Loading...
224 results
Search Results
Now showing 1 - 10 of 224
- General and abdominal adiposity and hypertension in eight world regions: a pooled analysis of 837 population-based studies with 7·5 million participantsPublication . NCD Risk Factor Collaboration (NCD-RisC); Brito, MiguelBackground: Adiposity can be measured using BMI (which is based on weight and height) and indices of abdominal adiposity. We examined the association between BMI and waist-to-height ratio (WHtR) within and across populations of different world regions. We quantified how well these two metrics discriminate between people with and without hypertension. Methods: We used data from studies carried out from 1990 to 2023 on BMI, WHtR, and hypertension in people aged 20-64 years in representative samples of the general population in eight world regions. We graphically compared the regional distributions of BMI and WHtR and calculated Pearson's correlation coefficients between BMI and WHtR within each region. We used mixed-effects linear regression to estimate the extent to which WHtR varies across regions at the same BMI. We graphically examined the prevalence of hypertension and the distribution of people who have hypertension both about BMI and WHtR, and we assessed how closely BMI and WHtR discriminate between participants with and without hypertension using C-statistic and net reclassification improvement (NRI). Findings: The correlation between BMI and WHtR ranged from 0·76 to 0·89 within different regions. After adjusting for age and BMI, mean WHtR was highest in South Asia for both sexes, followed by Latin America and the Caribbean and the region of central Asia, the Middle East, and North Africa. Mean WHtR was lowest in central and eastern Europe for both sexes, in the high-income western region for women, and Oceania for men. Conversely, to achieve an equivalent WHtR, the BMI of the population of South Asia would need to be, on average, 2·79 kg/m2 (95% CI 2·31-3·28) lower for women and 1·28 kg/m2 (1·02-1·54) lower for men than in the high-income western region. In every region, hypertension prevalence increased with both BMI and WHtR. Models with either of these two adiposity metrics had virtually identical C-statistics and NRIs for every region and sex, with C-statistics ranging from 0·72 to 0·81 and NRIs ranging from 0·34 to 0·57 in different region and sex combinations. When both BMI and WHtR were used, performance improved only slightly compared with using either adiposity measure alone. Interpretation: BMI can distinguish young and middle-aged adults with higher versus lower amounts of abdominal adiposity with moderate-to-high accuracy, and both BMI and WHtR distinguish people with or without hypertension. However, at the same BMI level, people in South Asia, Latin America, the Caribbean, and the region of central Asia, the Middle East, and North Africa have higher WHtR than in the other regions.
- Micronutrients intake associated with DNA damage assessed by in a human biomonitoring studyPublication . Ladeira, Carina; Viegas, Susana; Carolino, Elisabete; Gomes, Manuel C.; Brito, MiguelNutrition science has evolved into a multidisciplinary field that applies molecular biology and integrates individual health with the epidemiologic investigation of population health. Nutritional genomics studies the functional interaction of food and its components, macro and micronutrients, with the genome at the molecular, cellular, and systemic level. Diet can influence cancer development in several ways, namely direct action of carcinogens in food that can damage DNA, diet components (macro or micronutrients) that can block or induce enzymes involved in activation or deactivation of carcinogenic substances. Moreover, inadequate intake of some molecules involved in DNA synthesis, repair or methylation can influence mutation rate or changes in gene expression. Several studies support the idea that diet can influence the risk of cancer; however information concerning the precise dietary factor that determines human cancer is an ongoing debate. A lot of epidemiological studies, involving food frequency questionnaires, have been developed providing important information concerning diet and cancer, however, diet is a complex composite of various nutrients (macro and micronutrients) and non-nutritive food constituents that makes the search for specific factors almost limitless.
