Rectourethral fistula after perirectal spacer placement requiring pelvic exenteration.

Despite the widespread use of perirectal spacers to reduce radiation-induced rectal toxicity during prostate cancer treatment, postmarketing data reveal rare but significant complications. This case report details a severe complication of rectourethral fistula necessitating robotic pelvic exenteration with urinary and faecal diversion following perirectal spacer placement. Although SpaceOAR has been shown to reduce rectal radiation dose, the ensuing clinical benefit remains inconclusive in real-world data.

Dissecting current rectification through asymmetric nanopores.

Rectification, the tendency of bidirectional ionic conductors to favor ion flow in a specific direction, is an intrinsic property of many ion channels and synthetic nanopores. Despite its frequent occurrence in ion channels and its phenomenological explanation using Eyring's rate theory, a quantitative relationship between the rectified current and the underlying ion-specific and voltage-dependent free energy profile has been lacking. In this study, we designed nanopores in which potassium and chloride current rectification can be manipulated by altering the electrostatic pore polarity.

Retinal perivascular macrophages regulate immune cell infiltration during neuroinflammation in mouse models of ocular disease.

The blood-retina barrier (BRB), which is disrupted in diabetic retinopathy (DR) and uveitis, is an important anatomical characteristic of the retina, regulating nutrient, waste, water, protein, and immune cell flux. The BRB is composed of endothelial cell tight junctions, pericytes, astrocyte end feet, a collagen basement membrane, and perivascular macrophages. Despite the importance of the BRB, retinal perivascular macrophage function remains unknown.

Smoking is not associated with wound complications in augmented urethroplasty: a NSQIP analysis.

Objective: To investigate if predictors of wound complications differed between patients undergoing excision and primary anastomosis urethroplasty (EPA) and augmented urethroplasty.

Methods: The National Surgical Quality Improvement Program database from 2006 to 2018 was queried for male patients undergoing urethroplasty. Thirty-day wound complications were identified and categorized (superficial/deep/organ-space surgical site infections and dehiscence).

Cationic Polysaccharides Bind to the Endothelial Cell Surface Extracellular Matrix Involving Heparan Sulfate.

Cationic polysaccharides have been extensively studied for drug delivery via the bloodstream, yet few have progressed to clinical use. Endothelial cells lining the blood vessel wall are coated in an anionic extracellular matrix called the glycocalyx. However, we do not fully comprehend the charged polysaccharide interactions with the glycocalyx.

Multi-Institutional Outcomes of Dorsal Onlay Buccal Mucosal Graft Urethroplasty in Patients With Postprostatectomy, Postradiation Anastomotic Stenosis.

Purpose: The treatment of urethral stenosis after a combination of prostatectomy and radiation therapy for prostate cancer is understudied. We evaluate the clinical and patient-related outcomes after dorsal onlay buccal mucosal graft urethroplasty (D-BMGU) in men who underwent prostatectomy and radiation therapy.

Materials And Methods: A multi-institutional, retrospective review of men with vesicourethral anastomotic stenosis or bulbomembranous urethral stricture disease after radical prostatectomy and radiation therapy from 8 institutions between 2013 to 2021 was performed.

Comparing the rate of immunotherapy treatment change due to toxicity by sex.

Background: Immuno-oncology therapy (IO) is associated with a variety of treatment-related toxicities. However, the impact of toxicity on the treatment discontinuation rate between males and females is unknown. We hypothesized that immune-related adverse events would lead to more frequent treatment changes in females since autoimmune diseases occur more frequently in females.

NR4A1 deletion promotes pro-angiogenic polarization of macrophages derived from classical monocytes in a mouse model of neovascular age-related macular degeneration.

Background: Neovascular age-related macular degeneration causes vision loss from destructive angiogenesis, termed choroidal neovascularization (CNV). Cx3cr1 mice display alterations in non-classical monocytes and microglia with increased CNV size, suggesting that non-classical monocytes may inhibit CNV formation. NR4A1 is a transcription factor that is necessary for maturation of non-classical monocytes from classical monocytes.

Disentangling Positive Selection from Relaxed Selection in Animal Mitochondrial Genomes.

AbstractDisentangling different types of selection is a common goal in molecular evolution. Elevated / ratios (the ratio of nonsynonymous to synonymous substitution rates) in focal lineages are often interpreted as signs of positive selection. Paradoxically, relaxed purifying selection can also result in elevated / ratios, but tests to distinguish these two causes are seldomly implemented.

Fasciocutaneous Flap Perineal Closure with Testicular Thigh Pouch for Scrotal Defects: Surgical Technique and Initial Experience.

Objective: To describe the surgical technique and evaluate the safety, feasibility, and preliminary outcomes of perineal closure with fasciocutaneous flaps as an alternative to scrotoplasty for large genital wounds.

Methods: Cases of perineal closure with fasciocutaneous flaps and thigh pouch creation for patients having undergone scrotectomy from January 2015 until August 2022 were reviewed for operative details and surgical outcomes.

