Studies of MHC class I antigen presentation & the origins of the immunopeptidome

La présentation d'antigène par les molécules d'histocompatibilité majeure de classe I (CMHI) permet au système immunitaire adaptatif de détecter et éliminer les agents pathogènes intracellulaires et des cellules anormales. La surveillance immunitaire est effectuée par les lymphocytes T CD8 qui interagissent avec le répertoire de peptides associés au CMHI présentés à la surface de toutes cellules nucléées. Les principaux gènes humains de CMHI, HLA-A et HLA-B, sont très polymorphes et par conséquent montrent des différences dans la présentation des antigènes. Nous avons étudié les différences qualitatives et quantitatives dans l'expression et la liaison peptidique de plusieurs allotypes HLA. Utilisant la technique de cytométrie de flux quantitative nous avons établi une hiérarchie d'expression pour les quatre HLA-A, B allotypes enquête. Nos résultats sont compatibles avec une corrélation inverse entre l'expression allotypique et la diversité des peptides bien que d'autres études soient nécessaires pour consolider cette hypothèse. Les origines mondiales du répertoire de peptides associés au CMHI restent une question centrale à la fois fondamentalement et dans la recherche de cibles immunothérapeutiques. Utilisant des techniques protéogénomiques, nous avons identifié et analysé 25,172 peptides CMHI isolées à partir des lymphocytes B de 18 personnes qui exprime collectivement 27 allotypes HLA-A,B. Alors que 58% des gènes ont été la source de 1-64 peptides CMHI par gène, 42% des gènes ne sont pas représentés dans l'immunopeptidome. Dans l'ensemble, l’immunopeptidome présenté par 27 allotypes HLA-A,B ne couvrent que 17% des séquences exomiques exprimées dans les cellules des sujets. Nous avons identifié plusieurs caractéristiques des transcrits et des protéines qui améliorent la production des peptides CMHI. Avec ces données, nous avons construit un modèle de régression logistique qui prédit avec une grande précision si un gène de notre ensemble de données ou à partir d'ensembles de données indépendants génèrerait des peptides CMHI. Nos résultats montrent la sélection préférentielle des peptides CMHI à partir d'un répertoire limité de produits de gènes avec des caractéristiques distinctes. L'idée que le système immunitaire peut surveiller des peptides CMHI couvrant seulement une fraction du génome codant des protéines a des implications profondes dans l'auto-immunité et l'immunologie du cancer.

Studies of MHC class I antigen presentation & the origins of the immunopeptidome

La présentation d'antigène par les molécules d'histocompatibilité majeure de classe I (CMHI) permet au système immunitaire adaptatif de détecter et éliminer les agents pathogènes intracellulaires et des cellules anormales. La surveillance immunitaire est effectuée par les lymphocytes T CD8 qui interagissent avec le répertoire de peptides associés au CMHI présentés à la surface de toutes cellules nucléées. Les principaux gènes humains de CMHI, HLA-A et HLA-B, sont très polymorphes et par conséquent montrent des différences dans la présentation des antigènes. Nous avons étudié les différences qualitatives et quantitatives dans l'expression et la liaison peptidique de plusieurs allotypes HLA. Utilisant la technique de cytométrie de flux quantitative nous avons établi une hiérarchie d'expression pour les quatre HLA-A, B allotypes enquête. Nos résultats sont compatibles avec une corrélation inverse entre l'expression allotypique et la diversité des peptides bien que d'autres études soient nécessaires pour consolider cette hypothèse. Les origines mondiales du répertoire de peptides associés au CMHI restent une question centrale à la fois fondamentalement et dans la recherche de cibles immunothérapeutiques. Utilisant des techniques protéogénomiques, nous avons identifié et analysé 25,172 peptides CMHI isolées à partir des lymphocytes B de 18 personnes qui exprime collectivement 27 allotypes HLA-A,B. Alors que 58% des gènes ont été la source de 1-64 peptides CMHI par gène, 42% des gènes ne sont pas représentés dans l'immunopeptidome. Dans l'ensemble, l’immunopeptidome présenté par 27 allotypes HLA-A,B ne couvrent que 17% des séquences exomiques exprimées dans les cellules des sujets. Nous avons identifié plusieurs caractéristiques des transcrits et des protéines qui améliorent la production des peptides CMHI. Avec ces données, nous avons construit un modèle de régression logistique qui prédit avec une grande précision si un gène de notre ensemble de données ou à partir d'ensembles de données indépendants génèrerait des peptides CMHI. Nos résultats montrent la sélection préférentielle des peptides CMHI à partir d'un répertoire limité de produits de gènes avec des caractéristiques distinctes. L'idée que le système immunitaire peut surveiller des peptides CMHI couvrant seulement une fraction du génome codant des protéines a des implications profondes dans l'auto-immunité et l'immunologie du cancer.

