A prospective, multicenter head-to-head comparative study in patients with primary high-risk prostate cancer investigating the bone lesion detection of conventional imaging and F-PSMA-PET/CT.

Purpose: Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) is an emerging staging tool for patients with primary high-risk prostate cancer (PCa). Patients with primary metastatic disease are staged using PSMA-PET/CT imaging, while previously published randomized clinical trials relied on conventional imaging (i.e.

Management impact of F-DCFPyL PET/CT in hormone-sensitive prostate cancer patients with biochemical recurrence after definitive treatment: a multicenter retrospective study.

Purpose: The aim of this study was to investigate whether an early, accurate identification of disease using F-DCFPyL PET/CT imaging resulted in a change of decision on treatment management, for individual patients with biochemically recurrent (BCR), hormone-sensitive prostate cancer.

Methods: In this retrospective study, a total of 253 patients with BCR who underwent restaging F-DCFPyL PET/CT were assessed. Two urologists specialized in uro-oncology were asked to formulate a preferred treatment for each patient before and after knowing the results of the F-DCFPyL PET/CT.

Clinical verification of 18F-DCFPyL PET-detected lesions in patients with biochemically recurrent prostate cancer.

Purpose: Radiolabeled Prostate-Specific Membrane Antigen (PSMA) PET/CT is the current standard-of-care for lesion detection in patients with biochemically recurrent (BCR) prostate cancer (PCa). However, rigorous verification of detected lesions is not always performed in routine clinical practice. To aid future 18F-radiolabeled PSMA PET/CT interpretation, we aimed to identify clinical/imaging characteristics that increase the likelihood that a PSMA-avid lesion is malignant.

Design and Synthesis of Selective Phosphodiesterase 4D (PDE4D) Allosteric Inhibitors for the Treatment of Fragile X Syndrome and Other Brain Disorders.

Novel pyridine- and pyrimidine-based allosteric inhibitors are reported that achieve PDE4D subtype selectivity through recognition of a single amino acid difference on a key regulatory domain, known as UCR2, that opens and closes over the catalytic site for cAMP hydrolysis. The design and optimization of lead compounds was based on iterative analysis of X-ray crystal structures combined with metabolite identification. Selectivity for the activated, dimeric form of PDE4D provided potent memory enhancing effects in a mouse model of novel object recognition with improved tolerability and reduced vascular toxicity over earlier PDE4 inhibitors that lack subtype selectivity.

Preoperative CSF Melatonin Concentrations and the Occurrence of Delirium in Older Hip Fracture Patients: A Preliminary Study.

Background: Delirium is characterized by disturbances in circadian rhythm. Melatonin regulates our circadian rhythm. Our aim was to compare preoperative cerebrospinal fluid (CSF) melatonin levels in patients with and without postoperative delirium.

Discovery of potent macrocyclic HCV NS5A inhibitors.

HCV NS5A inhibitors have demonstrated impressive in vitro virologic profiles in HCV replicon assays and robust HCV RNA titer reduction in the clinic making them attractive components for inclusion in an all oral fixed-dose combination (FDC) regimen for the treatment of HCV infection. Merck's effort in this area identified MK-4882 and MK-8325 as early development leads. Herein, we describe the discovery of potent macrocyclic NS5A inhibitors bearing the MK-8325 or MK-4882 core structure.

Population based study of predictors of adverse pathology among candidates for active surveillance with Gleason 6 prostate cancer.

Purpose: Approximately a third of prostate cancer cases with a Gleason score of 6 are upgraded at radical prostatectomy. We studied trends and predictors of upgrading and up staging among men with Gleason 6 prostate cancer who were potential candidates for active surveillance in a population based cohort.

Materials And Methods: From 2007 to 2011, 13,159 men were diagnosed with Gleason 6, clinical stage T1c/T2 prostate cancer in the NPCR (National Prostate Cancer Register of Sweden).

Systematic review of complications of prostate biopsy.

Context: Prostate biopsy is commonly performed for cancer detection and management. The benefits and risks of prostate biopsy are germane to ongoing debates about prostate cancer screening and treatment.

Objective: To perform a systematic review of complications from prostate biopsy.

4-Phenyl tetrahydroisoquinolines as dual norepinephrine and dopamine reuptake inhibitors.

Novel 4-phenyl tetrahydroisoquinolines that inhibit both dopamine and norepinephrine transporters were designed and prepared. In this Letter, we describe the synthesis, in vitro activity and associated structure-activity relationships of this series. We also report the ex vivo NET occupancy of a representative compound, 41.

Clinical differentiation between acute appendicitis and acute mesenteric lymphadenitis in children.

Introduction: Acute mesenteric lymphadenitis in children has a clinical presentation very similar to that of acute appendicitis. The aim of this study was to evaluate whether it is possible to clinically differentiate between acute appendicitis and acute mesenteric lymphadenitis in children.

Methods: A prospective cohort analysis was performed for all children (<17 years) presenting to the emergency department of our institution with acute abdominal pain between June 2005 and July 2006.

A new chemical tool for exploring the physiological function of the PDE2 isozyme.

Oxindole (2) is a potent and selective PDE2 inhibitor with a favorable ADME, physiochemical and pharmacokinetic profile to allow for use as a chemical tool in elucidating the physiological role of PDE2.