Translational models for vascular cognitive impairment: a review including larger species.

BACKGROUND: Disease models are useful for prospective studies of pathology, identification of molecular and cellular mechanisms, pre-clinical testing of interventions, and validation of clinical biomarkers. Here, we review animal models relevant to vascular cognitive impairment (VCI). A synopsis of each model was initially presented by expert practitioners. Synopses were refined by the authors, and subsequently by the scientific committee of a recent conference (International Conference on Vascular Dementia 2015). Only peer-reviewed sources were cited. METHODS: We included models that mimic VCI-related brain lesions (white matter hypoperfusion injury, focal ischaemia, cerebral amyloid angiopathy) or reproduce VCI risk factors (old age, hypertension, hyperhomocysteinemia, high-salt/high-fat diet) or reproduce genetic causes of VCI (CADASIL-causing Notch3 mutations). CONCLUSIONS: We concluded that (1) translational models may reflect a VCI-relevant pathological process, while not fully replicating a human disease spectrum; (2) rodent models of VCI are limited by paucity of white matter; and (3) further translational models, and improved cognitive testing instruments, are required

PANDA Phase One - PANDA collaboration

The Facility for Antiproton and Ion Research (FAIR) in Darmstadt, Germany, provides unique possibilities for a new generation of hadron-, nuclear- and atomic physics experiments. The future antiProton ANnihilations at DArmstadt (PANDA or P¯ANDA) experiment at FAIR will offer a broad physics programme, covering different aspects of the strong interaction. Understanding the latter in the non-perturbative regime remains one of the greatest challenges in contemporary physics. The antiproton–nucleon interaction studied with PANDA provides crucial tests in this area. Furthermore, the high-intensity, low-energy domain of PANDA allows for searches for physics beyond the Standard Model, e.g. through high precision symmetry tests. This paper takes into account a staged approach for the detector setup and for the delivered luminosity from the accelerator. The available detector setup at the time of the delivery of the first antiproton beams in the HESR storage ring is referred to as the Phase One setup. The physics programme that is achievable during Phase One is outlined in this paper

The authors reply: Safety and feasibility of platelet rich fibrin matrix injections for treatment of common urologic conditions

Purpose: Autologous platelet rich plasma (PRP) is used increasingly in a variety of settings. PRP injections have been used for decades to improve angiogenesis and wound healing. They have also been offered commercially in urology with little to no data on safety or efficacy. PRP could theoretically improve multiple urologic conditions, such as erectile dysfunction (ED), Peyronie's disease (PD), and stress urinary incontinence (SUI). A concern with PRP, however, is early washout, a situation potentially avoided by conversion to platelet rich fibrin matrix (PRFM). Before clinical trials can be performed, safety analysis is desirable. We reviewed an initial series of patients receiving PRFM for urologic pathology to assess safety and feasibility. Materials and Methods: Data were reviewed for patients treated with PRFM at our center from November 2012 to July 2017. Patients were observed immediately post-injection and at follow-up for complications and tolerability. Where applicable, International Index of Erectile Function (IIEF-5) scores were reviewed before and after injections for ED and/or PD. Pad use data was collected pre/post injection for SUI. Results: Seventeen patients were identified, with a mean receipt of 2.1 injections per patient. Post-procedural minor adverse events were seen in 3 men, consisting of mild pain at injection site and mild penile bruising. No patients experienced complications at follow-up. No decline was observed in men completing pre/post IIEF-5 evaluations. Conclusions: PRFM appears to be a safe and feasible treatment modality in patients with urologic disease. Further placebo-controlled trials are warranted

Infection following penile prosthesis placement at an academic training center remains low despite involvement of surgeons-in-training

Purpose: Primary care providers harbor misconceptions regarding penile prosthetic surgery, largely overestimating the rate of infection. Rates of infection following surgery for primary placement and revision are estimated as 1% to 3% and 10% to 18%, respectively. Our objective was to determine the contemporary incidence of infection following inflatable penile prostheses surgery at an academic training center where surgeons-in-training are routinely involved. Materials and Methods: Review of a prospectively collected single-surgeon database was performed. All cases of inflatable penile prostheses placement from January 2011 through June 2017 were reviewed. Information regarding training level of assistant surgeon(s) was collected, and follow-up data was compiled regarding postoperative infections and need for revision surgery. Results: Three hundred nine cases meeting inclusion criteria were identified. Mean patient age was 64.2 years, and mean follow-up was 28.7 months. Distribution involved 257 (83.2%) for primary placement, 45 (14.6%) for removal/replacement, and 7 (2.3%) in setting of prior device removal. Diabetes was noted in 31.1% of men. Surgeon-in-training involvement was noted in 100% of cases. Infection was confirmed in a patient who had skin breakdown over an area of corporal reconstruction with polytetrafluoroethylene. The overall postoperative infection rate was 0.3%. Conclusions: In this series from an academic training center, infection following penile prosthetic surgery is low, similar to other centers of excellence, even with 100% involvement of surgeons-in-training. This data should be used to better inform primary care providers and members of the general public potentially interested in restoration of sexual function

Understanding the dopaminergic pathway relative to men's sexual dysfunction in patients with Parkinson's disease: a narrative review with implications for future research

Parkinson's disease (PD) is often most recognized for motor symptoms but associated non-motor symptoms such as sexual dysfunction can significantly impact quality of life. This condition involves a hormonal disruption and has a predilection for male patients, yet there are no formal guidelines for screening or management of sexual health pathology in these patients. While prior publications have addressed the presence of sexual dysfunction (SD) among men with PD, there has been a paucity of work examining the hypothalamic-pituitary-gonadal (HPG) axis and the interplay between dopamine, prolactin (PRL), and testosterone. This review provides an overview of data extracted from the existing peer-reviewed literature regarding hormonal and sexual health changes in men with PD and the impact of dopaminergic and/or androgen replacement therapy. Furthermore, while some research suggests that PD patients are at higher risk for prolactin elevation and testosterone deficiency, heterogeneity of the data limits extrapolation. Additionally, data related to pharmacologic optimization of the HPG axis in this patient population is similarly limited. Prospective studies are needed to better characterize the hormonal pathophysiology of PD as it relates to sexual dysfunction such that men at risk can be effectively identified so as to offer interventions that may improve quality of life

An evaluation of the Manufacturer And User Facility Device Experience database that inspired the United States Food and Drug Administration's Reclassification of transvaginal mesh

Purpose: To assess the utility of the Manufacturer And User Facility Device Experience (MAUDE) database in objectively capturing adverse events for transvaginal mesh in the United States. Materials and Methods: We reviewed 1,103 individual medical device reports submitted to the MAUDE database that inspired the United States (US) Food and Drug Administration's 2008 Public Health Notification. Entries were compiled into a categorical database that reported manufacturer, brand, reporter type, report source, and type of adverse event. Results: There were numerous examples of missing, duplicated, and non-standardized entries. Analysis revealed 64 reports with duplicated information, and six reports representing multiple patients. Forty-seven percent of medical device reports did not identify a reporter source. At least 28% of reported devices are no longer on the US market. There was wide variability in the quality and completeness of submitted reports and true adverse event rates could not be accurately calculated because the number of total cases was unknown. Conclusions: The MAUDE database was limited in its ability to collect, quantify, and standardize real-life adverse events related to transvaginal mesh. While it functions to collect information related to isolated adverse events, systematic limitations of the MAUDE database, that no doubt extend to other medical devices, necessitate the development of new reporting systems. Alternatives are under development, which may allow regulators to more accurately scrutinize the safety profiles of specific medical devices