medRxiv : serveur de preprint pour les sciences médicales

Background In Nigeria, approximately one in ten women of reproductive age report experiences of sexual violence in the past year, with potentially enduring consequences. The impact of sexual violence can be particularly devastating for younger women and adolescents, who may face long-lasting physical, psychological, and social effects. To address this, MTV Shuga Naija utilizes entertainment education programming, anchored by a TV serial drama, to promote gender equality and challenge sexual violence norms and behaviors. This research examines the impact of MTV Shuga Naija on disclosure of sexual violence, stigma and victim-blaming attitudes, and greater dialogue about sexual violence. Methods This evaluation uses a panel survey of Nigerian youth aged 15-24 (574 females; 317 males) with data collected before and after the airing of MTV Shuga Naija programming. The baseline wave was conducted in person, while the endline wave was conducted via telephone due to the COVID-19 pandemic. Using the Theory of Planned Behavior, survey questions focused on norms, attitudes, beliefs, and behaviors related to sexual harassment and sexual violence. We analyze changes in self-reported sexual harassment, attitudes towards victims, and discussions with adults and family members about sexual violence for those in in MTV Shuga Naija program areas relative to those in two comparator states. The analysis uses a fixed-effects, doubly robust difference-in-differences (DID) estimation strategy to improve the comparability of treatment and control groups by adjusting for observed differences, thereby allowing for more precise estimation of the causal effects of MTV Shuga Naija. Results At baseline, the majority of both males and females across all study areas reported attitudes blaming victims rather than perpetrators for experiences of sexual violence. However, results from the doubly-robust DID models reveal significant changes in these attitudes among youth in areas exposed to MTV Shuga Nija programming, as well as greater disclosure of incidents of sexual violence to interviewers, possibly due to greater awareness of what constitutes sexual violence. For example, agreement with the statement, "women who wear clothes that expose their bodies are asking to be raped," decreased by 36.6 percentage points [95% CI: -46.8pp, -26.3pp] for women and by 31.8 pp [95% CI: -45.6pp, -18.1pp] for men in areas with MTV Shuga Naija sexual violence programming relative to those in comparison areas. Similarly, acceptance of the attitude that "it is not rape if a woman does not fight back" declined by 28.3 pp [95% CI: -40.2pp, -16.4pp] for women and by 19.3 pp [95% CI: -35.6pp, -3.0pp] for men in treatment versus comparison areas. Contrary to hypotheses, respondents in comparison areas showed larger increases in the likelihood of talking with parents and family about sexual violence than respondents in areas targeted by MTV Shuga Naija, although no information was collected on the initiators, circumstances, nor content of dialogue with parents and family members, rendering difficult the interpretation of this unexpected finding. Conclusion This study provides evidence that the entertainment education approach of MTV Shuga Naija can indeed bring about significant progress in shifting attitudes and behaviors related to sexual violence. Even with this progress, however, victim-blaming norms and attitudes, as well as experiences of sexual violence among women -- and men -- are still widely prevalent. While MTV Shuga Naija has made headway in shifting the landscape surrounding this often-taboo subject in Nigeria, more work is needed to understand how communication and dialogue within families, schools, and communities, alongside greater efforts to support victims of sexual violence, can be improved and enhanced to ensure continued progress.

