Antiviral Development for the Polio Endgame: Current Progress and Future Directions.

As the world is approaching the eradication of wild poliovirus serotype 1, the last of the three wild types, the question of how to maintain a polio-free world becomes imminent. To mitigate the risk of sporadic vaccine-associated paralytic polio (VAPP) caused by oral polio vaccines (OPVs) that are routinely used in global immunization programs, the Polio Antivirals Initiative (PAI) was established in 2006. The primary goal of the PAI is to facilitate the discovery and development of antiviral drugs to stop the excretion of immunodeficiency-associated vaccine-derived poliovirus (iVDPV) in B cell-deficient individuals.

An automated assay platform for the evaluation of antiviral compounds against polioviruses.

High-throughput screening requires assays that have flexibility to test large numbers of specimens while being accurate to ensure reproducibility across all specimens and variables tested. Previously, we used a low-throughput, cell-based assay to identify compounds with antiviral activity against polioviruses. In this report, we report the development and implementation of a high-throughput automation platform for the identification of compounds with antiviral activity against polioviruses.

The effects of a low carbohydrate diet on erectile function and serum testosterone levels in hypogonadal men with metabolic syndrome: a randomized clinical trial.

Purpose: Metabolic syndrome is a risk factor for several diseases. The relationship between metabolic syndrome and hypogonadism is well known. Our objetive is to assess whether a low carbohydrate diet can increase total serum testosterone and improve erectile function in hypogonadal men with metabolic syndrome.

An automated high-throughput enterovirus D68 microneutralization assay platform.

Virus neutralization assays, widely used to detect and quantify antibodies induced by virus infection, are considered the gold standard for enterovirus serology testing. Conventional microneutralization assays have been used to assess enterovirus D68 (EV-D68) seroprevalence. While manual or automated 96-well assays are valuable, higher-density assays that increase throughput provide the opportunity to more efficiently screen large, population-based serology collections, as well as to test sample sets against multiple virus strains on the same plate or within the same run.

Weight Loss Through Bariatric Surgery in Men Presents Beneficial Effects on Sexual Function, Symptoms of Testosterone Deficiency, and Hormonal Profile.

Introduction: Male obesity has a negative correlation with plasma testosterone (T) levels and sexual function (SF).

Aim: To evaluate the effect of weight loss through bariatric surgery (BS) on SF, low T symptoms, and hormonal profiles in obese men.

Methods: Thirty-three men who underwent BS participated in this cohort study.

Antifungal Triazole Posaconazole Targets an Early Stage of the Parechovirus A3 Life Cycle.

Viruses in species () are associated with a wide variety of clinical manifestations. Parechovirus A3 (PeV-A3) is known to cause sepsis-like illness, meningitis, and encephalitis in infants and young children. To date, no specific therapies are available to treat PeV-A3-infected children.

Effects of perioperative pelvic floor muscle training on early recovery of urinary continence and erectile function in men undergoing radical prostatectomy: a randomized clinical trial.

Aims: Radical prostatectomy (RP) can result in urinary incontinence (UI) and erectile dysfunction (ED), which negatively impact quality of life (QoL). This study aimed to evaluate the effects of a perioperative pelvic floor muscle training (PFMT) program versus usual care on early recovery of urinary continence and erectile function after RP.

Materials And Methods: Of 59 eligible men, 31 were randomly allocated into 2 groups: Group 1 (Control, N=15) received usual post-RP care; and Group 2 (Physical therapy, N=16) received two pre-RP physical therapist-guided PFMT sessions, including exercises and electromyographic biofeedback, and verbal and written instructions to continue PFMT until RP, which was then resumed after urethral catheter removal.

In Vitro Antiviral Activity of New Oxazoline Derivatives as Potent Poliovirus Inhibitors.

The final stages of polio eradication are proving more difficult than the early phases, and the development of effective drugs and treatments is considered a priority; thus, the research is ongoing. A screening of our in-house chemical library against poliovirus Sabin strains led to the identification of compounds 5 and 6 as hits active at submicromolar concentrations. Derivatives of these compounds were synthesized as a preliminary structure-activity-relationship study.

Oxidative stress in the bladder of men with LUTS undergoing open prostatectomy: a pilot study.

