Untangling the immune basis of disease susceptibility

© 2020 Copyright Ribeiro and Graca. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are creditedInteractions between immune cell receptors and proteins that determine disease susceptibility shed light on how different arms of the immune system are involved in three viral infections and Crohn's disease.info:eu-repo/semantics/publishedVersio

T-cell immunology : the maths of memory

© Copyright Borghans and Ribeiro. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.Mathematical modeling reveals that long-term immunological memory is maintained in a manner that is even more dynamic than previously thought.info:eu-repo/semantics/publishedVersio

Introduction to modeling viral infections and immunity

Copyright © 2018 John Wiley & Sons, Inc. All rights reserved.Infectious agents, such as HIV, hepatitis B virus (HBV), hepatitis C virus (HCV), malaria, and influenza remain significant public health threats, with ~41 million people chronically infected by HIV, ~331 million infected by HBV, ~148 million infected by HCV, and ~351 million cases of malaria, according to the Global Burden of Disease 2013 study. In addition, threats of new influenza pandemics or emerging viruses, such as Ebola and Zika, have created alarm in the United States and in many parts of the world. Despite intensive research efforts by public and private institutions, there are still no vaccines for HIV, HCV, malaria, Ebola, Zika, and many other pathogens. Even though there has been enormous progress with antiviral therapies for chronic infections, we are still unable to cure HIV and HBV, and life‐long treatment is needed.info:eu-repo/semantics/publishedVersio

A new Paxillus MacLeay, 1819 (Coleoptera: Passalidae: Passalinae) from Brazilian Amazon

Paxillus MacLeay, 1819 is a genus widely distributed throughout the Americas and currently holds sixteen species. Seven species are known in the Amazon. Herein Paxillus elatus n. sp. is described and illustrated based on eight males and four females collected in the Brazilian Amazonian states Acre, Amazonas and Rondônia.Paxillus MacLeay, 1819 es un género distribuido en toda América y actualmente tiene dieciséis especies. Siete especies son conocidas para la Amazonia. En el presente trabajo Paxillus elatus n. sp., es descrita e ilustrada basándose en ocho machos y cuatro hembras colectados en los estados brasileños Amazónicos: Acre, Amazonas y Rondônia

The role of infected cell proliferation in the clearance of acute HBV Infection in humans

© 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).Around 90–95% of hepatitis B virus (HBV) infected adults do not progress to the chronic phase and, instead, recover naturally. The strengths of the cytolytic and non-cytolytic immune responses are key players that decide the fate of acute HBV infection. In addition, it has been hypothesized that proliferation of infected cells resulting in uninfected progeny and/or cytokine-mediated degradation of covalently closed circular DNA (cccDNA) leading to the cure of infected cells are two major mechanisms assisting the adaptive immune response in the clearance of acute HBV infection in humans. We employed fitting of mathematical models to human acute infection data together with physiological constraints to investigate the role of these hypothesized mechanisms in the clearance of infection. Results suggest that cellular proliferation of infected cells resulting in two uninfected cells is required to minimize the destruction of the liver during the clearance of acute HBV infection. In contrast, we find that a cytokine-mediated cure of infected cells alone is insufficient to clear acute HBV infection. In conclusion, our modeling indicates that HBV clearance without lethal loss of liver mass is associated with the production of two uninfected cells upon proliferation of an infected cell.This work was funded by National Institutes of Health grants R01-AI116868 (RMR), R01-AI028433 (ASP) and R01-OD011095 (ASP). Portions of this work were performed under the auspices of the U.S. Department of Energy under contract DE-AC52-06NA25396.info:eu-repo/semantics/publishedVersio

Noise is not error : detecting parametric heterogeneity between epidemiologic time series

© Copyright © 2018 Romero-Severson, Ribeiro and Castro. This is an open-accessarticle distributed under the terms of the Creative Commons Attribution License (CCBY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Mathematical models play a central role in epidemiology. For example, models unify heterogeneous data into a single framework, suggest experimental designs, and generate hypotheses. Traditional methods based on deterministic assumptions, such as ordinary differential equations (ODE), have been successful in those scenarios. However, noise caused by random variations rather than true differences is an intrinsic feature of the cellular/molecular/social world. Time series data from patients (in the case of clinical science) or number of infections (in the case of epidemics) can vary due to both intrinsic differences or incidental fluctuations. The use of traditional fitting methods for ODEs applied to noisy problems implies that deviation from some trend can only be due to error or parametric heterogeneity, that is noise can be wrongly classified as parametric heterogeneity. This leads to unstable predictions and potentially misguided policies or research programs. In this paper, we quantify the ability of ODEs under different hypotheses (fixed or random effects) to capture individual differences in the underlying data. We explore a simple (exactly solvable) example displaying an initial exponential growth by comparing state-of-the-art stochastic fitting and traditional least squares approximations. We also provide a potential approach for determining the limitations and risks of traditional fitting methodologies. Finally, we discuss the implications of our results for the interpretation of data from the 2014-2015 Ebola epidemic in Africa.This work was funded by NIH grants R01-AI087520 and R01-AI104373; grants FIS2013-47949-C2-2-P and FIS2016-78883-C2-2-P and PRX 16/00287 (Spain); and PIRSES-GA-2012-317893 (7th FP, EU).info:eu-repo/semantics/publishedVersio

