Correction: Unique characteristics of new complete blood count parameters, the Immature Platelet Fraction and the Immature Platelet Fraction Count, in dengue patients.

[This corrects the article DOI: 10.1371/journal.pone.0258936.].

Heat-related mortality and ambulance transport after a power outage in the Tokyo metropolitan area.

Background: Air conditioners can prevent heat-related illness and mortality, but the increased use of air conditioners may enhance susceptibility to heat-related illnesses during large-scale power failures. Here, we examined the risks of heat-related illness ambulance transport (HIAT) and mortality associated with typhoon-related electricity reduction (ER) in the summer months in the Tokyo metropolitan area. Methods: We conducted event study analyses to compare temperature-HIAT and mortality associations before and after the power outage (July to September 2019). To better understand the role of temperature during the power outage, we then examined whether the temperature-HIAT and mortality associations were modified by different power outage levels (0%, 10%, and 20% ER). We computed the ratios of relative risks to compare the risks associated with various ER values to the risks associated without ER. Results: We analyzed the data of 14,912 HIAT cases and 74,064 deaths. Overall, 93,200 power outage cases were observed when the typhoon hit. Event study results showed that the incidence rate ratio was 2.01 (95% confidence interval [CI] = 1.42, 2.84) with effects enduring up to 6 days, and 1.11 (95% CI = 1.02, 1.22) for mortality on the first 3 days after the typhoon hit. Comparing 20% to 0% ER, the ratios of relative risks of heat exposure were 2.32 (95% CI = 1.41, 3.82) for HIAT and 0.95 (95% CI = 0.75, 1.22) for mortality. Conclusions: A 20% ER was associated with a two-fold greater risk of HIAT because of summer heat during the power outage, but there was little evidence for the association with all-cause mortality.

Association between ambient temperature and genitourinary emergency ambulance dispatches in Japan: A nationwide case-crossover study.

Background: Although the effects of temperature on genitourinary morbidity and mortality have been investigated in several countries, it remains largely unexplored in Japan. We investigated the association between ambient temperature and genitourinary emergency ambulance dispatches (EADs) in Japan and the modifying roles of sex, age, and illness severity. Methods: We conducted a time-stratified case-crossover study with conditional quasi-Poisson regression to estimate the association between mean temperature and genitourinary EADs in all prefectures of Japan between 2015 and 2019. A mixed-effects meta-analysis was used to pool the association at the country level. Subgroup analyses were performed to explore differences in associations stratified by sex, age, and illness severity. Results: We found an increased risk of genitourinary EAD associated with higher temperatures. The cumulative relative risk (RR) at the 99th temperature percentile compared with that at the 1st percentile was 1.74 (95% confidence interval (CI) = [1.60, 1.89]). We observed higher heat-related RRs in males (RR = 1.89; 95% CI = [1.73, 2.07]) than females (RR = 1.56; 95% CI = [1.37, 1.76]), and in the younger (RR = 2.13; 95% CI = [1.86, 2.45]) than elderly (RR = 1.39; 95% CI = [1.22, 1.58]). We found a significant association for those with mild or moderate cases (RR = 1.77; 95% CI = [1.62, 1.93]), but not for severe or life-threatening cases (RR = 1.20; 95% CI = [0.80, 1.82]). Conclusion: Our study revealed heat effects on genitourinary EADs in Japan. Men, youth, and mild-moderate illnesses were particularly vulnerable subgroups. These findings underscore the need for preventative measures aimed at mitigating the impact of temperature on genitourinary emergencies.

A comprehensive assessment of deworming coverage among pregnant women in low- and middle-income countries, 2000-30.

Background: Intestinal parasitic infections pose a significant global public health issue, particularly among pregnant women, who are generally more susceptible due to their elevated need for iron and nutrients. Deworming stands as a secure and efficacious public health intervention. The World Health Organization (WHO) set a target for the national deworming coverage rate among pregnant women at 75% by 2030. Nonetheless, the existing body of evidence on deworming among pregnant women in low- and middle-income countries (LMICs) remains limited. Methods: Based on Demographic Health Survey (DHS) data from 56 LMICs (n = 924 277) between 2000 and 2022, we used Bayesian hierarchical models to estimate trends of deworming coverage up to 2030 and to analyse determinant factors of deworming. Results: We found that, despite progress in deworming coverage estimates for most countries, only 11 (<20%) are on track to achieve the WHO target coverage at the national level. Inequality gaps were projected to increase in most LMICs. A multilevel model showed that increased numbers of antenatal care, access to safe water, and a higher wealth index were associated with higher odds of deworming. Conclusions: The progress on deworming coverage and inequality in many countries remains insufficient for achieving the WHO target by 2030. Additional investments in the health sector towards the expansion of deworming programmes, along with integration with existing health services, are urgently required, as is the introduction of effective policies and strengthening programmes within the context of the 'Leave No One Behind' agenda.

