Helper T cell immunity in humans with inherited CD4 deficiency.

CD4+ T cells are vital for host defense and immune regulation. However, the fundamental role of CD4 itself remains enigmatic. We report seven patients aged 5-61 years from five families of four ancestries with autosomal recessive CD4 deficiency and a range of infections, including recalcitrant warts and Whipple's disease. All patients are homozygous for rare deleterious CD4 variants impacting expression of the canonical CD4 isoform. A shorter expressed isoform that interacts with LCK, but not HLA class II, is affected by only one variant. All patients lack CD4+ T cells and have increased numbers of TCRαß+CD4-CD8- T cells, which phenotypically and transcriptionally resemble conventional Th cells. Finally, patient CD4-CD8- αß T cells exhibit intact responses to HLA class II-restricted antigens and promote B cell differentiation in vitro. Thus, compensatory development of Th cells enables patients with inherited CD4 deficiency to acquire effective cellular and humoral immunity against an unexpectedly large range of pathogens. Nevertheless, CD4 is indispensable for protective immunity against at least human papillomaviruses and Trophyrema whipplei.

Predictors of balance in individuals with Parkinson's disease: A cross-sectional study.

INTRODUCTION: Some previous studies investigated predictors of balance in individuals with Parkinson's Disease (PD). However, outcomes commonly evaluated in the rehabilitation of individuals with PD that could predict balance deficits have not yet been investigated. OBJECTIVE: To determine whether the variables muscle strength, physical activity and depression are predictors of balance in individuals with PD. MATERIAL AND METHODS: This is a cross-sectional study in which the investigated variables included: trunk and knee extensors' muscle strength (modified sphygmomanometer test - MST), physical activity level (Adjusted Human Activity Profile score) and depression (Patient Health Questionnaire-9 - PHQ-9). The outcome variable was balance, as assessed by the Mini-BESTest. Multiple regression analysis was used to determine which predictor variables explain the outcome variable. RESULTS: A total of 50 individuals with PD, mean age 67 ± 8.8 years, 68% male, 40% HY 2.5 were included. The mean value of the dominant limb extensor muscle strength was 139 ± 45 mmHg, and the mean trunk extensor muscle strength value was 81.9 ± 19 mmHg. More than half of the sample (52%, n = 26) was classified as moderately active. Most of the sample (78%) had mild depression. The average Mini-BESTest score was 21 ± 5.4. The physical activity level explained 29% of the balance variance. When depression was included in the model, the explained variance increased to 35%. The other independent variables were not included in the model. CONCLUSION: The findings of the present study showed that the physical activity level and depression were able to explain 35% of the balance variation.

Renal toxicity caused by diethylene glycol: an overview.

Diethylene glycol (DEG) is nephrotoxic, potentially resulting in high morbidity and mortality. Its main nephrotoxic by-product is diglycolic acid (DGA). This narrative overview summarizes selected literature with a focus on clinical findings, pathophysiology, diagnosis including morphological features of renal biopsies, and management. The kidney injury in DEG poisoning is secondary to proximal tubular necrosis caused by DGA. Marked vacuolization and edema of epithelial cells obstruct the lumen, reducing urine flow and, consequently, resulting in anuria and uremia. The clinical alterations due to DEG poisoning are dose-dependent. Patients may present with gastrointestinal symptoms and anion gap metabolic acidosis, followed by renal failure, and, later, encephalopathy and neuropathy. Although this three-phase pattern has been described, signs and symptoms may be overlapping. Data about DEG intoxication is scarce. Sometimes the diagnosis is challenging. The management includes supportive care, gastric decontamination, correction of acid-base disorders, and hemodialysis. The understanding of the metabolic processes related to DEG poisoning may contribute to its management, preventing death, serious sequels, or irreversible lesions.

Adenoid cystic carcinoma in atypical site: case report

Adenoid cystic carcinoma (ACC) is a rare form of malignant neoplasm of the salivary glands, with slow growth and late symptoms. One of the challenges presented by this tumor is its high rate of metastasis, with tropism to the nervous system, liver and bones. Treatment is based on surgical resection of the tumor, radiotherapy, and chemotherapy ­ it varies depending on the condition of each patient. In view of the low frequency of ACC, this study aims to report a case of ACC in a female patient, with anatomopathological diagnosis of basaloid cell neoplasm

Kappa free light chains: Diagnostic performance in multiple sclerosis and utility in a clinical laboratory.

