Correlation between cellular expression of complement regulatory proteins with depletion and repopulation of B lymphocytes in peripheral blood of patients with rheumatoid arthritis treated with rituximab

Objetivos: Correlacionar a expressão basal das proteínas reguladoras do complemento (PRC)CD55, CD59, CD35 e CD46 nos linfócitos B do sangue periférico de uma coorte de 10 pacientescom artrite reumatoide (AR) iniciando tratamento com rituximabe (RTX) com a deplec¸ão etempo de repopulac¸ão dessas células.Métodos: Dez pacientes com AR receberam duas infusões de 1 g de RTX com intervalo de14 dias. Análises imunofenotípicas para detecc¸ão de CD55, CD59, CD35 e CD46 nos linfócitosB foram feitas imediatamente antes da primeira infusão. A populac¸ão de linfócitos B foianalisada por meio da expressão de CD19 basal e após um, dois e seis meses após a infusãode RTX e então trimestralmente até a recaída clínica. Deplec¸ão de linfócitos B no sangueperiférico foi definida como expressão de CD19 < 0,005 × 109/l.Resultados: Dez mulheres com mediana de 49 anos e DAS 28 basal de 5,6 foram avali-adas; nove eram soropositivas para o fator reumatoide. Cinco pacientes apresentaramrepopulac¸ão de linfócitos B após dois meses e as outras cinco aos seis meses. Houvecorrelac¸ão entre a expressão basal de CD46 e o tempo de repopulac¸ão (coeficientede correlac¸ão -0,733, p = 0,0016). Tendência semelhante foi observada com CD35, porém semsignificância estatística (coeficiente de correc¸ão 0,522, p = 0,12).Conclusão: Expressão aumentada de CD46 foi preditora de repopulac¸ão mais rápida de lin-fócitos B em pacientes tratados com RTX. Estudos com um número maior de pacientesserão necessários para confirmar a utilidade da expressão basal das PRC como preditora deresposta clínica.Objectives: To correlate the basal expression of complement regulatory proteins (CRPs) CD55, CD59, CD35, and CD46 in B-lymphocytes from the peripheral blood of a cohort of 10 patients with rheumatoid arthritis (RA) initiating treatment with rituximab (RTX) with depletion and time repopulation of such cells. Methods: Ten patients with RA received two infusions of 1 g of RTX with an interval of 14 days. Immunophenotypic analysis for the detection of CD55, CD59, CD35, and CD46 on B-lymphocytes was carried out immediately before the first infusion. The population of B-lymphocytes was analyzed by means of basal CD19 expression and after 1, 2, and 6 months after the infusion of RTX, and then quarterly until clinical relapse. Depletion of B-lymphocytes in peripheral blood was defined as a CD19 expression <0,005 × 109/L. Results: Ten women with a median of 49 years and a baseline DAS28 = 5.6 were evalu- ated; 9 were seropositive for rheumatoid factor. Five patients showed a repopulation of B-lymphocytes after 2 months, and the other five after 6 months. There was a corre- lation between the basal expression of CD46 and the time of repopulation (correlation coefficient = -0.733, p = 0.0016). A similar trend was observed with CD35, but without statistical significance (correction coefficient = -0.522, p = 0.12). Conclusion: The increased CD46 expression was predictive of a faster repopulation of B-lymphocytes in patients treated with RTX. Studies involving a larger number of patients will be needed to confirm the utility of basal expression of CRPs as a predictor of clinical response

Sistema Web Aplicado à Genética de Populações

- Este trabalho tem o objetivo de auxiliar, estudantes e pesquisadores, na precisão dos cálculos sobre genética populacional, por meio de um software educativo: o Popgenelation. As técnicas de melhoramento genético trazem diversos benefícios, porém frequentemente para chegar a resultados satisfatórios, é necessária a realização de cálculos de equações complexas e que geralmente são solucionadas, pelos estudantes e pesquisadores, sem o auxilio de um sistema informatizado. Além disso, os sistemas existentes que realizam cálculos similares, porém não específicos para a genética de população, são pagos ou possuem restrições de acesso e não possuem caráter educativo, ou seja, sua usabilidade não é satisfatória. Diante do exposto, verifica-se a necessidade de aumentar a confiabilidade e precisão dos cálculos feitos por pesquisadores (da área de Genética), além de automatizar essa etapa com a ajuda de um sistema informatizado e ainda auxiliar estudantes que necessitam aprender o conteúdo de genética populacional via um software educativo. A pesquisa é metodológica, pois se refere à realidade, e nos leva a caminhos, formas ou procedimentos para alcançar um determinado fim. E aplicada, pois tem um objetivo concreto que é o software de melhoramento genético, que visa sanar um problema real, logo é algo prático, com uma solução concreta. Os resultados encontrados pela análise dos questionários evidenciaram a usabilidade do sistema, caracterizando-o como um software educativo. &nbsp

