Disease outbreaks are increasing in frequency and complexity, disproportionately affecting children in humanitarian settings. Large numbers of zero-dose children live in conflict-affected contexts, heightening vulnerability to vaccine-preventable and emerging viral diseases. Effective pediatric vaccination and pandemic preparedness require integrated, context-adapted strategies encompassing community engagement, infodemic management, resilient delivery systems, service integration, and reliable surveillance. Innovations such as mobile teams, novel financing, and improved data coordination offer promise but require stronger evidence. Lessons from coronavirus disease of 2019 (COVID-19) underscore persistent inequities and the need for ethical, data-driven, and One Health-informed approaches to protect children's right to health and strengthen global health security.

Obstructive sleep apnea (OSA) has a broad and clinically important effect on cognition, most often impairing attention, executive function, memory, processing speed, and visuospatial ability, while language and immediate recall are relatively preserved. A substantial proportion of adults referred to sleep clinics already meet criteria for mild cognitive impairment at initial evaluation, particularly in moderate-to-severe OSA. This cognitive burden reflects multiple interacting mechanisms. Intermittent hypoxia promotes oxidative stress, mitochondrial dysfunction, and hippocampal injury through recurrent ischemia-reperfusion cycles. Sleep fragmentation disrupts slow-wave and REM sleep, impairing memory consolidation and glymphatic clearance. Neuroinflammation, endothelial dysfunction, and structural brain changes, including hippocampal atrophy, white matter hyperintensities, and reduced frontoparietal connectivity, may further compound injury over time. REM-related hypoxemia appears especially important for cerebrovascular injury and memory impairment. Measures such as hypoxic burden and oxygen desaturation indices may better capture brain risk than the apnea-hypopnea index alone. Older age, APOE ε4 genotype, obesity, hypertension, diabetes, depression, and prior cerebrovascular disease increase vulnerability and should guide screening and treatment priorities. Cognitive assessment in OSA should be domain-sensitive rather than based only on a single global cutoff. Effective therapy, especially positive airway pressure with adequate REM-period coverage, can improve alertness and selected cognitive outcomes, although attention may remain impaired despite improved oxygenation. In children, OSA can disrupt memory consolidation and working memory, and adenotonsillectomy often leads to only partial cognitive recovery. Cognition should therefore be considered a primary treatment outcome in both clinical care and future research.

The avian respiratory tract is a major portal of entry for respiratory pathogens, and the dynamic interactions between the mucosal immune system and resident microbial communities constitute an important component of local defense. Although these interactions are increasingly recognized, substantial knowledge gaps remain regarding the molecular mediators of the gut-lung axis, the interplay between the microbiota and tissue-resident memory T (TRM) cells, and the mechanisms that maintain local homeostasis. This review synthesizes multidisciplinary advances in avian respiratory immunology and microbiome research. We distinguish direct evidence obtained in avian species from mechanisms inferred from mammalian studies and identify the latter as hypotheses requiring validation in birds. We discuss a putative regulatory axis linking dominant respiratory and intestinal microbial taxa, microbial metabolites such as short-chain fatty acids (SCFAs) and pyrroloquinoline quinone (PQQ), and mucosal immune effectors including secretory immunoglobulin A (sIgA) and interferon lambda 3 (IFN-λ3). We further examine the proposed pathways through which dysbiosis may contribute to the progression from local barrier disruption to systemic disease. Considering avian anatomical and immunological characteristics, including nasal-associated lymphoid tissue (NALT) and the absence of conventional draining lymph nodes in chickens and turkeys, we propose a host-microbiota-environment framework for organizing the determinants of respiratory homeostasis and disease susceptibility. Furthermore, we review the application of high-throughput sequencing and gene-editing technologies to target discovery and discuss the potential translation of microecological interventions into poultry production. Collectively, this review provides a conceptual basis for investigating avian respiratory microecology and supports the evaluation of microbiota-directed approaches as potential complements to vaccination, biosecurity, environmental management, and antimicrobial stewardship.

