Pulmonary Inflammation Is Regulated by the Levels of the Vesicular Acetylcholine Transporter

Acetylcholine (ACh) plays a crucial role in physiological responses of both the central and the peripheral nervous system. Moreover, ACh was described as an anti-inflammatory mediator involved in the suppression of exacerbated innate response and cytokine release in various organs. However, the specific contributions of endogenous release ACh for inflammatory responses in the lung are not well understood. To address this question we have used mice with reduced levels of the vesicular acetylcholine transporter (VAChT), a protein required for ACh storage in secretory vesicles. VAChT deficiency induced airway inflammation with enhanced TNF-alpha and IL-4 content, but not IL-6, IL-13 and IL-10 quantified by ELISA. Mice with decreased levels of VAChT presented increased collagen and elastic fibers deposition in airway walls which was consistent with an increase in inflammatory cells positive to MMP-9 and TIMP-1 in the lung. In vivo lung function evaluation showed airway hyperresponsiveness to methacholine in mutant mice. The expression of nuclear factor-kappa B (p65-NF-kappa B) in lung of VAChT-deficient mice were higher than in wild-type mice, whereas a decreased expression of janus-kinase 2 (JAK2) was observed in the lung of mutant animals. Our findings show the first evidence that cholinergic deficiency impaired lung function and produce local inflammation. Our data supports the notion that cholinergic system modulates airway inflammation by modulation of JAK2 and NF-kappa B pathway. We proposed that intact cholinergic pathway is necessary to maintain the lung homeostasis

