Educational disparities in brain health and dementia across Latin America and the United States.

BACKGROUND: Education influences brain health and dementia. However, its impact across regions, specifically Latin America (LA) and the United States (US), is unknown. METHODS: A total of 1412 participants comprising controls, patients with Alzheimer's disease (AD), and frontotemporal lobar degeneration (FTLD) from LA and the US were included. We studied the association of education with brain volume and functional connectivity while controlling for imaging quality and variability, age, sex, total intracranial volume (TIV), and recording type. RESULTS: Education influenced brain measures, explaining 24%-98% of the geographical differences. The educational disparities between LA and the US were associated with gray matter volume and connectivity variations, especially in LA and AD patients. Education emerged as a critical factor in classifying aging and dementia across regions. DISCUSSION: The results underscore the impact of education on brain structure and function in LA, highlighting the importance of incorporating educational factors into diagnosing, care, and prevention, and emphasizing the need for global diversity in research. HIGHLIGHTS: Lower education was linked to reduced brain volume and connectivity in healthy controls (HCs), Alzheimer's disease (AD), and frontotemporal lobar degeneration (FTLD). Latin American cohorts have lower educational levels compared to the those in the United States. Educational disparities majorly drive brain health differences between regions. Educational differences were significant in both conditions, but more in AD than FTLD. Education stands as a critical factor in classifying aging and dementia across regions.

The healthy beverage index is not associated with insulin resistance, prediabetes and type 2 diabetes risk in the Rotterdam Study.

PURPOSE: Whether beverage quality affects changes in glycaemic traits and type 2 diabetes (T2D) risk is unknown. We examined associations of a previously developed Healthy Beverage Index (HBI) with insulin resistance, and risk of prediabetes and T2D. METHODS: We included 6769 participants (59% female, 62.0 ± 7.8 years) from the Rotterdam Study cohort free of diabetes at baseline. Diet was assessed using food-frequency questionnaires at baseline. The HBI included 10 components (energy from beverages, meeting fluid requirements, water, coffee and tea, low-fat milk, diet drinks, juices, alcohol, full-fat milk, and sugar-sweetened beverages), with a total score ranging from 0 to 100. A higher score represents a healthier beverage pattern. Data on study outcomes were available from 1993 to 2015. Multivariable linear mixed models and Cox proportional-hazards regression models were used to examine associations of the HBI (per 10 points increment) with two measurements of HOMA-IR (a proxy for insulin resistance), and risk of prediabetes and T2D. RESULTS: During follow-up, we documented 1139 prediabetes and 784 T2D cases. Mean ± SD of the HBI was 66.8 ± 14.4. Higher HBI score was not associated with HOMA-IR (ß: 0.003; 95% CI - 0.007, 0.014), or with risk of prediabetes (HR: 1.01; 95% CI 0.97, 1.06), or T2D (HR: 1.01; 95% CI 0.96, 1.07). CONCLUSION: Our findings suggest no major role for overall beverage intake quality assessed with the HBI in insulin resistance, prediabetes and T2D incidence. The HBI may not be an adequate tool to assess beverage intake quality in our population.

[Metabolic and cardiorespiratory fitness changes in women undergoing a physical exercise program assisted by a mobile application. A non-randomized controlled study]. / Cambios metabólicos y de aptitud cardiorrespiratoria en mujeres intervenidas con un programa de ejercicio físico asistido con una aplicación móvil: un estudio controlado no randomizado.

