Klinefelter syndrome is most commonly associated with a 47,XXY karyotype, though rarer variants such as 48,XXXY, 48,XXYY, 49,XXXXY, and mosaic forms occur. The clinical spectrum includes intellectual disability, psychiatric disorders, endocrinopathies, and infertility, while epilepsy is rarely reported. The syndrome is also linked to an increased risk of malignancies, including breast cancer and mediastinal germ cell tumors. Multinodular and vacuolating neuronal tumors (MVNTs) are rare glioneuronal neoplasms.

We report a 9-year-old male with a 2-year history of epilepsy, in whom brain MRI revealed an MVNT in the left posterior temporal lobe. Chromosomal microarray analysis showed a 2.5 Mb duplication at Xp22.33, a 152.9 Mb duplication from Xp22.33 to Xq28, and a 280 kb deletion at 5q33.1. Karyotyping confirmed a 47,XXY karyotype, consistent with Klinefelter syndrome.

While MVNTs are typically sporadic or monogenic, this case raises the possibility of an association with Klinefelter syndrome. To our knowledge, this is the second reported case, contributing to the expanding clinical and genetic spectrum of Klinefelter syndrome-associated neurological findings.

Rapid tranquillisation is a widely used restrictive practice, but evidence suggests that ethnic minorities are disproportionately exposed compared with majority populations. This retrospective qualitative multiple-case study explored how staff clinical decision-making regarding rapid tranquillisation, as reflected in clinical documentation, may vary by ethnicity in adult forensic mental health inpatient settings. Nineteen cases involving rapid tranquillisation use between 01 Jul 2021 and 31 Jan 2025 were purposively selected using paper-based forensic registration forms and electronic health records. Cases were categorised dichotomously by ethnicity using country of birth (ethnic minorities vs. the majority population), and data from clinical documentation were analysed using content analysis, guided by a four-component framework of clinical decision-making, examining similarities and differences within and between cases. The SRQR standards were used for reporting. Overall patterns of rapid tranquillisation use were broadly similar across groups. However, differences were reported in the temporal unfolding of situations leading to rapid tranquillisation, negotiation and planning processes and the documentation of distress, severity and risk. Escalating distress and behaviour tended to be recognised later among ethnic minorities, often shortly before rapid tranquillisation, whereas escalation among the majority population was more frequently documented over longer periods. Documentation of proactive planning, voluntary medication negotiation and debriefing was limited overall but less visible for ethnic minorities. Clinical decision-making appeared iterative and cyclical, with repeated rapid tranquillisation use occurring across both groups. Ethnicity may influence clinical decision-making regarding rapid tranquillisation, with disparities emerging through cumulative, process-oriented variations in practice. Further research is required to confirm these findings.

Adolescence is a period notable for increased risk-taking behaviors, including substance use (SU). Longitudinal work has linked behavioral disinhibition, particularly impulsive dispositions and externalizing tendencies with SU, but the underlying neurobiological manifestations remain less well-defined. This study examined whether individual differences in reward-related striatal activity and impulsivity predicted mental health (externalizing symptoms) and SU outcomes (cannabis, nicotine, alcohol) over a year later.

Adolescents (n = 140; M _age = 14.9 years) from a larger longitudinal cohort completed a Monetary Incentive Delay (MID) fMRI task at baseline along with a measure of self-reported impulsivity. At follow-up, they reported externalizing symptoms and days of cannabis, e-cigarette, and alcohol use. Task behavior [response times [RTs], hit rates [HRs]] and striatal responses to anticipatory gain cues were extracted. Serial mediation models tested whether impulsivity and externalizing mediated an association between striatal activity and subsequent SU.

Behaviorally, gain cues elicited faster target-related RTs and higher HRs (vs. loss or neutral trials), and performance scaled with incentive magnitude. Gain (vs. neutral) cues elicited greater bilateral caudate activity where more left caudate activity correlated with faster RTs and lower impulsivity. Serial mediation revealed that less left striatal activity during reward anticipation linked with higher impulsivity, which predicted more subsequent externalizing symptoms that, in turn, linked with more cannabis [indirect effect = -0.01, 95%CI (-0.04, -0.001)] and e-cigarette use days [indirect effect = -0.02, 95% CI (-0.05, -0.004)]. No indirect or direct effects emerged for alcohol use.

