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Abstract Background Cardiovascular diseases (CVD), including coronary heart disease (CHD), display a higher prevalence in men than women. This study aims to evaluate the variations in the intestinal microbiota between men and women afflicted with CHD and delineate these against a non-CVD control group for each sex. Methods Our research was conducted in the framework of the CORDIOPREV study, a clinical trial which involved 837 men and 165 women with CHD. We contrasted our findings with a reference group of 375 individuals (270 men, 105 women) without CVD. The intestinal microbiota was examined through 16S metagenomics on the Illumina MiSeq platform and the data processed with Quiime2 software. Results Our results showed a sex-specific variation (beta diversity) in the intestinal microbiota, while alpha-biodiversity remained consistent across both sexes. Linear discriminant analysis effect size (LEfSe) analysis revealed sex-centric alterations in the intestinal microbiota linked to CVD. Moreover, using random forest (RF) methodology, we identified seven bacterial taxa—g_UBA1819 (Ruminococcaceae), g_Bilophila, g_Subdoligranulum, g_Phascolarctobacterium, f_Barnesiellaceae, g_Ruminococcus, and an unknown genus from the Ruminococcaceae family (Ruminococcaceae incertae sedis)—as key discriminators between men and women diagnosed with CHD. The same taxa also emerged as critical discriminators between CHD-afflicted and non-CVD individuals, when analyzed separately by sex. Conclusion Our findings suggest a sex-specific dysbiosis in the intestinal microbiota linked to CHD, potentially contributing to the sex disparity observed in CVD incidence. Trial registration Clinical Trials.gov.Identifier NCT00924937. Graphical Abstract

Abstract Objective We aimed to identify a lipidic profile associated with type 2 diabetes mellitus (T2DM) development in coronary heart disease (CHD) patients, to provide a new, highly sensitive model which could be used in clinical practice to identify patients at T2DM risk. Methods This study considered the 462 patients of the CORDIOPREV study (CHD patients) who were not diabetic at the beginning of the intervention. In total, 107 of them developed T2DM after a median follow-up of 60 months. They were diagnosed using the American Diabetes Association criteria. A novel lipidomic methodology employing liquid chromatography (LC) separation followed by HESI, and detection by mass spectrometry (MS) was used to annotate the lipids at the isomer level. The patients were then classified into a Training and a Validation Set (60–40). Next, a Random Survival Forest (RSF) was carried out to detect the lipidic isomers with the lowest prediction error, these lipids were then used to build a Lipidomic Risk (LR) score which was evaluated through a Cox. Finally, a production model combining the clinical variables of interest, and the lipidic species was carried out. Results LC-tandem MS annotated 440 lipid species. From those, the RSF identified 15 lipid species with the lowest prediction error. These lipids were combined in an LR score which showed association with the development of T2DM. The LR hazard ratio per unit standard deviation was 2.87 and 1.43, in the Training and Validation Set respectively. Likewise, patients with higher LR Score values had lower insulin sensitivity (P = 0.006) and higher liver insulin resistance (P = 0.005). The receiver operating characteristic (ROC) curve obtained by combining clinical variables and the selected lipidic isomers using a generalised lineal model had an area under the curve (AUC) of 81.3%. Conclusion Our study showed the potential of comprehensive lipidomic analysis in identifying patients at risk of developing T2DM. In addition, the lipid species combined with clinical variables provided a new, highly sensitive model which can be used in clinical practice to identify patients at T2DM risk. Moreover, these results also indicate that we need to look closely at isomers to understand the role of this specific compound in T2DM development. Trials registration NCT00924937.

Highlights Accumulating evidences show that the alterations in the gut microbiota associated to metabolic diseases are different in men and women, and these differences may influence sex differences in the development and prevalence of metabolic diseases. The key aspects involved in these pathologies include lipopolysaccharide-inflammation, gut barrier integrity, gut microbiota-derived metabolites and gut–brain axis. Sex steroids, mainly estrogen and testosterone, are thought to play a prominent role in the sexual dimorphism of gut microbiota. The influence of sex hormones is reflected both in men and women, and among women themselves due to hormonal changes associated with the menopause. The interaction between sex steroids and the gut microbiota plays a prominent role in the development of metabolic diseases.

Abstract Background Type 2 diabetes mellitus (T2DM) is one of the most widely spread diseases, affecting around 90% of the patients with diabetes. Metabolomics has proven useful in diabetes research discovering new biomarkers to assist in therapeutical studies and elucidating pathways of interest. However, this technique has not yet been applied to a cohort of patients that have remitted from T2DM. Methods All patients with a newly diagnosed T2DM at baseline (n = 190) were included. An untargeted metabolomics approach was employed to identify metabolic differences between individuals who remitted (RE), and those who did not (non-RE) from T2DM, during a 5-year study of dietary intervention. The biostatistical pipeline consisted of an orthogonal projection on the latent structure discriminant analysis (O-PLS DA), a generalized linear model (GLM), a receiver operating characteristic (ROC), a DeLong test, a Cox regression, and pathway analyses. Results The model identified a significant increase in 12 metabolites in the non-RE group compared to the RE group. Cox proportional hazard models, calculated using these 12 metabolites, showed that patients in the high-score tercile had significantly (p-value

