Bowel Dysfunction after Hysterectomy for Benign Conditions: Meta-Analysis and Systematic Review

The aim of this study was to determine whether hysterectomy for a benign indication can cause functional gastrointestinal disorders (FGIDs). A systematic review was completed with the studies, which used a prospective design and validated quality of life questionnaires. A search strategy using Medline and Embase allowed the relevant studies published between 1950 and October 2010 to be found. Meta-analyses were also performed using the studies, which had similar research objectives. The search revealed 29 potentially suitable articles, of which 5 used a prospective design and validated quality of life questionnaires. The meta-analyses showed that the type of hysterectomy (total or subtotal) did not have an impact on whether a patient is likely to develop gastrointestinal symptoms post-surgery. The prospective studies did not show that hysterectomy for a benign indication causes FGIDs. The belief that hysterectomy can cause gastrointestinal dysfunction is based on the results of retrospective studies

Birth Weight in Relation to Fetal and Maternal Leptin and Insulin: A Systematic Review and Meta-analysis

Abstract leptin and insulin have been implicated in fetal growth regulation and investigated repeatedly with controversial outcomes. A systematic review and meta-analysis were conducted according to MOOSE guidelines to establish if consistency exists in the reported literature so that the role of maternal and fetal insulin and leptin in fetal growth could be assessed. A robust recognised systematic methodology was used in the literature search and data extraction and analysis to avoid bias. SPSS version 16 and RevMan 4.2 were used for statistical analysis and the results presented as a Weighted Mean Difference (WMD) and 95% CI. Nineteen studies were included. Large for gestational age babies (LGA) had significantly higher cord serum insulin and leptin levels than was adequate for gestational age (AGA) ones[3.16 µIU/ml (0.85, 5.48) and -4.33 ng/ml (-5.30, -3.36) respectively]. Small for gestational age babies (SGA) had similar insulin levels but significantly lower cord leptin[21 µIU/ml (-5.69, 1.27)] than AGA babies [-3.07ng/ml (-4.57, -1.58)]. Maternal serum levels of leptin were similar between mothers of LGA, SGA and AGA babies. Conclusion: although both fetal insulin and leptin reflect the degree of fetal adiposity, leptin may have growth promoting properties

Prenatal Exposure to Perfluoroalkyl Acids and Serum Testosterone Concentrations at 15 Years of Age in Female ALSPAC Study Participants

Background: Exposure to perfluorooctane sulfonic acid (PFOS) or to perfluorooctanoic acid (PFOA) increases mouse and human peroxisome proliferator–activated receptor alpha (PPARα) subtype activity, which influences lipid metabolism. Because cholesterol is the substrate from which testosterone is synthesized, exposure to these substances has the potential to alter testosterone concentrations. Objectives: We explored associations of total testosterone and sex hormone–binding globulin (SHBG) concentrations at age 15 years with prenatal exposures to PFOS, PFOA, perfluorohexane sulfonic acid (PFHxS), and perfluoronanoic acid (PFNA) in females. Methods: Prenatal concentrations of the perfluoroalkyl acids (PFAAs) were measured in serum collected from pregnant mothers at enrollment (1991–1992) in the Avon Longitudinal Study of Parents and Children (ALSPAC). The median gestational age when the maternal blood sample was obtained was 16 weeks (interquartile range, 11–28 weeks). Total testosterone and SHBG concentrations were measured in serum obtained from their daughters at 15 years of age. Associations between prenatal PFAAs concentrations and reproductive outcomes were estimated using linear regression models (n = 72). Results: Adjusted total testosterone concentrations were on average 0.18-nmol/L (95% CI: 0.01, 0.35) higher in daughters with prenatal PFOS in the upper concentration tertile compared with daughters with prenatal PFOS in the lower tertile. Adjusted total testosterone concentrations were also higher in daughters with prenatal concentrations of PFOA (β = 0.24; 95% CI: 0.05, 0.43) and PFHxS (β = 0.18; 95% CI: 0.00, 0.35) in the upper tertile compared with daughters with concentrations in the lower tertile. We did not find evidence of associations between PFNA and total testosterone or between any of the PFAAs and SHBG. Conclusions: Our findings were based on a small study sample and should be interpreted with caution. However, they suggest that prenatal exposure to some PFAAs may alter testosterone concentrations in females

Socioeconomic conditions across life related to multiple measures of the endocrine system in older adults:Longitudinal findings from a British birth cohort study

AbstractBackgroundLittle is known about how socioeconomic position (SEP) across life impacts on different axes of the endocrine system which are thought to underlie the ageing process and its adverse consequences. We examined how indicators of SEP across life related to multiple markers of the endocrine system in late midlife, and hypothesized that lower SEP across life would be associated with an adverse hormone profile across multiple axes.MethodsData were from a British cohort study of 875 men and 905 women followed since their birth in March 1946 with circulating free testosterone and insulin-like growth factor-I (IGF-I) measured at both 53 and 60–64 years, and evening cortisol at 60–64 years. Indicators of SEP were ascertained prospectively across life—paternal occupational class at 4, highest educational attainment at 26, household occupational class at 53, and household income at 60–64 years. Associations between SEP and hormones were investigated using multiple regression and logistic regression models.ResultsLower SEP was associated with lower free testosterone among men, higher free testosterone among women, and lower IGF-I and higher evening cortisol in both sexes. For example, the mean standardised difference in IGF-I comparing the lowest with the highest educational attainment at 26 years (slope index of inequality) was −0.4 in men (95% CI -0.7 to −0.2) and −0.4 in women (−0.6 to −0.2). Associations with each hormone differed by SEP indicator used and sex, and were particularly pronounced when using a composite adverse hormone score. For example, the odds of having 1 additional adverse hormone concentration in the lowest compared with highest education level were 3.7 (95% CI: 2.1, 6.3) among men, and 1.6 (1.0, 2.7) among women (P (sex interaction) = 0.02). We found no evidence that SEP was related to apparent age-related declines in free testosterone or IGF-I.ConclusionsLower SEP was associated with an adverse hormone profile across multiple endocrine axes. SEP differences in endocrine function may partly underlie inequalities in health and function in later life, and may reflect variations in biological rates of ageing. Further studies are required to assess the likely functional relevance of these associations

Xeno-free trans-differentiation of adipose tissue-derived mesenchymal stem cells into glial and neuronal cells.

