Notes

Agonist-promoted kappa opioid receptor (KOR) phosphorylation features behaviour endpoint-dependent and sex-specific outcomes.
Interest in excitotoxicity expanded following its implication in the pathogenesis of ischemic brain injury in the 1980s, but waned subsequent to the failure of N-methyl-D-aspartate (NMDA) antagonists in high profile clinical stroke trials. Nonetheless there has been steady progress in elucidating underlying mechanisms. This review will outline the historical path to current understandings of excitotoxicity in the ischemic brain, and suggest that this knowledge should be leveraged now to develop neuroprotective treatments for stroke.Spatiotemporal event sequences (STESs) are the ordered series of event types whose instances frequently follow each other in time and are located close-by. An STES is a spatiotemporal frequent pattern type, which is discovered from moving region objects whose polygon-based locations continiously evolve over time. Previous studies on STES mining require significance and prevalence thresholds for the discovery, which is usually unknown to domain experts. The quality of the discovered sequences is of great importance to the domain experts who use these algorithms. We introduce a novel algorithm to find the most relevant STESs without threshold values. We tested the relevance and performance of our threshold-free algorithm with a case study on solar event metadata, and compared the results with the previous STES mining algorithms.Virtual reality exposure therapy (VRET) is becoming popular for treating phobia and anxiety disorder. The recent pandemic of COVID-19 not only causes infection per se but also has an impact on mental health. This case series aimed to explore the role of VRET in the intervention of psychiatric illnesses with chief complaints of fear of COVID-19 infection. In vivo exposure therapy for fear of COVID-19 infection is not possible due to the risk of virus infection; in this scenario, the VRET provides an immersive experience and can act as adjunctive therapy for treating phobias and anxiety disorders arising due to novel coronavirus pandemic. Clinical presentation and findings as well as management and procedures of VRET are discussed. Medical record of three patients (two male and one female) at the Shenzhen Mental Health Center (Shenzhen Kangning Hospital), China, was included in the present case series. Patients were assessed with the Hamilton Anxiety Rating Scale and Fear of COVID-19 Scale to measure anxiety and fear, respectively. Throughout VRET sessions, we gradually and systematically exposed the patient to virtual COVID-19 scenarios (for example, touching stained door handle which may have viruses, watching pandemic news, watching frontline health care workers, etc.). In our study, VRET intervention significantly reduced the related symptoms caused by fear of COVID-19 infection. Furthermore, virtual reality can provide relevant theoretical and practical support for exploring the remote psychological counseling of patients in isolation wards.This study provides new empirical evidence on the relationship between information about air pollution and avoidance behavior. Many countries provide real-time information to describe the current level of air pollution exposure. However, little research has been done on people's reactions to that real-time information. Using data on attendance at professional baseball games in South Korea, this study investigates whether real-time information on particulate matter affects individuals' decisions to participate in outdoor activities. Regression models that include various fixed effects are used for the analysis, with the results showing that real-time alerts reduce the number of baseball game spectators by 7%, and that the size of the effect is not statistically different from that of air pollution forecasts. The study demonstrates that providing real-time information can be a way to protect the public's health from the threat of air pollution. Moreover, the findings suggest that having easy access to the relevant information and an awareness of the risks involved are necessary for a real-time information policy to succeed.
To examine associations between fathers' and mothers' appraisals of family management and physical and emotional health-related quality of life (QOL) for young adult survivors of childhood brain tumors.

Cross-sectional.

47 mothers and 39 fathers (39-67 years old); 47 survivors (18-33 years old).

Analyses evaluated relationships among family management (Survivor's Daily Life, Condition Management Ability, Condition Management Effort, Family Life Difficulty, View of Condition Impact, Parental Mutuality), quality of life, and parental role.

Except for Parental Mutuality, family management ratings were not significantly different for mothers and fathers, and parental views of survivors' physical and emotional QOL improved with better family management. click here Parental role moderated associations between physical and emotional QOL and Survivors' Daily Life and between emotional QOL and Condition Management Ability, Condition Management Effort, and View of Condition Impact.