These findings suggest blunted striatal activity may reflect reduced motivational drive for lower-intensity rewards (e.g., fictitious MID monetary gains), which contribute to SU vulnerability via heightened behavioral disinhibition in pursuit of higher-intensity stimulation. Intervention strategies that upregulate everyday reward value and strengthen self-regulation may offer utility in reducing teen SU.

Previous findings for the association of fish intake and its related metabolites on risk of metabolic syndrome (MetS) are inconsistent and limited. The prevalence of fish and shellfish consumers are high in Japan where it contributes to one fourth of the protein intake. We aimed to investigate the relationship of fish and fish-related metabolites with MetS risk factors in a community-dwelling Japanese population.

In this cross-sectional study, 1047 Japanese men and women aged 40-59 years were included. Four in-depth multiple-pass 24-h dietary recalls, two timed 24-h urine collections, blood collection, extensive questionnaire and anthropometric measurements were collected for each participant. Urinary and serum profiles were obtained using ¹H Nuclear magnetic resonance (NMR) spectroscopy.

Mean fish intake was 47.0 (SD 28.8) g per 1000 kcal. Urinary trimethylamine-N-oxide (TMAO) and taurine, and serum creatine and threonine were significantly correlated with fish intake and homarine was associated with shellfish intake (p < 0.01). Significant inverse associations were found between triglycerides and total fish intake, low omega-3 fish, urinary TMAO, taurine and between urinary taurine with systolic blood pressure. Direct association between urinary TMAO and serum threonine with high-density lipoprotein cholesterol were found.

We found several metabolites related to fish intake and risk factors of MetS in habitual fish-consuming country, Japan. When stratified by seafood type, raw and high omega-3 fish intake showed the strongest associations with urinary and serum metabolomes, while fried fish had weaker or non-significant correlations, suggesting that cooking methods may modulate the bioavailability or metabolic impact of fish nutrients. The combined panel of urinary TMAO and taurine with plasma creatine and threonine, reflecting seafood intake, was associated with a favorable lipid profile and lower blood pressure.

The INTERMAP study is registered as NCT00005271 at www.

gov .

Proactive referral, defined as a strategy to connect smokers with smoking cessation programs under the responsibility of healthcare professionals, is effective in increasing the uptake of such programs. A feasibility study in a health check-up setting of the Brief Tobacco Intervention with Proactive Referral (BTI-PR), our smoker-level implementation strategy for smoking cessation treatment (SCT), revealed that the BTI-PR could be delivered to 85.7% of smokers as intended by healthcare professionals following provider-level guidance on implementation, which included educational sessions and the provision of materials. The present study aimed to estimate smoker uptake of SCT following a multifaceted, provider-level implementation strategy in Japanese real-world health check-up settings.

This single-arm, multi-center, uncontrolled hybrid type 3 effectiveness-implementation study is focused on providing stakeholders with the evidence necessary to support adoption of the BTI-PR together with its provider-level implementation strategy. The BTI-PR is a smoker-level implementation strategy for SCT which acts by motivating smokers to schedule an online SCT appointment by themselves. The provider-level implementation strategy consists of eight components: (a) conduct a training session, (b) provide a guide on the BTI-PR, (c) provide a checksheet for the BTI-PR, (d) provide a flyer on the online SCT, (e) conduct a kickoff meeting and request to discuss pre-specifiable matters, (f) schedule a pre-implementation phase, (g) request holding a review meeting and report, and (h) conduct a plenary meeting to share local knowledge. Primary outcome is the penetration of online SCT, namely the proportion of smokers eligible for the BTI-PR who attend the first session of the online SCT within 3 months after receiving the BTI-PR.

Data collection was completed in February 2026. A total of 24 healthcare professionals who received the provider-level implementation strategy delivered the BTI-PR to smokers to explore the primary outcome. The final analyses were commenced in March 2026.

This study is expected to support the adoption of proactive referral together with an implementation strategy in health check-up settings, although causal inference remains limited. The findings will contribute to the implementation of effective smoking cessation support into preventive health services.

https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000064502; UMIN-CTR, number UMIN000056447.

