Exploring heterogeneity: a dive into preclinical models of cancer cachexia.

Cancer cachexia (CC) is a multifactorial and complex syndrome experienced by up to 80% of patients with cancer and implicated in ∼40% of cancer-related deaths. Given its significant impact on patients' quality of life and prognosis, there has been a growing emphasis on elucidating the underlying mechanisms of CC using preclinical models. However, the mechanisms of cachexia appear to differ across several variables including tumor type and model and biologic variables such as sex. These differences may be exacerbated by variance in experimental approaches and data reporting. This review examines literature spanning from 2011 to March 2024, focusing on common preclinical models of CC, including Lewis Lung Carcinoma, pancreatic KPC, and colorectal colon-26 and Apcmin/+ models. Our analysis reveals considerable heterogeneity in phenotypic outcomes, and investigated mechanisms within each model, with particular attention to sex differences that may be exacerbated through methodological differences. Although searching for unified mechanisms is critical, we posit that effective treatment approaches are likely to leverage the heterogeneity presented by the tumor and pertinent biological variables to direct specific interventions. In exploring this heterogeneity, it becomes critical to consider methodological and data reporting approaches to best inform further research.

The mechanosensitive gene arrestin domain containing 2 regulates myotube diameter with direct implications for disuse atrophy with aging.

Arrestin domain containing 2 and 3 (Arrdc2/3) are genes whose mRNA contents are decreased in young skeletal muscle following mechanical overload. Arrdc3 is linked to the regulation of signaling pathways in nonmuscle cells that could influence skeletal muscle size. Despite a similar amino acid sequence, Arrdc2 function remains undefined. The purpose of this study was to further explore the relationship of Arrdc2/Arrdc3 expression with changes in mechanical load in young and aged muscle and define the effect of Arrdc2/3 expression on C2C12 myotube diameter. In young and aged mice, mechanical load was decreased using hindlimb suspension whereas mechanical load was increased by reloading previously unloaded muscle or inducing high-force contractions. Arrdc2 and Arrdc3 mRNAs were overexpressed in C2C12 myotubes using adenoviruses. Myotube diameter was determined 48-h posttransfection, and RNA sequencing was performed on those samples. Arrdc2 and Arrdc3 mRNA content was higher in the unloaded muscle within 1 day of disuse and remained higher up through 10 days. The induction of Arrdc2 mRNA was more pronounced in aged muscle than young muscle in response to unloading. Reloading previously unloaded muscle of young and aged mice restored Arrdc2 and Arrdc3 levels to ambulatory levels. Increasing mechanical load beyond normal ambulatory levels lowered Arrdc2 mRNA, but not Arrdc3 mRNA, in young and aged muscle. Arrdc2 overexpression only was sufficient to lower myotube diameter in C2C12 cells in part by altering the transcriptome favoring muscle atrophy. These data are consistent with Arrdc2 contributing to disuse atrophy, particularly in aged muscle.NEW & NOTEWORTHY We establish Arrdc2 as a novel mechanosensitive gene highly induced in response to mechanical unloading, particularly in aged muscle. Arrdc2 induction in C2C12 myotubes is sufficient to produce thinner myotubes and a transcriptional landscape consistent with muscle atrophy and disuse.

Transcriptional Analysis of Cancer Cachexia: Conserved and Unique Features Across Pre-Clinical Models and Biological Sex.

Studies suggest heterogeneity in cancer cachexia (CC) among models and biological sexes, yet examinations comparing models and sexes are scarce. We compared the transcriptional landscape of skeletal muscle across murine CC models and biological sexes during early and late CC. Global gene expression analyses were performed on gastrocnemius (LLC-Lewis Lung Carcinoma), quadriceps (KPC-pancreatic), and tibialis anterior (C26-colorectal and ApcMin/+) muscles across biological sexes. Differentially expressed genes (DEGs) were identified using an adj-p-value of <0.05, followed by pathway and computational cistrome analyses. Integrating all controls, early, and late-stage of all models and sexes revealed up to 68% of DEGs and pathways were enriched at early and late CC, indicating a conserved transcriptional profile during CC development. Comparing DEGs and pathways within sexes and across models, in early-CC, the transcriptional response was highly heterogeneous. At late-stage, 11.5% of upregulated and 10% of downregulated genes were shared between models in males, while 18.9% of upregulated and 7% of downregulated DEGs were shared in females. Shared DEGs were enriched in proteasome and mitophagy/autophagy pathways (upregulated), and downregulation of energy metabolism pathways in males only. Between sexes, though proportion of shared DEGs was low (<16%), similar pathway enrichment was observed, including proteasome and mitophagy at late-stage CC. In early-CC, Osmr upregulation was the only commonality across all models and sexes, while CLOCK and ARNTL/BMAL1 were predicted transcriptional factors associated with dysregulations in all three male models. This study highlights sex and model differences in CC progression and suggests conserved transcriptional changes as potential therapeutic targets.

