of questions. We developed the study into an electronic cohort, linking all 17 979 sampled participants aged 18-74 years to mortality and hospital admission records with 10-year follow-up and full recording of migration both within and out of the borough. Readers with an interest in collaborative use of the data should contact Professor David Fone, Principal Investigator.

A Proposed Modification to the McDonald 2010 Criteria for the Diagnosis of Primary Progressive Multiple Sclerosis Multiple Sclerosis (Houndmills, Basingstoke, England). Nov, 2012 | Pubmed ID: 23132903 BACKGROUND: The diagnostic criteria for primary-progressive multiple sclerosis (PPMS) have undergone revision over the last 20 years. Cerebrospinal fluid oligoclonal bands (CSFOBs) have received less emphasis in recent revisions of the McDonald criteria. The aim of this study was to examine the sensitivity of the diagnostic criteria for PPMS with particular reference to spinal cord criteria and examine the utility of CSFOBs in a cohort of PPMS patients. METHODS: All new PPMS diagnoses between 1990 and 2011 were identified. Baseline clinical details and paraclinical evaluations including MRI of the brain, spinal cord, CSF and visually evoked responses (VERs) were assessed. The proportion of patients who met the requirements for diagnosis of PPMS on the basis of Thompson's and the McDonald Criteria (2001, 2005, 2010) were determined. RESULTS: There were 88/95 PPMS patients who had at least two diagnostic investigations. The sensitivity of Thompson's and the McDonald 2001 criteria was 64%; the McDonald 2010 revisions gave the highest sensitivity (77%); the McDonald 2005 criteria had intermediate sensitivity (74%). The combination of CSFOBs and MRI of the brain yielded the greatest number of patients demonstrating dissemination in space (DIS) on only two investigations. VERs did not aid diagnosis. Reducing requirements for the number of spinal cord lesions (symptomatic or not) to one increased diagnostic sensitivity to 84%. CONCLUSION: An alternative criterion requiring two of: i) MRI of the brain with one or more lesions in two of three regions typical for demyelination; ii) the presence of one T2-weighted spinal cord plaque (typical for demyelination); iii) CSFOBs; would increase the diagnostic sensitivity for PPMS.

Comparative Genomics Suggests an Independent Origin of Cytoplasmic Incompatibility in Cardinium Hertigii PLoS Genetics. Oct, 2012 | Pubmed ID: 23133394 Terrestrial arthropods are commonly infected with maternally inherited bacterial symbionts that cause cytoplasmic incompatibility (CI). In CI, the outcome of crosses between symbiont-infected males and uninfected females is reproductive failure, increasing the relative fitness of infected females and leading to spread of the symbiont in the host population. CI symbionts have profound impacts on host genetic structure and ecology and may lead to speciation and the rapid evolution of sex determination systems. Cardinium hertigii, a member of the Bacteroidetes and symbiont of the parasitic wasp Encarsia pergandiella, is the only known bacterium other than the Alphaproteobacteria Wolbachia to cause CI. Here we report the genome sequence of Cardinium hertigii cEper1. Comparison with the genomes of CI-inducing Wolbachia pipientis strains wMel, wRi, and wPip provides a unique opportunity to pinpoint shared proteins mediating host cell interaction, including some candidate proteins for CI that have not previously been investigated. The genome of Cardinium lacks all major biosynthetic pathways but harbors a complete biotin biosynthesis pathway, suggesting a potential role for Cardinium in host nutrition. Cardinium lacks known protein secretion systems but encodes a putative phage-derived secretion system distantly related to the antifeeding prophage of the entomopathogen Serratia entomophila. Lastly, while Cardinium and Wolbachia genomes show only a functional overlap of proteins, they show no evidence of laterally transferred elements that would suggest common ancestry of CI in both lineages. Instead, comparative genomics suggests an independent evolution of CI in Cardinium and Wolbachia and provides a novel context for understanding the mechanistic basis of CI.

Conditional Requirement for Exopolysaccharide in the Mesorhizobium-Lotus Symbiosis Molecular Plant-microbe Interactions : MPMI. Nov, 2012 | Pubmed ID: 23134480 Rhizobial surface polysaccharides are required for nodule formation on the roots of at least some legumes but the mechanism(s) by which they act are yet to be determined. As a first step to investigate the function of exopolysaccharide (EPS) in the formation of determinate nodules, we isolated Mesorhizobium loti mutants affected in various steps of EPS biosynthesis and characterised their symbiotic phenotypes on two Lotus species. The wild-type M. loti strain R7A produced both high-molecular-weight EPS and lower-molecular-weight (LMW) polysaccharide fractions whilst most mutant strains produced only LMW fractions. Mutants affected in predicted early biosynthetic steps (e.g. exoB) formed nitrogen-fixing nodules on L. corniculatus and L. japonicus cv. Gifu, whereas mutants affected in mid/late biosynthetic steps (e.g. exoU) induced uninfected nodule primordia, and occasionally a few infected nodules following a lengthy delay. These mutants were disrupted at the stage of infection thread (IT) development. Symbiotically-defective EPS and Nod factor mutants functionally complemented each other in co-inoculation experiments. The majority of full-length ITs observed harbored only the EPS mutant strain and did not show bacterial release, whereas the nitrogen-fixing nodules contained both mutants. Examination of the symbiotic proficiency of the exoU mutant on various L. japonicus ecotypes revealed both host and environmental factors were linked to the requirement for EPS. These results reveal a complex function for M. loti EPS in determinate nodule formation and suggest that EPS plays a signalling role at both the stages of IT initiation and bacterial release.

The Crossover Sign Overestimates Acetabular Retroversion Clinical Orthopaedics and Related Research. Nov, 2012 | Pubmed ID: 23136058 BACKGROUND: The crossover sign is a radiographic finding associated with cranial acetabular retroversion and has been associated with pincer-type femoroacetabular impingement (FAI) in patients with hip pain. Variable morphology, location, and size of the anterior inferior iliac spine (AIIS) may contribute to the crossover sign even in the absence of retroversion. Thus, the sign may overestimate the incidence of acetabular retroversion. QUESTIONS/PURPOSES: We asked: Can the crossover sign appear on standardized, well-positioned AP pelvis radiographs despite the absence of acetabular retroversion? And what is the contribution of variable size and morphology of the AIIS to a crossover sign? METHODS: We evaluated radiographs of 53 patients with symptomatic FAI in the absence of substantial chondral degenerative changes (Â 0.8) was found for AIIS types. CONCLUSIONS: A crossover sign is frequently present on well-positioned AP pelvis radiographs in the absence of acetabular retroversion. Variable AIIS morphology may explain the appearance of this sign in the presence or absence of acetabular retroversion. LEVEL OF EVIDENCE: Level III, diagnostic study. See Instructions for Authors for a complete description of levels of evidence.

The Association Between Unintended Pregnancy and Violence Among Incarcerated Men and Women Journal of Community Health Nursing. Oct, 2012 | Pubmed ID: 23136860 Background: In this article, we examine the association between unintended pregnancy and individual and community level indicators of violence in a population of both women and men in the criminal justice system. Methods: We conducted a cross-sectional survey with 290 women and 306 men in 3 correctional facilities in Kansas City and used logistic regression models to assess relationships between key independent variables and unintended pregnancy. Findings: In gender-specific logistic regression models, women with a history of intimate partner violence were 2.02 times more likely (CI 1.15, 3.56), and those with a history of sexual abuse before age 16 were 1.23 times more likely (CI 1.02-1.49) to have experienced unintended pregnancy. Men or their family members who were victimized by neighborhood violence were 1.82 times more likely to have experienced unintended pregnancy (CI 1.01, 3.28). Discussion: These findings suggest the need for gender and community-specific interventions that address the relationship between violence and unintended pregnancy.

Health Status of Migrant Farmworkers in the Shenandoah Valley Journal of Community Health Nursing. Oct, 2012 | Pubmed ID: 23136861 The purpose of this study is to describe the characteristics and health status of a sample of migrant farmworkers in the Shenandoah Valley. The methodology for this study is a retrospective record review and analysis of data on 390 male migrant farmworkers. The group included men from Mexico (57. 2%), Jamaica (26. 9%), and Haiti (13. 0%) with a mean age of 38.5 years. The most common health problems reported were work-related and included musculoskeletal pain, irritated eyes, and respiratory symptoms. This study identifies areas for community and public health nurses to target interventions to address health promotion/disease prevention efforts.

The Effect of Copper(ii), Iron(ii) Sulphate, and Vitamin C Combinations on the Weak Antimicrobial Activity of (+)-catechin Against Staphylococcus Aureus and Other Microbes Metallomics : Integrated Biometal Science. Nov, 2012 | Pubmed ID: 23138340 Few attempts have been made to improve the activity of plant compounds with low antimicrobial efficacy. (+)-Catechin, a weak antimicrobial tea flavanol, was combined with putative adjuncts and tested against different species of bacteria. Copper(ii) sulphate enhanced (+)-catechin activity against Pseudomonas aeruginosa but not Staphylococcus aureus, Proteus mirabilis or Escherichia coli. Attempts to raise the activity of (+)-catechin against two unresponsive species, S. aureus and E. coli, with iron(ii) sulphate, iron(iii) chloride, and vitamin C, showed that iron(ii) enhanced (+)-catechin against S. aureus, but not E. coli; neither iron(iii) nor combined iron(ii) and copper(ii), enhanced (+)-catechin activity against either species. Vitamin C enhanced copper(ii) containing combinations against both species in the absence of iron(ii). Catalase or EDTA added to active samples removed viability effects suggesting that active mixtures had produced H(2)O(2)via the action of added metal(ii) ions. H(2)O(2) generation by (+)-catechin plus copper(ii) mixtures and copper(ii) alone could account for the principal effect of bacterial growth inhibition following 30 minute exposures as well as the antimicrobial effect of (+)-catechin-iron(ii) against S. aureus. These novel findings about a weak antimicrobial flavanol contrast with previous knowledge of more active flavanols with transition metal combinations. Weak antimicrobial compounds like (+)-catechin within enhancement mixtures may therefore be used as efficacious agents. (+)-Catechin may provide a means of lowering copper(ii) or iron(ii) contents in certain crop protection and other products.

