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Conversely, some larger centers opted to continue routine transplant activity in order to balance waiting list mortality. To model these and other ethical tensions, we computed a QE score using 4 factors – Recipient Outcome, Donor/Graft Safety, Waiting List Mortality and Healthcare Resources for seven countries. The fluctuation of the QE score over time accurately reflects the dynamic changes in the ethical tensions surrounding transplant activity in a pandemic. Conclusions This four-dimensional model of Quadripartite Equipoise addresses the ethical tensions in the current pandemic. It serves as a universally applicable framework to guide regulation of transplant activity in response to the increasing burden on healthcare systems to allow greater global solidarity and transparency in these austere times.Neuropathic pain is a very complex chronic pain state, the detailed molecular mechanisms of which remain unclear. In the present study, Shank3 was found to play an important role in neuropathic pain in rats following spared nerve injury (SNI). Shank3 was upregulated in the spinal dorsal horn of rats subjected to SNI, and mechanical hypersensitivity to noxious stimuli in these rats could be alleviated by knock down of Shank3. Shank3 also interacted with hyperpolarization-activated cyclic nucleotide-gated channel 2 (HCN2) and promoted the expression of HCN2 in central neurons of the spinal dorsal. Together with the SNI-dependent increase of HCN2, we also found that the postsynaptic protein of excitatory synapse (PSD95) was increased in rats following SNI. Taken together, our results showed that Shank3 modulated neuropathic pain by facilitating the SNI-dependent increase of HCN2 and the expression of PSD95 in spinal dorsal horn neurons. Our findings revealed new synaptic remodeling mechanisms linking Shank3 with neuropathic pain.Previously, we have shown that Staphylococcus (S) aureus induces a glycolytic response in retinal residential (microglia) and infiltrated cells (neutrophils and macrophages) during endophthalmitis. In this study, we sought to investigate the physiological role of glycolysis in bacterial endophthalmitis using a glycolytic inhibitor, 2-deoxyglucose (2DG). Our data showed that 2DG treatment attenuated the inflammatory responses of mouse bone marrow-derived macrophages (BMDM) and neutrophils (BMDN) when challenged with either live or heat-killed S. aureus (HKSA). Among the inflammatory mediators, 2DG caused a significant reduction in levels of cytokines (TNF-α, IL-1β, IL-6) and chemokines (CXCL1 and CXCL2). Western blot analysis of 2DG treated cells showed downregulation of bacterial-induced MEK/ERK pathways. In vivo, intravitreal administration of 2DG both pre- and post-bacterial infection resulted in a significant reduction in intraocular inflammation in C57BL/6 mouse eyes and downregulation of ERK phosphorylation in retinal tissue. Collectively, our study demonstrates that 2DG attenuates inflammatory response in bacterial endophthalmitis and cultured innate immune cells via inhibition of ERK signaling. Thus glycolytic inhibitors in combination with antibiotics could mitigate inflammation-mediated tissue damage in ocular infections.Owing to its potent longterm neuroprotective and neurorestorative properties, glial cell line-derived neurotrophic factor (GDNF) is currently studied in neurodegenerative disease clinical trials. However, little is known about the longterm effect of GDNF on neurological recovery, brain remodeling and neuroplasticity in the post-acute phase of ischemic stroke. In a comprehensive set of experiments, we examined the effects of lentiviral GDNF administration after ischemic stroke. GDNF reduced neurological deficits, neuronal injury, blood-brain barrier permeability in the acute phase in mice. As compared with control, enhanced motor-coordination and spontaneous locomotor activity were noted in GDNF-treated mice, which were associated with increased microvascular remodeling, increased neurogenesis and reduced glial scar formation in the peri-infarct tissue. We observed reduced brain atrophy and increased plasticity of contralesional pyramidal tract axons that crossed the midline in order to innervate denervated neurons in the ipsilesional red and facial nuclei. Contralesional axonal plasticity by GDNF was associated with decreased abundance of the axonal growth inhibitors brevican and versican in contralesional and ipsilesional brain tissue, reduced abundance of the growth repulsive guidance molecule ephrin b1 in contralesional brain tissue, increased abundance of the midline growth repulsive protein Slit1 in contralesional brain tissue and reduced abundance of Slit1’s receptor Robo2 in ipsilesional brain tissue. These data indicate that GDNF potently induces longterm neurological recovery, peri-infarct brain remodeling and contralesional neuroplasticity, which are associated with the fine-tuned regulation of axonal growth inhibitors and guidance molecules that facilitate the growth of contralesional corticofugal axons in the direction to the ipsilesional hemisphere.Background & aims Alcohol dehydrogenase 1B (ADH1B) is involved in alcohol metabolism. The allele A (ADH1B*2) of rs1229984 A>G variant in ADH1B is associated a higher alcohol metabolizing activity, compared to the ancestral allele G (ADH1B*1). Moderate alcohol consumption is associated with reduced severity of nonalcoholic fatty liver disease (NAFLD), based on histologic analysis, compared with no alcohol consumption. However, it is unclear whether ADH1B*2 modifies the relationship between moderate alcohol consumption and severity of NAFLD. We examined the association between ADH1B*2 and moderate alcohol consumption and