Applying Least Absolute Shrinkage Selection Operator and Akaike Information Criterion Analysis to Find the Best Multiple Linear Regression Models between Climate Indices and Components of Cow’s Milk

This study focuses on multiple linear regression models relating six climate indices (temperature humidity THI, environmental stress ESI, equivalent temperature index ETI, heat load HLI, modified HLI (HLI new), and respiratory rate predictor RRP) with three main components of cow’s milk (yield, fat, and protein) for cows in Iran. The least absolute shrinkage selection operator (LASSO) and the Akaike information criterion (AIC) techniques are applied to select the best model for milk predictands with the smallest number of climate predictors. Uncertainty estimation is employed by applying bootstrapping through resampling. Cross validation is used to avoid over-fitting. Climatic parameters are calculated from the NASA-MERRA global atmospheric reanalysis. Milk data for the months from April to September, 2002 to 2010 are used. The best linear regression models are found in spring between milk yield as the predictand and THI, ESI, ETI, HLI, and RRP as predictors with p-value < 0.001 and R2 (0.50, 0.49) respectively. In summer, milk yield with independent variables of THI, ETI, and ESI show the highest relation (p-value < 0.001) with R2 (0.69). For fat and protein the results are only marginal. This method is suggested for the impact studies of climate variability/change on agriculture and food science fields when short-time series or data with large uncertainty are available.

Factores asociados a respuesta de abatacept subcutaneo en artritis reumatoide

INTRODUCCION Dado que la artritis reumatoide es la artropatía inflamatoria más frecuente en el mundo, siendo altamente discapacitante y causando gran impacto de alto costo, se busca ofrecer al paciente opciones terapéuticas y calidad de vida a través del establecimiento de un tratamiento oportuno y eficaz, teniendo presentes aquellos predictores de respuesta previo a instaurar determinada terapia. Existen pocos estudios que permitan establecer aquellos factores de adecuada respuesta para inicio de terapia biológica con abatacept, por lo cual en este estudio se busca determinar cuáles son esos posibles factores. METODOLOGIA Estudio analítico de tipo corte transversal de 94 pacientes con diagnóstico de AR, evaluados para determinar las posibles variables que influyen en la respuesta a terapia biológica con abatacept. Se incluyeron 67 de los 94 pacientes al modelo de regresión logística, que son aquellos pacientes en que fue posible medir la respuesta al tratamiento (respuesta EULAR) a través de la determinación del DAS 28 y así discriminar en dos grupos de comparación (respuesta y no respuesta). DISCUSION DE RESULTADOS La presencia de alta actividad de la enfermedad al inicio de la terapia biológica, aumenta la probabilidad de respuesta al tratamiento respecto al grupo con baja/moderada actividad de la enfermedad; OR 4,19 - IC 95%(1,18 – 14.9), (p 0,027). La ausencia de erosiones óseas aumenta la probabilidad de presentar adecuada respuesta a la terapia biológica respecto aquellos con erosiones, con un OR 3,1 (1,01-9,55), (p 0,048). Niveles de VSG y presencia de manifestaciones extra-articulares son otros datos de interés encontrados en el análisis bivariado. Respecto a las variables o características como predictores de respuesta al tratamiento con abatacept, se encuentran estudios que corroboran los hallazgos de este estudio, respecto al alto puntaje del DAS 28 al inicio de la terapia (9, 12). CONCLUSIONES Existen distintas variables que determinan la respuesta a los diferentes biológicos para manejo de AR. Es imprescindible evaluar dichos factores de manera individual con el fin de lograr de manera efectiva el control de la enfermedad y así mejorar la calidad de vida del individuo (medicina personalizada). Existen variables tales como la alta actividad de la enfermedad y la ausencia de erosiones como predictores de respuesta en la terapia con abatacept.

