Subcutaneous adipose tissue fatty acid desaturation in adults with and without rare adipose disorders

<p>Abstract</p> <p>Background</p> <p>Elevated stearoyl-CoA desaturase activity has been described in obese states, with an increased desaturation index (DI) suggesting enhanced lipogenesis. Differences in the DI among various phenotypes of abnormal adiposity have not been studied. Abnormal accumulation of subcutaneous adipose tissue occurs in rare adipose disorders (RADs) including Dercum's disease (DD), multiple symmetric lipomatosis (MSL), and familial multiple lipomatosis (FML). Examining the DI in subcutaneous fat of people with DD, MSL and FML may provide information on adipose tissue fatty acid metabolism in these disorders. The aims of this pilot study were: 1) to determine if differences in adipose tissue DIs are present among RADs, and 2) to determine if the DIs correlate to clinical or biochemical parameters.</p> <p>Methods</p> <p>Subcutaneous adipose tissue was obtained from human participants with DD (n = 6), MSL (n = 5), FML (n = 8) and obese Controls (n = 6). Fatty acid composition was determined by gas chromatography/mass spectrometry. The DIs (palmitoleic/palmitic, oleic/stearic, vaccenic/stearic ratios) were calculated from the gas chromatogram peak intensities. SCD1 gene expression was determined. Spearman's correlations between the DIs and available clinical or biochemical data were performed.</p> <p>Results</p> <p>In DD subjects, the vaccenic/stearic index was lower (<it>p </it>< 0.05) in comparison to Controls. Percent of total of the saturated fatty acid myristic acid was higher in DD compared with Controls and FML. Percent of monounsaturated vaccenic acid in DD trended lower when compared with Controls, and was decreased in comparison to FML. In MSL, total percent of the polyunsaturated fatty acids was significantly lower than in the Control group (<it>p </it>< 0.05). In the total cohort of subjects, the palmitoleic/palmitic and oleic/stearic DIs positively correlated with age, BMI, and percent body fat.</p> <p>Conclusions</p> <p>The positive associations between the DIs and measures of adiposity (BMI and percent body fat) support increased desaturase activity in obesity. The lower vaccenic/stearic DI in DD SAT compared with Controls suggests presence of other factors involved in fat accumulation in addition to lifestyle. Other mechanisms driving fat accumulation in DD such as inflammation or lymphatic dysfunction should be investigated.</p

The Disappearing Act of KH 15D: Photometric Results from 1995 to 2004

We present results from the most recent (2002-2004) observing campaigns of the eclipsing system KH 15D, in addition to re-reduced data obtained at Van Vleck Observatory (VVO) between 1995 and 2000. Phasing nine years of photometric data shows substantial evolution in the width and depth of the eclipses. The most recent data indicate that the eclipses are now approximately 24 days in length, or half the orbital period. These results are interpreted and discussed in the context of the recent models for this system put forward by Winn et al. and Chiang & Murray-Clay. A periodogram of the entire data set yields a highly significant peak at 48.37 +/- 0.01 days, which is in accord with the spectroscopic period of 48.38 +/- 0.01 days determined by Johnson et al. Another significant peak, at 9.6 days, was found in the periodogram of the out-of-eclipse data at two different epochs. We interpret this as the rotation period of the visible star and argue that it may be tidally locked in pseudosynchronism with its orbital motion. If so, application of Hut's theory implies that the eccentricity of the orbit is e = 0.65 +/- 0.01. Analysis of the UVES/VLT spectra obtained by Hamilton et al. shows that the v sin(i) of the visible star in this system is 6.9 +/- 0.3 km/sec. Using this value of v sin(i) and the measured rotation period of the star, we calculate the lower limit on the radius to be R = (1.3 +/- 0.1), R_Sun, which concurs with the value obtained by Hamilton et al. from its luminosity and effective temperature. Here we assume that i = 90 degrees since it is likely that the spin and orbital angular momenta vectors are nearly aligned.Comment: 55 pages, 18 figures, 1 color figure, to appear the September issue of the Astronomical Journa

The Orbit and Occultations of KH 15D

The unusual flux variations of the pre-main-sequence binary star KH 15D have been attributed to occultations by a circumbinary disk. We test whether or not this theory is compatible with newly available data, including recent radial velocity measurements, CCD photometry over the past decade, and photographic photometry over the past 50 years. We find the model to be successful, after two refinements: a more realistic motion of the occulting feature, and a halo around each star that probably represents scattering by the disk. The occulting feature is exceptionally sharp-edged, raising the possibility that the dust in the disk has settled into a thin layer, and providing a tool for fine-scale mapping of the immediate environment of a T Tauri star. However, the window of opportunity is closing, as the currently visible star may be hidden at all orbital phases by as early as 2008.Comment: To appear in ApJ [16 pages, 13 figures

