Relationship between dominance hierarchy steepness and rank-relatedness of benefits in primates.

In animal social groups, the extent to which individuals consistently win agonistic interactions and their ability to monopolize resources represent 2 core aspects of their competitive regime. However, whether these two aspects are closely correlated within groups has rarely been studied. Here, we tested the hypothesis that hierarchy steepness, which is generally used to represent power differentials between group members, predicts the variation in the distribution of fitness-related benefits (i.e. fecundity, infant survival, mating success, and feeding success) in relation to individual dominance ranks. We tested this hypothesis in primate groups using comparative phylogenetic meta-analytical techniques. Specifically, we reviewed published and unpublished studies to extract data on individual dominance ranks, their access to fitness-related benefits, and hierarchy steepness. We collected and included in our analysis a total of 153 data points, representing 27 species (including 2 chimpanzee sub-species). From these, we used 4 common methods to measure individual dominance ranks and hierarchy steepness, i.e. D ij -based normalized David's scores, randomized Elo-ratings, and David's scores and Elo-ratings estimated in Bayesian frameworks. We found that hierarchy steepness had no effect on the strength of the relationship between dominance rank and access to fitness-related benefits. Our results suggest that hierarchy steepness does not reflect between-group variation in the extent to which individual dominance affects the acquisition of fitness-related benefits in primates. Although the ability to win agonistic encounters is essential, we speculate that other behavioral strategies adopted by individuals may play crucial roles in resource acquisition in animal competitive regimes.

Deep multimodal saliency parcellation of cerebellar pathways: Linking microstructure and individual function through explainable multitask learning.

Parcellation of human cerebellar pathways is essential for advancing our understanding of the human brain. Existing diffusion magnetic resonance imaging tractography parcellation methods have been successful in defining major cerebellar fibre tracts, while relying solely on fibre tract structure. However, each fibre tract may relay information related to multiple cognitive and motor functions of the cerebellum. Hence, it may be beneficial for parcellation to consider the potential importance of the fibre tracts for individual motor and cognitive functional performance measures. In this work, we propose a multimodal data-driven method for cerebellar pathway parcellation, which incorporates both measures of microstructure and connectivity, and measures of individual functional performance. Our method involves first training a multitask deep network to predict various cognitive and motor measures from a set of fibre tract structural features. The importance of each structural feature for predicting each functional measure is then computed, resulting in a set of structure-function saliency values that are clustered to parcellate cerebellar pathways. We refer to our method as Deep Multimodal Saliency Parcellation (DeepMSP), as it computes the saliency of structural measures for predicting cognitive and motor functional performance, with these saliencies being applied to the task of parcellation. Applying DeepMSP to a large-scale dataset from the Human Connectome Project Young Adult study (n = 1065), we found that it was feasible to identify multiple cerebellar pathway parcels with unique structure-function saliency patterns that were stable across training folds. We thoroughly experimented with all stages of the DeepMSP pipeline, including network selection, structure-function saliency representation, clustering algorithm, and cluster count. We found that a 1D convolutional neural network architecture and a transformer network architecture both performed comparably for the multitask prediction of endurance, strength, reading decoding, and vocabulary comprehension, with both architectures outperforming a fully connected network architecture. Quantitative experiments demonstrated that a proposed low-dimensional saliency representation with an explicit measure of motor versus cognitive category bias achieved the best parcellation results, while a parcel count of four was most successful according to standard cluster quality metrics. Our results suggested that motor and cognitive saliencies are distributed across the cerebellar white matter pathways. Inspection of the final k = 4 parcellation revealed that the highest-saliency parcel was most salient for the prediction of both motor and cognitive performance scores and included parts of the middle and superior cerebellar peduncles. Our proposed saliency-based parcellation framework, DeepMSP, enables multimodal, data-driven tractography parcellation. Through utilising both structural features and functional performance measures, this parcellation strategy may have the potential to enhance the study of structure-function relationships of the cerebellar pathways.

Interventions for adolescent mental, sexual and reproductive health in West Africa: A scoping review.

