Cerebellar c9RAN proteins associate with clinical and neuropathological characteristics of C9ORF72 repeat expansion carriers.

Clinical and neuropathological characteristics associated with G4C2 repeat expansions in chromosome 9 open reading frame 72 (C9ORF72), the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia, are highly variable. To gain insight on the molecular basis for the heterogeneity among C9ORF72 mutation carriers, we evaluated associations between features of disease and levels of two abundantly expressed "c9RAN proteins" produced by repeat-associated non-ATG (RAN) translation of the expanded repeat. For these studies, we took a departure from traditional immunohistochemical approaches and instead employed immunoassays to quantitatively measure poly(GP) and poly(GA) levels in cerebellum, frontal cortex, motor cortex, and/or hippocampus from 55 C9ORF72 mutation carriers [12 patients with ALS, 24 with frontotemporal lobar degeneration (FTLD) and 19 with FTLD with motor neuron disease (FTLD-MND)].

A systematic review of randomised controlled trials of radiotherapy for localised prostate cancer.

Background: Prostate cancer is the second most frequently diagnosed cancer and the sixth leading cause of cancer death in males. A systematic review of randomised controlled trials (RCTs) of radiotherapy and other non-pharmacological management options for localised prostate cancer was undertaken.

Methods: A search of thirteen databases was carried out until March 2014.

Development of ProCaRS Clinical Nomograms for Biochemical Failure-free Survival Following Either Low-Dose Rate Brachytherapy or Conventionally Fractionated External Beam Radiation Therapy for Localized Prostate Cancer.

Purpose: Although several clinical nomograms predictive of biochemical failure-free survival (BFFS) for localized prostate cancer exist in the medical literature, making valid comparisons can be challenging due to variable definitions of biochemical failure, the disparate distribution of prognostic factors, and received treatments in patient populations. The aim of this investigation was to develop and validate clinically-based nomograms for 5-year BFFS using the ASTRO II "Phoenix" definition for two patient cohorts receiving low-dose rate (LDR) brachytherapy or conventionally fractionated external beam radiation therapy (EBRT) from a large Canadian multi-institutional database.

Methods And Materials: Patients were selected from the GUROC (Genitourinary Radiation Oncologists of Canada) Prostate Cancer Risk Stratification (ProCaRS) database if they received (1) LDR brachytherapy ≥ 144 Gy (n=4208) or (2) EBRT ≥ 70 Gy  (n=822).

The role of radiation therapy in the treatment of metastatic castrate-resistant prostate cancer.

In the setting of castrate-resistant prostate cancer, patients present with a variety of symptoms, including bone metastases, spinal cord compression and advanced pelvic disease. Fortunately, a variety of radiotherapeutic options exist for palliation. This article focuses on these options, including both external beam radiotherapy and radiopharmaceuticals.

Diminutive colorectal polyp resection comparing hot and cold snare and cold biopsy forceps polypectomy. Results of a pilot randomized, single-center study (with videos).

Background: The optimal method of diminutive polypectomy (< 6 mm) is unknown.

Objective: To assess the rates of incomplete resection of diminutive polyps of the colon using three standard polyp resection techniques (hot snare, cold snare, and cold biopsy forceps).

Design: Randomized, pilot study.

Beyond Gene Inactivation: Evolution of Tools for Analysis of Serotonergic Circuitry.

In the brain, serotonin (5-hydroxytryptamine, 5-HT) controls a multitude of physiological and behavioral functions. Serotonergic neurons in the raphe nuclei give rise to a complex and extensive network of axonal projections throughout the whole brain. A major challenge in the analysis of these circuits is to understand how the serotonergic networks are linked to the numerous functions of this neurotransmitter.

Genome-wide association study of corticobasal degeneration identifies risk variants shared with progressive supranuclear palsy.

Corticobasal degeneration (CBD) is a neurodegenerative disorder affecting movement and cognition, definitively diagnosed only at autopsy. Here, we conduct a genome-wide association study (GWAS) in CBD cases (n=152) and 3,311 controls, and 67 CBD cases and 439 controls in a replication stage. Associations with meta-analysis were 17q21 at MAPT (P=1.

