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Abstract Background Trans fatty acids (TFAs) have been hypothesised to influence breast cancer risk. However, relatively few prospective studies have examined this relationship, and well-powered analyses according to hormone receptor-defined molecular subtypes, menopausal status, and body size have rarely been conducted. Methods In the European Prospective Investigation into Cancer and Nutrition (EPIC), we investigated the associations between dietary intakes of TFAs (industrial trans fatty acids [ITFAs] and ruminant trans fatty acids [RTFAs]) and breast cancer risk among 318,607 women. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models, adjusted for other breast cancer risk factors. Results After a median follow-up of 8.1 years, 13,241 breast cancer cases occurred. In the multivariable-adjusted model, higher total ITFA intake was associated with elevated breast cancer risk (HR for highest vs lowest quintile, 1.14, 95% CI 1.06–1.23; P trend = 0.001). A similar positive association was found between intake of elaidic acid, the predominant ITFA, and breast cancer risk (HR for highest vs lowest quintile, 1.14, 95% CI 1.06–1.23; P trend = 0.001). Intake of total RTFAs was also associated with higher breast cancer risk (HR for highest vs lowest quintile, 1.09, 95% CI 1.01–1.17; P trend = 0.015). For individual RTFAs, we found positive associations with breast cancer risk for dietary intakes of two strongly correlated fatty acids (Spearman correlation r = 0.77), conjugated linoleic acid (HR for highest vs lowest quintile, 1.11, 95% CI 1.03–1.20; P trend = 0.001) and palmitelaidic acid (HR for highest vs lowest quintile, 1.08, 95% CI 1.01–1.16; P trend = 0.028). Similar associations were found for total ITFAs and RTFAs with breast cancer risk according to menopausal status, body mass index, and breast cancer subtypes. Conclusions These results support the hypothesis that higher dietary intakes of ITFAs, in particular elaidic acid, are associated with elevated breast cancer risk. Due to the high correlation between conjugated linoleic acid and palmitelaidic acid, we were unable to disentangle the positive associations found for these fatty acids with breast cancer risk. Further mechanistic studies are needed to identify biological pathways that may underlie these associations.

Abstract Background Nutrition and lifestyle have been long established as risk factors for colorectal cancer (CRC). Modifiable lifestyle behaviours bear potential to minimize long-term CRC risk; however, translation of lifestyle information into individualized CRC risk assessment has not been implemented. Lifestyle-based risk models may aid the identification of high-risk individuals, guide referral to screening and motivate behaviour change. We therefore developed and validated a lifestyle-based CRC risk prediction algorithm in an asymptomatic European population. Methods The model was based on data from 255,482 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) study aged 19 to 70 years who were free of cancer at study baseline (1992–2000) and were followed up to 31 September 2010. The model was validated in a sample comprising 74,403 participants selected among five EPIC centres. Over a median follow-up time of 15 years, there were 3645 and 981 colorectal cancer cases in the derivation and validation samples, respectively. Variable selection algorithms in Cox proportional hazard regression and random survival forest (RSF) were used to identify the best predictors among plausible predictor variables. Measures of discrimination and calibration were calculated in derivation and validation samples. To facilitate model communication, a nomogram and a web-based application were developed. Results The final selection model included age, waist circumference, height, smoking, alcohol consumption, physical activity, vegetables, dairy products, processed meat, and sugar and confectionary. The risk score demonstrated good discrimination overall and in sex-specific models. Harrell’s C-index was 0.710 in the derivation cohort and 0.714 in the validation cohort. The model was well calibrated and showed strong agreement between predicted and observed risk. Random survival forest analysis suggested high model robustness. Beyond age, lifestyle data led to improved model performance overall (continuous net reclassification improvement = 0.307 (95% CI 0.264–0.352)), and especially for young individuals below 45 years (continuous net reclassification improvement = 0.364 (95% CI 0.084–0.575)). Conclusions LiFeCRC score based on age and lifestyle data accurately identifies individuals at risk for incident colorectal cancer in European populations and could contribute to improved prevention through motivating lifestyle change at an individual level.

