Phospholipase C Zeta in Human Spermatozoa: A Systematic Review on Current Development and Clinical Application

During fertilization, the fusion of the spermatozoa with the oocytes causes the release of calcium from the oocyte endoplasmatic reticulum. This, in turn, triggers a series of calcium ion (Ca2+) oscillations, a process known as oocyte activation. The sperm-specific factor responsible for oocyte activation is phospholipase C zeta (PLCζ). Men undergoing intracytoplasmic sperm injection (ICSI) with their spermatozoa lacking PLCζ are incapable of generating Ca2+ oscillation, leading to fertilization failure. The immunofluorescence assay is the most used technique to assess the expression and localization of PLCζ and to diagnose patients with reduced/absent ability to activate the oocytes. In these patients, the use of assisted oocyte activation (AOA) technique can help to yield successful ICSI results and shorten the time of pregnancy. However, the production of a stable PLCζ recombinant protein represents a new powerful therapeutic approach to treating individuals with this condition. We aim to conduct a systematic review focusing on the expression, level, and localization of PLCζ, discussing the novel genetic mutation associated with its impairment. In addition, we highlight the benefits of AOA, looking at new and less invasive methods to diagnose and treat cases with PLCζ dysfunction.This research was funded by the Cátedra Human Fertility (A-GE-Cátedra Human Fertility 35.90.6Q..00.01) and Departamento de Biotecnología of the Universidad de Alicante (VIGROB-186)

Covid-19 and the role of smoking: the protocol of the multicentric prospective study COSMO-IT (COvid19 and SMOking in ITaly).

The emergency caused by Covid-19 pandemic raised interest in studying lifestyles and comorbidities as important determinants of poor Covid-19 prognosis. Data on tobacco smoking, alcohol consumption and obesity are still limited, while no data are available on the role of e-cigarettes and heated tobacco products (HTP). To clarify the role of tobacco smoking and other lifestyle habits on COVID-19 severity and progression, we designed a longitudinal observational study titled COvid19 and SMOking in ITaly (COSMO-IT). About 30 Italian hospitals in North, Centre and South of Italy joined the study. Its main aims are: 1) to quantify the role of tobacco smoking and smoking cessation on the severity and progression of COVID-19 in hospitalized patients; 2) to compare smoking prevalence and severity of the disease in relation to smoking in hospitalized COVID-19 patients versus patients treated at home; 3) to quantify the association between other lifestyle factors, such as e-cigarette and HTP use, alcohol and obesity and the risk of unfavourable COVID-19 outcomes. Socio-demographic, lifestyle and medical history information will be gathered for around 3000 hospitalized and 700-1000 home-isolated, laboratory-confirmed, COVID-19 patients. Given the current absence of a vaccine against SARS-COV-2 and the lack of a specific treatment for -COVID-19, prevention strategies are of extreme importance. This project, designed to highly contribute to the international scientific debate on the role of avoidable lifestyle habits on COVID-19 severity, will provide valuable epidemiological data in order to support important recommendations to prevent COVID-19 incidence, progression and mortality

Percutaneous treatment of patients with heart diseases: selection, guidance and follow-up. A review

Aortic stenosis and mitral regurgitation, patent foramen ovale, interatrial septal defect, atrial fibrillation and perivalvular leak, are now amenable to percutaneous treatment. These percutaneous procedures require the use of Transthoracic (TTE), Transesophageal (TEE) and/or Intracardiac echocardiography (ICE). This paper provides an overview of the different percutaneous interventions, trying to provide a systematic and comprehensive approach for selection, guidance and follow-up of patients undergoing these procedures, illustrating the key role of 2D echocardiography

Genetic and epigenetic profiling of the infertile male.

