Genetic Variability of SOX10-Related Disorders within an Italian Family: Straddling the Line between Kallmann and Waardenburg Syndrome.

Introduction: Kallmann syndrome (KS) is a genetically heterogeneous developmental disorder that most often manifests hypogonadotropic hypogonadism (HH) and hypo-/anosmia due to early embryonic impairment in the migration of gonadotropin-releasing hormone neurons. SOX10 (SRY-Box 10; MIM*602229), a key transcriptional activator involved in the development of neural crest cells, has been associated with KS and is identified as one of the causative genes of Waardenburg syndrome (WS). Case Presentation: A 28-year-old female patient, who was clinically diagnosed with KS in her childhood, presented with HH and anosmia, mild bilateral sensorineural hearing loss (SNHL), and pigmentation abnormalities. Next-generation sequencing analysis detected a missense heterozygous SOX10 pathogenic variant (NM_006941.4:c.506C>T) in the proposita and in her mother, whose phenotype included exclusively anosmia and hypopigmented skin patches. The same variant has been described by Pingault et al. [Clin Genet. 2015;88(4):352-9] in a patient with apparently isolated bilateral severe SNHL. Conclusion: Our finding substantiates the extreme phenotypic variability of SOX10-related disorders, which range from classical KS and/or WS to contracted endophenotypes that could share a common pathway in the development of neural crest cells and highlights the need for careful evaluation and long-term follow-up of SOX10 patients, with special focus on atypical/additional and/or late-onset phenotypic traits.

Serum cholesterol and impulsivity in a large sample of healthy young men.

Studies that have investigated the association between cholesterol levels and impulsivity are relatively few in number and have yielded equivocal results. In this study, we investigated the relationship between impulsivity, depression and serum lipids [total cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides] in a large sample (N=2051) of healthy young men who were remarkably homogeneous in terms of age, educational level, and socioeconomic conditions. Depression was assessed using the depression scale of the Minnesota Multiphasic Personality Inventory-2, and impulsivity was measured using the impulse control scale of the Big Five Questionnaire (BFQ). We found that subjects with a low serum cholesterol, defined as the lowest tenth of the total cholesterol distribution (< or =3.7 mmol/l), scored significantly lower on the impulse control scale of the BFQ. There was no significant association between depression and cholesterol concentrations. In addition, in a multiple regression model, both lower levels of total cholesterol and higher levels of HDL cholesterol emerged as significant predictors of impulsivity. However, since the regression model accounted for only 0.6% of the variance in the score on the impulse control scale of the BFQ, the biological significance of these correlations was negligible. Taken together, these findings suggest that, in healthy young men, a relationship between cholesterol and impulsivity emerges only when the statistical analysis focuses on subjects with very low levels of cholesterol.

Tadalafil in the treatment of erectile dysfunction; an overview of the clinical evidence.

Prevalence and severity of erectile dysfunction (ED) increase with aging and are often associated with illnesses, like diabetes mellitus, heart disease, and hypertension, pathologically characterized by endothelial dysfunction and whose prevalence increases with age. The assumption that ED is mainly a neurovascular disease is supported by the evidence that specific phosphodiesterase type 5 (PDE5) inhibition produces an efficient erection in a wide range of ages and conditions. The availability of specific PDE5 inhibitors has enabled the development of effective treatment strategies, in this contest, tadalafil may be considered as the least "typical" PDE5 inhibitor. In clinical trials, tadalafil significantly enhanced, in patients of different ages, all efficacy outcomes across disease etiologies and severities. With an effectiveness lasting up to 36h, tadalafil allows patients to choose when to have sexual activities without the need to time it, showing positive feedback in terms of quality of life related to the treatment. Headache and dyspepsia were the most frequent side-effects of tadalafil, followed by back pain, nasal congestion, myalgia, and flushing, but the impact that long time action could have on effectiveness and safety is not yet entirely defined. The aim of this article is to critically review the available evidence from the tadalafil clinical research program and give the physician a rational approach for intervention in the treatment of ED and related diseases.

New achievements and pharmacotherapeutic approaches to impotence in the elderly.

Erectile dysfunction (ED) has a negative impact on the quality of life of elderly men, but impotence is not an absolute concomitant of aging. Aging changes influencing sexual function in men consist of a decreased capacity to reach arousal by imagination or view, fragility of erection, and an increase in the refractory period. These events may be part of the andropause syndrome, which includes a decrease in intellectual activity, fatigue, depression, decreases in body hair, lean body mass and bone mineral density, accompanied by an increase in weight. As a consequence, the overlap of aging processes, concurrent diseases and social situations to which elderly men are subject, results in the great variability reported in epidemiological studies. In the same way, the complex physiology of erection depends on the social, environmental, or physical context in which it occurs. New achievements in research on intracellular mechanisms of erection and on the neuroendocrinology of aging contribute to better understanding the pathophysiology of ED in the elderly. For example, testosterone declines with age with great interindividual variability, since other hormonal changes are also involved. What currently can be easily identified is the alteration of LH-testosterone feedback alterations, although hormone levels fall in the normal range. Nevertheless, the extent to which age-dependent decline in hormones leads to health problems that may affect the quality of life remains to be clarified. Several concepts on aging-related processes have been challenged, and conditions that were once accepted as physiologically age-related are now thought to lead to medical problems, but until now erectile dysfunction remains underreported, underdiagnosed, and undertreated, especially in the elderly. Nowadays, we are witnessing a rapid growth in available pharmacotherapies, from intracavernous injections of vasoactive drugs, to powerful new oral agents, with differing pharmacological dynamic and kinetic properties. New options for treatment are therefore possible, taking into account both the possibility of changing ineffective drugs and augmenting efficacy by means of synergistic associations. This rich generation of progress is certainly contributing to a better medical approach to sexuality in aging people.