Mitochondrial antioxidant SkQ1 attenuates C26 cancer-induced muscle wasting in males and improves muscle contractility in female tumor-bearing mice.

Mitochondrial dysfunction is a hallmark of cancer cachexia (CC). Mitochondrial reactive oxygen species (ROS) are elevated in muscle shortly after tumor onset. Targeting mitochondrial ROS may be a viable option to prevent CC. The aim of this study was to evaluate the efficacy of a mitochondria-targeted antioxidant, SkQ1, to mitigate CC in both biological sexes. Male and female Balb/c mice were injected bilaterally with colon 26 adenocarcinoma (C26) cells (total 1 × 106 cells) or PBS (equal volume control). SkQ1 was dissolved in drinking water (∼250 nmol/kg body wt/day) and administered to mice beginning 7 days following tumor induction, whereas control groups consumed normal drinking water. In vivo muscle contractility of dorsiflexors, deuterium oxide-based protein synthesis, mitochondrial respiration and mRNA content of mitochondrial, protein turnover, and calcium channel-related markers were assessed at endpoint (25 days following tumor induction). Two-way ANOVAs, followed by Tukey's post hoc test when interactions were significant (P ≤ 0.05), were performed. SkQ1 attenuated cancer-induced atrophy, promoted protein synthesis, and abated Redd1 and Atrogin induction in gastrocnemius of C26 male mice. In female mice, SkQ1 decreased muscle mass and increased catabolic signaling in the plantaris of tumor-bearing mice, as well as reduced mitochondrial oxygen consumption, regardless of tumor. However, in females, SkQ1 enhanced muscle contractility of the dorsiflexors with concurrent induction of Ryr1, Serca1, and Serca2a in TA. In conclusion, the mitochondria-targeted antioxidant SkQ1 may attenuate CC-induced muscle loss in males, while improving muscle contractile function in tumor-bearing female mice, suggesting sexual dimorphism in the effects of this mitochondrial therapy in CC.NEW & NOTEWORTHY Herein, we assess the efficacy of the mitochondria-targeted antioxidant SkQ1 to mitigate cancer cachexia (CC) in both biological sexes. We demonstrate that SkQ1 administration attenuates muscle wasting induced by C26 tumors in male, but not female, mice. Conversely, we identify that in females, SkQ1 improves muscle contractility. These phenotypic adaptations to SkQ1 are aligned with respective responses in muscle protein synthesis, mitochondrial respiration, and mRNA content of protein turnover, as well as mitochondrial and calcium handling-related markers.

Associations Between Extreme Temperatures and Cardiovascular Cause-Specific Mortality: Results From 27 Countries.

BACKGROUND: Cardiovascular disease is the leading cause of death worldwide. Existing studies on the association between temperatures and cardiovascular deaths have been limited in geographic zones and have generally considered associations with total cardiovascular deaths rather than cause-specific cardiovascular deaths. METHODS: We used unified data collection protocols within the Multi-Country Multi-City Collaborative Network to assemble a database of daily counts of specific cardiovascular causes of death from 567 cities in 27 countries across 5 continents in overlapping periods ranging from 1979 to 2019. City-specific daily ambient temperatures were obtained from weather stations and climate reanalysis models. To investigate cardiovascular mortality associations with extreme hot and cold temperatures, we fit case-crossover models in each city and then used a mixed-effects meta-analytic framework to pool individual city estimates. Extreme temperature percentiles were compared with the minimum mortality temperature in each location. Excess deaths were calculated for a range of extreme temperature days. RESULTS: The analyses included deaths from any cardiovascular cause (32 154 935), ischemic heart disease (11 745 880), stroke (9 351 312), heart failure (3 673 723), and arrhythmia (670 859). At extreme temperature percentiles, heat (99th percentile) and cold (1st percentile) were associated with higher risk of dying from any cardiovascular cause, ischemic heart disease, stroke, and heart failure as compared to the minimum mortality temperature, which is the temperature associated with least mortality. Across a range of extreme temperatures, hot days (above 97.5th percentile) and cold days (below 2.5th percentile) accounted for 2.2 (95% empirical CI [eCI], 2.1-2.3) and 9.1 (95% eCI, 8.9-9.2) excess deaths for every 1000 cardiovascular deaths, respectively. Heart failure was associated with the highest excess deaths proportion from extreme hot and cold days with 2.6 (95% eCI, 2.4-2.8) and 12.8 (95% eCI, 12.2-13.1) for every 1000 heart failure deaths, respectively. CONCLUSIONS: Across a large, multinational sample, exposure to extreme hot and cold temperatures was associated with a greater risk of mortality from multiple common cardiovascular conditions. The intersections between extreme temperatures and cardiovascular health need to be thoroughly characterized in the present day-and especially under a changing climate.

