Role of protein kinase R in the killing of Leishmania major by macrophages in response to neutrophil elastase and TLR4 via TNF and IFN

In cutaneous leishmaniasis, Leishmania amazonensis activates macrophage double-stranded, RNA-activated protein kinase R (PKR) to promote parasite growth. In our study, Leishmania major grew normally in RAW cells, RAW-expressing dominant-negative PKR (PKR-DN) cells, and macrophages of PKR-knockout mice, revealing that PKR is dispensable for L. major growth in macrophages. PKR activation in infected macrophages with poly I:C resulted in parasite death. Fifty percent of L. major-knockout lines for the ecotin-like serine peptidase inhibitor (ISP2; Δisp2/isp3), an inhibitor of neutrophil elastase (NE), died in RAW cells or macrophages from 129Sv mice, as a result of PKR activation. Inhibition of PKR or NE or neutralization of Toll-like receptor 4 or 2(TLR4 or TLR2) prevented the death of Δisp2/isp3. Δisp2/isp3 grew normally in RAW-PKR-DN cells or macrophages from 129Sv pkr−/−, tlr2−/−, trif−/−, and myd88−/− mice, associating NE activity, PKR, and TLR responses with parasite death. Δisp2/isp3 increased the expression of mRNA for TNF-α by 2-fold and of interferon β (IFNβ) in a PKR-dependent manner. Antibodies to TNF-α reversed the 95% killing by Δisp2/isp3, whereas they grew normally in macrophages from IFN receptor–knockout mice. We propose that ISP2 prevents the activation of PKR via an NE-TLR4-TLR2 axis to control innate responses that contribute to the killing of L. major.—Faria, M. S., Calegari-Silva, T. C., de Carvalho Vivarini, A., Mottram, J. C., Lopes, U. G., Lima, A. P. C. A. Role of protein kinase R in the killing of Leishmania major by macrophages in response to neutrophil elastase and TLR4 via TNFα and IFNβ

Mortalidade neonatal em unidades de cuidados intensivos no Brasil Central

OBJETIVO: Identificar fatores prognósticos de mortalidade neonatal em unidades de cuidados intensivos. MÉTODOS: Realizou-se estudo de coorte de nascidos vivos do município de Goiânia, no período de novembro de 1999 a outubro de 2000. Procedeu-se à vinculação das bases de dados das declarações de nascidos vivos e de óbitos, das quais as variáveis de exposição foram extraídas. Adicionalmente, foi implementado um sistema ativo de vigilância de mortalidade neonatal. A variável de efeito foi constituída dos recém-nascidos admitidos nas unidades de cuidados intensivos que sobreviveram (n=713) e dos que morreram (n=162). Utilizou-se o modelo de regressão de Cox para identificar fatores associados à mortalidade neonatal e a curva Receiver Operating Characteristic para avaliar a acurácia de variáveis estatisticamente significantes em modelo multivariado. Taxas de mortalidade ajustadas por peso de nascimento e Apgar do quinto minuto foram calculadas para cada unidade de cuidados intensivos. RESULTADOS: Baixo peso ao nascer e Apgar do quinto minuto permaneceram associados ao óbito neonatal, de forma independente. Peso ao nascer igual a 2.500 g apresentou acurácia de 0,71 (IC 95%: 0,65-0,77) na predição de óbito neonatal (sensibilidade =72,2%). Observou-se ampla variação nas taxas de mortalidade entre as unidades de cuidados intensivos (9,5%-48,1%) sendo que duas delas permaneceram com taxas significantemente mais altas após o ajuste da mortalidade pelo peso de nascimento e Apgar. CONCLUSÕES: Os resultados mostraram que o peso de nascimento é uma variável sensível para uso em triagens em programas de vigilância de óbito neonatal e pode identificar as unidades de cuidados intensivos com altas taxas de mortalidade para implementação de ações preventivas e para intervenções no período intra-parto.OBJECTIVE: To identify potential prognostic factors for neonatal mortality among newborns referred to intensive care units. METHODS: A live-birth cohort study was carried out in Goiânia, Central Brazil, from November 1999 to October 2000. Linked birth and infant death certificates were used to ascertain the cohort of live born infants. An additional active surveillance system of neonatal-based mortality was implemented. Exposure variables were collected from birth and death certificates. The outcome was survivors (n=713) and deaths (n=162) in all intensive care units in the study period. Cox's proportional hazards model was applied and a Receiver Operating Characteristic curve was used to compare the performance of statistically significant variables in the multivariable model. Adjusted mortality rates by birth weight and 5-min Apgar score were calculated for each intensive care unit. RESULTS: Low birth weight and 5-min Apgar score remained independently associated to death. Birth weight equal to 2,500g had 0.71 accuracy (95% CI: 0.65-0.77) for predicting neonatal death (sensitivity =72.2%). A wide variation in the mortality rates was found among intensive care units (9.5-48.1%) and two of them remained with significant high mortality rates even after adjusting for birth weight and 5-min Apgar score. CONCLUSIONS: This study corroborates birth weight as a sensitive screening variable in surveillance programs for neonatal death and also to target intensive care units with high mortality rates for implementing preventive actions and interventions during the delivery period

