Geographical Patterns in Mortality Impacts Due To Heatwaves of Different Characteristics in Spanish Cities.

The impact of heatwaves (HWs) on human health is a topic of growing interest due to the global magnification of these phenomena and their substantial socio-economic impacts. As for other countries of Southern Europe, Spain is a region highly affected by heat and its increase under climate change. This is observed in the mean values and the increasing incidence of extreme weather events and associated mortality. Despite the vast knowledge on this topic, it remains unclear whether specific types and characteristics of HW are particularly harmful to the population and whether this shows a regional interdependency. The present study provides a comprehensive analysis of the relationship between HW characteristics and mortality in 12 Spanish cities. We used separated time series analysis in each city applying a quasi-Poisson regression model and distributed lag linear and non-linear models. Results show an increase in the mortality risk under HW conditions in the cities with a lower HW frequency. However, this increase exhibits remarkable differences across the cities under study not showing any general pattern in the HW characteristics-mortality association. This relationship is shown to be complex and strongly dependent on the local properties of each city pointing out the crucial need to examine and understand on a local scale the HW characteristics and the HW-mortality relationship for an efficient design and implementation of prevention measures.

Regional variation in the role of humidity on city-level heat-related mortality.

The rising humid heat is regarded as a severe threat to human survivability, but the proper integration of humid heat into heat-health alerts is still being explored. Using state-of-the-art epidemiological and climatological datasets, we examined the association between multiple heat stress indicators (HSIs) and daily human mortality in 739 cities worldwide. Notable differences were observed in the long-term trends and timing of heat events detected by HSIs. Air temperature (Tair) predicts heat-related mortality well in cities with a robust negative Tair-relative humidity correlation (CT-RH). However, in cities with near-zero or weak positive CT-RH, HSIs considering humidity provide enhanced predictive power compared to Tair. Furthermore, the magnitude and timing of heat-related mortality measured by HSIs could differ largely from those associated with Tair in many cities. Our findings provide important insights into specific regions where humans are vulnerable to humid heat and can facilitate the further enhancement of heat-health alert systems.

Heat, humidity and health impacts: how causal diagrams can help tell the complex story.

The global health burden associated with exposure to heat is a grave concern and is projected to further increase under climate change. While physiological studies have demonstrated the role of humidity alongside temperature in exacerbating heat stress for humans, epidemiological findings remain conflicted. Understanding the intricate relationships between heat, humidity, and health outcomes is crucial to inform adaptation and drive increased global climate change mitigation efforts. This article introduces 'directed acyclic graphs' (DAGs) as causal models to elucidate the analytical complexity in observational epidemiological studies that focus on humid-heat-related health impacts. DAGs are employed to delineate implicit assumptions often overlooked in such studies, depicting humidity as a confounder, mediator, or an effect modifier. We also discuss complexities arising from using composite indices, such as wet-bulb temperature. DAGs representing the health impacts associated with wet-bulb temperature help to understand the limitations in separating the individual effect of humidity from the perceived effect of wet-bulb temperature on health. General examples for regression models corresponding to each of the causal assumptions are also discussed. Our goal is not to prioritize one causal model but to discuss the causal models suitable for representing humid-heat health impacts and highlight the implications of selecting one model over another. We anticipate that the article will pave the way for future quantitative studies on the topic and motivate researchers to explicitly characterize the assumptions underlying their models with DAGs, facilitating accurate interpretations of the findings. This methodology is applicable to similarly complex compound events.

All-cause, cardiovascular, and respiratory mortality and wildfire-related ozone: a multicountry two-stage time series analysis.

