Pulmonary inflammation and viral replication define distinct clinical outcomes in fatal cases of COVID-19.

COVID-19 has affected more than half a billion people worldwide, with more than 6.3 million deaths, but the pathophysiological mechanisms involved in lethal cases and the host determinants that determine the different clinical outcomes are still unclear. In this study, we assessed lung autopsies of 47 COVID-19 patients and examined the inflammatory profiles, viral loads, and inflammasome activation. Additionally, we correlated these factors with the patient's clinical and histopathological conditions. Robust inflammasome activation was detected in the lungs of lethal cases of SARS-CoV-2. Experiments conducted on transgenic mice expressing hACE2 and infected with SARS-CoV-2 showed that Nlrp3-/- mice were protected from disease development and lethality compared to Nlrp3+/+ littermate mice, supporting the involvement of this inflammasome in disease exacerbation. An analysis of gene expression allowed for the classification of COVID-19 patients into two different clusters. Cluster 1 died with higher viral loads and exhibited a reduced inflammatory profile than Cluster 2. Illness time, mechanical ventilation time, pulmonary fibrosis, respiratory functions, histopathological status, thrombosis, viral loads, and inflammasome activation significantly differed between the two clusters. Our data demonstrated two distinct profiles in lethal cases of COVID-19, thus indicating that the balance of viral replication and inflammasome-mediated pulmonary inflammation led to different clinical outcomes. We provide important information to understand clinical variations in severe COVID-19, a process that is critical for decisions between immune-mediated or antiviral-mediated therapies for the treatment of critical cases of COVID-19.

The Meaning of Inchoative se in Brazilian Portuguese: A Replication of Lundquist et al.'s (2016) Experiment.

In the well-known causative alternation, a verb appears either in a causative-transitive or in an inchoative-intransitive form. The inchoative form is marked with a reflexive clitic in some languages, such as Norwegian, but is unmarked in others, such as English. There are two main proposals to explain the alternation: a lexical-derivational account (a lexical rule is responsible for the demotion of the cause argument), and a syntactic-derivational one (in a type of reflexivization, the theme/patient is construed as responsible for causing the event). A third type of approach posits that the alternation emerges when a verb can be found in different constructions and no derivation is involved. Lundquist et al. (Glossa J Gen Linguist 1:1-30, 2016) put the first two approaches to experimental testing and found that while the decausativization approach is adequate for English, the reflexivization approach explains the Norwegian facts. The present experimental study investigates which proposal is adequate to explain the alternation in Brazilian Portuguese. Differently from both English and Norwegian, Brazilian Portuguese allows reflexive-marked and unmarked inchoatives with the same verb. In a replication of Lundquist et al.'s (Glossa J Gen Linguist 1:1-30, 2016) experiment, our results show that Brazilian Portuguese assigns distinct meanings to the two forms of the inchoative. We conclude that the reflexive pronoun se indicates that the change of state described in the inchoative sentence was caused by some entity, but not an agent. We then argue that a non-derivational approach explains the alternation, as a single verb occurs in distinct syntactic configurations, with distinct meaning implications.

Gasdermin-D activation promotes NLRP3 activation and host resistance to Leishmania infection.

Intracellular parasites from the Leishmania genus cause Leishmaniasis, a disease affecting millions of people worldwide. NLRP3 inflammasome is key for disease outcome, but the molecular mechanisms upstream of the inflammasome activation are still unclear. Here, we demonstrate that despite the absence of pyroptosis, Gasdermin-D (GSDMD) is active at the early stages of Leishmania infection in macrophages, allowing transient cell permeabilization, potassium efflux, and NLRP3 inflammasome activation. Further, GSDMD is processed into a non-canonical 25 kDa fragment. Gsdmd-/- macrophages and mice exhibit less NLRP3 inflammasome activation and are highly susceptible to infection by several Leishmania species, confirming the role of GSDMD for inflammasome-mediated host resistance. Active NLRP3 inflammasome and GSDMD are present in skin biopsies of patients, demonstrating activation of this pathway in human leishmaniasis. Altogether, our findings reveal that Leishmania subverts the normal functions of GSDMD, an important molecule to promote inflammasome activation and immunity in Leishmaniasis.

Activity limitations in leprosy and their association to cognition and neuropsychiatric symptoms.