Objectives: A quarter of West Africa's population are adolescents 10-19 years. Their mental, sexual, and reproductive health is inter-related. We therefore aimed to examine published evidence on effectiveness of interventions for adolescent mental, sexual and reproductive health in the Economic Community of West African States (ECOWAS) to inform development, implementation and de-implementation of policies and programs. Study design: The study design was a scoping review. Methods: We considered all qualitative and quantitative research designs that included adolescents 10-19 years in any type of intervention evaluation that included adolescent mental, sexual and reproductive health. Outcomes were as defined by the researchers. PubMed/Medline, APA PsycINFO, CAIRN, and Google Scholar databases were searched for papers published between January 2000 and November 9, 2023.1526 English and French language papers were identified. After eliminating duplicates, screening abstracts and then full texts, 27 papers from studies in ECOWAS were included. Results: Interventions represented three categories: service access, quality, and utilization; knowledge and information access and intersectionality and social determinants of adolescent health. Most studies were small-scale intervention research projects and interventions focused on sexual and reproductive or mental health individually rather than synergistically. The most common evaluation designs were quasi-experimental (13/27) followed by observational studies (8/27); randomized, and cluster randomized controlled trials (5/27), and one realist evaluation. The studies that evaluated policies and programs being implemented at scale used observational designs. Conclusion: Research with robust evaluation designs on synergistic approaches to adolescent mental, sexual and reproductive health policies, interventions, implementation and de-implementation is urgently needed to inform adolescent health policies and programs.

Educational and occupational aspirations of adolescent and young adult cancer survivors: a qualitative analysis.

PURPOSE: Adolescent and young adult cancer survivors (AYACS) are patients diagnosed with cancer between 15 and 39 years of age. AYACS are often derailed from planned educational and occupational endeavors due to disruption from cancer treatment and its consequences. The study objective was to examine how a personal cancer diagnosis impacted AYACS' experiences related to these endeavors. METHODS: Semi-structured interviews were conducted as part of a larger study assessing psychosocial challenges among a younger AYACS subset aged 15-25 years old at the time of cancer diagnosis. Interviews were coded based on responses and were used to develop themes related to educational and occupational endeavors. RESULTS: Data were collected from 35 participants. Five themes emerged: (1) Pauses in educational attainment had a detrimental effect on educational goals for some participants, but further solidified and sculpted educational plans for others; (2) Although participants experienced challenges accomplishing educational goals, supportive school environments helped surmount these challenges; (3) Participants reflected on rethinking career aspirations, though some desired to pursue the same occupation planned before cancer diagnosis; (4) Participants experienced challenges, including physical and cognitive limitations, upon returning to work; and (5) Participants valued autonomy and normalcy through work and appreciated supportive and flexible work environments. CONCLUSIONS: AYACS prioritize professional achievement, yet encounter challenges in achieving professional goals. Our findings create a foundation for developing and testing prospective interventions to promote continuance of school and work during cancer treatment when feasible, and proactive reintegration strategies for those who paused professional goals due to cancer treatment.

Physical Activity and Sports for Children With Juvenile Idiopathic Arthritis.

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease of childhood, presenting clinically as inflammatory arthritis in children younger than 16 years. To date, while evidence supports physical activity for children with JIA, there is limited evidence on the recommended approach to physical activity and sports participation in this population, and no single structured therapeutic exercise program has been established as best practice. This review article presents what is known on the management of physical activity in children with JIA, including recommendations from the pediatric rheumatology and rehabilitation literature, where available, for sports participation, structured therapeutic exercise programs, and return to activity.

Schwann cell-secreted PGE2 promotes sensory neuron excitability during development.

Electrical excitability-the ability to fire and propagate action potentials-is a signature feature of neurons. How neurons become excitable during development and whether excitability is an intrinsic property of neurons remain unclear. Here, we demonstrate that Schwann cells, the most abundant glia in the peripheral nervous system, promote somatosensory neuron excitability during development. We find that Schwann cells secrete prostaglandin E2, which is necessary and sufficient to induce developing somatosensory neurons to express normal levels of genes required for neuronal function, including voltage-gated sodium channels, and to fire action potential trains. Inactivating this signaling pathway in Schwann cells impairs somatosensory neuron maturation, causing multimodal sensory defects that persist into adulthood. Collectively, our studies uncover a neurodevelopmental role for prostaglandin E2 distinct from its established role in inflammation, revealing a cell non-autonomous mechanism by which glia regulate neuronal excitability to enable the development of normal sensory functions.

