Perioperative infection prevention during inflatable penile prosthesis surgery: a narrative review.

Background And Objective: Penile prostheses are an option for the management of erectile dysfunction (ED). Over the years penile prosthesis surgery has become increasingly safe owing to improvements such as antibiotic usage, coated devices, and surgical techniques. However, infection remains a dreaded complication during prosthesis surgery.

Testosterone deficiency in men with end stage renal disease and kidney transplantation: a narrative review.

Testosterone deficiency is a prevalent condition that frequently affects individuals with end-stage renal disease (ESRD) and those who have undergone renal transplantation. While the etiology of this condition is complex, its implications in this population are far-reaching, impacting various domains such as endocrine profile, sexual and erectile function, bone mineral density (BMD), anemia, and graft survival following renal transplantation. Herein, we review the most recent literature exploring the pathophysiology of testosterone deficiency in ESRD and renal transplant patients, examining its diverse effects on this demographic, and assessing the advantages of testosterone replacement therapy (TRT).

Surgical Management of Extravaginal Testicular Torsion in a 16-Year-Old Male: A Case Report.

Extravaginal torsion (EVT) is a rare type of testicular torsion that usually occurs in neonates. The primary type of testicular torsion that occurs in adolescents is intravaginal torsion. In this case report, we describe the first case of EVT reported in a 16-year-old male with a contralateral bell clapper deformity and subsequent surgical management using a tunica vaginalis flap and bilateral orchiopexy.

Non-cutaneous presentation of mycosis fungoides involving the penile corpora: Case report and review of current literature.

Mycosis fungoides involvement of genitalia is rare. We present a 63-year-old man with history of cutaneous T cell lymphoma with large cell transformation status post multiple electron beam radiation cycles who presented with a new, enlarging penile mass. He underwent ultrasound, MRI, and excisional biopsy.

The use of low-intensity extracorporeal shockwave therapy in management of erectile dysfunction following prostate cancer treatment: a review of the current literature.

Background And Objective: Erectile dysfunction (ED) is a prevalent and impactful complication post definitive management of prostate cancer. The mechanism of ED is thought to be secondary to vascular and neural injury as well as corporal smooth muscle damage with resultant fibrosis. The use of penile rehabilitation in ED following treatment for prostate cancer has been studied.

Deciphering the Molecular Mechanism of HCV Protease Inhibitor Fluorination as a General Approach to Avoid Drug Resistance.

Third generation Hepatitis C virus (HCV) NS3/4A protease inhibitors (PIs), glecaprevir and voxilaprevir, are highly effective across genotypes and against many resistant variants. Unlike earlier PIs, these compounds have fluorine substitutions on the P2-P4 macrocycle and P1 moieties. Fluorination has long been used in medicinal chemistry as a strategy to improve physicochemical properties and potency.

Discovery of Quinoxaline-Based P1-P3 Macrocyclic NS3/4A Protease Inhibitors with Potent Activity against Drug-Resistant Hepatitis C Virus Variants.

The three pan-genotypic HCV NS3/4A protease inhibitors (PIs) currently in clinical use-grazoprevir, glecaprevir, and voxilaprevir-are quinoxaline-based P2-P4 macrocycles and thus exhibit similar resistance profiles. Using our quinoxaline-based P1-P3 macrocyclic lead compounds as an alternative chemical scaffold, we explored structure-activity relationships (SARs) at the P2 and P4 positions to develop pan-genotypic PIs that avoid drug resistance. A structure-guided strategy was used to design and synthesize two series of compounds with different P2 quinoxalines in combination with diverse P4 groups of varying sizes and shapes, with and without fluorine substitutions.

Drug Design Strategies to Avoid Resistance in Direct-Acting Antivirals and Beyond.

Drug resistance is prevalent across many diseases, rendering therapies ineffective with severe financial and health consequences. Rather than accepting resistance after the fact, proactive strategies need to be incorporated into the drug design and development process to minimize the impact of drug resistance. These strategies can be derived from our experience with viral disease targets where multiple generations of drugs had to be developed to combat resistance and avoid antiviral failure.

