Dietary Cholesterol or Egg Consumption and Cardiovascular Outcomes

To the Editor Based on an analysis of 6 prospective cohorts, Dr Zhong and colleagues concluded that “higher consumption of dietary cholesterol or eggs was significantly associated with higher risk of incident CVD [cardiovascular disease] and all-cause mortality in a dose-response manner” and noted these findings should be considered “in the development of dietary guidelines and updates.” At issue is whether their findings, which differ from some previously published meta-analyses onthis topic, are sufficiently robust to be considered in guidelines

Successful long-term weight loss among participants with diabetes receiving an intervention promoting an adapted Mediterranean-style dietary pattern: The Heart Healthy Lenoir Project

Objective: To examine weight change by diabetes status among participants receiving a Mediterraneanstyle diet, physical activity, and weight loss intervention adapted for delivery in the southeastern USA, where rates of cardiovascular disease (CVD) are disproportionately high. Research design and methods: The intervention included: Phase I (months 1-6), an individually tailored intervention promoting a Mediterranean-style dietary pattern and increased walking; Phase II (months 7-12), option of a 16-week weight loss intervention for those with BMI≥25 kg/m2 offered as 16 weekly group sessions or 5 group sessions and 10 phone calls, or a lifestyle maintenance intervention; and Phase III (months 13-24), weight loss maintenance intervention for those losing ≥8 pounds with all others receiving a lifestyle maintenance intervention. Weight change was assessed at 6, 12, and 24-month follow-up. Results: Baseline characteristics (n=339): mean age 56, 77% female, 65% African-American, 124 (37%) with diabetes; mean weight 103 kg for those with diabetes and 95 kg for those without. Among participants with diabetes, average weight change was -1.2 kg (95% CI -2.1 to -0.4) at 6 months (n=92), -1.5 kg (95% CI -2.9 to -0.2) at 12 months (n=96), and -3.7 kg (95% CI -5.2 to -2.1) at 24 months (n=93). Among those without diabetes, weight change was -0.4 kg (95% CI -1.4 to 0.6) at 24 months (n=154). Conclusions: Participants with diabetes experienced sustained weight loss at 24-month follow-up. High-risk US populations with diabetes may experience clinically important weight loss from this type of lifestyle intervention

Results Of A Genome-wide Genetic Screen For Panic Disorder

Panic disorder is characterized by spontaneous and recurrent panic attacks, often accompanied by agoraphobia. The results of family, twin, and segregation studies suggest a genetic role in the etiology of the illness. We have genotyped up to 23 families that have a high density of panic disorder with 540 microsatellite DNA markers in a first-pass genomic screen. The thirteen best families (ELOD > 6.0 under the dominant genetic model) have been genotyped with an ordered set of markers encompassing all the autosomes, at an average marker density of 11 cM. Over 110,000 genotypes have been generated on the whole set of families, and the data have been analyzed under both a dominant and a recessive model, and with the program SIBPAIR. No lod scores exceed 2.0 for either parametric model. Two markers give lod scores over 1.0 under the dominant model (chromosomes 1p and 20p), and four do under the recessive model (7p, 17p, 20q, and X/Y). One of these (20p) may be particularly promising. Analysis with SIBPAIR yielded P values equivalent to a lod score of 1.0 or greater (i.e., P < .016, one-sided, uncorrected for multiple tests) for 11 marker loci (2, 7p, 8p, 8q, 9p, 11q, 12q, 16p, 20p and 20q)

Gain-of-function RHOA mutations promote focal adhesion kinase activation and dependency in diffuse gastric cancer

Diffuse gastric cancer (DGC) is a lethal malignancy lacking effective systemic therapy. Among the most provocative recent results in DGC has been that of highly recurrent missense mutations in the GTPase RHOA. The function of these mutations has remained unresolved. We demonstrate that RHOAY42C, the most common RHOA mutation in DGC, is a gain-of-function oncogenic mutant, and that expression of RHOAY42C with inactivation of the canonical tumor suppressor Cdh1 induces metastatic DGC in a mouse model. Biochemically, RHOAY42C exhibits impaired Y42C GTP hydrolysis and enhances interaction with its effector ROCK. RHOA mutation and Cdh1 loss induce actin/cytoskeletal rearrangements and activity of focal adhesion kinase (FAK), which activates YAP–TAZ, PI3K–AKT, and β-catenin. RHOAY42C murine models were sensitive to FAK inhibition and to combined YAP and PI3K pathway blockade. These results, coupled with sensitivity to FAK inhibition in patient-derived DGC cell lines, nominate FAK as a novel target for these cancers. SIGNIFICANCE: The functional significance of recurrent RHOA mutations in DGC has remained unresolved. Through biochemical studies and mouse modeling of the hotspot RHOAY42C mutation, we establish that these mutations are activating, detail their effects upon cell signaling, and define how RHOA-mediated FAK activation imparts sensitivity to pharmacologic FAK inhibitors

Designing and implementing a comparative effectiveness study of two strategies for delivering high quality CHD prevention: Methods and participant characteristics for the Heart to Health study

10.1016/j.cct.2013.07.013Contemporary Clinical Trials362394-40

Natal dispersal and breeding dispersal of a subsocial spitting spider (Scytodes pallida) (Araneae: Scytodidae), from Singapore

10.1111/j.1469-7998.2005.00028.xJournal of Zoology2682121-126JOZO