Metabolic status is not associated with job stress in individuals with obesity: the ELSA-Brasil baseline.

PURPOSE: Job stress has proven to be a relevant cause of stress for adults, but its effect on the development of metabolic alterations in individuals with obesity is still poorly explored. We aimed to investigate the association between job stress and metabolically unhealthy obesity (MUO) phenotype in participants with obesity at the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) baseline assessment. METHODS: This study analyzed data collected at the baseline examination between 2008 and 2010. A total of 2371 individuals with obesity were included. Two metabolic phenotypes were characterized based on the US National Health and Nutrition Examination Survey criteria. The job stress scale was based on the Brazilian version of the Swedish Demand-Control-Support Questionnaire. The association between job stress domains and MUO phenotype was assessed by binary logistic models. RESULTS: In our sample, 1297 (54.7%) participants were women, mean age was 49.6 ± 7.1 years and 1696 (71.5%) had MUO. Low skill discretion was associated with MUO after adjustment for age, sex and race. However, in fully-adjusted models, the MUO phenotype was not associated with high job demand (odds ratio [OR] = 1.05; 95% confidence interval [95%CI] 0.82-1.35), low skill discretion (OR = 1.26; 95%CI 0.95-1.68), low decision authority (OR = 0.94; 95%CI 0.70-1.25) nor low social support (OR = 0.93; 95%CI 0.71-1.20). CONCLUSION: We found a significant association between low skill discretion and an adverse metabolic profile in models adjusted for age, sex and race. No associations were significant between job stress domains and the metabolic profile of individuals with obesity in full models.

Maternal Smoking: A Life Course Blood Pressure Determinant?

Introduction: Exposure to maternal smoking early in life may affect blood pressure (BP) control mechanisms. We examined the association between maternal smoking (before conception, during pregnancy, and 4 years after delivery) and BP in preschool children. Methods: We evaluated 4295 of Generation XXI children, recruited at birth in 2005-2006 and reevaluated at the age of 4. At birth, information was collected by face-to-face interview and additionally abstracted from clinical records. At 4-year follow-up, interviews were performed and children's BP measured. Linear regression models were fitted to estimate the association between maternal smoking and children's BP. Results: Children of smoking mothers presented significantly higher BP levels. After adjustment for maternal education, gestational hypertensive disorders, and child's body mass index, children exposed during pregnancy to maternal smoking presented a higher systolic BP (SBP) z-score (ß = 0.08, 95% confidence interval [CI] 0.04 to 0.14). In crude models, maternal smoking was associated with higher SBP z-score at every assessed period. However, after adjustment, an attenuation of the association estimates occurred (ß = 0.08, 95% CI 0.03 to 0.13 before conception; ß = 0.07, 95%CI 0.02 to 0.12; ß = 0.04, 95%CI -0.02 to 0.10; and ß = 0.06, 95%CI 0.00 to 0.13 for the first, second, and third pregnancy trimesters, respectively; and ß = 0.07, 95%CI 0.02 to 0.12 for current maternal smoking). No significant association was observed for diastolic BP z-score levels. Conclusion: Maternal smoking before, during, and after pregnancy was independently associated with systolic BP z-score in preschool children. This study provides additional evidence to the public health relevance of maternal smoking cessation programs if early cardiovascular health of children is envisaged. Implications: Using observational longitudinal data from the birth cohort Generation XXI, this study showed that exposure to maternal smoking-before pregnancy, during pregnancy, and 4 years after delivery-was associated with a systolic BP-raising effect in children at the age of 4. The findings of this study add an important insight into the need to support maternal smoke-free environments in order to provide long-term cardiovascular benefit, starting as early as possible in life.

trans-Chalcone, a flavonoid precursor, inhibits UV-induced skin inflammation and oxidative stress in mice by targeting NADPH oxidase and cytokine production.