Results: Twenty patients were identified undergoing this procedure.

Glycidamide-induced hypermutation in yeast single-stranded DNA reveals a ubiquitous clock-like mutational motif in humans.

Mutagens often prefer specific nucleotides or oligonucleotide motifs that can be revealed by studying the hypermutation spectra in single-stranded (ss) DNA. We utilized a yeast model to explore mutagenesis by glycidamide, a simple epoxide formed endogenously in humans from the environmental toxicant acrylamide. Glycidamide caused ssDNA hypermutation in yeast predominantly in cytosines and adenines.

Extended versus standard pelvic lymph node dissection yields no difference in 3-year biochemical recurrence rates.

Background: extended pelvic lymph node dissection (ePLND) increases the detection rate of lymph node positive prostate cancer compared to a standard pelvic lymph node dissection (sPLND). However, improvement of patient outcomes remains questionable. Here we report and compare 3-year postoperative PSA recurrence rates between patients that underwent sPLND versus ePLND at the time of prostatectomy.

Oxidative stress induces lysosomal membrane permeabilization and ceramide accumulation in retinal pigment epithelial cells.

Oxidative stress has been implicated in the pathogenesis of age-related macular degeneration, the leading cause of blindness in older adults, with retinal pigment epithelium (RPE) cells playing a key role. To better understand the cytotoxic mechanisms underlying oxidative stress, we used cell culture and mouse models of iron overload, as iron can catalyze reactive oxygen species formation in the RPE. Iron-loading of cultured induced pluripotent stem cell-derived RPE cells increased lysosomal abundance, impaired proteolysis and reduced the activity of a subset of lysosomal enzymes, including lysosomal acid lipase (LIPA) and acid sphingomyelinase (SMPD1).

Complications after Prostate Cancer Treatment: Pathophysiology and Repair of Post-Radiation Urethral Stricture Disease.

Radiation therapy (RT) in the management of pelvic cancers remains a clinical challenge to urologists given the sequelae of urethral stricture disease secondary to fibrosis and vascular insults. The objective of this review is to understand the physiology of radiation-induced stricture disease and to educate urologists in clinical practice regarding future prospective options clinicians have to deal with this condition. The management of post-radiation urethral stricture consists of conservative, endoscopic, and primary reconstructive options.

Topical and systemic GLP-1R agonist administration both rescue retinal ganglion cells in hypertensive glaucoma.

Glaucomatous neurodegeneration, a blinding disease affecting millions worldwide, has a need for the exploration of new and effective therapies. Previously, the glucagon-like peptide-1 receptor (GLP-1R) agonist NLY01 was shown to reduce microglia/macrophage activation, rescuing retinal ganglion cells after IOP elevation in an animal model of glaucoma. GLP-1R agonist use is also associated with a reduced risk for glaucoma in patients with diabetes.

Systematic literature review reveals suboptimal use of chemical probes in cell-based biomedical research.

Chemical probes have reached a prominent role in biomedical research, but their impact is governed by experimental design. To gain insight into the use of chemical probes, we conducted a systematic review of 662 publications, understood here as primary research articles, employing eight different chemical probes in cell-based research. We summarised (i) concentration(s) at which chemical probes were used in cell-based assays, (ii) inclusion of structurally matched target-inactive control compounds and (iii) orthogonal chemical probes.

Mathematical modeling of microscale biology: Ion pairing, spatially varying permittivity, and Born energy in glycosaminoglycan brushes.

Biological macromolecules including nucleic acids, proteins, and glycosaminoglycans are typically anionic and can span domains of up to hundreds of nanometers and even micron length scales. The structures exist in crowded environments that are dominated by multivalent electrostatic interactions that can be modeled using mean-field continuum approaches that represent underlying molecular nanoscale biophysics. We develop such models for glycosaminoglycan brushes using steady state modified Poisson-Boltzmann models that incorporate important ion-specific (Hofmeister) effects.

Transurethral ventral inlay buccal mucosa graft urethroplasty: technique and intermediate outcomes.

Objective: To outline our step-by-step surgical technique for a transurethral ventral buccal mucosa graft inlay urethroplasty to treat fossa navicularis and distal urethral strictures.

Methods: The transurethral ventral inlay urethroplasty is accomplished in four steps. First, after obtaining proper exposure the cicatrice is excised via a transurethral ventral urethrotomy until the lumen is at least 24fr.

Phenol-Croton Oil Chemical Peeling Induces Durable Improvement of Constitutional Periorbital Dark Circles.

Background: Constitutional periorbital dark circles (PDC) are common in skin of color and represent a therapeutic challenge.

Objective: To summarize the experience of the International Peeling Society on the safety and effectiveness of deep chemical peeling in the treatment of constitutional PDC.

Materials And Methods: Multi-institutional, retrospective case series (1990-2020) of constitutional PDC treated by deep chemical peeling.