Dada a importância do Instituto Oswaldo Cruz para as pesquisas biomédicas, em nível nacional e internacional, que visam ao desenvolvimento tecnológico, à inovação e ao fornecimento de serviços de referência para o diagnóstico de doenças infecciosas e genéticas e para o controle vetorial, um mapeamento da produtividade dos seus laboratórios pode contribuir para o planejamento dos recursos, considerando-se as necessidades e as prioridades das demandas de saúde regionais. O problema de pesquisa considerou o relato dos gestores a respeito da divisão dos laboratórios não se mostrar eficiente para atender às necessidades de investimento em pesquisas de saúde, devido à grande pulverização de recursos. O objetivo foi avaliar e apresentar as potencialidades de colaboração, de interação e de integração entre os laboratórios de pesquisa, considerando as publicações científicas dos seus pesquisadores, as áreas de pesquisa e as palavras-chave relacionadas aos laboratórios, também as áreas de conhecimento e os medical subject headings encontrados nas bases ISI Web of Science e PubMed, respectivamente. A metodologia utilizada compreendeu a análise de redes quanto à colaboração e à classificação científica das publicações; e a análise de textos instrumentalizada pelo software IRAMuTeQ. Como conclusão, foram apresentadas possibilidades de agrupamentos com diferentes abordagens. No entanto, esclarece-se que foram utilizadas apenas informações acerca de publicações científicas. Isso pode implicar um viés nos resultados encontrados, havendo, portanto, necessidade de um parecer de especialistas acerca desses resultados. A sugestão é que a pesquisa seja aprofundada, considerando os programas de pós-graduação do Instituto Oswaldo Cruz e de seus professores, além de trabalhos de dissertação e de tese defendidos nos últimos anos (como o E-lattes) e que os seus resultados sejam apresentados em outras publicações.

Background: Dioxins and polychlorobiphenyls (PCBs) are persistent organic pollutants that have demonstrated endocrine disrupting properties. Several of these chemicals are carcinogenic and positive associations have been suggested with breast cancer risk. In general population, diet represents the main source of exposure. Methods: Associations between dietary intake of 17 dioxins and 35 PCBs and breast cancer were evaluated in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort from nine European countries using multivariable Cox regressions. The present study included 318,607 women (mean ± SD age: 50.7 ± 9.7) with 13,241 incident invasive breast cancers and a median follow-up of 14.9 years (IQR = 13.5–16.4). Dietary intake of dioxins and PCBs was assessed combining EPIC food consumption data with food contamination data provided by the European Food Safety Authority. Results: Exposure to dioxins, dioxins + Dioxin-Like-PCBs, Dioxin-Like-PCBs (DL-PCBs), and Non-Dioxin-Like-PCBs (NDL-PCBs) estimated from reported dietary intakes were not associated with breast cancer incidence, with the following hazard ratios (HRs) and 95% confidence intervals for an increment of 1 SD: HRdioxins = 1.00 (0.98 to 1.02), HRdioxins+DL-PCB = 1.01 (0.98 to 1.03), HRDL-PCB = 1.01 (0.98 to 1.03), and HRNDL-PCB = 1.01 (0.99 to 1.03). Results remained unchanged when analyzing intakes as quintile groups, as well as when analyses were run separately per country, or separating breast cancer cases based on estrogen receptor status or after further adjustments on main contributing food groups to PCBs and dioxins intake and nutritional factors. Conclusions: This large European prospective study does not support the hypothesis of an association between dietary intake of dioxins and PCBs and breast cancer risk.

