Análise do microbioma intestinal humano de pacientes da população brasileira com transtorno depressivo e transtorno de ansiedade

TCC(graduação) - Universidade Federal de Santa Catarina. Centro de Ciências Biológicas. Biologia.A microbiota humana consiste em cerca de 10-100 trilhões de células microbianas simbióticas, o microbioma (MB) consiste nos genes que essas células carregam. O MB pode ser entendido como um ecossistema onde todos os organismos podem interagir entre si e com o ambiente. Em um indivíduo saudável, a microbiota patogênica e simbiótica coexistem sem problemas. Porém, o MB é dinâmico e muda influenciado por diferentes fatores, como dieta, uso de antibióticos, doenças entre outros. Se houver um distúrbio nesse equilíbrio ocorre a disbiose, interrompendo essas interações normais. Como resultado, o corpo pode se tornar mais suscetível às doenças. A depressão (DEP) é um transtorno psiquiátrico altamente prevalente, afetando o indivíduo de diferentes formas e pode ser acompanhada por outras perturbações psiquiátricas, tais como ansiedade (ANS). Os mecanismos biológicos envolvidos na DEP e ANS ainda não são bem compreendidos, mas a relação entre a DEP/ANS e as alterações na microbiota já é amplamente aceita. Neste trabalho, avaliamos o microbioma intestinal (MBI) de 29 indivíduos saudáveis (CON) e 29 pacientes afetados pela DEP e DEP/ANS da população brasileira. As amostras de DNA de fezes dos pacientes foram sequenciadas, utilizando a metodologia Shotgun. Os programas Metaphlan e Humann3 foram utilizados para inferir a abundância taxonômica e funcional das amostras. Posteriormente, com o pacote MaAsLin2 foi realizada uma análise diferencial de abundância para procurar possíveis alterações significativas entre grupos (p < 0,05). O perfil da MBI de pacientes da população brasileira utilizada como controle é composta majoritariamente por Bacteroidetes e Firmicutes em nível de filo, Bacteroides, Prevotella, Alistipes, Faecalibacterium, Parabacteroides, Eubacterium e Roseburia em nível de gênero. O perfil da microbiota de pacientes da população Brasileira acometida por DEP e DEP/ANS é composta majoritariamente por Bacteroidetes e Firmicutes em nível de filo, Bacteroides, Prevotella, Alistipes, Faecalibacterium, Parabacteroides, Eubacterium e Akkermansia em nível de gênero. Foram encontrados um total de 95 táxons em abundância diferencial entre pacientes CON vs DEP e CON vs DEP/ANS. O filo Bacteroidetes mostrou uma abundância reduzida em pacientes DEP, Bacteroides spp. estão envolvidos na produção de metabolitos relevantes para a DEP, tais como GABA. Diferentes estudos apontam para uma associação entre DEP e deficiência GABAérgica. Ainda, foram encontradas 32 vias diferencialmente abundantes. Pacientes com DEP, apresentaram alterações em diferentes vias relacionadas com metabolismo de carboidratos/aminoácidos e relacionadas com energia. O equilíbrio energético desempenha um papel essencial no funcionamento biológico normal e o eixo Hipotálamo-Pituitária-Adrenal (HPA) participa na regulação de diferentes sistemas, incluindo o sistema metabólico. Alterações no metabolismo do açúcar e no metabolismo energético podem ser resultado de distúrbios no eixo HPA. Desta forma, é possível concluir que indivíduos acometidos com DEP e ANS podem apresentar diversas alterações no microbioma intestinal. Alterações essas, que podem impactar o sistema imunológico afetando o indivíduo de uma maneira psíquica, mas também física. As nossas descobertas corroboram pesquisas anteriores e podem servir de base para uma maior compreensão do desenvolvimento da DEP e da ANS, especialmente em pacientes da população brasileira.The human microbiota consists of about 10-100 trillion symbiotic microbial cells, the microbiome (MB) consists of the genes that these cells carry. The MB can be understood as an independent and self-sufficient ecosystem, where all organisms can interact with each other and the environmen. In a healthy individual, the pathogenic and symbiotic microbiota coexist without problems. However, the MB is dynamic and changes influenced by different factors, such as diet, antibiotic use, disease, and so on. If there is a disturbance in this balance, dysbiosis occurs, disrupting these normal interactions. As a result, the body can become more susceptible to disease. Depression (DEP) is a common illness around the world, affecting the individual in different ways, and can be accompanied by other psychiatric disorders such as anxiety (ANS). The biological mechanisms involved in DEP and ANS are still not well understood, but the relationship between DEP/ANS and alterations in the microbiota is already widely accepted. In this work, we evaluated the gut microbiome (MBI) of 29 healthy individuals (CON) and 29 patients affected by DEP and DEP/ANS from the Brazilian population. Stool DNA samples from the patients were sequenced, using Shotgun methodology. The Metaphlan and Humann3 programs were used to infer the taxonomic and functional abundance of the samples. Subsequently, with the MaAsLin2 package a differential abundance analysis was performed to look for possible significant changes between groups (p< 0.05). The MBI profile of the control individuals was mostly composed of Bacteroidetes and Firmicutes at phylum level, Bacteroides, Prevotella, Alistipes, Faecalibacterium, Parabacteroides, Eubacterium and Roseburia at genus level. The microbiota profile of the individuals affected by DEP and DEP/ANS was composed mostly of Bacteroidetes and Firmicutes at the phylum level, Bacteroides, Prevotella, Alistipes, Faecalibacterium, Parabacteroides, Eubacterium and Akkermansia at the genus level. A total of 95 taxa were found in differential abundance between CON vs DEP and CON vs DEP/ANS patients. The phylum Bacteroidetes showed a reduced abundance in DEP patients, Bacteroides spp. are involved in the production of DEP relevant metabolites such as GABA. Different studies point to an association between DEP and GABAergic dysfunction. Furthermore, 32 differentially abundant pathways were found. Patients with DEP, showed alterations in different pathways related to carbohydrate/amino acid metabolism and related to energy. Energy balance plays an essential role in normal biological functioning and the HPA axis participates in the regulation of different systems, including the metabolic system. Changes in sugar metabolism and energy metabolism can be a result of disturbances in the HPA axis. Thus, we can conclude that individuals affected with DEP and ANS may have various alterations in the gut microbiome. These changes might impact the immune system, affecting the individual in a psychological as well as physical way. Our findings corroborate previous research and may serve as a basis for further understanding the development of DEP and ANS, especially in patients from the Brazilian population

