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The purpose of the present experiments was to systematically replicate Step it UP! Game interventions with adults with disabilities. Participants were divided into two competing teams, and the team with the highest step count participated in a prize drawing. Experiment 1 (N = 9) evaluated the efficacy of an extended version of the Step it UP! Game that included additional and longer sessions. Experiment 2 (N = 8) evaluated the addition of contingent experimenter attention during the Step it UP! Game. Baseline, Step it UP! Game, and Step it UP! Game plus interaction sessions were evaluated in a multielement design. The Step it UP! Game was effective with additional and longer sessions, and all participants took more steps during Step it UP! Game sessions. Adding experimenter interaction to the Step it UP! Game did not increase the efficacy of the intervention.

Abstract Background Most children with developmental disabilities (DD) live in low- and middle-income countries, but access to services is limited, impacting their ability to thrive. Pilot study findings of the World Health Organization’s Caregiver Skills Training (WHO CST) intervention, which equips caregivers with strategies to facilitate learning and adaptive behaviours in children with DD, are promising but evidence from an appropriately powered trial delivered by non-specialist facilitators is lacking. This study will investigate the effectiveness and the resource impacts and costs and consequences of the WHO CST intervention in four sites in rural and urban Kenya and Ethiopia. Methods This is a 2-arm multi-site hybrid type-1 effectiveness implementation cluster randomised controlled superiority trial. After baseline assessments (T0) are completed by participants in clusters comprising 7 to 10 caregiver-child dyads, the clusters will be randomised to either the WHO CST intervention arm or a waitlist enhanced care as usual control arm. Further assessments will be completed at endpoint (T1, 18 ± 2 weeks after randomisation) and follow-up (T2, 44 ± 2 weeks after randomisation). The intervention comprises three individualised home visits and nine group sessions with trained non-specialist facilitators. Participants in the control arm will receive the intervention after completing follow-up assessments. We aim to recruit 544 child-caregiver dyads, evenly distributed across the two arms and countries. The co-primary outcomes are the child-focused Child Behavior Checklist (assessing emotional and behavioural problems) and the caregiver-focused Pediatric Quality of Life Inventory (assessing caregiver quality of life), both assessed at endpoint. Secondary outcome measures comprise the two co-primary outcomes at follow-up and ten additional outcome measures at endpoint, assessing stigma-based experiences, depressive symptoms, household food insecurity, child disciplinary strategies and beliefs, CST knowledge and skill competencies, caregiver and child quality of life, social support, and children’s communication modes and functions. After quantitative follow-up assessments are completed, a mixed-methods evaluation approach will be used to investigate implementation processes and acceptability, feasibility, and potential sustainability of the intervention. Discussion The study’s findings will provide evidence of the effectiveness and resource impacts and costs and consequences of a non-specialist-delivered intervention in under-resourced contexts in one low-income and one middle-income country in East Africa. Findings will inform future research, intervention, and policy efforts to support children with DD and their families in under-resourced majority world contexts. Trial registration Pan African Clinical Trial Registry PACTR202310908063134. Registered on October 16, 2023.

Abstract Shift work and artificial light at night disrupt the entrainment of endogenous circadian rhythms in physiology and behavior to the day-night cycle. We hypothesized that exposure to dim light at night (dLAN) disrupts feeding rhythms, leading to sex-specific changes in autonomic signaling and day-night heart rate and blood pressure rhythms. Compared to mice housed in 12-hour light/12-hour dark cycles, mice exposed to dLAN showed reduced amplitudes in day-night feeding, heart rate, and blood pressure rhythms. In female mice, dLAN reduced the amplitude of day-night cardiovascular rhythms by decreasing the relative sympathetic regulation at night, while in male mice, it did so by increasing the relative sympathetic regulation during the daytime. Time-restricted feeding to the dim light cycle reversed these autonomic changes in both sexes. We conclude that dLAN induces sex-specific changes in autonomic regulation of heart rate and blood pressure, and time-restricted feeding may represent a chronotherapeutic strategy to mitigate the cardiovascular impact of light at night.

