EXPOSURE TO EXTREME HEAT EVENTS AND CHRONIC RESPIRATORY DISEASES AMONG A NATIONALLY REPRESENTATIVE SAMPLE OF THE UNITED STATES POPULATION

Previous studies have shown that extreme weather events are on the rise in response to our changing climate. Such events are projected to become more frequent, more intense, and longer lasting. A consistent exposure metric for measuring these extreme events as well as information regarding how these events lead to ill health are needed to inform meaningful adaptation strategies that are specific to the needs of local communities. Using federal meteorological data corresponding to 17 years (1997-2013) of the National Health Interview Survey, this research: 1) developed a location-specific exposure metric that captures individuals’ “exposure” at a spatial scale that is consistent with publicly available county-level health outcome data; 2) characterized the United States’ population in counties that have experienced higher numbers of extreme heat events and thus identified population groups likely to experience future events; and 3) developed an empirical model describing the association between exposure to extreme heat events and hay fever. This research confirmed that the natural modes of forcing (e.g., El Niño-Southern Oscillation), seasonality, urban-rural classification, and division of country have an impact on the number extreme heat events recorded. Also, many of the areas affected by extreme heat events are shown to have a variety of vulnerable populations including women of childbearing age, people who are poor, and older adults. Lastly, this research showed that adults in the highest quartile of exposure to extreme heat events had a 7% increased odds of hay fever compared to those in the lowest quartile, suggesting that exposure to extreme heat events increases risk of hay fever among US adults.

Chronic respiratory diseases and quality of life in elderly nursing home residents

Few studies have assessed the quality of life (QOL) related to chronic respiratory diseases in the elderly. In the framework of the geriatric study on the health effects of air quality in elderly care centers (GERIA) study, a questionnaire was completed by elderly subjects from 53 selected nursing homes. It included various sections in order to assess respiratory complaints, QOL (World Health Organization QOL (WHOQOL)-BREF), and the cognitive and depression status. The outcome variables were the presence of a score lower than 50 (<50) in each of the WHOQOL-BREF domains (physical health, psychological health, social relationships, and environmental health). Chronic bronchitis, frequent cough, current wheezing, asthma, and allergic rhinitis were considered as potential risk factors. The surveyed sample was (n = 887) 79% female, with a mean age of 84 years (SD: 7 years). In the multivariable analysis, a score of <50 in the physical domain was associated with wheezing in the previous 12 months (odds ratio (OR): 2.03, confidence interval (CI): 1.25-3.31) and asthma (OR: 1.95, CI: 1.12-3.38). The psychological domain was related with a frequent cough (OR: 1.43, CI: 0.95-2.91). A score of <50 in the environmental domain was associated with chronic bronchitis (OR: 2.89, CI: 1.34-6.23) and emphysema (OR: 3.89, CI: 1.27-11.88). In view of these findings, the presence of respiratory diseases seems to be an important risk factor for a low QOL among elderly nursing home residents.

Diaphragm muscle adaptation to sustained hypoxia: lessons from animal models with relevance to high altitude and chronic respiratory diseases

The diaphragm is the primary inspiratory pump muscle of breathing. Notwithstanding its critical role in pulmonary ventilation, the diaphragm like other striated muscles is malleable in response to physiological and pathophysiological stressors, with potential implications for the maintenance of respiratory homeostasis. This review considers hypoxic adaptation of the diaphragm muscle, with a focus on functional, structural, and metabolic remodeling relevant to conditions such as high altitude and chronic respiratory disease. On the basis of emerging data in animal models, we posit that hypoxia is a significant driver of respiratory muscle plasticity, with evidence suggestive of both compensatory and deleterious adaptations in conditions of sustained exposure to low oxygen. Cellular strategies driving diaphragm remodeling during exposure to sustained hypoxia appear to confer hypoxic tolerance at the expense of peak force-generating capacity, a key functional parameter that correlates with patient morbidity and mortality. Changes include, but are not limited to: redox-dependent activation of hypoxia-inducible factor (HIF) and MAP kinases; time-dependent carbonylation of key metabolic and functional proteins; decreased mitochondrial respiration; activation of atrophic signaling and increased proteolysis; and altered functional performance. Diaphragm muscle weakness may be a signature effect of sustained hypoxic exposure. We discuss the putative role of reactive oxygen species as mediators of both advantageous and disadvantageous adaptations of diaphragm muscle to sustained hypoxia, and the role of antioxidants in mitigating adverse effects of chronic hypoxic stress on respiratory muscle function.

