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BACKGROUND AND AIMS: We demonstrated in the randomized 18-month DIRECT PLUS trial (n = 294) that a Mediterranean (MED) diet, supplemented with polyphenol-rich Mankai duckweed, green tea, and walnuts and restricted in red/processed meat, caused substantial intrahepatic fat (IHF%) loss compared with 2 other healthy diets, reducing NAFLD by half, regardless of similar weight loss. Here, we investigated the baseline proteomic profile associated with IHF% and the changes in proteomics associated with IHF% changes induced by lifestyle intervention. APPROACH AND RESULTS: We calculated IHF% by proton magnetic resonance spectroscopy (normal IHF% <5% and abnormal IHF% ≥5%). We assayed baseline and 18-month samples for 95 proteomic biomarkers.Participants (age = 51.3 ± 10.8 y; 89% men; and body mass index = 31.3 ± 3.9 kg/m 2 ) had an 89.8% 18-month retention rate; 83% had eligible follow-up proteomics measurements, and 78% had follow-up proton magnetic resonance spectroscopy. At baseline, 39 candidate proteins were significantly associated with IHF% (false discovery rate <0.05), mostly related to immune function pathways (eg, hydroxyacid oxidase 1). An IHF% prediction based on the DIRECT PLUS by combined model ( R2 = 0.47, root mean square error = 1.05) successfully predicted IHF% ( R2 = 0.53) during testing and was stronger than separately inputting proteins/traditional markers ( R2 = 0.43/0.44). The 18-month lifestyle intervention induced changes in 18 of the 39 candidate proteins, which were significantly associated with IHF% change, with proteins related to metabolism, extracellular matrix remodeling, and immune function pathways. Thrombospondin-2 protein change was higher in the green-MED compared to the MED group, beyond weight and IHF% loss ( p = 0.01). Protein principal component analysis revealed differences in the third principal component time distinct interactions across abnormal/normal IHF% trajectory combinations; p < 0.05 for all). CONCLUSIONS: Our findings suggest novel proteomic signatures that may indicate MRI-assessed IHF state and changes during lifestyle intervention. Specifically, carbonic anhydrase 5A, hydroxyacid oxidase 1, and thrombospondin-2 protein changes are independently associated with IHF% change, and thrombospondin-2 protein change is greater in the green-MED/high polyphenols diet.
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BACKGROUND AND AIMS: Amiodarone-related interstitial lung disease (ILD) is the most severe adverse effect of amiodarone treatment. Most data on amiodarone-related ILD are derived from periods when amiodarone was given at higher doses than currently used. METHODS: A nationwide population-based study was conducted among patients with incident atrial fibrillation (AF) between 1 December 1999 and 31 December 31 2021. Amiodarone-exposed patients were matched 1:1 with controls unexposed to amiodarone based on age, sex, ethnicity, and AF diagnosis duration. The final patient cohort included only matched pairs where amiodarone therapy was consistent throughout follow-up. Directed acyclic graphs and inverse probability treatment weighting (IPTW) modelling were used. Patients with either prior ILD or primary lung cancer (PLC) were excluded. The primary outcome was the incidence of any ILD. Secondary endpoints were death and PLC. RESULTS: The final cohort included 6039 amiodarone-exposed patients who were matched with unexposed controls. The median age was 73.3 years, and 51.6% were women. After a mean follow-up of 4.2 years, ILD occurred in 242 (2.0%) patients. After IPTW, amiodarone exposure was not significantly associated with ILD [hazard ratio (HR): 1.45, 95% confidence interval (CI): 0.97, 2.44, P = 0.09]. There was a trivial higher relative risk of ILD among amiodarone-exposed patients between Years 2 and 8 of follow-up [maximal risk ratio (RR): 1.019]. Primary lung cancer occurred in 97 (0.8%) patients. After IPTW, amiodarone was not associated with PLC (HR: 1.18, 95% CI: 0.76, 2.08, P = 0.53). All-cause death occurred in 2185 (18.1%) patients. After IPTW, amiodarone was associated with reduced mortality risk (HR: 0.65, 95% CI: 0.60, 0.72, P < 0.001). The results were consistent across a variety of sensitivity analyses. CONCLUSION: In a contemporary AF population, low-dose amiodarone was associated with a trend towards increased risk of ILD (15%-45%) but a clinically negligible change in absolute risk (maximum of 1.8%), no increased risk of PLC, and a lower risk of all-cause mortality.
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Amiodarona , Fibrilação Atrial , Doenças Pulmonares Intersticiais , Neoplasias Pulmonares , Humanos , Feminino , Idoso , Masculino , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/epidemiologia , Antiarrítmicos/efeitos adversos , Israel/epidemiologia , Neoplasias Pulmonares/tratamento farmacológicoRESUMO
Obesity is associated with negative effects on the brain. We exploit Artificial Intelligence (AI) tools to explore whether differences in clinical measurements following lifestyle interventions in overweight population could be reflected in brain morphology. In the DIRECT-PLUS clinical trial, participants with criterion for metabolic syndrome underwent an 18-month lifestyle intervention. Structural brain MRIs were acquired before and after the intervention. We utilized an ensemble learning framework to predict Body-Mass Index (BMI) scores, which correspond to adiposity-related clinical measurements from brain MRIs. We revealed that patient-specific reduction in BMI predictions was associated with actual weight loss and was significantly higher in active diet groups compared to a control group. Moreover, explainable AI (XAI) maps highlighted brain regions contributing to BMI predictions that were distinct from regions associated with age prediction. Our DIRECT-PLUS analysis results imply that predicted BMI and its reduction are unique neural biomarkers for obesity-related brain modifications and weight loss.
