Hypospadias is one of the most common congenital anomalies of the male urogenital system, and di(2-ethylhexyl) phthalate (DEHP), a widely used endocrine-disrupting chemical (EDC), is considered a significant risk factor for this condition. Mono-2-ethylhexyl phthalate (MEHP), the toxic active metabolite of DEHP, has been proven to affect penile development and ultimately result in the hypospadias phenotype. However, while it is acknowledged that hypospadias arises from the aberrant development of multiple penile tissues, the specific impact of MEHP on human foreskin tissue development and its underlying molecular mechanisms of action remain unclear. In this study, we constructed an in vitro toxicity assay for MEHP using human foreskin fibroblasts and employed high-throughput RNA sequencing to investigate the molecular mechanisms subserving the defects in cellular function. We subsequently conducted multi-omics data analysis using public databases to analyze key target genes, and identified MMP11 as a chief downstream gene responsible for the effects of MEHP on HFF-1 cell migration. Through molecular docking analysis and molecular biology experiments, we further demonstrated that the nuclear receptor PPAR-gamma was activated upon binding with MEHP, leading to the suppression of MMP11 expression. Additionally, we found that epigenetic modifications induced by MEHP were also involved in its pathogenic effects on hypospadias. Our research highlights the crucial role of impaired cellular proliferation and migration in MEHP-induced hypospadias. We identified the MEHP/PPAR-gamma/MMP11 pathway as a novel pathogenic mechanism, providing important potential targets for future preventive strategies with respect to hypospadias.

BACKGROUND: Penile skin zipper entrapment is an emergent medical condition in which the penile skin, scrotal skin, or foreskin gets caught within the teeth of a zipper or the slider itself. This can lead to complications such as urethral involvement, skin loss, or tissue necrosis. We propose a novel technique to aid in the release of entrapped skin utilizing wire cutters directed at the inferior portion of the zipper pull.
OBJECTIVE: To describe a novel technique to free entrapped penile skin and compare its performance to the well-established median bar technique in a simulated setting.
METHODS: A randomized cross-over design was used to compare techniques on successful release, time to release and tissue injury using an animal model of raw chicken skin entrapped in a zipper. Statistical significance was assessed at p < 0.05.
RESULTS: Twenty-two participants were included. There was no statistically significant difference between the novel technique and the median bar technique regarding successful release (100% vs 95.5%, respectively), median time to release (29.1 vs 26.4 seconds, respectively), or frequency of tissue injury (22.7% vs 27.3%).
CONCLUSIONS: Performance using our novel technique for removal of penile skin from a zipper is similar to the median bar release technique regarding. Our novel technique may be a valid treatment option for the release of entrapped penile skin in a zipper mechanism in the emergency department setting.

BACKGROUND: Requests for circumcision revision are common in our American pediatric urology clinic. As parents are the surrogate decision maker for their child, there are several influences that can impact a parent\'s decision for or against circumcision.
OBJECTIVE: We sought to assess parents\' regret regarding their child\'s circumcision status and to correlate regret to factors that might have affected the original decision.
METHODS: From March 2023 to January 2024, we surveyed parents who brought their male child to our office for any reason, independent of circumcision status. The questionnaire was two-fold: a validated Decisional Regret Scale (DRS) (0-100 where higher scores = higher regret) and our questions regarding their decision-making process and outcome. Regret scores served as a function of each of the independent decision making and outcome variables.
RESULTS: Overall, decisional regret scores from both uncircumcised and circumcised parent groups were positively skewed with a median 0, mean 22, and ranged from 0 to 75. For those circumcised (n = 91), the median regret score was 0 (IQR 0-25). For those uncircumcised (n = 28), median regret score was 0 (IQR 0-24). Overall, 55% of both groups reported no regret (DRS = 0), 24% had low-mild regret (DRS 5-25), and 21% yielded moderate-strong regret (DRS 30-100). Parents who felt they made an informed decision or were counseled by any physician had lower regret scores. Parents who presented for issues related to their child\'s uncircumcised or circumcised penis (DRS score 37.5 and 25 respectively) had higher regret scores.
CONCLUSIONS: We found that a large portion of parents expressed no regret regarding their decision to have or not have their child circumcised (55%). There also was no difference in median regret scores between parent groups. However, a significant portion of parents did express moderate-strong regret (21%) and several influential factors were correlated with regret scores. These factors included informed decision making, physician counseling, appearance satisfaction, and problems related to their child\'s circumcised or uncircumcised penis. These factors are supported by other literature using the DRS and population studies. The limitations of our study included the limited recruitment of participants and potential time dependent bias of responses.
CONCLUSIONS: One in five parents of both circumcised and uncircumcised boys expressed moderate to strong regret regarding their decision about neonatal circumcision in our pediatric urology clinic. Our data suggests that ensuring parents have sufficient counseling prior to a decision regarding neonatal circumcision is important.