Chloroplast morphology changes during immunity, giving rise to tubule-like structures known as stromules. Stromules extend along microtubules and anchor to actin filaments along nuclei to promote perinuclear chloroplast clustering. This facilitates the transport of defense molecules/proteins from chloroplasts to the nucleus. Evidence for a direct role for stromules in immunity is lacking since, currently, there are no known genes that regulate stromule biogenesis. We show that a calponin homology (CH) domain containing kinesin, KIS1 (kinesin required for inducing stromules 1), is required for stromule formation during TNL [TIR (Toll/Interleukin-1 receptor)-type nucleotide-binding leucine-rich repeat]-immune receptor-mediated immunity. Furthermore, KIS1 is required for TNL-mediated immunity to bacterial and viral pathogens. The microtubule-binding motor domain of KIS1 is required for stromule formation while the actin-binding, CH domain is required for perinuclear chloroplast clustering. We show that KIS1 functions through early immune signaling components, EDS1 and PAD4, with salicylic acid-induced stromules requiring KIS1. Thus, KIS1 represents a player in stromule biogenesis.

Introduction: Misclassification of American Indian and Alaska Native (AI/AN) peoples exists across various databases in research and clinical practice. Oral health is associated with cancer incidence and survival; however, misclassification adds another layer of complexity to understanding the impact of poor oral health. The objective of this literature review was to systematically evaluate and analyze publications focused on racial misclassification of AI/AN racial identities among cancer surveillance data. Methods: The PRISMA Statement and the CONSIDER Statement were used for this systematic literature review. Studies involving the racial misclassification of AI/AN identity among cancer surveillance data were screened for eligibility. Data were analyzed in terms of the discussion of racial misclassification, methods to reduce this error, and the reporting of research involving Indigenous peoples. Results: A total of 66 articles were included with publication years ranging from 1972 to 2022. A total of 55 (83%) of the 66 articles discussed racial misclassification. The most common method of addressing racial misclassification among these articles was linkage with the Indian Health Service or tribal clinic records (45 articles or 82%). The average number of CONSIDER checklist domains was three, with a range of zero to eight domains included. The domain most often identified was Prioritization (60), followed by Governance (47), Methodologies (31), Dissemination (27), Relationships (22), Participation (9), Capacity (9), and Analysis and Findings (8). Conclusion: To ensure equitable representation of AI/AN communities, and thwart further oppression of minorities, specifically AI/AN peoples, is through accurate data collection and reporting processes.

Abstract Background The Ethiopian Primary Healthcare Clinical Guidelines (EPHCG) seek to improve quality of primary health care, while also expanding access to care for people with Non-Communicable Diseases and Mental Health Conditions (NCDs/MHCs). The aim of this study was to identify barriers and enablers to implementation of the EPHCG with a particular focus on NCDs/MHCs. Methods A mixed-methods convergent-parallel design was employed after EPHCG implementation in 18 health facilities in southern Ethiopia. Semi-structured interviews were conducted with 10 primary healthcare clinicians and one healthcare administrator. Organisational Readiness for Implementing Change (ORIC) questionnaire was self-completed by 124 health workers and analysed using Kruskal Wallis ranked test to investigate median score differences. Qualitative data were mapped to the Consolidated Framework for Implementation Science (CFIR) and the Theoretical Domains Framework (TDF). Expert Recommendations for Implementing Change (ERIC) were employed to select implementation strategies to address barriers. Results Four domains were identified: EPHCG training and implementation, awareness and meeting patient needs (demand side), resource constraints/barriers (supply side) and care pathway bottlenecks. The innovative facility-based training to implement EPHCG had a mixed response, especially in busy facilities where teams reported struggling to find protected time to meet. Key barriers to implementation of EPHCG were non-availability of resources (CFIR inner setting), such as laboratory reagents and medications that undermined efforts to follow guideline-based care, the way care was structured and lack of familiarity with providing care for people with NCDs-MHCs. Substantial barriers arose because of socio-economic problems that were interlinked with health but not addressable within the health system (CFIR outer setting). Other factors influencing effective implementation of EPHCG (TDF) included low population awareness about NCDs/MHCs and unaffordable diagnostic and treatment services (TDF). Implementation strategies were identified. ORIC findings indicated high scores of organisational readiness to implement the desired change with likely social desirability bias. Conclusion Although perceived as necessary, practical implementation of EPHCG was constrained by challenges across domains of internal/external determinants. This was especially marked in relation to expansion of care responsibilities to include NCDs/MHCs. Attention to social determinants of health outcomes, community engagement and awareness-raising are needed to maximize population impact.

