A case series of acute responses to high-intensity interval training in four males with permanent atrial fibrillation.

Background: Atrial fibrillation (AF) is a serious medical condition and a burgeoning patient population. Chronic exercise training, including high-intensity interval training (HIIT), has been shown to improve symptoms and quality of life in patients with AF. Yet, the acute responses to HIIT in this population remain understudied, leaving clinicians and patients hesitant about prescribing and engaging in high-intensity exercise, respectively. Case summary: This case series describes acute exercise responses [i.e. power output, heart rate (HR), blood pressure (BP), ratings of perceived exertion (RPE), symptoms] to 10 weeks (3 days/week) of HIIT. Participants were four white males (58-80 years old) with permanent AF, co-morbidities (diabetes, coronary artery disease, Parkinson's disease), and physical limitations. The increases in HR and BP during HIIT were modest across all participants, regardless of age and medication use. Differences in RPE were observed; the oldest participant perceived the sessions as more challenging despite a lower HR response. All patients complied with the HIIT prescription of 80-100% of peak power output by week 4. No adverse events were reported. Discussion: Patients' concerns regarding high-intensity exercise may discourage them from participating in HIIT, our results demonstrated no abnormal HR or BP (e.g. hypotension) responses during HIIT or cool-down. These findings align with the typical exercise responses noted in other cardiovascular populations. Notwithstanding the high metabolic demands of HIIT, male patients with permanent AF tolerated HIIT without problem. Further investigation of HIIT as an approach to enable those with AF to recover physical capacity and minimize symptomatology is warranted.

The Physical Activity Levels and Sitting Time of Adults Living With Atrial Fibrillation: The CHAMPLAIN-AF Study.

Background: The primary goal of this study was to determine the time spent completing moderate-to-vigorous intensity physical activity (MVPA) among adults with atrial fibrillation (AF). Secondary aims examined MVPA and sitting time (ST) by AF subtypes (ie, paroxysmal, persistent, long-standing persistent, and permanent) and associations between MVPA or ST and knowledge, task self-efficacy, and outcome expectations. Methods: An observational study was conducted in the Champlain region of Ontario, Canada. AF patients completed a survey to determine MVPA and ST using the Short-Form International Physical Activity Questionnaire. Results: A total of 619 patients (66% male; median age 65 years [95% CI 64-67 years]) completed the survey. Median MVPA and ST were 100 (60-120) min/wk and 6 (5-6) h/d; 56% of patients were not meeting the Canadian 24H Movement Guidelines. Most patients (54%) did not know/were unsure of the MVPA recommendations, yet 72% thought physical activity should be part of AF management. Positive correlations were found between higher MVPA levels and the following: (i) speaking to a healthcare professional about engaging in physical activity for managing AF (ρ = 0.108, P = 0.017); (ii) greater confidence regarding ability to perform physical activity and muscle-strengthening exercise (ρ = 0.421, P < 0.01); and (iii) patient agreement that AF would be better managed if they were active (ρ = 0.205, P < 0.01). Conclusions: Many AF patients do not meet the MVPA recommendations, which may be due to lack of physical activity knowledge. Exercise professionals may help educate patients on the benefits of physical activity, improve task-self efficacy, and integrate MVPA into patient lifestyles.

