Effect of severe obesity in childhood and adolescence on risk of type 2 diabetes in youth and early adulthood in an American Indian population.

Objectives: The risk of early-onset type 2 diabetes associated with the severity of obesity in youth is not well understood. This study aims to determine metabolic alterations and type 2 diabetes risk among American Indian children who are obese or severely obese.

Methods: Incidence rates of diabetes before 20 years (youth-onset) and 45 years were computed in 2728 children who were from 5 to <10 years and 4317 adolescents who were from 10 to <18 years without diabetes examined between 1965 and 2007.

Identity-by-Descent Mapping Identifies Major Locus for Serum Triglycerides in Amerindians Largely Explained by an Founder Mutation.

Background: Identity-by-descent mapping using empirical estimates of identity-by-descent allele sharing may be useful for studies of complex traits in founder populations, where hidden relationships may augment the inherent genetic information that can be used for localization.

Methods And Results: Through identity-by-descent mapping, using ≈400 000 single-nucleotide polymorphisms (SNPs), of serum lipid profiles, we identified a major linkage signal for triglycerides in 1007 Pima Indians (LOD=9.23; =3.

Admixture mapping in the Hispanic Community Health Study/Study of Latinos reveals regions of genetic associations with blood pressure traits.

Admixture mapping can be used to detect genetic association regions in admixed populations, such as Hispanics/Latinos, by estimating associations between local ancestry allele counts and the trait of interest. We performed admixture mapping of the blood pressure traits systolic and diastolic blood pressure (SBP, DBP), mean arterial pressure (MAP), and pulse pressure (PP), in a dataset of 12,116 participants from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Hispanics/Latinos have three predominant ancestral populations (European, African, and Amerindian), for each of which we separately tested local ancestry intervals across the genome.

Erratum: Large meta-analysis of genome-wide association studies identifies five loci for lean body mass.

A correction to this article has been published and is linked from the HTML version of this article.

Growth Tracking in Severely Obese or Underweight Children.

Objectives: To illustrate the difficulties in optimal growth monitoring of children with severe obesity or underweight by using the Centers for Disease Control and Prevention (CDC) 2000 age- and sex-specific BMI percentile growth charts. We also aimed to examine the utility of a new modified CDC BMI score chart to monitor growth in children with normal and extreme BMI percentiles by using real-life clinical scenarios.

Methods: Modified BMI score charts were created by using the 2000 CDC algorithm.

Serum lipids and mortality in an American Indian population: A longitudinal study.

Background: In Caucasians, lower triglycerides (TG), total or LDL cholesterol and high HDL cholesterol are generally associated with lower mortality. However, low cholesterol is associated with higher mortality in some Asian populations. This study examines the relationship between serum lipids and mortality in American Indians.

Shock Tube and Laser Absorption Study of CHO Oxidation via Simultaneous Measurements of OH and CO.

The oxidation of Ar-diluted stoichiometric CHO-O mixtures was studied behind reflected shock waves over temperatures of 1332-1685 K, at pressures of about 1.5 atm and initial CHO mole fractions of 500, 1500, and 5000 ppm. Quantitative and time-resolved concentration histories of OH and CO (at both v″ = 0 and v″ = 1) were measured by narrow-linewidth laser absorption at 306.

White blood cell fractions correlate with lesions of diabetic kidney disease and predict loss of kidney function in Type 2 diabetes.

Background: Inflammation linked to diabetic kidney disease (DKD) may affect white blood cell (WBC) counts and differentials. We examined the cross-sectional associations of total WBC count and WBC fractions with structural lesions of DKD in 108 Pima Indians with Type 2 diabetes who underwent research kidney biopsies. We also examined the longitudinal association of these WBC variables with renal function loss (RFL) in 941 Europeans with Type 2 diabetes from the SURDIAGENE study.

Atlanto-axial malformation in an adult Quarter horse gelding.

An adult gelding was evaluated for bilateral intermittent forelimb lameness of approximately 2 years duration. The horse was found to have grade 2/5 upper motor neuron-general proprioception ataxia with no cranial nerve deficits. During radiographic and gross necropsy examinations a novel atlanto-axial malformation of possible congenital etiology was found.

Synthetic Study toward Total Synthesis of (±)-Germine: Synthesis of (±)-4-Methylenegermine.

The total synthesis of 4-methylenegermine is described.

An In Vitro Model for Studying Cellular Transformation by Kaposi Sarcoma Herpesvirus.

Kaposi sarcoma (KS) is an unusual tumor composed of proliferating spindle cells that is initiated by infection of endothelial cells (EC) with KSHV, and develops most often in the setting of immunosuppression. Despite decades of research, optimal treatment of KS remains poorly defined and clinical outcomes are especially unfavorable in resource-limited settings. KS lesions are driven by pathological angiogenesis, chronic inflammation, and oncogenesis, and various in vitro cell culture models have been developed to study these processes.

Committed as a Violent Sexual Predator in His 10th Decade: A Case Study.

We report a case study of Atypical Offender (AO), a man who was civilly committed as a sexually violent person several years after his 90th birthday. In this article, we review the factors that usually contribute to virtually zero rates of sexual crime among nonagenarians for clues as to why these protective factors did not apply to this exceptional case. Psychological assessments and court records portrayed AO as having many of the features expected of persistent sexual offenders against children (e.

