Granzyme B in aging and age-related pathologies.

Aging is a major risk factor for pathologies that manifest later in life. Much attention is devoted towards elucidating how prolonged environmental exposures and inflammation promote biological (accelerated) tissue aging. Granzymes, a family of serine proteases, are increasingly recognized for their emerging roles in biological aging and disease. Widely recognized as intracellular mediators of cell death, granzymes, particularly granzyme B (GzmB), also accumulate in the extracellular milieu of tissues with age, contributing to chronic tissue injury, inflammation, and impaired healing. Consequently, this has prompted the field to reconsider how GzmB regulation, accumulation, and proteolysis impact health and disease with age. While GzmB is observed in numerous age-related conditions, the current review focuses on mechanistic studies where proof-of-concept has been forwarded.

Robust identification of environmental exposures and community characteristics predictive of rapid lung disease progression.

Environmental exposures and community characteristics have been linked to accelerated lung function decline in people with cystic fibrosis (CF), but geomarkers, the measurements of these exposures, have not been comprehensively evaluated in a single study. To determine which geomarkers have the greatest predictive potential for lung function decline and pulmonary exacerbation (PEx), a retrospective longitudinal cohort study was performed using novel Bayesian joint covariate selection methods, which were compared with respect to PEx predictive accuracy. Non-stationary Gaussian linear mixed effects models were fitted to data from 151 CF patients aged 6-20 receiving care at a CF Center in the midwestern US (2007-2017). The outcome was forced expiratory volume in 1 s of percent predicted (FEV1pp). Target functions were used to predict PEx from established criteria. Covariates included 11 routinely collected clinical/demographic characteristics and 45 geomarkers comprising 8 categories. Unique covariate selections via four Bayesian penalized regression models (elastic-net, adaptive lasso, ridge, and lasso) were evaluated at both 95 % and 90 % credible intervals (CIs). Resultant models included one to 6 geomarkers (air temperature, percentage of tertiary roads outside urban areas, percentage of impervious nonroad outside urban areas, fine atmospheric particulate matter, fraction achieving high school graduation, and motor vehicle theft) representing weather, impervious descriptor, air pollution, socioeconomic status, and crime categories. Adaptive lasso had the lowest information criteria. For PEx predictive accuracy, covariate selection from the 95 % CI elastic-net had the highest area under the receiver-operating characteristic curve (mean ± standard deviation; 0.780 ± 0.026) along with the 95 % CI ridge and lasso methods (0.780 ± 0.027). The 95 % CI elastic-net had the highest sensitivity (0.773 ± 0.083) while the 95 % CI adaptive lasso had the highest specificity (0.691 ± 0.087), suggesting the need for different geomarker sets depending on monitoring goals. Surveillance of certain geomarkers embedded in prediction algorithms can be used in real-time warning systems for PEx onset.

Prevalence of Unhealthy Lifestyles and Its Correlates Among College-Going Students in Rishikesh, India: A Cross-Sectional Study.

Introduction Non-communicable diseases (NCDs) have a significant impact on health concerns. The transition from school to college coincides with various stressors, affecting student health. The objective was to assess the prevalence of unhealthy lifestyles among college-going students and examine the association of composite lifestyle scores with selected demographic variables. Methods All undergraduate colleges of Rishikesh were included in the study. Cluster sampling with a population proportionate to size was used to select the participants. A structured questionnaire was administered using Google Forms or pen and paper. Index values for each lifestyle activity were added together to get a lifestyle composite score. An unhealthy lifestyle was considered with a score below 40. Association with risk factors was analyzed using a chi-square test and logistic regression. Results Among 742 participants, 166 (22.4%) lived an unhealthy lifestyle with a lifestyle score of <40. The majority of participants were either underweight or above normal weight. An unhealthy lifestyle was prevalent among fourth-year professional students (7; 58.5%), medical (33; 32%), dental (27; 34.6%), hosteller (79; 36%), and BSc Nursing (21; 56.8%) students. BSc Nursing course (AOR: 11.09; 95% CI: 1.17-104.74) and favorable attitude (AOR: 0.74; 95 % CI: 0.59- 0.93) were significant correlates of unhealthy lifestyles. Conclusion The current study indicates that nearly one-fourth of college students have unhealthy lifestyles. Four factors, i.e., health science stream, advancing professional year, hosteller, and unfavorable attitude toward health, were significantly associated with unhealthy lifestyles after adjusting for covariates.

