Obesity is a major global public health issue linked to a wide range of chronic diseases. Understanding its complex causal pathways requires robust analytical methods. Mendelian randomization (MR), which employs genetic variants as instrumental variables, effectively addresses confounding and reverse causation and has become a key tool in obesity research. This review summarizes the development of MR methodologies, from single-sample to multivariable, mediation, and time-series models, and highlights key findings from the past decade. MR studies have revealed causal associations between obesity and nine major disease categories, including cardiovascular, metabolic, cancer, psychiatric, respiratory, renal, reproductive, musculoskeletal, and dermatological disorders. Obesity influences disease risk through mechanisms involving energy metabolism, hormonal regulation, and inflammation, with heterogeneity by age, sex, and fat distribution. Key genes such as MC4R, LEPR, FTO, and FGF21 have been identified as potential therapeutic targets. Current challenges include instrument strength, pleiotropy, population stratification, and the external validity of GWAS data. Future research that integrates multi-ancestry GWAS, functional validation, and multi-omics approaches may further enhance the utility of Mendelian randomization. MR provides a robust genetic framework for elucidating obesity's causal effects and informing targeted interventions and personalized treatment strategies.

Methamphetamine (METH) dependence is a globally significant public health concern with no efficacious treatment. Trait impulsivity is associated with the initiation, maintenance, and recurrence of substance abuse. However, the presence of these associations in METH addiction, as well as the underlying neurobiological mechanisms, remains incompletely understood.

We scanned 110 individuals with METH use disorder (MUDs) and 55 matched healthy controls (HCs) using T1-weighted imaging and assessed their drug use characteristics and trait impulsivity. Surface-based morphometry and graph theoretical analysis were used to investigate group differences in brain morphometry and network attributes. Partial correlations were conducted to investigate the relationships between brain morphometric changes, drug use parameters, and trait impulsivity. Mediation analyses examined how trait impulsivity and drug craving influenced the link between brain morphometric change and MUD severity in patients.

MUDs exhibited thinner thickness in the left fusiform gyrus and right pars opercularis, as well as diminished small-world properties in their structural covariance networks (SCNs) compared to HCs. Furthermore, reduced cortical thickness in the right pars opercularis was linked to motor impulsivity (MI) and MUD severity, and the association between the right pars opercularis thickness and MUD severity was significantly mediated by both MI and cue-induced craving.

These findings suggest that MUDs exhibit distinct brain structural abnormalities in both the cortical thickness and SCNs and highlight the critical role of impulse control in METH addiction. This insight may offer a potential neurobiological target for developing therapeutic interventions to treat addiction and prevent relapse.

Alzheimer's disease (AD) risk variants have been identified in European ancestry cohorts that have stronger effects at certain ages, in individuals with a specific sex, or in those with specific isoforms of APOE, the strongest AD risk locus. However, sample sizes in African ancestry (AA) cohorts have been underpowered to perform stratified analyses.

We generated genome-wide association study datasets stratified by sex, age at onset (< 75 vs ≥ 75), and APOE-ε4 carrier status in AA cohorts from MVP and the Alzheimer's Disease Genetics Consortium (ADGC). Outcomes in MVP were AD and related dementias (ADRD; n = 4073 cases and 19,648 controls) and proxy dementia (i.e., reported dementia in a parent, n = 6216 cases and 21,566 controls) while ADGC analyses examined AD (n = 2425 cases and 5069 controls). The proxy dementia GWASs were included in the sex-stratified meta-analysis corresponding to the sex of the affected parent. The top genes were tested for differential expression in AA brain tissue.

In addition to the APOE region, genome-wide significant associations were observed in an intergenic region near the EPHA5 gene (rs141838133, p = 2.19 × 10^-8) in individuals with onset < 75 years, in GRIN3B near the known AD risk gene ABCA7 (rs115882880, p = 3.83 × 10^-8) in females, and near TSPEAR (rs139130053, p = 4.27 × 10^-8) in APOE-ε4 non-carriers. EPHA5 regulates glucose homeostasis, and ephrin receptors modify the strength of existing synapses in the brain and in pancreatic islets. It is unclear whether GRIN3B represents a locus distinct from ABCA7. Rs115882880 was a significant eQTL for GRIN3B but not ABCA7 in AA brain samples. TSPEAR regulates Notch signaling but has not been linked to neuronal function.

Age, sex, and APOE-stratified analyses of dementia in AA participants from two cohorts revealed potential new associations. Stratified analyses may yield critical information about the genetic heterogeneity underlying dementia risk and lead to advances in precision medicine.

