Creating a Sustainable Obesity Management Program: The Center for Better Health and Nutrition.

Over the past 30 years, obesity rates have more than tripled in the United States, and although rates seem to have stabilized over the past 5 years, about one- third of American children are still overweight or obese. The Center for Better Health and Nutrition (CBHN) is a comprehensive obesity treatment, manage- ment, and prevention arm of the Heart Institute within Cincinnati Children's Hospital Medical Center, offering necessary medical treatment to an often un- derserved population. With volumes increasing at substantial levels and services being reimbursed at low rates, the financial health of the program has been closely analyzed in order to determine the long-term sustainability of CBHN. Downstream revenue was analyzed and found to account for over $754,000 in fiscal year (FY) 2015; quality improvement efforts such as E/M coding and imple- menting the Nurse Practitioner role also added to increased revenue and a lower cost profile. Capturing all billable services, such as biometric measurement, was found to be valuable to the program's bottom line. By considering all applicable revenue sources, implementing quality improvement efforts, and billing for all relevant services, the program operates at a low level of profitability.

Clinical and molecular characterization of a severe form of partial lipodystrophy expanding the phenotype of PPARγ deficiency.

Familial partial lipodystrophy (FPLD) is characterized by abnormal fat distribution and a metabolic syndrome with hypertriglyceridemia. We identified a family with a severe form of FPLD3 with never-reported clinical features and a novel mutation affecting the DNA binding domain of PPARγ (E157D). Apart from the lipodystrophy and severe metabolic syndrome, individuals presented musculoskeletal and hematological issues. E157D heterozygotes had a muscular habitus yet displayed muscle weakness and myopathy. Also, E157D heterozygotes presented multiple cytopenias and a susceptibility to autoimmune disease. In vitro studies showed that the E157D mutation does not decrease the receptor's affinity to classical PPAR response elements or its responsiveness to a PPARγ agonist, yet it severely reduces its target gene transcription. Microarray experiments demonstrated a decreased activation of a wide array of genes, including genes involved in the PPAR response, the immune response, hematopoiesis, and metabolism in muscle. In addition, a subset of genes with cryptic PPAR response elements was activated. In summary, we describe a large family with a novel PPARγ mutation, which extends the clinical phenotype of FPLD3 to include muscular, immune, and hematological features. Together, our results support the role of PPARγ in controlling homeostasis of multiple systems beyond lipid metabolism.

Excess of rare variants in non-genome-wide association study candidate genes in patients with hypertriglyceridemia.

BACKGROUND: Rare variant accumulation studies can implicate genes in disease susceptibility when a significant burden is observed in patients versus control subjects. Such analyses might be particularly useful for candidate genes that are selected based on experiments other than genome-wide association studies (GWAS). We sought to determine whether rare variants in non-GWAS candidate genes identified from mouse models and human mendelian syndromes of hypertriglyceridemia (HTG) accumulate in patients with polygenic adult-onset HTG. METHODS AND RESULTS: We resequenced protein coding regions of 3 genes with established roles (APOC2, GPIHBP1, LMF1) and 2 genes recently implicated (CREB3L3 and ZHX3) in TG metabolism. We identified 41 distinct heterozygous rare variants, including 29 singleton variants, in the combined sample; in total, we observed 47 rare variants in 413 HTG patients versus 16 in 324 control subjects (odds ratio=2.3; P=0.0050). Post hoc assessment of genetic burden in individual genes using 3 different tests suggested that the genetic burden was most prominent in the established genes LMF1 and APOC2, and also in the recently identified CREB3L3 gene. CONCLUSIONS: These extensive resequencing studies show a significant accumulation of rare genetic variants in non-GWAS candidate genes among patients with polygenic HTG, and indicate the importance of testing specific hypotheses in large-scale resequencing studies.

An increased burden of common and rare lipid-associated risk alleles contributes to the phenotypic spectrum of hypertriglyceridemia.

OBJECTIVE: Earlier studies have suggested that a common genetic architecture underlies the clinically heterogeneous polygenic Fredrickson hyperlipoproteinemia (HLP) phenotypes defined by hypertriglyceridemia (HTG). Here, we comprehensively analyzed 504 HLP-HTG patients and 1213 normotriglyceridemic controls and confirmed that a spectrum of common and rare lipid-associated variants underlies this heterogeneity. METHODS AND RESULTS: First, we demonstrated that genetic determinants of plasma lipids and lipoproteins, including common variants associated with plasma triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) from the Global Lipids Genetics Consortium were associated with multiple HLP-HTG phenotypes. Second, we demonstrated that weighted risk scores composed of common TG-associated variants were distinctly increased across all HLP-HTG phenotypes compared with controls; weighted HDL-C and LDL-C risk scores were also increased, although to a less pronounced degree with some HLP-HTG phenotypes. Interestingly, decomposition of HDL-C and LDL-C risk scores revealed that pleiotropic variants (those jointly associated with TG) accounted for the greatest difference in HDL-C and LDL-C risk scores. The APOE E2/E2 genotype was significantly overrepresented in HLP type 3 versus other phenotypes. Finally, rare variants in 4 genes accumulated equally across HLP-HTG phenotypes. CONCLUSIONS: HTG susceptibility and phenotypic heterogeneity are both influenced by accumulation of common and rare TG-associated variants.

Excess of rare variants in genes identified by genome-wide association study of hypertriglyceridemia.

Genome-wide association studies (GWAS) have identified multiple loci associated with plasma lipid concentrations. Common variants at these loci together explain <10% of variation in each lipid trait. Rare variants with large individual effects may also contribute to the heritability of lipid traits; however, the extent to which rare variants affect lipid phenotypes remains to be determined. Here we show an accumulation of rare variants, or a mutation skew, in GWAS-identified genes in individuals with hypertriglyceridemia (HTG). Through GWAS, we identified common variants in APOA5, GCKR, LPL and APOB associated with HTG. Resequencing of these genes revealed a significant burden of 154 rare missense or nonsense variants in 438 individuals with HTG, compared to 53 variants in 327 controls (P = 6.2 x 10(-8)), corresponding to a carrier frequency of 28.1% of affected individuals and 15.3% of controls (P = 2.6 x 10(-5)). Considering rare variants in these genes incrementally increased the proportion of genetic variation contributing to HTG.

O que as gestantes sabem sobre cárie: uma avaliação dos conhecimentos de primigestas e multigestas quanto à própria saúde bucal / What pregnant women do know about dental caries: an evaluaation of the knowledge of primigravid and multigravid about their own oral health

A gravidez, dada a sua singularidade, remete a uma série de dúvidas. Estas por sua vez, podem funcionar como estímulo para que a gestante busque informações relativas à própria saúde. O propósito desta pesquisa é de avaliar, comparativamente, o nível de conhecimento que primigestas e multigestas têm sobre o tema cárie. Para tanto, foram entrevistadas 55 gestantes de nível socioeconômico baixo que aguardavam atendimento médico em núcleos de saúde pública da cidade de Anápolis-Goiás. Observou-se que 70 por cento das primigestas e 54,28 por cento das multigestas conhecem a cárie. A maioria da grávidas soube definir a cárie e indicar as causas dela. Grande parte das mulheres associou a gravidez ao aumento da incidência da cárie. A avaliação destes resultados permitiu concluir que primigestas e multigestas, em geral, possuem o mesmo domínio de informações a respeito da doença cárie. Além disso, as gestantes demonstraram uma carência de orientação quanto à questão dos cuidados com a saúde bucal