Extreme Temperatures and Stroke Mortality: Evidence From a Multi-Country Analysis.

BACKGROUND: Extreme temperatures contribute significantly to global mortality. While previous studies on temperature and stroke-specific outcomes presented conflicting results, these studies were predominantly limited to single-city or single-country analyses. Their findings are difficult to synthesize due to variations in methodologies and exposure definitions. METHODS: Within the Multi-Country Multi-City Network, we built a new mortality database for ischemic and hemorrhagic stroke. Applying a unified analysis protocol, we conducted a multinational case-crossover study on the relationship between extreme temperatures and stroke. In the first stage, we fitted a conditional quasi-Poisson regression for daily mortality counts with distributed lag nonlinear models for temperature exposure separately for each city. In the second stage, the cumulative risk from each city was pooled using mixed-effect meta-analyses, accounting for clustering of cities with similar features. We compared temperature-stroke associations across country-level gross domestic product per capita. We computed excess deaths in each city that are attributable to the 2.5% hottest and coldest of days based on each city's temperature distribution. RESULTS: We collected data for a total of 3 443 969 ischemic strokes and 2 454 267 hemorrhagic stroke deaths from 522 cities in 25 countries. For every 1000 ischemic stroke deaths, we found that extreme cold and hot days contributed 9.1 (95% empirical CI, 8.6-9.4) and 2.2 (95% empirical CI, 1.9-2.4) excess deaths, respectively. For every 1000 hemorrhagic stroke deaths, extreme cold and hot days contributed 11.2 (95% empirical CI, 10.9-11.4) and 0.7 (95% empirical CI, 0.5-0.8) excess deaths, respectively. We found that countries with low gross domestic product per capita were at higher risk of heat-related hemorrhagic stroke mortality than countries with high gross domestic product per capita (P=0.02). CONCLUSIONS: Both extreme cold and hot temperatures are associated with an increased risk of dying from ischemic and hemorrhagic strokes. As climate change continues to exacerbate these extreme temperatures, interventional strategies are needed to mitigate impacts on stroke mortality, particularly in low-income countries.

Global, regional, and national burden of heatwave-related mortality from 1990 to 2019: A three-stage modelling study.

BACKGROUND: The regional disparity of heatwave-related mortality over a long period has not been sufficiently assessed across the globe, impeding the localisation of adaptation planning and risk management towards climate change. We quantified the global mortality burden associated with heatwaves at a spatial resolution of 0.5°×0.5° and the temporal change from 1990 to 2019. METHODS AND FINDINGS: We collected data on daily deaths and temperature from 750 locations of 43 countries or regions, and 5 meta-predictors in 0.5°×0.5° resolution across the world. Heatwaves were defined as location-specific daily mean temperature ≥95th percentiles of year-round temperature range with duration ≥2 days. We first estimated the location-specific heatwave-mortality association. Secondly, a multivariate meta-regression was fitted between location-specific associations and 5 meta-predictors, which was in the third stage used with grid cell-specific meta-predictors to predict grid cell-specific association. Heatwave-related excess deaths were calculated for each grid and aggregated. During 1990 to 2019, 0.94% (95% CI: 0.68-1.19) of deaths [i.e., 153,078 cases (95% eCI: 109,950-194,227)] per warm season were estimated to be from heatwaves, accounting for 236 (95% eCI: 170-300) deaths per 10 million residents. The ratio between heatwave-related excess deaths and all premature deaths per warm season remained relatively unchanged over the 30 years, while the number of heatwave-related excess deaths per 10 million residents per warm season declined by 7.2% per decade in comparison to the 30-year average. Locations with the highest heatwave-related death ratio and rate were in Southern and Eastern Europe or areas had polar and alpine climates, and/or their residents had high incomes. The temporal change of heatwave-related mortality burden showed geographic disparities, such that locations with tropical climate or low incomes were observed with the greatest decline. The main limitation of this study was the lack of data from certain regions, e.g., Arabian Peninsula and South Asia. CONCLUSIONS: Heatwaves were associated with substantial mortality burden that varied spatiotemporally over the globe in the past 30 years. The findings indicate the potential benefit of governmental actions to enhance health sector adaptation and resilience, accounting for inequalities across communities.