Obtaining environmental favourability functions from logistic regression

Logistic regression is a statistical tool widely used for predicting species’ potential distributions starting from presence/absence data and a set of independent variables. However, logistic regression equations compute probability values based not only on the values of the predictor variables but also on the relative proportion of presences and absences in the dataset, which does not adequately describe the environmental favourability for or against species presence. A few strategies have been used to circumvent this, but they usually imply an alteration of the original data or the discarding of potentially valuable information. We propose a way to obtain from logistic regression an environmental favourability function whose results are not affected by an uneven proportion of presences and absences. We tested the method on the distribution of virtual species in an imaginary territory. The favourability models yielded similar values regardless of the variation in the presence/absence ratio. We also illustrate with the example of the Pyrenean desman’s (Galemys pyrenaicus) distribution in Spain. The favourability model yielded more realistic potential distribution maps than the logistic regression model. Favourability values can be regarded as the degree of membership of the fuzzy set of sites whose environmental conditions are favourable to the species, which enables applying the rules of fuzzy logic to distribution modelling. They also allow for direct comparisons between models for species with different presence/absence ratios in the study area. This makes themmore useful to estimate the conservation value of areas, to design ecological corridors, or to select appropriate areas for species reintroductions.

Risk assessment to improve food safety along different food chains

The great challenges of today pose great pressure on the food chain to provide safe and nutritious food that meets regulations and consumer health standards. In this context, Risk Analysis is used to produce an estimate of the risks to human health and to identify and implement effective risk-control measures. The aims of this work were 1) describe how QRA is used to evaluate the risk for consumers health, 2) address the methodology to obtain models to apply in QMRA; 3) evaluate solutions to mitigate the risk. The application of a QCRA to the Italian milk industry enabled the assessment of Aflatoxin M1 exposure, impact on different population categories, and comparison of risk-mitigation strategies. The results highlighted the most sensitive population categories, and how more stringent sampling plans reduced risk. The application of a QMRA to Spanish fresh cheeses evidenced how the contamination of this product with Listeria monocytogenes may generate a risk for the consumers. Two risk-mitigation actions were evaluated, i.e. reducing shelf life and domestic refrigerator temperature, both resulting effective in reducing the risk of listeriosis. A description of the most applied protocols for data generation for predictive model development, was provided to increase transparency and reproducibility and to provide the means to better QMRA. The development of a linear regression model describing the fate of Salmonella spp. in Italian salami during the production process and HPP was described. Alkaline electrolyzed water was evaluated for its potential use to reduce microbial loads on working surfaces, with results showing its effectiveness. This work showed the relevance of QRA, of predictive microbiology, and of new technologies to ensure food safety on a more integrated way. Filling of data gaps, the development of better models and the inclusion of new risk-mitigation strategies may lead to improvements in the presented QRAs.

Temporomandibular Dysfunction Post-craniotomy: Evaluation Between Pre- And Post-operative Status.

