Nitrates in drinking water and methemoglobin levels in pregnancy: a longitudinal study

This is the final version of the article. Available from BioMed Central via the DOI in this record.BACKGROUND: Private water systems are more likely to have nitrate levels above the maximum contaminant level (MCL). Pregnant women are considered vulnerable to the effects of exposure to high levels of nitrates in drinking water due to their altered physiological states. The level of methemoglobin in the blood is the biomarker often used in research for assessing exposure to nitrates. The objective of this study was to assess methemoglobin levels and examine how various factors affected methemoglobin levels during pregnancy. We also examined whether differences in water use practices existed among pregnant women based on household drinking water source of private vs. public supply. METHODS: A longitudinal study of 357 pregnant women was conducted. Longitudinal regression models were used to examine changes and predictors of the change in methemoglobin levels over the period of gestation. RESULTS: Pregnant women showed a decrease in methemoglobin levels with increasing gestation although <1% had levels above the physiologic normal of 2% methemoglobin, regardless of the source of their drinking water. The multivariable analyses did not show a statistically significant association between methemoglobin levels and the estimated nitrate intake from tap water among pregnant women around 36 weeks gestation (β = 0.046, p = 0.986). Four women had tap water nitrate levels above the MCL of 10 mg/L. At enrollment, a greater proportion of women who reported using water treatment devices were private wells users (66%) compared to public system users (46%) (p < 0.0001). Also, a greater proportion of private well users (27%) compared to public system users (13%) were using devices capable of removing nitrate from water (p < 0.0001). CONCLUSION: Pregnant women potentially exposed to nitrate levels primarily below the MCL for drinking water were unlikely to show methemoglobin levels above the physiologic normal. Water use practices such as the use of treatment devices to remove nitrates varied according to water source and should be considered in the assessment of exposure to nitrates in future studies

Anti-müllerian hormone is not associated with cardiometabolic risk factors in adolescent females

&lt;p&gt;Objectives: Epidemiological evidence for associations of Anti-Müllerian hormone (AMH) with cardiometabolic risk factors is lacking. Existing evidence comes from small studies in select adult populations, and findings are conflicting. We aimed to assess whether AMH is associated with cardiometabolic risk factors in a general population of adolescent females.&lt;/p&gt; &lt;p&gt;Methods: AMH, fasting insulin, glucose, HDLc, LDLc, triglycerides and C-reactive protein (CRP) were measured at a mean age 15.5 years in 1,308 female participants in the Avon Longitudinal Study of Parents and Children (ALSPAC). Multivariable linear regression was used to examine associations of AMH with these cardiometabolic outcomes.&lt;/p&gt; &lt;p&gt;Results: AMH values ranged from 0.16–35.84 ng/ml and median AMH was 3.57 ng/ml (IQR: 2.41, 5.49). For females classified as post-pubertal (n = 848) at the time of assessment median (IQR) AMH was 3.81 ng/ml (2.55, 5.82) compared with 3.25 ng/ml (2.23, 5.05) in those classed as early pubertal (n = 460, P≤0.001). After adjusting for birth weight, gestational age, pubertal stage, age, ethnicity, socioeconomic position, adiposity and use of hormonal contraceptives, there were no associations with any of the cardiometabolic outcomes. For example fasting insulin changed by 0% per doubling of AMH (95%CI: −3%,+2%) p = 0.70, with identical results if HOMA-IR was used. Results were similar after additional adjustment for smoking, physical activity and age at menarche, after exclusion of 3% of females with the highest AMH values, after excluding those that had not started menarche and after excluding those using hormonal contraceptives.&lt;/p&gt; &lt;p&gt;Conclusion: Our results suggest that in healthy adolescent females, AMH is not associated with cardiometabolic risk factors.&lt;/p&gt

Skp is a multivalent chaperone of outer membrane proteins

The trimeric chaperone Skp sequesters outer-membrane proteins (OMPs) within a hydrophobic cage, thereby preventing their aggregation during transport across the periplasm in Gram-negative bacteria. Here, we studied the interaction between Escherichia coli Skp and five OMPs of varying size. Investigations of the kinetics of OMP folding revealed that higher Skp/OMP ratios are required to prevent the folding of 16-stranded OMPs compared with their 8-stranded counterparts. Ion mobility spectrometry–mass spectrometry (IMS–MS) data, computer modeling and molecular dynamics simulations provided evidence that 10- to 16-stranded OMPs are encapsulated within an expanded Skp substrate cage. For OMPs that cannot be fully accommodated in the expanded cavity, sequestration is achieved by binding of an additional Skp trimer. The results suggest a new mechanism for Skp chaperone activity involving the coordination of multiple copies of Skp in protecting a single substrate from aggregation