Antimicrobial Activity of Nanocomposite Zirconium Nitride/silver Coatings to Combat External Bone Fixation Pin Infections The International Journal of Artificial Organs. Nov, 2012 | Pubmed ID: 23138705 During external fixation, temporary implants are used to penetrate the skin, muscle and bone to support severely fractured bones. This creates a biologically critical interface at the site of entry, which potentially allows a risk of infection. The aim of this study, therefore, was to investigate potential antimicrobial nanocomposites to combat infection. Magnetron sputtering was used to produce zirconium nitride/silver nanocomposite coatings, which were prepared at two different silver concentrations of 15.5 at.% and 29.8 at.%. These coatings were characterized for morphology, chemical composition, and antimicrobial activity in comparison to pure zirconium nitride and stainless steel. Staphylococcus aureus and Staphylococcus epidermidis were used as in vitro test organisms in a range of antimicrobial assays; retention of the bacteria on the surfaces and their survival using LiveDeadâ„¢ staining; the use of a metabolic redox dye to indicate a contact kill and zone of inhibition assays to indicate leaching of inhibitory silver ions. Antimicrobial tests demonstrated a significant kill when the bacterial cells came in contact with the coatings containing silver at both 15.5 at.% and 29.8 at.%. No inhibitory leaching from the surfaces occurred. These surfaces demonstrate potential for use as antimicrobial fixation pin coatings.

Identifying Older People at High Risk of Future Falls: Development and Validation of a Screening Tool for Use in Emergency Departments Emergency Medicine Journal : EMJ. Nov, 2012 | Pubmed ID: 23139096 BACKGROUND: Hospital emergency departments (EDs) treat a high proportion of older people, many as a direct consequence of falling. OBJECTIVE: To develop and externally validate a fall risk screening tool for use in hospital EDs and to compare the tool's predictive ability to existing screening tools. METHODS: This prospective cohort study involved two hospital EDs in Sydney, Australia. Potential participants were people aged 70+ years who presented to the ED after falling or with a history of 2+ falls in the previous year and were subsequently discharged. 219 people participated in the tool development study and 178 people participated in the external validation study. Study measures included number of fallers during the 6-month follow-up period, and physical status, medical history, fall history and community service use. RESULTS: 31% and 35% of participants fell in the development and external validation samples, respectively. The developed two-item screening tool included: 2+ falls in the past year (OR 4.18, 95% CI 2.61 to 6.68) and taking 6+ medications (OR 1.89, CI 1.18 to 3.04). The area under the receiver operating characteristic curve (AUC) was 0.70 (0.64-0.76). This represents significantly better predictive ability than the measure of 2+ previous falls alone (AUC 0.67, 0.62-0.72, p=0.02) and similar predictive ability to the FROP-Com (AUC 0.73, 0.67-0.79, p=0.25) and PROFET screens (AUC 0.70, 0.62-0.78, p=0.5). CONCLUSIONS: A simple, two-item screening tool demonstrated good external validity and accurately discriminated between fallers and non-fallers. This tool could identify high risk individuals who may benefit from onward referral or intervention after ED discharge.

Cardiorenal Syndrome: the Emerging Role of Protein-bound Uremic Toxins Circulation Research. Nov, 2012 | Pubmed ID: 23139286 Cardiorenal syndrome is a condition in which a complex interrelationship between cardiac dysfunction and renal dysfunction exists. Despite advances in treatment of both cardiovascular and kidney disease, cardiorenal syndrome remains a major global health problem. Characteristic of the pathophysiology of cardiorenal syndrome is bidirectional cross-talk; mediators/substances activated by the disease state of 1 organ can play a role in worsening dysfunction of the other by exerting their biologically harmful effects, leading to the progression of the syndrome. Accumulation of uremic toxins is a hallmark of renal excretory dysfunction. Removal of some toxins by conventional dialysis is particularly problematic because of their high protein binding. In this review, we demonstrate that protein-bound uremic toxins may play an important role in progression of cardiovascular disease in the setting of chronic kidney disease. The highly protein-bound uremic toxin indoxyl sulfate has emerged as a potent toxin adversely affecting both the kidney and heart. Direct cardiac effects of this toxin have been recently demonstrated both in vitro and in vivo. Specifically, potent fibrogenic and prohypertrophic effects, as well as oxidative stress-inducing effects, appear to play a central role in both renal and cardiac pathology. Many of these adverse effects can be suppressed by use of a gut adsorbent, AST-120. Potential mechanisms underlying indoxyl sulfate-induced cardiorenal fibrosis are discussed. Future research and clinical implications conclude this review.

Primary Prevention of Pediatric Abusive Head Trauma: A Cost Audit and Cost-utility Analysis Child Abuse & Neglect. Nov, 2012 | Pubmed ID: 23141137 OBJECTIVES: To obtain comprehensive, reliable data on the direct cost of pediatric abusive head trauma in New Zealand, and to use this data to evaluate the possible cost-benefit of a national primary prevention program. METHODS: A 5 year cohort of infants with abusive head trauma admitted to hospital in Auckland, New Zealand was reviewed. We determined the direct costs of hospital care (from hospital and Ministry of Health financial records), community rehabilitation (from the Accident Compensation Corporation), special education (from the Ministry of Education), investigation and child protection (from the Police and Child Protective Services), criminal trials (from the Police, prosecution and defence), punishment of offenders (from the Department of Corrections) and life-time care for moderate or severe disability (from the Accident Compensation Corporation). Analysis of the possible cost-utility of a national primary prevention program was undertaken, using the costs established in our cohort, recent New Zealand national data on the incidence of pediatric abusive head trauma, international data on quality of life after head trauma, and published international literature on prevention programs. RESULTS: There were 52 cases of abusive head trauma in the sample. Hospital costs totaled $NZ2,433,340, child protection $NZ1,560,123, police investigation $NZ1,842,237, criminal trials $NZ3,214,020, punishment of offenders $NZ4,411,852 and community rehabilitation $NZ2,895,848. Projected education costs for disabled survivors were $NZ2,452,148, and the cost of projected lifetime care was $NZ33,624,297. Total costs were $NZ52,433,864, averaging $NZ1,008,344 per child. Cost-utility analysis resulted in a strongly positive economic argument for primary prevention, with expected case scenarios showing lowered net costs with improved health outcomes. CONCLUSIONS: Pediatric abusive head trauma is very expensive, and on a conservative estimate the costs of acute hospitalization represent no more than 4% of lifetime direct costs. If shaken baby prevention programs are effective, there is likely to be a strong economic argument for their implementation. This study also provides robust data for future cost-benefit analysis in the field of abusive head trauma prevention.

Hsp104 Gives Clients the Individual Attention They Need Cell. Nov, 2012 | Pubmed ID: 23141530 Yeast heat shock protein 104 (Hsp104), the only known eukaryotic disaggregase, remodels both disordered protein aggregates and cross-Î² sheet amyloids. To handle this diverse clientele, DeSantis etÂ al. report that Hsp104 hexamers use distinct mechanisms-individual subunits are able to dissolve disordered aggregates, but global subunit cooperativity is required to untangle amyloids.

An Improved Quantitative Method to Assess Adhesive Properties of Trichomonas Vaginalis to Host Vaginal Ectocervical Cells Using Flow Cytometry Journal of Microbiological Methods. Nov, 2012 | Pubmed ID: 23142340 Microbial adhesion is a critical step for infection and colonization of the host. Trichomonas vaginalis, a human urogenital extracellular parasite, relies on host cell adhesion for infection and pathogenesis. Although host cell adhesion of T. vaginalis is strain-dependent and it may be influenced by many environmental factors, a technical limitation to quantify T. vaginalis adhesion falls upon a laborious and time-consuming protocol of fluorescent microscopy. This technical limitation reduces the ability of screening multiple parameters or detecting multiple cell types simultaneously. Here we tested the capability of using flow cytometry as a qualitative and quantitative method to measure adhesion of this human infectious microorganism to vaginal ectocervical cells. Various strains of T. vaginalis with different adhesion properties were stained with CellTracker Orange (CMTMR) prior to incubation with host cells. Analyses by flow cytometry revealed that adhered CMTMR-stained parasites were clearly distinguishable from the host cells and also enabled absolute cell counts to be determined. This method was validated with the comparison of parasite strains that display variable degrees of host cell adhesion. This assay can now be applied to test many variables and environmental factors simultaneously that may affect T. vaginalis adhesion.

LIBER8 Design and Methods: An Integrative Intervention for Loss of Control Eating Among African American and White Adolescent Girls Contemporary Clinical Trials. Nov, 2012 | Pubmed ID: 23142669 Loss of control (LOC) eating affects a significant number of adolescents of all racial and ethnic backgrounds and is associated with numerous psychosocial problems, including depression, anxiety, low self-esteem, body dissatisfaction, and weight concerns. However, empirically validated, culturally sensitive treatments for adolescents with these disordered eating behaviors are not available. This pilot project involved designing a developmentally and culturally appropriate treatment for LOC eating for adolescent girls. We intend to conduct multiple focus groups with adolescent girls who engage in LOC eating, and their primary caregivers. Data from these groups will inform the subsequent creation of a manualized treatment protocol. We will then evaluate the efficacy of this intervention (LIBER8-Linking Individuals Being Emotionally Real) to reduce LOC eating. This intervention will integrate components of dialectical behavior therapy, such as mindfulness and distress tolerance skills training, and cognitive-behavioral therapy. We will also integrate text-messaging, a key adolescent communication strategy, as a means of self-monitoring. Participants meeting study criteria will be offered participation in this 12-week randomized controlled trial comparing LIBER8 to a weight management control condition (2BFit). We hypothesize that this intervention will serve to reduce LOC eating, as well as improve psychosocial functioning as evidenced by decreased depression, anxiety, eating disorder cognitions, emotional eating, impulsivity, and improved quality of life. The feasibility and acceptability of this intervention will be extensively evaluated with the explicit intent of informing a subsequent larger randomized controlled trial.

Community-acquired Neonatal and Infant Sepsis in Developing Countries: Efficacy of WHO's Currently Recommended Antibiotics--systematic Review and Meta-analysis Archives of Disease in Childhood. Nov, 2012 | Pubmed ID: 23142784 OBJECTIVE: To review the aetiology and antibiotic resistance patterns of community-acquired sepsis in developing countries in infants where no clear focus of infection is clinically identified. To estimate the likely efficacy of WHO's recommended treatment for infant sepsis. DESIGN: A systematic review of the literature describing the aetiology of community-acquired neonatal and infant sepsis in developing countries. Using meta-analytical methods, susceptibility was determined to the antibiotic combinations recommended by WHO: (1) benzylpenicillin/ampicillin and gentamicin, (2) chloramphenicol and benzylpenicillin, and (3) third-generation cephalosporins. RESULTS: 19 studies were identified from 13 countries, with over 4000 blood culture isolates. Among neonates, Staphylococcus aureus, Klebsiella spp. and Escherichia coli accounted for 55% (39-70%) of culture positive sepsis on weighted prevalence. In infants outside the neonatal period, the most prevalent pathogens were S aureus, E coli, Klebsiella spp., Streptococcus pneumoniae and Salmonella spp., which accounted for 59% (26-92%) of culture positive sepsis. For neonates, penicillin/gentamicin had comparable in vitro coverage to third-generation cephalosporins (57% vs 56%). In older infants (1-12 months), in vitro susceptibility to penicillin/gentamicin, chloramphenicol/penicillin and third-generation cephalosporins was 63%, 47% and 64%, respectively. CONCLUSIONS: The high rate of community-acquired resistant sepsis-especially that caused by Klebsiella spp. and S aureus-is a serious global public health concern. In vitro susceptibility data suggest that third-generation cephalosporins are not more effective in treating sepsis than the currently recommended antibiotics, benzylpenicillin and gentamicin; however, with either regimen a significant proportion of bacteraemia is not covered. Revised recommendations for effective second-line antibiotics in neonatal and infant sepsis in developing countries are urgently needed.

