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Chloé Rauzier,1,2 Dominic J Chartrand,1,3 Natalie Alméras,1,3 Isabelle Lemieux,1 Eric Larose,1,4 Patrick Mathieu,1,5 Philippe Pibarot,1,4 Benoît Lamarche,6,7 Caroline Rhéaume,1,8,9 Paul Poirier,1,2 Jean-Pierre Després,1,3,9 Frédéric Picard1,2 1Centre de recherche de l’Institut universitaire de cardiologie et de pneumologie de Québec (IUCPQ) – Université Laval, Québec, QC, Canada; 2Faculté de pharmacie, Université Laval, Québec, QC, Canada; 3Département de kinésiologie, Faculté de médecine, Université Laval, Québec, QC, Canada; 4Département de médecine, Faculté de médecine, Université Laval, Québec, QC, Canada; 5Département de chirurgie, Faculté de médecine, Université Laval, Québec, QC, Canada; 6Centre Nutrition, santé et société (NUTRISS), Institut sur la nutrition et les aliments fonctionnels (INAF), Université Laval, Québec, QC, Canada; 7École de nutrition, Faculté des sciences de l’agriculture et de l’alimentation, Université Laval, Québec, QC, Canada; 8Département de médecine familiale et de médecine d’urgence, Faculté de médecine, Université Laval, Québec, QC, Canada; 9VITAM – Centre de recherche en santé durable, Québec, QC, CanadaCorrespondence: Frédéric Picard; Jean-Pierre Després, Email Frederic.Picard@criucpq.ulaval.ca; jean-pierre.despres.ciussscn@ssss.gouv.qc.caAbstract: Optimal non-invasive biomarkers for metabolic dysfunction-associated steatotic liver disease (MASLD) remain elusive, especially in the detection of early stages. This study tested in an asymptomatic cohort of 171 men (49.2 ± 8.6 years) and 131 women (51.8 ± 8.5 years) whether waist circumference (WC) and circulating levels of insulin-like growth factor-binding protein 2 (IGFBP-2) could identify individuals with liver fat > 5% as assessed by magnetic resonance spectroscopy. Participants with high WC (> 85 or 90 cm for women and men, respectively) and low IGFBP-2 (< 260 or 230 ng/mL for women and men, respectively) were characterized by a higher risk of having MASLD (46.3%, p < 0.0001). Among the 68 individuals with MASLD, 73.5% fell into the subgroup with high WC and low IGFBP-2 concentrations (p < 0.0001). When combined, these markers reached a sensitivity of 73.5% and specificity of 75.2% for MASLD. Thus, WC and plasma IGFBP-2 levels might be useful as a novel, simple, and non-invasive index to support existing tools in the identification of individuals at risk of early-stage MASLD.Keywords: humans, insulin-like growth factor-binding protein 2, waist circumference, hepatic fat, metabolic dysfunction-associated steatotic liver disease, biomarker, plasma, non-invasive

David C Rupp, David Canty, Catherine Rhéaume, Birgitte Sondergaard, Celina Niño, Ron S Broide, Amy D Brideau-Andersen Allergan Aesthetics, an AbbVie Company, Irvine, CA, USACorrespondence: David C Rupp, Allergan Aesthetics, an AbbVie Company, 2525 Dupont Drive, Irvine, CA, 92612, USA, Tel +1-714-246-4059, Email david.rupp@abbvie.comObjective: The goal of this study was to compare the unit-to-unit biological activity of the vacuum-dried formulation of prabotulinumtoxinA (prabotA) and onabotulinumtoxinA (onabotA) in preclinical assays.Methods: Reconstituted 100 U vials of prabotA and onabotA were tested in 3 distinct assays: plate-capture light chain activity (PC-LCA), measuringlight chain enzymatic activity after recovery of toxin from reconstituted product using a proprietary toxin capture step; cell-based potency assay (CBPA), measuring the intoxication steps of binding, translocation, and light chain activity (synaptosomal-associated protein 25 [SNAP25] cleavage); and mouse Digit Abduction Score (DAS), evaluating muscle paresis. Each assay tested 3 separate prabotA and onabotA lots on several independent test dates.Results: Multiple orthogonal assays established that when assessed on a unit-to-unit basis, the biological activity of prabotA is lower than that of onabotA. In the PC-LCA and CBPA assays, onabotA displayed 1.51 ± 0.14–fold higher (mean ± SD) and 1.33 ± 0.07–fold higher (mean of pooled lots ± SEM) activity than prabotA, respectively. Similarly, the mouse DAS data showed that onabotA had 1.4 ± 0.1–fold higher (mean ± SEM) potency than prabotA. Results of all 3 assays demonstrated differences in potency, efficacy, and duration of action between onabotA and prabotA on a unit-to-unit basis.Conclusion: Preclinical assays established differences in the biological activity of onabotA and prabotA, supporting that the units of biological activity are not interchangeable.Keywords: pharmaceutical preparations, biological assays, enzyme assays, animal studies, motor neurons, protein binding

Abstract Background To explore ways to reduce the overuse of antibiotics for acute respiratory infections (ARIs), we conducted a pilot clustered randomized controlled trial (RCT) to evaluate DECISION+, a training program in shared decision making (SDM) for family physicians (FPs). This pilot project demonstrated the feasibility of conducting a large clustered RCT and showed that DECISION+ reduced the proportion of patients who decided to use antibiotics immediately after consulting their physician. Consequently, the objective of this study is to evaluate, in patients consulting for ARIs, if exposure of physicians to a modified version of DECISION+, DECISION+2, would reduce the proportion of patients who decide to use antibiotics immediately after consulting their physician. Methods/design The study is a multi-center, two-arm, parallel clustered RCT. The 12 family practice teaching units (FPTUs) in the network of the Department of Family Medicine and Emergency Medicine of Université Laval will be randomized to a DECISION+2 intervention group (experimental group) or to a no-intervention control group. These FPTUs will recruit patients consulting family physicians and residents in family medicine enrolled in the study. There will be two data collection periods: pre-intervention (baseline) including 175 patients with ARIs in each study arm, and post-intervention including 175 patients with ARIs in each study arm (total n = 700). The primary outcome will be the proportion of patients reporting a decision to use antibiotics immediately after consulting their physician. Secondary outcome measures include: 1) physicians and patients' decisional conflict; 2) the agreement between the parties' decisional conflict scores; and 3) perception of patients and physicians that SDM occurred. Also in patients, at 2 weeks follow-up, adherence to the decision, consultation for the same reason, decisional regret, and quality of life will be assessed. Finally, in both patients and physicians, intention to engage in SDM in future clinical encounters will be assessed. Intention-to-treat analyses will be applied and account for the nested design of the trial will be taken into consideration. Discussion DECISION+2 has the potential to reduce antibiotics use for ARIs by priming physicians and patients to share decisional process and empowering patients to make informed, value-based decisions. Trial Registration ClinicalTrials.gov: NCT01116076