Cultural competence intentionally enhances the quality improvement process in healthcare. Therefore, the goal of this study was to evaluate the knowledge, skills, and comfort level of cultural competence and determine the important factors contributing to health disparities among male nursing students.

A cross-sectional, descriptive paper-based study was conducted among male nursing students at a Saudi University between March and May 2024. Data was collected using structured, pre-validated 47-item questionnaires and analyzed using the statistical package for social science version 27. For bivariate analysis, Chi-square or Fisher's Exact test was employed. A p-value < 0.05 was considered statistically significant.

The response rate obtained was 86%. Approximately half of the students (50.8%; n = 131) believed they were somewhat knowledgeable about the demographics of diverse racial and ethnic groups, while only 5% (n = 13) were very knowledgeable. Lifestyle (14%) and environment (12%) were important factors contributing to health disparities. The mean score for knowledge and skills of cultural competence was 67.99 ± (SD = 16.21), while it was 31.29 ± (SD = 12.31), for cross-cultural encounters and 43.32 ± (SD = 13.72) for factors contributing to health disparities. In this study, 50.4% (n = 130) of students reported good levels of knowledge and skills of cultural competence, and 53.5% (n = 138) of students showed good attitudes towards factors contributing to health disparities. There was a significant association between students' grade point average (GPA) and knowledge and skills in cultural competence, with those having higher GPAs demonstrating higher levels of knowledge and those with GPAs above 3.5 reporting higher levels of comfort than those with GPAs below 2 (p = 0.045). Conversely, a significant association was found between students' age group and GPA and their attitudes regarding variables contributing to health disparities (p = 0.0001). In addition, findings reveal that there is a statistically significant linear relationship between knowledge and skills of cultural competence and comfort in dealing with cross-cultural encounters (r = 0.438, p = 0.01) and factors contributing to health disparities (r = 0.376, p = 0.01).

This study found that male nursing students demonstrated a relatively good level of cultural competence, showing comfort in interacting with diverse cultural backgrounds and awareness of social, economic, and cultural determinants of health inequities. To further enhance their preparedness for diverse patient populations, structured training programs, real-world exposure, and reflective learning are recommended.

Not applicable.

Transgender individuals face stigma, violence, and healthcare disparities worldwide. Despite increasing research, data on access to care remain limited. This study aims to describe the demographic, social, and health characteristics of transgender patients attending of transgender individuals seeking care at a single center in Paris, France.

We conducted a retrospective, single-center, descriptive study of transgender individuals who sought care at the infectious diseases department of a tertiary care hospital in Paris, France, between June 2021 and June 2022.

A total of 50 transgender individuals were included, predominantly transgender women (49/50). Most participants were born in Brazil (39/50) and engaged in sex work (41/50). A large proportion faced precarious social conditions, with 35/50 being undocumented migrants and 23/50 lacking healthcare insurance. Despite 44/50 reporting good overall health, 37/50 expressed a need for primary healthcare, yet only 19/50 had consulted a general practitioner in France, primarily through word of mouth (8/19). Language barriers were a major obstacle to care (16/50). Comorbidities were common, including substance use (27/50), HIV (32/50), and at least one sexually transmitted infection in the past year (24/50). Participants also reported high rates of violence (33/50), anxiety (32/50), and depression (28/50).

Transgender individuals seeking care at our center experience significant social and medical vulnerability, with many healthcare needs remaining unmet. Strengthening social and administrative integration, along with leveraging community organizations and healthcare mediators, is essential to improving access to care and support for this population.

Inflammatory Bowel Disease (IBD) is increasing in incidence globally, with low- and middle-income countries (LMICs) facing a rapid surge in disease burden. However, the availability of structured training programs for IBD care remains highly unequal. This review evaluates the current global landscape of IBD workforce training, with an emphasis on identifying gaps and proposing solutions to enhance multidisciplinary preparedness. The IBD care team extends beyond gastroenterologists and includes surgeons, radiologists, pathologists, IBD nurses, dietitians, and mental health professionals. Yet, structured training pathways and credentialing mechanisms are scarce outside of high-income countries. Key barriers include limited access, financial constraints, inadequate infrastructure, and lack of standardized curricula. Emerging digital platforms, simulation-based education, and role-specific training frameworks offer promising strategies. Developing globally harmonized curricula, enhancing funding models, and fostering international collaborations are essential to build a resilient and equitable IBD workforce. Addressing these disparities is critical to improving global IBD outcomes.