Noncanonical G Recognition Mediates KSRP Regulation of Let-7 Biogenesis Nature Structural & Molecular Biology. Nov, 2012 | Pubmed ID: 23142982 Let-7 is an important tumor-suppressive microRNA (miRNA) that acts as an on-off switch for cellular differentiation and regulates the expression of a set of human oncogenes. Binding of the human KSRP protein to let-7 miRNA precursors positively regulates their processing to mature let-7, thereby contributing to control of cell proliferation, apoptosis and differentiation. Here we analyze the molecular basis for KSRP-let-7 precursor selectivity and show how the third KH domain of the protein recognizes a G-rich sequence in the pre-let-7 terminal loop and dominates the interaction. The structure of the KH3-RNA complex explains the protein recognition of this noncanonical KH target sequence, and we demonstrate that the specificity of this binding is crucial for the functional interaction between the protein and the miRNA precursor.

Digital Breast Tomosynthesis Versus Supplemental Diagnostic Mammographic Views for Evaluation of Noncalcified Breast Lesions Radiology. Nov, 2012 | Pubmed ID: 23143023 Purpose:To compare the diagnostic performance of breast tomosynthesis versus supplemental mammography views in classification of masses, distortions, and asymmetries.Materials and Methods:Eight radiologists who specialized in breast imaging retrospectively reviewed 217 consecutively accrued lesions by using protocols that were HIPAA compliant and institutional review board approved in 182 patients aged 31-60 years (mean, 50 years) who underwent diagnostic mammography and tomosynthesis. The lesions in the cohort included 33% (72 of 217) cancers and 67% (145 of 217) benign lesions. Eighty-four percent (182 of 217) of the lesions were masses, 11% (25 of 217) were asymmetries, and 5% (10 of 217) were distortions that were initially detected at clinical examination in 8% (17 of 217), at mammography in 80% (173 of 217), at ultrasonography (US) in 11% (25 of 217), or at magnetic resonance imaging in 1% (2 of 217). Histopathologic examination established truth in 191 lesions, US revealed a cyst in 12 lesions, and 14 lesions had a normal follow-up. Each lesion was interpreted once with tomosynthesis and once with supplemental mammographic views; both modes included the mediolateral oblique and craniocaudal views in a fully crossed and balanced design by using a five-category Breast Imaging Reporting and Data System (BI-RADS) assessment and a probability-of-malignancy score. Differences between modes were analyzed with a generalized linear mixed model for BI-RADS-based sensitivity and specificity and with modified Obuchowski-Rockette approach for probability-of-malignancy-based area under the receiver operating characteristic (ROC) curve.Results:Average probability-of-malignancy-based area under the ROC curve was 0.87 for tomosynthesis versus 0.83 for supplemental views (P < .001). With tomosynthesis, the false-positive rate decreased from 85% (989 of 1160) to 74% (864 of 1160) (P < .01) for cases that were rated BI-RADS category 3 or higher and from 57% (663 of 1160) to 48% (559 of 1160) for cases rated BI-RADS category 4 or 5 (P < .01), without a meaningful change in sensitivity. With tomosynthesis, more cancers were classified as BI-RADS category 5 (39% [226 of 576] vs 33% [188 of 576]; P = .017) without a decrease in specificity.Conclusion:Tomosynthesis significantly improved diagnostic accuracy for noncalcified lesions compared with supplemental mammographic views.Â© RSNA, 2012.

A Review of Blood Component Usage in a Large UK Emergency Department After Implementation of Simple Measures Emergency Medicine Journal : EMJ. Nov, 2012 | Pubmed ID: 23144079 OBJECTIVES: To review clinical indications and demographics of transfusion and the patterns of blood component ordering, transfusion, wastage and traceability, before (2007) and after (2011) implementation of simple improvement strategies. METHODS: Retrospective case note review of all patients presenting to the Royal Infirmary of Edinburgh (RIE) Emergency Department (ED) for whom a blood component was requested and historic comparison. Improvement measures implemented between 2007 and 2011 included (1) formal staff education, (2) use of e-learning Module One Safe Transfusion Practice (traceability update, Medicines and Healthcare products Regulatory Agency (MHRA) traceability regulations and importance of returning completed blood component tags), (3) an ED resuscitation room blood fridge, (4) introduction of a dedicated ED transfusion consultant and ED transfusion link nurse and (5) the presence of an ED consultant on the Hospital Transfusion Group. RESULTS: Between 1st January and 31st December 2011, blood components were requested for 255 patient episodes, totalling 1034 individual units. 687 units (66.4%) of blood component were transfused, 248 components (24.0%) were recycled, 90 components (8.7%) were discarded and nine units (0.9%) were unaccounted for. There was a 64% reduction in blood component ordering (3209 vs 1034 units), a 39% reduction in blood component transfusion (1131 vs 687 units) and a 96% reduction in unaccounted units (214 vs 9 units) between 2007 and 2011. There was a rise in the median age of the patient for whom a transfusion request was made from 63.9 years in 2007 to 67.0 years in 2011. CONCLUSIONS: Blood component ordering, usage and traceability within the ED have improved significantly since 2007 following implementation of simple strategies. The age of ED transfusion recipients is increasing.

Suppression of Wnt1-induced Mammary Tumor Growth and Lower Serum Insulin in Offspring Exposed to Maternal Blueberry Diet Suggest Early Dietary Influence on Developmental Programming Carcinogenesis. Nov, 2012 | Pubmed ID: 23144318 Despite the well-accepted notion that early maternal influences persist beyond fetal life and may underlie many adult diseases, the risks imposed by the maternal environment on breast cancer development and underlying biological mechanisms remain poorly understood. In this study, we investigated whether early exposure to blueberry (BB) via maternal diet alters oncogene Wnt1-induced mammary tumorigenesis in offspring. Wnt1-transgenic female mice were exposed to maternal Casein (CAS, control) or blueberry-supplemented (CAS + 3%BB) diets throughout pregnancy and lactation. Offspring were weaned to CAS and mammary tumor development was followed until age 8 months. Tumor incidence and latency were similar for both groups; however, tumor weight at killing and tumor volume within 2 weeks of initial detection were lower (by 50 and 60%, respectively) in offspring of BB- versus control-fed dams. Dietary BB exposure beginning at weaning did not alter mammary tumor parameters. Tumors from maternal BB-exposed offspring showed higher tumor suppressor (Pten and Cdh1) and lower proproliferative (Ccnd1), anti-apoptotic (Bcl2) and proangiogenic (Figf, Flt1 and Ephb4) transcript levels, and displayed attenuated microvessel density. Expression of Pten and Cdh1 genes was also higher in mammary tissues of maternal BB-exposed offspring. Mammary tissues and tumors of maternal BB-exposed offspring showed increased chromatin-modifying enzyme Dnmt1 and Ezh2 transcript levels. Body weight, serum insulin and serum leptin/adiponectin ratio were lower for maternal BB-exposed than control tumor-bearing offspring. Tumor weights and serum insulin were positively correlated. Results suggest that dietary influences on the maternal environment contribute to key developmental programs in the mammary gland to modify breast cancer outcome in adult progeny.

Singing Classes for Chronic Obstructive Pulmonary Disease: a Randomized Controlled Trial BMC Pulmonary Medicine. Nov, 2012 | Pubmed ID: 23145504 ABSTRACT: BACKGROUND: There is some evidence that singing lessons may be of benefit to patients with chronic obstructive pulmonary disease (COPD). It is not clear how much of this benefit is specific to singing and how much relates to the classes being a group activity that addresses social isolation. METHODS: Patients were randomised to either singing classes or a film club for eight weeks. Response was assessed quantitatively through health status questionnaires, measures of breathing control, exercise capacity and physical activity and qualitatively, through structured interviews with a clinical psychologist. RESULTS: The singing group (n=13 mean(SD) FEV1 44.4(14.4)%predicted) and film group (n=11 FEV1 63.5(25.5)%predicted) did not differ significantly at baseline. There was a significant difference between the response of the physical component score of the SF-36, favouring the singing group +12.9(19.0) vs -0.25(11.9) (p=0.02), but no difference in response of the mental component score of the SF-36, breathing control measures, exercise capacity or daily physical activity. In the qualitative element, positive effects on physical well-being were reported in the singing group but not the film group. CONCLUSION: Singing classes have an impact on health status distinct from that achieved simply by taking part in a group activity.Trials registrationRegistration Current Controlled Trials - ISRCTN17544114.

No Prognostic Impact of P2RY8-CRLF2 Fusion in Intermediate Cytogenetic Risk Childhood B-cell Acute Lymphoblastic Leukaemia British Journal of Haematology. Nov, 2012 | Pubmed ID: 23145900

Academic Dishonesty and Ethical Reasoning: Pharmacy and Medical School Students in New Zealand Medical Teacher. Nov, 2012 | Pubmed ID: 23146078 Background: There is ample evidence to suggest that academic dishonesty remains an area of concern and interest for academic and professional bodies. There is also burgeoning research in the area of moral reasoning and its relevance to the teaching of pharmacy and medicine. Aims: To explore the associations between self-reported incidence of academic dishonesty and ethical reasoning in a professional student body. Methods: Responses were elicited from 433 pharmacy and medicine students. A questionnaire eliciting responses about academic dishonesty (copying, cheating, and collusion) and their decisions regarding an ethical dilemma was distributed. Multivariate analysis procedures were conducted. Results: The findings suggested that copying and collusion may be linked to the way students make ethical decisions. Students more likely to suggest unlawful solutions to the ethical dilemma were more likely to disclose engagement in copying information and colluding with other students. Conclusions: These findings imply that students engaging in academic dishonesty may be using different ethical frameworks. Therefore, employing ethical dilemmas would likely create a useful learning framework for identifying students employing dishonest strategies when coping with their studies. Increasing understanding through dialog about engagement in academic honesty will likely construct positive learning outcomes in the university with implications for future practice.