Cardiovascular and respiratory responses to microinjection of L-glutamate into the caudal pressor area in conscious and anesthetized rats

The role of the caudal pressor area (CPA) in the maintenance of vasomotor tonus in anesthetized and decerebrate animals has been clearly established. In conscious animals, however, the participation of CPA in the cardiovascular control remains to be fully elucidated. In the present study, unilateral L-glutamate (L-Glu) (10 and/or 20 nmol/70 nl) microinjection into CPA, in conscious male Wistar rats (250-280 g) caused a significant increase in mean arterial blood pressure (MAP; control: 112 ± 1.9 mmHg; after 20 nmol L-Glu: 139 ± 4.5 mmHg, N = 12, P<0.05) and respiratory rate (control: 81 ± 3.5 breaths/min; after 10 nmol L-Glu: 92 ± 3 breaths/min, P<0.05; after 20 nmol L-Glu: 104 ± 5 breaths/min, N = 6, P<0.05). The subsequent anesthesia with urethane caused a significant increase in basal respiratory frequency (conscious: 81 ± 3.5 breaths/min; under urethane: 107 ± 1.3 breaths/min, N = 6, P<0.05). Anesthesia also significantly attenuated L-Glu-evoked pressor (conscious: deltaMAP = +27 mmHg; anesthetized: deltaMAP = +18 mmHg, P<0.05) and respiratory responses. These results suggest that glutamatergic receptors in the CPA are involved in cardiovascular and respiratory modulation in conscious rats.Universidade Federal do Espírito Santo Centro Biomédico Departamento de Ciências FisiológicasFAESA Faculdade de Saúde de VitóriaUniversidade Federal de São Paulo (UNIFESP) Disciplina de Fisiologia CardiovascularUNIFESP, Disciplina de Fisiologia CardiovascularSciEL

O peso da endocardite infeciosa em Portugal nos últimos 30 anos : uma revisão sistemática de estudos observacionais

© 2021 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. Este é um artigo Open Access sob uma licença CC BY-NC-ND (http://creativecommons.org/licenses/by-nc-nd/4.0/).Introduction: Infective endocarditis affects cardiac valves or devices and has a potentially uncertain prognosis. Little information is available on the epidemiology of this disease in Portugal. Objective: A systematic review of all evidence published in the last 30 years to assess epidemiological data in patients hospitalized with infective endocarditis in Portuguese hospital centers. Methods: Extensive search of all published evidence using Medline, Scopus, general search databases and in addition Portuguese medical journals was performed. All relevant studies in Portuguese or English that reported short- or long-term mortality were included. Results: Eighteen retrospective cohort studies (15 medical and three surgical series) were included with a total of 1872 patients assessed. The medical series included 1279 patients. Older males with predominant native left heart valve involvement were identified. Staphylococcus and streptococcus were the most frequent reported pathogens. Surgical intervention was performed on average in 29.8% of cases. The short-term mortality rate ranged from three to 37.2% (average 21.9%). Surgical cases involved older males with affected native left heart valves, emergent/urgent indication was dominant and short-term mortality ranged from 13.6 to 16%. Conclusions: The current study provides a descriptive analysis of the published series of infective endocarditis in Portugal over the last 30 years. Therefore, it may serve as a starting point for the development and implementation of a multicentric prospective registry on infective endocarditis patients in Portugal that will allow a better and more accurate characterization of this special patient population.Introdução: A endocardite infeciosa afeta válvulas ou dispositivos cardíacos e tem um prognóstico potencialmente incerto. Pouca informação está disponível sobre a sua epidemiologia em Portugal. Objetivo: Revisão sistemática de todos os estudos publicados nos últimos 30 anos que avaliaram dados epidemiológicos em pacientes hospitalizados com endocardite infeciosa em centros hospitalares portugueses. Métodos: Uma pesquisa detalhada de todos os estudos publicados, usando a Medline, Scopus, motores de busca generalistas e também revistas médicas portuguesas, foi realizada. Todos os estudos relevantes em português ou inglês que relataram mortalidade em curto ou longo prazo foram incluídos. Resultados: Dezoito estudos de coorte retrospetivos (15 séries médicas e 3 cirúrgicas) foram incluídos com um total de 1872 pacientes avaliados. As séries médicas incluíram 1279 doentes. Identificaram-se homens mais velhos com envolvimento predominante de válvulas cardíacas esquerdas nativas. Staphylococcus e Streptococcus foram os agentes envolvidos mais frequentemente. A intervenção cirúrgica foi realizada em 29,8% dos casos (valor médio). A taxa de mortalidade em curto prazo variou entre 3 e 37,2% (média 21,9%). Os casos cirúrgicos incluíram homens mais velhos com envolvimento das válvulas esquerdas nativas, a indicação emergente/urgente dominou e a mortalidade em curto prazo variou entre 13,6 e 16%. Conclusões: O estudo atual fornece uma análise descritiva de todas as séries de endocardite infeciosa publicadas em Portugal nos últimos 30 anos. Pode servir como ponto de partida para o desenvolvimento de um registo prospetivo multicêntrico em pacientes com endocardite infeciosa em Portugal, que permitirá uma caracterização mais rigorosa desta população específica de doentes.info:eu-repo/semantics/publishedVersio