Summary: Background: Subthreshold depression is a risk factor for major depression and is associated with increased morbidity and mortality, especially in older adults. There is emerging evidence that digital interventions, including self-help interventions, may reduce depressive symptoms. We aimed to evaluate the effectiveness of a mobile messaging intervention at reducing subthreshold depressive symptoms among older adults in Brazil. Methods: PRODIGITAL was a single blind, two-arm, individually randomised controlled trial conducted in 46 primary care clinics in the city of Guarulhos, Brazil. Individuals aged 60+ years were contacted by phone following a randomly ordered list for a screening assessment. Those who presented with anhedonia and/or depressed mood (Patient Health Questionnaire (PHQ)-2≥1), and who subsequently scored between 5 and 9 on the PHQ-9 were invited to participate. The intervention arm received the ‘Viva Vida’ digital self-help intervention consisting of automated multi-media messages sent via WhatsApp. Forty-eight audio and visual messages based on psychoeducation and behavioural activation were automatically delivered over six weeks. The control arm received a single message containing information about depression. The primary outcome was the difference in mean PHQ-9 scores between treatment arms at the three-month follow-up. All primary analyses were performed according to allocated arm with imputed data. The trial is registered with ReBEC, RBR-6c7ghfd. Findings: Participants were recruited between 8 September 2021 and 19 August 2022. Of the 454 participants enrolled, 223 were randomised to the intervention arm, 231 to the control arm. Participants’ mean age was 65.3 years (SD 5.0) and 64.0% (n = 292) were female. A total of 385 (84.8%) completed the three-month follow-up assessment; no difference in mean PHQ-9 scores between the treatment arms was observed (adjusted difference: −0.61; 95% CI: −1.75, 0.53; p = 0.29). Interpretation: These results demonstrate that the Viva Vida digital self-help intervention did not help to improve subthreshold depressive symptoms amongst older adults. Further research is needed to understand why this self-help intervention was not effective in this population, and to explore how it might be adapted to achieve this goal. Funding: São Paulo Research Foundation and UK Joint Global Health Trials.

Metaphyseal cones are frequently used in revision total knee arthroplasties (TKAs). However, during subsequent aseptic re-revisions, removing a well-fixed cone can be difficult. One innovative option is to retain the well-fixed cone and cement a new, stemmed revision component through the retained cone, yet minimal data exist on this technique. We describe a technique for retaining a well-fixed cone during re-revision TKA and report outcomes in 6 patients with 6 well-fixed metaphyseal cones. At a mean of 4 years follow-up, no retained cones with a new femoral or tibial component with stems were revised and there was no radiographic evidence of aseptic loosening. These early data suggest that retaining a well-fixed cone can be safe in re-revision TKA to minimize morbidity associated with cone removal. Level of evidence: IV (retrospective study).

Amyotrophic lateral sclerosis (ALS), a devastating neurodegenerative disease, is characterized by progressive motor neuron degeneration, leading to widespread weakness and respiratory failure. While a variety of mechanisms have been proposed as causes of this disease, a full understanding remains elusive. Electrophysiological alterations, including increased motor axon excitability, likely play an important role in disease progression. There remains a critical need for non-animal disease models that can integrate electrophysiological tools to better understand underlying mechanisms, track disease progression, and evaluate potential therapeutic interventions. This review explores the integration of electrophysiological technologies with ALS disease models. It covers cellular and clinical electrophysiological tools and their applications in ALS research. Additionally, we examine conventional animal models and highlight advancements in humanized models and 3D organoid technologies. By bridging the gap between these models, we aim to enhance our understanding of ALS pathogenesis and facilitate the development of new therapeutic strategies.