Shared Decision-Making in Colorectal Cancer Screening for Older Adults: A Secondary Analysis of a Cluster Randomized Clinical Trial.

Importance: Decisions about whether to stop colorectal cancer (CRC) screening tests in older adults can be difficult and may benefit from shared decision-making (SDM). Objective: To evaluate the effect of physician training in SDM and electronic previsit reminders (intervention) vs reminders only (comparator) on receipt of the patient-preferred approach to CRC screening and on overall CRC screening rates of older adults at 12 months. Design, Setting, and Participants: This was a secondary analysis of the Promoting Informed Decisions About Colorectal Cancer Screening in Older Adults (PRIMED) cluster randomized clinical trial. In the PRIMED trial, primary care physicians (PCPs) from 36 primary care practices in Massachusetts and Maine were enrolled between May 1 and August 30, 2019, and were randomized to the intervention group or the comparator group. Patients aged 76 to 85 years who were overdue for CRC screening and did not have a prior diagnosis of CRC enrolled between October 21, 2019, and April 8, 2021. Data analysis was performed between May 24, 2022, and May 10, 2023. Interventions: Primary care physicians in the intervention group completed an SDM training course and received previsit reminders of patients eligible for CRC testing discussion, whereas PCPs in the comparator group received reminders only. Main Outcomes and Measures: The primary outcome was concordance, or the percentage of patients who received their preferred screening approach. Postvisit surveys were administered to assess patient preference for testing, and electronic health record review was used to assess CRC testing at 12 months. Heterogeneity of treatment effect analyses examined interaction between study groups and different factors on concordance rates. Results: This study included 59 physicians and 466 older adults. Physicians had a mean (SD) age of 52.7 (9.4) years and a mean (SD) of 21.6 (10.2) years in practice; 30 (50.8%) were women and 16 (27.1%) reported prior training in SDM. Patients had a mean (SD) age of 80.3 (2.8) years; 249 (53.4%) were women and 238 (51.1%) reported excellent or very good overall health. Patients preferred stool-based tests (161 [34.5%]), followed by colonoscopy (116 [24.8%]) or no further screening (97 [20.8%]); 75 (16.1%) were not sure. The distribution of patient preferences was similar across groups (P = .36). At 12 months, test uptake was also similar for both the intervention group (29 [12.3%] for colonoscopy, 62 [26.3%] for stool-based tests, and 145 [61.4%] for no testing) and the comparator group (32 [13.9%] for colonoscopy, 35 [15.2%] for stool-based tests, and 163 [70.9%] for no testing; P = .08). Approximately half of patients in the intervention group received their preferred approach vs the comparator group (115 of 226 [50.9%] vs 103 of 223 [46.2%]; P = .47). Heterogeneity of treatment effect analyses found significantly higher rates with the intervention vs the comparator for patients with a strong intention to follow through with the preferred approach (adjusted odds ratio [AOR], 1.79 [95% CI, 1.11-2.89]; P = .02, P = .05 for interaction) and for patients who reported more than 5 minutes (AOR, 3.27 [95% CI, 1.25-8.59]; P = .02, P = .05 for interaction) of discussion with their PCP regarding screening. Higher rates were also observed among patients who reported 2 to 5 minutes of discussion with their PCP, although this finding was not significant (AOR, 1.89 [95% CI, 0.93-3.84]; P = .08, P = .05 for interaction). Conclusions and Relevance: In this secondary analysis of a cluster randomized clinical trial, approximately half of older patients received their preferred approach to CRC screening. Physician training in SDM did not result in higher concordance rates overall but may have benefitted some subgroups. Future work to refine and evaluate clinical decision support (in the form of an electronic advisory or reminder) as well as focused SDM skills training for PCPs may promote high-quality, preference-concordant decisions about CRC testing for older adults. Trial Registration: ClinicalTrials.gov Identifier: NCT03959696.

Interactive effects of sedimentary turbidity and elevated water temperature on the Pugnose Shiner (Miniellus anogenus), a threatened freshwater fish.