Introduction: Space agencies and private industries worldwide are planning long-duration missions, which come with complex medical challenges. Crews must be prepared for medical emergencies due to longer mission durations, increased travel distance, communication delays, and higher levels of isolation. This study aimed to systematically review the existing literature and knowledge gaps that could be related to the management of medical emergencies during long-duration space missions., Methods: A scoping review was conducted following the PRISMA extension for scoping reviews. Electronic databases, including ARC, Embase, IEEE Xplore, Medline Ovid, PsycINFO, and Web of Science, were searched from inception to June 1, 2023. Empirical study designs published in English or French were eligible for inclusion provided they described the management of at least 1 of 10 prioritized potentially mission-critical medical conditions., Results: A total of 484 full-text studies were assessed for eligibility, with 99 included in this review. Conditions with the highest representation were spaceflight-associated neuro-ocular syndrome (N = 23), herniated disk (N = 22), and nephrolithiasis (N = 22). Conditions with the least representation were cerebrovascular accidents (N = 4), eye penetration (N = 3), and retinal detachment (N = 2). The duration of missions varied between 5 and 438 d for studies conducted in space. The data reflected the scarcity of evidence concerning prolonged deep-space exposure beyond the Earth's magnetosphere., Discussion: Substantial medical autonomy is essential for the success of long-duration space missions, when medical support and even communication will be limited. Future research should prioritize knowledge gaps to improve preparedness and medical autonomy for space exploration activities. Tran K-A, Pollock NW, Dion P-M, Lapierre M, Tremblay S, Witteman W, Rhéaume C, Lafond D, Fortier F-A, Marion A, Dutil-Fafard L, Morin C, LePabic G, Monnot DPM, Archambault PM. Managing select medical emergencies during long-duration space missions. Aerosp Med Hum Perform. 2025; 96(2):143-154.

Background and Aims: Epicardial adiposity has been positively associated with visceral adipose tissue (VAT). Few studies have examined the association between cardiorespiratory fitness (CRF) and epicardial adiposity. Furthermore, whether this relationship was independent of VAT remains unexplored. Our purpose was to investigate the contribution of VAT in the relationships between CRF, physical activity (PA) and epicardial adipose tissue (EAT) in asymptomatic women and men., Methods and Results: We examined the associations between EAT and VAT measured by magnetic resonance imaging, CRF measured by cardiopulmonary exercise testing, and PA assessed using pedometers and a 3-day PA journal in 239 apparently healthy adults (43 % women). Participants were compared according to EAT tertiles and CRF level in both sexes. Participants with the highest EAT level presented more VAT (p < 0.001), lower CRF (p < 0.01), and a more deteriorated cardiometabolic health score (p < 0.01) than those with the lowest EAT level. CRF was negatively associated with EAT in both sexes (p < 0.01). No significant relationship was found with PA (p = NS). Stepwise multivariable regression analyses showed that VAT explained most of the variance in EAT in women and men. Mediation analyses confirmed that VAT was a mediator of the association between CRF and EAT in both sexes., Conclusion: In women and men, VAT appears as a major mediator of the association between CRF and EAT thereby suggesting that managing VAT by improving CRF could help in the prevention of cardiometabolic disorders related to excess EAT., Competing Interests: Declaration of competing interest Philippe Pibarot has received institutional funding from Edwards Lifesciences, Novartis, Medtronic and Pi-Cardia outside the submitted work and for which he has received no personal compensation. The other authors declared no conflict of interest., (Crown Copyright © 2024. Published by Elsevier B.V. All rights reserved.)

Background: Artificial intelligence (AI) predictive models in primary health care have the potential to enhance population health by rapidly and accurately identifying individuals who should receive care and health services. However, these models also carry the risk of perpetuating or amplifying existing biases toward diverse groups. We identified a gap in the current understanding of strategies used to assess and mitigate bias in primary health care algorithms related to individuals' personal or protected attributes., Objective: This study aimed to describe the attempts, strategies, and methods used to mitigate bias in AI models within primary health care, to identify the diverse groups or protected attributes considered, and to evaluate the results of these approaches on both bias reduction and AI model performance., Methods: We conducted a scoping review following Joanna Briggs Institute (JBI) guidelines, searching Medline (Ovid), CINAHL (EBSCO), PsycINFO (Ovid), and Web of Science databases for studies published between January 1, 2017, and November 15, 2022. Pairs of reviewers independently screened titles and abstracts, applied selection criteria, and performed full-text screening. Discrepancies regarding study inclusion were resolved by consensus. Following reporting standards for AI in health care, we extracted data on study objectives, model features, targeted diverse groups, mitigation strategies used, and results. Using the mixed methods appraisal tool, we appraised the quality of the studies., Results: After removing 585 duplicates, we screened 1018 titles and abstracts. From the remaining 189 full-text articles, we included 17 studies. The most frequently investigated protected attributes were race (or ethnicity), examined in 12 of the 17 studies, and sex (often identified as gender), typically classified as "male versus female" in 10 of the studies. We categorized bias mitigation approaches into four clusters: (1) modifying existing AI models or datasets, (2) sourcing data from electronic health records, (3) developing tools with a "human-in-the-loop" approach, and (4) identifying ethical principles for informed decision-making. Algorithmic preprocessing methods, such as relabeling and reweighing data, along with natural language processing techniques that extract data from unstructured notes, showed the greatest potential for bias mitigation. Other methods aimed at enhancing model fairness included group recalibration and the application of the equalized odds metric. However, these approaches sometimes exacerbated prediction errors across groups or led to overall model miscalibrations., Conclusions: The results suggest that biases toward diverse groups are more easily mitigated when data are open-sourced, multiple stakeholders are engaged, and during the algorithm's preprocessing stage. Further empirical studies that include a broader range of groups, such as Indigenous peoples in Canada, are needed to validate and expand upon these findings., Trial Registration: OSF Registry osf.io/9ngz5/; https://osf.io/9ngz5/., International Registered Report Identifier (irrid): RR2-10.2196/46684., (©Maxime Sasseville, Steven Ouellet, Caroline Rhéaume, Malek Sahlia, Vincent Couture, Philippe Després, Jean-Sébastien Paquette, David Darmon, Frédéric Bergeron, Marie-Pierre Gagnon. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 07.01.2025.)