To describe stress, coping behaviours, anxiety, psychological support and benzodiazepine use among French final-year medical students sitting a high-stakes national ranking examination and to explore how these patterns relate to exam ranking when interpreted through transactional stress and coping and 'coping reservoir' models.

Cross-sectional questionnaire survey.

Single university medical faculty in France; final-year students sitting the national Épreuves Dématérialisées Nationales (EDN) and 'national Objective Structured Clinical Examination (nOSCE)' clinical examination.

All 387 sixth-year students present for the 2025 nOSCE were invited; 192 (50%) completed the questionnaire (69% women; median age 25 years).

registered for the national exam and attending nOSCE; exclusion: non-attendance or incomplete questionnaire.

None.

Primary outcomes were self-rated stress for EDN and nOSCE and State-Trait Anxiety Inventory-Y (STAI-Y) state and trait anxiety scores. Secondary outcomes included stress management behaviours, psychological/psychiatric follow-up, benzodiazepine and other psychotropic use and final national ranking.

92% of respondents reported that stress impacted their daily life, particularly attention (83%), sleep (79%) and learning capacity (64%). Overall, 32% had consulted a psychologist/psychiatrist and 15% used benzodiazepines. Most reported regular sport (86%; ≥2 sports 69%) and breathing exercises (61%). Median nOSCE stress was 8/10; median STAI-Y state and trait scores were 45 and 46. Comparing very low versus high/very high trait-anxiety subgroups, ranking did not differ significantly, but low-anxiety students reported more sport (p=0.04), less benzodiazepine use (1/24 vs 10/37; p=0.003) and far less psychological follow-up (1/24 vs 19/46; p<0.0001). Self-reported coping strategies were not associated with better ranking.

Final-year medical students preparing for a high-stakes national ranking examination report pervasive stress, substantial functional impairment and frequent professional and pharmacological coping, with only limited linkage between anxiety and performance. Within transactional and coping reservoir frameworks, these results highlight the need for reflection on structural assessment practices and for longitudinal institutional strategies to protect learner well-being.

Intravenous thrombolysis is the standard early treatment for acute ischaemic stroke (AIS), yet a substantial proportion of patients, particularly those with mild disabling deficits, do not achieve favourable functional recovery. Tenecteplase (TNK), a fibrin-specific thrombolytic agent administered as a single bolus, and butylphthalide (NBP), a multi-mechanism neuroprotective agent, have each shown benefit in AIS. However, whether their combination confers additional benefit in mild disabling AIS remains unknown. This trial aims to determine whether adding NBP to TNK improves functional outcomes in patients with mild disabling ischaemic stroke treated within 4.5 hours of symptom onset.

BENEFIT-2 is a prospective, multicentre, randomised, double-blind, active-controlled trial. Eligible patients will be randomised 1:1 to receive either TNK plus NBP (combination group) or TNK plus placebo (control group) via block randomisation. The intervention comprises intravenous NBP 25 mg/100 mL two times per day for 7 days, followed by oral NBP 0.2 g three times per day up to day 14, with matching placebos for the control group. Key eligibility criteria include age 18-80 years, symptom onset within 4.5 hours, baseline National Institutes of Health Stroke Scale (NIHSS) score 2-5 with persistent unilateral weakness or speech impairment, and prestroke modified Rankin Scale (mRS) score 0 or 1. The primary outcome is the proportion of patients achieving mRS 0-1 at 90 days (allowable window ±7 days). Secondary endpoints include change in NIHSS, stroke recurrence, major vascular events, quality of life measured by EQ-5D and penumbral salvage on imaging. Safety endpoints comprise symptomatic intracranial haemorrhage, vascular death, all-cause mortality and other adverse events within 90 days. The primary analysis will follow the intention-to-treat principle.

