The Role of Angiopoietins in Cardiovascular Outcomes of Kidney Transplant Recipients: An Ancillary Study from the FAVORIT.

INTRODUCTION: Kidney transplant recipients (KTRs) have increased risk of cardiovascular disease (CVD) mortality. We investigated vascular biomarkers, angiopoietin-1, and angiopoietin-2 (angpt-1, -2), in CVD development in KTRs. METHODS: This ancillary study from the FAVORIT evaluates the associations of baseline plasma angpt-1, -2 levels in CVD development (primary outcome) and graft failure (GF) and death (secondary outcomes) in 2000 deceased donor KTRs. We used Cox regression to analyze the association of biomarker quartiles with outcomes. We adjusted for demographic; CVD- and transplant-related variables; medications; urine albumin-to-creatinine ratio; and randomization status. We calculated areas under the curves (AUCs) to predict CVD or death, and GF or death by incorporating biomarkers alongside clinical variables. RESULTS: Participants' median age was 52 IQR [45, 59] years: with 37% women and 73% identifying as white. Median time from transplantation was 3.99 IQR [1.58, 7.93] years and to CVD development was 2.54 IQR [1.11-3.80] years. Quartiles of angpt-1 were not associated with outcomes. Whereas higher levels of angpt-2 (quartile 4) were associated with about 2 times the risk of CVD, GF, and death (aHR 1.85 [1.25-2.73], p < 0.01; 2.24 [1.36-3.70)], p < 0.01; 2.30 [1.48-3.58], p < 0.01, respectively) as compared to quartile 1. Adding angiopoietins to preexisting clinical variables improved prediction of CVD or death (AUC improved from 0.70 to 0.72, p = 0.005) and GF or death (AUC improved from 0.68 to 0.70, p = 0.005). Angpt-2 may partially explain the increased risk of future CVD in KTRs. Further research is needed to assess the utility of using angiopoietins in the clinical care of KTRs. CONCLUSION: Angpt-2 may be a useful prognostic tool for future CVD in KTRs. Combining angiopoietins with clinical markers may tailor follow-up to mitigate CVD risk.

Is a smartphone application as accurate as a traditional goniometer for assessing finger joint angles in Dupuytren's disease?

OBJECTIVES: Smartphone applications are available using the smartphone accelerometer to measure angles. This study compared finger joint angle measurements using a traditional goniometer (TG) versus a smartphone application (SPA) in a group of patients with Dupuytren's disease, to determine if they were equally accurate. This was a clinical measurement case series. A group of patients with Dupuytren's disease were invited to participate. MATERIAL AND METHODS: The Apple iPhone 7 "Measure" application was used. Participants were asked to place their hand as flat as possible on the table in a clinic room. Each joint of the ring and little fingers was measured using the TG and the SPA. Power calculation by paired t-test determined a sample size of 25. RESULTS: 28 hands were measured. The Pearson correlation coefficients for the various finger joints were: metacarpophalangeal joint (MCPJ), 0.989; proximal interphalangeal joint (PIPJ), 0.997; and distal interphalangeal joint (DIPJ), 0.977. The root mean square errors (RMSE) for the various joints were: MCPJ, 3.190; PIPJ, 2.019; and DIPJ, 1.897. Bland-Altman analysis showed the two methods to be in agreement. CONCLUSION: The SPA was consistent, reliable and in agreement with a TG for assessing ring and little finger joint angles. The SPA could be used by healthcare professionals instead of a TG.

Delta-6 desaturase (Fads2) deficiency alters triacylglycerol/fatty acid cycling in murine white adipose tissue.