Background: Sedentary lifestyles, poor nutritional choices, inadequate sleep, risky substance use, limited social connections, and high stress contribute to the growing prevalence of chronic diseases. Lifestyle medicine, emphasizing therapeutic lifestyle changes for prevention and treatment, has demonstrated effectiveness but remains underutilized in clinical settings. The Complete Lifestyle Medicine Intervention Program-Ontario (CLIP-ON) was developed to educate the rural population of Northern Ontario in lifestyle medicine to improve health outcomes and engagement., Objective: This study evaluates the implementation and effectiveness of the CLIP-ON program for patients with chronic diseases in the Parry Sound area, focusing on lifestyle behaviors, health outcomes, enrollment, retention rates, and interdisciplinary team engagement., Methods: This observational cohort study guided by the RE-AIM framework (Reach, Effectiveness, Adoption, Implementation, and Maintenance) includes pre- and postintervention assessments from participants and health care providers. A hybrid type II mixed methods design evaluates the intervention's effectiveness and implementation process in real-world settings through quantitative and qualitative data collection. CLIP-ON is tailored to the residents of the Parry Sound catchment area in Northern Ontario. Participants (≥18 years old) with chronic conditions such as prediabetes, type II diabetes, systemic hypertension, cardiovascular vascular disease, dyslipidemia, or high BMI (≥25) will be recruited through self-referral or provider referral. Approximately 10 participants per cohort will be enrolled in the CLIP-ON program, consisting of 22 weeks of weekly group sessions and monthly individual consultations with physicians, health coaches, kinesiologists, and registered dieticians either in person or through a web-based platform. CLIP-ON will cover the 6 pillars of lifestyle medicine through 14 group sessions followed by an 8-week supervised exercise program. Anthropometric and cardiometabolic variables will be measured before and after the program. Participants will be surveyed on lifestyle habits, wellness, perceived barriers, and program satisfaction at 3 and 6 months. Focus groups and dropout interviews with participants (n=10 per cohort) and providers (n=6 per cohort) will guide program adaptations. Quantitative and qualitative data collected at baseline and follow-up will assess the program's implementation and identify barriers and opportunities for improvement., Results: This study was approved by the Laurentian University Research Ethics Board (6021397) on July 6, 2023. The first cohort was enrolled in late 2023 and is still under evaluation. The second cohort began in mid-2024, and data collection is currently underway. A mixed methods analysis will be used at enrollment, program completion (22 weeks), and follow-up (6 months after program completion). Focus groups assessing the program's effectiveness and implementation will take place after the 22-week intervention. Data will be analyzed in early 2025., Conclusions: This protocol provides insights into the implementation of this lifestyle medicine program and its impact on participants' health. The findings will guide future advancements and establish a scalable model for other communities., Trial Registration: ClinicalTrials.gov NCT06192251; https://clinicaltrials.gov/study/NCT06192251., International Registered Report Identifier (irrid): DERR1-10.2196/59179., (©Kush Patel, Lisa Allen, Karine Boucher, Michelle Fedele, Debbie Fong, Sangeeta Kumar, Deanna Lavigne, Elisa Marin-Couture, Magdalena Partyka-Sitnik, Nicole Rietze, Jenna Smith-Turchyn, Mylene Juneau, Caroline Rhéaume. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 31.12.2024.)

Background: People with chronic diseases can benefit from wearable devices in managing their health and encouraging healthy lifestyle habits. Wearables such as activity trackers or blood glucose monitoring devices can lead to positive health impacts, including improved physical activity adherence or better management of type 2 diabetes. Few literature reviews have focused on the intersection of various chronic diseases, the wearable devices used, and the outcomes evaluated in intervention studies, particularly in the context of primary health care., Objective: This study aims to identify and describe (1) the chronic diseases represented in intervention studies, (2) the types or combinations of wearables used, and (3) the health or health care outcomes assessed and measured., Methods: We conducted a scoping review following the Joanna Briggs Institute guidelines, searching the MEDLINE and Web of Science databases for studies published between 2012 and 2022. Pairs of reviewers independently screened titles and abstracts, applied the selection criteria, and performed full-text screening. We included interventions using wearables that automatically collected and transmitted data to adult populations with at least one chronic disease. We excluded studies with participants with only a predisposition to develop a chronic disease, hospitalized patients, patients with acute diseases, patients with active cancer, and cancer survivors. We included randomized controlled trials and cohort, pretest-posttest, observational, mixed methods, and qualitative studies., Results: After the removal of 1987 duplicates, we screened 4540 titles and abstracts. Of the remaining 304 articles after exclusions, we excluded 215 (70.7%) full texts and included 89 (29.3%). Of these 89 texts, 10 (11%) were related to the same interventions as those in the included studies, resulting in 79 studies being included. We structured the results according to chronic disease clusters: (1) diabetes, (2) heart failure, (3) other cardiovascular conditions, (4) hypertension, (5) multimorbidity and other combinations of chronic conditions, (6) chronic obstructive pulmonary disease, (7) chronic pain, (8) musculoskeletal conditions, and (9) asthma. Diabetes was the most frequent health condition (18/79, 23% of the studies), and wearable activity trackers were the most used (42/79, 53% of the studies). In the 79 included studies, 74 clinical, 73 behavioral, 36 patient technology experience, 28 health care system, and 25 holistic or biopsychosocial outcomes were reported., Conclusions: This scoping review provides an overview of the wearable devices used in chronic disease self-management intervention studies, revealing disparities in both the range of chronic diseases studied and the variety of wearable devices used. These findings offer researchers valuable insights to further explore health care outcomes, validate the impact of concomitant device use, and expand their use to other chronic diseases., Trial Registration: Open Science Framework Registries (OSF) s4wfm; https://osf.io/s4wfm., (©Marie-Pierre Gagnon, Steven Ouellet, Eugène Attisso, Wilfried Supper, Samira Amil, Caroline Rhéaume, Jean-Sébastien Paquette, Christian Chabot, Marie-Claude Laferrière, Maxime Sasseville. Originally published in the Interactive Journal of Medical Research (https://www.i-jmr.org/), 09.12.2024.)

