Portal vein-enriched metabolites as intermediate regulators of the gut microbiome in insulin resistance.

Diet and obesity contribute to insulin resistance and type 2 diabetes, in part via the gut microbiome. To explore the role of gut-derived metabolites in this process, we assessed portal/peripheral blood metabolites in mice with different risks of obesity/diabetes, challenged with a high-fat diet (HFD) + antibiotics. In diabetes/obesity-prone C57BL/6J mice, 111 metabolites were portally enriched and 74 were peripherally enriched, many of which differed in metabolic-syndrome-resistant 129S1/129S6 mice.

Epidemiology and Cardiovascular Benefits of Physical Activity and Exercise.

While humans evolved to perform routine endurance activity, recent secular trends in the United States and globally have resulted in a dramatic rise in the amount of time spent inactive in both occupational and leisure-time settings. The high burden of physical inactivity is responsible for a high risk of preventable noncommunicable disease including cardiovascular disease, cancer, and premature death. In this review, we focus on the beneficial effects of routine physical activity (PA) on the cardiovascular system, the different ways we can achieve and measure PA, and the evidence supporting key public health guidance on optimal PA goals for promoting health.

Integration of proteomics with prospective birth cohort to elucidate early life origins of cardiometabolic diseases: rationale, study design, lab assay, and quality control.

There is growing evidence that the plasma proteome provides insights into personal health status at different stages of life. However, limited data are available on high-throughput proteomic studies in pediatric populations, especially, using prospective birth cohorts. We launched a proteomics study in 990 children from a US predominantly urban, low-income, multi-ethnic prospective Boston Birth Cohort (BBC, referred as "BBC proteomics study"), which aimed to leverage proteomics to investigate the biological pathways underlying the link between preterm birth and child long-term cardiometabolic health.

Cross-Ancestry Comparison of Aptamer and Antibody Proteomics Measures.

Measures from affinity-proteomics platforms often correlate poorly, challenging interpretation of protein associations with genetic variants (pQTL) and phenotypes. Here, we examined 2,157 proteins measured on both SomaScan 7k and Olink Explore 3072 across 1,930 participants with genetic similarity to European, African, East Asian, and Admixed American ancestry references. Inter-platform correlation coefficients for these 2,157 proteins followed a bimodal distribution (median r=0.

Hepatic Steatosis and Fibrosis, Cardiorespiratory Fitness, and Metabolic Mediators in the Community.

Background And Aims: Individuals with steatotic liver disease (SLD) are at high cardiovascular disease (CVD) risk, but approaches to characterise and mitigate this risk are limited. By investigating relations, and shared metabolic pathways, of hepatic steatosis/fibrosis and cardiorespiratory fitness (CRF), we sought to identify new avenues for CVD risk reduction in SLD.

Methods: In Framingham Heart Study (FHS) participants (N = 2722, age 54 ± 9 years, 53% women), vibration-controlled transient elastography (VCTE) was performed between 2016-2019 to assess hepatic steatosis (continuous attenuation parameter [CAP]) and fibrosis (liver fibrosis measure [LSM]).

Plasma Proteomics of Exercise Blood Pressure and Incident Hypertension.

Importance: Blood pressure response during acute exercise (exercise blood pressure [EBP]) is associated with the future risk of hypertension and cardiovascular disease (CVD). Biochemical characterization of EBP could inform disease biology and identify novel biomarkers of future hypertension.

Objective: To identify protein markers associated with EBP and test their association with incident hypertension.

Proteomic analysis of cardiorespiratory fitness for prediction of mortality and multisystem disease risks.

Despite the wide effects of cardiorespiratory fitness (CRF) on metabolic, cardiovascular, pulmonary and neurological health, challenges in the feasibility and reproducibility of CRF measurements have impeded its use for clinical decision-making. Here we link proteomic profiles to CRF in 14,145 individuals across four international cohorts with diverse CRF ascertainment methods to establish, validate and characterize a proteomic CRF score. In a cohort of around 22,000 individuals in the UK Biobank, a proteomic CRF score was associated with a reduced risk of all-cause mortality (unadjusted hazard ratio 0.

Omics-driven investigation of the biology underlying intrinsic submaximal working capacity and its trainability.

Submaximal exercise capacity is an indicator of cardiorespiratory fitness with clinical and public health implications. Submaximal exercise capacity and its response to exercise programs are characterized by heritability levels of about 40%. Using physical working capacity (power output) at a heart rate of 150 beats/min (PWC150) as an indicator of submaximal exercise capacity in subjects of the HERITAGE Family Study, we have undertaken multi-omics and in silico explorations of the underlying biology of PWC150 and its response to 20 wk of endurance training.

Associations between Metabolomic Biomarkers of Avocado Intake and Glycemia in the Multi-Ethnic Study of Atherosclerosis.

Background: Avocado consumption is linked to better glucose homeostasis, but small associations suggest potential population heterogeneity. Metabolomic data capture the effects of food intake after digestion and metabolism, thus accounting for individual differences in these processes.

Objectives: To identify metabolomic biomarkers of avocado intake and to examine their associations with glycemia.

Association of healthy dietary patterns and cardiorespiratory fitness in the community.

