Multigenic Disease and Bilineal Inheritance in Dilated Cardiomyopathy Is Illustrated in Nonsegregating LMNA Pedigrees.

Background: We have previously described 19 pedigrees with apparent lamin ()-related dilated cardiomyopathy (DCM) manifesting in affected family members across multiple generations. In 6 of 19 families, at least 1 individual with idiopathic DCM did not carry the family's variant. We hypothesized that additional genetic cause may underlie DCM in these families.

A 10 year study of hospitalized atrial fibrillation-related stroke in England and its association with uptake of oral anticoagulation.

Aims: To determine whether changing patterns of anticoagulant use in atrial fibrillation (AF) have impacted on stroke rates in England.

Methods And Results: English national databases, 2006-2016, were interrogated to assess stroke admissions and oral anticoagulant use. The number of patients with known AF increased linearly from 692 054 to 983 254 (prevalence 1.

The Diverse Genomic Landscape of Clinically Low-risk Prostate Cancer.

Background: Among men with clinically low-risk prostate cancer, we have previously documented heterogeneity in terms of clinical characteristics and genomic risk scores.

Objective: To further study the underlying tumor biology of this patient population, by interrogating broader patterns of gene expression among men with clinically low-risk tumors.

Design, Setting, And Participants: Prostate biopsies from 427 patients considered potentially suitable for active surveillance underwent central pathology review and genome-wide expression profiling.

Laparoscopic extended liver resection: are postoperative outcomes different?

Background: Although laparoscopic major hepatectomy (LMH) is becoming increasingly common in specialized centers, data regarding laparoscopic extended major hepatectomies (LEMH) and their outcomes are limited. The aim of this study was to compare the perioperative characteristics and postoperative outcomes of LEMH to standard LMH.

Methods: All patients who underwent purely laparoscopic anatomical right or left hepatectomy and right or left trisectionectomy between February 1998 and January 2016 are enrolled.

Effectiveness of immunoglobulin prophylaxis in reducing clinical complications of hematopoietic stem cell transplantation: a systematic review and meta-analysis.

Background: Prophylactic immunoglobulin has been used with varying efficacy to reduce complications in hematopoietic stem cell transplant recipients.

Study Design And Methods: A systematic review and meta-analysis was conducted of randomized controlled trials that assessed clinical outcomes (overall survival, transplant-related mortality, graft-versus-host disease [GVHD], veno-occlusive disease [VOD], interstitial pneumonitis, disease relapse, cytomegalovirus [CMV] infection and disease, non-CMV infection) of immunoglobulin prophylaxis versus placebo in hematopoietic stem cell transplant recipients. MEDLINE, EMBASE, EBM Reviews, and the Cochrane Central Register of Controlled Trials were searched up to June 2017.

Development of a stress response therapy targeting aggressive prostate cancer.

Oncogenic lesions up-regulate bioenergetically demanding cellular processes, such as protein synthesis, to drive cancer cell growth and continued proliferation. However, the hijacking of these key processes by oncogenic pathways imposes onerous cell stress that must be mitigated by adaptive responses for cell survival. The mechanism by which these adaptive responses are established, their functional consequences for tumor development, and their implications for therapeutic interventions remain largely unknown.

Role of the HSPA9/HSC20 chaperone pair in promoting directional human iron-sulfur cluster exchange involving monothiol glutaredoxin 5.

Iron‑sulfur clusters are essential cofactors found across all domains of life. Their assembly and transfer are accomplished by highly conserved protein complexes and partners. In eukaryotes a [2Fe-2S] cluster is first assembled in the mitochondria on the iron‑sulfur cluster scaffold protein ISCU in tandem with iron, sulfide, and electron donors.

The water relations and xylem attributes of albino redwood shoots (Sequioa sempervirens (D. Don.) Endl.).

Plants that lack chlorophyll are rare and typically restricted to holoparasites that obtain their carbon, water and mineral resources from a host plant. Although not parasites in the traditional sense, albino foliage, such as the sprouts that sometimes develop from redwood tree trunks, are comparable in function. They occur sporadically, and can reach the size of shrubs and in rare cases, trees.

Introduction of clerking pro forma for surgical spinal patients at the Royal National Orthopaedic Hospital NHS Trust (London): an audit cycle.

As a tertiary referral centre of spinal surgery, the Royal National Orthopaedic Hospital (RNOH) handles hundreds of spinal cases a year, often with complex pathology and complex care needs. Despite this, issues were raised at the RNOH following lack of sufficient documentation of preoperative and postoperative clinical findings in spinal patients undergoing major surgery. This is not in keeping with guidelines provided by the Royal College of Surgeons.

Cancer survivorship care plans: Processes, effective strategies, and challenges in a Northern Plains rural state.

Objectives: Health systems face resource and time barriers to developing and implementing cancer survivorship care plans (SCPs) when active cancer treatment is completed. To address this problem, the South Dakota (SD) Department of Health partnered with two of SD's largest health systems to create the SD Survivorship Program. The purpose of this program evaluation study was to describe and compare SCP development and implementation at the two health systems.

An allogeneic 'off the shelf' therapeutic strategy for peripheral nerve tissue engineering using clinical grade human neural stem cells.

Artificial tissues constructed from therapeutic cells offer a promising approach for improving the treatment of severe peripheral nerve injuries. In this study the effectiveness of using CTX0E03, a conditionally immortalised human neural stem cell line, as a source of allogeneic cells for constructing living artificial nerve repair tissue was tested. CTX0E03 cells were differentiated then combined with collagen to form engineered neural tissue (EngNT-CTX), stable aligned sheets of cellular hydrogel.

