Inflatable penile prosthesis placement in Peyronie's disease: a review of surgical considerations, approaches, and maneuvers.

Peyronie's disease (PD) is a fibrotic disorder of the tunica albuginea that results in penile deformity and/or curvature. Patients usually present complaining of penile pain, shortening and deformity resulting in dissatisfaction with intercourse. Many patients with PD will present with concomitant erectile dysfunction (ED). This disease is a significant concern for patients as it impacts both sexual function and overall quality of life. While there are several interventions available for PD treatment, inflatable penile prosthesis (IPP) implantation is considered the gold standard approach for those with moderate to severe concomitant ED, refractory to medical therapy. The goal of treatment is to give a man a functionally straight erection. Placement of an IPP alone may achieve this. However, when curvature still exists, several adjunct procedures may be performed to include manual modeling, plication, plaque incision or excision and grafting. Additionally, advanced lengthening procedures may also be used. In this paper we will present a comprehensive review of the adjuvant straightening techniques that can be used during IPP placement in men with PD and refractory ED when curvature still exists. Patient selection is a key predictor of implant success, as is preoperative and postoperative management to optimize overall patient care and satisfaction. These topics along with the different surgical approaches to IPP insertion for PD will also be discussed, including the benefits and shortcomings of each. A flowchart to aid surgeons in their intraoperative decision making based on curvature characteristics and specific patient concerns is presented.

Primary ablation versus urinary diversion in posterior urethral valve: Systematic review and meta-analysis.

PURPOSE: To determine differences in long-term kidney and bladder outcomes in boys with posterior urethral valves (PUV) managed by a primary valve ablation or primary urinary diversion. MATERIALS AND METHODS: A systematic search was performed in March 2021. Comparative studies were evaluated according to Cochrane collaboration recommendations. Assessed measures included kidney outcomes (chronic kidney disease, end-stage renal disease, kidney function) and bladder outcomes. Odds ratios (OR) and mean difference (MD) with 95% confidence interval (CI) were extrapolated from available data for quantitative synthesis. Random-effects meta-analysis and meta-regression were performed according to study design, and potential covariates were assessed with subgroup analysis. The systematic review was prospectively registered on PROSPERO (CRD42021243967). RESULTS: Thirty unique studies describing 1547 boys with PUV were included in this synthesis. Overall effect estimates demonstrate that patients undergoing primary diversion have significantly increased odds of developing renal insufficiency [OR 0.60, 95% CI 0.44, 0.80; p < 0.001]. However, when adjusting for baseline kidney function between intervention groups, there was no significant difference in long term kidney outcomes [p = 0.09, 0.35], or the development of bladder dysfunction or requiring clean-intermittent catheterization with primary ablation rather than diversion [OR 0.89, 95% CI 0.49, 1.59; p = 0.68]. CONCLUSIONS: Current low-quality evidence suggests that medium-term kidney outcomes in children are similar between primary ablation and primary diversion after adjusting for baseline kidney function, while bladder outcomes are highly heterogenous. Further research with covariate control is warranted to investigate sources of heterogeneity. LEVEL OF EVIDENCE: Level III.

Tailored Medication Adherence Incentives Using mHealth for Children With High-Risk Asthma (TAICAM): Protocol for a Randomized Controlled Trial.