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Inteligência Artificial , Aprendizado Profundo , Humanos , Índice de Massa Corporal , Encéfalo/diagnóstico por imagem , Estilo de Vida , Imageamento por Ressonância Magnética , Obesidade/diagnóstico por imagem , Obesidade/terapia , Obesidade/complicações , Sobrepeso/diagnóstico por imagem , Sobrepeso/terapia , Redução de PesoRESUMO
BACKGROUND: The safety and efficacy of treatment with P2Y12 adenosine-diphosphate receptor inhibitors (P2Y12-RI) before coronary angiography among patients with non-ST-segment elevation acute coronary syndromes (NSTEACS) are questionable. AIMS: To assess the pretreatment rate with P2Y12-RI and its association with ischemic and bleeding risks among patients with NSTEACS. METHODS: The study comprised patients with NSTEACS referred for coronary angiography and included in the Acute Coronary Syndrome Israeli Surveys between 2013 and 2021. Patients were divided into two groups according to the timing of P2Y12-RI loading concerning coronary angiography: pretreatment and posttreatment. The primary endpoints were 30-day major adverse cardiovascular events (MACE; composite of cardiovascular mortality, myocardial infarction, stroke, stent thrombosis, and urgent revascularization) and 1-year all-cause mortality. RESULTS: Of 3076 patients, 2423 (78.8%) received pretreatment with a P2Y12-RI, and 653 (21.2%) received P2Y12-RI posttreatment. Prasugrel and ticagrelor were used more in the posttreatment group compared to the pretreatment group (16% vs. 6% and 38% vs. 25%, respectively, p < 0.001 for both). No difference was observed in the rate of 30-day MACE comparing pretreatment and posttreatment (5.3% vs. 2.2%, respectively, p = 0.62). A sensitivity analysis of 30-day MACE among patients from the 2021 survey demonstrated similar results (2.5% in the posttreatment group vs. 8.0% in the pretreatment group, p = 0.13). There were no differences in 1-year all-cause mortality rates between the pretreatment and posttreatment groups (4.8% vs. 3.8%, p = 0.31). CONCLUSIONS: Among patients with NSTEACS referred for an invasive strategy, the P2Y12-RI posttreatment strategy was associated with similar 30-day and 1-year MACE as the pretreatment strategy. These large-scale, multicenter, real-world data provide reassurance on the safety and efficacy of delaying P2Y12-IR until after coronary stratification to improve clinical decision-making.
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AIM: To explore the effect of Mankai, a cultivated aquatic duckweed green plant, on postprandial glucose (PG) excursions in type 2 diabetes (T2D). METHODS: In a 4-week, randomized crossover-controlled trial, we enrolled 45 adults with T2D (HbA1c range: 6.5%-8.5%) from two sites in Israel. Participants were randomized to drink Mankai (200 mL of raw-fresh-aquatic plant + 100 mL of water, 40 kcal, ~10 g of dry matter equivalent) or water (300 mL) following dinner, for 2 weeks each, with a 4-day washout interval, without dietary, physical activity or pharmacotherapy alterations. We used continuous glucose monitoring (CGM) devices. RESULTS: Forty patients (adherence rate = 88.5%; 743 person-intervention-days, 68.9% men, age = 64 years, HbA1c = 6.8%) completed the study with a consistent diet and complete CGM reads. Only two-thirds of the individuals responded beneficially to Mankai. Overall, Mankai significantly lowered the PG peak by 19.3% (∆peak = 24.3 ± 16.8 vs. 30.1 ± 18.5 mg/dL; P < .001) and delayed the time-to-peak by 20.0% (112.5 [interquartile range: 75-135] vs. 90 [60-105] min; P < .001) compared with water. The PG incline and decline slopes were shallower following postdinner Mankai (incline slope: 16.8 vs. water: 29.9 mg/[dL h]; P < .001; decline slope: -6.1 vs. water: -7.9 mg/[dL h]; P < .01). Mean postprandial net incremental area-under-the-glucose-curve was lowered by 20.1% with Mankai compared with water (P = .03). Results were consistent across several sensitivity and subgroup analyses, including across antidiabetic pharmacotherapy treatment groups. Within 2 weeks, the triglycerides/high-density lipoprotein cholesterol ratio in the Mankai group (-0.5 ± 1.3) decreased versus water (+0.3 ± 1.5, P = .05). CONCLUSIONS: Mankai consumption may mitigate the PG response in people with T2D with an ~20% improvement in glycaemic values. These findings provide case-study evidence for plant-based treatments in T2D to complement a healthy lifestyle and pharmacotherapy.
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BACKGROUND: Diabetes mellitus (DM) is associated with increased risk of embolic complications in non-valvular atrial fibrillation (NVAF). Impaired renal function (IRF) increases the risk of stroke as well, but this finding is not consistent among all studies. Our aim was to assess the incidence rates and risk of ischemic stroke and mortality by baseline Estimated Glomerular Filtration Rate (eGFR) levels Among individuals with AF and DM. METHODS: A prospective, historical cohort study using the Clalit Health Services electronic medical records database. Among patients with AF and DM, we compared three groups according to eGFR levels: eGFR ≥ 60, between 30 and 60, and ≤ 30 (mL/min/1.73m2). RESULTS: A total of 17,567 cases were included in the final analysis; of them, 11,013 (62.7%) had eGFR ≥ 60, 4930 (28%) had eGFR between 30 and 60, and 1624 (9.24%) with eGFR ≤ 30. The incidence of stroke per 100 person-years in the three study groups was: 1.88, 2.69, and 3.34, respectively (p < 0.001). IRF was associated with increased risk of stroke in univariate analysis, but not after multivariate adjustment (Adjusted Hazard Ratio (AHR) 0.96 {95%CI; 0.74-1.25} for eGFR 30-60 and 0.96 {95%CI; 0.60-1.55} for eGFR ≤ 30). Mortality per 100 person-years was 10.78, 21.49, and 41.55, respectively (p < 0.001). IRF was associated with increased mortality risk in univariate analysis, as well as in multivariate analysis (AHR 1.08 {95%CI; 0.98-1.18} for eGFR 30-60, and 1.59 {95%CI; 1.37-1.85} for eGFR ≤ 30. CONCLUSION: In patients with NVAF and DM, IRF was not associated with an increased risk of stroke, but severe IRF (eGFR ≤ 30) was associated with increased mortality risk.
