Miracle-dz/UniFAR-FTUs huggingface dataset:
Transient rise of serum testosterone level after single sildenafil treatment of adult male rats.

INTRODUCTION Phosphodiesterase type 5 (PDE5) inhibitors have been established in therapy for a variety of physiological disorders including erectile dysfunction. Despite its popularity and wide usage in erectile dysfunction treatment, the short-term effect of PDE5 inhibition on Leydig cell functionality and testosterone dynamics is missing. AIM This study was designed to assess the acute in vivo effects of sildenafil citrate (Viagra) treatment on testosterone production. METHODS Male adult rats were given sildenafil (1.25 mg/kg BW) per os, and testosterone production were analyzed 30, 60, 120, and 180 minutes after treatment. Additionally, in vitro effect of sildenafil extract on Leydig cell steroidogenesis was estimated. MAIN OUTCOME MEASURES The formation of testicular interstitial fluid (TIF), and testosterone, cyclic guanosine monophosphate (cGMP), cyclic adenosine monophosphate (cAMP) content was followed. Occurrence and phosphorylation of mature steroidogenic acute regulatory protein (StAR) and interaction with protein kinase G 1 (PRKG1) were assessed by immunoprecipitation and Western blot. RESULTS Serum testosterone was increased 60 and 120 minutes after sildenafil treatment. In 60 minutes, TIF volume was doubled and stayed increased till the end of the experimental period. cGMP and testosterone content in TIF were increased 30 minutes after treatment, and cAMP decreased in 60 minutes. Further, sildenafil-induced stimulation of testosterone production was abolished by ex vivo addition of PRKG1 inhibitor but not by protein kinase A inhibitor. Sildenafil treatment increased the level of phosphorylated and total StAR protein. Moreover, co-immunoprecipitation of StAR and PRKG1 was increased following sildenafil treatment suggesting the active role of this kinase in initiation of testosterone synthesis. Additionally, sildenafil extract applied in vitro on primary Leydig cell culture increased cGMP accumulation and testosterone production in time- and dose-dependent manner without effect on cAMP level. CONCLUSION Acute sildenafil treatment enlarged TIF volume but also stimulated testosterone production which may be significant considering the positive testosterone effect in regulation of sexual activity.
Molecular Mechanisms of Cytotoxicity and Apoptosis Induced by Inorganic Fluoride

Fluoride (F) is ubiquitous natural substance and widespread industrial pollutant. Although low fluoride concentrations are beneficial for normal tooth and bone development, acute or chronic exposure to high fluoride doses results in adverse health effects. The molecular mechanisms underlying fluoride toxicity are different by nature. Fluoride is able to stimulate G-proteins with subsequent activation of downstream signal transduction pathways such as PKA-, PKC-, PI3-kinase-, Ca2
FACIAL DISFIGUREMENT AND PERSONALITY

With the rapid advance of reconstruction surgery during the past decade in technic, in availability to the public and in the types of disfigurement that have been treated, new interest has developed in this field. The experience of surgeons has been, however, that the benefit derived is not always in keeping with the results. They have found patients who have benefited both in body and in mind but also patients who, although they have experienced very creditable surgical results, have remained unsatisfied and have shown that they are sick and maladjusted persons. A study was undertaken of the personality of patients coming to the Graduate Hospital of the University of Pennsylvania for plastic repair of facial disfigurement under the direction of Dr. Robert H. Ivy and his associates. There has been a total of 312 such patients. In this study, patients with disfigurements of recent traumatic origin were not included,
Hormonal causes of male sexual dysfunctions and their management (hyperprolactinemia, thyroid disorders, GH disorders, and DHEA).