Novel thermostable xylanase GH10 from Malbranchea pulchella expressed in Aspergillus nidulans with potential applications in biotechnology

Background: The search for novel thermostable xylanases for industrial use has intensified in recent years, and thermophilic fungi are a promising source of useful enzymes. The present work reports the heterologous expression and biochemical characterization of a novel thermostable xylanase (GH10) from the thermophilic fungus Malbranchea pulchella, the influence of glycosylation on its stability, and a potential application in sugarcane bagasse hydrolysis.Results: Xylanase MpXyn10A was overexpressed in Aspergillus nidulans and was active against birchwood xylan, presenting an optimum activity at pH 5.8 and 80°C. MpXyn10A was 16% glycosylated and thermostable, preserving 85% activity after 24 hours at 65°C, and deglycosylation did not affect thermostability. Circular dichroism confirmed the high alpha-helical content consistent with the canonical GH10 family (β/α)8 barrel fold observed in molecular modeling. Primary structure analysis revealed the existence of eight cysteine residues which could be involved in four disulfide bonds, and this could explain the high thermostability of this enzyme even in the deglycosylated form. MpXyn10A showed promising results in biomass degradation, increasing the amount of reducing sugars in bagasse in natura and in three pretreated sugarcane bagasses.Conclusions: MpXyn10A was successfully secreted in Aspergillus nidulans, and a potential use for sugarcane bagasse biomass degradation was demonstrated.Peer reviewedMicrobiology and Molecular Genetic

INTERNAÇÕES HOSPITALARES POR TRANSTORNOS MENTAIS DEVIDO AO USO DE ÁLCOOL E SUBSTÂNCIAS PSICOATIVAS: UMA AVALIAÇÃO DE 2018 A 2023

&nbsp; Brazil has the highest rates of anxiety disorders and is fifth in cases of depression, which drives individuals to use alcohol and psychoactive substances as a mechanism to alleviate mental suffering. This study aims to analyze the clinical and epidemiological landscape of dengue cases in the Southeast region of Brazil from 2014 to 2023. It is a descriptive, quantitative, and retrospective study based on data obtained from the Hospital Morbidity System (SIH) at the Department of Informatics of the Unified Health System (DATASUS). The total number of hospitalizations for mental disorders associated with the use of alcohol and psychoactive substances in Brazil between 2018 and 2023 was 435,923. The South region had the highest number of cases (n=181,455), with the state of Rio Grande do Sul accounting for over 54.69% of these hospitalizations. The age group with the highest frequency of cases was 30 to 39 years, corresponding to 26.89% (n=117,234) of the cases. The sample was predominantly composed of male individuals, accounting for 81.15% (n=353,754) of the total. The most frequent race/color in the analyzed sample was white, representing 45.88% (n=200,010) of the cases. Most of the care provided was in an emergency setting, corresponding to 84.61% of the cases. The average length of stay was 20.4 days. During the analyzed period, there were 2,472 deaths, with the majority occurring in individuals aged 50 to 59 years, representing 24.91% of the total. The study revealed a growing trend in the number of cases, particularly among the younger population, which may lead to severe chemical dependency.O Brasil é o país que apresenta as maiores taxas de transtornos de ansiedade e o quinto em casos de depressão, o que leva os indivíduos a buscar o uso de álcool e substâncias psicoativas como mecanismo para aliviar o sofrimento mental. O presente trabalho tem o objetivo de analisar o panorama clínico e epidemiológico dos casos de por transtorno mental associado ao uso de álcool e substâncias psicoativas no Brasil, entre 2018 e 2023. Trata-se de um estudo descritivo, quantitativo e retrospectivo, com base em dados obtidos através do Sistema de Morbidade Hospitalar (SIH) no Departamento de Informática do Sistema Único de Saúde (DATASUS). O total de internações por transtorno mental associado ao uso de álcool e substâncias psicoativas no Brasil, entre 2018 e 2023, foi de 435.923. A região Sul apresentou o maior número de casos (n=181.455), sendo o Rio Grande do Sul o estado responsável por mais de 54,69% dessas internações. A faixa etária com maior frequência de casos foi a de 30 a 39 anos, correspondendo a 26,89% (n=117.234) dos casos. A amostra foi, em sua maioria, composta por indivíduos do sexo masculino, correspondendo a 81,15% (n=353.754) do total. A cor/raça mais frequente na amostra analisada foi a branca, correspondendo a 45,88% (n=200.010) dos casos. A maioria dos atendimentos foi feita em caráter de urgência, correspondendo a 84,61% dos casos. A média de permanência foi de 20,4 dias de internação. Durante o período analisado, houve 2.472 óbitos, dos quais a maior parte eram indivíduos entre 50 e 59 anos, representando 24,91% do total. O estudo evidenciou um padrão de crescimento no número de casos, principalmente entre a população mais jovem, o que pode levar a uma grave dependência química.  