SARS-CoV-2 uses CD4 to infect T helper lymphocytes

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a major global outbreak of respiratory tract disease known as Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 infects mainly lungs and may cause several immune-related complications, such as lymphocytopenia and cytokine storm, which are associated with the severity of the disease and predict mortality. The mechanism by which SARS-CoV-2 infection may result in immune system dysfunction is still not fully understood. Here, we show that SARS-CoV-2 infects human CD4+ T helper cells, but not CD8+ T cells, and is present in blood and bronchoalveolar lavage T helper cells of severe COVID-19 patients. We demonstrated that SARS-CoV-2 spike glycoprotein (S) directly binds to the CD4 molecule, which in turn mediates the entry of SARS-CoV-2 in T helper cells. This leads to impaired CD4 T cell function and may cause cell death. SARS-CoV-2-infected T helper cells express higher levels of IL-10, which is associated with viral persistence and disease severity. Thus, CD4-mediated SARS-CoV-2 infection of T helper cells may contribute to a poor immune response in COVID-19 patients.</p

SARS-CoV-2 uses CD4 to infect T helper lymphocytes

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a major global outbreak of respiratory tract disease known as Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 infects mainly lungs and may cause several immune-related complications, such as lymphocytopenia and cytokine storm, which are associated with the severity of the disease and predict mortality. The mechanism by which SARS-CoV-2 infection may result in immune system dysfunction is still not fully understood. Here, we show that SARS-CoV-2 infects human CD4+ T helper cells, but not CD8+ T cells, and is present in blood and bronchoalveolar lavage T helper cells of severe COVID-19 patients. We demonstrated that SARS-CoV-2 spike glycoprotein (S) directly binds to the CD4 molecule, which in turn mediates the entry of SARS-CoV-2 in T helper cells. This leads to impaired CD4 T cell function and may cause cell death. SARS-CoV-2-infected T helper cells express higher levels of IL-10, which is associated with viral persistence and disease severity. Thus, CD4-mediated SARS-CoV-2 infection of T helper cells may contribute to a poor immune response in COVID-19 patients.</p

Alterações cognitivas na infecção pelo HIV: uma revisão sistemática: Cognitive changes in HIV infection: a systematic review

Provocada pelo vírus da imunodeficiência humana, com a síndrome da imunodeficiência adquirida, numa pessoa tem o seu sistema imunológico prejudicado, tornando-se suscetível a outras doenças e infecção. Tem-se a estimativa de que 50% dos infectados com o referido vírus podem sofrer alterações cognitivas. Diante disso, este estudo tem como objetivo refletir sobre mudanças estruturais cerebrais e comprometimento cognitivo em pacientes com HIV. Portanto, trata-se de uma revisão sistemática de literatura, desenvolvida a partir da seleção de estudos nas bases de dados Scielo, Pubmed e BVS/Medline a partir do uso de descritores DeCS/MeSH e aplicação de critérios de inclusão e exclusão. Após a análise e interpretação dos dados, concluiu-se que há uma significativa prevalência de HAND em adultos infectados por HIV, no que se refere a alterações cognitivas, especialmente entre pacientes do sexo feminino, de baixa escolaridade e renda, com diagnóstico tardio e baixa quantidade de linfócitos CD4 no início do tratamento. Entre essas pessoas, revelam-se comprometimentos quanto à memória, atenção, controle de impulsos, velocidade de processamento e motora, dentre outros

