Phenotypic variation within European carriers of the Y-chromosomal gr/gr deletion is independent of Y-chromosomal background.

BackgroundPrevious studies have compared sperm phenotypes between men with partial [1] deletions within the AZFc region of the Y chromosome with non-carriers, with variable results. Here, we have investigated a separate question, the basis of the variation in sperm phenotype within gr/gr deletion carriers, which ranges from normozoospermia to azoospermia. Differences in the genes removed by independent gr/gr deletions, the occurrence of subsequent duplications or the presence of linked modifying variants elsewhere on the chromosome have been suggested as possible causal factors. We set out to test these possibilities in a large sample of gr/gr deletion carriers with known phenotypes spanning the complete range.ResultsWe assembled a collection of 169 men diagnosed with gr/gr deletions from six centres in Europe and one in Australia, and characterized the DAZ and CDY1 copies retained, the presence or absence of duplications and the Y-chromosomal haplogroup. Although our study had good power to detect factors that accounted for 655.5% of the variation in sperm concentration, no such factor was detected. A negative effect of gr/gr deletions followed by b2/b4 duplication was observed within the normospermic group, which remains to be further explored in a larger study population. Finally, we observed significant geographical differences in the frequency of different subtypes of gr/gr deletions which may have relevance for the interpretation of case control studies dealing with admixed populations.ConclusionsWe conclude that the phenotypic variation of gr/gr carriers in men of European origin is largely independent of the Y-chromosomal background

Evaluation of patients with a recent clinical fracture and osteoporosis, a multidisciplinary approach

The aetiology of osteoporotic fractures is multifactorial, but little is known about the way to evaluate patients with a recent clinical fracture for the presence of secondary osteoporosis

Environment, human reproduction, menopause, and andropause.

As the hypothalamic gonadotropin-releasing hormone (GnRH) pulse generator is an integrator of hormonal, metabolic, and neural signals, it is not surprising that the function of the hypothalamogonadal axis is subject to the influence of a large array of environmental factors. Before puberty, the central nervous system (CNS) restrains the GnRH pulse generator. Undernutrition, low socioeconomic status, stress, and emotional deprivation, all delay puberty. During reproductive life, among peripheral factors that effect the reproductive system, stress plays an important role. Stress, via the release of corticotropin-releasing factor (CRF), eventually triggered by interleukin 1, inhibits GnRH release, resulting in hypogonadism. Effects of CRF are probably mediated by the opioid system. Food restriction and underweight (anorexia nervosa), obesity, smoking, and alcohol all have negative effects on the GnRH pulse generator and gonadal function. Age and diet are important determinants of fertility in both men and women. The age-associated decrease in fertility in women has as a major determinant chromosomal abnormalities of the oocyte, with uterine factors playing a subsidiary role. Age at menopause, determined by ovarian oocyte depletion, is influenced by occupation, age at menarche, parity, age at last pregnancy, altitude, smoking, and use of oral contraceptives. Smoking, however, appears to be the major determinant. Premature menopause is most frequently attributable to mosaicism for Turner Syndrome, mumps ovaritis, and, above all, total hysterectomy, which has a prevalence of about 12-15% in women 50 years old. Premature ovarian failure with presence of immature follicles is most frequently caused by autoimmune diseases or is the consequence of irradiation or chemotherapy with alkylating cytostatics. Plasma estrogens have a physiological role in the prevention of osteoporosis. Obese women have osteoporosis less frequently than women who are not overweight. Early menopause, suppression of adrenal function (corticoids), and thyroid hormone treatment all increase the frequency of osteoporosis. Aging in men is accompanied by decreased Leydig cell and Sertoli cell function, which has a predominantly primary testicular origin, although changes also occur at the hypothalamopituitary level. Plasma testosterone levels, sperm production, and sperm quality decrease, but fertility, although declining, is preserved until senescence. Stress and disease states accelerate the decline on Leydig cell function. Many occupational noxious agents have a negative effect on fertility.(ABSTRACT TRUNCATED AT 400 WORDS

Сутність та класифікація ризиків інвестиційної діяльності

Наводиться визначення поняттю "ризики інвестиційної діяльності" за рахунок поєднання його сутнісних характеристик, виконано узагальнення класифікації цих ризиків, запропоновано введення нової класифікаційної групи – "корпоративні ризики", які пов'язані з можливістю втрати контролю над підприємством інвестором-акціонером