To identify risk factors associated with post-operative temporomandibular joint dysfunction after craniotomy. The study sample included 24 patients, mean age of 37.3 ± 10 years; eligible for surgery for refractory epilepsy, evaluated according to RDC/TMD before and after surgery. The primary predictor was the time after the surgery. The primary outcome variable was maximal mouth opening. Other outcome variables were: disc displacement, bruxism, TMJ sound, TMJ pain, and pain associated to mandibular movements. Data analyses were performed using bivariate and multiple regression methods. The maximal mouth opening was significantly reduced after surgery in all patients (p = 0.03). In the multiple regression model, time of evaluation and pre-operative bruxism were significantly (p < .05) associated with an increased risk for TMD post-surgery. A significant correlation between surgery follow-up time and maximal opening mouth was found. Pre-operative bruxism was associated with increased risk for temporomandibular joint dysfunction after craniotomy.

[diet Quality And Associated Factors Among The Elderly: A Population-based Study In Campinas, São Paulo State, Brazil].

The aim of this study was to assess the quality of diet among the elderly and associations with socio-demographic variables, health-related behaviors, and diseases. A population-based cross-sectional study was conducted in a representative sample of 1,509 elderly participants in a health survey in Campinas, São Paulo State, Brazil. Food quality was assessed using the Revised Diet Quality Index (DQI-R). Mean index scores were estimated and a multiple regression model was employed for the adjusted analyses. The highest diet quality scores were associated with age 80 years or older, Evangelical religion, diabetes mellitus, and physical activity, while the lowest scores were associated with home environments shared with three or more people, smoking, and consumption of soft drinks and alcoholic beverages. The findings emphasize a general need for diet quality improvements in the elderly, specifically in subgroups with unhealthy behaviors, who should be targeted with comprehensive strategies.

Factors Associated With Reporting Of Abuse Against Children And Adolescents By Nurses Within Primary Health Care.

to analyze the factors associated with the underreporting on the part of nurses within Primary Health Care of abuse against children and adolescents. cross-sectional study with 616 nurses. A questionnaire addressed socio-demographic data, profession, instrumentation and knowledge on the topic, identification and reporting of abuse cases. Bivariate and multivariate logistic regression was used. female nurses, aged between 21 and 32 years old, not married, with five or more years since graduation, with graduate studies, and working for five or more years in PHC predominated. The final regression model showed that factors such as working for five or more years, having a reporting form within the PHC unit, and believing that reporting within Primary Health Care is an advantage, facilitate reporting. the study's results may, in addition to sensitizing nurses, support management professionals in establishing strategies intended to produce compliance with reporting as a legal device that ensures the rights of children and adolescents.

Determination Of Detergent And Dispensant Additives In Gasoline By Ring-oven And Near Infrared Hypespectral Imaging.

A method using the ring-oven technique for pre-concentration in filter paper discs and near infrared hyperspectral imaging is proposed to identify four detergent and dispersant additives, and to determine their concentration in gasoline. Different approaches were used to select the best image data processing in order to gather the relevant spectral information. This was attained by selecting the pixels of the region of interest (ROI), using a pre-calculated threshold value of the PCA scores arranged as histograms, to select the spectra set; summing up the selected spectra to achieve representativeness; and compensating for the superimposed filter paper spectral information, also supported by scores histograms for each individual sample. The best classification model was achieved using linear discriminant analysis and genetic algorithm (LDA/GA), whose correct classification rate in the external validation set was 92%. Previous classification of the type of additive present in the gasoline is necessary to define the PLS model required for its quantitative determination. Considering that two of the additives studied present high spectral similarity, a PLS regression model was constructed to predict their content in gasoline, while two additional models were used for the remaining additives. The results for the external validation of these regression models showed a mean percentage error of prediction varying from 5 to 15%.

