Impaired autophagy following ex vivo cooling of simulated hypothermic temperatures in peripheral blood mononuclear cells from young and older adults.

Hypothermia is a critical consequence of extreme cold exposure that increases the risk of cold-related injury and death in humans. While the initiation of cytoprotective mechanisms including the process of autophagy and the heat shock response (HSR) is crucial to cellular survival during periods of stress, age-related decrements in these systems may underlie cold-induced cellular vulnerability in older adults. Moreover, whether potential sex-related differences in autophagic regulation influence the human cold stress response remain unknown. We evaluated the effect of age and sex on mechanisms of cytoprotection (autophagy and the HSR) and cellular stress (apoptotic signaling and the acute inflammatory response) during ex vivo hypothermic cooling. Venous blood samples from 20 healthy young (10 females; mean [SD]: 22 [2] years) and 20 healthy older (10 females; 66 [5] years) adults were either isolated immediately (baseline) for peripheral blood mononuclear cells (PBMCs) or exposed to water bath temperatures maintained at 37, 35, 33, 31, or 4 °C for 90 min before PBMC isolation. Proteins associated with autophagy, apoptosis, the HSR, and inflammation were analyzed via Western blotting. Indicators of autophagic initiation and signaling (LC3, ULK1, and beclin-2) and the HSR (HSP90 and HSP70) increased when exposed to hypothermic temperatures in young and older adults (all p ≤ 0.007). Sex-related differences were only observed with autophagic initiation (ULK1; p = 0.015). However, despite increases in autophagic initiators ULK1 and beclin-2 (all p < 0.001), this was paralleled by autophagic dysfunction (increased p62) in all groups (all p < 0.001). Further, apoptotic (cleaved-caspase-3) and inflammatory (IL-6 and TNF-α) signaling increased in all groups (all p < 0.001). We demonstrated that exposure to hypothermic conditions is associated with autophagic dysfunction, irrespective of age or sex, although there may exist innate sex-related differences in cytoprotection in response to cold exposure as evidenced through altered autophagic initiation.

"Death Is a Possibility for Those without Shelter": A Thematic Analysis of News Coverage on Homelessness and the 2021 Heat Dome in Canada.

Among the most vulnerable to the health-harming effects of heat are people experiencing homelessness. However, during the 2021 Heat Dome, the deadliest extreme heat event (EHE) recorded in Canada to date, people experiencing homelessness represented the smallest proportion of decedents (n = 3, 0.5%)-despite the impacted region (British Columbia) having some of the highest rates of homelessness in the country. Thus, we sought to explore the 2021 Heat Dome as a media-based case study to identify potential actions or targeted strategies that were initiated by community support agencies, individuals and groups, and communicated in the news during this EHE that may have aided in the protection of this group or helped minimize the mortality impacts. Using media articles collated for a more extensive investigation into the effects of the 2021 Heat Dome (n = 2909), we identified a subset which included content on people experiencing homelessness in Canada (n = 274, 9%). These articles were thematically analysed using NVivo. Three main themes were identified: (i) public warnings issued during the 2021 Heat Dome directly addressed people experiencing homelessness, (ii) community support services explicitly targeting this population were activated during the heat event, and (iii) challenges and barriers faced by people experiencing homelessness during extreme heat were communicated. These findings suggest that mass-media messaging and dedicated on-the-ground initiatives led by various organizations explicitly initiated to support individuals experiencing homelessness during the 2021 Heat Dome may have assisted in limiting the harmful impacts of the heat on this community.

Greater hyperthermia in men with type 2 diabetes does not lead to higher serum levels of cellular stress biomarkers following exercise-heat stress.

