A riboside hydrolase that salvages both nucleobases and nicotinamide in the auxotrophic parasite Trichomonas vaginalis.

Pathogenic parasites of the Trichomonas genus are causative agents of sexually transmitted diseases affecting millions of individuals worldwide and whose outcome may include stillbirths and enhanced cancer risks and susceptibility to HIV infection. Trichomonas vaginalis relies on imported purine and pyrimidine nucleosides and nucleobases for survival, since it lacks the enzymatic activities necessary for de novo biosynthesis. Here we show that T.

Direct Measurement of Nucleoside Ribohydrolase Enzyme Activities in Cells Using F and C-Edited H NMR Spectroscopy.

Trichomoniasis is the most common nonviral sexually transmitted infection, affecting an estimated 275 million people worldwide. The causative agent is the parasitic protozoan . Although the disease itself is typically mild, individuals with trichomonal infections have a higher susceptibility to more serious conditions.

Outcomes in patients with moderate and asymptomatic severe aortic stenosis followed up in heart valve clinics.

Background: Heart valve clinics (HVC) have been introduced to manage patients with valvular heart disease within a multidisciplinary team.

Objective: To determine the outcome benefit of HVC approach compared with standard of care (SOC) for patients with moderate and asymptomatic severe aortic stenosis (mAS and asAS).

Methods: Single-centre, observational registry of patients with mAS and asAS with at least one cardiac ambulatory consultation at our Cardiovascular Centre.

Structure-Guided Insight into the Specificity and Mechanism of a Parasitic Nucleoside Hydrolase.

is the causative parasitic protozoan of the disease trichomoniasis, the most prevalent, nonviral sexually transmitted disease in the world. is a parasite that scavenges nucleosides from the host organism via catalysis by nucleoside hydrolase (NH) enzymes to yield purine and pyrimidine bases. One of the four NH enzymes identified within the genome of displays unique specificity toward purine nucleosides, adenosine and guanosine, but not inosine, and atypically shares greater sequence similarity to the pyrimidine hydrolases.

Comparative analysis of LVAD patients in regard of ischaemic or idiopathic cardiomyopathy: A propensity-score analysis of EUROMACS data.

Background: Despite recent advances in management of patients with advanced heart failure, mortality remains high. Aim of this study was to compare impact of different aetiology of ischaemic and idiopathic cardiomyopathy on early outcomes and long-term survival of patients after left ventricular assist device implantation.

Methods: European Registry for Patients with Mechanical Circulatory Support (EUROMACS) gathers clinical data and follow-up parameters of LVAD recipients.

Importance of In-Hospital Prospective Registry and Infectious Endocarditis Heart Team to Monitor and Improve Quality of Care in Patients with Infectious Endocarditis.

Aim: To investigate the value of prospective in-hospital registry data and the impact of an infectious endocarditis heart team approach (IEHT) on improvement in quality of care and monitor outcomes in hospitalized patients with IE.

Methods: Between December 2014 and the end of 2019, 160 patients were hospitalized in one centre with the definite diagnosis of infectious endocarditis (IE) and entered in a prospective registry. From 2017, an IEHT was introduced.

Changes in surgical revascularization strategy after fractional flow reserve.

Aims: In the randomized GRAFFITI trial, surgeons drew their strategy based on coronary angiography. When patients were randomized to fractional flow reserve (FFR)-guidance, surgeons were informed of the FFR values and asked to redraw their strategy. The aim of this study was to investigate the changes induced by FFR knowledge.

Coronary Artery Bypass Grafting or Fractional Flow Reserve-Guided Percutaneous Coronary Intervention in Diabetic Patients With Multivessel Disease.

Background: In diabetic patients with multivessel coronary artery disease, coronary artery bypass grafting (CABG) has shown long-term benefits over percutaneous coronary intervention (PCI). Physiology-guided PCI has shown to improve clinical outcomes in multivessel coronary artery disease, though its impact in diabetic patients has never been investigated. We evaluated long-term clinical outcomes of diabetic patients with multivessel coronary artery disease treated with fractional flow reserve (FFR)-guided PCI compared with CABG.