Digital Serious Games to Promote Behavior Change in Children With Chronic Diseases: Scoping Review and Development of a Self-Management Learning Framework.

BACKGROUND: Digital serious games (SGs) have rapidly become a promising strategy for entertainment-based health education; however, developing SGs for children with chronic diseases remains a challenge. OBJECTIVE: In this study, we attempted to provide an updated scope of understanding of the development and evaluation of SG educational tools and develop a framework for SG education development to promote self-management activities and behavior change in children with chronic diseases. METHODS: This study consists of a knowledge base and an analytical base. This study followed the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines. To build the knowledge base, 5 stages of research were developed, including refining the review question (stage 1), searching for studies (stage 2), selecting relevant studies (stage 3), charting the information (stage 4), and collating the results (stage 5). Eligible studies that developed SG prototypes and evaluated SG education for children with chronic diseases were searched for in PubMed, Embase, Google Scholar, and peer-reviewed journals. In the analytical base, the context-mechanism-output approach and game taxonomy were used to analyze relevant behavioral theories and essential game elements. Game taxonomy included social features, presentation, narrative and identity, rewards and punishment, and manipulation and control. A total of 2 researchers selected the domains for the included behavioral theories and game elements. The intended SG framework was finalized by assembling SG fragments. Those SG fragments were appropriately reintegrated to visualize a new SG framework. RESULTS: This scoping review summarized data from 16 randomized controlled trials that evaluated SG education for children with chronic diseases and 14 studies on SG frameworks. It showed that self-determination theory was the most commonly used behavioral theory (9/30, 30%). Game elements included feedback, visual and audio designs, characters, narratives, rewards, challenges, competitions, goals, levels, rules, and tasks. In total, 3 phases of a digital SG framework are proposed in this review: requirements (phase 1), design and development (phase 2), and evaluation (phase 3). A total of 6 steps are described: exploring SG requirements (step 1), identifying target users (step 2), designing an SG prototype (step 3), building the SG prototype (step 4), evaluating the SG prototype (step 5), and marketing and monitoring the use of the SG prototype (step 6). Safety recommendations to use digital SG-based education for children in the post-COVID-19 era were also made. CONCLUSIONS: This review summarizes the fundamental behavioral theories and game elements of the available literature to establish a new theory-driven step-by-step framework. It can support game designers, clinicians, and educators in designing, developing, and evaluating digital, SG-based educational tools to increase self-management activities and promote behavior change in children with chronic diseases.

The Association Between Social Isolation and Medication Adherence Among Chinese Older Adults With Chronic Diseases: Serial Mediation of Social Support and Loneliness.

BACKGROUND: Medication adherence is essential for chronic disease management among older adults. Previous studies have shown significant links among social isolation, social support, loneliness, and medication adherence, yet most were based on cross-sectional designs. PURPOSE: We conducted a longitudinal cohort study among Chinese older adults with chronic diseases to explore the mediating effects of social support and loneliness in the association between social isolation and medication adherence. METHODS: This study followed a cohort of 797 older adults with chronic diseases in China from 2022 to 2023. The serial mediation model was examined via bootstrapping techniques to evaluate the mediating effect of social support and loneliness in the association between social isolation and medication adherence. RESULTS: From baseline to follow-up, there were significant decreases in social support (from 26.6 ± 6.2 to 23.5 ± 6.7) and medication adherence (from 6.7 ± 1.2 to 6.0 ± 1.5) and significant increases in social isolation (from 1.8 ± 1.3 to 2.5 ± 1.4) and loneliness (13.2 ± 4.1 to 23.5 ± 6.7), all with p < .001. A serial mediation model was confirmed, where social support and loneliness serially and partially mediated the association between social isolation and medication adherence (total effect c = -0.216, 95% CI = -0.296 to -0.136; direct effect c' = -0.094, 95% CI = -0.171 to -0.017; total indirect effect ab = -0.122, 95% CI = -0.179 to -0.070). CONCLUSIONS: Our findings yield critical insights into the relationship between social isolation and medication adherence through various mediating mechanisms. These findings hold significant implications for devising psychosocial interventions to enhance medication adherence among older adults with chronic diseases, underscoring the pivotal role of bolstering social support and alleviating loneliness.