Background: Differences in affective processing have previously been shown in functional neurological disorder (FND); however, the mechanistic relevance is uncertain. We tested the hypotheses that highly arousing affective stimulation would result in elevated subjective functional neurological symptoms (FNS), and this would be associated with elevated autonomic reactivity. The possible influence of cognitive detachment was also explored. Methods: Individuals diagnosed with FND (motor symptoms/seizures; n=14) and healthy controls (HCs; n=14) viewed Positive, Negative, and Neutral images in blocks, whilst passively observing the stimuli (Watch) or detaching themselves (Distance). The FND group rated their primary FNS, and all participants rated subjective physical (arousal, pain, fatigue) and psychological states (positive/negative affect, dissociation), immediately after each block. Skin conductance (SC) and heartrate (HR) were monitored continuously. Results: FNS ratings were higher after Negative compared to Positive and Neutral blocks in the FND group (p=0.002, np2=0.386); however, this effect was diminished in the Distance condition relative to the Watch condition (p=0.018, np2=0.267). SC and/or HR correlated with FNS ratings in the Negative-Watch and Neutral-Distance conditions (r-values: 0.527-0.672, p-values: 0.035-0.006). The groups did not differ in subjective affect or perceived arousal (p-values: 0.541-0.919, np2: <0.001-0.015). Conclusions: Emotionally significant events may exert an influence on FNS which is related to autonomic activation rather than altered subjective affect or perceived arousal. This influence may be modulated by cognitive detachment. Further work is needed to determine the relevance and neural bases of these processes in specific FND phenotypes.

For orally administered drugs, palatability is key in ensuring patient acceptability and treatment compliance. Therefore, understanding children's taste sensitivity and preferences can support formulators in making paediatric medicines more acceptable. Presently, we explore if the application of computer-vision techniques to videos of children's reaction to gustatory taste strips can provide an objective assessment of palatability. Primary school children tasted four different flavoured strips: no taste, bitter, sweet and sour. Data was collected at home, under the supervision of a guardian, with responses recorded using the Aparito Atom5 app and smartphone camera. Participants scored each strip on a 5-point hedonic scale. Facial landmarks were identified in the videos, and quantitative measures such as changes around the eyes, nose and mouth were extracted to train models to classify strip taste and score. We received 197 videos and 256 self-reported scores from 64 participants. The hedonic scale elicited expected results: children like sweetness, dislike bitterness and have varying opinions for sourness. The findings revealed the complexity and variability of facial reactions and highlighted specific measures, such as eyebrow and mouth corner elevations, as significant indicators of palatability. This study into children's taste specificities can improve the measurement of paediatric medicine acceptability. An objective measure of how children feel about the taste of medicines has great potential in helping find the most palatable formulation. Moreover, collecting data in the home setting allows for natural behaviour, with minimal burden for participants.

Approved therapies for pulmonary arterial hypertension (PAH) mediate pulmonary vascular vasodilatation by targeting distinct biological pathways. Patients identified as intermediate-low risk, according to a four-strata risk assessment model, with an inadequate response to dual therapy with a phosphodiesterase type-5 inhibitor (PDE5i) and endothelin receptor antagonist (ERA), are recommended to either intensify oral therapy by adding a selective prostacyclin receptor (IP) agonist (selexipag), or switching from PDE5i to a soluble guanylate-cyclase stimulator (sGCS; riociguat). The clinical equipoise between these therapeutic choices provides opportunity for evaluation of individualised therapeutic effect. Traditionally, invasive/hospital-based investigations are required to comprehensively assess disease severity and demonstrate treatment benefit. Regulatory approved, minimally invasive monitors enable equivalent measurements to be obtained while patients are at home. In this 2x2 randomised crossover trial, patients with PAH established on guideline-recommended dual therapy and implanted with CardioMEMS (a wireless pulmonary artery sensor) and ConfirmRx (an insertable cardiac rhythm monitor), will receive ERA + sGCS, or PDEi + ERA + IP agonist. The study will evaluate clinical efficacy via established clinical investigations and remote monitoring technologies, with remote data relayed through regulatory approved online clinical portals. The primary aim will be establishing the change in right ventricular systolic volume measured by magnetic resonance imaging (MRI) from baseline to maximal tolerated dose with each therapy. Using data from MRI and other outcomes, including haemodynamics, physical activity, physiological measurements, quality of life, and side effect reporting, we will determine whether remote technology facilitates early evaluation of clinical efficacy, and investigate intra-patient efficacy of the two treatment approaches.