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Fibrilação Atrial , Diabetes Mellitus , Insuficiência Renal , Acidente Vascular Cerebral , Humanos , Fibrilação Atrial/epidemiologia , Estudos de Coortes , Estudos Prospectivos , Taxa de Filtração Glomerular , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Diabetes Mellitus/epidemiologia , Fatores de RiscoRESUMO
BACKGROUND: Epigenetic age is an estimator of biological age based on DNA methylation; its discrepancy from chronologic age warrants further investigation. We recently reported that greater polyphenol intake benefitted ectopic fats, brain function, and gut microbiota profile, corresponding with elevated urine polyphenols. The effect of polyphenol-rich dietary interventions on biological aging is yet to be determined. METHODS: We calculated different biological aging epigenetic clocks of different generations (Horvath2013, Hannum2013, Li2018, Horvath skin and blood2018, PhenoAge2018, PCGrimAge2022), their corresponding age and intrinsic age accelerations, and DunedinPACE, all based on DNA methylation (Illumina EPIC array; pre-specified secondary outcome) for 256 participants with abdominal obesity or dyslipidemia, before and after the 18-month DIRECT PLUS randomized controlled trial. Three interventions were assigned: healthy dietary guidelines, a Mediterranean (MED) diet, and a polyphenol-rich, low-red/processed meat Green-MED diet. Both MED groups consumed 28 g walnuts/day (+ 440 mg/day polyphenols). The Green-MED group consumed green tea (3-4 cups/day) and Mankai (Wolffia globosa strain) 500-ml green shake (+ 800 mg/day polyphenols). Adherence to the Green-MED diet was assessed by questionnaire and urine polyphenols metabolomics (high-performance liquid chromatography quadrupole time of flight). RESULTS: Baseline chronological age (51.3 ± 10.6 years) was significantly correlated with all methylation age (mAge) clocks with correlations ranging from 0.83 to 0.95; p < 2.2e - 16 for all. While all interventions did not differ in terms of changes between mAge clocks, greater Green-Med diet adherence was associated with a lower 18-month relative change (i.e., greater mAge attenuation) in Li and Hannum mAge (beta = - 0.41, p = 0.004 and beta = - 0.38, p = 0.03, respectively; multivariate models). Greater Li mAge attenuation (multivariate models adjusted for age, sex, baseline mAge, and weight loss) was mostly affected by higher intake of Mankai (beta = - 1.8; p = 0.061) and green tea (beta = - 1.57; p = 0.0016) and corresponded with elevated urine polyphenols: hydroxytyrosol, tyrosol, and urolithin C (p < 0.05 for all) and urolithin A (p = 0.08), highly common in green plants. Overall, participants undergoing either MED-style diet had ~ 8.9 months favorable difference between the observed and expected Li mAge at the end of the intervention (p = 0.02). CONCLUSIONS: This study showed that MED and green-MED diets with increased polyphenols intake, such as green tea and Mankai, are inversely associated with biological aging. To the best of our knowledge, this is the first clinical trial to indicate a potential link between polyphenol intake, urine polyphenols, and biological aging. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03020186.
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Dieta Mediterrânea , Microbioma Gastrointestinal , Humanos , Adulto , Pessoa de Meia-Idade , Metilação de DNA , Envelhecimento/genética , EtnicidadeRESUMO
BACKGROUND: Existing cardiac disease contributes to poor outcome in patients with coronavirus disease 2019 (COVID-19). Little information exists regarding COVID-19 infection in patients with a cardiac implantable electronic device (CIED). OBJECTIVES: To assess the association between CIEDs and severity of COVID-19 infection. METHODS: We performed a retrospective analysis including 13,000 patients > 18 years old with COVID-19 infection between January and December 2020. Patients with COVID-19 who had a permanent pacemaker or defibrillator were matched 1:4 based on age and sex followed by univariate and multivariate analyses. Baseline characteristics and clinical outcomes were assessed. RESULTS: Forty patients with CIED and 160 patients without CIED were included in the current analysis. Mean age was 72.6 ± 13 years, and approximately 50% were females. Majority of the patients in the study arm had a pacemaker (63%), whereas only 15 patients (37%) had a defibrillator. Patients with COVID-19 and CIED presented more often with atrial fibrillation, coronary artery disease, heart failure, hypertension, diabetes, and chronic kidney disease. They were more likely to be hospitalized in the intensive care unit (ICU) and required more ventilatory support (35% vs. 18.3%). Thirty-day mortality (22.5% vs. 13.8%) and 1-year mortality (25% vs. 15%) were higher among patients with COVID-19 and CIED. CONCLUSIONS: Patients with COVID-19 and CIED had a significantly higher prevalence of co-morbidities that were associated with increased mortality. Although, CIED by itself was not found as an independent risk factor for morbidity and mortality, it may serve as a warning for severe illness with COVID-19.