The impact of climate variation on the spread of Shiga toxin-producing E. coli.

BACKGROUND: Shiga toxin-producing Escherichia coli (STEC) is influenced by seasonality, but there is limited understanding of how specific climatic variables contribute to disease spread. This information aids in understanding disease transmission dynamics and could potentially inform public health modeling. METHODS: This retrospective cohort study analyzed public health data from Ontario, Canada, between 2012 and 2021, along with historical climate data from Environment Canada. We employed Seasonal Autoregressive Integrated Moving Average (S-ARIMA) models to assess how temperature and precipitation impact the incidence of STEC infections, measured per 10,000,000 population. RESULTS: The study included 1658 confirmed STEC cases. A significant correlation was found between STEC incidence and climatic variables. Each degree Celsius increase in maximum temperature was associated with a rise of 3 STEC cases per 10,000,000 population (Centers for Disease Control and Prevention (2024)). Additionally, each millimeter of increased precipitation correlated with an increase of 1.1 cases per 10,000,000 population. CONCLUSIONS: The findings demonstrate a significant impact of temperature and precipitation on STEC transmission, highlighting the importance of integrating meteorological data into public health surveillance. This integration may help inform public health responses and support healthcare systems in planning for future outbreaks. Further studies are needed to refine predictive models and develop effective early warning systems for clinical settings.

Short-term association between air temperature and mortality in seven cities in Norway: A time series analysis.

BACKGROUND: The association between ambient air temperature and mortality has not been assessed in Norway. This study aimed to quantify for seven Norwegian cities (Oslo, Bergen, Stavanger, Drammen, Fredrikstad, Trondheim and Tromsø) the non-accidental, cardiovascular and respiratory diseases mortality burden due to non-optimal ambient temperatures. METHODS: We used a historical daily dataset (1996-2018) to perform city-specific analyses with a distributed lag non-linear model with 14 days of lag, and pooled results in a multivariate meta-regression. We calculated attributable deaths for heat and cold, defined as days with temperatures above and below the city-specific optimum temperature. We further divided temperatures into moderate and extreme using cut-offs at the 1st and 99th percentiles. RESULTS: We observed that 5.3% (95% confidence interval (CI) 2.0-8.3) of the non-accidental related deaths, 11.8% (95% CI 6.4-16.4) of the cardiovascular and 5.9% (95% CI -4.0 to 14.3) of the respiratory were attributable to non-optimal temperatures. Notable variations were found between cities and subgroups stratified by sex and age. The mortality burden related to cold dominated in all three health outcomes (5.1%, 2.0-8.1, 11.4%, 6.0-15.4, and 5.1%, -5.5 to 13.8 respectively). Heat had a more pronounced effect on the burden of respiratory deaths (0.9%, 0.2-1.0). Extreme cold accounted for 0.2% of non-accidental deaths and 0.3% of cardiovascular and respiratory deaths, while extreme heat contributed to 0.2% of non-accidental and to 0.3% of respiratory deaths. CONCLUSIONS: Most of the burden could be attributed to the contribution of moderate cold. This evidence has significant implications for enhancing public-health policies to better address health consequences in the Norwegian setting.

Biological sex divergence in transcriptomic profiles during the onset of hindlimb unloading-induced atrophy.

