Vitamin D in polycystic ovary syndrome: Relationship to obesity and insulin resistance

Scope: Polycystic ovary syndrome (PCOS) is underpinned by insulin resistance (IR). In PCOS, the relationships between vitamin D, adiposity, and IR are unclear. We aim to explore these relationships in lean and overweight women with PCOS. Methods and results: This is a cross-sectional study conducted in a tertiary medical center. Participants included 42 women with PCOS and 34 controls without PCOS. Vitamin D and metabolic markers were measured. Detailed body composition and gold standard hyperinsulinemic euglycemic clamps were performed. The main outcome measures were plasma levels of vitamin D, adiposity measures, and glucose infusion rate. Vitamin D levels were lower in overweight women with PCOS compared with overweight controls (31.6 and 46.1 nmol/L, respectively, p = 0.01). Vitamin D was not associated with IR after adjustment for confounders; however, there was a significant interaction between PCOS and percentage body fat. Further analysis by PCOS status revealed that vitamin D was associated with IR in the PCOS group (β coefficient 2.1, 95% CI 0.2–4.0, p = 0.03), but not in the non-PCOS group. Conclusion: Vitamin D is associated with IR in women with PCOS, but not in controls. Large intervention studies are needed to determine if vitamin D supplementation can improve IR in PCOS.Anju E. Joham, Helena J. Teede, Samantha Cassar, Nigel K. Stepto, Boyd J. Strauss, Cheryce L. Harrison, Jacqueline Boyle and Barbora de Courte

Cellular expression, trafficking, and function of two isoforms of human ULBP5/RAET1G

Background: The activating immunoreceptor NKG2D is expressed on Natural Killer (NK) cells and subsets of T cells. NKG2D contributes to anti-tumour and anti-viral immune responses in vitro and in vivo. The ligands for NKG2D in humans are diverse proteins of the MIC and ULBP/RAET families that are upregulated on the surface of virally infected cells and tumours. Two splicing variants of ULBP5/RAET1G have been cloned previously, but not extensively characterised. Methodology/Principal Findings: We pursue a number of approaches to characterise the expression, trafficking, and function of the two isoforms of ULBP5/RAET1G. We show that both transcripts are frequently expressed in cell lines derived from epithelial cancers, and in primary breast cancers. The full-length transcript, RAET1G1, is predicted to encode a molecule with transmembrane and cytoplasmic domains that are unique amongst NKG2D ligands. Using specific anti-RAET1G1 antiserum to stain tissue microarrays we show that RAET1G1 expression is highly restricted in normal tissues. RAET1G1 was expressed at a low level in normal gastrointestinal epithelial cells in a similar pattern to MICA. Both RAET1G1 and MICA showed increased expression in the gut of patients with celiac disease. In contrast to healthy tissues the RAET1G1 antiserum stained a wide variety or different primary tumour sections. Both endogenously expressed and transfected RAET1G1 was mainly found inside the cell, with a minority of the protein reaching the cell surface. Conversely the truncated splicing variant of RAET1G2 was shown to encode a soluble molecule that could be secreted from cells. Secreted RAET1G2 was shown to downregulate NKG2D receptor expression on NK cells and hence may represent a novel tumour immune evasion strategy. Conclusions/Significance: We demonstrate that the expression patterns of ULBP5RAET1G are very similar to the well-characterised NKG2D ligand, MICA. However the two isoforms of ULBP5/RAET1G have very different cellular localisations that are likely to reflect unique functionality

Prenatal Vitamin D Supplementation and Child Respiratory Health: A Randomised Controlled Trial

PMCID: PMC3691177This 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

Vitamin D receptor ChIP-seq in primary CD4+ cells: relationship to serum 25-hydroxyvitamin D levels and autoimmune disease

PMCID: PMC3710212This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Using machine learning to speed up manual image annotation: application to a 3D imaging protocol for measuring single cell gene expression in the developing C. elegans embryo

