bluuebunny/crossref_metadata_2025_split huggingface dataset:
(085) Montelukast, a LRRC8A Inhibitor Decreases the Contractile Response to Phenylephrine in the Corpus Cavernosum of Diabetic Mice
Authors: Wilczynski S , Garnto D , Garnto A , Dos Anjos Moraes R , Choi H , Arishe O , Lamb F , Priviero F , Webb R C 
Published: May 2023

Abstract

Introduction
Increased reactive oxygen species are often correlated with erectile dysfunction (ED) by enhancing contractility and favoring the flaccid state of the penis (which is mainly mediated by α-adrenergic innervation) and decreasing the relaxation of the corpus cavernosum (CC) associated with decreased nitric oxide (NO) bioavailability. Leucine Rich Repeat Containing 8 (LRRC8) Volume Regulated Anion Channels (VRACs) regulates Nox1 and modulates the extracellular production of superoxide anion (O2•-). Downregulation of LRRC8 is associated with decreased production of O2•- and we have demonstrated improved relaxation and reduced contraction of the pudendal artery in LRRC8A knockout mice.

Objective
In this study, we aim to test the hypothesis that inhibition of Nox or LRRC8A decreases phenylephrine (PE)-induced contraction in the CC of diabetic mice.

Methods
To test this hypothesis, the CC of diabetic (dbdb-/-, 16-week-old) mice were mounted in myographs, and the contraction elicited by PE was performed in the absence and repeated in the presence of the LRRC8 inhibitor, montelukast or Nox1/Nox4 inhibitor, GKT137831. The maximal contraction in the absence of the inhibitor was taken as 100%, and the contraction in the presence of the inhibitor was calculated as a percentage of the maximal contraction attained in the absence of the inhibitor.

Results
Contraction induced by phenylephrine in the CC of diabetic mice (1.27 + 0.2 mN) was similar to that observed in the control mice (1.26 + 0.4 mN). In the presence of the LRRC8 inhibitor, montelukast, PE-induced contraction of the CC was significantly reduced, reaching maximal contraction of 69 + 7% and 65 + 10% in the control and diabetic group, respectively. In the presence of the Nox1/Nox4 inhibitor, GKT137831, the contraction elicited by PE was reduced only in the diabetic group (68 + 9% of the maximal contraction), whereas in the control group this reduction was not significant (82 + 14% of the maximal contraction).

Conclusions
This is the first study demonstrating that, in the CC, LRRC8 modulates the contractile response induced by α-adrenergic stimulation and this may be associated with O2•- production, which plays a role in the development of ED. Since a great number of diabetic patients are not benefited by phosphodiesterase 5 inhibitors therapy, LRRC8 might be a potential therapeutic target for the development of new drugs to improve sexual function in diabetes.

Disclosure
No
(087) Association of ESRα T397C (rs2234693) with Male Infertility: A Meta-analysis
Authors: Javed N , Irfan M , Arshad A , Bibi A , Nik Hussain N H , Ismail S B 
Published: May 2023

Abstract

Introduction
Infertility is the incapability to achieve fertilization after a certain period following sexual intercourse without any contraceptive measures which affects 1 in 6 couples. Male factors contribute 50%. The male reproductive system is affected by both environmental and genetic factors. Genetics variations include chromosomal aberrations, genomic and/or mitochondrial single gene mutations or polymorphism, and multiple gene mutations or polymorphism that result in spermatogenic failure. Genetic variations of key genes might have a role in male infertility. In this regard, polymorphism in the estrogen receptor gene may be an important factor increasing the risk of male infertility. In men, estrogen is produced in the testis by Sertoli cell, Leydig cell and germ cells that play an important role in the maturation and capacitation of sperms. The action of estrogen is mediated by two specific Receptors: Estrogen receptors α (ESRα) and Estrogen receptor β (ESRβ). ESRα gene is present on chromosome 6q25. It consists of 8 exons which are parted by 7 intronic regions having a complete size of 140 kb. ESRα codes for 595 amino acid proteins. The most widely studied single nucleotide polymorphism (SNP) in ESRα is T397C (rs2234693). It is found in intron 1 and divided by 46 bp. Few previously published studies reported an association between this SNP in ESRα and male infertility, while others found no association.

