Whole genome transcriptomic reveals heat stroke molecular signatures in humans.

An evolutionary heat shock response (HSR) protects most living species, including humans, from heat-induced macromolecular damage. However, its role in the pathogenesis of heat stroke is unknown. We examined the whole genome transcriptome in peripheral blood mononuclear cells of a cohort of subjects exposed to the same high environmental heat conditions, who developed heat stroke (n = 19) versus those who did not (n = 19). Patients with heat stroke had a mean rectal temperature at admission of 41.7 ± 0.8°C, and eight were in deep coma (Glasgow Coma Score = 3). The transcriptome showed that genes involved in more than half of the entire chaperome were differentially expressed relative to heat stress control. These include the heat shock protein, cochaperone, and chaperonin genes, indicating a robust HSR. Differentially expressed genes also encoded proteins related to unfolded protein response, DNA repair, energy metabolism, oxidative stress, and immunity. The analysis predicted perturbations of the proteome network and energy production. Cooling therapy attenuated these alterations without complete restoration of homeostasis. We validated the significantly expressed genes by a real-time polymerase chain reaction. The findings reveal the molecular signature of heat stroke. They also suggested that a powerful HSR may not be sufficient to protect against heat injury. The overwhelming proteotoxicity and energy failure could play a pathogenic role. KEY POINTS: Most living species, including humans, have inherent heat stress response (HSR) that shields them against heat-induced macromolecular damage. The role of the HSR in subjects exposed to environmental heat who progressed to heat stroke versus those that did not is unknown. Our findings suggest that heat stroke induces a broad and robust HSR of nearly half of the total heat shock proteins, cochaperones, and chaperonin genes. Heat stroke patients exhibited inhibition of genes involved in energy production, including oxidative phosphorylation and ATP production. Significant enrichment of neurodegenerative pathways, including amyloid processing signalling, the Huntington's and Parkinson's disease signalling suggestive of brain proteotoxicity was noted. The data suggests that more than a powerful HSR may be required to protect against heat stroke. Overwhelming proteotoxicity and energy failure might contribute to its pathogenesis.

Adherence of Healthcare Workers to Saudi Management Guidelines of Heat-Related Illnesses during Hajj Pilgrimage.

Heat-related illnesses (HRIs), such as heatstroke (HS) and heat exhaustion (HE), are common complications during Hajj pilgrims. The Saudi Ministry of Health (MoH) developed guidelines on the management of HRIs to ensure the safety of all pilgrims. This study aimed to assess healthcare workers' (HCWs) adherence to the updated national guidelines regarding pre-hospital and in-hospital management of HRIs. This was a cross-sectional study using a questionnaire based on the updated HRI management interim guidelines for the Hajj season. Overall, compliance with HE guidelines scored 5.5 out of 10 for basic management and 4.7 out of 10 for advanced management. Medical staff showed an average to above average adherence to pre-hospital HS management, including pre-hospital considerations (7.2), recognition of HS (8.1), case assessment (7.7), stabilizing airway, breathing, and circulation (8.7), and cooling (5). The overall compliance to in-hospital guidelines for HS management were all above average, except for special conditions (4.3). In conclusion, this survey may facilitate the evaluation of the adherence to Saudi HRIs guidelines by comparing annual levels of compliance. These survey results may serve as a tool for the Saudi MoH to develop further recommendations and actions.

Guidance for Health Risk Assessment at Recurrent Mass Gatherings: The Jeddah Tool Framework.

A wide range of natural and man-made hazards increases the health risks at mass gatherings (MGs). Building on the Sendai Framework for Disaster Risk Reduction 2015-2030, the World Health Organization (WHO) developed the Health Emergency and Disaster Risk Management (H-EDRM) framework to strengthen preparedness, response, and recovery from health emergencies in the communities and emergency-prone settings, such as MGs. The Jeddah tool is derived from the H-EDRM framework as an all-hazard MG risk assessment tool, which provides a benchmark for monitoring progress made in capacity strengthening over a given period for recurrent MGs. Additionally, it introduces a reputational risk assessment domain to complement vulnerability and capacity assessment matrixes. This paper describes the key elements of the Jeddah tool to improve the understanding of health risk assessment at MGs in the overarching contexts of health emergencies and disaster risk reduction, in line with international goals.