Notes

Inositol phosphate kinases in the eukaryote landscape.
Conclusion We report a case of chronic meningitis due to Candida dubliniensis in an immunocompetent woman with hepatitis C and a history of intravenous heroin use. Additional studies are needed to confirm risk factors for Candida dubliniensis colonization, which likely predisposes individuals to invasive candidiasis.Purpose To determine the association between overweight and high-sensitivity C-reactive protein (hs-CRP) with the odds of cognitive impairment as well as its subtypes based on the Asymptomatic Polyvascular Abnormalities Community (APAC) study in China. Materials and methods We conducted a cross-sectional analysis of the follow-up data of 2012 from the APAC study. The Chinese version of the MMSE was used as a cognitive screener, and an MMSE score less then 24 is generally accepted as indicating cognitive impairment. Multivariable logistic regression was used to estimate the interactions of hs-CRP levels with body mass index (BMI) on the effects of cognitive impairment and its subtypes. Results Three thousand eight hundred seventy-five participants aged 40-90 years (median age 51.64 y) were enrolled in this study, and 1,788 (46.1%) were overweight. Before and after adjusting for confounders, such as age, sex, BMI, education, current smoking, drinking, physical activity, hypertension, hyperlipidemia, diabetes, and hs-CRP, elevated hs-CRP levels were associated with cognitive impairment in normal-weight participants (crude OR 2.08, 95%CI 1.28-3.37, p = 0.003; adjusted OR 2.06, 95%CI 1.03-4.10, p = 0.04), but not in overweight participants. There was no statistically significant evidence for the interaction between hs-CRP and BMI on any cognitive sub-item. Conclusion Elevated hs-CRP levels increase the odds of cognitive impairment in normal-weight participants, but not in overweight participants.Background and Aims Disability-adjusted life years (DALYs) are an important measure of the global burden of disease that informs patient outcomes and policy decision-making. Our study aimed to compare the DALYs saved by endovascular thrombectomy (EVT) in the Australasian-based EXTEND-IA trial vs. clinical registry data from EVT in Australian routine clinical practice. Methods The 3-month modified Rankin scale (mRS) outcome and treatment status of consecutively enrolled Australian patients with large vessel occlusion (LVO) stroke were taken from the International Stroke Perfusion Imaging Registry (INSPIRE). DALYs were calculated as the summation of years of life lost (YLL) due to premature death and years lived with a disability (YLD). A generalized linear model (GLM) with gamma family and log link was used to compare the difference in DALYs for patients receiving/not receiving EVT while controlling for key covariates. Ordered logit regression model was utilized to compare the difference in functional outcome 2.51), a reduction of -1.09 DALY (95% CI -1.76 to -0.43, p = 0.002). The absolute magnitude of the treatment effect was lower than that seen in EXTEND-IA (-2.72 DALY reduction in EVT vs non-EVT patients). Conclusions EVT for the treatment of LVO in a registry of routine care was associated with significantly lower DALYs lost than medical care alone, but the saved DALYs are less than those reported in clinical trials, as there were major differences in the baseline characteristics of the patients.Epilepsy is a common neurological disease that is not always controlled, and the ketogenic diet shows good antiepileptic effects drug-resistant epilepsy or seizures caused by specific metabolic defects via regulating the metabolism. The brain is a vital organ with high metabolic demands, and epileptic foci tend to exhibit high metabolic characteristics. Accordingly, there has been growing interest in the relationship between brain metabolism and epilepsy in recent years. To date, several new antiepileptic therapies targeting metabolic pathways have been proposed (i.e., inhibiting glycolysis, targeting lactate dehydrogenase, and dietary therapy). Promising strategies to treat epilepsy via modulating the brain's metabolism could be expected, while a lack of thorough understanding of the role of brain metabolism in the control of epilepsy remains. Herein, this review aims to provide insight into the state of the art concerning the brain's metabolic patterns and their association with epilepsy. Regulation of neuronal excitation via metabolic pathways and antiepileptic therapies targeting metabolic pathways are emphasized, which could provide a better understanding of the role of metabolism in epilepsy and could reveal potential therapeutic targets.Background Neuropsychological deficits frequently occur in diffuse lower-grade glioma (DLGG) patients, but their relationship with molecular subgroups based on the 2016 World Health Organization (WHO) Classification of Tumors of the Central Nervous System (CNS) is unclear. Methods All patients enrolled for this study were divided into different subgroups according to the molecular-integrated 2016 CNS WHO and morphology-centric 2007 CNS WHO to compare their neurocognitive function (NCF) dysfunction. Univariate and multivariate analyses were used to assess the independent factors for NCF decline. The performance of NCF changes for discrimination of IDH and 1p19q status was evaluated by receiver operating characteristic (ROC). Results There was no significant difference in the clinical characteristics among the molecular and morphologic subgroups. In the molecular subgroups, significant differences in NCF alterations were found in terms of attention function, working memory and executive function in grade II gli of tumor and demographics (p less then 0.05). ROC curves suggested combined NCF tests model showed an advantage in the differentiation of IDH status. Conclusions NCF alteration