Autophagy has been linked with melanoma risk and survival, but no polymorphisms in autophagy-related (ATG) genes have been investigated in relation to melanoma progression. We examined five single-nucleotide polymorphisms (SNPs) in three ATG genes (ATG5; ATG10; and ATG16L) with known or suspected impact on autophagic flux in an international population-based case-control study of melanoma. DNA from 911 melanoma patients was genotyped. An association was identified between (GG) (rs2241880) and earlier stage at diagnosis (OR 0.47; 95% Confidence Intervals (CI) = 0.27-0.81, P = 0.02) and a decrease in Breslow thickness (P = 0.03). The ATG16L heterozygous genotype (AG) (rs2241880) was associated with younger age at diagnosis (P = 0.02). Two SNPs in ATG5 were found to be associated with increased stage (rs2245214 CG, OR 1.47; 95% CI = 1.11-1.94, P = 0.03; rs510432 CC, OR 1.84; 95% CI = 1.12-3.02, P = 0.05). Finally, we identified inverse associations between ATG5 (GG rs2245214) and melanomas on the scalp or neck (OR 0.20, 95% CI = 0.05-0.86, P = 0.03); ATG10 (CC) (rs1864182) and brisk tumor infiltrating lymphocytes (TILs) (OR 0.42; 95% CI = 0.21-0.88, P = 0.02), and ATG5 (CC) (rs510432) with nonbrisk TILs (OR 0.55; 95% CI = 0.34-0.87, P = 0.01). Our data suggest that ATG SNPs might be differentially associated with specific host and tumor characteristics including age at diagnosis, TILs, and stage. These associations may be critical to understanding the role of autophagy in cancer, and further investigation will help characterize the contribution of these variants to melanoma progression.

Regulatory authorities have indicated that new drugs to treat type 2 diabetes (T2D) should not be associated with an unacceptable increase in cardiovascular risk. Human genetics may be able to guide development of antidiabetic therapies by predicting cardiovascular and other health endpoints. We therefore investigated the association of variants in six genes that encode drug targets for obesity or T2D with a range of metabolic traits in up to 11,806 individuals by targeted exome sequencing and follow-up in 39,979 individuals by targeted genotyping, with additional in silico follow-up in consortia. We used these data to first compare associations of variants in genes encoding drug targets with the effects of pharmacological manipulation of those targets in clinical trials. We then tested the association of those variants with disease outcomes, including coronary heart disease, to predict cardiovascular safety of these agents. A low-frequency missense variant (Ala316Thr; rs10305492) in the gene encoding glucagon-like peptide-1 receptor (GLP1R), the target of GLP1R agonists, was associated with lower fasting glucose and T2D risk, consistent with GLP1R agonist therapies. The minor allele was also associated with protection against heart disease, thus providing evidence that GLP1R agonists are not likely to be associated with an unacceptable increase in cardiovascular risk. Our results provide an encouraging signal that these agents may be associated with benefit, a question currently being addressed in randomized controlled trials. Genetic variants associated with metabolic traits and multiple disease outcomes can be used to validate therapeutic targets at an early stage in the drug development process.

Candidate gene and genome-wide association studies (GWAS) have identified 15 independent genomic regions associated with bladder cancer risk. In search for additional susceptibility variants, we followed up on four promising single-nucleotide polymorphisms (SNPs) that had not achieved genome-wide significance in 6911 cases and 11 814 controls (rs6104690, rs4510656, rs5003154 and rs4907479, P < 1 × 10(-6)), using additional data from existing GWAS datasets and targeted genotyping for studies that did not have GWAS data. In a combined analysis, which included data on up to 15 058 cases and 286 270 controls, two SNPs achieved genome-wide statistical significance: rs6104690 in a gene desert at 20p12.2 (P = 2.19 × 10(-11)) and rs4907479 within the MCF2L gene at 13q34 (P = 3.3 × 10(-10)). Imputation and fine-mapping analyses were performed in these two regions for a subset of 5551 bladder cancer cases and 10 242 controls. Analyses at the 13q34 region suggest a single signal marked by rs4907479. In contrast, we detected two signals in the 20p12.2 region-the first signal is marked by rs6104690, and the second signal is marked by two moderately correlated SNPs (r(2) = 0.53), rs6108803 and the previously reported rs62185668. The second 20p12.2 signal is more strongly associated with the risk of muscle-invasive (T2-T4 stage) compared with non-muscle-invasive (Ta, T1 stage) bladder cancer (case-case P ≤ 0.02 for both rs62185668 and rs6108803). Functional analyses are needed to explore the biological mechanisms underlying these novel genetic associations with risk for bladder cancer.

