A patient-centered, coordinated care approach delivered by community and pediatric primary care providers to promote responsive parenting: pragmatic randomized clinical trial rationale and protocol.

Background: Economically disadvantaged families receive care in both clinical and community settings, but this care is rarely coordinated and can result in conflicting educational messaging. WEE Baby Care is a pragmatic randomized clinical trial evaluating a patient-centered responsive parenting (RP) intervention that uses health information technology (HIT) strategies to coordinate care between pediatric primary care providers (PCPs) and the Special Supplemental Nutrition Program for Women, Infant and Children (WIC) community nutritionists to prevent rapid weight gain from birth to 6 months. It is hypothesized that data integration and coordination will improve consistency in RP messaging and parent self-efficacy, promoting shared decision making and infant self-regulation, to reduce infant rapid weight gain from birth to 6 months.

Differentially methylated loci in NAFLD cirrhosis are associated with key signaling pathways.

Altered DNA methylation events contribute to the pathogenesis and progression of metabolic disorders, including nonalcoholic fatty liver disease (NAFLD). Investigations of global DNA methylation patterns in liver biopsies representing severe NAFLD fibrosis have been limited. We used the HumanMethylation 450K BeadChip to analyze genome-wide methylation in patients with biopsy-proven grade 3/4 NAFLD fibrosis/cirrhosis (N = 14) and age- and sex-matched controls with normal histology (N = 15).

Genetic variants help define the role of the MC4R C-terminus in signaling and cell surface stability.

Screening 92,445 subjects in the Geisinger-Regeneron DiscovEHR cohort, we identified 5 patients heterozygous for nonsense mutations causing early terminations at Glu307 or Leu328 on the C-terminus of melanocortin 4 receptor (MC4R). Two Q307Ter carriers are severely obese (BMI > 40), while one is overweight (BMI > 25). One L328Ter carrier is overweight and the other is lean.

Transcriptomic Profiling of Obesity-Related Nonalcoholic Steatohepatitis Reveals a Core Set of Fibrosis-Specific Genes.

Nonalcoholic steatohepatitis (NASH) is strongly associated with obesity and type 2 diabetes. The molecular factors underlying the development of inflammation and severe fibrosis in NASH remain largely unknown. The purpose of this study was to identify gene expression patterns related to obesity-related NASH inflammation and fibrosis.

Severe anemia after Roux-en-Y gastric bypass: a cause for concern.

Background: The current popularity of metabolic surgery has led to increasing attention to long-term nutritional complications.

Objective: The purpose of this retrospective study is to accurately define the long-term incidence of clinically significant anemia after Roux-en-Y gastric bypass (RYGB) and to identify factors that contribute to increased risk.

Methods: The study cohort consisted of 2116 patients who underwent RYGB with necessary laboratory information available, and with longitudinal follow-up available (mean 5.

Surgical weight-loss to improve functional status trajectories following total knee arthroplasty: SWIFT trial: Rationale, design, and methods.

Total Knee Arthroplasty (TKA, also known as total knee replacement) is a highly effective surgical intervention for the restoration of physical function and improving quality of life in patients with disabling knee osteoarthritis. Recent data suggest that obesity is a major risk factor in the pathogenesis and progression of knee osteoarthritis, with increases in body mass index (BMI, kg/m) directly correlating with the prevalence of knee osteoarthritis. However, recent data also suggest that there are increased risks associated with TKAs when performed in patients with morbid obesity (BMI > 40 kg/m).

Integrating and coordinating care between the Women, Infants, and Children Program and pediatricians to improve patient-centered preventive care for healthy growth.

New care delivery models call for integrating health services to coordinate care and improve patient-centeredness. Such models have been embraced to coordinate care with evidence-based strategies to prevent obesity. Both the Special Supplemental Program for Women, Infants and Children (WIC) Program and pediatricians are considered credible sources of preventive guidance, and coordinating these independent siloes would benefit a vulnerable population.

Altered expression of MALAT1 lncRNA in nonalcoholic steatohepatitis fibrosis regulates CXCL5 in hepatic stellate cells.

In the present study, we sought to identify long noncoding RNA (lncRNA) expression profiles in nonalcoholic steatohepatitis (NASH) patients with histologic evidence of lobular inflammation and advanced fibrosis. We profiled lncRNA expression using RNA-sequencing of wedge liver biopsies from 24 nonalcoholic fatty liver disease (NAFLD) patients with normal liver histology, 53 NAFLD patients with lobular inflammation, and 65 NAFLD patients with advanced fibrosis. Transcript profiling identified 4432 and 4057 differentially expressed lncRNAs in comparisons of normal tissue with lobular inflammation and fibrosis samples, respectively.

Gastric Bypass Surgery Produces a Durable Reduction in Cardiovascular Disease Risk Factors and Reduces the Long-Term Risks of Congestive Heart Failure.

Background: Obesity and its association with reduced life expectancy are well established, with cardiovascular disease as one of the major causes of fatality. Metabolic surgery is a powerful intervention for severe obesity, resulting in improvement in comorbid diseases and in cardiovascular risk factors. This study investigates the relationship between metabolic surgery and long-term cardiovascular events.

Initial weight loss goals: have they changed and do they matter?

Objective: Nearly 20 years ago, participants in behavioural weight loss programmes reported goals that greatly exceeded the amount of weight typically produced by these programmes. Whether having unrealistic weight loss goals impacts weight loss or attrition is unclear. The intent of the current study was to revisit current weight loss goals and examine whether goals impact outcomes.