Breast cancer is the most common malignancy in women, and its incidence is increasing worldwide. Type 2 diabetes mellitus (T2DM) is a significant comorbidity in patients with breast cancer that negatively affects prognosis. Metformin, a first-line antidiabetic drug, has been suggested to possess antineoplastic properties. This study investigated the effects of metformin on the demographic characteristics, pathological parameters, treatment response, and prognosis of breast cancer patients with T2DM in an Iranian population.

A retrospective cross-sectional study was conducted on 104 patients with breast cancer and T2DM at the Velayat Educational and Therapeutic Center, Qazvin, Iran, from 2019 to 2023. The patients were categorized into two groups: metformin users (n = 46) and non-users (n = 58). Data on demographic characteristics, disease stage, lymph node involvement, hormone receptor status, treatment response, prognosis, recurrence, and metastasis were collected. Statistical analyses were performed using SPSS version 25, with significance set at p < 0.05. Unadjusted and adjusted logistic regression analyses were performed to identify independent predictors of prognosis.

The mean disease duration was significantly shorter in the metformin group than in the non-metformin group (p = 0.036). A significant difference was observed in the stage of disease (p = 0.003), with metformin users more frequently presenting at earlier stages. Lymph node involvement was significantly lower in the metformin group (p = 0.008). Patients using metformin showed significantly better treatment response (p = 0.028) and prognosis (p = 0.009). However, no significant differences were observed in the estrogen receptor (ER) status (p = 0.293), human epidermal growth factor receptor 2 (HER2) status (p = 0.762), metastasis (p = 0.249), or recurrence rates (p = 0.770). After adjustment, disease duration, HER2 status, and metformin use remained independently associated with prognosis.

Metformin use in breast cancer patients with T2DM is associated with lower disease stage, fewer involved lymph nodes, improved treatment response, and better prognosis. These findings suggest that metformin may play a beneficial role in breast cancer progression and treatment outcomes. Further prospective studies are warranted to confirm these results in a clinical setting and to elucidate the underlying mechanisms.

This study aimed to synthesize evidence on the prevalence of Barrett's esophagus (BE), estimate its global burden, and examine variation across studies.

Accurate BE prevalence estimates are essential for developing effective screening and surveillance strategies.

A systematic search was conducted in PubMed, Scopus, Web of Science, and EMBASE from inception to January 2026. Full-text articles and reference lists were also screened manually. Studies reporting BE prevalence in general or clinical populations were included. Extracted data covered study design, population characteristics, diagnostic criteria, biopsy protocols, geographic region, and publication period. Study-level analyses assessed methodological variability and temporal trends. Linear regression and generalized additive models were used to project BE prevalence through 2050.

Fifty-two studies, including approximately 8.4 million participants from 24 countries, were analyzed. The pooled mean prevalence of BE was 5.76%, with estimates ranging from 0.06% to 37.4%. Prevalence was higher in symptomatic endoscopy cohorts than in population-based cohorts (4.8% vs. 1.2%, p < 0.001). Studies requiring histologic confirmation of intestinal metaplasia reported lower estimates than those using broader definitions. Significant heterogeneity was observed by region and publication period. Seattle biopsy protocol reporting was documented in 38.5% of studies and improved after 2010. Forecast models projected BE prevalence of 12.8-13.2% by 2050 using linear modeling and 11.2-11.8% using GAM.

Reported BE prevalence varies widely, mainly due to differences in diagnostic criteria, study populations, and methodology. Standardized definitions, biopsy protocols, and reporting practices are needed to improve epidemiologic accuracy and guide screening.

The interplay between recovery and immune responses is increasingly recognized but remains under-integrated in clinical and research frameworks. Recovery extends beyond physiological repair to include restoration of function, psychological adaptation, and social reintegration, while immunity provides dynamic protection and regulation. Emerging evidence suggests that recovery trajectories shape immune competence and long-term resilience.

This review synthesizes evidence on bidirectional recovery-immunity interactions across infectious and non-communicable diseases (NCDs). We examine immune- linked mechanisms of inflammation resolution, tissue repair/regeneration, and functional restoration, and discuss how recovery states feedback to immune competence. Illustrative contexts include viral, bacterial, parasitic, and fungal infections, as well as cancer, autoimmune, metabolic, cardiovascular, and neurodegenerative disorders.