trans-Chalcone is a plant flavonoid precursor, which lacks broad investigation on its biological activity in inflammatory processes. In the present study, anti-inflammatory and antioxidant mechanisms of systemic administration with trans-chalcone, a flavonoid precursor, on ultraviolet (UV) irradiation-induced skin inflammation and oxidative stress in hairless mice were investigated by the following parameters: skin edema, myeloperoxidase activity (neutrophil marker), matrix metalloproteinase-9 activity, reduced glutathione levels, catalase activity, lipid peroxidation products, superoxide anion production, gp91phox (NADPH oxidase subunit) mRNA expression by quantitative PCR and cytokine production by ELISA. Systemic treatment with trans-chalcone inhibited skin inflammation by reducing skin edema and neutrophil recruitment, and also inhibited matrix metalloproteinase-9 activity. trans-Chalcone also inhibited oxidative stress, gp91phox mRNA expression, and the production of a wide range of pro-inflammatory cytokines, while it did not affect anti-inflammatory cytokines induced by UV irradiation. However, trans-chalcone did not prevent oxidative stress in vitro, suggesting that its in vivo effect is more related to anti-inflammatory properties rather than a direct antioxidant effect. In conclusion, treatment with trans-chalcone inhibited UV-induced skin inflammation resulting in oxidative stress inhibition in vivo. Therefore, systemic supplementation with this compound may represent an important therapeutic approach in inflammatory skin diseases induced by UV irradiation.

Social inequalities in BMI trajectories: 8-year follow-up of the Pró-Saúde study in Rio de Janeiro, Brazil.

OBJECTIVE: In a cohort of government employees in Rio de Janeiro, Brazil, we investigated prospectively, sex-specific associations between education and BMI trajectories and their potential effect modification by race. DESIGN: Of the 4030 participants in Phase 1 (1999), 3253 (81 %) participated in Phase 2 (2003) and 3058 (76 %) participated in Phase 3 (2006). Education was categorized as elementary, high school or college graduate. Study participants self-identified as White, Black or Pardo. BMI was calculated from measured weight and height. BMI trajectories were modelled using a generalized additive regression model with mixed effects (GAMM). SETTING: The Pro-Saúde Study, a longitudinal investigation of social determinants of health. SUBJECTS: Women (n 1441) and men (n 1127) who participated in the three phases of data collection and had complete information for all study variables. RESULTS: Women and men with less than high school, or only a high school education, gained approximately 1 kg/m(2) more than college graduates (women: 1·06 kg/m(2) (P<0·001) and 1·06 kg/m(2) (P<0·001), respectively; men: 1·04 kg/m(2) (P=0·013) and 1·01 kg/m(2) (P=0·277), respectively). For women only, race was independently associated with weight gain. Women identifying as Pardo or Black gained 1·03 kg/m(2) (P=0·01) and 1·02 kg/m(2) (P=0·10), respectively, more than Whites. No effect modification by race was observed for either men or women. CONCLUSIONS: While both lower education and darker race were associated with greater weight gain, gender similarities and differences were observed in these associations. The relationship between weight gain and different indicators of social status are therefore complex and require careful consideration when addressing the obesity epidemic.

Recurrent cardiovascular and limb events in 294,428 patients with coronary or peripheral artery disease or ischemic stroke on antiplatelet monotherapy: The RESRISK cohort study.

BACKGROUND AND AIMS: Utilising real-world data, we quantified the burden of cardiovascular risk factors and long-term residual risk of atherothrombotic events among routine care cohorts with coronary (CAD) or peripheral (PAD) artery disease or ischemic stroke (IS) on guideline-recommended antiplatelet monotherapy (APMT). METHODS: Retrospective cohort study using data (2010-2020) from the United Kingdom Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics, including adults with CAD, PAD or IS who were first prescribed APMT (CAD/IS: aspirin; PAD: clopidogrel). Primary outcomes (recurrent events): major adverse cardiovascular events (MACE) for CAD/PAD/IS cohorts, major adverse limb events (MALE) for PAD. RESULTS: 266,478 CAD, 13,162 PAD, and 14,788 IS patients were included (mean age: 71 years; women 37.7%-47.5 %). Risk factor burden was high and attainment of recommended goals was low. There were 73,691, 3,121 and 7,137 MACE among CAD, PAD and IS patients, respectively (median follow-up: 89.9, 42.4 and 75.9 months, respectively), and 4,767 MALE among PAD patients. MACE incidence rate per 1000 person-years was higher in IS (268.7; 95%CI 265.3-272.0) than CAD (92.9; 95%CI 92.5-93.4) or PAD cohorts (97.2; 95%CI 94.6-99.8). MALE incidence rate was 195.9 (95%CI 192.2-199.6) per 1000 person-years. IS patients presented a lower rate of hospitalisations and longer time-to-first hospitalisation, but once hospitalised, they had a longer length-of-stay. PAD patients had the highest hospitalisation rate. CONCLUSIONS: Among a contemporary cohort with cardiovascular disease on APMT, long-term residual atherothrombotic risk remains high despite being on APMT. Greater attention to risk factor control and use of appropriate evidence-based therapy is required to reduce residual risk among this very high-risk population.