Determinantes de saúde em crianças dos 3 aos 10 anos

RESUMO 1: Introdução: Os estilos de vida atuais sugerem comportamentos de risco que estão na base do perfil de saúde do país. Objetivo: Avaliar os estilos de vida e sua associação com dados sociodemográficos numa amostra de crianças portuguesas dos 3 aos 10 anos de idade. Participantes e métodos: Estudo transversal de natureza quantitativa num universo de 1617 crianças dos jardins de infância e escolas do 1.º ciclo dos dois agrupamentos de escolas de Tondela e do agrupamento de escolas de Vouzela. A amostra do estudo foi constituída por um total de 1385 crianças. A análise estatística dos dados foi efetuada com recurso ao software estatístico IBM SPSS versão 21.0. A comparação de proporções foi realizada através do teste Qui-quadrado, onde as prevalências foram expressas em proporções, com base no nível de significância de p=0,05, com intervalos de confiança de 95%. Resultados: Constatou-se que as crianças com mais idade apresentavam uma menor adesão a comportamentos alimentares saudáveis, uma maior prevalência de atividade física (49,2%), no entanto, foram, também aquelas que apresentaram um maior índice de atividades sedentárias (27,1%). Os rapazes apresentaram maiores níveis de atividade física (51,6%) e índices mais elevados de comportamentos sedentários (28,6%). Relativamente à zona de residência, existiu uma maior prevalência de consumo de legumes (73,2%) e fastfood (24,0%) e de comportamentos sedentários (26,1%) em zonas urbanas. As crianças que pertenciam a agregados familares de rendimentos mais favoráveis e com maior nível de habilitações literárias consumiam mais leite e derivados, legumes e praticavam mais atividade física. No entanto, apresentaram maior prevalência de consumo de fastfood e comportamentos sedentários. Conclusões:Torna-se perceptível a necessidade de se intervir nos grupos mais vulneráveis no sentido de uma mais eficaz equidade em saúde. Palavras-chave: Crianças; estilos de vida; dados sociodemográficos; escolas.ABSTRACT 1: Introduction: The current lifestyles suggests risk behaviors that are the basis of a country's health profile. Objective: Assess the lifestyles and its association with sociodemographic variables among a sample of Portuguese children from 3 to 10 years old. Participants and methods: A Cross-sectional study was desgined with a total of 1617 children from public schools, from the two main school groups of Tondela and Vouzela. The final study sample was built with a total of 1385 children. Statistical analysis was performed using the IBM SPSS software version 21.0 for Windows. Comparison of proportions was performed using the “Chi-square” test, where prevalences were expressed as proportions, based on the significance level of p = 0.05, with a 95% confidence intervals. Results: It was found that the older children had a lower adherence to healthy eating habits and a higher prevalence of physical activity (49.2%). However, there were also those with higher rate of sedentary activities (27.1%). The boys had higher levels of physical activity (51.6%) and higher rates of sedentary behaviors (28.6%). With regard to residence area, there was a higher prevalence of consumption of vegetables (73.2%), fastfood (24.0%) and sedentary behaviors (26.1%) in urban areas. Children belonging to households of more favorable monthly earnings and a higher level of educational qualifications consumed more dairy product, vegetables and practiced more physical activity. However, they had a higher prevalence of fastfood consumption and sedentary behaviors. Conclusions: It becomes noticeable the need to make an intervention on the most vulnerable groups to obtain more effective health equity. Keywords: Children; lifestyles; sociodemographic data; schools.RESUMO 2: Introdução: As iniquidades de género na distribuição de recursos estão ainda profundamente associadas à saúde precária e à diminuição do bem-estar das mulheres e das crianças. Objetivo: Analisar a influência dos fatores materno-fetais nos estilos de vida numa amostra de crianças portuguesas dos 3 aos 10 anos de idade Participantes e métodos: Estudo transversal de natureza quantitativa num universo de 1617 crianças dos jardins de infância e escolas do 1.º ciclo dos dois agrupamentos de escolas de Tondela e do agrupamento de escolas de Vouzela. A amostra do estudo foi constituída por um total de 1385 crianças. A análise estatística dos dados foi efetuada com recurso ao software estatístico IBM SPSS versão 21.0. A comparação de proporções foi realizada através do teste Qui-quadrado, onde as prevalências foram expressas em proporções, com base no nível de significância de p=0,05, com intervalos de confiança de 95%. Resultados: As crianças que habitam em meio rural apresentavam um peso à nascença superior comparativamente às do meio urbano (93,7%). As grávidas com mais idade obtiveram uma prevalência de antecipação da primeira consulta de gravidez mais elevada (96,5%) assim como uma prevalência mais elevada de consultas de vigilância durante a gravidez (97,2%) quando comparadas com as grávidas mais novas. As mães com habilitações literárias superiores ao 9.º ano de escolaridade apresentavam uma prevalência de amamentação superior (58,0%) e os seus filhos uma prevalência de consumo de fastfood superior (64,9%) quando comparadas com as mães com habilitações literárias inferiores. Conclusões: Denota-se a importância da maturidade, formação e capacitação das mães para os cuidados maternos e neonatais. Palavras-chave: crianças; estilos de vida; fatores materno-fetais.ABSTRACT 2: Introduction: Gender inequalities in the distribution of resources is still deeply associated with poor health and reduced welfare of women and children. Objective: To analyze the influence of maternal and fetal factors in lifestyles of children, in a sample of children from 3 to 10 years old. Participants and methods: A Cross-sectional study was desgined with a total of 1617 children from public schools, from the two main school groups of Tondela and Vouzela. The final study sample was built with a total of 1385 children. Statistical analysis was performed using the IBM SPSS software version 21.0 for Windows. Comparison of proportions was performed using the “Chi-square” test, where prevalences were expressed as proportions, based on the significance level of p = 0.05, with a 95% confidence intervals. Results: Children who live in rural areas presented a higher birth weight compared to those who live in urban areas (93.7%). Older pregnant women obtained a higher prevalence of the first medical appointment antecipation (96.5%) as well as a higher prevalence of medical appointments during pregnancy (97.2%) when compared with younger pregnant women. Mothers with qualifications higher than the 9th grade showed a higher prevalence of breastfeeding (58.0%) and their children presented a higher prevalence of fastfood consumption (64.9%) when compared with mothers with lower educational qualifications. Conclusion: To denote the importance of maturity and training of mothers in maternal and neonatal care. Keywords: children; lifestyles; maternal fetal factors

Aedes aegypti salivary gland extract alleviates acute itching by blocking TRPA1 channels