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Calcinosis cutis (CC) is characterized by the deposition of calcium salts in the skin and subcutaneous tissues. CC involving the vulva or foreskin (prepuce) is uncommon. We present a 9-year-old female with vulvar CC and a 15-year-old male with preputial CC. Microscopic review of excisional specimens revealed calcification associated with follicular cysts in the vulvar case and lichen sclerosus in the preputial case, suggesting a dystrophic origin to a subset of cases of genital CC that might otherwise be classified as idiopathic. The clinical implication of these findings is the need for close histopathologic scrutiny and ongoing clinical surveillance of patients with genital CC initially deemed idiopathic.

Gram-positive catalase-negative cocci (GPCNCs) are significant components of the genital microbiota in sheep and goats. However, characterizing them can be difficult due to overlapping culture features and the limited information on their susceptibility to antibiotics. In this study, 97 foreskin and 13 vaginal swabs were investigated using a culturomic approach. Of 110 animals, 76 (69.09 %) hosted GPCNCs, including strains from Streptococcaceae (37, 33.64 %), Aerococcaceae (30, 27.27 %), Enterococcaceae (6, 5.45 %) and other minor species. With increasing antimicrobial resistance rates in livestock, surveillance programs are globally required, so we conducted a pilot study on GPCNCs isolated from the genital mucosa surfaces of sheep and goats using the minimal inhibitory concentration assay (MIC). Due to gaps in interpretative standard breakpoints, normalized resistance interpretation was used for setting epidemiological susceptibility cut-off values (COWTs). Of 57 suitable strains, the majority (80.71 %) showed high COWTs with decrease susceptibility to at least one antimicrobial class, with 22.81 % displaying multiresistant profiles. Of interest, combined resistances to beta-lactams, macrolides, lincosamides, and tetracyclines were detected in strains of Streptococcus plurianimalium. Further combinations, including resistance to beta-lactams, pleuromutilins, aminoglycosides, and lincosamides, were also recorded in both Streptococcus uberis and Enterococcus spp. strains. Being beta-lactams, macrolides, and tetracyclines the most used antibiotics in livestock worldwide, our results highlight the need for their prudent use. Collectively, our findings highlight that small ruminant genital microbiota can serve as reservoirs for opportunistic severe pathogens, often zoonotic, carrying multidrug resistances, thus standing for high risks for both animals and humans.

OBJECTIVE: Genital burns are rare injuries. Reconstruction of penile skin defects should consider cosmetic and functional outcomes. Skin grafts can develop scar contractures and carry hair follicles, causing unwanted results. These downsides remain unsolved issues. This work aimed to describe a new foreskin advancement flap method for completely reconstructing penile shaft skin defects in severely burned patients.
METHODS: From 2021 to 2023, four patients with third-degree burns in the genital area were enrolled in this investigation. We describe a series of cases with deep burns to the penile shaft and surrounding area that needed debridement and reconstruction using a novel technique called \"reverse circumcision,\" which consists of tangential excision of the penis and a foreskin advancement flap without longitudinal cuts with less morbidity, preservation of function, and a better aesthetic appearance. The patients had an average follow-up of nine months.
RESULTS: The reverse circumcision technique was established for patients with severe burns in the genital area. The four patients were satisfied with the postoperative results and the aesthetic results of the procedure without reporting any complications. No scarring or contractures were observed on the glans or penile shaft after surgery.
CONCLUSIONS: Compared with other flap methods, the use of a reverse circumcision foreskin advancement flap was more straightforward, feasible, and effective. In adults, the foreskin tissue completely covers the penile shaft skin defect. It is a viable reconstructive surgical technique that is easily reproducible and has excellent aesthetic and functional results. For this surgical technique, tissue transfers, bulky regional flaps, or skin grafts were not needed.

