Gender Quota Policy Plans and Female Members of the Board of Directors

The present study explored how gender quota policy plans hindered and supported the access of female board members serving on the board of directors of their nonprofit organizations. The gender organizational theory guided the theoretical framework of this study by exploring how gendering organizational processes replicated, challenged, and reproduced gender perceptions of women in caregiving roles rather than leadership roles. The qualitative phenomenological approach explored the lived experiences of 6 female board members from 6 different nonprofit organizations on gender quota policy plans. The results of the analysis revealed succession planning, the inclusiveness of the mission and vision statements, and mentoring programs support female board members on the board of directors of nonprofit organizations. The social change implication is understanding how gender quota policy plans supported by gendering organizational processes increased the number of female board members on the board of directors of their nonprofit organizations

Immunodetection of nmt55/p54(nrb) isoforms in human breast cancer

BACKGROUND: We previously identified and characterized a novel 55 kDa nuclear protein, termed nmt55/p54(nrb), whose expression was decreased in a subset of human breast tumors. The objective of this study was to determine if this reduced expression in human breast tumors was attributed to the regulation of mRNA transcription or the presence of altered forms of this protein. RESULTS: Northern blot analysis and ribonuclease protection assay indicated that nmt55/p54(nrb) mRNA is expressed at varying levels in estrogen receptor positive (ER+) and estrogen receptor negative (ER-) human breast tumors suggesting that reduced expression of nmt55/p54(nrb) protein in ER- tumors was not due to transcriptional regulation. To determine if multiple protein isoforms are expressed in breast cancer, we utilized Western blot and immunohistochemical analyses, which revealed the expression of an nmt55/p54(nrb) protein isoform in a subset of ER+ tumors. This subset of ER+ human breast tumors expressed an altered form of nmt55/p54(nrb) that was undetectable with an amino-terminal specific antibody suggesting that this isoform contains alterations or modifications within the amino terminal domain. CONCLUSIONS: Our study indicates that nmt55/p54(nrb) protein is post-transcriptionally regulated in human breast tumors leading to reduced expression in ER- tumors and the expression of an amino terminal altered isoform in a subset of ER+ tumors. The potential involvement of nmt55/p54(nrb) in RNA binding and pre-mRNA splicing may be important for normal cell growth and function; thus, loss or alteration of protein structure may contribute to tumor growth and progression

Are the adverse effects of glitazones linked to induced testosterone deficiency?

<p>Abstract</p> <p>Background</p> <p>Adverse side-effects of the glitazones have been frequently reported in both clinical and animal studies, especially with rosiglitazone (RGZ) and pioglitazone (PGZ), including congestive heart failure, osteoporosis, weight gain, oedema and anaemia. These led to consideration of an evidence-based hypothesis which would explain these diverse effects, and further suggested novel approaches by which this hypothesis could be tested.</p> <p>Presentation of hypothesis</p> <p>The literature on the clinical, metabolic and endocrine effects of glitazones in relation to the reported actions of testosterone in diabetes, metabolic syndrome, and cardiovascular disease is reviewed, and the following unifying hypothesis advanced: "<it>Glitazones induce androgen deficiency in patients with Type 2 Diabetes Mellitus resulting in pathophysiological changes in multiple tissues and organs which may explain their observed clinical adverse effects</it>." This also provides further evidence for the lipocentric concept of diabetes and its clinical implications.</p> <p>Testing of the hypothesis</p> <p>Clinical studies to investigate the endocrine profiles, including measurements of TT, DHT, SHBG, FT and estradiol, together with LH and FSH, in both men and women with T2DM before and after RGZ and PGZ treatment in placebo controlled groups, are necessary to provide data to substantiate this hypothesis. Also, studies on T treatment in diabetic men would further establish if the adverse effects of glitazones could be reversed or ameliorated by androgen therapy. Basic sciences investigations on the inhibition of androgen biosynthesis by glitazones are also warranted.</p> <p>Implications of the hypothesis</p> <p>Glitazones reduce androgen biosynthesis, increase their binding to SHBG, and attenuate androgen receptor activation, thus reducing the physiological actions of testosterone, causing relative and absolute androgen deficiency. This hypothesis explains the adverse effects of glitazones on the heart and other organs resulting from reversal of the action of androgens in directing the maturation of stem cells towards muscle, vascular endothelium, erythroid stem cells and osteoblasts, and away from adipocyte differentiation. The higher incidence of side-effects with RGZ than PGZ, may be explained by a detailed study of the mechanism by which glitazones down-regulate androgen biosynthesis and action, resulting in a state of androgen deficiency.</p

Evaluating the differential response approach in child protection : a systematic review of the evidence

In U.S. Fiscal Year 2017, states responded to 2.4 million calls reporting child abuse or neglect, spanning from inadequate supervision to severe physical maltreatment (U.S. Children’s Bureau, 2017). Since the mid-1990s, child welfare reformers have increasingly acknowledged that such a volume of reports warrants a wider, more flexible range of interventions than the standard fact-finding investigation. Today, the majority of states offer at least two distinct responses to child maltreatment reports through an approach known as Differential Response (DR). Despite the rapid proliferation of DR over the past two decades, critics have charged that it does not keep children as safe as traditional one-track systems, and some states have discontinued their pilot programs after mixed results. This report takes a systematic review approach to identify and assess the most rigorous published studies examining DR’s impact on child maltreatment recidivism. The balance of evidence supports the claim that DR, and in particular the Alternative Response (AR) track, has kept children equally as safe, or safer, than their counterparts served by the traditional investigative response. Qualitative research has also revealed that caregivers receive the Alternative Response intervention more positively than the traditional investigation. The report identifies key differences in jurisdictions’ implementation of DR that have led to varying levels of success and offers policy and practice recommendations based on state and county practices that have yielded the best outcomes. Disparate research methodologies also contributed to different findings on child safety outcomes. The report recommends more consistent analytic strategies to make state DR evaluations comparable to one another and to build a stronger national consensus on the efficacy of the approachPublic AffairsSocial Wor

Role of Androgens in Female Genitourinary Tissue Structure and Function: Implications in the Genitourinary Syndrome of Menopause.