BACKGROUND: Automated, technically simple analytical methods offering objective results are highly valued in clinical laboratories. Kappa free light chains (KFLC) in cerebrospinal fluid (CSF) are promising multiple sclerosis (MS) biomarkers, particularly kappa (K) index. METHODS: KFLC were determined in CSF and serum samples of patients diagnosed with MS, clinically/radiologically isolated syndrome (N, 39), and controls (N, 152; inflammatory and non-inflammatory neurological disorders). Diagnostic performance of several KFLC parameters, previously determined oligoclonal band (OCB) testing, and IgG index, was assessed. A K index decision threshold for sample screening was identified and reduction in performed OCB analyses estimated accordingly. RESULTS: Higher KFLC parameters were detected in the MS group and K index performed best among them (AUC 0.92). At a 7.25 cut-off it showed better sensitivity (85% vs. 77%) though less specificity (88% vs. 91%) than OCBs. Comparatively, IgG index's performance was inferior (AUC 0.83). A decision K index threshold of 2.55 (97% sensitivity) would reduce OCB testing by 52% in the studied population. CONCLUSIONS: The proposed 7.25 cut-off could assist MS diagnostics and identify some false negative cases from OCB studies. Sequential algorithms using K index for the decision to perform OCB detection would improve laboratory efficiency and substantially reduce costs.

The expansion of human T-bethighCD21low B cells is T cell dependent.

Accumulation of human CD21low B cells in peripheral blood is a hallmark of chronic activation of the adaptive immune system in certain infections and autoimmune disorders. The molecular pathways underpinning the development, function, and fate of these CD21low B cells remain incompletely characterized. Here, combined transcriptomic and chromatin accessibility analyses supported a prominent role for the transcription factor T-bet in the transcriptional regulation of these T-bethighCD21low B cells. Investigating essential signals for generating these cells in vitro established that B cell receptor (BCR)/interferon-γ receptor (IFNγR) costimulation induced the highest levels of T-bet expression and enabled their differentiation during cell cultures with Toll-like receptor (TLR) ligand or CD40L/interleukin-21 (IL-21) stimulation. Low proportions of CD21low B cells in peripheral blood from patients with defined inborn errors of immunity (IEI), because of mutations affecting canonical NF-κB, CD40, and IL-21 receptor or IL-12/IFNγ/IFNγ receptor/signal transducer and activator of transcription 1 (STAT1) signaling, substantiated the essential roles of BCR- and certain T cell­derived signals in the in vivo expansion of T-bethighCD21low B cells. Disturbed TLR signaling due to MyD88 or IRAK4 deficiency was not associated with reduced CD21low B cell proportions. The expansion of human T-bethighCD21low B cells correlated with an expansion of circulating T follicular helper 1 (cTfh1) and T peripheral helper (Tph) cells, identifying potential sources of CD40L, IL-21, and IFNγ signals. Thus, we identified important pathways to target autoreactive T-bethighCD21low B cells in human autoimmune conditions, where these cells are linked to pathogenesis and disease progression.

Variable immunodeficiency score upfront analytical link (VISUAL), a proposal for combined prognostic score at diagnosis of common variable immunodeficiency.

The broad and heterogeneous clinical spectrum that characterizes common variable immunodeficiency (CVID) is associated with quite different disease course and prognosis, highlighting the need to develop tools that predict complications. We developed a multianalyte VISUAL score (variable immunodeficiency score upfront analytical link) aimed to predict severity using individual CVID patient data at baseline of a cohort of 50 CVID patients from two different centers in Portugal and Spain. We retrospectively applied VISUAL to the CVID clinical severity scores proposed by Ameratunga and Grimbacher after 15 years follow-up of our cohort. VISUAL score at CVID diagnosis showed adequate performance for predicting infectious and non-infectious severe complications (Cluster B). Compared to switched memory B lymphocyte phenotype alone, VISUAL provided a more accurate identification of clinically meaningful outcome, with significantly higher sensitivity (85% vs 55%, p = 0.01), and negative predictive value (77% vs 58%) and AUC of the ROC curves (0.72 vs 0.64), with optimal cut-off level of 10. For every increase of 1 point in the VISUAL scale, the odds of being in the higher risk category (Cluster B) increased in 1.3 (p = 0.005) for Ameratunga's severity score and 1.26 (p = 0.004) for Grimbacher's severity score. At diagnosis of CVID, VISUAL score ≥ 10 showed 8.94-fold higher odds of severe prognosis than below this threshold. Kaplan-Meier estimates for the VISUAL ≥ 10 points showed significantly earlier progression to Cluster B than those with VISUAL < 10 (p = 0.0002). This prognostic laboratory score might allow close monitoring and more aggressive treatment in patients with scores ≥ 10 on a personalized basis approach. Further studies are needed to prospectively validate VISUAL score.

