Drawing a pandemic vulnerabilities' map: The SoNAR-global Vulnerabilities Assessment digital and its output

This paper describes the process, advantages and limitations of a qualitative methodology for defining and analyzing vulnerabilities during the COVID-19 pandemic. Implemented in Italy in two sites (Rome and outside Rome, in some small-medium sized municipalities in Latium) in 2021, this investigation employed a mixed digital research tool that was also used simultaneously in four other European countries. Its digital nature encompasses both processes of data collection. Among the most salient is that the pandemic catalyzed new vulnerabilities in addition to exacerbating old ones, particularly economic. Many of the vulnerabilities detected, in fact, are linked to previous situations, such as the uncertainties of labor markets, having in COVID-19 to the greatest negative effects on the most precarious workers (non-regular, part-time, and seasonal). The consequences of the pandemic are also reflected in other forms of vulnerability that appear less obvious, having exacerbated social isolation, not only out of fear of contagion, but because of the psychological challenges posed by containment measures themselves. These measures created not mere discomfort, but behavioral changes characterized by anxiety, fearfulness, and disorientation. More generally, this investigation reveals the strong influence of social determinants throughout the COVID-19 pandemic, creating new forms of vulnerability, as the effects of social, economic, and biological risk factors were compounded, in particular, among already marginalized populations

Hypothalamo-pituitary axis and puberty

Puberty is a complex process that culminates in the acquisition of psychophysical maturity and reproductive capacity. This elaborate and fascinating process marks the end of childhood. Behind it lies a complex, genetically mediated neuroendocrine mechanism through which the gonads are activated thanks to the fine balance between central inhibitory and stimulating neuromodulators and hormones with both central and peripheral action. The onset of puberty involves the reactivation of the hypothalamic-pituitary-gonadal (HPG) axis, supported by the initial “kiss” between kisspeptin and the hypothalamic neurons that secrete GnRH (the GnRH “pulse generator”). This pulsatile production of GnRH is followed by a rise in LH and, consequently, in gonadal steroids. The onset of puberty varies naturally between individuals, and especially between males and females, in the latter of whom it is typically earlier. However, pathological variations, namely precocious and delayed puberty, are also possible. This article reviews the scientific literature on the physiological mechanisms of puberty and the main pathophysiological aspects of its onset

Smoke, alcohol and drug addiction and male fertility

In recent decades, the decline in human fertility has become increasingly more worrying: while therapeutic interventions might help, they are vexing for the couple and often burdened with high failure rates and costs. Prevention is the most successful approach to fertility disorders in males and females alike. We performed a literature review on three of the most common unhealthy habits - tobacco, alcohol and drug addiction - and their reported effects on male fertility. Tobacco smoking is remarkably common in most first-world countries; despite a progressive decline in the US, recent reports suggest a prevalence of more than 30% in subjects of reproductive age - a disturbing perspective, given the well-known ill-effects on reproductive and sexual function as well as general health. Alcohol consumption is often considered socially acceptable, but its negative effects on gonadal function have been consistently reported in the last 30 years. Several studies have reported a variety of negative effects on male fertility following drug abuse - a worrying phenomenon, as illicit drug consumption is on the rise, most notably in younger subjects. While evidence in these regards is still far from solid, mostly as a result of several confounding factors, it is safe to assume that cessation of tobacco smoking, alcohol consumption and recreational drug addiction might represent the best course of action for any couple trying to achieve pregnancy

Serum homocysteine levels in men with and without erectile dysfunction: A systematic review and meta-analysis

Objectives. Elevated levels of serum homocysteine (Hcy) have been associated with cardiovascular diseases and endothelial dysfunction, conditions closely associated with erectile dysfunction (ED). This meta-analysis was aimed to assess serum Hcy levels in subjects with ED compared to controls in order to clarify the role of Hcy in the pathogenesis of ED. Methods. Medline, Embase, and the Cochrane Library were searched for publications investigating the possible association between ED and Hcy. Results were restricted by language, but no time restriction was applied. Standardized mean difference (SMD) was obtained by random effect models. Results. A total of 9 studies were included in the analysis with a total of 1320 subjects (489 subjects with ED; 831 subjects without ED). Pooled estimate was in favor of increased Hcy in subjects with ED with a SMD of 1.00, 95% CI 0.65-1.35, p < 0.0001. Subgroup analysis based on prevalence of diabetes showed significantly higher SMD in subjects without diabetes (1.34 (95% CI 1.08-1.60)) compared to subjects with diabetes (0.68 (95% CI 0.39-0.97), p < 0 0025 versus subgroup w/o diabetes). Conclusions. Results from our meta-analysis suggest that increased levels of serum Hcy are more often observed in subjects with ED; however, increase in Hcy is less evident in diabetic compared to nondiabetic subjects