Background: Previous research has raised concerns regarding inconsistencies between reported and pre-specified outcomes in randomized controlled trials (RCTs) across various biomedical disciplines. However, studies examining whether similar discrepancies exist in RCTs focusing on gastrointestinal and liver diseases are limited. This study aimed to assess the extent of discrepancies between registered and published primary outcomes in RCTs featured in journals specializing in gastroenterology and hepatology., Methods: We retrospectively retrieved RCTs published between January 1, 2017 and December 31, 2021 in the top three journals from each quartile ranking of the 2020 Journal Citation Reports within the "Gastroenterology and Hepatology" subcategory. We extracted data on trial characteristics, registration details, and pre-specified versus published primary outcomes. Pre-specified primary outcomes were retrieved from the World Health Organization's International Clinical Trials Registry Platform. Only trials reporting specific primary outcomes were included in analyzing primary outcome discrepancies. We also assessed whether there was a potential reporting bias that deemed to favor statistically significant outcomes. Statistical analyses included chi-square tests, Fisher's exact tests, univariate analyses, and logistic regression., Results: Of 362 articles identified, 312 (86.2%) were registered, and 79.8% of the registrations (249 out of 312) were prospective. Among the 285 trials reporting primary outcomes, 76 (26.7%) exhibited at least one discrepancy between registered and published primary outcomes. The most common discrepancies included different assessment times for the primary outcome (n = 32, 42.1%), omitting the registered primary outcome in publications (n = 21, 27.6%), and reporting the registered secondary outcomes as primary outcomes (n = 13, 17.1%). Univariate analyses revealed that primary outcome discrepancies were lower in the publication year 2020 compared to year 2021 (OR = 0.267, 95% CI: 0.101, 0.706, p = 0.008). Among the 76 studies with primary outcome discrepancies, 20 (26.3%) studies were retrospectively registered, and 32 (57.1%) of the prospectively registered trials with primary outcome discrepancies showed statistically significant results. However, no significant differences were found between journal quartiles regarding primary outcome consistency and potential reporting bias (p = 0.14 and p = 0.28, respectively)., Conclusions: This study highlights the disparities between registered and published primary outcomes in RCTs within gastroenterology and hepatology journals. Attention to factors such as the timing of primary outcome assessments in published trials and the consistency between registered and published primary outcomes is crucial. Enhanced scrutiny from journal editors and peer reviewers during the review process is necessary to ensure the reliability of gastrointestinal and hepatic trials., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Adriano R. Tonelli plays as an advisory board for Janssen and Merck and received grant from Janssen; Szymon Bialka is the secretary of the Silesian Branch of the Polish Society of Anesthesiology and Intensive Care from 2021 till now, the president of the Section of Regional Anesthesia and Pain Therapy and Polish Society of Anesthesiology and Intensive Care from 2021 til now, continued Treasurer of the Polish Society of Regional Anesthesia and Pain Therapy from 2023 till now, a co-creator patent device for isolating a patient with suspected infectious disease (exclusive right number: Pat.243051)., (Copyright: © 2024 Shang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Aortic valve calcification (AVC) indexation to the aortic annulus (AA) area measured by Doppler echocardiography (AVCd Echo ) provides powerful prognostic information in patients with aortic stenosis (AS). However, the indexation by AA measured by multidetector computed tomography (AVCd CT ) has never been evaluated. The aim of this study was to compare AVC, AVCd CT , and AVCd Echo with regard to hemodynamic correlations and clinical outcomes in patients with AS., Methods: Data from 889 patients, mainly White, with calcific AS who underwent Doppler echocardiography and multidetector computed tomography within the same episode of care were retrospectively analyzed. AA was measured both by Doppler echocardiography and multidetector computed tomography. AVCd CT severity thresholds were established using receiver operating characteristic curve analyses in men and women separately. The primary end point was the occurrence of all-cause mortality., Results: Correlations between gradient/velocity and AVCd were stronger (both P ≤0.005) using AVCd CT (r=0.68, P <0.001 and r=0.66, P <0.001) than AVC (r=0.61, P <0.001 and r=0.60, P <0.001) or AVCd Echo (r=0.61, P <0.001 and r=0.59, P <0.001). AVCd CT thresholds for the identification of severe AS were 334 Agatston units (AU)/cm 2 for women and 467 AU/cm 2 for men. On a median follow-up of 6.62 (6.19-9.69) years, AVCd CT ratio was superior to AVC ratio and AVCd Echo ratio to predict all-cause mortality in multivariate analyses (hazard ratio [HR], 1.59 [95% CI, 1.26-2.00]; P <0.001 versus HR, 1.53 [95% CI, 1.11-1.65]; P =0.003 versus HR, 1.27 [95% CI, 1.11-1.46]; P <0.001; all likelihood test P ≤0.004). AVCd CT ratio was superior to AVC ratio and AVCd Echo ratio to predict survival under medical treatment in multivariate analyses (HR, 1.80 [95% CI, 1.27-1.58]; P <0.001 compared with HR, 1.55 [95% CI, 1.13-2.10]; P =0.007; HR, 1.28 [95% CI, 1.03-1.57]; P =0.01; all likelihood test P <0.03). AVCd CT ratio predicts mortality in all subgroups of patients with AS., Conclusions: AVCd CT appears to be equivalent or superior to AVC and AVCd Echo to assess AS severity and predict all-cause mortality. Thus, it should be used to evaluate AS severity in patients with nonconclusive echocardiographic evaluations with or without low-flow status. AVCd CT thresholds of 300 AU/cm 2 for women and 500 AU/cm 2 for men seem to be appropriate to identify severe AS. Further studies are needed to validate these thresholds, especially in diverse populations., Competing Interests: Disclosures Dr Ludwig received travel compensation from Edwards Lifesciences, speaker honoraria from Abbott, advisory fees from Bayer, and was supported by a grant from the German Heart Foundation. Dr Clavel received funding from Edwards Lifesciences for computed tomography core laboratory analyses and a research grant from Medtronic in the field of surgical aortic valve bioprosthesis with no direct personal compensation.

Aging is not a disease; it is a natural evolution of human physiology. Medical advances have extended our life expectancy, but chronic diseases and geriatric syndrome continue to affect the increasingly aging population. Yet modern medicine perpetuates an approach based on treatment rather than prevention and education. In order to help solve this ever-growing problem, a new discipline has emerged: lifestyle medicine. Nutrition, physical activity, stress management, restorative sleep, social connection, and avoidance of risky substances are the pillars on which lifestyle medicine is founded. The aim of this discipline is to increase healthspan and reduce the duration of morbidity by making changes to our lifestyle. In this review, we propose the use of klotho protein as a novel biomarker for lifestyle medicine in order to quantify and monitor the health status of individuals, as no integrative tool currently exists.

Lay Summary: Obesity is frequently accompanied by a fatty liver. However, some individuals with high abdominal fat levels nevertheless have low levels of liver fat. Reasons for such discordant phenotypes are unclear. In this paper, we report that among asymptomatic individuals with high levels of visceral fat, low concentrations of IGFBP-2 in the circulation were associated with significantly higher hepatic fat content compared to those with high IGFBP-2 levels. We conclude that quantification of plasma IGFBP-2 concentrations may be useful to identify the early risk for liver fat accumulation in apparently healthy individuals without cardiovascular symptoms., Aim/hypothesis: Although excess visceral adiposity (VAT) is generally associated with increased liver fat (LF), recent evidence has revealed heterogeneity in LF content among adults with visceral obesity, potentially contributing to specific differences in cardiometabolic outcomes. Reasons for such discordant VAT-LF phenotypes are largely unknown. The present study aimed at assessing whether circulating levels of insulin growth-factor binding protein-2 (IGFBP-2) could be a useful biomarker in the identification of heterogenous and discordant VAT-LF phenotypes., Methods: A sample of 308 middle-aged Caucasian apparently healthy men and women without cardiovascular symptoms were studied for the present cross-sectional analyses. Fasting plasma glucose and lipid levels were assessed and an oral glucose tolerance test was performed. Hepatic fat fraction (HFF) was measured using magnetic resonance spectroscopy whereas VAT was assessed by magnetic resonance imaging. Plasma IGFBP-2 levels were quantified by ELISA. Participants were then classified on the basis of median VAT (81 mL) and IGFBP-2 levels (233 ng/mL)., Results: Individuals with high levels of VAT were characterized by higher waist circumference, lower insulin sensitivity, as well as by higher plasma triglyceride and lower HDL-cholesterol levels. Plasma IGFBP-2 levels were inversely correlated with HFF (r = -0.39, p < 0.0001). Among men and women with high levels of VAT, those with low levels of IGFBP-2 had significantly higher HFF (7.5 ± 0.7%), compared to participants with high IGFBP-2 concentrations (3.2 ± 0.5%, p < 0.0001)., Conclusion: In the presence of excess VAT, high IGFBP-2 concentrations are associated with low levels of LF. Although additional studies will be necessary to establish causality and further clarify the clinical implications of these observations, these findings are concordant with a novel function of IGFBP-2 in modulating susceptibility to non-alcoholic fatty liver disease (NAFLD) in the presence of visceral obesity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Rauzier, Chartrand, Alméras, Lemieux, Larose, Mathieu, Pibarot, Lamarche, Rhéaume, Poirier, Després and Picard.)