Inherited GATA2 Deficiency Is Dominant by Haploinsufficiency and Displays Incomplete Clinical Penetrance.

PURPOSE: Germline heterozygous mutations of GATA2 underlie a variety of hematological and clinical phenotypes. The genetic, immunological, and clinical features of GATA2-deficient patients with mycobacterial diseases in the familial context remain largely unknown. METHODS: We enrolled 15 GATA2 index cases referred for mycobacterial disease. We describe their genetic and clinical features including their relatives. RESULTS: We identified 12 heterozygous GATA2 mutations, two of which had not been reported. Eight of these mutations were loss-of-function, and four were hypomorphic. None was dominant-negative in vitro, and the GATA2 locus was found to be subject to purifying selection, strongly suggesting a mechanism of haploinsufficiency. Three relatives of index cases had mycobacterial disease and were also heterozygous, resulting in 18 patients in total. Mycobacterial infection was the first clinical manifestation in 11 patients, at a mean age of 22.5 years (range: 12 to 42 years). Most patients also suffered from other infections, monocytopenia, or myelodysplasia. Strikingly, the clinical penetrance was incomplete (32.9% by age 40 years), as 16 heterozygous relatives aged between 6 and 78 years, including 4 older than 60 years, were completely asymptomatic. CONCLUSION: Clinical penetrance for mycobacterial disease was found to be similar to other GATA2 deficiency-related manifestations. These observations suggest that other mechanisms contribute to the phenotypic expression of GATA2 deficiency. A diagnosis of autosomal dominant GATA2 deficiency should be considered in patients with mycobacterial infections and/or other GATA2 deficiency-related phenotypes at any age in life. Moreover, all direct relatives should be genotyped at the GATA2 locus.

Variable immunodeficiency study: Evaluation of two European cohorts within a variety of clinical phenotypes.

INTRODUCTION: Given the wide heterogeneity of common variable immunodeficiency (CVID), several groups have proposed clinical and immunological classifications to better define follow-up and prognostic algorithms. The present study aims to validate recent clinical and laboratory algorithms, based on different combinations of CVID biomarkers, to provide more personalized treatment and follow-up strategies. METHODS: We analysed clinical and immunological features of 80 patients with suspected or diagnosed CVID, in two reference centres of Portugal and Spain. Clinical manifestations were categorized into clinical phenotyping proposed by Chapel et al. [1] that included cytopenia; polyclonal lymphocytic infiltration; unexplained enteropathy; and no disease-related complications. RESULTS: 76% of patients in our cohort entered one of the four categories of clinical phenotyping, without overlap (cytopenia; polyclonal lymphocytic infiltration; unexplained enteropathy; and no disease-related complications). The most prominent phenotype was "cytopenia" (40%) followed by "polyclonal lymphocytic infiltration" (19%). The remaining 24% patients of our cohort had overlap of 2 clinical phenotypes (cytopenia and unexplained enteropathy mainly). A delay of CVID diagnosis in more than 6 years presented 3.7-fold higher risk of developing lymphoproliferation and/or malignancy (p < 0.05), and was associated with increased CD8+CD45RO + T-lymphocytes (p < 0.05). An association between decreased switched-memory B cells with lymphoproliferation and malignancy was observed (p < 0.03 and p < 0.05, respectively). CD4 + T-lymphocytopenia correlated with autoimmune phenotype, with 30% prevalence (p < 0.05). HLA-DR7 expression was related to CVID onset in early life in our patients (13 vs 25 years), and DQ2.5 or DQ2.2 with unexplained enteropathy (p < 0.05). CONCLUSIONS: The phenotypic and genetic study is crucial for an adequate clinical orientation of CVID patients. In these two independent cohorts of patients, classification based in clinical and laboratory algorithms, provides more personalized treatment and follow-up strategies.