Influence of different pulp capping materials to induce coronal tooth discoloration

Aim: This study aimed to evaluate the influence of white MTA, gray MTA, calcium hydroxide and calcium aluminate cement (CAC) in tooth color when used as pulp capping materials. Methodology: Extracted third molars were used (n = 50). According to the experimental groups, a 2 mm layer was placed in the pulp canal chamber: Group 1 – White MTA; Group 2 – Gray MTA; Group 3 – CAC; Group 4 – calcium hydroxide paste followed by calcium hydroxide cement. In the control group white gutta-percha was used. Vestibular, lingual, mesial and distal color readout was performed at baseline and after 30 days. Images were captured using a digital camera Nikon D80 and shade evaluation performed using Photoshop 7.0. The blue channel in red, green and blue color mode (RGB) was used to measure chromatic changes in a scale from 0 (darkest) to 255 (lightest). The data were evaluated by univariate analysis. Results: All teeth showed some discoloration after 30 days. The mean variation of pixel intensity for the blue channel was similar between groups. However, considering the mean pixel intensity for the blue channel after 30 days, teeth where CAC was used were significantly darker than those from the control group. Conclusions: This study demonstrated that all tested materials induced teeth shade changes after 30 days of simulated pulpotomy. The mean variation of color was similar between groups and CAC caused the higher color change

Cost analysis of photobiomodulation in tibia fracture in the Brazilian public health system

Managing tibial fractures requires substantial health resources, which costs the health system. This study aimed to describe the costs of photobiomodulation (PBM) with LEDs in the healing process of soft tissue lesions associated with tibial fracture compared to a placebo. Economic analysis was performed based on a randomized controlled clinical trial, with a simulation of the cost-effectiveness and incremental cost model. Adults (n = 27) hospitalized with tibia fracture awaiting definitive surgery were randomized into two distinct groups: the PBM Group (n = 13) and the Control Group with simulated phototherapy (n = 14). To simulate the cost-effectiveness and incremental cost model, the outcome was the evolution of wound resolution by the BATES-JENSEN scale and time of wound resolution in days. The total cost of treatment for the Control group was R$21,164.56, and a difference of R$7,527.10 more was observed when compared to the treatment of the PBM group. The proposed intervention did not present incremental cost since the difference in the costs to reduce measures between the groups was smaller for the PBM group. When analyzing the ICER (Incremental cost-effectiveness ratio), it would be possible to save R$3,500.98 with PBM and decrease by 2.15 points in the daily average on the BATES-JENSEN scale. It is concluded, therefore, that PBM can be a supportive therapy of clinical and economic interest in a hospital setting

Emergence of Two Distinct SARS-CoV-2 Gamma Variants and the Rapid Spread of P.1-like-II SARS-CoV-2 during the Second Wave of COVID-19 in Santa Catarina, Southern Brazil

The western mesoregion of the state of Santa Catarina (SC), Southern Brazil, was heavily affected as a whole by the COVID-19 pandemic in early 2021. This study aimed to evaluate the dynamics of the SARS-CoV-2 virus spreading patterns in the SC state from March 2020 to April 2021 using genomic surveillance. During this period, there were 23 distinct variants, including Beta and Gamma, among which the Gamma and related lineages were predominant in the second pandemic wave within SC. A regionalization of P.1-like-II in the Western SC region was observed, concomitant to the increase in cases, mortality, and the case fatality rate (CFR) index. This is the first evidence of the regionalization of the SARS-CoV-2 transmission in SC and it highlights the importance of tracking the variants, dispersion, and impact of SARS-CoV-2 on the public health systems

Gender inequality and not female mentors hinder female scientists career outcomes

Studies on gender disparity in academia generate constructive discussions to promote equality. In a recently published study, AlShebli et al. 2020 analyzed the role of informal mentorship in supporting early-career scientists and how gender may shape scientific careers. Besides presenting methodological flaws, the study culminates in the authors' conclusion that mentoring quality is determined by the mentor's gender, suggesting that female protégés reap more benefits when mentored by males rather than equally-impactful females. Despite acknowledging that possible causal factors were not considered in their analyses, they attest that the success of female scientists' careers relies on opposite-gender mentorships in terms of publication and impact. Although the authors state that these findings add a new perspective to the policy debate on the best ways to elevate the women in science, their conclusions reinforce the traditional patriarchal, biased scientific structure that stimulates a poorly diversified hierarchical chain in STEM. Here we highlight the study's methodological weaknesses and major issues that must be addressed to avoid the perpetuation of gender disparity in science