Metabolic syndrome (MetS) is prevalent in our population. The purpose of this study is to evaluate the effect of physical exercise, assisted by a mobile application (m-Health), on cardiorespiratory fitness (ACR) and cardiovascular risk markers in women with metabolic disorders typical of MetS, and to compare it with the effect of exercise monitored face to face in women with similar characteristics. MATERIALS AND METHODS: Controlled experimental study with two arms. Forty-one women with metabolic disorders were recruited; 14 completed the study and, for convenience, formed the intervention group with m-Health or the control group with the Vida Sana Program, both carried out for ten weeks. ACR, body composition, anthropometry, and blood pressure (BP) were evaluated before and after the intervention. RESULTS: 95% of the women presented low and very low basal ACR. The group treated with m-Health after 10 weeks increased VO2max (% change: + 44.4; p = 0.035) and decreased waist circumference (% change: -2.6; p = 0.022) and DBP (% change: -14.1; p = 0.036). Meanwhile, the control group decreased waist circumference (% change: -6.5; p = 0.015) and DBP (% change: -12.2; p = 0.05) but did not change VO2 max. Comparisons between groups did not show differences. CONCLUSIONS: A physical exercise program via m-Health improved ACR and anthropometric parameters in women with cardiometabolic disorders.

Dynamic interventions to control COVID-19 pandemic: a multivariate prediction modelling study comparing 16 worldwide countries.

To date, non-pharmacological interventions (NPI) have been the mainstay for controlling the coronavirus disease-2019 (COVID-19) pandemic. While NPIs are effective in preventing health systems overload, these long-term measures are likely to have significant adverse economic consequences. Therefore, many countries are currently considering to lift the NPIs-increasing the likelihood of disease resurgence. In this regard, dynamic NPIs, with intervals of relaxed social distancing, may provide a more suitable alternative. However, the ideal frequency and duration of intermittent NPIs, and the ideal "break" when interventions can be temporarily relaxed, remain uncertain, especially in resource-poor settings. We employed a multivariate prediction model, based on up-to-date transmission and clinical parameters, to simulate outbreak trajectories in 16 countries, from diverse regions and economic categories. In each country, we then modelled the impacts on intensive care unit (ICU) admissions and deaths over an 18-month period for following scenarios: (1) no intervention, (2) consecutive cycles of mitigation measures followed by a relaxation period, and (3) consecutive cycles of suppression measures followed by a relaxation period. We defined these dynamic interventions based on reduction of the mean reproduction number during each cycle, assuming a basic reproduction number (R0) of 2.2 for no intervention, and subsequent effective reproduction numbers (R) of 0.8 and 0.5 for illustrative dynamic mitigation and suppression interventions, respectively. We found that dynamic cycles of 50-day mitigation followed by a 30-day relaxation reduced transmission, however, were unsuccessful in lowering ICU hospitalizations below manageable limits. By contrast, dynamic cycles of 50-day suppression followed by a 30-day relaxation kept the ICU demands below the national capacities. Additionally, we estimated that a significant number of new infections and deaths, especially in resource-poor countries, would be averted if these dynamic suppression measures were kept in place over an 18-month period. This multi-country analysis demonstrates that intermittent reductions of R below 1 through a potential combination of suppression interventions and relaxation can be an effective strategy for COVID-19 pandemic control. Such a "schedule" of social distancing might be particularly relevant to low-income countries, where a single, prolonged suppression intervention is unsustainable. Efficient implementation of dynamic suppression interventions, therefore, confers a pragmatic option to: (1) prevent critical care overload and deaths, (2) gain time to develop preventive and clinical measures, and (3) reduce economic hardship globally.

Associations of statin use with glycaemic traits and incident type 2 diabetes.

AIMS: There are several epidemiological studies on the association between statins and incident diabetes, but most of them lack details. In this study, we aimed to investigate the association of statin use with glycaemic traits and incident type 2 diabetes. METHODS: Using the prospective population-based Rotterdam Study, we included 9535 individuals free from diabetes at baseline (>45 years) during the study period between 1997 and 2012. Linear regression analysis was applied to examine the cross-sectional associations between statin use and glycaemic traits including fasting blood serum of glucose and insulin concentrations, and insulin resistance. In a longitudinal follow-up study, we applied a Cox regression analysis to determine adjusted hazard ratios (HR) for incident type 2 diabetes in new users of statins. RESULTS: The mean age at baseline was 64.3 ± 10.1 years and 41.7% were men. In the fully adjusted model, compared to never users of statins, baseline use of statins was associated with higher concentrations of serum fasting insulin (ß = 0.07; 95% CI: 0.02-0.13) and insulin resistance (ß = 0.09; 95% CI: 0.03-0.14). Ever use of statins was associated with a 38% higher risk of incident type 2 diabetes (HR = 1.38; 95% CI: 1.09-1.74). This risk was more prominent in subjects with impaired glucose homeostasis and in overweight/obese individuals. CONCLUSIONS: Individuals using statins may be at higher risk for hyperglycaemia, insulin resistance and eventually type 2 diabetes. Rigorous preventive strategies such as glucose control and weight reduction in patients when initiating statin therapy might help minimize the risk of diabetes.