Aedes aegypti (Ae. aegypti) saliva induces a variety of anti-inflammatory and immunomodulatory activities. Interestingly, although it is known that mosquito bites cause allergic reactions in sensitised hosts, the primary exposure of humans to Ae. aegypti does not evoke significant itching. Whether active components in the saliva of Ae. aegypti can counteract the normal itch reaction to injury produced by a histaminergic or non-histaminergic pathway in vertebrate hosts is unknown. This study investigated the effects of Ae. aegypti mosquito salivary gland extract (SGE) on sensitive reactions such as itching and associated skin inflammation. Acute pruritus and plasma extravasation were induced in mice by the intradermal injection of either compound 48/80 (C48/80), the Mas-related G protein-coupled receptor (Mrgpr) agonist chloroquine (CQ), or the transient receptor potential ankyrin 1 (TRPA1) agonist allyl isothiocyanate (AITC). The i.d. co-injection of Ae. aegypti SGE inhibited itching, plasma extravasation, and neutrophil influx evoked by C48/80, but it did not significantly affect mast cell degranulation in situ or in vitro. Additionally, SGE partially reduced CQ- and AITC-induced pruritus in vivo, suggesting that SGE affects pruriceptive nerve firing independently of the histaminergic pathway. Activation of TRPA1 significantly increased intracellular Ca2+ in TRPA-1-transfected HEK293t lineage, which was attenuated by SGE addition. We showed for the first time that Ae. aegypti SGE exerts anti-pruriceptive effects, which are partially regulated by the histamine-independent itch TRPA1 pathway. Thus, SGE may possess bioactive molecules with therapeutic potential for treating nonhistaminergic itch

Evaluation and comparison between methods of measurement of systolic blood pressure in healthy conscious cats

Após validação de dois diferentes métodos de mensuração de pressão arterial sistólica (PAS) não invasivos ou indiretos (oscilométrico e Doppler vascular) com o invasivo ou direto (cateterização arterial padrão ouro) em 12 gatos hígidos anestesiados de mesma faixa etária, os métodos não invasivos foram avaliados e comparados em 24 gatos hígidos e conscientes, divididos em quatro grupos de idade. Em cada animal, procedeu-se à mensuração da pressão pelos métodos Doppler e oscilométrico. O método oscilométrico foi o primeiro a ser realizado, e, logo em seguida, o método Doppler. Os valores considerados foram obtidos das médias de sete medidas consecutivas para cada método, com intervalo de 30 segundos entre elas. A primeira medida e as medidas discrepantes (variação ˃ 20% PAS), obtidas com sinais óbvios de estresse e/ou com movimentação do animal, foram descartadas. Os métodos de mensuração oscilométrico e Doppler, embora tenham apresentado médias estatisticamente diferentes em todos os grupos, quando comparados em cada grupo, apresentaram uma correlação significativa, alta e positiva. Ou seja, sempre que for obtido um valor elevado por um método, o mesmo fato ocorrerá com o outro método e vice-versa. Clinicamente, a diferença observada não é relevante, uma vez que a diferença média dos valores obtida pelos dois métodos, em cada grupo, foi menor que 1,1%.After two different validation systolic blood pressure measurement methods (PAS), not invasive or indirect (oscillometric and doppler vascular) with invasive or direct (arterial catheterization - Gold Standard) in 12 anesthetized healthy cats of the same age group, not invasive methods were evaluated and compared in 24 healthy conscious cats, divided into four age groups. In each animal, we proceeded to measure the pressure by Doppler and oscillometric methods. The oscillometric method was the first to be performed, and, shortly thereafter, the doppler method. The values considered were obtained from averages from seven consecutive measurements for each method with an interval of thirty seconds between them. The first measurement and disparate measurements (range ˃ 20% PAS) obtained with obvious signs of stress and / or animal movement were discarded. Methods of oscillometric and doppler measurement, although statistically different averages were shown in all groups when compared, each group showed a significant high positive correlation, meaning that when a high value is obtained by a method, the same occurs with the other method, and vice versa. Clinically, the observed difference is not relevant since the mean difference values obtained by the two methods, in each group was lower than 1.1%

MAMMALS IN PORTUGAL : A data set of terrestrial, volant, and marine mammal occurrences in P ortugal