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.

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.

Associations between short-term exposure to ambient temperature and renal disease mortality in Japan during 1979-2019: A time-stratified case-crossover analysis.

Background: Previous studies have indicated that renal disease mortality is sensitive to ambient temperatures. However, most have been limited to the summer season with inconclusive evidence for changes in population vulnerability over time. Objective: This study aims to examine the association between short-term exposure to ambient temperatures and mortality due to renal diseases in Japan, and how this association varied over time. Methods: We conducted a two-stage, time-stratified case-crossover study from 1979 to 2019 across 47 prefectures of Japan. We obtained the data of daily mortality counts for all renal diseases, acute renal failure, and chronic renal disease. We fitted a conditional quasi-Poisson regression model with a distributed lag nonlinear model. A random-effects meta-analysis was applied to calculate national averages. We performed additional analyses by four subperiods, sex, and age groups. Results: We analyzed 997,590 renal mortality cases and observed a reversed J-shaped association. Lower temperatures were associated with increased mortality in all renal disease categories. The cumulative relative risks at 2.5th percentile compared to the minimum mortality temperature percentile were 1.34 (95% confidence interval [CI] = 1.29, 1.40), 1.51 (95% CI = 1.33, 1.71), and 1.33 (95% CI = 1.24, 1.43) for all renal, acute renal failure, and chronic renal disease mortality, respectively. The associations were observed in individuals of both sexes and aged 65 years and above. The associations of kidney mortality with low temperature remained consistent, while the associations with high temperature were pronounced in the past, but not in recent periods. Conclusions: Protection for individuals with impaired renal function from exposure to low temperatures during cold seasons is warranted.

Reconstructing individual-level exposures in cohort analyses of environmental risks: an example with the UK Biobank.

Recent developments in linkage procedures and exposure modelling offer great prospects for cohort analyses on the health risks of environmental factors. However, assigning individual-level exposures to large population-based cohorts poses methodological and practical problems. In this contribution, we illustrate a linkage framework to reconstruct environmental exposures for individual-level epidemiological analyses, discussing methodological and practical issues such as residential mobility and privacy concerns. The framework outlined here requires the availability of individual residential histories with related time periods, as well as high-resolution spatio-temporal maps of environmental exposures. The linkage process is carried out in three steps: (1) spatial alignment of the exposure maps and residential locations to extract address-specific exposure series; (2) reconstruction of individual-level exposure histories accounting for residential changes during the follow-up; (3) flexible definition of exposure summaries consistent with alternative research questions and epidemiological designs. The procedure is exemplified by the linkage and processing of daily averages of air pollution for the UK Biobank cohort using gridded spatio-temporal maps across Great Britain. This results in the extraction of exposure summaries suitable for epidemiological analyses of both short and long-term risk associations and, in general, for the investigation of temporal dependencies. The linkage framework presented here is generally applicable to multiple environmental stressors and can be extended beyond the reconstruction of residential exposures. IMPACT: This contribution describes a linkage framework to assign individual-level environmental exposures to population-based cohorts using high-resolution spatio-temporal exposure. The framework can be used to address current limitations of exposure assessment for the analysis of health risks associated with environmental stressors. The linkage of detailed exposure information at the individual level offers the opportunity to define flexible exposure summaries tailored to specific study designs and research questions. The application of the framework is exemplified by the linkage of fine particulate matter (PM2.5) exposures to the UK Biobank cohort.

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.

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.

Enhancing health resilience in Japan in a changing climate.