Uropathogenic E. coli Induce Different Immune Response in Testicular and Peritoneal Macrophages: Implications for Testicular Immune Privilege

Infertility affects one in seven couples and ascending bacterial infections of the male genitourinary tract by Escherichia coli are an important cause of male factor infertility. Thus understanding mechanisms by which immunocompetent cells such as testicular macrophages (TM) respond to infection and how bacterial pathogens manipulate defense pathways is of importance. Whole genome expression profiling of TM and peritoneal macrophages (PM) infected with uropathogenic E. coli (UPEC) revealed major differences in regulated genes. However, a multitude of genes implicated in calcium signaling pathways was a common feature which indicated a role of calcium-dependent nuclear factor of activated T cells (NFAT) signaling. UPEC-dependent NFAT activation was confirmed in both cultured TM and in TM in an in vivo UPEC infectious rat orchitis model. Elevated expression of NFATC2-regulated anti-inflammatory cytokines was found in TM (IL-4, IL-13) and PM (IL-3, IL-4, IL-13). NFATC2 is activated by rapid influx of calcium, an activity delineated to the pore forming toxin alpha-hemolysin by bacterial mutant analysis. Alpha-hemolysin suppressed IL-6 and TNF-α cytokine release from PM and caused differential activation of MAP kinase and AP-1 signaling pathways in TM and PM leading to reciprocal expression of key pro-inflammatory cytokines in PM (IL-1α, IL-1β, IL-6 downregulated) and TM (IL-1β, IL-6 upregulated). In addition, unlike PM, LPS-treated TM were refractory to NFκB activation shown by the absence of degradation of IκBα and lack of pro-inflammatory cytokine secretion (IL-6, TNF-α). Taken together, these results suggest a mechanism to the conundrum by which TM initiate immune responses to bacteria, while maintaining testicular immune privilege with its ability to tolerate neo-autoantigens expressed on developing spermatogenic cells

Testosterone Replacement Therapy

Male hypogonadism (HG) can be defined according to its etiology as primary (pHG) when caused by any diseases affecting the testes, or as secondary (sHG) when due to a pituitary or hypothalamic dysfunction. Both fertility and testosterone (T) can be theoretically restored in sHG by removing the precipitating cause and/or by appropriate endocrine therapy. Conversely, only T treatment can be offered to patients with pHG. Symptoms and signs are quite similar independent of the underlying causes. Conversely, the phenotype of the hypogonadal patient is more often affected by the age of hypogonadism onset. Late-onset hypogonadism (LOH) that occurs in adulthood is probably the most common form of HG. In this chapter, the criteria defining LOH and the available T formulations along with their outcomes and main important side effects are analyzed in detail

Support for people who use Anabolic Androgenic Steroids: A Systematic Scoping Review into what they want and what they access.

BACKGROUND: Since there is a paucity of research on support for people using Anabolic Androgenic Steroids (AAS), we aimed to identify and synthesise the available evidence in this field. Gaining an understanding of the support both accessed and wanted by recreational AAS users will be of use to professionals who provide services to intravenous substance users and also to those working in the fields of public health and social care, with the aim to increase engagement of those using AAS. METHODS: A systematic scoping review of the literature to explore and identify the nature and scope of information and support both accessed and wanted by non-prescribed AAS users. Any support services or information designed to help people who use AAS were considered. RESULTS: We identified 23 papers and one report for review, which indicated that AAS users access a range of sources of information on: how to inject, substance effectiveness, dosages and side effects, suggesting this is the type of information users want. AAS users sought support from a range of sources including medical professionals, needle and syringe programmes, friends, dealers, and via the internet, suggesting that, different sources were used dependent on the information or support sought. DISCUSSION: AAS users tended to prefer peer advice and support over that of professionals, and access information online via specialist forums, reflecting the stigma that is experienced by AAS users. These tendencies can act as barriers to accessing services provided by professionals. CONCLUSIONS: Support needs to be specific and targeted towards AAS users. Sensitivity to their perceptions of their drug-use and the associated stigma of being classified in the same sub-set as other illicit drug users is relevant to facilitating successful engagement