Total urinary polyphenols and longitudinal changes of bone properties. The InCHIANTI study

SummaryThe aim of this study was to evaluate the association of levels of urinary total polyphenols considered as a proxymeasure of polyphenol intake, with longitudinal changes of bone properties, in the InCHIANTI study. Dietary intake ofpolyphenols appears to be associated with future accelerated deterioration of bone health.IntroductionPolyphenols, micronutrients ingested through plant-based foods, have antioxidant and anti-inflammatory propertiesand may contribute to osteoporosis prevention. We evaluated associations of high levels of urinary total polyphenols (UTP), aproxy measure of polyphenol intake, with longitudinal changes of bone properties in a representative cohort of free-livingparticipants of the InCHIANTI study.MethodsThe InCHIANTI study enrolled representative samples from the registry list of two towns in Tuscany, Italy. Baselinedata were collected in 1998 and follow-up visits in 2001 and 2004. Of the 1453 participants enrolled, 956 consented to donate a24-h urine sample used to assess UTP, had dietary assessment, a physical examination, and underwent a quantitative comput-erized tomography (pQCT) of the tibia. From pQCT images, we estimated markers of bone mass (BM), diaphyseal design (DD),and material quality (MQ). Mixed models were used to study the relationship between baseline tertiles of UTP with changes ofthe bone characteristics over the follow-up.ResultsAt baseline, higher levels of UTP were positively correlated with markers of BM, DD, and MQ. Compared with lowertertile of UTP, participants in the intermediate and highest tertiles had higher cortical bone area, cortical mineral content, andcortical thickness. However, participants in the intermediate and highest UTP tertiles experienced accelerated deterioration ofthese same parameters over the follow-up compared with those in the lowest UTP tertile.ConclusionsDietary intake of polyphenols estimated by UTP and dietary questionnaire was associated with long-term acceler-ated deterioration of bone health. Our study does not support the recommendation of increasing polyphenol intake for osteopo-rosis prevention

Power Spectrum Estimation from Peculiar Velocity Catalogues

The peculiar velocities of galaxies are an inherently valuable cosmological probe, providing an unbiased estimate of the distribution of matter on scales much larger than the depth of the survey. Much research interest has been motivated by the high dipole moment of our local peculiar velocity field, which suggests a large scale excess in the matter power spectrum, and can appear to be in some tension with the LCDM model. We use a composite catalogue of 4,537 peculiar velocity measurements with a characteristic depth of 33 h-1 Mpc to estimate the matter power spectrum. We compare the constraints with this method, directly studying the full peculiar velocity catalogue, to results from Macaulay et al. (2011), studying minimum variance moments of the velocity field, as calculated by Watkins, Feldman & Hudson (2009) and Feldman, Watkins & Hudson (2010). We find good agreement with the LCDM model on scales of k > 0.01 h Mpc-1. We find an excess of power on scales of k < 0.01 h Mpc-1, although with a 1 sigma uncertainty which includes the LCDM model. We find that the uncertainty in the excess at these scales is larger than an alternative result studying only moments of the velocity field, which is due to the minimum variance weights used to calculate the moments. At small scales, we are able to clearly discriminate between linear and nonlinear clustering in simulated peculiar velocity catalogues, and find some evidence (although less clear) for linear clustering in the real peculiar velocity data.Comment: 10 pages, 13 figures, updated to match version accepted by MNRA

Four Eremophilane Sesquiterpenes from the Mangrove Endophytic Fungus Xylaria sp. BL321

Three new eremophilane sesquiterpenes (1–3) were isolated from the mangrove endophytic fungus Xylaria sp. BL321 together with 07H239-A (4), a known analogue of the new compounds. The structures of these compounds were elucidated by analysis of their MS, 1D and 2D NMR spectroscopic data. Compound 4 showed activation activity on α-glucosidase at 0.15 μM (146%), and then, 4 gradually produced inhibitory activity on α-glucosidase with increasing concentration, and the IC50 value is 6.54 μM

Validation of volumetric and single-slice MRI adipose analysis using a novel fully automated segmentation method.