Leisure Time Physical Activity and Incidence of Arterial Hypertension in ELSA-Brasil Participants. / Atividade Física no Tempo Livre e Incidência de Hipertensão Arterial em Participantes do ELSA-Brasil.

BACKGROUND: Evidence indicates that physical activity (PA) has a protective effect against chronic diseases, including high arterial hypertension (AH). OBJECTIVE: This study investigated, longitudinally, the association between changes in leisure time physical activity (LTPA) and the incidence of hypertension in ELSA-Brasil participants. METHODS: Data from 8,968 participants were analyzed at two different times (2008-2010 and 2012-2014). The International Physical Activity Questionnaire (IPAQ), long version, was used to assess LTPA. The association between LTPA and AH was tested using Poisson regression with relative risk (RR) estimation, with a significance level of 5% and a 95% confidence interval. RESULTS: When the LTPA level variable was categorized as sufficient and insufficient, no statistically significant associations were found between LTPA and AH incidence as a function of changes in PA during follow-up. However, when the LTPA variable was categorized as inactive, little active, active, and very active, a statistically significant association was observed between LTPA and AH in participants classified as very physically active. The risk of AH was reduced by 35% among men RR 0.65 (95% CI 0.50-0.86) and by 66% among women RR 0.34 (95% CI 0.20-0.58) who maintained high levels of LTPA at both moments of follow-up. CONCLUSION: These results suggest that maintaining high levels of PA over time is associated with a lower risk of developing AH, highlighting the importance of PA in preventing this condition, for both men and women.

FUNDAMENTO: Evidências apontam que a atividade física (AF) apresenta efeito protetor para as doenças crônicas, incluindo a hipertensão arterial (HA). OBJETIVO: Este estudo investigou, de forma longitudinal, a associação entre as mudanças na atividade física no tempo livre (AFTL) e a incidência de HA em participantes do ELSA-Brasil. MÉTODOS: Foram analisados dados de 8.968 participantes em dois momentos distintos (2008-2010 e 2012-2014). Foi utilizado o Questionário Internacional de Atividade Física (IPAQ), versão longa, para avaliação da AFTL. A associação entre AFTL e HA foi testada por regressão de Poisson com estimativa do risco relativo (RR), com nível de significância de 5% e intervalo de confiança de 95%. RESULTADOS: Quando a variável nível de AFTL foi categorizada em suficiente e insuficiente, não foram encontradas associações estatisticamente significantes entre AFTL e a incidência HA em função das mudanças na AF durante o seguimento. No entanto, a variável AFTL quando categorizada em inativo, pouco ativo, ativo e muito ativo, observou-se associação estatisticamente significante entre AFTL e HA em participantes classificados como muito ativos fisicamente. O risco de HA foi reduzido em 35% entre homens RR 0,65 (IC 95% 0,50-0,86) e em 66% entre as mulheres RR 0,34 (IC 95% 0,20-0,58) que mantiveram altos níveis de AFTL em ambos os momentos do seguimento. CONCLUSÃO: Esses resultados sugerem que a manutenção de altos níveis de AF ao longo do tempo está associada a um menor risco de desenvolver HA, destacando a importância da AF na prevenção dessa condição, tanto para homens quanto para mulheres.

Quercetin reduces neutrophil recruitment induced by CXCL8, LTB4, and fMLP: inhibition of actin polymerization.

Recent in vitro data have suggested that the flavonoid quercetin (1) does not affect the functioning of neutrophils. Therefore, we evaluated in vivo and in vitro whether or not 1 affects neutrophil function, focusing on recruitment. The in vivo treatment with 1 inhibited in a dose-dependent manner the recruitment of neutrophils to the peritoneal cavity of mice induced by known chemotatic factors such as CXCL1, CXCL5, LTB(4), and fMLP. Furthermore, 1 also inhibited in a concentration-dependent manner the chemoattraction of human neutrophils induced by CXCL8, LTB(4), and fMLP in a Boyden chamber. In vitro treatment with 1 did not affect human neutrophil surface expression of CXCR1, CXCR2, BLT1, or FLPR1, but rather reduced actin polymerization. These results suggest that 1 inhibits actin polymerization, hence, explaining the inhibition of neutrophil recruitment in vivo and in vitro and highlighting its possible usefulness to diminish excessive neutrophil migration during inflammation.