Type 2 diabetes (T2D) is associated with worsening age-related impairments in heat loss, causing higher core temperature during exercise. We evaluated whether these thermoregulatory impairments occur with altered serum protein responses to heat stress by measuring cytoprotection, inflammation, and tissue damage biomarkers in middle-aged-to-older men (50-74 years) with (n = 16) and without (n = 14) T2D following exercise in 40°C. There were no changes in irisin, klotho, HSP70, sCD14, TNF-α, and IL-6, whereas NGAL (+539 pg/mL, p = 0.002) and iFABP (+250 pg/mL, p < 0.001) increased similarly across groups. These similar response patterns occurred despite elevated core temperature in individuals with T2D, suggesting greater heat vulnerability.

"Breaking down in tears, soaked in sweat, and sick from the heat": Media-based composite narratives of first responders working during the 2021 Heat Dome.

BACKGROUND: During the summer of 2021, a deadly, unprecedented multiday Heat Dome engulfed western Canada. As a result of this extreme heat event (EHE), emergency dispatchers received an unparalleled increase in incoming 911 calls for ambulance, police, and fire (as first responders) services to attend to hundreds of heat-vulnerable community members succumbing to the heat. With 103 all-time heat records broken during this EHE and indoor temperatures of nearly 40°C, the first responders attending these calls faced extensive job demands and highly challenging operating conditions. Initial investigations have explored the health system-level impacts; however, little has been done to explore the impact on the first responders themselves. Therefore, this study aimed to improve our understanding of EHEs' impacts on the operational capabilities and health of first responders, specifically police, fire, ambulance, and dispatch services. METHODS: A systematized review and content analysis of media articles published on the 2021 Heat Dome in Canada was conducted (n = 2909), and four media-based composite narratives were developed highlighting police, fire, ambulance, and dispatch services. The Job Demands-Resources (JD-R) model was applied as a theoretical framework for occupational burnout. RESULTS: The media-based composite narratives highlighted that first responders faced record-breaking call volumes, increased mental-health-related claims, and exhaustive heat-related physiological stress. Using the JD-R model as a theoretical framework for occupational burnout, we identified three measures of stressful job demand: work overload (e.g., the surge in call volume, firefighters responding to medical emergencies), emotional demands (e.g., severe medical emergencies, sudden deaths, unresponsive patients, distraught family members), and physical demands (e.g., resuscitation in personal protective equipment, heat-related illness). CONCLUSION: The experiences described underscore the importance of supporting first responders during work in extreme heat conditions. These findings have important implications for addressing rising rates of burnout during and following public health crises, such as EHEs, a problem that is increasingly being recognized as a threat to the Canadian public healthcare system.

Biological sex-related differences in the postprandial triglyceride response to intermittent hypoxaemia in young adults: a randomized crossover trial.

Obstructive sleep apnoea is characterized by chronic intermittent hypoxaemia and is independently associated with an increased risk of metabolic comorbidities (e.g. type II diabetes and ischaemic heart disease). These comorbidities could be attributable to hypoxaemia-induced alterations in blood lipid profiles. However, it remains unclear whether intermittent hypoxaemia alters triglyceridaemia differently between biological sexes. Therefore, we used a randomized crossover design to examine whether 6 h of moderate intermittent hypoxaemia (15 hypoxaemic cycles/h, 85% oxyhaemoglobin saturation) alters plasma triglyceride levels differently between men and women after a high-fat meal. Relative to men, women displayed lower levels of total triglycerides, in addition to denser triglyceride-rich lipoprotein triglycerides (TRL-TG; mainly very low-density lipoprotein triglycerides and chylomicron remnant triglycerides) and buoyant TRL-TG (mainly chylomicron triglycerides) during normoxia (ambient air) and intermittent hypoxaemia (sex × time: all P ≤ 0.008). Intermittent hypoxaemia led to higher triglyceride levels (condition: all P ≤ 0.016); however, this effect was observed only in men (sex × condition: all P ≤ 0.002). Compared with normoxia, glucose levels were higher in men and lower in women during intermittent hypoxaemia (sex × condition: P < 0.001). The different postprandial responses between biological sexes occurred despite similar reductions in mean oxyhaemoglobin saturation and similar elevations in insulin levels, non-esterified fatty acid levels and mean heart rate (sex × condition: all P ≥ 0.185). These results support growing evidence showing that intermittent hypoxaemia impacts men and women differently, and they might help to explain biological sex-related discrepancies in the rate of certain comorbidities associated with intermittent hypoxaemia. KEY POINTS: Intermittent hypoxaemia is a key characteristic of obstructive sleep apnoea and alters lipid metabolism in multiple tissues, resulting in increased circulating triglyceride levels, an important risk factor for cardiometabolic diseases. Circulating triglyceride levels are regulated differently between biological sexes, with women typically displaying much lower fasting and postprandial triglyceride levels than men, partly explaining why women of all ages experience lower mortality rates from cardiometabolic diseases. In this study, healthy young men and women consumed a high-fat meal and were then exposed to 6 h of intermittent hypoxaemia or ambient air. We show that postprandial triglyceride levels are significantly lower in women compared with men and that intermittent hypoxaemia leads to higher postprandial triglyceride levels in men only. These results might help us to understand better why women living with obstructive sleep apnoea experience lower rates of cardiometabolic diseases (e.g. type II diabetes and ischaemic heart disease) than men living with obstructive sleep apnoea.