BACKGROUND: Wildfire activity is an important source of tropospheric ozone (O3) pollution. However, no study to date has systematically examined the associations of wildfire-related O3 exposure with mortality globally. METHODS: We did a multicountry two-stage time series analysis. From the Multi-City Multi-Country (MCC) Collaborative Research Network, data on daily all-cause, cardiovascular, and respiratory deaths were obtained from 749 locations in 43 countries or areas, representing overlapping periods from Jan 1, 2000, to Dec 31, 2016. We estimated the daily concentration of wildfire-related O3 in study locations using a chemical transport model, and then calibrated and downscaled O3 estimates to a resolution of 0·25°â€ˆ× 0·25° (approximately 28 km2 at the equator). Using a random-effects meta-analysis, we examined the associations of short-term wildfire-related O3 exposure (lag period of 0-2 days) with daily mortality, first at the location level and then pooled at the country, regional, and global levels. Annual excess mortality fraction in each location attributable to wildfire-related O3 was calculated with pooled effect estimates and used to obtain excess mortality fractions at country, regional, and global levels. FINDINGS: Between 2000 and 2016, the highest maximum daily wildfire-related O3 concentrations (≥30 µg/m3) were observed in locations in South America, central America, and southeastern Asia, and the country of South Africa. Across all locations, an increase of 1 µg/m3 in the mean daily concentration of wildfire-related O3 during lag 0-2 days was associated with increases of 0·55% (95% CI 0·29 to 0·80) in daily all-cause mortality, 0·44% (-0·10 to 0·99) in daily cardiovascular mortality, and 0·82% (0·18 to 1·47) in daily respiratory mortality. The associations of daily mortality rates with wildfire-related O3 exposure showed substantial geographical heterogeneity at the country and regional levels. Across all locations, estimated annual excess mortality fractions of 0·58% (95% CI 0·31 to 0·85; 31 606 deaths [95% CI 17 038 to 46 027]) for all-cause mortality, 0·41% (-0·10 to 0·91; 5249 [-1244 to 11 620]) for cardiovascular mortality, and 0·86% (0·18 to 1·51; 4657 [999 to 8206]) for respiratory mortality were attributable to short-term exposure to wildfire-related O3. INTERPRETATION: In this study, we observed an increase in all-cause and respiratory mortality associated with short-term wildfire-related O3 exposure. Effective risk and smoke management strategies should be implemented to protect the public from the impacts of wildfires. FUNDING: Australian Research Council and the Australian National Health and Medical Research Council.

Analyzing the effects of drought at different time scales on cause-specific mortality in South Africa.

South Africa (SA) is highly vulnerable to the effects of drought on the environment, economy, and society. However, its effect on human health remains unclear. Understanding the mortality risk associated with different types of droughts in different population groups and by specific causes would help clarify the potential mechanisms involved. The study aims to comprehensively assess the effect of droughts of varying time scales on cause-specific mortality (all; infectious and parasitic; endocrine, nutritional, and metabolic; cardiovascular; respiratory) in SA (from 2009-2016) and identify more vulnerable profiles based on sex and age. We also evaluated the urbanicity and district-level socioeconomic deprivation as potential risk modifiers. We used a two-stage time-series study design, with the weekly standardized precipitation-evapotranspiration index (SPEI) calculated at 1, 6, 12, and 15 months of accumulation to identify droughts of different duration (SPEI1, 6, 12, 15, respectively). We applied a quasi-Poisson regression adjusted by mean temperature to assess the association between each type of drought and weekly mortality in all district municipalities of SA, and then pooled the estimates in a meta-regression model. We reported relative risks (RRs) for one unit increase of drought severity. Overall, we found a positive association between droughts (regardless the time scale) and all causes of death analyzed. The strongest associations were found for the drought events more prolonged (RR [95%CI]: 1.027 [1.018, 1.036] (SPEI1); 1.035 [1.021, 1.050] (SPEI6); 1.033 [1.008, 1.058] (SPEI12); 1.098 [1.068, 1.129] (SPEI15)) and respiratory mortality (RRs varied from 1.037 [1.021, 1.053] (SPEI1) to 1.189 [1.14, 1.241] (SPEI15)). An indication of greater vulnerability was found in younger adults for the shortest droughts, in older adults for medium-term and long-term droughts, and children for very long-term droughts. However, differences were not significant. Further evidence of the relevance of urbanicity and demographic and socioeconomic conditions as potential risk modifiers is needed.

Global and Regional Cardiovascular Mortality Attributable to Nonoptimal Temperatures Over Time.