INTRODUCTION Besides hypogonadism, other endocrine disorders have been associated with male sexual dysfunction (MSD). AIM To review the role of the pituitary hormone prolactin (PRL), growth hormone (GH), thyroid hormones, and adrenal androgens in MSD. METHODS A systematic search of published evidence was performed using Medline (1969 to September 2011). Oxford Centre for Evidence-Based Medicine-Levels of Evidence (March 2009) was applied when possible. MAIN OUTCOME MEASURES The most important evidence regarding the role played by PRL, GH, thyroid, and adrenal hormone was reviewed and discussed. RESULTS Only severe hyperprolactinemia (>35 ng/mL or 735 mU/L), often related to a pituitary tumor, has a negative impact on sexual function, impairing sexual desire, testosterone production, and, through the latter, erectile function due to a dual effect: mass effect and PRL-induced suppression on gonadotropin secretion. The latter is PRL-level dependent. Emerging evidence indicates that hyperthyroidism is associated with an increased risk of premature ejaculation and might also be associated with erectile dysfunction (ED), whereas hypothyroidism mainly affects sexual desire and impairs the ejaculatory reflex. However, the real incidence of thyroid dysfunction in subjects with sexual problems needs to be evaluated. Prevalence of ED and decreased libido increase in acromegalic patients; however, it is still a matter of debate whether GH excess (acromegaly) may create effects due to a direct overproduction of GH/insulin-like growth factor 1 or because of the pituitary mass effects on gonadotropic cells, resulting in hypogonadism. Finally, although dehydroepiandrosterone (DHEA) and its sulfate have been implicated in a broad range of biological derangements, controlled trials have shown that DHEA administration is not useful for improving male sexual function. CONCLUSIONS While the association between hyperprolactinemia and hypoactive sexual desire is well defined, more studies are needed to completely understand the role of other hormones in regulating male sexual functioning.
Presence of diabetes mellitus and steatosis is associated with liver stiffness in a general population: The Rotterdam study

Given that little is known about the prevalence of, and factors associated with, liver fibrosis in the general population, we aimed to investigate this in a large, well‐characterized cohort by means of transient elastography (TE). This study was part of the Rotterdam Study, a population‐based study among individuals ≥45 years. All participants underwent abdominal ultrasound and TE. Liver stiffness measurement (LSM) ≥8.0 kilopascals (kPa) was used as a cutoff suggesting clinically relevant fibrosis. Of 3,041 participants (age, 66.0 ± 7.6 years) with reliable LSM, 169 (5.6%) participants had LSM ≥8.0 kPa. Age (odds ratio [OR]: 2.40; 95% confidence interval [CI]: 1.72‐3.36; P < 0.001), alanine aminotransferase (ALT; OR, 1.24; 95% CI: 1.12‐1.38; P < 0.001), smoking (OR, 1.77; 95% CI: 1.16‐2.70; P = 0.008), spleen size (OR, 1.23; 95% CI: 1.09‐1.40; P = 0.001), hepatitis B surface antigen, or anti–hepatitis C virus positivity (OR, 5.38; 95% CI: 1.60‐18.0; P = 0.006), and combined presence of diabetes mellitus (DM) and steatosis (OR, 5.20; 95% CI: 3.01‐8.98; P < 0.001 for combined presence) were associated with LSM ≥8.0 kPa in multivariable analyses. The adjusted predicted probability of LSM ≥8.0 kPa increased per age decade, with probabilities ranging from 1.4% (0.9‐3.6) in participants ages 50‐60 years to 9.9% (6.8‐14.5) in participants >80 years. Participants with both DM and steatosis had the highest probabilities of LSM ≥8.0 kPa (overall probability: 17.2% [12.5‐23.4]; this probability did not increase with age [P = 0.8]). Conclusion: In this large population‐based study of older adults, LSM ≥8.0 kPa, suggestive of clinically relevant fibrosis, was present in 5.6% and was strongly associated with steatosis and DM. In the context of an aging population and an increased prevalence of DM and obesity, this study illustrates that liver fibrosis may become a more prominent public health issue in the near future. (Hepatology 2016;63:138–147)
Review of penile prosthetic reservoir: complications and presentation of a modified reservoir placement technique.

