Sperm mitochondrial DNA copy numbers in normal and abnormal semen analysis: A systematic review and meta-analysis.

BACKGROUND: Normal mature sperm have a considerably reduced number of mitochondria, which provide the energy required for progressive sperm motility. Literature suggests that disorders of sperm motility may be linked to abnormal sperm mitochondrial number and function. OBJECTIVES: To summarise the evidence from literature regarding the association of mitochondrial DNA copy numbers and semen quality with a particular emphasis on the sperm motility. SEARCH STRATEGY: Standard methodology recommended by Cochrane. SELECTION CRITERIA: All published primary research reporting on the association between mitochondrial DNA copy numbers and semen quality. DATA COLLECTION AND ANALYSIS: Using standard methodology recommended by Cochrane we pooled results using a random effects model and the findings were reported as a standardised mean difference. MAIN RESULTS: We included ten studies. The primary outcome was sperm mitochondrial DNA copy numbers. A meta-analysis including five studies showed significantly higher mitochondrial DNA copy numbers in abnormal semen analysis compared with normal semen analysis (standardised mean difference 1.08, 95% CI 0.74-1.43). Seven studies included in the meta-analysis showed a significant negative correlation between mitochondrial DNA copy numbers and semen parameters. The quality of evidence was assessed as good to very good in 60% of studies. CONCLUSIONS: Our review demonstrates significantly higher mitochondrial DNA in human sperm cells of men with abnormal semen analysis in comparison to men with normal semen analysis. TWEETABLE ABSTRACT: There is significantly higher mitochondrial DNA in sperm cells of men with abnormal semen analysis in comparison to men with normal semen analysis.

Do taxes and transfers reduce gender income inequality? Evidence from eight European welfare states.

We examine how taxes and transfers affect the incomes of men and women. Using microsimulation and intra-household income splitting rules, we measure the differences in the level and composition of individual disposable income by gender in eight European countries covering various welfare regime types. We quantify the extent to which taxes and transfers can counterbalance the gender gap in earnings, as well as which policy instruments contribute most to reducing the gender income gap. We find that with the exception of old-age public pensions, all taxes and transfers significantly reduce gender income inequality but cannot compensate for high gender earnings gaps. Our findings suggest that gender income equality is more likely to be achieved by promoting the universal/dual breadwinner model, whereby women's labour force participation and wages are on a par with men. To achieve this, men will likely need to work less and care more.

The probability of poverty for mothers after childbirth and divorce in Europe: The role of social stratification and tax-benefit policies.

This paper looks at the effects of tax-benefit systems and social stratification determinants on the probability of poverty among mothers after childbirth and divorce/separation. The analysis was carried out for twelve EU countries, which represent a variety of welfare regimes providing different degrees of defamilialisation. We applied the stress-testing methodology using microsimulation techniques as proposed by Atkinson (2009) and carried out a regression analysis of the simulated results. We show that the degree of income replacement provided by the welfare state is higher for childbirth than for divorce. Countries with low post-childbirth poverty include those with an explicit pro-natalist orientation and socio-democratic regimes. High post-childbirth poverty rates are found in pro-traditional and South European conservative countries, and especially in the liberal regimes. The same is true for the post-divorce poverty rates. Moreover, our findings confirm that the mother's occupational class has a statistically significant effect for predicting poverty in the case of both events, with a stronger social gradient in case of divorce. Cross-country variation in the social gradient for post-childbirth poverty was insignificant. For post-divorce poverty we find weaker social class effects in the highly defamilialised welfare systems (Scandinavian countries and France) and stronger social class effects in the UK and the post-socialist countries.

Over-specification of small, borderline cardinalities and color in referential communication: the role of visual context, modifier position, and consistency.