BackgroundUndergraduate programs in public health are becoming increasingly popular in the United States (US). The recent pandemic, growing climate instability, and the aging baby boomers have led to higher demands for skilled public health professionals at various levels of the workforce. This study examines the nature of courses being delivered in undergraduate public health programs across the United States. The goal is to assess domains, themes, competencies, and other specialized skills that are currently covered in these academic programs.MethodologyA search was conducted in February 2023 using the online CEPH program database to identify undergraduate public health programs in the US. In total, 86 institutions and 90 CEPH-accredited undergraduate public health programs were identified. Lists of public health courses were retrieved from each program, and a total of 2,259 unduplicated courses were extracted and analyzed. A content analysis of the extracted topics was conducted to generate 38 common themes among the courses offered. Coded course themes were mapped to the public health domains and competencies listed by the ASPPH and CEPH to evaluate the distribution of themes across course offerings.ResultsAnalysis of course themes found that Foundations of Public Health, Epidemiology, Public Health Management, Policy, and Leadership, Climate and Environmental Health, and Global Health Issues were the most prevalent. When course themes were mapped onto the ASPPH and CEPH domains of critical public health learning, “overview of public health” and “determinants of health” were the most populated domains. Programs had different emphases according to their approach, but overall, about two-thirds of course themes were focused on foundational and theoretical concepts of public health, and one-third were directed toward practical applications of public health concepts.ConclusionAs the demand for skilled public health workers continues to rise, programs will need to watch the skills and competencies required in the current working environment, as well as the ASPPH and CEPH criteria, and adjust their approach accordingly. Given the rapid changes in the public health landscape, schools and programs of public health should evaluate their curricula to ensure that they are meeting the needs of the workforce and the world.

Abstract Current rodent models of anorexia nervosa (AN) often have accelerated weight loss that often do not allow for investigation of physiological ramifications of prolonged low weight status characteristic of AN. The purpose of this project was to refine a rodent model of AN to extend the duration of low weight status and allow for investigation of recovery. Eight‐week‐old female Sprague Dawley rats underwent 50%–60% food restriction for 30 days. Rats were group‐housed except during feeding, where AN rats were individually housed and given up to 2 h to consume food. Control (CON) rats were allowed to consume food ad libitum. To simulate recovery, a separate cohort of animals underwent the same food restriction protocol for 30 days, then rats (AN‐R) were allowed to consume food ad libitum to facilitate weight recovery for an additional 30 days. AN‐R rats were compared to age matched controls (CON‐R). AN rats lost ~15% bodyweight and were ~30% lighter than CON. Compared to CON, AN rats had ~35% lower fat content, ~18% lower bone mineral density, ~22% smaller plantaris muscle mass and ~52% smaller ovaries. Upon reintroduction of food, AN‐R rats achieved comparable bodyweights to CON‐R rats after ~10 days. However, after 30 days of recovery, AN‐R rats still had ~14% lower bone mineral density and ~11% smaller plantaris mass and ~21% smaller ovaries. This refinement of rodent AN results in physiological side effects of AN without reaching excessive weight loss requiring euthanasia. Moreover, some physiological consequences of simulated AN are not resolved with weight restoration.

Abstract Visual analysis and authentication of artworks are challenging tasks central to art history and criticism. This preliminary study presents a computational tool for scholars examining and authenticating a restricted class of paintings, with a specific focus on the paintings of Raffaello Sanzio da Urbino, more popularly known as Raphael. We applied transfer learning to the ResNet50 deep neural network for feature extraction and used a support vector machine (SVM) binary classifier in support of authentication. Edge detection and analysis algorithms, considered to be crucial for capturing the essence of Raphael’s artistic style, including the brushwork signatures, were also integrated and are used as an authentication tool. The machine learning approach we have developed demonstrates an accuracy of 98% in image-based classification tasks during validation using a test set of well known and authentic paintings by Raphael. Of course, a full authentication protocol relies on provenance, history, material studies, iconography, studies of a work’s condition, and more. Our work, then, contributes to just a portion of a full authentication protocol. Our findings suggest that machine learning methods, properly employed by experts aware of context, may enhance and expand traditional visual analysis for problems in art authentication.

Skeletal muscle size and strength are important for overall health for astronauts. However, how male and female muscle may respond differently to micro- and partial-gravity environments is not fully understood. The purpose of this study was to determine how biological sex and sex steroid hormones influence the progression of muscle atrophy after long term exposure to micro and partial gravity environments in male and female rats. Male and female Fisher rats (n ​= ​120) underwent either castration/ovariectomy or sham surgeries. After two weeks recovery, animals were divided into microgravity (0g), partial-gravity (40% of weight bearing, 0.4g), or full weight bearing (1g) interventions for 28 days. Measurements of muscle size and strength were evaluated prior to and after interventions. At 0g, females lost more dorsiflexion strength, plantar flexion strength, and other metrics of muscle size compared to males; castration/ovariectomy did not influence these differences. Additionally, at 0.4g, females lost more dorsiflexion strength, plantar flexion strength, and other metrics of muscle strength compared to males; castration/ovariectomy did not influence these differences. Females have greater musculoskeletal aberrations during exposure to both microgravity and partial-gravity environments; these differences are not dependent on the presence of sex steroid hormones. Correspondingly, additional interventions may be necessary to mitigate musculoskeletal loss in female astronauts to protect occupational and overall health.

