Tempol improves neuroinflammation and delays motor dysfunction in a mouse model (SOD1G93A) of ALS

The development of new therapeutic strategies to treat amyotrophic lateral sclerosis (ALS) is of utmost importance. The use of cyclic nitroxides such as tempol may provide neuroprotection and improve lifespan. We investigated whether tempol (50 mg/kg) presents therapeutic potential in SOD1G93A transgenic mice. Tempol treatment began at the asymptomatic phase of the disease (10th week) and was administered every other day until week 14, after which it was administered twice a week until the final stage of the disease. The animals were sacrificed at week 14 (initial stage of symptoms—ISS) and at the end stage (ES) of the disease. The lumbar spinal cord of the animals was dissected and processed for use in the following techniques: Nissl staining to evaluate neuronal survival; immunohistochemistry to evaluate astrogliosis and microgliosis (ISS and ES); qRT-PCR to evaluate the expression of neurotrophic factors and pro-inflammatory cytokines (ISS); and transmission electron microscopy to evaluate the alpha-motoneurons (ES). Behavioral analyses considering the survival of animals, bodyweight loss, and Rotarod motor performance test started on week 10 and were performed every 3 days until the end-stage of the disease. The results revealed that treatment with tempol promoted greater neuronal survival (23%) at ISS compared to untreated animals, which was maintained until ES. The intense reactivity of astrocytes and microglia observed in vehicle animals was reduced in the lumbar spinal cords of the animals treated with tempol. In addition, the groups treated with tempol showed reduced expression of proinflammatory cytokines (IL1β and TNFα) and a three-fold decrease in the expression of TGFβ1 at ISS compared with the group treated with vehicle. Altogether, our results indicate that treatment with tempol has beneficial effects, delaying the onset of the disease by enhancing neuronal survival and decreasing glial cell reactivity during ALS progression in SOD1G93A mice161CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP300553/2013-9; 303085/2017-72013/16168-8; 2014/06892-3; 2017/02895-6; 2018/05006-

Prevalence of dental fluorosis in Curitiba, Brazil, in the years of 2006 and 2016 / Prevalência da fluorose dental em Curitiba, Brasil, nos anos de 2006 e 2016

Objective. The objective of this study was to describe the prevalence of dental fluorosis (DF) in 12-year-old schoolchildren from Curitiba, Brazil, in the years of 2006 and 2016.Methods. Participants were randomly selected from municipal, state and private schools. Schoolchildren were randomly chosen from within the Health Districts (HD), and thus a total of 679 and 934 participated in the years of 2006 and 2016 respectively. They were examined and their DF was classified according to the modified Dean index. The data were analyzed to determine distribution and the Chi-square test was used to search for associations between the outcome (DF) and the dependent variables (gender and HD), using SPSS, version 21.0.Results. There was an overall decrease in DF cases from 27.7% to 17.0 % (OR = 1.83; 95% CI: 1.44 - 2.33) in the period analyzed. There was an increase in cases of moderate DF from 16.5% in 2006 to 20.5% in 2016 however, without statistical significance (OR = 0.76; 95% CI: 0.44 - 1.31). When the variables gender and HD were included in the bivariate analysis, they presented no significant association with the outcome (p> 0.05).Conclusions. The decrease in the prevalence of DF was significant in the period, although the values remained high, and that the dependent variables were not significantly associated with the outcome.