Disuse-induced muscle atrophy is a common clinical problem observed mainly in older adults, intensive care units patients, or astronauts. Previous studies presented biological sex divergence in progression of disuse-induced atrophy along with differential changes in molecular mechanisms possibly underlying muscle atrophy. The aim of this study was to perform transcriptomic profiling of male and female mice during the onset and progression of unloading disuse-induced atrophy. Male and female mice underwent hindlimb unloading (HU) for 24, 48, 72, and 168 h (n = 8/group). Muscles were weighed for each cohort and gastrocnemius was used for RNA-sequencing analysis. Females exhibited muscle loss as early as 24 h of HU, whereas males after 168 h of HU. In males, pathways related to proteasome degradation were upregulated throughout 168 h of HU, whereas in females these pathways were upregulated up to 72 h of HU. Lcn2, a gene contributing to regulation of myogenesis, was upregulated by 6.46- to 19.86-fold across all time points in females only. A reverse expression of Fosb, a gene related to muscle degeneration, was observed between males (4.27-fold up) and females (4.57-fold down) at 24-h HU. Mitochondrial pathways related to tricarboxylic acid (TCA) cycle were highly downregulated at 168 h of HU in males, whereas in females this downregulation was less pronounced. Collagen-related pathways were consistently downregulated throughout 168 h of HU only in females, suggesting a potential biological sex-specific protective mechanism against disuse-induced fibrosis. In conclusion, females may have protection against HU-induced skeletal muscle mitochondrial degeneration and fibrosis through transcriptional mechanisms, although they may be more vulnerable to HU-induced muscle wasting compared with males.NEW & NOTEWORTHY Herein, we have assessed the transcriptomic response across biological sexes during the onset and progression of unloading disuse-induced atrophy in mice. We have demonstrated an inverse expression of Fosb between males and females, as well as differentially timed patterns of expressing atrophy-related pathways between sexes that are concomitant to the accelerated atrophy in females. We also identified in females signs of mechanisms to combat disuse-induced mitochondrial degeneration and fibrosis.

The time-course of cancer cachexia onset reveals biphasic transcriptional disruptions in female skeletal muscle distinct from males.

BACKGROUND: Cancer-cachexia (CC) is a debilitating condition affecting up to 80% of cancer patients and contributing to 40% of cancer-related deaths. While evidence suggests biological sex differences in the development of CC, assessments of the female transcriptome in CC are lacking, and direct comparisons between sexes are scarce. This study aimed to define the time course of Lewis lung carcinoma (LLC)-induced CC in females using transcriptomics, while directly comparing biological sex differences. RESULTS: We found the global gene expression of the gastrocnemius muscle of female mice revealed biphasic transcriptomic alterations, with one at 1 week following tumor allograft and another during the later stages of cachexia development. The early phase was associated with the upregulation of extracellular-matrix pathways, while the later phase was characterized by the downregulation of oxidative phosphorylation, electron transport chain, and TCA cycle. When DEGs were compared to a known list of mitochondrial genes (MitoCarta), ~ 47% of these genes were differently expressed in females exhibiting global cachexia, suggesting transcriptional changes to mitochondrial gene expression happens concomitantly to functional impairments previously published. In contrast, the JAK-STAT pathway was upregulated in both the early and late stages of CC. Additionally, we observed a consistent downregulation of Type-II Interferon signaling genes in females, which was associated with protection in skeletal muscle atrophy despite systemic cachexia. Upregulation of Interferon signaling was noted in the gastrocnemius muscle of cachectic and atrophic male mice. Comparison of female tumor-bearing mice with males revealed ~ 70% of DEGs were distinct between sexes in cachectic animals, demonstrating dimorphic mechanisms of CC. CONCLUSION: Our findings suggest biphasic disruptions in the transcriptome of female LLC tumor-bearing mice: an early phase associated with ECM remodeling and a late phase, accompanied by the onset of systemic cachexia, affecting overall muscle energy metabolism. Notably, ~ 2/3 of DEGs in CC are biologically sex-specific, providing evidence of dimorphic mechanisms of cachexia between sexes. Downregulation of Type-II Interferon signaling genes appears specific to CC development in females, suggesting a new biological sex-specific marker of CC not reliant on the loss of muscle mass, that might represent a protective mechanism against muscle loss in CC in female mice.

Asthma hospitalisations and heat exposure in England: a case-crossover study during 2002-2019.

