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-speci fi c cardiovascular deaths. METHODS: We used uni fi ed data collection protocols within the Multi-Country Multi-City Collaborative Network to assemble a database of daily counts of speci fi c cardiovascular causes of death from 567 cities in 27 countries across 5 continents in overlapping periods ranging from 1979 to 2019. City-speci fi c daily ambient temperatures were obtained from weather stations and climate reanalysis models. To investigate cardiovascular mortality associations with extreme hot and cold temperatures, we fi t 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

Rapamycin and the transcription factor C/EBPβ as a switch in osteoclast differentiation: implications for lytic bone diseases

Lytic bone diseases and in particular osteoporosis are common age-related diseases characterized by enhanced bone fragility due to loss of bone density. Increasingly, osteoporosis poses a major global health-care problem due to the growth of the elderly population. Recently, it was found that the gene regulatory transcription factor CCAAT/enhancer binding protein beta (C/EBPβ) is involved in bone metabolism. C/EBPβ occurs as different protein isoforms of variable amino terminal length, and regulation of the C/EBPβ isoform ratio balance was found to represent an important factor in osteoclast differentiation and bone homeostasis. Interestingly, adjustment of the C/EBPβ isoform ratio by the process of translational control is downstream of the mammalian target of rapamycin kinase (mTOR), a sensor of the nutritional status and a target of immunosuppressive and anticancer drugs. The findings imply that modulating the process of translational control of C/EBPβ isoform expression could represent a novel therapeutic approach in osteolytic bone diseases, including cancer and infection-induced bone loss

Seasonality of mortality under climate change: a multicountry projection study

Data sharing: All data used in our study were obtained from the MCC Collaborative Research Network under a data-sharing agreement and cannot be made publicly available. Researchers can refer to collaborators of the Network, who are listed as coauthors of this Article (primary contact: Antonio Gasparrini, [email protected]), for information on accessing the data for each country. The R code is available on request, and a reproducible example is publicly available on the personal GitHub website of the first author (https://github.com/LinaMadaniyazi).For more on the MCC see https://mccstudy.lshtm.ac.uk/Supplementary Material is available online at: https://www.sciencedirect.com/science/article/pii/S2542519623002693#sec1 .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.This study was primarily supported by the Environment Research and Technology Development Fund (grant number JPMEERF20231007) of the Environmental Restoration and Conservation Agency, provided by the Ministry of the Environment of Japan. MH was supported by the Japan Science and Technology Agency as part of the Strategic International Collaborative Research Program (grant number JPMJSC20E4). AG was supported by the UK Medical Research Council (grant number MR/V034162/1) and the EU's Horizon 2020 research project Exhaustion (grant number 820655). AU and JK were supported by the Czech Science Foundation (project 22–24920S). JJKJ was supported by the Academy of Finland (grant number 310372; Global Health Risks Related to Atmospheric Composition and Weather Consortium). FS was supported by the Italian Ministry of University and Research, Department of Excellence project 2023–2027, Rethinking Data Science—Department of Statistics, Computer Science and Applications—University of Florence

Global, regional, and national burden of mortality associated with non-optimal ambient temperatures from 2000 to 2019: a three-stage modelling study