BACKGROUND: Poor adherence to inhaled corticosteroid medications for children with high-risk asthma is both well documented and poorly understood. It has a disproportionate prevalence and impact on children of minority demographics in urban settings. Financial incentives have been shown to be a compelling method to engage those in a high-risk asthma population, but whether adherence can be maintained by offering financial incentives and how these incentives can be used to sustain high adherence are unknown. OBJECTIVE: The aim of this study is to determine the marginal effects of a financial incentive-based intervention on inhaled corticosteroid adherence, health care system use, and costs. METHODS: Participants include children aged 5 to 12 years who have had either at least two hospitalizations or one hospitalization and one emergency department visit for asthma in the year prior to their enrollment (and their caregivers). Participants are given an electronic inhaler sensor in order to track their medication use over a period of 7 months. After a 1-month period of observation, participants are randomized to 1 of 3 arms for a 3-month period. Participants in arm 1 receive daily text message reminders, feedback, and gain-framed, nominal financial incentives; participants in arm 2 receive daily text message reminders and feedback only, and participants in arm 3 receive no reminders, feedback, or incentives. All participants are subsequently observed for an additional 3-month period with no reminders, feedback, or incentives to assess whether any sustained effects are apparent. RESULTS: Study enrollment began in September 2019 with a target sample size of N=125 children. As of June 2020, 61 children have been enrolled. Data collection is estimated to be completed in June 2022, and analyses will be completed by June 2023. CONCLUSIONS: This study will provide data that will help to determine whether a financial incentive-based mobile health intervention for promoting inhaled corticosteroid use can be effective in patients with high-risk asthma over longer periods. TRIAL REGISTRATION: Clinicaltrial.gov NCT03907410; https://clinicaltrials.gov/ct2/show/NCT03907410. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/16711.

Association Between Daily Water Intake and 24-hour Urine Volume Among Adolescents With Kidney Stones.

OBJECTIVE: To determine the association between daily water intake and 24-hour urine volume among adolescents with nephrolithiasis in order to estimate a "fluid prescription," the additional water intake needed to increase urine volume to a target goal. METHODS: We conducted a secondary analysis of an ecological momentary assessment study that prospectively measured daily water intake of 25 adolescents with nephrolithiasis over 7 days. We identified 24-hour urine volumes obtained for clinical care within 12 months of water intake assessment. A linear regression model was fit to estimate the magnitude of the association between daily water intake and 24-hour urine volume, adjusting for age, sex, race, and daily temperature. RESULTS: Twenty-two participants completed fifty-seven 24-hour urine collections within 12 months of the study period. Median daily water intake was 1.4 L (IQR 0.67-1.94). Median 24-hour urine volume was 2.01 L (IQR 1.20-2.73). A 1 L increase in daily water intake was associated with a 710 mL increase in 24-hour urine output (95%CI 0.55-0.87). Using the model output, the equation was generated to estimate the additional fluid intake needed fluid prescription (FP) to produce the desired increase in urine output (dUOP): FP = dUOP/0.71. CONCLUSION: The FP equation (FP = dUOP)/0.71), which reflects the relationship between water intake and urine volume, could be used to help adolescents with nephrolithiasis achieve urine output goals to decrease stone recurrence.

Ecological Momentary Assessment of Factors Associated with Water Intake among Adolescents with Kidney Stone Disease.

PURPOSE: Maintaining high water intake decreases kidney stone recurrence but is difficult to do. Strategies to reduce stone recurrence among adolescents are lacking. We conducted an ecological momentary assessment study to identify factors associated with water intake in adolescents with nephrolithiasis. MATERIALS AND METHODS: The study population consisted of 15 female and 10 male patients 12 to 18 years old with at least 1 prior kidney stone. For 7 days participants used "smart" bottles to self-monitor water intake and received questionnaires randomly 4 times daily, which were completed in real time on mobile devices. The questionnaires ascertained awareness of water intake volume, awareness of water intake goals, perceived need to drink, access to water, alternative beverage consumption and attitudes toward bathrooms. Linear mixed effects models were fit to estimate the association between momentary responses and daily water intake. RESULTS: During 175 person-days 595 assessments (85%) were completed. Median daily water intake was 1,304 ml (IQR 848-1,832) and 20% of participants met their intake goal for 4 days or more. Unawareness of water intake volume was associated with drinking 690 ml less water per day (p = 0.04). A strong self-perceived need to drink more was associated with drinking 1,954 ml less water each day compared to no self-perceived need to drink more (p <0.01). Unawareness of intake goals was weakly associated with drinking 1,129 ml less water each day (p = 0.1). Access to water, alternative beverage consumption and bathroom aversion were not associated with water intake. CONCLUSIONS: Unawareness of water volume consumed and low responsiveness to perceived need to drink more were associated with low water intake. Interventions that help adolescents recognize when and identify how to increase water intake may be effective in decreasing stone recurrence.