GOOD SYNDROME: CYTOMEGALOVIRUS RETINITIS CASE CHALLENGE.

PURPOSE: To describe cytomegalovirus retinitis in a patient with Good syndrome (hypogammaglobulinemia and thymoma), ocular progression despite treatment and fatal outcome. METHODS: A 71-year-old woman with unilateral panuveitis of unknown cause and a history of thymoma resection was referred to the clinic. Visual acuity was 20/100 in her right eye and light perception in her left eye. In slit-lamp examination, the right eye had inferior, fine, pigmented keratic precipitates, 2+ anterior chamber cells, cataract, and 2+ vitreous cells, with no fundus detail and normal ocular ultrasound results. Left eye presented a white cataract, chronic hypotony, and increased choroidal thickness with calcifications. Laboratory evaluations showed normal or negative results for common causes of infection and inflammation. Prednisolone acetate eye drops were started, with improvement of AC inflammation. Cataract surgery was performed, reaching visual acuity of 20/30. Two years later, visual acuity had decreased and 2+ vitritis and retinitis were found. On clinical suspicion of masquerade syndrome, a vitrectomy biopsy was performed; pathologic assessments reported no data on ocular lymphoma. Leukopenia and lymphopenia were found: immunoglobulin levels, CD4 count, and viral load revealed systemic immunosuppression. The aqueous tap was positive for cytomegalovirus. Oral valganciclovir and intravitreal ganciclovir were initiated. RESULTS: In a patient with previous resection of thymoma and hypogammaglobulinemia, final diagnosis was Good syndrome, with cytomegalovirus retinitis being secondary to immunosuppression. Despite treatment, cytomegalovirus retinitis progressed and systemic deterioration resulted in mortal outcome. CONCLUSION: Good syndrome is an extremely rare disease, and association with cytomegalovirus retinitis is uncommon. To the authors' knowledge, only 14 cases exist in the literature.

Comparative genomics sheds light on transcription factor-mediated regulation in the extreme acidophilic Acidithiobacillia representatives.

Extreme acidophiles thrive in acidic environments, confront a multitude of challenges, and demonstrate remarkable adaptability in their metabolism to cope with the ever-changing environmental fluctuations, which encompass variations in temperature, pH levels, and the availability of electron acceptors and donors. The survival and proliferation of members within the Acidithiobacillia class rely on the deployment of transcriptional regulatory systems linked to essential physiological traits. The study of these transcriptional regulatory systems provides valuable insights into critical processes, such as energy metabolism and nutrient assimilation, and how they integrate into major genetic-metabolic circuits. In this study, we examined the transcriptional regulatory repertoires and potential interactions of forty-three Acidithiobacillia complete and draft genomes, encompassing nine species. To investigate the function and diversity of Transcription Factors (TFs) and their DNA Binding Sites (DBSs), we conducted a genome-wide comparative analysis, which allowed us to identify these regulatory elements in representatives of Acidithiobacillia. We classified TFs into gene families and compared their occurrence among all representatives, revealing conservation patterns across the class. The results identified conserved regulators for several pathways, including iron and sulfur oxidation, the main pathways for energy acquisition, providing new evidence for viable regulatory interactions and branch-specific conservation in Acidithiobacillia. The identification of TFs and DBSs not only corroborates existing experimental information for selected species, but also introduces novel candidates for experimental validation. Moreover, these promising candidates have the potential for further extension to new representatives within the class.

Good syndrome and cytomegalovirus retinitis: A literature review.