<p>Abstract</p> <p>Background</p> <p>Image analysis is an essential component in many biological experiments that study gene expression, cell cycle progression, and protein localization. A protocol for tracking the expression of individual <it>C. elegans </it>genes was developed that collects image samples of a developing embryo by 3-D time lapse microscopy. In this protocol, a program called StarryNite performs the automatic recognition of fluorescently labeled cells and traces their lineage. However, due to the amount of noise present in the data and due to the challenges introduced by increasing number of cells in later stages of development, this program is not error free. In the current version, the error correction (<it>i.e</it>., editing) is performed manually using a graphical interface tool named AceTree, which is specifically developed for this task. For a single experiment, this manual annotation task takes several hours.</p> <p>Results</p> <p>In this paper, we reduce the time required to correct errors made by StarryNite. We target one of the most frequent error types (movements annotated as divisions) and train a support vector machine (SVM) classifier to decide whether a division call made by StarryNite is correct or not. We show, via cross-validation experiments on several benchmark data sets, that the SVM successfully identifies this type of error significantly. A new version of StarryNite that includes the trained SVM classifier is available at <url>http://starrynite.sourceforge.net</url>.</p> <p>Conclusions</p> <p>We demonstrate the utility of a machine learning approach to error annotation for StarryNite. In the process, we also provide some general methodologies for developing and validating a classifier with respect to a given pattern recognition task.</p

Lifetime physical activity and risk of breast cancer in pre-and post-menopausal women

© 2015 Springer Science+Business Media New York To investigate the association between different types of physical activity (PA) and breast cancer. A case–control study of breast cancer was conducted in Western Australia from 2009 to 2011, in which 1205 women with breast cancer and 1789 frequency age-matched breast cancer-free control women were recruited. A self-administered questionnaire was used to collect information about lifetime and age-period recreational, household, occupational and transport physical activities. Detailed questions about demographic characteristics, and relevant reproductive, medical and lifestyle factors were also included. Logistic regression and restrictive cubic spline analyses were applied to investigate the association and dose–response relationship between PA and breast cancer risk. Subgroup analysis was performed regarding menopausal status. We found non-linear dose–response associations between PA and risk of breast cancer. Overall, 95–130 MET-hours/week of total lifetime PA was associated with the lowest breast cancer risk. The effects were stronger among post-menopausal women. We also found that the medium amounts of recreational PA (up to 21 MET-hours/week) were associated with lower breast cancer risk among post-menopausal women. Further analysis on the intensity of recreational PA demonstrated different dose–response associations between moderate- and vigorous-intensity recreational PA and breast cancer risk. We found that PA was associated with a reduced risk of breast cancer among post-menopausal women, but not in a linear fashion. Recreational PA of different intensities may have different dose–response associations with risk of breast cancer

A comparison of prognostic significance of strong ion gap (SIG) with other acid-base markers in the critically ill: a cohort study

BACKGROUND: This cohort study compared the prognostic significance of strong ion gap (SIG) with other acid-base markers in the critically ill. METHODS: The relationships between SIG, lactate, anion gap (AG), anion gap albumin-corrected (AG-corrected), base excess or strong ion difference-effective (SIDe), all obtained within the first hour of intensive care unit (ICU) admission, and the hospital mortality of 6878 patients were analysed. The prognostic significance of each acid-base marker, both alone and in combination with the Admission Mortality Prediction Model (MPM0 III) predicted mortality, were assessed by the area under the receiver operating characteristic curve (AUROC). RESULTS: Of the 6878 patients included in the study, 924 patients (13.4 %) died after ICU admission. Except for plasma chloride concentrations, all acid-base markers were significantly different between the survivors and non-survivors. SIG (with lactate: AUROC 0.631, confidence interval [CI] 0.611-0.652; without lactate: AUROC 0.521, 95 % CI 0.500-0.542) only had a modest ability to predict hospital mortality, and this was no better than using lactate concentration alone (AUROC 0.701, 95 % 0.682-0.721). Adding AG-corrected or SIG to a combination of lactate and MPM0 III predicted risks also did not substantially improve the latter's ability to differentiate between survivors and non-survivors. Arterial lactate concentrations explained about 11 % of the variability in the observed mortality, and it was more important than SIG (0.6 %) and SIDe (0.9 %) in predicting hospital mortality after adjusting for MPM0 III predicted risks. Lactate remained as the strongest predictor for mortality in a sensitivity multivariate analysis, allowing for non-linearity of all acid-base markers. CONCLUSIONS: The prognostic significance of SIG was modest and inferior to arterial lactate concentration for the critically ill. Lactate concentration should always be considered regardless whether physiological, base excess or physical-chemical approach is used to interpret acid-base disturbances in critically ill patients