Climate change poses significant threats to human health, propelling Japan to take decisive action through the Climate Change Adaptation Act of 2018. This Act has led to the implementation of climate change adaptation policies across various sectors, including healthcare. In this review, we synthesized existing scientific evidence on the impacts of climate change on health in Japan and outlined the adaptation strategies and measures implemented by the central and local governments. The country has prioritized tackling heat-related illness and mortality and undertaken various adaptation measures to mitigate these risks. However, it faces unique challenges due to its super-aged society. Ensuring effective and coordinated strategies to address the growing uncertainties in vulnerability to climate change and the complex intersectoral impacts of disasters remains a critical issue. To combat the additional health risks by climate change, a comprehensive approach embracing adaptation and mitigation policies in the health sector is crucial. Encouraging intersectoral communication and collaboration will be vital for developing coherent and effective strategies to safeguard public health in the face of climate change.

Net impact of air conditioning on heat-related mortality in Japanese cities.

BACKGROUND: Air conditioning (AC) presents a viable means of tackling the ill-effects of heat on human health. However, AC releases additional anthropogenic heat outdoors, and this could be detrimental to human health, especially in urban communities. This study determined the excess heat-related mortality attributable to anthropogenic heat from AC use under various projected global warming scenarios in seven Japanese cities. The overall protection from AC use was also measured. METHODS: Daily average 2-meter temperatures in the hottest month of August from 2000 to 2010 were modeled using the Weather Research and Forecasting (WRF) model with BEP+BEM (building effect parameterization and building energy model). Risk functions for heat-mortality associations were generated with and without AC use from a two-stage time series analysis. We coupled simulated August temperatures and heat-mortality risk functions to estimate averted deaths and unavoidable deaths from AC use. RESULTS: Anthropogenic heat from AC use slightly augmented the daily urban temperatures by 0.046 °C in Augusts of 2000-2010 and up to 0.181 °C in a future with 3 °C urban warming. This temperature rise was attributable to 3.1-3.5 % of heat-related deaths in Augusts of 2000-2010 under various urban warming scenarios. About 36-47 % of heat-related deaths could be averted by air conditioning use under various urban warming scenarios. DISCUSSION: AC has a valuable protective effect from heat despite some unavoidable mortality from anthropogenic heat release. Overall, the use of AC as a major adaptive strategy requires careful consideration.

Interactive effects of ambient fine particulate matter and ozone on daily mortality in 372 cities: two stage time series analysis.

OBJECTIVE: To investigate potential interactive effects of fine particulate matter (PM2.5) and ozone (O3) on daily mortality at global level. DESIGN: Two stage time series analysis. SETTING: 372 cities across 19 countries and regions. POPULATION: Daily counts of deaths from all causes, cardiovascular disease, and respiratory disease. MAIN OUTCOME MEASURE: Daily mortality data during 1994-2020. Stratified analyses by co-pollutant exposures and synergy index (>1 denotes the combined effect of pollutants is greater than individual effects) were applied to explore the interaction between PM2.5 and O3 in association with mortality. RESULTS: During the study period across the 372 cities, 19.3 million deaths were attributable to all causes, 5.3 million to cardiovascular disease, and 1.9 million to respiratory disease. The risk of total mortality for a 10 µg/m3 increment in PM2.5 (lag 0-1 days) ranged from 0.47% (95% confidence interval 0.26% to 0.67%) to 1.25% (1.02% to 1.48%) from the lowest to highest fourths of O3 concentration; and for a 10 µg/m3 increase in O3 ranged from 0.04% (-0.09% to 0.16%) to 0.29% (0.18% to 0.39%) from the lowest to highest fourths of PM2.5 concentration, with significant differences between strata (P for interaction <0.001). A significant synergistic interaction was also identified between PM2.5 and O3 for total mortality, with a synergy index of 1.93 (95% confidence interval 1.47 to 3.34). Subgroup analyses showed that interactions between PM2.5 and O3 on all three mortality endpoints were more prominent in high latitude regions and during cold seasons. CONCLUSION: The findings of this study suggest a synergistic effect of PM2.5 and O3 on total, cardiovascular, and respiratory mortality, indicating the benefit of coordinated control strategies for both pollutants.

Joint effect of heat and air pollution on mortality in 620 cities of 36 countries.