RELAÇÃO ENTRE INFIDELIDADE E INFECÇÃO AO HIV/AIDS NA VISÃO DE HOMENS HETEROSSEXUAIS

Considerando a infidelidade dos homens com relacionamento estável, um comportamento propício à infecção pelo HIV/AIDS, o estudo tem como objetivo investigar a relação entre o comportamento infiel desses homens e o risco de infecção pelo HIV/AIDS. Trata-se de um estudo qualitativo usando etnoenfermagem nas fases: observação primária e a escuta, observação com participação limitada, participação primária e reflexão primária com reconfirmação dos dados. Os pacientes eram homens heterossexuais que estavam sendo tratados para a AIDS em hospital de referência do Brasil. Os resultados mostraram que os fatores motivadores da infidelidade eram o confito civil, a atividade de trabalho, a tentação pelo novo e o senso de controle/poder. Conclui-se que a enfermagem pode atuar em conjunto com a população masculina no despertar da consciência do panorama do HIV/AIDS, ajudando na desconstrução de valores enraizados na sociedade, levando os homens a refetir sobre comportamentos que promovem a prevenção desse vírus

R534C mutation in hERG causes a trafficking defect in iPSC-derived cardiomyocytes from patients with type 2 long QT syndrome

Patient-specific cardiomyocytes obtained from induced pluripotent stem cells (CM-iPSC) offer unprecedented mechanistic insights in the study of inherited cardiac diseases. The objective of this work was to study a type 2 long QT syndrome (LQTS2)-associated mutation (c.1600C > T in KCNH2, p.R534C in hERG) in CM-iPSC. Peripheral blood mononuclear cells were isolated from two patients with the R534C mutation and iPSCs were generated. In addition, the same mutation was inserted in a control iPSC line by genome editing using CRISPR/Cas9. Cells expressed pluripotency markers and showed spontaneous differentiation into the three embryonic germ layers. Electrophysiology demonstrated that action potential duration (APD) of LQTS2 CM-iPSC was significantly longer than that of the control line, as well as the triangulation of the action potentials (AP), implying a longer duration of phase 3. Treatment with the IKr inhibitor E4031 only caused APD prolongation in the control line. Patch clamp showed a reduction of IKr on LQTS2 CM-iPSC compared to control, but channel activation was not significantly affected. Immunofluorescence for hERG demonstrated perinuclear staining in LQTS2 CM-iPSC. In conclusion, CM-iPSC recapitulated the LQTS2 phenotype and our findings suggest that the R534C mutation in KCNH2 leads to a channel trafficking defect to the plasma membrane.Fil: Mesquita, Fernanda C. P.. Universidade Federal do Rio de Janeiro; BrasilFil: Arantes, Paulo C.. Universidade Federal do Rio de Janeiro; BrasilFil: Kasai Brunswick, Tais H.. Universidade Federal do Rio de Janeiro; BrasilFil: Araujo, Dayana S.. Universidade Federal do Rio de Janeiro; BrasilFil: Gubert, Fernanda. Universidade Federal do Rio de Janeiro; BrasilFil: Monnerat, Gustavo. Universidade Federal do Rio de Janeiro; BrasilFil: Silva dos Santos, Danúbia. Universidade Federal do Rio de Janeiro; BrasilFil: Neiman, Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Leitão, Isabela C.. Universidade Federal do Rio de Janeiro; BrasilFil: Barbosa, Raiana A. Q.. Universidade Federal do Rio de Janeiro; BrasilFil: Coutinho, Jorge L.. National Institute Of Cardiology; BrasilFil: Vaz, Isadora M.. Pontificia Universidad Catolica de Parana; BrasilFil: dos Santos, Marcus N.. Universidade Federal do Rio de Janeiro; BrasilFil: Borgonovo, Tamara. Pontificia Universidad Catolica de Parana; BrasilFil: Cruz, Fernando E. S.. National Institute of Cardiology; BrasilFil: Miriuka, Santiago Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Medei, Emiliano H.. Universidade Federal do Rio de Janeiro; BrasilFil: Campos de Carvalho, Antonio C.. Universidade Federal do Rio de Janeiro; Brasil. National Institute of Cardiology; Brasil. National Institute for Science and Technology in Regenerative Medicine; BrasilFil: Carvalho, Adriana B.. Universidade Federal do Rio de Janeiro; Brasil. National Institute for Science and Technology in Regenerative Medicine; Brasi