Ethics approval has been obtained from the Independent Ethics Committee of Xiangya Hospital (No. 2026020399), Central South University. Results will be published in peer-reviewed journals and presented at academic conferences.

NCT07369999.

Critical congenital heart disease (CHD) is associated with neurodevelopmental disorders, recognised as the most common long-term morbidity in affected children. In critical CHD, that is, CHD requiring cardiac surgery within the first 3 months of life, 30%-50% of children have lower developmental scores. Therefore, early identification of at-risk infants is crucial, yet there is no scientifically evaluated care programme in France. This study aims to evaluate early neurodevelopmental status in infants with prenatally diagnosed critical CHD and to determine how intrinsic susceptibility, prenatal and postnatal factors are functionally associated with developmental delay in this population.

Caractérisation et Accompagnement des Troubles du neurodéveloppement Associés aux MAlfoRmations cArdiaques coNgénitales (CATAMARAN) is a prospective, multicentre cohort study including 150 fetuses with critical CHD and their parents across eight French tertiary CHD centres. The primary objective will be to estimate the proportion of developmental delay at 6 months using the Bayley Scales of Infant and Toddler Development. Secondary objectives will include exploring potential prenatal, perinatal, perioperative determinants of developmental delay. Data collection will span pregnancy to 6 months of age including clinical assessments, maternal questionnaires (stress and nutrition), multimodal imaging and extensive biobanking (placenta, cord and peripheral blood, stool samples). To explore potential genetic and other multi-omic factors involved in the occurrence of a developmental delay, a case-control analysis will be conducted within the cohort.

Clinical and biological data will be collected through a secure system, with anonymised samples analysed in specialised facilities under collaborative agreements. Data confidentiality, traceability and long-term storage are ensured through controlled access and audit trails. Study results will be published and shared with families and the public through the patient association Petit Coeur de Beurre. This study received approval from a French ethics committee in November 2024 (no. 2024-A00425-42).

NCT06690151.

To explore how participants in the UK's Targeted Lung Health Check (TLHC) programme understand and respond to incidental findings of coronary artery calcification (CAC) and to identify patient preferences for communication that might enhance engagement with cardiovascular prevention such as lipid-lowering therapy (LLT).

Qualitative study using semi-structured interviews and thematic analysis.

One general practice participating in the National Health Service TLHC programme in North-East England, an area of high social deprivation.

Ten adults aged 59-71 years with CAC detected on TLHC CT scans and a calculated QRISK >10%.

To explore patient understanding of incidental CAC findings and how this influences engagement with cardiovascular prevention.

To identify patient preferences for receiving and discussing CAC results, including preferred communication methods, terminology and the role of the clinician in shaping preventive treatment decisions.

Patients initially reported understanding their findings but deeper exploration revealed misconceptions about personal cardiovascular disease risk. A lack of trust in doctors and reliance on non-clinical information sources (social media, family and friends) were barriers to LLT uptake. Trust in the medical professional giving the advice also shaped acceptance of LLT.

Enhancing patient education on CAC findings, fostering doctor-patient trust and tailoring communication strategies may improve LLT uptake. Personalised follow-up and clearer risk explanations could reduce hesitancy and improve engagement with preventive care.

Literature guiding the use of long-acting injectable antipsychotics (LAIAs) versus oral antipsychotics (OAs) in people with intellectual disability (PWID) remains scarce.

Examining the associations of LAIAs vs OAs with healthcare utilisation among PWID.

This self-controlled case series study used electronic health records from Hong Kong. We included adults with intellectual disability prescribed both LAIAs and OAs at different periods in 2004-2023. We compared within-individual LAIA and OA periods, adjusting for age, calendar year, season, inpatient stay and concomitant psychotropic use, using conditional Poisson regression to estimate incidence rate ratios (IRRs) for all-cause emergency department (ED) visits; all-cause hospitalisations; hospitalisations for psychiatric disorders, schizophrenia/bipolar disorder, behaviour-related problems, somatic disorders and cardiovascular diseases (CVDs) and diagnosis records of extrapyramidal symptoms (EPS); falls and fractures. Subgroup analyses were conducted by diagnosis of schizophrenia or bipolar disorder.

