Short-term effects of traffic noise on suicides and emergency hospital admissions due to anxiety and depression in Madrid (Spain)

Studies show a relationship between some mental illnesses and suicides and different environmental variables such as air pollution, characterized by stress at the neuropsychological level. Despite the fact that traffic noise is also a powerful neurological stressor, studies that relate traffic noise to these mental disorders are practically non-existent. The objective is to analyze the short-term impact that chemical air pollution, traffic noise and thermal extremes have on emergency hospital admissions due to anxiety, dementia and suicides in the city of Madrid. This ecological, longitudinal study uses generalized linear models with Poisson link to analyze the short-term impact of the average daily concentrations of chemical pollutants (NO2, PM10, PM2.5, O3), noise pollution indicators (Leqday, Leqnight and Leq24h) and temperatures during heat waves (Theat) and cold waves (Tcold) on daily admissions to emergency services in the city of Madrid from 2010 to 2013 due to anxiety (ICD-10: F32), depression (ICD-10: F40-F42) and suicide (ICD-10: X60-X84). The results show no association between any of the chemical pollutants considered and the dependent variables studied. On the contrary, the values of Leqday are associated with the three variables analyzed in lag 0 for the cases of anxiety and depression and in lag 1 for suicides, with RR: 1.20 (IC95% 1.14 1.26), RR: 1.11 (IC95% 1.06 1.16) and RR: 1.17 (IC95% 1.05 1.30), respectively, for increases of 1 dB(A) in the values of Leqday. An association was also found between Tcold and admissions for anxiety in lag 9 with RR: 1.62 (IC95% 1.18 2.22) for increases of 1 °C in the values of Tcold. Traffic noise can be considered an important risk factor related to the illnesses and anxiety and depression and for suicides in the city of Madrid, although new studies are needed to support the findings shown here.The authors gratefully acknowledge Project ENPY 376/18 and Project ENPY 107/18 grants from the Institute of Health Carlos III.S

Determination of heat wave definition temperatures in Spain at an isoclimatic level: time trend of heat wave duration and intensity across the decade 2009–2018

Background: In line with WHO guidelines for the implementation of public health prevention plans targeted at the impacts of high temperatures, a heat wave defnition temperature (Tthreshold) was calculated for 182 so called “isoclimatic zones” (IZ) in Spain. As the dependent variable for determining this Tthreshold, we analysed daily all-cause mortality data (ICD-10: A00-R99) for each IZ across the period 2009–2018. The independent variable used was the mean value of the maximum daily temperature of the summer months recorded at meteorological observatories in each IZ. We used Box–Jenkins models to ascertain mortality anomalies, and scatterplots to link these anomalies to the temperatures at which they occurred, thereby determining the Tthreshold for each IZ. We then calculated how many heat waves had occurred in each IZ, as well as their intensity, and analysed their time trend over this period. Results: The results showed that in 52.5% of the IZ, the percentile of the maximum temperatures series of the summer months to which Tthreshold corresponded was below the 95th percentile of the meteorological heat wave defnition in Spain: indeed, it only coincided in 30.7% of cases. The geographical distribution of these percentiles displayed great heterogeneity as a consequence of the local factors that infuence the temperature–mortality relationship. The trend in the number of heat waves analysed indicated an overall increase in Spain at a rate of 3.9 heat waves per decade, and a similar rise in mean annual intensity of 9.5 °C/decade. These time-trend values were higher than those yielded by analysing the trend in meteorological heat waves based on the 95th percentile. Conclusions: The results obtained in this study indicate the need to use a heat wave defnition based on epidemiological temperature–mortality studies, rather than on values based on meteorological percentiles. This could be minimising estimated health impacts in analyses of future impacts attributable to heat.Acknowledgements and funding The authors would like to express their gratitude for the following grants from the Carlos III Institute of Health (Instituto de Salud Carlos III/ISCIII) for the ENPY 304/20, and ENPY 436/21 projects.S

Evolution of the threshold temperature definition of a heat wave vs. evolution of the minimum mortality temperature: a case study in Spain during the 1983–2018 period

An area of current study concerns analysis of the possible adaptation of the population to heat, based on the temporal evolution of the minimum mortality temperature (MMT). It is important to know how is the evolution of the threshold temperatures (Tthreshold) due to these temperatures provide the basis for the activation of public health prevention plans against high temperatures. The objective of this study was to analyze the temporal evolution of threshold temperatures (Tthreshold) produced in different Spanish regions during the 1983–2018 period and to compare this evolution with the evolution of MMT. The dependent variable used was the raw rate of daily mortality due to natural causes ICD X: (A00-R99) for the considered period. The independent variable was maximum daily temperature (Tmax) during the summer months registered in the reference observatory of each region. Threshold values were determined using dispersion diagrams (annual) of the prewhitened series of mortality temperatures and Tmax. Later, linear fit models were carried out between the different values of Tthreshold throughout the study period, which permitted detecting the annual rate of change in Tthreshold.This research project was funded by the Carlos III Health Institute (ISCIII) under file number ENPY 470/19 and is supported by the Biodiversity Foundation of the Ministry for Ecological Transition and Demographic Challenge, in addition to the research projects ISCIII: ENPY107/18 and ENPY 376/1