Mesenchymal Stem Cells Therapies on Fibrotic Heart Diseases

Stem cell therapy is a promising alternative approach to heart diseases. The most prevalent source of multipotent stem cells, usually called somatic or adult stem cells (mesenchymal stromal/stem cells, MSCs) used in clinical trials is bone marrow (BM-MSCs), adipose tissue (AT-MSCs), umbilical cord (UC-MSCs) and placenta. Therapeutic use of MSCs in cardiovascular diseases is based on the benefits in reducing cardiac fibrosis and inflammation that compose the cardiac remodeling responsible for the maintenance of normal function, something which may end up causing progressive and irreversible dysfunction. Many factors lead to cardiac fibrosis and failure, and an effective therapy is lacking to reverse or attenuate this condition. Different approaches have been shown to be promising in surpassing the poor survival of transplanted cells in cardiac tissue to provide cardioprotection and prevent cardiac remodeling. This review includes the description of pre-clinical and clinical investigation of the therapeutic potential of MSCs in improving ventricular dysfunction consequent to diverse cardiac diseases

Prospects for bone marrow cell therapy in amyotrophic lateral sclerosis: how far are we from a clinical treatment?

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that causes progressive muscular atrophy and death within 3–5 years after its onset. Despite the significant advances in knowledge of ALS pathology, no effective treatment is available. Therefore, it is imperative to search for new alternatives to treat ALS. Cell therapy, especially using bone-marrow cells, has showed to be very useful to protect the neural tissue in different brain disease or traumatic lesions. In ALS, most published results show beneficial effects of the use bone marrow cells, especially mesenchymal stromal cells. However, until now, the best outcome extends animal's lifespan by only a few weeks. It is essential to continue the search for a really effective therapy, testing different cells, routes and time-windows of administration. Studying the mechanisms that initiate and spread the degenerative process is also important to find out an effective therapy. Therefore, we discussed here some progresses that have been made using bone-marrow cell therapy as a therapeutic tool for ALS

On strategies to help reduce contamination on public transit: a multilayer network approach

Abstract In times of a global pandemic, public transit can be crucial to spreading viruses, especially in big cities. Many works have shown that the human infection risk could be extremely high due to the length of exposure time, transmission routes, and structural characteristics during public transportation, and this can result in the rapid spread of the infection. Vaccines are often part of strategies to reduce contagion; however, they can be scarce in pandemic settings. Considering real-world and large-scale traffic data, this work proposes using time-varying multilayer networks to identify the main critical places to be prioritized in interventions, such as vaccination campaigns, to help reduce contagion on public transit. We exemplify our strategy in different vaccination scenarios. First, when considering only critical bus stops as priority vaccination points, determined by our approach, we indicate that focusing on vaccination in these locations reduces the spread of infection using fewer doses than a random vaccination. In another experiment, we demonstrate the flexibility of our approach in identifying other critical points of interest, healthcare units in this case. Vaccination in these vital health units could also be a viable strategy to curb contagion using a predetermined number of doses. The approach proposed in this study is not limited to vaccination strategies. It also applies to other problems that share similar properties, even in several different contexts, such as optimization in public transit or exploring different points of interest to gather insights from other issues of interest

Characterization of Public Transit Mobility Patterns of Different Economic Classes

This paper analyzes public transit mobility of different economic classes of Curitiba, Brazil, exploring an official smart card dataset provided by the city. With the population divided into subsets corresponding to economic strata, we characterized vital spatial-temporal transit usage patterns, such as departure times and destinations reached by different economic classes. We also constructed a network representing the common origin and destination of public transit users, enabling discovering distinct patterns. Among the results, we observe that with the increase in wealth, the morning activity is postponed (on average for 2 h), and the spatial distribution of the trips becomes more localized compared with lower classes. We also show that our model captures fairly well realistic mobility patterns exploring a cheaper and larger-scale data source by comparing our results with a household travel survey from Curitiba. Understand how people in different economic classes appropriate urban spaces help to provide subsidies for, e.g., more sustainable economic development propositions