PURPOSE: To validate a fully automated adipose segmentation method with magnetic resonance imaging (MRI) fat fraction abdominal imaging. We hypothesized that this method is suitable for segmentation of subcutaneous adipose tissue (SAT) and intra-abdominal adipose tissue (IAAT) in a wide population range, easy to use, works with a variety of hardware setups, and is highly repeatable. MATERIALS AND METHODS: Analysis was performed comparing precision and analysis time of manual and automated segmentation of single-slice imaging, and volumetric imaging (78-88 slices). Volumetric and single-slice data were acquired in a variety of cohorts (body mass index [BMI] 15.6-41.76) including healthy adult volunteers, adolescent volunteers, and subjects with nonalcoholic fatty liver disease and lipodystrophies. A subset of healthy volunteers was analyzed for repeatability in the measurements. RESULTS: The fully automated segmentation was found to have excellent agreement with manual segmentation with no substantial bias across all study cohorts. Repeatability tests showed a mean coefficient of variation of 1.2 ± 0.6% for SAT, and 2.7 ± 2.2% for IAAT. Analysis with automated segmentation was rapid, requiring 2 seconds per slice compared with 8 minutes per slice with manual segmentation. CONCLUSION: We demonstrate the ability to accurately and rapidly segment regional adipose tissue using fat fraction maps across a wide population range, with varying hardware setups and acquisition methods. J. Magn. Reson. Imaging 2015;41:233-241. © 2014 Wiley Periodicals, Inc

Delineation of prognostic biomarkers in prostate cancer

Prostate cancer is the most frequently diagnosed cancer in American men(1,2). Screening for prostate-specific antigen (PSA) has led to earlier detection of prostate cancer(3), but elevated serum PSA levels may be present in non-malignant conditions such as benign prostatic hyperlasia (BPH). Characterization of gene-expression profiles that molecularly distinguish prostatic neoplasms may identify genes involved in prostate carcinogenesis, elucidate clinical biomarkers, and lead to an improved classification of prostate cancer(4-6). Using microarrays of complementary DNA, we examined gene-expression profiles of more than 50 normal and neoplastic prostate specimens and three common prostate-cancer cell lines. Signature expression profiles of normal adjacent prostate (NAP), BPH, localized prostate cancer, and metastatic, hormone-refractory prostate cancer were determined. Here we establish many associations between genes and prostate cancer. We assessed two of these genes-hepsin, a transmembrane serine protease, and pim-1, a serine/threonine kinase-at the protein level using tissue microarrays consisting of over 700 clinically stratified prostate-cancer specimens. Expression of hepsin and pim-1 proteins was significantly correlated with measures of clinical outcome. Thus, the integration of cDNA microarray, high-density tissue microarray, and linked clinical and pathology data is a powerful approach to molecular profiling of human cancer.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62849/1/412822a0.pd

Detected fluctuations in SDSS LRG magnitudes: Bulk flow signature or systematic?

In this paper we search for a signature of a large scale bulk flow by looking for fluctuations in the magnitudes of distant LRGs. We take a sample of LRGs from the Sloan Digital Sky Survey with redshifts of z>0.08 over a contiguous area of sky. Neighboring LRG magnitudes are averaged together to find the fluctuation in magnitudes as a function of R.A.. The result is a fluctuation of a few percent in flux across roughly 100 degrees. The source of this fluctuation could be from a large scale bulk flow or a systematic in our treatment of the data set, or the data set itself. A bulk flow model is fitted to the observed fluctuation, and the three bulk flow parameters, its direction and magnitude: alpha_b, delta_b, v_b are constrained. We find that the bulk flow direction is consistent with the direction found by other authors, with alpha_b 180, delta_b -50. The bulk flow magnitude however was found to be anomalously large with v_b>4000km/s. The LRG angular selection function cannot be sufficiently taken into account in our analysis with the available data, and may be the source of either the anomalous magnitude of the bulk flow signal, or possibly the entire fluctuation. However, the fluctuation indicates a bulk flow direction very close to those found using other data sets and analyses. Further investigation with upcoming data is required to confirm this detection.Comment: 10 pages, 7 figures, 1 table. V2: citations added to the introduction and a paragraph to the discussion. V3: Accepted by MNRAS. 1 figure, additional clarifications, discussion and references adde

