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Within the Canadian university sports context, athletics departments are increasingly partnering with community sports organizations to promote youth sports participation, while simultaneously providing student-athletes with volunteer opportunities aimed at developing civically engaged young adults. The purpose of this study was to examine the experiences of varsity student-athlete volunteers (n = 10) within a university athletics-community sports partnership program. Volunteers discussed their motivations to volunteer in the partnership program and highlighted various benefits for themselves (e.g., transferable skill development), the youth athletes (e.g., having relatable role models), and the institution and community more broadly (e.g., enhanced community outreach, credibility of programming). Key takeaways and practical recommendations are provided with the aim of fostering quality volunteer experiences within these partnership programs.

Abstract Most published prediction models for Coronavirus Disease 2019 (COVID-19) were poorly reported, at high risk of bias, and heterogeneous in model performance. To tackle methodological challenges faced in previous prediction studies, we investigated whether model updating and extending improves mortality prediction, using the Intensive Care Unit (ICU) as a proxy. All COVID-19 patients admitted to seven ICUs in the Euregio-Meuse Rhine during the first pandemic wave were included. The 4C Mortality and SEIMC scores were selected as promising prognostic models from an external validation study. Five predictors could be estimated based on cohort size. TRIPOD guidelines were followed and logistic regression analyses with the linear predictor, APACHE II score, and country were performed. Bootstrapping with backward selection was applied to select variables for the final model. Additionally, shrinkage was performed. Model discrimination was displayed as optimism-corrected areas under the ROC curve and calibration by calibration slopes and plots. The mortality rate of the 551 included patients was 36%. Discrimination of the 4C Mortality and SEIMC scores increased from 0.70 to 0.74 and 0.70 to 0.73 and calibration plots improved compared to the original models after updating and extending. Mortality prediction can be improved after updating and extending of promising models.

A repeat expansion in the C9orf72 (C9) gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here we investigate single nucleus transcriptomics (snRNA-seq) and epigenomics (snATAC-seq) in postmortem motor and frontal cortices from C9-ALS, C9-FTD, and control donors. C9-ALS donors present pervasive alterations of gene expression with concordant changes in chromatin accessibility and histone modifications. The greatest alterations occur in upper and deep layer excitatory neurons, as well as in astrocytes. In neurons, the changes imply an increase in proteostasis, metabolism, and protein expression pathways, alongside a decrease in neuronal function. In astrocytes, the alterations suggest activation and structural remodeling. Conversely, C9-FTD donors have fewer high-quality neuronal nuclei in the frontal cortex and numerous gene expression changes in glial cells. These findings highlight a context-dependent molecular disruption in C9-ALS and C9-FTD, indicating unique effects across cell types, brain regions, and diseases.

Abstract Digital biomarkers that remotely monitor symptoms have the potential to revolutionize outcome assessments in future disease-modifying trials in Parkinson’s disease (PD), by allowing objective and recurrent measurement of symptoms and signs collected in the participant’s own living environment. This biomarker field is developing rapidly for assessing the motor features of PD, but the non-motor domain lags behind. Here, we systematically review and assess digital biomarkers under development for measuring non-motor symptoms of PD. We also consider relevant developments outside the PD field. We focus on technological readiness level and evaluate whether the identified digital non-motor biomarkers have potential for measuring disease progression, covering the spectrum from prodromal to advanced disease stages. Furthermore, we provide perspectives for future deployment of these biomarkers in trials. We found that various wearables show high promise for measuring autonomic function, constipation and sleep characteristics, including REM sleep behavior disorder. Biomarkers for neuropsychiatric symptoms are less well-developed, but show increasing accuracy in non-PD populations. Most biomarkers have not been validated for specific use in PD, and their sensitivity to capture disease progression remains untested for prodromal PD where the need for digital progression biomarkers is greatest. External validation in real-world environments and large longitudinal cohorts remains necessary for integrating non-motor biomarkers into research, and ultimately also into daily clinical practice.

Introduction Tobacco-related diseases have a substantial economic impact in terms of medical expenses, loss of productivity, and premature death. Tobacco use is estimated to be responsible for more than 90000 deaths each year in Italy. We aimed to evaluate the annual direct economic impact on the National Health System of hospitalizations attributable to tobacco smoking in Italy. Methods We analyzed data from all the hospitalizations of patients aged ≥30 years that occurred in Italy for 12 selected tobacco-related diseases, during 2018. These diseases included oropharyngeal cancer, esophageal cancer, gastric cancer, lung cancer, pancreatic cancer, bladder cancer, laryngeal cancer, ischemic heart disease, stroke, diseases of arteries, arterioles, and capillaries, pneumonia and influenza, and chronic obstructive pulmonary disease. We obtained information on 984322 hospital discharge records, including each hospitalization's direct costs. Using relative risk estimates from the scientific literature, we computed the population attributable fraction for various tobacco-related diseases to estimate the economic impact attributable to tobacco smoking. Results One-third of all hospitalizations occurred in 2018 in Italy among people aged ≥30 years for 12 tobacco-related diseases were found to be attributable to smoking, accounting for a total cost of €1.64 billion. Among the diseases considered, those with the highest expenditures attributable to tobacco smoking were ischemic heart disease, cerebrovascular disease, and lung cancer, accounting for €556 million, €290 million, and €229 million, respectively. Conclusions Tobacco has a substantial economic impact in Italy, accounting for around 6% of the total cost of hospitalizations in 2018. This figure is expected to be largely underestimated due to several conservative assumptions adopted in the statistical analyses. It is imperative to prioritize comprehensive tobacco control measures to counteract the huge healthcare costs due to tobacco smoking.