Outer membrane protein folding from an energy landscape perspective

The cell envelope is essential for the survival of Gram-negative bacteria. This specialised membrane is densely packed with outer membrane proteins (OMPs), which perform a variety of functions. How OMPs fold into this crowded environment remains an open question. Here, we review current knowledge about OFMP folding mechanisms in vitro and discuss how the need to fold to a stable native state has shaped their folding energy landscapes. We also highlight the role of chaperones and the β-barrel assembly machinery (BAM) in assisting OMP folding in vivo and discuss proposed mechanisms by which this fascinating machinery may catalyse OMP folding

Comorbidity, age, race and stage at diagnosis in colorectal cancer: a retrospective, parallel analysis of two health systems

© 2008 Zafar et al; licensee BioMed Central Ltd. This 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.Background : Stage at diagnosis plays a significant role in colorectal cancer (CRC) survival. Understanding which factors contribute to a more advanced stage at diagnosis is vital to improving overall survival. Comorbidity, race, and age are known to impact receipt of cancer therapy and survival, but the relationship of these factors to stage at diagnosis of CRC is less clear. The objective of this study is to investigate how comorbidity, race and age influence stage of CRC diagnosis. Methods : Two distinct healthcare populations in the United States (US) were retrospectively studied. Using the Cancer Care Outcomes Research and Surveillance Consortium database, we identified CRC patients treated at 15 Veterans Administration (VA) hospitals from 2003–2007. We assessed metastatic CRC patients treated from 2003–2006 at 10 non-VA, fee-for-service (FFS) practices. Stage at diagnosis was dichotomized (non-metastatic, metastatic). Race was dichotomized (white, non-white). Charlson comorbidity index and age at diagnosis were calculated. Associations between stage, comorbidity, race, and age were determined by logistic regression. Results : 342 VA and 340 FFS patients were included. Populations differed by the proportion of patients with metastatic CRC at diagnosis (VA 27% and FFS 77%) reflecting differences in eligibility criteria for inclusion. VA patients were mean (standard deviation; SD) age 67 (11), Charlson index 2.0 (1.0), and were 63% white. FFS patients were mean age 61 (13), Charlson index 1.6 (1.0), and were 73% white. In the VA cohort, higher comorbidity was associated with earlier stage at diagnosis after adjusting for age and race (odds ratio (OR) 0.76, 95% confidence interval (CI) 0.58–1.00; p = 0.045); no such significant relationship was identified in the FFS cohort (OR 1.09, 95% CI 0.82–1.44; p = 0.57). In both cohorts, no association was found between stage at diagnosis and either age or race. Conclusion : Higher comorbidity may lead to earlier stage of CRC diagnosis. Multiple factors, perhaps including increased interactions with the healthcare system due to comorbidity, might contribute to this finding. Such increased interactions are seen among patients within a healthcare system like the VA system in the US versus sporadic interactions which may be seen with FFS healthcare

QCD and strongly coupled gauge theories : challenges and perspectives

We highlight the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment. We discuss how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as to searches for physics beyond the Standard Model. We also discuss how success in describing the strong interaction impacts other fields, and, in turn, how such subjects can impact studies of the strong interaction. In the course of the work we offer a perspective on the many research streams which flow into and out of QCD, as well as a vision for future developments.Peer reviewe

Protein kinase C and cardiac dysfunction: a review

Heart failure (HF) is a physiological state in which cardiac output is insufficient to meet the needs of the body. It is a clinical syndrome characterized by impaired ability of the left ventricle to either fill or eject blood efficiently. HF is a disease of multiple aetiologies leading to progressive cardiac dysfunction and it is the leading cause of deaths in both developed and developing countries. HF is responsible for about 73,000 deaths in the UK each year. In the USA, HF affects 5.8 million people and 550,000 new cases are diagnosed annually. Cardiac remodelling (CD), which plays an important role in pathogenesis of HF, is viewed as stress response to an index event such as myocardial ischaemia or imposition of mechanical load leading to a series of structural and functional changes in the viable myocardium. Protein kinase C (PKC) isozymes are a family of serine/threonine kinases. PKC is a central enzyme in the regulation of growth, hypertrophy, and mediators of signal transduction pathways. In response to circulating hormones, activation of PKC triggers a multitude of intracellular events influencing multiple physiological processes in the heart, including heart rate, contraction, and relaxation. Recent research implicates PKC activation in the pathophysiology of a number of cardiovascular disease states. Few reports are available that examine PKC in normal and diseased human hearts. This review describes the structure, functions, and distribution of PKCs in the healthy and diseased heart with emphasis on the human heart and, also importantly, their regulation in heart failure