Background: The Central African Republic (CAR) is one of the countries with the highest prevalence of viral hepatitis infection in the world. The present study describes the geographic distribution of viral hepatitis infections and molecular characterization of these viruses in the CAR. Methodology: Out of12,599 persons enrolled during the 4th Multiple Indicator Cluster Survey of 2010 in the CAR, 10,621 Dried Blood Spot (DBS) samples were obtained and stored at -20{degrees}C. Of these DBS, 4,317 samples were randomly selected to represent all regions of the CAR. Serological tests for hepatitis B, D, and C viruses were performed using the ELISA technique. Molecular characterization was performed to identify strains. Results: Of the 4,317 samples included, 53.2% were males and 46.8% females. The HBsAg prevalence among participants was 12.9% and that HBc-Ab was 19.7%. The overall prevalence of the HCV was 0.6%. Co-infection of HIV/HBV was 1.41% and that of HBV/HDV was 16.6%. A total of 77 HBV, 6 HIV, and 6 HDV isolates were successfully sequenced, with 72 HBV (93.5%) strains belonging to genotype E and 5 (6.5%) isolates belonging to genotype D. The 6 HDV isolates all belonged to clade 1, while 4 recombinants sub-type were identified among the 6 isolates of HIV. Conclusion: Our study found a high prevalence of HBV, HBV/HDV and HBV/HIV co-infection, but a low prevalence of HCV. CAR is still in an area of high HBV endemicity. This studys data and analyses would be useful for establishing an integrated viral hepatitis and HIV surveillance program in the CAR.

Background: Prolonged SARS-CoV-2 infections in immunocompromised hosts may predict or source the emergence of highly mutated variants. The types of immunosuppression placing patients at highest risk for prolonged infection and associated intrahost viral evolution remain unclear. Methods: Adults aged >18 years were enrolled at 5 hospitals and followed from 4/11/2022-2/1/2023. Eligible patients were SARS-CoV-2 positive in the previous 14 days and had a moderate or severely immunocompromising condition or treatment. Nasal specimens were tested by rRT-PCR every 2-4 weeks until negative in consecutive specimens. Positive specimens underwent viral culture and whole genome sequencing. A Cox proportional hazards model was used to assess factors associated with duration of infection. Results: We enrolled 150 patients with: B cell malignancy or anti-B cell therapy (n=18), solid organ or hematopoietic stem cell transplant (SOT/HSCT) (n=59), AIDS (n=5), non-B cell malignancy (n=23), and autoimmune/autoinflammatory conditions (n=45). Thirty-eight (25%) were rRT-PCR positive and 12 (8%) were culture-positive [≥]21 days after initial SARS-CoV-2 detection or illness onset. Patients with B cell dysfunction had longer duration of rRT-PCR positivity compared to those with autoimmune/autoinflammatory conditions (aHR 0.32, 95% CI 0.15-0.64). Consensus (>50% frequency) spike mutations were identified in 5 individuals who were rRT-PCR positive >56 days; 61% were in the receptor-binding domain (RBD). Mutations shared by multiple individuals were rare (<5%) in global circulation.

Objective: Pediatric patients have different diseases and outcomes than adults; however, existing phecodes do not capture the distinctive pediatric spectrum of disease. We aim to develop specialized pediatric phecodes (Peds-Phecodes) to enable efficient, large-scale phenotypic analyses of pediatric patients. Materials and Methods: We adopted a hybrid data- and knowledge-driven approach leveraging electronic health records (EHRs) and genetic data from Vanderbilt University Medical Center to modify the most recent version of phecodes to better capture pediatric phenotypes. First, we compared the prevalence of patient diagnoses in pediatric and adult populations to identify disease phenotypes differentially affecting children and adults. We then used clinical domain knowledge to remove phecodes representing phenotypes unlikely to affect pediatric patients and create new phecodes for phenotypes relevant to the pediatric population. We further compared phenome-wide association study (PheWAS) outcomes replicating known pediatric genotype-phenotype associations between Peds-Phecodes and phecodes. Results: The Peds-Phecodes aggregate 15,533 ICD-9-CM codes and 82,949 ICD-10-CM codes into 2,051 distinct phecodes. Peds-Phecodes replicated more known pediatric genotype-phenotype associations than phecodes (248 versus 192 out of 687 SNPs, p<0.001). Discussion: We introduce Peds-Phecodes, a high-throughput EHR phenotyping tool tailored for use in pediatric populations. We successfully validated the Peds-Phecodes using genetic replication studies. Our findings also reveal the potential use of Peds-Phecodes in detecting novel genotype-phenotype associations for pediatric conditions. We expect that Peds-Phecodes will facilitate large-scale phenomic and genomic analyses in pediatric populations. Conclusion: Peds-Phecodes capture higher-quality pediatric phenotypes and deliver superior PheWAS outcomes compared to phecodes.