Characterization and stability study of a water-in-oil microemulsion incorporating quercetin.

BACKGROUND: The effectiveness of a water/oil (w/o) microemulsion containing quercetin against ultraviolet B radiation (UVB) induced damage was recently demonstrated by our group. However, during the development of new pharmaceutical products, the evaluation of percutaneous absorption and in vivo effectiveness should be accompanied by evaluation of stability parameters as an integral part of the process. OBJECTIVE: The aim was to investigate the stability of the final microemulsion formulation considering the temperature ranges of storage and application. METHODS: The physical, chemical, and functional stability of this formulation under different conditions of storage during 12 months and the photostability of quercetin incorporated into this system over UVB exposure for 7 days were evaluated. RESULTS: Although the results indicated a notable physical stability of the w/o microemulsions during the experimental period under all employed conditions, in both, the chemical and functional studies, a significant loss of quercetin content and antioxidant activity was found after 6 months of storage at 30°C/70% relative humidity and after 2 months at 40°C/70% relative humidity. The photostability study results demonstrated that the incorporation of quercetin into the w/o microemulsion maintained the previously demonstrated photostability of this flavonoid under forced exposure to UVB irradiation. CONCLUSION: Thus, this work demonstrates that special storage conditions (at 4 ± 2°C) are necessary to maintain the functionality of the w/o microemulsion containing quercetin and mainly emphasizes the importance of studying physical, chemical, and functional parameters at the same time during stability evaluation of active principles.

Evaluation of protective effect of a water-in-oil microemulsion incorporating quercetin against UVB-induced damage in hairless mice skin.

PURPOSE: In the present study, histological aspects were considered in order to evaluate the in vivo photoprotective effect of a w/o microemulsion containing quercetin against UVB irradiation-induced dermal damages. The toxicity in cell culture and the potential skin irritation resulting from topical application of this formulation were also investigated. METHODS: Mouse dorsal surfaces were treated topically with 300 mg of the unloaded and quercetin-loaded (0.3%, w/w) microemulsions before and after exposure to UVB (2.87 J/cm2) irradiation. The untreated control groups irradiated and non-irradiated were also evaluated. UVB-induced histopathological changes as well as the photoprotective effect of this formulation were evaluated considering the parameters of infiltration of inflammatory cells, epidermis thickening (basale and spinosum layers) and collagen and elastic fiber contents. The cytotoxicity of the reported formulation was evaluated in L929 mice fibroblasts by MTT assay and the skin irritation was investigated after topical application of both unloaded and quercetin-loaded microemulsions once a day for 15 days. RESULTS: The results demonstrated that the w/o microemulsion containing quercetin reduced the incidence of histological skin alterations, mainly the connective-tissue damage, induced by exposure to UVB irradiation, this allows the suggestion that protective effects of this formulation against UV-induced responses are not secondary to the interference of UV transmission (i.e., blocking the UVB radiation from being absorbed by the skin), as is usually done with UVB absorbers and sunscreens, but is instead due to different biological effects of this flavonoid. Furthermore, by evaluating the cytotoxic effect on L929 cells and histological aspects such as infiltration of inflammatory cells and epidermis thickness of hairless mice, the present study also demonstrated no toxicity of the proposed system. CONCLUSIONS: Therefore, based on these mouse models, a detailed characterization of the w/o microemulsion incorporating quercetin effects as a photochemoprotective agent on human skin is thus indicated.

Bifunctional Therapeutic Application of Low-Frequency Ultrasound Associated with Zinc Phthalocyanine-Loaded Micelles.

