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Oxford ragwort (Senecio squalidus) is one of only two homoploid hybrid species known to have originated very recently, so it is a unique model for determining genomic changes and stabilization following homoploid hybrid speciation. Here, we provide a chromosome-level genome assembly of S. squalidus with 95% of the assembly contained in the 10 longest scaffolds, corresponding to its haploid chromosome number. We annotated 30,249 protein-coding genes and estimated that ∼62% of the genome consists of repetitive elements. We then characterized genome-wide patterns of linkage disequilibrium, polymorphism, and divergence in S. squalidus and its two parental species, finding that (1) linkage disequilibrium is highly heterogeneous, with a region on chromosome 4 showing increased values across all three species but especially in S. squalidus; (2) regions harboring genetic incompatibilities between the two parental species tend to be large, show reduced recombination, and have lower polymorphism in S. squalidus; (3) the two parental species have an unequal contribution (70:30) to the genome of S. squalidus, with long blocks of parent-specific ancestry supporting a very rapid stabilization of the hybrid lineage after hybrid formation; and (4) genomic regions with major parent ancestry exhibit an overrepresentation of loci with evidence for divergent selection occurring between the two parental species on Mount Etna. Our results show that both genetic incompatibilities and natural selection play a role in determining genome-wide reorganization following hybrid speciation and that patterns associated with homoploid hybrid speciation-typically seen in much older systems-can evolve very quickly following hybridization.

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BACKGROUND: Accurate assessment of body composition during infancy is an important marker of early growth. This study aimed to develop anthropometric models to predict body composition in 3-24-month-old infants from diverse socioeconomic settings and ethnic groups. METHODS: An observational, longitudinal, prospective, multi-country study of infants from 3 to 24 months with body composition assessed at three monthly intervals using deuterium dilution (DD) and anthropometry. Linear mixed modelling was utilized to generate sex-specific fat mass (FM) and fat-free mass (FFM) prediction equations, using length(m), weight-for-length (kg/m), triceps and subscapular skinfolds and South Asian ethnicity as variables. The study sample consisted of 1896 (942 measurements from 310 girls) training data sets, 941 (441 measurements from 154 girls) validation data sets of 3-24 months from Brazil, Pakistan, South Africa and Sri Lanka. The external validation group (test) comprised 349 measurements from 250 (185 from 124 girls) infants 3-6 months of age from South Africa, Australia and India. RESULTS: Sex-specific equations for three age categories (3-9 months; 10-18 months; 19-24 months) were developed, validated on same population and externally validated. Root mean squared error (RMSE) was similar between training, validation and test data for assessment of FM and FFM in boys and in girls. RMSPE and mean absolute percentage error (MAPE) were higher in validation compared to test data for predicting FM, however, in the assessment of FFM, both measures were lower in validation data. RMSE for test data from South Africa (M/F-0.46/0.45 kg) showed good agreement with validation data for assessment of FFM compared to Australia (M/F-0.51/0.33 kg) and India(M/F-0.77/0.80 kg). CONCLUSIONS: Anthropometry-based FFM prediction equations provide acceptable results. Assessments based on equations developed on similar populations are more applicable than those developed from a different population.

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The use of electrical current to modulate neurons for autonomic regulation requires the ability to both up-regulate and down-regulate the nervous system. An implanted system employing this electrical neuromodulation would also need to adapt to changes in autonomic state in real-time. Stimulation of autonomic nerves at frequencies in the range 1-30 Hz has been a well-established technique for increasing neural activity. Vagus nerve stimulation (VNS) has been shown to be sensitive to frequency adjustments, which can be used to more precisely control the effect as compared to amplitude modulation. Kilohertz frequency alternating current (KHFAC) is a proven technique for blocking action potential conduction to reduce neural activity. Additionally, KHFAC can be reliably modulated by simple amplitude modulation. Although there are many types of commonly used closed-loop controllers, many conventional methods do not respond well to long system delays or discontinuities. Fuzzy logic control (FLC) is a state-based controller that can describe the discontinuities of the system linguistically and then translate the state transition to a continuous output signal. In our preparation, a single bipolar electrode was placed on the vagus nerve and controlled by a fuzzy logic controller to deliver both stimulation and KHFAC to control heart rate. The FLC was able to both change the heart rate to selected values and maintain the heart rate at a constant value in response to a physiological perturbation.