Inherited p40phox deficiency differs from classic chronic granulomatous disease.

Biallelic loss-of-function (LOF) mutations of the NCF4 gene, encoding the p40phox subunit of the phagocyte NADPH oxidase, have been described in only 1 patient. We report on 24 p40phox-deficient patients from 12 additional families in 8 countries. These patients display 8 different in-frame or out-of-frame mutations of NCF4 that are homozygous in 11 of the families and compound heterozygous in another. When overexpressed in NB4 neutrophil-like cells and EBV-transformed B cells in vitro, the mutant alleles were found to be LOF, with the exception of the p.R58C and c.120_134del alleles, which were hypomorphic. Particle-induced NADPH oxidase activity was severely impaired in the patients' neutrophils, whereas PMA-induced dihydrorhodamine-1,2,3 (DHR) oxidation, which is widely used as a diagnostic test for chronic granulomatous disease (CGD), was normal or mildly impaired in the patients. Moreover, the NADPH oxidase activity of EBV-transformed B cells was also severely impaired, whereas that of mononuclear phagocytes was normal. Finally, the killing of Candida albicans and Aspergillus fumigatus hyphae by neutrophils was conserved in these patients, unlike in patients with CGD. The patients suffer from hyperinflammation and peripheral infections, but they do not have any of the invasive bacterial or fungal infections seen in CGD. Inherited p40phox deficiency underlies a distinctive condition, resembling a mild, atypical form of CGD.

Fatores relacionados ao óbito de pacientes sépticos na Unidade de Terapia Intensiva

Introdução: A sepse é uma problemática constante nas Unidades de Terapia Intensiva (UTI) e importante causa de óbitos, com letalidade alta e crescente, configurando um desafio para profissionais em todo o globo. bjetivo: Identificar os fatores de risco relacionados ao óbito de pacientes com sepse sob cuidados intensivos. Materiais e métodos: Estudo retrospectivo, do tipo caso-controle, realizado na Fundação Pública Estadual Hospital das Clínicas Gaspar Vianna (FHCGV), Belém, Pará, por meio da coleta de dados em prontuários de pacientes sépticos internados na UTI adulto do FHCGV no período de 01 de janeiro a 31 de dezembro de 2016, considerando dois grandes grupos: caso, pacientes sépticos ou em choque séptico que evoluíram a óbito e controle, pacientes sépticos que receberam alta deste serviço. Utilizou-se o programas Microsoft Excel 2013 para a compilação dos dados e Minitab 18 para o tratamento estatístico. Foram definidos como estatisticamente significativos os valores de p 18mg/DL (p< 0,000) e média de hemoglobina 9,95±1,98 foram altamente preditivos para o óbito. Conclusão: Pacientes sépticos idosos apresentam quase 140 vezes mais chances de óbito que indivíduos mais jovens. Lactatemia, baixos valores de hemoglobina no diagnóstico e a evolução para o choque séptico representam importantes fatores de risco para o óbito

Introduction: Sepsis is a constant problem in Intensive Care Units (ICUs) and an important cause of death, with high and increasing lethality, posing a challenge for professionals across the globe. Objective: To identify the risk factors related to the death of patients with sepsis under intensive care. Materials and methods: A cross-sectional, retrospective, case-control study was performed at the Gaspar Vianna Hospital Public Clinics Foundation (FHCGV), Belém, Pará, Brazil, through the collection of data in medical records of septic patients admitted to the FHCGV adult ICU in the period from January 1 to December 31, 2016, considering two large groups: case, septic or septic shock patients who evolved to death and control, septic patients who were discharged from this service. We used the Microsoft Excel 2013 programs for data compilation and Minitab18 for statistical treatment. Values of p 18mg / DL (p <0.000) were highly predictive of death. Conclusion: Elderly septic patients present almost 140 times more chances of death than younger individuals, lactatemia in the diagnosis and the evolution to septic shock represent important risk factors for death

Chronic granulomatous disease as a risk factor for cutaneous lupus in childhood.

