Ethnicity and attitudes to deceased kidney donation: a survey in Barbados and comparison with Black Caribbean people in the United Kingdom

<p>Abstract</p> <p>Background</p> <p>Black minority ethnic groups in the UK have relatively low rates of deceased donation and report a higher prevalence of beliefs that are regarded as barriers to donation. However there is little data from migrants' countries of origin. This paper examines community attitudes to deceased kidney donation in Barbados and compares the findings with a survey conducted in a disadvantaged multi-ethnic area of south London.</p> <p>Methods</p> <p>Questionnaires were administered at four public health centres in Barbados and at three private general practices. Adjusted odds ratios were calculated to compare attitudinal responses with a prior survey of 328 Caribbean and 808 White respondents in south London.</p> <p>Results</p> <p>Questionnaires were completed by 327 respondents in Barbados (93% response); 42% men and 58% women, with a mean age of 40.4 years (SD 12.6). The main religious groups were Anglican (29%) and Pentecostal (24%). Educational levels ranged from 18% not completing 5th form to 12% with university education. Attitudes to the notion of organ donation were favourable, with 73% willing to donate their kidneys after their death and only 5% definitely against this. Most preferred an opt-in system of donation. Responses to nine attitudinal questions identified 18% as having no concerns and 9% as having 4 or more concerns. The highest level of concern (43%) was for lack of confidence that medical teams would try as hard to save the life of a person who has agreed to donate organs. There was no significant association between age, gender, education or religion and attitudinal barriers, but greater knowledge of donation had some positive effect on attitudes. Comparison of attitudes to donation in south London and Barbados (adjusting for gender, age, level of education, employment status) indicated that a significantly higher proportion of the south London Caribbean respondents identified attitudinal barriers to donation.</p> <p>Conclusions</p> <p>Community attitudes in Barbados are favourable to deceased donation based on a system of informed consent. Comparison with south London data supports the hypothesis that the relatively high prevalence of negative attitudes to deceased donation among disadvantaged ethnic minorities in high income countries may reflect feelings of marginalisation and lack of belonging.</p

Polypyrrole-Fe2O3 nanohybrid materials for electrochemical storage

We report on the synthesis and electrochemical characterization of nanohybrid polypyrrole (PPy) (PPy/Fe2O3) materials for electrochemical storage applications. We have shown that the incorporation of nanoparticles inside the PPy notably increases the charge storage capability in comparison to the “pure” conducting polymer. Incorporation of large anions, i.e., paratoluenesulfonate, allows a further improvement in the capacity. These charge storage modifications have been attributed to the morphology of the composite in which the particle sizes and the specific surface area are modified with the incorporation of nanoparticles. High capacity and stability have been obtained in PC/NEt4BF4 (at 20 mV/s), i.e., 47 mAh/g, with only a 3% charge loss after one thousand cyles. The kinetics of charge–discharge is also improved by the hybrid nanocomposite morphology modifications, which increase the rate of insertion–expulsion of counter anions in the bulk of the film. A room temperature ionic liquid such as imidazolium trifluoromethanesulfonimide seems to be a promising electrolyte because it further increases the capacity up to 53 mAh/g with a high stability during charge–discharge processes

Srf1 Is a Novel Regulator of Phospholipase D Activity and Is Essential to Buffer the Toxic Effects of C16:0 Platelet Activating Factor

During Alzheimer's Disease, sustained exposure to amyloid-β42 oligomers perturbs metabolism of ether-linked glycerophospholipids defined by a saturated 16 carbon chain at the sn-1 position. The intraneuronal accumulation of 1-O-hexadecyl-2-acetyl-sn-glycerophosphocholine (C16:0 PAF), but not its immediate precursor 1-O-hexadecyl-sn-glycerophosphocholine (C16:0 lyso-PAF), participates in signaling tau hyperphosphorylation and compromises neuronal viability. As C16:0 PAF is a naturally occurring lipid involved in cellular signaling, it is likely that mechanisms exist to protect cells against its toxic effects. Here, we utilized a chemical genomic approach to identify key processes specific for regulating the sensitivity of Saccharomyces cerevisiae to alkyacylglycerophosphocholines elevated in Alzheimer's Disease. We identified ten deletion mutants that were hypersensitive to C16:0 PAF and five deletion mutants that were hypersensitive to C16:0 lyso-PAF. Deletion of YDL133w, a previously uncharacterized gene which we have renamed SRF1 (Spo14 Regulatory Factor 1), resulted in the greatest differential sensitivity to C16:0 PAF over C16:0 lyso-PAF. We demonstrate that Srf1 physically interacts with Spo14, yeast phospholipase D (PLD), and is essential for PLD catalytic activity in mitotic cells. Though C16:0 PAF treatment does not impact hydrolysis of phosphatidylcholine in yeast, C16:0 PAF does promote delocalization of GFP-Spo14 and phosphatidic acid from the cell periphery. Furthermore, we demonstrate that, similar to yeast cells, PLD activity is required to protect mammalian neural cells from C16:0 PAF. Together, these findings implicate PLD as a potential neuroprotective target capable of ameliorating disruptions in lipid metabolism in response to accumulating oligomeric amyloid-β42