Objective: To develop a new method for reliable and rapid determination of the fitness of SARS-CoV-2 variants of concern., Methods: Competition experiments between two SARS-CoV-2 variants were performed in cells of the upper (nasal human airway epithelium) and lower (Calu-3 cells) respiratory tracts followed by quantification of variant ratios by droplet digital reverse transcription (ddRT)-PCR., Results: In competition experiments, the delta variant outcompeted the alpha variant in both cells of the upper and lower respiratory tracts. A 50/50% mixture of delta and omicron variants indicated a predominance of omicron in the upper respiratory tract whereas delta predominated in the lower respiratory tract. There was no evidence of recombination events between variants in competition as assessed by whole gene sequencing., Conclusion: Differential replication kinetics were shown between variants of concern which may explain, at least partly, the emergence and disease severity associated with new SARS-CoV-2 variants., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Low circulating levels of insulin-like growth-factor binding protein-2 (IGFBP-2) have been associated with increased adiposity and metabolic alterations such as insulin resistance, dyslipidemia, and nonalcoholic fatty liver disease in individuals with obesity. However, whether IGFBP-2 affects energy metabolism in the early stages of these disorders remains unclear. Herein, we hypothesized that plasma IGFBP-2 concentrations are inversely associated with early liver fat accumulation and alterations in lipid and glucose homeostasis in apparently healthy and asymptomatic men and women. Three hundred thirty-three middle-aged Caucasian men and women apparently healthy and without cardiovascular symptoms were enrolled for a cross-sectional cardiometabolic imaging study. Individuals with BMI ≥ 40 kg/m 2 , cardiovascular disease, dyslipidemia, hypertension, and diabetes were excluded. Fasting glucose and lipid profiles were measured and an oral glucose tolerance test was performed. Liver fat content was assessed by magnetic resonance spectroscopy. Volume of visceral adipose tissue (VAT) was evaluated by magnetic resonance imaging. Plasma IGFBP-2 levels were quantified by ELISA. Participants with low IGFBP-2 levels were characterized by a higher body fat mass ( P < 0.0001), insulin resistance ( P < 0.0001), higher plasma triglyceride (TG) ( P < 0.0001), and lower HDL-cholesterol levels ( P < 0.0001) in a sex-independent manner. IGFBP-2 levels were inversely correlated with hepatic fat fraction in both men ( r = -0.36, P < 0.0001) and women ( r = -0.40, P < 0.0001). IGFBP-2 concentrations were negatively associated with hepatic fat fraction independently of age and VAT in both men ( R 2  = 0.23, P = 0.012) and women ( R 2  = 0.27, P = 0.028). In conclusion, our findings show that even in asymptomatic, apparently healthy individuals, low IGFBP-2 levels are associated with a more deteriorated cardiometabolic risk profile and with a high hepatic fat content in a VAT-independent manner. However, IGFBP-2 does not appear to influence the established sexual dimorphism observed for metabolic variables and hepatic fat fraction. Additional studies are required to better understand the relationships between IGFBP-2 and liver fat content. NEW & NOTEWORTHY Faced with a paucity of reliable clinical etiologic markers for fatty liver, this research article demonstrates, for the first time, that low blood levels of the protein IGFBP-2 are associated with a more deteriorated cardiometabolic risk profile and with a high hepatic fat content independently of visceral fat volume and sex, even in asymptomatic, apparently healthy individuals.

Background: The current literature identifies several potential benefits of artificial intelligence models for populations' health and health care systems' efficiency. However, there is a lack of understanding on how the risk of bias is considered in the development of primary health care and community health service artificial intelligence algorithms and to what extent they perpetuate or introduce potential biases toward groups that could be considered vulnerable in terms of their characteristics. To the best of our knowledge, no reviews are currently available to identify relevant methods to assess the risk of bias in these algorithms. The primary research question of this review is which strategies can assess the risk of bias in primary health care algorithms toward vulnerable or diverse groups?, Objective: This review aims to identify relevant methods to assess the risk of bias toward vulnerable or diverse groups in the development or deployment of algorithms in community-based primary health care and mitigation interventions deployed to promote and increase equity, diversity, and inclusion. This review looks at what attempts to mitigate bias have been documented and which vulnerable or diverse groups have been considered., Methods: A rapid systematic review of the scientific literature will be conducted. In November 2022, an information specialist developed a specific search strategy based on the main concepts of our primary review question in 4 relevant databases in the last 5 years. We completed the search strategy in December 2022, and 1022 sources were identified. Since February 2023, two reviewers independently screened the titles and abstracts on the Covidence systematic review software. Conflicts are solved through consensus and discussion with a senior researcher. We include all studies on methods developed or tested to assess the risk of bias in algorithms that are relevant in community-based primary health care., Results: In early May 2023, almost 47% (479/1022) of the titles and abstracts have been screened. We completed this first stage in May 2023. In June and July 2023, two reviewers will independently apply the same criteria to full texts, and all exclusion motives will be recorded. Data from selected studies will be extracted using a validated grid in August and analyzed in September 2023. Results will be presented using structured qualitative narrative summaries and submitted for publication by the end of 2023., Conclusions: The approach to identifying methods and target populations of this review is primarily qualitative. However, we will consider a meta-analysis if quantitative data and results are sufficient. This review will develop structured qualitative summaries of strategies to mitigate bias toward vulnerable populations and diverse groups in artificial intelligence models. This could be useful to researchers and other stakeholders to identify potential sources of bias in algorithms and try to reduce or eliminate them., Trial Registration: OSF Registries qbph8; https://osf.io/qbph8., International Registered Report Identifier (irrid): DERR1-10.2196/46684., (©Maxime Sasseville, Steven Ouellet, Caroline Rhéaume, Vincent Couture, Philippe Després, Jean-Sébastien Paquette, Karine Gentelet, David Darmon, Frédéric Bergeron, Marie-Pierre Gagnon. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 26.06.2023.)

