First-In-Human Demonstration of High Frequency Electrical Motor Nerve Block: Case Report.

ABSTRACT: This feasibility study tested the capability of high frequency stimulation (HFS) to block muscle contractions elicited by electrical stimulation of the same nerve proximally. During a tendon lengthening surgery in the forearm, the anterior interosseous nerve (AIN) was exposed. A specialized nerve cuff electrode was placed around the nerve, and a stimulating probe held on the nerve 1 cm proximal to the cuff electrode delivered pulses of current causing the pronator quadratus muscle to contract. Through the cuff electrode, 20 kHz HFS was delivered to the nerve for 10 seconds during proximal stimulation. HFS amplitudes between 5 and 10 mA peak-to-peak were tested to determine which produced complete and partial block of the electrically induced contractions. The minimum HFS amplitude that produced complete block was 8 mA, with lower amplitudes producing partial block. In all trials, muscle contractions resumed immediately after HFS was turned off. This demonstration of high frequency electrical nerve block is a milestone in the road to clinical implementation of HFS mediated motor block for spasticity.

Non-specific markers of inflammation in bare-nosed wombats (Vombatus ursinus) with sarcoptic mange.

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.

Gender-sensitive community weight-loss programmes to address overweight and obesity in men: a scoping review.

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.

A qualitative exploration of the reasons and influencing factors for pregnancy termination among young women in Soweto, South Africa: a Socio-ecological perspective.

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.

Remotely-delivered exercise training program for improving physical and cognitive functions among older adults with multiple sclerosis: Protocol for an NIH stage-I randomized controlled trial.

BACKGROUND: Older adults with multiple sclerosis (MS) present with low physical activity participation, cognitive and ambulatory dysfunctions, and compromised quality of life (QOL). OBJECTIVE: We propose a NIH Stage-I, randomized controlled trial (RCT) that examines the feasibility and efficacy of a 16-week theory-based, remotely-delivered, exercise training program for improving cognitive and physical functions in older adults with MS who have moderate mobility disability without severe cognitive impairment. METHODS: This Stage-I study utilizes a parallel-group RCT design. Participants (N = 50; age ≥ 50 years) will be randomly assigned into exercise training (combined aerobic and resistance exercise) or active control (flexibility and stretching) conditions. The conditions will be undertaken within a participant's home/community over a 16-week period, and monitored remotely and supported by Zoom-based chats guided by social cognitive theory (SCT) via a behavioral coach. Participants will receive training manuals and equipment, one-on-one behavioral coaching, action-planning calendars, self-monitoring logs, and SCT-based newsletters. The primary outcomes include feasibility (e.g., recruitment and retention rates), exercise behavior and physical activity; other outcomes include physical function (lower-extremity function, mobility, walking), cognition (processing speed, learning and memory, executive function), MS symptoms, QOL, and vascular function. We will collect outcome data at baseline (Week 0), post-intervention (Week 16), and follow-up (Week-32). Data analysis will follow intent-to-treat principles using linear mixed-effects models. DISCUSSION: This Stage-I trial adopts an innovative approach for exercise training via telerehabilitation and is convenient and accessible for older adults with MS. If successful, the study will provide foundations for future research using remotely-delivered exercise intervention for managing the consequences of aging with MS. TRIAL REGISTRATION NUMBER: NCT05930821.

The MindMoves Trial: Cross-Sectional Analyses of Baseline Vascular Risk and Cognition in Older Women with Cardiovascular Disease.

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.

The effects of buprenorphine and morphine during pregnancy: Impact of exposure length on maternal brain, behavior, and offspring neurodevelopment.

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.

Individual differences in the boldness of female zebrafish are associated with alterations in serotonin function.