The advent of disease modifying therapies in spinal muscular atrophy (SMA) has increased life expectancy but also raising new challenges. We aimed to explore the neurobehavioral profile in SMA type I subjects and in those identified by newborn screening (NBS). Behavioral assessment included screening questionnaires (strengths and difficulties questionnaire (SDQ), social communication questionnaire (SCQ), and sensory profile 2 (SP2)), neurobehavioral observation, CARS2 and DSM-5 criteria. The cohort included thirty-one children (25 type I and 6 NBS) aged 2-10 years. On SDQ prosocial scale, 14/31 showed borderline or abnormal results. 6/14 had borderline scores at the SCQ questionnaire, while none had abnormal scores. Neurobehavioral observation suggested the presence of ASD in 3/31, confirmed by CARS2 and DSM-5 criteria. 5/31 showed other behavioral disorders. Our findings suggest that autism is present in SMA infants in a percentage slightly higher than in the general population. Other neurobehavioral difficulties are less frequent. Our study highlighted the challenges to select appropriate tools in infants with limited mobility and the need for a clear diagnostic pathway, starting with screening questionnaires followed by more appropriate diagnostic tools to reduce the number of false positive results.

Human's abilities to reason about what others may be feeling undergo prolonged development throughout childhood and adolescence, yet the mechanisms driving the emergence of these skills remain elusive. This set of studies, conducted within the same sample of 5- to 10-year-old children, examines how spontaneous perceptual discrimination of facial configurations and activation of conceptual knowledge about emotions become integrated across development. Perceptual discrimination is measured using an EEG frequency tagging paradigm (Study 1). Conceptual knowledge is evaluated with a conceptual similarity rating task (Study 2). Two behavioral tasks (sorting and matching) are employed to assess emotion understanding (Study 3). Representational similarity analysis assesses the predictive effects of perceptual discrimination and conceptual knowledge on children's behavioral judgments. Here we show that while the ability to discriminate stereotypical facial configurations emerges by preschool age, its influence diminishes with age. In contrast, children's inferences about other people's emotions come to rely more on conceptual knowledge with increasing age (and, presumably, social experience).

This study aimed to explore the relationship between Bipolar Disorder (BD) and endocrine hormones, as well as the relationship between psychotropics and endocrine hormones. We recruited 55 drug-naïve women patients with BD, 66 long-term medicated women patients with BD, and 53 healthy controls. Serum levels of thyroid hormones, reproductive hormones, and insulin were measured in all participants. Clinical symptoms of depression and mania were measured in all patients with BD. After controlling for confounding factors, drug-naïve patients showed higher levels of free triiodothyronine (FT3), FT3/free thyroxine (FT4), and luteinizing hormone (LH) than controls, and medicated patients showed higher levels of FT3/FT4, thyroid stimulating hormone (TSH), anti-müllerian hormone (AMH), and insulin than drug-naïve patients. In addition, medicated patients showed a higher prevalence of subclinical hypothyroidism (24.24%) than drug-naïve patients (1.82%). In General Linear Model (GLM) analysis, use of lithium was associated with TSH levels (β = 0.22, p = 0.034), and use of antipsychotics was associated with AMH (β = 0.38, p = 0.005) and insulin levels (β = 0.27, p = 0.039). BD itself and its medication treatment are associated with alterations of thyroid and reproductive hormones, suggesting BD may interfere with hormone homeostasis through neuroendocrine mechanisms. Lithium, valproate, and antipsychotics should be prescribed carefully in BD patients with pre-existing hormone abnormalities.

The Individual Recovery Outcomes Counter (I.ROC) is a recovery orientated measure, originating from Scotland, which is increasingly used in Dutch mental health care. The aim of this study is to extend previous research into the structural validity of the I.ROC. We investigated the factor structure of the Dutch I.ROC among mental health care clients treated in various settings using data (N = 8635) from five Dutch mental health care organisations. We conducted an exploratory factor analysis (EFA, N = 4295) and confirmatory factor analysis (CFA, N = 4340), and tested the fit of factor structures found in previous research. EFA revealed support for both a one- and a two-factor structure: 'Total-scale' (12 items; α = 0.88), 'Empowerment' (8 items; α = 0.86) and 'Vitality and Activity' (4 items; α = 0.67). CFA indicated a good fit for a modified two-factor model found in previous research on a representative sample of the Dutch population comprising 'Wellbeing, control, network and meaningfulness' and 'Health safety and abilities' (CFI = 0.944). Furthermore, the two-factor solution of this study showed a good fit (CFI = 0.940). However, these findings were not conclusive, as the one and alternative two-, three-, or four-factor models of other studies also demonstrated an acceptable fit. For use with individual patients, inspection of scores on individual items (in a spider graph) is most useful. As proven in several studies, the one-factor structure can be used for summarisation. Additionally, multiple solutions for subscale scores proved to be a good fit. Overall, the structural validity of the I.ROC requires further investigation and research with longitudinal data is recommended.