This study investigated the relationship between social isolation, medication adherence, and psychosocial factors (social support and loneliness) in Chinese older adults with chronic diseases. We observed decreases in social support and medication adherence and increases in social isolation and loneliness from baseline to follow-up. The findings revealed that social support and loneliness sequentially and partially mediated the association between social isolation and medication adherence. These results highlight the importance of psychosocial interventions to improve medication adherence among older adults by enhancing social support and addressing feelings of loneliness. This study contributes to our understanding of the complex factors influencing medication adherence in this population and offers insights for designing effective interventions.

A microfluidic chip with integrated plasma separation for sample-to-answer detection of multiple chronic disease biomarkers in whole blood.

Point-of-care testing of multiple chronic disease biomarkers is crucial for timely intervention and management of chronic diseases. Here, a "sample-to-answer" microfluidic chip was developed for simultaneous detection of multiple chronic disease biomarkers in whole blood by integrating a plasma separation module. The whole detection process is very convenient, i.e., just add whole blood and get the results. The chip successfully achieved the simultaneous detection of total cholesterol, triglycerides, uric acid, and glucose in undiluted whole blood within 21 min, including 6 min for plasma separation and 15 min for enzymatic chromogenic reactions. Moreover, the sensitivity levels of on-chip detection of chronic disease biomarkers can also meet clinically relevant thresholds. The chip is easy to use and has significant potential to improve home self-management of chronic diseases and enhance healthcare outcomes.

The effectiveness of the Mediterranean Diet for primary and secondary prevention of cardiovascular disease: An umbrella review.

AIMS: This study aimed to review meta-analyses of randomised controlled trials that evaluated the effectiveness of the Mediterranean Diet for the primary and secondary prevention of cardiovascular disease. METHODS: Five databases (Medline, Embase, Cochrane, CINAHL and ProQuest) were searched from inception to November 2022. Inclusion criteria were: (i) systematic review of randomised controlled studies with metanalysis; (ii) adults ≥18 years from the general population with (secondary prevention) and without (primary prevention) established cardiovascular disease; (iii) Mediterranean Diet compared with another dietary intervention or usual care. Review selection and quality assessment using AMSTAR-2 were completed in duplicate. GRADE was extracted from each review, and results were synthesised narratively. RESULTS: Eighteen meta-analyses of 238 randomised controlled trials were included, with an 8% overlap of primary studies. Compared to usual care, the Mediterranean Diet was associated with reduced cardiovascular disease mortality (n = 4 reviews, GRADE low certainty; risk ratio range: 0.35 [95% confidence interval: 0.15-0.82] to 0.90 [95% confidence interval: 0.72-1.11]). Non-fatal myocardial infarctions were reduced (n = 4 reviews, risk ratio range: 0.47 [95% confidence interval: 0.28-0.79] to 0.60 [95% confidence interval: 0.44-0.82]) when compared with another active intervention. The methodological quality of most reviews (n = 16/18; 84%) was low or critically low and strength of evidence was generally weak. CONCLUSIONS: This review showed that the Mediterranean Diet can reduce fatal cardiovascular disease outcome risk by 10%-67% and non-fatal cardiovascular disease outcome risk by 21%-70%. This preventive effect was more significant in studies that included populations with established cardiovascular disease. Better quality reviews are needed.

Utilizing technology for diet and exercise change in complex chronic conditions across diverse environments (U-DECIDE): feasibility randomised controlled trial.

