Cyclooxygenase-1 and -2 modulate sweating but not cutaneous vasodilation during exercise in the heat in young men

We recently reported that the nonselective cyclooxygenase (COX) inhibitor ketorolac attenuated sweating but not cutaneous vasodilation during moderate‐intensity exercise in the heat. However, the specific contributions of COX‐1 and COX‐2 to the sweating response remained to be determined. We tested the hypothesis that COX‐1 but not COX‐2 contributes to sweating with no role for either COX isoform in cutaneous vasodilation during moderate‐intensity exercise in the heat. In thirteen young males (22 ± 2 years), sweat rate and cutaneous vascular conductance were measured at three forearm skin sites that were continuously treated with (1) lactated Ringer\u27s solution (Control), (2) 150 μmmol·L−1 celecoxib, a selective COX‐2 inhibitor, or (3) 10 mmol L−1 ketorolac, a nonselective COX inhibitor. Participants first rested in a non heat stress condition (≥85 min, 25°C) followed by a further 70‐min rest period in the heat (35°C). They then performed 50 min of moderate‐intensity cycling (~55% peak oxygen uptake) followed by a 30‐min recovery period. At the end of exercise, sweat rate was lower at the 150 μmol·L−1 celecoxib (1.51 ± 0.25 mg·min−1·cm−2) and 10 mmol·L−1 ketorolac (1.30 ± 0.30 mg·min−1·cm−2) treated skin sites relative to the Control site (1.89 ± 0.27 mg·min−1·cm−2) (both P ≤ 0.05). Additionally, sweat rate at the ketorolac site was attenuated relative to the celecoxib site (P ≤ 0.05). Neither celecoxib nor ketorolac influenced cutaneous vascular conductance throughout the experiment (both P > 0.05). We showed that both COX‐1 and COX‐2 contribute to sweating but not cutaneous vasodilation during moderate‐intensity exercise in the heat in young men

Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

The road to greater well-being: exploring the impact of an undergraduate positive education course on university students’ well-being

Abstract The profile of subjective well-being (SWB) in university students is perturbing in many respects. Indeed, university students are in need of tools to combat stress and promote SWB now more than ever given the adverse repercussions of the COVID-19 pandemic. Positive education could serve as a SWB tool to help university students deal with academic, personal, and global stressors. While a number of studies have quantitatively reported the impact of positive education on student SWB, few have considered students’ experiences and perceptions of changes in their SWB as a result of taking a positive education course. Therefore, the purpose of this study was to qualitatively explore university students’ experiences in a positive education course and their perceptions of its influence on their SWB immediately after taking the course. Undergraduate students (n = 17) who had taken a positive education course during the Winter term of 2020 (January–April) were recruited via volunteer sampling. Data were collected by means of semi-structured interviews and analyzed using reflexive thematic analysis. Analyses revealed that the course improved the students’ SWB, self-compassion, mindfulness, and optimism. Mechanisms such as greater self-reflection, implementation of intentional positive activities, and big picture thinking underlie these reported improvements. Our findings support positive education’s effectiveness in enhancing student SWB and expand on the current literature by proposing novel mechanisms linking positive education to enhanced student SWB, self-compassion, mindfulness, and optimism

Examining Model Similarity for Exercise Self-Efficacy among Adults Recovering from a Stroke: A Community-Based Exercise Program

We used a single-case experimental research design to examine the effect of modelling (peer versus non-peer) on exercise self-efficacy in stroke survivors who participated in a community-based exercise program. Data were obtained using an ABCA design: (A1) no model/baseline 1 (3 weeks); (B) peer model (6 weeks); (C) non-peer model (6 weeks); and (A2) no model/baseline 2 (3 weeks). Four participants completed self-efficacy questionnaires after each weekly session. Overall, participants reported higher exercise self-efficacy in the model conditions (Cohen’s d range from −0.37 to 4.22), with ratings appearing highest for the non-peer model. Modelling in general may help stroke survivors increase their exercise self-efficacy. Lastly, we provide our reflections on the pragmatics of completing a study within a community setting.Other UBCReviewedOthe

Effectiveness of complete primary vaccination against COVID-19 at primary care and community level during predominant Delta circulation in Europe: multicentre study analysis by age-group, vaccine brand and time since vaccination, I-MOVE-COVID-19 and ECDC networks, July–August 2021

Introduction In July and August 2021, the SARS-CoV-2 Delta variant dominated in Europe. We measured COVID-19 vaccine effectiveness (VE) against symptomatic infection, using a multicentre test-negative study at primary care/community level in Europe. Methods Patients presenting with COVID-19/ARI symptoms at primary care/community level in 10 countries were tested for SARS-CoV-2. We measured complete primary course overall VE among those aged 30–44, 45–59, 60–74 and ≥75 years, and among those 30–59 and ≥60 years by vaccine brand and by time since vaccination. Results Overall VE was 74% (95%CI: 69–79), 76% (95%CI: 71–80), 63% (95%CI: 48–75), 63% (95%CI: 16–83) among those aged 30–44, 45–59, 60–74 and ≥75 years, respectively. VE among those aged 30–59 years was 78% (95%CI: 75–81), 66% (95%CI: 58–73), 91% (95%CI: 87–94) and 52% (95%CI: 40–61), for Comirnaty, Vaxzevria, Spikevax and COVID-19 Vaccine Janssen, respectively. VE among those aged ≥60 years was 67% (95%CI: 52–77), 65% (95%CI: 48–76), 83% (95%CI: 64–92) for Comirnaty, Vaxzevria and Spikevax, respectively. Comirnaty VE among those aged 30–59 years was 87% (95%CI: 83–89) and 65% (95%CI: 56–71%) at 14–29 days and ≥90 days between vaccination and onset of symptoms, respectively. Conclusions VE against the symptomatic SARS-CoV-2 Delta variant infection varied among brands, ranging from 52–91%. While some waning of the vaccine effect may be present (sample size limited this analysis to only Comirnaty), protection was 65% ≥90 days between vaccination and onset

Effectiveness of complete primary vaccination against COVID-19 at primary care and community level during predominant Delta circulation in Europe: multicentre analysis, I-MOVE-COVID-19 and ECDC networks, July to August 2021.

This project received funding from the European Centre for Disease Prevention and Control (ECDC) under the contract ECD.11486. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 101003673.Introduction : In July and August 2021, the SARS-CoV-2 Delta variant dominated in Europe. Aim: Using a multicentre test-negative study, we measured COVID-19 vaccine effectiveness (VE) against symptomatic infection.  Methods : Individuals with COVID-19 or acute respiratory symptoms at primary care/community level in 10 European countries were tested for SARS-CoV-2. We measured complete primary course overall VE by vaccine brand and by time since vaccination.  Results : Overall VE was 74% (95% CI: 69-79), 76% (95% CI: 71-80), 63% (95% CI: 48-75) and 63% (95% CI: 16-83) among those aged 30-44, 45-59, 60-74 and ≥ 75 years, respectively. VE among those aged 30-59 years was 78% (95% CI: 75-81), 66% (95% CI: 58-73), 91% (95% CI: 87-94) and 52% (95% CI: 40-61), for Comirnaty, Vaxzevria, Spikevax and COVID-19 Vaccine Janssen, respectively. VE among people 60 years and older was 67% (95% CI: 52-77), 65% (95% CI: 48-76) and 83% (95% CI: 64-92) for Comirnaty, Vaxzevria and Spikevax, respectively. Comirnaty VE among those aged 30-59 years was 87% (95% CI: 83-89) at 14-29 days and 65% (95% CI: 56-71%) at ≥ 90 days between vaccination and onset of symptoms.  Conclusions : VE against symptomatic infection with the SARS-CoV-2 Delta variant varied among brands, ranging from 52% to 91%. While some waning of the vaccine effect may be present (sample size limited this analysis to only Comirnaty), protection was 65% at 90 days or more between vaccination and onset.Publisher PDFPeer reviewe

Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

10.1371/journal.pone.0139981PLoS ONE1010e013998

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field