Abstract Background Bilirubin, a byproduct of hemoglobin breakdown and purported anti-oxidant, is thought to be cancer preventive. We conducted complementary serological and Mendelian randomization (MR) analyses to investigate whether alterations in circulating levels of bilirubin are associated with risk of colorectal cancer (CRC). We decided a priori to perform analyses separately in men and women based on suggestive evidence that associations may differ by sex. Methods In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC), pre-diagnostic unconjugated bilirubin (UCB, the main component of total bilirubin) concentrations were measured by high-performance liquid chromatography in plasma samples of 1386 CRC cases and their individually matched controls. Additionally, 115 single-nucleotide polymorphisms (SNPs) robustly associated (P

Approximately 95% of patients receiving radiotherapy (RT) will ultimately develop radiation-induced dermatitis (RID) during or after the course of treatment, with major consequences on quality of life and treatment outcomes. This paper reviews the pathophysiology of RID and currently used topical products for the prevention and treatment of RID. Although there is no consensus on the appropriate management, recent evidence suggests that the use of topical products supports to protect and promote tissue repair in patients with RID. Basic recommendations include advice to wear loose clothing, using electric razors if necessary, and avoiding cosmetic products, sun exposure or extreme temperatures. Based on mechanisms involved and on the clinical characteristics of oncological patients, the profile of the ideal topical product for addressing RID can be designed; it should have limited risk of adverse events, systemic adsorption and drug–drug interactions, should be characterized by multiple clinical activities, with a special focus on localized pain, and should have a careful formulation as some vehicles can block the RT beam.

Este estudo trata das ações do Centro de Educação a Distância (CEAD) da Universidade de Brasília (UnB) no cenário da internacionalização educacional. Considera a internacionalização como processo de integrar uma dimensão internacional e intercultural na educação superior, por meio de interação e práticas colaborativas. Com o objetivo de analisar as ações do CEAD voltadas para a internacionalização, com foco na extensão, a pesquisa exploratória, após análise documental, revelou que esse Centro contribui com ações inovadoras, por meio dos programas Universidade Aberta do Brasil e Aprendizagem para o 3º Milênio (A3M), com o destaque para o convênio com a Universidade Aberta de Portugal (UAb), e se materializa, primordialmente, em ações de divulgação.

Introdução: Mulheres com autoimagem genital negativa podem apresentar disfunções sexuais (DS). Ainda, as DS podem estar relacionadas a desconfortos no assoalho pélvico. Objetivo: Investigar a relação entre autoimagem genital, função sexual e desconforto no assoalho pélvico em mulheres jovens universitárias. Métodos: Estudo observacional e transversal com 102 acadêmicas de graduação e pós-graduação entre 18 a 29 anos, sexualmente ativas. Foram aplicadas uma ficha de identificação, os questionários Female Sexual Function Index (FSFI), Pelvic Floor Distress Inventory (PFDI-SF-20) e Female Genital Self-Image Scale (FGSIS). Resultados: O escore total do FGSIS indicou autoimagem genital positiva, FSFI boa função sexual e o PFDI-20 desconforto no assoalho pélvico baixo. Observou-se relação positiva entre autoimagem genital e função sexual e relação inversa com o desconforto no assoalho pélvico. Conclusão: As mulheres apresentaram autoimagem genital positiva, boa função sexual e baixo desconforto no assoalho pélvico, e as variáveis se relacionavam entre si.