The Δ-6 desaturase (D6D) enzyme is not only critical for the synthesis of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from α-linolenic acid (ALA), but recent evidence suggests that it also plays a role in adipocyte lipid metabolism and body weight; however, the mechanisms remain largely unexplored. The goal of this study was to investigate if a D6D deficiency would inhibit triacylglycerol storage and alter lipolytic and lipogenic pathways in mouse white adipose tissue (WAT) depots due to a disruption in EPA and DHA production. Male C57BL/6J D6D knockout (KO) and wild-type (WT) mice were fed either a 7% w/w lard or flax (ALA rich) diet for 21 weeks. Energy expenditure, physical activity, and substrate utilization were measured with metabolic caging. Inguinal and epididymal WAT depots were analyzed for changes in tissue weight, fatty acid composition, adipocyte size, and markers of lipogenesis, lipolysis, and insulin signaling. KO mice had lower body weight, higher serum nonesterified fatty acids, smaller WAT depots, and reduced adipocyte size compared to WT mice without altered food intake, energy expenditure, or physical activity, regardless of the diet. Markers of lipogenesis and lipolysis were more highly expressed in KO mice compared to WT mice in both depots, regardless of the diet. These changes were concomitant with lower basal insulin signaling in WAT. Collectively, a D6D deficiency alters triacylglycerol/fatty acid cycling in WAT by promoting lipolysis and reducing fatty acid re-esterification, which may be partially attributed to a reduction in WAT insulin signaling.

De-risking clinical trial failure through mechanistic simulation.

Drug development typically comprises a combination of pre-clinical experimentation, clinical trials, and statistical data-driven analyses. Therapeutic failure in late-stage clinical development costs the pharmaceutical industry billions of USD per year. Clinical trial simulation represents a key derisking strategy and combining them with mechanistic models allows one to test hypotheses for mechanisms of failure and to improve trial designs. This is illustrated with a T-cell activation model, used to simulate the clinical trials of IMA901, a short-peptide cancer vaccine. Simulation results were consistent with observed outcomes and predicted that responses are limited by peptide off-rates, peptide competition for dendritic cell (DC) binding, and DC migration times. These insights were used to hypothesise alternate trial designs predicted to improve efficacy outcomes. This framework illustrates how mechanistic models can complement clinical, experimental, and data-driven studies to understand, test, and improve trial designs, and how results may differ between humans and mice.

Analysis of cellular kinetic models suggest that physiologically based model parameters may be inherently, practically unidentifiable.

Physiologically-based pharmacokinetic and cellular kinetic models are used extensively to predict concentration profiles of drugs or adoptively transferred cells in patients and laboratory animals. Models are fit to data by the numerical optimisation of appropriate parameter values. When quantities such as the area under the curve are all that is desired, only a close qualitative fit to data is required. When the biological interpretation of the model that produced the fit is important, an assessment of uncertainties is often also warranted. Often, a goal of fitting PBPK models to data is to estimate parameter values, which can then be used to assess characteristics of the fit system or applied to inform new modelling efforts and extrapolation, to inform a prediction under new conditions. However, the parameters that yield a particular model output may not necessarily be unique, in which case the parameters are said to be unidentifiable. We show that the parameters in three published physiologically-based pharmacokinetic models are practically (deterministically) unidentifiable and that it is challenging to assess the associated parameter uncertainty with simple curve fitting techniques. This result could affect many physiologically-based pharmacokinetic models, and we advocate more widespread use of thorough techniques and analyses to address these issues, such as established Markov Chain Monte Carlo and Bayesian methodologies. Greater handling and reporting of uncertainty and identifiability of fit parameters would directly and positively impact interpretation and translation for physiologically-based model applications, enhancing their capacity to inform new model development efforts and extrapolation in support of future clinical decision-making.

Longitudinal advocacy training for medical students: a virtual workshop series.

Advocacy curricula in Canadian medical schools vary significantly. Expert-led, interactive workshops can effectively teach students how to address social determinants of health and advocate for patients. The Longitudinal Advocacy Training Series (LATS) is a free-of-charge, virtual program providing advocacy training created for Canadian medical students by students. The program was straightforward to implement and had high participation rates with 1140 participants representing 9.7% of enrolled Canadian medical students. As well, the program had high satisfaction reported by 87.6% of participants. The LATS toolkit enables health professional programs to develop similar programs for empowering effective health advocates.