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COVID-19 , Desfibriladores Implantáveis , Marca-Passo Artificial , Feminino , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Adolescente , Masculino , Estudos Retrospectivos , Desfibriladores Implantáveis/efeitos adversos , COVID-19/epidemiologia , COVID-19/terapia , COVID-19/etiologia , Marca-Passo Artificial/efeitos adversos , Fatores de RiscoRESUMO
BACKGROUND & AIMS: We evaluated the efficacy and safety of diet-modulated autologous fecal microbiota transplantation (aFMT) for treatment of weight regain after the weight-loss phase. METHODS: In the DIRECT PLUS (Dietary Intervention Randomized Controlled Trial Polyphenols-Unprocessed) weight-loss trial (May 2017 through July 2018), abdominally obese or dyslipidemic participants in Israel were randomly assigned to healthy dietary guidelines, Mediterranean diet, and green-Mediterranean diet weight-loss groups. All groups received free gym membership and physical activity guidelines. Both isocaloric Mediterranean groups consumed 28 g/d walnuts (+440 mg/d polyphenols provided). The green-Mediterranean dieters also consumed green tea (3-4 cups/d) and a Wolffia globosa (Mankai strain, 100 g/d) green shake (+800 mg/d polyphenols provided). After 6 months (weight-loss phase), 90 eligible participants (mean age, 52 years; mean weight loss, 8.3 kg) provided a fecal sample that was processed into aFMT by frozen, opaque, and odorless capsules. The participants were then randomly assigned to groups that received 100 capsules containing their own fecal microbiota or placebo until month 14. The primary outcome was regain of the lost weight over the expected weight-regain phase (months 6-14). Secondary outcomes were gastrointestinal symptoms, waist circumference, glycemic status, and changes in the gut microbiome, as measured by metagenomic sequencing and 16s ribosomal RNA. We validated the results in a parallel in vivo study of mice specifically fed with Mankai compared with control chow diet. RESULTS: Of the 90 participants in the aFMT trial, 96% ingested at least 80 of 100 oral aFMT or placebo frozen capsules during the transplantation period. No aFMT-related adverse events or symptoms were observed. For the primary outcome, although no significant differences in weight regain were observed among the participants in the different lifestyle interventions during months 6-14 (aFMT, 30.4% vs placebo, 40.6%; P = .28), aFMT significantly attenuated weight regain in the green-Mediterranean group (aFMT, 17.1%, vs placebo, 50%; P = .02), but not in the dietary guidelines (P = .57) or Mediterranean diet (P = .64) groups (P for the interaction = .03). Accordingly, aFMT attenuated waist circumference gain (aFMT, 1.89 cm vs placebo, 5.05 cm; P = .01) and insulin rebound (aFMT, -1.46 ± 3.6 µIU/mL vs placebo, 1.64 ± 4.7 µIU/mL; P = .04) in the green-Mediterranean group but not in the dietary guidelines or Mediterranean diet (P for the interaction = .04 and .03, respectively). The green-Mediterranean diet was the only intervention to induce a significant change in microbiome composition during the weight-loss phase, and to prompt preservation of weight-loss-associated specific bacteria and microbial metabolic pathways (mainly microbial sugar transport) after the aFMT. In mice, Mankai-modulated aFMT in the weight-loss phase compared with control diet aFMT, significantly prevented weight regain and resulted in better glucose tolerance during a high-fat diet-induced regain phase (all, P < .05). CONCLUSIONS: Autologous FMT, collected during the weight-loss phase and administrated in the regain phase, might preserve weight loss and glycemic control, and is associated with specific microbiome signatures. A high-polyphenols, green plant-based or Mankai diet better optimizes the microbiome for an aFMT procedure. ClinicalTrials.gov number, NCT03020186.
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Transplante de Microbiota Fecal , Obesidade/dietoterapia , Aumento de Peso , Adulto , Animais , Dieta Mediterrânea , Modelos Animais de Doenças , Exercício Físico , Feminino , Humanos , Israel , Estilo de Vida , Masculino , Camundongos , Pessoa de Meia-Idade , Circunferência da Cintura , Redução de PesoRESUMO
BACKGROUND: Mediterranean (MED) diet is a rich source of polyphenols, which benefit adiposity by several mechanisms. We explored the effect of the green-MED diet, twice fortified in dietary polyphenols and lower in red/processed meat, on visceral adipose tissue (VAT). METHODS: In the 18-month Dietary Intervention Randomized Controlled Trial PoLyphenols UnproceSsed (DIRECT-PLUS) weight-loss trial, 294 participants were randomized to (A) healthy dietary guidelines (HDG), (B) MED, or (C) green-MED diets, all combined with physical activity. Both isocaloric MED groups consumed 28 g/day of walnuts (+ 440 mg/day polyphenols). The green-MED group further consumed green tea (3-4 cups/day) and Wolffia globosa (duckweed strain) plant green shake (100 g frozen cubes/day) (+ 800mg/day polyphenols) and reduced red meat intake. We used magnetic resonance imaging (MRI) to quantify the abdominal adipose tissues. RESULTS: Participants (age = 51 years; 88% men; body mass index = 31.2 kg/m2; 29% VAT) had an 89.8% retention rate and 79.3% completed eligible MRIs. While both MED diets reached similar moderate weight (MED: - 2.7%, green-MED: - 3.9%) and waist circumference (MED: - 4.7%, green-MED: - 5.7%) loss, the green-MED dieters doubled the VAT loss (HDG: - 4.2%, MED: - 6.0%, green-MED: - 14.1%; p < 0.05, independent of age, sex, waist circumference, or weight loss). Higher dietary consumption of green tea, walnuts, and Wolffia globosa; lower red meat intake; higher total plasma polyphenols (mainly hippuric acid), and elevated urine urolithin A polyphenol were significantly related to greater VAT loss (p < 0.05, multivariate models). CONCLUSIONS: A green-MED diet, enriched with plant-based polyphenols and lower in red/processed meat, may be a potent intervention to promote visceral adiposity regression. TRIAL REGISTRATION: ClinicalTrials.gov , NCT03020186.