- Drug resistance and epigenetic modulatory potential of epigallocatechin-3-gallate against Staphylococcus aureusPublication . Zeferino, Ana Sofia; Mira, Ana Rita; Delgadinho, Mariana; Brito, Miguel; Ponte, Tomás; Ribeiro, EdnaAntimicrobial resistance of human pathogens, such as methicillin-resistant Staphylococcus aureus, is described by the World Health Organization as a health global challenge and efforts must be made for the discovery of new effective and safe compounds. This work aims to evaluate epigallocatechin-3-gallate (EGCG) epigenetic and modulatory drug potential against S. aureus in vitro and in vivo. S. aureus strains were isolated from the commensal flora of healthy volunteers. Antibiotic susceptibility and synergistic assay were assessed through disk diffusion accordingly to EUCAST guidelines with and without co-exposure to EGCG at final concentrations of 250 µg/ml, 100 µg/ml, 50 µg/ml, and 25 µg/ml. Transcriptional expression of orfx, spdC, and WalKR was performed through qRT-PCR. A 90-day interventional study was performed with daily consumption of 225 mg of EGCG. Obtained data revealed a high prevalence of S. aureus colonization in healthcare workers and clearly demonstrated the antimicrobial and synergistic potential of EGCG as well as divergent resistant phenotypes associated with altered transcriptional expression of epigenetic and drug response modulators genes. Here, we demonstrate the potential of EGCG for antimicrobial treatment and/or therapeutic adjuvant against antibiotic-resistant microorganisms and report divergent patterns of epigenetic modulators expression associated with phenotypic resistance profiles.
- Identification of a 0.4 Kb deletion region in 10q26 associated with endometrial carcinomaPublication . Alves, Margarida; Carreira, Isabel; Liberato, Paulo; Ramos, Sância; Mafra, Manuela; Inverno, Alexandra S.; Maia, Ana T.; Martins, Ana Paula; Brito, Miguel; Monteiro, CarolinoWe have identified an allelic deletion common region in the q26 region of chromosome 10 in endometrial carcinomas, which has been reported previously as a potential target of genetic alterations related to this neoplasia. An allelotyping analysis of 19 pairs of tumoral and non-tumoral samples was accomplished using seven microsatellite polymorphic markers mapping in the 10q26 chromosomal region. Loss of heterozygosity for one or more loci was detected in 29% of the endometrial carcinoma samples. The observed pattern of loss enabled the identification of a 3.5 Mb common deleted region located between the D10S587 and D10S186 markers. An additional result from an endometrial sample with evidence of a RER phenotype may suggest a more centromeric region of loss within the above-mentioned interval. This 401.84 Kb interval flanked by the D10S587 and D10S216 markers may be a plausible location for a putative suppressor gene involved in early stage endometrial carcinogenesis.
- Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participantsPublication . NCD Risk Factor Collaboration (NCD-RisC); Brito, MiguelBackground: Hypertension can be detected at the primary healthcare level and low-cost treatments can effectively control hypertension. We aimed to measure the prevalence of hypertension and progress in its detection, treatment, and control from 1990 to 2019 for 200 countries and territories. Methods: We used data from 1990 to 2019 on people aged 30-79 years from population-representative studies with measurement of blood pressure and data on blood pressure treatment. We defined hypertension as having systolic blood pressure 140 mm Hg or greater, diastolic blood pressure 90 mm Hg or greater, or taking medication for hypertension. We applied a Bayesian hierarchical model to estimate the prevalence of hypertension and the proportion of people with hypertension who had a previous diagnosis (detection), who were taking medication for hypertension (treatment), and whose hypertension was controlled to below 140/90 mm Hg (control). The model allowed for trends over time to be non-linear and to vary by age. Findings: The number of people aged 30-79 years with hypertension doubled from 1990 to 2019, from 331 (95% credible interval 306-359) million women and 317 (292-344) million men in 1990 to 626 (584-668) million women and 652 (604-698) million men in 2019, despite stable global age-standardized prevalence. In 2019, age-standardized hypertension prevalence was