Au Canada, les programmes de formation en matière de promotion et de défense des droits varient considérablement d'une faculté de médecine à l'autre. Les ateliers interactifs dirigés par des experts constituent un outil efficace pour enseigner aux étudiants la façon aborder les déterminants sociaux de la santé afin de défendre les droits des patients. La Longitudinal Advocacy Training Series (LATS) est un programme virtuel gratuit de formation à la défense des droits, créé par des étudiants pour les étudiants. Le programme, facile à mettre en œuvre, a connu un taux de participation élevé, à savoir 1140 participants représentant 9,7 % des étudiants en médecine au Canada. En outre, 87,6 % des participants se sont dits très satisfaits du programme. La trousse à outils LATS permet aux programmes de formation des professions de la santé de mettre sur pied des modules similaires pour donner aux étudiants les moyens de devenir des défenseurs de la santé efficaces.

Improving the mental and physical health of older community-dwellers with a museum participatory art-based activity: results of a multicentre randomized controlled trial.

BACKGROUND: The aim of this randomized controlled trial (RCT) was to examine the mental and physical effects of a participatory art-based activity carried out at museums in older community-dwellers. METHODS: Based on a bicentre (the Montreal Museum of Fine Arts (MMFA), Montreal, Quebec, Canada; the Fuji Museum, Tokyo, Japan) single-blind RCT in two parallel groups (intervention group versus control group), 228 community-dwelling older adults (mean age 71.1 ± 5.4 years, 76.3% female) were enrolled. The intervention was a participatory art-based activity carried out at the MMFA and the Fuji Museum. The intervention group met weekly for 2 h over a 12-week period. The control group did not participate in any art-based intervention over the study period. Well-being was assessed before and after the first (M0) and the twelfth (M3) workshops, and quality of life and frailty before workshops at M0 and M3. These outcomes were assessed with standardized questionnaires with the same schedule in both groups. RESULTS: Well-being and quality of life improved significantly in the intervention group compared to the control group. Mixed results were observed with frailty. Although there were significantly more vigorous and fewer mildly frail participants by the end of the session when comparing intervention to control group participants, only a trend was observed in the decrease in mean value of the intervention group's frailty score. INTERPRETATION: This RCT confirmed that a participatory art-based activity performed weekly over a 3-month period may improve both mental and physical health in older community-dwellers. TRIAL REGISTRATION: NCT03679715; Title: A-Health RCT: Effects of Participatory Art-Based Activity on Health of Older Community Dwellers; First posted date: September 20, 2018; prospectively registered: https://clinicaltrials.gov/ct2/show/NCT03679715.

Responses of the Soil Bacterial Community, Resistome, and Mobilome to a Decade of Annual Exposure to Macrolide Antibiotics.

Biosolids that are applied to agricultural soil as an organic fertilizer are frequently contaminated with pharmaceutical residues that have persisted during wastewater treatment and partitioned into the organic phase. Macrolide antibiotics, which serve as a critically important human medicine, have been detected within biosolids. To determine the impacts of macrolide antibiotics on soil bacteria, every year for a decade, a series of replicated field plots received an application of a mixture of erythromycin, clarithromycin, and azithromycin at a realistic (0.1 mg kg soil-1) or an unrealistically high (10 mg kg soil-1) dose or were left untreated. The effects of repeated antibiotic exposure on the soil bacterial community, resistome, mobilome, and integron gene cassette content were evaluated by 16S rRNA and integron gene cassette amplicon sequencing, as well as whole-metagenome sequencing. At the unrealistically high dose, the overall diversity of the resistome and mobilome was altered, as 21 clinically important antibiotic resistance genes predicted to encode resistance to 10 different antibiotic drug classes were increased and 20 mobile genetic element variants (tnpA, intI1, tnpAN, and IS91) were increased. In contrast, at the realistic dose, no effect was observed on the overall diversity of the soil bacterial community, resistome, mobilome, or integron gene cassette-carrying genes. Overall, these results suggest that macrolide antibiotics entrained into soil at concentrations anticipated with biosolid applications would not result in major changes to these endpoints. IMPORTANCE Biosolids, produced from the treatment of sewage sludge, are rich in plant nutrients and are a valuable alternative to inorganic fertilizer when applied to agricultural soil. However, the use of biosolids in agriculture, which are frequently contaminated with pharmaceuticals, such as macrolide antibiotics, may pose a risk to human health by selecting for antibiotic resistance genes that could be transferred to plant-based food destined for human consumption. The consequences of long-term, repeated macrolide antibiotic exposure on the diversity of the soil bacterial community, resistome, and mobilome were evaluated. At unrealistically high concentrations, macrolide antibiotics alter the overall diversity of the resistome and mobilome, enriching for antibiotic resistance genes and mobile genetic elements of concern to human health. However, at realistic antibiotic concentrations, no effect on these endpoints was observed, suggesting that current biosolids land management practices are unlikely to pose a risk to human health due to macrolide antibiotic contamination alone.