Hot Topic: A Systematic Review and Content Analysis of Heat-Related Messages During the 2021 Heat Dome in Canada.

CONTEXT: During the summer of 2021, western Canada experienced a deadly heat event. From the first heat alert to postevent reporting, thousands of media articles were published that reference the heat event. However, a gap remains in understanding how this communication chain-from the release of a public heat alert to information shared through media outlets to the public-currently operates to disseminate heat-related messaging across Canada. OBJECTIVE: To understand the role of digital media in delivering heat-health messaging during an extreme heat event in Canada. DESIGN: A qualitative content analysis was conducted using Canadian news articles published on the 2021 Heat Dome between June 2021 and February 2022 (n = 2909). The coding frame was designed to align with the basic framework for information gathering used in journalism (who, what, where, when, and how) and included both concept-driven and data-driven codes. RESULTS: Overall, 2909 unique media articles discussing the 2021 Heat Dome were identified, with the majority (74%) published by online news agencies (how). The highest article count was on June 29, 2021 (n = 159), representing 5% of the total data set (n = 2909) spanning 260 days (when); 57% of the identified locations were in British Columbia (where). Although we found that the top voices providing media-based heat-health messages are government officials (who), only 23% of articles included heat-health messaging that aligns with the government health alert bulletins released during extreme heat. In addition, heat-health messaging frequently included contradictory content, inconsistent language, or incorrect advice (what). CONCLUSION: The findings demonstrate clear opportunities to improve health communication related to extreme heat, perhaps most importantly, including updates to mass media messaging educating the public on heat-protective behaviors.

The intensity-dependent effects of exercise and superimposing environmental heat stress on autophagy in peripheral blood mononuclear cells from older men.