Pancreatitis As a Complication of Aspirin Desensitization for Aspirin-exacerbated Respiratory Disease The Journal of Allergy and Clinical Immunology. Nov, 2012 | Pubmed ID: 23146377

The Association Between Early Life and Adult Body Mass Index and Physical Activity with Risk of Non-Hodgkin Lymphoma: Impact of Gender Annals of Epidemiology. Nov, 2012 | Pubmed ID: 23146413 PURPOSE: To evaluate the association of body mass index (BMI) and physical activity (PA) during adulthood and at the age of 18 years with risk of non-Hodgkin lymphoma (NHL). METHODS: We enrolled 950 newly diagnosed NHL patients and 1146 frequency-matched clinic-based controls. Height, weight, and PA (recent adult and at the age of 18 years) were self-reported. Odds ratios (ORs), 95% confidence intervals, and tests for trend were estimated using unconditional logistic regression adjusted for age, gender, and residence. RESULTS: BMI at the age of 18 years was associated with an increased NHL risk (OR, 1.38 for highest vs. lowest quartile; p-trendÂ = .0012), which on stratified analysis was specific to females (OR, 1.90; p-trendÂ = .00025). There was no association of adult BMI with NHL risk. Higher PA in adulthood (OR, 1.03; p-trendÂ = .85) or at the age of 18 years (OR, 0.88; 95% confidence interval, 0.72-1.07) was not associated with risk, but there was an inverse association for adult PA that was specific to females (OR, 0.71; p-trendÂ = .039). Only BMI at the age of 18 years remained significantly associated with NHL risk when modeled together with PA in adulthood or at the age of 18 years. There was little evidence for heterogeneity in these results for the common NHL subtypes. CONCLUSIONS: Early adult BMI may be of greatest relevance to NHL risk, particularly in females.

Cannabis Withdrawal in Chronic Cannabis Users with Schizophrenia Journal of Psychiatric Research. Nov, 2012 | Pubmed ID: 23146560 BACKGROUND: Chronic users of cannabis often report withdrawal symptoms after abstinence from use, but little is known about cannabis withdrawal in people with schizophrenia. METHODS: Cannabis use patterns and withdrawal symptoms in adults with schizophrenia who had at least weekly cannabis use before attempting to quit without formal treatment were assessed with the Marijuana Quit Questionnaire (MJQQ), a 176-item, semi-structured questionnaire. RESULTS: 120 participants, predominantly African-American (62.5%) and male (76.7%), met inclusion criteria. 20.1% reported that their first regular cannabis use (median age 15 years [range 8-48]) preceded their age at first psychotic symptoms (20 [4-50] years). Twenty (16.7%) participants met lifetime criteria for cannabis abuse; 98 (81.7%) met surrogate criteria for lifetime cannabis dependence. Withdrawal symptoms were reported by 113 (94.2%) participants, with 74.2% reporting â‰¥4 symptoms. The most frequently reported withdrawal symptoms were craving for cannabis (59.2%), feeling anxious (52.57%), feeling bored (47.5%), feeling sad or depressed (45.8%), feeling irritable or jumpy (45.0%), feeling restless (43.3%), and trouble failing asleep (33.3%). One hundred-and-four (92.0%) participants took some action to relieve at least one of their withdrawal symptoms during their index-quit attempt, including 26 (23.0%) participants who reported resuming cannabis use. CONCLUSION: Cannabis withdrawal is a clinically significant feature of cannabis use among people with schizophrenia, may serve as a negative reinforcer for relapse, and deserves greater attention in treatment and research. Clinical Trials registration NCT00679016.

Patterns of Structural Head Injury in Children Younger Than 3 Years: A 10-year Review of 519 Patients The Journal of Trauma and Acute Care Surgery. Nov, 2012 | Pubmed ID: 23147184 BACKGROUND: Abusive head injury is a major contributor to morbidity and mortality in infants and toddlers, but data comparing patterns of injury in corroborated accidental trauma and confessed child abuse are scarce. METHODS: This is a retrospective review of head injuries with abnormal neuroimaging in children younger than 3 years during a 10-year period in Auckland, New Zealand. Histories were assumed to be true. Results were analyzed for incongruity then compared with data on confessed abuse and corroborated accidental injury. RESULTS: Five hundred nineteen cases were analyzed. Most cases were congruent with the history, and their pattern was consistent with the literature on accidental head trauma in childhood. However, a spike of subdural hemorrhage was seen in the first 6 months of life, explained neither by mechanism nor by published data on birth trauma. The age distribution of retinal hemorrhage was also inconsistent with published data on birth trauma. In infants younger than 6 months, retinal and subdural hemorrhages were associated with the absence of a history of trauma. In older children (6 months-3 years), subdural hemorrhage was more common after minor falls (2 m, 20%) (p = 0.002). CONCLUSION: We conclude that when a young child (particularly an infant younger than 6 months) presents with traumatic intracranial pathology and either no history of trauma or a history of a minor fall, it must be seriously considered that the history is false. LEVEL OF EVIDENCE: Observational study, case series, level III.

Locked Intramedullary Nailing in the Treatment of Femoral Shaft Fractures in Children Younger Than 12 Years of Age: Indications and Preliminary Report of Outcomes Journal of Pediatric Orthopedics. Dec, 2012 | Pubmed ID: 23147619 : Although flexible intramedullary nailing is a popular treatment option for femoral shaft fractures in juvenile and young adolescent patients, it may not be appropriate in some patients because of patient size and/or fracture configuration.

Thalamic Shape and Connectivity Abnormalities in Children with Attention Deficit/hyperactivity Disorder Psychiatry Research. Nov, 2012 | Pubmed ID: 23149038 Attention-deficit/hyperactivity disorder (ADHD) is characterized by widespread structural and functional abnormalities in the cortico-striato-thalmo-cortical (CSTC) loops that subserve attention and executive functions. In this study, we analyzed thalamic shape and its white matter connections using structural MRI and diffusion tensor imaging (DTI) data acquired from children with ADHD (n=19) and controls (n=19). Shape morphology of the thalamus was assessed using shape-based analysis, while connectivity between the thalamus and other brain regions was determined using probabilistic diffusion tractography. Shape-based analysis indicated significant regional atrophy in the left thalamus in children with ADHD compared to controls. Group analyses of white matter connectivity measures showed significantly decreased mean fractional anisotropy (FA) and volume of the tracts between thalamus and striatum, hippocampus, and prefrontal lobe in children with ADHD compared to controls. The structural abnormalities within the thalamus and the reduced integrity of the white matter tracks between thalamus and other brain regions, as shown from the results of this study, may be the anatomical bases of the impaired cognitive performances in the attention and executive function domains in ADHD.

The Application of Plastic Compression to Modulate Fibrin Hydrogel Mechanical Properties Journal of the Mechanical Behavior of Biomedical Materials. Oct, 2012 | Pubmed ID: 23149099 The inherent biocompatibility of fibrin hydrogels makes them an attractive material for use in a wide range of tissue engineering applications. Despite this, their relatively low stiffness and high compliance limits their potential for certain orthopaedic applications. Enhanced mechanical properties are desirable so as to withstand surgical handling and in vivo loading after implantation and additionally, can provide important cues to cells seeded within the hydrogel. Standard methods used to enhance the mechanical properties of biological scaffolds such as chemical or thermal crosslinking cannot be used with fibrin hydrogels as cell seeding and gel formation occurs simultaneously. The objective of this study was to investigate the use of plastic compression as a means to improve the mechanical properties of chondrocyte-seeded fibrin hydrogels and to determine the influence of such compression on cell viability within these constructs. It was found that the application of 80% strain to fibrin hydrogels for 30min (which resulted in a permanent strain of 47.4%) produced a 2.1-fold increase in the subsequent compressive modulus. Additionally, chondrocyte viability was maintained in the plastically compressed gels with significant cellular proliferation and extracellular matrix accumulation observed over 28 days of culture. In conclusion, plastic compression can be used to modulate the density and mechanical properties of cell-seeded fibrin hydrogels and represents a useful tool for both in theatre and in vitro tissue engineering applications.

'Every Pregnant Woman Needs a Midwife'-The Experiences of HIV Affected Women in Maternity Care Midwifery. Nov, 2012 | Pubmed ID: 23149240 TITLE: 'Every pregnant woman needs a midwife'-the experiences of HIV affected women in Northern Ireland. OBJECTIVE: to explore HIV positive women's experiences of pregnancy and maternity care, with a focus on their interactions with midwives. DESIGN: a prospective qualitative study. SETTING: regional HIV unit in Northern Ireland. PARTICIPANTS: 22 interviews were conducted with 10 women at different stages of their reproductive trajectories. FINDINGS: the pervasive presence of HIV related stigma threatened the women's experience of pregnancy and care. The key staff attributes that facilitated a positive experience were knowledge and experience, empathy and understanding of their unique needs and continuity of care. KEY CONCLUSIONS: pregnancy in the context of HIV, whilst offering a much needed sense of normality, also increases woman's sense of anxiety and vulnerability and therefore the need for supportive interventions that affirm normality is intensified. A maternity team approach, with a focus on providing 'balanced care' could meet all of the woman and child's medical needs, whilst also emphasising the normalcy of pregnancy.

Novel Checkpoint Pathway Organization Promotes Genome Stability in Stationary Phase Yeast Cells Molecular and Cellular Biology. Nov, 2012 | Pubmed ID: 23149941 Most DNA alterations occur during DNA replication in S phase of the cell cycle. However, the majority of eukaryotic cells exist in a non-dividing, quiescent state. Little is known about the factors involved in preventing DNA instability within this stationary-phase cell population. Previously, we utilized a unique assay system to identify mutations that increased minisatellite alterations specifically in quiescent cells in Saccharomyces cerevisiae. Here, we conducted a modified version of the Synthetic Genetic Array analysis to determine if checkpoint signaling components play a role in stabilizing minisatellites in stationary phase yeast cells. Our results revealed that a subset of checkpoint components, specifically MRC1, CSM3, TOF1, DDC1, RAD17, MEC3, TEL1, MEC1 and RAD53, prevent stationary-phase minisatellite alterations within the quiescent cell subpopulation of stationary phase cells. Pathway analysis revealed at least three pathways, with MRC1, CSM3 and TOF1 acting in a pathway independent of MEC1 and RAD53. Overall, our data indicate that some well-characterized checkpoint components maintain minisatellite stability in stationary-phase cells, but are regulated differently in those cells compared to actively growing cells. For the MRC1-dependent pathway, the checkpoint itself may not be the important element, but rather loss of the checkpoint proteins' other functions that contribute to DNA instability.