Abstract Introduction Since the majority of hospitalisations due to RSV occur in young children, the illness profoundly influences the entire family. However, comprehensive evidence regarding its overall effects remains limited. The ResQ Family study aims to investigate the burden of RSV-induced pediatric hospitalisation on affected families. Methods Spanning the 2022–2023 RSV season, an interdisciplinary, observational study was conducted in Germany, France, Italy and Sweden. Using an online questionnaire, parents and caregivers of children (

We used a single-case experimental research design to examine the effect of modelling (peer versus non-peer) on exercise self-efficacy in stroke survivors who participated in a community-based exercise program. Data were obtained using an ABCA design: (A1) no model/baseline 1 (3 weeks); (B) peer model (6 weeks); (C) non-peer model (6 weeks); and (A2) no model/baseline 2 (3 weeks). Four participants completed self-efficacy questionnaires after each weekly session. Overall, participants reported higher exercise self-efficacy in the model conditions (Cohen’s d range from −0.37 to 4.22), with ratings appearing highest for the non-peer model. Modelling in general may help stroke survivors increase their exercise self-efficacy. Lastly, we provide our reflections on the pragmatics of completing a study within a community setting.

Abstract Background Drug induced bile duct injury is a frequently observed clinical problem leading to a wide range of pathological features. During the past decades, several agents have been identified with various postulated mechanisms of bile duct damage, however, mostly still poorly understood. Methods Here, we investigated the mechanisms of chlorpromazine (CPZ) induced bile duct injury using advanced in vitro cholangiocyte cultures. Intrahepatic cholangiocyte organoids (ICOs) were driven into mature cholangiocyte like cells (CLCs), which were exposed to CPZ under cholestatic or non-cholestatic conditions through the addition of a bile acid cocktail. Results CPZ caused loss of monolayer integrity by reducing expression levels of tight junction protein 1 (TJP1), E-cadherin 1 (CDH1) and lysyl oxidase homolog 2 (LOXL2). Loss of zonula occuludens-1 (ZO-1) and E-cadherin was confirmed by immunostaining after exposure to CPZ and rhodamine-123 leakage further confirmed disruption of the cholangiocyte barrier function. Furthermore, oxidative stress seemed to play a major role in the early damage response by CPZ. The drug also decreased expression of three main basolateral bile acid transporters, ABCC3 (ATP binding cassette subfamily C member 3), SLC51A/B (solute carrier family 51 subunit alpha/beta) and multidrug resistance transporter ABCB1 (ATP binding cassette subfamily B member 1), thereby contributing to bile acid accumulation. CPZ did not induce an inflammatory response by itself, but addition of TNFα revealed a synergistic effect. Conclusion These results show that ICOs present a model to identify toxic drugs affecting the bile ducts while providing mechanistic insights into hepatotoxicity.

Bioglass 58S is a bioactive material that can be used to help bone regeneration. In this article we present the fabrication of macroporous 58S Bioglass scaffolds with 3D interconnected porosity, that were prepared by immersing a PMMA microsphere monolith into a 58S sol. The resulting composite samples were calcined leaving macroporous 58S BG scaffolds, which were characterized by SEM, DSC-TGA, XRD and FTIR spectroscopy. These were compared to 58S Bioglass powders prepared using the same sol and calcined under the same conditions. Apart from the presence of macropores, the main difference between the two types of Bioglass 58S samples was the presence of carbonate species in the samples prepared using the PMMA monolith. Finally, the bioactivity of the macroporous 58S scaffolds and 58S powders were evaluated using SBF and cell viability assays. The macroporous 58S scaffolds were found to greatly improve the cell viability compared to the 58S powders which could be attributed to the presence of carbonate species.