OBJECTIVES: to analyze activity limitations in patients with leprosy and their association to cognition and neuropsychiatric symptoms. METHODS: this cross-sectional design study included sixty patients with multibacillary leprosy assisted at a reference center. Participants were divided according to their physical disability and submitted to instruments assessing daily activities (basic and instrumental), cognitive functions, and neuropsychiatric symptoms. The order of the instruments was random to avoid any interference of test sequence on the results. RESULTS: fifty-five percent of the participants presented physical disabilities. All patients were independent in performing basic activities but sixty-six percent presented difficulties in performing instrumental activities. Cognitive decline and neuropsychiatric symptoms were seen in advanced stages of the disease, but they were more associated to patient age than to leprosy. CONCLUSIONS: leprosy patients presented physical disabilities and difficulties in performing instrumental daily activities. Cognitive decline and neuropsychiatric symptoms were more associated to aging than to leprosy itself.

Activity limitations in leprosy and their association to cognition and neuropsychiatric symptoms / Limitaciones de tarea en la enfermedad de Hansen y su relación con cognición y síntomas neuropsiquiátricos / Limitações de tarefa na hanseníase e sua associação com cognição e sintomas neuropsiquiátricos

ABSTRACT Objectives: to analyze activity limitations in patients with leprosy and their association to cognition and neuropsychiatric symptoms. Methods: this cross-sectional design study included sixty patients with multibacillary leprosy assisted at a reference center. Participants were divided according to their physical disability and submitted to instruments assessing daily activities (basic and instrumental), cognitive functions, and neuropsychiatric symptoms. The order of the instruments was random to avoid any interference of test sequence on the results. Results: fifty-five percent of the participants presented physical disabilities. All patients were independent in performing basic activities but sixty-six percent presented difficulties in performing instrumental activities. Cognitive decline and neuropsychiatric symptoms were seen in advanced stages of the disease, but they were more associated to patient age than to leprosy. Conclusions: leprosy patients presented physical disabilities and difficulties in performing instrumental daily activities. Cognitive decline and neuropsychiatric symptoms were more associated to aging than to leprosy itself.

RESUMEN Objetivo: analizar limitaciones de tarea en pacientes con Lepra y su relación con cognición y síntomas neuropsiquiátricos. Métodos: este estudio transversal incluyó 60 pacientes con Lepra multibacilar atendidos en centro de referencia. Participantes fueron divididos segundo la disfunción física y evaluados cuanto a las actividades diarias (básicas y instrumentales), funciones cognitivas y síntomas neuropsiquiátricos. Orden de aplicación de los instrumentos aleatoria para evitar interferencia de la secuencia de tests sobre los resultados. Resultados: de los participantes, 55% presentaron disfunción física. Todos pacientes eran independientes en las actividades básicas, pero 66% mostraron dificultades en las actividades instrumentales. Declive cognitivo y síntomas neuropsiquiátricos fueron observados en etapas avanzadas de la enfermedad, pero estos estaban más relacionados a la edad del paciente que a la Lepra. Conclusiones: pacientes con Lepra evidenciaron disfunción física y dificultades en las actividades instrumentales. Declive cognitivo y síntomas neuropsiquiátricos están más relacionados al envejecimiento que a la Lepra.

RESUMO Objetivo: analisar as limitações de tarefa em pacientes com hanseníase e sua associação com cognição e sintomas neuropsiquiátricos. Métodos: este estudo transversal incluiu 60 pacientes com hanseníase multibacilar atendidos em um centro de referência. Os participantes foram divididos segundo a disfunção física e avaliados quanto às atividades diárias (básicas e instrumentais), às funções cognitivas e aos sintomas neuropsiquiátricos. A ordem de aplicação dos instrumentos foi aleatória para evitar interferência da sequência dos testes sobre os resultados. Resultados: dos participantes, 55% apresentaram disfunção física. Todos os pacientes eram independentes nas atividades básicas, mas 66% mostraram dificuldades nas atividades instrumentais. Declínio cognitivo e sintomas neuropsiquiátricos foram observados em estágios avançados da doença, porém estes estavam mais associados à idade do paciente do que à hanseníase. Conclusões: pacientes com hanseníase evidenciaram disfunção física e dificuldades nas atividades diárias instrumentais. Declínio cognitivo e sintomas neuropsiquiátricos estão mais associados ao envelhecimento do que à hanseníase.