Axial Spondylectomy and Circumferential Reconstruction Via a Posterior Approach Neurosurgery. Nov, 2012 | Pubmed ID: 23149951 BACKGROUND:: Spinal metastases of the second cervical vertebra are a subset of tumors that is particularly difficult to address surgically. Previously described techniques require highly morbid circumferential dissection posterior to the pharynx for resection and reconstruction. OBJECTIVE:: To perform a biomechanical analysis of instrumented reconstruction configurations used after axial spondylectomy and demonstrate safe use of a novel construct in a patient case report. METHODS:: Several different published and novel reconstruction configurations were inserted into 7 occipitocervical spines that underwent axial spondylectomy. A biomechanical analysis of the constructs' stiffness in flexion and extension, lateral bending, and rotation was performed. A patient then underwent a posterior-only approach for axial spondylectomy and circumferential reconstruction. RESULTS:: Biomechanical analysis of different constructs demonstrated that anterior column reconstruction with bilateral cages spanning C1 lateral mass to C3 facet in combination with occipitocervical instrumentation was superior in flexion-extension and equivalent in lateral bending and rotation to currently used constructs. In the patient in which this construct was placed via a posterior-only approach for axial spondylectomy and instrumentation, the patient remained at neurological baseline and demonstrated no recurrence of local disease or failure of instrumentation to date. CONCLUSION:: When comparing C1 lateral mass to C3 facet bilateral cage plus occipitocervical instrumentation to existing anterior and posterior constructs, this novel reconstruction is biomechanically equivalent if not superior in performance. In a patient, the posterior-only approach for C2 spondylectomy with the novel reconstruction was safe, durable, and avoided the morbidity of the anterior approach.

Hepatic Cyp2d and Cyp26a1 MRNAs and Activities Are Increased During Mouse Pregnancy Drug Metabolism and Disposition: the Biological Fate of Chemicals. Nov, 2012 | Pubmed ID: 23150428 There is considerable evidence that drug disposition is altered during human pregnancy and based on probe drug studies, CYP2D6 activity increases during human pregnancy. The aim of this study was to determine whether the changes of CYP2D6 activity observed during human pregnancy could be replicated in the mouse, and explore possible mechanisms of increased CYP2D6 activity during pregnancy. Cyp2d11, Cyp2d22, Cyp2d26 and Cyp2d40 mRNA was increased (p 0.05) in Cyp2d9 and Cyp2d10 mRNA. In agreement with the increased Cyp2d mRNA, Cyp2d-mediated dextrorphan formation from dextromethorphan was increased 2.7-fold (p

Bacteria of the Human Gut Microbiome Catabolize Red Seaweed Glycans with Carbohydrate-active Enzyme Updates from Extrinsic Microbes Proceedings of the National Academy of Sciences of the United States of America. Nov, 2012 | Pubmed ID: 23150581 Humans host an intestinal population of microbes-collectively referred to as the gut microbiome-which encode the carbohydrate active enzymes, or CAZymes, that are absent from the human genome. These CAZymes help to extract energy from recalcitrant polysaccharides. The question then arises as to if and how the microbiome adapts to new carbohydrate sources when modern humans change eating habits. Recent metagenome analysis of microbiomes from healthy American, Japanese, and Spanish populations identified putative CAZymes obtained by horizontal gene transfer from marine bacteria, which suggested that human gut bacteria evolved to degrade algal carbohydrates-for example, consumed in form of sushi. We approached this hypothesis by studying such a polysaccharide utilization locus (PUL) obtained by horizontal gene transfer by the gut bacterium Bacteroides plebeius. Transcriptomic and growth experiments revealed that the PUL responds to the polysaccharide porphyran from red algae, enabling growth on this carbohydrate but not related substrates like agarose and carrageenan. The X-ray crystallographic and biochemical analysis of two proteins encoded by this PUL, BACPLE_01689 and BACPLE_01693, showed that they are Î²-porphyranases belonging to glycoside hydrolase families 16 and 86, respectively. The product complex of the GH86 at 1.3 Ã… resolution highlights the molecular details of porphyran hydrolysis by this new porphyranase. Combined, these data establish experimental support for the argument that CAZymes and associated genes obtained from extrinsic microbes add new catabolic functions to the human gut microbiome.

A Review of Anti-inflammatory Agents for Symptoms of Schizophrenia Journal of Psychopharmacology (Oxford, England). Nov, 2012 | Pubmed ID: 23151612 Schizophrenia is a chronic debilitating mental disorder that affects about 1% of the US population. The pathophysiology and etiology remain unknown, thus new treatment targets have been challenging and few novel treatments with new mechanisms of action have come to market in the past few decades. Increasing attention has been paid to the role of inflammation in schizophrenia and new data suggests that decreasing inflammation and inflammatory biomarkers may play some role in schizophrenia treatment. This review summarizes the clinical trial literature regarding medications that possess anti-inflammatory properties that have been tested for schizophrenia symptoms and covers such medications as non-steroidal anti-inflammatory agents, such as the cyclo-oxygenase-2 (COX-2) inhibitors and aspirin, omega-3 fatty acids, neurosteroids and minocycline. Overall, there is accumulating evidence, albeit mostly adjunctive treatments, that agents working on inflammatory pathways have some benefits in people with schizophrenia. In the next few years the field will begin to see data on many treatments with anti-inflammatory properties that are currently under study. Hopefully advancements in understanding inflammation and effective treatments having anti-inflammatory properties may help revolutionize our understanding and provide new targets for prevention and treatment in schizophrenia.

In Vivo Tungsten Exposure Alters B Cell Development and Increases DNA Damage in Murine Bone Marrow Toxicological Sciences : an Official Journal of the Society of Toxicology. Nov, 2012 | Pubmed ID: 23152188 High environmental tungsten levels were identified near the site of a childhood pre-B acute lymphoblastic leukemia (preB-ALL) cluster, however a causal link between tungsten and leukemogenesis has not been established. The major site of tungsten deposition is bone, the site of B cell development. In addition, our in vitro data suggest that developing B lymphocytes are susceptible to tungsten-induced DNA damage and growth inhibition. To extend these results, we assessed whether tungsten exposure altered B-cell development and induced DNA damage in vivo. Wild-type mice were exposed to tungsten in their drinking water for up to 16 weeks. Tungsten concentration in bone was analyzed by inductively coupled plasma mass spectrometry (ICP-MS), and correlated with B-cell development and DNA damage within the bone marrow. Tungsten exposure resulted in a rapid deposition within the bone following one week, and continued to accumulate thereafter, albeit at a decreased rate. Flow cytometric analyses revealed a transient increase in mature IgD(+) B-cells in the first 8 weeks of treatment, in animals of the highest and intermediate exposure groups. Following 16 weeks exposure, all tungsten groups had a significantly greater percentage of cells in the late pro/large preB developmental stages. DNA damage was increased in both whole marrow and isolated B-cells, most notably at the lowest tungsten concentration tested. These findings confirm an immunological effect of tungsten exposure, and suggest that tungsten could act as a tumor promoter, providing leukemic "hits" in multiple forms to developing B lymphocytes within the bone marrow.

A Mixed-method Examination of Food Marketing Directed Towards Children in Australian Supermarkets Health Promotion International. Nov, 2012 | Pubmed ID: 23154998 The purpose of this study was to determine the prevalence of children's food requests, and parents' experiences of food marketing directed towards children, in the supermarket environment. A mixed-method design was used. Firstly, intercept interviews were conducted with parents accompanied by a child/children on exiting supermarkets (sampled from a large regional centre in Australia). Parents were asked about the prevalence and types of food requests by child/children during their supermarket visit and whether they purchased these foods. Secondly, focus groups (n = 13) and telephone interviews (n = 3) were conducted exploring parents' experiences of supermarket shopping with children and the impact of child-directed marketing. Of the 158 intercept survey participants (30% response rate), 73% reported a food request during the supermarket visit. Most requested food items (88%) were unhealthy foods, with chocolate/confectionery being the most common food category requested (40%). Most parents (70%) purchased at least one food item requested during the shopping trip. Qualitative interviews identified four themes associated with food requests and prompts in the supermarket: parents' experience of pester power in the supermarket; prompts for food requests in the supermarket; parental responses to pestering in the supermarket environment, and; strategies to manage pestering and minimize requests for food items. Food requests from children are common during supermarket shopping. Despite the majority of the requests being unhealthy, parents often purchase these foods. Parents reported difficulties dealing with constant requests and expressed desire for environmental changes including confectionery-free checkouts, minimization of child friendly product placement and reducing children's exposure to food marketing.

A Pain in the Neck--medical Student Attitudes to the Orthopaedic Spine Irish Medical Journal. Sep, 2012 | Pubmed ID: 23155915 Considerable deficiencies exist in the teaching of Orthopaedic medicine. This study aimed (i) to determine if spinal surgery was the Orthopaedic specialty that students found most difficult, (ii) to appraise attitudes towards teaching of the spine, and (iii) to suggest ways teaching might be improved. A questionnaire on Orthopaedic teaching was given to 238 final year medical students in Ireland. Perceived difficulties with spinal surgery were compared to seven other Orthopaedic sub-specialties. Suggestions made on how to maximise teaching potential included 69 (29%) for more tutorials, 43 (18%) for more lectures, 26 (11%) suggested a more structured training programme and 17 (7%) for increased use of online resources. The spine is one of the least popular Orthopaedic subspecialties and considerable deficiencies exist in its education.

Deep Brain Stimulation in Ireland for Parkinson's Disease and Essential Tremor Irish Medical Journal. Sep, 2012 | Pubmed ID: 23155918 Deep brain stimulation (DBS) is highly effective neurosurgery for idiopathic Parkinson's disease (IPD), essential tremor (ET) and primary dystonia. DBS involves stereotactic surgical implantation of a battery-operated stimulator into deep brain nuclei. Irish patients are referred abroad for DBS and have to travel repeatedly for pre and post-operative care resulting in stress, anxiety and hardship. Safe pre and post-operative care of these complex, ageing patients is compromised by the absence of a DBS service in Ireland. Moreover, both DBS surgery and the subsequent post-operative care abroad incurs substantial cost to the state. The Dublin Neurological Institute at the Mater Misericordiae University Hospital (DNI) is a non-profit institute for the care of patients with neurological diseases. The DNI developed, in collaboration with the Mater Private Hospital (MPH) and the Walton Centre, Liverpool, a DBS programme in 2008/2009. We performed DBS at the Mater Campus on three carefully selected patients from a cohort of movement disorder patients attending the DNI and continue to provide pre-operative assessment and post operative care for patients following DBS in Ireland and abroad.

Legitimacy in Legacy: a Discussion Paper of Historical Scholarship Published in the Journal of Advanced Nursing, 1976-2011 Journal of Advanced Nursing. Nov, 2012 | Pubmed ID: 23157468 AIMS: This paper presents a discussion of historical scholarship published in the Journal of Advanced Nursing. BACKGROUND: The Journal of Advanced Nursing provides a forum for disseminating high-quality research and scholarship. For over 35Â years, scholars have used the Journal of Advanced Nursing to disseminate research into aspects of nursing, including nursing history. DATA SOURCES: The data source was Wiley Online electronic database for the Journal of Advanced Nursing for the period 1976-December 2011. DISCUSSION: Relative to other academic concerns, nursing history represents a topic of limited concern to nursing scholars, as evidenced in published scholarship in the Journal of Advanced Nursing. The trends in historical scholarship in the journal have been on disciplinary development, the place and context of practice, and gendered relationships. While these are legitimate academic concerns, they suggest a lack of attention to clinical practice in historical research, that which confers social legitimacy on the discipline. IMPLICATIONS FOR NURSING: Nursing derives its social legitimacy, in part, through its history, including reliable accounts of the legacy of nursing work in the development of healthcare systems. Disciplinary development in nursing is advanced by giving greater prominence to nursing history in nursing scholarship, including the history of nursing practice CONCLUSIONS: Relative to other academic concerns, nursing scholarship affords little prominence to the topic of nursing history and less still to the history of practice, as evidenced in the outputs of one of nursing's major organs of scholarship. Not to assign due importance to the history of nursing and its practice demonstrates nursing's lack of disciplinary maturity.