Plant and marine N3-PUFA regulation of fatty acid trafficking along the adipose tissue-liver axis varies according to nutritional state.

Marine sourced N3-PUFA regulate lipid metabolism in adipose tissue and liver; however, less is known about plant sourced N3-PUFA. The goal of this study was to investigate plant and marine N3-PUFA regulation of fatty acid trafficking along the adipose tissue-liver axis according to nutritional state. Mice were fed low-fat diets (7% w/w) containing either lard, flaxseed, or menhaden oils for 8 weeks, and were euthanized in either fed or fasted states. Substrate utilization and physical activity were assessed during the transition from a fed to fasted state. Plasma biomarkers (triacylglycerol [TAG], non-esterified fatty acids [NEFA]), as well as liver and epididymal adipose tissue (eWAT) lipogenic and lipolytic markers, were measured. Neither plant nor marine N3-PUFA influenced substrate utilization or activity during the transition from a fed to fasted state. In the fed state, marine N3-PUFA reduced plasma TAG levels compared to the other diets, with no further reduction seen in fasted mice. Hepatic lipogenic markers (Fasn, Acc, Scd1, and Elovl6) were reduced in the fed state with marine N3-PUFA, but not plant N3-PUFA. In the fasted state, mice fed either N3-PUFA accumulated less liver TAG, had lower plasma NEFA, and suppressed eWAT HSL activity compared to lard. Marine N3-PUFA are more potent regulators of lipogenesis than plant N3-PUFA in the fed state, whereas both N3-PUFA influence eWAT lipolysis and plasma NEFA in the fasted state. This work provides novel insights regarding N3-PUFA regulation of fatty acid trafficking along the adipose tissue-liver axis according to nutritional state.

Vitamin D Supplementation and Cognition in Adults: A Systematic Review of Randomized Controlled Trials.

BACKGROUND: The role of vitamin D supplementation in improving cognition and slowing the incidence of minor and major neurocognitive disorders is a matter of debate. To our knowledge, no systematic review of randomized controlled trials (RCTs) has examined this question in adults. OBJECTIVES: The purpose of this systematic review is to synthesize the evidence regarding the effects of vitamin D supplementation on cognitive performance and neurocognitive disorders in adults. METHODS: A systematic search of scientific articles in English or French was conducted. The MEDLINE (PubMed), EMBASE (Ovid, EMBASE), PsychINFO, and Cochrane Central databases were searched for records without any limit on publication date in May 2021. Inclusion criteria were (1) human participants, (2) RCT, (3) participant age ≥ 18, (4) vitamin D supplementation as the intervention, and (5) cognition (i.e., cognitive performance or cognitive status such as cognitively healthy or minor and major neurocognitive disorder) as the primary outcome. Two independent reviewers both assessed all eligible studies' full texts and the risk of bias arising from methodological issues using a standardized procedure. RESULTS: Of the 2137 abstracts identified, 61 (2.9%) met screening inclusion criteria. After full text examination, 41 records (67.2%) were excluded. As a result, 20 RCTs (32.8%) were included in the systematic review. The review yielded mixed findings and, thus, failed to find evidence supporting cognitive benefits from vitamin D supplementation or suggesting a causal association between vitamin D and cognitive function. Half of the RCTs reported mixed results, one quarter negative results, and the last quarter positive effects for vitamin D supplementation on cognitive performance. The variability in serum 25-dihydroxyvitamin D concentration thresholds, the cognitive tests employed, the supplementation doses, and the samples' characteristics (i.e., ethnicity or number of participants) may explain these mixed findings. CONCLUSION: This systematic review of RCTs does not support a role for vitamin D supplementation in enhancing cognition in adults.