Mesenchymal stem cells (MSCs) are undifferentiated cells that have the ability of self-renewal and trans-differentiation into other cell types. They hold out hope for finding a cure for many diseases. Nevertheless, there are still some obstacles that limit their clinical transplantation. One of these obstacles are the xenogeneic substances added in either proliferation or differentiation media with subsequent immunogenic and infectious transmission problems. In this study, we aimed to replace fetal bovine serum (FBS), the main nutrient source for MSC proliferation with xeno-free blood derivatives. We tested the effect of human activated pure platelet-rich plasma (P-PRP) and advanced platelet-rich fibrin (A-PRF) on the proliferation of human adipose derived-MSCs (AD-MSCs) at different concentrations. For the induction of MSC neural differentiation, we used human cerebrospinal fluid (CSF) at different concentrations in combination with P-PRP to effect xeno-free/species-specific neuronal/glial differentiation and we found that media with 10% CSF and 10% PRP promoted glial differentiation, while media with only 10% PRP induced a neuron-like phenotype

Effect of metformin on maternal and fetal outcomes in obese pregnant women (EMPOWaR):a randomised, double-blind, placebo-controlled trial

Background: Maternal obesity is associated with increased birthweight, and obesity and premature mortality in adult offspring. The mechanism by which maternal obesity leads to these outcomes is not well understood, but maternal hyperglycaemia and insulin resistance are both implicated. We aimed to establish whether the insulin sensitising drug metformin improves maternal and fetal outcomes in obese pregnant women without diabetes. Methods: We did this randomised, double-blind, placebo-controlled trial in antenatal clinics at 15 National Health Service hospitals in the UK. Pregnant women (aged ≥16 years) between 12 and 16 weeks' gestation who had a BMI of 30 kg/m2 or more and normal glucose tolerance were randomly assigned (1:1), via a web-based computer-generated block randomisation procedure (block size of two to four), to receive oral metformin 500 mg (increasing to a maximum of 2500 mg) or matched placebo daily from between 12 and 16 weeks' gestation until delivery of the baby. Randomisation was stratified by study site and BMI band (30–39 vs ≥40 kg/m2). Participants, caregivers, and study personnel were masked to treatment assignment. The primary outcome was Z score corresponding to the gestational age, parity, and sex-standardised birthweight percentile of liveborn babies delivered at 24 weeks or more of gestation. We did analysis by modified intention to treat. This trial is registered, ISRCTN number 51279843. Findings: Between Feb 3, 2011, and Jan 16, 2014, inclusive, we randomly assigned 449 women to either placebo (n=223) or metformin (n=226), of whom 434 (97%) were included in the final modified intention-to-treat analysis. Mean birthweight at delivery was 3463 g (SD 660) in the placebo group and 3462 g (548) in the metformin group. The estimated effect size of metformin on the primary outcome was non-significant (adjusted mean difference −0·029, 95% CI −0·217 to 0·158; p=0·7597). The difference in the number of women reporting the combined adverse outcome of miscarriage, termination of pregnancy, stillbirth, or neonatal death in the metformin group (n=7) versus the placebo group (n=2) was not significant (odds ratio 3·60, 95% CI 0·74–17·50; p=0·11). Interpretation: Metformin has no significant effect on birthweight percentile in obese pregnant women. Further follow-up of babies born to mothers in the EMPOWaR study will identify longer-term outcomes of metformin in this population; in the meantime, metformin should not be used to improve pregnancy outcomes in obese women without diabetes

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

<p>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.</p> <p>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.</p> <p>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.</p> <p>Conclusion: Our results suggest that in healthy adolescent females, AMH is not associated with cardiometabolic risk factors.</p&gt

Genetically unmatched human iPSC and ESC exhibit equivalent gene expression and neuronal differentiation potential

Abstract The potential uniformity between differentiation and therapeutic potential of human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) remains debatable. We studied the gene expression profiles, pathways analysis and the ability to differentiated into neural progenitor cells (NPCs) and motor neurons (MNs) of genetically unmatched integration-free hiPSC versus hESC to highlight possible differences/similarities between them at the molecular level. We also provided the functional information of the neurons derived from the different hESCs and hiPSCs lines using the Neural Muscular Junction (NMJ) Assay. The hiPSC line was generated by transfecting human epidermal fibroblasts (HEF) with episomal DNAs expressing Oct4, Sox2, Klf4, Nanog, L-Myc and shRNA against p53. For the hESCs line, we used the NIH-approved H9 cell line. Using unsupervised clustering both hESCs and hiPSCs were clustered together implying homogeneous genetic states. The genetic profiles of hiPSCs and hESCs were clearly similar but not identical. Collectively, our data indicate close molecular similarities between genetically unmatched hESCs and hiPS in term of gene expression, and signaling pathways. Moreover, both cell types exhibited similar cholinergic motor neurons differentiation potential with marked ability of the differentiated hESCs and hiPSCs-derived MNs to induce contraction of myotubes after 4 days of co-culture