Lean Yet Unhealthy: Asian American Adults Had Higher Risks for Metabolic Syndrome than Non-Hispanic White Adults with the Same Body Mass Index: Evidence from NHANES 2011-2016.

(1) Background: Despite having consistently lower rates of obesity than other ethnic groups, Asian Americans (AAs) are more likely to be identified as metabolically obese, suggesting an ethnic-specific association between BMI and cardiometabolic outcomes. The goal of this study was to provide an estimate of metabolic syndrome (MetS) prevalence among AAs using national survey data and to compare this rate to that of non-Hispanic Whites (NHWs) over the BMI continuum. (2) Methods: Using the NHANES 2011-2016 data, we computed age-adjusted, gender-specific prevalence of MetS and its individual components for three BMI categories. Furthermore, we conducted multivariate binary logistic regression to examine the risk of MetS in AAs compared to NHWs, controlling for sociodemographic and lifestyle factors. The analysis sample consisted of 2121 AAs and 6318 NHWs. (3) Results: Among AAs, the prevalence of MetS and its components increased with higher BMI levels, with overall prevalence being 5.23% for BMI < 23, 38.23% for BMI of 23-27.4, and 77.68% for BMI ≥ 27.5 in men; and 18.61% for BMI < 23, 47.82% for BMI of 23-27.4, and 67.73% for BMI ≥ 27.5 in women. We also found that for those with a BMI > 23, AAs had a higher predicted risk of MetS than their NHW counterparts of the same BMI level, in both men and women. (4) Conclusions: Our findings support the use of lower BMI ranges for defining overweight and obesity in Asian populations, which would allow for earlier and more appropriate screening for MetS and may better facilitate prevention efforts.

A case study of pulmonary embolism from the right atrial shunt after acute type a aortic dissection surgery.

This is one case report of a 46-year-old Chinese male with type A acute aortic dissection. It is an emergent surgery including Bentall procedure, interposition graft replacement of aortic arch, stented descending aorta with the modified right atrial shunt technique. In the early post operation period, the patient was complicated with pulmonary embolism. Pulmanary arteriography showed that the right main pulmonary embolism without an extrinsic compression. After the anticoagulant therapy, the patient was well recovered and discharged from hospital 1 month later. The origin of pulmonary embolism in the patient was believed to be the thrombosis in the shunt fistula. The right atrial shunt-related complications haven't been reported for more than thirty years. Pulmonary embolism could be a severe complication after the right atrial shunt in acute type A aortic dissection.

LY2801653 is an orally bioavailable multi-kinase inhibitor with potent activity against MET, MST1R, and other oncoproteins, and displays anti-tumor activities in mouse xenograft models.

The HGF/MET signaling pathway regulates a wide variety of normal cellular functions that can be subverted to support neoplasia, including cell proliferation, survival, apoptosis, scattering and motility, invasion, and angiogenesis. MET over-expression (with or without gene amplification), aberrant autocrine or paracrine ligand production, and missense MET mutations are mechanisms that lead to activation of the MET pathway in tumors and are associated with poor prognostic outcome. We report here preclinical development of a potent, orally bioavailable, small-molecule inhibitor LY2801653 targeting MET kinase. LY2801653 is a type-II ATP competitive, slow-off inhibitor of MET tyrosine kinase with a dissociation constant (Ki) of 2 nM, a pharmacodynamic residence time (Koff) of 0.00132 min(-1) and t1/2 of 525 min. LY2801653 demonstrated in vitro effects on MET pathway-dependent cell scattering and cell proliferation; in vivo anti-tumor effects in MET amplified (MKN45), MET autocrine (U-87MG, and KP4) and MET over-expressed (H441) xenograft models; and in vivo vessel normalization effects. LY2801653 also maintained potency against 13 MET variants, each bearing a single-point mutation. In subsequent nonclinical characterization, LY2801653 was found to have potent activity against several other receptor tyrosine oncokinases including MST1R, FLT3, AXL, MERTK, TEK, ROS1, DDR1/2 and against the serine/threonine kinases MKNK1/2. The potential value of MET and other inhibited targets within a number of malignancies (such as colon, bile ducts, and lung) is discussed. LY2801653 is currently in phase 1 clinical testing in patients with advanced cancer (trial I3O-MC-JSBA, NCT01285037).

Dicer is required for embryonic angiogenesis during mouse development.

Dicer is a multi-domain protein responsible for the generation of short interfering RNAs (siRNAs) from long double-stranded RNAs during RNA interference. It is also involved in the maturation of microRNAs, some of which are transcriptional regulators of developmental timing in nematodes. To assess the role of Dicer in mammals, we generated Dicerex1/2 mice with a deletion of the amino acid sequences corresponding to the first and second exons of the dicer gene via homologous recombination. We found that Dicerex1/2 homozygous embryos displayed a retarded phenotype and died between days 12.5 and 14.5 of gestation. Thus, these results show that dicerex1/2 is severely hypomorphic and that Dicer is essential for normal mouse development. Interestingly, we also found that blood vessel formation/maintenance in dicerex1/2 embryos and yolk sacs were severely compromised, suggesting a possible role for Dicer in angiogenesis. This finding is consistent with the altered expression of vegf, flt1, kdr, and tie1 in the mutant embryos. Taken together, the results of this study indicate that Dicer exerts its function on mouse embryonic angiogenesis probably through its role in the processing of microRNAs that regulate the expression levels of some critical angiogenic regulators in the cell.