BACKGROUND: The association between nonoptimal temperatures and cardiovascular mortality risk is recognized. However, a comprehensive global assessment of this burden is lacking. OBJECTIVES: The goal of this study was to assess global cardiovascular mortality burden attributable to nonoptimal temperatures and investigate spatiotemporal trends. METHODS: Using daily cardiovascular deaths and temperature data from 32 countries, a 3-stage analytical approach was applied. First, location-specific temperature-mortality associations were estimated, considering nonlinearity and delayed effects. Second, a multivariate meta-regression model was developed between location-specific effect estimates and 5 meta-predictors. Third, cardiovascular deaths associated with nonoptimal, cold, and hot temperatures for each global grid (55 km × 55 km resolution) were estimated, and temporal trends from 2000 to 2019 were explored. RESULTS: Globally, 1,801,513 (95% empirical CI: 1,526,632-2,202,831) annual cardiovascular deaths were associated with nonoptimal temperatures, constituting 8.86% (95% empirical CI: 7.51%-12.32%) of total cardiovascular mortality corresponding to 26 deaths per 100,000 population. Cold-related deaths accounted for 8.20% (95% empirical CI: 6.74%-11.57%), whereas heat-related deaths accounted for 0.66% (95% empirical CI: 0.49%-0.98%). The mortality burden varied significantly across regions, with the highest excess mortality rates observed in Central Asia and Eastern Europe. From 2000 to 2019, cold-related excess death ratios decreased, while heat-related ratios increased, resulting in an overall decline in temperature-related deaths. Southeastern Asia, Sub-Saharan Africa, and Oceania observed the greatest reduction, while Southern Asia experienced an increase. The Americas and several regions in Asia and Europe displayed fluctuating temporal patterns. CONCLUSIONS: Nonoptimal temperatures substantially contribute to cardiovascular mortality, with heterogeneous spatiotemporal patterns. Effective mitigation and adaptation strategies are crucial, especially given the increasing heat-related cardiovascular deaths amid climate change.

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.

Comparison for the effects of different components of temperature variability on mortality: A multi-country time-series study.

BACKGROUND: Temperature variability (TV) is associated with increased mortality risk. However, it is still unknown whether intra-day or inter-day TV has different effects. OBJECTIVES: We aimed to assess the association of intra-day TV and inter-day TV with all-cause, cardiovascular, and respiratory mortality. METHODS: We collected data on total, cardiovascular, and respiratory mortality and meteorology from 758 locations in 47 countries or regions from 1972 to 2020. We defined inter-day TV as the standard deviation (SD) of daily mean temperatures across the lag interval, and intra-day TV as the average SD of minimum and maximum temperatures on each day. In the first stage, inter-day and intra-day TVs were modelled simultaneously in the quasi-Poisson time-series model for each location. In the second stage, a multi-level analysis was used to pool the location-specific estimates. RESULTS: Overall, the mortality risk due to each interquartile range [IQR] increase was higher for intra-day TV than for inter-day TV. The risk increased by 0.59% (95% confidence interval [CI]: 0.53, 0.65) for all-cause mortality, 0.64% (95% CI: 0.56, 0.73) for cardiovascular mortality, and 0.65% (95% CI: 0.49, 0.80) for respiratory mortality per IQR increase in intra-day TV0-7 (0.9 °C). An IQR increase in inter-day TV0-7 (1.6 °C) was associated with 0.22% (95% CI: 0.18, 0.26) increase in all-cause mortality, 0.44% (95% CI: 0.37, 0.50) increase in cardiovascular mortality, and 0.31% (95% CI: 0.21, 0.41) increase in respiratory mortality. The proportion of all-cause deaths attributable to intra-day TV0-7 and inter-day TV0-7 was 1.45% and 0.35%, respectively. The mortality risks varied by lag interval, climate area, season, and climate type. CONCLUSIONS: Our results indicated that intra-day TV may explain the main part of the mortality risk related to TV and suggested that comprehensive evaluations should be proposed in more countries to help protect human health.

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.

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.

Evaluation of the utility and cost of secondary confirmatory testing for Neisseria gonorrhoeae identification from culture.

Current guideline recommends the use of two identification methods for Neisseria gonorrhoeae. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) is now used for primary identification and may be sufficient for definitive identification of N. gonorrhoeae. The performance of three secondary tests (BactiCard, RapID NH and NET test) were compared using 45 bacterial isolates, including 37 Neisseria species. These secondary tests demonstrated diminished specificity (67% - 88%) for N. gonorrhoeae compared with MALDI-TOF. Additionally, data from six clinical microbiology laboratories was used to compare confirmatory test costs and the agreement of results with MALDI-TOF. Discrepancies were documented for 9.4% of isolates, though all isolates (n= 288) identified by MALDI-TOF as N. gonorrhoeae were confirmed by the reference laboratory. These data demonstrate that MALDI-TOF alone is sufficient for N. gonorrhoeae identification, as secondary did not add diagnostic value but do add costs to the testing process.

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.

Seasonality of mortality under climate change: a multicountry projection study.