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Dieta Mediterrânea , Adiposidade , Dieta , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade Abdominal , Polifenóis , Chá , Redução de PesoRESUMO
OBJECTIVE: To examine the effectiveness of green-Mediterranean (MED) diet, further restricted in red/processed meat, and enriched with green plants and polyphenols on non-alcoholic fatty liver disease (NAFLD), reflected by intrahepatic fat (IHF) loss. DESIGN: For the DIRECT-PLUS 18-month randomized clinical trial, we assigned 294 participants with abdominal obesity/dyslipidaemia into healthy dietary guidelines (HDG), MED and green-MED weight-loss diet groups, all accompanied by physical activity. Both isocaloric MED groups consumed 28 g/day walnuts (+440 mg/day polyphenols provided). The green-MED group further consumed green tea (3-4 cups/day) and Mankai (a Wolffia globosa aquatic plant strain; 100 g/day frozen cubes) green shake (+1240 mg/day total polyphenols provided). IHF% 18-month changes were quantified continuously by proton magnetic resonance spectroscopy (MRS). RESULTS: Participants (age=51 years; 88% men; body mass index=31.3 kg/m2; median IHF%=6.6%; mean=10.2%; 62% with NAFLD) had 89.8% 18-month retention-rate, and 78% had eligible follow-up MRS. Overall, NAFLD prevalence declined to: 54.8% (HDG), 47.9% (MED) and 31.5% (green-MED), p=0.012 between groups. Despite similar moderate weight-loss in both MED groups, green-MED group achieved almost double IHF% loss (-38.9% proportionally), as compared with MED (-19.6% proportionally; p=0.035 weight loss adjusted) and HDG (-12.2% proportionally; p<0.001). After 18 months, both MED groups had significantly higher total plasma polyphenol levels versus HDG, with higher detection of Naringenin and 2-5-dihydroxybenzoic-acid in green-MED. Greater IHF% loss was independently associated with increased Mankai and walnuts intake, decreased red/processed meat consumption, improved serum folate and adipokines/lipids biomarkers, changes in microbiome composition (beta-diversity) and specific bacteria (p<0.05 for all). CONCLUSION: The new suggested strategy of green-Mediterranean diet, amplified with green plant-based proteins/polyphenols as Mankai, green tea, and walnuts, and restricted in red/processed meat can double IHF loss than other healthy nutritional strategies and reduce NAFLD in half. TRIAL REGISTRATION NUMBER: NCT03020186.
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Araceae , Dieta Mediterrânea , Hepatopatia Gordurosa não Alcoólica/dietoterapia , Polifenóis/administração & dosagem , Chá , Dieta Redutora , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Lifestyle dietary interventions are an essential practice in treating obesity, hence neural factors that may assist in predicting individual treatment success are of great significance. Here, in a prospective, open-label, three arms study, we examined the correlation between brain resting-state functional connectivity measured at baseline and weight loss following 6 months of lifestyle intervention in 92 overweight participants. We report a robust subnetwork composed mainly of sensory and motor cortical regions, whose edges correlated with future weight loss. This effect was found regardless of intervention group. Importantly, this main finding was further corroborated using a stringent connectivity-based prediction model assessed with cross-validation thus attesting to its robustness. The engagement of senso-motor regions in this subnetwork is consistent with the over-sensitivity to food cues theory of weight regulation. Finally, we tested an additional hypothesis regarding the role of brain-gastric interaction in this subnetwork, considering recent findings of a cortical network synchronized with gastric activity. Accordingly, we found a significant spatial overlap with the subnetwork reported in the present study. Moreover, power in the gastric basal electric frequency within our reported subnetwork negatively correlated with future weight loss. This finding was specific to the weight loss related subnetwork and to the gastric basal frequency. These findings should be further corroborated by combining direct recordings of gastric activity in future studies. Taken together, these intriguing results may have important implications for our understanding of the etiology of obesity and the mechanism of response to dietary intervention.
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Encéfalo/diagnóstico por imagem , Dieta Mediterrânea , Obesidade/dietoterapia , Córtex Sensório-Motor/diagnóstico por imagem , Redução de Peso , Adulto , Encéfalo/fisiopatologia , Regras de Decisão Clínica , Conectoma , Exercício Físico , Feminino , Neuroimagem Funcional , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiopatologia , Obesidade/fisiopatologia , Sobrepeso/dietoterapia , Sobrepeso/fisiopatologia , Polifenóis , Córtex Sensório-Motor/fisiopatologia , Estômago/fisiopatologia , Resultado do TratamentoRESUMO
BACKGROUND: Obesity is associated with elevated blood pressure (BP). In patients with obesity and hypertension, weight loss lowers BP, but the long-term effect of weight loss on BP is less clear. OBJECTIVE: We aimed to assess the effect of long-term weight loss intervention on BP in normotensive and hypertensive subjects. DESIGN: Randomized controlled trial. PARTICIPANTS: Two hundred seventy-eight subjects (mean age 47.9 ± 9.3 years, 89% male, 56% hypertensive) with abdominal obesity or elevated serum triglycerides and low high-density lipoprotein cholesterol were recruited. INTERVENTION: Eighteen-month weight loss intervention. MAIN MEASURES: Body weight and BP were measured at baseline, after 6 and 18 months. RESULTS: After 6 months of intervention, in the weight loss phase, body mass index (BMI) decreased by an average of -2.2±1.5 kg/m2 (p<0.001) and both diastolic BP (DBP) and systolic BP (SBP) decreased by -2.1±8.8 mmHg and -2.3±12.9 mmHg, respectively (p<0.01 for both). The change in BMI was similar in normotensive and hypertensive subjects (-2.0±1.6 and -2.3±1.5, p = 0.246). However, DBP and SBP decreased significantly (-5.2±7.1 mmHg and -6.2±12.5 mmHg, respectively, p<0.001 for both) in hypertensive subjects, and increased in normotensive subjects (1.8±9.3 mmHg, p = 0.041 and 2.7±11.7 mmHg, p = 0.017, respectively). After 18 months, in the weight maintenance phase, BMI slightly increased (0.9±1.3 kg/m2, p<0.001) but remained significantly lower than at baseline (p<0.0001). Unlike BMI, DBP and SBP increased significantly in hypertensive subjects (p<0.001) and returned almost to baseline levels. CONCLUSION: Weight-loss intervention reduced BP in hypertensive patients, but this was not maintained in the long run. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01530724.