Objective
The present study aims to estimate the association between ESRα T397C (rs2234693) and male infertility.

Methods
PUBMED, CENTRAL, Google Scholar and PMC articles were searched, whereas case-control, published studies regarding ESRα T397C (rs2234693) and male infertility were selected for this meta-analysis.

Results
Four studies finally fulfilled the criteria of the meta-analysis. No significant association (p &gt; 0.05) was found overall, between ER alpha polymorphism and male infertility, based on all of the four genetic models. However, when stratified into two ethnic groups, ER polymorphism was found to be significantly associated with male infertility in the Caucasian group based on the dominant model (CC + CT vs TT: OR= 1.43, 95% CI [1.08-1.91], I2 = 89%) as well as recessive model (CC vs CT+TT: OR= 1.34, 95% CI [1.01-1.76], I2 = 0%), whereas, in the Asian group, only the dominant model (CC + CT vs TT: OR= 1.97, 95% CI [1.58-2.46], I2 = 98%) indicated significant association of ER alpha polymorphism with male infertility.

Conclusions
ESRα T397C (rs2234693) polymorphism is linked with male infertility in the two ethnic groups, i.e., homozygous conditions in Caucasian and dominant conditions in Asian populations.

Disclosure
No
(096) Chronic Oral Exposure to Short Chain - Chlorinated Paraffins Induced Testicular Toxicity by Promoting NRF2-mediated Oxidative Stress
Authors: Li C 
Published: May 2023

Abstract

Introduction
Chlorinated paraffins (CPs) are important additives in a variety of chemical processing. Based on the lengths of the carbon chains, CPs are classified into short-chain CPs (SCCPs, C10-13), medium-chain CPs (MCCPs, C14-17) and long-chain CPs (LCCPs, C18-30) with the chlorine content ranging from 30%-70%. SCCPs were listed in the persistent organic pollutants (POPs) by Stockholm Convention due to its toxicity, bioaccumulation potential, long range transport potential and environmental persistence. Numerous studies have analyzed the toxicities of SCCPs in various organisms, with the toxic effects including lethality and carcinogenicity, developmental toxicity, endocrine disrupting effect and immunomodulatory effect.

Objectives
As a widespread environmental contaminant, short chain chlorinated paraffins (SCCPs) has attracted great attention. However, the toxicity of SCCPs on male reproductive system remains ambiguous. In this study, we investigated the toxic effects of SCCPs on testis.

Methods
We treated mice with 1,10 or 100 mg/kg bm/d SCCPs by gavage once a day for 35 days. The tissues and blood samples were collected after treatment. The weight of mice and testes were measured. The organ index is the body weight divided by the weight of the testis. The left testes were used for protein extraction, RNA extraction and measurement of SOD, CAT, GST and MDA. The left epididymis was used for analysis of sperm parameters. The right testis and epididymis were fixed in Bouin’s solution for H&E and TUNEL staining. GC2 cell (mouse spermatocyte) treated with SCCPs was used to examined the cell viability by CCK8 kits. Cellular ROS generation was evaluated by 2',7'Dichlorodihydrofluorescein diacetate (DCFH-DA). We used Apoptosis Detection Kit to detect the cell apoptosis by dual staining cells with Annexin V-fluorescein isothiocyanate (FITC) and propidium iodide (PI).

Results
SCCPs resulted in disorderly arranged seminiferous epithelium and increased apoptotic cells in testes. Both in vivo and in vitro experiments indicated that the oxidative stress was induced after SCCPs exposure, and dysfunction of nuclear factor erythroid-related factor (NRF2) signaling pathway played a role in this process. Moreover, resveratrol, an NRF2 activator, could alleviate the damage of SCCPs on spermatogenetic cells in vitro. Our study indicated that oxidative stress is the key point for explaining the testicular toxicity caused by SCCPs, and NRF2 could be used as a potential target for clinical treatment to alleviate the reproductive toxicity induced by SCCPs.

Conclusions
Our study is the first to evaluate the toxic effects of SCCPs on male reproductive system, which is associated with overproduction of ROS. This study also indicates that NRF2/ARE pathway plays the vital role in the toxic effects of SCCPs in spermatogenesis, thus providing a target for the prophylaxis and treatment.