Chronic granulomatous disease (CGD) is a primaryimmunodeficiency disorder that affects the phagocyticcells of the innate immune system. It is characterizedby recurrent or persistent infections with granulomaformation. Lupus-like lesions have been reported incarriers of CGD and less frequently, in patients withCGD. Immunological study in these patients areusually negative. We describe the case of an 8-yearoldboy with CGD who developed chronic and acutecutaneous lupus erythematous with angular cheilitis,oral ulcers, Raynaud phenomenon, and positiveserologies for antinuclear, anticentromere, and anti-Saccharomyces cerevisiae antibodies.

The relationship between risk factors for metabolic syndrome in the physically active elderly / A relação entre os fatores de risco para a síndrome metabólica em idosos fisicamente ativos

Aging has a significant impact on the decrease of lean body mass and physical activity level, being related to the reduction in basal metabolic rate and the increase of overweight and obesity in the elderly. The aim of this study is to identify correlations among the risk factors of metabolic syndrome (MS) from the measurement of abdominal perimeter (AP) and body mass index (BMI) with blood parameters for fasting blood glucose (FBG), total cholesterol (TC) and triglycerides (TG) in active elderly people. Measurements of weight and height were adopted to classify criteria by the World Health Organization (WHO) and to calculate BMI. The measurement of AP was done in centimeters. Blood parameters for FBG, TC, and TG were assessed by collecting blood from the fingertip and analyzing it using the Accutrend Plus (Roche) equipment. For data analysis, the Pearson correlation coefficient between anthropometric measures (independent variables) and blood parameters (dependent variables) was calculated. Simple linear regression was applied to the significant variables (0.05%). The BMI assessment shows 71% of the elderly were overweight and 34% were obese. Over the cut-off point recommended, 57% of the sample was indicated by AP. The correlation test shows evidence regarding the existence of a significant association between FBG and AP and also between AP and TG as compared to the use of BMI. The AP measurement seems to be an efficient indication of the relationship between risk factors for MS and should be incorporated into routines to assess the elderly as an indicator of abdominal obesity. (AU)

O envelhecimento tem um impacto significativo na diminuição de massa magra e do nível de atividade física, estando relacionado à redução na taxa metabólica basal e ao aumento de sobrepeso e obesidade em idosos. O objetivo deste estudo foi identificar correlações entre os fatores de risco da síndrome metabólica (SM) e a medição do perímetro abdominal (PA) e do índice de massa corporal (IMC) com os parâmetros sanguíneos de glicemia de jejum (GJ), colesterol total (CT) e triglicerídeos (TG) em idosos ativos. Para cálculo do IMC, foram coletadas medidas de peso e altura e adotados os critérios de classificação da Organização Mundial da Saúde (OMS). A medida do PA foi efetuada em centímetros. Os parâmetros sanguíneos de GJ, CT e TGL foram avaliados pelo método de coleta de sangue na ponta de dedo com leitura em equipamento Accutrend Plus (Roche). Para análise dos resultados, foi realizado o cálculo do coeficiente de correlação de Pearson entre as medidas antropométricas (variáveis independentes) e parâmetros sanguíneos (variáveis dependentes). A regressão linear simples foi aplicada sobre as variáveis significativas (0.05%). A avaliação do IMC mostrou que 71% dos idosos estavam acima do peso e 34% eram obesos. No ponto de corte recomendado, 57% da amostra foram indicados por PA. O teste de correlação mostrou evidências sobre a existência de uma associação significativa entre GJ e PA e também entre PA e TG em comparação ao uso do IMC. A medição de PA parece seruma indicação eficaz da relação entre os fatores de risco para a SM e deve ser incorporada nas rotinas para avaliar idosos como um indicador de obesidade abdominal. (AU)

The relationship between risk factors for metabolic syndrome in the physically active elderly / A relação entre os fatores de risco para a síndrome metabólica em idosos fisicamente ativos

