To test the validity of survey techniques for measuring diet and activity patterns of Pima Indians, sequential 24-hour recalls, a food frequency questionnaire (FFQ), and an activity questionnaire were compared to free-living energy expenditure. Total energy expenditure (TEE) measured by doubly labeled water was 13.27 +/- 2.95 MJ/d for the 12 males (mean +/- SD: 35 +/- 14 yr; 97 +/- 35 kg; 32 +/- 9% body fat) and 11.67 +/- 1.85 MJ/d for the 9 females (31 +/- 13 yr; 106 +/- 32 kg; 49 +/- 6% body fat). Energy intake assessed by 24-hour recall was 13.59 +/- 7.81 MJ/d for men and 9.29 +/- 2.77 MJ/d for women, compared to 12.84 + 2.85 and 9.40 + 2.61 MJ/d for men and women, respectively, by FFQ. Both dietary methods indicated significant underreporting by women when compared to TEE. Energy intake assessed by FFQ was significantly correlated with TEE (r=0.48, p=0.03). This was true with 24-hour recall energy intake only when data from two extremely large alcohol consumers were eliminated (r=0.64, p=0.03, N=19). Although a low level of activity was apparent, the activity questionnaire produced significant correlations with measurements of energy expenditure and therefore represents an important tool for examining the relationship between physical activity and diseases.

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OBJECTIVE -In short-term studies, adoption of a traditional diet is associated with reduction in metabolic abnormalities often found in populations experiencing rapid lifestyle changes. We examined the long-term effects of a self-assessed traditional or nontraditional dietary pattern on the development of type 2 diabetes in 165 nondiabetic Pima Indians.RESEARCH DESIGN AND METHODS -Dietary intake was assessed in 1988 by a quantitative food frequency method, and subjects were asked to classify their diet as "Indian," "Anglo," or "mixed." The Indian diet reflects a preference for Sonoran-style and traditional desert foods. The Anglo diet reflects a preference for non-Sonoran-style foods typical of the remaining regions of the U.S.RESULTS -In women, the intake of complex carbohydrates, dietary fiber, insoluble fiber, vegetable proteins, and the proportion of total calories from complex carbohydrate and vegetable proteins were significantly higher (P Ͻ 0.05) in the Indian than in the Anglo diet. The mixed diet was intermediate in of all these constituents. In men, the intake for these nutrients was also higher in the Indian than in the Anglo group, but not significantly. Diabetes developed in 36 subjects (8 men and 28 women) during 6.2 years of follow-up (range 0.9 -10.9). The crude incidence rates of diabetes were 23, 35, and 63 cases per 1,000 person-years in the Indian, mixed, and Anglo groups, respectively. After adjustment for age, sex, BMI, and total energy intake in a proportional hazards model, the risk of developing diabetes in the Anglo-diet group was 2.5 times as high (95% CI 0.9 -7.2) and the rate in the mixed-diet group was 1.3 times as high (0.6 -3.3) as in the Indian-diet group.CONCLUSIONS -This study suggests that the adoption of an Anglo diet may increase the risk of developing diabetes in Pima Indians, but it does not provide unequivocal evidence for or against this hypothesis.

The Milestones are designed only for use in evaluation of resident physicians in the context of their participation in ACGME-accredited residency or fellowship programs. The Milestones provide a framework for the assessment of the development of the resident physician in key dimensions of the elements of physician competency in a specialty or subspecialty. The Milestones represent neither the entirety of the dimensions of the 6 domains of physician competency nor are they designed to be relevant in any other context.

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are emerging worldwide epidemics, projected to become the leading cause of liver transplants. The strongest genetic risk factor for NAFLD/NASH susceptibility and progression is a single-nucleotide polymorphism (SNP) in the patatin-like phospholipase domain-containing 3 gene (PNPLA3), rs738409, encoding the missense mutation I148M. This aminoacidic substitution interferes with the normal remodeling of lipid droplets in hepatocytes. It is also thought to play a key role in promoting liver fibrosis by inhibiting the release of retinol from hepatic stellate cells. Reducing PNPLA3 levels in individuals homozygous for 148M may be an effective treatment for the entire spectrum of NAFLD, based on gene dosage analysis in the human population, as well as the protective effect of another naturally occurring SNP (rs2294918) in PNPLA3 which, when co-inherited, reduces PNPLA3 mRNA levels to 50% and counteracts disease risk. By screening a clinical compound library targeting specific signaling pathways active in primary human hepatocytes, we identified momelotinib, a drug evaluated in clinical trials to treat myelofibrosis, as a potent down-regulator of PNPLA3 expression, across all genotypes. We found that momelotinib treatment yielded >80% reduction in PNPLA3 mRNA in human primary hepatocytes and stellate cells, as well as in vivo via acute and chronic treatment of WT mice. Using a human multilineage 3D spheroid model of NASH homozygous for the PNPLA3 mutant protein, we additionally show that it decreases PNPLA3 mRNA as well as intracellular lipid content. Furthermore, we show that the effects on PNPLA3 coincide with changes in chromatin accessibility within regulatory regions of the PNPLA3 locus, consistent with inhibition occurring at the level of transcription. In addition to its primary reported targets, the JAK kinases, momelotinib inhibits several non-JAK kinases, including ACVR1. Using a combination of targeted siRNA knockdowns and signaling pathway perturbations, we show that momelotinib reduces the expression of the PNPLA3 gene largely through the inhibition of BMP signaling rather than the JAK/STAT pathway. Overall, our work identified momelotinib as a potential NASH therapeutic and uncovered previously unrecognized connections between signaling pathways and PNPLA3. These pathways may be exploited by drug modalities to “tune down” the level of gene expression, and therefore offer a potential therapeutic benefit to a high at-risk subset of NAFLD/NASH patients.

This paper describes the development and psychometric evaluation of scales measuring the dimensions of 'will' (belief, confidence, prior action and desire) for heart health promotion specifically and health promotion in general at both an individual and organizational level. Content validity was established through a series of focus groups and expert opinion assessments, based on a compilation of capacity-assessment instruments developed by other provinces involved in the Canadian Heart Health Initiative and the literature. Psychometric analyses of questionnaire data provided empirical evidence of the construct validity and reliability of the 16 individual and 21 organizational level 'will' scales. A series of principal component analyses assisted in verifying the unidimensionality of the measures and all scales yielded high internal consistencies with Cronbach's alpha coefficients ranging between 0.73 and 0.96. These measures can be used by both researchers and practitioners for assessing the 'will' to promote heart health specifically and health promotion in general.

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Species-specific calling songs of male field crickets attract conspecific females. Each wing closure results in a pulse of sound, and the song is composed of pulses arranged in species-specific patterns of short chirps, long continuous trills, or intermediates between chirps and trills. California Gryllus integer has a song with pulses of sound delivered in groups of two or three to produce a chirp, but in central Texas, the G. integer song has a variable number of pulses delivered in long continuous trills. Gryllus rubens occurs from eastern Texas to Florida and has a trilling song with a slower pulse rate than that of Texas G. integer. Identification of these three groups in the laboratory was confirmed by recording and analyzing songs for California and Texas G. integer and G. rubens males. All possible crosses were performed in the laboratory between conspecifics and heterospecifics. No progeny resulted in California G. integer and Texas G. integer or California G. integer and G. rubens crosses. Hybrids were produced in G. rubens and Texas G. integer crosses. Results suggest that California and Texas G. integer are different species, or at least populations geographically separated enough to result in reproductive incompatibility and different song types. Texas G. integer and G. rubens are apparently closely related species.