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Hipertensão , Redução de Peso , Adulto , Pressão Sanguínea , Índice de Massa Corporal , Feminino , Humanos , Hipertensão/terapia , Masculino , Pessoa de Meia-Idade , Obesidade/terapiaRESUMO
BACKGROUND AND AIMS: In the CENTRAL trial context, we found diverse liver fat dynamics in response to different dietary interventions. Epigenetic mechanisms may contribute to the intraindividual variation. Moreover, genetic factors are involved in developing nonalcoholic fatty-liver disease (NAFLD), a disease reflected by an increase in intrahepatic fat (IHF). In this exploratory analysis, we primarily aimed to examine the effect of lifestyle interventions on DNA-methylation of NAFLD related genes associated with IHF. METHODS: For 120 participants from the CENTRAL trial, an 18-month regimen of either low-fat (LF) or Mediterranean-low carbohydrate (MED/LC) diets, with or without physical activity (PA+/PA-), was instructed. Magnetic resonance imaging was used to measure IHF%, which was analysed for association with CpG specific DNA-methylation levels of 41 selected candidate genes. Single-nucleotide polymorphisms known to be associated with NAFLD within the studied genes were genotyped by TaqMan assays. RESULTS: At baseline, participants (92% men; body mass index = 30.2 kg/m2 ) had mean IHF of 10.7% (59% NAFLD). Baseline-IHF% was inversely correlated with DNA-methylation at individual CpGs within AC074286.1, CRACR2A, A2MP1, FARP1 (P < .05 for all multivariate models). FARP1 rs9584805 showed association with IHF, with the prevalence of NAFLD and baseline methylation level of the CpG site (cg00071727) associated with IHF%. Following 18-month lifestyle intervention, differential DNA-methylation patterns were observed between diets at cg14335324 annotated to A2MP1 (P = .04, LF vs. MED/LC), and differential DNA-methylation between PA groups within AC074286.1, CRACR2A, and FARP1 CpGs (P < .05 for all, PA-vs. PA+). CONCLUSIONS: This study suggests epigenetic markers for IHF and potential epigenetic remodeling after long-term lifestyle interventions.
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Fígado , Hepatopatia Gordurosa não Alcoólica , Proteínas de Ligação ao Cálcio , Epigênese Genética , Exercício Físico , Feminino , Humanos , Estilo de Vida , Masculino , Hepatopatia Gordurosa não Alcoólica/genéticaRESUMO
BACKGROUND: We aimed to assess whether distinct lifestyle strategies can differentially affect specific body adipose depots. METHODS: We performed an 18-month randomized controlled trial among 278 sedentary adults with abdominal obesity (75%) or dyslipidemia in an isolated workplace with a monitored provided lunch. Participants were randomized to isocaloric low-fat or Mediterranean/low-carbohydrate (MED/LC) diet+28 g walnuts/day with/without added moderate physical activity (PA; 80% aerobic; supervised/free gym membership). Overall primary outcome was body fat redistribution, and the main specific end point was visceral adipose tissue (VAT). We further followed the dynamics of different fat depots (deep and superficial subcutaneous, liver, pericardial, muscle, pancreas, and renal sinus) by magnetic resonance imaging. RESULTS: Of 278 participants (age, 48 years, 89% men, body mass index, 30.8 kg/m2), 86% completed the trial with good adherence. The low-fat group preferentially decreased reported fat intake (-21.0% versus -11.5% for the MED/LC; P<0.001), and the MED/LC group decreased reported carbohydrates intake (-39.5% versus -21.3% for the low-fat group; P<0.001). The PA+ groups significantly increased the metabolic equivalents per week versus the PA- groups (19.0 versus 2.1; P=0.009). Whereas final moderate weight loss was indifferent, exercise attenuated the waist circumference rebound with the greatest effect in the MED/LCPA+ group (P<0.05). VAT (-22%), intrahepatic (-29%), and intrapericardial (-11%) fats declines were higher than pancreatic and femur intermuscular fats (1% to 2%) loss. Independent of weight loss, PA+ with either diet had a significantly greater effect on decreasing VAT (mean of difference, -6.67cm2; 95% confidence interval, -14.8 to -0.45) compared with PA-. The MED/LC diet was superior to the low-fat diet in decreasing intrahepatic, intrapericardial, and pancreatic fats (P<0.05 for all). In contrast, renal sinus and femoral intermuscular fats were not differentially altered by lifestyle interventions but by weight loss per se. In multivariate models further adjusted for weight loss, losing VAT or intrahepatic fat was independently associated with improved lipid profile, losing deep subcutaneous adipose tissue with improved insulin sensitivity, and losing superficial subcutaneous adipose tissue remained neutral except for an association with decreased leptin. CONCLUSIONS: Moderate weight loss alone inadequately reflects the significant lifestyle effects on atherogenic and diabetogenic fat depots. The MED/LC diet mobilizes specific ectopic fat depots, and exercise has an independent contribution to VAT loss. Fat depots exhibit diverse responsiveness and are differentially related to cardiometabolic markers. Distinct lifestyle protocols may uniquely induce fat mobilization from specific anatomic sites. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01530724.