Effects of local factors on adaptation to heat in Spain (1983-2018)

The European Union is currently immersed in policy development to address the effects of climate change around the world. Key plans and processes for facilitating adaptation to high temperatures and for reducing the adverse effects on health are among the most urgent measures. Therefore, it is necessary to understand those factors that influence adaptation. The aim of this study was to provide knowledge related to the social, climate and economic factors that are related to the evolution of minimum mortality temperatures (MMT) in Spain in the rural and urban contexts, during the 1983-2018 time period. For this purpose, local factors were studied regarding their relationship to levels of adaptation to heat. MMT is an indicator that allows for establishing a relationship to between mortality and temperature, and is a valid indicator to assess the capacity of adaptation to heat of a certain population. MMT is obtained through the maximum daily temperature and daily mortality of the study period. The evolution of MMT values for Spain was established in a previous paper. An ecological, longitudinal and retrospective study was carried out. Generalized linear models (GLM) were performed to identify the variables that appeared to be related to adaptation. The adaptation was calculated as the difference in variation in MMT based on the average increase in maximum daily temperatures. In terms of adaptation to heat, urban populations have adapted more than non-urban populations. Seventy-nine percent (n = 11) of urban provinces have adapted to heat, compared to twenty-one percent (n = 3) of rural provinces that have not adapted. In terms of urban zones, income level and habituation to heat (values over the 95th percentile) were variables shown to be related to adaptation. In contrast, among non-urban provinces, a greater number of housing rehabilitation licenses and a greater number of health professionals were variables associated with higher increases in MMT, and therefore, with adaptation. These results highlight the need to carry out studies that allow for identifying the local factors that are most relevant and influential in population adaptation. More studies carried out at a small scale are needed.The authors gratefully acknowledge the grants for projects ENPY107/18; ENPY 376/18, ENPY 470/19 and ENPY 340/20 from the Carlos III Institute of Health, and is supported by the Biodiversity Foundation of the Ministry for Ecological Transition and Demographic Challenge. Likewise, to the UNED for the financing for the publication in Open Access.S

Laboratorio escénico de técnicas performativas

Depto. de Literaturas Hispánicas y BibliografíaFac. de FilologíaFALSEsubmitte

Gender differences in adaptation to heat in Spain (1983-2018)

In Spain the average temperature has increased by 1.7 °C since pre-industrial times. There has been an increase in heat waves both in terms of frequency and intensity, with a clear impact in terms of population health. The effect of heat waves on daily mortality presents important territorial differences. Gender also affects these impacts, as a determinant that conditions social inequalities in health. There is evidence that women may be more susceptible to extreme heat than men, although there are relatively few studies that analyze differences in the vulnerability and adaptation to heat by sex. This could be related to physiological causes. On the other hand, one of the indicators used to measure vulnerability to heat in a population and its adaptation is the minimum mortality temperature (MMT) and its temporal evolution. The aim of this study was to analyze the values of MMT in men and women and its temporal evolution during the 1983-2018 period in Spain's provinces. An ecological, longitudinal retrospective study was carried out of time series data, based on maximum daily temperature and daily mortality data corresponding to the study period. Using cubic and quadratic fits between daily mortality rates and the temperature, the minimum values of these functions were determined, which allowed for determining MMT values. Furthermore, we used an improved methodology that provided for the estimation of missing MMT values when polynomial fits were inexistent. This analysis was carried out for each year. Later, based on the annual values of MMT, a linear fit was carried out to determine the rate of evolution of MMT for men and for women at the province level. Average MMT for all of Spain's provinces was 29.4 °C in the case of men and 28.7 °C in the case of women. The MMT for men was greater than that of women in 86 percent of the total provinces analyzed, which indicates greater vulnerability among women. In terms of the rate of variation in MMT during the period analyzed, that of men was 0.39 °C/decade, compared to 0.53 °C/decade for women, indicating greater adaptation to heat among women, compared to men. The differences found between men and women were statistically significant. At the province level, the results show great heterogeneity. Studies carried out at the local level are needed to provide knowledge about those factors that can explain these differences at the province level, and to allow for incorporating a gender perspective in the implementation of measures for adaptation to high temperatures.The authors wish to thank the funding provided by the ENPY 304/20, ENPY 376/18 and ENPY 107/18 projects of the Carlos III Health Institute III (ISCIII). They also wish to thank the UNED for funding this publication in open access.S