Seasonal influenza A and B viruses may cause severe infections requiring therapeutic interventions. Baloxavir, the latest antiviral drug approved against those infections, targets the endonuclease activity encoded by the polymerase acidic (PA) protein. While appearing effective at cessation of viral shedding, baloxavir demonstrated a low barrier of resistance. Herein, we aimed to assess the impact of PA-I38T substitution, a major marker of baloxavir-resistance, on the fitness of contemporary influenza B viruses. Recombinant wild-type (WT) influenza B/Phuket/2073/13 (B/Yamagata/16/88-like) and B/Washington/02/19 (B/Victoria/2/87-like) viruses and their respective PA-I38T mutants were used to evaluate replication kinetics in vitro, using A549 and Calu3 cells, and ex vivo, using nasal human airway epithelium (HAE) cells. Infectivity was also assessed in guinea pigs. In the B/Washington/02/19 background, there were no major differences between the recombinant WT virus and its I38T mutant when viral replication kinetics were evaluated in human lung cell lines and HAE as well as in nasal washes of experimentally infected guinea pigs. By contrast, the I38T mutation moderately impacted the B/Phuket/2073/13 viral fitness. In conclusion, contemporary influenza B viruses that may acquire baloxavir-resistance through the PA-I38T substitution could retain a significant level of fitness, highlighting the importance of monitoring the emergence of such variant.

Background: Many projects related to technology implementation in the context of chronic diseases have been developed over the years to better manage lifestyle medicine interventions and improve patient care. However, technology implementation in primary care settings remains challenging., Objective: The aim is to carry out a strengths, weaknesses, opportunities, and threats (SWOT) analysis (1) to assess satisfaction among patients with type 2 diabetes using an activity tracker to increase motivation for physical activity (PA) and (2) to explore the research and health care team's perceptions of this technology's implementation in a primary care setting., Methods: A 3-month hybrid type 1 study, which included 2 stages, was conducted in an academic primary health center in Quebec City, Quebec, Canada. In stage 1, a total of 30 patients with type 2 diabetes were randomized to the intervention (activity tracker) group or the control group. In stage 2, a SWOT analysis was performed on both patients and health care professionals to determine the components of successful technology implementation. Two questionnaires were used to gather feedback: a satisfaction and acceptability questionnaire concerning an activity tracker (15 patients in the intervention group) and a questionnaire based on the SWOT elements (15 patients in the intervention group and 7 health care professionals). Both questionnaires contained quantitative and qualitative questions. Qualitative variables from open questions were synthesized in a matrix and ranked according to apparition frequency and global importance. A thematic analysis was performed by the first author and validated by 2 coauthors separately. The information gathered was triangulated to propose recommendations that were then approved by the team. Both quantitative (randomized controlled trial participants) and qualitative (randomized controlled trial participants and team) results were combined for recommendations., Results: In total, 86% (12/14) of the participants were satisfied with their activity tracker use and 75% (9/12) felt that it incited them to stick to their PA program. The main strengths of the team members' perspectives were the project initiation and involvement of a patient partner, the study design, the team, and the device. The weaknesses were the budgetary constraints, the turnover, and the technical issues. The opportunities were the primary care setting, the loan of equipment, and common technology. The threats were recruitment issues, administrative challenges, technological difficulties, and a single research site., Conclusions: Patients with type 2 diabetes were satisfied with their activity tracker used to improve motivation for PA. Health care team members agreed that implementation can be done in primary care, but some challenges remain in using this technological tool in clinical practice regularly., Trial Registration: ClinicalTrials.gov NCT03709966; https://clinicaltrials.gov/ct2/show/NCT03709966., (©Cynthia Pelletier, Christian Chabot, Marie-Pierre Gagnon, Caroline Rhéaume. Originally published in JMIR Formative Research (https://formative.jmir.org), 10.03.2023.)

Systemic hypertension has been recognized as a modifiable traditional cardiovascular risk factor and influenced by many factors such as eating habits, physical activity, diabetes, and obesity. The objective of this cross-sectional study was to identify factors that predict changes in blood pressure induced by a one-year lifestyle intervention in primary care settings involving a collaboration between family physicians, dietitians, and exercise specialists. Patients with metabolic syndrome diagnosis were recruited by family physicians participating in primary care lifestyle intervention among several family care clinics across Canada. Participants for whom all cardiometabolic data at the beginning (T0) and the end (T12) of the one-year intervention were available were included in the present analysis (n = 101). Patients visited the dietitian and the exercise specialist weekly for the first three months and monthly for the last nine months. Diet quality, exercise capacity, anthropometric indicators, and cardiometabolic variables were evaluated at T0 and at T12. The intervention induced a statistically significant decrease in waist circumference (WC), systolic (SBP) and diastolic (DBP) blood pressure, and plasma triglycerides, and an increase in cardiorespiratory fitness (estimated VO2max). Body weight (p < 0.001), body mass index (BMI) (p < 0.001), and fasting blood glucose (p = 0.006) reduction, and VO2max increase (p = 0.048) were all related to changes in SBP. WC was the only variable for which changes were significantly correlated with those in both SBP (p < 0.0001) and DBP (p = 0.0004). Variations in DBP were not associated with changes in other cardiometabolic variables to a statistically significant extent. Twelve participants were identified as adverse responders (AR) in both SBP and DBP and displayed less favorable changes in WC. The beneficial effects of the primary care lifestyle intervention on blood pressure were significantly associated with cardiometabolic variables, especially WC. These findings suggest that a structured lifestyle intervention in primary care can help improve cardiometabolic risk factors in patients with metabolic syndrome and that WC should be systematically measured to better stratify the patient’s hypertension risk.

Background: Adopting healthy lifestyle habits reduces the risk of type 2 diabetes (T2D) and its complications. The use of an activity tracker to monitor physical activity (PA) could favor behavior changes in patients with chronic diseases such as diabetes. The aims of this study were: (I) to evaluate the impact of an activity tracker on PA and cardiometabolic risk variables in patients with T2D; (II) to assess the feasibility of its implantation in a primary care setting., Methods: This 3-month study was a pilot randomized controlled trial of 30 patients with T2D followed at a university-affiliated Family Medicine Group. Patients were randomly assigned to either: (I) control group, including a PA promotion intervention supported by a kinesiologist or (II) intervention group, including a PA promotion intervention supported by a kinesiologist with the addition of an activity tracker (Fitbit). Cardiometabolic risk variables, PA and motivation were assessed at baseline and after three months. Satisfaction and acceptability of wearing the activity tracker were measured in the intervention group., Results: PA assessed by questionnaires increased in both groups, change being greater in the intervention group (P<0.05). Autonomous motivation in both groups was higher than controlled motivation (P<0.001). Eighty-six percent of the participants in the intervention group were satisfied with their activity tracker use and the compliance remained high. High-density lipoprotein cholesterol increased in the intervention group and decreased in the control group (P=0.014). Resting systolic and diastolic blood pressure decreased over time in both groups (P<0.05) whereas glycated hemoglobin tended to decrease in both groups (P=0.080). Significant correlations were observed between average steps per day and changes in waist circumference (pre: -0.721, P=0.044; post: -0.736, P=0.038), body mass index (pre: -0.764, P=0.010; post: -0.771, P=0.009) and fat percentage (pre: -0.654, P=0.040; post: -0.686, P=0.028) in the intervention group., Conclusions: Our pilot study shows that the use of an activity tracker improves cardiometabolic risk variables in patients with T2D and could potentially be a motivation tool to increase PA in primary care setting., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/mhealth-20-154). Dr. JPD reports grants from Canadian Institutes of Health Research, outside the submitted work. The other authors have no conflicts of interest to declare., (2021 mHealth. All rights reserved.)

