Alcohol Abuse Promotes Changes in Non-Synaptic Epileptiform Activity with Concomitant Expression Changes in Cotransporters and Glial Cells

Non-synaptic mechanisms are being considered the common factor of brain damage in status epilepticus and alcohol intoxication. the present work reports the influence of the chronic use of ethanol on epileptic processes sustained by non-synaptic mechanisms. Adult male Wistar rats administered with ethanol (1, 2 e 3 g/kg/d) during 28 days were compared with Control. Non-synaptic epileptiform activities (NEAs) were induced by means of the zero-calcium and high-potassium model using hippocampal slices. the observed involvement of the dentate gyrus (DG) on the neurodegeneration promoted by ethanol motivated the monitoring of the electrophysiological activity in this region. the DG regions were analyzed for the presence of NKCC1, KCC2, GFAP and CD11b immunoreactivity and cell density. the treated groups showed extracellular potential measured at the granular layer with increased DC shift and population spikes (PS), which was remarkable for the group E1. the latencies to the NEAs onset were more prominent also for the treated groups, being correlated with the neuronal loss. in line with these findings were the predispositions of the treated slices for neuronal edema after NEAs induction, suggesting that restrict inter-cell space counteracts the neuronal loss and subsists the hyper-synchronism. the significant increase of the expressions of NKCC1 and CD11b for the treated groups confirms the existence of conditions favorable to the observed edematous necrosis. the data suggest that the ethanol consumption promotes changes on the non-synaptic mechanisms modulating the NEAs. for the lower ethanol dosage the neurophysiological changes were more effective suggesting to be due to the less intense neurodegenertation.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Univ Fed Sao Joao del Rei, Dept Engn Biossistemas, Lab Neurociencia Expt & Computac, Sao Joao Del Rei, MG, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Disciplina Neurol Expt, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Ciencia & Tecnol, Sao Jose Dos Campos, SP, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Disciplina Fisiol, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Disciplina Neurol Expt, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Ciencia & Tecnol, Sao Jose Dos Campos, SP, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Disciplina Fisiol, São Paulo, BrazilWeb of Scienc

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

A industrialização e a dinâmica ambiental: O caso da Vila Industrial Jundiaí - Anápolis/GO

A Vila Industrial Jundiaí localiza-se na parte sul da cidade de Anápolis A vila surgiu para abrigar as indústrias ainda nascentes na cidade, por volta dos anos 50, com o crescimento da cidade acabou se tornado uma ilha entre as residências. Ela abriga em torno de 30 pequenas e médias empresas e setores comerciais de grande porte. Algumas dessas indústrias provocam poluição tanto sonora como de ar e solo, por vezes incomoda as pessoas que residem próximo ao local. O objetivo desse estudo foi verificar as condições de sustentabilidade ambiental existentes na Vila Industrial Jundiaí. A investigação foi dividida em duas partes: a primeira de caráter bibliográfico e documental. E a segunda uma pesquisa de campo por meio da aplicação de 27 questionários e entrevistas as empresas e 76 aos residentes do entorno as indústrias. A problematização em foco é de como o meio ambiente em Anápolis está sendo agredido pelas empresas da Vila Industrial Jundiaí. Os impactos ambientais decorrentes da presença das empresas na Vila seguem dois eixos: os positivos, que são: geração de empregos, melhoria em infra-estrutura e os negativos como  poluição,e problemas de saúde   como os cárdios-respiratórios

Ação antioxidante do Ácido Ascórbico na toxicidade do catecol em células da linhagem GL-15.

Introdução: A toxicidade do Catecol está relacionada com a formação de quinonas seguido de promoção de apoptose, ambos os efeitos suprimidos pela superóxido dismutase. Objetivo: Neste trabalho foi estudada a ação antioxidante do ácido ascórbico em células GL-15 após o estresse oxidativo induzido pelo catecol, a fim de comparar os dados e gerar mais informações sobre a citotoxicidade do catecol nesta linhagem celular. Metodologia: Uma vez que trabalhos anteriores mostraram que o valor de IC50 nestas células foi de 230 μM, após 72 horas de exposição, foram utilizadas as concentrações de catecol desde 300 μM até 600 μM. Conclusão: As concentrações sub-tóxicas de ácido ascórbico (600 μM - 3000μM) protegeram as células GL-15 contra danos oxidativos induzidos pelo catecol e reverteram completamente a formação de quinonas, confirmando que a toxicidade do catecol contra células GL-15 está essencialmente relacionada com a formação de quinonas reativas

Effect of Parenteral Vaccination of Newborn Holstein Calves against Viral Agents Involved in Bovine Respiratory Disease (BRD)