HSV infects keratinocytes in the epidermis of skin via nectin-1. We established a human foreskin explant infection model to investigate HSV entry and spread. HSV1 entry could only be achieved by the topical application of virus via high density microarray projections (HD-MAPs) to the epidermis, which penetrated beyond one third of its thickness, simulating in vivo microtrauma. Rapid lateral spread of HSV1 to a mean of 13 keratinocytes wide occurred after 24 hours and free virus particles were observed between keratinocytes, consistent with an intercellular route of spread. Nectin-1 staining was markedly decreased in foci of infection in the epidermis and in the human keratinocyte HaCaT cell line. Nectin-1 was redistributed, at the protein level, in adjacent uninfected cells surrounding infection, inducible by CCL3, IL-8 (or CXCL8), and possibly CXCL10 and IL-6, thus facilitating spread. These findings provide the first insights into HSV1 entry and spread in human inner foreskin in situ.

BACKGROUND: Blood supply to preputial flap drives outcomes of hypospadias repair. Unfortunately, we only have surgeon\'s subjective assessment to evaluate flap perfusion which may not be accurate. Indocyanine green (ICG) has been used in a multitude of surgeries for perfusion assessment, however, no standardized protocol has been described for use of ICG in hypospadias repairs. The aim of this study is to develop a standardized protocol of ICG use in proximal hypospadias and establish perfusion patterns of preputial flaps.
METHODS: A pilot study was conducted using ICG in patients with proximal hypospadias undergoing first stage repair with a preputial flap. The Stryker SPY PHI system and novel quantification software, SPY-QP, were used for ICG imaging. An adaptive approach was taken to develop and implement a standardized protocol (Summary Figure). Per the protocol, ICG was administered at 3 time points which were felt to be critical for assessment of flap perfusion. Of the study patients who have undergone second stage repair, ICG was also used to reassess the flap prior to tubularization of the urethra.
RESULTS: A total of 14 patients underwent first stage hypospadias repair with preputial flaps and intraoperative use of ICG. Median ICG uptake of the prepuce after degloving (dose 1) was 58.5% (IQR 43-76). ICG uptake decreased after flap harvest and mobilization (dose 2) with a median ICG uptake of 34% (IQR 26-46). ICG uptake remained stable after securing the flap in place and closing the skin (dose 3) with a median ICG uptake of 34% (IQR 25-48). ICG was able to delineate subtle findings in the preputial flaps not visible to the naked eye and in one case impacted intraoperative decision making. To date, 5 patients have undergone second stage repair. Flap assessment prior to tubularization of the urethra showed hypervascularity with a median ICG uptake of 159%.
CONCLUSIONS: A standardized protocol for ICG use in proximal hypospadias was successfully developed and implemented. ICG uptake in the preputial flap decreased with increasing manipulation and mobilization of the flap. ICG was able to detect changes to flap perfusion which were not able to be seen with the naked eye. Reliance on surgeon\'s subjective assessment of flap perfusion may be inadequate and ICG could provide a useful tool for surgeons to improve preputial flap outcomes. ICG may also enhance the learning experience for trainees and early career urologists in these complex surgeries.

BACKGROUND: Bioscaffolds and cells are two main components in the regeneration of damaged tissues via cell therapy. Umbilical cord stem cells are among the most well-known cell types for this purpose. The main objective of the present study was to evaluate the effect of the pretreatment of the foreskin acellular matrix (FAM) by monophosphoryl lipid A (MPLA) and Lactobacillus casei supernatant (LCS) on the attraction of human umbilical cord mesenchymal stem cells (hucMSC).
RESULTS: The expression of certain cell migration genes was studied using qRT-PCR. In addition to cell migration, transdifferentiation of these cells to the epidermal-like cells was evaluated via immunohistochemistry (IHC) and immunocytochemistry (ICC) of cytokeratin 19 (CK19). The hucMSC showed more tissue tropism in the presence of MPLA and LCS pretreated FAM compared to the untreated control group. We confirmed this result by scanning electron microscopy (SEM) analysis, glycosaminoglycan (GAG), collagen, and DNA content. Furthermore, IHC and ICC data demonstrated that both treatments increase the protein expression level of CK19.
CONCLUSIONS: Pretreatment of acellular bioscaffolds by MPLA or LCS can increase the migration rate of cells and also transdifferentiation of hucMSC to epidermal-like cells without growth factors. This strategy suggests a new approach in regenerative medicine.