Introduction: A distinctive gut microbiome have been linked to type 2 diabetes mellitus (T2DM). Objectives: We aimed to evaluate whether gut microbiota composition, in addition to clinical biomarkers, could improve the prediction of new incident cases of diabetes in patients with coronary heart disease. Methods: All the patients from the CORDIOPREV (Clinical Trials.gov.Identifier: NCT00924937) study without T2DM at baseline were included (n = 462). Overall, 107 patients developed it after a median of 60 months. The gut microbiota composition was determined by 16S rRNA gene sequencing and predictive models were created using hold-out method. Results: A gut microbiota profile associated with T2DM development was determined through a microbiome-based predictive model. The addition of microbiome data to clinical parameters (variables included in FINDRISC risk score and the diabetes risk score of the American Diabetes Association, HDL, triglycerides and HbA1c) improved the prediction increasing the area under the curve from 0.632 to 0.946. Furthermore, a microbiome-based risk score including the ten most discriminant genera, was associated with the probability of develop T2DM. Conclusion: These results suggest that a microbiota profile is associated to the T2DM development. An integrate predictive model of microbiome and clinical data that can improve the prediction of T2DM is also proposed, if is validated in independent populations to prevent this disease.

IntroductionMild cognitive impairment (MCI) can progress to Alzheimer’s disease (AD). When MCI is not properly controlled, the speed of deterioration can dramatically increase. Reduction of oxidative stress/inflammation and the modulation of the gut-brain axis could be new potential therapeutic targets for the prevention and treatment of AD. Consumption of specific nutrients, diets and probiotic supplementation have been evaluated for neurodegenerative disorders. We focus on a detailed description of the study methods and baseline characteristics of a clinical trial aiming to evaluate the efficacy of a combined nutritional intervention, i.e., a Mediterranean diet with probiotics, on cognitive capacity in a population with MCI.MethodsIn this randomized, latin-square crossover, double-blind, and controlled dietary intervention trial (clinicaltrials.gov NCT05029765), 47 MCI patients were randomized to consume three dietary interventions for 24-weeks each: (1) A Mediterranean diet supplemented with probiotics (109 colony-forming units of Lactobacillus rhamnosus and Bifidobacterium longum); (2) A Mediterranean diet + placebo; and (3) A Healthy diet according to the World Health Organization (WHO) recommendations. Participants will be evaluated before and after each of the three intervention periods (each 24-weeks, with a total of 72-weeks) for adherence to the assigned diet, blood tests, cognitive performance, gut microbiota analysis and functional neuroimaging studies.ResultsFifty patients, ≥60 years-old and diagnosed with MCI, underwent randomization. A total of 47 patients completed follow-up dietary interventions (57.4% males), with a good glycemic control (HbA1c 5.8 ± 0.1%, fasting glucose and insulin 99.7 ± 3.3 mg/dL and 10.4 ± 0.9 mU/L, respectively), elevated systolic blood pressure (136.9 ± 2.1 mmHg) and increased degree of inflammation (high-sensitivity C-reactive protein, 8.8 ± 0.9 mg/dL). Baseline adherence to the Mediterranean diet was medium (7.5 ± 0.3 points on the score that ranged from 0 to 14 points).ConclusionThe results of this clinical study would provide more evidence on the need for dietary therapeutic strategies, for clinical and individual practice, in the management of MCI patients to reduce the risk of AD development. Targeting lifestyle modifications in high-risk populations could prevent substantial cases of cognitive decline.Clinical trial registration[ClinicalTrials.gov], identifier [NCT05029765].

Introdução: A pandemia de COVID-19 impactou no diagnóstico e tratamento da tuberculose (TB), principalmente em relação a descoberta precoce dos casos de tuberculose e supervisão do tratamento diretamente observado. Além disto, a coinfecção TB e COVID-19 deve ser estudada no sentido de compreender a interação destes dois patógenos e o impacto na apresentação e desfechos clínicos. Objetivo: Descrever e avaliar o desfecho dos casos de coinfecção tuberculose/COVID-19 em um hospital de referência. Método: Trata-se de um estudo descritivo, realizado com dados secundários do banco de dados dos casos internados por Síndrome Respiratória Aguda Grave de um hospital de referência do interior paulista e do Sistema de Informação TB-WEB para confirmação dos casos notificados de tuberculose. Foram selecionados os casos de COVID-19 confirmados por RT-PCR ou critério clínico radiológico, internados no hospital, que tinham tuberculose ativa (história prévia ou atual de tuberculose). Analisado as variáveis sociodemográficas (sexo, idade e raça/cor), forma clínica (pulmonar, extrapulmonar, pulmonar e extrapulmonar), comorbidades e desfecho dos casos internados (alta para tratamento ambulatorial, óbito). Resultados: Dentre os 2.565 casos de COVID-19 positivos, 2.383 foram internados. Tuberculose e COVID-19 foi diagnosticada em 14 casos, em 8 a tuberculose foi diagnosticada e curada previamente e em 6 o diagnóstico de tuberculose ativa ocorreu durante a internação por COVID-19. Das variáveis sociodemográficas, 79,0% eram do sexo masculino, 71,0% tinham mais de 40 anos de idade, 79,0% eram brancos. Em relação a forma clínica, 86,0% tinham a forma pulmonar, 14,0% a forma extrapulmonar. Quanto as comorbidades, 29,0% faziam uso de álcool, 21,0% de drogas, 21,0% tinham doença renal, 7,0% HIV, 7,0% diabetes. Em relação ao desfecho dos casos durante a internação, 9 (64%) casos receberam alta hospitalar e 5 (36,0%) foram a óbito. Dos que foram a óbito, 4 pacientes receberam o diagnóstico de TB ativa e iniciaram o tratamento intra-hospitalar, eram predominantemente adultos jovens, que faziam uso de drogas e que apresentaram resultados microbiológicos baciloscopia, TRM-TB e cultura positivos. Conclusão: Observou-se a ocorrência de diagnóstico tardio de tuberculose entre os casos positivos de COVID-19 que foram internados associado à elevada letalidade.