Adverse pathophysiological influence of early testosterone therapy on the testes of boys with higher grade sex chromosome aneuploidies (HGAs): a retrospective, cross-sectional study

Purpose: Higher grade aneuploidies (HGAs) of the male sex chromosomes are a rare genetic group of pathologies caused by nondisjunction meiotic events. The aim of this study was to evaluate the impact of early androgenic therapy on the testicular secretory hormone profile, and the pathophysiological implications. Patients and methods: In this cross-sectional study, 18 HGA subjects aged 6–8 years were recruited. They were divided into two groups, based on whether or not they had previously undergone testosterone therapy (group 1: 11 untreated subjects; group 2: 7 treated subjects). Serum FSH, LH, testosterone (T), inhibin B (INHB) and anti-Müllerian hormone (AMH) were determined, and auxological parameters were assessed. Five group 1 patients and four group 2 patients were treated with hCG (human chorionic gonadotropin) for inguinal cryptorchidism; their hormone profile and auxological parameters were assessed both pre- and post-hCG treatment. Results: Group 1 subjects showed significantly higher testicular volume and higher levels of AMH and INHB (p < 0.0001). Subjects who had undergone hCG therapy showed a significantly higher testicular volume, penis length (respectively, p = 0.008 and p = 0.0005 for group 1 and p = 0.04 and p = 0.001 for group 2) and T (p = 0.005 for group 1 and p = 0.004 for group 2). Conclusions: HGA patients undergoing early testosterone therapy show an earlier and persistent suppression of testicular secretory function. At this age, the testes are still responsive to stimulation with hCG. The selection of patients to be treated must be accompanied by a thorough clinical and hormonal evaluation

Targeting the NO-cGMP-PDE5 pathway in COVID-19 infection

A pandemic outbreak of COVID-19 has been sweeping the world since December. It begins as a respiratory infection that, mainly in men with diabetes or renal impairment, evolves into a systemic disease, with SARDS, progressive endothelial cell damage, abnormal clotting and impaired cardiovascular and liver function. Some clinical trials are testing biological drugs to limit the immune system dysregulation, "cytokines storm", that causes the systemic complications of COVID-19. The contraindications of these drugs and their cost raise concerns over the implications of their widespread availability. Numerous clinical and experimental studies have revealed a role for the nitric oxide (NO)-cyclic GMP-phosphodiesterase type 5 (PDE5) pathway in modulating low-grade inflammation in patients with metabolic diseases, offering cardiovascular protection. PDE5 inhibition favors an anti-inflammatory response by modulating activated T cells, reducing cytokine release, lowering fibrosis, increasing oxygen diffusion, stimulating vascular repair. PDE5 is highly expressed in the lungs, where its inhibition improves pulmonary fibrosis, a complication of severe COVID-19 disease. We performed a systematic review of all evidence documenting any involvement of the NO-cGMP-PDE5 axis in the pathophysiology of COVID-19, presenting the ongoing clinical trials aimed at modulating this axis, including our own "silDEnafil administration in DiAbetic and dysmetaboLic patients with COVID-19 (DEDALO trial)". The reviewed evidence suggests that PDE5 inhibitors could offer a new strategy in managing COVID-19 by (i) counteracting the Ang-II-mediated downregulation of AT-1 receptor; (ii) acting on monocyte switching, thus reducing pro-inflammatory cytokines, interstitial infiltration and the vessel damage responsible for alveolar hemorrhage-necrosis; (iii) inhibiting the transition of endothelial and smooth muscle cells to mesenchymal cells in the pulmonary artery, preventing clotting and thrombotic complications. If the ongoing trials presented herein should provide positive findings, the low cost, wide availability and temperature stability of PDE5 inhibitors could make them a major resource to combat COVID-19 in developing countries

“Management of andrological disorders from childhood and adolescence to transition age: guidelines from the Italian Society of Andrology and Sexual Medicine (SIAMS) in collaboration with the Italian Society for Pediatric Endocrinology and Diabetology (SIEDP)—Part-1”