Abstract: OnabotulinumtoxinA (BoNT-A) is an Food and Drug Administration-approved, peripherally acting preventive migraine drug capable of inhibiting meningeal nociceptors. Expanding our view of how else this neurotoxin attenuates the activation of the meningeal nociceptors, we reasoned that if the stimulus that triggers the activation of the nociceptor is lessened, the magnitude and/or duration of the nociceptors' activation could diminish as well. In the current study, we further examine this possibility using electrocorticogram recording techniques, immunohistochemistry, and 2-photon microscopy. We report (1) that scalp (head) but not lumbar (back) injections of BoNT-A shorten the period of profound depression of spontaneous cortical activity that follows a pinprick-induced cortical spreading depression (CSD); (2) that neither scalp nor lumbar injections prevent the induction, occurrence, propagation, or spreading velocity of a single wave of CSD; (3) that cleaved SNAP25-one of the most convincing tools to determine the anatomical targeting of BoNT-A treatment-could easily be detected in pericranial muscles at the injection sites and in nerve fibers of the intracranial dura, but not within any cortical area affected by the CSD; (4) that the absence of cleaved SNAP25 within the cortex and pia is unrelated to whether the blood-brain barrier is intact or compromised; and (5) that BoNT-A does not alter vascular responses to CSD. To the best of our knowledge, this is the first report of peripherally applied BoNT-A's ability to alter a neuronal function along a central nervous system pathway involved in the pathophysiology of migraine., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

Clostridium botulinum neurotoxin serotype A (BoNT/A) is a potent neurotoxin that serves as an effective therapeutic for several neuromuscular disorders via induction of temporary muscular paralysis. Specific binding and internalization of BoNT/A into neuronal cells is mediated by its binding domain (H C /A), which binds to gangliosides, including GT1b, and protein cell surface receptors, including SV2. Previously, recombinant H C /A was also shown to bind to FGFR3. As FGFR dimerization is an indirect measure of ligand-receptor binding, an FCS & TIRF receptor dimerization assay was developed to measure rH C /A-induced dimerization of fluorescently tagged FGFR subtypes (FGFR1-3) in cells. rH C /A dimerized FGFR subtypes in the rank order FGFR3c (EC 50 ≈ 27 nM) > FGFR2b (EC 50 ≈ 70 nM) > FGFR1c (EC 50 ≈ 163 nM); rH C /A dimerized FGFR3c with similar potency as the native FGFR3c ligand, FGF9 (EC 50 ≈ 18 nM). Mutating the ganglioside binding site in H C /A, or removal of GT1b from the media, resulted in decreased dimerization. Interestingly, reduced dimerization was also observed with an SV2 mutant variant of H C/ A. Overall, the results suggest that the FCS & TIRF receptor dimerization assay can assess FGFR dimerization with known and novel ligands and support a model wherein H C /A, either directly or indirectly, interacts with FGFRs and induces receptor dimerization.

Background: Future long-duration space exploration missions, such as traveling to Mars, will create an increase in communication time delays and disruptions and remove the viability of emergency returns to Earth for timely medical treatment. Thus, higher levels of medical autonomy are necessary. Crew selection is proposed as the first line of defense to minimize medical risk for future missions; however, the second proposed line of defense is medical preparedness and crew member autonomy. In an effort to develop a decision support system, the Canadian Space Agency mandated a team of scientists from Thales Research and Technology Canada (Québec, QC) and Université Laval (Québec, QC) to create an evidence-based medical condition database linking mission-critical human conditions with key causal factors, diagnostic and treatment information, and probable outcomes., Objective: To complement this database, we are currently conducting a scoping review to better understand the depth and breadth of evidence about managing medical conditions in space., Methods: This scoping review will adhere to quality standards for scoping reviews, employing Levac, Colquhoun, and O'Brien's 6-stage methodology; the reported results will follow the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) extension for scoping reviews. In stage 1, we identified the research question in collaboration with the Canadian Space Agency (CSA), the main knowledge user. We prioritized 10 medical conditions: (1) acute coronary syndrome, (2) atrial fibrillation, (3) eye penetration, (4) herniated disk, (5) nephrolithiasis, (6) pulmonary embolism, (7) retinal detachment, (8) sepsis, (9) stroke, and (10) spaceflight associated neuro-ocular syndrome. In stage 2, with the help of an information specialist from Cochrane Canada Francophone, papers were identified through searches of the following databases: ARC, Embase, IeeeXplore, Medline Ovid, PsychINFO, and Web of Science. In stage 3, studies will be selected and assessed using a 3-step process and emerging, refined exclusion criteria. In stage 4, the data will be charted in a table based on parameters required by the CSA and developed using Google spreadsheets for shared access. In stage 5, evidence-based descriptive summaries will be produced for each condition, as well as descriptive analyses of collected data. Finally, in stage 6, the findings will be shared with the CSA to guide the completion of this project., Results: This study was planned in December 2018. Stage 1 has been completed. The initial database search strategy with all target conditions combined identified a total of 10,403 citations to review through title and abstract screening and after duplicate removal. We plan to complete stages 2-6 by the beginning of 2021., Conclusions: This scoping review will map the literature on the management of 10 priority medical conditions in space. It will also enable us to identify knowledge gaps that must be addressed in future research, ensuring successful and medically safe future missions as humankind embarks upon new frontiers of space exploration., International Registered Report Identifier (irrid): DERR1-10.2196/24323., (©Kim-Anh Tran, Neal William Pollock, Caroline Rhéaume, Payal Sonya Razdan, Félix-Antoine Fortier, Lara Dutil-Fafard, Camille Morin, David Pierre-Marie Monnot, Maxime Huot-Lavoie, Philippe Simard-Sauriol, Sam Chandavong, Geneviève Le Pabic, Jean-Philippe LeBlanc, Daniel Lafond, Andréanne Marion, Patrick Michel Archambault. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 29.03.2021.)