Evolution of robotic-assisted kidney transplant: successes and barriers to overcome.

Purpose Of Review: The aim of this study was to provide an updated review of robotic-assisted kidney transplant (RAKT) with an emphasis on advantages over the open kidney transplant (OKT), utility in special populations and resources available to overcome the learning curve of robotic surgery.

Recent Findings: The majority of the reported studies showed that RAKT and OKT have similar functional outcomes including similar ischemia times and time to postoperative normalization of creatinine. However, RAKT results in fewer wound complications, decreased estimated blood loss and pain.

Avoiding Drug Resistance by Substrate Envelope-Guided Design: Toward Potent and Robust HCV NS3/4A Protease Inhibitors.

Hepatitis C virus (HCV) infects millions of people worldwide, causing chronic liver disease that can lead to cirrhosis, hepatocellular carcinoma, and liver transplant. In the last several years, the advent of direct-acting antivirals, including NS3/4A protease inhibitors (PIs), has remarkably improved treatment outcomes of HCV-infected patients. However, selection of resistance-associated substitutions and polymorphisms among genotypes can lead to drug resistance and in some cases treatment failure.

Resistance outside the substrate envelope: hepatitis C NS3/4A protease inhibitors.

Direct acting antivirals have dramatically increased the efficacy and tolerability of hepatitis C treatment, but drug resistance has emerged with some of these inhibitors, including nonstructural protein 3/4 A protease inhibitors (PIs). Although many co-crystal structures of PIs with the NS3/4A protease have been reported, a systematic review of these crystal structures in the context of the rapidly emerging drug resistance especially for early PIs has not been performed. To provide a framework for designing better inhibitors with higher barriers to resistance, we performed a quantitative structural analysis using co-crystal structures and models of HCV NS3/4A protease in complex with natural substrates and inhibitors.

Molecular Mechanism of Resistance in a Clinically Significant Double-Mutant Variant of HCV NS3/4A Protease.

Despite significant progress in hepatitis C virus (HCV) protease inhibitor (PI) drug design, resistance remains a problem causing treatment failure. Double-substitution variants, notably Y56H/D168A, have emerged in patients who fail therapy with a PI-containing regimen. The resistance conferred by Asp168 substitutions has been well characterized and avoided in newer inhibitors.

Quinoxaline-Based Linear HCV NS3/4A Protease Inhibitors Exhibit Potent Activity against Drug Resistant Variants.

A series of linear HCV NS3/4A protease inhibitors was designed by eliminating the P2-P4 macrocyclic linker in grazoprevir, which, in addition to conferring conformational flexibility, allowed structure-activity relationship (SAR) exploration of diverse quinoxalines at the P2 position. Biochemical and replicon data indicated preference for small hydrophobic groups at the 3-position of P2 quinoxaline for maintaining potency against resistant variants R155K, A156T, and D168A/V. The linear inhibitors, though generally less potent than the corresponding macrocyclic analogues, were relatively easier to synthesize and less susceptible to drug resistance.

Purification of metal-dependent lysine deacetylases with consistently high activity.

Metal-dependent lysine deacetylases (KDACs) are involved in regulation of numerous biological and disease processes through control of post-translational acetylation. Characterization of KDAC activity and substrate identification is complicated by inconsistent activity of prepared enzyme and a range of multi-step purifications. We describe a simplified protocol based on two-step affinity chromatography.

Hepatitis C Virus NS3/4A Protease Inhibitors Incorporating Flexible P2 Quinoxalines Target Drug Resistant Viral Variants.

A substrate envelope-guided design strategy is reported for improving the resistance profile of HCV NS3/4A protease inhibitors. Analogues of 5172-mcP1P3 were designed by incorporating diverse quinoxalines at the P2 position that predominantly interact with the invariant catalytic triad of the protease. Exploration of structure-activity relationships showed that inhibitors with small hydrophobic substituents at the 3-position of P2 quinoxaline maintain better potency against drug resistant variants, likely due to reduced interactions with residues in the S2 subsite.