BACKGROUND: The epidemiological evidence on the interaction between heat and ambient air pollution on mortality is still inconsistent. OBJECTIVES: To investigate the interaction between heat and ambient air pollution on daily mortality in a large dataset of 620 cities from 36 countries. METHODS: We used daily data on all-cause mortality, air temperature, particulate matter ≤ 10 µm (PM10), PM ≤ 2.5 µm (PM2.5), nitrogen dioxide (NO2), and ozone (O3) from 620 cities in 36 countries in the period 1995-2020. We restricted the analysis to the six consecutive warmest months in each city. City-specific data were analysed with over-dispersed Poisson regression models, followed by a multilevel random-effects meta-analysis. The joint association between air temperature and air pollutants was modelled with product terms between non-linear functions for air temperature and linear functions for air pollutants. RESULTS: We analyzed 22,630,598 deaths. An increase in mean temperature from the 75th to the 99th percentile of city-specific distributions was associated with an average 8.9 % (95 % confidence interval: 7.1 %, 10.7 %) mortality increment, ranging between 5.3 % (3.8 %, 6.9 %) and 12.8 % (8.7 %, 17.0 %), when daily PM10 was equal to 10 or 90 µg/m3, respectively. Corresponding estimates when daily O3 concentrations were 40 or 160 µg/m3 were 2.9 % (1.1 %, 4.7 %) and 12.5 % (6.9 %, 18.5 %), respectively. Similarly, a 10 µg/m3 increment in PM10 was associated with a 0.54 % (0.10 %, 0.98 %) and 1.21 % (0.69 %, 1.72 %) increase in mortality when daily air temperature was set to the 1st and 99th city-specific percentiles, respectively. Corresponding mortality estimate for O3 across these temperature percentiles were 0.00 % (-0.44 %, 0.44 %) and 0.53 % (0.38 %, 0.68 %). Similar effect modification results, although slightly weaker, were found for PM2.5 and NO2. CONCLUSIONS: Suggestive evidence of effect modification between air temperature and air pollutants on mortality during the warm period was found in a global dataset of 620 cities.

Hedgehog signaling guides migration of primordial germ cells to the Drosophila somatic gonad.

In addition to inducing nonautonomous specification of cell fate in both Drosophila and vertebrates, the Hedgehog pathway guides cell migration in a variety of different tissues. Although its role in axon guidance in the vertebrate nervous system is widely recognized, its role in guiding the migratory path of primordial germ cells (PGCs) from the outside surface of the Drosophila embryo through the midgut and mesoderm to the SGPs (somatic gonadal precursors) has been controversial. Here we present new experiments demonstrating (1) that Hh produced by mesodermal cells guides PGC migration, (2) that HMG CoenzymeA reductase (Hmgcr) potentiates guidance signals emanating from the SGPs, functioning upstream of hh and of 2 Hh pathway genes important for Hh-containing cytonemes, and (3) that factors required in Hh receiving cells in other contexts function in PGCs to help direct migration toward the SGPs. We also compare the data reported by 4 different laboratories that have studied the role of the Hh pathway in guiding PGC migration.

Lifestyle Risk Behaviours and Nutritional Status Associated with Mental Health Problems among Myanmar Adolescents: Secondary Analysis of a Nationwide 2016 School Survey.

Engaging in unhealthy lifestyles may be considered a risk factor for mental health problems, but there is limited evidence. This study aimed to identify the relationship between unhealthy lifestyles and mental health problems among Myanmar school-going adolescents. Global School Based Student Health Survey (GSHS) data from 2838 school-going adolescents from Myanmar were analysed. Bivariable and multivariable logistic regression analyses were applied. After adjusting for confounding variables, adolescents who were seated for more than three hours per day had higher odds of loneliness, anxiety-induced sleep disturbance, suicide ideation, and suicide attempts compared to others. Moreover, students who ate fruit less than one time per day were more likely to experience anxiety-induced sleep disturbance and suicidal ideation. Being a current drinker was significantly associated with suicidal ideation and attempt. Obese students were more likely to feel lonely compared to normal weight students. Our study indicates there is a strong association between unhealthy lifestyle behaviours and mental health problems among school adolescents in Myanmar.

Multi-OMIC analysis of Huntington disease reveals a neuroprotective astrocyte state.