This paper reports on two flash-mode experiments that test redundant descriptions of small (2-4) cardinalities, borderline (5-8) cardinalities, and color in referential communication. It provides further support for the idea that small cardinalities are more salient (due to subitizing), less sensitive to visual context, and therefore give rise to higher over-specification rates than color. Because of greater salience, Russian speakers more often use prenominal positions for numerals than for color adjectives. The paper also investigates borderline cardinalities and argues for the order factor that affects their salience, since ordered items can be perceived in small subitized parts. The ordered mode of presentation of the borderline cardinalities leads to higher over-specification rates and to higher percentages of prenominal positions than the unordered one. The paper provides further evidence for the consistency of small, borderline cardinalities, and color in people's choices to minimally specify or over-specify given objects in referential communication.

Surface modification and antibacterial properties of superelastic Ti-Zr-based alloys for medical application.

To date, significant progress has been achieved in the development of biomedical superelastic Ti-based alloys with high mechanical properties. In view of the high probability of implant-associated infection, an urgent task is to impart bactericidal properties to the material. Herein, advanced superelastic Ti-18Zr-15Nb alloys were surface-etched in a piranha solution, and then Ag nanoparticles were deposited on their surface using a polyol process. This led to the formation of a porous surface layer with a thickness of approximately 100 nm and pore size of less than 20 nm, filled with metallic Ag nanoparticles with an average size of 14 nm. The surface-modified samples showed superior antibacterial activity against E.coli cells. The enhanced bactericidal efficiency is explained by the combination of a higher rate of Ag+ ions release and direct contact of E.coli cells with Ag nanoparticles.

High spatially sensitive quantitative phase imaging assisted with deep neural network for classification of human spermatozoa under stressed condition.

Sperm cell motility and morphology observed under the bright field microscopy are the only criteria for selecting a particular sperm cell during Intracytoplasmic Sperm Injection (ICSI) procedure of Assisted Reproductive Technology (ART). Several factors such as oxidative stress, cryopreservation, heat, smoking and alcohol consumption, are negatively associated with the quality of sperm cell and fertilization potential due to the changing of subcellular structures and functions which are overlooked. However, bright field imaging contrast is insufficient to distinguish tiniest morphological cell features that might influence the fertilizing ability of sperm cell. We developed a partially spatially coherent digital holographic microscope (PSC-DHM) for quantitative phase imaging (QPI) in order to distinguish normal sperm cells from sperm cells under different stress conditions such as cryopreservation, exposure to hydrogen peroxide and ethanol. Phase maps of total 10,163 sperm cells (2,400 control cells, 2,750 spermatozoa after cryopreservation, 2,515 and 2,498 cells under hydrogen peroxide and ethanol respectively) are reconstructed using the data acquired from the PSC-DHM system. Total of seven feedforward deep neural networks (DNN) are employed for the classification of the phase maps for normal and stress affected sperm cells. When validated against the test dataset, the DNN provided an average sensitivity, specificity and accuracy of 85.5%, 94.7% and 85.6%, respectively. The current QPI + DNN framework is applicable for further improving ICSI procedure and the diagnostic efficiency for the classification of semen quality in regard to their fertilization potential and other biomedical applications in general.

Partially spatially coherent digital holographic microscopy and machine learning for quantitative analysis of human spermatozoa under oxidative stress condition.

Semen quality assessed by sperm count and sperm cell characteristics such as morphology and motility, is considered to be the main determinant of men's reproductive health. Therefore, sperm cell selection is vital in assisted reproductive technology (ART) used for the treatment of infertility. Conventional bright field optical microscopy is widely utilized for the imaging and selection of sperm cells based on the qualitative analysis by experienced clinicians. In this study, we report the development of a highly sensitive quantitative phase microscopy (QPM) using partially spatially coherent light source, which is a label-free, non-invasive and high-resolution technique to quantify various biophysical parameters. The partial spatial coherence nature of light source provides a significant improvement in spatial phase sensitivity and hence reconstruction of the phase of the entire sperm cell is demonstrated, which was otherwise not possible using highly spatially coherent light source. High sensitivity of the system enables quantitative phase imaging of the specimens having very low refractive index contrast with respect to the medium like tail of the sperm cells. Further, it also benefits with accurate quantification of 3D-morphological parameters of sperm cells which might be helpful in the infertility treatment. The quantitative analysis of more than 2500 sperm cells under hydrogen peroxide (H2O2) induced oxidative stress condition is demonstrated. It is further correlated with motility of sperm cell to study the effect of oxidative stress on healthy sperm cells. The results exhibit a decrease in the maximum phase values of the sperm head as well as decrease in the sperm cell's motility with increasing oxidative stress, i.e., H2O2 concentration. Various morphological and texture parameters were extracted from the phase maps and subsequently support vector machine (SVM) based machine learning algorithm is employed for the classification of the control and the stressed sperms cells. The algorithm achieves an area under the receiver operator characteristic (ROC) curve of 89.93% based on the all morphological and texture parameters with a sensitivity of 91.18%. The proposed approach can be implemented for live sperm cells selection in ART procedure for the treatment of infertility.

Author Correction: Partially spatially coherent digital holographic microscopy and machine learning for quantitative analysis of human spermatozoa under oxidative stress condition.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Live-cell imaging of human spermatozoa using structured illumination microscopy.

Structural details of spermatozoa are interesting from the perspectives of fundamental biology and growing reproductive health problems. Studies of nanostructural details of these extremely motile cells have been limited to fixed cells, largely using electron microscopy. Here we provide the protocols for and demonstrate live-cell multi-color super-resolution imaging of human spermatozoa using structured illumination microscopy (SIM). By using patches of agarose for immobilization, we achieved four-channel 3D SIM imaging of the plasma membrane, nucleus, mitochondria and microtubulin in the same living sperm cells. We expect that high-resolution imaging of living spermatozoa will be implemented for research on fundamental cellular mechanisms together with morphological aberrations involved in male infertility for a future improved cell selection process in in vitro fertilization treatments.

Integrated economic and experimental framework for screening of primary recovery technologies for high cell density CHO cultures.

Increases in mammalian cell culture titres and densities have placed significant demands on primary recovery operation performance. This article presents a methodology which aims to screen rapidly and evaluate primary recovery technologies for their scope for technically feasible and cost-effective operation in the context of high cell density mammalian cell cultures. It was applied to assess the performance of current (centrifugation and depth filtration options) and alternative (tangential flow filtration (TFF)) primary recovery strategies. Cell culture test materials (CCTM) were generated to simulate the most demanding cell culture conditions selected as a screening challenge for the technologies. The performance of these technology options was assessed using lab scale and ultra scale-down (USD) mimics requiring 25-110mL volumes for centrifugation and depth filtration and TFF screening experiments respectively. A centrifugation and depth filtration combination as well as both of the alternative technologies met the performance selection criteria. A detailed process economics evaluation was carried out at three scales of manufacturing (2,000L, 10,000L, 20,000L), where alternative primary recovery options were shown to potentially provide a more cost-effective primary recovery process in the future. This assessment process and the study results can aid technology selection to identify the most effective option for a specific scenario.

Representative mammalian cell culture test materials for assessment of primary recovery technologies: a rapid method with industrial applicability.

Mammalian cell culture material is often difficult to produce accurately and reproducibly for downstream studies. This article presents a methodology for the creation of a set of cell culture test materials where key variables including cell density, cell viability, product, and the host cell protein (HCP) load can be manipulated individually. The methodology was developed using a glutamine synthetase Chinese hamster ovary cell line cultured at 5-L and 70-L scales. Cell concentration post-cell growth was manipulated using tangential flow filtration to generate a range of target cell densities of up to 100 × 10(6) cells/mL. A method to prepare an apoptotic cell stock to achieve target viabilities of 40-90% is also described. In addition, a range of IgG1 and HCP concentrations was achieved. The results illustrate that the proposed methodology is able to mimic different cell culture profiles by decoupling the control of the key variables. The cell culture test materials were shown to be representative of typical cell culture feed material in terms of particle size distribution and HCP population. This provides a rapid method to create the required feeds for assessing the feasibility of primary recovery technologies designed to cope with higher cell density cultures.