Factors associated with the prevalence of hypertension and control practices among elderly residents of São Paulo city, Brazil

The aim of this study was to analyze the prevalence of hypertension and control practices among the elderly. The survey analyzed data from 872 elderly people in São Paulo, Brazil, through a cluster sampling, stratified according to education and income. A Poisson multiple regression model checked for the existence of factors associated with hypertension. The prevalence of self-reported hypertension among the elderly was 46.9%. Variables associated with hypertension were self-rated health, alcohol consumption, gender, and hospitalization in the last year, regardless of age. The three most common measures taken to control hypertension, but only rarely, are oral medication, routine salt-free diet and physical activity. Lifestyle and socioeconomic status did not affect the practice of control, but knowledge about the importance of physical activity was higher among those older people with higher education and greater income. The research suggests that health policies that focus on primary care to encourage lifestyle changes among the elderly are necessary.

Wives of pathological gamblers: personality traits, depressive symptoms and social adjustment

Objective: Wives of pathological gamblers tend to endure long marriages despite financial and emotional burden. Difficulties in social adjustment, personality psychopathology, and comorbidity with psychiatric disorders are pointed as reasons for remaining on such overwhelming relationships. The goal was to examine the social adjustment, personality and negative emotionality of wives of pathological gamblers. Method: The sample consisted of 25 wives of pathological gamblers, mean age 40.6, SD = 9.1 from a Gambling Outpatient Unit and at GAM-ANON, and 25 wives of non-gamblers, mean age 40.8, SD = 9.1, who answered advertisements placed at the Universidade de São Paulo hospital and medical school complex. They were selected in order to approximately match demographic characteristics of the wives of pathological gamblers. Subjects were assessed by the Social Adjustment Scale, Temperament and Character Inventory, Beck Depression Inventory and State-Trait Anxiety Inventory. Results: Three variables remained in the final Multiple Logistic Regression model, wives of pathological gamblers presented greater dissatisfaction with their marital bond, and higher scores on Reward Dependence and Persistence temperament factors. Both, Wives of pathological gamblers and wives of non-gamblers presented well-structured character factors excluding personality disorders. Conclusion: This personality profile may explain wives of pathological gamblers emotional resilience and their marriage longevity. Co-dependence and other labels previously used to describe them may work as a double edged sword, legitimating wives of pathological gamblers problems, while stigmatizing them as inapt and needy.

Mortalidade cardiovascular por sexo e faixa etária em São Paulo, Brasil: 1996 a 1998 e 2003 a 2005

FUNDAMENTO: O conhecimento da evolução da mortalidade cardiovascular é importante para levantar hipóteses sobre a sua ocorrência e subsidiar medidas de prevenção e controle. OBJETIVOS: Comparar a mortalidade pelo conjunto das doenças cardiovasculares e seus principais subgrupos: doença isquêmica do coração e cerebrovasculares (DIC e DCBV), no município de São Paulo, por sexo e idade, de 1996 a 1998 e 2003 a 2005. MÉTODOS: Foram usados dados de óbitos do Programa de Aprimoramento das Informações de Mortalidade para o Município (PROAIM) e estimativas populacionais da Fundação Sistema Estadual de Análise de Dados (SEADE) do Estado de São Paulo. A magnitude na mortalidade e as mudanças entre os triênios foram medidas pela descrição de coeficientes e variação percentual relativa. O modelo de regressão de Poisson foi usado também para estimar a mudança na mortalidade entre os períodos. RESULTADOS: Observou-se redução importante da mortalidade cardiovascular. Os coeficientes aumentam com a idade em ambos os sexos. Também são mais elevados na população masculina, na faixa a partir dos 70 anos. Os coeficientes de mortalidade por DIC são maiores que aqueles por DCBV, tanto nos homens como nas mulheres de 50 anos ou mais. O declínio pelo conjunto das doenças cardiovasculares foi maior em mulheres de 20 a 29 anos (-30%) e em homens de 30 a 39 anos (-26%). CONCLUSÃO: A força da intensidade da mortalidade cardiovascular diminuiu entre 1996 e 1998, a 2003 e 2005. Ainda assim há diferenças entre os grupos. Essa redução pode significar, em parte, um maior acesso aos métodos diagnósticos e terapêuticos.