High turbidity and elevated water temperature are environmental stressors that can co-occur in freshwater ecosystems such as when deforestation increases solar radiation and sedimentary runoff. However, we have limited knowledge about their combined impacts on fish behaviour and physiology. We explored independent and interactive effects of sedimentary turbidity and temperature on the swimming activity and both thermal and hypoxia tolerance of the Pugnose Shiner (Miniellus anogenus, formerly Notropis anogenus), a small leuciscid fish listed as Threatened under Canada's Species at Risk Act (SARA). Fish underwent a 15-week acclimation to two temperatures (16°C or 25°C) crossed with two turbidities (~0 NTU or 8.5 NTU). Swimming activity was measured during the first 8 weeks of acclimation. Fish in warm water were more active compared to those in cold water, but turbidity had no effect on activity. Behavioural response to hypoxia was measured after 12 weeks of acclimation, as the oxygen level at which fish used aquatic surface respiration (ASR). Fish in warm water engaged in ASR behaviour at higher oxygen thresholds, indicating less tolerance to hypoxia. Turbidity had no effect on ASR thresholds. Finally, thermal tolerance was measured as the critical thermal maximum (CTmax) after 13-15 weeks of acclimation. Acclimation to warm water increased fish CTmax and Tag (agitation temperature) but reduced the agitation window (°C difference between Tag and CTmax) and thermal safety margin (°C difference between the acclimation temperature and CTmax). Furthermore, fish in warm, turbid water had a lower CTmax and smaller thermal safety margin than fish in warm, clear water, indicating an interaction between turbidity and temperature. This reduced thermal tolerance observed in Pugnose Shiner in warm, turbid water highlights the importance of quantifying independent and interactive effects of multiple stressors when evaluating habitat suitability and conservation strategies for imperilled species.

PATIENT RECRUITMENT USING ELECTRONIC HEALTH RECORDS UNDER SELECTION BIAS: A TWO-PHASE SAMPLING FRAMEWORK.

Electronic health records (EHRs) are increasingly recognized as a cost-effective resource for patient recruitment in clinical research. However, how to optimally select a cohort from millions of individuals to answer a scientific question of interest remains unclear. Consider a study to estimate the mean or mean difference of an expensive outcome. Inexpensive auxiliary covariates predictive of the outcome may often be available in patients' health records, presenting an opportunity to recruit patients selectively, which may improve efficiency in downstream analyses. In this paper we propose a two-phase sampling design that leverages available information on auxiliary covariates in EHR data. A key challenge in using EHR data for multiphase sampling is the potential selection bias, because EHR data are not necessarily representative of the target population. Extending existing literature on two-phase sampling design, we derive an optimal two-phase sampling method that improves efficiency over random sampling while accounting for the potential selection bias in EHR data. We demonstrate the efficiency gain from our sampling design via simulation studies and an application evaluating the prevalence of hypertension among U.S. adults leveraging data from the Michigan Genomics Initiative, a longitudinal biorepository in Michigan Medicine.

Derangement in Nicotinamide Adenine Dinucleotide Metabolism is Observed During Acute Kidney Injury Among Male Agricultural Workers at Risk for Mesoamerican Nephropathy.

Introduction: Mesoamerican nephropathy (MeN) is a chronic kidney disease (CKD) which may be caused by recurrent acute kidney injury (AKI). We investigated urinary quinolinate-to-tryptophan ratio (Q/T), a validated marker of nicotinamide adenine dinucleotide (NAD+) biosynthesis that is elevated during ischemic and inflammatory AKI, in a sugarcane worker population in Nicaragua with high rates of MeN. Methods: Among 693 male sugarcane workers studied, we identified 45 who developed AKI during the harvest season. We matched them 1:1 based on age and job category with 2 comparison groups: (i) "no kidney injury," active sugarcane workers with serum creatinine (sCr) <1.1 mg/dl; and (ii) "CKD," individuals no longer working in sugarcane due to their CKD, who had additional 1:1 matching for sCr. We measured urine metabolites using liquid chromatography coupled tandem mass spectrometry (LC-MS/MS) and compared Q/T and other metabolic features between the AKI and comparison groups. Results: Urine Q/T was significantly higher in workers with AKI than in those with no kidney injury (median interquartile Range [IQR]: 0.104 [0.074-0.167] vs. 0.060 [0.045-0.091], P < 0.0001) and marginally higher than in workers with CKD (0.086 [0.063-0.142], P = 0.059). Urine levels of the NAD+ precursor nicotinamide were lower in the AKI group than in comparison groups. Conclusion: Workers at risk for MeN who develop AKI demonstrate features of impaired NAD+ biosynthesis, thereby providing new insights into the metabolic mechanisms of injury in this population. Therapeutic use of oral nicotinamide, which may ameliorate NAD+ biosynthetic derangement and fortify against kidney injury, should be investigated to prevent AKI in this setting.

