Penile Rehabilitation Therapy with PDE-V Inhibitors Following Radical Prostatectomy: Proceed with Caution

Penile rehabilitation therapy following radical prostatectomy is a much debated topic. Erectile dysfunction is still a significant contributor to postoperative morbidity following radical prostatectomy, despite meticulous nerve-sparing technique. Secondary smooth muscle changes in the penis have been identified as the underlying causes of penile atrophy, veno-occlusive dysfunction, and fibrosis. Initial observations that intracavernous injection therapies used on a regular basis postoperatively resulted in improvements in the return of spontaneous erectile function led to the development of penile rehabilitation protocols. Chronic dosing of PDE-V inhibitors is now commonly used by urologists after radical prostatectomy. Despite the current enthusiasm of penile rehabilitation therapy, current scientific evidence with clinical trials is still limited

Association between purchase of over-the-counter medications and ovarian cancer diagnosis in the Cancer Loyalty Card Study (CLOCS):observational case-control study

BACKGROUND: Over-the-counter (OTC) medications are frequently used to self-care for nonspecific ovarian cancer symptoms prior to diagnosis. Monitoring such purchases may provide an opportunity for earlier diagnosis. OBJECTIVE: The aim of the Cancer Loyalty Card Study (CLOCS) was to investigate purchases of OTC pain and indigestion medications prior to ovarian cancer diagnosis in women with and without ovarian cancer in the United Kingdom using loyalty card data. METHODS: An observational case-control study was performed comparing purchases of OTC pain and indigestion medications prior to diagnosis in women with (n=153) and without (n=120) ovarian cancer using loyalty card data from two UK-based high street retailers. Monthly purchases of pain and indigestion medications for cases and controls were compared using the Fisher exact test, conditional logistic regression, and receiver operating characteristic (ROC) curve analysis. RESULTS: Pain and indigestion medication purchases were increased among cases 8 months before diagnosis, with maximum discrimination between cases and controls 8 months before diagnosis (Fisher exact odds ratio [OR] 2.9, 95% CI 2.1-4.1). An increase in indigestion medication purchases was detected up to 9 months before diagnosis (adjusted conditional logistic regression OR 1.38, 95% CI 1.04-1.83). The ROC analysis for indigestion medication purchases showed a maximum area under the curve (AUC) at 13 months before diagnosis (AUC=0.65, 95% CI 0.57-0.73), which further improved when stratified to late-stage ovarian cancer (AUC=0.68, 95% CI 0.59-0.78). CONCLUSIONS: There is a difference in purchases of pain and indigestion medications among women with and without ovarian cancer up to 8 months before diagnosis. Facilitating earlier presentation among those who self-care for symptoms using this novel data source could improve ovarian cancer patients' options for treatment and improve survival. TRIAL REGISTRATION: ClinicalTrials.gov NCT03994653; https://clinicaltrials.gov/ct2/show/NCT03994653

The Mass of the White Dwarf Companion in the Self-Lensing Binary KOI-3278: Einstein vs. Newton

KOI-3278 is a self-lensing stellar binary consisting of a white-dwarf secondary orbiting a Sun-like primary star. Kruse and Agol (2014) noticed small periodic brightenings every 88.18 days in the Kepler photometry and interpreted these as the result of microlensing by a white dwarf with about 63$\%$ of the mass of the Sun. We obtained two sets of spectra for the primary that allowed us to derive three sets of spectroscopic estimates for its effective temperature, surface gravity, and metallicity for the first time. We used these values to update the Kruse and Agol (2014) Einsteinian microlensing model, resulting in a revised mass for the white dwarf of $0.539^{+0.022}_{-0.020} \, M_{\odot}$. The spectra also allowed us to determine radial velocities and derive orbital solutions, with good agreement between the two independent data sets. An independent Newtonian dynamical MCMC model of the combined velocities yielded a mass for the white dwarf of $0.5122^{+0.0057}_{-0.0058} \, M_{\odot}$. The nominal uncertainty for the Newtonian mass is about four times better than for the Einsteinian, $\pm 1.1\%$ vs. $\pm 4.1\%$ and the difference between the two mass determinations is $5.2 \%$. We then present a joint Einsteinian microlensing and Newtonian radial velocity model for KOI-3278, which yielded a mass for the white dwarf of $0.5250^{+0.0082}_{-0.0089} \, M_{\odot}$. This joint model does not rely on any white dwarf evolutionary models or assumptions on the white dwarf mass-radius relation. We discuss the benefits of a joint model of self-lensing binaries, and how future studies of these systems can provide insight into the mass-radius relation of white dwarfs.Comment: ApJ Accepted; 22 Pages, 8 Figures, 6 Tables and 4 Supplementary Table