Characteristics of patients with venous thromboembolism and atrial fibrillation in Venezuela

<p>Abstract</p> <p>Background</p> <p>Studies describing venous thromboembolic event (VTEE) and atrial fibrillation (AF) in South American populations are limited. The aim of this cross-sectional study was to describe the characteristics of Venezuelan patients admitted and treated for these conditions.</p> <p>Methods</p> <p>A retrospective medical record review of 1397 consecutive patients admitted to three private hospitals or clinics between January 2000 and December 2005 was performed. Data was collected on demographics, anthropometrics, hospital visit, comorbidities and treatment.</p> <p>Results</p> <p>Among 401 VTEE and 996 AF patients, men were more likely to have AF (58%) while more women experienced a VTEE (58%). Most patients were admitted via the emergency room (87%) and had only one event during the study period (83%). Common comorbidities included hypertension (46%), heart failure (17%), diabetes (12%) and congestive heart failure (11%). Characteristics of Venezuelan patients with VTEE and AF are similar to that reported in the literature for other populations.</p> <p>Conclusions</p> <p>These results provide background characteristics for future studies assessing risk factors for AF and VTEE in South American populations.</p

IsoBED: a tool for automatic calculation of biologically equivalent fractionation schedules in radiotherapy using IMRT with a simultaneous integrated boost (SIB) technique

<p>Abstract</p> <p>Background</p> <p>An advantage of the Intensity Modulated Radiotherapy (IMRT) technique is the feasibility to deliver different therapeutic dose levels to PTVs in a single treatment session using the Simultaneous Integrated Boost (SIB) technique. The paper aims to describe an automated tool to calculate the dose to be delivered with the SIB-IMRT technique in different anatomical regions that have the same Biological Equivalent Dose (BED), i.e. IsoBED, compared to the standard fractionation.</p> <p>Methods</p> <p>Based on the Linear Quadratic Model (LQM), we developed software that allows treatment schedules, biologically equivalent to standard fractionations, to be calculated. The main radiobiological parameters from literature are included in a database inside the software, which can be updated according to the clinical experience of each Institute. In particular, the BED to each target volume will be computed based on the alpha/beta ratio, total dose and the dose per fraction (generally 2 Gy for a standard fractionation). Then, after selecting the reference target, i.e. the PTV that controls the fractionation, a new total dose and dose per fraction providing the same isoBED will be calculated for each target volume.</p> <p>Results</p> <p>The IsoBED Software developed allows: 1) the calculation of new IsoBED treatment schedules derived from standard prescriptions and based on LQM, 2) the conversion of the dose-volume histograms (DVHs) for each Target and OAR to a nominal standard dose at 2Gy per fraction in order to be shown together with the DV-constraints from literature, based on the LQM and radiobiological parameters, and 3) the calculation of Tumor Control Probability (TCP) and Normal Tissue Complication Probability (NTCP) curve versus the prescribed dose to the reference target.</p

Domain-swapped T cell receptors improve the safety of TCR gene therapy

T cells engineered to express a tumor-specific αβ T cell receptor (TCR) mediate anti-tumor immunity. However, mispairing of the therapeutic αβ chains with endogenous αβ chains reduces therapeutic TCR surface expression and generates self-reactive TCRs. We report a general strategy to prevent TCR mispairing: swapping constant domains between the α and β chains of a therapeutic TCR. When paired, domain-swapped (ds)TCRs assemble with CD3, express on the cell surface, and mediate antigen-specific T cell responses. By contrast, dsTCR chains mispaired with endogenous chains cannot properly assemble with CD3 or signal, preventing autoimmunity. We validate this approach in cell-based assays and in a mouse model of TCR gene transfer-induced graft-versus-host disease. We also validate a related approach whereby replacement of αβ TCR domains with corresponding γδ TCR domains yields a functional TCR that does not mispair. This work enables the design of safer TCR gene therapies for cancer immunotherapy