Health benefits of "Thursdays at the Montreal Museum of Fine Arts": Results of a randomized clinical trial.

OBJECTIVE: . This study aims to examine and compare changes in frailty status, well-being and quality of life in community-dwelling older adults living in Montreal (Quebec, Canada) participating in a 3-month session of weekly "Thursdays at the Museum" and in their control counterparts who did not participate in art-based activities. METHODS: . 165 older community dwellers were recruited to a randomized controlled trial with two parallel groups (intervention versus control). The intervention was weekly participatory art-based activities over a 3-month period carried out at the Montreal Museum of Fine Arts (MMFA, Montreal, Quebec, Canada). Frailty, well-being and quality of life were assessed using standardized questionnaires completed at baseline (M0) and before the fifth (M1), ninth (M2) and twelfth (M3) workshops in the intervention group. The control group completed these questionnaires according to the same schedule. The outcomes were mean values of frailty, well-being and quality of life scores, as well as the distribution of frailty categories (vigorous versus mild, moderate and severe frailty) at M0, M1, M2 and M3. RESULTS: . The intervention group showed significant improvements in frailty, well-being and quality of life scores (P≤0.004) when compared with the control group. CONCLUSION: . The results suggest that the 3-month session of weekly "Thursdays at the Museum" may improve both physical and mental health in Montreal community-dwelling older adults.

Predicted limited redistribution of T cells to secondary lymphoid tissue correlates with increased risk of haematological malignancies in asplenic patients.

The spleen, a secondary lymphoid tissue (SLT), has an important role in generation of adaptive immune responses. Although splenectomy remains a common procedure, recent studies reported poor prognosis and increased risk of haematological malignancies in asplenic patients. The high baseline trafficking of T lymphocytes to splenic tissue suggests splenectomy may lead to loss of blood-borne malignant immunosurveillance that is not compensated for by the remaining SLT. To date, no quantitative analysis of the impact of splenectomy on the human T cell trafficking dynamics and tissue localisation has been reported. We developed a quantitative computational model that describes organ distribution and trafficking of human lymphocytes to explore the likely impact of splenectomy on immune cell distributions. In silico splenectomy resulted in an average reduction of T cell numbers in SLT by 35% (95%CI 0.12-0.97) and a comparatively lower, 9% (95%CI 0.17-1.43), mean decrease of T cell concentration in SLT. These results suggest that the surveillance capacity of the remaining SLT insufficiently compensates for the absence of the spleen. This may, in part, explain haematological malignancy risk in asplenic patients and raises the question of whether splenectomy has a clinically meaningful impact on patient responses to immunotherapy.

Quantifying the limits of CAR T-cell delivery in mice and men.

CAR (Chimeric Antigen Receptor) T cells have demonstrated clinical success for the treatment of multiple lymphomas and leukaemias, but not for various solid tumours, despite promising data from murine models. Lower effective CAR T-cell delivery rates to human solid tumours compared to haematological malignancies in humans and solid tumours in mice might partially explain these divergent outcomes. We used anatomical and physiological data for human and rodent circulatory systems to calculate the typical perfusion of healthy and tumour tissues, and estimated the upper limits of immune cell delivery rates across different organs, tumour types and species. Estimated maximum delivery rates were up to 10 000-fold greater in mice than humans yet reported CAR T-cell doses are typically only 10-100-fold lower in mice, suggesting that the effective delivery rates of CAR T cells into tumours in clinical trials are far lower than in corresponding mouse models. Estimated delivery rates were found to be consistent with published positron emission tomography data. Results suggest that higher effective human doses may be needed to drive efficacy comparable to mouse solid tumour models, and that lower doses should be tested in mice. We posit that quantitation of species and organ-specific delivery and homing of engineered T cells will be key to unlocking their potential for solid tumours.