PURPOSE: Sonodynamic therapy (SDT) is a new therapeutic modality for the noninvasive cancer treatment based on the association of ultrasound and sonosensitizer drugs. Topical SDT requires the development of delivery systems to properly transport the sonosensitizer, such as zinc phthalocyanine (ZnPc), to the skin. In addition, the delivery system itself can participate in sonodynamic events and influence the therapeutic response. This study aimed to develop ZnPc-loaded micelle to evaluate its potential as a topical delivery system and as a cavitational agent for low-frequency ultrasound (LFU) application with the dual purpose of promoting ZnPc skin penetration and generating reactive oxygen species (ROS) for SDT. METHODS: ZnPc-loaded micelles were developed by the thin-film hydration method and optimized using the Quality by Design approach. Micelles' influence on LFU-induced cavitation activity was measured by potassium iodide dosimeter and aluminum foil pits experiments. In vitro skin penetration of ZnPc was assessed after pretreatment of the skin with LFU and simultaneous LFU treatment using ZnPc-loaded micelles as coupling media followed by 6 h of passive permeation of ZnPc-loaded micelles. The singlet oxygen generation by LFU irradiation of the micelles was evaluated using two different hydrophilic probes. The lipid peroxidation of the skin was estimated using the malondialdehyde assay after skin treatment with simultaneous LFU using ZnPc-loaded micelles. The viability of the B16F10 melanoma cell line was evaluated using resazurin after treatment with different concentrations of ZnPc-loaded micelles irradiated or not with LFU. RESULTS: The micelles increased the solubility of ZnPc and augmented the LFU-induced cavitation activity in two times compared to water. After 6 h ZnPc-loaded micelles skin permeation, simultaneous LFU treatment increased the amount of ZnPc in the dermis by more than 40 times, when compared to non-LFU-mediated treatment, and by almost 5 times, when compared to LFU pretreatment protocol. The LFU irradiation of micelles induced the generation of singlet oxygen, and the lipoperoxidation of the skin treated with the simultaneous LFU was enhanced in three times in comparison to the non-LFU-treated skin. A significant reduction in cell viability following treatment with ZnPc-loaded micelles and LFU was observed compared to blank micelles and non-LFU-treated control groups. CONCLUSION: LFU-irradiated mice can be a potential approach to skin cancer treatment by combining the functions of increasing drug penetration and ROS generation required for SDT.

Religious Service Attendance, Educational Attainment, and Hypertension at Baseline of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

BACKGROUND: Some religious dimensions have been associated with different health-related outcomes over many years. Attending religious services is one of these dimensions that were associated with hypertension, with inconsistent results. And religious involvement seems to be closely influenced by sociodemographic factors, such as education. Therefore, this study aimed to investigate the association between religious service attendance and hypertension according to levels of education. METHODS: We analyzed baseline data of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Frequency of religious service attendance and presence of hypertension were assessed in all 15,105 participants at baseline. The analyses were stratified by two levels of education (less than high school and high school or more). Logistic regression models were used to obtain the association between religious service attendance and hypertension in both groups. RESULTS: For those with high school or more, attending religious services was positively associated with hypertension (adjusted odds ratio [OR] = 1.14, 95% confidence interval [CI] 1.02-1.28). In contrast, for those with less than high school, attending services was inversely associated with presence of hypertension (adjusted OR = 0.73, 95% CI 0.55-0.96). CONCLUSIONS: There seems to be a paradox in the association of religious service attendance and hypertension depending on the level of education.

Identifying patterns of diurnal blood pressure variation among ELSA-Brasil participants.

Ambulatory blood pressure monitoring (ABPM) is the gold standard method for the diagnosis of hypertension. ABPM provides a set of repeated measurements for blood pressure (BP), usually over 24 h. Traditional approaches characterize diurnal BP variation by single ABPM parameters such as average and standard deviation, regardless of the temporal nature of the data. In this way, information about the pattern of diurnal BP variation and relationship between parameters is lost. The objective of this study was to identify and characterize daily BP patterns considering the set of repeated measures from 24-h ABPM. A total of 859 adult participants of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) performed a 24-h ABPM record. Hypertension, sex, age, race/color, education, marital status, smoking, alcohol, physical activity, and BMI were the covariables analyzed. Techniques for longitudinal clustering, multinomial models, and models with mixed effects were used. Three daily BP patterns were identified. Daily BP patterns with high BP presented higher standard deviation and morning surge and lower nocturnal dipping. They showed greater systolic BP variability and faster rise than fall in diastolic BP during sleep. Hypertensive, "pardos," and men had greater odds to present these patterns. Daily BP patterns with high BP presented the worst profile concerning ABPM parameters associated with cardiovascular risk. The daily BP patterns identified contribute to the characterization of diurnal BP variation.

Association between diabetes and cognitive function at baseline in the Brazilian Longitudinal Study of Adult Health (ELSA- Brasil).

