Future climate projections suggest an increase in heat-related mortality and a decrease in cold-related deaths under warming scenarios. Understanding the health impacts of extreme heat, and their implications for healthcare demand is essential for assessing the future burden of climate-related illnesses. In this study, we examined the relationship between extreme heat events and Emergency Department Visits (EDV) for heat-related illnesses (HRIs) across the United States from 2018 to 2025. Using data from the Centers for Disease Control and Prevention (CDC) Heat and Health Tracker and other relevant sources, we analyzed EDV rates standardized to 100,000 population. We aggregated daily into the 10 U.S. Health and Human Services (HHS) Regions. We used 0.5° × 0.5° gridded maximum daily temperature data (aggregated to HHS regions with proportional area weighting) and daily maximum heat index extracted from the CDC data portal (estimated using the US National Weather Service methodology and aggregated to HHS regions using total population weighting) to characterize seasonal patterns and regional variability. The association between peak heat events and EDV time series was explored using log-linear mixed-effects models, which accounted for seasonal trends, climate variables, and their regional variability. Random effects were used to capture regional heterogeneity in predictor-response relationships, accommodating variation in associations across regions. Model performance was evaluated using prediction error metrics and goodness-of-fit assessments. Maximum temperature and heat index were both significant predictors, with the heat index offering a slightly better fit. Associations were largely contemporaneous, with peak correlations at lag zero, underscoring the need for real-time response. EDV increased several days before peak environmental conditions, consistent with early exposure effects. While temperature-EDV relationships varied regionally, heat index associations were more stable. This work underscores the urgent need for regionally adaptive public health strategies in the face of intensifying climate extremes and outlines future directions for research and policy to strengthen health systems' preparedness in a warming world.

This study aimed to explore the protective mechanism of silybin against heat stress-induced liver injury in Peking ducks as a result of oxidative stress, inflammation, and lipid metabolism. One hundred and ninety-five 1-day-old healthy male Peking ducks with similar body weights were randomly divided into a control group, a heat-stress group, and three intervention groups treated with 400, 800, and 1600 mg/kg silybin under heat-stress from 21 d to 35 d for two weeks. The function indices, oxidative stress, inflammatory factor levels, histopathological changes and non-targeted lipidomic profiling in liver as well as growth performance were evaluated. Results showed that silybin supplementation partially alleviated the heat-stress-induced decreases in average daily feed intake and body weight gain (p > 0.05). Silybin supplementation at 400 and 800 mg/kg significantly reduced the heat-stress-induced increases in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and γ-glutamyl transpeptidase (γ-GGT) (p < 0.05), whereas the effect of 1600 mg/kg silybin was not significant. Albumin (ALB) and globulin (GLB) levels were mainly improved in the 800 mg/kg group, and GLB was also increased in the 400 mg/kg group (p < 0.05). Silybin supplementation significantly improved hepatic antioxidant capacity, especially in the 400 and 800 mg/kg groups, as indicated by increased superoxide dismutase (SOD) activity and total antioxidant capacity (T-AOC), and decreased malondialdehyde (MDA) and reactive oxygen species (ROS) levels (p < 0.05). In addition, the 400 and 800 mg/kg groups showed more significant reductions in the pro-inflammatory factors IL-6 and TNF-α, while IL-10 was increased in silybin-supplemented groups (p < 0.05). Lipid metabolism disorders were improved through regulation of the sphingolipid and glycerophospholipid metabolism pathways, while it alleviated heat stress damage by reducing the expression of heat shock proteins. In conclusion, silybin holds promise as an effective feed additive to alleviate heat stress in poultry. This study provides a theoretical basis and practical approach for improving the health and productive performance of Peking ducks under heat-stress conditions.