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Background: Individual perceptions compounded with socio-cultural beliefs and health system factors are key determinants of people's health seeking behavior and are widely cited as the causes of delayed breast cancer diagnosis among women from structurally vulnerable settings. Asking: "how do women with a non-lived experience of cancer understand the disease and, what informs their health seeking behaviors?", we explored individual, sociocultural and health system elements from a conceptual model derived from the Socioecological, Health Belief and Cancer Stigma Frameworks, to understand perspectives of breast cancer in a South African urban community setting. Methods: Using a deductive approach, we conducted a qualitative study consisting of 6 focus group discussions among 34 women from Soweto, Johannesburg (aged 35-74 years) and followed-up with 20 semi-structured in-depth interviews. Results: Findings revealed some awareness of breast and other cancers, but confusion and gaps in understanding of the disease, resulting in socio-culturally influenced misperceptions of risks, causes, and outcomes following treatment of breast cancer. This fueled perceptions of profound fear and stigma against people with breast and other cancers. These findings together with participant perceptions of primary healthcare providers being unwelcoming, under-resourced, and insufficiently trained to deal with breast cancer, resulted in women reporting being reluctant to participating in screening/early detection care seeking behavior. They only accessed primary care when experiencing extreme pain or ill-health. Participants suggested as solutions for future interventions, the need for sustained community engagement, harnessing existing clinic and community stakeholders and resources to provide clear and understandable breast cancer information and encouragement for screening uptake. Conclusions: Health literacy gaps surrounding breast cancer fuels socio-culturally influenced misperceptions, fear, stigma, and fatalism among community women from Soweto, South Africa. Women perceive primary care providers of having insufficient knowledge, skills, and resources to provide effective breast cancer screening services. Participants suggested the need for greater community engagement involving primary clinics and existing community stakeholders working hand in hand. Clear, understandable, and consistent information about breast cancer must be regularly disseminated and communities must be regularly encouraged to utilise breast cancer screening services.

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BACKGROUND: Type 2 diabetes mellitus (T2DM) and chronic heart failure (CHF) present a decrease in functional capacity due to the intrinsic nature of both pathologies. It is not known about the potential impact of T2DM on functional capacity when assessed by 6-min step test (6MST) and its effect as a prognostic marker for fatal and non-fatal events in patients with CHF. OBJECTIVE: to evaluate the coexistence of T2DM and CHF in functional capacity through 6MST when compared to CHF non-T2DM, as well as to investigate the different cardiovascular responses to 6MST and the risk of mortality, decompensation of CHF and acute myocardial infarction (AMI) over 36 months. METHODS: This is a prospective cohort study with 36 months of follow-up in individuals with T2DM and CHF. All participants completed a clinical assessment, followed by pulmonary function testing, echocardiography, and 6MST. The 6MST was performed on a 20 cm high step and cardiovascular responses were collected: heart rate, systemic blood pressure, oxygen saturation, BORG dyspnea and fatigue. The risk of mortality, acute myocardial infarction and decompensation of CHF was evaluated. RESULTS: Eighty-six participants were included. The CHF-T2DM group had a significantly lower functional capacity than the CHF non-T2DM group (p < 0.05). Forced Expiratory Volume in one second (L), ejection fraction (%), gender and T2DM influence and are predictors of functional capacity (p < 0.05; adjusted R squared: 0.419). CHF-T2DM group presented a higher risk of mortality and acute myocardial infarction over the 36 months of follow-up (p < 0.05), but not to the risk of decompensation (p > 0.05). CONCLUSION: T2DM negatively affects the functional performance of 6MST in patients with CHF. Gender, ejection fraction (%), FEV1 (L) and T2DM itself negatively influence exercise performance.

