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Background: Excessive heat stress led to more than 400 deaths in the United States from 2011 to 2021. Common methods for heat injury prevention revolve around measurements of the environment and fail to account for the unique individual response to stressors. Methods: An observational approach was utilized with nine helicopter-based emergency medical services personnel during emergency flights to compare core temperature readings obtained from an ingestible temperature monitoring pill and the estimated core temperature reading of the Slate Safety Band V2 wearable device. Comparison of data was conducted within Microsoft Excel programming to determine the mean square error (MSE), root mean square error (RMSE), mean absolute error (MAE), mean biased error (MBE), and Bland–Altman plot development. Findings: A significant bias (t = 17.58, p <.001) toward the Slate Safety device reading higher with an average difference of −0.48°C (−0.86°F) was found, meaning the average temperature reading is 0.48°C (−0.86°F) higher with the Slate Safety device. A significant correlation of.26 (p <.001) was noted between the ingestible pill and the wearable device with a 95% confidence interval of 0.23 to 0.29. Aggregate core temperature data demonstrated an MSE of 0.43, an RMSE of 0.65, an MAE of 0.54, and an MBE of −0.48. Conclusions/Application to Practice: The ability to monitor the physiological parameters of a worker remotely adds safety tools relative to the risks of heat stress. The slightly higher reading associated with the Slate Safety wearable device provides an added safety margin to protect our workers. [ABSTRACT FROM AUTHOR]

This study was conducted to investigate the systemic hemodynamic and vascular changes in women during and after two commonly used clinical blood flow restriction (BFR) pressures at rest. There are minimal data regarding the independent effects of BFR on hemodynamic and systemic vascular changes due to pressor response, particularly among women. Therefore, this study investigated BFR‐induced alterations in pressor response and systemic flow redistribution at rest during two commonly used pressures (50% and 80% limb occlusion pressure [LOP]). Fifteen women (22.1 ± 4.2 years) completed two randomised sessions involving 8‐min of bilateral, lower limb restriction at 50% or 80% LOP followed by 8‐min of recovery post‐deflation. Changes in vascular (arterial diameter [DIA], time‐averaged mean velocity [TAMV], volume flow [VF], and area) and hemodynamic (heart rate [HR] and blood pressure) measures over time (pre‐, during, post‐occlusion) and by session (50% vs. 80% LOP) were tested using repeated measures analysis of variance. Repeated measures correlations (rrm) quantified common intraindividual associations between BFR‐induced hemodynamic and vascular responses. HR increased from baseline during 50% LOP and remained elevated during recovery (p < 0.05). HR increased from baseline during 80% LOP, while tibial VF and TAMV decreased (p < 0.03 for all). HR and TAMV values returned to baseline during recovery, while brachial artery VF decreased (p < 0.05). Changes in HR, brachial VF, and brachial TAMV were similar between 50% and 80% LOP (rrm = 0.32–0.70, p < 0.05 for all). At 80% LOP, changes in HR were positively correlated with brachial VF (rrm = 0.38) and TAMV (rrm = 0.43) and negatively correlated with tibial VF (rrm = −0.36) and TAMV (rrm = −0.30) (p < 0.05 for all). Results suggest that BFR at 80% LOP elicits an acute systemic pressor reflex without concomitant increases in brachial arterial flow, while 50% LOP elicits a subdued response. [ABSTRACT FROM AUTHOR]

Background Bemnifosbuvir (AT-527) is a novel oral guanosine nucleotide antiviral drug for the treatment of persons with COVID-19. Direct assessment of drug disposition in the lungs, via bronchoalveolar lavage, is necessary to ensure antiviral drug levels at the primary site of SARS-CoV-2 infection are achieved. Objectives This Phase 1 study in healthy subjects aimed to assess the bronchopulmonary pharmacokinetics, safety and tolerability of repeated doses of bemnifosbuvir. Methods A total of 24 subjects were assigned to receive bemnifosbuvir twice daily at doses of 275, 550 or 825 mg for up to 3.5 days. Results AT-511, the free base of bemnifosbuvir, was largely eliminated from the plasma within 6 h post dose in all dosing groups. Antiviral drug