Heat stress poses a major constraint to rabbit production by impairing reproductive performance, compromising embryo survival, and increasing oxidative stress. Spirulina, known for its rich content of proteins, antioxidants, and bioactive compounds, has been proposed as a natural dietary supplement to mitigate these detrimental effects. The present study aimed to prepare nano size spirulina to evaluate its impact on reproductive performance and embryo survival of New Zealand White rabbit does under heat stress conditions. Sixty healthy pluriparous does were allocated into four groups: control (G1), heat stress (G2), and two heat-stressed groups (G3 and G4) supplemented with spirulina nanoparticles at two different levels. Reproductive traits, hormonal profiles, oxidative stress markers, proinflammatory cytokines and histopathological changes were assessed. The results revealed that heat stress significantly reduced fertility rates, progesterone levels, and increased embryonic loss, accompanied by oxidative damage and inflammatory responses. Supplementation with spirulina nanoparticles improved the general health condition of mothers and alleviated the adverse effects of heat stress; elevated antioxidant capacity, number of oocytes, conception and implantation. However, spirulina nanoparticle supplementation also exerted immunomodulatory effects that were associated with inadequate development of the placental spiral arteries and increased early embryonic loss in the treated groups. These findings suggest that spirulina nanoparticles may offer protective benefits against heat stress in rabbits, but caution was advised regarding using nanoparticles for does kept for breeding.

Extreme heat is an escalating public health concern. Although prior studies have examined heat-health associations, their reliance on restricted diagnoses and diagnostic categories may miss or misclassify heat-related illness. Here, we conducted a heat-wide association study to evaluate acute-care diagnoses associated with extreme heat in Chicago, Illinois. Using 916,904 acute-care visits-including emergency department and urgent care encounters-among 372,140 adults across four health care systems from 2011 to 2023, we applied a two-stage analytic approach: quasi-Poisson regression to screen diagnosis codes associated with heat, followed by distributed lag nonlinear models in a time-stratified case-crossover design to characterize exposure-response and lag patterns. Stage 1 retained 44 diagnosis codes, and 33 clinically reportable diagnoses were retained after stage 2. We observed elevated cumulative odds over lags 0 to 3 for multiple diagnoses, including fluid-balance and renal disorders, dermatologic and pressure-related conditions, multiple sclerosis, a cannabinoid-related mental and behavioral disorder, varicose veins of the lower extremities, and multiple injuries and external causes. By analyzing the full diagnostic spectrum of acute-care services, this study improves the clinical characterization of heat-associated morbidity in acute-care settings.

Fever-range hyperthermia (38-41 °C) is a typical physiological response to infection, inflammation, and systemic stress. Although increased temperatures are known to affect blood rheology and erythrocyte activity, their comprehensive impact on red blood cell (RBC) structure, mechanics, and lifespan remains incompletely understood. This review summarizes current understanding of how moderate hyperthermia affects RBC membrane structure, internal behavior, mechanical properties, and clearance cues. Evidence shows that brief exposure to febrile temperatures primarily induces reversible biophysical modifications, including heightened membrane fluidity, increased membrane fluctuations, changes in hemoglobin-water interactions, and short-term improvements in deformability. These changes reflect adaptive adjustments within the membrane-cytosol-cytoskeleton system, potentially temporarily boosting microcirculatory flow. On the other hand, prolonged or repeated heat stress causes oxidative damage, hemoglobin auto-oxidation, accumulation of membrane-bound hemoglobin, band 3 clustering, cytoskeletal restructuring, calcium imbalance, and disruption of membrane lipid asymmetry. These effects weaken membrane stability and lead to vesiculation, shape changes, increased cell fragility, altered aggregation, enhanced adhesion, and activation of clearance mechanisms. A primary focus is the transition from reversible membrane softening to permanent structural damage over time. The research supports a model in which temperature affects RBC mechanics and related membrane, cytosolic, and signaling processes that influence RBC viability. We propose interpreting febrile hyperthermia as a dynamic factor that shifts RBCs from an adaptive phase to accelerated aging and removal during prolonged heat exposure. This perspective enhances our understanding of RBC behavior during fever and systemic inflammation and underscores the role of temperature in shaping erythrocyte function and lifespan.

Noise-induced hearing loss (NIHL) is a major public health problem caused by damage to cochlear hair cells, synapses, and spiral ganglion neurons (SGNs). Since effective treatments are lacking, we investigated cellular stress responses induced by moderate and loud noise in a mouse model of cochlear synaptopathy. RNA sequencing and spatial transcriptomics revealed that noise exposure elicited a robust but transient upregulation of endoplasmic reticulum chaperones and proteasome subunits in SGNs and their supporting cells. To target this response, we administered TRC051384, a small-molecule activator of the heat shock transcription factor Hsf1, prior to noise exposure. TRC051384 crossed the blood-labyrinth barrier and reached the cochlea, induced heat shock protein gene expression, and restored ubiquitin-proteasome function in SGNs. Notably, TRC051384 treatment enhanced auditory brainstem response threshold recovery, preserved Wave I amplitudes, and maintained ribbon synapse density. Together with the existing literature, these findings identify proteotoxic stress in spiral ganglion neurons as a contributor to noise-induced hearing loss and support pharmacological activation of HSF1 as a promising therapeutic strategy.