BACKGROUND: Diet and exercise are important components of treatment for complex chronic conditions, however access to allied health support is limited. When available, support is often siloed and fragmented. Digital health incorporating patient choice may help to align health care services with preferences and goals. This study evaluated the implementation of a ubiquitously accessible patient-centred digital health diet and exercise service. METHODS: U-DECIDE was a single-centre, 26-week randomised controlled trial set in kidney and liver disease clinics in a tertiary hospital in Brisbane, Australia. Participants were adults with a complex chronic condition referred for dietetic consultation with at least one feature of the metabolic syndrome. All participants received a dietary consultation, an activity monitor and usual care. Intervention participants were offered one text message per week and access to additional digital health options (increased text message frequency, nutrition app, exercise app, group-based diet and/or exercise video consultations). The primary outcome of feasibility was determined by safety (study-related serious adverse events: SRSAEs), recruitment (≥ 50% eligible patients), retention (≥ 70%), exposure uptake (≥ 75% of intervention group had greater access to health professional contact than comparator) and video consultation adherence (≥ 80% attendance). Secondary outcomes included process evaluation metrics and clinical outcomes. RESULTS: Of 67 participants (intervention n = 33, comparator n = 34), 37 (55%) were men, median (IQR) age was 51 (41-58) years. The most chosen digital health options were the nutrition app (n = 29, 88%) and exercise video consultations (n = 26, 79%). Only one participant chose no additional digital health options. The intervention group had no SRSAEs. The study exceeded targets for recruitment (52%), retention (81%) and exposure uptake (94%). Video consultation adherence was 42%. Engagement across digital health options was inconsistent. CONCLUSIONS: Digital health options incorporating patient choice were feasible and can be offered to people with complex chronic disease as a service model option. TRIAL REGISTRATION: Australia and New Zealand Trials Register: Trial Registration Number: ACTRN12620001282976. Registered 27th November 2020.

Building and validating trend-based multiple sclerosis case definitions: a population-based cohort study for Manitoba, Canada.

OBJECTIVE: This study aims to (1) build and validate model-based case definitions for multiple sclerosis (MS) that use trends (ie, trend-based case definitions) and (2) to apply dynamic classification to identify the average number of data years needed for classification (ie, average trend needed). DESIGN: Retrospective cohort study design. PARTICIPANTS: 608 MS cases and 59 620 MS non-cases. SETTING: Data from 1 April 2004 to 31 March 2022 were obtained from the Manitoba Population Research Data Repository. MS case status was ascertained from homecare records and linked to health data. Trend-based case definitions were constructed using multivariate generalised linear mixed models applied to annual numbers of general and specialist physician visits, hospitalisations and MS healthcare contacts or medication dispensations. Dynamic classification, which ascertains cases and non-cases annually, was used to estimate mean classification time. Classification accuracy performance measures, including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), proportion correctly classified (PCC) and F1-scores, were compared for trend-based case definitions and a deterministic case definition of 3+MS healthcare contacts or medication dispensations. RESULTS: When applied to the full study period, classification accuracy performance measure estimates for all case definitions exceeded 0.90, except sensitivity and PPV for the trend-based dynamic case definition (0.88, 0.64, respectively). PCC was high for all case definitions (0.94-0.99); F1-scores were lower for the trend-based case definitions compared with the deterministic case definition (0.74-0.93 vs 0.96). Dynamic classification identified 5 years as the average trend needed. When applied to the average trend windows, accuracy estimates for trend-based case definitions were lower than the estimates from the full study period (sensitivity: 0.77-0.89; specificity: 0.90-0.97; PPV: 0.54-0.81; NPV: 0.97-0.99; F1-score: 0.64-0.84). Accuracy estimates for the deterministic case definition remained high, except sensitivity (0.42-0.80). F1-score was variable (0.59-0.89). CONCLUSIONS: Trend-based and deterministic case definitions classifications were similar to a population-based clinician assessment reference standard for multiple measures of classification accuracy. However, accuracy estimates for both trend-based and deterministic case definitions varied as the years of data used for classification were reduced. Dynamic classification appears to be a viable option for identifying the average trend needed for trend-based case definitions.

The impact of adverse childhood experiences on multimorbidity: a systematic review and meta-analysis.