Effects of Pregnancy Planning, Fertility, and Assisted Reproductive Treatment on Child Behavioral Problems at 5 and 7 Years: Evidence from the Millennium Cohort Study Fertility and Sterility. Nov, 2012 | Pubmed ID: 23158833 OBJECTIVE: To examine the effects of pregnancy planning, time to conception (TTC), and assisted reproductive technologies (ART) on child behavior. DESIGN: Prospective cohort study. SETTING: Not applicable. PATIENT(S): A total of 12,380 singletons recruited at 9 months and followed-up at 5 and 7 years. Conceptions were divided into "unplanned" (unplanned, unhappy), "mistimed" (unplanned, happy), "planned" (planned, TTC

Hydrogels Derived from Central Nervous System Extracellular Matrix Biomaterials. Nov, 2012 | Pubmed ID: 23158935 Biologic scaffolds composed of extracellular matrix (ECM) are commonly used repair devices in preclinical and clinical settings; however the use of these scaffolds for peripheral and central nervous system (CNS) repair has been limited. Biologic scaffolds developed from brain and spinal cord tissue have recently been described, yet the conformation of the harvested ECM limits therapeutic utility. An injectable CNS-ECM derived hydrogel capable of inÂ vivo polymerization and conformation to irregular lesion geometries may aid in tissue reconstruction efforts following complex neurologic trauma. The objectives of the present study were to develop hydrogel forms of brain and spinal cord ECM and compare the resulting biochemical composition, mechanical properties, and neurotrophic potential of a brain derived cell line to a non-CNS-ECM hydrogel, urinary bladder matrix. Results showed distinct differences between compositions of brain ECM, spinal cord ECM, and urinary bladder matrix. The rheologic modulus of spinal cord ECM hydrogel was greater than that of brain ECM and urinary bladder matrix. All ECMs increased the number of cells expressing neurites, but only brain ECM increased neurite length, suggesting a possible tissue-specific effect. All hydrogels promoted three-dimensional uni- or bi-polar neurite outgrowth following 7 days in culture. These results suggest that CNS-ECM hydrogels may provide supportive scaffolding to promote inÂ vivo axonal repair.

Design of a Phosphorylatable PDZ Domain with Peptide-Specific Affinity Changes Structure (London, England : 1993). Nov, 2012 | Pubmed ID: 23159126 Phosphorylation is one of the most common posttranslational modifications controlling cellular protein activity. Here, we describe a combined computational and experimental strategy to design new phosphorylation sites into globular proteins to regulate their functions. We target a peptide recognition protein, the Erbin PDZ domain, to be phosphorylated by cAMP-dependent protein kinase. Comparing the five successful designs to the unsuccessful cases, we find a trade-off between protein stability and the ability to be modified by phosphorylation. In two designs, Erbin's peptide binding function is modified by phosphorylation, where the presence of the phosphate group destabilizes peptide binding. One of these showed an additional switch in specificity byÂ introducing favorable interactions betweenÂ a designed arginine in the peptide and phosphoserine on the PDZ domain. Because of the diversity of PDZ domains, this opens avenues for the design of related phosphoswitchable domains to createÂ a repertoire of regulatable interaction parts for synthetic biology.

Engineering Osteochondral Constructs Through Spatial Regulation of Endochondral Ossification Acta Biomaterialia. Nov, 2012 | Pubmed ID: 23159563 Chondrogenically primed bone marrow derived mesenchymal stem cells (MSCs) have been shown to become hypertrophic and undergo endochondral ossification when implanted in vivo. Modulating this endochondral phenotype may be an attractive approach to engineering the osseous phase of an osteochondral implant. The objective of this study was to engineer an osteochondral tissue by promoting endochondral ossification in one layer of a bi-layered construct and stable cartilage in the other. The top-half of bi-layered agarose hydrogels were seeded with culture expanded chondrocytes (termed chondral layer) and the bottom half of the bi-layered agarose hydrogels with MSCs (termed osseous layer). Constructs were cultured in a chondrogenic medium for 21 days and thereafter were either maintained in a chondrogenic medium, transferred to a hypertrophic medium, or implanted subcutaneously into nude mice. This structured chondrogenic bi-layered co-culture was found to enhance chondrogenesis in the chondral layer, appearing to help re-establish the chondrogenic phenotype that is lost in chondrocytes during monolayer expansion. Furthermore, the bi-layered co-culture appeared to suppress hypertrophy and mineralisation in the osseous layer. The addition of hypertrophic factors to the media was found to induce mineralisation of the osseous layer in vitro. A similar result was observed in vivo where endochondral ossification was restricted to the osseous layer of the construct leading to the development of an osteochondral tissue. This novel approach represents a potential new treatment strategy for the repair of osteochondral defects.

Scaffold Architecture Determines Chondrocyte Response to Externally Applied Dynamic Compression Biomechanics and Modeling in Mechanobiology. Nov, 2012 | Pubmed ID: 23160843 It remains unclear how specific mechanical signals generated by applied dynamic compression (DC) regulate chondrocyte biosynthetic activity. It has previously been suggested that DC-induced interstitial fluid flow positively impacts cartilage-specific matrix production. Modifying fluid flow within dynamically compressed hydrogels therefore represents a promising approach to controlling chondrocyte behavior, which could potentially be achieved by changing the construct architecture. The objective of this study was to first determine the influence of construct architecture on the mechanical environment within dynamically compressed agarose hydrogels using finite element (FE) modeling and to then investigate how chondrocytes would respond to this altered environment. To modify construct architecture, an array of channels was introduced into the hydrogels. Increased magnitudes of fluid flow were predicted in the periphery of dynamically compressed solid hydrogels and also around the channels in the dynamically compressed channeled hydrogels. DC was found to significantly increase sGAG synthesis in solid constructs, which could be attributed at least in part to an increase in DNA. DC was also found to preferentially increase collagen accumulation in regions of solid and channeled constructs where FE modeling predicted higher levels of fluid flow, suggesting that this stimulus is important for promoting collagen production by chondrocytes embedded in agarose gels. In conclusion, this study demonstrates how the architecture of cell-seeded scaffolds or hydrogels can be modified to alter the spatial levels of biophysical cues throughout the construct, leading to greater collagen accumulation throughout the engineered tissue rather than preferentially in the construct periphery. This system also provides a novel approach to investigate how chondrocytes respond to altered levels of biophysical stimulation.

Metastatic Biomarker Discovery Through Proteomics Cancer Genomics & Proteomics. Nov, 2012 | Pubmed ID: 23162074 Tumor heterogeneity has been a stumbling block in the development of effective cancer treatments. Personalized medicine has evolved with the theory that matching therapies with the unique misregulated pathways often present in tumors will increase patient prognosis. Of particular interest is prediction or determination of the metastatic potential of a tumor. Thus, biomarkers that can predict metastases represent an enormous advance to our understanding over the clinical treatment of cancer. Considerable effort has been expended to characterize the cancer proteome for early detection, however, fewer efforts have been made to develop biomarkers to distinguish the potential for and the nature of metastasis. In this review, we discuss proteomic technologies as well as existing potential metastatic biomarkers for various cancers. In the conclusion, we discuss forward thinking as to what the field needs to enable translation to the clinic.

Mouse Models of PAK Function Cellular Logistics. Apr, 2012 | Pubmed ID: 23162740 p21-activated kinases are a family of highly conserved protein serine/threonine kinases that are increasingly recognized as playing essential roles in a variety of key signaling processes. Genetic analyses in mice, using constitutive or regulated gene disruption, have provided important new insights into PAK function. In this paper, we review the genetic analysis of all six PAK genes in mice. These data address the singular and redundant functions of the various PAK genes and suggest therapeutic possibilities for small molecule PAK inhibitors or activators.

Fire Mosaics and Reptile Conservation in a Fire-Prone Region Conservation Biology : the Journal of the Society for Conservation Biology. Nov, 2012 | Pubmed ID: 23163245 Fire influences the distribution of fauna in terrestrial biomes throughout the world. Use of fire to achieve a mosaic of vegetation in different stages of succession after burning (i.e., patch-mosaic burning) is a dominant conservation practice in many regions. Despite this, knowledge of how the spatial attributes of vegetation mosaics created by fire affect fauna is extremely scarce, and it is unclear what kind of mosaic land managers should aim to achieve. We selected 28 landscapes (each 12.6 km(2) ) that varied in the spatial extent and diversity of vegetation succession after fire in a 104,000 km(2) area in the semiarid region of southeastern Australia. We surveyed for reptiles at 280 sites nested within the 28 landscapes. The landscape-level occurrence of 9 of the 22 species modeled was associated with the spatial extent of vegetation age classes created by fire. Biogeographic context and the extent of a vegetation type influenced 7 and 4 species, respectively. No species were associated with the diversity of vegetation ages within a landscape. Negative relations between reptile occurrence and both extent of recently burned vegetation (â‰¤10 years postfire, n = 6) and long unburned vegetation (>35 years postfire, n = 4) suggested that a coarse-grained mosaic of areas (e.g. >1000 ha) of midsuccessional vegetation (11-35 years postfire) may support the fire-sensitive reptile species we modeled. This age class coincides with a peak in spinifex cover, a keystone structure for reptiles in semiarid and arid Australia. Maintaining over the long term a coarse-grained mosaic of large areas of midsuccessional vegetation in mallee ecosystems will need to be balanced against the short-term negative effects of large fires on many reptile species and a documented preference by species from other taxonomic groups, particularly birds, for older vegetation. Mosaicos de Fuego y la ConservaciÃ³n de Reptiles en una RegiÃ³n Propensa al Fuego.