levels of bemnifosbuvir were consistently achieved in the lungs with bemnifosbuvir 550 mg twice daily. The mean level of the guanosine nucleoside metabolite AT-273, the surrogate of the active triphosphate metabolite of the drug, measured in the epithelial lining fluid of the lungs was 0.62 µM at 4–5 h post dose. This exceeded the target in vitro 90% effective concentration (EC90) of 0.5 µM for antiviral drug exposure against SARS-CoV-2 replication in human airway epithelial cells. Bemnifosbuvir was well tolerated across all doses tested, and most treatment-emergent adverse events reported were mild in severity and resolved. Conclusions The favourable pharmacokinetics and safety profile of bemnifosbuvir demonstrates its potential as an oral antiviral treatment for COVID-19, with 550 mg bemnifosbuvir twice daily currently under further clinical evaluation in persons with COVID-19. [ABSTRACT FROM AUTHOR]

Although a variety of tools to monitor recovery have been developed, many are impractical for daily use due to cost, time, and challenges with interpretation. The Perceived Recovery Status (PRS) scale was recently developed as an expeditious, noninvasive tool to assess recovery status. While PRS has been strongly associated with repeated sprinting performance, a paucity of research exists relating PRS and performance recovery following resistance exercise. Purpose: The purpose of this study was to evaluate the sensitivity of PRS as a subjective marker of recovery up to 72 hours after a high-volume back-squat protocol. Methods: Eleven resistance-trained men reported to the laboratory on 5 separate occasions (1 familiarization session and 4 testing sessions). The first testing session was considered the baseline session and consisted of a nonfatiguing performance assessment (ie, countermovement jumps and back squats) and a fatiguing back-squat protocol of 8 sets of 10 at 70% 1-repetition maximum separated by 2 minutes of recovery. Participants returned 24, 48, and 72 hours following baseline to provide a PRS rating and complete the performance assessment. Results: Repeated-measures correlations revealed strong associations between PRS countermovement jump (r =.84) and mean bar velocity (r =.80) (both P <.001). Conclusions: The current findings suggest that PRS can be used as a method to effectively assess daily recovery following a fatiguing bout of resistance exercise. Practitioners are cautioned that the relationship between PRS and performance recovery is individualized, and equivalent PRS scores between individuals are not indicative of similar recovery. [ABSTRACT FROM AUTHOR]

Purpose: This study examined the agreement between %Fat measurements using a smartphone‐based application (IMAGE) across different environmental conditions. Methods: A single reference image was obtained using an 8 MP smartphone camera under Ambient Light in front of a white background. Additional photos were obtained using a 0.7 MP, 5 MP, and 12 MP smartphone cameras; low‐, moderate‐, and bright‐lighting conditions; and various color backgrounds including black, green, orange, and gray. Results: %Fat measured using the 0.7 MP camera (27.8 ± 6.2 %Fat) was higher than the reference (26.8 ± 6.1 %Fat) (p < 0.001). The black (32.0 ± 12.0 %Fat), green (27.5 ± 6.3 %Fat), and gray (27.8 ± 6.3 %Fat) backgrounds yielded higher %Fat than the white (p = 0.03, 0.01, and 0.001). All camera, lighting, and background conditions were strongly correlated with the reference (all intraclass correlation coefficient [ICC] >0.98, all standard error of the estimate [SEE] <1.5 %Fat, all p < 0.001), except the black background which yielded poorer agreement with the white background (ICC = 0.69, SEE = 4.5%, p < 0.001). Conclusion: %Fat from IMAGE were strongly correlated across various environmental conditions. [ABSTRACT FROM AUTHOR]

