Elevated serum IL-6 levels predict treatment interruption in patients with moderate to severe psoriasis: a 6-year real-world cohort study

Abstract Background: Real-world, primary data on the treatment of psoriasis are scarce, especially concerning the role of soluble biomarkers as outcome predictors. Objective: The authors evaluated the utility of Th1/Th17 serum cytokines along with clinical characteristics as predictors of drug survival in the treatment of psoriasis. Methods: The authors consecutively included participants with moderate to severe psoriasis who were followed up for 6 years. Baseline interferon-α, tumor necrosis factor-α, and inter-leukin (IL)-2, IL-4, IL-6, IL-10, and IL-17A were measured using a cytometric bead array; clinical data were assessed. The authors calculated hazard ratios (HRs) for drug survival using a Cox proportional hazards model. Results: The authors included 262 patients, most of whom used systemic immunosuppressants or biologics. In the multivariate model, poor quality of life measured by the Dermatology Life Quality Index (HR = 1.04; 95% CI 1.01-1.07; p = 0.012) and elevated baseline IL-6 (HR = 1.99; 95% CI 1.29-3.08; p = 0.002) were associated with treatment interruption. Study limitations: The main limitation of any cohort study is the presence of confounders that could not be detected in clinical evaluation. Conclusions: Poor quality of life and elevated baseline serum IL-6 level predicted treatment interruption in patients with moderate to severe psoriasis. Although IL-6 is not the most important mediator of the inflammatory pathway in the skin environment, it is an interesting biomarker candidate for predicting psoriasis treatment response.

Different profiles of chemokines, cytokines and cell growth factors in plasma samples from patients with leprosy, leprosy reactions and households contacts

BACKGROUND Leprosy is a highly neglected disease that is considered a serious public health problem in many countries. This illness is characterised by a variety of clinical and histopathological manifestations that are related to the patient immune response. OBJECTIVES This work aimed evaluate the profile of circulating immune mediators in the plasma from patients classified clinically as paucibacillary (PB), multibacillary (MB), households contacts (HHC), type1 leprosy reaction (T1R), type2 leprosy reaction (T2R) and control individuals without medical history of leprosy (CTL). METHODS To assessment of the plasma immune mediators was used multiplex microbeads immunoassay "Luminex". FINDINGS The results showed that patients (PB) had a regulatory-biased profile, while MB revealed a pro-inflammatory trend of highly expressed biomarkers. HHC display conspicuously increased levels in the plasma of the chemokines (CCL2, CCL3, CCL4, CCL5 and CXCL8), pro-inflammatory cytokines (IFN-γ,TNF and IL-1β), modulating cytokines (IL-9 and IL-1Ra) and growth factors (PDGF, G-CSF and IL-2). Interestingly, HHC displayed superior production of IFN-γ as compared to other leprosy groups, indicating a putative protective role for this cytokine during chronic Mycobacterium leprae exposure. MAIN CONCLUSION Further investigations are currently underway to elucidate the potential of these mediators as biomarkers applicable to the diagnosis/prognosis of leprosy and also T1R and T2R leprosy reactions.

Association between inflammatory molecules, nitric oxide metabolites and leg ulcers in individuals with sickle cell anemia

Abstract Introduction Leg ulcers (LUs) are relatively common in patients with sickle cell anemia (SCA). The role of inflammation and nitric oxide (NO) pathways in the pathophysiology of the LU is not understood. Objective The aim of this study was to verify the association between inflammatory molecules and nitric oxide metabolites (NOx) and the occurrence of the LU in patients with SCA. Method It was a cross-sectional study on adult participants with SCA followed at Fundação Hemominas, a public blood center in Brazil. Eligible participants were recruited and included in one of two groups: Group 1, comprised of cases with SCA (Hb SS) and at least one LU at the time of inclusion in the study and Group 2, comprised of controls with SCA without a history of LU, matched by sex and age to cases. Participants were interviewed to obtain sociodemographic data and blood samples were collected. Clinical and laboratory data were abstracted from medical records. Nitric oxide metabolites (NOx) and inflammatory molecules were quantified using an immunoassay and Multiplex xMAP® technology, respectively. Eighty-seven individuals were included, ranging in age from 17 to 61 years (mean 40 ± 10.7 years); 30 had LU and 57 were controls without LU. Results Participants with LU had significantly higher levels of interleukin 8 (IL-8), IL-10, IL-15, NOx and platelet and white blood cell (WBC) counts, when compared to those without LU. Participants with LU had a significantly higher risk of having a history of osteomyelitis and a higher use of antiseptic soap in bathing, when compared to those without LU. Conclusion In conclusion, our results showed that NOx, inflammatory molecules and hematological features were associated with LU in Brazilian adults with SCA.