Adaptação ao calor e desigualdades sociais em saúde em função do género, da idade e do território: Revisão de estudos na Espanha (1983-2018)

[ES] Los efectos del cambio climático sobre la salud exacerban las desigualdades sanitarias y sociales existentes. La desigualdad expone a las poblaciones más vulnerables, haciéndolas más vulnerables a los daños y limitando su capacidad de adaptación. Para proteger a la población de las consecuencias del cambio climático es necesario conocer los factores que intervienen en los procesos de adaptación. Un indicador que permite evaluar la capacidad de adaptación al calor de una población es la Temperatura Mínima Mortalidad (TMM). A través de su evolución a lo largo del tiempo permite conocer si una población muestra adaptación o no. Se propone a través de esta revisión de estudios, conocer la adaptación de población en España en función de tres ejes de desigualdad como son el territorio, la edad y el género entre 1983 a 2018 mediante el análisis de la evolución de la TMM y su comparación con la evolución de la temperatura máxima diaria. La población española en general mostró adaptación al calor, si bien se encontraron diferencias geográficas. A nivel de territorio las provincias no urbanas mostraron una mayor adaptación que las provincias urbanas. Con respecto a las diferencias por género, las mujeres mostraron mayor capacidad de adaptación frente a los hombres. Asimismo, las personas mayores también mostraron capacidad de adaptación.Es necesario entender qué factores influyen en la adaptación para articular medidas que reduzcan el impacto de las altas temperaturas, sobre todo en colectivos que presentan desigualdades sociales en salud. [EN] The health effects of climate change exacerbate existing health and social inequalities. Inequality exposes the most vulnerable populations, making them more vulnerable to damage and limiting their ability to adapt. In order to protect the population from the consequences of climate change it is necessary to understand the factors involved in adaptation processes. An indicator for assessing the adaptability to heat of a population is the Minimum Mortality Temperature (MMT). Its evolution over time makes it possible to know whether a population is adapting or not. The aim of this review of studies is to determine the adaptation of the Spanish population along three axes of inequality-territory, age and gender-between 1983 and 2018 by studying the evolution of the MMT and comparing it to the evolution of the maximum daily temperature. The Spanish population showed in general adaptation to heat, although geographical differences were found. At the territorial level, non-urban provinces showed greater adaptation than urban provinces. With respect to gender differences, women showed greater adaptability than men. In addition, the elderly also showed adaptability.It is necessary to understand which factors influence adaptation in order to design measures for reducing the impact of high temperatures on-especially-groups affected by social inequalities in health. [PT] Os efeitos das alterações climáticas na saúde exacerbam as desigualdades sociais e de saúde existentes. A desigualdade expõe as populações mais vulneráveis, tornando-as mais vulneráveis a danos e limitando a sua capacidade de adaptação. Para proteger a população das consequências das alterações climáticas, é necessário conhecer os fatores que intervêm nos processos de adaptação. Um indicador que permite avaliar a capacidade de adaptação ao calor de uma população é a Temperatura de Mortalidade Mínima (TMM). Através da sua evolução ao longo do tempo, permite saber se uma população apresenta adaptação ou não.Propõe-se através desta revisão de estudos, conhecer a adaptação da população na Espanha com base em três eixos de desigualdade como são o território, a idade e o género entre, 1983 a 2018, através da análise da evolução da TMM e a sua comparação com a evolução da temperatura máxima diária. A população espanhola em geral mostrou adaptação ao calor, embora tenham sido encontradas diferenças geográficas. Ao nível do território, as províncias não urbanas mostraram maior adaptação do que as províncias urbanas. Em relação às diferenças por género, as mulheres apresentaram maior capacidade de adaptação em relação aos homens. Da mesma forma, os idosos também demonstraram capacidade de adaptação.É necessário compreender quais os fatores que influenciam na adaptação para articular medidas que reduzam o impacto das altas temperaturas, principalmente em grupos que apresentam desigualdades sociais em saúde.Los autores agradecen las subvenciones para los proyectos ENPY304/20, ENPY107/18, ENPY376/18 ENPY470/19 del Instituto de Salud Carlos III (ISCIII) con número de expediente ENPY470/19, cuenta con el apoyo de la Fundación Biodiversidad, del Ministerio para la Transición Ecológica y el Reto Demográfico.S