Good syndrome (GS) is a rare primary immunodeficiency in adults consisting of hypogammaglobulinemia and thymoma that affects both cellular and humoral immunity. It usually appears in patients between the 4th and 6th decade of life and affects both genders equally. Ophthalmological clinical presentation is highly variable; associations with herpetic keratitis, toxoplasmosis, and cytomegalovirus retinitis (CMVR) have been described. GS associated with CMVR is uncommon. Ophthalmologists may be the first to diagnose systemic disease and change the outcome. Only18 cases of CMVR have been described, most of them unilateral with poor visual outcomes. We discuss the clinical features of CMVR in patients with reported GS, pathogenesis, and outline a work-up for diagnosis. CMVR in an apparently healthy patient should encourage the clinician to search for human immunodeficiency virus (HIV) and non-HIV-associated immunosuppression.

Effectiveness of Resistance Training Program on Body Composition in Adults Following Vegan Diet versus Omnivorous Diet; Developed in Mobile Health Modality.

BACKGROUND: The vegan diet (VEGD) has gained popularity in recent years for ecological and ethical reasons, as well as for its health benefits. In addition to the type of diet, the resistance training program (RTP) plays a fundamental role as one of the main natural anabolic stimuli to increase musculoskeletal mass and reduce fat mass. METHODS: The study was a 16-week non-randomized controlled clinical trial consisting of three RTP sessions per week. The sample included 70 Chilean individuals, aged between 18 and 59 years, who had been following a VEGD or omnivorous diet (OMND) for the past 6 months. Four groups were established: Vegan Diet Resistance Training Program (VEGD-RTP), Vegan Diet Control (VEGD-C), Omnivorous Diet Resistance Training Program (OMND-RTP), and Omnivorous Diet Control (OMND-C). RESULTS: The sample consisted of 47 women and 23 men, with a mean age of 30.1 (±8.6) years. A reduction of 1.20% in the percentage of fat mass (%FM) was observed in the VEGD-RTP group (r = 0.554, p = 0.016), as well as a reduction of 0.70 kg in kilograms of fat mass (KFM) (r = 0.480, p = 0.036). The OMND-RTP group decreased %FM by 0.90% (r = 0.210, p = 0.432) and KFM by 0.50 kg (r = 0.109, p = 0.683). CONCLUSIONS: RTP combined with VEGD or OMND significantly reduced the percentage of fat mass, although its effect was more significant in the VEGD-RTP participants.

Strategies to promote language inclusion at 17 CTSA hubs.

The prioritization of English language in clinical research is a barrier to translational science. We explored promising practices to advance the inclusion of people who speak languages other than English in research conducted within and supported by NIH Clinical Translational Science Award (CTSA) hubs. Key informant interviews were conducted with representatives (n = 24) from CTSA hubs (n = 17). Purposive sampling was used to identify CTSA hubs focused on language inclusion. Hubs electing to participate were interviewed via Zoom. Thematic analysis was performed to analyze interview transcripts. We report on strategies employed by hubs to advance linguistic inclusion and influence institutional change that were identified. Strategies ranged from translations, development of culturally relevant materials and consultations to policies and procedural changes and workforce initiatives. An existing framework was adapted to conceptualize hub strategies. Language justice is paramount to bringing more effective treatments to all people more quickly. Inclusion will require institutional transformation and CTSA hubs are well positioned to catalyze change.

Association analysis between an epigenetic alcohol risk score and blood pressure.

