The functional Q84R polymorphism of mammalian tribbles homolog TRB3 is associated with insulin resistance and related cardiovascular risk in Caucasians from Italy

Insulin resistance plays a major role in dyslipidemia, cardiovascular disease, and type 2 diabetes. TRB3, a mammalian tribbles homolog, whose chromosomal region 20p13-p12 has been linked to human type 2 diabetes, impairs insulin signaling through the inhibition of Akt phosphorylation and is overexpressed in murine models of insulin resistance. We here report that the prevalent TRB3 missense Q84R polymorphism is significantly (P < 0.05) associated with several insulin resistance-related abnormalities in two independent cohorts (n = 178 and n = 605) of nondiabetic individuals and with the presence of a cluster of insulin resistance-related cardiovascular risk factors in 716 type 2 diabetic patients (OR 3.1 [95% CI 1.2-8.2], P = 0.02). In 100 additional type 2 diabetic patients who suffered from myocardial ischemia, age at myocardial ischemia was progressively and significantly (P = 0.03) reduced from Q84Q to Q84R to R84R individuals. To test the functional role of TRB3 variants, either Q84 or R84 TRB3 full-length cDNAs were transfected in human HepG2 hepatoma cell lines. As compared with control HepG2 cells, insulin-induced Ser473-Akt phosphorylation was reduced by 22% in Q84- (P < 0.05 vs. control cells) and by 45% in R84-transfected cells (P < 0.05 vs. Q84 transfected and P < 0.01 vs. control cells). These data provide the first evidence that TRB3 gene plays a role in human insulin resistance and related clinical outcomes

Calibration of the Solar-B x-ray optics

The Solar-B X-ray telescope (XRT) is a grazing-incidence modified Wolter I X-ray telescope, of 35 cm inner diameter and 2.7 m focal length. XRT, designed for full sun imaging over the wavelength 6-60 Angstroms, will be the highest resolution solar X-Ray telescope ever flown. Images will be recorded by a 2048 X 2048 back-illuminated CCD with 13.5 µm pixels (1 arc-sec/pixel ) with full sun field of view. XRT will have a wide temperature sensitivity in order to observe and discriminate both the high (5-10 MK) and low temperature (1-5 MK) phenomena in the coronal plasma. This paper presents preliminary results of the XRT mirror calibration performed at the X-ray Calibration Facility, NASA-MSFC, Huntsville, Alabama during January and February 2005. We discuss the methods and the most significant results of the XRT mirror performance, namely: characteristics of the point response function (PSF), the encircled energy and the effective area. The mirror FWHM is 0.8” when corrected for 1-g, finite source distance, and CCD pixelization. With the above corrections the encircled energy at 27m and 1keV is 52%. The effective area is greater than 2cm2 at 0.5keV and greater than 1.7cm2 at 1.0ke

The nutritional risk in oncology: a study of 1,453 cancer outpatients

There is little information about the nutritional status of cancer outpatients because the practice of nutritional screening is rarely performed. This study aims to define the pattern of scores of nutritional risk in 1,453 outpatients and factors associated with a high nutrition risk score, to facilitate the identification of such patients by the oncologists. We prospectively screened the nutritional status of cancer outpatients according to the NRS-2002 score which combines indicators of malnutrition and of severity of the disease (1-3 points, respectively). A score a parts per thousand yen3 indicates "nutritional risk". The association of the nutritional scores with some patient/tumour/therapy-related variables was investigated through univariable and multivariable linear regression models. Thirty-two percent of outpatients were at nutritional risk. Primary tumour site, Eastern Cooperative Oncology Group score and presence of anorexia or fatigue were significantly associated with the nutrition risk score. Depending on the combination of these variables, it was possible to estimate different probabilities of nutritional risk. The frequency of a relevant nutritional risk was higher than expected considering the favourably selected population. The nutritional risk was associated with common clinical variables which are usually recorded in the charts and could easily alert the oncologist on the need of a further nutritional assessment or a nutritional support

GADA Titer-Related Risk for Organ-Specific Autoimmunity in LADA Subjects Subdivided according to Gender (NIRAD Study 6)

Context: Latentautoimmunediabetes in adults(LADA)includesaheterogeneous population wherein, based on glutamic acid decarboxylase antibody (GADA) titer, different subgroups of subjects can be identified. Objective: The aim of the present study was to evaluateGADAtiter-related risk for-cell and other organ-specific autoimmunity in LADA subjects. Methods: Adult-onsetautoimmunediabetes subjects (n236)andtype 2 diabetes (T2DM) subjects (n 450) were characterized for protein tyrosine phosphatase (IA-2IC and IA-2256–760), zinc transporter 8 (ZnT8), thyroid peroxidase, (TPO), steroid 21-hydroxylase (21-OH), tissue transglutaminase (tTG), and antiparietal cell (APC) antibodies. Results: High GADA titer compared to low GADA titer showed a significantly higher prevalence of IA-2IC, IA-2256–760, ZnT8, TPO, and APC antibodies (P 0.04 for all comparison). 21-OH antibodies were detected in 3.4% of high GADA titer. A significant decreasing trend was observed from high GADA to low GADA and to T2DM subjects for IA-2256–760, ZnT8, TPO, tTG, and APC antibodies (P for trend0.001).TPOwas the only antibody showing a different prevalence between gender; low GADA titer and T2DM female patients had a higher frequency of TPO antibody compared to males (P0.0004 and P0.0006, respectively), where the presence of highGADAtiter conferred an odds ratio of 8.6 for TPO compared to low GADA titer. After subdividing high and low GADA titer subjects according to the number of antibodies, we observed that 73.3% of high GADA titer subjects were positive for at least one or more antibodies, compared to 38.3% of low GADA titer (P 0.0001). Conclusions: In LADA subjects, high GADA titer was associated with a profile of more severe autoimmunity and, in male gender, specifically predisposed to thyroid autoimmunity. A regular screening for other antibodies is recommended in LADA patients according to GADA titer and gender