IgE-reactivity pattern of tomato seed and peel nonspecific lipid-transfer proteins after in vitro gastrointestinal digestion

The influence of gastrointestinal digestion on the immunological properties of three different nonspecific lipid-transfer proteins (nsLTPs) described in tomato fruit has been assessed using an in vitro system mimicking the stomach and intestine digestion conditions. Tomato peel/pulp nsLTP, Sola l 3, was degraded after digestion, although the immunoglobulin E (IgE) recognition of intact protein and a 10 kDa band were still observed after 30 min of duodenal digestion in the presence of phosphatidylcholine. The tomato seed nsLTP, Sola l 7, showed a higher stability than the other seed allergen, Sola l 6, during digestion. Sola l 7 showed an IgE immunoreactive 6.5 kDa band in immunoblotting analysis, retaining up to 7% of its IgE-binding capacity in inhibition ELISA test after 60 min of duodenal digestion and keeping intact its ability to activate basophils after digestion. These results suggest that the tomato seed allergen Sola l 7 might be considered as an important allergen in the induction of allergic responses to tomato due to its high stability against gastrointestinal digestion.This work was supported by grants SAF2017-86483-R from the Ministerio de Economía y Competitividad and PI13/00928 Instituto de Salud Carlos III (ISCIII), ISCIII cofounded by Fondo Europeo de Desarrollo Regional – FEDER for the Thematic Networks and Co-operative Research Centres; RIRAAF RD16/0006/0024 and ARADyAL (RD16/0006/0001; RD16/0006/0013; RD16/0006/0014); and EAACI Exchange Research Fellowship 2016. The authors would like to thank the excellent technical support of Sara Abián. S.B. was supported by a Juan de la Cierva Incorporación contract from the Spanish Ministerio de Ciencia, Innovación y Universidades.Peer reviewe

Gasdermin B over-expression modulates HER2-targeted therapy resistance by inducing protective autophagy through Rab7 activation

Gasdermin B (GSDMB) over-expression promotes poor prognosis and aggressive behavior in HER2 breast cancer by increasing resistance to therapy. Decoding the molecular mechanism of GSDMB-mediated drug resistance is crucial to identify novel effective targeted treatments for HER2/GSDMB aggressive tumors. Different in vitro approaches (immunoblot, qRT-PCR, flow cytometry, proteomic analysis, immunoprecipitation, and confocal/electron microscopy) were performed in HER2 breast and gastroesophageal carcinoma cell models. Results were then validated using in vivo preclinical animal models and analyzing human breast and gastric cancer samples. GSDMB up-regulation renders HER2 cancer cells more resistant to anti-HER2 agents by promoting protective autophagy. Accordingly, the combination of lapatinib with the autophagy inhibitor chloroquine increases the therapeutic response of GSDMB-positive cancers in vitro and in zebrafish and mice tumor xenograft in vivo models. Mechanistically, GSDMB N-terminal domain interacts with the key components of the autophagy machinery LC3B and Rab7, facilitating the Rab7 activation during pro-survival autophagy in response to anti-HER2 therapies. Finally, we validated these results in clinical samples where GSDMB/Rab7/LC3B co-expression associates significantly with relapse in HER2 breast and gastric cancers. Our findings uncover for the first time a functional link between GSDMB over-expression and protective autophagy in response to HER2-targeted therapies. GSDMB behaves like an autophagy adaptor and plays a pivotal role in modulating autophagosome maturation through Rab7 activation. Finally, our results provide a new and accessible therapeutic approach for HER2/GSDMB + cancers with adverse clinical outcome. The online version contains supplementary material available at 10.1186/s13046-022-02497-w

Chromatin regulation by Histone H4 acetylation at Lysine 16 during cell death and differentiation in the myeloid compartment

Histone H4 acetylation at Lysine 16 (H4K16ac) is a key epigenetic mark involved in gene regulation, DNA repair and chromatin remodeling, and though it is known to be essential for embryonic development, its role during adult life is still poorly understood. Here we show that this lysine is massively hyperacetylated in peripheral neutrophils. Genome-wide mapping of H4K16ac in terminally differentiated blood cells, along with functional experiments, supported a role for this histone post-translational modification in the regulation of cell differentiation and apoptosis in the hematopoietic system. Furthermore, in neutrophils, H4K16ac was enriched at specific DNA repeats. These DNA regions presented an accessible chromatin conformation and were associated with the cleavage sites that generate the 50 kb DNA fragments during the first stages of programmed cell death. Our results thus suggest that H4K16ac plays a dual role in myeloid cells as it not only regulates differentiation and apoptosis, but it also exhibits a non-canonical structural role in poising chromatin for cleavage at an early stage of neutrophil cell death