Haemostasis in Open Carpal Tunnel Release: Tourniquet vs Local Anaesthetic and Adrenaline

Open carpal tunnel release is one of the commonest performed procedures in hand surgery. We performed a prospective randomised control trial to compare the efficacy and patient satisfaction of the traditional arm tourniquet versus infiltration of adrenaline and local anaesthetic solution to achieve haemostasis during the procedure. Using a combination of objective and subjective measures we concluded that infiltration of local anaesthetic and adrenaline not only provided adequate haemostasis but also provided a significantly more tolerable experience for the patient during the procedure

DNA methylation in interleukin-11 predicts clinical response to antidepressants in GENDEP

Transcriptional differences in interleukin-11 (IL11) after antidepressant treatment have been found to correspond to clinical response in major depressive disorder (MDD) patients. Expression differences were partly mediated by a single-nucleotide polymorphism (rs1126757), identified as a predictor of antidepressant response as part of a genome-wide association study. Here we attempt to identify whether DNA methylation, another baseline factor known to affect transcription factor binding, might also predict antidepressant response, using samples collected from the Genome-based Therapeutic Drugs for Depression project (GENDEP). DNA samples from 113 MDD individuals from the GENDEP project, who were treated with either escitalopram (n=80) or nortriptyline (n=33) for 12 weeks, were randomly selected. Percentage change in Montgomery-� sberg Depression Rating Scale scores between baseline and week 12 were utilized as our measure of antidepressant response. The Sequenom EpiTYPER platform was used to assess DNA methylation across the only CpG island located in the IL11 gene. Regression analyses were then used to explore the relationship between CpG unit methylation and antidepressant response. We identified a CpG unit predictor of general antidepressant response, a drug by CpG unit interaction predictor of response, and a CpG unit by rs1126757 interaction predictor of antidepressant response. The current study is the first to investigate the potential utility of pharmaco-epigenetic biomarkers for the prediction of antidepressant response. Our results suggest that DNA methylation in IL11 might be useful in identifying those patients likely to respond to antidepressants, and if so, the best drug suited to each individual

Autotaxin-lysophosphatidic acid receptor signalling regulates hepatitis C virus replication

Background & Aims Chronic hepatitis C is a global health problem with an estimated 170 million hepatitis C virus (HCV) infected individuals at risk of progressive liver disease and hepatocellular carcinoma (HCC). Autotaxin (ATX, gene name: ENPP2) is a phospholipase with diverse roles in the physiological and pathological processes including inflammation and oncogenesis. Clinical studies have reported increased ATX expression in chronic hepatitis C, however, the pathways regulating ATX and its role in the viral life cycle are not well understood. Methods In vitro hepatocyte and ex vivo liver culture systems along with chimeric humanized liver mice and HCC tissue enabled us to assess the interplay between ATX and the HCV life cycle. Results HCV infection increased hepatocellular ATX RNA and protein expression. HCV infection stabilizes hypoxia inducible factors (HIFs) and we investigated a role for these transcription factors to regulate ATX. In vitro studies show that low oxygen increases hepatocellular ATX expression and transcriptome analysis showed a positive correlation between ATX mRNA levels and hypoxia gene score in HCC tumour tissue associated with HCV and other aetiologies. Importantly, inhibiting ATX-lysophosphatidic acid (LPA) signalling reduced HCV replication, demonstrating a positive role for this phospholipase in the viral life cycle. LPA activates phosphoinositide-3-kinase that stabilizes HIF-1α and inhibiting the HIF signalling pathway abrogates the pro-viral activity of LPA. Conclusions Our data support a model where HCV infection increases ATX expression which supports viral replication and HCC progression. Lay summary Chronic hepatitis C is a global health problem with infected individuals at risk of developing liver disease that can progress to hepatocellular carcinoma. Autotaxin generates the biologically active lipid lysophosphatidic acid that has been reported to play a tumorigenic role in a wide number of cancers. In this study we show that hepatitis C virus infection increases autotaxin expression via hypoxia inducible transcription factor and provides an environment in the liver that promotes fibrosis and liver injury. Importantly, we show a new role for lysophosphatidic acid in positively regulating hepatitis C virus replication.Research in the McKeating laboratory was funded by the MRC, NIHR Birmingham Liver BRU, EU FP7 PathCO and H2020 grant Hep-CAR. Research in the Wakelam lab is supported by BBSRC and Hep-CAR. Stephanie Roessler was supported by Hep-CAR, DFG grant RO4673, the Olympia-Morata Programme, a Brigitte-Schieben-Lange Fellowship and a Heidelberg School of Oncology Fellowship

