Treatment of male stress urinary incontinence at time of inflatable penile prosthesis placement a review of contemporary literature.

Background and Objective: Male stress urinary incontinence (SUI) and erectile dysfunction (ED) are well established diagnoses within Men's Health, often more specifically within the prostate cancer survivorship cohort. Taken individually, well defined treatment algorithms exist with which many surgeons are comfortable; however, treatment of both in a single setting or staged fashion introduces complexity. Emerging treatment options also exist, and there is immature or minimal data when these are combined with inflatable penile prosthesis (IPP) insertion, radiation history, and/or variable degrees of incontinence. Our objective was to describe and summarize the currently available treatment options for SUI particularly at the time of IPP insertion. Methods: A literature review was performed to summarize contemporary treatment of SUI at time of IPP placement. Anecdotal experience was added from high volume, subspecialty trained Men's Health and Reconstructive Urologists. Key Content and Findings: Non-invasive approaches such as pelvic floor muscle training (PFMT), behavioral modification, and external compression devices play some limited role in treatment and/or management of SUI, particularly in the early post operative period, or for those unwilling or unable to undergo more definitive intervention. More invasive options such as artificial urinary sphincter (AUS) implantation, male sling, or other implantable devices are more appropriate for good surgical candidates with higher bother and/or more severe incontinence. These options can be concomitant or staged relative to IPP placement. Climacturia, particularly with mild or no bothersome SUI, can successfully be addressed at the time of penile prosthesis placement with the utilization of the Mini-Jupette suburethral sling. Conclusions: A variety of treatment options exist for concomitant treatment of SUI at time of IPP, and both safety and efficacy have been demonstrated for many in the same operative setting. As with treatment of ED or SUI in isolation, patient selection, careful counseling, and management of expectations can lead to high patient satisfaction.

Exciton Transfer Between Extended Electronic States in Conjugated Inter-Polyelectrolyte Complexes.

Artificial light harvesting, a process that involves converting sunlight into chemical potential energy, is considered to be a promising part of the overall solution to address urgent global energy challenges. Conjugated polyelectrolyte complexes (CPECs) are particularly attractive for this purpose due to their extended electronic states, tunable assembly thermodynamics, and sensitivity to their local environment. Importantly, ionically assembled complexes of conjugated polyelectrolytes can act as efficient donor-acceptor pairs for electronic energy transfer (EET). However, to be of use in material applications, we must understand how modifying the chemical structure of the CPE backbone alters the EET rate beyond spectral overlap considerations. In this report we investigate the dependence of the EET efficiency and rate on the electronic structure and excitonic wave function of the CPE backbone. To do so, we synthesized a series of alternating copolymers where the electronic states are systematically altered by introducing comonomers with electron withdrawing and electron-rich character while keeping the linear ionic charge density nearly fixed. We find evidence that the excitonic coupling may be significantly affected by the exciton delocalization radius, in accordance with analytical models based on the line-dipole approximation and quantum chemistry calculations. Our results imply that care should be taken when selecting CPE components for optimal CPEC EET. These results have implications for using CPECs as key components in water-based light-harvesting materials, either as standalone assemblies or as adsorbates on nanoparticles and thin films.

Transcriptome-wide characterization of genetic perturbations.

Single cell CRISPR screens such as Perturb-seq enable transcriptomic profiling of genetic perturbations at scale. However, the data produced by these screens are often noisy due to cost and technical constraints, limiting power to detect true effects with conventional differential expression analyses. Here, we introduce TRanscriptome-wide Analysis of Differential Expression (TRADE), a statistical framework which estimates the transcriptome-wide distribution of true differential expression effects from noisy gene-level measurements. Within TRADE, we derive multiple novel, interpretable statistical metrics, including the "transcriptome-wide impact", an estimator of the overall transcriptional effect of a perturbation which is stable across sampling depths. We analyze new and published large-scale Perturb-seq datasets to show that many true transcriptional effects are not statistically significant, but detectable in aggregate with TRADE. In a genome-scale Perturb-seq screen, we find that a typical gene perturbation affects an estimated 45 genes, whereas a typical essential gene perturbation affects over 500 genes. An advantage of our approach is its ability to compare the transcriptomic effects of genetic perturbations across contexts and dosages despite differences in power. We use this ability to identify perturbations with cell-type dependent effects and to find examples of perturbations where transcriptional responses are not only larger in magnitude, but also qualitatively different, as a function of dosage. Lastly, we expand our analysis to case/control comparison of gene expression for neuropsychiatric conditions, finding that transcriptomic effect correlations are greater than genetic correlations for these diagnoses. TRADE lays an analytic foundation for the systematic comparison of genetic perturbation atlases, as well as differential expression experiments more broadly.

High-dimensional phenotyping to define the genetic basis of cellular morphology.

The morphology of cells is dynamic and mediated by genetic and environmental factors. Characterizing how genetic variation impacts cell morphology can provide an important link between disease association and cellular function. Here, we combine genomic sequencing and high-content imaging approaches on iPSCs from 297 unique donors to investigate the relationship between genetic variants and cellular morphology to map what we term cell morphological quantitative trait loci (cmQTLs). We identify novel associations between rare protein altering variants in WASF2, TSPAN15, and PRLR with several morphological traits related to cell shape, nucleic granularity, and mitochondrial distribution. Knockdown of these genes by CRISPRi confirms their role in cell morphology. Analysis of common variants yields one significant association and nominate over 300 variants with suggestive evidence (P < 10-6) of association with one or more morphology traits. We then use these data to make predictions about sample size requirements for increasing discovery in cellular genetic studies. We conclude that, similar to molecular phenotypes, morphological profiling can yield insight about the function of genes and variants.