Soroprevalência e fatores associados a infecções crônicas entre idosos residentes na comunidade / Seroprevalence and factors associated with chronic infections among community-dwelling elderly individuals

Resumo Infecções crônicas podem contribuir com o processo de envelhecimento, mas isso ainda é pouco explorado na América Latina. O objetivo foi avaliar a prevalência e os fatores associados ao citomegalovírus (CMV), Herpes simples 1 (HSV-1), Chlamydia pneumoniae e Helicobacter pylori entre idosos. Participaram 1.320 indivíduos da linha de base da Coorte de Idosos de Bambuí. Foram avaliados anticorpos (IgG) para as infecções e variáveis exploratórias (sociodemográficas, comportamentos em saúde e condições de saúde). Utilizaram-se modelos de regressão de Poisson com variância robusta. A prevalência foi de 99,4% para CMV, 96,7% para HSV-1, 56,0% para C. pneumoniae e 70,5% para H. pylori. Os mais velhos, mulheres, fumantes, diabéticos, incapazes e com maiores níveis de IL-6 tinham maior prevalência de CMV. HSV-1 foi menos frequente entre as mulheres. Infecção por C. pneumoniae foi maior entre os mais velhos e diabéticos; e menor entre mulheres e os menos escolarizados. H. pylori foi menos frequente entre as mulheres e naqueles com maiores níveis de IL-1β, mas mais comuns entre os fumantes. Os achados mostram elevada prevalência de infecções crônicas e diferentes perfis epidemiológicos para cada patógeno, permitindo a detecção de grupos vulneráveis a essas infecções.

Abstract Chronic infections can contribute to the aging process, but this issue is less studied in Latin America. The aim was to assess the prevalence and factors associated with cytomegalovirus (CMV), Herpes Simplex 1 (HSV-1), Chlamydia pneumoniae and Helicobacter pylori among the elderly. A total of 1,320 individuals participated from the baseline of the Elderly Cohort of Bambuí. IgG antibodies against infections and explanatory variables (sociodemographic factors, health behaviors and health conditions) were evaluated. Poisson regression models with robust variance were used. Seroprevalence rates were 99.4% for CMV, 96.7% for HSV-1, 56% for C. pneumoniae and 70.5% for H. pylori. Elderly men, women, smokers, diabetics, the disabled and those with high levels of IL-6 had a higher prevalence of CMV. HSV-1 was less frequent among women. The prevalence of C. pneumoniae was higher at ages >75 and among diabetics; it was lower among women and individuals with less schooling. H. pylori was less frequent among women and those with detectable levels of IL-1β, but more common among smokers. The findings show a high prevalence of chronic infection and a different epidemiologic profile for each pathogen, making it possible to detect groups that are vulnerable to these infections.

Increased platelet distribution width and reduced IL-2 and IL-12 are associated with thrombocytopenia in Plasmodium vivax malaria

BACKGROUND Thrombocytopenia in malaria involves platelet destruction and consumption; however, the cellular response underlying this phenomenon has still not been elucidated. OBJECTIVE To find associations between platelet indices and unbalanced Th1/Th2/Th17 cytokines as a response to thrombocytopenia in Plasmodium vivax infected (Pv-MAL) patients. METHODS Platelet counts and quantification of Th1/Th2/Th17 cytokine levels were compared in 77 patients with uncomplicated P. vivax malaria and 37 healthy donors from the same area (endemic control group - ENCG). FINDINGS Thrombocytopenia was the main manifestation in 55 patients, but was not associated with parasitaemia. The Pv-MAL patients showed increases in the mean platelet volume (MPV), which may be consistent with larger or megaplatelets. Contrary to the findings regarding the endemic control group, MPV and platelet distribution width (PDW) did not show an inverse correlation, due the increase in the heterogeneity of platelet width. In addition, the Pv-MAL patients presented increased IL-1β and reduced IL-12p70 and IL-2 serum concentrations. Furthermore, the reduction of these cytokines was associated with PDW values. MAIN CONCLUSIONS Our data demonstrate that an increase in MPV and the association between reductions of IL-2 and IL-12 and PDW values may be an immune response to thrombocytopenia in uncomplicated P. vivax malaria.

Inflammatory markers and occurrence of falls: Bambuí Cohort Study of Aging / Marcadores inflamatórios e ocorrência de quedas: coorte de idosos de Bambuí

ABSTRACT OBJECTIVE Analyze whether inflammatory markers are associated with falls among older adults living in Bambuí. METHODS Study that analyzed baseline data from a Bambuí Cohort Study of Aging, involving 1,250 participants. Data about falls were collected from previous 12 months, classified as single or multiple occurrence and severity (participant seeking health services). Information about sociodemographic characteristics, health behaviors and health condition was also collected and used as confounding factors. The exposures of interest included interleukins (IL-1β, IL-6, IL-8, IL-10, IL-12), tumor necrosis factor (TNF), ultra-sensitive C-reactive protein (us-CRP) and chemokines (CXCL9, CCL5, CCL10, MCP1). Data were processed through logistic regression, obtaining odds ratio and 95% confidence interval (95%CI). RESULTS The prevalence of falls was 27.1%; 40.1% of the older adults reported multiple falls and 33.3% sought health services. After adjustments, the following elevated levels were associated with falls: us-CRP (OR = 1.46, 95%CI 1.04-2.03), CCL5 (OR = 1.38, 95%CI 1.01-1.90) and CXCL9 (OR = 1.43, 95%CI 1.02-2.02). An association was observed between the number of elevated markers and the occurrence of falls: two (OR = 1.47, 95%CI 1.02-2.12) and three (OR = 2.08, 95%CI 1.12-3.87) elevated biomarkers indicated fall probability of 32.0% and 39.4%, respectively. CONCLUSIONS Elevated levels of us-CRP, CCL5 and CXCL9, which were associated with falls, may contribute to a proper understanding of the mechanism associated with the occurrence of falls among older people.

RESUMO OBJETIVO Analisar se marcadores inflamatórios estão associados a quedas em idosos vivendo na comunidade. MÉTODOS Estudo da coorte de idosos de Bambuí, envolvendo 1.250 participantes da linha de base do projeto. Foram coletadas informações sobre quedas nos últimos 12 meses, classificadas quanto à ocorrência (única ou múltipla) e gravidade (procura por serviços de saúde). O inquérito também continha informações a respeito das características sociodemográficas, comportamentais e condições de saúde, as quais foram utilizadas como fatores de confusão. As exposições pesquisadas incluíram: interleucinas (IL-1β, IL-6, IL-8, IL-10 e IL-12), fator de necrose tumoral (TNF), proteína C reativa ultrassensível (PCRus) e quimiocinas (CXCL9, CCL5, CCL10 e MCP1). O tratamento dos dados foi realizado por meio de regressão logística, obtendo-se odds ratio e intervalo de 95% de confiança (IC95%). RESULTADOS A prevalência de queda foi 27,1%; 40,1% dos idosos relataram quedas múltiplas e 33,3% procuraram serviços de saúde. Após ajustes, permaneceram associados às quedas os níveis elevados de PCRus (OR = 1,46; IC95% 1,04-2,03), CCL5 (OR = 1,38; IC95% 1,01-1,90) e CXCL9 (OR = 1,43; IC95% 1,02-2,02). Houve associação entre o número de marcadores elevados e a ocorrência de quedas: dois (OR = 1,47; IC95% 1,02-2,12) e três (OR = 2,08; IC95% 1,12-3,87) biomarcadores aumentados predisseram probabilidades de quedas iguais a 32,0% e 39,4%, respectivamente. CONCLUSÕES Os níveis elevados de PCRus, CCL5 e CXCL9, que estiveram associados a quedas, podem contribuir para o adequado entendimento do mecanismo associado à ocorrência desse evento em idosos.

Associação entre síndrome metabólica e marcadores inflamatórios em idosos residentes na comunidade / Asociación entre síndrome metabólico y marcadores inflamatorios en ancianos residentes en comunidades / Association of metabolic syndrome with inflammatory markers in a sample of community-dwelling older adults

O objetivo do trabalho foi identificar os pontos de corte dos marcadores inflamatórios que melhor discriminassem a ocorrência da síndrome metabólica entre idosos residentes na comunidade. Foram utilizados os dados da linha de base da coorte de idosos conduzida na cidade de Bambuí, Minas Gerais, Brasil. A exposição de interesse foi a presença da síndrome metabólica, definida pelo critério Adult Treatment Panel III, e os desfechos incluíram os seguintes marcadores inflamatórios: citocinas (IL-1β, IL-6, IL-10, IL-12 e TNF), quimiocinas (CXCL8, CXCL9, CCL2, CXCL10 e CCL5) e proteína C-reativa (PCR). A definição dos pontos de corte dos marcadores inflamatórios foi baseada no método Classification and Regression Tree (CART). As associações entre esses marcadores e a síndrome metabólica foram estimadas por modelos de regressão logística, obtendo-se odds ratio e intervalos de 95% de confiança (IC95%), considerando o ajustamento por fatores de confusão. A prevalência da síndrome metabólica foi de 49,1%, e os níveis de IL-1β, IL-12 e TNF não se mostraram associados a essa exposição. Após ajustamento, a presença da síndrome metabólica foi associada a maiores valores de IL-6 e PCR e a menores valores de CXCL8 e CCL5. Associações significativas ainda foram observadas com níveis séricos intermediários de CXCL9 e CXCL10. Além disso, a combinação dos marcadores apresentou associação significativa e consistente com a síndrome metabólica. Além de demonstrar associação entre síndrome metabólica e uma ampla gama de biomarcadores, alguns ainda não descritos na literatura, os resultados ressaltam que essa associação ocorre em níveis muito inferiores aos já demonstrados, sugerindo que a síndrome metabólica desempenha importante papel no perfil inflamatório dos idosos.

El objetivo del trabajo fue identificar los puntos de corte de los marcadores inflamatorios que mejor discriminaran la ocurrencia del síndrome metabólico entre ancianos residentes en comunidades. Se utilizaron datos de referencia de una cohorte de ancianos, realizada en la ciudad de Bambuí, Minas Gerais, Brasil. La exposición de interés fue la presencia del síndrome metabólico, definida por el criterio Adult Treatment Panel III, y los desenlaces incluyeron los siguientes marcadores inflamatorios: citocinas (IL-1β, IL-6, IL-10, IL-12 e TNF), quimiocinas (CXCL8, CXCL9, CCL2, CXCL10 y CCL5) y proteína C-reactiva (PCR). La definición de los puntos de corte de los marcadores inflamatorios se basó en el método Classification and Regression Tree (CART). Las asociaciones entre esos marcadores y el síndrome metabólico se estimaron mediante modelos de regresión logística, obteniéndose odds ratio e intervalos con 95% de confianza, considerando el ajuste por factores de confusión. La prevalencia del síndrome metabólico fue de 49,1%, y los niveles de IL-1β, IL12 y TNF no se mostraron asociados a esa exposición. Tras el ajuste, la presencia del síndrome metabólico se asoció a mayores valores de IL-6 y PCR y a menores valores de CXCL8 y CCL5. Las asociaciones significativas se observaron incluso con niveles séricos intermedios de CXCL9 y CXCL10. Asimismo, la combinación de los marcadores presentó una asociación significativa y consistente con el síndrome metabólico. Además de demostrar asociación entre el síndrome metabólico y una amplia gama de biomarcadores, algunos todavía no descritos en la literatura, los resultados resaltan que esa asociación ocurre en niveles muy inferiores a los ya demostrados, sugiriendo que el síndrome metabólico desempeña un importante papel en el perfil inflamatorio de los ancianos.

The study aimed to identify the cutoff points for inflammatory markers that best discriminate the occurrence of metabolic syndrome in community-dwelling older adults. Baseline data were used from the elderly cohort in the city of Bambuí, Minas Gerais State, Brazil. The target exposure was presence of metabolic syndrome, defined according to the Adult Treatment Panel III criterion, and the outcomes included the following inflammatory markers: cytokines (IL-1β, IL-6, IL-10, IL-12 e TNF), chemokines (CXCL8, CXCL9, CCL2, CXCL10, and CCL5), and C-reactive protein (CRP). Definition of the cutoff points for the inflammatory markers was based on the Classification and Regression Tree (CART) method. The associations between these markers and metabolic syndrome were estimated by logistic regression models, obtaining odds ratios and 95% confidence intervals, considering adjustment for confounding factors. Prevalence of metabolic syndrome was 49.1%, and IL-1β, IL-12, and TNF levels were not associated statistically with this exposure. After adjustment, presence of metabolic syndrome was associated with higher IL-6 and CRP levels and lower CXCL8 and CCL5. Significant associations were also observed with intermediate serum CXCL9 and CXCL10 levels. The combination of markers also showed a significant and consistent association with metabolic syndrome. In addition to demonstrating an association between metabolic syndrome and a wide range of biomarkers (some not previously described in the literature), the results highlight that this association occurs at much lower levels than previously demonstrated, suggesting that metabolic syndrome plays an important role in the inflammatory profile of the older adults.

Associação entre marcadores inflamatórios e ocorrência de hospitalizações: evidências da linha de base da coorte de idosos de Bambuí / Association between inflammatory markers and hospitalizations: evidence from the Bambuí cohort of aging baseline

RESUMO: Introdução: A inflamação exerce um importante papel no processo de envelhecimento. Objetivo: Este estudo transversal objetiva examinar a associação entre marcadores inflamatórios e a ocorrência de hospitalizações entre idosos, considerando fatores predisponentes e facilitadores do uso de serviços de saúde e condições de saúde como potenciais fatores de confusão. Métodos: Foram utilizados dados de 1.393 participantes (≥ 60 anos) da linha de base da coorte de Bambuí. Os marcadores considerados foram dez citocinas e quimiocinas (interleucina (IL)-1, IL-6, IL-10, IL-12, fator de necrose tumoral (TNF), CCL2, CCL5, CXCL8, CXCL9 e CXCL10). A variável de desfecho foi a ocorrência de uma ou mais hospitalizações nos 12 meses precedentes. Resultados: Níveis séricos elevados da IL-6 apresentaram associações significantes com a ocorrência de hospitalizações (razão de prevalência - RP = 1,38; intervalo de confiança - IC95% 1,01 - 1,87; e RP = 1,38; IC95% 1,01 - 1,88, para os tercis intermediário e superior, respectivamente). Níveis elevados da CXCL9 também apresentaram associações independentes com o desfecho (RP = 1,38; IC95% 1,02 - 1,89 e RP = 1,46; IC95% 1,07 - 2,00, respectivamente). Os demais marcadores não apresentaram associações estatisticamente significantes com a ocorrência de hospitalizações. Conclusão: Entre os 10 marcadores examinados, IL-6 e CXCL9 apresentaram associação com a ocorrência de hospitalizações.

ABSTRACT: Introduction: Inflammation plays an important role in the aging process. Objective: This cross-sectional study aims to examine the association between inflammatory markers and hospitalizations among older adults, considering as potential confounding factors the predisposing and enabling factors for the use of health services and health conditions. Methods: We used data from 1,393 participants (≥ 60 years) in the baseline cohort from Bambuí. The markers assessed were ten cytokines and chemokines [interleukin (IL)-1, IL-6, IL-10, IL-12, tumor necrosis factor (TNF), CCL2, CCL5, CXCL8, CXCL9, and CXCL10]. The outcome variable was one or more hospitalizations in the preceding 12 months. Results: Elevated serum levels of IL-6 were significantly associated with hospitalizations [prevalence ratio (PR) = 1.38; confidence interval of 95% (95%CI) 1.02 - 1.87 and PR = 1.38; 95%CI 1.01 - 1.88 for the intermediate and highest tertiles, respectively]. High levels of CXCL9 were also independently associated with the outcome (PR = 1.38; 95%CI 1.01 - 1.89 and PR = 1.46; 95%CI 1.07 - 2.00, respectively). Other markers showed no statistically significant association with hospitalizations. Conclusion: Among the ten markers analyzed, only IL-6 and CXCL9 were associated with hospitalizations.

Immune response and biochemistry of calves immunized with rMSP1a ( Anaplasma marginale) using carbon nanotubes as carrier molecules / Resposta imunológica e bioquímica de bezerros imunizados com rMSP1 a (Anaplasma marginale) utilizando nanotubos de carbono como moléculas carreadoras

Abstract Vaccination against Anaplasma marginale has been considered an important control strategy for bovine anaplasmosis. Recently, mice immunized with rMSP1 a linked to carbon nanotubes (MWNT) showed significant immune responses, generating a new possibility for use of an inactivated vaccine. The objective of this study was to investigate the cellular and humoral responses in calves immunized with MWNT+rMSP1a , associated with inactivated vaccine of A. marginale produced in vitro, and evaluate the toxic effects of the MWNT on renal and hepatic function. rMSP1a was covalently linked to MWNT. Inactivated vaccine (AmUFMG2) was produced by cultivating A. marginale in IDE8 cells. Twenty-four Holstein calves were divided (four groups) and immunized subcutaneously with PBS and non-carboxylated MWNT (control, G1), AmUFMG2 (G2), MWNT+rMSP1a (G3), and AmUFMG2 with MWNT+rMSP1a (G4). Blood samples were collected for total leukocyte counts, biochemical profiling and evaluation of the cellular and humoral response. Immunization with MWNT+rMSP1a induced increase in the total number of leukocytes, NK cells, in the lymphocyte populations and higher levels of antibodies compared to calves immunized only with AmUFMG2. Furthermore, MWNT did not induce changes in the biochemical profile. These data indicate that MWNT+rMSP1a were able to induce the immune responses more efficiently than AmUFMG2 alone, without generating toxicity.

Resumo Vacinação contra Anaplasma marginale tem sido considerada uma importante estratégia de controle da anaplasmose bovina. Recentemente, camundongos imunizados com rMSP1a funcionalizada à nanotubos de carbono (MWNT) apresentaram resposta imune significante, gerando nova possibilidade para o uso da vacina inativada. O objetivo desse estudo foi investigar a resposta celular e humoral em bezerros imunizados com MWNT+rMSP1a, associado com a vacina inativada de A. marginale produzida in vitro, e avaliar os efeitos tóxicos dos MWNT nas funções hepática e renal. rMSP1 a foi ligada covalentemente aos MWNT. Vacina inativada (AmUFMG2) foi produzida através do cultivo de A. marginale em células IDE8. Vinte e quatro bezerros Holandeses foram divididos (quatro grupos) e imunizados subcutaneamente com: PBS e MWNT não-carboxilados (controle, G1), AmUFMG2 (G2), MWNT+rMSP1 a (G3), e AmUFMG2 com MWNT+rMSP1a (G4). Amostras de sangue foram coletadas para contagem de leucócitos, perfil bioquímico e avaliação da resposta celular e humoral. Imunização com MWNT+rMSP1a induziu aumento dos leucócitos totais, células NK, na população de linfócitos e altos níveis de anticorpos comparado com animais imunizados apenas com AmUFMG2. Além disso, MWNT não induziu alterações no perfil bioquímico. Esses dados indicam que MWNT+rMSP1a foram capazes de induzir eficientemente a resposta imune comparado com AmUFMG2 sozinho, sem gerar toxicidade.

Analysis of the immunological biomarker profile during acute Zika virus infection reveals the overexpression of CXCL10, a chemokine linked to neuronal damage

BACKGROUND Infection with Zika virus (ZIKV) manifests in a broad spectrum of disease ranging from mild illness to severe neurological complications and little is known about Zika immunopathogenesis. OBJECTIVES To define the immunologic biomarkers that correlate with acute ZIKV infection. METHODS We characterized the levels of circulating cytokines, chemokines, and growth factors in 54 infected patients of both genders at five different time points after symptom onset using microbeads multiplex immunoassay; comparison to 100 age-matched controls was performed for statistical analysis and data mining. FINDINGS ZIKV-infected patients present a striking systemic inflammatory response with high levels of pro-inflammatory mediators. Despite the strong inflammatory pattern, IL-1Ra and IL-4 are also induced during the acute infection. Interestingly, the inflammatory cytokines IL-1β, IL-13, IL-17, TNF-α, and IFN-γ; chemokines CXCL8, CCL2, CCL5; and the growth factor G-CSF, displayed a bimodal distribution accompanying viremia. While this is the first manuscript to document bimodal distributions of viremia in ZIKV infection, this has been documented in other viral infections, with a primary viremia peak during mild systemic disease and a secondary peak associated with distribution of the virus to organs and tissues. MAIN CONCLUSIONS Biomarker network analysis demonstrated distinct dynamics in concurrence with the bimodal viremia profiles at different time points during ZIKV infection. Such a robust cytokine and chemokine response has been associated with blood-brain barrier permeability and neuroinvasiveness in other flaviviral infections. High-dimensional data analysis further identified CXCL10, a chemokine involved in foetal neuron apoptosis and Guillain-Barré syndrome, as the most promising biomarker of acute ZIKV infection for potential clinical application.

Toxoplasma gondii infection and chronic schizophrenia: is there any association?

ABSTRACT Background: Toxoplasma gondii (T. gondii) infection has been identified as a risk factor for schizophrenia. Objectives: Herein, we sought to evaluate the association between T. gondii infection and clinical symptoms and quality of life in patients with schizophrenia. Methods: We conducted a cross-sectional study with 48 patients with chronic schizophrenia and 40 controls. Peripheral blood was drawn, and IgM and IgG anti-T. gondii antibodies were evaluated by Enzyme-Linked Immunosorbent Assay (ELISA). Depressive, positive and negative symptoms were assessed, respectively, by the Calgary Depression Scale (CDS) and the Positive and Negative Syndrome Scale (PANSS). Cognitive performance was assessed in patients by the Brazilian version of the Schizophrenia Cognition Rating Scale (SCoRS-BR). Quality of life was assessed by the Brazilian version of the Quality of Life in Schizophrenia scale (QLS-BR). Results: The prevalence and titers of T. gondii IgM and IgG antibodies did not differ between patients and controls. The positive serology for T. gondii IgG antibodies was not associated with illness symptoms, cognitive performance, depressive symptoms or quality of life. Discussion: Our findings suggest that toxoplasmosis infection is not associated with severity of symptoms, quality of life, cognitive or depressive symptoms in schizophrenia patients.

Avaliação da atenção à saúde do adulto em um município-polo do Vale do Jequitinhonha (MG) / Evaluation of adult health care in a city pole of Vale do Jequitinhonha (MG)

A qualidade da Atenção Primária à Saúde é avaliada a partir da presença e extensão dos atributos essenciais e derivados. O presente estudo avaliou esses atributos (saúde do adulto) na Estratégia Saúde da Família de um município do Vale do Jequitinhonha (MG). Os dados foram coletados por meio do PCATool. Foi observado escore geral abaixo do valor considerado satisfatório (≥6,6), e escores satisfatórios foram identificados para apenas dois atributos. Percebeu-se uma melhor orientação para os atributos em apenas uma área de abrangência. Acredita-se que este trabalho poderá subsidiar futuras práticas e decisões acerca do investimento público, visando ao fortalecimento da atenção primária pelos gestores.

The quality of Primary Health Care is evaluated from the presence and the extent of the essential and derived attributes. This current study has evaluated those attributes (adults´ health) in the Family Health Strategy of a municipality located in the Vale of Jequitinhonha (MG). Data were harvested by PCAtool. It was observed general score below the value considered satisfactory (≥6,6) and satisfying scores were identified for only two attributes: It was noticed a better orientation for the attributes in only one area of coverage. It is believed that this work may subsidize future practices and decisions about public investment, aiming at the strengthening of the Primary Care by municipal managers.

Experimental benznidazole treatment of Trypanosoma cruzi II strains isolated from children of the Jequitinhonha Valley, Minas Gerais, Brazil, with Chagas disease

Trypanosoma cruzi strains from distinct geographic areas show differences in drug resistance and association between parasites genetic and treatment response has been observed. Considering that benznidazole (BZ) can reduce the parasite burden and tissues damage, even in not cured animals and individuals, the goal is to assess the drug response to BZ of T. cruzi II strains isolated from children of the Jequitinhonha Valley, state of Minas Gerais, Brazil, before treatment. Mice infected and treated with BZ in both phases of infection were compared with the untreated and evaluated by fresh blood examination, haemoculture, polymerase chain reaction, conventional (ELISA) and non-conventional (FC-ALTA) serologies. In mice treated in the acute phase, a significant decrease in parasitaemia was observed for all strains. Positive parasitological and/or serological tests in animals treated during the acute and chronic (95.1-100%) phases showed that most of the strains were BZ resistant. However, beneficial effect was demonstrated because significant reduction (p < 0.05%) and/or suppression of parasitaemia was observed in mice infected with all strains (acute phase), associated to reduction/elimination of inflammation and fibrosis for two/eight strains. BZ offered some benefit, even in not cured animals, what suggest that BZ use may be recommended at least for recent chronic infection of the studied region.

Reticulocyte count: comparison among methods / Contagem de reticulócitos: comparação entre métodos

Introduction: The automated counting of reticulocytes has some advantages over the manual method routinely used in clinical laboratories. Technological innovations provide more statistically reliable results, while optimizing the time to perform this test. However, the cost for implementing the automated procedure in laboratory routines still constitutes a barrier to its use in small- and medium-size Brazilian laboratories. Objective: This study evaluated the performance of a new laboratory protocol for reticulocyte counting by flow cytometry using acridine orange (FC/AO), compared with the manual method and with another automated one by flow cytometry using the commercial kit BD Retic-Count (FC/RC) Conclusion: The results showed that, besides being comparable to the manual method, still considered standard, the evaluated new protocol is economically more advantageous than the automated methods currently available, and its cost is comparable to that of the manual method for laboratories that already have appropriate equipment and infrastructure. .

Introdução: A contagem automatizada de reticulócitos apresenta vantagens em relação ao método manual, rotineiramente utilizado em laboratórios clínicos. Inovações tecnológicas permitem resultados estatisticamente mais confiáveis, além de otimizarem o tempo para realização desse exame. No entanto, o custo para aplicação do procedimento automatizado em rotinas laboratoriais ainda constitui uma barreira para sua implementação em laboratórios brasileiros de pequeno e médio porte. Objetivo: O presente estudo avaliou o desempenho de um protocolo laboratorial para contagem de reticulócitos por citometria de fluxo utilizando acridine orange (CF/AO), comparando-o com o método manual e o automatizado por citometria de fluxo utilizando o kit comercial BD Retic-Count (CF/RC). Conclusão: Os resultados mostraram que, além de ser comparável com o método manual, ainda considerado padrão, o protocolo avaliado é economicamente mais vantajoso do que os métodos automatizados atualmente disponíveis, sendo o seu custo comparável com o do método manual para laboratórios que já apresentam aparelhagem e infraestrutura adequadas. .

Contagem de reticulócitos por citometria de fluxo utilizando acridine orange: validação de um novo protocolo / Flow cytometry reticulocyte counting using acridine orange: validation of a new protocol

Introduction: Currently, the reticulocyte counting is a challenge for clinical laboratories in Brazil, mainly for the ordinary ones, which still use the manual method. This method has some limitations, since it consists of a laborious method, time consuming, with low accuracy. Objectives: This study has developed and evaluated the performance of a New Laboratory Protocol for flow cytometry (FC) reticulocytes counting using acridine orange (AO) as dye, aiming to standardize a more precise, easy, fast implementation, and low cost protocol. After standardization of the New Protocol (FC/AO), it was compared with the manual method. The results were analyzed according to the recommendations of the National Committee for Clinical Laboratory Standards (NCCLS), now known as Clinical and Laboratory Standards Institute (CLSI), to evaluate the interchangeability of methods in linear regression analysis and paired t test, besides other quality control tests. Conclusion: Based on these results concerning to the correlation between the methods and the tests related to quality control, we can admit that FC/AO for reticulocyte counting shows undeniable advantages when compared to the preexisting manual method...

Introdução: Atualmente, a contagem de reticulócitos representa um desafio para os laboratórios clínicos no Brasil, principalmente os de pequeno e médio porte, nos quais ainda se utiliza o método manual. Este método apresenta algumas limitações, classificando-se como tedioso, demorado e de baixa precisão. Objetivos: O presente estudo desenvolveu e avaliou o desempenho de um novo protocolo laboratorial para contagem de reticulócitos por citometria de fluxo (CF) utilizando acridine orange (AO) como corante, visando padronizar um protocolo preciso, de fácil e rápida execução e custo acessível. Após a padronização do novo protocolo desenvolvido (CF/AO), fez-se a comparação com o método manual. Os resultados foram analisados de acordo com recomendações do National Committee for Clinical Laboratory Standards (NCCLS), atualmente Clinical and Laboratory Standards Institute (CLSI), para avaliar a intercambialidade entre os métodos, por meio da análise de regressão linear e teste t pareado, além de outros testes de controle de qualidade. Conclusão: Diante dos resultados obtidos referentes à correlação entre os métodos e os testes voltados ao controle de qualidade, pode-se admitir que o CF/AO estabelecido para contagem de reticulócitos possui vantagens inegáveis quando comparado com o método manual...

Distinct cytokine profiles of circulating mononuclear cells stimulated with Staphylococcus aureus enterotoxin A in vitro during early and late episodes of chronic osteomyelitis

We investigated the cytokine profile of peripheral mononuclear cells from chronic osteomyelitis (OST) patients following in vitro stimulation with staphylococcal enterotoxin A (SEA). We demonstrate that stimulation with SEA induced prominent lymphocyte proliferation and high levels of tumour necrosis factor (TNF)-α, interleukin (IL)-4 and IL-10 secretion in both OST and non-infected individuals (NI). Even though stimulation with SEA had no impact on IL-6 production in either patient group, the baseline level of IL-6 production by cells from OST patients was always significantly less than that produced by cells from NI. After classifying the osteomyelitic episodes based on the time after the last reactivation event as "early" (1-4 months) or "late" osteomyelitis (5-12 months), we found that increased levels of TNF-α and IL-4 in combination with decreased levels of IL-6 were observed in the early episodes. By contrast, increased levels of IL-10, IL-2 and IL-6 were hallmarks of late episodes. Our data demonstrate that early osteomyelitic episodes are accompanied by an increased frequency of "high producers" of TNF-α and IL-4, whereas late events are characterised by increased frequencies of "high producers" of IL-10, IL-6 and IL-2. These findings demonstrate the distinct cytokine profiles in chronic osteomyelitis, with a distinct regulation of IL-6 production during early and late episodes.

Tétano grave associado a choque séptico em uma paciente idosa internada em unidade de terapia intensiva / Tétanos grave asociado con choque séptico en una paciente anciana ingresada en la unidad de cuidados intensivos / Severe tetanus associated with septic shock in an elderly patient admitted to the intensive care unit

Nós relatamos um caso de tétano grave associado a choque séptico em uma paciente de 61 anos admitida na Unidade de Terapia Intensiva (UTI) após perfurar o pé direito. A paciente apresentou perda de força muscular, paresia em membro inferior direito e disfagia. A paciente evoluiu com espasmos musculares generalizados, dispnéia e insuficiência respiratória. O espasmo intenso levou ao uso prolongado de ventilação mecânica invasiva, sedação e bloqueador neuromuscular. A evolução favorável deste caso está provavelmente relacionada aos avanços na gestão de UTI e uma equipe médica e de enfermagem bem treinadas.

Se presenta un caso de tétanos relacionado con choque séptico grave en una paciente de 61 años ingresada en la Unidad de Cuidados Intensivos (UCI) después de perforar el pie derecho. El paciente tenía pérdida de fuerza muscular, parálisis de la pierna derecha y disfagia. El paciente desarrolló espasmos musculares generalizados, disnea e insuficiencia respiratoria. El espasmo intenso llevó al uso prolongado de ventilación mecánica, sedación y bloqueo neuromuscular. La evolución favorable de este caso está probablemente relacionada con los avances en la gestión de cuidados intensivos y un personal médico y de enfermería bien capacitado.

We report a case of severe tetanus associated with septic shock in a 61-year-old female admitted to the Intensive Care Unit (ICU) after perforating injury in the right foot. The patient presented with loss of muscle strength, paresis in the right lower limb and dysphagia. The patient’s conditions worsened, progressing to generalized muscle spasms, dyspnea, and respiratory failure. Intense spasm made the prolonged use of invasive mechanical ventilation, sedation, and neuromuscular blockers necessary. The favorable outcome in the present case is probably related to advances in ICU management and well-trained medical and nursing staff.

In-house ELISA method to analyze anti-Trypanosoma cruzi IgG reactivity for differential diagnosis and evaluation of Chagas disease morbidity / Método de ELISA in-house na análise da reatividade de IgG anti-Trypanosoma cruzi para o diagnóstico diferencial e avaliação da morbidade da doença de Chagas

INTRODUCTION: The goal was to develop an in-house serological method with high specificity and sensitivity for diagnosis and monitoring of Chagas disease morbidity. METHODS: With this purpose, the reactivities of anti-T. cruzi IgG and subclasses were tested in successive serum dilutions of patients from Berilo municipality, Jequitinhonha Valley, Minas Gerais, Brazil. The performance of the in-house ELISA was also evaluated in samples from other relevant infectious diseases, including HIV, hepatitis C (HCV), syphilis (SYP), visceral leishmaniasis (VL), and American tegumentary leishmaniasis (ATL), and noninfected controls (NI). Further analysis was performed to evaluate the applicability of this in-house methodology for monitoring Chagas disease morbidity into three groups of patients: indeterminate (IND), cardiac (CARD), and digestive/mixed (DIG/Mix), based on their clinical status. RESULTS: The analysis of total IgG reactivity at serum dilution 1:40 was an excellent approach to Chagas disease diagnosis (100 percent sensitivity and specificity). The analysis of IgG subclasses showed cross-reactivity, mainly with NI, VL, and ATL, at all selected serum dilutions. Based on the data analysis, the IND group displayed higher IgG3 levels and the DIG/Mix group presented higher levels of total IgG as compared with the IND and CARD groups. CONCLUSIONS: These findings demonstrated that methodology presents promising applicability in the analysis of anti-T. cruzi IgG reactivity for the differential diagnosis and evaluation of Chagas disease morbidity.

INTRODUÇÃO: O objetivo foi desenvolver um método sorológico in-house de alta especificidade e sensibilidade para diagnosticar e monitorar a morbidade da doença de Chagas. MÉTODOS: Para tal, a reatividade sorológica de IgG e subclasses foi testada em soros de pacientes chagásicos de Berilo, Vale do Jequitinhonha/MG/Brasil. A reatividade sorológica foi também avaliada em amostras de pacientes com outras doenças infecto-contagiosas relevantes, incluindo o HIV, vírus da hepatite C (VHC), sífilis (SYP), leishmaniose visceral (LV), leishmaniose tegumentar americana (LTA) e controles não infectados (NI) para verificar o desempenho do método. Outras análises foram feitas para avaliar a aplicabilidade desta metodologia no monitoramento da morbidade da doença de Chagas. Com este propósito os pacientes com doença de Chagas foram anteriormente classificados em três grupos: indeterminados (IND), cardíacos (CARD) e digestivos/mistos (DIG/Mis) conforme seu estado clínico. RESULTADOS: A análise da reatividade sorológica de IgG total na diluição 1:40 mostrou ser uma abordagem importante no diagnóstico da doença de Chagas (100 por cento de sensibilidade e especificidade e ausência de reação cruzada com as demais infecções). A análise das subclasses de IgG mostrou reação cruzada principalmente com NI, LV e LTA em todas as diluições. O grupo IND apresentou a maior reatividade para IgG3 e o grupo DIG/Mis apresentou nível mais elevado de IgG se comparados aos grupos IND e CARD. CONCLUSÕES: Estes achados demonstram que o método de ELISA in-house apresenta uma promissora aplicabilidade no diagnóstico diferencial e na avaliação da morbidade da doença de Chagas.