A Decreased Frequency of Regulatory T Cells in Patients with Common Variable Immunodeficiency

Introduction: Common variable immunodeficiency disorder (CVID) is a heterogeneous syndrome, characterized by deficient antibody production and recurrent bacterial infections in addition abnormalities in T cells. CD4(+)CD25(high) regulatory T cells (Treg) are essential modulators of immune responses, including down-modulation of immune response to pathogens, allergens, cancer cells and self-antigens.Objective: in this study we set out to investigate the frequency of Treg cells in CVID patients and correlate with their immune activation status.Materials and Methods: Sixteen patients (6 males and 10 females) with CVID who had been treated with regular intravenous immunoglobulin and 14 controls were enrolled. Quantitative analyses of peripheral blood mononuclear cells (PBMC) were performed by multiparametric flow cytometry using the following cell markers: CD38, HLA-DR, CCR5 ( immune activation); CD4, CD25, FOXP3, CD127, and OX40 (Treg cells); Ki-67 and IFN-gamma (intracellular cytokine).Results: A significantly lower proportion of CD4(+)CD25(high) FOXP3 T cells was observed in CVID patients compared with healthy controls (P<0.05). in addition to a higher proportion of CD8(+) T cells from CVID patients expressing the activation markers, CD38(+) and HLA-DR(+) (P<0.05), we observed no significant correlation between Tregs and immune activation.Conclusion: Our results demonstrate that a reduction in Treg cells could have impaired immune function in CVID patients.Universidade Federal de São Paulo, São Paulo, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilWeb of Scienc

HIPERTEXTO NA EDUCAÇÃO A DISTÂNCIA (EAD): INTERAÇÃO MIDIÁTICA E O MÚLTIPLO LEITOR

A investigação direciona-se aos aspectos da leitura e dos sujeitos eminteração nos processos de aprendizado e comunicacionais em cenários da EaD.. Aquestão central que norteia a pesquisa liga-se ao hipertexto presente nas linguagensde EaD e a leitura realizada pelo discente. Além de mapear e averiguar se as propostascurriculares abrem novas possibilidades para pesquisa e aprofundamento deconteúdos. Investiga o papel do professor na relação estabelecida entre os alunos eo conhecimento. Procurou-se saber em que medida os recursos disponíveis no ambientevirtual são utilizados pelos estudantes e como estão refletidos nas produçõesdiscursivas dos discentes

Community pharmacies and pharmacists in Brazil: A missed opportunity

The Brazilian National Health System (BR-NHS) is one of the largest public health systems in the world. In 2019 Brazil had 114,352 community pharmacies (76.8% private owned), that represent the first point of access to healthcare in Brazil due to their wide distribution. Unfortunately, from the government's point of view, the main expected activity of private and public community pharmacies is related to dispensing medicines and other health products. Public community pharmacies can be part of a healthcare center or be in a separate location, sometimes without the presence of a pharmacist. Pharmacists working in these separated locations do not have access to patients’ medical records, and they have difficulty in accessing other members of the patient care team. Pharmacists working in public pharmacies located in healthcare centers may have access to patients’ medical records, but pharmacy activities are frequently under other professional’s supervision (e.g., nurses). Private pharmacies are usually open 24/7 with the presence of a pharmacist for 8 hours on business days. Private community pharmacies have a very limited integration in the BR-NHS and pharmacists are the third largest healthcare workforce in Brazil with more than 221,000 registered in the Brazilian Federal Pharmacist Association [CFF - Conselho Federal de Farmácia]. A University degree in pharmacy is the only requirement to entry into the profession, without any proficiency exam for maintenance or career progression. The Brazilian pharmacist's annual income is ranked as the 2nd better-paid profession with an annual average income of € 5502.37 (in 2020). Description of clinical activities for pharmacies by the CFF increased in the recent years, however there is still a long way to effectively implement them into practice

Cytokine Production but Lack of Proliferation in Peripheral Blood Mononuclear Cells from Chronic Chagas' Disease Cardiomyopathy Patients in Response to T. cruzi Ribosomal P Proteins