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Purpose: Injectable biologics have not only been described and developed to treat dermal wounds, cardiovascular disease, and cancer, but have also been reported to treat chronic pain conditions. Despite emerging evidence supporting regenerative medicine therapy for pain, many aspects remain controversial. Methods: The American Society of Pain and Neuroscience (ASPN) identified the educational need for an evidence-based guideline on regenerative medicine therapy for chronic pain. The executive board nominated experts spanning multiple specialties including anesthesiology, physical medicine and rehabilitation, and sports medicine based on expertise, publications, research, and clinical practice. A steering committee selected preliminary questions, which were reviewed and refined. Evidence was appraised using the United States Preventive Services Task Force (USPSTF) criteria for evidence level and degree of recommendation. Using a modified Delphi approach, consensus points were distributed to all collaborators and each collaborator voted on each point. If collaborators provided a decision of "disagree" or "abstain", they were invited to provide a rationale in a non-blinded fashion to the committee chair, who incorporated the respective comments and distributed revised versions to the committee until consensus was achieved. Results: Sixteen questions were selected for guideline development. Questions that were addressed included type of injectable biologics and mechanism, evidence in treating chronic pain indications (eg, tendinopathy, muscular pathology, osteoarthritis, intervertebral disc disease, neuropathic pain), role in surgical augmentation, dosing, comparative efficacy between injectable biologics, peri-procedural practices to optimize therapeutic response and quality of injectate, federal regulations, and complications with mitigating strategies. Conclusion: In well-selected individuals with certain chronic pain indications, use of injectable biologics may provide superior analgesia, functionality, and/or quality of life compared to conventional medical management or placebo. Future high-quality randomized clinical trials are warranted with implementation of minimum reporting standards, standardization of preparation protocols, investigation of dose-response associations, and comparative analysis between different injectable biologics.

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PURPOSE: 4-1BB (CD137) is a costimulatory immune receptor expressed on activated T cells, activated B cells, natural killer cells and tumor-infiltrating lymphocytes, making it a promising target for cancer immunotherapy. Cinrebafusp alfa, a monoclonal antibody-like bispecific protein targeting HER2 and 4-1BB, aims to localize 4-1BB activation to HER2-positive tumors. This study evaluated the safety, tolerability, and preliminary efficacy of cinrebafusp alfa in patients with previously treated HER2-positive malignancies. EXPERIMENTAL DESIGN: This was a multi-center dose escalation study involving patients with HER2-positive malignancies who had received prior treatment. The study assessed the safety and efficacy of cinrebafusp alfa across various dose levels. Patients were assigned to different cohorts, and antitumor responses were evaluated. The study aimed to determine the maximum tolerated dose (MTD) and to observe any clinical activity at different dose levels. RESULTS: Out of 40 evaluable patients in the 'active dose' efficacy cohorts, 5 showed an antitumor response, resulting in an overall response rate (ORR) of 12.5% and a disease control rate of 52.5%. Clinical activity was observed at the 8 mg/kg and 18 mg/kg dose levels, with confirmed objective response rates of 28.6% and 25.0%, respectively. Cinrebafusp alfa was safe and tolerable, with Grade ≤2 infusion-related reactions being the most frequent treatment-related adverse event. MTD was not reached during the study. CONCLUSION: Cinrebafusp alfa demonstrates promising activity in patients with HER2-positive malignancies who have progressed on prior HER2-targeting regimens. Its acceptable safety profile suggests it could be a treatment option for patients not responding to existing HER2-directed therapies.