Purpose: The objective of this systematic review was to give an overview of clinical investigations regarding hip and knee arthroplasty implants published in peer-reviewed scientific medical journals before entry into force of the EU Medical Device Regulation in May 2021. Methods: We systematically reviewed the medical literature for a random selection of hip and knee implants, to identify all peer-reviewed clinical investigations published within 10years before and up to 20years after regulatory approval. We report study characteristics, methodologies, outcomes, measures to prevent bias, and timing of clinical investigations, of 30 current implants. The review process was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: We identified 2912 publications and finally included 151 papers published between 1995 and 2021 (63 on hip stems, 34 on hip cups, 54 on knee systems). We identified no clinical studies published before CE-marking for any selected device, and no studies even up to 20 years after CE-marking in one quarter of devices. There were very few randomized controlled trials, and registry-based studies generally had larger sample sizes and better methodology. Conclusions: The peer-reviewed literature alone is insufficient as source of clinical investigations of these high-risk devices intended for life-long use. A more systematic, efficient and faster way to evaluating safety and performance is necessary. Using a phased introduction approach, nesting comparative studies of observational and experimental design in existing registries, increasing use of benefit measures, and accelerating surrogate outcomes research, will help to minimise risks and maximise benefits.

Objective: Uterine leiomyoma (UL), the most prevalent benign gynecologic tumor among reproductive-aged women, lacks sufficient research on the potential association between dietary intake and its occurrence in Korean women. Addressing this research gap, this study aims to evaluate the potential link between dietary intake and the prevalence of UL in Korean women. Methods : In this cross-sectional study, a cohort of 672 women, aged 25 to 65, were enrolled, with 383 (57%) being premenopausal. Dietary intake was assessed using a validated food frequency questionnaire (FFQ), and UL presence was determined through ultrasonography. The analysis focused exclusively on items within ten categories, including vegetables/fruit, vegetables, fruits, red meat, processed meat, poultry, fish, dairy product, milk, and alcohol. Multiple logistic regression models were employed to explore the relationship between dietary intake and the prevalence of UL, calculating odds ratios (ORs) and 95 % confidence intervals (CIs) while adjusting for confounding factors. Results : Within the total cohort, 219 (32.6%) women were diagnosed with UL. High intakes of fish and poultry showed an association with higher UL prevalence. Odds ratios (95% CIs) for the upper quartiles compared to the lower quartiles were 1.70 (1.02-2.84; p trend = 0.049) for fish intake and 1.85 (1.09 -3.14; p trend = 0.07) for poultry intake. Conversely, an inverse relationship emerged between dairy product intake and UL prevalence, with an odds ratio of 0.59 (95% CI 0.36-0.98; p trend = 0.06). Stratifying the analysis by menopausal status revealed a parallel pattern, with heightened UL prevalence with fish intake and reduced prevalence with dairy product intake. However, the link between poultry intake and UL prevalence was primarily observed among postmenopausal women. Among premenopausal women, elevated vegetable intake was linked to a decreased UL prevalence (OR 0.47, 95% CI 0.22-1.01 for top vs. bottom quartiles; p trend = 0.01). Conclusion : We found that high consumption of fish and poultry, coupled with low intake of dairy products, correlated with an elevated prevalence of UL. Furthermore, vegetable intake exhibited an inverse relationship with UL prevalence, particularly among premenopausal women.