One of the most prevalent axes of behavioral variation in both humans and animals is risk taking, where individuals that are more willing to take risk are characterized as bold while those that are more reserved are regarded as shy. Brain monoamines (i.e. serotonin, dopamine and noradrenaline) have been found to play a role in a variety of behaviors related to risk taking. Using zebrafish, we investigated whether there was a relationship between monoamine function and boldness behavior during exploration of a novel tank. We found a correlation between serotonin metabolism (5-HIAA:5-HT ratio) and boldness during the initial exposure to the tank in female animals. The DOPAC:DA ratio correlated with boldness behavior on the third day in male fish. There was no relationship between boldness and noradrenaline. To probe differences in serotonergic function in bold and shy fish, we administered a selective serotonin reuptake inhibitor, escitalopram, and assessed exploratory behavior. We found that escitalopram had opposing effects on thigmotaxis in bold and shy female animals: the drug caused bold fish to spend more time near the center of the tank and shy fish spent more time near the periphery. Taken together, our findings indicate that variation in serotonergic function has sex-specific contributions to individual differences in risk-taking behavior.

Leukemia Cutis in Relapsed Acute Myeloid Leukemia: A Call for Distinct Classification.

BACKGROUND Acute myeloid leukemia is characterized by dysregulated proliferation and maturation arrest of myeloid precursors, precipitating a spectrum of complications. Among these, leukemia cutis refers specifically to ectopic deposition and proliferation of malignant myeloid cells within the skin. This infiltration pathogenesis remains unclear. Although there are numerous reports of leukemia cutis in the setting of acute myeloid leukemia or primary acute myeloid leukemia, there are no specific reports of leukemia cutis in the setting of relapsed acute myeloid leukemia. CASE REPORT A 59-year-old woman, with a history of remission from poor-risk acute myeloid leukemia, previously treated with chemotherapy and allogenic bone marrow transplant, presented with shortness of breath, lethargy, anemia, thrombocytopenia, and subcutaneous nodules on lower extremities. Leukemia cutis was diagnosed, in the setting of relapsed acute myeloid leukemia. After unsuccessful salvage chemotherapy and being deemed unsuitable for further treatment, she pursued palliative care and died a month later. CONCLUSIONS Our case highlights a lack of reporting or making a distinction of those patients with relapsed acute myeloid leukemia and leukemia cutis. Consequently, it can be deduced that patients who simultaneously have relapsed acute myeloid leukemia and leukemia cutis are expected to fare worse in terms of clinical outcomes than those with primary acute myeloid leukemia and leukemia cutis. Relapsed acute myeloid leukemia patients with leukemia cutis should be classified as a distinct group, warranting further research into aggressive therapeutic targets and survival rates, while emphasizing the need for more vigilant follow-up and lower biopsy thresholds for cutaneous lesions in patients with treated hematologic malignancies.

Variability of polygenic prediction for body mass index in Africa.

BACKGROUND: Polygenic prediction studies in continental Africans are scarce. Africa's genetic and environmental diversity pose a challenge that limits the generalizability of polygenic risk scores (PRS) for body mass index (BMI) within the continent. Studies to understand the factors that affect PRS variability within Africa are required. METHODS: Using the first multi-ancestry genome-wide association study (GWAS) meta-analysis for BMI involving continental Africans, we derived a multi-ancestry PRS and compared its performance to a European ancestry-specific PRS in continental Africans (AWI-Gen study) and a European cohort (Estonian Biobank). We then evaluated the factors affecting the performance of the PRS in Africans which included fine-mapping resolution, allele frequencies, linkage disequilibrium patterns, and PRS-environment interactions. RESULTS: Polygenic prediction of BMI in continental Africans is poor compared to that in European ancestry individuals. However, we show that the multi-ancestry PRS is more predictive than the European ancestry-specific PRS due to its improved fine-mapping resolution. We noted regional variation in polygenic prediction across Africa's East, South, and West regions, which was driven by a complex interplay of the PRS with environmental factors, such as physical activity, smoking, alcohol intake, and socioeconomic status. CONCLUSIONS: Our findings highlight the role of gene-environment interactions in PRS prediction variability in Africa. PRS methods that correct for these interactions, coupled with the increased representation of Africans in GWAS, may improve PRS prediction in Africa.

A quantitative feedback intervention to reduce binge drinking in young adults.

