PIEZO1 expression at the glio-vascular unit adjusts to neuroinflammation in seizure conditions.

Mechanosensors are emerging players responding to hemodynamic and physical inputs. Their significance in the central nervous system remains relatively uncharted. Using human-derived brain specimens or cells and a pre-clinical model of mesio-temporal lobe epilepsy (MTLE), we examined how the mRNA levels of the mechanosensitive channel PIEZO1 adjust to disease-associated pro-inflammatory trajectories. In brain tissue micro-punches obtained from 18 drug-resistant MTLE patients, PIEZO1 expression positively correlated with pro-inflammatory biomarkers TNFα, IL-1ß, and NF-kB in the epileptogenic hippocampus compared to the adjacent amygdala and temporal cortex tissues. In an experimental MTLE model, hippocampal Piezo1 and cytokine expression levels were increased post-status epilepticus (SE) and during epileptogenesis. Piezo1 expression positively correlated with Tnfα, Il1ß, and Nf-kb in the hippocampal foci. Next, by combining RNAscope with immunohistochemistry, we identified Piezo1 in glio-vascular cells. Post-SE and during epileptogenesis, ameboid IBA1 microglia, hypertrophic GFAP astrocytes, and damaged NG2DsRed pericytes exhibited time-dependent patterns of increased Piezo1 expression. Digital droplet PCR analysis confirmed the Piezo1 trajectory in isolated hippocampal microvessels in the ipsi and contralateral hippocampi. The combined examinations performed in this model showed Piezo1 expression returning towards basal levels after the epileptogenesis-associated peak inflammation. From these associations, we next asked whether pro-inflammatory players directly regulate PIEZO1 expression. We used human-derived brain cells and confirmed that endothelium, astrocytes, and pericytes expressed PIEZO1. Exposure to human recombinant TNFα or IL1ß upregulated NF-kB in all cells. Furthermore, TNFα induced PIEZO1 expression in a dose and time-dependent manner, primarily in astrocytes. This exploratory study describes a spatiotemporal dialogue between PIEZO1 brain cell-mechanobiology and neuro-inflammatory cell remodeling. The precise functional mechanisms regulating this interplay in disease conditions warrant further investigation.

Musculoskeletal Manifestations Observed in Patients Diagnosed With Chikungunya Virus in 2 Municipalities of the Brazilian Amazon Region.

BACKGROUND: Chikungunya virus fever is an emerging disease that is rapidly spreading and becoming a global public health issue because of its clinical manifestations that cause physical limitations and high rates of chronification. No studies have characterized musculoskeletal manifestations in Brazilian patients with chikungunya. OBJECTIVE: To describe the musculoskeletal manifestations of patients with chikungunya infection in municipalities of the Brazilian Amazon region. METHODS: This study was an observational, descriptive, and analytical study conducted from March to May 2018. The gender, age, time of infection, clinical manifestations reported during the acute phase, and results of a physical examination of the musculoskeletal system were collected. RESULTS: The medical records of 63 patients with a laboratory confirmation of chikungunya virus fever were analyzed. Eighty-three percent of these patients were women, with a mean age of 50.6 ± 14.5 years and 3.3 ± 3.1 months of infection. The main clinical manifestations reported during the acute phase were arthralgia (100%), fever (91%), and exanthema (65%). The physical examination revealed that the main joints affected by arthralgia resulted in a polyarticular (57%, 5-10 joints) and symmetrical pattern (62%) that mainly affected the ankles (53%) and knees (51%). Regarding arthritis, the most frequently affected area was the wrist (42%), with an oligoarticular pattern (42%, 2-4 joints). CONCLUSIONS: In general, the clinical manifestations described in the Brazilian Amazon population are similar to those reported in publications from other countries; however, the main arthritis pattern identified is oligoarticular, with a predominance of the wrist. Moreover, the chronicity rate is 48%.

A Expectativa Profissional do Futuro Médico: Análise do Quadriênio 2014-2017 / Professional Expectations of Future Doctors: Analysis of the Quadriennium 2014-2017