Background: At least 12-month dual antiplatelet therapy (DAPT) is one of the standards of care following Percutaneous Coronary Intervention (PCI) in patients with acute coronary syndrome. However, study on prolonged DAPT for acute myocardial infarction (AMI) patients without revascularization is limited. Methods: We studied 1744 AMI patients without revascularization from the China Acute Myocardial Infarction registry between January 2013 and September 2014. These patients were on DAPT and did not experience AMI, stroke, or bleeding events at 12-month follow-up. We divided them into two groups: 12-month DAPT group (DAPT for at least 12 months but less than 18 months) and 18-month DAPT group (DAPT for at least 18 months). The primary outcome is 24-month all-cause death. Results: Overall, 1221 (70.0%) patients took DAPT for ?12 months but <18 months, while 523 (30.0%) patients took DAPT for ?18 months. The two groups had comparable proportions with high ischemic risk (27.0% vs. 25.6%, P = 0.5418), as well as high bleeding risk (29.0% vs. 28.5%, P = 0.8316). At 24 months, the all-cause mortality rate of 18-month DAPT group was significantly lower than that for 12-month DAPT group (3.7% vs 5.9%, P = 0.0471). Adjusted hazard ratio for all-cause death also showed statistical significance (0.59, 95% CI: 0.35-0.99, P = 0.0444). Conclusions: DAPT for at least 18 months was associated with lower 24-month mortality for non-revascularization AMI patients without events within 12 months after onset.

Effective management of retinoblastoma (RB), the most prevalent childhood eye cancer, depends on reliable monitoring and diagnosis. A promising candidate in this context is the secreted trefoil family factor peptide 1 (TFF1), recently discovered as a promising new biomarker in patients with a more advanced subtype of retinoblastoma. The present study investigated TFF1 expression within aqueous humor (AH) of enucleated eyes and com-pared TFF1 levels in AH and corresponding blood serum samples from RB patients un-dergoing intravitreal chemotherapy (IVC). TFF1 was consistently detectable in AH, con-firming its potential as a biomarker. Crucially, our data confirmed that TFF1 secreting cells within the tumor mass originate from RB tumor cells, not from surrounding stromal cells. IVC therapy responsive patients exhibited remarkably reduced TFF1 levels post-therapy. By contrast, RB patients` blood serum displayed low to undetectable levels of TFF1 even after sample concentration and no therapy-dependent changes were ob-served. Our findings suggest that compared to blood serum AH represents the more relia-ble source for TFF1 if used for liquid biopsy RB marker analysis in RB patients. Thus, analysis of TFF1 in AH of RB patients potentially provides a minimal invasive tool for monitoring RB therapy efficacy, suggesting its importance for effective treatment regi-mens.

OBJECTIVES: To analyze the symptoms and severity of coronavirus disease 2019 (COVID-19) in people with multiple sclerosis (pwMS) on immunotherapy using data from the COVID-19 in multiple sclerosis (MS) Global Data Sharing Initiative dataset provided by PhysioNet. METHODS: The open-access COVID-19 in MS Global Data Sharing Initiative dataset was obtained through credentialed access using PhysioNet. The variables analyzed included body mass index (BMI), symptoms of COVID-19, age, current use of disease-modifying therapy (DMT), efficacy of DMT, comorbidities, hospitalization status, and type of MS. A linear regression analysis was completed. Data analysis and visualization were completed using STATA v1.5, R-Studio v1.1.447, Python v3.8, and its associated libraries, including NumPy, Pandas, and Matplotlib. RESULTS: A total of 1141 participants were included in the analysis. 904 women and 237 men were diagnosed with MS. Among the pwMS included in the study; 208 (19.54%) had a suspected infection with COVID-19 and only 49 (5.25%) were confirmed. Any COVID-19 symptom was present in 360 individuals. The commonly reported DMT agents included dimethyl fumarate (12.71%) and fingolimod (10.17%). 101 in total (8.85%) reported not using any DMT. Factors associated with hospitalization and/or admission to the ICU included having any comorbidity (p = 0.01), neuromuscular disorder (p = 0.046), hypertension (p = 0.005), chronic kidney disease (p < 0.001), and immunodeficiency (p = 0.003). The type of MS, the duration of the disease, and high-efficacy DMT therapy did not have a statistically significant influence on hospitalization. CONCLUSION: This study underscores the importance of comorbidities, especially neuromuscular disorders, hypertension, chronic kidney disease (CKD), and immunodeficiencies, as possible prognostic indicators for worse outcomes of COVID-19 in pwMS. On the contrary, the type of MS, the duration of the disease, and the efficacy of disease-modifying therapy did not significantly affect the severity of the symptoms of COVID-19 in this cohort.