Purpose: This study aims to evaluate the link between preoperative parameters and oxidative stress (OS) markers in the bladder wall of men undergoing open prostatectomy.

Materials And Methods: From July 2014 to August 2016, men aged ≥ 50 years and presenting with LUTS were prospectively enrolled. Preoperative assessment included validated questionnaires (IPSS and OAB - V8), lower urinary tract ultrasound and urodynamics.

Incidence and risk factors for retinopathy of prematurity: a retrospective cohort study.

Background And Objectives: Advances in neonatal care promoted increased survival rates of preterm infants, with a consequent increase in the number of children affected by retinopathy of prematurity (ROP). This study estimates the incidence of ROP and evaluates potential risk factors associated.

Methods: A retrospective cohort study of preterm infants born in a tertiary neonatal intensive care unit was conducted from March 2005 to August 2015.

Testosterone replacement maintains smooth muscle content in the corpus cavernosum of orchiectomized rats.

Objective: To evaluate the effects of testosterone (T) on the maintenance of corpus cavernosum (CC) structure and apoptosis.

Methods: Animals were divided into three groups: sham operation group ( = 8) underwent sham operation; Orchiectomized (Orchiec)+ oily vehicle group ( = 8) underwent bilateral orchiectomy and received a single dose of oily vehicle by intramuscular injection (i.m.

Prognostic impact of changes in base excision repair machinery in sporadic colorectal cancer.

Objective: to evaluate the prognostic value of base excision repair proteins in sporadic colorectal cancer.

Methods: Pre-treatment tumor samples from 72 patients with sporadic colorectal adenocarcinoma were assessed for APC, MPG, Polβ, XRCC1 and Fen1 expression by immunohistochemistry. The associations of molecular data were analyzed in relation to clinical features and TNM staging as a prognosis predictor and disease-free survival.

Antifungal azoles itraconazole and posaconazole exhibit potent in vitro antiviral activity against clinical isolates of parechovirus A3 (Picornaviridae).

Parechovirus A3 (Par-A3, formerly human parechovirus 3) is an emerging viral infection of the central nervous system in children. We used an automated, homogeneous, cell based assay to identify itraconazole and posaconazole as inhibitors of Par-A3, with antiviral activity below concentrations clinically attainable in pediatric patients. Currently, there is no approved antiviral treatment for Par-A3 infection, despite numerous reports of serious Par-A3 disease in neonates and infants.

Collagen content in the bladder of men with LUTS undergoing open prostatectomy: A pilot study.

Aims: To evaluate the collagen content in the bladder wall of men undergoing open prostate surgery.

Methods: From July 2014 to August 2016, men aged ≥ 50 years, presenting LUTS and undergoing open prostate surgery due to benign prostatic enlargement (BPE) or prostate cancer were prospectively enrolled. Preoperative assessment included validated questionnaires (IPSS and OAB-V8), lower urinary tract ultrasound, and urodynamics.

Low Testosterone Levels and Metabolic Syndrome in Aging Male.

Advances in medicine and progressive improvements in the health of the general population in developed countries have led to considerable increases in life expectancy over recent years. Metabolic syndrome (MetS) affects approximately 25% of the adult population and its prevalence is increasing all over the world. Central obesity plays an important role in emergence of MetS.

Antiviral Activity of Pocapavir in a Randomized, Blinded, Placebo-Controlled Human Oral Poliovirus Vaccine Challenge Model.

Background: Immunodeficient individuals who excrete vaccine-derived polioviruses threaten polio eradication. Antivirals address this threat.

Methods: In a randomized, blinded, placebo-controlled study, adults were challenged with monovalent oral poliovirus type 1 vaccine (mOPV1) and subsequently treated with capsid inhibitor pocapavir or placebo.

Total testosterone levels are correlated to metabolic syndrome components.

Introduction: Metabolic syndrome (MetS) is a constellation of interrelated risk factors of metabolic origin. Some studies suggest a possible link between low total testosterone (TT) levels and the presence of MetS.

Aim: To analyze the strength and independence of associations between TT and MetS components in non-diabetic men.

In Vitro Efficacy of Antiviral Compounds against Enterovirus D68.