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PURPOSE: This study examined the impact of cannabis use disorder (CUD) on inpatient morbidity, length of stay (LOS), and inpatient cost (IC) of patients undergoing urologic oncologic surgery. METHODS: The National Inpatient Sample (NIS) from 2003 to 2014 was analyzed for patients undergoing prostatectomy, nephrectomy, or cystectomy (n = 1,612,743). CUD was identified using ICD-9 codes. Complex-survey procedures were used to compare patients with and without CUD. Inpatient major complications, high LOS (4th quartile), and high IC (4th quartile) were examined as endpoints. Univariable and multivariable analysis (MVA) were performed to compare groups. RESULTS: The incidence of CUD increased from 51 per 100,000 admissions in 2003 to 383 per 100,000 in 2014 (p < 0.001). Overall, 3,503 admissions had CUD. Patients with CUD were more frequently younger (50 vs. 61), male (86% vs. 78.4%), Black (21.7% vs. 9.2%), and had 1st quartile income (36.1% vs. 20.6%); all p < 0.001. CUD had no impact on any complication rates (all p > 0.05). However, CUD patients had higher LOS (3 vs. 2 days; p < 0.001) and IC ($15,609 vs. $12,415; p < 0.001). On MVA, CUD was not an independent predictor of major complications (p = 0.6). Conversely, CUD was associated with high LOS (odds ratio (OR) 1.31; 95% CI 1.08-1.59) and high IC (OR 1.33; 95% CI 1.12-1.59), both p < 0.01. CONCLUSION: The incidence of CUD at the time of urologic oncologic surgery is increasing. Future research should look into the cause of our observed phenomena and how to decrease LOS and IC in CUD patients.

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We compare, the prevalence, fate, and sources of Bisphenol A both globally and in India. India has the highest concentration of BPA and Bisphenol S(BPS) in general, with vegetables, particularly corn, beans, strings, and raw or canned vegetables, being the largest contributors. Among all the matrices, bisphenols (BPs) are found in the highest concentration in food, followed by surface water, wastewater, and indoor dust. BPA, BPS, and BPF are the most commonly reported analogues in India, with BPA being the most dominant category used worldwide. The highest concentration of BPs is observed in Uttar Pradesh, Punjab and Haryana that are three major agricultural states of India however, there is still a research gap regarding the dietary exposure to BPs on an individual level. Environmentally detected BPA occurs in a range of below detection to 10636 ng. L-1, with significant geographic variations. Interestingly, the order of abundance in India was maximum for BPS, which is contrary to the global average, where BPA is observed as most abundant. BPS is found to be the most common BPs analogue in surface water worldwide, with limited removal efficiency by both naturally remediation and conventional treatment methods. Similar patterns were observed in the US-India and Japan-Korea regions in terms of their source-sink-prevalence-fate dynamics. The probability of exceeding safe concentrations of BPs is higher in India and Korea, suggesting that these countries are more vulnerable to high prevalence concentrations and the subsequent public health hazards.

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Micro and nanobubbles (MNBs), as an efficient and convenient method, have been widely used in water treatment. Composed of gas and water, MNBs avoid directly introducing potential secondary pollutants. Notably, MNBs exhibit significant advantages through interface reactions in assisting AOPs. They overcome barriers like low mass transfer coefficients and limited reactive sites, and shorten the distance between pollutants and oxidants, achieving higher pollutant removal efficiency. However, there is a lack of systematic summary and in-depth discussion on the fundamental mechanisms of MNBs-assisted AOPs. In this critical review, the characteristics of MNBs related to water treatment are outlined first. Subsequently, the recent applications, performance, and mechanisms of MNBs-assisted AOPs including ozone, plasma, photocatalytic, and Fenton oxidation are overviewed. We conclude that MNBs can improve pollutant removal mainly by enhancing the utilization of reactive oxygen species (ROS) generated by AOPs due to the effective interface reactions. Furthermore, we calculated the electrical energy per order of reaction (EE/O) parameter of different MNBs-assisted AOPs, suggesting that MNBs can reduce the total energy consumption in most of the tested cases. Finally, future research needs/opportunities are proposed. The fundamental insights in this review are anticipated to further facilitate an in-depth understanding of the mechanisms of MNBs-assisted AOPs and supply critical guidance on developing MNBs-based technologies for water treatment.