Huntington disease (HD) is an incurable neurodegenerative disease characterized by neuronal loss and astrogliosis. One hallmark of HD is the selective neuronal vulnerability of striatal medium spiny neurons. To date, the underlying mechanisms of this selective vulnerability have not been fully defined. Here, we employed a multi-omic approach including single nucleus RNAseq (snRNAseq), bulk RNAseq, lipidomics, HTT gene CAG repeat length measurements, and multiplexed immunofluorescence on post-mortem brain tissue from multiple brain regions of HD and control donors. We defined a signature of genes that is driven by CAG repeat length and found it enriched in astrocytic and microglial genes. Moreover, weighted gene correlation network analysis showed loss of connectivity of astrocytic and microglial modules in HD and identified modules that correlated with CAG-repeat length which further implicated inflammatory pathways and metabolism. We performed lipidomic analysis of HD and control brains and identified several lipid species that correlate with HD grade, including ceramides and very long chain fatty acids. Integration of lipidomics and bulk transcriptomics identified a consensus gene signature that correlates with HD grade and HD lipidomic abnormalities and implicated the unfolded protein response pathway. Because astrocytes are critical for brain lipid metabolism and play important roles in regulating inflammation, we analyzed our snRNAseq dataset with an emphasis on astrocyte pathology. We found two main astrocyte types that spanned multiple brain regions; these types correspond to protoplasmic astrocytes, and fibrous-like - CD44-positive, astrocytes. HD pathology was differentially associated with these cell types in a region-specific manner. One protoplasmic astrocyte cluster showed high expression of metallothionein genes, the depletion of this cluster positively correlated with the depletion of vulnerable medium spiny neurons in the caudate nucleus. We confirmed that metallothioneins were increased in cingulate HD astrocytes but were unchanged or even decreased in caudate astrocytes. We combined existing genome-wide association studies (GWAS) with a GWA study conducted on HD patients from the original Venezuelan cohort and identified a single-nucleotide polymorphism in the metallothionein gene locus associated with delayed age of onset. Functional studies found that metallothionein overexpressing astrocytes are better able to buffer glutamate and were neuroprotective of patient-derived directly reprogrammed HD MSNs as well as against rotenone-induced neuronal death in vitro. Finally, we found that metallothionein-overexpressing astrocytes increased the phagocytic activity of microglia in vitro and increased the expression of genes involved in fatty acid binding. Together, we identified an astrocytic phenotype that is regionally-enriched in less vulnerable brain regions that can be leveraged to protect neurons in HD.

Global short-term mortality risk and burden associated with tropical cyclones from 1980 to 2019: a multi-country time-series study.

BACKGROUND: The global spatiotemporal pattern of mortality risk and burden attributable to tropical cyclones is unclear. We aimed to evaluate the global short-term mortality risk and burden associated with tropical cyclones from 1980 to 2019. METHODS: The wind speed associated with cyclones from 1980 to 2019 was estimated globally through a parametric wind field model at a grid resolution of 0·5°â€ˆ× 0·5°. A total of 341 locations with daily mortality and temperature data from 14 countries that experienced at least one tropical cyclone day (a day with maximum sustained wind speed associated with cyclones ≥17·5 m/s) during the study period were included. A conditional quasi-Poisson regression with distributed lag non-linear model was applied to assess the tropical cyclone-mortality association. A meta-regression model was fitted to evaluate potential contributing factors and estimate grid cell-specific tropical cyclone effects. FINDINGS: Tropical cyclone exposure was associated with an overall 6% (95% CI 4-8) increase in mortality in the first 2 weeks following exposure. Globally, an estimate of 97 430 excess deaths (95% empirical CI [eCI] 71 651-126 438) per decade were observed over the 2 weeks following exposure to tropical cyclones, accounting for 20·7 (95% eCI 15·2-26·9) excess deaths per 100 000 residents (excess death rate) and 3·3 (95% eCI 2·4-4·3) excess deaths per 1000 deaths (excess death ratio) over 1980-2019. The mortality burden exhibited substantial temporal and spatial variation. East Asia and south Asia had the highest number of excess deaths during 1980-2019: 28 744 (95% eCI 16 863-42 188) and 27 267 (21 157-34 058) excess deaths per decade, respectively. In contrast, the regions with the highest excess death ratios and rates were southeast Asia and Latin America and the Caribbean. From 1980-99 to 2000-19, marked increases in tropical cyclone-related excess death numbers were observed globally, especially for Latin America and the Caribbean and south Asia. Grid cell-level and country-level results revealed further heterogeneous spatiotemporal patterns such as the high and increasing tropical cyclone-related mortality burden in Caribbean countries or regions. INTERPRETATION: Globally, short-term exposure to tropical cyclones was associated with a significant mortality burden, with highly heterogeneous spatiotemporal patterns. In-depth exploration of tropical cyclone epidemiology for those countries and regions estimated to have the highest and increasing tropical cyclone-related mortality burdens is urgently needed to help inform the development of targeted actions against the increasing adverse health impacts of tropical cyclones under a changing climate. FUNDING: Australian Research Council and Australian National Health and Medical Research Council.