In 2014, the United States experienced a large outbreak of severe respiratory illness associated with enterovirus D68 (EV-D68). We used a homogeneous, cell-based assay to assess the antiviral activity of compounds developed for EV/rhinovirus infection or other indications. Three of 15 compounds were highly active against all four strains tested (the prototype and three 2014 strains), with 50% effective concentrations of 0.

Effects of L-arginine and L-NAME on ischemia-reperfusion in rat liver.

Purpose: To evaluated the effects of L-arginine (a NO donor) and L-NAME (Nw-nitro-L-arginine methyl ester - a NOS inhibitor) on ischemia-reperfusion in rat livers.

Methods: One hundred fifty two male Wistar rats were divided into four groups: control (simulated surgery); hepatic IR; pretreatment with L-arginine plus hepatic IR; and L-NAME plus hepatic IR. The hepatocellular damage was evaluated at the first, third and seventh days after the procedures through the alanine-aminotransferase (ALT) and aspartate-aminotransaminase (AST) levels, as well as histopathological features: vascular congestion (VC); steatosis (STE); necrosis (NEC); and inflammatory infiltration (INF).

First use of investigational antiviral drug pocapavir (v-073) for treating neonatal enteroviral sepsis.

Neonatal enteroviral sepsis is a potentially fatal condition. Perinatally acquired infection and severe coagulopathy can be associated with a poor clinical outcome, and antiviral therapy is currently unavailable. Pocapavir (V-073) is an investigational drug candidate being developed for poliovirus indications, but also has variable antiviral activity against nonpolio enteroviruses.

H1PVAT is a novel and potent early-stage inhibitor of poliovirus replication that targets VP1.

A novel small molecule, H1PVAT, was identified as a potent and selective inhibitor of the in vitro replication of all three poliovirus serotypes, whereas no activity was observed against other enteroviruses. Time-of-drug-addition studies revealed that the compound interfered with an early stage of virus replication. Four independently-selected H1PVAT-resistant virus variants uniformly carried the single amino acid substitution I194F in the VP1 capsid protein.

Importance of prostate-specific antigen (PSA) as a predictive factor for concordance between the Gleason scores of prostate biopsies and RADICAL prostatectomy specimens.

Objective: To evaluate the concordance between the Gleason scores of prostate biopsies and radical prostatectomy specimens, thereby highlighting the importance of the prostate-specific antigen (PSA) level as a predictive factor of concordance.

Methods: We retrospectively analyzed 253 radical prostatectomy cases performed between 2006 and 2011. The patients were divided into 4 groups for the data analysis and dichotomized according to the preoperative PSA, <10 ng/mL and ≥10 ng/mL.

Anti-poliovirus activity of protease inhibitor AG-7404, and assessment of in vitro activity in combination with antiviral capsid inhibitor compounds.

The National Research Council has recommended that at least one, preferably two, polio antiviral drugs be developed as a supplement to the tools currently available for control of polio outbreaks post-eradication. The primary application of such drugs is expected to be the resolution of chronic poliovirus excretion in persons with primary immunodeficiency disorders. We have assessed the in vitro activity of AG-7404 (also known as "compound 1"), an inhibitor of picornaviral 3C protease, against a large panel of programmatically important poliovirus strains and its activity in combination with two poliovirus capsid inhibitors, V-073 and BTA798.

Neck circumference and central obesity are independent predictors of coronary artery disease in patients undergoing coronary angiography.

Excess of adiposity is a risk factor for coronary artery disease, but it remains unclear if the distribution of fat is an effect modifier or if the risk is mediate by hypertension, diabetes and dyslipidemia. We investigated the association of central in addition to general obesity with coronary artery disease (CAD). A case-control study was conducted in 376 patients, aged 40 years or more, with chronic coronary disease, undergoing elective coronary angiography.

Evaluation of endothelial function with brachial artery ultrasound in men with or without erectile dysfunction and classified as intermediate risk according to the Framingham Score.

Introduction: Flow-mediated vasodilation (FMD) of the brachial artery is a noninvasive tool used for endothelial function evaluation. There is increasing evidence that endothelial dysfunction is a common etiological factor for erectile dysfunction (ED) and cardiovascular events.

Aim: To evaluate endothelial function with a high-resolution ultrasound device, to assess FMD in men diagnosed with ED and without clinical evidence of significant atherosclerotic disease, classified as "intermediate risk" according to the Framingham risk score (FRS).