Paraoxanase-1 (PON1) is an HDL-associated enzyme that contributes to the antioxidant and antiatherosclerotic properties of HDL. Lack of PON1 results in dysfunctional HDL. HHcy is a risk factor for cardiovascular disorders, and instigates vascular dysfunction and ECM remodeling. Although studies have reported HHcy during atherosclerosis, the exact mechanism is unclear. Here, we hypothesize that dysfunctional HDL due to lack of PON1 contributes to endothelial impairment and atherogenesis through HHcy-induced ECM re-modeling. To verify this hypothesis, we used C57BL6/J and PON1 knockout mice (KO) and fed them an atherogenic diet. The expression of Akt, ADMA, and DDAH, as well as endothelial gap junction proteins such as Cx-37 and Cx-40 and eNOS was measured for vascular dysfunction and inflammation. We observed that cardiac function was decreased and plasma Hcy levels were increased in PON1 KO mice fed the atherogenic diet compared with the controls. Expression of Akt, eNOS, DDAH, Cx-37, and Cx-40 was decreased, and the expression of MMP-9 andADMA was increased in PON1 KO mice fed an atherogenic diet compared with the controls. Our results suggest that HHcy plays an intricate role in dysfunctional HDL, owing to the lack of PON1. This contributes to vascular endothelial impairment and atherosclerosis through MMP-9-induced vascular remodeling. Key words: atherosclerosis, homocysteine, Akt, eNOS, Cx-37 and--40, MMP-9. La paraoxanase 1 (PON1) est une enzyme associee aux HDL qui contribue a leurs proprietes antioxydantes et antiatherosclerosantes. De fait, un manque de PON1 est associe a des HDL dysfonctionnelles. Par ailleurs, l'hyperhomocysteinemie (HHcy) est un facteur de risque des troubles cardiovasculaires qui entraine des dysfonctions vasculaires et le remodelage de la matrice extracellulaire. Bien que des etudes aient fait etat d'une association entre l'HHcy et l'atherosclerose, le mecanisme exact n'a pas ete elucide. Dans les presents travaux, nous posons l'hypothese selon laquelle des HDL dysfonctionnelles en raison d'un deficit de PON1 contribuent a l'affaiblissement de l'endothelium et a l'atherogenese par un remodelage de la matrice extracellulaire entraine par l'HHcy. En vue de verifier cette hypothese, nous avons utilise des souris <> C57BL6/J et PON1 et leur avons administre un regime alimentaire atherosclerosant. Les expressions d'Akt, de la dimethylarginine asymetrique (ADMA), de la dimethylarginine dimethylaminohydrolase (DDAH), de proteines de jonctions gap endotheliales comme les connexines 37 et 40 ainsi que de la NO synthase endotheliale (eNOS) ont ete mesurees a l'egard de la dysfonction vasculaire et l'inflammation. Nous avons observe que la fonction cardiaque etait alteree et que les taux d'Hcy etaient augmentes davantage chez les souris <> PON1 auxquelles un regime alimentaire atherosclerosant etait administre que dans le groupe temoin. De plus, les expressions d'Akt, de la eNOS, de la DDAH et des connexines-37 et 40 etaient diminuees et les expressions de la metalloproteinase matricielle 9 (MMP-9) et de la ADMA etaient augmentees, et ce, davantage chez les souris <> PON1 auxquelles un regime alimentaire atherosclerosant etait administre que dans le groupe temoin. Nos resultats laissent entendre que l'HHcy jouerait un role complexe dans le dysfonctionnement des HDL entraine par un deficit en PON1, ce qui contribuerait a l'affaiblissement de l'endothelium vasculaire et a l'atherosclerose causes pour leur part par un remodelage vasculaire induit par la MMP-9. [Traduit par la Redaction] Mots-cles: atherosclerose, homocysteine, Akt, eNOS, connexines 37 et 40, MMP-9., Introduction Atherosclerosis is one of the major contributing factors for acute coronary syndrome (Gotlieb 2005), during which plaque builds up in the vascular lumen and either narrows blood vessels or [...]

Introduction: Hyperhomocysteinemia (HHcy) is associated with inflammatory diseases and is known to increase the production of reactive oxygen species (ROS), matrix metalloproteinase (MMP)-9, and inducible nitric oxide synthase, and to decrease endothelial nitric oxide production. However, the impact of HHcy on macrophage phenotype differentiation is not well-established. It has been documented that macrophages have 2 distinct phenotypes: the 'classically activated/destructive' (M1), and the 'alternatively activated/constructive' (M2) subtypes. We hypothesize that HHcy increases M1 macrophage differentiation through extracellular matrix metalloproteinase inducer (EMMPRIN), a known inducer of matrix metalloproteinases. Methods: murine J774A.1 and Raw 264.7 macrophages were treated with 100 and 500 µmol/L Hcy, respectively, for 24 h. Samples were analyzed using Western blotting and immunocytochemistry. Results: Homocysteine treatment increased cluster of differentiation 40 (CD40; M1 marker) in J774A.1 and Raw 264.7 macrophages. MMP-9 was induced in both cell lines. EMMPRIN protein expression was also increased in both cell lines. Blocking EMMPRIN function by pre-treating cells