Combined Ab Initio, Kinetic Modeling, and Shock Tube Study of the Thermal Decomposition of Ethyl Formate.

The potential energy surfaces (PESs) and reaction rate constants of the unimolecular decomposition of ethyl formate (EF) were investigated using high-precision theoretical methods at the CCSD(T)/CBS(T-Q)//M06-2X/6-311++G(d,p) level of theory. The calculated PESs of EF dissociation and molecular decomposition reactions indicate that the intramolecular H-shift to produce formic acid and ethylene is the dominant decomposition pathway. A detailed chemical kinetic mechanism for EF pyrolysis was constructed by incorporating the important reactions of EF and its radicals into an existing mechanism previously developed for small methyl esters.

Autoantibodies against PFDN2 are associated with an increased risk of type 2 diabetes: A case-control study.

Background: The adaptive immune system is involved in type 2 diabetes mellitus (T2DM), indicating the presence of unidentified autoantibodies that might be useful biomarkers for emerging immunomodulatory therapy. A prior microarray study with a small number of participants suggested the association of novel autoantibodies with T2DM in Southwest American Indians. We therefore sought to determine whether antibodies against 14 target proteins are associated with T2DM in a large case-control study.

Large meta-analysis of genome-wide association studies identifies five loci for lean body mass.

Lean body mass, consisting mostly of skeletal muscle, is important for healthy aging. We performed a genome-wide association study for whole body (20 cohorts of European ancestry with n = 38,292) and appendicular (arms and legs) lean body mass (n = 28,330) measured using dual energy X-ray absorptiometry or bioelectrical impedance analysis, adjusted for sex, age, height, and fat mass. Twenty-one single-nucleotide polymorphisms were significantly associated with lean body mass either genome wide (p < 5 × 10) or suggestively genome wide (p < 2.

One-hour and two-hour postload plasma glucose concentrations are comparable predictors of type 2 diabetes mellitus in Southwestern Native Americans.

Aims/hypothesis: Elevated 2-h plasma glucose concentration (2 h-PG) during a 75 g OGTT predict the development of type 2 diabetes mellitus. However, 1-h plasma glucose concentration (1 h-PG) is associated with insulin secretion and may be a better predictor of type 2 diabetes. We aimed to investigate the association between 1 h-PG and 2 h-PG using gold standard methods for measuring insulin secretion and action.

Leveraging Technology to Address the Quality Chasm in Children's Evidence-Based Psychotherapy.

The quality of psychosocial treatment delivery is highly variable in community practice settings, even among well-trained providers. This column discusses the potential to improve patient outcomes by targeting two important quality-of-care indicators through technology: provider fidelity and children's engagement. A case example describes one provider's use of numerous tablet-based activities in the context of evidence-based psychotherapy.

Entanglement distillation between solid-state quantum network nodes.

The impact of future quantum networks hinges on high-quality quantum entanglement shared between network nodes. Unavoidable imperfections necessitate a means to improve remote entanglement by local quantum operations. We realize entanglement distillation on a quantum network primitive of distant electron-nuclear two-qubit nodes.

Discovery of Clinical Candidate 2-((2S,6S)-2-Phenyl-6-hydroxyadamantan-2-yl)-1-(3'-hydroxyazetidin-1-yl)ethanone [BMS-816336], an Orally Active Novel Selective 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitor.

BMS-816336 (6n-2), a hydroxy-substituted adamantyl acetamide, has been identified as a novel, potent inhibitor against human 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme (IC 3.0 nM) with >10000-fold selectivity over human 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2). 6n-2 exhibits a robust acute pharmacodynamic effect in cynomolgus monkeys (ED 0.

Relationship violence victimization and binge drinking trajectories among a nationally representative sample of adolescents.

The present study evaluated the impact of relationship violence (RV) victimization on the longitudinal trajectory of binge drinking (BD) among 3614 US adolescents (51.2% male) who participated in an initial telephone interview regarding physical and sexual RV victimization and binge drinking. Two follow-up phone interviews were completed over approximately three years.

A Genome-Wide Association Study of IVGTT-Based Measures of First-Phase Insulin Secretion Refines the Underlying Physiology of Type 2 Diabetes Variants.

Understanding the physiological mechanisms by which common variants predispose to type 2 diabetes requires large studies with detailed measures of insulin secretion and sensitivity. Here we performed the largest genome-wide association study of first-phase insulin secretion, as measured by intravenous glucose tolerance tests, using up to 5,567 individuals without diabetes from 10 studies. We aimed to refine the mechanisms of 178 known associations between common variants and glycemic traits and identify new loci.

A Genome-Wide Association Study Using a Custom Genotyping Array Identifies Variants in Associated With Reduced Energy Expenditure in American Indians.

Pima Indians living in Arizona have a high prevalence of obesity, and we have previously shown that a relatively lower energy expenditure (EE) predicts weight and fat mass gain in this population. EE is a familial trait (heritability = 0.52); therefore, in the current study, we aimed to identify genetic variants that affect EE and thereby influence BMI and body fatness in Pima Indians.