Introdução: O relatório global da Organização Mundial de Saúde mostrou que o número de casos novos notificados de tuberculose (TB) caiu de 7,1 para 5,8 milhões entre os anos de 2019 e 2020. Revelou também que houve aumento do número de óbitos por tuberculose, fato ocorrido pela primeira vez na última década. Objetivo: Comparar a apresentação, diagnóstico e desfecho do tratamento dos casos novos notificados de tuberculose em período prévio e durante a pandemia de COVID-19. Método: Trata-se de um estudo descritivo, observacional, a partir de dados secundários do sistema de informação TB-WEB referente às notificações de tuberculose de um Hospital Universitário de referência para tuberculose multirresistente, HIV e transplantes do estado de São Paulo no período pré-pandêmico (2018/2019) e pandêmico (2020/2021) de COVID-19. Foram analisadas as variáveis apresentação clínica, comorbidades e o desfecho dos casos em ambos os períodos. Resultados: Entre janeiro de 2018 a dezembro de 2021, foram notificados 349 casos de tuberculose no hospital, sendo 206 em 2018/2019 e 143 em 2020/2021, o que representou um declínio de 30,6% das notificações no período pandêmico. Em relação as comorbidades associadas, o acometimento pulmonar foi observado em 63% (220/349) dos casos e 37% (129/349) apresentavam forma extrapulmonar ou disseminada, 20% (70/349) dos pacientes tinham HIV associado, 10,9% (38/349) diabetes mellitus e 57,1% (199/349) outras comorbidades. Não foram observadas diferenças estatisticamente significativas na forma de apresentação da doença e frequência das comorbidades entre os dois períodos avaliados. Dos 349 pacientes notificados, 302 tiveram desfecho no hospital, 5 foram transferidos e os demais permanecem em tratamento. O desfecho do tratamento da TB foi favorável em 74% (148/200) dos casos no pré-pandêmico e 54% (54/102) no pandêmico (p = 0,001). As taxas de óbito e o óbito por tuberculose também diferiram de forma significativa na comparação entre os períodos (p < 0,05). Conclusão: Houve uma redução do número de casos notificados com tuberculose. As apresentações clínicas foram semelhantes nos dois períodos, entretanto o grau de severidade necessita ser avaliado bem como a co-apresentação TB/COVID-19. A elevação nas taxas de óbitos por tuberculose requer a reorganização dos serviços para a suspeição, diagnóstico e tratamento de forma hierarquizada na dinâmica do SUS para retomar as metas de controle da doença.

MicroRNAs (miRNAs) regulate the expression of genes associated with the development of diseases, including type 2 diabetes mellitus (T2DM). However, the use of miRNAs to predict T2DM remission has been poorly studied. Therefore, we aimed to investigate whether circulating miRNAs could be used to predict the probability of T2DM remission in patients with coronary heart disease. We included the newly diagnosed T2DM (n = 190) of the 1,002 patients from the CORDIOPREV study. Seventy-three patients reverted from T2DM after 5 years of dietary intervention with a low-fat or Mediterranean diet. Plasma levels of 56 miRNAs were measured by OpenArray. Generalized linear model, receiver operating characteristic (ROC), Cox regression, and pathway analyses were performed. ROC analysis based on clinical variables showed an area under the curve (AUC) of 0.66. After a linear regression analysis, seven miRNAs were identified as the most important variables in the group’s differentiation. The addition of these miRNAs to clinical variables showed an AUC of 0.79. Cox regression analysis using a T2DM remission score including miRNAs showed that high-score patients have a higher probability of T2DM remission (hazard ratio [HR]low versus high, 4.44). Finally, 26 genes involved in 10 pathways were related to the miRNAs. We have identified miRNAs (hsa-let-7b, hsa-miR-101, hsa-miR-130b-3p, hsa-miR-27a, hsa-miR-30a-5p, hsa-miR-375, and hsa-miR-486) that contribute to the prediction of T2DM remission in patients with coronary heart disease.

Circulating microRNAs (miRNAs) have been proposed as biomarkers for type 2 diabetes (T2D). Adipose tissue (AT), for which dysfunction is widely associated with T2D development, has been reported as a major source of circulating miRNAs. However, the role of dysfunctional AT in the altered pattern of circulating miRNAs associated with T2D onset remains unexplored. Herein, we investigated the relationship between T2D-associated circulating miRNAs and AT function, as well as the role of preadipocytes and adipocytes as secreting cells of candidate circulating miRNAs. Among the plasma miRNAs related to T2D onset in the CORonary Diet Intervention with Olive oil and cardiovascular PREVention (CORDIOPREV) cohort, baseline miR-223-3p levels (diminished in patients who next developed T2D [incident-T2D]) were significantly related to AT insulin resistance (IR). Baseline serum from incident-T2D participants induced inflammation and IR in 3T3-L1 adipocytes. We demonstrated that tumor necrosis factor (TNF)-α inhibited miR-223-3p secretion while enhancing miR-223-3p intracellular accumulation in 3T3-L1 (pre)adipocytes. Overexpression studies showed that an intracellular increase of miR-223-3p impaired glucose and lipid metabolism in these cells. Our findings provide mechanistic insights into the alteration of circulating miRNAs preceding T2D, unveiling both preadipocytes and adipocytes as miR-223-3p-secreting cells and suggesting that inflammation promotes miR-223-3p intracellular accumulation, which might contribute to (pre)adipocyte dysfunction and body metabolic dysregulation.

