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Enhancing central nervous system (CNS) myelin regeneration is recognized as an important strategy to ameliorate the devastating consequences of demyelinating diseases such as multiple sclerosis. Previous findings have indicated that myelin proteins, which accumulate following demyelination, inhibit remyelination by blocking the differentiation of rat oligodendrocyte progenitor cells (OPCs) via modulation of PKCα. We therefore screened drugs for their potential to overcome this differentiation block. From our screening, tamoxifen emerges as a potent inducer of OPC differentiation in vitro . We show that the effects of tamoxifen rely on modulation of the estrogen receptors ERα, ERβ and GPR30. Furthermore, we demonstrate that administration of tamoxifen to demyelinated rats in vivo accelerates remyelination. Tamoxifen is a well-established drug and is thus a promising candidate for a drug to regenerate myelin, as it will not require extensive safety testing. In addition, Tamoxifen plays an important role in biomedical research as an activator of inducible genetic models. Our results highlight the importance of appropriate controls when using such models.

The last decade has seen the development of a wide set of tools, such as wavefront shaping, computational or fundamental methods, that allow us to understand and control light propagation in a complex medium, such as biological tissues or multimode fibers. A vibrant and diverse community is now working in this field, which has revolutionized the prospect of diffraction-limited imaging at depth in tissues. This roadmap highlights several key aspects of this fast developing field, and some of the challenges and opportunities ahead.

Stress urinary incontinence is a financially burdensome and socially isolating problem and can be experienced by men as a result of radical prostatectomy, radiation therapy, or other urologic surgery. Artificial urinary sphincter (AUS) placement for stress urinary incontinence is considered the ‘gold standard’ for male stress urinary incontinence. While initially only placed by specialized prosthetic surgeons, changes in urologic training have made implantation of the device by general urologists more widespread. Additionally, even though a minority of urologists place the majority of implants, many urologists may find themselves caring for patients with these devices even if they have never placed them themselves. For this reason, it is paramount that the urologic surgeon implanting the device and those caring for patients with prostheses are familiar with the various perioperative and postoperative complications of AUS implantation. This review discusses the most commonly reported complications of AUS implantation as well as those that are rarely described. Knowledge of these potential complications is necessary in order to care for patients with urologic implants.

Management of complex and recurrent ureteral stricture disease remains one of the more challenging aspects of reconstructive urology. While standard techniques such as ureteroureterostomy, psoas hitch, Boari flap, and ileal ureter creation serve as the foundation of ureteral reconstruction, each technique has limitations, particularly when faced with recurrence, long strictures, and previously irradiated fields. Two alternative techniques—buccal mucosal graft (BMG) ureteroplasty and appendiceal onlay/interposition—have been previously described and are now being utilized more frequently in recent years. Furthermore, the advancement of robotic-assisted laparoscopic surgery has allowed for even more reconstructive capabilities. BMG ureteroplasty and appendiceal onlay/interposition can serve as valuable augmentations to the aforementioned surgical techniques. BMG has now long been established in urethral reconstruction and serves as a viable graft option for longer segment ureteral strictures, given its panvascular lamina propria and epithelium well-suited to a wet environment. Similarly, the appendix has other uses in urologic surgery, including the Mitrofanoff channel in pediatric surgery, and is chiefly used in right-sided ureteral stricture repair. Both of these techniques allow the surgeons to take on more complex ureteral stricture cases and avoid the morbidity of bowel harvest. In this perspective, we argue for a broader recognition and adoption of BMG and appendiceal onlay/interposition in ureteral reconstructive surgery. In this article, we highlight the rationale for use, technical considerations, outcomes, and clinical evidence suggesting their advantages over traditional approaches. By incorporating these techniques into practice, urologists can expand their ability to manage more complex ureteral stricture cases with improved outcomes.

Hypospadias is a congenital malformation resulting from the disruption of normal urethral formation with varying global prevalence. Hypospadias repair, especially that of proximal hypospadias (in which reconstruction of a long urethra is necessary), remains a surgical challenge despite more than two decades of surgical technique development and refinement. The lack of tissue substitutes with mechanical and biological properties similar to those of native urethra is a challenge for which the field of tissue engineering might offer promising solutions. However, the use of tissue-engineered constructs in preclinical studies is still hindered by complications such as strictures or fistulae, which have slowed progression to clinical application. Furthermore, the generation of uniform tubular constructs remains a challenge. Exciting advances in the application of nanotechnology and 3D bioprinting to urethral tissue engineering might present solutions to these issues.In this Review, Chan and colleagues discuss the need for improved management options for hypospadias and describe advances in urethral tissue engineering and barriers to clinical application of tissue-engineered constructs in hypospadias repair.

PurposePatients often receive antibiotic prophylaxis after urethroplasty to minimize the risk of urinary tract infection (UTI). The aim of this study was to determine the frequency of UTIs after urethroplasty and its impact on urethral and incisional healing.MethodsPatients undergoing urethroplasty by a single surgeon from 2000 to 2012 were retrospectively reviewed. All patients received preoperative antibiotic prophylaxis and postoperative prophylaxis for 30 days or until catheter removal. We reviewed urine cultures obtained within 30 days after urethroplasty in symptomatic patients, and rates of stricture recurrence and wound complications. A positive culture was defined as > 1000 cfu/mL of an organism.Results398 patients were included with a mean age of 43.5 years at time of surgery. We identified 102 positive urine cultures (25.6%) within 30 days of urethroplasty. 78 stricture recurrences (19.6%) occurred at an average of 3 years after surgery and 18 (4.5%) experienced a wound complication, with a 52 month mean follow-up. There were no significant differences in stricture recurrence (p = 0.36) or wound complications (p = 0.42) between patients who had a positive and negative urine culture. On multivariate analysis, positive urine cultures (HR 1.0, 95% CI 0.6–1.8, p = 0.88) were not associated with stricture recurrence, while lichen sclerosis (HR 3.2, 95% CI 1.1–9.2, p = 0.03) and previous urethroplasty (HR 2.3, 95% CI 1.1–4.6, p = 0.03) were.ConclusionBacterial colonization and UTIs despite antimicrobial prophylaxis are common in urethroplasty patients. This, however, does not appear to impair urethral healing or influence wound healing, suggesting that postoperative prophylaxis may in fact offer no benefit.

In 2020, the UK government funded a portfolio of platform trials to develop new treatments for COVID-19. A key feature was the independent prioritization of candidate drugs with central coordination to prevent duplication, accelerating recruitment to deliver definitive trial results. A similar approach could be used for non-communicable diseases where treatment advances have been limited.In 2020, the UK government funded a portfolio of platform trials to develop new treatments for COVID-19. A key feature was the independent prioritization of candidate drugs with central coordination to prevent duplication, accelerating recruitment to deliver definitive trial results. A similar approach could be used for non-communicable diseases where treatment advances have been limited.