Representação social da aposentadoria para professores universitários / Social representations of retirement for teachers at public universities

O objetivo do presente estudo foi analisar as representações sociais da aposentadoria para professores que trabalham em duas universidades federais do nordeste brasileiro. Foram realizadas vinte entrevistas narrativas, pareadas por sexo e instituição, com professores universitários que possuíam 50 anos ou mais de idade. As entrevistas transcritas foram analisadas com auxílio de software de análise textual, do tipo lexicográfica. Os resultados indicaram a composição de seis classes textuais e as representações sociais mais fortes se referiam à aposentadoria como nova etapa de vida, retorno à família, envelhecimento, viagens e lazer. Para os entrevistados, as representações sociais da aposentadoria foram positivas, no entanto, a perspectiva de um trabalho satisfatório, somado ao medo em relação às mudanças previdenciárias e a própria vida, reforçam a intenção de adiar a aposentadoria. Não houve diferenças significativas entre instituições, o que demonstra certa homogeneidade das representações para esse grupo profissional. (AU)

This study aimed to analyze social representations of retirement among professors that work at two federal universities in northeastern Brazil. Twenty narrative interviews were carried out, paired by gender and institution, with university professors aged 50 and above. The transcribed interviews were analyzed with the aid of lexicographical text analysis software. The results indicated six text categories and the strongest social representations referred to retirement as a new phase in life, a return to family, aging, travel and leisure. For the interviewees, the social representations of retirement were positive, however, the prospect of a satisfactory job, added to the fear in relation to social security changes and life itself, reinforce the intention to postpone retirement. There were no significant differences between institutions, which demonstrates a certain homogeneity in representations among this professional group. (AU)

Sobrepeso e obesidade infantil: fatores predisponentes para alterações ortopédicas / Overweight and obesity in children: predisposing factors for orthopedic alterations

Introdução: O sobrepeso e a obesidade infantil apresentam prevalência elevada no Brasil e podem estar ligadas a importantes alterações posturais adaptativas. Objetivo: Avaliar as principais alterações ortopédicas em crianças de 4 a 10 anos de idade, com sobrepeso e obesidade, de uma escola da rede pública da cidade de Patrocínio/MG; correlacionar essas alterações com o índice de massa corporal (IMC) e avaliar o pé de maior apoio plantar. Métodos: Estudo transversal realizado com 94 estudantes que utilizou a classificação de sobrepeso e obesidade segundo cálculo de IMC preconizado pela OMS. Para avaliação postural utilizou-se fotogrametria e os dados foram analisados no software de avaliação postural SAPO®. Para avaliação dos pés utilizou-se Plantigrama e índice de Chippaux-Smirak. Os dados foram analisados através de estatística descritiva e teste W de Shapiro-Wilk. Resultados: Na avaliação postural foi observada uma tendência à retificação lombar e joelhos valgos, porém não foram observadas diferenças significativas em relação às angulações médias de coluna vertebral e dos joelhos de acordo com o IMC e o gênero. A maioria das crianças apresentou pé plano e tinham maior apoio sob o pé direito. Conclusão: Foi observada uma maior prevalência de obesidade e sobrepeso entre os meninos. Na avaliação postural, observou-se que as crianças com sobrepeso e obesidade apresentaram tendência à retificação da lordose lombar, joelhos valgos e pés planos.(AU)

Introduction: Overweight and obesity in children have high prevalence in Brazil and may be related to important adaptive postural changes. Objective: To assess the main orthopedic disorders in children between 4 and 10 years old, with overweight and obesity, attending a public school in the city of Patrocinio/MG; to correlate these changes with BMI and assess the foot with more support. Methods: Cross-sectional study with 94 overweighted or obese students according to BMI calculation recommended by WHO. For postural evaluation was used photogrammetry and data were analyzed with the postural assessment software SAPO®. For evaluation of the feet we used Plantigrama and Chippaus-Smirak index. Data were analyzed using descriptive statistics and Shapiro-Wilk W test. Results: In the postural evaluation a tendency to lumbar rectification and valgus knees was observed, but no significant differences were observed in relation to the means spine and knee angulation according to BMI and gender. Most of the children had flat feet and greater support under the right foot. Conclusion: A higher prevalence of obesity and overweight was observed among boys. In the postural evaluation we observed that overweighted and obese children presented a tendency to rectify lumbar lordosis, valgus knees and flat feet. (AU)