Diabetes has been associated with cognitive changes and an increased risk of vascular dementia and Alzheimer's disease, but it is unclear whether there are associations between diabetes and early alterations in cognitive performance. The present study consisted of a cross-section analysis of 14,444 participants aged 35-74 years and from a developing country at baseline in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil); these participants were recruited between 2008 and 2010. We investigated whether there was an association between diabetes and early changes in the cognitive performance of this Brazilian population. To assess cognitive domains, we used the word-list learning, word-list delayed recall and word recognition tests along. Phonemic verbal fluency tests included semantic phonemic test (animals) and a phonemic test (words beginning with the letter F). Executive functions associated with attention, concentration and psychomotor speed were evaluated using the Trail Making Test B. The exposure variable in the study was defined as diabetes. Multiple linear regression was used to estimate the association between diabetes and cognitive performance. The results were adjusted for age, sex, education, hypertension, coronary disease, depression, physical activity, smoking, alcohol consumption, and the cholesterol/HDL-C ratio. We found a significant association between diabetes and decreased memory, language and executive function (attention, concentration and psychomotor speed) performance in this population from a country with a distinct epidemiological profile, even after adjusting for the main intervening variables.

Four-year adiposity change and remission of hypertension: an observational evaluation from the Longitudinal Study of Adult Health (ELSA-Brasil).

The degree to which weight reduction leads to the remission of hypertension in population studies is not clear. We investigated whether the changes in adiposity measures predicted the remission of hypertension in a racially admixed population over a mean 4-year follow-up. All 4847 hypertensive individuals at baseline (2008-2010) from the multicenter Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) were included. Changes in weight, waist circumference (WC), or body mass index (BMI) (reduction or increase ≥5% from baseline values, vs stability) and remission of hypertension (SBP < 140 and DBP < 90 mmHg and no use of antihypertensive medication at follow-up visit, in 2012-2014) were investigated using mixed effects logistic regression models. Proportional attributable benefit was additionally calculated. Analyses were stratified by sex and antihypertensive medication use at baseline. Remission of hypertension was 11.3% (n = 546). Among men, after adjustments, the reduction of weight (OR = 1.52 95% CI 1.10-2.10), WC (OR = 1.56 95% CI 1.04-2.35) or BMI (OR = 1.60 95% CI 1.13-2.27) was associated with the remission of hypertension. Among those not taking antihypertensive medication at baseline, after adjustments, the reduction of weight (OR = 1.64 95% CI 1.18-2.27), WC (OR = 1.76 95% CI 1.18-2.61) or BMI (OR = 1.57 95% CI 1.10-2.25) was associated with the remission of hypertension. Proportional attributable benefit among those with adiposity reduction was about 30%, indicating its potential for prevention. In conclusion, our study reinforces the role of adiposity-reducing strategies (e.g., healthy diet and regular physical activity) for the treatment and prevention of hypertension, which might have potential applications for clinical practice.

Quercetin reduces inflammatory pain: inhibition of oxidative stress and cytokine production.

Quercetin (1) is known to have both antioxidant and antinociceptive effects. However, the mechanism involved in its antinociceptive effect is not fully elucidated. Cytokines and reactive oxygen species have been implicated in the cascade of events resulting in inflammatory pain. Therefore, we evaluated the antinociceptive mechanism of 1 focusing on the role of cytokines and oxidative stress. Intraperitoneal and oral treatments with 1 dose-dependently inhibited inflammatory nociception induced by acetic acid and phenyl-p-benzoquinone and also the second phase of formalin- and carrageenin-induced mechanical hypernociception. Compound 1 also inhibited the hypernociception induced by cytokines (e.g., TNFalpha and CXCL1), but not by inflammatory mediators that directly sensitize the nociceptor such as PGE2 and dopamine. On the other hand, 1 reduced carrageenin-induced IL-1beta production as well as carrageenin-induced decrease of reduced glutathione (GSH) levels. These results suggest that 1 exerts its analgesic effect by inhibiting pro-nociceptive cytokine production and the oxidative imbalance mediation of inflammatory pain.

Association of Pubertal Development With Adiposity and Cardiometabolic Health in Girls and Boys-Findings From the Generation XXI Birth Cohort.