Reasons for Conversion and Adverse Intraoperative Events in Robotically Enhanced Minimally Invasive Coronary Artery Revascularization.

Objective: The transition from sternotomy access to minimally invasive coronary artery bypass grafting is associated with steep learning curves. This study reports the reasons for sternotomy conversions from robotically enhanced minimally invasive direct coronary artery bypass grafting (RE-MIDCAB) and describes potential risk reduction strategies.

Methods: The perioperative data of 759 RE-MIDCAB patients (mean age 65.

Discovery of Ligand-Efficient Scaffolds for the Design of Novel Uridine Nucleoside Ribohydrolase Inhibitors Using Fragment Screening.

Trichomoniasis is caused by the parasitic protozoan . The increasing prevalence of strains resistant to the current 5-nitroimidazole treatments creates the need for novel therapies. cannot synthesize purine and pyrimidine rings and requires salvage pathway enzymes to obtain them from host nucleosides.

Fractional flow reserve in patients with reduced ejection fraction.

Aims: Fractional flow reserve (FFR) has never been investigated in patients with reduced ejection fraction and associated coronary artery disease (CAD). We evaluated the impact of FFR on the management strategies of these patients and related outcomes.

Methods And Results: From 2002 to 2010, all consecutive patients with left ventricular ejection fraction (LVEF) ≤50% undergoing coronary angiography with ≥1 intermediate coronary stenosis [diameter stenosis (DS)% 50-70%] treated based on angiography (Angiography-guided group) or according to FFR (FFR-guided group) were screened for inclusion.

Results of primary biventricular support: an analysis of data from the EUROMACS registry.

Objectives: The purpose of this study was to describe pre- and postoperative data from the EUROMACS registry with regard to indications, for and survival and complication rates of patients with primary continuous flow and pulsatile biventricular long-term assist devices (BiVADs) versus total artificial hearts (TAHs) or left ventricular assist devices (LVADs) + short-term right ventricular assist device (RVAD) implants.

Methods: We investigated patients who received implants between 1 January 2011 and 21 October 2017. Clinical baseline information about comorbidities, laboratory results, medical and device therapies and echocardiographic, haemodynamic and right ventricle (RV) parameters were evaluated along with the rates of deaths and complications.

NMR-Based Activity Assays for Determining Compound Inhibition, IC50 Values, Artifactual Activity, and Whole-Cell Activity of Nucleoside Ribohydrolases.

NMR spectroscopy is often used for the identification and characterization of enzyme inhibitors in drug discovery, particularly in the context of fragment screening. NMR-based activity assays are ideally suited to work at the higher concentrations of test compounds required to detect these weaker inhibitors. The dynamic range and chemical shift dispersion in an NMR experiment can easily resolve resonances from substrate, product, and test compounds.

Graft patency after FFR-guided versus angiography-guided coronary artery bypass grafting: the GRAFFITI trial.

Aims: The aim of this study was to assess prospectively the clinical benefits of fractional flow reserve (FFR) in guiding coronary artery bypass grafting (CABG).

Methods And Results: GRAFFITI is a single-blinded, prospective, multicentre, randomised controlled trial of FFR-guided versus angiography-guided CABG. We enrolled patients undergoing coronary angiography, having a significantly diseased left anterior descending artery or left main stem and at least one more major coronary artery with intermediate stenosis, assessed by FFR.

The Belgian experience with concomitant surgical ablation of atrial fibrillation: a multi-centre prospective registry.

The Belgian 'National Institute for Health and Disability Insurance (RIZIV-INAMI)' requested prospective collection of data on all ablations in Belgium to determine the outcomes of surgical ablation of atrial fibrillation (AF) during concomitant cardiac surgery. 890 patients undergoing concomitant ablation for AF between 2011 and 2016 were prospectively followed. Freedom from AF with and without anti-arrhythmic drugs was calculated for 817 patients with follow-up beyond the 3-month blanking period and for 574 patients with sufficient rhythm-related follow-up consisting of at least one Holter registration or a skipped Holter due to AF being evident on ECG.