Background: Epigenome-wide association studies have revealed multiple DNA methylation sites (CpGs) associated with alcohol consumption, an important lifestyle risk factor for cardiovascular diseases. Results: We generated an alcohol consumption epigenetic risk score (ERS) based on previously reported 144 alcohol-associated CpGs and examined the association of the ERS with systolic blood pressure (SBP), diastolic blood pressure (DBP), and hypertension (HTN) in 3,898 Framingham Heart Study (FHS) participants. We found an association of alcohol intake with the ERS in the meta-analysis with 0.09 units higher ERS per drink consumed per day (p < 0.0001). Cross-sectional analyses in FHS revealed that a one-unit increment of the ERS was associated with 1.93 mm Hg higher SBP (p = 4.64E-07), 0.68 mm Hg higher DBP (p = 0.006), and an odds ratio of 1.78 for HTN (p < 2E-16). Meta-analysis of the cross-sectional association of the ERS with BP traits in eight independent external cohorts (n = 11,544) showed similar relationships with blood pressure levels, i.e., a one-unit increase in ERS was associated with 0.74 (p = 0.002) and 0.50 (p = 0.0006) mm Hg higher SBP and DBP, but could not confirm the association with hypertension. Longitudinal analyses in FHS (n = 3,260) and five independent external cohorts (n = 4,021) showed that the baseline ERS was not associated with a change in blood pressure over time or with incident HTN. Conclusions: Our findings provide proof-of-concept that utilizing an ERS is a useful approach to capture the recent health consequences of lifestyle behaviors such as alcohol consumption.

Association analysis between an epigenetic risk score and blood pressure.

Background: Epigenome-wide association studies have revealed multiple DNA methylation sites (CpGs) associated with alcohol consumption, an important lifestyle risk factor for cardiovascular diseases. Results: We generated an alcohol consumption epigenetic risk score (ERS) based on previously reported 144 alcohol-associated CpGs and examined the association of the ERS with systolic blood pressure (SBP), diastolic blood pressure (DBP), and hypertension (HTN) in 3,898 Framingham Heart Study (FHS) participants. We found an association of alcohol intake with the ERS in the meta-analysis with 0.09 units higher ERS per drink consumed per day (p < 0.0001). Cross-sectional analyses in FHS revealed that a one-unit increment of the ERS was associated with 1.93 mm Hg higher SBP (p = 4.64E-07), 0.68 mm Hg higher DBP (p = 0.006), and an odds ratio of 1.78 for HTN (p < 2E-16). Meta-analysis of the cross-sectional association of the ERS with BP traits in eight independent external cohorts (n = 11,544) showed similar relationships with blood pressure levels, i.e., a one-unit increase in ERS was associated with 0.74 (p = 0.002) and 0.50 (p = 0.0006) mm Hg higher SBP and DBP, but could not confirm the association with hypertension. Longitudinal analyses in FHS (n = 3,260) and five independent external cohorts (n = 4,021) showed that the baseline ERS was not associated with a change in blood pressure over time or with incident HTN. Conclusions: Our findings provide proof-of-concept that utilizing an ERS is a useful approach to capture the recent health consequences of lifestyle behaviors such as alcohol consumption.

Eurypsychrophilic acidophiles: From (meta)genomes to low-temperature biotechnologies.

Low temperature and acidic environments encompass natural milieus such as acid rock drainage in Antarctica and anthropogenic sites including drained sulfidic sediments in Scandinavia. The microorganisms inhabiting these environments include polyextremophiles that are both extreme acidophiles (defined as having an optimum growth pH < 3), and eurypsychrophiles that grow at low temperatures down to approximately 4°C but have an optimum temperature for growth above 15°C. Eurypsychrophilic acidophiles have important roles in natural biogeochemical cycling on earth and potentially on other planetary bodies and moons along with biotechnological applications in, for instance, low-temperature metal dissolution from metal sulfides. Five low-temperature acidophiles are characterized, namely, Acidithiobacillus ferriphilus, Acidithiobacillus ferrivorans, Acidithiobacillus ferrooxidans, "Ferrovum myxofaciens," and Alicyclobacillus disulfidooxidans, and their characteristics are reviewed. Our understanding of characterized and environmental eurypsychrophilic acidophiles has been accelerated by the application of "omics" techniques that have aided in revealing adaptations to low pH and temperature that can be synergistic, while other adaptations are potentially antagonistic. The lack of known acidophiles that exclusively grow below 15°C may be due to the antagonistic nature of adaptations in this polyextremophile. In conclusion, this review summarizes the knowledge of eurypsychrophilic acidophiles and places the information in evolutionary, environmental, biotechnological, and exobiology perspectives.