Background: Obstetric risk factors are among the leading preventable causes of Acute Kidney Injury (AKI) in hospitalized reproductive age women. Obstetric-related AKI (ORAKI) has been linked to a significant increase in the overall burden of AKI in resource-constrained settings, resulting in poor maternal and perinatal outcomes. As a result, understanding the impact of these factors on the progression of AKI is critical for a positive outcome. The study sought to determine the incidence of CKD and death, and the effect of obstetric risk factors on these outcomes among reproductive age women with dialysis requiring AKI at the national renal transplant center in Ethiopia. Methods: A retrospective cohort study was conducted on 127 AKI cases (57 ORAKI and 70 None-ORAKI) who were on dialysis at the center from January 2018 to June 2020. A post-hoc power analysis was calculated using G*Power 3.19.4. Data characterization and comparison was made using frequencies with percentages, median with interquartile range, chi-square test/ Fischer's exact test and Mann-Whitney U test. A Robust Poisson regression model was used to identify factors that influence the progression of AKI to CKD and death, with Adjusted Relative Risk (ARR), 95% CIs for ARR, and P-values reported for result interpretation. Results: The overall incidence rate (IR) of CKD was 5.4 per 1000 Person-days (PD) (ORAKI group=0 and None-ORAKI group= 9.7 per 1000 PD) and the overall incidence rate of death was 7.8 per 1000 PD (ORAKI group=5.5 per 1000 PD and None-ORAKI group= 9.7 per 1000 PD). According to the multivariable regression analysis, participants with ORAKI had a 22% lower risk of progression to CKD or death than those with None-ORAKI (ARR=0.78, 95%CI=0.67-0.90, p=0.001). Conclusions: Although having obstetric related risk factors has been linked to an increased risk of developing AKI, once it occurs, those with ORAKI have a significantly better prognosis than those with None-ORAKI. Continued efforts to prevent AKI in pregnant women and to slow its progression once it has developed are critical for a better maternal and fetal outcome.

Background: Chronic Fatigue is a major clinical unmet need among patients with Rheumatoid Arthritis (RA). Current therapies are limited to non-pharmacological interventions, such as personalised exercise programmes (PEP) and cognitive behavioural approaches (CBA), however, still most patients continue to report severe fatigue. To inform more effective therapies, we conducted an MRI brain study of PEP and CBA, nested within a randomised controlled trial (RCT), to identify their neurobiological mechanisms of fatigue reduction in RA. Methods: A sub-group of RA subjects (n=90), participating in a RCT of PEP/CBA for fatigue, undertook a multi-modal MRI brain scan following randomisation to either usual care (UC) alone or in addition to PEP/CBA, and again after the intervention (6 months). Brain regional volumetric, functional, and structural connectivity indices were curated and then computed employing a causal analysis framework. The primary outcome was fatigue improvement (Chalder Fatigue Scale). Findings: Several structural and functional connections were identified as mediators of fatigue improvement in both PEP and CBA compared to UC. PEP had a more pronounced effect on functional connectivity than CBA, however, structural connectivity between the left isthmus cingulate cortex (L-ICC) and left paracentral lobule (L-PCL) was shared and the size of mediation effect ranked highly for both PEP/CBA (BAverage=-0.46, SD 0.61; BAverage=-0.32, SD 0.47, respectively). Interpretation: The structural connection between the L-ICC and L-PCL appears to be a dominant mechanism for how both PEP/CBA reduces fatigue among RA patients. This supports its potential as a substrate of fatigue neurobiology and a putative candidate for future targeting.

