Risk of Diabetes After Hysterectomy With or Without Oophorectomy in Postmenopausal Women

Abstract The aim of this study was to determine the associations between hysterectomy, bilateral salpingo-oophorectomy (BSO), and incidence of diabetes in postmenopausal women participating in the Women's Health Initiative (WHI), a series of trials conducted in the United States, during the period 1993–1998. A total of 67,130 postmenopausal women aged 50–79 years were followed for a mean of 13.4 years. Among them, 7,430 cases of diabetes were diagnosed. Multivariable Cox proportional hazards models were used to assess the association between hysterectomy/oophorectomy status and diabetes incidence. Compared with women without hysterectomy, women with hysterectomy had a significantly higher risk of diabetes (hazard ratio = 1.13, 95% confidence interval: 1.06, 1.21). The increased risk of diabetes was similar for women with hysterectomy only and for women with hysterectomy with concomitant BSO. Compared with hysterectomy alone, hysterectomy with BSO was not associated with additional risk of diabetes after stratification by age at hysterectomy and hormone therapy status. In our large, prospective study, we observed that hysterectomy, regardless of oophorectomy status, was associated with increased risk of diabetes among postmenopausal women. However, our data did not support the hypothesis that early loss of ovarian estrogens is a risk factor for type 2 diabetes. The modest increased risk of diabetes associated with hysterectomy may be due to residual confounding, such as the reasons for hysterectomy

Running on empty:A metabolomics approach to investigating changing energy metabolism during fasted exercise and rest

Understanding the metabolic processes in energy metabolism, particularly during fasted exercise, is a growing area of research. Previous work has focused on measuring metabolites pre and post exercise. This can provide information about the final state of energy metabolism in the participants, but it does not show how these processes vary during the exercise and any subsequent post-exercise period. To address this, the work described here took fasted participants and subjected them to an exercise and rest protocol under laboratory settings, which allowed for breath and blood sampling both pre, during and post exercise. Analysis of the data produced from both the physiological measurements and the untargeted metabolomics measurements showed clear switching between glycolytic and ketolytic metabolism, with the liquid chromatography-mass spectrometry (LC-MS) data showing the separate stages of ketolytic metabolism, notably the transport, release and breakdown of long chain fatty acids. Several signals, putatively identified as short peptides, were observed to change in a pattern similar to that of the ketolytic metabolites. This work highlights the power of untargeted metabolomic methods as an investigative tool for exercise science, both to follow known processes in a more complete way and discover possible novel biomarkers

Vitamin D levels and menopause-related symptoms.

Objective: To determine whether vitamin D levels are associated with menopause-related symptoms in older women. Methods: A randomly selected subset of 1,407 women, among 26,104 potentially eligible participants of the Women’s Health Initiative Calcium and Vitamin D (CaD) trial of postmenopausal women aged 51-80 years, had 25-hydroxyvitamin D [25(OH)D] levels measured at the CaD trial baseline visit. Information about menopause-related symptoms at baseline was obtained by questionnaire and included overall number of symptoms and composite measures of sleep disturbance, emotional well-being, and energy/fatigue, as well as individual symptoms. After exclusions for missing data, 530 women [mean age 66.2 years (SD 6.8)] were included in these analyses. Results: There were borderline significant associations between 25(OH)D levels and total number of menopausal symptoms (p values ranging from 0.05 to 0.06 for fully adjusted models); however, the effect was clinically insignificant and disappeared with correction for multiple testing. There were no associations between 25(OH)D levels and composite measures of sleep disturbance, emotional well-being, or energy/fatigue (p’s > 0.10 for fully adjusted models). Conclusions: There was no evidence of a clinically important association between serum 25(OH)D levels and menopause-related symptoms in postmenopausal women

Patients undergoing surgery for lumbar spinal stenosis experience unique courses of pain and disability: A group-based trajectory analysis