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Children require opportunities to participate in unstructured, unrestricted active play as infants, to encourage positive health, socioemotional and developmental outcomes in life. Certain social and environmental factors in the home setting can limit participation in play, particularly in low resource settings. As caregivers are their infants' first teachers, they have the important role of providing opportunities and space for children to learn through play. This mixed methods, cross-sectional study aimed to test the acceptability of an intervention developed to improve health literacy around play and development with mothers from Soweto, South Africa. Fifteen mothers with infants aged 0-3 months were included to form a Community Advisory Group (CAG). Two rounds of focus group discussions (FGDs) were conducted to explore the understanding of, and barriers to play and development, and to determine the acceptability of an intervention prototype. The prototype included developmentally appropriate activities presented in video format, demonstrations of how to make toys, infographics and other educational material which would be delivered to participants as part of the intervention. A further questionnaire was administered to participants one week after the FGD to determine the acceptability of intervention activities which the participants completed at home, with their infants. Participants reported several barriers to play, including limited options for safe outdoor play, overcrowding, insufficient time, limited resources, and conflicting information. Participants suggested that the intervention content be delivered every 1-2 weeks, through a data-free app. Overall, the prototype activities tested at home were deemed acceptable. The reported barriers, together with reduced motivation and self-efficacy observed in the participants, guided the researchers to develop intervention content focused on improving health literacy in play and development, delivered in the form of an interactive mobile app. Future research will develop and test the efficacy of this intervention in a low resource setting in South Africa.

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Hypertension is associated with decreased endothelial function through reduced contributions of NO. We previously discovered that flow-induced NO production in resistance arteries of mice and humans critically depends on endothelial inwardly-rectifying K+ channels (Kir2.1). The goal of this study was to establish whether these channels contribute to the impairment of endothelial function, measured by flow-induced vasodilation (FIV) in peripheral resistance arteries of humans with hypertension. We measured FIV in vessels isolated from subcutaneous fat biopsies from normotensive (n=19; SBP: 115±27mmHg; DBP: 75.3±5.7mmHg) and hypertensive subjects (n=13; SBP: 146.1±15.2 mmHg; DBP: 94.4±6.9mmHg). We find that FIV is impaired in hypertensive adults as demonstrated by a significant reduction in FIV when compared to the normotensive adults, which is partially attributed to a reduction in Kir2.1-dependent vasodilation. Specifically, we show that pharmacologically inhibiting Kir2.1 or functionally downregulating Kir2.1 with endothelial-specific adenoviral vector dnKir2.1 result in a significant reduction in FIV in normotensive subjects but with a smaller effect in hypertensive adults. The Kir2.1-dependent vasodilation was negatively correlated to SBP and DBP, indicating that Kir2.1 contribution to FIV decreases as blood pressure increases. Furthermore, exposing vessels from normotensive adults to acute high-pressure results in loss of Kir2.1 contribution, as high-pressure impairs vasodilation. No effect is seen when these vessels were incubated with dnKir2.1. Overexpressing wtKir2.1 in the endothelium resulted in some improvement in vasodilation in arteries from all participants, with a greater recovery in hypertensive adults. Our data suggest that high pressure-induced suppression of Kir2.1 is an important mechanism underlying endothelial dysfunction in hypertension.

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There is a critical need for advancements in disease management strategies for wildlife, but free-living animals pose numerous challenges that can hinder progress. Most disease management attempts involve fixed interventions accompanied by post hoc outcome assessments focused on success or failure. Though these approaches have led to valuable management advances, there are limitations to both the rate of advancement and amount of information that can be gained. As such, strategies that support more rapid progress are required. Sarcoptic mange, caused by epidermal infection with Sarcoptes scabiei mites, is a globally emerging and re-emerging panzootic that exemplifies this problem. The bare-nosed wombat (Vombatus ursinus), a marsupial endemic to southeastern Australia, is impacted by sarcoptic mange throughout its geographic range and enhanced disease management capabilities are needed to improve upon existing in situ methods. We sought to advance in situ wildlife disease management for sarcoptic mange in free-living bare-nosed wombats, implementing an adaptive approach using fluralaner (Bravecto, MSD Animal Health) and a structured process of learning and method-optimisation. By using surveillance of treated wombats to inform real-time management changes, we have demonstrated the efficacy of topically administered fluralaner at 45 and 85 mg/kg against sarcoptic mange. Importantly, we observed variation in the effects of 45 mg/kg doses, but through our adaptive approach found that 85 mg/kg doses consistently reduced mange severity. Through modifying our surveillance program, we also identified individual-level variation in wombat observability and used this to quantify the level of surveillance needed to assess long-term management success. Our adaptive intervention represents the first report of sarcoptic mange management with fluralaner in free-living wildlife and evaluation of its efficacy in situ. This study illustrates how adapting interventions in real time can advance wildlife disease management and may be applicable to accelerating in situ improvements for other host-pathogen systems.

