Mycobacterium leprae causes leprosy, a dermatoneurological disease which affects the skin and peripheral nerves. One of several cellular structures affected during M. leprae infection is the endoplasmic reticulum (ER). Infection by microorganisms can result in ER stress and lead to the accumulation of unfolded or poorly folded proteins. To restore homeostasis in the cell, the cell induces a series of signaling cascades known as the unfolded protein response called UPR (unfolded protein response). The present work is aimed at investigating the in situ expression of these markers in cutaneous lesions of clinical forms of leprosy and establish possible correlation expression patterns and types of lesion. A total of 43 samples from leprosy patients were analyzed by immunohistochemistry with monoclonal antibodies against GRP78/BiP, PERK, IRE1α, and ATF6. A statistically significant difference between the indeterminate, tuberculoid, and lepromatous clinical forms was detected, with high expression of GRP78/BiP, PERK, IRE1α, and ATF6 in tuberculoid forms (TT) when compared to lepromatous leprosy (LL) and indeterminate (I) leprosy. These results represent the first evidence of ER stress in samples of skin lesions from leprosy patients. We believe that they will provide better understanding of the complex pathogenesis of the disease and facilitate further characterization of the cascade of molecular events elicited during infection.

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Resumo O avanço da medicina aprimorou o tratamento de enfermidades, modificando o padrão de morbimortalidade da população, com aumento de doenças crônicas. Esse fenômeno tornou urgente interpretar adequadamente a terminalidade da vida. Considerando essa necessidade, este estudo, de corte transversal, descritivo e analítico, analisou dados sobre a percepção de 111 estudantes do sexto ano de medicina acerca dos cuidados paliativos no fim da vida. Os dados foram coletados entre agosto e novembro de 2016, por meio de questionário e analisados por testes estatísticos com o programa Iramuteq. 37,3% dos estudantes relataram dificuldade em comunicar a morte do paciente à família; 60% sentem-se despreparados ou com dúvidas sobre como lidar com óbitos em serviço de urgência; 25% desconheciam o termo “eutanásia”, 53% “ortotanásia”, e 56% “distanásia”. Os resultados mostram que ainda há lacunas no conhecimento desses estudantes, explicitando a necessidade de que escolas médicas reforcem práticas pedagógicas sobre a morte.

Objective:To describe the clinical manifestations of patients with pulmonary infection caused by mycobacteria of the Mycobacterium abscessus complex (MABSC), and to compare these manifestations with those of patients infected with other nontuberculous mycobacteria (NTM). Methods:This was a retrospective cohort study involving 43 patients divided into two groups: the MABSC group, consisting of patients with pulmonary infection caused by MABSC (n = 17); and the NTM group, consisting of patients with pulmonary infection caused by NTM other than MABSC (n = 26). Patients were previously treated with a regimen of rifampin, isoniazid, pyrazinamide, and ethambutol before the diagnosis of NTM was confirmed by two culture-positive sputum samples. The nucleotide sequences of the hsp65, 16S rRNA, and/or rpoB genes were analyzed to identify the mycobacteria. Data were collected on demographic, clinical, and radiological characteristics, as well as on treatment responses and outcomes. Results:Loss of appetite was the only clinical manifestation that was significantly more common in the MABSC group than in the NTM group (p = 0.0306). The chance of having to use a second treatment regimen was almost 12 times higher in the MABSC group than in the NTM group. Treatment success was significantly higher in the NTM group than in the MABSC group (83.2% vs. 17.6%; p < 0.0001). The chance of recurrence was approximately 37 times higher in the MABSC group than in the NTM group. Conclusions:In the study sample, treatment response of pulmonary disease caused by MABSC was less favorable than that of pulmonary disease caused by other NTM.

ObjectiveLeprosy is a chronic infectious disease presenting with a spectrum of clinical manifestations that correspond to the type of immune response that develops in the host. Factors that may be involved in this process include inflammasomes, cytosolic proteins responsible for the activation of caspase 1, IL-1β and IL-18 secretion, and induction of a type of death called pyroptosis.Patients and methodsWe evaluated the expression of inflammasome markers (nucleotide-binding oligomerization domain-like receptor containing pyrin domain 1 [NLRP1], nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 [NLRP3], caspase 1, IL-1β, and IL-18) by immunohistochemistry in 43 samples of skin lesions of leprosy patients from the groups indeterminate (I) leprosy (13 patients), tuberculoid (TT) leprosy (15 patients), and lepromatous leprosy (LL; 15 patients).ResultsThe evaluated markers were most upregulated in LL lesions, followed by lesions of TT leprosy and I leprosy. Differences were statistically significant between the I leprosy and LL leprosy forms and between the I leprosy and TT leprosy forms. Positive and significant correlations were found between IL-18 and caspase 1 in LL (r=0.7516, P=0.0012) and TT leprosy (r=0.7366, P=0.0017). In I leprosy, correlations were detected between caspase 1 and IL-1β (r=0.6412, P=0.0182), NLRP1 and IL-18 (r=0.5585, P=0.473), NLRP3 and IL-18 (r=0.6873, P=0.0094), and NLRP1 and NLRP3 (r=0.8040, P=0.0009).ConclusionThe expression of inflammasome markers in LL lesions indicates the ineffectiveness of this protein complex in controlling the infection. Caspase 1 may be involved in the pyroptotic cell death in the lepromatous form of the disease. Inflammasomes may act together in the initial phase of I leprosy; this phenomenon may influence the clinical outcome of the disease.