© 2021 The Author(s). Background: Exposure to cold or hot temperatures is associated with premature deaths. We aimed to evaluate the global, regional, and national mortality burden associated with non-optimal ambient temperatures. Methods: In this modelling study, we collected time-series data on mortality and ambient temperatures from 750 locations in 43 countries and five meta-predictors at a grid size of 0·5° × 0·5° across the globe. A three-stage analysis strategy was used. First, the temperature–mortality association was fitted for each location by use of a time-series regression. Second, a multivariate meta-regression model was built between location-specific estimates and meta-predictors. Finally, the grid-specific temperature–mortality association between 2000 and 2019 was predicted by use of the fitted meta-regression and the grid-specific meta-predictors. Excess deaths due to non-optimal temperatures, the ratio between annual excess deaths and all deaths of a year (the excess death ratio), and the death rate per 100 000 residents were then calculated for each grid across the world. Grids were divided according to regional groupings of the UN Statistics Division. Findings: Globally, 5 083 173 deaths (95% empirical CI [eCI] 4 087 967–5 965 520) were associated with non-optimal temperatures per year, accounting for 9·43% (95% eCI 7·58–11·07) of all deaths (8·52% [6·19–10·47] were cold-related and 0·91% [0·56–1·36] were heat-related). There were 74 temperature-related excess deaths per 100 000 residents (95% eCI 60–87). The mortality burden varied geographically. Of all excess deaths, 2 617 322 (51·49%) occurred in Asia. Eastern Europe had the highest heat-related excess death rate and Sub-Saharan Africa had the highest cold-related excess death rate. From 2000–03 to 2016–19, the global cold-related excess death ratio changed by −0·51 percentage points (95% eCI −0·61 to −0·42) and the global heat-related excess death ratio increased by 0·21 percentage points (0·13–0·31), leading to a net reduction in the overall ratio. The largest decline in overall excess death ratio occurred in South-eastern Asia, whereas excess death ratio fluctuated in Southern Asia and Europe. Interpretation: Non-optimal temperatures are associated with a substantial mortality burden, which varies spatiotemporally. Our findings will benefit international, national, and local communities in developing preparedness and prevention strategies to reduce weather-related impacts immediately and under climate change scenarios. Funding: Australian Research Council and the Australian National Health and Medical Research Council.Australian Research Council; Australian National Health and Medical Research Council

Percepção materna sobre transtornos psiquiátricos no puerpério: implicações na relação mãe-filho

Objetivou-se analisar as implicações dos transtornos psiquiátricos na relação mãe-filho na percepção da mulher em puerpério. Utilizou-se abordagem qualitativa descritiva com dados colhidos em entrevista semiestruturada aplicada a dez puerperas, selecionadas pelo diagnóstico de transtorno psíquico no puerpério. Os dados coletados foram discutidos pela técnica de análise de conteúdo. Os resultados apontam dificuldades das pacientes em se perceber doentes, devido a fatores culturais e sociais que agem frente aos fatores biológicos na definição de diagnóstico e tratamento dos transtornos, havendo prejuízo no prognóstico, acarretando danos na relação mãe-filho. Concluiu-se que, apesar da incidência e gravidade dos transtornos psiquiátricos no ciclo gestacional, os serviços e profissionais de saúde precisam ser provocados na efetivação de ações preventivas para minimizar o sofrimento psíquico a mulheres acometidas

Isolation and quantification of microRNAs from human saliva

Oral premalignant disorders (OPMD) have relatively high malignant transformation rates to Oral Cancers (OC). Oral carcinogenesis is a multistep process that originates as epithelial hyperplasia followed by epithelial dysplasia, leading to fully malignant phenotypes. Early detection can be lifesaving but is currently not possible due to the lack of early diagnostic tools. The current diagnostic methods such as biopsy sampling, tumor tissue staining, and imaging techniques require skilled personnel and are invasive, painful, time-consuming, and expensive. Saliva has gained momentum as the diagnostic fluid of the future due to its noninvasive nature, ease of sampling, multiple samples can be collected with ease and more importantly does not require skilled personnel. The use of saliva in cancer diagnostics is an emerging and an expanding field. MicroRNA (miRNA) play a role in cancer initiation and progression and the expression changes of miRNA have been investigated as a potential biomarker in cancer studies. In this chapter, we describe a robust and cost-effective protocol to isolate and enrich miRNA from saliva samples. Profiling miRNAs in saliva samples can form part of the clinical management of OPMD and OC patients in the future

The intriguing biology of the tumour necrosis factor/tumour necrosis factor receptor superfamily: players, rules and the games

The members of the tumour necrosis factor (TNF)/tumour necrosis factor receptor (TNFR) superfamily are critically involved in the maintenance of homeostasis of the immune system. The biological functions of this system encompass beneficial and protective effects in inflammation and host defence as well as a crucial role in organogenesis. At the same time, members of this superfamily are responsible for host damaging effects in sepsis, cachexia, and autoimmune diseases. This review summarizes recent progress in the immunbiology of the TNF/TNFR superfamily focusing on results obtained from animal studies using gene targeted mice. The different modes of signalling pathways affecting cell proliferation, survival, differentiation, apoptosis, and immune organ development as well as host defence are reviewed. Molecular and cellular mechanisms that demonstrate a therapeutic potential by targeting individual receptors or ligands for the treatment of chronic inflammatory or autoimmune diseases are discussed