We identified 1675 PWID who had been prescribed both OAs and LAIAs at different periods during the study period. LAIA use was associated with lower risks of incident all-cause ED visits (adjusted IRR: 0.71, 95% CI 0.51 to 0.98), all-cause hospitalisations (0.91, 0.85-0.98); hospitalisations for psychiatric disorders (0.90, 0.81-0.99); for schizophrenia/bipolar disorder (0.86, 0.75-0.99) and EPS (0.34, 0.23-0.51), compared with OAs. In PWID with schizophrenia/bipolar disorder, LAIAs were associated with lower risks of all-cause hospitalisations, hospitalisations for psychiatric disorders, schizophrenia/bipolar disorder, behaviour-related problems and somatic disorders, and EPS, but a higher risk of hospitalisations for CVDs (with hypertensive disease being the most common), compared with OAs. In contrast, among PWID without such diagnoses, LAIA use was associated with higher risks of all-cause hospitalisations, hospitalisations for somatic disorders; a lower risk of incident all-cause ED visits and hospitalisations for CVDs, but no significant difference in hospitalisations for behaviour-related problems, compared with OAs.

These findings are consistent with potential benefit of LAIAs among PWID with schizophrenia or bipolar disorder, while raising concern about off-label use in those without these diagnoses.

LAIAs may be considered in PWID with schizophrenia or bipolar disorder; off-label use in those without these diagnoses should be approached cautiously, and deprescribing may be considered where appropriate if these results are replicated.

The United States heart allocation system prioritizes transplant candidates using therapy-based categorical urgency tiers that measure treatment decisions rather than biological risk. This miscalibration is associated with observable downstream issues: status exception rates exceeding 40% of adult listings, systematic escalation of temporary mechanical circulatory support in hemodynamically stable candidates, missed opportunities for myocardial recovery, and structural inequities in access. This review argues that meaningful reform requires a sequenced agenda: developing validated continuous urgency scores grounded in objective biological variables for both adult and pediatric candidates, reforming the exception process through standardized prospectively applied criteria, and building a new allocation policy using accurate inputs.

Sex differences after cardiac transplantation are well described; whether similar sex differences exist after simultaneous heart-kidney transplantation (SHKT) remains unknown.

Adults (≥18 years) undergoing first-time SHKT between January 1, 1999, and September 30, 2024, were identified in the United Network for Organ Sharing registry. Rates of SHKT by sex were examined across allocation-policy eras. Post-transplant survival was compared by sex using multivariable Cox regression. Among 3068 recipients (19.7% women), women were more likely to have nonischemic cardiomyopathy and a higher pulmonary vascular resistance and less likely to have durable left ventricular assist device support at the time of transplant. Unadjusted survival did not differ by sex at 1 or 5 years (log-rank P = .236 and P = .593, respectively). After multivariable adjustment, as sex violated proportional hazards, a piecewise constant Cox model showed a numerically higher perioperative than postperioperative sex hazard, neither significant in the full cohort (adjusted hazard ratio [aHR] 1.38 [P = .061] and aHR 1.19 [P = .473]). The perioperative disparity was significant in the prespecified 90-day landmark analysis (days 0-90, aHR 1.58, 95% confidence interval 1.12-2.22 [P = .009]; days 91-365, aHR 0.91 [P = .729]) and in the contemporary allocation era (aHR 1.78, 95% confidence interval 1.19-2.65, P = .005). No sex differences were observed at 5 years and no significant sex interactions were identified across 10 prespecified effect modifiers (all P > .005).

Women demonstrated an early post-transplant mortality signal concentrated within the first 90 days after SHKT, without excess long-term risk. These findings underscore the need for earlier referral and perioperative optimization of high-risk women to improve equity in SHKT outcomes.