Overweight and obesity constitute a major global public health problem. Healthy dietary patterns induce changes at the molecular level. Currently, there are no studies evaluating the effect of a diet based on fruit, avocado, whole grains, and trout (FAWGT diet) on the expression of obesity-related genes. This randomized controlled crossover study included 44 obese Colombians with BMI ≥30 kg/m2 who followed either a FAWGT diet or a usual diet (UD) characterized by a high intake of saturated fat and foods rich in processed carbohydrates. After 8 weeks of intervention, a postprandial expression study of inflammation and oxidative stress-related genes was carried out with a real-time PCR. The intervention with a FAWGT diet decreased the expression of inflammatory (NFKB1, IL6, IL1β) and oxidative stress (NFE2L2) genes compared with the intake of the UD. Finally, the postprandial expression of NFkB1 was positively correlated with triglyceride levels after a dietary intervention with the FAWGT diet and the IL1β gene, and likewise with insulin levels after following the usual diet. The consumption of the FAWGT diet for 8 weeks reduced the inflammatory status; thus, it can be considered a valid alternative to other healthy diets, since it induces beneficial changes on the genes involved in inflammation and oxidative stress in obese people.

We investigated whether long-term consumption of two healthy diets (low-fat (LF) or Mediterranean (Med)) interacts with SIRT1 genotypes to modulate aging-related processes such as leucocyte telomere length (LTL), oxidative stress (OxS) and inflammation in patients with coronary heart disease (CHD). LTL, inflammation, OxS markers (at baseline and after 4 years of follow-up) and SIRT1-Single Nucleotide Polymorphisms (SNPs) (rs7069102 and rs1885472) were determined in patients from the CORDIOPREV study. We analyzed the genotype-marker interactions and the effect of diet on these interactions. Regardless of the diet, we observed LTL maintenance in GG-carriers for the rs7069102, in contrast to carriers of the minor C allele, where it decreased after follow-up (p = 0.001). The GG-carriers showed an increase in reduced/oxidized glutathione (GSH/GSSG) ratio (p = 0.003), lower lipid peroxidation products (LPO) levels (p < 0.001) and a greater decrease in tumor necrosis factor-alpha (TNF-α) levels (p < 0.001) after follow-up. After the LF diet intervention, the GG-carriers showed stabilization in LTL which was significant compared to the C allele subjects (p = 0.037), although the protective effects found for inflammation and OxS markers remained significant after follow-up with the two diets. Patients who are homozygous for the SIRT1-SNP rs7069102 (the most common genotype) may benefit from healthy diets, as suggested by improvements in OxS and inflammation in patients with CHD, which may indicate the slowing-down of the aging process and its related diseases.

Metabolic disease: a red flag for diabetes risk Tiny RNA molecules circulating in the blood could give early warning of type 2 diabetes risk. MicroRNAs help regulate the expression of other genes, and recent research has linked irregularities in these molecules to many different diseases. Researchers led by José López Miranda of the University of Córdoba in Spain monitored a cohort of 462 patients for several years to assess how plasma levels of certain microRNAs are deregulated before the onset and progression of diabetes. They observed a striking ‘signature’ of altered expression in four microRNAs for patients who developed diabetes over the course of the study. Intriguingly, patients with markedly elevated blood sugar—state known as prediabetes—exhibited a similar signature, but with more modest alteration in the gene expression levels, indicating that these microRNAs could help clinicians track and prevent disease onset.

Background: Type-2 diabetes mellitus (T2DM) is a major health problem with increasing incidence, which severely impacts cardiovascular disease. Because T2DM is associated with altered gene expression and aberrant splicing, we hypothesized that dysregulations in splicing machinery could precede, contribute to, and predict T2DM development. Methods: A cohort of patients with cardiovascular disease (CORDIOPREV study) and without T2DM at baseline (at the inclusion of the study) was used (n = 215). We determined the expression of selected splicing machinery components in fasting and 4 h-postprandial peripheral blood mononuclear cells (PBMCs, obtained at baseline) from all the patients who developed T2DM during 5-years of follow-up (n = 107 incident-T2DM cases) and 108 randomly selected non-T2DM patients (controls). Serum from incident-T2DM and control patients was used to analyze in vitro the modulation of splicing machinery expression in control PBMCs from an independent cohort of healthy subjects. Findings: Expression of key splicing machinery components (e.g. RNU2, RNU4 or RNU12) from fasting and 4 h-postprandial PBMCs of incident-T2DM patients was markedly altered compared to non-T2DM controls. Moreover, in vitro treatment of healthy individuals PBMCs with serum from incident-T2DM patients (compared to non-T2DM controls) reduced the expression of splicing machinery elements found down-regulated in incident-T2DM patients PBMCs. Finally, fasting/postprandial levels of several splicing machinery components in the PBMCs of CORDIOPREV patients were associated to higher risk of T2DM (Odds Ratio > 4) and could accurately predict (AUC > 0.85) T2DM development. Interpretation: Our results reveal the existence of splicing machinery alterations that precede and predict T2DM development in patients with cardiovascular disease. Fund: ISCIII, MINECO, CIBERObn. Keywords: Peripheral blood mononuclear cells (PBMCs), Postprandial state, Spliceosome, OGTT, RNUs