Aging has a significant impact on the decrease of lean body mass and physical activity level, being related to the reduction in basal metabolic rate and the increase of overweight and obesity in the elderly. The aim of this study is to identify correlations among the risk factors of metabolic syndrome (MS) from the measurement of abdominal perimeter (AP) and body mass index (BMI) with blood parameters for fasting blood glucose (FBG), total cholesterol (TC) and triglycerides (TG) in active elderly people. Measurements of weight and height were adopted to classify criteria by the World Health Organization (WHO) and to calculate BMI. The measurement of AP was done in centimeters. Blood parameters for FBG, TC, and TG were assessed by collecting blood from the fingertip and analyzing it using the Accutrend Plus (Roche) equipment. For data analysis, the Pearson correlation coefficient between anthropometric measures (independent variables) and blood parameters (dependent variables) was calculated. Simple linear regression was applied to the significant variables (0.05%). The BMI assessment shows 71% of the elderly were overweight and 34% were obese. Over the cut-off point recommended, 57% of the sample was indicated by AP. The correlation test shows evidence regarding the existence of a significant association between FBG and AP and also between AP and TG as compared to the use of BMI. The AP measurement seems to be an efficient indication of the relationship between risk factors for MS and should be incorporated into routines to assess the elderly as an indicator of abdominal obesity.

O envelhecimento tem um impacto significativo na diminuição de massa magra e do nível de atividade física, estando relacionado à redução na taxa metabólica basal e ao aumento de sobrepeso e obesidade em idosos. O objetivo deste estudo foi identificar correlações entre os fatores de risco da síndrome metabólica (SM) e a medição do perímetro abdominal (PA) e do índice de massa corporal (IMC) com os parâmetros sanguíneos de glicemia de jejum (GJ), colesterol total (CT) e triglicerídeos (TG) em idosos ativos. Para cálculo do IMC, foram coletadas medidas de peso e altura e adotados os critérios de classificação da Organização Mundial da Saúde (OMS). A medida do PA foi efetuada em centímetros. Os parâmetros sanguíneos de GJ, CT e TGL foram avaliados pelo método de coleta de sangue na ponta de dedo com leitura em equipamento Accutrend Plus (Roche). Para análise dos resultados, foi realizado o cálculo do coeficiente de correlação de Pearson entre as medidas antropométricas (variáveis independentes) e parâmetros sanguíneos (variáveis dependentes). A regressão linear simples foi aplicada sobre as variáveis significativas (0.05%). A avaliação do IMC mostrou que 71% dos idosos estavam acima do peso e 34% eram obesos. No ponto de corte recomendado, 57% da amostra foram indicados por PA. O teste de correlação mostrou evidências sobre a existência de uma associação significativa entre GJ e PA e também entre PA e TG em comparação ao uso do IMC. A medição de PA parece seruma indicação eficaz da relação entre os fatores de risco para a SM e deve ser incorporada nas rotinas para avaliar idosos como um indicador de obesidade abdominal.

Effects of acupuncture on leucopenia, neutropenia, NK, and B cells in cancer patients: a randomized pilot study.

Chemotherapy is one of most significant therapeutic approaches to cancer. Immune system functional state is considered a major prognostic and predictive impact on the success of chemotherapy and it has an important role on patients' psychoemotional state and quality of life. In Chinese medicine, chemotherapy is understood as "toxic cold" that may induce a progressive hypofunctional state of immune system, thus compromising the fast recovery of immunity during chemotherapy. In this study, we performed a standardized acupuncture and moxibustion protocol to enhance immunity in cancer patients undergoing chemotherapy and to assess if the improvement of immunity status correlates with a better psychoemotional state and quality of life.

Reactive oxygen species deficiency induces autoimmunity with type 1 interferon signature.

AIMS: Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by mutations in the phagocyte reactive oxygen species (ROS)-producing NOX2 enzyme complex and characterized by recurrent infections associated with hyperinflammatory and autoimmune manifestations. A translational, comparative analysis of CGD patients and the corresponding ROS-deficient Ncf1(m1J) mutated mouse model was performed to reveal the molecular pathways operating in NOX2 complex deficient inflammation. RESULTS: A prominent type I interferon (IFN) response signature that was accompanied by elevated autoantibody levels was identified in both mice and humans lacking functional NOX2 complex. To further underline the systemic lupus erythematosus (SLE)-related autoimmune process, we show that naïve Ncf1(m1J) mutated mice, similar to SLE patients, suffer from inflammatory kidney disease with IgG and C3 deposits in the glomeruli. Expression analysis of germ-free Ncf1(m1J) mutated mice reproduced the type I IFN signature, enabling us to conclude that the upregulated signaling pathway is of endogenous origin. INNOVATION: Our findings link the previously unexplained connection between ROS deficiency and increased susceptibility to autoimmunity by the discovery that activation of IFN signaling is a major pathway downstream of a deficient NOX2 complex in both mice and humans. CONCLUSION: We conclude that the lack of phagocyte-derived oxidative burst is associated with spontaneous autoimmunity and linked with type I IFN signature in both mice and humans.