Effects of Desert Dust and Sandstorms on Human Health: A Scoping Review.

Desert dust and sandstorms are recurring environmental phenomena that are reported to produce serious health risks worldwide. This scoping review was conducted to identify the most likely health effects of desert dust and sandstorms and the methods used to characterize desert dust exposure from the existing epidemiological literature. We systematically searched PubMed/MEDLINE, Web of Science, and Scopus to identify studies that reported the effects of desert dust and sandstorms on human health. Search terms referred to desert dust or sandstorm exposure, names of major deserts, and health outcomes. Health effects were cross-tabulated with study design variables (e.g., epidemiological design and methods to quantify dust exposure), desert dust source, health outcomes and conditions. We identified 204 studies that met the inclusion criteria for the scoping review. More than half of the studies (52.9%) used a time-series study design. However, we found a substantial variation in the methods used to identify and quantify desert dust exposure. The binary metric of dust exposure was more frequently used than the continuous metric for all desert dust source locations. Most studies (84.8%) reported significant associations between desert dust and adverse health effects, mainly for respiratory and cardiovascular mortality and morbidity causes. Although there is a large body of evidence on the health effects of desert dust and sandstorms, the existing epidemiological studies have significant limitations related to exposure measurement and statistical analysis that potentially contribute to inconsistencies in determining the effect of desert dust on human health.

Short-Term Association between Sulfur Dioxide and Mortality: A Multicountry Analysis in 399 Cities.

BACKGROUND: Epidemiological evidence on the health risks of sulfur dioxide (SO2) is more limited compared with other pollutants, and doubts remain on several aspects, such as the form of the exposure-response relationship, the potential role of copollutants, as well as the actual risk at low concentrations and possible temporal variation in risks. OBJECTIVES: Our aim was to assess the short-term association between exposure to SO2 and daily mortality in a large multilocation data set, using advanced study designs and statistical techniques. METHODS: The analysis included 43,729,018 deaths that occurred in 399 cities within 23 countries between 1980 and 2018. A two-stage design was applied to assess the association between the daily concentration of SO2 and mortality counts, including first-stage time-series regressions and second-stage multilevel random-effect meta-analyses. Secondary analyses assessed the exposure-response shape and the lag structure using spline terms and distributed lag models, respectively, and temporal variations in risk using a longitudinal meta-regression. Bi-pollutant models were applied to examine confounding effects of particulate matter with an aerodynamic diameter of ≤10µm (PM10) and 2.5µm (PM2.5), ozone, nitrogen dioxide, and carbon monoxide. Associations were reported as relative risks (RRs) and fractions of excess deaths. RESULTS: The average daily concentration of SO2 across the 399 cities was 11.7 µg/m3, with 4.7% of days above the World Health Organization (WHO) guideline limit (40 µg/m3, 24-h average), although the exceedances occurred predominantly in specific locations. Exposure levels decreased considerably during the study period, from an average concentration of 19.0 µg/m3 in 1980-1989 to 6.3 µg/m3 in 2010-2018. For all locations combined, a 10-µg/m3 increase in daily SO2 was associated with an RR of mortality of 1.0045 [95% confidence interval (CI): 1.0019, 1.0070], with the risk being stable over time but with substantial between-country heterogeneity. Short-term exposure to SO2 was associated with an excess mortality fraction of 0.50% [95% empirical CI (eCI): 0.42%, 0.57%] in the 399 cities, although decreasing from 0.74% (0.61%, 0.85%) in 1980-1989 to 0.37% (0.27%, 0.47%) in 2010-2018. There was some evidence of nonlinearity, with a steep exposure-response relationship at low concentrations and the risk attenuating at higher levels. The relevant lag window was 0-3 d. Significant positive associations remained after controlling for other pollutants. DISCUSSION: The analysis revealed independent mortality risks associated with short-term exposure to SO2, with no evidence of a threshold. Levels below the current WHO guidelines for 24-h averages were still associated with substantial excess mortality, indicating the potential benefits of stricter air quality standards. https://doi.org/10.1289/EHP11112.