RESUMO O objetivo deste trabalho é descrever as expectativas dos estudantes de Medicina quanto à carreira profissional. Foi realizado um estudo transversal, descritivo e analítico, no período de janeiro de 2014 a dezembro de 2017, com 116 estudantes concluintes em 2014, 116 de 2015, 91 de 2016 e 110 de 2017, totalizando uma amostra de 431 sujeitos. Foi aplicado um questionário para obtenção de informações sobre idade, gênero, ano de formatura, desejos de atuação profissional para os dez anos seguintes, a especialidade que deseja seguir, o nível de atenção no qual deseja trabalhar, a renda a ser alcançada, o número de empregos que acha necessário para alcançá-la e o número de empregos que pretende ter. O estudo demonstrou predomínio de homens (58,7%), e a média de idade foi de 26,4 ± 3,91 anos. Entre as especialidades pretendidas pelos egressos, Clínica Médica foi a mais almejada em todos os anos estudados, exceto no ano de 2016, em que predominou Pediatria. Sobre os desejos profissionais para dez anos após a formação, a docência foi almejada por cerca da metade deles, variando entre 46% e 59%, enquanto a quase totalidade da amostra demonstrou o desejo de trabalhar com assistência (atendimento direto ao paciente). Não houve predomínio entre as atividades ambulatorial/consultório e hospitalar, assim como entre o setor público e o privado. Em relação ao desejo de atuar nos diferentes níveis de atenção à saúde, os formandos de 2014 e 2016 expressaram desejo de atuar predominantemente no nível terciário (40,5 ± 29,3% e 41,1 ± 29,7%, respectivamente) em relação aos demais níveis de atenção. Sobre a pretensão de renda salarial, predominou a faixa acima de dez salários mínimos, sendo que a maioria expressou achar necessários pelo menos três empregos para alcançá-la, embora o desejo da maior parte dos estudados tenha sido manter apenas dois empregos. Conclui-se que as chamadas áreas básicas, como Clínica Médica, Cirurgia Geral e Pediatria, ainda são bastante almejadas pelos formandos. Contudo, mais do que o desejo de segui-las, provavelmente isto representa a necessidade de pré-requisito para acesso a outras especialidades. No geral, os egressos pretendem trabalhar com assistência, têm uma expectativa salarial alta, admitem a necessidade de diversos vínculos empregatícios para atingir esta meta e têm pouco interesse em trabalhar no nível primário de atenção à saúde. Tal realidade poderia ser discutida no âmbito da academia, a fim de oferecer informações realistas aos estudantes sobre o mercado de trabalho e a carreira médica, minimizando frustrações futuras durante o exercício profissional.

ABSTRACT The objective of this work is to describe the expectations of medical students regarding their professional career. In order to do this, a cross-sectional descriptive and analytical study was conducted, from January 2014 to December 2017, with 116 senior students of the class of 2014, 116 of 2015, 91 of 2016 and 110 of 2017, with a total of 431 individuals. A survey was applied to obtain information about their age, gender, graduation year, professional expectations for the 10 years to follow, intended specialty, level of care at which they want to work, intended income, the number of jobs they think they will need to work in to reach that level of income and the number of jobs they expect to have. The study showed that there are more male students (58%) than female, and the average age is 26.4 ± 3.91 years old. General Medicine was the most sought specialty by the graduate students, except for those of the year 2016, when the predominant specialty was Pediatrics. Concerning the professional goals for the 10 years after graduation, teaching was an objective of approximately half of them, ranging between 46% and 59%, while almost all of them demonstrated a wish to perform assistance work (direct patient care). No predominance was found when comparing the expectation of working in a hospital or in private clinics, nor between the private and public sector. Concerning the wish to work at different health care levels, the senior students from the classes of 2014 and 2016 expressed their wish to work predominantly at care level 3 (40.5 ± 29.3% and 41.1 ± 29.7%, respectively). Concerning the intended income, the most popular range was above 10 minimum monthly salaries. Most students stated they believe that at least three jobs would be necessary to reach this salary level, but they also expressed the wish of having only two jobs. We conclude that the so-called basic areas, such as General Medicine, General Surgery and Pediatrics are the most coveted by the senior students. However, this is probably due not only to a desire to follow these specialties, but also because they represent a prerequisite to access other specialties. In general, the graduates intend to work with direct care and have high salary expectations, which is only achieved by having multiple jobs. They have little interest in working at care level one. This reality could be discussed in academic circles, in order to offer realistic information to students about the job market and medical career, minimizing future frustrations during their professional practice.

Doença ulcerosa péptica: realmente é possível identificá-la por meio das características da dor epigástrica? / Peptic ulcer disease: is it really possible to identify it through the characteristics of epigastric pain?