A counterbalanced cross-over study of the effects of visual, auditory and no feedback on performance measures in a simulated cardiopulmonary resuscitation

<p>Abstract</p> <p>Background</p> <p>Previous research has demonstrated that trained rescuers have difficulties achieving and maintaining the correct depth and rate of chest compressions during both in and out of hospital cardiopulmonary resuscitation (CPR). Feedback on rate and depth mitigate decline in performance quality but not completely with the residual performance decline attributed to rescuer fatigue. The purpose of this study was to examine the effects of feedback (none, auditory only and visual only) on the quality of CPR and rescuer fatigue.</p> <p>Methods</p> <p>Fifteen female volunteers performed 10 minutes of 30:2 CPR in each of three feedback conditions: none, auditory only, and visual only. Visual feedback was displayed continuously in graphic form. Auditory feedback was error correcting and provided by a voice assisted CPR manikin. CPR quality measures were collected using SkillReporter^®software. Blood lactate (mmol/dl) and perceived exertion served as indices of fatigue. One-way and two way repeated measures analyses of variance were used with alpha set <it>a priori </it>at 0.05.</p> <p>Results</p> <p>Visual feedback yielded a greater percentage of correct compressions (78.1 ± 8.2%) than did auditory (65.4 ± 7.6%) or no feedback (44.5 ± 8.1%). Compression rate with auditory feedback (87.9 ± 0.5 compressions per minute) was less than it was with both visual and no feedback (p < 0.05). CPR performed with no feedback (39.2 ± 0.5 mm) yielded a shallower average depth of compression and a lower percentage (55 ± 8.9%) of compressions within the accepted 38-50 mm range than did auditory or visual feedback (p < 0.05). The duty cycle for auditory feedback (39.4 ± 1.6%) was less than it was with no feedback (p < 0.05). Auditory feedback produced lower lactate concentrations than did visual feedback (p < 0.05) but there were no differences in perceived exertion.</p> <p>Conclusions</p> <p>In this study feedback mitigated the negative effects of fatigue on CPR performance and visual feedback yielded better CPR performance than did no feedback or auditory feedback. The perfect confounding of sensory modality and periodicity of feedback (visual feedback provided continuously and auditory feedback provided to correct error) leaves unanswered the question of optimal form and timing of feedback.</p

Return of naturally sourced Pb to Atlantic surface waters

Anthropogenic emissions completely overwhelmed natural marine lead (Pb) sources during the past century, predominantly due to leaded petrol usage. Here, based on Pb isotope measurements, we reassess the importance of natural and anthropogenic Pb sources to the tropical North Atlantic following the nearly complete global cessation of leaded petrol use. Significant proportions of up to 30-50% of natural Pb, derived from mineral dust, are observed in Atlantic surface waters, reflecting the success of the global effort to reduce anthropogenic Pb emissions. The observation of mineral dust derived Pb in surface waters is governed by the elevated atmospheric mineral dust concentration of the North African dust plume and the dominance of dry deposition for the atmospheric aerosol flux to surface waters. Given these specific regional conditions, emissions from anthropogenic activities will remain the dominant global marine Pb source, even in the absence of leaded petrol combustion

Changes in chromatin structure during processing of wax-embedded tissue sections

The use of immunofluorescence (IF) and fluorescence in situ hybridisation (FISH) underpins much of our understanding of how chromatin is organised in the nucleus. However, there has only recently been an appreciation that these types of study need to move away from cells grown in culture and towards an investigation of nuclear organisation in cells in situ in their normal tissue architecture. Such analyses, however, especially of archival clinical samples, often requires use of formalin-fixed paraffin wax-embedded tissue sections which need addition steps of processing prior to IF or FISH. Here we quantify the changes in nuclear and chromatin structure that may be caused by these additional processing steps. Treatments, especially the microwaving to reverse fixation, do significantly alter nuclear architecture and chromatin texture, and these must be considered when inferring the original organisation of the nucleus from data collected from wax-embedded tissue sections