The Arabian Peninsula region, particularly the Gulf Cooperative Countries (GCC) experience extreme heat with a warming trend and frequent and intense heat waves. Summer maximum temperatures (June, July, and August 'JJA') routinely soar above 50 °C. In this study, we analyzed the heat index (HI) for every hour of the last 14 years (2012-2025) in Kuwait. Heat Index is the combined metric incorporating ambient air temperature and relative humidity (RH) - or the ''feels like'' temperature. Specifically, we used the US National Weather Service (NWS) HI and classified three risk-threshold systems: HI classified according to Kuwait Oil Company "KOC thresholds", HI classified according to Saudi Arabia Aramco "Aramco thresholds", and HI classified according to the NWS "NWS thresholds". We divided hours and days into four HI category ranges (Extreme Danger, Danger, Extreme Caution, and Caution). Results show a positive linear trend for the annual minimum, average, and maximum temperature and RH during the study period. The mean annual numbers of days of 'Maximum' HI levels in the 'Danger' category were (119.71 (32%), 96.78 (26.51%), 101.64 (27.84%)) for KOC, Aramco, and NWS thresholds, respectively. The total annual number of days of 'Maximum' HI levels exceeded the 'Extreme Danger' category for KOC (≥ 46 °C), Aramco (≥ 52 °C), and NWS (≥ 54 °C) by 282 days (77%), 29 (7.9%), and 5 days (1.36%), respectively. The year 2025 demonstrated the highest number of days on which daily maximum HI exceeded the 'Extreme Danger', particularly in August. A total of 17 h exceeded the NWS threshold (≥ 54 °C), and the hours ranged from as early as 9 am to 4 pm. Moreover, HI as high as 52 °C was observed, in some instances, as early as 7 am and as late as 7 pm and midnight. This study provides a basis for heat stress extremities in hot arid environments, especially in the era of climate change. Temporal variability in thermal stress is essential to understand for both public and occupational health.

Heat shock proteins (HSPs) are a family of conserved molecular chaperons present in both prokaryotic and eukaryotic species, playing a crucial role in maintaining cellular proteostasis and enhancing stress resilience. HSPs have a multitude of roles in regulating cell signaling transduction, antioxidant defenses, apoptosis, and protein folding, thereby contributing to overall cellular homeostasis. Insulin resistance is characterized by elevated oxidative stress, dysregulated pro-inflammatory signaling, and impaired cellular stress response, ultimately leading to deficient glucose uptake in skeletal muscle. Many studies have illustrated the benefits of exercise in improving insulin resistance and reducing the risk of metabolic disorders, such as type 2 diabetes. Habitual exercise and lifestyle modifications have been shown to activate heat shock response, enhancing HSP70 expression and promoting cellular adaptations that protect against metabolic dysfunction. However, the link between HSPs, particularly HSP70, and skeletal muscle insulin resistance remains complex and not fully elucidated. In this review, we discuss the mechanistic pathways by which HSP70 modulates insulin resistance, mitochondrial function, and inflammatory responses in skeletal muscle. Additionally, we discuss the protective effects of exercise-induced HSP70 expression and its potential as a therapeutic target for improving insulin sensitivity and metabolic health.

