Primary hypothermia arises from prolonged exposure to low environmental temperatures without underlying pathology, whereas secondary hypothermia is triggered by impaired thermoregulation due to factors such as disease, trauma, or substance use. This study aimed to investigate core temperature changes in rats exposed to specific water temperatures over time, with a focus on differentiating primary and secondary hypothermia induced by alcohol and benzodiazepines.Survival analysis was performed using Kaplan–Meier survival curves to compare the time to event (in minutes) among three experimental groups: Control, ethanol, and Diazepam. Core temperatures were recorded at five key points: baseline (normal temperature), post-ketamine anesthesia, during immersion, at hypothermia onset, and at the time of death. Survival times were also recorded and statistically analyzed. Median survival times were highest in the control group (35 minutes), followed by Diazepam (29 minutes) and ethanol (28 minutes). Pairwise comparisons using the log-rank test, adjusted for multiple comparisons via the Benjamini-Hochberg method, revealed a statistically significant difference between the control and diazepam groups (p = 0.018), with the control group demonstrating longer survival time. A significant interaction between Diazepam and time was observed (β = -0.23, 95% CI: -0.35 to -0.12, p < 0.001), indicating that the rate of temperature decline over time was significantly greater in the Diazepam group compared to the control group. Our results indicate that Diazepam accelerates the decrease in body temperature over time, which may contribute to its observed effect on survival, and that Diazepam administration is associated with a significant reduction in survival time compared with untreated controls. Ethanol did not significantly alter the measured thermoregulatory or survival outcomes in this pilot study. Any potential forensic relevance of ethanol-induced hypothermia remains speculative and requires further investigation in larger, adequately powered studies. Our results could have potential forensic implications in differentiating between primary and drug-induced as secondary hypothermia in medico-legal investigations.

Climate change significantly affects human physiology and contributes to increased morbidity and mortality, with heat stress representing one of the most severe consequences of thermal imbalance. The aim of this study was to analyze morphological changes to leukocytes on the peripheral blood smears of Wistar rats exposed to hyperthermia using the geometric morphometrics method. A total of forty Wistar albino rats were divided into three experimental groups according to water temperature exposure (37 °C, 41 °C, and 44 °C). Peripheral blood smears were prepared, stained, and digitally recorded using Motic Images Plus 2.0 software, after which selected images were analyzed using geometric morphometric programs (tpsDig, tpsUtil, and MorphoJ) to evaluate leukocyte shape variations. Comparative analysis demonstrated statistically significant morphological changes in polymorphonuclear cell shapes between the control group (37 °C) and rats exposed to 41 °C (p = 0.009). Significant differences were also identified in mononuclear cell morphology between the antemortem and postmortem groups (p = 0.00307). The findings indicate that exposure to elevated temperatures induces measurable alterations in white blood cell morphology, confirming that hyperthermia produces significant structural changes in polymorphonuclear cells and mononuclear cells detectable through geometric morphometric analysis.

Background/Objectives: Accurate post-mortem interval (PMI) estimation becomes increasingly difficult when bodies decompose under extreme heat. Hyperthermal Mediterranean environments accelerate soft-tissue degradation, induce early mummification, and distort classical thanatological indicators, often resulting in substantial PMI overestimation. This study analyzes three forensic cases affected by climate-driven decomposition anomalies and presents a climate-adaptive, AI-assisted diagnostic framework applied uniformly across all cases to improve PMI interpretation. Methods: A retrospective case series analysis was conducted on three individuals recovered during summer heatwaves. Crime scene investigation, post-mortem computed tomography (PMCT), autopsy, and genetic identification were integrated with 5–15-year meteorological datasets. Classical PMI estimations were compared with circumstantial data. A multimodal AI model, incorporating environmental features, decomposition morphology, and microenvironmental modifiers, was operationalized for each case using a hybrid Random Forest–LSTM architecture. Engineered indices included Accumulated Degree Days (ADD), a Decomposition Index, and climate-stress metrics (Thermal Load Index, Desiccation Pressure Factor, Microenvironmental Distortion Coefficient). Quantile regression provided calibrated prediction intervals. Results: Morphological assessments overestimated PMI in every case, suggesting intervals of 1–6 months despite true PMIs of approximately 20 days (Cases 1–2) or 36–48 h (Case 3). The AI model yielded conceptual outputs more consistent with verified PMIs, ~21 days (Case 1), ~23 days (Case 2), and ~42 h (Case 3), each accompanied by 50% and 90% prediction intervals. Explainability analyses identified thermal load, desiccation pressure, and microenvironmental distortion, particularly insulation in Case 3, as dominant drivers. Conclusions: Extreme heat fundamentally alters decomposition trajectories, rendering classical PMI methods unreliable. Applying a climate-aware, AI-assisted diagnostic framework across all three cases improved interpretability, providing uncertainty-aware estimates aligned with true PMIs. The AI framework is presented as a conceptual, non-trained, proof-of-concept system, and reported outputs represent operational demonstrations rather than validated predictions, offering a promising foundation for next-generation PMI diagnostics in hyperthermal forensic settings.