Probing the Electrostatic Effects of H-Ras Tyrosine 32 Mutations on Intrinsic GTP Hydrolysis Using Vibrational Stark Effect Spectroscopy of a Thiocyanate Probe.

The wildtype H-Ras protein functions as a molecular switch in a variety of cell signaling pathways, and mutations to key residues result in a constitutively active oncoprotein. However, there is some debate regarding the mechanism of the intrinsic GTPase activity of H-Ras. It has been hypothesized that ordered water molecules are coordinated at the active site by Q61, a highly transforming amino acid site, and Y32, a position that has not previously been investigated. Here, we examine the electrostatic contribution of the Y32 position to GTP hydrolysis by comparing the rate of GTP hydrolysis of Y32X mutants to the vibrational energy shift of each mutation measured by a nearby thiocyanate vibrational probe to estimate changes in the electrostatic environment caused by changes at the Y32 position. We further compared vibrational energy shifts for each mutation to the hydration potential of the respective side chain and demonstrated that Y32 is less critical for recruiting water molecules into the active site to promote hydrolysis than Q61. Our results show a clear interplay between a steric contribution from Y32 and an electrostatic contribution from Q61 that are both critical for intrinsic GTP hydrolysis.

Human B Cell Receptor Repertoire Sequencing.

Next-generation sequencing has the potential to uncover the complex nature of B cell immunity by revealing the full complexity of B cell receptor (BCR) repertoires in health and disease. However, there are drawbacks which can compromise the validity of the repertoire analysis caused by quantitative bias and accumulation of sequencing errors during the library preparation and sequencing. Here, we provide an optimized protocol designed to minimize bias for reproducible and accurate preparation of human BCR repertoire libraries for high-throughput sequencing.

Contemporary Patterns of Financial Toxicity Among Patients With Rheumatologic Disease in the United States.

BACKGROUND/OBJECTIVE: Rheumatologic diseases encompass a group of disabling conditions that often require expensive clinical treatments and limit an individual's ability to work and maintain a steady income. The purpose of this study was to evaluate contemporary patterns of financial toxicity among patients with rheumatologic disease and assess for any associated demographic factors. METHODS: The cross-sectional National Health Interview Survey was queried from 2013 to 2018 for patients with rheumatologic disease. Patient demographics and self-reported financial metrics were collected or calculated including financial hardship from medical bills, financial distress, food insecurity, and cost-related medication (CRM) nonadherence. Multivariable logistic regressions were used to assess for factors associated with increased financial hardship. RESULTS: During the study period, 20.2% of 41,502 patients with rheumatologic disease faced some degree of financial hardship due to medical bills, 55.0% of whom could not pay those bills. Rheumatologic disease was associated with higher odds of financial hardship from medical bills (adjusted odds ratio, 1.29; 95% confidence interval, 1.22-1.36; p < 0.001) with similar trends for patients suffering from financial distress, food insecurity, and CRM nonadherence (p < 0.001 for all). Financial hardship among patients with rheumatologic disease was associated with being younger, male, Black, and uninsured ( p < 0.001 for all). CONCLUSION: In this nationally representative study, we found that a substantial proportion of adults with rheumatologic disease in the United States struggled with paying their medical bills and suffered from food insecurity and CRM nonadherence. National health care efforts and guided public policy should be pursued to help ease the burden of financial hardship for these patients.

Intestinal Blastocystis is linked to healthier diets and more favorable cardiometabolic outcomes in 56,989 individuals from 32 countries.