Climate change is increasing the frequency, intensity, and duration of heatwaves, making extreme heat a recurrent public health challenge with important nutritional implications. High ambient temperatures affect human health through thermoregulatory strain, sweating, dehydration, electrolyte imbalance, cardiovascular and renal stress, impaired cognitive and physical performance, and exacerbation of chronic diseases. Diet and hydration may therefore represent modifiable, although still underinvestigated, components of heat-health prevention. This narrative review synthesizes evidence on hydration, electrolyte balance, meal composition, dietary quality, vulnerable populations, Mediterranean dietary patterns, seasonality, environmental sustainability, and public health strategies for reducing heat-related health risks. Evidence from climate-health research, physiology, nutrition science, occupational and sports medicine, geriatrics, pediatrics, and public health guidance was integrated. Particular attention was given to distinguishing direct heat-health evidence from recommendations based on indirect evidence, physiological plausibility, or expert consensus. Regular water intake, water-rich foods, avoidance of alcohol, moderation of sugar-sweetened beverages, and individualized electrolyte replacement during prolonged or intense sweating are supported by physiological rationale and public health guidance, although direct heatwave-specific intervention studies remain limited. Dietary recommendations should prioritize smaller, digestible, nutrient-dense meals that preserve nutritional adequacy while reducing unnecessary digestive and metabolic burden. However, evidence on meal size, macronutrient composition, and heat-related outcomes remains largely indirect. Vulnerable groups, including older adults, children, pregnant women, individuals with chronic diseases, outdoor workers, athletes, and socioeconomically disadvantaged populations, require tailored strategies. The Mediterranean diet may provide a useful regional model because it emphasizes seasonal plant foods, fruits and vegetables with high water content, legumes, whole grains, olive oil, culinary simplicity, and environmental sustainability; however, its specific role in heat adaptation requires further study. Integrating nutrition and hydration into heat-health action plans may improve preparedness and support climate-resilient food systems. Future studies should evaluate hydration protocols, meal patterns, Mediterranean diet adherence, biomarkers of nutritional heat resilience, and nutrition-sensitive interventions in real-world heat exposure settings.

Extreme heat events are intensifying worldwide due to climate change, posing significant health risks and economic challenges. The urban heat island effect poses extra challenges to the inhabitants of cities, especially in the global South.

Heat shock factor 1 (HSF1) masters cellular proteostasis under stress by upregulating molecular chaperones that help refold or degrade misfolded proteins. HSF1 activation involves its monomer-to-oligomer transition and binding to its recognition sequence: the heat shock elements (HSEs) on its target gene promoters. HSF1 activity declines with age as well as in neurodegenerative disorders (NDs) such as Parkinson's disease, highlighting the need for therapeutic strategies to restore its function. Azadiradione (AZD), a limonoid isolated from Azadirachta indica seeds, directly activates HSF1 in cellular and preclinical ND models, unlike other small-molecule activators reported elsewhere. In this study, the molecular basis of AZD-mediated HSF1 activation was investigated using purified variants of HSF1, including those lacking its oligomerization and transactivation domains. Fluorescence polarization and dynamic light scattering assays revealed that AZD promotes the oligomerization of monomeric HSF1 to enhance its HSEs-binding affinity by engaging its DNA-binding domain (DBD). The oligomerization domain, which is required for stress-induced HSF1 activation, appears redundant in AZD-mediated activation. Furthermore, evidence suggests that AZD-induced conformational alterations in the HSEs-DNA facilitate its binding to the HSF1 monomer. Intriguingly, AZD was found to compromise the DNA-binding ability of pre-assembled trimeric/oligomeric HSF1. This finding also highlighted a potential anticancer effect of AZD, as cancer cells heavily depend on this HSF1 population for rapid proliferation and survival. Overall, these findings offer new insights into the functional regulation of HSF1 and suggest a framework for developing small-molecule HSF1 activators with therapeutic potential for protein conformational disorders.

Despite their well-known efficacy, forced-air warming during operations has its drawbacks, mainly high energy consumption and risk of hyperthermia. We therefore investigated two warming strategies in a prospective randomized study with the aim of reducing the incidence of hyperthermia without increasing the risk of intraoperative hypothermia. In the standard of care group temperature of the forced-air warmer was reduced to 32 °C when core temperature reached 37.3 °C. In the modified warming group this reduction was performed when core temperature reached 36.5 °C. The difference in the duration of normothermia between standard of care and the modified warming strategy was estimated to be 3.9% (90%-CI: 0.8% to 7.1%) and was within the predefined equivalence bounds of ± 20% (p < 0.001). In both treatment groups no intraoperative hyperthermia ocurred. Average energy consumption per hour was significantly higher in the standard-of-care group (0.51 kWh/h; 95%-CI: 0.47-0.56) compared with the modified warming strategy (0.40 kWh/h; 95%-CI: 0.35-0.46; p = 0.002). By strictly limiting the heat supply, intraoperative hyperthermia can be safely prevented during craniotomies. A lower threshold value of 36.5 °C allows for a meaningful reduction in energy consumption.