Purpose: Andrological pathologies in the adulthood are often the results of conditions that originate during childhood and adolescence and sometimes even during gestation and neonatal period. Unfortunately, the reports in the literature concerning pediatric andrological diseases are scares and mainly concerning single issues. Furthermore, no shared position statement are so far available. Methods: The Italian Society of Andrology and Sexual Medicine (SIAMS) commissioned an expert task force involving the Italian Society of Pediatric Endocrinology and Diabetology (SIEDP) to provide an updated guideline on the diagnosis and management of andrological disorders from childhood and adolescence to transition age. Derived recommendations were based on the grading of recommendations, assessment, development, and evaluation (GRADE) system. Results: A literature search of articles in English for the term “varicoceles”, “gynecomastia”, “fertility preservation”, “macroorchidism”, “precocious puberty” and “pubertal delay” has been performed. Three major aspects for each considered disorder were assessed including diagnosis, clinical management, and treatment. Recommendations and suggestions have been provided for each of the mentioned andrological disorders. Conclusions: These are the first guidelines based on a multidisciplinary approach that involves important societies related to the field of andrological medicine from pediatric to transition and adult ages. This fruitful discussion allowed for a general agreement on several recommendations and suggestions to be reached, which can support all stakeholders in improving andrological and general health of the transitional age

Molecular study of the presence and transcriptional activity of HPV in semen

Purpose: Human Papillomavirus (HPV) in semen represents a controversial topic. Recent evidence suggests a correlation with poor semen quality, but its detection is still unstandardized in this biological fluid. Thus, the aims of this study were to verify the ability of nested PCR to reveal HPV-DNA in semen; to evaluate association of seminal HPV with sperm parameters and risk factors for infection; to investigate the rate of HPV-DNA positivity in patients with and without risk factors; to assess HPV transcriptional activity. Methods: We enrolled sexually active men and collected clinical and anamnestic data during andrological and sexually transmitted infections (STIs) evaluation. For each patient, we performed semen analysis and nested PCR to detect HPV-DNA in semen. In positive semen samples, we proceeded with genotyping and RNA quantification to detect HPV transcriptional activity. Results: We enrolled 185 men (36.0 ± 8.3 years), of which 85 with (Group A) and 100 without HPV risk factors (Group B). Nested PCR was able to reveal HPV-DNA in semen, discovering a prevalence of 8.6% (11.8% in Group A and 6% in Group B, respectively). We observed no correlation between sperm quality and seminal HPV. Genital warts and previous anogenital infection were significantly associated with the risk of HPV positivity in semen. Moreover, no viral transcriptional activity was detected in positive semen samples. Conclusions: Our study suggests that searching for seminal HPV could be important in patients both with and without risk factors, especially in assisted reproduction where the risk of injecting sperm carrying HPV-DNA is possible

Diagnostic accuracy of ultrasonographic features in detecting thyroid cancer in the transition age: a meta-analysis

Context: Significant uncertainty exists about the diagnostic accuracy of ultrasonographic (US) features used to predict the risk of thyroid cancer in the pediatric population. Moreover, there are no specific indications for thyroid nodule evaluation in patients during the transition age. Objective: The meta-analysis aimed to address the following question: which thyroid nodule US features have the highest accuracy in predicting malignancy in the transition age. Methods: We performed a meta-analysis of observational/cohort/diagnostic accuracy studies dealing with thyroid nodule sonography, reporting US features, and using histology as a reference standard for the diagnosis of malignancy and histology or cytology for the diagnosis of benignity in the transition age (mean/median age 12-21 years). Results: The inclusion criteria were met by 14 studies, published between 2005 and 2020, including 1306 thyroid nodules (mean size 17.9 mm) from 1168 subjects. The frequency of thyroid cancer was 36.6%. The US features with the highest diagnostic odds ratio (DOR) for malignancy were the presence of suspicious lymph nodes (DOR: 56.0 (95% CI: 26.0-119.0)), a 'taller than wide' shape of the nodule (6.0 (95% CI: 2.0-16.0)), the presence of microcalcifications (13.0 (95% CI: 6.0-29.0)) and irregular margins (9.0 (95% CI: 5.0- 17.0)). Heterogeneity among the studies was substantial. Conclusions: Following the diagnosis of a thyroid nodule in the transition age, a thorough US examination of the neck is warranted. The detection of suspicious lymph nodes and/ or thyroid nodules with a 'taller than wide' shape, microcalcifications, and irregular margins is associated with the highest risk of malignancy in the selection of nodules candidates for biopsy