Design and Synthesis of Novel Kinase Inhibitors for the Treatment of Chronic Respiratory Diseases

In 2017, Chronic Respiratory Diseases accounted for almost four million deaths worldwide. Unfortunately, current treatments are not definitive for such diseases. This unmet medical need forces the scientific community to increase efforts in the identification of new therapeutic solutions. PI3K delta plays a key role in mechanisms that promote airway chronic inflammation underlying Asthma and COPD. The first part of this project was dedicated to the identification of novel PI3K delta inhibitors. A first SAR expansion of a Hit, previously identified by a HTS campaign, was carried out. A library of 43 analogues was synthesised taking advantage of an efficient synthetic approach. This allowed the identification of an improved Hit of nanomolar enzymatic potency and moderate selectivity for PI3K delta over other PI3K isoforms. However, this compound exhibited low potency in cell-based assays. Low cellular potency was related to sub optimal phys-chem and ADME properties. The analysis of the X-ray crystal structure of this compound in human PI3K delta guided a second tailored SAR expansion that led to improved cellular potency and solubility. The second part of the thesis was focused on the rational design and synthesis of new macrocyclic Rho-associated protein kinases (ROCKs) inhibitors. Inhibition of these kinases has been associated with vasodilating effects. Therefore, ROCKs could represent attractive targets for the treatment of pulmonary arterial hypertension (PAH). Known ROCK inhibitors suffer from low selectivity across the kinome. The design of macrocyclic inhibitors was considered a promising strategy to obtain improved selectivity. Known inhibitors from literature were evaluated for opportunities of macrocyclization using a knowledge-based approach supported by Computer Aided Drug Design (CADD). The identification of a macrocyclic ROCK inhibitor with enzymatic activity in the low micro molar range against ROCK II represented a promising result that validated this innovative approach in the design of new ROCKs inhibitors.

Inatividade física no lazer de adultos e fatores associados

OBJETIVO: Analisar a associação entre inatividade física no lazer de adultos com fatores sociodemográficos e indicadores de risco e proteção para doenças crônicas. MÉTODOS: Estudo transversal com indivíduos com idade de 18 anos e superior (n=1996). Foram utilizados dados obtidos do Sistema Municipal de Monitoramento de Fatores de Risco para Doenças Crônicas Não Transmissíveis, por meio de entrevistas telefônicas, em Florianópolis, SC, 2005. Analisaram-se fatores sociodemográficos e comportamentais de proteção e de risco. Os resultados das análises de regressão múltipla para associação entre inatividade física no lazer e variáveis independentes foram expressos por razões de prevalência. RESULTADOS: A prevalência da inatividade física no lazer foi de 54,6% (47,3% homens, 61,4% mulheres). Após análise ajustada, entre os homens, maior probabilidade de inatividade física no lazer foi associada ao aumento da faixa etária, à diminuição do nível de escolaridade e ao fato de trabalharem; menor probabilidade de inatividade física no lazer foi associada ao consumo abusivo de bebida alcoólica, independentemente da faixa etária, nível de escolaridade e trabalho. Entre as mulheres, maior probabilidade de inatividade foi observada entre as que relataram nível de escolaridade inferior a 12 anos de estudo e que trabalhavam. Análises ajustadas pelo nível de escolaridade e trabalho mostraram maior probabilidade de inatividade física no lazer para mulheres que relataram consumo de frutas e hortaliças com freqüência inferior a cinco vezes por dia e consumo de leite integral. CONCLUSÕES: Os fatores associados à inatividade física no lazer apresentaram perfil diferente entre homens e mulheres. Para mulheres, a inatividade física se associou a comportamentos de risco para doenças crônicas, em especial aos hábitos alimentares, e para os homens, se associaram a fatores sociodemográficos.