Mammals are threatened worldwide, with 26% of all species being includedin the IUCN threatened categories. This overall pattern is primarily associatedwith habitat loss or degradation, and human persecution for terrestrial mam-mals, and pollution, open net fishing, climate change, and prey depletion formarine mammals. Mammals play a key role in maintaining ecosystems func-tionality and resilience, and therefore information on their distribution is cru-cial to delineate and support conservation actions. MAMMALS INPORTUGAL is a publicly available data set compiling unpublishedgeoreferenced occurrence records of 92 terrestrial, volant, and marine mam-mals in mainland Portugal and archipelagos of the Azores and Madeira thatincludes 105,026 data entries between 1873 and 2021 (72% of the data occur-ring in 2000 and 2021). The methods used to collect the data were: live obser-vations/captures (43%), sign surveys (35%), camera trapping (16%),bioacoustics surveys (4%) and radiotracking, and inquiries that represent lessthan 1% of the records. The data set includes 13 types of records: (1) burrowsjsoil moundsjtunnel, (2) capture, (3) colony, (4) dead animaljhairjskullsjjaws, (5) genetic confirmation, (6) inquiries, (7) observation of live animal (8),observation in shelters, (9) photo trappingjvideo, (10) predators dietjpelletsjpine cones/nuts, (11) scatjtrackjditch, (12) telemetry and (13) vocalizationjecholocation. The spatial uncertainty of most records ranges between 0 and100 m (76%). Rodentia (n=31,573) has the highest number of records followedby Chiroptera (n=18,857), Carnivora (n=18,594), Lagomorpha (n=17,496),Cetartiodactyla (n=11,568) and Eulipotyphla (n=7008). The data setincludes records of species classified by the IUCN as threatened(e.g.,Oryctolagus cuniculus[n=12,159],Monachus monachus[n=1,512],andLynx pardinus[n=197]). We believe that this data set may stimulate thepublication of other European countries data sets that would certainly contrib-ute to ecology and conservation-related research, and therefore assisting onthe development of more accurate and tailored conservation managementstrategies for each species. There are no copyright restrictions; please cite thisdata paper when the data are used in publications.info:eu-repo/semantics/publishedVersio

Mammals in Portugal: a data set of terrestrial, volant, and marine mammal occurrences in Portugal

Mammals are threatened worldwide, with ~26% of all species being included in the IUCN threatened categories. This overall pattern is primarily associated with habitat loss or degradation, and human persecution for terrestrial mammals, and pollution, open net fishing, climate change, and prey depletion for marine mammals. Mammals play a key role in maintaining ecosystems functionality and resilience, and therefore information on their distribution is crucial to delineate and support conservation actions. MAMMALS IN PORTUGAL is a publicly available data set compiling unpublished georeferenced occurrence records of 92 terrestrial, volant, and marine mammals in mainland Portugal and archipelagos of the Azores and Madeira that includes 105,026 data entries between 1873 and 2021 (72% of the data occurring in 2000 and 2021). The methods used to collect the data were: live observations/captures (43%), sign surveys (35%), camera trapping (16%), bioacoustics surveys (4%) and radiotracking, and inquiries that represent less than 1% of the records. The data set includes 13 types of records: (1) burrows | soil mounds | tunnel, (2) capture, (3) colony, (4) dead animal | hair | skulls | jaws, (5) genetic confirmation, (6) inquiries, (7) observation of live animal (8), observation in shelters, (9) photo trapping | video, (10) predators diet | pellets | pine cones/nuts, (11) scat | track | ditch, (12) telemetry and (13) vocalization | echolocation. The spatial uncertainty of most records ranges between 0 and 100 m (76%). Rodentia (n =31,573) has the highest number of records followed by Chiroptera (n = 18,857), Carnivora (n = 18,594), Lagomorpha (n = 17,496), Cetartiodactyla (n = 11,568) and Eulipotyphla (n = 7008). The data set includes records of species classified by the IUCN as threatened (e.g., Oryctolagus cuniculus [n = 12,159], Monachus monachus [n = 1,512], and Lynx pardinus [n = 197]). We believe that this data set may stimulate the publication of other European countries data sets that would certainly contribute to ecology and conservation-related research, and therefore assisting on the development of more accurate and tailored conservation management strategies for each species. There are no copyright restrictions; please cite this data paper when the data are used in publications

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation