Children with cerebral malaria or severe malarial anaemia lack immunity to distinct variant surface antigen subsets

Abstract Variant surface antigens (VSAs) play a critical role in severe malaria pathogenesis. Defining gaps, or “lacunae”, in immunity to these Plasmodium falciparum antigens in children with severe malaria would improve our understanding of vulnerability to severe malaria and how protective immunity develops. Using a protein microarray with 179 antigen variants from three VSA families as well as more than 300 variants of three other blood stage P. falciparum antigens, reactivity was measured in sera from Malian children with cerebral malaria or severe malarial anaemia and age-matched controls. Sera from children with severe malaria recognized fewer extracellular PfEMP1 fragments and were less reactive to specific fragments compared to controls. Following recovery from severe malaria, convalescent sera had increased reactivity to certain non-CD36 binding PfEMP1s, but not other malaria antigens. Sera from children with severe malarial anaemia reacted to fewer VSAs than did sera from children with cerebral malaria, and both of these groups had lacunae in their seroreactivity profiles in common with children who had both cerebral malaria and severe malarial anaemia. This microarray-based approach may identify a subset of VSAs that could inform the development of a vaccine to prevent severe disease or a diagnostic test to predict at-risk children

Hipertensão arterial na população adulta de Salvador (BA) - Brasil Arterial hypertension in the adult population of Salvador (BA) - Brazil

OBJETIVO: Estimar a prevalência (Pr) da hipertensão arterial (HA) e da sua associação com outros fatores de risco cardiovascular em população fortemente miscigenada. MÉTODOS: Estudo de corte transversal, realizado em amostra populacional de 1.439 adultos e > 20 anos, em Salvador-Brasil. Todos responderam a questionário em domicilio e tiveram medidos: pressão arterial, peso, altura, circunferência da cintura (CC), glicemia e lípidas séricas. O critério para HA foi a média da PAS > 140 e/ou PAD > 90mmHg. Foram estimadas Pr da HA com IC a 95%. As associações foram medidas pelo OR ajustado (ORaj), por análise de regressão. RESULTADOS: A Pr total foi da HA foi 29,9%: 27,4% IC (23,9-31,2) em homens e 31,7%, IC(28,5-34,9) em mulheres. Em negros a Pr foi 31,6% para homens e 41,1% para mulheres. Em brancos foi 25,8% nos homens e 21,1% nas mulheres. A HA apresentou associação significante com idades > 40 anos, sobrepeso/obesidade [ORaj = 2,37(1,57-3,60)] para homens e 1,62(1,02-2,58) para mulheres. Nos homens a HA associou-se à escolaridade elevada e nas mulheres com a cor da pele parda e negra, com obesidade abdominal, ORaj = 2,05 IC(1,31-3,21), diabetes ORaj = 2,16 IC(1,19-3,93) e com a menopausa. CONCLUSÃO: A HA predominou em negros de ambos os sexos, e em mulheres. Excetuando-se o sobrepeso/obesidade, as variáveis que se mantiveram independentemente associadas à HA diferiram entre os sexos. Os resultados sugerem aprofundamento do estudo da HA em negros e necessidade de intervenções educacionais contínuas e de início precoce.<br>OBJECTIVE: To estimate the prevalence of hypertension (H) and its association with other cardiovascular risk factors in a highly multiracial population. METHODS: A cross-sectional study carried out in Salvador, Brazil, in a population sample of 1439 adults > 20 years of age. All participants completed a questionnaire at home and had the following measurements taken: blood pressure, body weight, height, waist circumference (WC), and serum glucose and lipids. Hypertension was defined as mean SBP e"140 and/or DBP > 90 mmHg. Hypertension prevalence was estimated with a 95% confidence interval (CI). The associations were measured by the adjusted odds ratio (AOR), using regression analysis. RESULTS: Overall prevalence of HA was 29.9%: 27.4% CI (23.9-31.2) in men and 31.7%, CI (28.5-34.9) in women. Among black men, this prevalence was 31.6%, and among black women, 41.1%. Among white men it was 25.8%, and among white women, 21.1%. Arterial hypertension was significantly associated with age > 40, overweight/obesity (aOR = 2.37[1.57-3.60]) for men and 1,62 (1.02 - 2.58) for women. Among men, HA was associated with a high level of education and among women, with dark brown and black skin, abdominal obesity, aOR = 2.05 CI (1.31-3.21), diabetes aOR = 2.16 CI (1.19-3.93), and menopause. CONCLUSION: Arterial hypertension predominated among black people of both genders, and in women. Those variables that remained independently associated with AH differed in both genders, except overweight/obesity. Our results suggest the need for an in-depth study of AH among black people and early, continuing educational interventions

Arquivos Brasileiros de Cardiologia

p.747-756OBJETIVO: Estimar a prevalência (Pr) da hipertensão arterial (HA) e da sua associação com outros fatores de risco cardiovascular em população fortemente miscigenada. MÉTODOS: Estudo de corte transversal, realizado em amostra populacional de 1.439 adultos e > 20 anos, em Salvador-Brasil. Todos responderam a questionário em domicilio e tiveram medidos: pressão arterial, peso, altura, circunferência da cintura (CC), glicemia e lípidas séricas. O critério para HA foi a média da PAS > 140 e/ou PAD > 90mmHg. Foram estimadas Pr da HA com IC a 95%. As associações foram medidas pelo OR ajustado (ORaj), por análise de regressão. RESULTADOS: A Pr total foi da HA foi 29,9%: 27,4% IC (23,9-31,2) em homens e 31,7%, IC(28,5-34,9) em mulheres. Em negros a Pr foi 31,6% para homens e 41,1% para mulheres. Em brancos foi 25,8% nos homens e 21,1% nas mulheres. A HA apresentou associação significante com idades > 40 anos, sobrepeso/obesidade [ORaj = 2,37(1,57-3,60)] para homens e 1,62(1,02—2,58) para mulheres. Nos homens a HA associou-se à escolaridade elevada e nas mulheres com a cor da pele parda e negra, com obesidade abdominal, ORaj = 2,05 IC(1,31-3,21), diabetes ORaj = 2,16 IC(1,19-3,93) e com a menopausa. CONCLUSÃO: A HA predominou em negros de ambos os sexos, e em mulheres. Excetuando-se o sobrepeso/obesidade, as variáveis que se mantiveram independentemente associadas à HA diferiram entre os sexos. Os resultados sugerem aprofundamento do estudo da HA em negros e necessidade de intervenções educacionais contínuas e de início precoce

Comprehensive analysis by liquid chromatography Q?Orbitrap mass spectrometry : fast screening of peptides and organic molecules.

The number of substances nominally listed in the prohibited list of the World Anti? Doping Agency increases each year. Moreover, many of these substances do not have a single analytical target and must be monitored through different metabolites, artifacts, degradation products, or biomarkers. A new analytical method was developed and validated for the simultaneous analysis of peptides and organic molecules using a single sample preparation and LC?Q?HRMS detection. The simultaneous analysis of 450 target molecules was performed after cleanup on a mixed?mode solid?phase extraction cartridge, combined with untreated urine. The cleanup solvent and reconstitution solvent were the most important parameters for achieving a comprehensive sample preparation approach. A fast chromatographic run based on a multistep gradient was optimized under different flows; the detection of all substances without isomeric coelution was achieved in 11 minutes, and the chromatographic resolution was considered a critical parameter, even in high?resolution mass spectrometry detection. The mass spectrometer was set to operate by switching between positive and negative ionization mode for FULL?MS, all?ion fragmentation, and FULL?MS/MS2 . The suitable parameters for the curved linear trap (c?trap) conditions were determined and found to be the most important factors for the development of the method. Only FULL?MS/ MS2 enables the detection of steroids and peptides at concentrations lower than the minimum required performance levels set by World Anti?Doping Agency (1 ng mL?1 ). The combination of the maximum injection time of the ions into the c?trap, multiplexing experiments, and loop count under optimized conditions enabled the method to be applied to over 10 000 samples in only 2 months during the 2016 Rio Summer Olympic and Paralympic Games. The procedure details all aspects, from sample preparation to mass spectrometry detection. FULL?MS data acquisition is performed in positive and negative ion mode simultaneously and can be applied to untargeted approaches

Identification of Seroreactive Proteins of <i>Leptospira interrogans</i> Serovar Copenhageni Using a High-Density Protein Microarray Approach

<div><p>Background</p><p>Leptospirosis is a widespread zoonotic disease worldwide. The lack of an adequate laboratory test is a major barrier for diagnosis, especially during the early stages of illness, when antibiotic therapy is most effective. Therefore, there is a critical need for an efficient diagnostic test for this life threatening disease.</p><p>Methodology</p><p>In order to identify new targets that could be used as diagnostic makers for leptopirosis, we constructed a protein microarray chip comprising 61% of <i>Leptospira interrogans</i> proteome and investigated the IgG response from 274 individuals, including 80 acute-phase, 80 convalescent-phase patients and 114 healthy control subjects from regions with endemic, high endemic, and no endemic transmission of leptospirosis. A nitrocellulose line blot assay was performed to validate the accuracy of the protein microarray results.</p><p>Principal findings</p><p>We found 16 antigens that can discriminate between acute cases and healthy individuals from a region with high endemic transmission of leptospirosis, and 18 antigens that distinguish convalescent cases. Some of the antigens identified in this study, such as LipL32, the non-identical domains of the Lig proteins, GroEL, and Loa22 are already known to be recognized by sera from human patients, thus serving as proof-of-concept for the serodiagnostic antigen discovery approach. Several novel antigens were identified, including the hypothetical protein LIC10215 which showed good sensitivity and specificity rates for both acute- and convalescent-phase patients.</p><p>Conclusions</p><p>Our study is the first large-scale evaluation of immunodominant antigens associated with naturally acquired leptospiral infection, and novel as well as known serodiagnostic leptospiral antigens that are recognized by antibodies in the sera of leptospirosis cases were identified. The novel antigens identified here may have potential use in both the development of new tests and the improvement of currently available assays for diagnosing this neglected tropical disease. Further research is needed to assess the utility of these antigens in more deployable diagnostic platforms.</p></div