Stressor-Induced Increase in Muscle Fatigability of Young Men and Women is Predicted by Strength but Not Voluntary Activation

This study investigated mechanisms for the stressor-induced changes in muscle fatigability in men and women. Participants performed an isometric-fatiguing contraction at 20% maximal voluntary contraction (MVC) until failure with the elbow flexor muscles. Study one (n = 55; 29 women) involved two experimental sessions: 1) a high-stressor session that required a difficult mental-math task before and during a fatiguing contraction and 2) a control session with no mental math. For some participants (n = 28; 14 women), cortical stimulation was used to examine mechanisms that contributed to muscle fatigability during the high-stressor and control sessions. Study two (n = 23; nine women) determined the influence of a low stressor, i.e., a simple mental-math task, on muscle fatigability. In study one, the time-to-task failure was less for the high-stressor session than control (P \u3c 0.05) for women (19.4%) and men (9.5%): the sex difference response disappeared when covaried for initial strength (MVC). MVC force, voluntary activation, and peak-twitch amplitude decreased similarly for the control and high-stressor sessions (P \u3c 0.05). In study two, the time-to-task failure of men or women was not influenced by the low stressor (P \u3e 0.05). The greater fatigability, when exposed to a high stressor during a low-force task, was not exclusive to women but involved a strength-related mechanism in both weaker men and women that accelerated declines in voluntary activation and slowing of contractile properties

Stressor-Induced Increase in Muscle Fatigability of Young Men and Women is Predicted by Strength but Not Voluntary Activation

This study investigated mechanisms for the stressor-induced changes in muscle fatigability in men and women. Participants performed an isometric-fatiguing contraction at 20% maximal voluntary contraction (MVC) until failure with the elbow flexor muscles. Study one (n = 55; 29 women) involved two experimental sessions: 1) a high-stressor session that required a difficult mental-math task before and during a fatiguing contraction and 2) a control session with no mental math. For some participants (n = 28; 14 women), cortical stimulation was used to examine mechanisms that contributed to muscle fatigability during the high-stressor and control sessions. Study two (n = 23; nine women) determined the influence of a low stressor, i.e., a simple mental-math task, on muscle fatigability. In study one, the time-to-task failure was less for the high-stressor session than control (P \u3c 0.05) for women (19.4%) and men (9.5%): the sex difference response disappeared when covaried for initial strength (MVC). MVC force, voluntary activation, and peak-twitch amplitude decreased similarly for the control and high-stressor sessions (P \u3c 0.05). In study two, the time-to-task failure of men or women was not influenced by the low stressor (P \u3e 0.05). The greater fatigability, when exposed to a high stressor during a low-force task, was not exclusive to women but involved a strength-related mechanism in both weaker men and women that accelerated declines in voluntary activation and slowing of contractile properties

Maintenance N-acetyl cysteine treatment for bipolar disorder : a double-blind randomised placebo controlled trial

Background N-acetyl cysteine (NAC) is a glutathione precursor that has been shown to have antidepressant efficacy in a placebo-controlled trial. The current study aimed to investigate the maintenance effects of NAC following eight weeks of open-label treatment for bipolar disorder.Method The efficacy of a double blind randomized placebo controlled trial of 2 g/day NAC as adjunct maintenance treatment for bipolar disorder was examined. Participants (n = 149) had a Montgomery Asberg Depression Rating Score of [greater than or equal to]12 at trial entry and, after eight weeks of open-label NAC treatment, were randomized to adjunctive NAC or placebo, in addition to treatment as usual. Participants (primarily outpatients) were recruited through public and private services and through newspaper advertisements. Time to intervention for a mood episode was the primary endpoint of the study, and changes in mood symptoms, functionality and quality of life measures were secondary outcomes.Results There was a substantial decrease in symptoms during the eight-week open-label NAC treatment phase. During the subsequent double-blind phase, there was minimal further change in outcome measures with scores remaining low. Consequently, from this low plateau, between-group differences did not emerge on recurrence, clinical functioning or quality of life measures.Conclusions There were no significant between-group differences in recurrence or symptomatic outcomes during the maintenance phase of the trial; however, these findings may be confounded by limitations. Trial Registration The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12607000074493)

Long-Term Continuous Corticosterone Treatment Decreases VEGF Receptor-2 Expression in Frontal Cortex

Objective: Stress and increased glucocorticoid levels are associated with many neuropsychiatric disorders including schizophrenia and depression. Recently, the role of vascular endothelial factor receptor-2 (VEGFR2/Flk1) signaling has been implicated in stress-mediated neuroplasticity. However, the mechanism of regulation of VEGF/Flk1 signaling under longterm continuous glucocorticoid exposure has not been elucidated. Material and Methods: We examined the possible effects of long-term continuous glucocorticoid exposure on VEGF/Flk1 signaling in cultured cortical neurons in vitro, mouse frontal cortex in vivo, and in post mortem human prefrontal cortex of both control and schizophrenia subjects. Results: We found that long-term continuous exposure to corticosterone (CORT, a natural glucocorticoid) reduced Flk1 protein levels both in vitro and in vivo. CORT treatment resulted in alterations in signaling molecules downstream to Flk1 such as PTEN, Akt and mTOR. We demonstrated that CORT-induced changes in Flk1 levels are mediated through glucocorticoid receptor (GR) and calcium. A significant reduction in Flk1-GR interaction was observed following CORT exposure. Interestingly, VEGF levels were increased in cortex, but decreased in serum following CORT treatment. Moreover, significant reductions in Flk1 and GR protein levels were found in postmortem prefrontal cortex samples from schizophrenia subjects. Conclusions: The alterations in VEGF/Flk1 signaling following long-term continuous CORT exposure represents a molecula

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Association of contemporary sensitive troponin I levels at baseline and change at 1 year with long-term coronary events following myocardial infarction or unstable angina: results from the LIPID study (Long-Term Intervention with Pravastatin in Ischaemic

Objectives This study sought to assess whether baseline and change in contemporary sensitive troponin I (TnI) levels predicts coronary heart disease (CHD) death and myocardial infarction (MI), and to determine the effects of pravastatin on TnI levels