Assuntos
Tecido Adiposo/diagnóstico por imagem , Adiposidade , Dislipidemias/dietoterapia , Estilo de Vida Saudável , Lipídeos/sangue , Imageamento por Ressonância Magnética , Obesidade Abdominal/dietoterapia , Comportamento de Redução do Risco , Tecido Adiposo/metabolismo , Tecido Adiposo/fisiopatologia , Adulto , Idoso , Dieta com Restrição de Carboidratos , Dieta com Restrição de Gorduras , Dieta Mediterrânea , Dislipidemias/sangue , Dislipidemias/diagnóstico por imagem , Dislipidemias/fisiopatologia , Exercício Físico , Feminino , Humanos , Israel , Masculino , Pessoa de Meia-Idade , Obesidade Abdominal/sangue , Obesidade Abdominal/diagnóstico por imagem , Obesidade Abdominal/fisiopatologia , Valor Preditivo dos Testes , Fatores de Tempo , Resultado do Tratamento , Redução de PesoRESUMO
BACKGROUND & AIM: It is unclear if a reduction in hepatic fat content (HFC) is a major mediator of the cardiometabolic benefit of lifestyle intervention, and whether it has prognostic significance beyond the loss of visceral adipose tissue (VAT). In the present sub-study, we hypothesized that HFC loss in response to dietary interventions induces specific beneficial effects independently of VAT changes. METHODS: In an 18-month weight-loss trial, 278 participants with abdominal obesity/dyslipidemia were randomized to low-fat (LF) or Mediterranean/low-carbohydrate (MED/LCâ¯+â¯28â¯g walnuts/day) diets with/without moderate physical activity. HFC and abdominal fat-depots were measured using magnetic resonance imaging at baseline, after 6 (sub-study, nâ¯=â¯158) and 18â¯months. RESULTS: Of 278 participants (mean HFC 10.2% [range: 0.01%-50.4%]), the retention rate was 86.3%. The %HFC substantially decreased after 6â¯months (-6.6% absolute units [-41% relatively]) and 18â¯months (-4.0% absolute units [-29% relatively]; pâ¯<0.001 vs. baseline). Reductions of HFC were associated with decreases in VAT beyond weight loss. After controlling for VAT loss, decreased %HFC remained independently associated with reductions in serum gamma glutamyltransferase and alanine aminotransferase, circulating chemerin, and glycated hemoglobin (pâ¯<0.05). While the reduction in HFC was similar between physical activity groups, MED/LC induced a greater %HFC decrease (pâ¯=â¯0.036) and greater improvements in cardiometabolic risk parameters (pâ¯<0.05) than the LF diet, even after controlling for VAT changes. Yet, the greater improvements in cardiometabolic risk parameters induced by MED/LC were all markedly attenuated when controlling for HFC changes. CONCLUSIONS: %HFC is substantially reduced by diet-induced moderate weight loss and is more effectively reduced by the MED/LC diet than the LF diet, independently of VAT changes. The beneficial effects of the MED/LC diet on specific cardiometabolic parameters appear to be mediated more by decreases in %HFC than VAT loss. LAY SUMMARY: High hepatic fat content is associated with metabolic syndrome, type 2 diabetes mellitus, and coronary heart disease. In the CENTRAL 18-month intervention trial, a Mediterranean/low-carbohydrate diet induced a greater decrease in hepatic fat content than a low-fat diet, conferring beneficial health effects that were beyond the favorable effects of visceral fat loss. ClinicalTrials.gov Identifier: NCT01530724.
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Dieta com Restrição de Gorduras , Dieta Mediterrânea , Dislipidemias/dietoterapia , Fígado Gorduroso/dietoterapia , Obesidade Abdominal/dietoterapia , Adulto , Estudos de Coortes , Dislipidemias/diagnóstico por imagem , Exercício Físico , Fígado Gorduroso/diagnóstico por imagem , Feminino , Humanos , Gordura Intra-Abdominal , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Obesidade Abdominal/diagnóstico por imagem , Resultado do Tratamento , Redução de PesoRESUMO
BACKGROUND: Decreased dietary meat may deplete iron stores, as plant-derived iron bioavailability is typically limited. OBJECTIVES: We explored the effect of a low-meat Mediterranean (green-MED) diet, supplemented with Wolffia globosa duckweed (Mankai: rich in protein and iron) as a food source for humans, on iron status. We further examined the iron bioavailability of Mankai in rats. METHODS: Two hundred and ninety-four abdominally obese/dyslipidemic [mean age = 51.1 y; body mass index (kg/m2) = 31.3; 88% men] nonanemic participants were randomly assigned to physical activity (PA), PA + MED diet, or PA + green-MED diet. Both isocaloric MED groups consumed 28 g walnuts/d and the low-meat green-MED group further consumed green tea (800 mL/d) and Mankai (100 g green shake/d). In a complementary animal experiment, after 44 d of an iron deficiency anemia-inducing diet, 50 female rats (age = 3 wk; Sprague Dawley strain) were randomly assigned into: iron-deficient diet (vehicle), or vehicle + iso-iron: ferrous gluconate (FG) 14, Mankai 50, and Mankai 80 versions (1.7 mg · kg-1 · d-1 elemental iron), or FG9.5 and Mankai 50-C version (1.15 mg · kg-1 · d-1 elemental iron). The specific primary aim for both studies was changes in iron homeostasis parameters. RESULTS: After 6 mo of intervention, iron status trajectory did not differ between the PA and PA + MED groups. Hemoglobin modestly increased in the PA + green-MED group (0.23 g/dL) compared with PA (-0.1 g/dL; P < 0.001) and PA + MED (-0.1 g/dL; P < 0.001). Serum iron and serum transferrin saturation increased in the PA + green-MED group compared with the PA group (8.21 µg/dL compared with -5.23 µg/dL and 2.39% compared with -1.15%, respectively; P < 0.05 for both comparisons), as did folic acid (P = 0.011). In rats, hemoglobin decreased from 15.7 to 9.4 mg/dL after 44 d of diet-induced anemia. After depletion treatment, the vehicle-treated group had a further decrease of 1.3 mg/dL, whereas hemoglobin concentrations in both FG and Mankai iso-iron treatments similarly rebounded (FG14: +10.8 mg/dL, Mankai 50: +6.4 mg/dL, Mankai 80: +7.3 mg/dL; FG9.5: +5.1 mg/dL, Mankai 50-C: +7.1 mg/dL; P < 0.05 for all vs. the vehicle group). CONCLUSIONS: In humans, a green-MED low-meat diet does not impair iron homeostasis. In rats, iron derived from Mankai (a green-plant protein source) is bioavailable and efficient in reversal of anemia. This trial was registered at clinicaltrials.gov as NCT03020186.
