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- 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.
- 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.
- 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.
- Prevalência de fibrilhação auricular na Província do Bengo, Angola: resultados de um estudo de base populacionalPublication . Gonçalves, Mauer A. A.; Pedro, João Mário; Silva, Carina; Magalhães, Pedro; Brito, MiguelIntrodução: A fibrilhação auricular é a arritmia sustentada mais comum na população adulta com significado clínico, representando um importante problema de saúde pública. Não existe na literatura dados publicados acerca da prevalência da fibrilhação auricular em Angola. Objetivo: O presente estudo foi realizado com o objetivo de determinar a prevalência de fibrilhação auricular numa população do Bengo, uma província do norte de Angola, estratificada por sexo e idade e análise da sua relação com alguns fatores de risco cardiovascular. Materiais e Métodos: Os dados são provenientes do estudo CardioBengo, um estudo transversal de base comunitária, do qual foi selecionada uma amostra aleatória de indivíduos com idades compreendidas entre os 15 e os 84 anos. No total foram incluídos 2 379 indivíduos na análise final. Resultados: A idade média dos participantes foi de 35 anos e 63% da amostra era do sexo feminino. Verificou-se que a frequência de consumo de álcool era de 35,8%, a prevalência de acidente vascular isquémico ou acidente isquémico transitório foi de 0,4%; insuficiência cardíaca congestiva, 0,3%; doença cardíaca isquémica, 0,3% e hipertrofia ventricular esquerda, 37,2%. A fibrilhação auricular foi identificada em dois indivíduos, o que representa uma prevalência de 0,084%. Conclusão: O nosso estudo mostra uma baixa prevalência de fibrilhação auricular, quando comparada com as encontradas em estudos realizados em países desenvolvidos, mas semelhante à encontrada em estudos da África Subsariana.
- Ocular repercussions in COVID-19 patients: structural changes of the retina and choroidPublication . Poças, Ilda Maria; Cunha, João Paulo; Camacho, Pedro; Silva, Carina; Ribeiro, Edna; Brito, Miguel; Mendonça, Paula; Barroqueiro, Olga; Lino, Pedro Miguel; Condado, Patrícia; Nicho, Inês; Carmo, Rita; Castelhano, Mariana; Carvalho, Francisca; Almeida, Júlio Costa; Prieto, IsabelPurpose: In March 2022, after 1 year of the emergence of the pandemic by Covid-10 in Portugal, 3413013 positive cases were recorded. The eye can be not only the gateway for coronaviruses (CoV) but also one of their target organs. Conjunctivitis, uveitis, vasculitis, retinitis, and optic neuritis have been documented in animal models. Although most studies focus on respiratory tract involvement, ocular surface involvement such as tears are also reported in other CoVs and their relationship should be valued and studied as a form of treatment, contagion, and transmission. Also, the neurotropism of CoVs, not only through hematogenous dissemination but also through the retrograde neuronal route, associated or not with vascular/ischemic compromise of COVID-19 and its brain sequela may justify the use of non-invasive methodologies to characterize the retina and choroid of patients infected with COVID-19. The possible neurodegeneration associated with the coronavirus will be important to assess the thickness of the innermost layers of the upper hemiretin, with involvement described in other neurodegenerative diseases.
- Are genetic modifiers the answer to different responses to hydroxyurea treatment? A pharmacogenetic study in sickle cell anemia Angolan childrenPublication . Ginete, Catarina; Delgadinho, Mariana; Santos, Brígida; Pinto, Vera; Silva, Carina; Miranda, Armandina; Brito, MiguelSickle cell anemia (SCA) is an inherited disease affecting the hemoglobin that is particularly common in sub-Saharan Africa. Although monogenic, phenotypes are markedly heterogeneous in terms of severity and life span. Hydroxyurea is still the most common treatment for these patients, and the response to treatment is highly variable and seems to be an inherited trait. Therefore, identifying the variants that might predict hydroxyurea response is important for identifying patients who will have a poorer or non-response to treatment, and the ones that are more prone to suffer from severe side effects. In the present pharmacogenetic study, we analyzed the exons of 77 genes described in the literature as potentially associated with hydroxyurea metabolism in Angolan children treated with hydroxyurea and evaluated the drug response considering fetal hemoglobin levels, other hematological and biochemical parameters, hemolysis, number of vaso-occlusive crises and hospitalizations. Thirty variants were identified in 18 of those genes as possibly associated with drug response, five of them in gene DCHS2. Other polymorphisms in this gene were also associated with hematological, biochemical, and clinical parameters. Further research examining the maximum tolerated dose and fixed-dose with a larger sample size is necessary to corroborate these findings.