OBJECTIVE: Existing binge drinking reduction interventions such as brief intervention and personalized normative feedback have shown modest impact. The purpose of this study was to evaluate the feasibility (recruitment and retention rates), acceptability, and preliminary efficacy testing of a short-term "know your numbers (KYN)" intervention on motivating young adults to reduce their engagement in binge drinking. METHOD: Young adults (N=94, mean age 21 years) with a history of binge drinking received a 4-week KYN intervention that included information about their U.S. Alcohol Use Disorders Test (USAUDIT) scores and the alcohol biomarker phosphatidylethanol (PEth) level in relationship to different risk levels of alcohol use. At baseline and 4-weeks, measures included USAUDIT scores, PEth levels, motivation (Alcohol Contemplation Ladder) and other drinking measures. Focus groups were conducted at 4-weeks for feedback on the KYN approach. RESULTS: The recruitment rate was 82.26% (retention rate 76.9%). At 4-weeks there was a 62% increase in contemplation scores (indicating higher motivation), a decrease in USADUIT scores with an increase in the percent of participants classified as low-risk drinkers. No differences were found between baseline and 4-week PEth levels or number of binge episodes. Focus group results revealed satisfaction with the KYN approach but the need to understand how PEth levels and USAUDIT scores corresponded to health consequences and alcohol use levels. CONCLUSIONS: Results from this pilot study support the acceptability and potential use of a KYN approach in helping young adults understand their drinking levels.

Synthesis of recovery patterns in microbial communities across environments.

BACKGROUND: Disturbances alter the diversity and composition of microbial communities. Yet a generalized empirical assessment of microbiome responses to disturbance across different environments is needed to understand the factors driving microbiome recovery, and the role of the environment in driving these patterns. RESULTS: To this end, we combined null models with Bayesian generalized linear models to examine 86 time series of disturbed mammalian, aquatic, and soil microbiomes up to 50 days following disturbance. Overall, disturbances had the strongest effect on mammalian microbiomes, which lost taxa and later recovered their richness, but not their composition. In contrast, following disturbance, aquatic microbiomes tended away from their pre-disturbance composition over time. Surprisingly, across all environments, we found no evidence of increased compositional dispersion (i.e., variance) following disturbance, in contrast to the expectations of the Anna Karenina Principle. CONCLUSIONS: This is the first study to systematically compare secondary successional dynamics across disturbed microbiomes, using a consistent temporal scale and modeling approach. Our findings show that the recovery of microbiomes is environment-specific, and helps to reconcile existing, environment-specific research into a unified perspective. Video Abstract.

Young women's social support networks during pregnancy in Soweto, South Africa.

BACKGROUND: Although studies from high-income countries have examined social support during pregnancy, it remains unclear what type of support is received by expectant mothers from low- and middle-income country settings. AIM: To explore young women's social support networks during pregnancy in Soweto, South Africa. SETTING: This study was undertaken in an academic hospital based in the Southwestern Townships (Soweto), Johannesburg, in Gauteng province, South Africa. METHODS: An exploratory descriptive qualitative approach was employed. Eighteen (18) young pregnant women were recruited using a purposive sampling approach. In-depth interviews were conducted, and data were analysed using inductive thematic analysis. RESULTS: Analysis of the data resulted in the development of two superordinate themes namely; (1) relationships during pregnancy and (2) network involvement. Involvement of the various social networks contributed greatly to the young women having a greater sense of potential parental efficacy and increased acceptance of their pregnancies. Pregnant women who receive sufficient social support from immediate networks have increased potential to embrace and give attention to pregnancy-related changes. CONCLUSION: Focusing on less-examined characteristics that could enhance pregnant women's health could help in the reduction of deaths that arise because of pregnancy complications and contribute in globally accelerating increased accessibility to adequate reproductive health.Contribution: This study's findings emphasise the necessity for policymakers and healthcare providers to educate the broader community about the importance of partner, family and peer support to minimise risks that may affect pregnancy care and wellbeing of mothers.

Race has no impact on prostate cancer-specific mortality, when comparing patients with similar risk of other-cause mortality: An analysis of a population-based cohort.