Circulating microRNAs (miRNAs) have been proposed as type 2 diabetes biomarkers, and they may be a more sensitive way to predict development of the disease than the currently used tools. Our aim was to identify whether circulating miRNAs, added to clinical and biochemical markers, yielded better potential for predicting type 2 diabetes. The study included 462 non-diabetic patients at baseline in the CORDIOPREV study. After a median follow-up of 60 months, 107 of them developed type 2 diabetes. Plasma levels of 24 miRNAs were measured at baseline by qRT-PCR, and other strong biomarkers to predict diabetes were determined. The ROC analysis identified 9 miRNAs, which, added to HbA1c, have a greater predictive value in early diagnosis of type 2 diabetes (AUC = 0.8342) than HbA1c alone (AUC = 0.6950). The miRNA and HbA1c-based model did not improve when the FINDRISC was included (AUC = 0.8293). Cox regression analyses showed that patients with low miR-103, miR-28-3p, miR-29a, and miR-9 and high miR-30a-5p and miR-150 circulating levels have a higher risk of disease (HR = 11.27; 95% CI = 2.61–48.65). Our results suggest that circulating miRNAs could potentially be used as a new tool for predicting the development of type 2 diabetes in clinical practice. Keywords: type 2 diabetes mellitus, miRNAs, biomarkers, predictive models

Abstract This prospective study evaluated whether baseline cholesterol efflux is associated with future development of type 2 diabetes (T2DM) in cardiovascular patients. We measured cholesterol efflux in all CORDIOPREV study (NCT00924937) participants free of T2DM at baseline (n = 462) and assessed its relationship with T2DM incidence during a 4.5 years of follow-up. Cholesterol efflux was quantified by incubation of cholesterol-loaded THP-1 cells with the participants’ apoB-depleted plasma. Disposition index was estimated as beta-cell function indicator. During follow-up 106 individuals progressed to T2DM. The cholesterol efflux/apoA-1 ratio was inversely associated with T2DM development independently of traditional risk factors (model-1, OR: 0.647, 95%CI: 0.495–0.846), and after additional adjustment for glycaemic parameters (model-2, OR: 0.670, 95%CI: 0.511–0.878). When cumulative incidence of diabetes was analysed by quartiles of cholesterol efflux/apoA-I, incidence of T2DM was reduced by 54% in subjects who were in the higher cholesterol efflux/apoA-I quartile compared to subjects in the lowest quartile (p = 0.018 and p = 0.042 for model-1 and 2). Moreover, participants who were in the higher cholesterol efflux/apoA-I presented significantly higher disposition index (β = 0.056, SE = 0.026; p = 0.035). In conclusion, HDL-cholesterol efflux normalised to apoA-I was inversely associated with T2DM development in cardiovascular patients. This association was independent of several T2DM risk factors, and may be related to a preserved beta-cell function.

Pet ownership positively influences clinical outcomes in cardiovascular prevention. Additionally, cardiovascular disease (CVD) has been previously linked to microbiota dysbiosis. We evaluated the influence of owning a pet and its relationship with the intestinal microbiota. We analyzed the gut microbiota from 162 coronary patients from the CORDIOPREV study (NCT00924937) according to whether they owned pets (n = 83) or not (n = 79). The pet-owner group was further divided according to whether they owned dogs only (n = 28) or not (n = 55). A 7-item pet-owners test score was used. Patients who owned pets had less risk of metabolic syndrome (MetS) (OR = 0.462) and obesity (OR = 0.519) and were younger (p < 0.001) than patients who did not own pets. Additionally, patients who owned dogs had less risk of MetS (OR = 0.378) and obesity (OR = 0.418) and were younger (p < 0.001) than patients who did not own pets. A preponderance of the genera Serratia and Coprococcus was found in the group of owners, while the genera Ruminococcus, an unknown genus of Enterobacteriaceae and Anaerotruncus were preponderant in the group of non-owners. In patients who owned dogs, Methanobrevibacter and two more genera, Coprococcus and Oscillospira, were more common. Our study suggests that the prevalence of MetS and obesity in CVD patients is lower in pet owners, and that pet ownership could be a protective factor against MetS through the shaping of the gut microbiota. Thus, owning a pet could be considered as a protective factor against cardiometabolic diseases.

Obesity is one of the major health problems worldwide. Following healthy dietary patterns can be difficult in some countries due to the lack of availability of certain foods; thus, alternative foods are needed. Our aim was to evaluate the effect of a dietary pattern consisting of fruit, avocado, whole grains, and trout (FAWGT) on postprandial insulinemia and lipemia in obese Colombian subjects. A randomized controlled crossover study was conducted, in which 44 subjects with BMI ≥ 30 kg/m2 followed either a FAWGT diet or a diet high in saturated fat and rich in processed carbohydrates. Levels of lipids and carbohydrates were measured during the postprandial state. The FAWGT diet reduced fasting insulin, VLDL, and HOMA-IR after 8 weeks (p < 0.05), while there was a lower postprandial increase in TG, VLDL, and insulin levels after both acute and chronic intake of FAWGT diet (p < 0.05). The intake of FAWGT-diet was characterized by high consumption of foods rich in fiber, MUFAs, and vitamins C and E (p < 0.05). The consumption of a diet composed of fruit, avocado, whole grains, and trout has emerged as a valid alternative to the foods included in other heart-healthy diets since it improves postprandial lipemia and insulinemia in obese people and has similar beneficial effects to these healthy models.