with anti-EMMPRIN antibody, with or without Hcy, resulted in significantly lower expression of CD40 in both cell lines by comparison with the controls. A DCFDA assay demonstrated increased ROS production in both cell lines with Hcy treatment when compared with the controls. Conclusion: Our results suggest that HHcy results in an increase of the M1 macrophage phenotype. This effect seems to be at least partially mediated by EMMPRIN induction. Key words: macrophage, M1, homocysteine, MMP-9, EMMPRIN, ROS. Introduction: L'hyperhomocysteinemie est associee aux maladies inflammatoires, et on sait qu'elle entrame une augmentation de la production de derives reactifs de l'oxygene, de la metalloproteinase matricielle-9 (MMP-9) et de iNOS ainsi qu'une reduction de la production de NO par l'endothelium. Cependant, les repercussions de l'hyperhomocysteinemie sur la differenciation du phenotype des macrophages n'ont pas ete bien etablies. On a documente que les macrophages disposent de deux phenotypes distincts: les sous-types M1 (<< actives par la voie classique/destructeurs >>) et M2 (<< actives par la voie alterne/ constructeurs >>). Nous avons formule l'hypothese selon laquelle l'hyperhomocysteinemie entrame une augmentation de la differenciation des macrophages M1 par l'EMMPRIN, un inducteur connu des metalloproteinases matricielles. Methodologie: Des macrophages murins J774A.1 et Raw 264.7 ont ete traites pendant 24 heures au moyen d'homocysteine a 100 et a 500 µmol/L, respectivement. Les echantillons ont ete analyses a l'aide de techniques de Western blot et d'immunocytochimie. Resultats: Le traitement par l'homocysteine a entrame une augmentation de CD40 (un marqueur du sous-type M1) dans les macrophages J774A.1 et Raw 264.7. La production de MMP-9 a ete induite dans les deux lignees cellulaires. L'expression de la proteine EMMPRIN a aussi augmente dans les deux lignees cellulaires. Le blocage fonctionnel d'EMMPRIN par les cellules pretraitees par l'anticorps anti-EMMPRIN, avec et sans homocysteine, a nettement reduit l'expression de CD40 dans les deux lignees cellulaires comparativement au groupe temoin. Une epreuve a la dichlorodihydrofluoresceine a permis de demontrer une augmentation de la production de derives reactifs de l'oxygene dans les deux lignees cellulaires avec le traitement par l'homocysteine comparativement au groupe temoin. Conclusion: Nos resultats laissent entendre que l'hyperhomocysteinemie entrame une augmentation du nombre de macrophages du phenotype M1. Cet effet semble passer, au moins en partie, par une induction par l'EMMPRIN. [Traduit par la Redaction] Mots-cles: macrophage, M1, homocysteine, metalloproteinase matricielle-9, EMMPRIN, derives reactifs de l'oxygene., Introduction Homocysteine (Hcy), a sulfhydryl amino acid derived from methionine, has been widely identified as a risk factor in numerous disease states. Hyperhomocysteinemia (HHcy), demonstrating plasma Hcy levels > 15 [...]

Regular exercise is a great medicine with its benefits encompassing everything from prevention of cardiovascular risk to alleviation of different muscular myopathies. Interestingly, elevated levels of homocysteine (Hcy), also known as hyperhomocysteinemia (HHcy), antagonizes beta-2 adrenergic receptors ([β.sub.2]AR), gamma amino butyric acid (GABA), and peroxisome proliferator-activated receptor-gamma (PPARγ) receptors. HHcy also stimulates an elevation of the M1/M2 macrophage ratio, resulting in a more inflammatory profile. In this review we discuss several potential targets altered by HHcy that result in myopathy and excessive fat accumulation. Several of these HHcy mediated changes can be countered by exercise and culminate into mitigation of HHcy induced myopathy and metabolic syndrome. We suggest that exercise directly impacts levels of Hcy, matrix metalloproteinase 9 (MMP-9), macrophages, and G-protein coupled receptors (GPCRs, especially [G.sub.s]). While HHcy promotes the M1 macrophage phenotype, it appears that exercise may diminish the M1/M2 ratio, resulting in a less inflammatory phenotype. HHcy through its influence on GPCRs, specifically [β.sub.2]AR, PPARγ and GABA receptors, promotes accumulation of white fat, whereas exercise enhances the browning of white fat and counters HHcy-mediated effects on GPCRs. Alleviation of HHcy-associated pathologies with exercise also includes reversal of excessive MMP-9 activation. Moreover, exercise, by reducing plasma