Shared pathways connecting recovery and immunity include cytokine signaling, macrophage polarization, and regenerative programs. Recovery outcomes are further modified by host and contextual factors such as genetics, aging, nutrition, comorbidities, and psychosocial stress. Clinical and translational approaches, such as immunotherapy, rehabilitation, vaccination, and precision medicine, offer practical ways to support recovery, but they must be applied with careful attention to the immune trade-offs they may introduce. Advances in biomarkers, multi- omics profiling, and AI-enabled modeling offer promising tools to quantify recovery phenotypes and predict immune resilience.

Positioning recovery as an active immunological state enables more coherent frameworks for understanding disease trajectories and guiding interventions. Integrating recovery biology with immune regulation may enhance patient outcomes and support durable, resilient health across diverse disease settings.

Obesity, diabetes, and hypertension are major global health burdens influenced not only by lifestyle factors but also by genetic predisposition, sleep quality, chrononutrition, and circadian rhythms. This review examined how these factors interact in metabolic and cardiovascular diseases, with emphasis on sex-specific differences. A narrative review was conducted using PubMed, Scopus, and Web of Science databases for studies published between 2006 and 2026. A total of 112 studies were synthesized, including randomized trials, observational studies, systematic reviews, meta-analyses, Mendelian randomization, and mechanistic investigations. Evidence indicates that genetic susceptibility and circadian disruption contribute significantly to obesity, diabetes, and hypertension. Sleep deprivation, obstructive sleep apnea, and circadian misalignment were consistently associated with insulin resistance, appetite dysregulation, elevated blood pressure, and increased cardiometabolic risk, particularly among shift workers. Hormonal and metabolic pathways involving leptin, ghrelin, cortisol, and melatonin appear to mediate these effects. Important sex differences were observed, with women showing greater vulnerability to sleep-related appetite disturbances and men presenting a higher prevalence of visceral adiposity, sleep apnea, and hypertension. Chrononutrition strategies, including time-restricted eating and Mediterranean dietary patterns, showed beneficial effects on sleep quality, glycemic control, inflammation, and metabolic health. Emerging evidence also suggests bidirectional interactions between gut microbiota rhythmicity and circadian regulation. Genetic predisposition, sleep disturbances, and circadian disruption interact to influence metabolic and cardiovascular disease risk. Integrative approaches combining chrononutrition, sleep hygiene, circadian alignment, and personalized nutritional strategies may improve the prevention and management of cardiometabolic diseases.

To characterize the topography of hyperreflective spots (HRSs) and hard exudates (HEs) and to analyze their association with localized retinal sensitivity in diabetic retinal disease (DRD).

In this prospective cross-sectional study, diabetic patients (type I/II) underwent increased axial resolution optical coherence tomography (OCT) and mesopic microperimetry. HRSs (<30 µm, without back shadowing) and HEs (>30 µm, with back shadowing) were annotated in OCT scans and spatially matched to microperimetry test points across Early Treatment Diabetic Retinopathy Study (ETDRS) subfields. Eyes with confounding OCT biomarkers (disorganization of the retinal inner layers, ellipsoid zone/external limiting membrane disruption, vitreomacular traction) were excluded. Linear mixed-effects models were used to evaluate the associations between lesion types and localized retinal sensitivity.

Fifty-one eyes of 51 patients were included (mean age, 55.9 ± 14.8 years; diabetic retinopathy severity scale, 3.3 ± 1.6; hemoglobin A1c, 7.6% ± 2.0%). HRSs (n = 2308) were present in all study eyes, while HEs (n = 1222) were present in 21 eyes. Normalized to ETDRS subfield area, both HRSs (229.2 /mm2) and HEs (82.8 /mm2) showed the highest densities in the central subfield. Higher HRS load was independently associated with reduced retinal sensitivity (β = -0.06, P = 0.011), whereas no significant association was observed for HEs (P = 0.461); this finding should be interpreted with caution given the limited number of eyes with HEs.

HRSs and HEs demonstrate distinct spatial distributions and functional associations in DRD, with HRSs independently linked to localized sensitivity loss.

HRSs may serve as an accessible biomarker of early neuroretinal impairment and could improve patient stratification and treatment evaluation in clinical trials.