BACKGROUND: Climate change can directly impact temperature-related excess deaths and might subsequently change the seasonal variation in mortality. In this study, we aimed to provide a systematic and comprehensive assessment of potential future changes in the seasonal variation, or seasonality, of mortality across different climate zones. METHODS: In this modelling study, we collected daily time series of mean temperature and mortality (all causes or non-external causes only) via the Multi-Country Multi-City Collaborative (MCC) Research Network. These data were collected during overlapping periods, spanning from Jan 1, 1969 to Dec 31, 2020. We projected daily mortality from Jan 1, 2000 to Dec 31, 2099, under four climate change scenarios corresponding to increasing emissions (Shared Socioeconomic Pathways [SSP] scenarios SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5). We compared the seasonality in projected mortality between decades by its shape, timings (the day-of-year) of minimum (trough) and maximum (peak) mortality, and sizes (peak-to-trough ratio and attributable fraction). Attributable fraction was used to measure the burden of seasonality of mortality. The results were summarised by climate zones. FINDINGS: The MCC dataset included 126 809 537 deaths from 707 locations within 43 countries or areas. After excluding the only two polar locations (both high-altitude locations in Peru) from climatic zone assessments, we analysed 126 766 164 deaths in 705 locations aggregated in four climate zones (tropical, arid, temperate, and continental). From the 2000s to the 2090s, our projections showed an increase in mortality during the warm seasons and a decrease in mortality during the cold seasons, albeit with mortality remaining high during the cold seasons, under all four SSP scenarios in the arid, temperate, and continental zones. The magnitude of this changing pattern was more pronounced under the high-emission scenarios (SSP3-7.0 and SSP5-8.5), substantially altering the shape of seasonality of mortality and, under the highest emission scenario (SSP5-8.5), shifting the mortality peak from cold seasons to warm seasons in arid, temperate, and continental zones, and increasing the size of seasonality in all zones except the arid zone by the end of the century. In the 2090s compared with the 2000s, the change in peak-to-trough ratio (relative scale) ranged from 0·96 to 1·11, and the change in attributable fraction ranged from 0·002% to 0·06% under the SSP5-8.5 (highest emission) scenario. INTERPRETATION: A warming climate can substantially change the seasonality of mortality in the future. Our projections suggest that health-care systems should consider preparing for a potentially increased demand during warm seasons and sustained high demand during cold seasons, particularly in regions characterised by arid, temperate, and continental climates. FUNDING: The Environment Research and Technology Development Fund of the Environmental Restoration and Conservation Agency, provided by the Ministry of the Environment of Japan.

Ozone-related acute excess mortality projected to increase in the absence of climate and air quality controls consistent with the Paris Agreement.

Short-term exposure to ground-level ozone in cities is associated with increased mortality and is expected to worsen with climate and emission changes. However, no study has yet comprehensively assessed future ozone-related acute mortality across diverse geographic areas, various climate scenarios, and using CMIP6 multi-model ensembles, limiting our knowledge on future changes in global ozone-related acute mortality and our ability to design targeted health policies. Here, we combine CMIP6 simulations and epidemiological data from 406 cities in 20 countries or regions. We find that ozone-related deaths in 406 cities will increase by 45 to 6,200 deaths/year between 2010 and 2014 and between 2050 and 2054, with attributable fractions increasing in all climate scenarios (from 0.17% to 0.22% total deaths), except the single scenario consistent with the Paris Climate Agreement (declines from 0.17% to 0.15% total deaths). These findings stress the need for more stringent air quality regulations, as current standards in many countries are inadequate.

Impact of population aging on future temperature-related mortality at different global warming levels.

Older adults are generally amongst the most vulnerable to heat and cold. While temperature-related health impacts are projected to increase with global warming, the influence of population aging on these trends remains unclear. Here we show that at 1.5 °C, 2 °C, and 3 °C of global warming, heat-related mortality in 800 locations across 50 countries/areas will increase by 0.5%, 1.0%, and 2.5%, respectively; among which 1 in 5 to 1 in 4 heat-related deaths can be attributed to population aging. Despite a projected decrease in cold-related mortality due to progressive warming alone, population aging will mostly counteract this trend, leading to a net increase in cold-related mortality by 0.1%-0.4% at 1.5-3 °C global warming. Our findings indicate that population aging constitutes a crucial driver for future heat- and cold-related deaths, with increasing mortality burden for both heat and cold due to the aging population.

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.

Lessons to be popular: the chemical basis of aggregation in Trypanosoma cruzi-infected and non-infected Chagasic bugs.