Aims: To evaluate the associations of dietary indices and quantitative cardiorespiratory fitness (CRF) measures in a large, community-based sample harnessing metabolomic profiling to interrogate shared biology.

Methods And Results: Framingham Heart Study (FHS) participants underwent maximum effort cardiopulmonary exercise tests for CRF quantification (via peak VO2) and completed semi-quantitative food frequency questionnaires. Dietary quality was assessed by the Alternative Healthy Eating Index (AHEI) and Mediterranean-style Diet Score (MDS), and fasting blood concentrations of 201 metabolites were quantified.

Mixed meal tolerance testing highlights in diabetes altered branched-chain ketoacid metabolism and pathways associated with all-cause mortality.

Background: Elevated BCAA levels are strongly associated with diabetes, but how diabetes affects BCAA, branched-chain ketoacids (BCKAs), and the broader metabolome after a meal is not well known.

Objective: To compare quantitative BCAA and BCKA levels in a multiracial cohort with and without diabetes after a mixed meal tolerance test (MMTT) as well as to explore the kinetics of additional metabolites and their associations with mortality in self-identified African Americans.

Methods: We administered an MMTT to 11 participants without obesity or diabetes and 13 participants with diabetes (treated with metformin only) and measured the levels of BCKAs, BCAAs, and 194 other metabolites at 8 time points across 5 h.

Association of Healthy Dietary Patterns and Cardiorespiratory Fitness in the Community.

Aims: To evaluate the associations of dietary indices and quantitative CRF measures in a large, community-based sample harnessing metabolomic profiling to interrogate shared biology.

Methods: Framingham Heart Study (FHS) participants underwent maximum effort cardiopulmonary exercise tests for CRF quantification (via peak VO ) and completed semi-quantitative FFQs. Dietary quality was assessed by the Alternative Healthy Eating Index (AHEI) and Mediterranean-style Diet Score (MDS), and fasting blood concentrations of 201 metabolites were quantified.

Plasma Proteomic Risk Markers of Incident Type 2 Diabetes Reflect Physiologically Distinct Components of Glucose-Insulin Homeostasis.

Unlabelled: High-throughput proteomics allows researchers to simultaneously explore the roles of thousands of biomarkers in the pathophysiology of diabetes. We conducted proteomic association studies of incident type 2 diabetes and physiologic responses to an intravenous glucose tolerance test (IVGTT) to identify novel protein contributors to glucose homeostasis and diabetes risk. We tested 4,776 SomaScan proteins measured in relation to 18-year incident diabetes risk in participants from the Cardiovascular Health Study (N = 2,631) and IVGTT-derived measures in participants from the HERITAGE Family Study (N = 752).

An Unusual Cause of Functional Mitral Stenosis: A Left Atrial Intimal Sarcoma.

Primary cardiac tumors are rare, with an incidence of <0.1% in postmortem series; sarcomas comprise 75% of these. Cardiac sarcomas may be life-threatening at the time of presentation.

Effect of Educational Intervention on the Rate of Rarely Appropriate Outpatient Echocardiograms Ordered by Attending Academic Cardiologists: A Randomized Clinical Trial.

Importance: Appropriate use criteria-based educational initiatives have been shown to improve transthoracic echocardiography (TTE) ordering practices of physicians in training. Whether such an intervention is successful with attending cardiologists remains unknown.

Objective: To prospectively investigate the effect of an appropriate use criteria-based educational intervention on ordering of outpatient TTEs by attending academic cardiologists.

Clinical and Echocardiographic Factors Associated With In-Hospital Mortality in Patients With Infective Endocarditis Affecting the Native Tricuspid Valve.

Infective endocarditis (IE) is a highly morbid disease, for which most outcomes data come from patients with left-sided valvular lesions. Echocardiographic findings such as vegetation size and prosthetic valve involvement have been identified as important predictors of mortality in left-sided IE, but predictors of outcomes in right-sided IE are less well characterized. Therefore, the aim of this study was to identify clinical and echocardiographic findings predictive of mortality in tricuspid valve (TV) IE.

Reliability of medical record abstraction by non-physicians for orthopedic research.

Background: Medical record review (MRR) is one of the most commonly used research methods in clinical studies because it provides rich clinical detail. However, because MRR involves subjective interpretation of information found in the medical record, it is critically important to understand the reproducibility of data obtained from MRR. Furthermore, because medical record review is both technically demanding and time intensive, it is important to establish whether trained research staff with no clinical training can abstract medical records reliably.

An analysis of adaptive design variations on the sequential parallel comparison design for clinical trials.

Background: Currently, a growing placebo response rate has been observed in clinical trials for antidepressant drugs, a phenomenon that has made it increasingly difficult to demonstrate efficacy. The sequential parallel comparison design (SPCD) is a clinical trial design that was proposed to address this issue. The SPCD theoretically has the potential to reduce the sample-size requirement for a clinical trial and to simultaneously enrich the study population to be less responsive to the placebo.

Inhibition of HIV derived lentiviral production by TAR RNA binding domain of TAT protein.

Background: A critical step in the production of new HIV virions involves the TAT protein binding to the TAR element. The TAT protein contains in close proximity its TAR RNA binding domain and protein transduction domain (PTD). The PTD domain of TAT has been identified as being instrumental in the protein's ability to cross mammalian cell and nuclear membranes.