Objectives: To explore the perceptions and experiences of barriers and facilitators to accessing Long COVID community rehabilitation. Design: We used a qualitative descriptive design over two rounds of data collection with three participant groups: i) people with experience of rehabilitation for Long COVID (PwLC), ii) NHS staff delivering and/or managing community rehabilitation services (allied health professionals (AHPs)), and iii) NHS staff involved in strategic planning around Long COVID in their health board (Long COVID leads). Setting: Four NHS Scotland territorial health boards. Participants: 51 interviews: eight Long COVID leads (11 interviews), 15 AHPs (25 interviews), and 15 PwLC (15 interviews). Results: Three key themes were identified: i) Accessing care for PwLC, ii) Understanding Long COVID and its management, and iii) Strengths and limitations of existing Long COVID rehabilitation services. Conclusions: Organisational delivery of Long COVID community rehabilitation is complex and presents multiple challenges. In addition, access to Long COVID community rehabilitation can be challenging. When accessed, these services are valued by PwLC but require adequate planning, publicity, and resource. The findings presented here can be used by those developing and delivering services for people with Long COVID.

The role of physical inactivity as a contributor to non-communicable diseases (NCDs) risk in children and youth is widely recognized. Air pollution and built environment can limit participation in physical activity and exacerbate NCD risk; however, the relationships between perceptions of air pollution, built environment, and health behaviors are not fully understood, particularly among children and youth in low and middle-income countries. Currently, there are no studies capturing how child and youth perceptions of air pollution and built environment influence physical activity in India, thus, this study investigates the association between perceived air pollution and built environmental factors on moderate-to-vigorous physical activity (MVPA) levels of children and youth in both rural and urban India. Online surveys captured MVPA, perception of air pollution and built environment factors, as well as relevant sociodemographic characteristics from parents and children aged 5 to 17 years in partnership with 41 schools across 28 urban and rural locations during the Coronavirus disease lockdowns in 2021. After adjusting for age, gender, and location, a significant association was found between the perception of air pollution and MVPA levels ({beta} = -18.365, p < 0.001). Similarly, the perception of a high crime rate was associated with lower MVPA levels ({beta} = -23.383, p = 0.002). Reporting the presence of zebra crossings and pedestrian signals or attractive natural sightings was associated with higher MVPA levels; however, this association varied across sociodemographic groups. These findings emphasize the importance of addressing air pollution and improving the built environment to facilitate outdoor active living, including active transportation -- solutions that are particularly relevant not only for NCD risk mitigation, but also for climate change adaptation.

Since early 2022, in the aftermath of two extreme weather events, Malawi experienced its largest ever cholera outbreak, with over 58,000 reported cases and 1,761 deaths as of May 2023. We generated 49 high-quality, near-complete Vibrio cholerae genomes in Malawi from isolates collected between December 2022 and March 2023 from all three regions of Malawi. Using phylogenetic methods with 2159 publicly available genomes, we present evidence suggesting that the Malawi outbreak strains originated from the Pakistan outbreak, the estimated most recent ancestor of this lineage, named T15, was during the Pakistan floods, and once introduced into Malawi was exacerbated by major floods between June and October 2022. The extreme weather events and humanitarian crises in Malawi provided the environment for the spread of V. cholerae, and the subsequent movement of large numbers of people may have facilitated its spread to susceptible populations in areas relatively unaffected by cholera for over a decade.