Introduction: Le principal objectif de la présente étude était de déterminer le temps consacré à faire de l'activité physique modérée à vigoureuse (APMV) chez les adultes atteints de fibrillation auriculaire (FA). Les objectifs secondaires visaient à examiner l'APMV et le temps en position assise (TA) selon les sous-types de FA (c.-à-d. paroxystique, persistante, persistante de longue durée et permanente) et les associations entre l'APMV ou le TA et les connaissances, le sentiment d'auto-efficacité et les attentes de résultats. Méthodes: Nous avons réalisé une étude observationnelle dans la région de Champlain, en Ontario, au Canada. Les patients atteints de FA ont rempli une enquête pour déterminer l'APMV et le TA à l'aide du questionnaire court International Physical Activity Questionnaire (IPAQ). Résultats: Un total de 619 patients (66 % d'hommes; âge médian de 65 ans [IC à 95 % 64-67 ans]) a rempli l'enquête. L'APMV et le TPA médians étaient de 100 (60-120) min/sem et de 6 (5-6) h/j; 56 % des patients ne répondaient pas aux Directives canadiennes en matière de mouvement sur 24 heures. La plupart des patients (54 %) ne connaissaient pas les recommandations d'APMV ou n'étaient pas certains de les connaître, mais 72 % pensaient que l'activité physique devrait faire partie de la prise en charge de la FA. Nous avons observé des corrélations positives entre les degrés plus élevés d'APMV et ce qui suit : (i) le fait de parler à un professionnel de la santé de la pratique de l'activité physique pour prendre en charge la FA (ρ = 0,108, P = 0,017); (ii) la confiance accrue quant à la capacité de faire de l'activité physique et les exercices de renforcement musculaire (ρ = 0,421, P < 0,01); (iii) l'accord du patient sur le fait que la pratique de l'activité physique contribuerait à une meilleure prise en charge de la FA (ρ = 0,205, P < 0,01). Conclusions: Plusieurs patients atteints de FA ne répondaient pas aux recommandations d'APMV, possiblement en raison du manque de connaissances concernant l'activité physique. Les professionnels de l'activité physique peuvent contribuer à l'éducation des patients afin de leur faire connaître les avantages de l'activité physique, améliorer leur auto-efficacité et intégrer l'APMV à leur mode de vie.

TAOK3 phosphorylates the methylenecyclopropane nucleoside MBX 2168 to its monophosphate.

Monohydroxymethyl methylenecyclopropane nucleosides (MCPNs) with ether or thioether substituents at the 6-position show promise as broad-spectrum herpes virus inhibitors. Their proposed mechanism of action involves sequential phosphorylation to a triphosphate, which can then inhibit viral DNA polymerase. The inhibition of herpes simplex virus (HSV) by these compounds is not dependent on the viral thymidine kinase (TK), which is known to phosphorylate acyclovir (ACV), a standard treatment for HSV infections. Previous studies on the mechanism of action of these compounds against human cytomegalovirus (HCMV) implicated a host kinase in addition to HCMV UL97 kinase in performing the initial phosphorylation. After first eliminating other candidate HSV-1 encoded kinases (UL13 and US3) as well as potential host nucleoside kinases, using activity-based fractionation, we have now identified the host serine-threonine protein kinase TAOK3 as the kinase responsible for transforming the representative monohydroxymethyl MCPN analog MBX 2168 to its monophosphate.

Human cytomegalovirus UL97 kinase is involved in the mechanism of action of methylenecyclopropane analogs with 6-ether and -thioether substitutions.

Methylenecyclopropane nucleoside (MCPN) analogs are being investigated for treatment of human cytomegalovirus (HCMV) infection because of favorable preclinical data and limited ganciclovir cross-resistance. Monohydroxymethyl MCPNs bearing ether and thioether functionalities at the purine 6 position have antiviral activity against herpes simplex virus (HSV) and varicella-zoster virus (VZV) in addition to HCMV. The role of the HCMV UL97 kinase in the mechanism of action of these derivatives was examined. When tested against a kinase-inactive UL97 K355M virus, a moderate 5- to 7-fold increase in 50% effective concentration (EC50) was observed, in comparison to a 13- to 25-fold increase for either cyclopropavir or ganciclovir. Serial propagation of HCMV under two of these compounds selected for three novel UL97 mutations encoding amino acid substitutions D456N, C480R,and Y617del. When transferred to baseline laboratory HCMV strains, these mutations individually conferred resistance to all of the tested MCPNs, ganciclovir, and maribavir. However, the engineered strains also demonstrated severe growth defects and abnormal cytopathic effects similar to the kinase-inactive mutant. Expressed and purified UL97 kinase showed in vitro phosphorylation of the newly tested MCPNs. Thus, HCMV UL97 kinase is involved in the antiviral action of these MCPNs, but the in vitro selection of UL97-defective viruses suggests that their activity against more typical ganciclovir-resistant growth-competent UL97 mutants may be relatively preserved.