Abusive head trauma (AHT), is considered a leading cause of fatalities resulting from physical abuse in infants under 2 years of age, with a peak incidence between 1 and 2 months after birth. The incidence of AHT ranges from 14 to approximately 40 cases per 100,000 children in industrialized countries with a mortality rate ranging from 10 to 20%. The absence of internationally recognized best practices or guidelines especially in the field of forensic medicine has resulted in methodological variability in the management of these cases across different settings. In response to this gap, a comparative working group involving experts from Italy and the Balkan countries was established, leading to the creation of a shared discussion platform. The aim of this collaborative effort was to identify strengths and critical issues in the forensic handling of abusive head trauma, ultimately with the goal of developing a shared workflow chart for the management of these complex cases within the network.

Immigrant populations frequently encounter barriers when accessing healthcare services, potentially affecting patient safety, healthcare utilization, and clinical outcomes. Understanding these barriers is essential for improving equitable and patient-centered care. A systematic review of qualitative and quantitative studies was conducted in accordance with PRISMA 2020 guidelines. PubMed/MedLINE, Embase, Cochrane Library, PsycINFO, EconLit, Web of Science (WoS), and CINAHL were searched from January 2005 to August 2023. Inductive thematic analysis was used to synthesize findings across studies. The review was not prospectively registered, included only English-language studies, and relied predominantly on qualitative evidence. Heterogeneity across study designs and healthcare settings may limit generalizability. The authors received no external funding for this study. Three interconnected themes consistently emerged: limited transcultural competence, language barriers, and discrimination in healthcare. Inadequate cultural competence was associated with communication difficulties and reduced care effectiveness. Language barriers contributed to miscommunication, delayed care, and increased healthcare utilization. Experiences of discrimination were linked to reduced trust in healthcare systems and poorer patient engagement. These factors negatively influenced patient safety, satisfaction, and clinical outcomes. Immigrant patients face persistent and interrelated barriers to healthcare access. Strengthening culturally responsive care, improving access to professional interpreter services, and addressing discriminatory practices are essential to improving patient safety, satisfaction, and clinical outcomes. Future research should evaluate targeted interventions aimed at improving communication, cultural competence, and healthcare equity.

Background/Objectives: Forensic DNA phenotyping (FDP) enables the prediction of externally visible characteristics (EVCs) such as eye, hair, and skin color, ancestry, and age from biological traces. However, low template DNA (LT-DNA), often derived from degraded or trace samples, poses significant challenges due to allelic dropout, contamination, and incomplete profiles. This review evaluates recent advances in FDP from LT-DNA, focusing on the integration of machine learning (ML) models to improve predictive accuracy and operational readiness, while addressing ethical and population-related considerations. Methods: A comprehensive literature review was conducted on FDP and ML applications in forensic genomics. Key areas examined include SNP-based trait modeling, genotype imputation, epigenetic age estimation, and probabilistic inference. Comparative performance of ML algorithms (Random Forests, Support Vector Machines, Gradient Boosting, and deep learning) was assessed using datasets such as the 1000 Genomes Project, UK Biobank, and forensic casework samples. Ethical frameworks and validation standards were also analyzed. Results: ML approaches significantly enhance phenotype prediction from LT-DNA, achieving AUC > 0.9 for eye color and improving SNP recovery by up to 15% through imputation. Tools like HIrisPlex-S and VISAGE panels remain robust for eye and hair color, with moderate accuracy for skin tone and emerging capabilities for age and facial morphology. Limitations persist in admixed populations and traits with polygenic complexity. Interpretability and bias mitigation remain critical for forensic admissibility. Conclusions: L integration strengthens FDP from LT-DNA, offering valuable investigative leads in challenging scenarios. Future directions include multi-omics integration, portable sequencing platforms, inclusive reference datasets, and explainable AI to ensure accuracy, transparency, and ethical compliance in forensic applications.