PURPOSE: Early timing of pubertal development is associated with worse cardiometabolic health in adulthood. We aimed to evaluate this association in 10-year-old girls and boys and clarify if it is independent of previous body mass index (BMI). METHODS: Pubertal development was evaluated through the Tanner scale in 4,548 children from the birth cohort Generation XXI. Data on anthropometrics, body composition, blood pressure, lipid profile, fasting plasma glucose, insulin, homeostatic model assessment-insulin resistance (HOMA-IR), and high-sensitivity C-reactive protein were collected. Bonferroni correction was applied, using an alpha of .004 for statistical significance. Regression coefficients and 99.6% confidence intervals were computed using linear regression models. RESULTS: Girls with a Tanner stage ≥2 presented statistically significant higher values of BMI, waist circumference (WC), waist-to-height ratio, fat mass index, blood pressure, glucose, insulin, HOMA-IR, triglycerides, and high-sensitivity C-reactive protein and lower values of high-density lipoprotein cholesterol. Boys with a Tanner stage ≥2 presented statistically significant higher values of BMI, WC, systolic blood pressure, and HOMA-IR and lower values of high-density lipoprotein cholesterol. After adjustment, including previous BMI, a Tanner stage ≥2 remained associated with BMI z-score (girls ß = .41 [.32, .50]; boys ß = .10 [.01, .19]) and WC (girls ß = 2.64 cm [1.86, 3.43]; boys ß = .81 cm [.11, 1.51]), and only in girls with waist-to-height ratio (ß = .01 [.00, .01]), fat mass index (ß = .31 kg/m2 [.08; .54]), glucose (ß = 1.59 mg/dL [.85, 2.33]), insulin (ß = 1.73 µU/mL [.68, 2.78]), and HOMA-IR (ß = .40 [.16, .64]). CONCLUSIONS: Independently of previous BMI, preteens with early puberty already had more adiposity at age 10 years. In addition, girls had higher glucose, insulin, and HOMA-IR, which may predict a worse glucose metabolism. These preteens should be a target for public health interventions.

Atividade Física no Tempo Livre e Incidência de Hipertensão Arterial em Participantes do ELSA-Brasil / Leisure Time Physical Activity and Incidence of Arterial Hypertension in ELSA-Brasil Participants

Resumo Fundamento: Evidências apontam que a atividade física (AF) apresenta efeito protetor para as doenças crônicas, incluindo a hipertensão arterial (HA). Objetivo: Este estudo investigou, de forma longitudinal, a associação entre as mudanças na atividade física no tempo livre (AFTL) e a incidência de HA em participantes do ELSA-Brasil. Métodos: Foram analisados dados de 8.968 participantes em dois momentos distintos (2008-2010 e 2012-2014). Foi utilizado o Questionário Internacional de Atividade Física (IPAQ), versão longa, para avaliação da AFTL. A associação entre AFTL e HA foi testada por regressão de Poisson com estimativa do risco relativo (RR), com nível de significância de 5% e intervalo de confiança de 95%. Resultados: Quando a variável nível de AFTL foi categorizada em suficiente e insuficiente, não foram encontradas associações estatisticamente significantes entre AFTL e a incidência HA em função das mudanças na AF durante o seguimento. No entanto, a variável AFTL quando categorizada em inativo, pouco ativo, ativo e muito ativo, observou-se associação estatisticamente significante entre AFTL e HA em participantes classificados como muito ativos fisicamente. O risco de HA foi reduzido em 35% entre homens RR 0,65 (IC 95% 0,50-0,86) e em 66% entre as mulheres RR 0,34 (IC 95% 0,20-0,58) que mantiveram altos níveis de AFTL em ambos os momentos do seguimento. Conclusão: Esses resultados sugerem que a manutenção de altos níveis de AF ao longo do tempo está associada a um menor risco de desenvolver HA, destacando a importância da AF na prevenção dessa condição, tanto para homens quanto para mulheres.

Abstract Background: Evidence indicates that physical activity (PA) has a protective effect against chronic diseases, including high arterial hypertension (AH). Objective: This study investigated, longitudinally, the association between changes in leisure time physical activity (LTPA) and the incidence of hypertension in ELSA-Brasil participants. Methods: Data from 8,968 participants were analyzed at two different times (2008-2010 and 2012-2014). The International Physical Activity Questionnaire (IPAQ), long version, was used to assess LTPA. The association between LTPA and AH was tested using Poisson regression with relative risk (RR) estimation, with a significance level of 5% and a 95% confidence interval. Results: When the LTPA level variable was categorized as sufficient and insufficient, no statistically significant associations were found between LTPA and AH incidence as a function of changes in PA during follow-up. However, when the LTPA variable was categorized as inactive, little active, active, and very active, a statistically significant association was observed between LTPA and AH in participants classified as very physically active. The risk of AH was reduced by 35% among men RR 0.65 (95% CI 0.50-0.86) and by 66% among women RR 0.34 (95% CI 0.20-0.58) who maintained high levels of LTPA at both moments of follow-up. Conclusion: These results suggest that maintaining high levels of PA over time is associated with a lower risk of developing AH, highlighting the importance of PA in preventing this condition, for both men and women.