- Identification of genetic variants in 65 obesity related genes in a cohort of Portuguese obese individualsPublication . Ginete, Catarina; Serrasqueiro, Bernardo; Silva-Nunes, José; Veiga, Luisa; Brito, MiguelObesity is a major public health problem, which has a strong genetic component that interplays with environmental factors. Several genes are known to be implicated in the regulation of body weight. The identification of alleles that can be associated with obesity is a key element to control this pandemic. On the basis of a Portuguese population, 65 obesity-related genes are sequenced using Next-Generation Sequencing (NGS) in 72 individuals with obesity, in order to identify variants associated with monogenic obesity and potential risk factors. A total of 429 variants are identified, 129 of which had already been associated with the phenotype. Comparing our results with the European and Global frequencies, from the 1000 Genomes project, 23 potential risk variants are identified. Six new variants are discovered in heterozygous carriers: four missense (genes ALMS1-NM_015120.4:c.5552C>T; SORCS1-NM_001013031.2:c.1072A>G and NM_001013031.2: c.2491A>C; TMEM67-NM_153704.5:c.158A>G) and two synonymous (genes BBS1-NM_024649.4:c.1437C>T; TMEM67-NM_153704.5:c.2583T>C). Functional studies should be performed to validate these new findings and evaluate their penetrance and pathogenicity. Regardless of no cases of monogenic obesity being identified, this kind of investigational study is important when we are still trying to understand the etiology and pathophysiology of obesity. This will allow the identification of rare variants associated with obesity and the study of their prevalence in specific populational groups.
- Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adultsPublication . NCD Risk Factor Collaboration (NCD-RisC); Brito, MiguelBackground: Underweight and obesity are associated with adverse health outcomes throughout the life course. We estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from 1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories. Methods: We used data from 3663 population-based studies with 222 million participants that measured height and weight in representative samples of the general population. We used a Bayesian hierarchical model to estimate trends in the prevalence of different BMI categories, separately for adults (age ≥20 years) and school-aged children and adolescents (age 5–19 years), from 1990 to 2022 for 200 countries and territories. For adults, we report the individual and combined prevalence of underweight (BMI <18·5 kg/m2) and obesity (BMI ≥30 kg/m2). For school-aged children and adolescents, we report thinness (BMI <2 SD below the median of the WHO growth reference) and obesity (BMI >2 SD above the median). Findings: From 1990 to 2022, the combined prevalence of underweight and obesity in adults decreased in 11 countries (6%) for women and 17 (9%) for men with a posterior probability of at least 0·80 that the observed changes were true decreases. The combined prevalence increased in 162 countries (81%) for women and 140 countries (70%) for men with a posterior probability of at least 0·80. In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia, Micronesia, and countries in the Middle East and North Africa. Obesity prevalence was higher than underweight with a posterior probability of at least 0·80 in 177 countries (89%) for women and 145 (73%) for men in 2022, whereas the converse was true in 16 countries (8%) for women, and 39 (20%) for men. From 1990 to 2022, the combined prevalence of thinness and obesity decreased among girls in five countries (3%) and among boys in 15 countries (8%) with a posterior probability of at least 0·80, and increased among girls in 140 countries (70%) and boys in 137 countries (69%) with a posterior probability of at least 0·80. The countries with the highest combined prevalence of thinness and obesity in school-aged children and adolescents in 2022 were Polynesia Micronesia and the Caribbean for both sexes and Chile and Qatar for boys. Combined prevalence was also high in some countries in South Asia, such as India and Pakistan, where thinness remained prevalent despite having declined. In 2022, obesity in school-aged children and adolescents was more prevalent than thinness with a posterior probability of at least 0·80 among girls in 133 countries (67%) and boys in 125 countries (63%), whereas the converse was true in 35 countries (18%) and 42 countries (21%), respectively. In almost all countries for both adults and school-aged children and adolescents, the increases in double burden were driven by increases in obesity and decreases in double burden by declining underweight or thinness. Interpretation: The combined burden of underweight and obesity has increased in most countries, driven by an increase in obesity, while underweight and thinness remain prevalent in South Asia and parts of Africa. A healthy nutrition transition that enhances access to nutritious foods is needed to address the remaining burden of being underweight while curbing and reversing the increase in obesity.
- Glucose homeostasis in obese women is not associated to unacylated ghrelin plasma levelsPublication . Veiga, Luisa; Brito, Miguel; Silva, Carina; Silva-Nunes, JoséIntroduction: Unacylated ghrelin (UAG) is the major form of circulating ghrelin. Initially considered as a nonfunctional peptide, soon after, UAG has been associated with an insulin-sensitizing action and to negative action on energy balance. The aim of this study was to analyze the association between the serum levels of UAG and glucose metabolism parameters in obese women, independently from the eventual influence of anthropometrics. Methods: One hundred lean and 254 obese Caucasian women were studied. Each woman was characterized by anthropometrics, fasting glucose, insulin, HbA1c, and UAG. In addition, obese women were subjected to a classic oral glucose tolerance test (oGTT) to assess glucose and insulin at 120 minutes. Insulin resistance was assessed by the homeostasis model assessment (HOMA-IR). Obese women were classified into three glycemic status subgroups (normoglycemia, prediabetes, and diabetes) according to HbA1c and fasting, and oGTT glucose values. Results: In comparison with the lean group, significantly lower levels of UAG were observed in obese women. However, no significant difference was observed through obesity classes I to III. UAG levels were not significantly different among glycemic status subgroups and did not show any association with glucose, insulin, HOMA-IR, or HbA1c. Conclusions: Although anthropometry can influence the level of the unacylated form of ghrelin, UAG plasma levels do not associate with glucose homeostasis parameters.