Type-2 diabetes mellitus (T2DM) has become a major health problem worldwide. T2DM risk can be reduced with healthy dietary interventions, but the precise molecular underpinnings behind this association are still incompletely understood. We recently discovered that the expression profile of the splicing machinery is associated with the risk of T2DM development. Thus, the aim of this work was to evaluate the influence of 3-year dietary intervention in the expression pattern of the splicing machinery components in peripheral blood mononuclear cells (PBMCs) from patients within the CORDIOPREV study. Expression of splicing machinery components was determined in PBMCs, at baseline and after 3 years of follow-up, from all patients who developed T2DM (Incident-T2DM, n = 107) and 108 randomly selected non-T2DM subjects, who were randomly enrolled in two healthy dietary patterns (Mediterranean or low-fat diets). Dietary intervention modulated the expression of key splicing machinery components (i.e., up-regulation of SPFQ/RMB45/RNU6, etc., down-regulation of RNU2/SRSF6) after three years, independently of the type of healthy diet. Some of these changes (SPFQ/RMB45/SRSF6) were associated with key clinical features and were differentially induced in Incident-T2DM patients and non-T2DM subjects. This study reveals that splicing machinery can be modulated by long-term dietary intervention, and could become a valuable tool to screen the progression of T2DM.

Multiple studies suggest that hypoxia, together with inflammation, could be one of the phenomena involved in the onset and progression of obesity-related insulin resistance. In addition, dysfunction of adipose tissue in obese subjects with metabolic syndrome is associated with decreased angiogenesis. However, some subjects with a high body mass index do not develop metabolic abnormalities associated with obesity. The aim of the current study was to examine the neovascular properties of visceral adipose tissue-derived multipotent mesenchymal cells subjected to hypoxia (hypox-visASCs) from normal-weight subjects (Nw) and obese patients with metabolic syndrome (MS) and without metabolic syndrome (NonMS).This was a 2-year study to enroll subjects who underwent bariatric surgery or cholecystectomy. Eight patients who underwent either bariatric surgery or cholecystectomy (27 patients) participated in the study. Visceral adipose tissue samples from Nw, MS and NonMS subjects were processed by enzymatic digestion. VisASCs cultured under hypoxic conditions were characterized by tubule formation assay, ELISA, flow cytometry, migration rate, and qRT-PCR, and the effects of visASCs-conditioned medium on survival and endothelial cell tubule formation were evaluated.Hypox-visASCs from NonMS subjects showed a greater capacity for tubule formation than hypox-visASCs from Nw and MS subjects. The lower percentage of CD140b+/CD44+ and CD140b+/CD184+ cells observed in hypox-visASCs from NonMS subjects compared to MS subjects was accompanied not only by a lower migration rate from the chemotactic effects of stromal cell derived factor 1α, but also by lower levels of NOX5 mRNA expression. While the levels of monocyte chemoattractant protein 1 mRNA expressed by hypox-visASCs correlated positively with the body mass index and waist circumference of the subjects, the concentration of vascular endothelial growth factor present in hypox-visASC-conditioned culture medium decreased significantly with increasing plasma glucose. The survival rate and tubules formed by endothelial cells cultured in hypox-visASC-conditioned medium decreased significantly with increasing homeostasis model assessment to quantify insulin resistance.Our results suggest that hypox-visASCs from NonMS subjects could promote healthy adipose tissue expansion, while hypox-visASCs from MS subjects appear to contribute to the decreased angiogenic potential and increased inflammation underlying adipose tissue dysfunction in obesity. Our results emphasize the importance of taking into account not only the BMI but also the metabolic profile of the subjects during the implementation of ASCs-based therapy to promote neovascularization.

Intestinal microbiota changes are associated with the development of obesity. However, studies in humans have generated conflicting results due to high inter-individual heterogeneity in terms of diet, age, and hormonal factors, and the largely unexplored influence of gender. In this work, we aimed to identify differential gut microbiota signatures associated with obesity, as a function of gender and changes in body mass index (BMI). Differences in the bacterial community structure were analyzed by 16S sequencing in 39 men and 36 post-menopausal women, who had similar dietary background, matched by age and stratified according to the BMI. We observed that the abundance of the Bacteroides genus was lower in men than in women (P 33. In fact, the abundance of this genus decreased in men with an increase in BMI (P

Recent data suggest that the presence of associated metabolic abnormalities may be important modifiers of the association of obesity with a poorer prognosis in coronary heart disease. We determined the influence of isolated overweight and obesity on carotid intima media thickness (IMT-CC), and also assessed whether this influence was determined by the presence of metabolic abnormalities.1002 participants from the CordioPrev study were studied at entry. We determined their metabolic phenotypes and performed carotid ultrasound assessment. We evaluated the influence of obesity, overweight and metabolic phenotypes on the IMT-CC.Metabolically sick participants (defined by the presence of two or more metabolic abnormalities) showed a greater IMT-CC than metabolically healthy individuals (p = 4 * 10(-6)). Overweight and normal weight patients who were metabolically healthy showed a lower IMT-CC than the metabolically abnormal groups (all p

[This corrects the article DOI: 10.1371/journal.pone.0153096.].