lowest in Canada and Peru for both men and women; in Taiwan, South Korea, Japan, and some countries in western Europe including Switzerland, Spain, and the UK for women; and in several low-income and middle-income countries such as Eritrea, Bangladesh, Ethiopia, and the Solomon Islands for men. Hypertension prevalence surpassed 50% for women in two countries and men in nine countries, in central and eastern Europe, central Asia, Oceania, and Latin America. Globally, 59% (55-62) of women and 49% (46-52) of men with hypertension reported a previous diagnosis of hypertension in 2019, and 47% (43-51) of women and 38% (35-41) of men were treated. Control rates among people with hypertension in 2019 were 23% (20-27) for women and 18% (16-21) for men. In 2019, treatment and control rates were highest in South Korea, Canada, and Iceland (treatment >70%; control >50%), followed by the USA, Costa Rica, Germany, Portugal, and Taiwan. Treatment rates were less than 25% for women and less than 20% for men in Nepal, Indonesia, and some countries in sub-Saharan Africa and Oceania. Control rates were below 10% for women and men in these countries and for men in some countries in North Africa, central and south Asia, and eastern Europe. Treatment and control rates have improved in most countries since 1990, but we found little change in most countries in sub-Saharan Africa and Oceania. Improvements were largest in high-income countries, central Europe, and some upper-middle-income and recently high-income countries including Costa Rica, Taiwan, Kazakhstan, South Africa, Brazil, Chile, Turkey, and Iran. Interpretation: Improvements in the detection, treatment, and control of hypertension have varied substantially across countries, with some middle-income countries now outperforming most high-income nations. The dual approach of reducing hypertension prevalence through primary prevention and enhancing its treatment and control is achievable not only in high-income countries but also in low-income and middle-income settings.
- Os cílios primários regulam os níveis de tiorredoxina redutase 1 e de yH2AX em resposta a níveis elevados de glucosePublication . Marques, Rira; Paiva, Mariana; Ginete, Catarina; Nolasco, Sofia; Marinho, Susana H.; Veiga, Luisa; Brito, Miguel; Soares, Helena; Carmona, BrunoA diabetes caracteriza-se por uma anormal capacidade de controlar o nível de glucose na corrente sanguínea, podendo levar a outras complicações, tais como hipertensão, doenças cardiovasculares, e retinopatia. A desregulação dos níveis de glucose na retina tem demonstrado aumentar os níveis de peróxido de hidrogénio, conduzindo a uma rutura na barreira sanguínea da retina, uma das causas de retinopatia diabética. O cílio primário é um organelo que demonstrou ter um papel no controlo do equilíbrio energético e da homeostase da glucose. Defeitos na estrutura e função dos cílios podem resultar no desenvolvimento de várias doenças, conhecidas como ciliopatias, e que incluem fenótipos como obesidade e diabetes. Neste trabalho pretendemos estudar o papel do aumento dos níveis de glucose na montagem de cílios primários em culturas de células do epitélio pigmentar da retina (RPE-1), bem como o papel dos cílios na resposta celular aos níveis elevados de glucose. Para isso, suplementámos os meios de crescimento das células RPE-1 com diferentes concentrações de glucose (5 mM, 25 mM e 5 mM de glucose + 20 mM manitol). Estas células também foram induzidas a montar cílios antes ou depois da suplementação com a glucose. Neste estudo observámos que a suplementação de glucose não afetou o número de células ciliadas, sendo que o comprimento dos cílios foi menor em células suplementadas com 25 mM de glucose. Também avaliámos os níveis nucleares de tiorredoxina redutase 1 (TXNRD1), uma das principais enzimas intervenientes na resposta ao stress oxidativo desencadeado pela hiperglicemia, e de γH2AX, um marcador celular de quebras no DNA e de senescência celular. Observámos que os níveis nucleares de TXNRD1 e de γH2AX são afetados pela adição de glucose e que a existência de cílios modula a resposta das células em resposta a níveis elevados de glucose. Estes resultados mostram que a presença de cílios primários afeta drasticamente a resposta celular às elevadas concentrações de glucose que provavelmente induzem o stress oxidativo, podendo ter um papel crucial no desenvolvimento de retinopatia diabética.
- Cytostatics occupational exposure: genotoxic effects assessmentPublication . Ladeira, Carina; Viegas, Susana; Carolino, Elisabete; Gomes, M. C.; Brito, MiguelThe use of cytostatics drugs in anticancer therapy is increasing. Health care workers can be occupationally exposed to these drugs classified as carcinogenic, mutagenic or teratogenic. Workers may be exposed to this drug, being in the hospital settings the main focus dwelled upon the pharmacy, and nursing personnel. Although the potential therapeutic benefits of hazardous drugs outweigh the risks of side effects for ill patients, exposed health care workers can have the same side effects with no therapeutic benefit. The exposure to these substances is epidemiologically linked to cancer and nuclear changes detected by the cytokinesis-block micronucleus test (CBMN). This method is extensively used in molecular epidemiology, since it determines several biomarkers of genotoxicity, such as micronuclei (MN), which are biomarkers of chromosomes breakage or loss, nucleoplasmic bridges (NPB), common biomarkers of chromosome rearrangement, poor repair and/or telomeres fusion, and nuclear buds (NBUD), biomarkers of elimination of amplified DNA.
- Role of macronutrients and micronutrients in DNA damage: results from a food frequency questionnairePublication . Ladeira, Carina; Carolino, Elisabete; Gomes, Manuel C.; Brito, MiguelThe links between diet and genomic instability have been under investigation for several decades, and evidence suggests a significant causal or preventive role for various dietary factors. This study investigates the influence of macronutrients (calories, protein, and glucides) and micronutrients, such as vitamins and minerals, as assessed by a food frequency questionnaire, on genotoxicity biomarkers measured by cytokinesis-blocked micronucleus assay and comet assay. The results found significant positive and negative correlations. Micronucleus frequency tends to increase with higher intake of caffeine, calcium, magnesium, zinc, and protein (P < .05, Spearman correlation). Calorie and omega-6 intakes are negatively correlated with DNA damage measured by the comet assay. These results are somewhat controversial because some of the correlations found are contrary to dominant views in the literature; however, we suggest that unraveling the association between diet and genetic instability requires a much better understanding of the modulating role of macronutrients and micronutrients.
- The D1822V APC polymorphism interacts with fat, calcium, and fiber intakes in modulating the risk of colorectal cancer in Portuguese personsPublication . Guerreiro, Catarina Sousa; Cravo, Marília; Brito, Miguel; Vidal, Pedro L.; Fidalgo, Paulo O.; Leitão, Carlos NobreBackground - Both genetic and environmental factors affect the risk of colorectal cancer (CRC). Objective - We aimed to examine the interaction between the D1822V polymorphism of the APC gene and dietary intake in persons with CRC. Design - Persons with CRC (n = 196) and 200 healthy volunteers, matched for age and sex in a case-control study, were evaluated with respect to nutritional status and lifestyle factors and for the D1822V polymorphism. Results - No significant differences were observed in energy and macronutrient intakes. Cases had significantly (P < 0.05) lower intakes of carotenes, vitamins C and E, folate, and calcium than did controls. Fiber intake was significantly (P = 0.004) lower in cases than in controls, whereas alcohol consumption was associated with a 2-fold risk of CRC. In addition, cases were significantly (P = 0.001) more likely than were controls to be sedentary. The homozygous variant for the APC gene (VV) was found in 4.6% of cases and in 3.5% of controls. Examination of the potential interactions between diet and genotype found that a high cholesterol intake was associated with a greater risk of colorectal cancer only in noncarriers (DD) of the D1822V APC allele (odds ratio: 1.66; 95% CI: 1.00, 2.76). In contrast, high fiber and calcium intakes were more markedly associated with a lower risk of CRC in patients carrying the polymorphic allele (DV/VV) (odds ratio: 0.50; 95% CI: 0.27, 0.94 for fiber; odds ratio: 0.51; 95% CI: 0.28, 0.93 for calcium) than in those without that allele. Conclusion - These results suggest a significant interaction between the D1822V polymorphism and the dietary intakes of cholesterol, calcium, and fiber for CRC risk.