"Emergency Room Evaluation and Recommendations" (ER2) Tool for the Screening of Older Emergency Department Visitors With Major Neurocognitive Disorders: Results From the ER2 Database.

Purpose: The Emergency Room Evaluation and Recommendation (ER2) is an application in the electronic medical file of patients visiting the Emergency Department (ED) of the Jewish General Hospital (JGH; Montreal, Quebec, Canada). It screens for older ED visitors at high risk of undesirable events. The aim of this study is to examine the performance criteria (i.e., sensitivity, specificity, positive predictive value [PPV], negative predictive value [NPV], positive likelihood ratio [LR+], negative likelihood ratio [LR-] and area under the receiver operating characteristic curve [AUROC]) of the ER2 high-risk level and its "temporal disorientation" item alone to screen for major neurocognitive disorders in older ED visitors at the JGH. Methods: Based on a cross-sectional design, 999 older adults (age 84.9 ± 5.6, 65.1% female) visiting the ED of the JGH were selected from the ER2 database. ER2 was completed upon the patients' arrival at the ED. The outcomes were ER2's high-risk level, the answer to ER2's temporal disorientation item (present vs. absent), and the diagnosis of major neurocognitive disorders (yes vs. no) which was confirmed when it was present in a letter or other files signed by a physician. Results: The sensitivities of both ER2's high-risk level and temporal disorientation item were high (≥0.91). Specificity, the PPV, LR+, and AROC were higher for the temporal disorientation item compared to ER2's high-risk level, whereas a highest sensitivity, LR-, and NPV were obtained with the ER2 high-risk level. Both area under the receiver operating characteristic curves were high (0.71 for ER2's high-risk level and 0.82 for ER2 temporal disorientation item). The odds ratios (OR) of ER2's high-risk level and of temporal disorientation item for the diagnosis of major neurocognitive disorders were positive and significant with all OR above 18, the highest OR being reported for the temporal disorientation item in the unadjusted model [OR = 26.4 with 95% confidence interval (CI) = 17.7-39.3]. Conclusion: Our results suggest that ER2 and especially its temporal disorientation item may be used to screen for major neurocognitive disorders in older ED users.

Motoric cognitive risk syndrome and incident dementia in older adults from the Québec NuAge cohort.

BACKGROUND: The co-occurrence of slow walking speed and subjective cognitive complaint (SCC) in non-demented individuals defines motoric cognitive risk syndrome (MCR), which is a pre-dementia stage. There is no information on the association between MCR and incident dementia in Québec's older population. OBJECTIVE: The study aims to examine the association of MCR and its individual components (i.e. SCC and slow walking speed) with incident dementia in community-dwelling older adults living in the province of Québec (Canada). DESIGN: Québec older people population-based observational cohort study with 3 years of follow-up. SETTING: Community dwellings. SUBJECTS: A subset of participants (n = 1,098) in 'Nutrition as a determinant of successful aging: The Québec longitudinal study' (NuAge). METHODS: At baseline, participants with MCR were identified. Incident dementia was measured at annual follow-up visits using the Modified Mini-Mental State (≤79/100) test and Instrumental Activity Daily Living scale (≤6/8) score values. RESULTS: The prevalence of MCR was 4.2% at baseline and the overall incidence of dementia was 3.6%. MCR (Hazard Ratio (HR) = 5.18, with 95% confidence interval (CI) = [2.43-11.03] and P ≤ 0.001) and SCC alone (HR = 2.54, with 95% CI = [1.33-4.85] and P = 0.005) were associated with incident dementia, but slow walking speed was not (HR = 0.81, with 95%CI = [0.25-2.63] and P = 0.736). CONCLUSIONS: MCR and SCC are associated with incident dementia in NuAge study participants.