Assess and address survivor QOL through family management from multiple perspectives.
Assess and address survivor QOL through family management from multiple perspectives.Noninvasive assessment of aortic distensibility (AD) is feasible with cardiac magnetic resonance (CMR). We investigated the relationship between AD (assessed by CMR) and coronary artery disease (CAD) severity (assessed by the SYNTAX score) in patients with premature CAD. We recruited 125 patients with CAD confirmed by coronary angiography (males were less then 55 years old and females less then 65 years old). We excluded patients with significant aortic disease or contraindications to CMR. We also recruited 25 age- and sex-matched healthy patients as controls. One-year follow-up was also carried out. Aortic distensibility at the aortic root (AR) and descending aorta (DA) was significantly (P less then .001 for both) lower in the patient group. There was a significant negative correlation between SYNTAX score and AD at the AR (r = -0.56; P less then .001) and DA (r = -0.34; P less then .001), but insignificant correlation with distensibility at the ascending aorta (AA; r = -0.03; P = .81). AR, AA, and DA distensibility, as well as left ventricular ejection fraction were predictors of adverse events. The severity of CAD in young patients is associated with decreased AD, especially at the level of the AR. Aortic distensibility can predict adverse events in these patients.Fluorescence-based hydrogel glucose sensors with boronic acid-based glucose recognition are promising regarding their potential to improve continuous glucose monitoring by facilitating long-lasting accuracy. However, these sensors typically become encapsulated after implantation, and the dynamic range decreases following long-term implantation and use. Herein, a four-arm polyethylene glycol (PEG) hydrogel is developed with an immobilized glucose-responsive fluorescence dye (GF-PEG-gel); this hydrogel is effective in mitigating foreign body reactions (FBRs) that hinder stable glucose responses in vivo. The GF-PEG-gel attached to an implantable device successfully traces blood glucose concentrations in diabetic model rats for 45 days. A pig experiment shows that the device measures the glucose concentration with an equivalent accuracy to that required for clinically available settings.The conserved GxGxxG motif of protein kinases forms a beta turn at the tip of the flexible glycine-rich loop and creates much of the ATP pocket binding surface. Notable exceptions to this sequence include GGGxxG in ABL kinase and GxGxxA in protein kinase C isoforms. We constructed the corresponding mutants of PKA, T51G, and G55A, and tested quinazoline inhibitors that were designed to bind via glycine-rich loop interactions, testing also staurosporine for comparison. The quinazoline inhibitors have significantly reduced binding strengths in both mutants. In striking contrast to these results, the binding of the "pan-kinome" inhibitor staurosporine is strengthened in the mutants. Surface plasmon resonance (SPR) shows that the tightened binding of staurosporine arises from increased kon rates, changes not offset by more moderately increased koff rates. The SPR results fit best to a two step binding process for staurosporine in wild type PKA, but not the mutants.Melleolides and armillyl orsellinates are protoilludene-type aryl esters that are synthesized exclusively by parasitic fungi of the globally distributed genus Armillaria (Agaricomycetes, Physalacriaceae). Several of these compounds show potent antimicrobial and cytotoxic activities, making them promising leads for the development of new antibiotics or drugs for the treatment of cancer. We recently cloned and characterized the Armillaria gallica gene Pro1 encoding protoilludene synthase, a sesquiterpene cyclase catalyzing the pathway-committing step to all protoilludene-type aryl esters. Fungal enzymes representing secondary metabolic pathways are sometimes encoded by gene clusters, so we hypothesized that the missing steps in the pathway to melleolides and armillyl orsellinates might be identified by cloning the genes surrounding Pro1. Here we report the isolation of an A. gallica gene cluster encoding protoilludene synthase and four cytochrome P450 monooxygenases. Heterologous expression and functional analysis resulted in the identification of protoilludene-8α-hydroxylase, which catalyzes the first committed step in the armillyl orsellinate pathway. This confirms that ∆-6-protoilludene is a precursor for the synthesis of both melleolides and armillyl orsellinates, but the two pathways already branch at the level of the first oxygenation step. Our results provide insight into the synthesis of these valuable natural products and pave the way for their production by metabolic engineering. KEY POINTS • Protoilludene-type aryl esters are bioactive metabolites produced by Armillaria spp. • The pathway-committing step to these compounds is catalyzed by protoilludene synthase. • We characterized CYP-type enzymes in the cluster and identified novel intermediates.Home treatment for heart failure (HF) is one of the most important problems in patients after discharge as a secondary preventive measure for rehospitalization for HF. However, there are no detailed studies on gender differences in sociopsychological factors such as living alone for HF rehospitalization among patients with acute HF (AHF).This prospective multicenter cohort study enrolled patients with AHF between April 2015 and August 2017. Patients of each gender with first AHF were divided into those living alone and those not living alone. The primary endpoint was defined as rehospitalization for HF after discharge. Cox proportional hazard analysis was performed to determine the association between living alone and the endpoint.Overall, 581 patients were included in this study during the 3-year follow-up. The proportion of rehospitalization for HF was significantly higher in patients living alone than in those not living alone among male patients. However, female patients showed no difference in endpoints between the two groups. The difference was independently maintained even after adjusting for differences in social backgrounds in male patients (adjusted hazard ratio (HR) 2.02; 95% confidence interval (CI), 1.07-3.70). In female patients, the HR for rehospitalization for HF showed no difference between the two groups (adjusted HR, 0.99; 95% CI, 0.56-1.69).In this study population, male patients living alone after first AHF discharge had a higher risk of rehospitalization for HF than those not living alone, but these differences were not observed in female patients.
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