Corticosterone-mediated microglia activation affects dendritic spine plasticity and motor learning functions in minimal hepatic encephalopathy

Minimal hepatic encephalopathy (MHE) is characterized as cognitive deficits including memory and learning dysfunctions after liver injuries or hepatic diseases. Our understandings of neurological mechanisms of MHE-associated cognitive syndromes, however, are far from complete. In the current study we generated a mouse MHE model by repetitive administrations of thioacetamide (TAA), which induced hyperammonemia plus elevated proinflammatory cytokines in both the general circulation and motor cortex. MHE mice presented prominent motor learning deficits, which were associated with excess dendritic spine pruning in the motor cortex under 2-photon in vivo microscopy. The pharmaceutical blockade of glucocorticoid receptor or suppression of its biosynthesis further rescued motor learning deficits and synaptic protein loss. Moreover, MHE mice presented microglial activation, which can be alleviated after glucocorticoid pathway inhibition. In sum, our data demonstrates corticosterone-induced microglial activation, synaptic over-pruning and motor learning impairments in MHE, providing new insights for MHE pathogenesis and potential targets of clinical interventions.     

Lifestyle and lifetime occupational exposures may not play a role in the pathogenesis of Modic changes on the lumbar spine MR images

BACKGROUND CONTEXTModic changes (MCs) have long been suspected as a pathologic cause of back pain. Although much attention has been focused on clinical perspectives, the etiology of MCs remains unclear. Although some studies have reported that sex, body mass index (BMI), cigarette smoking, and physical loading may associate with MCs, the observed associations are inconsistent among studies.PURPOSETo investigate associations between MCs and lifestyle and lifetime occupational exposures using a general population sample.STUDY DESIGNCross-sectional study.PATIENT SAMPLEThe study was an extension of the Hangzhou Lumbar Spine Study, a population-based study of mainland Chinese focusing on lumbar degenerative changes. A total of 644 randomly selected subjects from a typical community in Hangzhou, Eastern China participated.OUTCOME MEASURESThe presence and type of MCs in the lumbosacral spine were evaluated on sagittal magnetic resonance images. Demographics, lifestyle factors, and occupational exposures were measured using a structured interview.METHODSUnivariate and multivariate logistic regressions were used to examine the associations of MCs with various environmental exposures.RESULTSAmong the 644 subjects (52.6±13.9 years; range 20–88 years) included in this study, 44.7% had MCs. In univariate regression analyses, the presence of MCs was associated with greater age, higher BMI, greater cigarette smoking, regular exercise, and absence of daily vehicle vibration. Modic changes were not univariately associated with sex or alcohol consumption. In addition, all occupational loading measurements were associated with the occurrence of MCs in univariate analyses, except work time spent in vehicles and work-related back injuries. However, in multivariate regression analyses, no statistically significant associations between the occurrence of MCs and lifestyle or lifetime occupational exposures were observed after adjusting for age, sex, and BMI.CONCLUSIONSAge is an important determinant of MCs, with BMI and sex also playing a role. Lifestyle and occupational factors appear to have minor effects, if any, on the pathogenesis of MCs in the lumbar spine.     

Prosthetic choice in mitral valve replacement for severe chronic ischemic mitral regurgitation: Long-term follow-up

BackgroundProsthetic choice for mitral valve replacement is generally driven by patient age and patient and surgeon preference, and current guidelines do not discriminate between different etiologies of mitral valve disease. Our objective was to assess and compare short- and long-term outcomes after mitral valve replacement among patients with biological or mechanical prostheses in the setting of severe ischemic mitral regurgitation.MethodsBetween 2000 and 2016, 424 patients underwent mitral valve replacement for severe ischemic mitral regurgitation at our institution, using biological prosthesis in 188 (44%) and mechanical prosthesis in 236 (56%). A 1:1 propensity score match (n = 126 per group) and inverse probability of treatment weighting were used to compare groups. Short-term outcomes included in-hospital mortality and other cardiovascular adverse events. Long-term outcomes included survival and hospital readmission for cardiovascular causes, stroke, and major bleeding.ResultsIn-hospital mortality and early postoperative adverse events were similar between groups in the propensity score match and inverse probability of treatment weighting cohorts. Overall long-term survival was similar at 5 and 9 years, but mechanical prosthesis recipients were more frequently readmitted to hospital for cardiovascular causes, including stroke and non-neurological bleeding in propensity score matching and inverse probability of treatment weighting analyses (all P values < .004). Type of prosthesis did not independently influence all-cause mortality (hazard ratio, 1.01; 95% confidence interval, 0.71-1.43; P = .959), but placement of a mechanical prosthesis was associated with increased risk of readmission for cardiovascular events (hazard ratio, 1.65; 95% confidence interval, 1.17-2.32; P = .004) among matched patients.ConclusionsThe type of prosthesis has no influence on long-term survival among patients with severe ischemic mitral regurgitation undergoing mitral valve replacement. There may be an increased risk of neurologic events and serious bleeding associated with mechanical prostheses.