is closely related to molecular-integrated subgroups with varying degrees and frequencies in DLGG. Patients with IDHwt gliomas are more susceptible to suffer from severe and extensive NCF decline than other subgroups.Background Penumbral brain tissue identified with multimodal imaging can be salvaged with reperfusion in an extended time window. The risk of severe hemorrhagic complications after reperfusion therapy increases with worsening disruption of the blood-brain barrier (BBB). The relationship between penumbral tissue and BBB disruption has not been previously studied. Methods Stroke patients presenting in an extended time window without a large vessel occlusion who underwent diffusion-perfusion MRI within 24 h of last-seen-normal were included. The volume of penumbral tissue was calculated using mismatch on MRI. Mean permeability derangement (MPD) of the BBB was measured within the ischemic lesion. A target profile (TP) for treatment was defined based on the EXTEND trial. Results 222 patients were included with a median age of 73 and 55% women. The median NIHSS was 6, the mean core volume was 14 ml, the mean ischemic volume was 47 mL and the mean mismatch volume was 33 mL. Higher MPD was significantly associated with less mismatch volume (p = 0.001). A target profile was associated with lower MPD (OR 0.97; CI 0.960.99; p 20% suggesting an increased risk of hemorrhage. Thus, 33% (74/222) of patients had a favorable profile for benefit and safety. Conclusions Patients presenting in an extended time window with a favorable penumbral profile for treatment have less severe BBB disruption. Up to a third of patients who currently go untreated could be considered for enrollment in a clinical trial of thrombolysis in an extended time window.Background Tissue-type plasminogen activator (t-PA) has been the mainstay of therapeutic thrombolysis for patients with acute ischaemic stroke (AIS). However, t-PA can cause devastating intracerebral hemorrhage. t-PA can also influence the CNS in part by modulation of BBB permeability. Complement activation also occurs after AIS and has also been reported to increase BBB permeability. The complement components, C3 and C5, can also be activated by t-PA via plasmin formation and cell intrinsic complement may be involved in this process. Tenecteplase (TNK-tPA) is a t-PA variant with a longer plasma half-life, yet the ability of TNK-tPA to modulate the BBB and complement is less clear. Aim To evaluate the effect of C5 and C5a-receptor 1 (C5aR1) inhibitors on t-PA- and TNK-tPA-mediated opening of the BBB. Methods We used an in vitro model of the BBB where human brain endothelial cells and human astrocytes were co-cultured on the opposite sides of a porous membrane assembled in transwell inserts. The luminal (endothelial) compartment was stimulated with t-PA or TNK-tPA together with plasminogen, in the presence of PMX205 (a non-competitive C5aR1 antagonist), Avacopan (a competitive C5aR1 antagonist) or Eculizumab (a humanized monoclonal inhibitor of human C5). BBB permeability was assessed 5 and 24 h later. Immunofluorescence was also used to detect changes in C5 and C5aR1 expression in endothelial cells and astrocytes. Results PMX205, but not Avacopan or Eculizumab, blocked t-PA-mediated increase in BBB permeability at both the 5 and 24 h time points. PMX205 also blocked TNK-tPA-mediated increase in BBB permeability. Immunofluorescence analysis revealed intracellular staining of C5 in both cell types. C5aR1 expression was also detected on the cell surfaces and also located intracellularly in both cell types. Conclusion t-PA and TNK-tPA-mediated increase in BBB permeability involves C5aR1 receptor activation from cell-derived C5a. Selective inhibitors of C5aR1 may have therapeutic potential in AIS.Posterior cortical atrophy (PCA) is widely considered as an atypical variant of Alzheimer disease and is characterized by a progressive decline in visual function. PCA has been investigated from the standpoints of brain structure and metabolism, but tau deposition and its relationship to disease severity still remain unclear. Here, we used a novel tau ligand, [18F]PI2620, to visualize tau deposition in a PCA patient. The results showed that high [18F]PI2620 uptake in posterior cortical regions was associated with clinical manifestations, morphologic changes in the brain observed by magnetic resonance imaging (MRI), and hypometabolism detected by [18F] fluorodeoxyglucose (FDG) positron emission tomography (PET). This is the first report demonstrating a clinical anatomical correspondence between [18F]PI2620 PET results, clinical manifestations, MRI, and [18F]FDG PET findings in a Chinese patient with PCA. The results also support the utility of [18F]PI2620 for visualizing tau aggregation in PCA.The experience of "coming out" (CO) to parents is often a crucial event in the lives of lesbian and bisexual (LB) women, associated with lower internalized sexual stigma (ISS) and higher positive LB identity. Few studies have compared the experiences of LB women in the CO process. Rather, most prior research has either (1) not addressed bisexuality or eliminated bisexual individuals from the analysis; (2) combined bisexual women and bisexual men in the same sexual orientation group; or (3) examined bisexual participants alongside lesbian women and gay men, using a single monolithic measure. Thus, the present research aimed at investigating the role of ISS and positive LB identity in inhibiting or encouraging CO to parents in a sample of 241 lesbian women (Mage = 27.61, SD = 7.19) and 186 bisexual women (Mage = 25.23, SD = 5.81), aged 18-40 years. Most participants reported that they had already revealed their sexual orientation to their mother (69%) and their father (52%). More lesbian women had CO to both their mother and their father than had bisexual women.
Website: