Pelvic floor muscle function in a general female population in relation with age and parity and the relation between voluntary and involuntary contractions of the pelvic floor musculature

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How Contemporary Human Reproductive Behaviors Influence the Role of Fertility-Related Genes: The Example of the P53 Gene

Studies on human fertility genes have identified numerous risk/protective alleles involved in the occurrence of reproductive system diseases causing infertility or subfertility. Investigations we carried out in populations at natural fertility seem to suggest that the clinical relevance that some fertility genes are now acquiring depends on their interaction with contemporary reproductive behaviors (birth control, delayed childbearing, and spacing birth order, among others). In recent years, a new physiological role in human fertility regulation has emerged for the tumor- suppressor p53 gene (P53), and the P53 Arg72Pro polymorphism has been associated with recurrent implantation failure in humans. To lend support to our previous observations, we examined the impact of Arg72Pro polymorphism on fertility in two samples of Italian women not selected for impaired fertility but collected from populations with different (premodern and modern) reproductive behaviors. Among the women at near-natural fertility (n = 98), the P53 genotypes were not associated with different reproductive efficiency, whereas among those with modern reproductive behaviors (n = 68), the P53 genotypes were associated with different mean numbers of children [Pro/Pro = 0.75<Pro/Arg = 1.7<Arg/Arg = 2, (p = 0.056)] and a significant negative relationship between the number of children and P53 Pro allele frequencies (p = 0.028) was observed. These results are consistent with those of clinical studies reporting an association between the P53 Pro allele and recurrent implantation failure. By combining these findings with previous ones, we suggest here that some common variants of fertility genes may have become “detrimental” following exposure to modern reproductive patterns and might therefore be associated with reduced reproductive success. Set within an evolutionary framework, this change could lead to the selection of a set of gene variants fitter to current reproductive behaviors as the shift to later child-bearing age in developed countries

π-π stacking tackled with density functional theory

Through comparison with ab initio reference data, we have evaluated the performance of various density functionals for describing π-π interactions as a function of the geometry between two stacked benzenes or benzene analogs, between two stacked DNA bases, and between two stacked Watson–Crick pairs. Our main purpose is to find a robust and computationally efficient density functional to be used specifically and only for describing π-π stacking interactions in DNA and other biological molecules in the framework of our recently developed QM/QM approach "QUILD". In line with previous studies, most standard density functionals recover, at best, only part of the favorable stacking interactions. An exception is the new KT1 functional, which correctly yields bound π-stacked structures. Surprisingly, a similarly good performance is achieved with the computationally very robust and efficient local density approximation (LDA). Furthermore, we show that classical electrostatic interactions determine the shape and depth of the π-π stacking potential energy surface

Miscarriage rates after dehydroepiandrosterone (DHEA) supplementation in women with diminished ovarian reserve: a case control study

<p>Abstract</p> <p>Background</p> <p>Dehydroepinadrosterone (DHEA) supplementation improves pregnancy chances in women with diminished ovarian reserve (DOR), by possibly reducing aneuploidy. Since a large majority of spontaneous miscarriages are associated with aneuploidy, one can speculate that DHEA supplementation may also reduce miscarriage rates.</p> <p>Methods</p> <p>We retroactively compared, utilizing two independent statistical models, miscarriage rates in 73 DHEA supplemented pregnancies at two independent North American infertility centers, age-stratified, to miscarriages reported in a national U.S. in vitro fertilization (IVF) data base.</p> <p>Results</p> <p>After DHEA supplementation the miscarriage rate at both centers was 15.1% (15.0% and 15.2%, respectively). For DHEA supplementation Mantel-Hänszel common odds ratio (and 95% confidence interval), stratified by age, was significantly lower, relative to odds of miscarriage in the general IVF control population [0.49 (0.25-0.94; p = 0.04)]. Miscarriage rates after DHEA were significantly lower at all ages but most pronounced above age 35 years.</p> <p>Discussion</p> <p>Since DOR patients in the literature are reported to experience significantly higher miscarriage rates than average IVF patients, the here observed reduction in miscarriages after DHEA supplementation exceeds, however, all expectations. Miscarriage rates after DHEA not only were lower than in an average national IVF population but were comparable to rates reported in normally fertile populations. Low miscarriage rates, comparable to those of normal fertile women, are statistically impossible to achieve in DOR patients without assumption of a DHEA effect on embryo ploidy. Beyond further investigations in infertile populations, these data, therefore, also suggest the investigations of pre-conception DHEA supplementation in normal fertile populations above age 35 years.</p

Theoretical description of hydrogen bonding in oxalic acid dimer and trimer based on the combined extended-transition-state energy decomposition analysis and natural orbitals for chemical valence (ETS-NOCV)

In the present study we have analyzed hydrogen bonding in dimer and trimer of oxalic acid, based on a recently proposed charge and energy decomposition scheme (ETS-NOCV). In the case of a dimer, two conformations, α and β, were considered. The deformation density contributions originating from NOCV’s revealed that the formation of hydrogen bonding is associated with the electronic charge deformation in both the σ—(Δρσ) and π-networks (Δρπ). It was demonstrated that σ-donation is realized by electron transfer from the lone pair of oxygen on one monomer into the empty \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\rho_{H - O}^*$$\end{document} orbital of the second oxalic acid fragment. In addition, a covalent contribution is observed by the density transfer from hydrogen of H-O group in one oxalic acid monomer to the oxygen atom of the second fragment. The resonance assisted component (Δρπ), is based on the transfer of electron density from the π—orbital localized on the oxygen of OH on one oxalic acid monomer to the oxygen atom of the other fragment. ETS-NOCV allowed to conclude that the σ(O---HO) component is roughly eight times as important as π (RAHB) contribution in terms of energetic estimation. The electrostatic factor (ΔEelstat) is equally as important as orbital interaction term (ΔEorb). Finally, comparing β-dimer of oxalic acid with trimer we found practically no difference concerning each of the O---HO bonds, neither qualitative nor quantitative

External validation and calibration of IVFpredict:A national prospective cohort study of 130,960 in vitro fertilisation Cycles

© 2015 Smith et al. Background Accurately predicting the probability of a live birth after in vitro fertilisation (IVF) is important for patients, healthcare providers and policy makers. Two prediction models (Templeton and IVFpredict) have been previously developed from UK data and are widely used internationally. The more recent of these, IVFpredict, was shown to have greater predictive power in the development dataset. The aim of this study was external validation of the two models and comparison of their predictive ability. Methods and Findings 130,960 IVF cycles undertaken in the UK in 2008-2010 were used to validate and compare the Templeton and IVFpredict models. Discriminatory power was calculated using the area under the receiver-operator curve and calibration assessed using a calibration plot and Hosmer-Lemeshow statistic. The scaled modified Brier score, with measures of reliability and resolution, were calculated to assess overall accuracy. Both models were compared after updating for current live birth rates to ensure that the average observed and predicted live birth rates were equal. The discriminative power of both methods was comparable: the area under the receiver-operator curve was 0.628 (95% confidence interval (CI): 0.625-0.631) for IVFpredict and 0.616 (95% CI: 0.613-0.620) for the Templeton model. IVFpredict had markedly better calibration and higher diagnostic accuracy, with calibration plot intercept of 0.040 (95% CI: 0.017-0.063) and slope of 0.932 (95% CI: 0.839 - 1.025) compared with 0.080 (95% CI: 0.044-0.117) and 1.419 (95% CI: 1.149-1.690) for the Templeton model. Both models underestimated the live birth rate, but this was particularly marked in the Templeton model. Updating the models to reflect improvements in live birth rates since the models were developed enhanced their performance, but IVFpredict remained superior. Conclusion External validation in a large population cohort confirms IVFpredict has superior discrimination and calibration for informing patients, clinicians and healthcare policy makers of the probability of live birth following IVF

Impact of female age and male infertility on ovarian reserve markers to predict outcome of assisted reproduction technology cycles

<p>Abstract</p> <p>Background</p> <p>This study was designed to assess the capability of ovarian reserve markers, including baseline FSH levels, baseline anti-Müllerian hormone (AMH) levels, and antral follicle count (AFC), as predictors of live births during IVF cycles, especially for infertile couples with advanced maternal age and/or male factors.</p> <p>Methods</p> <p>A prospective cohort of 336 first IVF/ICSI cycles undergoing a long protocol with GnRH agonist was investigated. Patients with endocrine disorders or unilateral ovaries were excluded.</p> <p>Results</p> <p>Among the ovarian reserve tests, AMH and age had a greater area under the receiving operating characteristic curve than FSH in predicting live births. Furthermore, AMH and age were the sole predictive factors of live births for women greater than or equal to 35 years of age; while AMH was the major determinant of live births for infertile couples with absence of male factors by multivariate logistic regression analysis. However, all the studied ovarain reserve tests were not preditive of live births for women < 35 years of age or infertile couples with male factors.</p> <p>Conclusion</p> <p>The serum AMH levels were prognostic for pregnancy outcome for infertile couples with advanced female age or absence of male factors. The predictive capability of ovarian reserve tests is clearly influenced by the etiology of infertility.</p

Towards neuro-inspired symbolic models of cognition: linking neural dynamics to behaviors through asynchronous communications

A computational architecture modeling the relation between perception and action is proposed. Basic brain processes representing synaptic plasticity are first abstracted through asynchronous communication protocols and implemented as virtual microcircuits. These are used in turn to build mesoscale circuits embodying parallel cognitive processes. Encoding these circuits into symbolic expressions gives finally rise to neuro-inspired programs that are compiled into pseudo-code to be interpreted by a virtual machine. Quantitative evaluation measures are given by the modification of synapse weights over time. This approach is illustrated by models of simple forms of behaviors exhibiting cognition up to the third level of animal awareness. As a potential benefit, symbolic models of emergent psychological mechanisms could lead to the discovery of the learning processes involved in the development of cognition. The executable specifications of an experimental platform allowing for the reproduction of simulated experiments are given in “Appendix”