Context-dependence of race self-classification: Results from a highly mixed and unequal middle-income country.

Ethnic-racial classification criteria are widely recognized to vary according to historical, cultural and political contexts. In Brazil, the strong influence of individual socio-economic factors on race/colour self-classification is well known. With the expansion of genomic technologies, the use of genomic ancestry has been suggested as a substitute for classification procedures such as self-declaring race, as if they represented the same concept. We investigated the association between genomic ancestry, the racial composition of census tracts and individual socioeconomic factors and self-declared race/colour in a cohort of 15,105 Brazilians. Results show that the probability of self-declaring as black or brown increases according to the proportion of African ancestry and varies widely among cities. In Porto Alegre, where most of the population is white, with every 10% increase in the proportion of African ancestry, the odds of self-declaring as black increased 14 times (95%CI 6.08-32.81). In Salvador, where most of the population is black or brown, that increase was of 3.98 times (95%CI 2.96-5.35). The racial composition of the area of residence was also associated with the probability of self-declaring as black or brown. Every 10% increase in the proportion of black and brown inhabitants in the residential census tract increased the odds of self-declaring as black by 1.33 times (95%CI 1.24-1.42). Ancestry alone does not explain self-declared race/colour. An emphasis on multiple situational contexts (both individual and collective) provides a more comprehensive framework for the study of the predictors of self-declared race/colour, a highly relevant construct in many different scenarios, such as public policy, sociology and medicine.

Quercetin in w/o microemulsion: in vitro and in vivo skin penetration and efficacy against UVB-induced skin damages evaluated in vivo.

The present study evaluated the potential of a w/o microemulsion as a topical carrier system for delivery of the antioxidant quercetin. Topical and transdermal delivery of quercetin were evaluated in vitro using porcine ear skin mounted on a Franz diffusion cell and in vivo on hairless-skin mice. Skin irritation by topical application of the microemulsion containing quercetin, and the protective effect of the formulation on UVB-induced decrease of endogenous reduced glutathione levels and increase of cutaneous proteinase secretion/activity were also investigated. The w/o microemulsion increased the penetration of quercetin into the stratum corneum and epidermis plus dermis at 3, 6, 9 and 12h post-application in vitro and in vivo at 6h post-application. No transdermal delivery of quercetin occurred. By evaluating established endpoints of skin irritation (erythema formation, epidermis thickening and infiltration of inflammatory cells), the study demonstrated that the daily application of the w/o microemulsion for up to 2 days did not cause skin irritation. W/o microemulsion containing quercetin significantly prevented the UVB irradiation-induced GSH depletion and secretion/activity of metalloproteinases.

Evaluation of in vivo efficacy of topical formulations containing soybean extract.

In the present study it was evaluated the: (i) functional stability of the soybean extract as a raw material and dispersed in two different topical formulations, (ii) skin retention using modified Franz diffusion cells, and (iii) in vivo activity of these formulations to inhibit 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced hydrogen peroxide (H(2)O(2)) and malondialdehyde (MDA) increases in the skin of hairless mice. The physico-chemical stability was evaluated by pH, globule size and centrifugation test. Furthermore, functional stability was also evaluated by antilipoperoxidative activity. The two topical formulations were stored at 4 degrees C, 30 degrees C/60% RH and 40 degrees C/70% RH for 6 months. The evaluation of the antiperoxidative stability of soybean extract itself and incorporated in formulations did not demonstrate loss of activity by storage at 4 degrees C/6 months. During 6 months of the study in different storage conditions the formulations 1 and 2 added or not with soybean extract were stable to physico-chemical tests. The effect of antioxidant compounds detected by the inhibition of MDA formation was time-dependent for formulation 2 as detected in the skin retention study. Pretreatment with formulation 1 or 2 significantly diminished TPA-induced H(2)O(2) and MDA generation. In conclusion, the present results suggest for the first time that formulations containing soybean extract may be a topical source of antioxidant compounds that decrease oxidative damages of the skin.