Background There is controversy about associations between total dietary fatty acids, their classes (saturated fatty acids [SFAs], monounsaturated fatty acids, and polyunsaturated fatty acids), and risk of coronary heart disease (CHD). Specifically, the relevance of food sources of SFAs to CHD associations is uncertain. Methods and Results We conducted a case‐cohort study involving 10 529 incident CHD cases and a random subcohort of 16 730 adults selected from a cohort of 385 747 participants in 9 countries of the EPIC (European Prospective Investigation into Cancer and Nutrition) study. We estimated multivariable adjusted country‐specific hazard ratios (HRs) and 95% CIs per 5% of energy intake from dietary fatty acids, with and without isocaloric macronutrient substitutions, using Prentice‐weighted Cox regression models and pooled results using random‐effects meta‐analysis. We found no evidence for associations of the consumption of total or fatty acid classes with CHD, regardless of macronutrient substitutions. In analyses considering food sources, CHD incidence was lower per 1% higher energy intake of SFAs from yogurt (HR, 0.93 [95% CI, 0.88–0.99]), cheese (HR, 0.98 [95% CI, 0.96–1.00]), and fish (HR, 0.87 [95% CI, 0.75–1.00]), but higher for SFAs from red meat (HR, 1.07 [95% CI, 1.02–1.12]) and butter (HR, 1.02 [95% CI, 1.00–1.04]). Conclusions This observational study found no strong associations of total fatty acids, SFAs, monounsaturated fatty acids, and polyunsaturated fatty acids, with incident CHD. By contrast, we found associations of SFAs with CHD in opposite directions dependent on the food source. These findings should be further confirmed, but support public health recommendations to consider food sources alongside the macronutrients they contain, and suggest the importance of the overall food matrix.

BackgroundFood biodiversity, encompassing the variety of plants, animals, and other organisms consumed as food and drink, has intrinsic potential to underpin diverse, nutritious diets and improve Earth system resilience. Dietary species richness (DSR), which is recommended as a crosscutting measure of food biodiversity, has been positively associated with the micronutrient adequacy of diets in women and young children in low- and middle-income countries (LMICs). However, the relationships between DSR and major health outcomes have yet to be assessed in any population.Methods and findingsWe examined the associations between DSR and subsequent total and cause-specific mortality among 451,390 adults enrolled in the European Prospective Investigation into Cancer and Nutrition (EPIC) study (1992 to 2014, median follow-up: 17 years), free of cancer, diabetes, heart attack, or stroke at baseline. Usual dietary intakes were assessed at recruitment with country-specific dietary questionnaires (DQs). DSR of an individual's yearly diet was calculated based on the absolute number of unique biological species in each (composite) food and drink. Associations were assessed by fitting multivariable-adjusted Cox proportional hazards regression models. In the EPIC cohort, 2 crops (common wheat and potato) and 2 animal species (cow and pig) accounted for approximately 45% of self-reported total dietary energy intake [median (P10-P90): 68 (40 to 83) species consumed per year]. Overall, higher DSR was inversely associated with all-cause mortality rate. Hazard ratios (HRs) and 95% confidence intervals (CIs) comparing total mortality in the second, third, fourth, and fifth (highest) quintiles (Qs) of DSR to the first (lowest) Q indicate significant inverse associations, after stratification by sex, age, and study center and adjustment for smoking status, educational level, marital status, physical activity, alcohol intake, and total energy intake, Mediterranean diet score, red and processed meat intake, and fiber intake [HR (95% CI): 0.91 (0.88 to 0.94), 0.80 (0.76 to 0.83), 0.69 (0.66 to 0.72), and 0.63 (0.59 to 0.66), respectively; PWald < 0.001 for trend]. Absolute death rates among participants in the highest and lowest fifth of DSR were 65.4 and 69.3 cases/10,000 person-years, respectively. Significant inverse associations were also observed between DSR and deaths due to cancer, heart disease, digestive disease, and respiratory disease. An important study limitation is that our findings were based on an observational cohort using self-reported dietary data obtained through single baseline food frequency questionnaires (FFQs); thus, exposure misclassification and residual confounding cannot be ruled out.ConclusionsIn this large Pan-European cohort, higher DSR was inversely associated with total and cause-specific mortality, independent of sociodemographic, lifestyle, and other known dietary risk factors. Our findings support the potential of food (species) biodiversity as a guiding principle of sustainable dietary recommendations and food-based dietary guidelines.