Efficacy of Ultraviolet (UV-C) Light in a Thin-Film Turbulent Flow for the Reduction of Milkborne Pathogens.

Nonthermal technologies are being investigated as viable alternatives to, or supplemental utilization, with thermal pasteurization in the food-processing industry. In this study, the effect of ultraviolet (UV)-C light on the inactivation of seven milkborne pathogens (Listeria monocytogenes, Serratia marcescens, Salmonella Senftenberg, Yersinia enterocolitica, Aeromonas hydrophila, Escherichia coli, and Staphylococcus aureus) was evaluated. The pathogens were suspended in ultra-high-temperature whole milk and treated at UV doses between 0 and 5000 J/L at a flow rate of 4300 L/h in a thin-film turbulent flow-through pilot system.

Nadir testosterone within first year of androgen-deprivation therapy (ADT) predicts for time to castration-resistant progression: a secondary analysis of the PR-7 trial of intermittent versus continuous ADT.

Purpose: Three small retrospective studies have suggested that patients undergoing continuous androgen deprivation (CAD) have superior survival and time to progression if lower castrate levels of testosterone (< 0.7 nmol/L) are achieved. Evidence from prospective large studies has been lacking.

Salvage low-dose-rate permanent seed brachytherapy for locally recurrent prostate cancer: Association between dose and late toxicity.

Purpose: Rates of late toxicity are higher for salvage treatment of local recurrence after prior radiotherapy. We present our experience with salvage prostate brachytherapy (BT) for local recurrence after definitive external beam radiotherapy with attention to the relationship between dose and late toxicity.

Methods And Materials: From 2005 to 2012, 18 patients with biopsy proven locally recurrent prostate cancer and negative staging received low-dose-rate BT with a prescribed dose of 130-144 Gy.

Improving complete EMR of colorectal neoplasia: a randomized trial comparing snares and injectate in the resection of large sessile colon polyps.

Background: There are few randomized studies examining efficacy of snares and agents in EMR.

Objective: To compare the use of a combined needle and snare unit with injectate versus a spiral wire and injectate (primary); saline solution versus hydroxypropyl methylcellulose (secondary).

Design: Prospective, randomized, factorial, single center.

Effect of aging and long-term erectile function after iodine-125 prostate brachytherapy.

Purpose: To evaluate long-term erectile function (EF) in men treated with iodine-125 prostate brachytherapy (PB) and to determine factors predictive for erectile dysfunction (ED), including natural decline because of aging.

Methods: Two thousand nine hundred twenty-nine patients (implanted July 1989-June 2012) with baseline EF and greater than 10-month followup (FU) are included. About 78.

The role of intermittent androgen deprivation therapy in the management of biochemically recurrent or metastatic prostate cancer.

Androgen deprivation therapy (ADT) is a well-established treatment for locally advanced, biochemically recurrent and metastatic prostate cancer. However, it is associated with significant side effects including hot flashes, loss of libido and erectile function, muscular atrophy, metabolic abnormalities, and osteoporosis. In attempt to mitigate the side effects of ADT while retaining the oncological benefits, an approach of intermittent ADT (IAD) has been investigated.

The potential of induced pluripotent stem cells in models of neurological disorders: implications on future therapy.

There is an urgent need for new and advanced approaches to modeling the pathological mechanisms of complex human neurological disorders. This is underscored by the decline in pharmaceutical research and development efficiency resulting in a relative decrease in new drug launches in the last several decades. Induced pluripotent stem cells represent a new tool to overcome many of the shortcomings of conventional methods, enabling live human neural cell modeling of complex conditions relating to aberrant neurodevelopment, such as schizophrenia, epilepsy and autism as well as age-associated neurodegeneration.

Erratum: Diminutive colorectal polyp resection comparing hot and cold snare and cold biopsy forceps polypectomy. Results of a pilot randomized, single-center study.

