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[CD8.sup.+] T cells destroy insulin-producing pancreatic [beta] cells in type 1 diabetes through HLA class I- restricted presentation of self-antigens. Combinatorial peptide library screening was used to produce a preferred peptide recognition landscape for a patient-derived T cell receptor (TCR) that recognized the preproinsulin-derived (PPI-derived) peptide sequence LWMRLLPLL in the context of disease risk allele HLA A*24:02. Data were used to generate a strong superagonist peptide, enabling production of an autoimmune HLA A*24:02-peptide-TCR structure by crystal seeding. TCR binding to the PPI epitope was strongly focused on peptide residues Arg4 and Leu5, with more flexibility at other positions, allowing the TCR to strongly engage many peptides derived from pathogenic bacteria. We confirmed an epitope from Klebsiella that was recognized by PPI-reactive T cells from 3 of 3 HLA A*24:02+ patients. Remarkably, the same epitope selected T cells from 7 of 8 HLA A*24* healthy donors that cross-reacted with PPI, leading to recognition and killing of HLA A*24:02+ cells expressing PPI. These data provide a mechanism by which molecular mimicry between pathogen and self-antigens could have resulted in the breaking of self-tolerance to initiate disease., Introduction Multiple lines of evidence show that type 1 diabetes (T1D) develops due to [CD8.sup.+] T cell-mediated destruction of insulin-producing pancreatic [beta] cells. Human leukocyte antigen class I (HLA-I), the [...]

ObjectiveClinical practice guidelines (CPGs) serve as frameworks to unify diagnostic criteria and guide clinical decision-making. There is a paucity of literature surrounding the uptake of CPGs in urology practice settings with varied levels of resources worldwide. This study aims to evaluate reported use of CPGs within the context of international urology practice, identify local barriers to uptake, and evaluate the role of stakeholders in the CPG-development process.MethodsThis was an international, multi-center, cross-sectional study. An online survey collecting variables pertaining to the use of CPGs was distributed to attending/consultant urologists in Latin America, Africa, and China. Statistical analysis was conducted using R software.ResultA total of 249 practicing urologists from 28 countries completed the survey. The majority of participants were males, aged 36 to 45, and practiced in a non-academic setting. Ninety-three percent of urologists used CPGs in their everyday clinical practice, and 43% believed CPGs were very important to medical decision-making. However, barriers such as the lack of adaptability or applicability of CPGs to local settings were mentioned by 29% and 24% of participants, respectively. Urologists believed scientific associations (81%), national urology boards (68%), and ministries of health (56%), were important stakeholders to consult to foster the development of local CPGs.ConclusionsGlobally, CPGs are widely used tools for clinical practice. However, there are concerns about the adaptability and applicability of CPGs to settings that may lack the resources to implement their recommendations. Efforts should be directed towards incorporating scientific and medical stakeholders into the review and adaptation of urology CPGs to suit the unique features of local health care systems.

ObjectiveTo promote the recognition and care of patients with female genital mutilation/cutting (FGM/C), we aimed to evaluate the awareness, clinical experience and knowledge of FGM/C among female pelvic medicine and reconstructive surgery (FPMRS) specialists. FGM/C is a cultural practice whereby there is removal of external female genitalia for non-therapeutic reasons. Despite the high prevalence of urogynecologic complications, there is a paucity of literature discussing FGM/C from the lens of urologists and urogynecologists.MethodsBy cross-sectional design, we distributed a 27-item survey via email to members of the Society of Urodynamics, Female Pelvic Medicine and Reconstructive Surgery. We collected variables pertaining to previous FGM/C education, clinical confidence, cultural and medical knowledge, and desire for future education.ResultsA total of 54 US-based, mostly urologists and FPMRS specialists, completed the survey. All providers had heard of FGM/C; however only 13% received formal education during medical training. Over 50% had encountered a patient with FGM/C in clinical practice. Only 19% and 13% felt completely confident recognizing and discussing FGM/C, respectively. Seventy percent believed religious doctrine informed FGM/C practice and 24% correctly identified FGM/C type on clinical representation. Finally, only 17% of respondents were aware of FGM/C guidelines, and providers expressed a desire for increased availability of multimodal resources.ConclusionEducation regarding FGM/C remains sparse and variable for US FPMRS specialists. Cultural and clinical knowledge is also lacking, which is a detriment to patient care. In order to strengthen awareness and knowledge, we must develop high-quality FGM/C educational resources for urologists and gynecologists.

