Metabolomic profiles are gender, disease and time specific in the interleukin-10 gene-deficient mouse model of inflammatory bowel disease.

Metabolomic profiling can be used to study disease-induced changes in inflammatory bowel diseases (IBD). The aim of this study was to investigate the difference in the metabolomic profile of males and females as they developed IBD. Using the IL-10 gene-deficient mouse model of IBD and wild-type mice, urine at age 4, 6, 8, 12, 16, and 20 weeks was collected and analyzed by nuclear magnetic resonance (NMR) spectroscopy. Multivariate data analysis was employed to assess differences in metabolomic profiles that occurred as a consequence of IBD development and severity (at week 20). These changes were contrasted to those that occurred as a consequence of gender. Our results demonstrate that both IL-10 gene-deficient and wild-type mice exhibit gender-related changes in urinary metabolomic profile over time. Some male-female separating metabolites are common to both IL-10 gene-deficient and control wild-type mice and, therefore, appear to be related predominantly to gender maturation. In addition, we were able to identify gender-separating metabolites that are unique for IL-10 gene-deficient and wild-type mice and, therefore, may be indicative of a gender-specific involvement in the development and severity of the intestinal inflammation. The comparison of the gender-separating metabolomic profile from IL-10 gene-deficient mice and wild-type mice during the development of IBD allowed us to identify changes in profile patterns that appear to be imperative in the development of intestinal inflammation, but yet central to gender-related differences in IBD development. The knowledge of metabolomic profile differences by gender and by disease severity has potential clinical implications in the design of both biomarkers of disease as well as the development of optimal therapies

Outcome of coronary plaque burden: a 10-year follow-up of aggressive medical management

<p>Abstract</p> <p>Background</p> <p>The effect of aggressive medical therapy on quantitative coronary plaque burden is not generally known, especially in ethnic Chinese.</p> <p>Aims</p> <p>We reasoned that Cardiac CT could conveniently quantify early coronary atherosclerosis in our patient population, and hypothesized that serial observation could differentiate the efficacy of aggressive medical therapy regarding progression and regression of the atherosclerotic process, as well as evaluating the additional impact of life-style modification and the relative effects of the application of statin therapy.</p> <p>Methods</p> <p>We employed a standardized Cardiac CT protocol to serially scan 113 westernized Hong Kong Chinese individuals (64 men and 49 women) with Chest Pain and positive coronary risk factors. In all cases included for this serial investigation, subsequent evaluation showed no significantly-obstructive coronary disease by functional studies and angiography. After stringent risk factor modification, including aggressive statin therapy to achieve LDL-cholesterol lowering conforming to N.C.E.P. ATP III guidelines, serial CT scans were performed 1-12 years apart for changes in coronary artery calcification (CAC), using the Agatston Score (AS) for quantification.</p> <p>Results</p> <p>At baseline, the mean AS was 1413.6 for males (mean age 54.4 years) and 2293.3 for females (mean age 62.4 years). The average increase of AS in the entire study population was 24% per year, contrasting with 16.4% per year on strict risk factor modification plus statin therapy, as opposed to 33.2% per year for historical control patients (p < 0.001). Additionally, 20.4% of the 113 patients demonstrated decreasing calcium scores. Medical therapy also yielded a remarkably low adverse event rate during the follow-up period --- 2 deaths, 2 strokes and only 1 case requiring PCI.</p> <p>Conclusions</p> <p>This study revealed that aggressive medical therapy can positively influence coronary plaque aiding in serial regression of calcium scores.</p

Search for gravitational-lensing signatures in the full third observing run of the LIGO-Virgo network