BACKGROUND: Adverse childhood experiences (ACEs) have been implicated in the aetiology of a range of health outcomes, including multimorbidity. In this systematic review and meta-analysis, we aimed to identify, synthesise, and quantify the current evidence linking ACEs and multimorbidity. METHODS: We searched seven databases from inception to 20 July 2023: APA PsycNET, CINAHL Plus, Cochrane CENTRAL, Embase, MEDLINE, Scopus, and Web of Science. We selected studies investigating adverse events occurring during childhood (< 18 years) and an assessment of multimorbidity in adulthood (≥ 18 years). Studies that only assessed adverse events in adulthood or health outcomes in children were excluded. Risk of bias was assessed using the ROBINS-E tool. Meta-analysis of prevalence and dose-response meta-analysis methods were used for quantitative data synthesis. This review was pre-registered with PROSPERO (CRD42023389528). RESULTS: From 15,586 records, 25 studies were eligible for inclusion (total participants = 372,162). The prevalence of exposure to ≥ 1 ACEs was 48.1% (95% CI 33.4 to 63.1%). The prevalence of multimorbidity was 34.5% (95% CI 23.4 to 47.5%). Eight studies provided sufficient data for dose-response meta-analysis (total participants = 197,981). There was a significant dose-dependent relationship between ACE exposure and multimorbidity (p < 0.001), with every additional ACE exposure contributing to a 12.9% (95% CI 7.9 to 17.9%) increase in the odds for multimorbidity. However, there was heterogeneity among the included studies (I2 = 76.9%, Cochran Q = 102, p < 0.001). CONCLUSIONS: This is the first systematic review and meta-analysis to synthesise the literature on ACEs and multimorbidity, showing a dose-dependent relationship across a large number of participants. It consolidates and enhances an extensive body of literature that shows an association between ACEs and individual long-term health conditions, risky health behaviours, and other poor health outcomes.

Real-World Outcomes of the 0.19 mg Fluocinolone Acetonide Intravitreal Implant for Diabetic Macular Edema.

Purpose: To evaluate the real-world clinical and safety outcomes of a 0.19 mg fluocinolone acetonide intravitreal implant to treat diabetic macular edema (DME). Methods: This retrospective analysis comprised patients treated with a single fluocinolone acetonide intravitreal implant for the clinical indication of ME secondary to diabetic retinopathy. Primary outcomes included changes in best-corrected visual acuity (BCVA), central subfield thickness (CST), and the frequency of DME-related treatments 12 months before and up to 36 months after fluocinolone acetonide administration. Safety outcomes were also assessed. Results: One hundred forty-eight eyes (115 patients) were followed for a mean (±SD) of 12.3 ± 4.2 months before and 29.4 ± 14.5 months after fluocinolone acetonide administration. A 0.8-letter decrease (Early Treatment Diabetic Retinopathy Study) in the mean BCVA was observed at month 24. The BCVA was 70 letters (20/40 Snellen equivalent) or more in 20.6% of eyes at baseline and in 23.7% of eyes 24 months after implant administration. The mean CST was 379.9 µm and 323.7 µm, respectively. The CST was 300 µm or less in 58.7% of eyes at month 24 (P < .001). The mean frequency of intravitreal antivascular endothelial growth factor injections or laser photocoagulation decreased from 4.9 to 1.5 per year after fluocinolone acetonide administration (P < .001). Implant migration to the anterior chamber occurred in 3 eyes, 2 of which were vitrectomized and later required removal. Conclusions: The 0.19 mg fluocinolone acetonide intravitreal implant provided long-term stabilization of VA and macular anatomy in patients with DME, despite a significant reduction in treatment frequency.

A real-world analysis of pharmacotherapy adherence and the factors influencing it in Serbia: a nationwide, population-based, cross-sectional study.