Evaluation of reproductive quality of spermatozoa by standard semen analysis is often inadequate to predict ART outcome. Men may be prone to meiotic error and have higher proportion of spermatozoa with fragmented chromatin, capable of affecting the conceptus' health. In men with unexplained infertility, supplementary tests may be pivotal to gain insight into the paternal contribution to the zygotic genome. A total of 113 consenting men were included in the study, with an additional 5 donor specimens used as control. Among study participants, 87 were screened for sperm aneuploidy by fluorescent in situ hybridization (FISH) and ranked according to their increasing age. A total of 18 men were assessed by whole exome sequencing and categorized according to their reproductive outcome as either fertile or infertile. Another set of men (n = 13) had their gene expression analyzed by RNA-seq and were profiled according to their reproductive capacity. FISH revealed that the average aneuploidy rate was highest for men over-55 age group (9.6%), while men >55 had the highest average disomy for chromosomes 17(1.2%) and 18(1.3%). ART results for the entire cohort comprised 157 cycles, stratified by paternal age. The youngest age group (25-30 years) had a fertilization rate of 87.7% which decreased to 46.0% in the >55 age group. Clinical pregnancy rate was highest in the 25-30yr group (80.0%) while no pregnancies were attained in the >55 age groups. Pregnancy loss was characterized by a steadily increasing trend, highest in the 51-55 age group (50.0%). NGS was performed on a cohort of patients classified as having recurrent pregnancy loss. This cohort was classified as the infertile group (n = 10) and was compared to a control group (n = 8) consisting of patients successfully treated by ART. Eight couples in 17 ICSI cycles achieved a clinical pregnancy rate of 82.4% while 10 infertile couples treated in 21 cycles achieved a pregnancy rate of 23.8%, all resulting in pregnancy loss. DNA-sequencing on spermatozoa from these patients yielded overall aneuploidy of 4.0% for fertile and 8.6% for the infertile group (P<0.00001). In the infertile cohort, we identified 17 genes with the highest mutation rate, engaged in key roles of gametogenesis, fertilization and embryo development. RNA-seq was performed on patients (n = 13) with normal semen analyses. Five men unable to attain a pregnancy after ART were categorized as the infertile group, while 8 men who successfully sustained a pregnancy were established as the fertile control. Analysis resulted in 86 differentially expressed genes (P<0.001). Of them, 24 genes were overexpressed and 62 were under-expressed in the infertile cohort. DNA repair genes (APLF, CYB5R4, ERCC4 and TNRFSF21) and apoptosis-modulating genes (MORC1, PIWIL1 and ZFAND6) were remarkably under-expressed (P<0.001). Sperm aneuploidy assessment supported by information on gene mutations may indicate subtle dysfunctions of the spermatozoon. Furthermore, by querying noncoding RNA we may gather knowledge on embryo developmental competence of spermatozoa, providing crucial information on the etiology of unexplained infertility of the infertile male

Variable selection in high-dimensional regression: a nonparametric procedure for business failure prediction

Business failure prediction models are important in providing warning for preventing financial distress and giving stakeholders time to react in a timely manner to a crisis. The empirical approach to corporate distress analysis and forecasting has recently attracted new attention from financial institutions, academics, and practitioners. In fact, this field is as interesting today as it was in the 1930s, and over the last 80 years, a remarkable body of both theoretical and empirical studies on this topic has been published. Nevertheless, some issues are still under investigation, such as the selection of financial ratios to define business failure and the identification of an optimal subset of predictors. For this purpose, there exist a large number of methods that can be used, although their drawbacks are usually neglected in this context. Moreover, most variable selection procedures are based on some very strict assumptions (linearity and additivity) that make their application difficult in business failure prediction. This paper proposes to overcome these limits by selecting relevant variables using a nonparametric method named Rodeo that is consistent even when the aforementioned assumptions are not satisfied. We also compare Rodeo with two other variable selection methods (Lasso and Adaptive Lasso), and the empirical results demonstrate that our proposed procedure outperforms the others in terms of positive/negative predictive value and is able to capture the nonlinear effects of the selected variables

Polyoxomolybdate-Calix[4]arene Hybrid: A Catalyst for Sulfoxidation Reactions with Hydrogen Peroxide

An easily accessible polyoxomolybdate−calix[4]arene hybrid 1 has been synthesized and applied as a heterogeneous catalyst in the sulfoxidation of thioethers to sulfoxides and to sulfones under strictly stoichiometric amounts of 30% H2O2 in CH3CN as the solvent. This study represents the first promising example of successful employment of calixarenes−polyoxometalate (POM) hybrid materials in the area of catalytic oxidations