Postmenopausal Women With Greater Paracardial Fat Have More Coronary Artery Calcification Than Premenopausal Women: The Study of Women's Health Across the Nation (SWAN) Cardiovascular Fat Ancillary Study.

BackgroundVolumes of paracardial adipose tissue (PAT) and epicardial adipose tissue (EAT) are greater after menopause. Interestingly, PAT but not EAT is associated with estradiol decline, suggesting a potential role of menopause in PAT accumulation. We assessed whether volumes of heart fat depot (EAT and PAT) were associated with coronary artery calcification (CAC) in women at midlife and whether these associations were modified by menopausal status and estradiol levels.Methods and resultsEAT and PAT volumes and CAC were measured using electron beam computed tomography scans. CAC was evaluated as (1) the presence of CAC (CAC Agatston score ≥10) and (2) the extent of any CAC (log CAC Agatston score >0). The study included 478 women aged 50.9 years (58% pre- or early perimenopausal, 10% late perimenopausal, and 32% postmenopausal). EAT was significantly associated with CAC measures, and these associations were not modified by menopausal status or estradiol. In contrast, associations between PAT and CAC measures were modified by menopausal status (interaction-P≤0.01). Independent of study covariates including other adiposity measures, each 1-SD unit increase in log PAT was associated with 102% higher risk of CAC presence (P=0.04) and an 80% increase in CAC extent (P=0.008) in postmenopausal women compared with pre- or early perimenopausal women. Additional adjustment for estradiol and hormone therapy attenuated these differences. Moreover, the association between PAT and CAC extent was stronger in women with lower estradiol levels (interaction P=0.004).ConclusionsThe findings suggest that PAT is a potential menopause-specific coronary artery disease risk marker, supporting the need to monitor and target this fat depot for intervention in women at midlife

An Alternative Flight Software Trigger Paradigm: Applying Multivariate Logistic Regression to Sense Trigger Conditions Using Inaccurate or Scarce Information

In late 2014, NASA will fly the Orion capsule on a Delta IV-Heavy rocket for the Exploration Flight Test-1 (EFT-1) mission. For EFT-1, the Orion capsule will be flying with a new GPS receiver and new navigation software. Given the experimental nature of the flight, the flight software must be robust to the loss of GPS measurements. Once the high-speed entry is complete, the drogue parachutes must be deployed within the proper conditions to stabilize the vehicle prior to deploying the main parachutes. When GPS is available in nominal operations, the vehicle will deploy the drogue parachutes based on an altitude trigger. However, when GPS is unavailable, the navigated altitude errors become excessively large, driving the need for a backup barometric altimeter to improve altitude knowledge. In order to increase overall robustness, the vehicle also has an alternate method of triggering the parachute deployment sequence based on planet-relative velocity if both the GPS and the barometric altimeter fail. However, this backup trigger results in large altitude errors relative to the targeted altitude. Motivated by this challenge, this paper demonstrates how logistic regression may be employed to semi-automatically generate robust triggers based on statistical analysis. Logistic regression is used as a ground processor pre-flight to develop a statistical classifier. The classifier would then be implemented in flight software and executed in real-time. This technique offers improved performance even in the face of highly inaccurate measurements. Although the logistic regression-based trigger approach will not be implemented within EFT-1 flight software, the methodology can be carried forward for future missions and vehicles

Metabolomics Reveals New Mechanisms for Pathogenesis in Barth Syndrome and Introduces Novel Roles for Cardiolipin in Cellular Function

Barth Syndrome is the only known Mendelian disorder of cardiolipin remodeling, with characteristic clinical features of cardiomyopathy, skeletal myopathy, and neutropenia. While the primary biochemical defects of reduced mature cardiolipin and increased monolysocardiolipin are well-described, much of the downstream biochemical dysregulation has not been uncovered, and biomarkers are limited. In order to further expand upon the knowledge of the biochemical abnormalities in Barth Syndrome, we analyzed metabolite profiles in plasma from a cohort of individuals with Barth Syndrome compared to age-matched controls via 1H nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry. A clear distinction between metabolite profiles of individuals with Barth Syndrome and controls was observed, and was defined by an array of metabolite classes including amino acids and lipids. Pathway analysis of these discriminating metabolites revealed involvement of mitochondrial and extra-mitochondrial biochemical pathways including: insulin regulation of fatty acid metabolism, lipid metabolism, biogenic amine metabolism, amino acid metabolism, endothelial nitric oxide synthase signaling, and tRNA biosynthesis. Taken together, this data indicates broad metabolic dysregulation in Barth Syndrome with wide cellular effects

Control of hyperuricemia in subjects with refractory gout, and induction of antibody against poly(ethylene glycol) (PEG), in a phase I trial of subcutaneous PEGylated urate oxidase