Introduction: Monitoring the pharmacotherapy adherence in society is crucial for identifying occurance and causes of potential inadequate use of drugs and inform providers about the need for better customer counceling. It is necessary component of the strategic planning of the quality of healthcare services. This population- based study aimed to assess the medication intake adherence in the Republic of Serbia and the individual factors and health system variables influencing its pattern. Methods: We applied a cross-sectional approach to study medication intake adherence using a secondary analysis of the latest 2019 Serbian National Health Survey data. The statistical modeling of the pharmacotherapy adherence incorporated sociodemographic data, self-reported disease, and lifestyle behavior. Results: In 2019, in the representative sample of 12,066 adults in Serbia, requiring prescribed medicine, 49.8% did comply with the prescribed drugs, and 50.2% do not. Participants who adhered to prescribed medication were significantly (p < 0.001) older (62.4 ± 14 years), predominantly female (55.3%), had secondary education (48.5%), resided in southern and eastern parts of Serbia (55.5%), and belonged to the lowest income quintile (21.4%). The participants most often take prescribed drugs for hypertension (64.1%) and lower back pain (30.5%), while around 20% take medication for coronary disease, diabetes mellitus, and high blood cholesterol. About 85-92% of participants with financial or general difficulties using prescribed medication. Conclusion: There is poor medication intake adherence to prescribed medication in Serbia. Gender, age, and region determine the adherence. Also, health-related and healthcare system-related factors impact the use of prescribed medication. Study findings can inform planning the counceling interventions in the target groups where improving medication adherence is necessary, as well as to enhance training of healthcare providers about pharmacotherapy adherence.

Telehealth-Supported Exercise or Physical Activity Programs for Knee Osteoarthritis: Systematic Review and Meta-Analysis.

BACKGROUND: The integration of telehealth-supported programs in chronic disease management has become increasingly common. However, its effectiveness for individuals with knee osteoarthritis (KOA) remains unclear. OBJECTIVE: This study aimed to assess the effectiveness of telehealth-supported exercise or physical activity programs for individuals with KOA. METHODS: A comprehensive literature search encompassing Embase, MEDLINE, CENTRAL, Web of Science, PubMed, Scopus, PEDro, GreyNet, and medRxiv from inception to September 2023 was conducted to identify randomized controlled trials comparing telehealth-supported exercise or physical activity programs to a control condition for KOA. Data were extracted and qualitatively synthesized across eligible studies, and a meta-analysis was performed to evaluate the effects. The study was reported according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020. RESULTS: In total, 23 studies met eligibility criteria, with 20 included in the meta-analysis. Results showed that telehealth-supported exercise or physical activity programs reduced pain (g=-0.39; 95% CI -0.67 to -0.11; P<.001), improved physical activity (g=0.13; 95% CI 0.03-0.23; P=.01), and enhanced physical function (g=-0.51; 95% CI -0.98 to -0.05; P=.03). Moreover, significant improvements in quality of life (g=0.25; 95% CI 0.14-0.36; P<.001), self-efficacy for pain (g=0.72; 95% CI 0.53-0.91; P<.001), and global improvement (odds ratio 2.69, 95% CI 1.41-5.15; P<.001) were observed. However, self-efficacy for physical function (g=0.14; 95% CI -0.26 to 0.53; P=.50) showed insignificant improvements. Subgroup analyses based on the World Health Organization classification of digital health (pain: χ22=6.5; P=.04 and physical function: χ22=6.4; P=.04), the type of teletechnology in the intervention group (pain: χ24=4.8; P=.31 and function: χ24=13.0; P=.01), and active or inactive controls (pain: χ21=5.3; P=.02 and physical function: χ21=3.4; P=.07) showed significant subgroup differences. CONCLUSIONS: Telehealth-supported exercise or physical activity programs might reduce knee pain and improve physical activity, physical function, quality of life, self-efficacy, and global improvement in individuals with KOA. Future research should consider longer implementation durations and assess the feasibility of incorporating wearables and standardized components into large-scale interventions to evaluate the effects. TRIAL REGISTRATION: PROSPERO CRD42022359658; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=359658.

Perceived Taste and Olfactory Dysfunctions and Subsequent Stroke Risk.