histologic severity of NAFLD. Finerenone datasheet Methods We collected data from 1557 multi-ethnic adult patients with biopsy-proven NAFLD enrolled into 4 different studies conducted by the NASH Clinical Research Network. Histories of alcohol consumption were obtained from answers to standardized questionnaires. Liver biopsies were analyzed by histology and scored centrally according to the NASH CRN criteria. We p of an NAFLD activity score of 4 or higher (ADH1B*2 OR, 0.83; P=.012 vs ADH1B*1 OR, 0.96; P=.048) (P less then .01 for the difference in the effect of moderate alcohol consumption between alleles). The relationship between body mass index and NAFLD severity was significantly modified by ADH1B*2, even after we controlled for alcohol consumption. Conclusions ADH1B*2 reduces the risk of NASH and fibrosis in adults with NAFLD regardless of alcohol consumption status. ADH1B*2 might modify the association between high body mass index and NAFLD severity.Purpose To evaluate impact of processing technique and slab selection on the repeatability of choriocapillaris (CC) flow deficit (FD) measurements as assessed using optical coherence tomography angiography (OCTA) Design prospective, cross-sectional study METHODS Healthy subjects were imaged with four consecutive 3x3mm OCTA using a swept source OCT (PLEX elite 9000, Carl Zeiss Meditec, Dublin, CA). OCTA images were generated using the Max projection, and three 10 μm-thick slabs starting 11, 21 and 31 μm posterior to the automatically segmented retinal pigment epithelium (RPE) band. The resultant images were binarized using Phansalkar’s method with a 43.94 μm radius and then the CCFD% was computed. The intraclass correlation coefficient (ICC) and coefficient of variation (CV) were computed for the four acquisitions to assess the repeatability of the CCFD%. This entire analysis was repeated after separately modulating several parameters 1) Sum instead of the Max projection, 2) RPE-fit instead of the RPE band as which parameter was modulated, the 21-31 micron slab was the most repeatable. Conclusions In normal eyes, en face CC OCTA images generated using the Max projection and a 10μm thick slab offset of 21 microns below the instrument-generated RPE band yielded the most repeatable CCFD%. These findings have implications for the design of standardized processing algorithms for quantitative CC assessment.Purpose To determine the effects on childhood myopia of parental myopia, parental education, children’s outdoor time and children’s near wok. Design Population-based cross-sectional study METHODS A total of 6,155 subjects in 2,055 family trios. Cycloplegic auto-refraction was measured for children and non-cycloplegic auto-refraction for parents. Parental education, children’s outdoor time and near work were collected by questionnaires. Children were categorized into ten groups based on parental myopia levels. Associations of the above factors with myopia were evaluated by regression analyses. The areas under the receiver operating characteristic curve (AUROC) for myopia were evaluated. Results Mild parental myopia did not increase childhood myopia’s risk, but the risk was 11.22-folds when both parents were highly myopic. Higher parental education (Father OR=1.08, P=0.046; Mother OR=1.11, P=0.001) and more reading time of children were risk factors (OR=1.21, P=0.044). Reduced odds of myopia were associated with more time spent on outdoor activities (OR=0.78, P=0.017) and on electronic devices (OR=0.80, P=0.005). Notably, all these factors became insignificant after adjustment, except for parental myopia. Children with more severe parental myopia spent more time on reading, but less on electronic devices. Parental myopic status alone accounted for 11.82% of myopia variation in children. With age and parental myopia, the AUROC for myopia was 0.731. Conclusions Among parental and environmental factors, parental myopia confers, in a dose-related manner, the strongest independent effect on childhood myopia. Therefore children with high risk of myopia can be identified for early prevention, based on parental myopia data.Plasmodium vivax remains an important cause of malaria in South America and Asia, and analyses of the antibody immune response are being used to identify biomarker of parasite exposure. The IgG antibody naturally acquired predominantly occurs against targets on blood-stage parasites, including C-terminal of the merozoite surface protein 1 (MSP1-19). Epidemiological and immunological evidence has been showed that antibodies to malaria parasite antigens are lost in the absence of ongoing exposure. We describe the IgG antibody response in individuals living in an unstable malaria transmission area in Pará state, Amazon region, Brazil, where an epidemic of P. vivax malaria was recorded and monitored over time. As indicated by epidemiological data, the number of P. vivax-caused malaria cases decreased by approximately 90% after three years and the prevalence of IgG positive to PvMSP1-19 decreased significantly over time, in 2010 (93.4%), 2012 (78.3%), and 2013 (85.1%). Acquisition and decay of the IgG antibody against P. vivax MSP1-19 showed variability among individuals living in areas with recent circulating parasites, where the malaria epidemic was being monitored until transmission had been completely controlled. We also found that previous malaria episodes were associated with an increased in the IgG positivity . Our results showed epidemiological, spatial, temporal and individual variability. The understanding on dynamics of antibodies may have implications for the design of serosurveillance tools for monitoring parasite circulation, especially in a context with spatial and temporal changes in P. vivax malaria transmission.