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Virology Sep 2023COVID-19 is a global health problem caused by SARS-CoV-2, which has led to over 600 million infections and 6 million deaths. Developing novel antiviral drugs is of...
COVID-19 is a global health problem caused by SARS-CoV-2, which has led to over 600 million infections and 6 million deaths. Developing novel antiviral drugs is of pivotal importance to slow down the epidemic swiftly. In this study, we identified five azo compounds as effective antiviral drugs to SARS-CoV-2, and mechanism study revealed their targets for impeding viral particles' ability to bind to host receptors. Direct Blue 53, which displayed the strongest inhibitory impact, inhibited five mutant strains at micromole. In vitro, mechanism study demonstrated Direct Blue 53 inhibited viral infection through interaction with the spike of SARS-CoV-2. And 25 mg/kg/d compound treatment showed 50% or 60% survival protection against lethal Delta or Omicron BA.2 infection in vivo. Taken together, our results demonstrate that azo compounds with dimethyl-biphenyl-diyl-bis(azo)bis structure may be promising anti-SARS-CoV-2 drug candidates, which provide practicable therapies with the aid of structural optimizations and further research.
Topics: Humans; COVID-19; SARS-CoV-2; Angiotensin-Converting Enzyme 2; Antiviral Agents; Azo Compounds; Spike Glycoprotein, Coronavirus
PubMed: 37531695
DOI: 10.1016/j.virol.2023.07.006 -
International Journal of Sports... Aug 2023Mental fatigue causes decreases in aspects of athletes' performance. Elite coaches commonly undertake cognitively demanding tasks and are seemingly at similar risk of...
PURPOSE
Mental fatigue causes decreases in aspects of athletes' performance. Elite coaches commonly undertake cognitively demanding tasks and are seemingly at similar risk of subsequent performance impairment. However, elite sport coaches' experiences of mental fatigue, alongside other markers of psychobiological stress, have yet to be quantified.
METHODS
Three elite coaching and performance staff (2 women and 1 man) provided 100-mm visual analog scale ratings of mental fatigue, physical fatigue, readiness to perform, and salivary samples for later cortisol (sCort) and alpha-amylase (sAA) analysis. Data were obtained on the same morning each week across a 16-week preseason. Data were subset by individual coach for descriptive and repeated-measures correlational analyses.
RESULTS
Fluctuating mental fatigue was observed over the 16 weeks (min-max; coach 1 = 25-86 AU; coach 2 = 0-51 AU; and coach 3 = 15 - 76 AU). Elevated levels of mental fatigue were reported at multiple time points, with individual variability observed. sCort (in nanomoles per liter), sAA (in micromoles per liter), and sAA:sCort indicated that coaches experienced psychophysiological stress (min-max; coach 1 sCort = 8.42-17.31, sAA = 52.40-113.06, sAA:sCort = 3.20-12.80; coach 2 sCort = 4.20-9.70, sAA = 158.80-307.20, sAA:sCort = 21.10-61.70; and coach 3 sCort = 6.81-19.66, sAA = 86.55-495.85, sAA:sCort = 4.90-35.50). A significant inverse relationship between mental fatigue and readiness to perform (r = -.44 [-.64 to -.17], P = .002) was identified.
CONCLUSIONS
Elite sport coaches report elevated instances of mental fatigue during a preseason training period. Those involved in elite sports should act to understand the presence and potential subsequent impacts of staff mental fatigue and consider management or mitigation strategies. Optimization of the cognitive performance of coaches and performance staff presents as a potential source of competitive advantage.
Topics: Male; Humans; Female; Athletes; Mentoring; Athletic Performance; Mental Fatigue; Competitive Behavior
PubMed: 37311561
DOI: 10.1123/ijspp.2023-0033 -
Rheumatology (Oxford, England) Jul 2023To investigate associations between treat-to-target urate-lowering therapy (ULT) and hospitalizations for gout.
OBJECTIVE
To investigate associations between treat-to-target urate-lowering therapy (ULT) and hospitalizations for gout.
METHODS
Using linked Clinical Practice Research Datalink and NHS Digital Hospital Episode Statistics data, we described the incidence and timing of hospitalizations for flares in people with index gout diagnoses in England from 2004-2020. Using Cox proportional hazards and propensity models, we investigated associations between ULT initiation, serum urate target attainment, colchicine prophylaxis, and the risk of hospitalizations for gout.
RESULTS
Of 292 270 people with incident gout, 7719 (2.64%) had one or more hospitalizations for gout, with an incidence rate of 4.64 hospitalizations per 1000 person-years (95% CI 4.54, 4.73). There was an associated increased risk of hospitalizations within the first 6 months after ULT initiation, when compared with people who did not initiate ULT [adjusted Hazard Ratio (aHR) 4.54; 95% CI 3.70, 5.58; P < 0.001]. Hospitalizations did not differ significantly between people prescribed vs not prescribed colchicine prophylaxis in fully adjusted models. From 12 months after initiation, ULT associated with a reduced risk of hospitalizations (aHR 0.77; 95% CI 0.71, 0.83; P < 0.001). In ULT initiators, attainment of a serum urate <360 micromol/l within 12 months of initiation associated with a reduced risk of hospitalizations (aHR 0.57; 95% CI 0.49, 0.67; P < 0.001) when compared with people initiating ULT but not attaining this target.
CONCLUSION
ULT associates with an increased risk of hospitalizations within the first 6 months of initiation but reduces hospitalizations in the long term, particularly when serum urate targets are achieved.
Topics: Humans; Uric Acid; Cohort Studies; Gout Suppressants; Gout; Hospitalization; Colchicine; England
PubMed: 36355461
DOI: 10.1093/rheumatology/keac638