PEG-modified recombinant mammalian urate oxidase (PEG-uricase) is being developed as a treatment for patients with chronic gout who are intolerant of, or refractory to, available therapy for controlling hyperuricemia. In an open-label phase I trial, single subcutaneous injections of PEG-uricase (4 to 24 mg) were administered to 13 such subjects (11 had tophaceous gout), whose plasma uric acid concentration (pUAc) was 11.3 ± 2.1 mg/dl (mean ± SD). By day seven after injection of PEG-uricase, pUAc had declined by an average of 7.9 mg/dl and had normalized in 11 subjects, whose mean pUAc decreased to 2.8 ± 2.2 mg/dl. At doses of 8, 12, and 24 mg, the mean pUAc at 21 days after injection remained no more than 6 mg/dl. In eight subjects, plasma uricase activity was still measurable at 21 days after injection (half-life 10.5 to 19.9 days). In the other five subjects, plasma uricase activity could not be detected beyond ten days after injection; this was associated with the appearance of relatively low-titer IgM and IgG antibodies against PEG-uricase. Unexpectedly, these antibodies were directed against PEG itself rather than the uricase protein. Three PEG antibody-positive subjects had injection-site reactions at 8 to 9 days after injection. Gout flares in six subjects were the only other significant adverse reactions, and PEG-uricase was otherwise well tolerated. A prolonged circulating life and the ability to normalize plasma uric acid in markedly hyperuricemic subjects suggest that PEG-uricase could be effective in depleting expanded tissue stores of uric acid in subjects with chronic or tophaceous gout. The development of anti-PEG antibodies, which may limit efficacy in some patients, is contrary to the general assumption that PEG is non-immunogenic. PEG immunogenicity deserves further investigation, because it has potential implications for other PEGylated therapeutic agents in clinical use

Transcriptome Analysis in Spleen Reveals Differential Regulation of Response to Newcastle Disease Virus in Two Chicken Lines.

Enhancing genetic resistance of chickens to Newcastle Disease Virus (NDV) provides a promising way to improve poultry health, and to alleviate poverty and food insecurity in developing countries. In this study, two inbred chicken lines with different responses to NDV, Fayoumi and Leghorn, were challenged with LaSota NDV strain at 21 days of age. Through transcriptome analysis, gene expression in spleen at 2 and 6 days post-inoculation was compared between NDV-infected and control groups, as well as between chicken lines. At a false discovery rate <0.05, Fayoumi chickens, which are relatively more resistant to NDV, showed fewer differentially expressed genes (DEGs) than Leghorn chickens. Several interferon-stimulated genes were identified as important DEGs regulating immune response to NDV in chicken. Pathways predicted by IPA analysis, such as "EIF-signaling", "actin cytoskeleton organization nitric oxide production" and "coagulation system" may contribute to resistance to NDV in Fayoumi chickens. The identified DEGs and predicted pathways may contribute to differential responses to NDV between the two chicken lines and provide potential targets for breeding chickens that are more resistant to NDV

A Community Outbreak of Cryptosporidiosis in Sydney Associated with a Public Swimming Facility: A Case-Control Study

In February, 2008, the South Eastern Sydney Illawarra Public Health Unit investigated an outbreak of cryptosporidiosis within the south east region of Sydney, Australia. Thirty-one cases with laboratory-confirmed cryptosporidiosis and 97 age- and geographically matched controls selected by random digit dialling were recruited into a case-control study and interviewed for infection risk factors. Cryptosporidiosis was associated with swimming at Facility A (matched odds ratio = 19.4, 95% confidence interval: 3.7–100.8) and exposure to household contacts with diarrhoea (matched odds ratio = 7.7, 95% confidence interval: 1.9–31.4) in multivariable conditional logistic regression models. A protective effect for any animal contact was also found (matched odds ratio = 0.2, 95% confidence interval: 0.1–0.7). Cryptosporidium hominis subtype IbA10G2 was identified in 8 of 11 diagnostic stool samples available for cases. This investigation reaffirms the importance of public swimming pools as potential sources of Cryptosporidium infection and ensuring their compliance with water-quality guidelines. The protective effect of animal contact may be suggestive of past exposure leading to immunity

Prevention Across the Spectrum: a randomized controlled trial of three programs to reduce risk factors for both eating disorders and obesity

Author version made available in accordance with publisher copyright policy.Background: A randomized-controlled trial (RCT) of 3 school-based programs and a no intervention control group was conducted to evaluate their efficacy in reducing eating disorder and obesity risk factors. Methods: N = 1,316 Grade 7 and 8 girls and boys (M age = 13.21 years) across three Australian states were randomly allocated to: Media Smart; Life Smart; Helping, Encouraging, Listening and Protecting Peers Initiative (HELPP) or control (usual school class). Risk factors were measured at baseline, post-program (5-weeks later), and 6- and 12-month follow-up. Results: Media Smart girls had half the rate of onset of clinically significant concerns about shape and weight than control girls at 12-month follow-up. Media Smart and HELPP girls reported significantly lower weight and shape concern than Life Smart girls at 12-month follow-up. Media Smart and control girls scored significantly lower than HELPP girls on eating concerns and perceived pressure at 6-month follow-up. Media Smart and HELPP boys experienced significant benefit on media internalization compared to control boys and these were sustained at 12-month follow-up in Media Smart boys. A group x time effect found Media Smart participants reported more physical activity than control and HELPP participants at 6-month follow-up, while a main effect for group found Media Smart participants reported less screen time than controls. Conclusions: Media Smart was the only program to show benefit on both disordered eating and obesity risk factors. Whilst further investigations are indicated, this study suggests that this program is a promising approach to reducing risk factors for both problems