The tenth data release of the Sloan digital sky survey: First spectroscopic data from the SDSS-iii apache point observatory galactic evolution experiment

The Sloan Digital Sky Survey (SDSS) has been in operation since 2000 April. This paper presents the tenth public data release (DR10) from its current incarnation, SDSS-III. This data release includes the first spectroscopic data from the Apache Point Observatory Galaxy Evolution Experiment (APOGEE), along with spectroscopic data from the Baryon Oscillation Spectroscopic Survey (BOSS) taken through 2012 July. The APOGEE instrument is a near-infrared R ~ 22,500 300-fiber spectrograph covering 1:514-1:696 μm. The APOGEE survey is studying the chemical abundances and radial velocities of roughly 100,000 red giant star candidates in the bulge, bar, disk, and halo of the Milky Way. DR10 includes 178,397 spectra of 57,454 stars, each typically observed three or more times, from APOGEE. Derived quantities from these spectra (radial velocities, effective temperatures, surface gravities, and metallicities) are also included. DR10 also roughly doubles the number of BOSS spectra over those included in the ninth data release. DR10 includes a total of 1,507,954 BOSS spectra, comprising 927,844 galaxy spectra; 182,009 quasar spectra; and 159,327 stellar spectra, selected over 6373.2 deg2.This is an author-created, un-copyedited version of an article accepted for publication in The Astrophysical Journal Supplement Series. The publisher is not responsible for any errors or omissions in this version of the manuscript or any version derived from it. The Version of Record is available online at http://dx.doi.org/10.1088/0067-0049/211/2/17. The accepted version will be under embargo until the 18th March 2015

Population‐based cohort study of outcomes following cholecystectomy for benign gallbladder diseases

Background The aim was to describe the management of benign gallbladder disease and identify characteristics associated with all‐cause 30‐day readmissions and complications in a prospective population‐based cohort. Methods Data were collected on consecutive patients undergoing cholecystectomy in acute UK and Irish hospitals between 1 March and 1 May 2014. Potential explanatory variables influencing all‐cause 30‐day readmissions and complications were analysed by means of multilevel, multivariable logistic regression modelling using a two‐level hierarchical structure with patients (level 1) nested within hospitals (level 2). Results Data were collected on 8909 patients undergoing cholecystectomy from 167 hospitals. Some 1451 cholecystectomies (16·3 per cent) were performed as an emergency, 4165 (46·8 per cent) as elective operations, and 3293 patients (37·0 per cent) had had at least one previous emergency admission, but had surgery on a delayed basis. The readmission and complication rates at 30 days were 7·1 per cent (633 of 8909) and 10·8 per cent (962 of 8909) respectively. Both readmissions and complications were independently associated with increasing ASA fitness grade, duration of surgery, and increasing numbers of emergency admissions with gallbladder disease before cholecystectomy. No identifiable hospital characteristics were linked to readmissions and complications. Conclusion Readmissions and complications following cholecystectomy are common and associated with patient and disease characteristics

Histopathological cutaneous alterations in systemic sclerosis: a clinicopathological study

Introduction: The aims of the present study were to identify histopathological parameters which are linked to local clinical skin disease at two distinct anatomical sites in systemic sclerosis (SSc) patients with skin involvement (limited cutaneous systemic sclerosis (lcSSc) or diffuse cutaneous systemic sclerosis (dcSSc)) and to determine the sensitivity of SSc specific histological alterations, focusing on SSc patients without clinical skin involvement (limited SSc (lSSc)). Methods: Histopathological alterations were systematically scored in skin biopsies of 53 consecutive SSc patients (dorsal forearm and upper inner arm) and 18 controls (upper inner arm). Clinical skin involvement was evaluated using the modified Rodnan skin score. In patients with lcSSc or dcSSc, associations of histopathological parameters with local clinical skin involvement were determined by generalised estimation equation modelling. Results: The hyalinised collagen score, the myofibroblast score, the mean epidermal thickness, the mononuclear cellular infiltration and the frequency of focal exocytosis differed significantly between biopsies with and without local clinical skin involvement. Except for mononuclear cellular infiltration, all of the continuous parameters correlated with the local clinical skin score at the dorsal forearm. Parakeratosis, myofibroblasts and intima proliferation were present in a minority of the SSc biopsies, but not in controls. No differences were found between lSSc and controls. Conclusions: Several histopathological parameters are linked to local clinical skin disease. SSc-specific histological alterations have a low diagnostic sensitivity