OBJETIVO: Determinar se características da dor epigástrica são capazes de identificar pacientes com doença ulcerosa péptica. MÉTODOS: Estudo caso-controle, com coleta de dados de setembro de 2014 a junho de 2016. Foram incluídos pacientes com mais de 18 anos com dispepsia que realizaram endoscopia digestiva alta ambulatorialmente. Os pacientes foram abordados antes de realizar a endoscopia digestiva alta, verificando, em suas guias, a presença de dispepsia, tendo sido convidados a responder um questionário, e, posteriormente, o prontuário de cada entrevistado foi avaliado para verificação do diagnóstico, sendo, então, divididos entre o Grupo Doença Ulcerosa Péptica (casos), com 32 pacientes, e o Grupo Controle, com 44 pacientes com dispepsia atribuída a outras causas. RESULTADOS: Dos pacientes com dispepsia não ulcerosa, 52,27% caracterizaram a dor como em queimação, sendo 47,72% moderada e que piorava com alimentação. Dentre os demais sintomas, 45,45% relataram náuseas e 25% desconforto pós-prandial, com 52,27% relatando histórico familiar negativo de doença ulcerosa péptica. Em contrapartida, dos pacientes com doença ulcerosa péptica, 53,12% referiram dor em queimação e de moderada intensidade, e 50% relataram piora com alimentação. Dentre os demais sintomas, prevaleceram também náuseas (53,12%) e desconforto pós-prandial (40,62%). A maioria (81,25%) relatou histórico familiar de doença ulcerosa péptica. Observou-se diferença estatística em dor noturna, predominando na doença ulcerosa péptica (p=0,0225) e dor em cólica na dispepsia não ulcerosa (p=0,0308), assim como na ausência de histórico familiar entre os pacientes com dispepsia não ulcerosa (p=0,0195). CONCLUSÃO: A dispepsia relacionada à doença ulcerosa péptica relaciona-se, principalmente, à piora noturna, sendo que a intensidade da dor, a relação com alimentação e os sintomas associados não auxiliaram na diferenciação da dispepsia não ulcerosa, diferentemente do que a literatura tradicionalmente informa. (AU)

To determine whether it is possible to identify Peptic Ulcer Disease through the characteristics of epigastric pain. METHODS: This is a case-control study with data collected between September 2014 and June 2016 including patients over 18 years of age with dyspepsia who underwent upper gastrointestinal endoscopy as outpatients. The patients were approached before the upper gastrointestinal endoscopy when their test requisition form indicated the presence of dyspepsia. The subjects were invited to answer a questionnaire and, afterwards, the records of all interviewees were evaluated to check for the diagnosis. Then, they were divided into a peptic ulcer disease group (cases), with 32 patients, and a control group, with 44 patients with dyspepsia from other causes. RESULTS: Among non-ulcer dyspepsia patients, 52.27% described the pain as a "burning pain", with 47.72% reporting it as moderate and aggravated by food intake. As for other symptoms, 45.45% of subjects reported nausea, and 25% reported postprandial discomfort; 52.27% had no family history of peptic ulcer disease. In contrast, 53.12% of peptic ulcer disease patients reported "burning" and moderate pain, and 50% said the pain was aggravated by eating. As for the other symptoms, nausea (53.12%) and postprandial discomfort (40.62%) prevailed; most of the patients (81.25%) had family history of peptic ulcer disease. There was a statistical difference in night pain, which was more prevalent in peptic ulcer disease (p=0.0225), and colicky pain, which was more frequent in nonulcer dyspepsia (p=0.0308), as well as absence of family history in non-ulcer dyspepsia patients (p=0.0195). CONCLUSION: Dyspepsia caused by peptic ulcer disease is mainly related to night worsening, and pain intensity, the relationship with food intake, and associated symptoms did not help differentiate nonulcer dyspepsia, differently from what the medical literature traditionally suggests. (AU)

Assessment of matrix metalloproteinase (MMP)-2, MMP-8, MMP-9, and their inhibitors, the tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2 in obese children and adolescents.

OBJECTIVES: To compare the circulating levels of matrix metalloproteinase (MMP)-8, pro-MMP-2, pro-MMP-9, and total MMP-9, their endogenous inhibitors, the tissue inhibitors of metalloproteinases (TIMP)-1 and TIMP-2, and the MMP-8/TIMP-1, MMP-9/TIMP-1, and MMP-2/TIMP-2 ratios in normotensive obese children and adolescents with those found in non obese children and adolescents. DESIGN AND METHODS: We studied 40 obese and 40 non obese (controls) children and adolescents in this cross-sectional study. MMP and TIMP concentrations were measured in plasma samples by gelatin zymography and ELISA. RESULTS: Obese children and adolescents had higher circulating MMP-8 concentrations, lower plasma TIMP-1 concentrations, and higher MMP-8/TIMP-1 ratios than non obese controls (P<0.05). We found no differences in pro-MMP-9 or total MMP-9 levels, or in MMP-9/TIMP-1 ratios between groups (P>0.05). While we found no significant differences in pro-MMP-2 levels (P>0.05) obese subjects had higher TIMP-2 concentrations and lower pro-MMP-2/TIMP-2 ratios (P<0.05) than non obese controls. CONCLUSIONS: In conclusion, we found evidence indicating higher net MMP-8 (but not MMP-9 and MMP-2) activity in childhood obesity. The increased MMP-8 levels found in obese children suggest a possibly relevant pathophysiological mechanism that may be involved in the increase of cardiovascular risk associated with childhood obesity.