The relationship between physical aspects of quality of life and extreme levels of regular physical activity in adults.

This study aimed to check for any significant differences in perceived quality of life, specifically aspects of a physical nature, among volunteers who are more physically active and those less physically active in a university community. The sample consisted of 1,966 volunteers in a university community in Brazil. To assess physical activity levels, volunteers responded to the International Physical Activity Questionnaire (IPAQ), and to analyse the perception of quality of life they responded to WHOQOL-bref, which is classified into three groups according to level of physical activity, taking into account the metabolic equivalent index (MET) over a full week. For comparison, consideration was given to the first and third tertiles, respectively, namely groups of more and less active students. The results indicated that individuals who engaged in more physical activity had a more positive perception of quality of life compared to those who were less active in physical aspects related to the ability to work, energy for day-to-day activities and locomotion.

The relationship between physical aspects of quality of life and extreme levels of regular physical activity in adults / Relação entre os aspectos físicos da qualidade de vida e níveis extremos de atividade física regular em adultos / Relación entre la calidad de vida y niveles extremos de actividad física regular en adultos

This study aimed to check for any significant differences in perceived quality of life, specifically aspects of a physical nature, among volunteers who are more physically active and those less physically active in a university community. The sample consisted of 1,966 volunteers in a university community in Brazil. To assess physical activity levels, volunteers responded to the International Physical Activity Questionnaire (IPAQ), and to analyse the perception of quality of life they responded to WHOQOL-bref, which is classified into three groups according to level of physical activity, taking into account the metabolic equivalent index (MET) over a full week. For comparison, consideration was given to the first and third tertiles, respectively, namely groups of more and less active students. The results indicated that individuals who engaged in more physical activity had a more positive perception of quality of life compared to those who were less active in physical aspects related to the ability to work, energy for day-to-day activities and locomotion.

O objetivo desse estudo foi avaliar a percepção da qualidade de vida, entre os voluntários mais fisicamente ativos e os menos fisicamente ativos de uma comunidade universitária. A amostra foi formada por 1.966 voluntários entre estudantes e servidores de uma comunidade universitária do Brasil. Para a avaliação do nível de atividade física foi utilizado o Questionário Internacional de Atividade Física (IPAQ) e para análise da percepção da qualidade de vida o WHOQOL-bref. Os participantes foram classificados em três grupos considerando o índice de equivalente metabólico (MET) ao longo de uma semana completa. A análise do nível de atividade física indicou, dentre os 1.966 avaliados, 51,5% ativos, 14% muito ativos, 21,3% insuficientemente ativo B; 4,7% insuficientemente ativo A e 5,8% sedentários. Os dados sugerem associação entre a prática da atividade física e percepção positiva da qualidade de vida nos aspectos do domínio físico que estão relacionados com a capacidade para o trabalho, energia para as atividades do dia a dia e locomoção.

El objetivo de este estudio fue comprobar la calidad de vida percibida por los voluntarios que son físicamente más activos y los menos activos en una comunidad universitaria. La muestra, constituida por 1.966 voluntarios, estaba formada por estudiantes y personal docente en una comunidad universitaria en Brasil. Para evaluar el nivel de actividad física, se utilizó Cuestionario Internacional de Actividad Física (IPAQ), y para la percepción de la calidad de vida: WHOQOL-bref. Los participantes se clasificaron en tres grupos, según el nivel de actividad física, teniendo en cuenta índice equivalente metabólico (MET) durante una semana completa. El nivel de actividad física mostró que la muestra se clasificó como un 51,5% activo; un 14% muy activo; B un 21,3% insuficientemente activo; un 4,7% insuficientemente activo A y un 5,8% eran sedentarios. Las personas que participan en más actividades físicas tenían una percepción más positiva de la calidad de vida, en los aspectos físicos relacionados con la capacidad de trabajo, energía para las actividades del día a día y la locomoción, en comparación con aquellos que eran menos activos.