Racial disparities in the SOFA score among patients hospitalized with COVID-19

BACKGROUND: Sequential Organ Failure Assessment (SOFA) score predicts probability of in-hospital mortality. Many crisis standards of care suggest the use of SOFA scores to allocate medical resources during the COVID-19 pandemic. RESEARCH QUESTION: Are SOFA scores elevated among Non-Hispanic Black and Hispanic patients hospitalized with COVID-19, compared to Non-Hispanic White patients? STUDY DESIGN AND METHODS: Retrospective cohort study conducted in Yale New Haven Health System, including 5 hospitals with total of 2681 beds. Study population drawn from consecutive patients aged ≥18 admitted with COVID-19 from March 29th to August 1st, 2020. Patients excluded from the analysis if not their first admission with COVID-19, if they did not have SOFA score recorded within 24 hours of admission, if race and ethnicity data were not Non-Hispanic Black, Non-Hispanic White, or Hispanic, or if they had other missing data. The primary outcome was SOFA score, with peak score within 24 hours of admission dichotomized as \u3c6 or ≥6. RESULTS: Of 2982 patients admitted with COVID-19, 2320 met inclusion criteria and were analyzed, of whom 1058 (45.6%) were Non-Hispanic White, 645 (27.8%) were Hispanic, and 617 (26.6%) were Non-Hispanic Black. Median age was 65.0 and 1226 (52.8%) were female. In univariate logistic screen and in full multivariate model, Non-Hispanic Black patients but not Hispanic patients had greater odds of an elevated SOFA score ≥6 when compared to Non-Hispanic White patients (OR 1.49, 95%CI 1.11-1.99). INTERPRETATION: Given current unequal patterns in social determinants of health, US crisis standards of care utilizing the SOFA score to allocate medical resources would be more likely to deny these resources to Non-Hispanic Black patients

Chlamydial Pre-Infection Protects From Subsequent Herpes Simplex Virus-2 Challenge in a Murine Vaginal Super-Infection Model

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Chlamydia trachomatis and Herpes Simplex Virus-2 (HSV-2) genital tract co-infections have been reported in humans and studied in vitro but the clinical consequences are unknown. Limited epidemiologic evidence suggests that these co-infections could be more severe than single infections of either pathogen, but the host-pathogen interactions during co-infection remain uncharacterized. To determine whether disease progression and/or pathogen shedding differs between singly-infected and super-infected animals, we developed an in vivo super-infection model in which female BALB/c mice were vaginally infected with Chlamydia muridarum (Cm) followed later by HSV-2. Pre-infection with Chlamydia 3 or 9 days prior to HSV-2 super-infection conferred significant protection from HSV-2-induced neurologic disease and significantly reduced viral recovery compared to HSV-2 singlyinfected controls. Neither protection from mortality nor reduced viral recovery were observed when mice were i) super-infected with HSV-2 on day 27 post Cm; ii) infected with UV-irradiated Cm and super-infected with HSV-2; or iii) azithromycin-treated prior to HSV-2 super-infection. Therefore, protection from HSV-2-induced disease requires active infection with viable chlamydiae and is not observed after chlamydial shedding ceases, either naturally or due to antibiotic treatment. Thus, Chlamydia-induced protection is transient and requires the continued presence of chlamydiae or their components. These data demonstrate that chlamydial pre-infection can alter progression of subsequent HSV-2 infection, with implications for HSV-2 transmission from co-infected humans

Opposing Roles of Membrane and Soluble Forms of the Receptor for Advanced Glycation End Products in Primary Respiratory Syncytial Virus Infection

Respiratory syncytial virus (RSV), a common respiratory pathogen in infants and the older population, causes pulmonary inflammation and airway occlusion that leads to impairment of lung function. Here, we have established a role for receptor for advanced glycation end products (RAGE) in RSV infection. RAGE-deficient (ager−/−) mice were protected from RSV-induced weight loss and inflammation. This protection correlated with an early increase in type I interferons, later decreases in proinflammatory cytokines, and a reduction in viral load. To assess the contribution of soluble RAGE (sRAGE) to RSV-induced disease, wild-type and ager−/− mice were given doses of sRAGE following RSV infection. Of interest, sRAGE treatment prevented RSV-induced weight loss and neutrophilic inflammation to a degree similar to that observed in ager−/− mice. Our work further elucidates the roles of RAGE in the pathogenesis of respiratory infections and highlights the opposing roles of membrane and sRAGE in modulating the host response to RSV infection

Integrative Genomic Analyses Identify BRF2 as a Novel Lineage-Specific Oncogene in Lung Squamous Cell Carcinoma

William Lockwood and colleagues show that the focal amplification of a gene, BRF2, on Chromosome 8p12 plays a key role in squamous cell carcinoma of the lung