El cráter Chicxulub, parte de un grupo selecto de rasgos geológicos, constituye un laboratorio para investigar los procesos de formación de cráteres y los efectos de impactos en el planeta. Chicxulub es uno de tres cráteres complejos multi–anillos documentados en el registro terrestre y el impacto es relacionado a los cambios ambientales y climáticos que marcan la frontera Cretácico/Paleógeno (K/Pg) y las extinciones masivas de organismos. El cráter, localizado en la porción noroeste de la península de Yucatán, está cubierto por sedimentos carbonatados y fue identificado inicialmente en los estudios dentro del programa de exploración de Petróleos Mexicanos. En la superficie, evidencias del cráter sepultado incluyen al anillo de cenotes y rasgos topográficos semicirculares, los cuales se asocian a la compactación diferencial de los materiales fragmentados en el impacto y que forman parte del relleno de la estructura. El cráter tiene un diámetro aproximado de 200 km, esta una parte en el mar y otra en tierra y puede ser investigado usando métodos geofísicos terrestres, marinos y aéreos. Las características de la plataforma carbonatada, que no ha sido afectada por actividad tectónica o volcánica reciente, permiten tener mayor resolución en los estudios geofísicos e investigar la estructura del cráter con una alta precisión. La formación del cráter y el evento de impacto ocurren en un corto tiempo del orden de centenas de segundos, con una alta liberación de energía y la excavación de una cavidad con profundidades del orden de 25 km, afectando toda la corteza. La corteza inferior y manto superior son deformados y se tiene un levantamiento en la parte central de la excavación de varias decenas de kilómetros que forma un levantamiento de basamento que caracteriza a estos cráteres complejos. La zona de impacto es deformada y fracturada. Los estudios de la dinámica del impacto, formación del cráter, efectos globales de la liberación de energía y ondas sísmicas y los modelados del comportamiento de materiales sujetos a altas presiones y temperaturas forman parte de los problemas en estudio, representado retos interesantes en geociencias. La capa de eyecta con el material fragmentado identificada como la capa K/Pg constituye un marcador estratigráfico a escala global, permitiendo correlaciones estratigráficas y análisis de procesos en la transición del Mesozoico al Cenozoico. En los últimos 20 años las investigaciones han aportado información importante sobre el cráter Chicxulub y los eventos que marcan la frontera K/Pg, sin embargo, son las preguntas formuladas a partir de los estudios quizá la parte más relevante. Estas interrogantes incluyen temas fundamentales sobre impactos, formación de cráteres y la evolución del sistema solar. doi: https://doi.org/10.22201/igeof.00167169p.2011.50.1.125

Side effects of antimalarial drug can overlap with malaria symptoms. We evaluated 50 patients with vivax malaria in Mâncio Lima, Acre, treated with chloroquine and primaquine. Patients were evaluated for the presence of 21 symptoms before and after treatment and for reported side effects of these drugs after treatment was started. The most frequent symptoms before medication were headache, fever, chills, sweating, arthralgia, back pain, and weakness, which were present in between 40% and 76% of respondents. The treatment reduced the occurrence of these symptoms and reduced the lack of appetite, but gastrointestinal symptoms and choluria increased in frequency. There were no reports of pale stools before medication, but 12% reported the occurrence of this symptom after treatment started. Other symptoms such as blurred vision (54%), pruritus (22%), paresthesia (6%), insomnia (46%), and “stings” into the skin (22%) were reported after chloroquine was taken. The antimalarial drugs used to treat P. vivax malaria reduce much of the systemic and algic symptoms but cause mainly gastrointestinal side effects that may lead to lack of adherence to drug treatment. It is important to guide the patient for the appearance and the transience of such side effects in order to avoid abandoning treatment.

Introduction. Children under 5 years of age are more susceptible to developing morbidities such as diarrhea, respiratory infections, anemia, and malnutrition. The objective of the study is to evaluate the prevalence of reported morbidities in this age group in the city of Iñapari (Peru) and the access to health services in this municipality. Methods. Data collection using interviews that assessed socioeconomic and demographic conditions, child morbidity, and access to health services was performed in 2011. Statistical analysis was performed using SPSS 13.0. Results. Regarding morbidities that occurred during lifetime, 39.8% reported previous anemia and intestinal parasite infection. About 53.7% of the children reported any type of morbidities in the last 15 days before interview, being most frequent respiratory symptoms (38.9%), diarrhea (23,4%), and fever (23,1%). Only 63.1% of those reporting recent morbidities sought health care. These morbidities were associated with precarious sanitation and lack of infrastructure, the presence of other comorbidities, and poor access to health services. Conclusion. The main referred morbidities in Amazonian Peruvian children were diarrhea, respiratory symptoms, anemia, and vomiting. Incentives and improvements in the health and sanitation conditions would be important measures to improve the quality of life of the Amazonian child population.