INTRODUCTION Multiple modifications have been made to the inflatable penile prosthesis (IPP) since its inception in the 1970s. These modifications have made reservoir-related mechanical malfunctions highly unlikely in current IPP models. Although these complications are rare, it would be incumbent upon the implanting surgeon to be aware of these potential complications, how they present, how they are best treated, and how to prevent them from occurring. AIMS The aim of this article was to present our experience with complications associated with penile prosthesis reservoirs, perform a review of the literature regarding reservoir-related complications, and present our modified technique to place the reservoir into the space of Retzius. MAIN OUTCOME MEASURES Reservoir-related complications including inguinal herniation, erosion into bladder or bowel, intraperitoneal reservoir placement with subsequent visceral injury, vascular injury, autoinflation, and infection. METHODS We retrospectively reviewed our experience with penile prosthesis reservoir complications or procedures requiring an alternative implantation approach at our center over the past 10 years where over 400 devices were implanted. We also review reservoir-related complications published in the English literature since the 1980s. RESULTS While exceedingly rare, reservoir complications do occur. Six cases from our institution are presented including one reservoir herniation, one postoperative direct inguinal hernia, one bladder laceration during revision surgery, one ectopic reservoir placement due to morbid obesity, one iliac vein compression syndrome, and one vascular laceration during reservoir revision. Reported reservoir complications include inguinal herniation, erosion into the bladder or bowel, intraperitoneal reservoir placement with subsequent injury to the ureter or bowel, vascular injury, autoinflation, and infection. CONCLUSION Penile prosthesis reservoirs rarely fail mechanically but are associated with a variety of complications or may require alternate implantation technique. In our experience, the Jorgensen scissors technique allows safe entry into the space of Retzius with diminished risk of hernia as well as vascular, bladder, or bowel injury.
Distal Tibiofibular Bone Bridge in Transtibial Amputation

Ertl bone bridging at the time of primary or revision transtibial (below knee) amputation is currently the most controversial issue facing surgeons involved in the care of young, active amputees. Although Ertl suggested that bone bridging allows end bearing weight bearing, many experts now suggest that the bone bridge has the capacity to enhance prosthetic limb fitting by creating a larger, more stable bony platform for load transfer during weight bearing with a prosthetic limb. This discussion highlights the potential benefits afforded by a bone bridge and the role of an enhanced soft tissue envelope in decreasing pain for active lower extremity amputees.
HCV vertical transmission in pregnancy: New horizons in the era of DAAs

R outine prenatal hepatitis C virus (HCV) screening is not recommended in women lacking risk factors for infection. This is partially because of the absence of options in the management of maternal to neonatal transmission and the perceived low prevalence of HCV in pregnancy. Vertical transmission rates of HCV have been reported to be as high as 8%. Reducing maternal viremia may be beneficial given its role as a requirement for vertical transmission. Recent advances in HCV infection combination therapy have made high rates of sustained virological response and HCV-RNA clearance in nonpregnant adults achievable. Currently, there are no therapies to prevent HCV vertical transmission. However, certain direct-acting antiviral agents (DAAs) may have substantially more favorable profiles in pregnancy in comparison to past medications. Given that maternal viremia has been linked to vertical neonatal transmission, the use of DAAs may considerably lower HCV vertical transmission in pregnancy and warrant future studies. The prevalence of HCV infection in pregnancy has been estimated to be similar to the reported 0.5%-1.4% seropositivity in low-risk blood donors. Presently, routine prenatal HCV screening is not recommended by the American College of Obstetricians and Gynecologists and Centers for Disease Control and Prevention, except for women with significant risk factors for infection. This policy is the result of a lack of any available preor postnatal pharmacological, immunological, or interventional measures to decrease the risk of vertical transmission. HCV vertical transmission rates have been reported between 2% and 10% and HCV chronically infects an estimated 25,000-50,000 children with 750 new cases a year acquired through vertical transmission. Furthermore, though high rates of spontaneous resolution have been reported for children acquiring HCV infection at birth, many still become chronically infected. Current long-term outcome data on these chronically infected children is significantly limited given that HCV disease morbidity in general takes longer than two decades to develop. Clinicians frequently delay treatment for HCV until after pregnancy given limited experience with the use of interferon (IFN) in pregnancy and the absolute contraindication for ribavirin (RBV) use. Recent developments in HCV infection combination therapy have made persistent normalization of transaminase levels and HCV-RNA clearance in nonpregnant adults possible. Given that maternal viremia has been linked to vertical neonatal transmission, the use of DAAs for prevention of HCV transmission alone or in association with IFN warrants more-intense future study.
Readiness to Screen for Domestic Violence against Women in Healthcare Uganda: Associations with Demographic, Professional and Work Environmental Factors