Body Adiposity Partially Mediates the Association between FTO rs9939609 and Lower Adiponectin Levels in Chilean Children.

Children carrying the minor allele 'A' at the fat mass and obesity-associated protein (FTO) gene have higher obesity prevalence. We examined the link between FTO rs9939609 polymorphism and plasma adiponectin and the mediating role of body adiposity, in a cross-sectional study comprising 323 children aged 6-11 years. Adiponectin and FTO genotypes were assessed using a commercial kit and a real-time polymerase chain reaction with high-resolution melting analysis, respectively. Body adiposity included body mass index z-score, body fat percentage and waist-to-hip ratio. To investigate adiponectin (outcome) associations with FTO and adiposity, linear regressions were implemented in additive models and across genotype categories, adjusting for sex, age and Tanner's stage. Using mediation analysis, we determined the proportion of the association adiponectin-FTO mediated by body adiposity. Lower adiponectin concentrations were associated with one additional risk allele (ßadditive = -0.075 log-µg/mL [-0.124; -0.025]), a homozygous risk genotype (ßAA/TT = -0.150 [-0.253; -0.048]) and a higher body mass index z-score (ß = -0.130 [-0.176; -0.085]). Similar results were obtained for body fat percentage and waist-to-hip ratio. Body adiposity may mediate up to 29.8% of the FTO-adiponectin association. In conclusion, FTO rs9939609-related differences in body adiposity may partially explain lower adiponectin concentrations. Further studies need to disentangle the biological pathways independent from body adiposity.

Association of habitual coffee consumption and kidney function: A prospective analysis in the Rotterdam Study.

BACKGROUND & AIMS: Population-based studies have suggested a protective effect of coffee against development of chronic kidney disease (CKD), possibly through coffee's anti-inflammatory and antioxidant compounds. Studies on coffee and kidney function decline in the general population are scarce. We studied associations of habitual coffee consumption with repeated assessments of estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (ACR). METHODS: We used data from 7,914 participants of the population-based Rotterdam Study. Baseline coffee consumption data (cups/day) were obtained from home interviews and validated food frequency questionnaires (1997-2008). Repeated assessments of eGFR (ml/min per 1.73 m2, 1997-2014) were calculated according to the creatinine-based CKD Epidemiology Collaboration equation of 2012. Repeated assessments of urinary albumin and creatinine were used to estimate ACR (mg/g, 2006-2014). Data were analyzed by applying linear mixed models, adjusted for sociodemographic, lifestyle and dietary factors, and cardiovascular disease risk factors. Predefined subgroup analyses were performed stratified by CKD risk factors. RESULTS: Participants' mean (SD) baseline age was 66 (10) years, 57% were women and median [IQR] coffee consumption was 3.0 [2.0, 5.0] cups/day. Those drinking more coffee were more likely to smoke, and to have type 2 diabetes (T2D) and obesity. Mean eGFR was 79 (15) ml/min per 1.73 m2. In the total study population, coffee was not associated with longitudinal eGFR during a median of 5.4 years of follow-up (ß = 0.04 ml/min per 1.73 m2 per one cup/day [95% CI: -0.10,0.18]). However, among those aged >70 years, one additional coffee cup/day was associated with on average 0.84 (0.51,1.18) ml/min per 1.73 m2 higher longitudinal eGFR. Among obese participants this estimate was 0.32 (0.01,0.63). A protective trend was also observed among former smokers (0.17 [-0.03,0.39]) and those with T2D (0.42 [-0.05,0.88]). Coffee was not associated with longitudinal ACR (0.01 mg/ml [-0.01,0.02]). CONCLUSION: While coffee was not associated with eGFR and ACR in the total population, more coffee consumption was associated with higher longitudinal eGFR among those at higher risk for CKD, i.e., among those aged 70+ and obese participants. These findings require confirmation in other prospective cohort studies.

C-reactive protein partially mediates the inverse association between coffee consumption and risk of type 2 diabetes: The UK Biobank and the Rotterdam study cohorts.