How much leaf area do insects eat? A data set of insect herbivory sampled globally with a standardized protocol

Herbivory is ubiquitous. Despite being a potential driver of plant distribution and performance, herbivory remains largely undocumented. Some early attempts have been made to review, globally, how much leaf area is removed through insect feeding. Kozlov et al., in one of the most comprehensive reviews regarding global patterns of herbivory, have compiled published studies regarding foliar removal and sampled data on global herbivory levels using a standardized protocol. However, in the review by Kozlov et al., only 15 sampling sites, comprising 33 plant species, were evaluated in tropical areas around the globe. In Brazil, which ranks first in terms of plant biodiversity, with a total of 46,097 species, almost half (43%) being endemic, a single data point was sampled, covering only two plant species. In an attempt to increase knowledge regarding herbivory in tropical plant species and to provide the raw data needed to test general hypotheses related to plant–herbivore interactions across large spatial scales, we proposed a joint, collaborative network to evaluate tropical herbivory. This network allowed us to update and expand the data on insect herbivory in tropical and temperate plant species. Our data set, collected with a standardized protocol, covers 45 sampling sites from nine countries and includes leaf herbivory measurements of 57,239 leaves from 209 species of vascular plants belonging to 65 families from tropical and temperate regions. They expand previous data sets by including a total of 32 sampling sites from tropical areas around the globe, comprising 152 species, 146 of them being sampled in Brazil. For temperate areas, it includes 13 sampling sites, comprising 59 species

Mapping 123 million neonatal, infant and child deaths between 2000 and 2017

Since 2000, many countries have achieved considerable success in improving child survival, but localized progress remains unclear. To inform efforts towards United Nations Sustainable Development Goal 3.2—to end preventable child deaths by 2030—we need consistently estimated data at the subnational level regarding child mortality rates and trends. Here we quantified, for the period 2000–2017, the subnational variation in mortality rates and number of deaths of neonates, infants and children under 5 years of age within 99 low- and middle-income countries using a geostatistical survival model. We estimated that 32% of children under 5 in these countries lived in districts that had attained rates of 25 or fewer child deaths per 1,000 live births by 2017, and that 58% of child deaths between 2000 and 2017 in these countries could have been averted in the absence of geographical inequality. This study enables the identification of high-mortality clusters, patterns of progress and geographical inequalities to inform appropriate investments and implementations that will help to improve the health of all populations

Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017

Background The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk–outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk–outcome pairs, and new data on risk exposure levels and risk–outcome associations. Methods We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk–outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017. Findings In 2017, 34·1 million (95% uncertainty interval [UI] 33·3–35·0) deaths and 1·21 billion (1·14–1·28) DALYs were attributable to GBD risk factors. Globally, 61·0% (59·6–62·4) of deaths and 48·3% (46·3–50·2) of DALYs were attributed to the GBD 2017 risk factors. When ranked by risk-attributable DALYs, high systolic blood pressure (SBP) was the leading risk factor, accounting for 10·4 million (9·39–11·5) deaths and 218 million (198–237) DALYs, followed by smoking (7·10 million [6·83–7·37] deaths and 182 million [173–193] DALYs), high fasting plasma glucose (6·53 million [5·23–8·23] deaths and 171 million [144–201] DALYs), high body-mass index (BMI; 4·72 million [2·99–6·70] deaths and 148 million [98·6–202] DALYs), and short gestation for birthweight (1·43 million [1·36–1·51] deaths and 139 million [131–147] DALYs). In total, risk-attributable DALYs declined by 4·9% (3·3–6·5) between 2007 and 2017. In the absence of demographic changes (ie, population growth and ageing), changes in risk exposure and risk-deleted DALYs would have led to a 23·5% decline in DALYs during that period. Conversely, in the absence of changes in risk exposure and risk-deleted DALYs, demographic changes would have led to an 18·6% increase in DALYs during that period. The ratios of observed risk exposure levels to exposure levels expected based on SDI (O/E ratios) increased globally for unsafe drinking water and household air pollution between 1990 and 2017. This result suggests that development is occurring more rapidly than are changes in the underlying risk structure in a population. Conversely, nearly universal declines in O/E ratios for smoking and alcohol use indicate that, for a given SDI, exposure to these risks is declining. In 2017, the leading Level 4 risk factor for age-standardised DALY rates was high SBP in four super-regions: central Europe, eastern Europe, and central Asia; north Africa and Middle East; south Asia; and southeast Asia, east Asia, and Oceania. The leading risk factor in the high-income super-region was smoking, in Latin America and Caribbean was high BMI, and in sub-Saharan Africa was unsafe sex. O/E ratios for unsafe sex in sub-Saharan Africa were notably high, and those for alcohol use in north Africa and the Middle East were notably low. Interpretation By quantifying levels and trends in exposures to risk factors and the resulting disease burden, this assessment offers insight into where past policy and programme efforts might have been successful and highlights current priorities for public health action. Decreases in behavioural, environmental, and occupational risks have largely offset the effects of population growth and ageing, in relation to trends in absolute burden. Conversely, the combination of increasing metabolic risks and population ageing will probably continue to drive the increasing trends in non-communicable diseases at the global level, which presents both a public health challenge and opportunity. We see considerable spatiotemporal heterogeneity in levels of risk exposure and risk-attributable burden. Although levels of development underlie some of this heterogeneity, O/E ratios show risks for which countries are overperforming or underperforming relative to their level of development. As such, these ratios provide a benchmarking tool to help to focus local decision making. Our findings reinforce the importance of both risk exposure monitoring and epidemiological research to assess causal connections between risks and health outcomes, and they highlight the usefulness of the GBD study in synthesising data to draw comprehensive and robust conclusions that help to inform good policy and strategic health planning

Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: A systematic analysis for the Global Burden of Disease Study 2017

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017) includes a comprehensive assessment of incidence, prevalence, and years lived with disability (YLDs) for 354 causes in 195 countries and territories from 1990 to 2017. Previous GBD studies have shown how the decline of mortality rates from 1990 to 2016 has led to an increase in life expectancy, an ageing global population, and an expansion of the non-fatal burden of disease and injury. These studies have also shown how a substantial portion of the world's population experiences non-fatal health loss with considerable heterogeneity among different causes, locations, ages, and sexes. Ongoing objectives of the GBD study include increasing the level of estimation detail, improving analytical strategies, and increasing the amount of high-quality data. Methods: We estimated incidence and prevalence for 354 diseases and injuries and 3484 sequelae. We used an updated and extensive body of literature studies, survey data, surveillance data, inpatient admission records, outpatient visit records, and health insurance claims, and additionally used results from cause of death models to inform estimates using a total of 68 781 data sources. Newly available clinical data from India, Iran, Japan, Jordan, Nepal, China, Brazil, Norway, and Italy were incorporated, as well as updated claims data from the USA and new claims data from Taiwan (province of China) and Singapore. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between rates of incidence, prevalence, remission, and cause of death for each condition. YLDs were estimated as the product of a prevalence estimate and a disability weight for health states of each mutually exclusive sequela, adjusted for comorbidity. We updated the Socio-demographic Index (SDI), a summary development indicator of income per capita, years of schooling, and total fertility rate. Additionally, we calculated differences between male and female YLDs to identify divergent trends across sexes. GBD 2017 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting. Findings: Globally, for females, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and haemoglobinopathies and haemolytic anaemias in both 1990 and 2017. For males, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and tuberculosis including latent tuberculosis infection in both 1990 and 2017. In terms of YLDs, low back pain, headache disorders, and dietary iron deficiency were the leading Level 3 causes of YLD counts in 1990, whereas low back pain, headache disorders, and depressive disorders were the leading causes in 2017 for both sexes combined. All-cause age-standardised YLD rates decreased by 3·9% (95% uncertainty interval [UI] 3·1-4·6) from 1990 to 2017; however, the all-age YLD rate increased by 7·2% (6·0-8·4) while the total sum of global YLDs increased from 562 million (421-723) to 853 million (642-1100). The increases for males and females were similar, with increases in all-age YLD rates of 7·9% (6·6-9·2) for males and 6·5% (5·4-7·7) for females. We found significant differences between males and females in terms of age-standardised prevalence estimates for multiple causes. The causes with the greatest relative differences between sexes in 2017 included substance use disorders (3018 cases [95% UI 2782-3252] per 100 000 in males vs 1400 [1279-1524] per 100 000 in females), transport injuries (3322 [3082-3583] vs 2336 [2154-2535]), and self-harm and interpersonal violence (3265 [2943-3630] vs 5643 [5057-6302]). Interpretation: Global all-cause age-standardised YLD rates have improved only slightly over a period spanning nearly three decades. However, the magnitude of the non-fatal disease burden has expanded globally, with increasing numbers of people who have a wide spectrum of conditions. A subset of conditions has remained globally pervasive since 1990, whereas other conditions have displayed more dynamic trends, with different ages, sexes, and geographies across the globe experiencing varying burdens and trends of health loss. This study emphasises how global improvements in premature mortality for select conditions have led to older populations with complex and potentially expensive diseases, yet also highlights global achievements in certain domains of disease and injury