Gravitational lensing by massive objects along the line of sight to the source causes distortions of gravitational wave-signals; such distortions may reveal information about fundamental physics, cosmology and astrophysics. In this work, we have extended the search for lensing signatures to all binary black hole events from the third observing run of the LIGO--Virgo network. We search for repeated signals from strong lensing by 1) performing targeted searches for subthreshold signals, 2) calculating the degree of overlap amongst the intrinsic parameters and sky location of pairs of signals, 3) comparing the similarities of the spectrograms amongst pairs of signals, and 4) performing dual-signal Bayesian analysis that takes into account selection effects and astrophysical knowledge. We also search for distortions to the gravitational waveform caused by 1) frequency-independent phase shifts in strongly lensed images, and 2) frequency-dependent modulation of the amplitude and phase due to point masses. None of these searches yields significant evidence for lensing. Finally, we use the non-detection of gravitational-wave lensing to constrain the lensing rate based on the latest merger-rate estimates and the fraction of dark matter composed of compact objects

Search for eccentric black hole coalescences during the third observing run of LIGO and Virgo

Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass M&gt;70 M⊙) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities 0&lt;e≤0.3 at 0.33 Gpc−3 yr−1 at 90\% confidence level

Ultralight vector dark matter search using data from the KAGRA O3GK run

Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)B−L gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)B−L gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM

Development and Validation of a High-Throughput Mass Spectrometry Based Urine Metabolomic Test for the Detection of Colonic Adenomatous Polyps

Background: Colorectal cancer is one of the leading causes of cancer deaths worldwide. The detection and removal of the precursors to colorectal cancer, adenomatous polyps, is the key for screening. The aim of this study was to develop a clinically scalable (high throughput, low cost, and high sensitivity) mass spectrometry (MS)-based urine metabolomic test for the detection of adenomatous polyps. Methods: Prospective urine and stool samples were collected from 685 participants enrolled in a colorectal cancer screening program to undergo colonoscopy examination. Statistical analysis was performed on 69 urine metabolites measured by one-dimensional nuclear magnetic resonance spectroscopy to identify key metabolites. A targeted MS assay was then developed to quantify the key metabolites in urine. A MS-based urine metabolomic diagnostic test for adenomatous polyps was established using 67% samples (un-blinded training set) and validated using the remaining 33% samples (blinded testing set). Results: The MS-based urine metabolomic test identifies patients with colonic adenomatous polyps with an AUC of 0.692, outperforming the NMR based predictor with an AUC of 0.670. Conclusion: Here we describe a clinically scalable MS-based urine metabolomic test that identifies patients with adenomatous polyps at a higher level of sensitivity (86%) over current fecal-based tests (&lt;18%)

Metabolomic profiles are gender, disease and time specific in the interleukin-10 gene-deficient mouse model of inflammatory bowel disease.

Metabolomic profiling can be used to study disease-induced changes in inflammatory bowel diseases (IBD). The aim of this study was to investigate the difference in the metabolomic profile of males and females as they developed IBD. Using the IL-10 gene-deficient mouse model of IBD and wild-type mice, urine at age 4, 6, 8, 12, 16, and 20 weeks was collected and analyzed by nuclear magnetic resonance (NMR) spectroscopy. Multivariate data analysis was employed to assess differences in metabolomic profiles that occurred as a consequence of IBD development and severity (at week 20). These changes were contrasted to those that occurred as a consequence of gender. Our results demonstrate that both IL-10 gene-deficient and wild-type mice exhibit gender-related changes in urinary metabolomic profile over time. Some male-female separating metabolites are common to both IL-10 gene-deficient and control wild-type mice and, therefore, appear to be related predominantly to gender maturation. In addition, we were able to identify gender-separating metabolites that are unique for IL-10 gene-deficient and wild-type mice and, therefore, may be indicative of a gender-specific involvement in the development and severity of the intestinal inflammation. The comparison of the gender-separating metabolomic profile from IL-10 gene-deficient mice and wild-type mice during the development of IBD allowed us to identify changes in profile patterns that appear to be imperative in the development of intestinal inflammation, but yet central to gender-related differences in IBD development. The knowledge of metabolomic profile differences by gender and by disease severity has potential clinical implications in the design of both biomarkers of disease as well as the development of optimal therapies