Este trabalho tem por escopo uma análise do Mestrado Nacional Profissional em Ensino de Física (MNPEF), Programa de Pós-Graduação (PPG) stricto sensu desenvolvido por rede de 58 instituições públicas de ensino superior, coordenado pela Sociedade Brasileira de Física (SBF) e avaliado e fomentado pela Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Capes). A analítica proposta se detém aos temas, às bases teóricas e aos métodos utilizados por estudantes nas suas pesquisas, de 2013 a 2021, com vistas a apresentar aportes ao planejamento pedagógico, à avaliação e ao desenvolvimento do PPG, com ênfase no contexto de ensino de física na Educação Básica. Utilizou-se pesquisa bibliográfica e análise de conteúdo sobre o corpus textual formado por títulos, resumos e palavras-chave das produções de uma das unidades do MNPEF, a Universidade de Brasília (UnB), em caráter ilustrativo. Os resultados indicaram que as ideias encontradas são compatíveis com o escopo do PPG, já que demonstraram uma tendência de propostas de sequências didáticas que desenvolvam o conhecimento científico do estudante de física, principalmente do Ensino Médio, baseado em Ausubel e Vygotsky. Os temas recorrentes foram: energia, robótica, elétrico, geométrico, óptico, cosmologia, eletromagnetismo, Lei de Newton, inércia, fenômeno, partícula, grandeza, astronomia, plasma, termodinâmica, eletrodinâmica, mecânica e cinemática. O estudo é considerado original por propor a análise de conteúdo como instrumento de avaliação da produção científica de um PPG profissional na área de ensino de física; além disso, é tido como replicável a contextos similares, dado o caráter homogêneo da organização universitária brasileira.

Polyphenols are bioactive compounds from plants with antioxidant properties that may have a protective role against body weight gain, with adipose tissue and systemic oxidative stress as potential targets. We aimed to investigate the dietary intake of individual polyphenols and their association with 5-year body weight change in a sub-cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC). This study included 349,165 adult participants from nine European countries. Polyphenol intake was estimated through country-specific validated dietary questionnaires and the Phenol-Explorer database. Body weight was obtained at recruitment and after a mean follow-up time of 5 years. Associations were estimated using multilevel mixed linear regression models. From 91 polyphenols included, the majority (n = 67) were inversely associated with 5-year body weight change after FDR-correction (q < 0.05). The greatest inverse associations were observed for quercetin 3-O-rhamnoside (change in weight for doubling in intake: −0.071 (95% CI: −0.085; −0.056) kg/5 years). Only 13 polyphenols showed positive associations with body weight gain, mainly from the subclass hydroxycinnamic acids (HCAs) with coffee as the main dietary source, such as 4-caffeoylquinic acid (0.029 (95% CI: 0.021; 0.038) kg/5 years). Individual polyphenols with fruit, tea, cocoa and whole grain cereals as the main dietary sources may contribute to body weight maintenance in adults. Individual HCAs may have different roles in body weight change depending on their dietary source.

Knee osteoarthritis is a common cause of pain and disability in old subjects. Pain may predispose to the development of frailty. Studies on mechanisms underlying pain in osteoarthritis models during aging are lacking. In this work, we used the monosodium iodoacetate model of osteoarthritis in adult (11-week-old) and old (20-month-old) C57BL/6J mice to compare hypersensitivity, locomotion, neuroinflammation, and the effects of morphine treatment. After osteoarthritis induction in adult and old mice, weight-bearing asymmetry, mechanical allodynia, and thermal hyperalgesia similarly developed, while locomotion and frailty were more affected in old than in adult animals. When behavioral deficits were present, the animals were treated for 7 days with morphine. This opioid counteracts the behavioral alterations and the frailty index worsening both in adult and old mice. To address the mechanisms that underlie pain, we evaluated neuroinflammatory markers and proinflammatory cytokine expression in the sciatic nerve, DRGs, and spinal cord. Overexpression of cytokines and glia markers were present in osteoarthritis adult and old mice, but the activation was qualitatively and quantitatively more evident in aged mice. Morphine was able to counteract neuroinflammation in both age groups. We demonstrate that old mice are more vulnerable to pain’s detrimental effects, but prompt treatment is successful at mitigating these effects.