Expression in Escherichia coli, purification, refolding and antifungal activity of an osmotin from Solanum nigrum

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Profile of Self-Care Capacity and Alcohol Use in Elderly Brazilians during the COVID-19 Outbreak: An Online Study

Background: Preventive and positive online coping strategies are essential for harm reduction associated with alcohol abuse among older adults in pandemic and social isolation scenarios. The objectives were to examine the relationship between alcohol use/abuse and physical capacity/self-care to perform the physical activities of daily living or impairment of the functional capacity of the elderly in the COVID-19 pandemic. Methods: An online cross-sectional survey was carried out. One hundred and one elderly people in the city of São Paulo, Brazil, participated in a community program. Results: Most participants (52.5%) showed excellent self-care skills. Approximately 12% of participants reported problems related to alcohol use/abuse. There was no association between self-care ability and abuse and probable alcohol dependence. Conclusions: Although most participants have excellent self-care and functional capacity and have not evidenced alcohol use/abuse, health professionals need to systematically provide information to prevent alcohol abuse, especially in scenarios of great emotional distress, such as in a pandemic. In addition, the online meetings held by the UAPI program were shown to be opportunities for social interaction and were essential to minimize the negative effects of the possible presence of alcohol use/abuse and the deteriorating performance of physical activities of daily living during a pandemic outbreak for the elderly

Factors associated with thrombocytopenia in severe leptospirosis (Weil's disease)

OBJECTIVE: This study was conducted to investigate factors associated with thrombocytopenia in a large cohort of patients with leptospirosis in an endemic area. METHODS: This retrospective study included 374 consecutive patients with leptospirosis who were admitted to tertiary hospitals in Fortaleza, Brazil. All patients had a diagnosis of severe leptospirosis (Weil's disease). Acute kidney injury was defined according to the RIFLE criteria. Thrombocytopenia was defined as a platelet coun

The effects of Pilates vs. aerobic training on cardiorespiratory fitness, isokinetic muscular strength, body composition, and functional tasks outcomes for individuals who are overweight/obese: a clinical trial