Analysis of RNA binding by the dengue virus NS5 RNA capping enzyme.

Flaviviruses are small, capped positive sense RNA viruses that replicate in the cytoplasm of infected cells. Dengue virus and other related flaviviruses have evolved RNA capping enzymes to form the viral RNA cap structure that protects the viral genome and directs efficient viral polyprotein translation. The N-terminal domain of NS5 possesses the methyltransferase and guanylyltransferase activities necessary for forming mature RNA cap structures. The mechanism for flavivirus guanylyltransferase activity is currently unknown, and how the capping enzyme binds its diphosphorylated RNA substrate is important for deciphering how the flavivirus guanylyltransferase functions. In this report we examine how flavivirus NS5 N-terminal capping enzymes bind to the 5' end of the viral RNA using a fluorescence polarization-based RNA binding assay. We observed that the K(D) for RNA binding is approximately 200 nM Dengue, Yellow Fever, and West Nile virus capping enzymes. Removal of one or both of the 5' phosphates reduces binding affinity, indicating that the terminal phosphates contribute significantly to binding. RNA binding affinity is negatively affected by the presence of GTP or ATP and positively affected by S-adensyl methoninine (SAM). Structural superpositioning of the dengue virus capping enzyme with the Vaccinia virus VP39 protein bound to RNA suggests how the flavivirus capping enzyme may bind RNA, and mutagenesis analysis of residues in the putative RNA binding site demonstrate that several basic residues are critical for RNA binding. Several mutants show differential binding to 5' di-, mono-, and un-phosphorylated RNAs. The mode of RNA binding appears similar to that found with other methyltransferase enzymes, and a discussion of diphosphorylated RNA binding is presented.

Infectious alphavirus production from a simple plasmid transfection+.

We have developed a new method for producing infectious double subgenomic alphaviruses from plasmids transfected into mammalian cells. A double subgenomic Sindbis virus (TE3'2J) was transcribed from a cytomegalovirus PolII promoter, which results in the production of infectious virus. Transfection of as little as 125 ng of plasmid is able to produce 1 × 10(8) plaque forming units/ml (PFU/ml) of infectious virus 48 hours post-transfection. This system represents a more efficient method for producing recombinant Sindbis viruses.

A high-throughput screening assay for the identification of flavivirus NS5 capping enzyme GTP-binding inhibitors: implications for antiviral drug development.

There are no effective antivirals currently available for the treatment of flavivirus infection in humans. As such, the identification and characterization of novel drug target sites are critical to developing new classes of antiviral drugs. The flavivirus NS5 N-terminal capping enzyme (CE) is vital for the formation of the viral RNA cap structure, which directs viral polyprotein translation and stabilizes the 5' end of the viral genome. The structure of the flavivirus CE has been solved, and a detailed understanding of the CE-guanosine triphosphate (GTP) and CE-RNA cap interactions is available. Because of the essential nature of the interaction for viral replication, disrupting CE-GTP binding is an attractive approach for drug development. The authors have previously developed a robust assay for monitoring CE-GTP binding in real time. They adapted this assay for high-throughput screening and performed a pilot screen of 46 323 commercially available compounds. A number of small-molecule inhibitors capable of displacing a fluorescently labeled GTP in vitro were identified, and a second functional assay was developed to identify false positives. The results presented indicate that the flavivirus CE cap-binding site is a valuable new target site for antiviral drug discovery and should be further exploited for broad-spectrum anti-flaviviral drug development.