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Anemia Ferropriva/dietoterapia , Araceae , Dieta Mediterrânea , Suplementos Nutricionais , Ferro/metabolismo , Adulto , Anemia Ferropriva/metabolismo , Animais , Araceae/química , Disponibilidade Biológica , Suplementos Nutricionais/análise , Modelos Animais de Doenças , Dislipidemias/dietoterapia , Dislipidemias/metabolismo , Feminino , Homeostase , Humanos , Ferro da Dieta/administração & dosagem , Ferro da Dieta/farmacocinética , Masculino , Pessoa de Meia-Idade , Fenômenos Fisiológicos da Nutrição , Obesidade Abdominal/dietoterapia , Obesidade Abdominal/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
INTRODUCTION: Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of morbidity. Data regarding MRSA infections in children in Israel are scarce. OBJECTIVES: We assessed MRSA prevalence, risk factors and clinical manifestations in children with Staphylococcus aureus infections in southern Israel. METHODS: Our medical center is the sole hospital in southern Israel. All medical files of Staphylococcus aureus infections during the period 2005-2015, were reviewed retrospectively. RESULTS: Overall, 1,062 SA infections (MRSA; n=164, 15%) were identified; 687 (65%) skin and soft tissue infections (SSTI), and 375 (35%) invasive infections. MRSA was significantly more common in children <5 years (18% vs. 13% in children ≥5 years), Bedouin ethnicity (19% vs. 8% in Jewish children), burns (24% vs. 15%), congenital insensitivity to pain with anhidrosis (CIPA; 90% vs. 15%) and SSTI (17% vs. 12% in invasive infections). Blood count parameters and hospital-associated vs. community-acquired infection rates were similar comparing MRSA and Methicillin-susceptible Staphylococcus aureus (MSSA). In multivariate analysis, age (odds ratio, OR=0.953), Bedouin ethnicity (OR=2.698), burns (OR=2.036) and SSTI (OR=1.674) were associated with MRSA. MRSA isolates were more frequently resistant than MSSA to clindamycin (30% vs. 14%), erythromycin (34% vs. 15%), co-trimoxazole, tetracycline, rifampicin, ciprofloxacin and gentamicin (4% vs. 0.5%, all). All isolates were vancomycin susceptible. CONCLUSIONS: MRSA infections are common in young, Bedouin children and burns, and are more commonly multidrug resistant than MSSA in our region. Our data should be used to better identify and treat children with MRSA infection.
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Infecções Comunitárias Adquiridas , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Antibacterianos , Criança , Humanos , Israel/epidemiologia , Meticilina , Resistência a Meticilina , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Estudos Retrospectivos , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/epidemiologia , Staphylococcus aureusAssuntos
Inteligência Artificial/normas , COVID-19/diagnóstico por imagem , Ultrassonografia/instrumentação , Inteligência Artificial/estatística & dados numéricos , COVID-19/fisiopatologia , Estudos de Viabilidade , Humanos , Unidades de Terapia Intensiva/organização & administração , Unidades de Terapia Intensiva/estatística & dados numéricos , Sistemas Automatizados de Assistência Junto ao Leito/estatística & dados numéricos , Ultrassonografia/métodos , Ultrassonografia/estatística & dados numéricosRESUMO
Introduction: An ST-elevation myocardial infarction (STEMI) is a clinical syndrome defined by symptoms of myocardial ischemia, persistent electrocardiographic ST-segment elevation and subsequent release of biomarkers suggestive of myocardial necrosis. In clinical practice, echocardiography has become essential in evaluating patients after acute myocardial infarction. We aimed to assess clinical and echocardiographic parameters that may affect LV function recovery in patients after STEMI. Methods: This study is a retrospective observational study from a tertiary referral center in Israel. We collected patients that were admitted with STEMI and a left ventricular ejection fraction (LVEF) below 35% on preliminary echocardiography at the index hospitalization and compared the findings to a follow-up study performed within 1-6 months after that event, in order to see if there are predictors of LVEF change > 10% within 90 days following STEMI. Results: This study included 101 patients that were admitted between 2016 and 2021. Within a median follow-up of 9.7 weeks (IQR 5.9-17.1), 27 (25.2%) patients had improved their LVEF, and 74 (69.2%) had no change or further reduced LVEF. Compared to patients without LVEF improvement, those with improved LVEF were more likely to be female (29.6% vs. 9.5%, p = 0.01), less likely to suffer from hypertension (33.3% vs. 56.8%, p = 0.04) and had marginally higher rates of thrombolysis treatment (14.1% vs. 4.1%, p = 0.06). Conclusions: in the population of STEMI patients with residual LVEF < 35%, approximately a quarter will improve at least 10% in their follow-up LVEF, and there were no clear echocardiographic predictors for this improvement.