Hcy levels, may prevent skeletal muscle myopathy, improve exercise capacity and rescue the obese phenotype. The purpose of this review is to summarize the pathological conditions surrounding HHcy and to clarify the importance of regular exercise as a method of disease prevention. Key words: homocysteine, macrophage, exercise, cardiovascular, GPCR, MMP-9, skeletal muscle, PPAR. L'exercice regulier est une excellente medication dont les benefices vont de la prevention du risque cardiovasculaire au soulagement de differentes myopathies. Fait interessant, des niveaux eleves d'homocysteine (Hcy), aussi connus sous le terme d'hyperhomocysteinemie (HHcy), antagonisent les recepteurs beta 2 adrenergiques ([β.sub.2]AR), le recepteur de l'acide gamma amino butyrique (GABA : gamma amino butyric acid) et le recepteur active par les proliferateurs de peroxysomes gamma (PPARγ : peroxysome proliferator-activated receptor-gamma). La HHcy stimule aussi une elevation du ratio des macrophages M1/M2, resultant en un profil davantage inflammatoire. Dans cet article de revue, les auteurs discutent de differentes cibles potentielles modifiees par l'HHcy qui resultent en une myopathie et en une accumulation excessive de graisse. Plusieurs de ces changements operes par l'intermediaire de l'HHc peuvent etre contrecarres par l'exercice et ils culminent par une attenuation de la myopathie et du syndrome metabolique induits par l'HHcy. Les auteurs suggerent que l'exercice a un impact direct sur les niveaux d'Hcy, sur la metalloprotease de la matrice (MMP-9), les macrophages et les recepteurs couples aux proteines G (RCPG, notamment [G.sub.s]). Alors que l'HHcy favorise le phenotype M1 chez les macrophages, il semble que l'exercice puisse diminuer le ratio M1/M2, resultant en un phenotype moins inflammatoire. L'HHcy, par son influence sur les RCPG, notamment les recepteurs [β.sub.2]AR, PPARγ et GABA, favorise l'accumulation de graisse blanche, alors que l'exercice favorise la transformation de graisse blanche en graisse brune et contrecarre les effets de l'HHcy sur les RCPG. L'attenuation des pathologies associees a l'HHcy par l'exercice inclut aussi le renversement de l'activation excessive de MMP-9. De plus, l'exercice, en reduisant les niveaux plasmatiques de Hcy, peut prevenir la myopathie squelettique, ameliorer la capacite a l'exercice et venir en aide aux personnes obeses. Le but de cet article de revue est de resumer les conditions pathologiques qui entourent l'HHcy et de clarifier l'importance de l'exercice regulier comme methode de prevention de la maladie. [Traduit par la Redaction] Mots-cles : homocysteine, macrophage, exercice, cardiovasculaire, RCPG, MMP-9, muscle squelettique, PPAR., Exercise: The forgotten medicine It has been well-established that regular exercise is associated with improvements in overall physical fitness, maintenance of health, a decreased risk of many disease states and, [...]

The study aimed to assess cardiovascular responses to low-intensity aerobic exercise with varying levels of limb occlusion pressures (LOP) in a healthy population of men and women 30 to 60 years. The study was a single-session repeated measures design. Thirty individuals completed the study. All subjects participated in a single bout of low-intensity cycling (30-39% HRR) with bilateral lower extremity (LE) BFR for four 5-minute stages [0% (No BFR), 40%, 60%, and 80% LOP] with a 2-minute active rest between stages (BFR pressure released). The subjects' systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR), oxygen saturation (SpO2), and ratings of perceived exertion (RPE) were measured at rest, peak, immediately post, post-15 minutes, and post-30 minutes. Peak SBP (no BFR 160.7 ±19.1 mmHg; 40% LOP 173.6 ± 18.7 mmHg; 60 % LOP; 182.5 ± 21.1 mmHg; 80% LOP 193.5± 23.3 mmHg; p<0.001; η²P=.747), DBP (no BFR 74.9 ± 8.5 mmHg; 40% LOP (83.0 ± 9.0 mmHg;60 % LOP 90.4 ± 8.7 mmHg; 80% LOP 97.7 ± 9.5 mmHg ;p<0.001; η²P=.924), MAP (no BFR 103.5 ± 10.1 mmHg; 40% LOP 113.2 ± 10.5 mmHg; 60% LOP 121.1 ± 11.7 mmHg; 80% LOP 129.7 ± 12.9 mmHg; p<0.001; η²P=.960), and RPE (No BFR 10.0 ± 2.0; 40 % LOP 11.5 ± 2.3; 60% LOP 13.2 ± 2.6; 80% LOP 14.5 ± 3.; p<0.001; η²P=.826) were significantly higher with each progressing stage. The results indicate that low-intensity cycling with bilateral LE BFR for each LOP stage resulted in elevated SBP, DBP, MAP, and RPE despite maintaining a fixed HR. [ABSTRACT FROM AUTHOR]