Planet Hunters VII. Discovery of a New Low-Mass, Low-Density Planet (PH3 c) Orbiting Kepler-289 with Mass Measurements of Two Additional Planets (PH3 b and d)

We report the discovery of one newly confirmed planet ($P=66.06$ days, $R_{\rm{P}}=2.68\pm0.17R_\oplus$) and mass determinations of two previously validated Kepler planets, Kepler-289 b ($P=34.55$ days, $R_{\rm{P}}=2.15\pm0.10R_\oplus$) and Kepler-289-c ($P=125.85$ days, $R_{\rm{P}}=11.59\pm0.10R_\oplus$), through their transit timing variations (TTVs). We also exclude the possibility that these three planets reside in a $1:2:4$ Laplace resonance. The outer planet has very deep ($\sim1.3$), high signal-to-noise transits, which puts extremely tight constraints on its host star's stellar properties via Kepler's Third Law. The star PH3 is a young ($\sim1$ Gyr as determined by isochrones and gyrochronology), Sun-like star with $M_*=1.08\pm0.02M_\odot$, $R_*=1.00\pm0.02R_\odot$, and $T_{\rm{eff}}=5990\pm38$ K. The middle planet's large TTV amplitude ($\sim5$ hours) resulted either in non-detections or inaccurate detections in previous searches. A strong chopping signal, a shorter period sinusoid in the TTVs, allows us to break the mass-eccentricity degeneracy and uniquely determine the masses of the inner, middle, and outer planets to be $M=7.3\pm6.8M_\oplus$, $4.0\pm0.9M_\oplus$, and $M=132\pm17M_\oplus$, which we designate PH3 b, c, and d, respectively. Furthermore, the middle planet, PH3 c, has a relatively low density, $\rho=1.2\pm0.3$ g/cm$^3$ for a planet of its mass, requiring a substantial H/He atmosphere of $2.1^{+0.8}_{-0.3}$ by mass, and joins a growing population of low-mass, low-density planets.Comment: 21 pages, 10 figures, 5 tables, accepted into Ap

Hippocampal CA1 Transcriptional Profile of Sleep Deprivation: Relation to Aging and Stress

BACKGROUND: Many aging changes seem similar to those elicited by sleep-deprivation and psychosocial stress. Further, sleep architecture changes with age suggest an age-related loss of sleep. Here, we hypothesized that sleep deprivation in young subjects would elicit both stress and aging-like transcriptional responses. METHODOLOGY/PRINCIPAL FINDINGS: F344 rats were divided into control and sleep deprivation groups. Body weight, adrenal weight, corticosterone level and hippocampal CA1 transcriptional profiles were measured. A second group of animals was exposed to novel environment stress (NES), and their hippocampal transcriptional profiles measured. A third cohort exposed to control or SD was used to validate transcriptional results with Western blots. Microarray results were statistically contrasted with prior transcriptional studies. Microarray results pointed to sleep pressure signaling and macromolecular synthesis disruptions in the hippocampal CA1 region. Animals exposed to NES recapitulated nearly one third of the SD transcriptional profile. However, the SD-aging relationship was more complex. Compared to aging, SD profiles influenced a significant subset of genes. mRNA associated with neurogenesis and energy pathways showed agreement between aging and SD, while immune, glial, and macromolecular synthesis pathways showed SD profiles that opposed those seen in aging. CONCLUSIONS/SIGNIFICANCE: We conclude that although NES and SD exert similar transcriptional changes, selective presynaptic release machinery and Homer1 expression changes are seen in SD. Among other changes, the marked decrease in Homer1 expression with age may represent an important divergence between young and aged brain response to SD. Based on this, it seems reasonable to conclude that therapeutic strategies designed to promote sleep in young subjects may have off-target effects in the aged. Finally, this work identifies presynaptic vesicular release and intercellular adhesion molecular signatures as novel therapeutic targets to counter effects of SD in young subjects