Abstract Introduction Genitourinary conditions in women increase in prevalence with age. Androgens are prerequisite hormones of estrogen biosynthesis, are produced in larger amounts than estrogens in women, and decrease throughout adulthood. However, research and treatment for genitourinary complaints have traditionally focused on estrogens to the exclusion of other potential hormonal influences. Aim To summarize and evaluate the evidence that androgens are important for maintaining genitourinary health in women and that lack of androgenic activity can contribute to the development of symptoms of the genitourinary syndrome of menopause. Methods The role of androgens in the pathophysiology, diagnosis, and treatment of genitourinary syndrome of menopause was discussed by an international and multidisciplinary panel during a consensus conference organized by the International Society for the Study of Women's Sexual Health. A subgroup further examined publications from the PubMed database, giving preference to clinical studies or to basic science studies in human tissues. Main Outcome Measures Expert opinion evaluating trophic and functional effects of androgens, their differences from estrogenic effects, and regulation of androgen and estrogen receptor expression in female genitourinary tissues. Results Androgen receptors have been detected throughout the genitourinary system using immunohistochemical, western blot, ligand binding, and gene expression analyses. Lower circulating testosterone and estradiol concentrations and various genitourinary conditions have been associated with differential expression of androgen and estrogen receptors. Supplementation of androgen and/or estrogen in postmenopausal women (local administration) or in ovariectomized animals (systemic administration) induces tissue-specific responses that include changes in androgen and estrogen receptor expression, cell growth, mucin production, collagen turnover, increased perfusion, and neurotransmitter synthesis. Conclusion Androgens contribute to the maintenance of genitourinary tissue structure and function. The effects of androgens can be distinct from those of estrogens or can complement estrogenic action. Androgen-mediated processes might be involved in the full or partial resolution of genitourinary syndrome of menopause symptoms in women. Traish AM, Vignozzi L, Simon JA, et al. Role of Androgens in Female Genitourinary Tissue Structure and Function: Implications in the Genitourinary Syndrome of Menopause. Sex Med Rev 2018;6:558–571

Streptozotocin-induced diabetes in the rat is associated with changes in vaginal hemodynamics, morphology and biochemical markers

BACKGROUND: Diabetes is associated with declining sexual function in women. However, the effects of diabetes on genital tissue structure, innervation and function remains poorly characterized. In control and streptozotocin-treated female rats, we investigated the effects of diabetes on vaginal blood flow, tissue morphology, and expression of arginase I, endothelial nitric oxide synthase (eNOS) and cGMP-dependent protein kinase (PKG), key enzymes that regulate smooth muscle relaxation. We further related these changes with estrogen receptor alpha (ERα) and androgen receptor (AR) expression. RESULTS: In addition to significantly elevated blood glucose levels, diabetic rats had decreased mean body weight, lower levels of plasma estradiol, and higher plasma testosterone concentration, compared to age-matched controls. Eight weeks after administration of buffer (control) or 65 mg/kg of streptozotocin (diabetic), the vaginal blood flow response to pelvic nerve stimulation was significantly reduced in diabetic rats. Histological examination of vaginal tissue from diabetic animals showed reduced epithelial thickness and atrophy of the muscularis layer. Diabetic animals also had reduced vaginal levels of eNOS and arginase I, but elevated levels of PKG, as assessed by Western blot analyses. These alterations were accompanied by a reduction in both ERα and AR in nuclear extracts of vaginal tissue from diabetic animals. CONCLUSION: In ovariectomized (estrogen deficient) animals, previous reports from our lab and others have documented changes in blood flow, tissue structure, ERα, arginase I and eNOS that parallel those observed in diabetic rats. We hypothesize that diabetes may lead to multiple disruptions in sex steroid hormone synthesis, metabolism and action. These pathological events may cause dramatic changes in tissue structure and key enzymes that regulate cell growth and smooth muscle contractility, ultimately affecting the genital response during sexual arousal

ROLE OF TESTOSTERONE IN THE TREATMENT OF ED

Hypogonadism may play a significant role in the pathophysiology of erectile dysfunction (ED). A threshold level of testosterone may be necessary for normal erectile function. Testosterone replacement therapy is indicated in hypogonadal patients and is beneficial in patients with ED and hypogonadism. Monotherapy with testosterone for ED is of limited effectiveness and may be most promising in young patients with hypogonadism and without vascular risk factors for ED. A number of laboratory and human studies have shown the combination of testosterone and other ED treatments, such as phosphodiesterase type 5 (PDE5) inhibitors, to be beneficial in patients with ED and hypogonadism, who fail PDE5 inhibitor therapy alone. There is increasing evidence that combination therapy is effective in treating the symptoms of ED in patients for whom treatment failed with testosterone or PDE5 inhibitors alone. Testosterone replacement therapy has potentially evolved from a monotherapy for ED in cases of low testosterone, to a combination therapy with PDE5 inhibitors. Screening for hypogonadism may be useful in men with ED who fail prior PDE5 inhibitors, especially in populations at risk for hypogonadism such as type 2 diabetes and the metabolic syndrome