Diet impacts human health, influencing body adiposity and the risk of developing cardiometabolic diseases. The gut microbiome is a key player in the diet-health axis, but while its bacterial fraction is widely studied, the role of micro-eukaryotes, including Blastocystis, is underexplored. We performed a global-scale analysis on 56,989 metagenomes and showed that human Blastocystis exhibits distinct prevalence patterns linked to geography, lifestyle, and dietary habits. Blastocystis presence defined a specific bacterial signature and was positively associated with more favorable cardiometabolic profiles and negatively with obesity (p < 1e-16) and disorders linked to altered gut ecology (p < 1e-8). In a diet intervention study involving 1,124 individuals, improvements in dietary quality were linked to weight loss and increases in Blastocystis prevalence (p = 0.003) and abundance (p < 1e-7). Our findings suggest a potentially beneficial role for Blastocystis, which may help explain personalized host responses to diet and downstream disease etiopathogenesis.

Fetal alcohol spectrum disorder resources for health professionals: a scoping review.

OBJECTIVES: This scoping review aimed to identify and critically appraise resources for health professionals to identify, diagnose, refer, and support individuals with fetal alcohol spectrum disorder (FASD)-including the extent to which the resources are appropriate for use in communities with First Nations Peoples. METHOD: Seven peer-reviewed databases (April 2022) and 14 grey literature websites (August 2022) were searched. The reference lists of all sources that underwent full-text review were handsearched, and FASD experts were consulted for additional sources. Resources were assessed using the Appraisal of Guidelines for REsearch and Evaluation II instrument and an adapted version of the National Health and Medical Research Council FORM Framework and iCAHE Guideline Quality Checklist. RESULTS: A total of 41 resources underwent data extraction and critical appraisal, as screening and/or diagnosis guidelines were excluded because they are covered in other reviews. Most were recently published or updated (n=24), developed in the USA (n=15, 36.6%) or Australia (n=12, 29.3%) and assisted with FASD patient referral or support (n=40). Most management guidelines scored 76%-100% on overall quality assessment (n=5/9) and were recommended for use in the Australian context with modifications (n=7/9). Most of the guides (n=15/22) and factsheets (n=7/10) received a 'good' overall score. Few (n=3/41) resources were explicitly designed for or with input from First Nations Australians. CONCLUSION: High-quality resources are available to support health professionals providing referrals and support to individuals with FASD, including language guides. Resources should be codesigned with people living with FASD to capture and integrate their knowledge and preferences.

Engaging With Health Consumers in Scientific Conferences-As Partners not Bystanders.

INTRODUCTION: It is now widely recognised that engaging consumers in research activities can enhance the quality, equity and relevance of the research. Much of the commentary about consumer engagement in research focuses on research processes and implementation, rather than dissemination in conference settings. This article offers reflections and learnings from consumers, researchers and conference organisers on the 12th Health Services Research Conference, a biennial conference hosted by the Health Services Research Association of Australia and New Zealand (HSRAANZ). METHOD: We were awarded funds via a competitive application process by Bellberry Limited, a national not-for-profit agency with a focus on improving research quality, to incorporate consumer engagement strategies in conference processes and evaluate their impact. FINDINGS: Strategies included consumer scholarships, a buddy system, designated quiet space and consumer session co-chairs; the reflections explored in this paper were collected in the funded, independent evaluation. Our insights suggest a need for more structured consumer involvement in conference planning and design, as well as the development of specific engagement strategies. CONCLUSION: To move toward active partnership in scientific conference settings, our experience reinforces the need to engage consumers as members in designing and conducting research and in presenting research and planning conference content and processes. PUBLIC CONTRIBUTION: Consumer engagement in research dissemination at conferences is the focus of this viewpoint article. Consumers were involved in the conception of this article and have contributed to authorship at all stages of revisions and edits.

Immune gene regulation is associated with age and environmental adversity in a nonhuman primate.

