Clay modeling as a learning tool for medical trainees in urology: a narrative review and pilot study.

Background and Objective: Coronavirus disease 2019 (COVID-19) necessitated a transition to virtual education which limits hands-on opportunities and student engagement. To adapt, a pilot study investigating clay modeling as an alternative educational tool for medical students was incorporated in a virtual and in-person sub-internship for prospective urology applicants. We aim to review the literature supporting the use of clay modeling in medical education as well as describe our experience with the activity as a way to engage trainees and evaluate early surgical skills. Methods: The current literature on clay modeling in medical and early surgical education was reviewed using multiple search queries in PubMed. A total of thirteen publications were identified and analyzed, with zero articles specifically discussing urological anatomy or surgery. The pilot study was conducted through the traditional in-person sub-internship as well as through a novel virtual sub-internship at a single academic U.S. Urology residency program. Students were instructed to create a three-dimensional model of a genitourinary organ using modeling clay. Anonymized surveys were collected. Responses of virtual and in-person students were compared. Key Content and Findings: Clay modeling has been shown in the literature to be beneficial in medical and early surgical education through the use of active learning. Twenty-five total virtual (N=6) and in-person (N=19) students participated in the clay modeling activity. Survey ratings were mixed, with 100% positive responses amongst the virtual group in the areas of "relevance" and "creatively challenging" compared to the in-person cohort, 31.6% of whom responded positively to "relevance" and 47.4% for "creatively challenging" respectively. Overall, students responded positively for the exercise being "creatively challenging" (n=15, 60%) and "enjoyable" (n=16, 64%). Positive results echoed the student perspectives described in the current literature on clay modeling. Conclusions: Clay modeling has previously been used in the in-person classroom setting as a learning supplement or replacement for dissection classes but has not been previously described for use in the virtual learning environment or within the field of Urology. With ongoing need to develop novel teaching modalities, clay modeling may be a unique tool to enhance learning, and evaluate technical skill, and boost engagement for medical trainees.

Potential Association of Weight-Based Gentamicin with Increased Acute Kidney Injury in Urologic Prosthetic Surgery.

BACKGROUND: Despite the known nephrotoxicity of gentamicin, in 2008 the American Urological Association recommended a weight-based gentamicin dose of 5 mg/kg for antimicrobial prophylaxis during urologic prosthetic surgery. AIM: To identify and characterize rates of acute kidney injury (AKI) in urologic prosthetic surgery, both before and after the implementation of weight-based gentamicin dosing. METHODS: We performed a single-institution retrospective study of patients receiving perioperative gentamicin during implant, revision, salvage, or explant of inflatable penile prostheses, malleable penile prostheses, or artificial urinary sphincters between the years 2000 and 2017. Patients were stratified into 2 groups, based on administration of either weight-based gentamicin (5 mg/kg or 2-3 mg/kg in cases of poor renal function) or standard-dose gentamicin (80 mg). Patient characteristics and perioperative outcomes were identified. Patients with available preoperative and postoperative (≤7 days) serum creatinine values were included. AKI was defined by Kidney Disease: Improving Global Outcomes criteria. Comparative analyses were performed between groups. MAIN OUTCOME MEASURE: Our primary outcome was incidence of AKI, with secondary outcomes including device infection rate and length of stay. RESULTS: Of the 415 urologic prosthetic surgeries performed during the study period, 124 met inclusion criteria with paired preoperative and postoperative serum creatinine values. 57 received weight-based gentamicin (median dose 5.06 mg/kg, interquartile range [IQR] 3.96-5.94) and 67 received standard-dose gentamicin (median dose 1.07 mg/kg, IQR 1.04-1.06), P < .001. There were no significant differences in preoperative renal function or comorbidities between groups; however, the weight-based group was older (median age 64.0 years, IQR 60.0-68.5) compared with the standard-dose group (median age 61.0 years, IQR 55.0-66.0), P = .01, and comprised fewer explant cases (1.8%, 1 of 57) than the standard-dose group (13.4%, 9 of 67), P = .02. The AKI rate was significantly higher in the weight-based group (15.8%, 9 of 57) compared with the standard-dose group (3.0%, 2 o67), P = .02. Device infection rate was similar between groups (5.3%, 3/56 vs 5.2%, 3 of 58), P = 1.00. CLINICAL IMPLICATIONS: Our data suggest weight-based perioperative gentamicin prophylaxis may be associated with an increased AKI risk, without noticeably improving infection rates. STRENGTH & LIMITATIONS: Strengths of our study include the Veterans Affairs population analyzed, as well as rigorous inclusion criteria that allowed for a sensitive assessment of postoperative renal function. Limitations include the retrospective design and small sample size. CONCLUSION: Weight-based gentamicin dosing may warrant closer perioperative monitoring of renal function, and merits larger investigations to further elucidate risks and benefits. Moore RH, Anele UA, Krzastek SC. Potential Association of Weight-Based Gentamicin with Increased Acute Kidney Injury in Urologic Prosthetic Surgery. J Sex Med 2019;16:137-144.