The offspring of the diabetic mother--short- and long-term implications.

In the 1980s, David Barker and Colleagues proposed that the major causes of cardiovascular and metabolic diseases have their roots in early development. There is now robust evidence that an hyperglycemic intrauterine environment is responsible not only for significant short-term morbidity in the fetus and the neonate but also for an increased risk of developing diabetes as well as other chronic, noncommunicable diseases at adulthood. The risk is higher in pregestational diabetes, but unrecognized and/or poorly managed gestational diabetes (GDM) may have similar consequences. Although a relatively clear picture of the pathogenesis of the fetal and neonatal complications of maternal diabetes and of their interrelationship is available today, the intimate molecular mechanisms involved in the long term are far from being understood. While the rate of GDM is sharply increasing in association with the pandemic of obesity and of type 2 diabetes over the world, we review here the current understanding of short- and long-term outcomes of fetuses exposed to a diabetic environment.

Produção pesqueira artesanal: diagnóstico ergonômico e bases para um planejamento nutricional situado e a promoção da saúde dos jangadeiros

The traditional fishing with rafts is characterized by unpredictability, high stakes and inadequate work conditions. The extensive working hours, physical wear, inadequate nutrition, unsanitary conditions, lack of salvage equipment and instruments suitable working, added by the presence of changes in the nutritional status of fisherman, that contribute to the picture of insecurity in high seas, injuries and health. This study aimed to analyze the activity of the fisherman s from Ponta Negra, Natal / RN, and check the conditions of supply of these fishermen and their implications on health and development of their work. To this finality, was used a methodology based on the ergonomic work analysis employing techniques such as observational and interactional conversational action, listening to the answers, observation protocols, photographic and video records. The script conversational dynamic action was developed from literature searches about the artisanal fisheries, culture and food habits of this population, and analyzes the overall situation of focus and two reference situations. To collect data on the usual diet of fisherman as well as quantitative and qualitative analysis that was used for data analysis and 24h recall the Food Frequency Questionnaire (FFQ). The impact of this power to the health of fisherman was evaluated performing a nutritional assessment. The results revealed that the fishermen carry out their activities with poor working conditions, health and nutrition. Feeding practices of these fishermen undertake development work, making it even more stressful, as well contributing to the emergence of Chronic Noncommunicable Diseases. The management of the activity, as well as the current structure of the vessel, also contributes to the adoption of inappropriate feeding practices during the shipment of catch. The results of this indicate the need for adequate interventions in order to assist in recovery and / or maintenance of health of fisherman minimizing reflections of nutritional disorders for the development activity by improving the quality of life in this population

Capacidade funcional, composição corporal e condições de saúde de idosos longevos

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Factors associated with sarcopenia in subjects aged 80 years and over

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Brazilian Longitudinal Study of Adult Health (ELSA-Brasil): Objectives and Design

Although low- and middle-income countries still bear the burden of major infectious diseases, chronic noncommunicable diseases are becoming increasingly common due to rapid demographic, epidemiologic, and nutritional transitions. However, information is generally scant in these countries regarding chronic disease incidence, social determinants, and risk factors. The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) aims to contribute relevant information with respect to the development and progression of clinical and subclinical chronic diseases, particularly cardiovascular diseases and diabetes. In this report, the authors delineate the study's objectives, principal methodological features, and timeline. At baseline, ELSA-Brasil enrolled 15,105 civil servants from 5 universities and 1 research institute. The baseline examination (2008-2010) included detailed interviews, clinical and anthropometric examinations, an oral glucose tolerance test, overnight urine collection, a 12-lead resting electrocardiogram, measurement of carotid intima-media thickness, echocardiography, measurement of pulse wave velocity, hepatic ultrasonography, retinal fundus photography, and an analysis of heart rate variability. Long-term biologic sample storage will allow investigation of biomarkers that may predict cardiovascular diseases and diabetes. Annual telephone surveillance, initiated in 2009, will continue for the duration of the study. A follow-up examination is scheduled for 2012-2013.