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OBJECTIVES: To examine how gender-sensitive community weight-loss programmes have been used to address overweight and obesity in men and to identify what can be learnt from this rapidly evolving field. DESIGN: Scoping review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping review checklist for reporting. DATA SOURCES: A database search was conducted using EBSCOhost (Academic Search Complete, CINAHL Complete, Global Health, Health Source: Consumer Edition, Health Source: Nursing/Academic Edition and Medline Complete), Google, Google Scholar, Open Access Theses and Dissertations platform and Scopus. ELIGIBILITY CRITERIA: All weight-loss programmes using a gender-sensitive approach to address men's overweight and obesity in community settings. DATA EXTRACTION AND SYNTHESIS: Narrative synthesis was conducted based on the research questions and objectives. Primary outcomes include operationalisation, context and concept of the gender-sensitive approach. Information was reviewed and extracted to Microsoft Excel by two reviewers. RESULTS: A total of 40 studies (28 quantitative, eight mixed methods and four qualitative) were identified from 4617 records. Gender-sensitive approaches were undertaken in a range of settings and contexts including professional sports clubs (n=21), non-professional sporting clubs (n=16), workplace-based (n=2) and commercial organisation-based (n=1). The most common analysis approaches were evaluating the effect of the programmes (n=31) where positive impact was predominantly shown (eg, up to 3.9 kg weight reduction at 3-month follow-up). Programmes (ie, Football Fans in Training) were short-term cost-effective (eg, the cost was £862-£2228 per 5% weight reduction at 12-month follow-up). Qualitative evidence highlights factors that influenced men's participation (eg, camaraderie) and identifies areas for improvement. CONCLUSION: The findings demonstrate that gender-sensitive programmes for men's weight loss have been effectively applied using a range of different approaches and in a range of different contexts. Further evidence is needed to confirm the effectiveness of the programmes across diverse groups of men.

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BACKGROUND: Pregnancy termination is an essential component of reproductive healthcare. In Southern Africa, an estimated 23% of all pregnancies end in termination of pregnancy, against a backdrop of high rates of unintended pregnancies and unsafe pregnancy terminations, which contributes to maternal morbidity and mortality. Understanding the reasons for pregnancy termination may remain incomplete if seen in isolation of interpersonal (including family, peer, and partner), community, institutional, and public policy factors. This study therefore aimed to use a socio-ecological framework to qualitatively explore, in Soweto, South Africa, i) reasons for pregnancy termination amongst women aged 18-28 years, and ii) factors characterising the decision to terminate. METHODS: In-depth interviews were conducted between February to March 2022 with ten participants of varying parity, who underwent a termination of pregnancy since being enrolled in the Bukhali trial, set in Soweto, South Africa. A semi-structured, in-depth interview guide, based on the socioecological domains, was used. The data was analysed using reflexive thematic analysis, and a deductive approach. RESULTS: An application of the socio-ecological framework indicated that the direct reasons to terminate a pregnancy fell into the individual and interpersonal domains of the socioecological framework. Key reasons included financial dependence and insecurity, feeling unready to have a child (again), and a lack of support from family and partners for the participant and their pregnancy. In addition to these reasons, Factors that characterised the participants' decision experience were identified across all socio-ecological domains and included the availability of social support and (lack of) accessibility to termination services. The COVID-19 pandemic and resultant lockdown policies also indirectly impacted participants' decisions through detrimental changes in interpersonal support and financial situation. CONCLUSIONS: Amongst the South African women included in this study, the decision to terminate a pregnancy was made within a complex structural and social context. Insight into the reasons why women choose to terminate helps to better align legal termination services with women's needs across multiple sectors, for example by reducing judgement within healthcare settings and improving access to social and mental health support.