BACKGROUND: Other-cause mortality (OCM) can serve as a surrogate for access-to-care. The authors sought to compare prostate cancer-specific mortality (PCSM) in Black versus White men matched based on their calculated OCM risk. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was queried for Black and White men diagnosed with prostate cancer between 2004 to 2009, to collect long-term follow-up. A Cox regression was used to calculate the OCM risk using all available covariates. This calculated OCM risk was used to construct a 1:1 propensity score matched (PSM) cohort. Then, a competing-risks multivariable tested the impact of race on PCSM. RESULTS: A total of 94,363 patients were identified, with 19,398 Black men and 74,965 White men. The median (IQR) follow-up was 11.3 years (9.8-12.8). In the unmatched-cohort at 10-years, PCSM and OCM were 5.5% versus 3.5% and 13.8% versus 8.4% in non-Hispanic Black (NHB) versus non-Hispanic White (NHW) patients (all p < .0001). The standardized mean difference was <0.15 for all covariates, indicating a good match. In the matched cohort at 10-years, OCM was 13.6% and 10.0% in NHB versus NHW (p < .0001), whereas the PCSM was 5.3% versus 4.7% (p < .01). On competing-risks multivariable analysis on PCSM, Black men had a hazard ratio of 1.08 (95% confidence interval, 0.98-1.20) compared to White men with a p = .13. CONCLUSIONS: The results of this study showed similar PCSM in Black and White patients, when matched with their calculated OCM risk. This report is the first to indicate at a population-based level that race has no impact on PCSM. PLAIN LANGUAGE SUMMARY: Prostate cancer is a very common cancer among men and it is associated with health disparities that disproportionately impact Black men compared to White men. There is an on-going discussion of whether disparities between these two groups stem from genetic or environmental factors. This study sought to examine if matching based on overall health status, a proxy for the impact of social determinants of health, mitigated significant differences in outcomes. When matched using risk of death from any cause other than prostate cancer, Black and White men had no significant differences in prostate cancer death.

Evaluation of Platelet-rich Plasma and Microneedling for Facial Skin Rejuvenation.

Background: The regenerative properties of platelet growth factors make platelet-rich-plasma (PRP) an attractive modality for treatment of aging skin. The main objective of this study was to determine efficacy and safety of PRP injections and microneedling compared with saline injections in women with aging skin of the face. Methods: In this prospective, randomized clinical trial, 18 women with facial aging were randomized to receive either PRP injections to the unilateral face and saline injections to the contralateral side, or vice versa. Microneedling was performed after injections on the entire face. Physician assessment, photographs, and treatment satisfaction questionnaires were used for outcome assessment at baseline and 16- and 24-week follow-ups. Results: There was no evidence of improvement and suggestion of worsening in skin laxity and rhytides from baseline to weeks 4, 16, and 24 for PRP and saline (all P ≤ 0.004) and no notable difference in skin roughness between baseline and follow-up time points for PRP or saline (all P ≥ 0.19). The degree of change in skin laxity, rhytides, and skin roughness from baseline to follow-up time points was similar for PRP and saline. All patients experienced some degree of pain/discomfort and burning/stinging sensation at treatment weeks 4, 8, and 12 for both saline and PRP. Conclusions: PRP injections did not seem to be effective for treatment of aging skin of the face in women, with no notable macroscopic improvement in appearance when compared with baseline or saline injections. Advanced age of study participants (>45 years) and less-sensitive methods of evaluation may be potential contributing factors to the lack of detected response.

Cost-effectiveness of a complex continuum of care intervention targeting women and children: protocol for an economic evaluation of the Bukhali trial in South Africa.