Background: Taste and olfactory dysfunction are commonly associated with neurodegenerative diseases and cardiovascular risk factors, but their specific associations with stroke risk remain uncertain. Objectives: The purpose of this paper was to explore whether perceived taste and olfactory dysfunctions were associated with stroke risk. Methods: Included were 85,656 participants (mean age 51.0 ± 15.3 years) of the Kailuan study. Perceived olfactory and taste dysfunctions were assessed via a questionnaire at baseline (in 2014-2016). Incident stroke cases were confirmed by review of medical records. Cox proportional hazards models were used to investigate associations of perceived olfactory and taste dysfunctions with stroke risk, and mediation analysis was used to estimate the mediating effect of chronic disease statuses. Results: We documented 2,198 incident stroke cases during a mean of 5.6 years of follow-up. Perceived taste dysfunction was associated with a doubled risk of developing total stroke (adjusted HR: 2.03; 95% CI: 1.36-3.04; P < 0.001) even with adjustment of lifestyle factors, biomarkers (ie, blood lipids, blood glucose, blood pressure, and uric acid), and other potential confounders. However, perceived olfactory dysfunction (adjusted HR: 1.22; 95% CI: 0.79-1.90; P = 0.34) was not significantly associated with a high risk of total stroke. Similar results of both perceived taste and olfactory dysfunctions were observed for ischemic stroke. Presence of chronic diseases, including hypertension, diabetes, chronic kidney disease, and overweight/obesity, mediated 4% to 5% of the association of perceived taste dysfunction with both total stroke and ischemic stroke. Conclusions: In this large cohort study, perceived taste dysfunction was associated with a high risk of developing stroke.

Monocyte Single-Cell Multimodal Profiling in Cardiovascular Disease Risk States.

BACKGROUND: Monocytes are a critical innate immune system cell type that serves homeostatic and immunoregulatory functions. They have been identified historically by the cell surface expression of CD14 and CD16. However, recent single-cell studies have revealed that they are much more heterogeneous than previously realized. METHODS: We utilized cellular indexing of transcriptomes and epitopes by sequencing (cellular indexing of transcriptomes and epitopes by sequencing) and single-cell RNA sequencing to describe the comprehensive transcriptional and phenotypic landscape of 437 126 monocytes. RESULTS: This high-dimensional multimodal approach identified vast phenotypic diversity and functionally distinct subsets, including IFN-responsive, MHCIIhi, monocyte-platelet aggregates, as well as nonclassical, sand several subpopulations of classical monocytes. Using flow cytometry, we validated the existence of MHCII+CD275+ MHCIIhi, CD42b+ monocyte-platelet aggregates, CD16+CD99- nonclassical monocytes, and CD99+ classical monocytes. Each subpopulation exhibited unique characteristics, developmental trajectories, transcriptional regulation, and tissue distribution. In addition, alterations associated with cardiovascular disease risk factors, including race, smoking, and hyperlipidemia were identified. Moreover, the effect of hyperlipidemia was recapitulated in mouse models of elevated cholesterol. CONCLUSIONS: This integrative and cross-species comparative analysis provides a new perspective on the comparison of alterations in monocytes in pathological conditions and offers insights into monocyte-driven mechanisms in cardiovascular disease and the potential for monocyte subpopulation targeted therapies.

Nutritional status in the era of highly effective CFTR modulators.

Advances in cystic fibrosis (CF) diagnostics and therapeutics have led to improved health and longevity, including increased body weight and decreased malnutrition in people with CF. Highly effective CFTR modulator therapies (HEMT) are associated with increased weight through a variety of mechanisms, accelerating trends of overweight and obesity in the CF population. Higher body mass index (BMI) is associated with improved pulmonary function in CF, yet the incremental improvement at overweight and obese BMIs is not clear. Improvements in pulmonary health with increasing BMI are largely driven by increases in fat-free mass (FFM), and impact of HEMT on FFM is uncertain. While trends toward higher weight and BMI are generally seen as favorable in CF, the increased prevalence of overweight and obesity has raised concern for potential risk of traditional age- and obesity-related comorbidities. Such comorbidities, including impaired glucose tolerance, hypertension, cardiac disease, hyperlipidemia, fatty liver, colon cancer, and obstructive sleep apnea, may occur on top of pre-existing CF-related comorbidities. CF nutrition recommendations are evolving in the post-modulator era to more individualized approaches, in contrast to prior blanket high-fat, high-calorie prescriptions for all. Ultimately, it will be essential to redefine goals for optimal weight and nutritional status to allow for holistic health and aging in people with CF.