Abstract Light exposure is an essential driver of health and well-being, and individual behaviours during rest and activity modulate physiologically relevant aspects of light exposure. Further understanding the behaviours that influence individual photic exposure patterns may provide insight into the volitional contributions to the physiological effects of light and guide behavioural points of intervention. Here, we present a novel, self-reported and psychometrically validated inventory to capture light exposure-related behaviour, the Light Exposure Behaviour Assessment (LEBA). An expert panel prepared the initial 48-item pool spanning different light exposure-related behaviours. Responses, consisting of rating the frequency of engaging in the per-item behaviour on a five-point Likert-type scale, were collected in an online survey yielding responses from a geographically unconstrained sample (690 completed responses, 74 countries, 28 time zones). The exploratory factor analysis (EFA) on an initial subsample (n = 428) rendered a five-factor solution with 25 items (wearing blue light filters, spending time outdoors, using a phone and smartwatch in bed, using light before bedtime, using light in the morning and during daytime). In a confirmatory factor analysis (CFA) performed on an independent subset of participants (n = 262), we removed two additional items to attain the best fit for the five-factor solution (CFI = 0.95, TLI = 0.95, RMSEA = 0.06). The internal consistency reliability coefficient for the total instrument yielded McDonald’s Omega = 0.68. Measurement model invariance analysis between native and non-native English speakers showed our model attained the highest level of invariance (residual invariance CFI = 0.95, TLI = 0.95, RMSEA = 0.05). Lastly, a short form of the LEBA (n = 18 items) was developed using Item Response Theory on the complete sample (n = 690). The psychometric properties of the LEBA indicate the usability for measuring light exposure-related behaviours. The instrument may offer a scalable solution to characterise behaviours that influence individual photic exposure patterns in remote samples. The LEBA inventory is available under the open-access CC-BY license. Instrument webpage: https://leba-instrument.org/ GitHub repository containing this manuscript: https://github.com/leba-instrument/leba-manuscript .

Despite the established physical, social, and emotional benefits of participating in youth sport, such outcomes are not guaranteed. Indeed, purposeful efforts must be made to ensure that sport offerings are age-appropriate, promote engagement and enjoyment, and involve quality social relationships (e.g., Côté et al., 2020). The current article describes an integrated knowledge translation (iKT) partnership that developed a free story-based positive youth development (PYD) program for young ice hockey players (aged 10 to 12 years) in North America. The aim of the '1616 Program' is to use elite ice hockey players as role models--through storytelling--to serve as motivating agents to introduce and engage young athletes with important concepts pertaining to PYD. Content from the general and sport-specific PYD literature (e.g., Côté et al., 2010; Lerner, 2006) informed decisions during program development, with the process generally being guided by the Knowledge-To-Action (KTA) framework (Graham et al., 2006). Herein, we describe the iKT collaborative process that could serve as a template for other researchers interested in partnering with relevant invested partners to create youth development programs.

Stable isotopes are routinely applied to determine the impact of factors such as aging, disease, exercise, and feeding on whole-body protein metabolism. The most common approaches to quantify whole-body protein synthesis, breakdown, and oxidation rates and net protein balance are based on the quantification of plasma amino acid kinetics. In the postabsorptive state, plasma amino acid kinetics can easily be assessed using a constant infusion of one or more stable isotope labeled amino acid tracers. In the postprandial state, there is an exogenous, dietary protein-derived amino acid flux that needs to be accounted for. To accurately quantify both endogenous as well as exogenous (protein-derived) amino acid release in the circulation, the continuous tracer infusion method should be accompanied by the ingestion of intrinsically labeled protein. However, the production of labeled protein is too expensive and labor intensive for use in more routine research studies. Alternative approaches have either assumed that 100% of exogenous amino acids are released in the circulation or applied an estimated percentage based on protein digestibility. However, such estimations can introduce large artifacts in the assessment of whole-body protein metabolism. The preferred estimation approach is based on the extrapolation of intrinsically labeled protein-derived plasma bioavailability data obtained in a similar experimental design setting. Here, we provide reference data on exogenous plasma amino acid release that can be applied to allow a more accurate routine assessment of postprandial protein metabolism. More work in this area is needed to provide a more extensive reference data set.

Summary: The orbitofrontal cortex, one of the key neocortical areas in valuation and emotion, is critical for cognitive flexibility but its role in the consolidation of recently acquired information remains unclear. Here, we demonstrate orbitofrontal offline replay in the context of a place-reward association task on a maze with varying goal locations. When switches in place-reward coupling were applied, replay was enhanced relative to sessions with stable contingencies. Moreover, replay strength was positively correlated with the subsequent overnight change in behavioral performance. Interrogating relationships between orbitofrontal and hippocampal activity, we found that orbitofrontal and hippocampal replay could occur independently but became coordinated during a type of cortical state with strong spiking activity. These findings reveal a structured form of offline orbitofrontal ensemble activity that is correlated with cognitive flexibility required to adapt to changing task contingencies, and becomes associated with hippocampal replay only during a specific state of high cortical excitability.

Abstract A repeat expansion in the C9orf72 (C9) gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here we investigate single nucleus transcriptomics (snRNA-seq) and epigenomics (snATAC-seq) in postmortem motor and frontal cortices from C9-ALS, C9-FTD, and control donors. C9-ALS donors present pervasive alterations of gene expression with concordant changes in chromatin accessibility and histone modifications. The greatest alterations occur in upper and deep layer excitatory neurons, as well as in astrocytes. In neurons, the changes imply an increase in proteostasis, metabolism, and protein expression pathways, alongside a decrease in neuronal function. In astrocytes, the alterations suggest activation and structural remodeling. Conversely, C9-FTD donors have fewer high-quality neuronal nuclei in the frontal cortex and numerous gene expression changes in glial cells. These findings highlight a context-dependent molecular disruption in C9-ALS and C9-FTD, indicating unique effects across cell types, brain regions, and diseases.