Abstract Remote areas in Jordan often rely on expensive and polluting diesel generators to meet their electricity demand. This study investigates 100% renewable solutions to supply the electricity demand of off‐grid energy systems through optimal sizing of photovoltaics and energy storage systems. A linear programming approach is proposed to minimise the annualised cost of electricity supply including capital costs of equipment and their operation and maintenance costs. The optimisation determines the size of photovoltaics and energy storage required to satisfy electricity demand at every hour of a selected year. A Jordan campsite was used as a case study to assess and compare the performance of PV‐battery storage and PV‐hydrogen storage systems from economic and reliability perspectives. The results show that hydrogen storage was more economical for a 100% renewable energy system. However, introducing some diesel generation gave the battery system a significantly lower annualised cost of energy.

Objective: To ascertain whether sociodemographic and health-related characteristics known from previous research to have a substantive impact on recovery from depression modified the effect of a digital intervention designed to improve depressive symptoms (CONEMO). Methods: The CONEMO study consisted of two randomized controlled trials, one conducted in Lima, Peru, and one in São Paulo, Brazil. As a secondary trial plan analysis, mixed logistic regression was used to explore interactions between the treatment arm and subgroups of interest defined by characteristics measured before randomization – suicidal ideation, race/color, age, gender, income, type of mobile phone, alcohol misuse, tobacco use, and diabetes/hypertension – in both trials. We estimated interaction effects between the treatment group and these subgroup factors for the secondary outcomes using linear mixed regression models. Results: Increased effects of the CONEMO intervention on the primary outcome (reduction of at least 50% in depressive symptom scores at 3-month follow-up) were observed among older and wealthier participants in the Lima trial (p = 0.030 and p = 0.001, respectively). Conclusion: There was no evidence of such differential effects in São Paulo, and no evidence of impact of any other secondary outcomes in either trial. Clinical trial registration: NCT02846662 (São Paulo, Brazil – SP), NCT03026426 (Lima, Peru – LI). Funded by the U.S. National Institute of Mental Health (grant U19MH098780).

Abstract Neurogenic bladder (NB) affects people of all ages. Electric impedance myography (EIM) assesses localized muscle abnormalities. Here, we sought to investigate whether unique detrusor EIM signatures are present in NB due to spinal cord injury (SCI). Twenty-eight, 8–10 weeks old, C57BL/6J female mice were studied. Twenty underwent spinal cord transection; 8 served as controls. Cohorts were euthanized at 4 and 6 weeks after spinal cord transection. Each bladder was measured in-situ with EIM with applied frequencies of 1 kHz to 10 MHz, and then processed for molecular and histologic study. SCI mice had greater bladder-to-body weight ratio (p

Abstract Acute Compartment Syndrome (ACS) is one of the most devastating orthopedic conditions, affecting any of the body’s many compartments, which, if sufficiently severe, may result in disability and amputation. Currently, intra-compartmental pressure measurements serve as the gold standard for diagnosing ACS. Diagnosing limbs at risk for ACS before irreversible damage to muscle and nerve is critical. Standard approaches for diagnosing impending compartment syndrome include clinical evaluation of the limb, such as assessment for “tightness” of the overlying skin, reduced pulses distally, and degree of pain, none of which are specific or sensitive. We have proposed a novel method to detect ACS via electrical impedance myography (EIM), where a weak, high-frequency alternating current is passed between one pair of electrodes through a region of tissue, and the resulting surface voltages are measured via a second pair. We evaluated the ability of EIM to detect early muscle ischemia in an established murine model of compression-induced muscle injury, where we collected resistance, reactance, and their dimensionless product, defined as Relative Injury Index (RII) during the study. Our model generated reproducible hypoxia, confirmed by Hypoxyprobe™ staining of endothelial regions within the muscle. Under conditions of ischemia, we demonstrated a reproducible, stable, and significant escalation in resistance, reactance, and RII values, compared to uninjured control limbs. These data make a reasonable argument for additional investigations into using EIM for the early recognition of muscle hypoperfusion and ischemia. However, these findings must be considered preliminary steps, requiring further pre-clinical and clinical validation.