Aim: We assessed demographic, professional and work environmental determinants of readiness to screen for Intimate Partner Violence among healthcare practitioners in healthcare Uganda. Methods: The Domestic Violence Healthcare Provider Survey Scale and the Demand-Control-Support questionnaire was administered to a random sample of 376 health care providers (n = 279 valid responses) from Gulu, Anaka, Lacor and Iganga hospital situated in northern and eastern Uganda. Correlation tests, t-tests, ANOVA and Multiple Linear regression were used to analyse the data. Results: Male care providers were more likely than female peers to blame the victim for the occurrence of Intimate Partner Violence in a relationship. Participants from Lacorhospital graded a lower self-efficacy and a poorer support network with regard to screening for Intimate partner violence, and a higher propensity to blame the victim when contrasted with other hospitals. Doctors experienced a lower self-efficacy with regard to IPV screening than other professions. Blaming the victim for abuse was associated with a high work load and low support at work. In addition, with increasing work control and support, participants’ appraisal of system support and self-efficacy increased. Conclusion: Gender, profession, facility of work, work demand, control and support are important determinants of the readiness to screen for IPV in healthcare Uganda, and should inform strategy for the introduction and implementation of routine IPV inquiry in healthcare Uganda.
Analysis of erectile responses to BAY 41-8543 and muscarinic receptor stimulation in the rat.

INTRODUCTION Soluble guanylate cyclase (sGC) is the receptor for nitric oxide (NO) and in pathophysiologic conditions where NO formation or bioavailability is impaired, erectile dysfunction (ED) occurs. AIM The aim of this study was to investigate erectile responses to the sGC stimulator BAY 41-8543 in physiologic and pathophysiologic conditions. METHODS Increases in intracavernosal pressure (ICP) in response to intracavernosal (ic) injections of BAY 41-8543 were investigated in the anesthetized rat. MAIN OUTCOME MEASURES Increases in ICP/MAP in response to ic injections of BAY 41-8543 and the interaction of BAY 41-8543 with exogenous and endogenously released NO were investigated and the effect of the sGC stimulator on cavernosal nerve injury was assessed. The mechanism of the increase in ICP/MAP in response to ic injection of acetylcholine was investigated. RESULTS The ic injections of BAY 41-8543 increased ICP/MAP and the duration of the response. BAY 41-8543 was less potent than sodium nitroprusside (SNP) and ic injections of BAY 41-8543 and SNP produced a larger response than the algebraic sum of responses to either agent alone. Simultaneous ic injection of BAY 41-8543 and cavernosal nerve stimulation produced a greater response than either intervention alone. Atropine and cavernosal nerve crush injury decreased the response to nerve stimulation and ic injection of BAY 41-8543 restored the response. CONCLUSION These data show that BAY 41-8543 has significant erectile activity and can synergize with exogenous and endogenously released NO. This study shows that atropine and nerve crush attenuate the response to cavernosal nerve stimulation and that BAY 41-8543 can restore the response. The results with atropine, L-NAME and hexamethonium indicate that the response to ic injection of acetylcholine is mediated by muscarinic receptors and the release of NO with no significant role for nicotinic receptors. These results suggest that BAY 41-8543 would be useful in the treatment of ED.
Suicide Prevention Training Program for Gatekeepers Working in Community Hospice Settings