Larazotide Acetate in Patients with Coeliac Disease Undergoing a Gluten Challenge: a Randomised Placebo-controlled Study Alimentary Pharmacology & Therapeutics. Nov, 2012 | Pubmed ID: 23163616 BACKGROUND: Coeliac disease, an autoimmune disorder triggered by gluten ingestion, is managed by a gluten-free diet (GFD), which is difficult for many patients. Larazotide acetate is a first-in-class oral peptide that prevents tight junction opening, and may reduce gluten uptake and associated sequelae. AIM: To evaluate the efficacy and tolerability of larazotide acetate during gluten challenge. METHODS: This exploratory, double-blind, randomised, placebo-controlled study included 184 patients maintaining a GFD before and during the study. After a GFD run-in, patients were randomised to larazotide acetate (1, 4, or 8Â mg three times daily) or placebo and received 2.7 grams of gluten daily for 6Â weeks. Outcomes included an experimental biomarker of intestinal permeability, the lactulose-to-mannitol (LAMA) ratio and clinical symptoms assessed by Gastrointestinal Symptom Rating Scale (GSRS) and anti-transglutaminase antibody levels. RESULTS: No significant differences in LAMA ratios were observed between larazotide acetate and placebo groups. Larazotide acetate 1-mg limited gluten-induced symptoms measured by GSRS (PÂ =Â 0.002 vs. placebo). Mean ratio of anti-tissue transglutaminase IgA levels over baseline was 19.0 in the placebo group compared with 5.78 (PÂ =Â 0.010), 3.88 (PÂ =Â 0.005) and 7.72 (PÂ =Â 0.025) in the larazotide acetate 1-, 4-, and 8-mg groups, respectively. Adverse event rates were similar between larazotide acetate and placebo groups. CONCLUSIONS: Larazotide acetate reduced gluten-induced immune reactivity and symptoms in patients with coeliac disease undergoing gluten challenge and was generally well tolerated; however, no significant difference in LAMA ratios between larazotide acetate and placebo was observed. Results and design of this exploratory study can inform the design of future studies of pharmacological interventions in patients with coeliac disease.

The Development of a Family Intervention Competency Assessment and Reflection Scale (FICARS) for Psychosis Journal of Psychiatric and Mental Health Nursing. Nov, 2012 | Pubmed ID: 23163778 ACCESSIBLE SUMMARY: Family intervention (FI) has a robust evidence base yet no definitive instrument exists to outline what competences are required during and post FI training. A systematic approach commonly used in health outcomes measurement development identified and ratified components for a Family Intervention Competency Assessment and Reflection Scale (FICARS). FICARS implementation outcomes support the increasing emphasis on continuous learning and reflective practice integral to mental health practitioners' professional practice. ABSTRACT: Family intervention (FI) for psychosis has a robust evidence base. In recommending its use the revised NICE schizophrenia guideline states 'Healthcare professionals providing psychological interventions should have an appropriate level of competence'. Yet, no definitive instrument exists to outline what competences are required during and post FI training or help recruit staff with the appropriate knowledge and skill. This paper reports on the development of a Family Intervention Competency Assessment and Reflection Scale (FICARS). Using a systematic three-staged approach commonly used in health outcomes measurement development, a comprehensive literature review on UK-based FI training and commonly used assessment tools was undertaken. A FICARS draft was then constructed and revised in consultation with expert FI clinicians. Finally, a content validity study with FI trainers and students across three FI training programmes was undertaken to optimize FICARS aim to promote reflective assessment and professional development in FI skills and practice.

Sleep Deprivation Leads to Reduction in Polyp Detection Among Endoscopy Trainees Gastrointestinal Endoscopy. Dec, 2012 | Pubmed ID: 23164518

Expression of the Inflammatory Regulator A20 Correlates with Lung Function in Patients with Cystic Fibrosis Journal of Cystic Fibrosis : Official Journal of the European Cystic Fibrosis Society. Nov, 2012 | Pubmed ID: 23164641 BACKGROUND: A20 and TAX1BP1 interact to negatively regulate NF-ÎºB-driven inflammation. A20 expression is altered in F508del/F508del patients. Here we explore the effect of CFTR and CFTR genotype on A20 and TAX1BP1 expression. The relationship with lung function is also assessed. METHODS: Primary nasal epithelial cells (NECs) from CF patients (F508del/F508del, n=7, R117H/F508del, n=6) and controls (age-matched, n=8), and 16HBE14o- cells were investigated. A20 and TAX1BP1 gene expression was determined by qPCR. RESULTS: Silencing of CFTR reduced basal A20 expression. Following LPS stimulation A20 and TAX1BP1 expression was induced in control NECs and reduced in CF NECs, broadly reflecting the CF genotype: F508del/F508del had lower expression than R117H/F508del. A20, but not TAX1BP1 expression, was proportional to FEV(1) in all CF patients (r=0.968, p

Ribosomally Synthesized and Post-translationally Modified Peptide Natural Products: Overview and Recommendations for a Universal Nomenclature Natural Product Reports. Nov, 2012 | Pubmed ID: 23165928 Covering: 1988 to 2012This review presents recommended nomenclature for the biosynthesis of ribosomally synthesized and post-translationally modified peptides (RiPPs), a rapidly growing class of natural products. The current knowledge regarding the biosynthesis of the >20 distinct compound classes is also reviewed, and commonalities are discussed.

Mitotic Chromosomes Are Compacted Laterally by KIF4 and Condensin and Axially by Topoisomerase IIÎ± The Journal of Cell Biology. Nov, 2012 | Pubmed ID: 23166350 Mitotic chromosome formation involves a relatively minor condensation of the chromatin volume coupled with a dramatic reorganization into the characteristic "X" shape. Here we report results of a detailed morphological analysis, which revealed that chromokinesin KIF4 cooperated in a parallel pathway with condensin complexes to promote the lateral compaction of chromatid arms. In this analysis, KIF4 and condensin were mutually dependent for their dynamic localization on the chromatid axes. Depletion of either caused sister chromatids to expand and compromised the "intrinsic structure" of the chromosomes (defined in an in vitro assay), with loss of condensin showing stronger effects. Simultaneous depletion of KIF4 and condensin caused complete loss of chromosome morphology. In these experiments, topoisomerase IIÎ± contributed to shaping mitotic chromosomes by promoting the shortening of the chromatid axes and apparently acting in opposition to the actions of KIF4 and condensins. These three proteins are major determinants in shaping the characteristic mitotic chromosome morphology.

Effect of Testosterone on Inflammatory Markers in the Development of Early Atherogenesis in the Testicular-Feminized Mouse Model Endocrine Research. Nov, 2012 | Pubmed ID: 23167461 Background. Low levels of serum testosterone in men are associated with cardiovascular disease. Clinical studies show that testosterone replacement therapy (TRT) can improve symptoms of cardiovascular disease and reduce the inflammatory burden evident in atherosclerosis. Aim. We used an in vivo animal model to determine whether testosterone influences mediators of vascular inflammation as part of its beneficial effects on atherogenesis. Methods. Testicular-feminized (Tfm) mice, which express low endogenous testosterone and a non-functional androgen receptor (AR), were used to assess the effect of androgen status on atheroma formation, serum lipids, and inflammatory mediators. Tfm mice were fed a high-cholesterol diet, received saline or physiological (TRT), and were compared to saline-treated XY littermates. Results. A total of 28 weeks of high-cholesterol diet caused fatty streak formation in the aortic root of XY littermates and Tfm mice, an effect significantly amplified in Tfm mice. Tfm mice on normal diet showed elevated serum tumor necrosis factor-Î± (TFN-Î±) and interleukin-6 compared to XY littermates. High-cholesterol diet induced increased monocyte chemoattractant protein-1 (MCP-1) in Tfm mice, and TFN-Î± and MCP-1 in XY littermates. TRT reduced fatty streak formation and serum interleukin-6 in Tfm mice but had no significant effects on lipid profiles. Monocyte/macrophage staining indicated local inflammation in aortic root fatty streak areas of all mice, with TRT reducing local inflammation through plaque reduction in Tfm mice. Fractalkine (CX(3)CL1) and its receptor (CX(3)CR1) were present in fatty streaks of all mice fed a high-cholesterol diet, independent of androgen status. Conclusion. These results are consistent with AR-dependent and AR-independent anti-inflammatory actions of testosterone in atheroprotection, although the local anti-inflammatory mechanisms via which testosterone acts remain unknown.

Experiences of Carers Supporting Dying Renal Patients Managed Without Dialysis Journal of Advanced Nursing. Nov, 2012 | Pubmed ID: 23167619 AIM: To explore the impact of being a family carer to patients with stage 5 chronic kidney disease managed without dialysis. BACKGROUND: Increasing numbers of patients with renal disease worldwide are making the decision not to embark on dialysis. This group has significant physical and psychological symptom burdens similar to or greater than those in advanced cancer patients. Little is known about the impact on family carers. DESIGN: Exploratory, qualitative design. METHODS: The study was undertaken with 19 carers caring for patients managed in a Renal Supportive Care Service in the UK between 2006-2008. Sixty-one semi-structured interviews and detailed field notes inform the analysis. FINDINGS: 'Caring from diagnosis to death' was the overarching theme illustrated by three sub-themes: (i) Caregiver's plight - making sense of the disease and potential deterioration; (ii) Having to care indefinitely; and (iii) Avoiding talk of death. 'Caring from diagnosis to death' coincides with an original concept analysis of renal supportive care, which is considered an adjunct to the management of patients with renal disease at all stages of their illness. CONCLUSION: There is a clear need for further research internationally and theory-based nursing interventions to support carers of patients managed without dialysis. The development of a holistic, integrated care pathway based on carer perspectives, which includes identification of information needs related to original diagnosis, associated comorbidities, treatment options, prognosis, and assistance in developing strategies to manage communication with patients as the end of life approaches, is required.

An International View of How Recent-onset Atrial Fibrillation Is Treated in the Emergency Department Academic Emergency Medicine : Official Journal of the Society for Academic Emergency Medicine. Nov, 2012 | Pubmed ID: 23167856 This study was conducted to determine if there is practice variation for emergency physicians' (EPs) management of recent-onset atrial fibrillation (RAF) in various world regions (Canada, United States, United Kingdom, and Australasia).

Training Neonatal Staff for the Future in Neonatal Palliative Care Seminars in Fetal & Neonatal Medicine. Nov, 2012 | Pubmed ID: 23168299 Neonatal palliative care is an emerging specialty, developing in the context of the significant prevalence of life-limiting and life-threatening conditions amongst the population treated and cared for by neonatologists and neonatal nurses. In this paper we explore the need and provision for training among practitioners in neonatal palliative care to date. We describe several different educational and training programme models with attention to structure, content and impact on participants' knowledge, capacity, competency and confidence in delivering palliative care services suggesting what is needed to ensure the highest standards of care for newborns and babies with life-limiting illness and life-threatening conditions.