- Exposição ocupacional a formaldeído: avaliação da exposição e efeitos genotóxicosPublication . Ladeira, Carina; Viegas, Susana; Carolino, Elisabete; Gomes, Mário; Prista, João; Gomes, Manuel Carmo; Brito, MiguelO formaldeído (FA) foi classificado, em 2004, pela International Agency for Cancer Research como agente cancerígeno. Este agente químico ocupa a 25ª posição em toda a produção química dos Estados Unidos da América, com mais de 5 milhões de toneladas produzidas por ano. Devido à sua importância económica e uso diversificado, muitos indivíduos estão expostos profissionalmente a FA. Com o estudo desenvolvido pretendeu‑se avaliar a exposição a FA em dois contextos ocupacionais distintos – na produção de FA e resinas e em laboratórios de anatomia patológica (AP) e relacionar com eventuais efeitos para a saúde, comparando a frequência de micronúcleos (MN) em linfócitos do sangue periférico e em células esfoliadas da mucosa bucal dos trabalhadores expostos a FA com indivíduos não expostos (controlos). Como amostra foram estudados 80 trabalhadores ocupacionalmente expostos a FA: 30 trabalhadores da fábrica de produção de FA e resinas e 50 trabalhadores de 10 laboratórios de AP. Foi constituído um grupo controlo de 85 indivíduos com atividades profissionais que não envolviam a exposição a formaldeído ou qualquer outro agente químico com propriedades genotóxicas. Aplicaram‑se duas metodologias distintas de avaliação ambiental do FA com o objetivo de conhecer a exposição profissional. Compararam‑se os resultados obtidos com os valores limite para a exposição média ponderada (TLV‑TWA=0,75 ppm) e para a concentração máxima (VLE‑CM=0,3 ppm). A totalidade dos laboratórios apresentou resultados superiores ao valor de referência existente para a concentração máxima. Nenhum dos resultados obtidos para a exposição média ponderada foi superior ao valor de referência. O exame macroscópico obteve os valores das concentrações máximas mais elevadas em 90% dos laboratórios. Os valores de MN foram mais elevados nos indivíduos expostos a FA comparativamente com os controlos. No caso dos MN nos linfócitos, a média foi de 3,96 nos expostos e de 0,81 nos não expostos. Os MN nas células esfoliadas da boca apresentaram uma média de 0,96 nos expostos e de 0,16 nos controlos. Os resultados obtidos nesta acção de biomonitorização podem revelar‑se particularmente úteis para as organizações responsáveis em definir os níveis aceitáveis para a exposição humana a FA. ABSTRACT: Since 2004, formaldehyde (FA) has been classified by the International Agency for Cancer Research as a carcinogen. The FA ranks 25th in the overall United States chemical production, with more than 5 million tons produced each year. Due to its economic importance and varied use, many individuals are exposed to FA at their occupational settings. This study aimed to assess the exposure to FA in two occupational settings – FA production factory and pathology anatomy (PA) laboratories – and relate it to possible health effects by comparing frequency of micronuclei (MN) in peripheral blood lymphocytes and exfoliated cells from the oral mucosa of workers exposed to FA with individuals not exposed to this agent (controls). This study was performed in 80 workers occupationally exposed to FA: 30 workers of the FA factory and 50 workers in 10 PA laboratories. The control group comprised 85 subjects without exposure. We have applied two different methodologies for environmental monitoring of FA. The results were compared with the reference to the exposure weighted average (TLV‑TWA = 0.75 ppm) and ceiling concentration (VLE‑MC = 0.3 ppm). All laboratories had results higher than the reference value to CM (1.41 ppm). None of the results obtained for the TWA exposure (0.16 ppm) were higher than the reference value. Macroscopic examination obtained the highest values of CM in 90% of laboratories. MN values were higher in individuals exposed to FA as compared to controls. As for MN in lymphocytes, the average was 3.96 in exposed compared with 0.81 in the unexposed. The MN in exfoliated cells of the buccal mucosa had an average of 0.96 in exposed, compared with 0.16 in controls. The results of this biomonitoring can be particularly useful to organizations responsible for defining acceptable levels for human exposure to FA.