Factors associated with smoking in the elderly: a health survey in Sao Paulo (ISA-SP)

This article reports on smoking prevalence and associated factors in the elderly, based on a population-based cross-sectional study with multistage sampling including 1,954 individuals 60 years or older living in four areas of Sao Paulo State, Brazil. Overall smoking prevalence was 12.2%, and higher rates were associated with male gender, age 60-69 years, not belonging to an Evangelical church, lower income, low body weight, lack of leisure-time physical activity, depression/anxiety, and hypertension. There was a high prevalence of smokers among individuals with a history of stroke, cancer, and chronic obstructive pulmonary disease. The results point to the need for effective interventions in healthcare services to promote smoking cessation among the elderly, since many are unable to stop on their own, even when they have tobacco-related illnesses. Special attention should be paid to individuals that depend on the National Health System, since smoking prevalence is higher in underprivileged socioeconomic groups.

Estado nutricional aos 20 anos como fator de risco para incidência precoce de doenças crônicas não transmissíveis entre adultos de 30 a 49 anos

Introdução: O excesso de peso em adultos jovens está associado ao desenvolvimento de doenças crônicas não transmissíveis (DCNT) e à diminuição da qualidade de vida e ao aumento da mortalidade precoce. A transição da adolescência para a fase adulta é o período de maior risco para a incidência da obesidade. Objetivo: Estimar o efeito o índice de massa corpora (IMC) aos 20 anos sobre a incidência de DCNT em adultos brasileiros com idade entre 30 a 49 anos. Métodos: Foram selecionados 12.079 indivíduos de 30 a 49 anos da Pesquisa Nacional de Saúde (PNS), realizada no ano de 2013. O modelo adotado para determinação das DCNT foi aquele proposto pela Organização Mundial de Saúde. A incidência das DCNT (hipertensão, doenças cardiovasculares, diabetes e câncer, entre outras), informada pela data do diagnóstico, foi modelada como função do IMC aos 20 anos. Os indivíduos sem a doença até o presente foram considerados como censura. As estimativas de sobrevida foram calculadas com o método de Kaplan-Meier (KM) para cada uma das doenças, estratificada por sexo e ajustada por escolaridade. A análise dos fatores de risco para as doenças foi feita utilizando-se o modelo de riscos proporcionais de Cox. Resultados: Nas curvas de sobrevida KM, indivíduos com IMC >=25kg/m² apresentaram incidência mais elevada e precoce de DCNT, principalmente hipertensão, diabetes e depressão. A idade mediana para incidência do diabetes em obesos foi de 47 anos para homens e 48 anos para mulheres. A incidência da hipertensão arterial foi 4,2 por mil com sobrevida mediana de 48 e 44 anos em mulheres com excesso de peso e obesidade, respectivamente. Dentre os fatores de risco associados as DCNT, o tabagismo em idade precoce foi associado à incidência de depressão. Conclusão: O excesso de peso em adultos jovens aumenta a incidência precoce de DCNT, com efeitos negativos na qualidade de vida, lazer e produtividade, além de aumentar a demanda por serviços de saúde. Torna-se necessário que a intervenção para redução dessas doenças seja direcionada para o período da infância e adolescência com ações que promovam a redução da exposição desses indivíduos à alimentação de má qualidade e incentivo a prática de atividade, não uso do tabaco e consumo moderado de álcool.