Genetic and neural predictors of behavioral weight loss treatment: A preliminary study.

Objective: To examine neural mechanisms of action in behavioral weight loss treatment (BWL) and explore neural and genetic predictors of BWL.

Methods: Neural activation to milkshake receipt and genetics were compared in 17 women with obesity who received 12 weeks of BWL and 17 women who received no intervention. Participants were scanned twice using functional magnetic resonance imaging at baseline and 12 weeks.

Effect of Two Lipoprotein (a)-Associated Genetic Variants on Plasminogen Levels and Fibrinolysis.

Two genetic variants (rs3798220 and rs10455872) in the apolipoprotein (a) gene () have been implicated in cardiovascular disease (CVD), presumably through their association with lipoprotein (a) [Lp(a)] levels. While Lp(a) is recognized as a lipoprotein with atherogenic and thrombogenic characteristics, it is unclear whether or not the two Lp(a)-associated genetic variants are also associated with markers of thrombosis (, plasminogen levels and fibrinolysis). In the present study, we genotyped the two genetic variants in 2919 subjects of the Old Order Amish (OOA) and recruited 146 subjects according to the carrier and noncarrier status for rs3798220 and rs10455872, and also matched for gender and age.

Evaluation of the Association Between Preoperative Clinical Factors and Long-term Weight Loss After Roux-en-Y Gastric Bypass.

Importance: Weight loss after bariatric surgery varies, yet preoperative clinical factors associated with long-term suboptimal outcomes are not well understood.

Objective: To evaluate the association between preoperative clinical factors and long-term weight loss after Roux-en-Y gastric bypass (RYGB).

Design, Setting, And Participants: From June 2001 to September 2007, this retrospective cohort study followed up RYGB patients before surgery to 7 to 12 years after surgery.

The impact of bariatric surgery on inflammation: quenching the fire of obesity?

Purpose Of Review: Numerous lines of evidence support the likelihood that inflammation drives the transition from obese/metabolically healthy to obese/type 2 diabetes (T2D). Given the temporal flexibility of inflammation in obesity-associated T2D, investigators have hypothesized that a precipitous drop in diabetogenic cytokines is critical for rapid 'T2D remission' following surgery but prior to significant weight loss. We review the evidence that changes in diabetogenic cytokines play a role in outcomes of bariatric surgery, including improved glycemic control.

The impact of obstructive sleep apnea on nonalcoholic fatty liver disease in patients with severe obesity.

Objective: Obstructive sleep apnea (OSA) is common among candidates for bariatric surgery. OSA and its associated intermittent hypoxia have been implicated in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis. A large cohort of bariatric surgery patients was studied in an effort to explore the relationship between OSA severity, hypoxia, metabolic syndrome, and the severity of NAFLD.

High-throughput sequencing reveals altered expression of hepatic microRNAs in nonalcoholic fatty liver disease-related fibrosis.

Recent evidence suggests that microRNAs (miRNAs), small, noncoding RNA molecules that regulate gene expression, may play a role in the regulation of metabolic disorders, including nonalcoholic fatty liver disease (NAFLD). To identify miRNAs that mediate NAFLD-related fibrosis, we used high-throughput sequencing to assess miRNAs obtained from liver biopsies of 15 individuals without NAFLD fibrosis (F0) and 15 individuals with severe NAFLD fibrosis or cirrhosis (F3-F4), matched for age, sex, body mass index, type 2 diabetes status, hemoglobin A1c, and use of diabetes medications. We used DESeq2 and Kruskal-Wallis test to identify miRNAs that were differentially expressed between NAFLD patients with or without fibrosis, adjusting for multiple testing using Bonferroni correction.

Contribution of common non-synonymous variants in PCSK1 to body mass index variation and risk of obesity: a systematic review and meta-analysis with evidence from up to 331 175 individuals.

Polymorphisms rs6232 and rs6234/rs6235 in PCSK1 have been associated with extreme obesity [e.g. body mass index (BMI) ≥ 40 kg/m(2)], but their contribution to common obesity (BMI ≥ 30 kg/m(2)) and BMI variation in a multi-ethnic context is unclear.

Evidence for several independent genetic variants affecting lipoprotein (a) cholesterol levels.

Lipoprotein (a) [Lp(a)] is an independent risk factor for atherosclerosis-related events that is under strong genetic control (heritability = 0.68-0.98).

Extension of GWAS results for lipid-related phenotypes to extreme obesity using electronic health record (EHR) data and the Metabochip.

A variety of health-related data are commonly deposited into electronic health records (EHRs), including laboratory, diagnostic, and medication information. The digital nature of EHR data facilitates efficient extraction of these data for research studies, including genome-wide association studies (GWAS). Previous GWAS have identified numerous SNPs associated with variation in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG).

Does IRISIN Have a BRITE Future as a Therapeutic Agent in Humans?

The epidemic of obesity has contributed to the rapid rise in comorbid conditions such as cardiovascular disease, type 2 diabetes, sleep apnea, and hypertension among others. Therefore, there is a critical need to develop therapeutic strategies to reduce the prevalence of the disease. Skeletal muscle cells secrete signaling cytokines/peptides (referred to as myokines) that act in autocrine, paracrine, and endocrine fashion.

Long-term weight-loss in gastric bypass patients carrying melanocortin 4 receptor variants.

Background: The melanocortin 4 receptor (MC4R) critically regulates feeding and satiety. Rare variants in MC4R are predominantly found in obese individuals. Though some rare variants in MC4R discovered in patients have defects in localization, ligand binding and signaling to cAMP, many have no recognized defects.