Report of Three Cases of AKI Following Weight-Based Gentamicin Prophylaxis for IPP Implantation: Potential Concerns for Patients with Preexisting Conditions.

Despite the known nephrotoxicity of gentamicin, in 2008 the American Urological Association published guidelines recommending single high-dose weight-based gentamicin prophylaxis of 5 mg/kg for procedures involving urologic prostheses. These guidelines are based on the theoretical renal safety and improved antimicrobial activity of a single large dose of gentamicin. However, the risk of nephrotoxicity after weight-based gentamicin prophylaxis specifically in penile prosthetic surgery has never been established with evidence-based studies. This is of special concern in light of the known high rates of preexisting conditions in this specific population. Therefore, in order to expose potential safety issues, we present three cases of postoperative acute kidney injury following weight-based gentamicin prophylaxis after implantation of inflatable penile prostheses.

GIT1 utilizes a focal adhesion targeting-homology domain to bind paxillin.

The GIT proteins, GIT1 and GIT2, are GTPase-activating proteins for the ADP-ribosylation factor family of small GTP-binding proteins, but also serve as adaptors to link signaling proteins to distinct cellular locations. One role for GIT proteins is to link the PIX family of Rho guanine nucleotide exchange factors and their binding partners, the p21-activated protein kinases, to remodeling focal adhesions by interacting with the focal adhesion adaptor protein paxillin. We here identified the C-terminal domain of GIT1 responsible for paxillin binding. Combining structural and mutational analyses, we show that this region folds into an anti-parallel four-helix domain highly reminiscent to the focal adhesion targeting (FAT) domain of focal adhesion kinase (FAK). Our results suggest that the GIT1 FAT-homology (FAH) domain and FAT bind the paxillin LD4 motif quite similarly. Since only a small fraction of GIT1 is bound to paxillin under normal conditions, regulation of paxillin binding was explored. Although paxillin binding to the FAT domain of FAK is regulated by tyrosine phosphorylation within this domain, we find that tyrosine phosphorylation of the FAH domain GIT1 is not involved in regulating binding to paxillin. Instead, we find that mutations within the FAH domain may alter binding to paxillin that has been phosphorylated within the LD4 motif. Thus, despite apparent structural similarity in their FAT domains, GIT1 and FAK binding to paxillin is differentially regulated.

The GIT/PIX complex: an oligomeric assembly of GIT family ARF GTPase-activating proteins and PIX family Rac1/Cdc42 guanine nucleotide exchange factors.

GIT proteins are GTPase-activating proteins (GAPs) for ADP-ribosylation factor (ARF) small GTP-binding proteins, and interact with the PIX family of Rac1/Cdc42 guanine nucleotide exchange factors. GIT and PIX transiently localize p21-activated protein kinases (PAKs) to remodeling focal adhesions through binding to paxillin. To understand the role of these interactions, the association of GIT and PIX proteins was examined in detail. Two separable binding interactions link GIT and PIX proteins, GIT and PIX proteins each dimerize and a beta-PIX fragment containing the GIT-binding region failed to inhibit the association of the GIT and PIX proteins. Endogenous GIT and PIX co-fractionate at a very high molecular size. Purified 6xHis-tagged beta-PIX from Sf9 cells co-expressing untagged GIT1 yields recombinant GIT1/beta-PIX complexes that have equal amounts of beta-PIX and GIT1 and co-fractionate at the same large size as native GIT/PIX complexes. Thus, GIT and PIX proteins are tightly associated as a multimeric nexus capable of linking together important signaling molecules, including PAKs.