BACKGROUND Lower respiratory infections (LRIs) remain the world's leading infectious cause of death. This analysis from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 provides global, regional, and national estimates of LRI incidence, mortality, and disability-adjusted life-years (DALYs), with attribution to 26 pathogens, including 11 newly modelled pathogens, across 204 countries and territories from 1990 to 2023. With new data and revised modelling techniques, these estimates serve as an update and expansion to GBD 2021. Through these estimates, we also aimed to assess progress towards the 2025 Global Action Plan for the Prevention and Control of Pneumonia and Diarrhoea (GAPPD) target for pneumonia mortality in children younger than 5 years. METHODS Mortality from LRIs, defined as physician-diagnosed pneumonia or bronchiolitis, was estimated using the Cause of Death Ensemble model with data from vital registration, verbal autopsy, surveillance, and minimally invasive tissue sampling. The Bayesian meta-regression tool DisMod-MR 2.1 was used to model overall morbidity due to LRIs. DALYs were calculated as the sum of years of life lost (YLLs) and years lived with disability (YLDs) for all locations, years, age groups, and sexes. We modelled pathogen-specific case-fatality ratios (CFRs) for each age group and location using splined binomial regression to create internally consistent estimates of incidence and mortality proportions attributable to viral, fungal, parasitic, and bacterial pathogens. Progress was assessed towards the GAPPD target of less than three deaths from pneumonia per 1000 livebirths, which is roughly equivalent to a mortality rate of less than 60 deaths per 100 000 children younger than 5 years. FINDINGS In 2023, LRIs were responsible for 2·50 million (95% uncertainty interval [UI] 2·24-2·81) deaths and 98·7 million (87·7-112) DALYs, with children younger than 5 years and adults aged 70 years and older carrying the highest burden. LRI mortality in children younger than 5 years fell by 33·4% (10·4-47·4) since 2010, with a global mortality rate of 94·8 (75·6-116·4) per 100 000 person-years in 2023. Among adults aged 70 years and older, the burden remained substantial with only marginal declines since 2010. A mortality rate of less than 60 deaths per 100 000 for children younger than 5 years was met by 129 of the 204 modelled countries in 2023. At a super-regional level, sub-Saharan Africa had an aggregate mortality rate in children younger than 5 years (hereafter referred to as under-5 mortality rate) furthest from the GAPPD target. Streptococcus pneumoniae continued to account for the largest number of LRI deaths globally (634 000 [95% UI 565 000-721 000] deaths or 25·3% [24·5-26·1] of all LRI deaths), followed by Staphylococcus aureus (271 000 [243 000-298 000] deaths or 10·9% [10·3-11·3]), and Klebsiella pneumoniae (228 000 [204 000-261 000] deaths or 9·1% [8·8-9·5]). Among pathogens newly modelled in this study, non-tuberculous mycobacteria (responsible for 177 000 [95% UI 155 000-201 000] deaths) and Aspergillus spp (responsible for 67 800 [59 900-75 900] deaths) emerged as important contributors. Altogether, the 11 newly modelled pathogens accounted for approximately 22% of LRI deaths. INTERPRETATION This comprehensive analysis underscores both the gains achieved through vaccination and the challenges that remain in controlling the LRI burden globally. Furthermore, it demonstrates persistent disparities in disease burden, with the highest mortality rates concentrated in countries in sub-Saharan Africa. Globally, as well as in these high-burden locations, the under-5 LRI mortality rate remains well above the GAPPD target. Progress towards this target requires equitable access to vaccines and preventive therapies-including newer interventions such as respiratory syncytial virus monoclonal antibodies-and health systems capable of early diagnosis and treatment. Expanding surveillance of emerging pathogens, strengthening adult immunisation programmes, and combating vaccine hesitancy are also crucial. As the global population ages, the dual challenge of sustaining gains in child survival while addressing the rising vulnerability in older adults will shape future pneumonia control strategies. FUNDING Gates Foundation.