BACKGROUND: Previous studies have reported an association between warm temperature and asthma hospitalisation. They have reported different sex-related and age-related vulnerabilities; nevertheless, little is known about how this effect has changed over time and how it varies in space. This study aims to evaluate the association between asthma hospitalisation and warm temperature and investigate vulnerabilities by age, sex, time and space. METHODS: We retrieved individual-level data on summer asthma hospitalisation at high temporal (daily) and spatial (postcodes) resolutions during 2002-2019 in England from the NHS Digital. Daily mean temperature at 1 km×1 km resolution was retrieved from the UK Met Office. We focused on lag 0-3 days. We employed a case-crossover study design and fitted Bayesian hierarchical Poisson models accounting for possible confounders (rainfall, relative humidity, wind speed and national holidays). RESULTS: After accounting for confounding, we found an increase of 1.11% (95% credible interval: 0.88% to 1.34%) in the asthma hospitalisation risk for every 1°C increase in the ambient summer temperature. The effect was highest for males aged 16-64 (2.10%, 1.59% to 2.61%) and during the early years of our analysis. We also found evidence of a decreasing linear trend of the effect over time. Populations in Yorkshire and the Humber and East and West Midlands were the most vulnerable. CONCLUSION: This study provides evidence of an association between warm temperature and hospital admission for asthma. The effect has decreased over time with potential explanations including temporal differences in patterns of heat exposure, adaptive mechanisms, asthma management, lifestyle, comorbidities and occupation.

Public Health Implications of Drought in a Climate Change Context: A Critical Review.

Extreme weather events are expected to increase due to climate change, which could pose an additional burden of morbidity and mortality. In recent decades, drought severity has increased in several regions around the world, affecting health by increasing the risk of water-, food-, and vector-borne diseases, malnutrition, cardiovascular and respiratory illness, mental health disorders, and mortality. Drought frequency and severity are expected to worsen across large regions as a result of a decrease in precipitation and an increase in temperature and atmospheric evaporative demand, posing a pressing challenge for public health. Variation in impacts among countries and communities is due to multiple factors, such as aging, socioeconomic status, access to health care, and gender, affecting population resilience. Integrative proactive action plans focused on risk management are required, and resources should be transferred to developing countries to reduce their vulnerability and risk.

Heat-related first cardiovascular event incidence in the city of Madrid (Spain): Vulnerability assessment by demographic, socioeconomic, and health indicators.

While climate change and population ageing are expected to increase the exposure and vulnerability to extreme heat events, there is emerging evidence suggesting that social inequalities would additionally magnify the projected health impacts. However, limited evidence exists on how social determinants modify heat-related cardiovascular morbidity. This study aims to explore the association between heat and the incidence of first acute cardiovascular event (CVE) in adults in Madrid between 2015 and 2018, and to assess how social context and other individual characteristics modify the estimated association. We performed a case-crossover study using the individual information collected from electronic medical records of 6514 adults aged 40-75 living in Madrid city that suffered a first CVE during summer (June-September) between 2015 and 2018. We applied conditional logistic regression with a distributed lag non-linear model to analyse the heat-CVE association. Estimates were expressed as Odds Ratio (OR) for extreme heat (at 97.5th percentile of daily maximum temperature distribution), compared to the minimum risk temperature. We performed stratified analyses by specific diagnosis, sex, age (40-64, 65-75), country of origin, area-level deprivation, and presence of comorbidities. Overall, the risk of suffering CVE increased by 15.3% (OR: 1.153 [95%CI 1.010-1.317]) during extreme heat. Males were particularly more affected (1.248, [1.059-1.471]), vs 1.039 [0.810-1.331] in females), and non-Spanish population (1.869 [1.28-2.728]), vs 1.084 [0.940-1.250] in Spanish). Similar estimates were found by age groups. We observed a dose-response pattern across deprivation levels, with larger risks in populations with higher deprivation (1.228 [1.031-1.462]) and almost null association in the lowest deprivation group (1.062 [0.836-1.349]). No clear patterns of larger vulnerability were found by presence of comorbidity. We found that heat unequally increased the risk of suffering CVE in adults in Madrid, affecting mainly males and deprived populations. Local measures should pay special attention to vulnerable populations.

Low ambient temperature and hospitalization for cardiorespiratory diseases in Brazil.