FATORES DE RISCO PARA DOENÇAS CRÔNICAS NÃO TRANSMISSÍVEIS E VARIÁVEIS SOCIODEMOGRÁFICAS DE SERVIDORES PÚBLICOS

Objetivo: Associar fatores de risco para doenças crônicas não transmissíveis (DCNT) com variáveis sociodemográficas de servidores de uma instituição pública de ensino superior. Métodos: Estudo transversal, realizado no período de 2012 a 2013. Utilizou-se um questionário com variáveis sociodemográficas, fatores de risco para DCNT e aferição de peso e estatura. Classificou-se o estado nutricional de acordo com o índice de massa corporal. Analisaram-se os dados pelos programas Epi-Info 3.2.1 e Bioestat 5.0. As associações foram verificadas pelos testes qui-quadrado de Yates, de tendência e exato de Fisher (p≤0,05). Resultados: Participaram 225 servidores, maioria de mulheres (64,4%), na faixa etária entre 45-54 anos (37,3%) e escolaridade superior a 12 anos de estudo (85,8%). O sexo associou-se ao excesso de peso (p=0,034), consumo diário de leite integral (p=0,023), consumo insuficiente de frutas, legumes e verduras - FLV (p=0,020) e consumo insuficiente de feijão (p=0,000), sendo mais frequentes entre mulheres. Entre os homens, foi mais frequente o consumo excessivo de bebida alcoólica (p=0,000). O excesso de peso associou-se à faixa etária (p=0,008). O hábito de fumar (p=0,004) e o consumo diário de leite integral (p=0,016) apresentaram associação com a escolaridade. Conclusão: Encontrou-se elevada prevalência de fatores de risco para doenças crônicas não transmissíveis na amostra estudada, com associação para sexo, faixa etária e escolaridade. O excesso de peso apresentou maior ocorrência nas mulheres e nas idades acima de 45 anos, hábitos alimentares inadequados no sexo feminino, maior ingestão de bebida alcoólica no masculino e hábito de fumar nos indivíduos com maior escolaridade.

PREVALENCE AND FACTORS ASSOCIATED WITH THE PERFORMANCE OF MAMMOGRAPHY AND PAP SMEAR TEST

Objective: To estimate the prevalence and factors associated with the performance of mammography and pap smear test in women from the city of Maringá, Paraná. Methods: Population-based cross-sectional study conducted with 345 women aged over 20 years in the period from March 2011 to April 2012. An interview was carried out using a questionnaire proposed by the Ministry of Health, which addressed sociodemographic characteristics, risk factors for chronic noncommunicable diseases and issues related to mammographic and pap screening. Data were analyzed using bivariate analysis, crude analysis with odds ratio (OR) and chi-squared test using Epi Info 3.5.1 program; multivariate analysis using logistic regression was performed using the software Statistica 7.1, with a significance level of 5% and a confidence interval of 95%. Results: The mean age of the women was 52.19 (±5.27) years. The majority (56.5%) had from 0 to 8 years of education. Additionally, 84.6% (n=266) of the women underwent pap smear and 74.3% (n=169) underwent mammography. The lower performance of pap smear test was associated with women with 9-11 years of education (p=0.01), and the lower performance of mammography was associated with women without private health insurance (p<0.01). Conclusion: The coverage of mammography and pap smear test was satisfactory among the women from Maringá, Paraná. Low education level and women who depended on the public health system presented lower performance of mammography.

Glycemic index role on visceral obesity, subclinical inflammation and associated chronic diseases

Background: It is believed that the glycemic index (GI) may be used as a strategy to prevent and control noncommunicable diseases (NCD). Obesity is a multifactorial condition, a risk factor for development of other NCDs. Among the different types, abdominal obesity is highlighted, which is essential for the diagnosis of metabolic syndrome, and it is related to insulin resistance, dyslipi-demia, hypertension and changes in levels of inflammatory markers. Such indicators are closely related to the development of Type 2 Diabetes and cardiovascular disease. Objectives: Discuss the role of GI as a strategy for the prevention and/or treatment of visceral obesity, subclinical inflammation and chronic diseases. Results and discussion: The intake of low GI diets is associated with glycemic decreases, and lower and more consistent postprandial insulin release, avoiding the occurrence of hypoglycemia. Moreover, consumption of a low GI diet has been indicated as beneficial for reducing body weight, total body fat and visceral fat, levels of proinflammatory markers and the occurrence of dyslipidemia and hypertension. The intake of low GI foods should be encouraged in order to prevent and control non-communicable diseases.