INTRODUCTION: As nearly two-thirds of women presenting at their first antenatal visit are either overweight or obese in urban South Africa, the preconception period is an opportunity to optimise health and offset transgenerational risk of both obesity and non-communicable diseases. This protocol describes the planned economic evaluation of an individually randomised controlled trial of a complex continuum of care intervention targeting women and children in Soweto, South Africa (Bukhali trial). METHODS AND ANALYSIS: The economic evaluation of the Bukhali trial will be conducted as a within-trial analysis from both provider and societal perspectives. Incremental costs and health outcomes of the continuum of care intervention will be compared with standard care. The economic impact on implementing agencies (programme costs), healthcare providers, participants and their households will be estimated. Incremental cost-effectiveness ratios (ICERs) will be calculated in terms of cost per case of child adiposity at age years averted. Additionally, ICERs will also be reported in terms of cost per quality-adjusted life year gained. If Bukhali demonstrates effectiveness, we will employ a decision analytical model to examine the cost-effectiveness of the intervention over a child's lifetime. A Markov model will be used to estimate long-term health benefits, healthcare costs and cost-effectiveness. Probabilistic sensitivity analyses will be conducted to explore uncertainty and ensure robust results. An analysis will be conducted to assess the equity impact of the intervention, by comparing intervention impact within quintiles of socioeconomic status. ETHICS AND DISSEMINATION: The Bukhali trial economic evaluation has ethical approval from the Human Ethics Research Committee of the University of the Witwatersrand, Johannesburg, South Africa (M240162). The results of the economic evaluation will be disseminated in a peer-reviewed journal and presented at a relevant international conference. TRIAL REGISTRATION NUMBER: Pan African Clinical Trials Registry (PACTR201903750173871; https://pactr.samrc.ac.za).

Immunotherapy-related cognitive impairment after CAR T cell therapy in mice.

Persistent central nervous system (CNS) immune dysregulation and consequent dysfunction of multiple neural cell types is central to the neurobiological underpinnings of a cognitive impairment syndrome that can occur following traditional cancer therapies or certain infections. Immunotherapies have revolutionized cancer care for many tumor types, but the potential long-term cognitive sequelae are incompletely understood. Here, we demonstrate in mouse models that chimeric antigen receptor (CAR) T cell therapy for both CNS and non-CNS cancers can impair cognitive function and induce a persistent CNS immune response characterized by white matter microglial reactivity and elevated cerebrospinal fluid (CSF) cytokines and chemokines. Consequently, oligodendroglial homeostasis and hippocampal neurogenesis are disrupted. Microglial depletion rescues oligodendroglial deficits and cognitive performance in a behavioral test of attention and short-term memory function. Taken together, these findings illustrate similar mechanisms underlying immunotherapy-related cognitive impairment (IRCI) and cognitive impairment following traditional cancer therapies and other immune challenges.

Food insecurity and coping strategies associate with higher risk of anxiety and depression among South African households with children.

OBJECTIVE: To investigate food insecurity and related coping strategies, and their associations with the risk of anxiety and depression, among South African households with children. DESIGN: Nationally representative cross-sectional study. Tools for assessing food insecurity, coping strategies, risk of anxiety and depression were assessed from the Community Childhood Hunger Identification Project, Coping Strategies Index, Generalised Anxiety Disorder-7 and Patient Health Questionnaire-9, respectively. We used ordered logistic regression to test associations of food insecurity and coping strategies with the risk of anxiety and depression. Moderating effects of each coping strategy were tested in the associations of food insecurity with anxiety and depression. SETTING: South Africa, post COVID-19 restrictions, May-June 2022. PARTICIPANTS: 1,774 adults, weighted to 20,955,234 households. RESULTS: Food insecurity prevalence was 23·7 % among households with children. All coping strategies were used to some extent, but relying on less preferred and less expensive foods was the most used strategy (85·5 % of food-insecure households). Moving to a higher level of food insecurity was associated with >1·6 greater odds of being in a higher risk of anxiety and depression. Sending a household member to beg for food was the strongest associated factor (OR = 1·7, P < 0·001). All coping strategies partly moderated (lessened) the associations of food insecurity with a higher risk of anxiety and depression. CONCLUSIONS: Food insecurity among households with children was high following the COVID-19 pandemic. Collaborative efforts between government, private sector and civil society to eradicate food insecurity should prioritise poorer households with children, as these populations are the most vulnerable.