Studies have shown that larger temperature-related health impacts may be associated with cold rather than with hot temperatures. Although it remains unclear the cold-related health burden in warmer regions, in particular at the national level in Brazil. We address this gap by examining the association between low ambient temperature and daily hospital admissions for cardiovascular and respiratory diseases in Brazil between 2008 and 2018. We first applied a case time series design in combination with distributed lag non-linear modeling (DLNM) framework to assess the association of low ambient temperature with daily hospital admissions by Brazilian region. Here, we also stratified the analyses by sex, age group (15-45, 46-65, and >65 years), and cause (respiratory and cardiovascular hospital admissions). In the second stage, we performed a meta-analysis to estimate pooled effects across the Brazilian regions. Our sample included more than 23 million hospitalizations for cardiovascular and respiratory diseases nationwide between 2008 and 2018, of which 53% were admissions for respiratory diseases and 47% for cardiovascular diseases. Our findings suggest that low temperatures are associated with a relative risk of 1.17 (95% CI: 1.07; 1.27) and 1.07 (95% CI: 1.01; 1.14) for cardiovascular and respiratory admissions in Brazil, respectively. The pooled national results indicate robust positive associations for cardiovascular and respiratory hospital admissions in most of the subgroup analyses. In particular, for cardiovascular hospital admissions, men and older adults (>65 years old) were slightly more impacted by cold exposure. For respiratory admissions, the results did not indicate differences among the population groups by sex and age. This study can help decision-makers to create adaptive measures to protect public health from the effects of cold temperature.

The effect modification of extreme temperatures on mental and behavior disorders by environmental factors and individual-level characteristics in Canada.

OBJECTIVE: Ambient extreme temperatures have been associated with mental and behavior disorders (MBDs). However, few studies have assesed whether vulnerability factors such as ambient air pollution, pre-existing mental health conditions and residential environmental factors increase susceptibility. This study aims to evaluate the associations between short-term variations in outdoor ambient extreme temperatures and MBD-related emergency department (ED) visits and how these associations are modified by vulnerability factors. METHODS: We conducted a case-crossover study of 9,958,759 MBD ED visits in Alberta and Ontario, Canada made between March 1st, 2004 and December 31st, 2020. Daily average temperature was assigned to individual cases with ED visits for MBD using gridded data at a 1 km × 1 km spatial resolution. Conditional logistic regression was used to estimate associations between extreme temperatures (i.e., risk of ED visit at the 2.5th percentile temperature for cold and 97.5th percentile temperature for heat for each health region compared to the minimal temperature risk) and MBD ED visits. Age, sex, pre-existing mental health conditions, ambient air pollution (i.e. PM2.5, NO2 and O3) and residential environmental factors (neighborhood deprivation, residential green space exposure and urbanization) were evaluated as potential effect modifiers. RESULTS: Cumulative exposure to extreme heat over 0-5 days (odds ratio [OR] = 1.145; 95% CI: 1.121-1.171) was associated with ED visits for any MBD. However, cumulative exposure to extreme cold was associated with lower risk of ED visits for any MBD (OR = 0.981; 95% CI: 0.976-0.987). We also found heat to be associated with ED visits for specific MBDs such as substance use disorders, dementia, neurotic disorders, schizophrenia and personality behavior disorder. Individuals with pre-existing mental health conditions, those exposed to higher daily concentrations of NO2 and O3 and those residing in neighborhoods with greater material and social deprivation were at higher risk of heat-related MBD ED visits. Increasing tree canopy coverage appeared to mitigate risks of the effect of heat on MBD ED visits. CONCLUSIONS: Findings provide evidence that the impacts of heat on MBD ED visits may vary across different vulnerability factors.

Short-term air pollution exposure and hospital admissions for cardiorespiratory diseases in Brazil: A nationwide time-series study between 2008 and 2018.