Arboviruses, such as yellow fever virus (YFV), dengue virus (DENV), and chikungunya virus (CHIKV), present wide global dissemination and a pathogenic profile developed in infected individuals, from non-specific clinical conditions to severe forms, characterised by the promotion of significant lesions in different organs of the harbourer, culminating in multiple organ dysfunction. An analytical cross-sectional study was carried out via the histopathological analysis of 70 samples of liver patients, collected between 2000 and 2017, with confirmed laboratory diagnoses, who died due to infection and complications due to yellow fever (YF), dengue fever (DF), and chikungunya fever (CF), to characterise, quantify, and compare the patterns of histopathological alterations in the liver between the samples. Of the histopathological findings in the human liver samples, there was a significant difference between the control and infection groups, with a predominance of alterations in the midzonal area of the three cases analysed. Hepatic involvement in cases of YF showed a greater intensity of histopathological changes. Among the alterations evaluated, cell swelling, microvesicular steatosis, and apoptosis were classified according to the degree of tissue damage from severe to very severe. Pathological abnormalities associated with YFV, DENV, and CHIKV infections showed a predominance of changes in the midzonal area. We also noted that, among the arboviruses studied, liver involvement in cases of YFV infection was more intense.

Arboviruses such as yellow fever virus (YFV), dengue virus (DENV), and chikungunya virus (CHIKV) presenting wide global dissemination and the pathogenic profile developed in infected individuals, which develop from nonspecific clinical conditions to severe forms, characterized by the promotion of significant lesions in different organs of the harborer, culminating in multiple organ dysfunction. To characterize, quantify, and compare the patterns of histopathological alterations in human liver samples from patients with yellow fever (YF), dengue fever (DF), and chikungunya fever (CF). Analytical cross-sectional study by histopathological analysis with 70 samples of liver patients, collected from 2000 to 2017, with confirmed laboratory diagnosis who died due to infection and complications by the YF, DF, and CF. Of the histopathological findings in human liver samples there was a significant difference between the control and infection groups, with a predominance of alterations in the midzonal area of the three cases analyzed, among the arboviruses studied, the hepatic involvement in cases of YF showed greater intensity of histopathological changes. Among the alterations evaluated, cell swelling, microvesicular steatosis and apoptosis were classified as degree of tissue damage from severe to very severe. The pathological abnormalities associated with infection by YFV, DENV, and CHIKV showed predominance of changes in the midzonal area. We also noted that in among of the arboviruses studied, liver involvement in cases of YFV infection was more intense.

Introduction: Faculty development in medical education has shown an increasing focus on universities. Changes in the learning style, the broad access to digital knowledge and new society demands in terms of medical competences have induced the need for updates in teaching practices, especially during the Covid-19 pandemic. Objective: To evaluate the needs of faculty development, reported educational practices and the view on teaching and learning from medical teachers’ perspectives. Methods: this study has a cross-sectional design with a convenience sample of undergraduate medical teachers from a medical school in São Paulo, who coordinate educational units in the curricula. Data collection took place between August and September 2020, by completing an electronic questionnaire. The data were analyzed using proportions, the chi-square test or Fisher’s exact test, with p <0.05 being considered significant. Results: There were 68 medical teachers coordinating curricula units and 47 (69.1%) accepted to participate. Of the total of 47 participants, 26 (55.3%) are female and 21 (44.7%) are male, 17 (36.2%) teachers taught disciplines from first biennium, 20 (42.6%) from the second biennium and 10 (21.1%) from the third biennium. Most of medical teachers reported being motivated to participate in faculty development courses (93.6%), with focus on the inclusion of innovations in their educational practice (85.1%). They reported the need to update teaching and assessment methods. The women reported more frequently the need for training in assessment methods (p = 0.04). In the reported educational practices, women incorporate more attitudes (p = 0.02) and skills in educational planning (p = 0.007), as well as the use of formative assessment (p = 0.03) and more previous training in the use of active methodologies (p = 0.02). Although the recognition of the importance of the dialogue with students being reported by most teachers, student-centered practices were described in a lower percentage of responses. Conclusion: Teachers are motivated to engage in faculty development actions, with several needs regarding educational practices being identified, with differences being observed between genders. Although they reported a dialogic view of the teaching-learning process, this concept is not yet implemented in the reported practice in their disciplines.