The relationship between the acute effects of psychedelics and their persisting neurobiological and psychological effects is poorly understood. Here, we tracked brain changes with longitudinal precision functional mapping in healthy adults before, during, and for up to 3 weeks after oral psilocybin and methylphenidate (17 MRI visits per participant) and again 6+ months later. Psilocybin disrupted connectivity across cortical networks and subcortical structures, producing more than 3-fold greater acute changes in functional networks than methylphenidate. These changes were driven by desynchronization of brain activity across spatial scales (area, network, whole brain). Psilocybin-driven desynchronization was observed across association cortex but strongest in the default mode network (DMN), which is connected to the anterior hippocampus and thought to create our sense of self. Performing a perceptual task reduced psilocybin-induced network changes, suggesting a neurobiological basis for grounding, connecting with physical reality during psychedelic therapy. The acute brain effects of psilocybin are consistent with distortions of space-time and the self. Psilocybin induced persistent decrease in functional connectivity between the anterior hippocampus and cortex (and DMN in particular), lasting for weeks but normalizing after 6 months. Persistent suppression of hippocampal-DMN connectivity represents a candidate neuroanatomical and mechanistic correlate for pro-plasticity and anti-depressant effects of psilocybin.

Background Gateopener colonoscopy-based screening is an innovative concept to better target colonoscopy to those most likely to benefit. It combines invitations to screening colonoscopy with the offer of pretesting with a single gateopener fecal immunochemical test (FIT) which is applied with a lower positivity threshold than in conventional screening. We explored optimized use of this approach for reducing CRC incidence and mortality. Methods and Findings Using COSIMO, a validated Markov-based simulation tool, we compared outcomes of gateopener screening to those of conventional FIT- or colonoscopy-based screening strategies. Gateopener screening was modelled using SENTiFIT-FOB Gold (Sentinel Diagnostics) as exemplary gateopener FIT. We assessed various low hemoglobin cut-offs (10,8,6,4, and 3 {micro}g/g feces). We found that gateopener screening at cut-offs of 6, 4 or 3 {micro}g/g outperformed conventional screening colonoscopy in terms of CRC incidence reduction, with 16-25%, 50-57% and 66-72% more prevented cases, respectively, after ten years. All gateopener scenarios significantly increased prevented deaths, at low cut-offs more than doubling the numbers achieved by conventional screening colonoscopy. Compared to biennial FIT, gateopener screening prevented 7-163% more CRC cases, with lower cut-offs associated with higher gains, and prevented approximately equal to significantly higher (12-21%) numbers of CRC deaths. Cut-offs of 10 and 8 {micro}g/g required fewer colonoscopies per prevented case and death. Conclusions Gateopener screening outperforms conventional CRC screening by offering considerably stronger reduction of CRC incidence and mortality rates as well as considerably increased screening effectiveness. The feasibility of the concept should be assessed by a pilot study in real-life practice.

Background: Real-time (RT) exercise cardiac magnetic resonance imaging (exCMR) is an emerging approach for cardiac stress testing as part of a comprehensive cardiovascular imaging assessment. It has advantages over alternative approaches due to its high spatial resolution and use of non-pharmacological stress. As access to exCMR increases, there is a need to establish reference ranges in healthy adults for clinical interpretation. Methods: We analysed data from 162 healthy adults who had no known cardiovascular disease, did not harbour genetic variants associated with cardiomyopathy, and who completed an exCMR protocol using a pedal ergometer. Participants were imaged at rest and after exercise with left ventricular parameters measured using commercial software by two readers. Prediction intervals were calculated for each parameter. Results: Exercise caused an increase in heart rate (64{+/-}9 bpm vs 133{+/-}19 bpm, P < 0.001), left ventricular end-diastolic volume (140{+/-}32 ml vs 148{+/-}36 ml, P < 0.001), stroke volume (82{+/-}18 ml vs 102{+/-}26 ml, P < 0.001), ejection fraction (59{+/-}6% vs 69{+/-}7%, P < 0.001), and cardiac output (5.2{+/-}1.2 l/min vs 10.0{+/-}3.1 l/min, P < 0.001), with a decrease in left ventricular end-systolic volume (58{+/-}18 ml vs 46{+/-}16 ml, P < 0.001). There was an effect of gender and age on response to exercise across most parameters. Measurements showed moderate to excellent intra- and inter-observer agreement. Conclusion: In healthy adults, an increase in cardiac output after exercise is driven by a rise in heart rate with both increased ventricular filling and emptying. We establish normal ranges for exercise response, stratified by age and gender, as a reference for the use of exCMR in clinical practice.