Autophagy is a vital cellular process, essential to maintaining cellular function during acute physiological stressors including exercise and heat stress. We previously showed that autophagy occurs during exercise in an intensity-dependent manner in peripheral blood mononuclear cells (PBMCs) from young men, with elevated responses in the heat. However, given autophagy declines with age, it is unclear whether a similar pattern of response occurs in older adults. Therefore, we evaluated autophagy and the cellular stress response [i.e., apoptosis, inflammation, and the heat shock response (HSR)] in PBMCs from 10 healthy older men [mean (SD): aged 70 yr (5)] in response to 30 min of semirecumbent cycling at low, moderate, and vigorous intensities [40, 55, and 70% maximal oxygen consumption (V̇o2max), respectively] in a temperate (25°C) environment, with an additional vigorous-intensity bout (70% of V̇o2max) performed in a hot environment (40°C). Responses were evaluated before and after exercise, as well as throughout a 6-h seated recovery period performed in the same environmental conditions as the respective exercise bout. Proteins were assessed via Western blot. Although we observed elevations in mean body temperature with each increase in exercise intensity, autophagy was only stimulated during vigorous-intensity exercise, where we observed elevations in LC3-II (P < 0.05). However, when the same exercise was performed in the heat, the LC3-II response was attenuated, which was accompanied by significant p62 accumulation (P < 0.05). Altogether, our findings demonstrate that older adults exhibit autophagic impairments when the same vigorous-intensity exercise is performed in hot environments, potentially underlying heat-induced cellular vulnerability in older men.NEW & NOTEWORTHY We demonstrate that autophagic stimulation occurs in response to short-duration (30-min) vigorous-intensity exercise in peripheral blood mononuclear cells from older adults; however, no changes in autophagy occur during low- or moderate-intensity exercise. Moreover, older adults exhibit autophagic impairments when the same vigorous-intensity exercise is performed in hot ambient conditions. When paired with an attenuated heat shock response, as well as elevated apoptotic responses, older men may exhibit greater cellular vulnerability to exertional heat stress.

Elevations in serum brain-derived neurotrophic factor following occupational heat stress are not influenced by age or common chronic disease.

With global warming, workers are increasingly exposed to strenuous occupations in hot environments. Given age- and disease-associated declines in thermoregulatory function, older workers are at an elevated risk of developing heat-related injuries. Brain-derived neurotrophic factor (BDNF) is thought to confer neuroprotection during acute exercise, however, the influence of environmental heat on BDNF responses during prolonged work remains unclear. Therefore, we evaluated serum BDNF concentrations before and after 180 min of moderate-intensity treadmill walking (200 W/m2) and after 60 min of post-exercise recovery in temperate (wet-bulb globe temperature (WBGT) 16°C) and hot (WBGT 32°C) environments in 13 healthy young men (mean [SD; 22 [3] years), 12 healthy older men (59 [4] years), 10 men with hypertension (HTN) (60 [4] years), and 9 men with type 2 diabetes (T2D) (60 [5] years). In the temperate condition, all but one participant (1 HTN) completed the 180 min of exercise. While exercise tolerance in the heat was lower in older men with HTN (117 min [45]) and T2D (123 min [42]) compared to healthy older men (159 min [31]) (both p ≤ 0.049), similar end-exercise rectal temperatures (38.9°C [0.4]) were observed across groups, paralleled by similar elevations in serum BDNF across groups at end-exercise (+1106 pg/mL [203]) and end-recovery (+938 pg/mL [146]; all p ≤ 0.01) in the heat. No changes in serum BDNF were observed in the temperate condition. Our findings indicate similar BDNF responses in individuals with HTN or T2D compared to their healthy counterparts, despite exhibiting reduced tolerance to heat.

No impact of a high-fat meal coupled with intermittent hypoxemia on acute kidney injury biomarkers in adults with and without obstructive sleep apnea.

Obstructive sleep apnea (OSA) is characterized by chronic intermittent hypoxemia, which is associated with progressive loss of kidney function, where postprandial fluctuations in renal physiology may further compromise oxygen supply and kidney function. Therefore, we measured biomarkers of acute kidney injury (AKI) following a high-fat meal with and without intermittent hypoxemia. Eighteen healthy young men (mean age [SD]: 22.7 years [3.1]) and seven middle-aged to older individuals with OSA (54.4 years [6.4]) consumed a high-fat meal during normoxia or intermittent hypoxemia (~15 hypoxic cycles per hour, ~85% oxyhemoglobin saturation) for 6 h. We observed no changes in estimated glomerular filtration rate and plasma concentrations of creatinine, neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) at any measured time points. In both groups, plasma concentrations of interleukin-18 (IL-18) increased after 6 h during normoxia only (p = 0.033, ηp 2 = 0.122), and plasma concentrations of liver-type fatty acid-binding protein (L-FABP) transiently decreased after 3 h in both conditions (p = 0.008, ηp 2 = 0.152). These findings indicate that AKI biomarkers are not acutely elevated during the postprandial state with or without intermittent hypoxemia, suggesting that other mechanisms may play more important roles in the progression of kidney disease in OSA.