Disclosure
No
(100) Extended Reality-Assisted Surgery (XRAS): A Novel Surgical Training Tool During Cadaver Lab
Authors: Hakky T , Carrion RE , Crespo R , Henry G D , Jay Simhan J S , Shridharani A , Carrion R E 
Published: May 2023

Abstract

Introduction
XRAS (extended reality-assisted surgery) is a revolutionary modality that assists the surgeon in real-time by overlaying 3-dimensional computer-generated images into the users’ field of view.

Objective
To insert a Titan 3-piece inflatable penile implant (IPP) on cadaver A and a male virtue sling on cadaver B while utilizing XRAS as a training tool.

Methods
Two cadavers were used for this lab. While 2 surgeons were present and operating on the physical bodies, 2 additional physicians were remote and communicating via HoloLens 2 Developer Editions. By utilizing the Apoqlar©Hamburg, Germany application, the 2 remote surgeons could communicate, observe, and advise the live surgery. Cadaver A was in the supine position for a penoscrotal approach while B was in the lithotomy position for placement of the male virtue sling. A questionnaire was issued to attendees after the procedures to evaluate the role of the HoloLens in the operating room.

Results
While performing the respective surgeries on the two cadavers, XRAS was successfully implemented in real-time. Superimposed virtual surgical devices were placed and manipulated in 3D space during surgery to allow for augmented surgical technique during penile implant and male virtue sling insertion. The questionnaire yielded findings that, of the 4 attendees who participated in the surgery, all were in favor of integrating XRAS into the operating room. Attendees reported minimal overheating and discomfort, and sufficient battery life for a 90-minute interval.

Conclusions
XRAS represents the next paradigm shift in surgery and surgical training. It provides an augmented surgical view all while ergonomically positioned on the head of the surgeon. Implementation of XRAS in surgery can improve efficiency, education, accuracy, and surgical outcomes. Further studies and evolution of the software are needed to elucidate the value of such technology for real-time surgery.

Disclosure
Yes, this is sponsored by industry/sponsor: Coloplast

Clarification
Industry funding only - investigator initiated and executed study
Any of the authors act as a consultant, employee or shareholder of an industry for: Coloplast
(115) Mechanical and Anatomic Indications for Inflatable Penile Prosthesis Revision
Authors: Smelser A , Nealon S , Badkhshan S , Sanders S , Monaghan T , Langford B , Vandyke M , Morey A 
Published: May 2023

Abstract

Introduction
Implantation of an inflatable penile prosthesis (IPP) is considered the gold standard for definitive treatment of men with refractory erectile dysfunction. As mechanical devices, IPPs have a finite lifespan, thus often requiring surgical revision or replacement of components over time.

Objective
To characterize the location of IPP mechanical component failure in patients presenting for revision or explant and stratify them by device manufacturer [Boston Scientific (BSc) and Coloplast (CP)].

Methods
A retrospective chart review of our large, single-surgeon, tertiary referral center penile prosthesis database between 2007-2022 was completed to identify all men who underwent IPP revision (partial or full device) or explant. Only cases having intraoperative documentation of cause for IPP failure and device manufacturer were included. Reasons for revision or replacement surgery were categorized into mechanical (tubing, cylinder, or reservoir leak and pump malfunction) and non-mechanical (component herniation, erosion, or crossover). All revisions performed due to non-mechanical reasons were excluded from analysis. Chi-square analysis was used to assess failure rates and causes. A Student’s T-test was used to assess time to revision and demographics.

Results
Among 933 IPP cases, we identified 133 patients who underwent 272 revision procedures; 154 met inclusion criteria (96 BSc and 58 CP). Forty-four (29%) of those surgeries were revisions of devices placed by outside surgeons, and 110 (71%) were revisions of IPPs inserted at our institution. Average patient age was 67 years for BSc and 63 years for CP (p = 0.086), and the average BMI was 28.7 for BSc and 30.8 for CP (p = 0.122). Time to revision was similar between brands at an average of 39 months for BSc and 56 months for CP (p = 0.11). Eighty-one (53%) of the surgeries were revisions of one affected implant component, 56 (36%) were full device removal/replacement, and 17 (11%) were full explants. Coloplast devices required revision more frequently due to tubing fracture (p &lt; 0.01), and BSc devices required revision more frequently due to pump malfunction (p = 0.02). Both devices rarely failed due to cylinder or reservoir defects (Figure).