© 2019 Hebert et al. 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. Objective Identify patient subgroups defined by trajectories of pain and disability following surgery for degenerative lumbar spinal stenosis, and investigate the construct validity of the subgroups by evaluating for meaningful differences in clinical outcomes. Methods We recruited patients with degenerative lumbar spinal stenosis from 13 surgical spine centers who were deemed to be surgical candidates. Study outcomes (leg and back pain numeric rating scales, modified Oswestry disability index) were measured before surgery, and after 3, 12, and 24 months. Group-based trajectory models were developed to identify trajectory subgroups for leg pain, back pain, and pain-related disability. We examined for differences in the proportion of patients achieving minimum clinically important change in pain and disability (30%) and clinical success (50% reduction in disability or Oswestry score ≤22) 12 months from surgery. Results Data from 548 patients (mean[SD] age = 66.7[9.1] years; 46% female) were included. The models estimated 3 unique trajectories for leg pain (excellent outcome = 14.4%, good outcome = 49.5%, poor outcome = 36.1%), back pain (excellent outcome = 13.1%, good outcome = 45.0%, poor outcome = 41.9%), and disability (excellent outcome = 30.8%, fair outcome = 40.1%, poor outcome = 29.1%). The construct validity of the trajectory subgroups was confirmed by between-trajectory group differences in the proportion of patients meeting thresholds for minimum clinically important change and clinical success after 12 postoperative months (p \u3c .001). Conclusion Subgroups of patients with degenerative lumbar spinal stenosis can be identified by their trajectories of pain and disability following surgery. Although most patients experienced important reductions in pain and disability, 29% to 42% of patients were classified as members of an outcome trajectory subgroup that experienced little to no benefit from surgery. These findings may inform appropriate expectation setting for patients and clinicians and highlight the need for better methods of treatment selection for patients with degenerative lumbar spinal stenosis

Alcelaphine herpesvirus 1 glycoprotein B:recombinant expression and antibody recognition

The gammaherpesvirus alcelaphine herpesvirus 1 (AlHV-1) causes fatal malignant catarrhal fever (MCF) in susceptible species including cattle, but infects its reservoir host, wildebeest, without causing disease. Pathology in cattle may be influenced by virus-host cell interactions mediated by the virus glycoproteins. Cloning and expression of a haemagglutinin-tagged version of the AlHV-1 glycoprotein B (gB) was used to demonstrate that the AlHV-1-specific monoclonal antibody 12B5 recognised gB and that gB was the main component of the gp115 complex of AlHV-1, a glycoprotein complex of five components identified on the surface of AlHV-1 by immunoprecipitation and radiolabelling. Analysis of AlHV-1 virus particles showed that the native form of gB was detected by mAb 12B5 as a band of about 70 kDa, whilst recombinant gB expressed by transfected HEK293T cells appeared to be subject to additional cleavage and incomplete post-translational processing. Antibody 12B5 recognised an epitope on the N-terminal furin-cleaved fragment of gB on AlHV-1 virus particles. It could be used to detect recombinant and virus-expressed gB on western blots and on the surface of infected cells by flow cytometry, whilst recombinant gB was detected on the surface of transfected cells by immunofluorescence. Recombinant gB has potential as an antigen for ELISA detection of MCF virus infection and as a candidate vaccine antigen

Cysteamine Inhibits Glycine Utilisation and Disrupts Virulence in Pseudomonas aeruginosa.

Pseudomonas aeruginosa is a major opportunistic human pathogen which employs a myriad of virulence factors. In people with cystic fibrosis (CF) P. aeruginosa frequently colonises the lungs and becomes a chronic infection that evolves to become less virulent over time, but often adapts to favour persistence in the host with alginate-producing mucoid, slow-growing, and antibiotic resistant phenotypes emerging. Cysteamine is an endogenous aminothiol which has been shown to prevent biofilm formation, reduce phenazine production, and potentiate antibiotic activity against P. aeruginosa, and has been investigated in clinical trials as an adjunct therapy for pulmonary exacerbations of CF. Here we demonstrate (for the first time in a prokaryote) that cysteamine prevents glycine utilisation by P. aeruginosa in common with previously reported activity blocking the glycine cleavage system in human cells. Despite the clear inhibition of glycine metabolism, cysteamine also inhibits hydrogen cyanide (HCN) production by P. aeruginosa, suggesting a direct interference in the regulation of virulence factor synthesis. Cysteamine impaired chemotaxis, lowered pyocyanin, pyoverdine and exopolysaccharide production, and reduced the toxicity of P. aeruginosa secreted factors in a Galleria mellonella infection model. Thus, cysteamine has additional potent anti-virulence properties targeting P. aeruginosa, further supporting its therapeutic potential in CF and other infections