Effects of Tic Suppression: Ability to Suppress, Rebound, Negative Reinforcement, and Habituation to the Premonitory Urge Behaviour Research and Therapy. Oct, 2012 | Pubmed ID: 23168328 The comprehensive behavioral intervention for tics (CBIT) represents a safe, effective non-pharmacological treatment for Tourette's disorder that remains underutilized as a treatment option. Contributing factors include the perceived negative consequences of tic suppression and the lack of a means through which suppression results in symptom improvement. Participants (nÂ =Â 12) included youth ages 10-17 years with moderate-to-marked tic severity and noticeable premonitory urges who met Tourette's or chronic tic disorder criteria. Tic frequency and urge rating data were collected during an alternating sequence of tic freely or reinforced tic suppression periods. Even without specific instructions regarding how to suppress tics, youth experienced a significant, robust (72%), stable reduction in tic frequency under extended periods (40Â min) of contingently reinforced tic suppression in contrast to periods of time when tics were ignored. Following periods of prolonged suppression, tic frequency returned to pre-suppression levels. Urge ratings did not show the expected increase during the initial periods of tic suppression, nor a subsequent decline in urge ratings during prolonged, effective tic suppression. Results suggest that environments conducive to tic suppression result in reduced tic frequency without adverse consequences. Additionally, premonitory urges, underrepresented in the literature, may represent an important enduring etiological consideration in the development and maintenance of tic disorders.

Integrated MiRNA, MRNA and Protein Expression Analysis Reveals the Role of Post-transcriptional Regulation in Controlling CHO Cell Growth Rate BMC Genomics. Nov, 2012 | Pubmed ID: 23170974 ABSTRACT: BACKGROUND: To study the role of microRNA (miRNA) in the regulation of Chinese hamster ovary (CHO) cell growth, qPCR, microarray and quantitative LC-MS/MS analysis were utilised for simultaneous expression profiling of miRNA, mRNA and protein. The sample set under investigation consisted of clones with variable cellular growth rates derived from the same population. In addition to providing a systems level perspective on cell growth, the integration of multiple profiling datasets can facilitate the identification of non-seed miRNA targets, complement computational prediction tools and reduce false positive and false negative rates. RESULTS: 51 miRNAs were associated with increased growth rate (35 miRNAs upregulated and 16 miRNAs downregulated). Gene ontology (GO) analysis of genes (n=432) and proteins (n=285) found to be differentially expressed (DE) identified biological processes driving proliferation including mRNA processing and translation. To investigate the influence of miRNA on these processes we combined the proteomic and transcriptomic data into two groups. The first set contained candidates where evidence of translational repression was observed (n=158). The second group was a mixture of proteins and mRNAs where evidence of translational repression was less clear (n=515). The TargetScan algorithm was utilised to predict potential targets within these two groups for anti-correlated DE miRNAs. CONCLUSIONS: The evidence presented in this study indicates that biological processes such as mRNA processing and protein synthesis are correlated with growth rate in CHO cells. Through the integration of expression data from multiple levels of the biological system a number of proteins central to these processes including several hnRNPs and components of the ribosome were found to be post-transcriptionally regulated. We utilised the expression data in conjunction with in-silico tools to identify potential miRNA-mediated regulation of mRNA/proteins involved in CHO cell growth rate. These data have allowed us to prioritise candidates for cell engineering and/or biomarkers relevant to industrial cell culture. We also expect the knowledge gained from this study to be applicable to other fields investigating the role of miRNAs in mammalian cell growth.

Suppression of the SUGAR-DEPENDENT1 Triacylglycerol Lipase Family During Seed Development Enhances Oil Yield in Oilseed Rape (Brassica Napus L.) Plant Biotechnology Journal. Nov, 2012 | Pubmed ID: 23171303 Increasing the productivity of oilseed crops is an important challenge for plant breeders and biotechnologists. To date, attempts to increase oil production in seeds via metabolic pathway engineering have focused on boosting synthetic capacity. However, in the tissues of many organisms, it is well established that oil levels are determined by both anabolism and catabolism. Indeed, the oil content of rapeseed (Brassica napus L.) has been reported to decline by approximately 10% in the final stage of development, as the seeds desiccate. Here, we show that RNAi suppression of the SUGAR-DEPENDENT1 triacylglycerol lipase gene family during seed development results in up to an 8% gain in oil yield on either a seed, plant or unit area basis in the greenhouse, with very little adverse impact on seed vigour. Suppression of lipolysis could therefore constitute a new method for enhancing oil yield in oilseed crops.

Ultrasound-guided Interscalene Block Anesthesia for Shoulder Arthroscopy: a Prospective Study of 1319 Patients The Journal of Bone and Joint Surgery. American Volume. Nov, 2012 | Pubmed ID: 23172321 Ultrasound guidance improves the localization of anesthetic placement during regional anesthesia, but a decreased rate of adverse events has not been demonstrated in the current literature. In this large prospective study, we evaluated the safety, efficacy, and patient satisfaction associated with ultrasound-guided interscalene block.

SAGA Complex Components and Acetate Repression in Aspergillus Nidulans G3 (Bethesda, Md.). Nov, 2012 | Pubmed ID: 23173087 Alongside the well-established carbon catabolite repression by glucose and other sugars, acetate causes repression in Aspergillus nidulans. Mutations in creA, encoding the transcriptional repressor involved in glucose repression, also affect acetate repression, but mutations in creB or creC, encoding components of a deubiquitination system, do not. To understand the effects of acetate, we used a mutational screen that was similar to screens that uncovered mutations in creA, creB, and creC, except that glucose was replaced by acetate to identify mutations that were affected for repression by acetate but not by glucose. We uncovered mutations in acdX, homologous to the yeast SAGA component gene SPT8, which in growth tests showed derepression for acetate repression but not for glucose repression. We also made mutations in sptC, homologous to the yeast SAGA component gene SPT3, which showed a similar phenotype. We found that acetate repression is complex, and analysis of facA mutations (lacking acetyl CoA synthetase) indicates that acetate metabolism is required for repression of some systems (proline metabolism) but not for others (acetamide metabolism). Although plate tests indicated that acdX- and sptC-null mutations led to derepressed alcohol dehydrogenase activity, reverse-transcription quantitative real-time polymerase chain reaction showed no derepression of alcA or aldA but rather elevated induced levels. Our results indicate that acetate repression is due to repression via CreA together with metabolic changes rather than due to an independent regulatory control mechanism.

Procedural Safety in Emergency Care: a Conceptual Model and Recommendations Joint Commission Journal on Quality and Patient Safety / Joint Commission Resources. Nov, 2012 | Pubmed ID: 23173399

Effects of Short-term Dietary Nitrate Supplementation on Blood Pressure, O2 Uptake Kinetics, and Muscle and Cognitive Function in Older Adults American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. Nov, 2012 | Pubmed ID: 23174856 Dietary nitrate (NO(3)(-)) supplementation has been shown to reduce resting blood pressure and alter the physiological response to exercise in young adults. We investigated whether these effects might also be evident in older adults. In a double-blind, randomized, crossover study, twelve healthy, older (60-70 yrs) adults supplemented their diet for three days with either nitrate-rich concentrated beetroot juice (BR; 2 x 70 mlâ€¢d(-1), ~9.6 mmolâ€¢d(-1) NO(3)(-)) or a nitrate-depleted beetroot juice placebo (PL; 2 x70 mlâ€¢d(-1), ~0.01 mmolâ€¢d(-1) NO(3)(-)). Before and after the intervention periods, resting blood pressure and plasma [nitrite] were measured and subjects completed a battery of physiological and cognitive tests. Nitrate supplementation significantly increased plasma [nitrite] and reduced resting systolic (BR:115 Â± 9 vs. PL:120 Â± 6 mmHg; P

SDHA Mutations in Adult and Pediatric Wild-type Gastrointestinal Stromal Tumors Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc. Nov, 2012 | Pubmed ID: 23174939 Most gastrointestinal stromal tumors (GISTs) harbor oncogenic mutations in KIT or platelet-derived growth factor receptor-Î±. However, a small subset of GISTs lacks such mutations and is termed 'wild-type GISTs'. Germline mutation in any of the subunits of succinate dehydrogenase (SDH) predisposes individuals to hereditary paragangliomas and pheochromocytomas. However, germline mutations of the genes encoding SDH subunits A, B, C or D (SDHA, SDHB, SDHC or SDHD; collectively SDHx) are also identified in GISTs. SDHA and SDHB immunohistochemistry are reliable techniques to identify pheochromocytomas and paragangliomas with mutations in SDHA, SDHB, SDHC and SDHD. In this study, we investigated if SDHA immunohistochemistry could also identify SDHA-mutated GISTs. Twenty-four adult wild-type GISTs and nine pediatric/adolescent wild-type GISTs were analyzed with SDHB, and where this was negative, then with SDHA immunohistochemistry. If SDHA immunohistochemistry was negative, sequencing analysis of the entire SDHA coding sequence was performed. All nine pediatric/adolescent GISTs and seven adult wild-type GISTs were negative for SDHB immunohistochemistry. One pediatric GIST and three SDHB-immunonegative adult wild-type GISTs were negative for SDHA immunohistochemistry. In all four SDHA-negative GISTs, a germline SDHA c.91C>T transition was found leading to a nonsense p.Arg31X mutation. Our results demonstrate that SDHA immunohistochemistry on GISTs can identify the presence of an SDHA germline mutation. Identifying GISTs with deficient SDH activity warrants additional genetic testing, evaluation and follow-up for inherited disorders and paragangliomas.Modern Pathology advance online publication, 23 November 2012; doi:10.1038/modpathol.2012.186.

Pop Goes the O2: a Case of Popper-induced Methaemoglobinamia BMJ Case Reports. 2012 | Pubmed ID: 23175012 A 39-year-old man presented to the emergency department after falling downstairs after he consumed a large quantity of alcohol. On examination, he had altered mental state (GCS 14), central cyanosis and low oxygen saturation of 86%, despite 100% oxygen being administered. His arterial blood gas confirmed diagnosis of methaemoglobinaemia with a methaemoglobin percentage of 14.08. He was treated successfully with methylthioninium chloride. The patient later admitted to use of recreational poppers (amyl nitrates) the previous evening. The emergency physician is challenged by the presentation of a patient with altered mental state and unexplained low oxygen saturation with concurrent alcohol intoxication but must have a high index of suspicion for methaemoglobinaemia particularly with a history of recreational drug ingestion.

TNF-Î± and TGF-Î² Synergistically Stimulate Elongation of Human Endothelial Cells Without Transdifferentiation to Smooth Muscle Cell Phenotype Cytokine. Jan, 2013 | Pubmed ID: 23116662 We earlier reported synergy between tumor necrosis factor-Î± (TNF-Î±) and transforming growth factor-Î²(1) (TGF-Î²(1)) for apoptosis in human umbilical vein endothelium (HUVEC). Here, we study morphological change by circularity measurement of HUVEC surviving this cytokine induced synergistic apoptosis. Contrasting with reports by others studying bovine endothelium, HUVEC did not change morphology in response to TGF-Î²(1). TNF-Î± markedly elongated cells (p

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