In South Africa, where the number of unintended pregnancies is high, we need an improved understanding of the main reasons why women terminate their pregnancies and what factors characterise this decision. Aside from individual factors, this should also be seen within the context of their environment, including relationships, community, and institutions. We therefore aimed to explore women's reasons for choosing to terminate their pregnancy through semi-structured in-depth interviews with participants. We included ten participants from Soweto, South Africa, who had undergone a pregnancy termination. The main reasons for terminating a pregnancy had to do with personal factors and reasons related to their social relationships and support. These included financial insecurity, not feeling ready to have a child (again), and lack of support from family or partners. We also found factors that characterised how the participant experienced the decision, such as barriers to getting a safe (legal) pregnancy termination. We found that amongst South African women, the decision to terminate is made in the context of their complex (social) environment. Insight into the reasons why women choose to terminate helps to better align legal termination services with women's needs, for example by reducing judgement within healthcare settings and improving access to social and mental health support.

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OBJECTIVES: This study examined whether changes in late-life physical performance are associated with contemporaneous changes in blood pressure (BP) in older men. DESIGN: prospective cohort study over 7 years. SETTING AND PARTICIPANTS: Physical performance (gait speed, grip strength, chair stand performance) and clinic-measured BP at baseline and at least one follow-up (year 7 or 9) were assessed in 3,135 men aged ≥65 y enrolled in the Osteoporotic Fractures in Men Study (MrOS). METHODS: Generalized estimating equation analysis of multivariable models with standardized point estimates (ß [95% CI]) described longitudinal associations between physical performance and BP changes in participants overall, and stratified by baseline cardiovascular disease (CVD), antihypertensive medication use (none, ≥1), and enrollment age (<75 years; ≥75 years). RESULTS: Overall, positive associations (z-score units) were found between each increment increase in gait speed and systolic (SBP) (0.74 [0.22, 1.26]) and grip strength (0.35 [0.04, 0.65]) or gait speed (0.55 [0.24, 0.85]) with diastolic (DBP). Better grip strength and chair stand performance over time were associated with 1.83 [0.74, 2.91] and 3.47 [0.20, 6.74] mmHg higher SBP, respectively in men with CVD at baseline (both interaction P < .05). Gait speed increases were associated with higher SBP in men without CVD (0.76 [0.21, 1.32]), antihypertensive medication non-users (0.96 [0.30, 1.62]), aged <75 years (0.73 [0.05, 1.41]) and ≥75 years (0.76 [0.06, 1.47]). Similar positive, but modest associations for DBP were observed with grip strength in men with CVD, antihypertensive medication non-users, and aged <75 years, and with gait speed in men without CVD, aged <75 years, and irrespective of antihypertensive medication use. CONCLUSION: In older men, better physical performance is longitudinally associated with higher BP. Mechanisms and implications of these seemingly paradoxical findings, which appears to be modified by CVD status, antihypertensive medication use, and age, requires further investigation.