Ligand-Efficient Inhibitors of Trichomonas vaginalis Adenosine/Guanosine Preferring Nucleoside Ribohydrolase.

Trichomoniasis is caused by the parasitic protozoan Trichomonas vaginalis and is the most prevalent, nonviral sexually transmitted disease. The parasite has shown increasing resistance to the current 5-nitroimidazole therapies indicating the need for new therapies with different mechanisms. T.

Six-Year Follow-Up of Fractional Flow Reserve-Guided Versus Angiography-Guided Coronary Artery Bypass Graft Surgery.

Background: Fractional flow reserve (FFR)-guided coronary artery bypass graft (CABG) surgery has been associated with lower number of graft anastomoses, lower rate of on-pump surgery, and higher graft patency rate as compared with angiography-guided CABG surgery. However, no clinical benefit has been reported to date.

Methods And Results: Consecutive patients (n=627) treated by CABG between 2006 and 2010 were retrospectively included.

Druggability of the guanosine/adenosine/cytidine nucleoside hydrolase from Trichomonas vaginalis.

Trichomonas vaginalis infects approximately 300 million people worldwide annually. Infected individuals have a higher susceptibility to more serious conditions such as cervical and prostate cancer. The parasite has developed increasing resistance to current drug therapies, with an estimated 5% of clinical cases resulting from resistant strains, creating the need for new therapeutic strategies with novel mechanisms of action.

Endoscopic port access surgery for isolated atrioventricular valve endocarditis.

Objectives: Our goal was to report the clinical and echocardiographic outcomes of endoscopic port access surgery for isolated active and convalescent atrioventricular valve endocarditis (AVVE).

Methods: Our current surgical team performed endoscopic port access surgery in 66 consecutive patients with isolated AVVE (mean age, 65.5 ± 12.

Reasons for conversion and adverse intraoperative events in Endoscopic Port Access™ atrioventricular valve surgery and minimally invasive aortic valve surgery.

Objectives: This study reports the factors that contribute to sternotomy conversions (SCs) and adverse intraoperative events in minimally invasive aortic valve surgery (MI-AVS) and minimally invasive Endoscopic Port Access™ atrioventricular valve surgery (MI-PAS).

Methods: In total, 3780 consecutive patients with either aortic valve disease or atrioventricular valve disease underwent minimally invasive valve surgery (MIVS) at our institution between 1 February 1997 and 31 March 2016. MI-AVS was performed in 908 patients (mean age 69.

Understanding Treatment Burden and Quality of Life Impact of Participating in an Early-Phase Pediatric Oncology Clinical Trial: A Pilot Study.

Purpose: Early-phase clinical trials (EPTs) have led to new, more effective treatment options for children with cancer. Despite the extensive use of EPTs in pediatric oncology, little is known about parent and child experiences during EPT participation. The purposes of this pilot study were to assess the feasibility and preliminary results of having children with cancer and their parents complete measures of treatment burden and quality of life (QOL) concurrent with EPT participation.

Endoscopic Port Access Surgery for Late Orthotopic Cardiac Transplantation Atrioventricular Valve Disease.

Background: The study aim was to present details of the perioperative and long-term outcomes of redo-endoscopic port access surgery (REPAS) for late atrioventricular valve disease (AVVD) in orthotopic cardiac transplant (OCT) patients.

Methods: Between February 2004 and October 2015, REPAS was performed for late AVVD in seven consecutive OCT patients (mean age 57.9 ± 17.

Intratumoral Injection of HSV1716, an Oncolytic Herpes Virus, Is Safe and Shows Evidence of Immune Response and Viral Replication in Young Cancer Patients.

HSV1716 is an oncolytic herpes simplex virus-1 (HSV-1) studied in adults via injection into the brain and superficial tumors. To determine the safety of administering HSV1716 to pediatric patients with cancer, we conducted a phase I trial of image-guided injection in young patients with relapsed or refractory extracranial cancers. We delivered a single dose of 10 to 10 infectious units of HSV1716 via computed tomography-guided intratumoral injection and measured tumor responses by imaging.