Background: Newborn calves are born immunosuppressed, hypogammaglobulinemic, immunologically immature, and therefore more vulnerable to many infectious diseases. During pregnancy, the fetal-placental environment is regulated by Th2-type cytokines that neutralize Th1 responses, an important factor for immune defense against viral agents. The ingestion and absorption of colostral immunoglobulins enhance the immunity of the neonate. However, the presence of maternal antibodies might negatively affect the success of parental vaccination in the first two months of life. This study aimed to evaluate the effecacy of parenteral vaccination in newborn calves with high titers of maternal antibodies against respiratory viruses.Materials, Methods & Results: Twenty-eight Holstein calves were allocated to the vaccinated group (VAC, n = 18) or an unvaccinated control group (NVAC, n = 10). The initial vaccination with 5 mL of a commercial vaccine occurred around the 14th day of life (D14) and the booster at D35. Respiratory and diarrhea symptoms were evaluated at D12, D14, D16, D20, D31, D36, D45, D53, and D60. Blood samples were taken for leukogram, haptoglobin, and seroneutralization of BVDV, BoHV-1, BRSV, and BPI3V, at the time of vaccination at D14 (T1), at booster (D35, T2), and 21 days after the booster (D56, T3). Despite the increased prevalence of BRD during the period of the study, no calves from either group exhibited respiratory disease at D12 or D14. In subsequent assessments, the frequency of BRD increased over time in the VAC group until it reached a maximum prevalence of 38.9% (7/18) at D31. In the NVAC group, the maximum prevalence observed was 40% at D45 and D60. A comparison of the frequencies for BRD cases showed a statistical trend at D36 (P = 0.07), with a higher prevalence for the NVAC group (30%) in relation to the VAC group (5.6%). For the NVAC group, a greater number of total leukocytes was observed at T3 (P = 0.038) and granulocytes (trend) at T2 (P = 0.066). Time analysis demonstrated a decrease in haptoglobin concentration in both groups (NVAC, P = 0.005 and VAC, P = 0.006), with a reduction in the values at T1 and T3 (NVAC = 0.005 and VAC = 0.024). Antibody titers were similar between groups for BVDV, BoHV-1, and BRSV. Higher titers for BPI3V were observed for the VAC group at D56 (P = 0.045).Discussion: The early-onset BRD was present in both groups between 30 and 60 days of age, based on the higher prevalence observed. These data reinforce the importance of early immunization programmes before infection. Factors such as management practices and facilities may have also contributed to the higher prevalence of BRD. The increased number of leukocytes and neutrophils at T2 (D35) and T3 (D56) in the NVAC group points to a stronger inflammatory response to various types of potential challenges. The inflammatory leukocyte profile explains the higher haptoglobin values observed in the NVAC group at T2 (D35). The similarity of titers of antibodies against BVDV, BoHV-1, and BRSV between groups may indicate that vaccinating the calves at 14 days of age did not induce a humoral immune response to these viruses, likely due to interference from the maternal antibodies. Early vaccination prevented a drop in specific viral antibodies and promoted partial protection for vaccinated calves around 14 days of age, with a decrease in the intensity of the inflammatory response at the peak of the disease and a higher concentration of antibodies against BPI3V after the booster

Hematological changes in dogs fed with Tenebrio molitor larvae meal

The aim of this study was to evaluate the haematological and biochemical parameters of dogs submitted to different levels of inclusion of mealworm meal (0, 2.5, 5 and 7.5%) in their diet. Four adult females aged 5 years, castrated, with an average weight of 15.8 kg were used. A Latin square design was used, with 4 treatments and 4 replications. The base diets were calculated based on the NRC and provided in the proportion of 80% dry food and 20% wet food. The animals were dewormed, clinically evaluated and adapted to the base diet for 10 days prior to the insertion of me. After fitting, blood was collected for evaluation of haematological and biochemical parameters. The experimental period of each treatment was 14 days, with a new blood collection on the 15th day, with the animals in the fasted state. The blood parameters evaluated were blood count and biochemical tests, composed of urea, creatinine, alanine aminotransferase, alkaline phosphatase, cholesterol, total proteins and their fractions, glucose, triglycerides, C-reactive protein, fibrinogen and immunoglobulin E. The data obtained were subjected to multiple analysis of variance at the 5% significance level. The results showed that none of the mealworm protein inclusion levels showed blood alterations. Therefore, it can be concluded that the use of mealworm meal did not harm the health of the animals tested in experiment, showing that it can be an alternative protein source and can be safely included up to a level of 7.5% in dog foods

Nissl stain analysis.

<p>A: After Nissl staining, the typical morphology of the granule layer of DG for each group investigated (control, E1, E2 and E3) are shown. B: Effect of the non-synaptic activity induction on the cell morphology, performed for the group E3 in comparison with control. Before seizure induction, the normal morphology of the granule layer (a) is replaced by the presence of whitish zones, somas with swelling (thick arrows) and dark cells (thin arrows) (b). After seizure induction, the slices of the control group showed edematous cell bodies and a few dark cells (thin arrows) (c). However, the slices from the group E3 appeared with intense edematous necrosis, as shown in (d). Several cell bodies with intense swelling (thick arrows) and dark cells (thin arrows) can be seen.</p

DG immune-stained for CD11b.

<p>(A) Control, E1, E2 e E3 (Magnification 100x). Insets show typical microglial morphology of each group (Magnification 1000x). Arrows head indicate microglial activation also shown in the insets. (B) Optical densitometry analysis of the immuno-reactivity to CD11b. E2 and E3 groups exhibited increased immuno-staining in comparison with Control and E1. Statistical comparisons were done with one-way ANOVA with Dunnett’s test. Data are presented as mean ± SEM. Error bars indicate SEM. *<i>p</i><0.05.</p

DG immuno-stained for NKCC1 and KCC2.

<p>Typical images for NKCC1 (Magnification: 400x). All alcohol treated groups expressed more intense staining for NKCC1 than Control (A). For KCC2 the immuno-reactivity was more intense for the group E3 (K) (Magnification: 1000x). The transition between the granule and molecular layers exhibited the most intense staining for both NKCC1, comparing E3 (G) with Control (E), and KCC2, comparing E3 (N) with Control (L). Statistical comparisons were done with one-way ANOVA with Dunnett’s test. Data are presented as mean ± SEM. Error bars indicate SEM. *<i>p</i><0.05.</p

Typical non-synaptic epileptiform activities induced in hippocampus slices and recorded in the granular layer of the dentate gyrus according to the groups.

<p>(A) control, (B) E1, (C) E2 and (D) E3.</p