Telemedicine for housebound older persons during the Covid-19 pandemic.

Targeting older at-risk patients with decision-making algorithms is a priority at a time when hospitals are receiving an influx of Covid-19 patients that may exceed their capacity. Such screening could likely be extended to primary care settings in order to identify older community dwellers with Covid-19, but also those experiencing the adverse consequences of prolonged home confinement. The Centre of Excellence on Longevity of McGill University (Quebec, Canada) designed a short assessment for Montreal's housebound community-dwelling older adults. It acts as the first step in connecting older community dwellers who are housebound during the Covid-19 outbreak to telemedicine.

CLR01 protects dopaminergic neurons in vitro and in mouse models of Parkinson's disease.

Parkinson's disease (PD) affects millions of patients worldwide and is characterized by alpha-synuclein aggregation in dopamine neurons. Molecular tweezers have shown high potential as anti-aggregation agents targeting positively charged residues of proteins undergoing amyloidogenic processes. Here we report that the molecular tweezer CLR01 decreased aggregation and toxicity in induced pluripotent stem cell-derived dopaminergic cultures treated with PD brain protein extracts. In microfluidic devices CLR01 reduced alpha-synuclein aggregation in cell somas when axonal terminals were exposed to alpha-synuclein oligomers. We then tested CLR01 in vivo in a humanized alpha-synuclein overexpressing mouse model; mice treated at 12 months of age when motor defects are mild exhibited an improvement in motor defects and a decreased oligomeric alpha-synuclein burden. Finally, CLR01 reduced alpha-synuclein-associated pathology in mice injected with alpha-synuclein aggregates into the striatum or substantia nigra. Taken together, these results highlight CLR01 as a disease-modifying therapy for PD and support further clinical investigation.

Effects of "Thursdays at the Museum" at the Montreal Museum of Fine Arts on the mental and physical health of older community dwellers: the art-health randomized clinical trial protocol.

BACKGROUND: Recently, we demonstrated that the Montreal Museum of Fine Arts' (MMFA) participatory art-based activity, known as "Thursdays at the Museum," improved the well-being, quality of life, and physical health (i.e., frailty) of older community dwellers by using a pre-post intervention, single arm, prospective and longitudinal experimental design. The present randomized clinical trial (RCT), known as the Art-Health RCT (A-Health RCT), aims to compare changes in well-being, quality of life, frailty, and physiological measures in older community dwellers who participate in "Thursdays at the Museum" (intervention group) and in their counterparts who do not participate in this art-based activity (control group). METHODS/DESIGN: The current unicenter, randomized, clinical, controlled, comparative trial recruits 150 older community dwellers to two parallel arms (75 participants in the intervention group and 75 participants in the control group). The intervention is a 3-month cycle of weekly "Thursdays at the Museum," which are structured 2-h-long art-based workshops performed in a group setting at the MMFA. The control group is composed of participants who do not take part in art-based activities, receive their usual health and/or social services, and commit to report any other activity practiced during the same time. Assessments of the primary outcome (well-being) and the secondary outcomes (quality of life, frailty, and physiological measures including heart rate, daily step count, sleep duration, and its phases) are performed on six occasions: at baseline, at the beginning of the second and third months, at the end of the third month, as well as 6 and 12 months after the last workshop. Statistical analyses are performed with the intention to treat and per protocol. Comparisons of changes in outcome measures between intervention and control groups use repeated measures tests. DISCUSSION: Art-based activities carried out at museums have been receiving increased interest from researchers and policy-makers because of their benefits to mental and physical health. There are few robust studies, such as RCTs, that focus on older community dwellers or assess the efficacy of these participatory museum activities. The A-Health RCT study provides an opportunity to confirm the benefits of a participatory art-based museum activity on the elderly population and to show the key role played by museums in public health promotion. TRIAL REGISTRATION: NCT03679715 ; Title: A-Health RCT: Effects of Participatory Art-Based Activity on Health of Older Community Dwellers; First posted date: September 20, 2018; prospectively registered.