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Sarcoptic mange, caused by epidermal infection with Sarcoptes scabiei, negatively impacts the health, welfare, and local abundance of bare-nosed wombats (Vombatus ursinus) in Australia. Improved understanding of the host immune response to disease and its contribution to pathophysiology could be used to inform management actions for this species in and ex situ. To evaluate the immune response of bare-nosed wombats to sarcoptic mange, we validated three assays (haptoglobin, agarose gel electrophoresis, and micro-erythrocyte sedimentation rate) measuring non-specific markers of inflammation using serum samples from free-living wombats from Tasmania (n = 33). We then analysed correlations between the assay results for each non-specific marker of inflammation and wombat's sarcoptic mange scores, and performed histopathological examinations to investigate association of the acute phase response with systemic amyloidosis. We present evidence that haptoglobin and erythrocyte sedimentation rate increased, and albumin decreased, in association with sarcoptic mange scores. This research demonstrates links between the acute phase response and sarcoptic mange severity in bare-nosed wombats, highlighting the utility of non-specific markers of inflammation for aiding assessment of the systemic effects of mange. Showing the value of agarose gel electrophoresis, we also identified specific acute phase proteins warranting future evaluation and found evidence of an immunoglobulin response in mange-affected wombats, revealed by increasing γ-globulins in association with apparent disease severity. Meanwhile, owing to its relatively low resource requirements and rapidity, the erythrocyte sedimentation rate assay may be useful as a point-of-care test to support therapeutic decisions in the field. Our methods and findings are likely to be applicable to a range of other clinical and population health scenarios in captive and free-living wombats, and species impacted by sarcoptic mange globally.

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Background: Vascular diseases, including atherosclerotic cardiovascular disease (ASCVD) and stroke, increase the risk of Alzheimer's disease and cognitive impairment. Serum biomarkers, such as brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and insulin-like growth factor 1 (IGF-1), may be indicators of cognitive health. Objective: We examined whether vascular risk was associated with levels of cognition and serum biomarkers in older women with cardiovascular disease (CVD). Methods: Baseline data from a lifestyle trial in older women (n = 253) with CVD (NCT04556305) were analyzed. Vascular risk scores were calculated for ASCVD (ASCVD risk estimator) and stroke (CHA2DS2-VASc) based on published criteria. Cognition-related serum biomarkers included BDNF, VEGF, and IGF-1. Cognition was based on a battery of neuropsychological tests that assessed episodic memory, semantic memory, working memory, and executive function. A series of separate linear regression models were used to evaluate associations of vascular risk scores with outcomes of cognition and serum biomarkers. All models were adjusted for age, education level, and racial and ethnic background. Results: In separate linear regression models, both ASCVD and CHA2DS2-VASc scores were inversely associated with semantic memory (ß= -0.22, p = 0.007 and ß= -0.15, p = 0.022, respectively), with no significant findings for the other cognitive domains. There were no significant associations between vascular risk scores and serum biomarkers. Conclusions: Future studies should prospectively examine associations between vascular risk and cognition in other populations and additionally consider other serum biomarkers that may be related to vascular risk and cognition.

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The escalating incidence of opioid-related issues among pregnant women in the United States underscores the critical necessity to understand the effects of opioid use and Medication for Opioid Use Disorders (MOUDs) during pregnancy. This research employed a translational rodent model to examine the impact of gestational exposure to buprenorphine (BUP) or morphine on maternal behaviors and offspring well-being. Female rats received BUP or morphine before conception, representing established use, with exposure continuing until postnatal day 2 or discontinued on gestational day 19 to mimic treatment cessation before birth. Maternal behaviors - including care, pup retrieval, and preference - as well as hunting behaviors and brain neurotransmitter levels were assessed. Offspring were evaluated for mortality, weight, length, milk bands, surface righting latency, withdrawal symptoms, and brain neurotransmitter levels. Our results reveal that regardless of exposure length (i.e., continued or discontinued), BUP resulted in reduced maternal care in contrast to morphine-exposed and control dams. Opioid exposure altered brain monoamine levels in the dams and offspring, and was associated with increased neonatal mortality, reduced offspring weight, and elevated withdrawal symptoms compared to controls. These findings underscore BUP's potential disruption of maternal care, contributing to increased pup mortality and altered neurodevelopmental outcomes in the offspring. This study calls for more comprehensive research into prenatal BUP exposure effects on the maternal brain and infant development with the aim to mitigate adverse outcomes in humans exposed to opioids during pregnancy.

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