Aggregation is one of the most remarkable behaviours in the animal kingdom-a process that is usually governed by pheromones. Triatomines are blood-sucking bugs that act as vectors of Trypanosoma cruzi, the etiological agent of Chagas disease in mammals, including humans. Triatomines usually gather in roosting refuges by using aggregation pheromones of unknown chemical structure. In terms of vector control, one option to reduce triatomine-human contact is via capturing the insects into traps baited with lures based on such aggregation pheromones. As a first step towards this aim, we elucidated the aggregation pheromone in the triatomine Triatoma pallidipennis, using T. cruzi-infected and non-infected bugs. We used different extraction techniques and gas chromatography coupled to mass spectrometry for the identification. Also, two different bioassays were implemented for evaluating the attractant and arrestant activity of the pheromone. We found that T. pallidipennis produced short-chain aldehydes as attractants, and nitrogen-derived compounds as arrestants. We detected differences in the production and perception of these compounds according to whether animals were infected or not. These findings show that T. cruzi may influence triatomine chemical ecology and are promising tools for triatomine control.

Fluctuating risk of acute kidney injury-related mortality for four weeks after exposure to air pollution: A multi-country time-series study in 6 countries.

BACKGROUND: Recent studies have reported that air pollution is related to kidney diseases. However, the global evidence on the risk of death from acute kidney injury (AKI) owing to air pollution is limited. Therefore, we investigated the association between short-term exposure to air pollution-particulate matter ≤ 2.5 µm (PM2.5), ozone (O3), and nitrogen dioxide (NO2)-and AKI-related mortality using a multi-country dataset. METHODS: This study included 41,379 AKI-related deaths in 136 locations in six countries during 1987-2018. A novel case time-series design was applied to each air pollutant during 0-28 lag days to estimate the association between air pollution and AKI-related deaths. Moreover, we calculated AKI deaths attributable to non-compliance with the World Health Organization (WHO) air quality guidelines. RESULTS: The relative risks (95% confidence interval) of AKI-related deaths are 1.052 (1.003, 1.103), 1.022 (0.994, 1.050), and 1.022 (0.982, 1.063) for 5, 10, and 10 µg/m3 increase in lag 0-28 days of PM2.5, warm-season O3, and NO2, respectively. The lag-distributed association showed that the risk appeared immediately on the day of exposure to air pollution, gradually decreased, and then increased again reaching the peak approximately 20 days after exposure to PM2.5 and O3. We also found that 1.9%, 6.3%, and 5.2% of AKI deaths were attributed to PM2.5, warm-season O3, and NO2 concentrations above the WHO guidelines. CONCLUSIONS: This study provides evidence that public health policies to reduce air pollution may alleviate the burden of death from AKI and suggests the need to investigate the several pathways between air pollution and AKI death.

Consultas tardías en los servicios de emergencias pediátricas durante la pandemia por COVID-19 en Uruguay, entre el 13 de marzo y el 29 de julio de 2020 / Delayed visits to Pediatric Emergency Departments during the COVID-19 pandemic in Uruguay between March 13 and July 29, 2020 / Consultas tardias nos Serviços de Emergência Pediátrica durante a pandemia de COVID-19 no Uruguai entre 13 de março e 29 de julho de 2020

En diciembre de 2019, en Wuhan, China, se detectaron los primeros casos de SARS-CoV-2. En Uruguay, desde el 16 de marzo de 2020 se suspendieron las actividades de enseñanza, deportivas y espectáculos públicos. Varios países reportaron una marcada disminución de las visitas a urgencias. Algunos niños presentaron enfermedades ocasionales o descompensaciones de enfermedades crónicas, consultando en forma tardía con el riesgo que ello implica. El objetivo de este trabajo es realizar una descripción de las consultas tardías durante la pandemia. Se realizó un estudio multicéntrico y descriptivo entre el 13 de marzo y el 29 de julio de 2020. Se definió consulta tardía como los ingresos por injurias agudas con más de 6 horas de evolución, fiebre mayor a 72 horas de evolución, dificultad respiratoria con más de 12 horas de evolución, síntomas agudos, como dolor abdominal, de más de 24 horas de evolución, síntomas de más de 12 horas de evolución en niños con enfermedades crónicas que determinaron descompensación e ingreso. Se incluyeron 27 centros. Se registraron un total de 34.260 consultas en urgencia, se incluyeron 189 niños para el estudio. El promedio de edad fue de 6 años; 17 pacientes requirieron ingreso a unidad de cuidados intensivos (UCI). Predominó la apendicitis entre los diagnósticos al alta. Esta investigación puso en evidencia la existencia de consultas tardías en nuestro país. Esto contribuye a ponderar el impacto negativo de la pandemia en la población pediátrica.