Gatekeepers in community hospice settings encounter patients and caregivers struggling with suicidal thoughts. Limited guidance is available for training staff on the prevention of suicide in hospice care. This study evaluated one promising, evidence-based, suicide prevention program with a behavioral rehearsal practice session. A pre- and post-, one group design, was utilized to measure the training impact and educational needs of staff working in community hospice settings (N =39). Training increased awareness of the risk factors for suicide, as reported by nearly 80% of participants. Self-efficacy scores showed a statistically significant Increase, t(df = 35), −9.59, p= . 00 (two-tailed), from pretraining (n=36, M=2.21, SD= .65) to posttraining (n=36, M=3.03, SD=.56). Satisfaction and the need for additional devoted time for suicide prevention training were highly rated. Suicide prevention training programs can enhance self-efficacy, knowledge, and skills for gatekeepers working in community hospice settings.
High‐throughput T‐cell receptor sequencing across chronic liver diseases reveals distinct disease‐associated repertoires

Hepatic T‐cell infiltrates and a strong genetic human leukocyte antigen association represent characteristic features of various immune‐mediated liver diseases. Conceptually the presence of disease‐associated antigens is predicted to be reflected in T‐cell receptor (TCR) repertoires. Here, we aimed to determine if disease‐associated TCRs could be identified in the nonviral chronic liver diseases primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), and alcoholic liver disease (ALD). We performed high‐throughput sequencing of the TCRβ chain complementarity‐determining region 3 of liver‐infiltrating T cells from PSC (n = 20), PBC (n = 10), and ALD (n = 10) patients, alongside genomic human leukocyte antigen typing. The frequency of TCRβ nucleotide sequences was significantly higher in PSC samples (2.53 ± 0.80, mean ± standard error of the mean) compared to PBC samples (1.13 ± 0.17, P < 0.0001) and ALD samples (0.62 ± 0.10, P < 0.0001). An average clonotype overlap of 0.85% was detected among PSC samples, significantly higher compared to the average overlap of 0.77% seen within the PBC (P = 0.024) and ALD groups (0.40%, P < 0.0001). From eight to 42 clonotypes were uniquely detected in each of the three disease groups (≥30% of the respective patient samples). Multiple, unique sequences using different variable family genes encoded the same amino acid clonotypes, providing additional support for antigen‐driven selection. In PSC and PBC, disease‐associated clonotypes were detected among patients with human leukocyte antigen susceptibility alleles. Conclusion: We demonstrate liver‐infiltrating disease–associated clonotypes in all three diseases evaluated, and evidence for antigen‐driven clonal expansions. Our findings indicate that differential TCR signatures, as determined by high‐throughput sequencing, may represent an imprint of distinctive antigenic repertoires present in the different chronic liver diseases; this thereby opens up the prospect of studying disease‐relevant T cells in order to better understand and treat liver disease. (Hepatology 2016;63:1608‐1619)
Natural killer cells regulate T cell immune responses in primary biliary cirrhosis

The hallmark of primary biliary cirrhosis (PBC) is the presence of autoreactive T‐ and B‐cell responses that target biliary epithelial cells (BECs). Biliary cell cytotoxicity is dependent upon initiation of innate immune responses followed by chronic adaptive, as well as bystander, mechanisms. Critical to these mechanisms are interactions between natural killer (NK) cells and BECs. We have taken advantage of the ability to isolate relatively pure viable preparations of liver‐derived NK cells, BECs, and endothelial cells, and studied interactions between NK cells and BECs and focused on the mechanisms that activate autoreactive T cells, their dependence on interferon (IFN)‐γ, and expression of BEC major histocompatibility complex (MHC) class I and II molecules. Here we show that at a high NK/BEC ratio, NK cells are cytotoxic for autologous BECs, but are not dependent on autoantigen, yet still activate autoreactive CD4+ T cells in the presence of antigen presenting cells. In contrast, at a low NK/BEC ratio, BECs are not lysed, but IFN‐γ production is induced, which facilitates expression of MHC class I and II molecules on BEC and protects them from lysis upon subsequent exposure to autoreactive NK cells. Furthermore, IFN‐γ secreted from NK cells after exposure to autologous BECs is essential for this protective function and enables autoreactive CD4+ T cells to become cytopathic. Conclusions: NK cell‐mediated innate immune responses are likely critical at the initial stage of PBC, but also facilitate and maintain the chronic cytopathic effect of autoantigen‐specific T cells, essential for progression of disease. (Hepatology 2015;62:1817‐1827)