Calderonrye9116

Spontaneous intracerebral hemorrhage (ICH) commonly causes secondary hippocampal damage and delayed cognitive impairments, but the mechanisms remain elusive. Here, we sought to identify the molecular mechanisms underlying these hemorrhagic outcomes in a rat autologous blood model of ICH. First, a significant increase in phosphatase and tensin homolog (PTEN) expression was observed in nonhemorrhagic ipsilateral hippocampus. However, systemic administration of PTEN inhibitor BPV or hippocampal injection of PTEN siRNA could prevent hippocampal neuronal injury and cognitive dysfunctions after ICH. Furthermore, we also found that ICH robustly triggered autophagic neuronal death in the ipsilateral hippocampus, but which were strongly reduced by PTEN knockdown. Notably, suppression of autophagy effectively attenuated poststroke hippocampal inflammation, neuronal damage, and cognitive decline, suggesting the beneficial effects of PTEN deletion was associated with autophagy inactivation. Specifically, PTEN antagonized the PI3K/AKT signaling and downstream effector FoxO3a phosphorylation and subsequently enhanced nuclear translocation of FoxO3a to drive proautophagy gene program, but these changes were diminished upon PTEN inhibition. More importantly, lentivirus-mediated FoxO3a overexpression apparently abrogated the antiauotphagy effect of PTEN deletion via enhancing autophagy-related gene (ATG) transcription. check details Collectively, these results suggest that knockdown of PTEN alleviated progressive hippocampal injury and cognitive deficits by suppression of autophagy induction involving the AKT/FoxO3a/ATG axis after ICH. Thus, this study provides a novel and promising therapeutic target for the treatment of hemorrhagic stroke.Reactive oxygen species (ROS) production by activation of microglia is considered to be a major cause of neuronal dysfunction, which can lead to damage and death through direct oxidative damage to neuronal macromolecules or derangement of neuronal redox signaling circuits. BAP31, an integral ER membrane protein, has been defined as a regulatory molecule in the CNS. Our latest studies have found that BAP31 deficiency leads to activation of microglia. In this study, we discovered that BAP31 deficiency upregulated LPS-induced superoxide anion production in BV2 cells and mice by upregulating the expression level of p22phox and by inhibiting the activation of Nrf2-HO-1 signaling. Knockdown of p22phox/keap1 or use of an NADPH oxidase inhibitor (apocynin) reversed the production of superoxide anion and inflammatory cytokines, which then reduced neuronal damage and death in vitro and in vivo. These results suggest that BAP31 deficiency contributes to microglia-related superoxide anion production and neuroinflammation through p22phox and keap1. Furthermore, the excess superoxide anion cooperated with inflammatory cytokines to induce the damage and death of neurons. Thus, we determined that BAP31 is an important regulator in superoxide anion production and neuroinflammation, and the downstream regulators or agonists of BAP31 could therefore be considered as potential therapeutic targets in microglial-related superoxide anion production and neuroinflammation.

Understanding how religion and spirituality influence health-related quality of life (HRQoL) is important for developing holistic, patient-centered treatment. This study determined distinct latent classes of religiousness/spirituality for adult persons living with HIV (PLWH) and associations between latent class membership and HRQoL.

Baseline data was collected from 223 patients in the FAmily CEntered (FACE) Advance Care Planning (ACP) clinical trial for PLWH. Patients completed the Brief Multidimensional Measurement of Religiousness/Spirituality (BMMRS-adapted), Patient Health Questionnaire (PHQ-9), Medical Outcome Study-HIV Survey (MOS-HIV) and the Palliative care Outcome Scale (POS). The optimal number of latent classes was determined by comparing K-Class model with (K-1)-Class model iteratively. The relationship between latent class membership, HRQoL and demographic characteristics was assessed.

Patients were 56.1% male, 86.1% Black/African American, aged 22-77 (Mean=50.83). 75.3% were Christian. LCmpact of health disparities within the Black and LGBTQ communities.Forecasts support decision making in a variety of applications. Statistical models can produce accurate forecasts given abundant training data, but when data is sparse or rapidly changing, statistical models may not be able to make accurate predictions. Expert judgmental forecasts-models that combine expert-generated predictions into a single forecast-can make predictions when training data is limited by relying on human intuition. Researchers have proposed a wide array of algorithms to combine expert predictions into a single forecast, but there is no consensus on an optimal aggregation model. This review surveyed recent literature on aggregating expert-elicited predictions. We gathered common terminology, aggregation methods, and forecasting performance metrics, and offer guidance to strengthen future work that is growing at an accelerated pace.

head and neck cancers have essentially been a disease of the elderly but recent studies are beginning to demonstrate their increasing incidence in young people with infections such as human papilloma virus (HPV). This study was carried out to determine the prevalence of high risk Human papilloma virus (hrHPV) related oropharyngeal carcinoma and its prevalent genotypes as well as their strength of association with HIV in adult Nigerian subjects.

this was a cross-sectional study of 41 patients with oropharyngeal carcinomas seen over a 2-year period. Patients had incisional and/or excisional biopsy done under anesthesia. A portion of the specimen from which the DNA was extracted was placed in Digene HC2 DNA collection device while the 2

portion for histopathological analysis was fixed using 10% Neutral Buffered Formalin (NBF) and embedded in paraffin blocks. Oropharyngeal cancer HPV genotyping was done using HPV genotypes 14 real-tm quant kit (SACACE, Italy). The data was analyzed using SPSS version 23.

prevalence of HPV was 17.