Cardiorespiratory fitness (CRF) is positively associated with insulin sensitivity, whereas excessive levels of visceral adipose tissue (AT) and liver fat (LF) are both associated with insulin resistance and impaired plasma glucose-insulin homeostasis. To what extent levels of visceral AT and LF content contribute to the relationship between CRF and indices of plasma glucose-insulin homeostasis is uncertain. Our objective was to explore the interactions among CRF, visceral AT, and LF with glucose tolerance/insulin levels in asymptomatic and apparently healthy individuals. CRF was measured in 135 women and 177 men with a maximal treadmill graded exercise test. Indices of plasma glucose-insulin homeostasis were derived from a 3-h oral glucose tolerance test (OGTT) performed in the morning after a 12-h fast. Visceral AT levels and LF content were measured using magnetic resonance imaging and spectroscopy. For any given CRF level, women presented significantly lower visceral AT and LF than men as well as lower homeostasis model assessment of insulin resistance (HOMA-IR) and plasma glucose-insulin levels during the OGTT compared with men. In both sexes, there were significant negative correlations between CRF and HOMA-IR as well as glucose and insulin levels measured during the OGTT. Both glucose and insulin levels during the OGTT correlated positively with visceral AT and LF. In women and men, being in the top CRF tertile was associated with low levels of visceral AT and LF. Multivariable linear regression analyses suggested that visceral AT and LF were plausible mediators of the association between CRF and indices of plasma glucose-insulin homeostasis.

Differences in botulinum neurotoxin manufacturing, formulation, and potency evaluation can impact dose and biological activity, which ultimately affect duration of action. The potency of different labeled vials of incobotulinumtoxinA (Xeomin ® ; 50 U, 100 U, or 200 U vials; incobotA) versus onabotulinumtoxinA (BOTOX ® ; 100 U vial; onabotA) were compared on a unit-to-unit basis to assess biological activity using in vitro (light-chain activity high-performance liquid chromatography (LCA-HPLC) and cell-based potency assay (CBPA)) and in vivo (rat compound muscle action potential (cMAP) and mouse digit abduction score (DAS)) assays. Using LCA-HPLC, incobotA units displayed approximately 54% of the protease activity of label-stated equivalent onabotA units. Lower potency, reflected by higher EC 50 , ID 50 , and ED 50 values (pooled mean ± SEM), was displayed by incobotA compared to onabotA in the CBPA (EC 50 : incobotA 7.6 ± 0.7 U/mL; onabotA 5.9 ± 0.5 U/mL), cMAP (ID 50 : incobotA 0.078 ± 0.005 U/rat; onabotA 0.053 ± 0.004 U/rat), and DAS (ED 50 : incobotA 14.2 ± 0.5 U/kg; onabotA 8.7 ± 0.3 U/kg) assays. Lastly, in the DAS assay, onabotA had a longer duration of action compared to incobotA when dosed at label-stated equivalent units. In summary, onabotA consistently displayed greater biological activity than incobotA in two in vitro and two in vivo assays. Differences in the assay results do not support dose interchangeability between the two products., Competing Interests: A. Brideau-Andersen, M.F. Brin, R.S. Broide, D. Canty, B.P. Jacky, L. Le, G. Nicholson, C. Rhéaume, D. Rupp, and L.E. Steward are full-time employees of AbbVie and receive salary and/or stocks/stock options as compensation. M. Washburn and J. Wang were formerly full-time employees of Allergan (now AbbVie). W.G. Philipp-Dormston has been a scientific lecturer, clinical trial investigator, and consultant for Allergan, an AbbVie company, Galderma, and Merz. This study was sponsored by Allergan (prior to its acquisition by AbbVie), with study design, data collection, and data analysis being conducted by AbbVie employees. Data interpretation and publication decisions were determined by all authors.

Background: Metabolic syndrome (MetS) is a health disorder characterized by metabolic abnormalities that predict an increased risk to develop cardiovascular disease (CVD) and type 2 diabetes (T2DM). It can be resolved, and its complications reduced, by lifestyle interventions offered in primary care. The objectives of this study were to evaluate the impact of the exercise program of the CHANGE feasibility study on physical fitness and physical activity habits, and assess associations between changes in MetS components and cardiorespiratory fitness (CRF)., Methods: In this analysis of 192 of the 293 adults with MetS in the overall study, the impact on physical fitness [aerobic capacity, muscular fitness and flexibility], and non-supervised physical activities was investigated over 12 months. In the CHANGE program, aerobic capacity, muscular fitness and flexibility were assessed at baseline, after 3 months of weekly supervised exercise, and following 9 additional months during which participants had one monthly session of supervised exercise. Additionally, CRF response was also examined in relation to changes in MetS components [fasting glucose, high-density lipoprotein (HDL) cholesterol, triglycerides, blood pressure, waist circumference (WC)]., Results: Fitness variables were significantly increased at 12 months with most of the improvements reached by 3 months (estimated VO 2 max: 6 and 12%; partial curl-ups: 55 and 80%; push-ups: 50 and 100%; flexibility: 22 and 10% in men and women, respectively, p  <  0.001). As expected, the duration and intensity of supervised aerobic physical activity increased during the first 3 months of supervision in both men and women, and remained unchanged for the duration of the program. The duration of non-supervised physical activities did not change during the program in men whereas an increase in manual work of moderate intensity was recorded in women between 3 and 12 months. In women, mean changes in WC were significantly greater among high VO 2 max responders than low responders, between 0 and 12 months, as well as between 3 and 12 months (- 3.42 cm and - 4.32 cm, respectively, p  <  0.05). No associations were seen with MetS components in men. Higher intensity activities were maintained by both sexes at one year., Conclusion: Patients with MetS participating in the CHANGE lifestyle program improved physical fitness and physical activity habits by three months and maintained these gains over one year. Women who achieved a greater VO 2 max increase had greater reductions in WC compared to low VO 2 max responders., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s). 2020.)

Human metapneumovirus (hMPV) is an important respiratory pathogen especially in young children and elderly subjects. Our objective was to assess the immunogenicity and protection conferred by predominant pre- and post-fusion (F) hMPV-F constructs in Balb/C mice. Immunizations without adjuvant were not immunogenic whereas alum-adjuvanted hMPV-F proteins, regardless of their conformations, generated comparable neutralizing antibody titers with undetectable pulmonary viral titers following viral challenge. In conclusion, we found no apparent advantage for mixtures of predominant pre-fusion F proteins over post-fusion conformations for hMPV vaccination in opposite to recent data obtained with the human respiratory syncytial virus., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The relationship between salt intake and cardiovascular diseases is a contemporary scientific controversy, which has been attributed to the limits of the measures of salt intake used in the studies. Thus, this article sought to systematically review the literature on the methods used to estimate salt intake in different study designs. Of the 124 articles, 60.5% used only biochemical measures, 26.6% only self-report measures and 12.9% reported the combined use of both methods. The 24-hour urinary sodium excretion was the predominant biochemical method (79.1%) and the Food Frequency Questionnaire was the predominant self-report measure (36.4%). Interventional studies used mostly 24-hour urinary sodium excretion; while longitudinal studies used self-report measures. The question guiding the study and its design, as well as constraints related to costs, sample size and feasibility seems to influence the choice of the type of measurement.