Polyphenols: potent protectors against chronic diseases.

Polyphenols, abundant in plant-based foods like fruits, vegetables, tea, coffee, wine, and chocolate, offer significant health benefits. Known for their potent antioxidant properties, they combat oxidative stress by neutralising free radicals, crucial in preventing chronic noncommunicable diseases (NCDs) such as cancer, cardiovascular issues, obesity, and diabetes. Polyphenols also exhibit anti-inflammatory effects, modulating gene expression and reducing inflammation associated with NCDs. Their anticancer activities involve inhibiting cancer cell growth and promoting apoptosis through various pathways. They enhance cardiovascular health by improving endothelial function, lowering blood pressure, and inhibiting atherosclerosis. Additionally, polyphenols improve metabolic health by enhancing insulin sensitivity and regulating glucose metabolism, aiding in diabetes and obesity management. These bioactive compounds interact with cellular pathways and gut microbiota, highlighting their multifaceted mechanisms. Integrating polyphenol-rich foods into diets could significantly improve health outcomes and alleviate NCD burdens, advocating for their inclusion in public health strategies and further research to optimise their potential.

Leveraging and learning from the long COVID experience: Translating telerehabilitation into practice.

BACKGROUND: Telerehabilitation, or the delivery of rehabilitation services through telehealth platforms, has existed since the late 1990 s. Telerehabilitation was characterized by unprecedented, exponential growth at the beginning of the novel coronavirus-2019 (COVID-19) pandemic. Medical systems sought to reduce the likelihood of disease transmission by using telerehabilitation to limit physical proximity during routine care. This dramatic change in how medical care was delivered forced many professions to adapt processes and practices. Following the change, debates sparked regarding the best path to move forward for the betterment of patients, clinicians, systems, and society. Long COVID has emerged as a complex chronic health condition arising from COVID-19. The unique needs and dynamic disease process of Long COVID has incentivized medical systems to create equitable ways for patients to safely access interdisciplinary care. OBJECTIVES: The purpose of this commentary is to describe what medical systems must consider when deploying high-quality telerehabilitation to deliver rehabilitation through asynchronous (e.g., text, portal) and synchronous modalities (e.g., phone or video). We highlight lessons learned to help guide decision-makers on key actions to support their patients and clinicians. METHODS: Not applicable. RESULTS: Not applicable. CONCLUSIONS: Key action steps from our lessons learned may be used to address complex chronic health conditions such as Long COVID and prepare for future challenges that may disrupt medical systems.

Experiences of children with bronchiectasis and their parents in a novel play-based therapeutic exercise programme: a qualitative analysis.

OBJECTIVES: To explore the experiences and perceptions of children with bronchiectasis and their parents regarding an 8-week play-based therapeutic exercise programme. DESIGN: Qualitative study with inductive content analysis. SETTING: Individual semistructured interviews were conducted. Interview recordings were transcribed verbatim, and coding was guided by the content. Content categories were established via consensus moderation. PARTICIPANTS: 10 parents and 10 children with bronchiectasis aged 5-12 years. RESULTS: From the perspective of children, the most important components of the programme were fun with friends and being active at home as a family. Parents valued the community-based sessions, perceived the programme to be engaging and motivating. Parents perceived improvements in their child's endurance, coordination and physical activity level. They described the home programme as fun but noted that finding time was difficult. Both parents and children thought that in-person exercise sessions would be better than exercise sessions delivered online. CONCLUSIONS: Children who participated in the play-based exercise programme, found it fun, motivating and accessible. Parents perceived positive impacts on fitness, coordination and physical activity. TRIAL REGISTRATION NUMBER: The trial was registered with, Australian and New Zealand Clinical Trials Register (ACTRN12619001008112).