Haemostasis in Open Carpal Tunnel Release: Tourniquet vs Local Anaesthetic and Adrenaline

Open carpal tunnel release is one of the commonest performed procedures in hand surgery. We performed a prospective randomised control trial to compare the efficacy and patient satisfaction of the traditional arm tourniquet versus infiltration of adrenaline and local anaesthetic solution to achieve haemostasis during the procedure. Using a combination of objective and subjective measures we concluded that infiltration of local anaesthetic and adrenaline not only provided adequate haemostasis but also provided a significantly more tolerable experience for the patient during the procedure

Effects of exposure to cigarette smoke prior to pregnancy in diabetic rats

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to evaluate the effects of cigarette smoke exposure before pregnancy on diabetic rats and their offspring development.</p> <p>Methods</p> <p>Diabetes was induced by streptozotocin and cigarette smoke exposure was conducted by mainstream smoke generated by a mechanical smoking device and delivered into a chamber. Diabetic female Wistar rats were randomly distributed in four experimental groups (n minimum = 13/group): nondiabetic (ND) and diabetic rats exposed to filtered air (D), diabetic rats exposed to cigarette smoke prior to and into the pregnancy period (DS) and diabetic rats exposed to cigarette smoke prior to pregnancy period (DSPP). At day 21 of pregnancy, rats were killed for maternal biochemical determination and reproductive outcomes.</p> <p>Results</p> <p>The association of diabetes and cigarette smoke in DSPP group caused altered glycemia at term, reduced number of implantation and live fetuses, decreased litter and maternal weight, increased pre and postimplantation loss rates, reduced triglyceride and VLDL-c concentrations, increased levels of thiol groups and MDA. Besides, these dams presented increased SOD and GSH-Px activities. However, the increased antioxidant status was not sufficient to prevent the lipid peroxidation observed in these animals.</p> <p>Conclusion</p> <p>Despite the benefits stemming from smoking interruption during the pregnancy of diabetic rats, such improvement was insufficient to avoid metabolic alterations and provide an adequate intrauterine environment for embryofetal development. Therefore, these results suggest that it is necessary to cease smoking extensive time before planning pregnancy, since stopping smoking only when pregnancy is detected may not contribute effectively to fully adequate embryofetal development.</p

Pathogenic Mechanism of the FIG4 Mutation Responsible for Charcot-Marie-Tooth Disease CMT4J

CMT4J is a severe form of Charcot-Marie-Tooth neuropathy caused by mutation of the phosphoinositide phosphatase FIG4/SAC3. Affected individuals are compound heterozygotes carrying the missense allele FIG4-I41T in combination with a null allele. Analysis using the yeast two-hybrid system demonstrated that the I41T mutation impairs interaction of FIG4 with the scaffold protein VAC14. The critical role of this interaction was confirmed by the demonstration of loss of FIG4 protein in VAC14 null mice. We developed a mouse model of CMT4J by expressing a Fig4-I41T cDNA transgene on the Fig4 null background. Expression of the mutant transcript at a level 5× higher than endogenous Fig4 completely rescued lethality, whereas 2× expression gave only partial rescue, providing a model of the human disease. The level of FIG4-I41T protein in transgenic tissues is only 2% of that predicted by the transcript level, as a consequence of the protein instability caused by impaired interaction of the mutant protein with VAC14. Analysis of patient fibroblasts demonstrated a comparably low level of mutant I41T protein. The abundance of FIG4-I41T protein in cultured cells is increased by treatment with the proteasome inhibitor MG-132. The data demonstrate that FIG4-I41T is a hypomorphic allele encoding a protein that is unstable in vivo. Expression of FIG4-I41T protein at 10% of normal level is sufficient for long-term survival, suggesting that patients with CMT4J could be treated by increased production or stabilization of the mutant protein. The transgenic model will be useful for testing in vivo interventions to increase the abundance of the mutant protein