Background Some studies have been conducted to verify the effects of Pilates for individuals who are obese, but conclusive results are not yet available due to methodological concerns. The present study aims to verify and compare the effects of Pilates and aerobic training on cardiorespiratory fitness, isokinetic muscular strength, body composition, and functional task outcomes for individuals who are overweight/obese. Methods Of the sixty participants, seventeen were allocated to the control group, since the intervention protocol (Pilates or walking sessions) was during their working hours. The remaining 44 participants were randomly allocated to one of two experimental groups (Pilates (n = 22)) or aerobic groups (n = 21).The Pilates and aerobic groups attended 60-min exercise sessions, three times per week for 8 weeks. The aerobic group performed walking training at a heart rate corresponding to the ventilatory threshold. The Pilates group performed exercises on the floor, resistance apparatus, and 1-kg dumbbells. The control group received no intervention. All volunteers were evaluated at the beginning and end of the intervention. The following assessments were conducted: food intake, cardiorespiratory maximal treadmill test, isokinetic strength testing, body composition and anthropometry, abdominal endurance test, trunk extensor endurance test, flexibility test and functional (stair and chair) tests. Results There was no significant difference pre- and post-intervention in calorie intake [F(2, 57) = 0.02744, p = 0.97)]. A significant improvement in oxygen uptake at ventilatory threshold (p = 0.001; d = 0.60), respiratory compensation point (p = 0.01; d = 0.48), and maximum effort (p = 0.01; d = 0.33) was observed only in the Pilates group. Isokinetic peak torque for knee flexor and extensor muscles did not change for any groups. Lean mass (p = 0.0005; d = 0.19) and fat mass (p = 0.0001; d = 0.19) improved only in the Pilates group. Waist and hip circumference measurements decreased similarly in both experimental groups. Abdominal test performance improved more in the Pilates group (p = 0.0001; d = 1.69) than in the aerobic group (p = 0.003; d = 0.95). Trunk extensor endurance and flexibility improved only in the Pilates group (p = 0.0003; d = 0.80 and p = 0.0001; d = 0.41, respectively). The Pilates group showed greater improvement on the chair and stair tests (p = 0.0001; d = 1.48 and p = 0.003; d = 0.78, respectively) than the aerobic group (p = 0.005; d = 0.75 and p = 0.05; d = 0.41, respectively). Conclusion Pilates can be used as an alternative physical training method for individuals who are overweight or obese since it promotes significant effects in cardiorespiratory fitness, body composition, and performance on functional tests

Isogeometric analysis for fluid shear stress in cancer cells

Este trabalho foi financiado pelo Concurso Anual para Projetos de Investigação, Desenvolvimento, Inovação e Criação Artística (IDI&CA) 2018 do Instituto Politécnico de Lisboa. Código de referência IPL/2018/IGACFC_ISELThe microenvironment of the tumor is a key factor regulating tumor cell invasion and metastasis. The effects of physical factors in tumorigenesis is unclear. Shear stress, induced by liquid flow, plays a key role in proliferation, apoptosis, invasion, and metastasis of tumor cells. The mathematical models have the potential to elucidate the metastatic behavior of the cells’ membrane exposed to these microenvironment forces. Due to the shape configuration of the cancer cells, Non-uniform Rational B-splines (NURBS) lines are very adequate to define its geometric model. The Isogeometric Analysis allows a simplified transition of exact CAD models into the analysis avoiding the geometrical discontinuities of the traditional Galerkin traditional techniques. In this work, we use an isogeometric analysis to model the fluid-generated forces that tumor cells are exposed to in the vascular and tumor microenvironments, in the metastatic process. Using information provided by experimental tests in vitro, we present a suite of numerical experiments which indicate, for standard configurations, the metastatic behavior of cells exposed to such forces. The focus of this paper is strictly on geometrical sensitivities to the shear stress’ exhibition for the cell membrane, this being its innovation.info:eu-repo/semantics/publishedVersio

Neutrophil elastase promotes Leishmania donovani infection via interferon-β

Visceral leishmaniasis is a deadly illness caused by Leishmania donovani that provokes liver and spleen inflammation and tissue destruction. In cutaneous leishmaniasis, the protein of L. major named inhibitor of serine peptidases (ISP2) inactivates neutrophil elastase (NE) present at the macrophage surface, resulting in blockade of TLR4 activation, prevention of TNF and IFN production and parasite survival. We report poor intracellular growth of L. donovani in macrophages from knock-out mice for NE (ela-/-), TLR4 or TLR2. NE and TLR4 co-localized with the parasite in the parasitophorous vacuole. Parasite load in the liver and spleen of ela-/- mice were reduced and accompanied by increased nitric oxide and decreased TGF production. Expression of ISP2 was not detected in L. donovani and a transgenic line constitutively expressing ISP2, displayed poor intracellular growth in macrophages and decreased burden in mice. Infected ela-/- macrophages displayed significantly lower IFN mRNA than background mice macrophages and the intracellular growth of was fully restored by exogenous IFN. We propose that L. donovani utilizes the host NE-TLR machinery to induce IFN necessary for parasite survival/growth during early infection. Low or absent expression of parasite ISP2 in L. donovani is necessary to preserve the activation of the NE-TLR pathway