In December 2019, the first cases of SARS-CoV-2 were detected in Wuhan. In Uruguay, since March 16, teaching, sports and public entertainment activities were suspended. Several countries reported a marked decrease in emergency room visits. Some children presented occasional illnesses or decompensations from chronic illnesses, consulting late with the risk that this implies. The objective of the work is to make a description of late consultations during the pandemic. A multicenter and descriptive study was carried out between March 13 and July 29, 2020. "Late consultation" was defined as admissions for: Acute injuries with more than 6 hours of evolution, fever greater than 72 hours of evolution, difficulty respiratory disease with more than 12 hours of evolution, acute symptoms such as abdominal pain of more than 24 hours of evolution, symptoms of more than 12 hours of evolution in children with chronic diseases that determined decompensation and admission. 27 centers were included. A total of 34260 emergency consultations were registered, 189 children were included for the study. The average age was 6 years. 17 patients required admission to the ICU. Appendicitis predominated among the diagnoses at discharge. This research revealed the existence of late consultations in our country. This helps to weigh the negative impact of the pandemic on the pediatric population.

Em dezembro de 2019, em Wuhan, foram detectados os primeiros casos de SARS-CoV-2. No Uruguai, desde 16 de março, as atividades de ensino, esporte e entretenimento público foram suspensas. Vários países relataram uma diminuição acentuada nas visitas ao pronto-socorro. Algumas crianças apresentavam doenças ocasionais ou descompensações de doenças crônicas, consultando tardiamente os riscos que isso implica. O objetivo do trabalho é fazer uma descrição das consultas tardias durante a pandemia. Um estudo multicêntrico e descritivo foi realizado entre 13 de março e 29 de julho de 2020. Consulta tardia foi definida como internações por: Lesões agudas com mais de 6 horas de evolução, febre maior que 72 horas de evolução, dificuldade respiratória com mais de 12 horas de evolução, sintomas agudos como dor abdominal com mais de 24 horas de evolução, sintomas com mais de 12 horas de evolução em crianças com doenças crônicas que determinaram descompensação e internação. 26 centros foram incluídos. Um total de 34.260 consultas de emergência foram registradas, 189 crianças foram incluídas no estudo. A idade média era de 6 anos. 17 pacientes necessitaram de internação na UTI. Apendicite predominou entre os diagnósticos na alta. Esta pesquisa revelou a existência de consultas tardias em nosso país. Isso ajuda a pesar o impacto negativo da pandemia na população pediátrica.

A Nationwide Comparative Analysis of Temperature-Related Mortality and Morbidity in Japan.

BACKGROUND: The impact of temperature on morbidity remains largely unknown. Moreover, extensive evidence indicates contrasting patterns between temperature-mortality and temperature-morbidity associations. A nationwide comparison of the impact of temperature on mortality and morbidity in more specific subgroups is necessary to strengthen understanding and help explore underlying mechanisms by identifying susceptible populations. OBJECTIVE: We performed this study to quantify and compare the impact of temperature on mortality and morbidity in 47 prefectures in Japan. METHODS: We applied a two-stage time-series design with distributed lag nonlinear models and mixed-effect multivariate meta-analysis to assess the association of temperature with mortality and morbidity by causes (all-cause, circulatory, and respiratory) at prefecture and country levels between 2015 and 2019. Subgroup analysis was conducted by sex, age, and regions. RESULTS: The patterns and magnitudes of temperature impacts on morbidity and mortality differed. For all-cause outcomes, cold exhibited larger effects on mortality, and heat showed larger effects on morbidity. At specific temperature percentiles, cold (first percentile) was associated with a higher relative risk (RR) of mortality [1.45; 95% confidence interval (CI): 1.39, 1.52] than morbidity (1.33; 95% CI: 1.26, 1.40), as compared to the minimum mortality/morbidity temperature. Heat (99th percentile) was associated with a higher risk of morbidity (1.30; 95% CI: 1.28, 1.33) than mortality (1.04; 95% CI: 1.02, 1.06). For cause-specific diseases, mortality due to circulatory diseases was more susceptible to heat and cold than morbidity. However, for respiratory diseases, both cold and heat showed higher risks for morbidity than mortality. Subgroup analyses suggested varied associations depending on specific outcomes. DISCUSSION: Distinct patterns were observed for the association of temperature with mortality and morbidity, underlying different mechanisms of temperature on different end points, and the differences in population susceptibility are possible explanations. Future mitigation policies and preventive measures against nonoptimal temperatures should be specific to disease outcomes and targeted at susceptible populations. https://doi.org/10.1289/EHP12854.