Background:Trypanosoma cruzi ribosomal P proteins, P2β and P0, induce high levels of antibodies in patients with chronic Chagas' disease Cardiomyopathy (CCC). It is well known that these antibodies alter the beating rate of cardiomyocytes and provoke apoptosis by their interaction with β1-adrenergic and M2-muscarinic cardiac receptors. Based on these findings, we decided to study the cellular immune response to these proteins in CCC patients compared to non-infected individuals.Methodology/Principal findings:We evaluated proliferation, presence of surface activation markers and cytokine production in peripheral blood mononuclear cells (PBMC) stimulated with P2β, the C-terminal portion of P0 (CP0) proteins and T. cruzi lysate from CCC patients predominantly infected with TcVI lineage. PBMC from CCC patients cultured with P2β or CP0 proteins, failed to proliferate and express CD25 and HLA-DR on T cell populations. However, multiplex cytokine assays showed that these antigens triggered higher secretion of IL-10, TNF-α and GM-CSF by PBMC as well as both CD4+ and CD8+ T cells subsets of CCC subjects. Upon T. cruzi lysate stimulation, PBMC from CCC patients not only proliferated but also became activated within the context of Th1 response. Interestingly, T. cruzi lysate was also able to induce the secretion of GM-CSF by CD4+ or CD8+ T cells.Conclusions/Significance:Our results showed that although the lack of PBMC proliferation in CCC patients in response to ribosomal P proteins, the detection of IL-10, TNF-α and GM-CSF suggests that specific T cells could have both immunoregulatory and pro-inflammatory potential, which might modulate the immune response in Chagas' disease. Furthermore, it was possible to demonstrate for the first time that GM-CSF was produced by PBMC of CCC patients in response not only to recombinant ribosomal P proteins but also to parasite lysate, suggesting the value of this cytokine to evaluate T cells responses in T. cruzi infection.Fil: Longhi, Silvia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Atienza, Augusto. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Perez Prados, Graciela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; ArgentinaFil: Buying, Alcinette. Torrey Pines Institute for Molecular Studies; Estados UnidosFil: Balouz, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Buscaglia, Carlos Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Santos, Radleigh. Torrey Pines Institute for Molecular Studies; Estados UnidosFil: Tasso, Laura Mónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Bonato, Ricardo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Chiale, Pablo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Pinilla, Clemencia. Torrey Pines Institute for Molecular Studies; Estados UnidosFil: Judkowski, Valeria A.. Torrey Pines Institute for Molecular Studies; Estados UnidosFil: Gomez, Karina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentin

Skewed Distribution of Circulating Activated Natural Killer T (NKT) Cells in Patients with Common Variable Immunodeficiency Disorders (CVID)

Common variable immunodeficiency disorder (CVID) is the commonest cause of primary antibody failure in adults and children, and characterized clinically by recurrent bacterial infections and autoimmune manifestations. Several innate immune defects have been described in CVID, but no study has yet investigated the frequency, phenotype or function of the key regulatory cell population, natural killer T (NKT) cells. We measured the frequencies and subsets of NKT cells in patients with CVID and compared these to healthy controls. Our results show a skewing of NKT cell subsets, with CD4+ NKT cells at higher frequencies, and CD8+ NKT cells at lower frequencies. However, these cells were highly activated and expression CD161. The NKT cells had a higher expression of CCR5 and concomitantly expression of CCR5+CD69+CXCR6 suggesting a compensation of the remaining population of NKT cells for rapid effector action

Comparative study of the biochemical changes and volatile compound formations during the production of novel whey-based kefir beverages and traditional milk kefir

Cheese whey (CW) and deproteinised cheese whey (DCW) were investigated for their suitability as novel substrates for the production of kefir-like beverages. Lactose consumption, ethanol production, as well as organic acids and volatile compounds formation, were determined during CW and DCW fermentation by kefir grains and compared with values obtained during the production of traditional milk kefir. The results showed that kefir grains were able to utilise lactose from CW and DCW and produce similar amounts of ethanol (7.8–8.3 g/l), lactic acid (5.0 g/l) and acetic acid (0.7 g/l) to those obtained during milk fermentation. In addition, the concentration of higher alcohols (2-methyl-1-butanol, 3-methyl-1-butanol, 1-hexanol, 2-methyl-1-propanol, and 1-propanol), ester (ethyl acetate) and aldehyde (acetaldehyde) in cheese whey-based kefir and milk kefir beverages were also produced in similar amounts. Cheese whey and deproteinised cheese whey may therefore serve as substrates for the production of kefir-like beverages similar to milk kefir.The authors acknowledge the financial support from Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES), CAPES-GRICES and Lactogal for supplying cheese whey powder

Impactos ambientais do manejo agroecológico da caatinga no Rio Grande do Norte.

O objetivo deste trabalho foi avaliar os impactos ambientais do manejo agroecológico da caatinga, em unidades de produção familiar no Rio Grande do Norte, pelo método Ambitec de produção animal - dimensão ambiental, desenvolvido pela Embrapa Meio Ambiente. Foram avaliadas sete unidades de produção familiar, em quatro projetos de assentamentos de reforma agrária do Município de Apodi, RN. Os dados para o levantamento foram obtidos por meio de questionários aplicados aos representantes das unidades produtivas familiares, que atribuíram, a cada variável estudada, um valor que representou a alteração proporcionada pela implementação da tecnologia. Após a inserção dos coeficientes de alteração de cada variável dos indicadores por unidade de produção, o coeficiente de impacto foi automaticamente calculado por meio da planilha Ambitec. O manejo agroecológico da caatinga resultou num impacto ambiental positivo, e suas maiores contribuições foram relacionadas aos efeitos positivos dos seguintes indicadores: capacidade produtiva do solo, uso de insumos materiais, qualidade do produto e diminuição da emissão de poluentes à atmosfera. Dois indicadores geraram efeitos negativos: o uso de energia e o uso de recursos naturais. Pela superioridade dos benefícios gerados, o manejo agroecológico da caatinga é uma inovação tecnológica geradora de impactos ambientais positivos