Consumo alimentar, estado nutricional e nível de atividade física em comunidade universitária brasileira / Food intake, nutritional status and level of physical activity in a Brazilian university community

OBJETIVO: Este estudo teve como objetivo avaliar a variabilidade e a frequência do consumo alimentar, o estado nutricional e o nível de atividade física em uma comunidade universitária brasileira. MÉTODOS: A amostra constitui-se de 303 voluntários (130 homens e 173 mulheres) pertencentes à comunidade universitária do interior de São Paulo e avaliada por meio da disponibilização pela Internet do Questionário de Frequência Alimentar do International Physical Activity Questionaire e por meio da coleta da descrição autorreferida do peso e da altura. Foi realizada análise descritiva dos dados, análise de frequência alimentar e teste do coeficiente de correlação de Spearman. RESULTADOS: Foram observados inadequação dos hábitos alimentares, sobrepeso e obesidade na amostra estudada. As correlações entre os grupos alimentares apresentaram valores de magnitude maiores no grupo de mulheres que se alimentam de forma mais adequada do que os homens, mas não foram observadas diferenças entre os sexos no nível de atividade física. Não houve correlação significativa entre grupos de alimentos consumidos, índice de massa corporal e nível de atividade física em ambos os sexos. CONCLUSÃO: A comunidade universitária estudada apresentou baixo consumo de frutas, legumes e verduras, bem como consumo insuficiente de alimentos do grupo de cereais e leguminosas.

OBJECTIVE: This study assessed the food intake variability and frequency, nutritional status and level of physical activity of a university community in Brazil. METHODS: The sample comprised 303 volunteers (130 men and 173 women) from a university community in São Paulo state. They answered the International Physical Activity Questionnaire online and reported their weight and height. Statistical treatment included descriptive analysis, analysis of food intake frequency (Dietsys) and Spearman's rank correlation coefficient. RESULTS: Eating habits were inappropriate and many individuals were overweight or obese. There were more correlations among food groups for women who had better diets than men but the level of physical activity did not differ between the genders. There was no significant correlation between food groups and body mass index or level of physical activity for men or women. CONCLUSION: The study university community consumes little fruit, non-starchy vegetables, grains and legumes.

IgM+IgD+CD27+ B cells are markedly reduced in IRAK-4-, MyD88-, and TIRAP- but not UNC-93B-deficient patients.

We studied the distribution of peripheral B-cell subsets in patients deficient for key factors of the TLR-signaling pathways (MyD88, TIRAP/MAL, IL-1 receptor-associated kinase 4 [IRAK-4], TLR3, UNC-93B, TRIF). All TLRs, except TLR3, which signals through the TRIF adaptor, require MyD88 and IRAK-4 to mediate their function. TLR4 and the TLR2 heterodimers (with TLR1, TLR6, and possibly TLR10) require in addition the adaptor TIRAP, whereas UNC-93B is needed for the proper localization of intracellular TLR3, TLR7, TLR8, and TLR9. We found that IgM(+)IgD(+)CD27(+) but not switched B cells were strongly reduced in MyD88-, IRAK-4-, and TIRAP-deficient patients. This defect did not appear to be compensated with age. However, somatic hypermutation of Ig genes and heavy-chain CDR3 size distribution of IgM(+)IgD(+)CD27(+) B cells were not affected in these patients. In contrast, the numbers of IgM(+)IgD(+)CD27(+) B cells were normal in the absence of TLR3, TRIF, and UNC-93B, suggesting that UNC-93B-dependent TLRs, and notably TLR9, are dispensable for the presence of this subset in peripheral blood. Interestingly, TLR10 was found to be expressed at greater levels in IgM(+)IgD(+)CD27(+) compared with switched B cells in healthy patients. Hence, we propose a role for TIRAP-dependent TLRs, possibly TLR10 in particular, in the development and/or maintenance of IgM(+)IgD(+)CD27(+) B cells in humans.