The established evidence associating air pollution with health is limited to populations from specific regions. Further large-scale studies in several regions worldwide are needed to support the literature to date and encourage national governments to act. Brazil is an example of these regions where little research has been performed on a large scale. To address this gap, we conducted a study looking at the relationship between daily PM2.5, NO2, and O3, and hospital admissions for circulatory and respiratory diseases across Brazil between 2008 and 2018. A time-series analytic approach was applied with a distributed lag modeling framework. We used a generalized conditional quasi-Poisson regression model to estimate relative risks (RRs) of the association of each air pollutant with the hospitalization for circulatory and respiratory diseases by sex, age group, and Brazilian regions. Our study population includes 23, 791, 093 hospital admissions for cardiorespiratory diseases in Brazil between 2008 and 2018. Among those, 53.1% are respiratory diseases, and 46.9% are circulatory diseases. Our findings suggest significant associations of ambient air pollution (PM2.5, NO2, and O3) with respiratory and circulatory hospital admissions in Brazil. The national meta-analysis for the whole population showed that for every increase of PM2.5 by 10 µg/m3, there is a 3.28% (95%CI: 2.61; 3.94) increase in the risk of hospital admission for respiratory diseases. For O3, we found positive associations only for some sub-group analyses by age and sex. For NO2, our findings suggest that a 10 ppb increase in this pollutant, there was a 35.26% (95%CI: 24.07; 46.44) increase in the risk of hospital admission for respiratory diseases. This study may better support policymakers to improve the air quality and public health in Brazil.

How ambient temperature affects mood: an ecological momentary assessment study in Switzerland.

BACKGROUND: Recent research has suggested that an increase in temperature can negatively affect mental health and increase hospitalization for mental illness. It is not clear, however, what factors or mechanisms mediate this association. We aimed to (1) investigate the associations between ambient temperatures and bad daily mood, and (2) identify variables affecting the strength of these associations (modifiers) including the time, the day of the week and the year of the mood rating, socio-demographic characteristics, sleep quality, psychiatric disorders and the personality trait neuroticism in the community. METHODS: Data stemmed from the second follow-up evaluation of CoLaus|PsyCoLaus, a prospective cohort study conducted in the general population of Lausanne (Switzerland). The 906 participants rated their mood level four times a day during seven days using a cell phone app. Mixed-effects logistic regression was used to determine the association between daily maximum temperature and mood level. Participant ID was inserted as a random effect in the model, whereas the time of the day, the day of the week and the year were inserted as fixed effects. Models were controlled for several confounders (socio-demographic characteristics, sleep quality, weather parameters and air pollutants). Stratified analyses were conducted based on socio-demographic characteristics, sleep quality, presence of psychiatric disorders or a high neuroticism. RESULTS: Overall, the probability of having a bad mood for the entire day decreased by 7.0% (OR: 0.93: 95% CI 0.88, 0.99) for each 5 °C increase in maximum temperature. A smaller and less precise effect (-3%; OR: 0.97: 95% CI 0.91, 1.03) was found when controlling for sunshine duration. A higher association was found in participants with bipolar disorder (-23%; OR: 0.77: 95% CI 0.51, 1.17) and in participants with a high neuroticism (-13%; OR: 0.87 95% CI 0.80, 0.95), whereas the association was reversed for participants with anxiety (20%; OR: 1.20: 95% CI 0.90, 1.59), depression (18%; OR: 1.18 95% CI 0.94, 1.48) and schizophrenia (193%; OR: 2.93 95% CI 1.17, 7.73). CONCLUSIONS: According to our findings, rising temperatures may positively affect mood in the general population. However, individuals with certain psychiatric disorders, such as anxiety, depression, and schizophrenia, may exhibit altered responses to heat, which may explain their increased morbidity when exposed to high temperatures. This suggests that tailored public health policies are required to protect this vulnerable population.

How to repel a killer; chemical identification and effective repellent activity of commercial essential oils against kissing bugs.

Triatomines are haematophagous insects, some species are vectors of Trypanosoma cruzi, the aetiological agent of Chagas disease. The main strategy for interrupting T. cruzi transmission is to avoid contact of the vector populations with humans. Volatiles from commercial essential oils are excellent candidates to serve as repellents of kissing bugs. We used an exposure device to assess the repellence effect of eight commercial essential oils on Triatoma pallidipennis. The most effective oils were blended and evaluated against T. infestans, T. pallidipennis and Rhodnius prolixus. The blend was also evaluated on parasitised T. pallidipennis. Data were compared with the commercial repellent NN-diethyl-3-methylbenzamide. We recorded the time the insects spent in the proximity of the host and determined if any of the evaluated oils served as kissing bug repellent. We found commercial essential oils and a blend that significantly reduced the time spent in the proximity of the host. The blend was effective for use by human males and females, repelling infected and non-infected insects. The study of essential oils as repellents of blood-sucking disease-vector insects could shed light on the development of new control strategies.