BACKGROUND: Coffee is among the most consumed beverages worldwide. Coffee consumption has been associated with lower risk of type 2 diabetes mellitus (T2D), but underlying mechanisms are not well understood. We aimed to study the role of classic and novel-T2D biomarkers with anti- or pro-inflammatory activity in the association between habitual coffee intake and T2D risk. Furthermore, we studied differences by coffee types and smoking status in this association. METHODS: Using two large population-based cohorts, the UK-Biobank (UKB; n = 145,368) and the Rotterdam Study (RS; n = 7111), we investigated associations of habitual coffee consumption with incident T2D and repeated measures of insulin resistance (HOMA-IR), using Cox proportional hazards and mixed effect models, respectively. Additionally, we studied associations between coffee and subclinical inflammation biomarkers including C-reactive protein (CRP) and IL-13, and adipokines, such as adiponectin and leptin, using linear regression models. Next, we performed formal causal mediation analyses to investigate the role of coffee-associated biomarkers in the association of coffee with T2D. Finally, we evaluated effect modification by coffee type and smoking. All models were adjusted for sociodemographic, lifestyle and health-related factors. RESULTS: During a median follow-up of 13.9 (RS) and 7.4 (UKB) years, 843 and 2290 incident T2D cases occurred, respectively. A 1 cup/day increase in coffee consumption was associated with 4% lower T2D risk (RS, HR = 0.96 [95%CI 0.92; 0.99], p = 0.045; UKB, HR = 0.96 [0.94; 0.98], p < 0.001), with lower HOMA-IR (RS, log-transformed ß = -0.017 [-0.024;-0.010], p < 0.001), and with lower CRP (RS, log-transformed ß = -0.014 [-0.022;-0.005], p = 0.002; UKB, ß = -0.011 [-0.012;-0.009], p < 0.001). We also observed associations of higher coffee consumption with higher serum adiponectin and IL-13 concentrations, and with lower leptin concentrations. Coffee-related CRP levels partially mediated the inverse association of coffee intake with T2D incidence (average mediation effect RS ß = 0.105 (0.014; 0.240), p = 0.016; UKB ß = 6.484 (4.265; 9.339), p < 0.001), with a proportion mediated by CRP from 3.7% [-0.012%; 24.4%] (RS) to 9.8% [5,7%; 25.8%] (UKB). No mediation effect was observed for the other biomarkers. Coffee-T2D and coffee-CRP associations were generally stronger among consumers of ground (filtered or espresso) coffee and among never and former smokers. CONCLUSIONS: Lower subclinical inflammation may partially mediate the beneficial association between coffee consumption and lower T2D risk. Consumers of ground coffee and non-smokers may benefit the most. KEYWORDS (MESH TERMS): coffee consumptions; diabetes mellitus, type 2; inflammation; adipokines; biomarkers; mediation analysis; follow-up studies.

Factors associated with healthy aging in Latin American populations.

Latin American populations may present patterns of sociodemographic, ethnic and cultural diversity that can defy current universal models of healthy aging. The potential combination of risk factors that influence aging across populations in Latin American and Caribbean (LAC) countries is unknown. Compared to other regions where classical factors such as age and sex drive healthy aging, higher disparity-related factors and between-country variability could influence healthy aging in LAC countries. We investigated the combined impact of social determinants of health (SDH), lifestyle factors, cardiometabolic factors, mental health symptoms and demographics (age, sex) on healthy aging (cognition and functional ability) across LAC countries with different levels of socioeconomic development using cross-sectional and longitudinal machine learning models (n = 44,394 participants). Risk factors associated with social and health disparities, including SDH (ß > 0.3), mental health (ß > 0.6) and cardiometabolic risks (ß > 0.22), significantly influenced healthy aging more than age and sex (with null or smaller effects: ß < 0.2). These heterogeneous patterns were more pronounced in low-income to middle-income LAC countries compared to high-income LAC countries (cross-sectional comparisons), and in an upper-income to middle-income LAC country, Costa Rica, compared to China, a non-upper-income to middle-income LAC country (longitudinal comparisons). These inequity-associated and region-specific patterns inform national risk assessments of healthy aging in LAC countries and regionally tailored public health interventions.