ObjectiveTo determine whether metabolic syndrome traits influence the postprandial lipemia response of coronary patients, and whether this influence depends on the number of MetS criteria.Materials and methods1002 coronary artery disease patients from the CORDIOPREV study were submitted to an oral fat load test meal with 0.7 g fat/kg body weight (12% saturated fatty acids, 10% polyunsaturated fatty acids, 43% monounsaturated fatty acids), 10% protein and 25% carbohydrates. Serial blood test analyzing lipid fractions were drawn at 0, 1, 2, 3 and 4 hours during the postprandial state. Total and incremental area under the curves of the different postprandial parameters were calculated following the trapezoid rule to assess the magnitude of change during the postprandial state.ResultsPostprandial lipemia response was directly related to the presence of metabolic syndrome. We found a positive association between the number of metabolic syndrome criteria and the response of postprandial plasma triglycerides (pConclusionsFasting triglycerides are the major contributors to the postprandial triglycerides levels. MetS influences the postprandial response of lipids in patients with coronary heart disease, particularly in non-hypertriglyceridemic patients.

This study aimed to evaluate the prevalence of serum IgG dengue in children in an Amazonian population, to assess the seroconversion rate in 12 months, and to estimate how many seropositive children had a prior clinical diagnosis of dengue. We conducted a population-based study between 2010 and 2011, with children aged 6 months to 12 years that were living in the urban area of a small town in the Brazilian Amazon. The prevalence of IgG antibodies against dengue antigens was determined by indirect ELISA technique, and seronegative children were reexamined after 12 months to determine seroconversion rates. Results showed seroprevalence of IgG antibodies against dengue type of 2.9%, with no significant association between age, race, and sex. In seropositive children, only 8.4% had received a clinical diagnosis of dengue, and the ratio of clinically diagnosed cases and subclinical cases was 1 : 11. The seroconversion rate between 2010 and 2011 was 1.4% (CI 3.8% to 35.1%). The seroprevalence of dengue in this pediatric population was low, and the vast majority of cases were not clinically detected, suggesting a difficulty in making the clinical diagnosis in children and a high frequency of asymptomatic infections.

TCF7L2 rs7903146 is an important genetic factor predicting type 2 diabetes (T2DM) which has also been linked to higher cardiovascular risk. To date, there is little information about the additional impact of this single nucleotide polymorphism (SNP) beyond glucose metabolism.We studied whether rs7903146 influenced postprandial lipid metabolism in three different populations (healthy young men, metabolic syndrome (MetS) patients and elderly persons). Eighty-eight healthy males were submitted to a single saturated fatty acid-rich test meal. Additionally, 110 middle-aged MetS patients and 20 healthy elderly persons (≥ 65 years) were submitted to three different dietary models followed by test meals. Minor allele homozygotes for rs7903146 showed a worse postprandial lipemia profile in young males, as seen by a lower HDL-cholesterol and Apo A1 concentration during the postprandial lipemia and a trend towards higher triglycerides (TG), than the other genotypes. In healthy elderly persons, carriers of the minor allele showed higher total cholesterol, LDL-cholesterol, Apo B and TG in the fasting state, and a higher postprandial area under the curve for total cholesterol, Apo B, small-triglyceride rich lipoprotein (TRL) cholesterol and small-(TRL) triglycerides. These results were accompanied by differential changes in adipokines. We did not observe any influence of rs7903146 on the postprandium of MetS patients.Healthy young males and elderly persons who are carriers of the mutant allele for rs7903146 have an impaired postprandial lipid metabolism that may be mediated by an alteration in adipokine regulation, and may be related to the higher cardiovascular risk observed in these persons.ClinicalTrials.gov NCT00429195.

A hanseníase é considerada um problema de saúde pública nos países em desenvolvimento. No período de 2001 a 2007, o Acre foi o 8º Estado com os maiores coeficientes de prevalência e incidência de hanseníase em todo o Brasil. Este é um estudo retrospectivo que utilizou os dados das fichas de notificação de casos de hanseníase do Sistema de Informação de Agravos de Notificação do município de Assis Brasil, Acre, entre 2003 e 2010. Os dados foram digitados e analisados no programa SPSS, sendo que médias e proporções foram comparadas com o Teste de Anova e o Teste do Qui-Quadrado. Foram notificados 25 casos novos, com coeficiente de detecção de 98,7/100.000 habitantes em 2010, sendo 56% casos índices e 44% contatos; oito (32%) casos de hanseníase paucibacilar e 17 (68%) de hanseníase multibacilar. Predominou a forma dimorfa (52%), seguido da forma tuberculóide (32%) e forma virchowiana (16%). A baciloscopia foi negativa em 75% dos testes. Nove pacientes foram considerados curados no tempo preconizado, um paciente necessitou de maior tempo de tratamento, oito pacientes ainda estavam em tratamento e seis casos tiveram evolução desconhecida. A alta frequência de casos de hanseníase multibacilar reforça a ideia da demora no diagnóstico e da dificuldade em detectar formas mais leves da doença, contribuindo para manter a transmissão, necessitando de maior ação do sistema de saúde.

O ensino médico há alguns anos vem passando por uma transição do modelo clássico teórico para abordagens práticas e baseadas em problemas. Fundamentando-se em uma abordagem prática ambulatorial, criou-se um projeto de extensão para o ensino simultâneo a alunos de diferentes anos do curso médico com uma população ribeirinha, em que cada acadêmico utilizou suas habilidades adquiridas no curso para a criação de um serviço ambulatorial (acolhimento, pré-consulta, consulta médica, vacinação e dispensação de medicamentos), de forma a promover um serviço de saúde. Esta ação ocorreu em áreas remotas da Amazônia brasileira, mostrando que é possível unir extensão e ensino na formação de médicos mais conscientes das diferentes realidades socioeconômicas e culturais brasileiras.

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