The Intersection of the COVID-19 Pandemic and the 2021 Heat Dome in Canadian Digital News Media: A Content Analysis.

During the 2021 Heat Dome, 619 people in British Columbia died due to the heat. This public health disaster was made worse by the ongoing COVID-19 pandemic. Few studies have explored the intersection of heat with COVID-19, and none in Canada. Considering that climate change is expected to increase the frequency of extreme heat events, it is important to improve our understanding of intersecting public health crises. Thus, this study aimed to explore media-based public health communication in Canada during the COVID-19 pandemic and the 2021 Heat Dome. A qualitative content analysis was conducted on a subset of media articles (n = 520) related to the COVID-19 pandemic which were identified through a previous media analysis on the 2021 Heat Dome (n = 2909). Many of the articles provided conflicting health messages that may have confused the public about which health protective actions to take. The articles also showed how the COVID-19 pandemic may have exacerbated the health impacts of the 2021 Heat Dome, as pandemic-related public health measures may have deterred people away from protecting themselves from heat. This study, which provides novel insight into the prioritization of public health messaging when an extreme heat event occurs concurrently with a pandemic, supports the need for consistent heat health guidance.

Working under the 2021 Heat Dome: A Content Analysis of Occupational Impacts Mentioned in the Canadian Media.

Extreme heat events directly impact worker health and cause additional cascading and transitional workplace impacts. However, current investigations on these impacts often rely on specific datasets (e.g., compensation claims, hospitalizations). Thus, to continue to work towards preventing and mitigating the occupational risks posed by extreme heat events, this study aimed to explore the occupational impacts of the 2021 Heat Dome in Canada using a qualitative content analysis method on a news-based dataset. A systematized review of news articles published before, during, and after the 2021 Heat Dome was conducted on academic (n = 8) and news (n = 5) databases, along with targeted grey literature. Two researchers qualitatively coded the articles in NVivo for occupational impacts or references mentioned within the articles. Overall, 52 different occupations were identified as being impacted by the 2021 Heat Dome. Impacts were diverse and ranged from work cancellations or delays to work modifications and reports of heat-related illnesses. The 2021 Heat Dome impacted the health and safety of many occupational groups and provided new insights into the expanding impacts that extreme heat events can have on the Canadian workforce. With climate projections showing a growing trend of more hot days and intense heat waves in Canada, addressing these concerns should be a critical priority.

Impacts of age, diabetes, and hypertension on serum endothelial monocyte-activating polypeptide-II after prolonged work in the heat.

BACKGROUND: With rising temperature extremes, older workers are becoming increasingly vulnerable to heat-related injuries because of age- and disease-associated decrements in thermoregulatory function. Endothelial monocyte-activating polypeptide-II (EMAP-II) is a proinflammatory cytokine that has not yet been well-characterized during heat stress, and which may mediate the inflammatory response to high levels of physiological strain. METHODS: We evaluated serum EMAP-II concentrations before and after 180 min of moderate-intensity work (200 W/m2 ) in temperate (wet-bulb globe temperature [WBGT] 16°C) and hot (WBGT 32°C) environments in heat-unacclimatized, healthy young (n = 13; mean [SD]; 22 [3] years) and older men (n = 12; 59 [4] years), and unacclimatized older men with hypertension (HTN) (n = 10; 60 [4] years) or type 2 diabetes (T2D) (n = 9; 60 [5] years). Core temperature and heart rate were measured continuously. RESULTS: In the hot environment, work tolerance time was lower in older men with HTN and T2D compared to healthy older men (both p < 0.049). While core temperature and heart rate reserve increased significantly (p < 0.001), they did not differ across groups. End-exercise serum EMAP-II concentrations were higher in young men relative to their older counterparts due to higher baseline levels (both p ≤ 0.02). Elevations in serum EMAP-II concentrations were similar between healthy older men and older men with HTN, while serum EMAP-II concentrations did not change in older men with T2D following prolonged work in the heat. CONCLUSION: Serum EMAP-II concentrations increased following prolonged moderate-intensity work in the heat and this response is influenced by age and the presence of HTN or T2D.