Conclusions
Although time to revision was similar between the two brands, CP devices malfunctioned more often due to tubing fracture whereas BSc devices failed more often due to pump malfunction.

Disclosure
Any of the authors act as a consultant, employee or shareholder of an industry for: Boston Scientific, Coloplast
(116) Comorbidity Profile Network Analysis of Men with Erectile Dysfunction
Authors: Greear G , Dadhich P , Stanaway I , Walsh T , Nicholson T , Wessells H , Holt S , Hehemann M 
Published: May 2023

Abstract

Introduction
The modern understanding of the comorbidities associated with erectile dysfunction (ED) has been shaped by the findings of decades-old survey-based epidemiologic studies. The demographic structure and comorbidities of the United States population have since changed. A contemporary assessment of the comorbidity profile of men with ED is timely and indispensable for the efficient care of these men.

Objective
The objectives are to describe the comorbidity profile of a contemporary cross-section of men with erectile dysfunction, to identify clinically meaningful health trends, and to evaluate whether clusters of men with distinct comorbidity profiles can be discerned.

Methods
A cross-sectional analysis of the MarketScan® administrative claims database from 2008 to 2019 was performed. Inclusion criteria were men 18 to 64 years of age with a diagnosis of ED or phosphodiesterase type 5 inhibitor (PDE5i) prescription with at least 1 year of enrollment before the index date, as well as age-matched controls without an ED diagnosis or related prescription. Comorbidities were extracted by ICD-9/10 diagnosis codes and categorized by the Elixhauser Comorbidity Index. The trends in prevalence of comorbidities and odds of comorbidity diagnosis, overall and by age group, were analyzed. To elucidate the relationships between common comorbidities, a novel comorbidity network was performed with comorbidity strength estimated by observed-to-expected ratio (OER) of disease (prevalence &gt; 0.01) in pairs with a comorbid prevalence &gt; 0.001.

Results
The prevalence of all comorbidities in men with and without ED increased over the study period. The five most prevalent comorbidities (and percentage increase) among men with ED were hypertension (108%), diabetes without complication (78%), obesity (357%), chronic pulmonary disease (124%), and depression (164%) (Figure 1). The association of ED with comorbidities such as complicated diabetes and paralysis tended to be more pronounced among men in the younger cohort (18-45 years of age, vs 46-64 years of age) (Figure 2). Between 2008 and 2014, a generalized increase in the strength of association of ED with prevalent comorbidities is observed (Figure 3).

Conclusions
The comorbidity profile of men with ED has evolved since its initial characterization nearly 30 years ago. Increases in comorbidities associated with obesity and metabolic syndrome, as well as mental health disorders, are particularly notable. The findings illustrate the complex interplay of chronic health conditions in men with ED, and serve to justify the comprehensive evaluation of men of all ages who present with ED.

Disclosure
No
(127) Relationship Between Severity of Erectile Dysfunction and Systemic Immune Inflammation Index and Neutrophil Lymphocyte Ratio
Authors: Culha M G , Ward S , Baran C , Ermec B 
Published: May 2023

Abstract

Introduction
Endothelial dysfunction has an important place in the pathogenesis of erectile dysfunction (ED).

Objective
The aim of this study was to evaluate the relationship between ED severity and systemic immune inflammation index (SII) and neutrophil lymphocyte ratio (NLR).

Methods
The data of male patients over the age of 18 who applied to the urology clinic with the complaint of ED between January 2018 and September 2021 were analyzed. Patients with known diabetes mellitus, hypertension, coronary artery disease, and previous pelvic surgery were excluded from the study. The erectile functions of the patients were evaluated with the international erectile function index-erectile function (IIEF-EF). The patients were divided into two groups according to the severity of ED as mild (IIEF-EF&gt;17) and moderate-severe (IIEF-EF≤17). Demographic data of the patients were recorded. SII value was calculated by neutrophil*platelet/lymphocyte formula and NLR was recorded.