ObjectiveClinical practice guidelines (CPGs) serve as frameworks to unify diagnostic criteria and guide clinical decision-making. There is a paucity of literature surrounding the uptake of CPGs in urology practice settings with varied levels of resources worldwide. This study aims to evaluate reported use of CPGs within the context of international urology practice, identify local barriers to uptake, and evaluate the role of stakeholders in the CPG-development process.MethodsThis was an international, multi-center, cross-sectional study. An online survey collecting variables pertaining to the use of CPGs was distributed to attending/consultant urologists in Latin America, Africa, and China. Statistical analysis was conducted using R software.ResultA total of 249 practicing urologists from 28 countries completed the survey. The majority of participants were males, aged 36 to 45, and practiced in a non-academic setting. Ninety-three percent of urologists used CPGs in their everyday clinical practice, and 43% believed CPGs were very important to medical decision-making. However, barriers such as the lack of adaptability or applicability of CPGs to local settings were mentioned by 29% and 24% of participants, respectively. Urologists believed scientific associations (81%), national urology boards (68%), and ministries of health (56%), were important stakeholders to consult to foster the development of local CPGs.ConclusionsGlobally, CPGs are widely used tools for clinical practice. However, there are concerns about the adaptability and applicability of CPGs to settings that may lack the resources to implement their recommendations. Efforts should be directed towards incorporating scientific and medical stakeholders into the review and adaptation of urology CPGs to suit the unique features of local health care systems.

AimsTreatment for urinary incontinence (UI) includes pelvic floor muscle training (PFMT). There is limited data appraising the characteristics of PFMT devices. We aimed to ascertain the primary use, strengths and weaknesses of PFMT devices available online, through evaluation of consumer reviews.MethodsWe performed an analysis of PFMT devices on Amazon.com. Four key device categories were recognized. Reviews from the five most frequently-reviewed products per category were analyzed (n = 20). W characterized device use, strengths and weaknesses using thematic analysis.ResultsWe evaluated 2574 PFMT device reviews including 1168 vibrating Kegel balls, 750 non-vibrating Kegel balls, 411 pelvic floor or thigh exercisers, and 245 electric probes. Non-vibrating Kegel balls were rated highest (4.6/5 stars), followed by vibrating Kegel balls, electric probes and pelvic floor or thigh exercisers (4.4/5, 4.1/5, and 3.8/5 stars, respectively). Most reviews were positive (77%) or negative (16%) with few neutral (7%). While all were marketed to treat UI, most reviews did not mention the intended use. Vibrating and non-vibrating Kegel balls and electric probes were most likely to be used for UI, and pelvic floor or thigh exercisers for toning. Some used non-vibrating and vibrating Kegel balls for sexual function. Electric probes were the most beneficial device for incontinence control (27%, 67/245). Twenty-five percent of all product reviews praised device ease of use and good quality or design. A minority of reviewers found products difficult to use, of poor quality or design and uncomfortable.ConclusionConsumers utilized online PFMT devices for multiple purposes, including UI, toning and sexual function. Reviewers generally praised PFMT products, particularly electric probes for UI.

AimsPenile clamps offer an alternative to manage male urinary incontinence in patients who are unfit for surgery. Patient experience with penile clamps is poorly understood. Our study elucidates patient opinions on commercially available penile clamps and the factors that associate with favorable and unfavorable opinions.MethodsWe collected Amazon reviews of all penile clamps marketed for male urinary incontinence from November 2011 to January 2020 and qualitatively assessed the overall sentiment towards penile clamps, key praises and key complaints. Covariates such as designated Amazon star rating were further explored for association with coding patterns.ResultsAmazon reviews of penile clamps were found to be more positive (n = 425) in overall sentiment than negative (n = 294). The most frequent praise was effective incontinence control (n = 334) and the most frequent complaint was bad design or material (n = 166). The majority of reviews were for lower priced penile clamps, had higher Amazon star ratings, were written for Wiesner-produced clamps, and were written more recently (i.e., 2015-2020). Penile clamps with higher Amazon star ratings were more often coded positive and with a praise compared to lower rated penile clamps.ConclusionsPenile clamps are seen favorably by users as an effective treatment modality for male urinary incontinence. User reviews suggest opportunities for improvement in penile clamp design. The most frequently reviewed clamp seen positively is the Wiesner Incontinence Clamp Penile Clamp whereas the most frequently reviewed clamp seen negatively is the Pacey Cuff Male Incontinence Device.