Phenotypic aging is ubiquitous across mammalian species, suggesting shared underlying mechanisms of aging. Aging is linked to molecular changes to DNA methylation and gene expression, and environmental factors, such as severe external challenges or adversities, can moderate these age-related changes. Yet, it remains unclear whether environmental adversities affect gene regulation via the same molecular pathways as chronological, or 'primary', aging. Investigating molecular aging in naturalistic animal populations can fill this gap by providing insight into shared molecular mechanisms of aging and the effects of a greater diversity of environmental adversities - particularly those that can be challenging to study in humans or laboratory organisms. Here, we characterised molecular aging - specifically, CpG methylation - in a sample of free-ranging rhesus macaques living off the coast of Puerto Rico (n samples = 571, n individuals = 499), which endured a major hurricane during our study. Age was associated with methylation at 78,661 sites (31% of all sites tested). Age-associated hypermethylation occurred more frequently in areas of active gene regulation, while hypomethylation was enriched in regions that show less activity in immune cells, suggesting these regions may become de-repressed in older individuals. Age-associated hypomethylation also co-occurred with increased chromatin accessibility while hypermethylation showed the opposite trend, hinting at a coordinated, multi-level loss of epigenetic stability during aging. We detected 32,048 CpG sites significantly associated with exposure to a hurricane, and these sites overlapped age-associated sites, most strongly in regulatory regions and most weakly in quiescent regions. Together, our results suggest that environmental adversity may contribute to aging-related molecular phenotypes in regions of active gene transcription, but that primary aging has specific signatures in non-regulatory regions.

Community health worker training on older adults: A qualitative needs assessment.

BACKGROUND: Community health workers (CHWs) are frontline public health personnel who serve as liaisons between vulnerable patient populations and the healthcare system. They are instrumental in health promotion and education for urban-dwelling older adults. However, no research exists on training that CHWs receive on age-friendly health care. This article explores CHW education on the 4Ms of an Age-Friendly Health System and identifies areas where additional training may be necessary. METHODS: As part of a two-pronged qualitative needs assessment, four focus groups were held with a total of 17 CHWs and semistructured interviews were conducted with 10 clinicians, including both healthcare providers and social workers. Focus group and interview transcripts were then analyzed for major themes in Dedoose, a qualitative coding software. RESULTS: Clinicians most often identified Mentation and Mobility as areas where CHWs can have the greatest impact. Correspondingly, CHWs felt under-equipped to assist patients in these areas and expressed strong interest in additional training. In general, CHWs and clinicians agreed that Medications and What Matters do not fall under CHW scope of practice. CONCLUSIONS: Our findings confirm the critical role that CHWs can play in promoting the health and well-being of urban-dwelling older adults. However, we also demonstrate that many CHWs lack adequate training in age-friendly care. To meet the social and medical needs of a rapidly aging US population, there is a pertinent need to develop a novel community health worker training curriculum on Mentation and Mobility.

Self-Reporting Conjugated Polymer Nanoparticles for Superoxide Generation and Detection.

Conjugated polymer nanoparticles (CPNs or Pdots) have become increasingly popular fluorophores for multimodal applications that combine imaging with phototherapeutic effects. Reports of CPNs in photodynamic therapy applications typically focus on their ability to generate singlet oxygen. Alternatively, CPN excited states can interact with oxygen to form superoxide radical anion and a CPN-based hole polaron, both of which can have deleterious effects on fluorescence properties. Here, we demonstrate that CPNs prepared from the common conjugated polymer poly[(9,9-dioctylfluorenyl-2,7-diyl)-alt-co-(1,4-benzo-{2,1',3}-thiadiazole)] (PFBT, also known as F8BT) generate superoxide upon irradiation. We use the same CPNs to detect superoxide by doping them with a superoxide-responsive hydrocyanine dye developed by Murthy and co-workers. Superoxide induces off-to-on fluorescence switching by converting quenching hydrocyanine dyes to fluorescent cyanine dyes that act as fluorescence resonance energy transfer (FRET) acceptors for PFBT chromophores. Amplified FRET from the multichromophoric CPNs yields fluorescence signal intensities that are nearly 50 times greater than when the dye is excited directly or over 100 times greater when signal readout is from the CPN channel. The dye loading level governs the maximum amount of superoxide that induces a change in fluorescence properties and also influences the rate of superoxide generation by furnishing competitive excited state deactivation pathways. These results suggest that CPNs can be used to deliver superoxide in applications in which it is desirable and provide a caution for fluorescence-based CPN applications in which superoxide can damage fluorophores.