Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

Incorporating avoidance and recolonization concepts in ecotoxicological risk assessment by using a non-forced exposure system

Trabajo presentado en la SETAC Europe 27th Annual Meeting (Environmental Quality Through Transdisciplinary Collaboration), celebrada en Bruselas del 7 al 11 de mayo de 2017.Traditional laboratory aquatic ecotoxicity assays aim to assess the potential toxicity of a natural samp le or contaminants on organisms, on which a given response is measured. Organisms are passively and mandatorily exposed to contamination with no possibility to avoid it. This approach, here called forced exposure, allows an obvious concentration-response relationship is derived; although we cannot neglect such direct effects, under natural conditions, mobile organisms can detect contamination and move to more favourable areas, avoiding suffering the toxic effects caused by continuous exposure. In this new scenario, no effect is expected to occur on individuals; therefore, measuring effects down to individual level lacks ecological relevance. When organisms respond to contamination moving towards undisturbed habitats, biological effects will be sensed firstly and more intensely on ecosystems as part (or the entire) population may abandon the disturbed habitat. Therefore, the contamination will affect the spatial distribution of the organisms and the processes of habitat selection (avoidance and recolonization). Secondly, the neighbouring undisturbed habitat, used by organisms as escape area, can be indirectly stressed due to the overpopulation of avoiders. This scenario is hard to be assessed in a forced exposure system. Therefore, a free-choice, multi-compartmented, nor-forced exposure system has been proposed as additional tool able to predict how contamination can affect both avoidance and recolonization responses. By using the non-forced exposure system, it is possible to assess the biological effects caused by a gradient or even patchy contamination up to the ecosystem level. Finally, the non -forced exposure system allows evaluating the environmental fragmentation caused by chemical barrier that contamination can create, blocking the free displacement among habitats. The present study brings a novel tool for ecotoxicity assays in which organisms are not forcedly exposed to contamination, so that avoidance and recolonization responses are added to the ecological risk assessment. The theoretical basis, the oper ational advantages and the ecological relevance of this approach are discussed. Our experience with the non-forced exposure system has shown that this approach can provide important information about the role of the contaminants as habitat disturbers even when individual toxic effects are not detected.N

Do Contaminants Influence the Spatial Distribution of Aquatic Species? How New Perspectives on Ecotoxicological Assays Might Answer This Question

Peer reviewe

Teoria de Abdellah: revisão narrativa da literatura

Poster apresentado nas III Jornadas Científicas Universitárias e Politécnicas da Egas Moniz, Monte de Caparica, 01-02-2023N/

An in situ postexposure feeding assay with Carcinus maenas for estuarine sediment-overlying water toxicity evaluations

This study developed and evaluated a short-term sublethal in situ toxicity assay for estuarine sediment-overlying waters, with the crab Carcinus maenas (L.) based on postexposure feeding. It consisted of a 48-h in situ exposure period followed by a short postexposure feeding period (30 min). A precise method for quantifying feeding, using the Polychaeta Hediste (Nereis) diversicolor Müller as food source, was first developed. The sensitivity of the postexposure feeding response was verified by comparing it to that of lethality, upon cadmium exposure. The influence of environmental conditions prevailing during exposure (salinity, temperature, substrate, light regime, and food availability) on postexposure feeding was also addressed. The potential of this in situ assay was then investigated by deploying organisms at ten sites, located in reference and contaminated Portuguese estuaries. Organism recovery ranged between 90% and 100% and a significant postexposure feeding depression (16.3-72.7%) was observed at all contaminated sites relatively to references.http://www.sciencedirect.com/science/article/B6VB5-4GJM3WP-1/1/25ffe8271cb177981ca98ef5429a2c5

Assessing the spatial distribution of the gastropod Olivella semistriata by using whole-sediment avoidance and recolonization assays

Trabajo presentado en la SETAC Europe 27th Annual Meeting (Environmental Quality Through Transdisciplinary Collaboration), celebrada en Bruselas del 7 al 11 de mayo de 2017.In situ observations seem to indicate that the spatial distribution of the snail Olivella semistriata on the Ecuadorian coast (city of Manta) is influenced by urban discharges. Therefore, contamination could determine habitable areas for snails. Firstly, the present study evaluated the ability of O. semistriata individuals to detect local contamination and avoid inhabiting contaminated sediments. Secondly, the ability of snails to recolonize contaminated sediments under recovery was studied. Sediment samples were taken in five points (El Murciélago beach - reference point, El Puerto, La Poza, Río Burro, Los Esteros, and Río Muerto) and evaluated for avoidance and recolonization trials. The tests were performed in a non-forced exposure system in which a contamination gradient was formed by mixing the test sample and the reference sediment. Higher avoidance percentage was observed in the samples of Rio Burro and Rio Muerto. Regarding recolonization tests, the reference sample was always preferred over all test samples. As there is no physical barrier to avoid the displacement of organisms between the studied areas, it is suggested that the absence (visual field observation) of snails in the Rio Burro and Rio Muerto sediments is due to the organisms' ability to avoid those areas. We can conclude that the spatial distribution of the snail may be directly affected by the presence of contaminants in the sediment, by triggering avoidance or even prevent colonization of contaminated areas. Contamination may, therefore, act as a chemical barrier that could cause habitat disruption and isolate populations.N

Laboratory assays with non-forced exposure to predict the preferential spatial distribution of fish in two ecuadorian rivers

Trabajo presentado en la SETAC Europe 27th Annual Meeting (Environmental Quality Through Transdisciplinary Collaboration), celebrada en Bruselas del 7 al 11 de mayo de 2017.Laboratory aquatic ecotoxicity assays used to provide data for ecological risk assessments assume that, under natural conditions, organisms living in a contaminated habitat are mandatorily and continuously exposed to contaminants. This assumption neglects the ability of the organisms to detect and avoid contamination moving towards less disturbed habitats such as expected in fluvial systems. Along a river, contaminants can be dispersed forming a gradient or even be patchy distributed, conditioning the habitat selection process by organisms as well as their avoidance and preference behavior. Therefore, in the present study, we assessed the avoidance and preference responses of the model fish Danio rerio when exposed to water samples from two Ecuadorian rivers (Pescadillo River and Oro River) with different disturbance levels. A non-forced exposure system, in which water samples from different river points are simultaneously assayed, allowing organisms to move freely between river samples and select the most favorable sample, was used. Results showed that organisms presented a trend to avoid Pescadillo River upstream samples, moving downstream towards to the confluence zone with Oro River. On the other hand, fish exposed to Oro River samples preferred moving upstream. When exposed to samples from both rivers simultaneously, fish tended to prefer Oro River samples. These results leaded us to predict that, as both rivers are connected, fish avoiding environmental disturbers in Pescadillo River would move to Oro River. Therefore, effects of potential stressful conditions present in Pescadillo River that trigger avoidance response by fish may depress fish populations in that river and, indirectly, affect Oro River by inducing an unexpected fish immigration.N