Results
A total of 185 patients were included in the study (mild ED: 74, moderate-severe: 111). The mean age of the patients was 48.18±11.58(20-79), and the mean IIEF-EF was 13.34±6.55 (0-25). The mean SII was 594.89±348.90, and the mean NLR was 2.27±1.19. The mean total testosterone level of the patients was 3.25±1.48ng/dl. When the patients were divided into two groups according to the severity of ED, a significant difference was observed between IIEF-EF scores and SII values of the patients (p&lt;0.001 for IIEF-EF, p=0.008 for SII). No significant difference was found with NLR values (p=0.950). There was a moderate negative correlation between IIEF-EF score and SII value (p=0.042, r=-0.569). No significant correlation was observed between NLR and IIEF-EF (p=0.625, r=-0.124). SII cut-off value was determined as 436.73 and AUC was 0.674 (CI 95%: 0.448-0.717). At this value, the sensitivity was 70.1% and the specificity was 64.8%.

Conclusions
SII index was negatively correlated according to the severity of ED, and erectile functions decreased with the increase in systemic inflammation. During the evaluation of patients, the severity of ED can be revealed more clearly with the use of SII. Further studies are needed to better understand the relationship between SII and ED.

Disclosure
No
(136) Long-term Durability of Response to Complete Vestibulectomy Surgery for Neuroproliferative Vestibulodynia
Authors: Yee A , Goldstein S , Drian A , Goldstein I 
Published: May 2023

Abstract

Introduction
In 2006, Goldstein et al published on the surgical outcomes of the largest-to-date patient series undergoing complete vestibulectomy with vaginal advancement flap reconstruction for neuroproliferative vestibulodynia (NPV). One hundred and thirty-four patients underwent surgery over a 5 year period, and 93% of the 104 patients who agreed to participate were satisfied/very satisfied with their surgical outcome. The mean time to follow up was 26 months, range 12 – 72 months. NPV is hypothesized to be, in part, a result of accumulation of excess mast cells in the epithelial basement membrane and sub-epithelial stroma that may release nerve growth factor promoting sub-epithelial nerve ending proliferation (Figure 1). The excess nerve endings are hypothesized to result in bothersome, persistent, and unrelenting provoked vestibular allodynia and hyperalgesia that are characteristic of NPV. Durability of post-operative outcomes past 72 months has yet to be addressed. It is still unknown if the pathologic findings of excess mast cells and nerve endings ever regenerate in the vestibule and cause recurrent allodynia, hyperalgesia and entrance dyspareunia.

Objective
We wished to assess, for the first time, the long-term surgical outcome durability data (&gt;5 years) of those NPV patients who claimed successful resolution of their entrance dyspareunia following complete vestibulectomy surgery in the first 5 years post-operatively.

Methods
We routinely perform post-operative follow-up of surgical patients who undergo complete vestibulectomy surgery with vaginal advancement flap reconstruction for NPV. We identified those who claimed successful resolution of their entrance dyspareunia following complete vestibulectomy surgery in the first year post-operatively and thereafter for the next 4 years, and asked them if they continued to have resolution of their entrance dyspareunia.

Results
Fifty-seven patients had complete vestibulectomy with vaginal advancement flap reconstruction between 2007 and 2017 (&gt; 5 years ago). Forty-one patients responded to the routine contact for long term follow-up. Thirty-four patients (78%) had resolution of pain in the first year post-operatively. Upon repeat interview, all 34 (100%) continued to note excellent durability of their surgical result, a mean of 9.3 years after their vestibulectomy (range 5-14 years).

Conclusions
Based on this small series, it appears that if a patient is a treatment responder following complete vestibulectomy, there is strong durability of the surgical result with no evidence of recurrent allodynia or hypoalgesia. These data suggest that in treatment responders, there is no evidence of re-accumulation of excess mast cells and nerve endings in the introitus. These data support that the pathology of NPV lies in the endodermal vestibule and that complete excision may be an important long-term treatment strategy in many NPV patients.

Disclosure
No