Prevalência de hipertensão arterial em militares jovens e fatores associados

OBJETIVO: Estimar a prevalência de hipertensão arterial entre militares jovens e fatores associados. MÉTODOS: Estudo transversal realizado com amostra de 380 militares do sexo masculino de 19 e 35 anos de idade em uma unidade da Força Aérea Brasileira em São Paulo, SP, entre 2000 e 2001. Os pontos de corte para hipertensão foram: >140mmHg para pressão sistólica e > 90mmHg para pressão diastólica. As variáveis estudadas incluíram fatores de risco e de proteção para hipertensão, como características comportamentais e nutricionais. Para análise das associações, utilizou-se regressão linear generalizada múltipla, com família binomial e ligação logarítmica, obtendo-se razões de prevalências com intervalo de 90% de confiança e seleção hierarquizada das variáveis. RESULTADOS: A prevalência de hipertensão arterial foi de 22% (IC 90%: 21;29). No modelo final da regressão múltipla verificou-se prevalência de hipertensão 68% maior entre os ex-fumantes em relação aos não fumantes (IC 90%: 1,13;2,50). Entre os indivíduos com sobrepeso (índice de massa corporal - IMC de 25 a 29kg/m2) e com obesidade (IMC>29kg/m2) as prevalências foram, respectivamente, 75% (IC 90%: 1,23;2,50) e 178% (IC 90%: 1,82;4,25) maiores do que entre os eutróficos. Entre os que praticavam atividade física regular, comparado aos que não praticavam, a prevalência foi 52% menor (IC 90%: 0,30;0,90). CONCLUSÕES: Ser ex-fumante e ter sobrepeso ou obesidade foram situações de risco para hipertensão, enquanto que a prática regular de atividade física foi fator de proteção em militares jovens.

A importância das quedas no mesmo nível entre idosos no estado de são paulo

OBJETIVO: Analisar as características das quedas no grupo etário com 60 anos ou mais, com ênfase nas quedas no mesmo nível, residentes no Estado de São Paulo, a partir da análise das diferentes fontes de informação oficiais. MÉTODOS: Foram analisadas as 1.328 mortes registradas no SIM em 2007, 20.726 internações no SIH/SUS em 2008 e os 359 atendimentos realizados em 24 UEs do Estado de São Paulo em 2007. Um teste de regressão logística foi utilizado para testar associações entre variáveis nos atendimentos em emergências. RESULTADOS: O sexo masculino preponderou nas mortes (51,2 %) enquanto o sexo feminino preponderou nas internações (61,1%) e atendimentos em emergências (60,4%). O coeficiente de mortalidade foi 31/100.000 habitantes, aumentando com a idade e atingindo o valor de 110,7/100.000 habitantes na faixa de 80 anos e mais. As quedas no mesmo nível foram responsáveis pela maior proporção de mortes definidas (35%), nas internações (47,5%) e também nas emergências (66%), crescendo de importância com o aumento das faixas etárias. A residência foi o local de ocorrência em 65,8% dos casos atendidos nas emergências. Os traumatismos de cabeça assumem importância nas mortes; as fraturas de fêmur foram as lesões mais frequentes nas internações e emergências. Nas emergências, as mulheres foram 1,55 vezes significativamente mais prováveis de serem atendidas por uma queda do que pelas outras causas externas que os homens. Comparativamente à faixa de 60 a 69 anos, os indivíduos na faixa de 70 a 79 anos foram 2,10 vezes e os indivíduos de 80 anos e mais foram 2,26 vezes significativamente mais prováveis de serem atendidos por uma queda do que pelas outras causas externas. Não houve diferença estatisticamente significante quanto ao sexo ou faixa etária quando se comparou os indivíduos que sofreram quedas no mesmo nível e outros tipos de queda. CONCLUSÃO: Recomenda-se que a prevenção das quedas entre idosos entre na pauta de discussão das políticas públicas sem mais demora.