Anthropometric measures and serum estrogen metabolism in postmenopausal women: the Women’s Health Initiative Observational Study

Background: Several anthropometric measures have been associated with hormone-related cancers. However, it is unknown whether estrogen metabolism plays an important role in these relationships. We examined whether measured current body mass index (BMI), waist-to-hip ratio (WHR), height, and self-reported BMI at age 18 years were associated with serum estrogens/estrogen metabolites using baseline, cross-sectional data from 1835 postmenopausal women enrolled in the Women’s Health Initiative Observational Study. Methods: Fifteen estrogens/estrogen metabolites were quantified using liquid chromatography-tandem mass spectrometry. Geometric means (GMs) of estrogens/estrogen metabolites (in picomoles per liter) were estimated using inverse probability weighted linear regression, adjusting for potential confounders and stratified on menopausal hormone therapy (MHT) use. Results: Among never or former MHT users, current BMI (≥30 vs. <25 kg/m2) was positively associated with parent estrogens (multivariable adjusted GM 432 vs. 239 pmol/L for estrone, 74 vs. 46 pmol/L for estradiol; p-trend < 0.001 for both) and all of the 2-, 4-, and 16-pathway estrogen metabolites evaluated (all p-trend ≤ 0.02). After additional adjustment for estradiol, unconjugated methylated 2-catechols were inversely associated (e.g., 2-methoxyestrone multivariable GM 9.3 vs. 12.0 pmol/L; p-trend < 0.001). Among current MHT users, current BMI was not associated with parent estrogens but was inversely associated with methylated catechols (e.g., 2-methoxyestrone multivariable GM 216 vs. 280 pmol/L; p-trend = 0.008). Similar patterns of association were found with WHR; however, the associations were not independent of BMI. Height and BMI at age 18 years were not associated with postmenopausal estrogens/estrogen metabolite levels. Conclusions: Our data suggest that postmenopausal BMI is associated with increased circulating levels of parent estrogens and reduced methylation of catechol estrogen metabolites, the estrogen metabolism patterns that have previously been associated with higher breast cancer risk. Electronic supplementary material The online version of this article (doi:10.1186/s13058-017-0810-0) contains supplementary material, which is available to authorized users

Relation of Serum Vitamin D to Risk of Mitral Annular and Aortic Valve Calcium (from the Multi-Ethnic Study of Atherosclerosis)

Serum 25-hydroxyvitamin D [25(OH)D] concentration has been identified as a possible modifiable risk factor for cardiovascular disease (CVD). We hypothesized that serum 25(OH)D concentration would be associated with calcifications of the left-sided heart valves, which are markers of CVD risk. Aortic valve calcium (AVC) and mitral annular calcium (MAC) were quantified from cardiac computed tomography scans performed on 5,530 Multi-Ethnic Study of Atherosclerosis participants at the baseline examination (2000 to 2002) and at a follow-up visit at either Examination 2 (2002 to 2004) or Examination 3 (2004 to 2005). 25(OH)D was measured from serum samples collected at the baseline examination. Using relative risk regression, we evaluated the multivariable-adjusted risk of prevalent and incident AVC and MAC in this ethnically diverse population free of clinical CVD at baseline. The mean age of participants was 62 ± 10 years; 53% were women, 40% white, 26% black, 21% Hispanic, and 12% Chinese. Prevalent AVC and MAC were observed in 12% and 9% of study sample, respectively. There were no significant associations between 25(OH)D and prevalent AVC or MAC. Over a mean follow-up of 2.5 years, 4% developed incident AVC and 5% developed incident MAC. After adjusting for demographic variables, each 10 ng/ml higher serum 25(OH)D was associated with a 15% (relative risk 0.85, 95% confidence interval 0.74 to 0.98) lower risk of incident MAC but not AVC. However, this association was no longer significant after adjusting for lifestyle and CVD risk factors. Results suggest a possible link between serum 25(OH)D and the risk for incident MAC, but future studies with longer follow-up are needed to further test this association

Correction to: Cluster identification, selection, and description in Cluster randomized crossover trials: the PREP-IT trials

An amendment to this paper has been published and can be accessed via the original article