Summary Background The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 estimates health loss from migraine, tension-type headache, and medication-overuse headache. This study presents updated results on headache-attributed burden from 1990 to 2023, along with clinical and public health implications. Methods Data on the prevalence, incidence, or remission of migraine, tension-type headache, and medication-overuse headache were extracted from published population-based studies. We used hierarchical Bayesian meta-regression modelling to estimate global, regional, and country-level prevalence of headache disorders. For the first time in GBD 2023, age-specific and sex-specific estimates of time in symptomatic state were applied by meta-analysing individual participant data from 41 653 individuals from the general populations of 18 countries from all parts of the world. Disability weights were applied to calculate years lived with disability (YLDs). Since medication-overuse headache is a sequela of a mistreated primary headache (due to medication overuse), its burden was reattributed to migraine or tension-type headache, informed by a meta-analysis of three longitudinal studies. Findings In 2023, 2·9 billion individuals (95% uncertainty interval 2·6–3·1) were affected by headache disorders, with a global age-standardised prevalence of 34·6% (31·6–37·5) and a YLD rate of 541·9 (373·4–739·9) per 100 000 population, with 487·5 (323·0–678·8) per 100 000 population attributed to migraine. The prevalence rates of these headache disorders have remained stable over the past three decades. YLD rates due to headache disorders were more than twice as high in females (739·9 [511·2–1011·5] per 100 000) as in males (346·1 [240·4–481·8] per 100 000). Medication-overuse headache contributed 58·9% of the YLD estimates for tension-type headache in males and 56·1% in females, as well as 22·6% of the YLD estimates for migraines in males and 14·1% in females. Interpretation Headache disorders, in particular migraine, continue to be a major global health challenge, emphasising the need for effective management and prevention strategies. Much headache-attributed burden could be averted or eliminated by avoiding overuse of medication (including over-the-counter medication), underscoring the importance of public education. Funding Gates Foundation.

Background: Many deaths during heat waves stem not only from body overheating but also from heat stress, which can intensify pre-existing medical conditions, leading to fatal outcomes. Aim: This study aimed to investigate whether the intensity of pathological changes in the heart muscle and lung tissue of albino rats exposed to hyperthermia correlates with different water temperatures (WT) and to determine whether the histological structure of the myocardium and lungs varies. Methods: A sample of 21 albino rats was exposed to water temperatures of 37°C, 41°C, and 44°C. Temperature readings were recorded before immersion, immediately after immersion, at the point of reaching hyperthermia, at 20 minutes, and at the time of death. Tissue samples were collected from the dissected rats, fixed in 10% buffered formalin at room temperature, embedded in paraffin, sectioned into 4–5 μm slices, and stained using the hematoxylin-eosin method. Results: The severity of myocardial histopathological alterations increased with both higher temperatures and longer exposure durations WT. However, the progression of morphological alterations in cardiomyocytes was not markedly significant, likely due to the brief exposure time, which limited the visualization of subcellular alterations in Hematoxylin and Eosin staining-stained tissue. All lung samples from the seven rats exposed to the highest temperatures displayed bronchiolitis and acute bronchitis, along with early bronchopneumonia. Conclusion: While some organs exhibit greater tolerance to heat stroke than other organs, most organs show similar alterations characterized by capillary dilation, vascular pathway disruption, and extravasation. The extent of pathological changes in myocardial and lung tissue intensified with higher temperatures and longer exposure durations to elevated WT. However, the progression of morphological alterations in cardiomyocytes did not demonstrate marked significance, likely because of the brief exposure period. This short duration may limit the detection of subcellular changes when using hematoxylin-eosin staining.