[This corrects the article DOI: 10.1055/s-0034-1390789.].

Brachytherapy improves biochemical failure-free survival in low- and intermediate-risk prostate cancer compared with conventionally fractionated external beam radiation therapy: a propensity score matched analysis.

Purpose: To compare, in a retrospective study, biochemical failure-free survival (bFFS) and overall survival (OS) in low-risk and intermediate-risk prostate cancer patients who received brachytherapy (BT) (either low-dose-rate brachytherapy [LDR-BT] or high-dose-rate brachytherapy with external beam radiation therapy [HDR-BT+EBRT]) versus external beam radiation therapy (EBRT) alone.

Methods And Materials: Patient data were obtained from the ProCaRS database, which contains 7974 prostate cancer patients treated with primary radiation therapy at four Canadian cancer institutions from 1994 to 2010. Propensity score matching was used to obtain the following 3 matched cohorts with balanced baseline prognostic factors: (1) low-risk LDR-BT versus EBRT; (2) intermediate-risk LDR-BT versus EBRT; and (3) intermediate-risk HDR-BT+EBRT versus EBRT.

Deformable image registration for defining the postimplant seroma in permanent breast seed implant brachytherapy.

Purpose: To demonstrate the benefit of deformable image registration (DIR) to define postimplant seromas in permanent breast seed implants (PBSIs) by adapting preimplant seromas to postimplant images.

Methods And Materials: Planning and Day 0 CT scans from 15 consecutive PBSI patients were included. Seromas were contoured on the preimplant CTs.

Association of MAPT haplotypes with Alzheimer's disease risk and MAPT brain gene expression levels.

Introduction: MAPT encodes for tau, the predominant component of neurofibrillary tangles that are neuropathological hallmarks of Alzheimer's disease (AD). Genetic association of MAPT variants with late-onset AD (LOAD) risk has been inconsistent, although insufficient power and incomplete assessment of MAPT haplotypes may account for this.

Methods: We examined the association of MAPT haplotypes with LOAD risk in more than 20,000 subjects (n-cases = 9,814, n-controls = 11,550) from Mayo Clinic (n-cases = 2,052, n-controls = 3,406) and the Alzheimer's Disease Genetics Consortium (ADGC, n-cases = 7,762, n-controls = 8,144).

Electrical stimulation using conductive polymer polypyrrole promotes differentiation of human neural stem cells: a biocompatible platform for translational neural tissue engineering.

Conductive polymers (CPs) are organic materials that hold great promise for biomedicine. Potential applications include in vitro or implantable electrodes for excitable cell recording and stimulation and conductive scaffolds for cell support and tissue engineering. In this study, we demonstrate the utility of electroactive CP polypyrrole (PPy) containing the anionic dopant dodecylbenzenesulfonate (DBS) to differentiate novel clinically relevant human neural stem cells (hNSCs).

Stability of increased adenoma detection at colonoscopy. Follow-up of an endoscopic quality improvement program-EQUIP-II.

Objectives: We recently completed a randomized controlled trial of an endoscopic quality improvement program (EQUIP) that demonstrated an improved adenoma detection rate (ADR) through simple educational interventions. The aim of this study (phase III) is to examine whether the improvement in ADR in the trained endoscopists remained stable with further follow-up.

Methods: We prospectively followed up 15 staff endoscopists who had previously been randomized to a quality improvement intervention.

Long-term oncologic outcomes of radical prostatectomy compared with brachytherapy-based approaches for intermediate- and high-risk prostate cancer.

Purpose: To review the recently published contemporary long-term outcomes from tertiary care urologic practices comparing brachytherapy-based management strategies and radical prostatectomy (RP) across intermediate- and high-risk groups.

Methods And Materials: Literature was reviewed for the past 5 years under the search terms localized prostate cancer, outcomes, brachytherapy, and adical prostatectomy. Abstracts were reviewed and excluded if results were not reported according to the recognized risk groupings or if followup was less than 5 years.