Dietary and supplemental intake of vitamins C and E is associated with altered DNA methylation in an epigenome-wide association study meta-analysis.

BACKGROUND: Dietary intake of antioxidants such as vitamins C and E protect against oxidative stress, and may also be associated with altered DNA methylation patterns. METHODS: We meta-analysed epigenome-wide association study (EWAS) results from 11,866 participants across eight population-based cohorts to evaluate the association between self-reported dietary and supplemental intake of vitamins C and E with DNA methylation. EWAS were adjusted for age, sex, BMI, caloric intake, blood cell type proportion, smoking status, alcohol consumption, and technical covariates. Significant results of the meta-analysis were subsequently evaluated in gene set enrichment analysis (GSEA) and expression quantitative trait methylation (eQTM) analysis. RESULTS: In meta-analysis, methylation at 4,656 CpG sites was significantly associated with vitamin C intake at FDR ≤ 0.05. The most significant CpG sites associated with vitamin C (at FDR ≤ 0.01) were enriched for pathways associated with systems development and cell signalling in GSEA, and were associated with downstream expression of genes enriched in the immune response in eQTM analysis. Furthermore, methylation at 160 CpG sites was significantly associated with vitamin E intake at FDR ≤ 0.05, but GSEA and eQTM analysis of the top most significant CpG sites associated with vitamin E did not identify significant enrichment of any biological pathways investigated. CONCLUSIONS: We identified significant associations of many CpG sites with vitamin C and E intake, and our results suggest that vitamin C intake may be associated with systems development and the immune response.

Dairy Product Consumption in Relation to Incident Prediabetes and Longitudinal Insulin Resistance in the Rotterdam Study.

Evidence suggests neutral or moderately beneficial effects of dairy intake on type 2 diabetes mellitus risk. Nevertheless, evidence on associations with early phases of type 2 diabetes remains inconsistent. We aimed to examine associations between dairy-type intake with prediabetes risk and longitudinal insulin resistance. The analytic sample consisted of 6770 participants (aged 62 ± 4 years, 59% female) free of (pre-)diabetes at baseline from the prospective population-based Rotterdam Study. Dairy intake was measured at baseline using food frequency questionnaires. Data on prediabetes (fasting blood glucose 6.1-6.9 mmol/L or non-fasting 7.7-11.1 mmol/L) and the longitudinal homeostatic model assessment of insulin resistance (HOMA-IR) were available from 1993-2015. Associations with these outcomes were analyzed with dairy intake in quartiles (Q4 vs. Q1) and continuous using multivariable Cox proportional hazard models and linear mixed models. During a mean follow-up of 11.3 ± 4.8 years, 1139 incident prediabetes cases were documented (18.8%). In models adjusting for sociodemographic, lifestyle and dietary factors, a higher intake of high-fat yogurt was associated with lower prediabetes risk (HRQ4vsQ1 0.70, 95% CI 0.54-0.91 and HRserving/day 0.67, 0.51-0.89). In addition, a higher intake of high-fat milk was associated with lower prediabetes risk (HRQ4vsQ1 0.81, 0.67-0.97, HRserving/day 0.88, 0.79-0.99). Associations were found for low-fat dairy, low-fat milk and total cheese with a higher prediabetes risk (HRserving/day ranging from 1.05-1.07, not significant in quartiles). Associations with longitudinal HOMA-IR were similar to prediabetes for high-fat yogurt, low-fat dairy and low-fat milk. Fermented dairy, low-fat yogurt, high-fat cheese, cream and ice cream were not associated with the outcomes. In conclusion, a higher intake of high-fat yogurt was associated with a lower prediabetes risk and lower longitudinal insulin resistance. Additionally, high-fat milk was associated with a lower prediabetes risk. Some low-fat dairy types were inconsistently associated with these outcomes. Studies are needed to confirm associations and to examine the influence of confounding by population characteristics.