Autophagic response to exercise in peripheral blood mononuclear cells from young men is intensity-dependent and is altered by exposure to environmental heat.

Autophagy is essential to maintaining cellular homeostasis in all eukaryotic cells and to tolerance of acute stressors such as starvation, heat, and recovery after exercise. Limited information exists regarding the exercise intensity-dependent autophagic response in humans, and it is unknown how environmental heat stress may modulate this response. Therefore, we evaluated autophagy and accompanying pathways of cellular stress [the heat-shock response (HSR), apoptosis, and acute inflammation] in peripheral blood mononuclear cells (PBMCs) from 10 young men (mean [SD]; 22 [2] years) before, immediately after and up to 6-h postexercise recovery from 30 min of low-, moderate-, and high-intensity semirecumbent cycling [40%, 55%, and 70% of maximal oxygen consumption (V̇o2max), respectively] in a temperate environment (25°C) and at 70% of V̇o2max in a hot environment (40°C). Changes in protein content were analyzed via Western blot. Each increase in exercise intensity was associated with elevations in mean body temperature. LC3-II increased after moderate-intensity exercise, with further increases after high-intensity exercise (P < 0.05). However, an increase in beclin-2 and ULK1, with a decrease in p62 was only observed after high-intensity exercise, which was paralleled by elevated TNF-α and cleaved-caspase-3, with the HSR peaking at 6 h after exercise (P < 0.05). When exercise was performed in the heat, greater LC3-II and cleaved-caspase-3 accumulation were observed; however, beclin-2 declined in recovery (P < 0.05). Therefore, our findings indicate that autophagy in PBMCs during exercise may be associated with greater heat strain exhibited during increasing exercise intensities, which is modulated by exposure to heat.

Physiological Responses to Hypoxia on Triglyceride Levels.

Hypoxia is a condition during which the body or specific tissues are deprived of oxygen. This phenomenon can occur in response to exposure to hypoxic environmental conditions such as high-altitude, or because of pathophysiological conditions such as obstructive sleep apnea. Circumstances such as these can restrict supply or increase consumption of oxygen, leading to oxyhemoglobin desaturation and tissue hypoxia. In certain cases, hypoxia may lead to severe health consequences such as an increased risk of developing cardiovascular diseases and type 2 diabetes. A potential explanation for the link between hypoxia and an increased risk of developing cardiovascular diseases lies in the disturbing effect of hypoxia on circulating blood lipids, specifically its capacity to increase plasma triglyceride concentrations. Increased circulating triglyceride levels result from the production of triglyceride-rich lipoproteins, such as very-low-density lipoproteins and chylomicrons, exceeding their clearance rate. Considerable research in murine models reports that hypoxia may have detrimental effects on several aspects of triglyceride metabolism. However, in humans, the mechanisms underlying the disturbing effect of hypoxia on triglyceride levels remain unclear. In this mini-review, we outline the available evidence on the physiological responses to hypoxia and their impact on circulating triglyceride levels. We also discuss mechanisms by which hypoxia affects various organs involved in the metabolism of triglyceride-rich lipoproteins. This information will benefit scientists and clinicians interested in the mechanistic of the regulatory cascade responsible for the response to hypoxia and how this response could lead to a deteriorated lipid profile and an increased risk of developing hypoxia-related health consequences.