Prevalence of Hypogammaglobulinemia in Adult Invasive Pneumococcal Disease.

Background: Patients with humoral immune deficiency are susceptible to invasive pneumococcal disease (IPD). This study estimates the prevalence of underlying hypogammaglobulinemia in admitted IPD cases and examines whether IPD cases had received preventative treatment.

Methods: All adult IPD cases (Streptococcus pneumoniae in blood or cerebrospinal fluid) admitted to The Ottawa Hospital (TOH) from January 2013 to December 2015 were identified through the Eastern Ontario Regional Laboratory.

Antimicrobial Metallopeptides.

Antimicrobial peptides are short amphipathic peptides that are produced by the innate immune system in order to protect a host from pathogens. They have been shown to have broad-spectrum antimicrobial activity toward Gram-positive and Gram-negative bacteria, as well as antifungal, antiprotozoan, and antiviral activity. These peptides are able to exert their activity through a variety of mechanisms that include inhibiting DNA and RNA replication, inhibiting protein synthesis, permeabilizing the cell membrane, disrupting proton and ion transmembrane gradients, and inhibiting cell wall biosynthesis.

Attenuation of West Nile Virus NS2B/NS3 Protease by Amino Terminal Copper and Nickel Binding (ATCUN) Peptides.

West Nile virus NS2B/NS3 protease (WNVP) is a viable target for the development of antiviral compounds. To that end, catalytic metallopeptides that incorporate the copper-binding ATCUN motif into either the N- or C-terminus of known WNVP targeting peptides have been developed as new families of peptide-based inhibitors. Each metallopeptide was evaluated based on its inhibitory constant (K), time-dependent inactivation of the protein, Michaelis-Menten parameters, and the ability to oxidatively modify WNVP.

Transition Probabilities of Co ii Weak Lines to the Ground and Low Metastable Levels.

New branching fraction (BF) measurements based primarily on data from a cross-dispersed echelle spectrometer are reported for 84 lines of Co ii. The BFs for 82 lines are converted to absolute atomic transition probabilities using radiative lifetimes from laser-induced fluorescence (LIF) measurements on 19 upper levels of the lines. A lifetime of 3.

Aire controls the recirculation of murine Foxp3 regulatory T-cells back to the thymus.

In the thymus, medullary thymic epithelial cells (mTEC) determine the fate of newly selected CD4 and CD8 single positive (SP) thymocytes. For example, mTEC expression of Aire controls intrathymic self-antigen availability for negative selection. Interestingly, alterations in both Foxp3 Regulatory T-cells (T-Reg) and conventional SP thymocytes in Aire mice suggest additional, yet poorly understood, roles for Aire during intrathymic T-cell development.

Regulation of human Nfu activity in Fe-S cluster delivery-characterization of the interaction between Nfu and the HSPA9/Hsc20 chaperone complex.

Iron-sulfur cluster biogenesis is a complex, but highly regulated process that involves de novo cluster formation from iron and sulfide ions on a scaffold protein, and subsequent delivery to final targets via a series of Fe-S cluster-binding carrier proteins. The process of cluster release from the scaffold/carrier for transfer to the target proteins may be mediated by a dedicated Fe-S cluster chaperone system. In human cells, the chaperones include heat shock protein HSPA9 and the J-type chaperone Hsc20.

Comparative Analysis of Biopsy Upgrading in Four Prostate Cancer Active Surveillance Cohorts.

Background: Active surveillance (AS) is increasingly accepted for managing low-risk prostate cancer, yet there is no consensus about implementation. This lack of consensus is due in part to uncertainty about risks for disease progression, which have not been systematically compared or integrated across AS studies with variable surveillance protocols and dropout to active treatment.

Objective: To compare risks for upgrading from a Gleason score (GS) of 6 or less to 7 or more across AS studies after accounting for differences in surveillance intervals and competing treatments and to evaluate tradeoffs of more versus less frequent biopsies.

Amino Terminal Copper and Nickel Binding Motif Derivatives of Ovispirin-3 Display Increased Antimicrobial Activity via Lipid Oxidation.

Antimicrobial peptides are short peptides secreted by the innate immune system to protect the host from pathogens. We have investigated the influence of the amino terminal copper and nickel binding (ATCUN) motif on derivatives of ovispirin-3 (OV-3), an α-helical peptide from the cathelicidin family, demonstrating an increased antimicrobial activity toward a broad range of bacteria, relative to OV-3, with MICs as low as 1.3 ± 0.

Metal complexes promoting catalytic cleavage of nucleic acids-biochemical tools and therapeutics.

The development of metal complexes that promote degradation of nucleic acids has garnered significant interest as a result of their broad range of potential application. This review focuses on recent progress in the design and synthesis of metal complexes as artificial nucleases that promote either hydrolytic or oxidative cleavage of nucleic acids. Illustrative examples demonstrate the versatility of artificial nucleases for in vitro applications as molecular tools to address biochemical problems, as well as their potential use as therapeutic agents.

Milk and other dairy foods in relation to prostate cancer recurrence: Data from the cancer of the prostate strategic urologic research endeavor (CaPSURE™).

Background: High-fat dairy, particularly whole milk, in healthy men may increase risk of aggressive prostate cancer. However, data are limited regarding dairy after prostate cancer diagnosis.

Method: We conducted a prospective study among 1334 men with non-metastatic prostate cancer in the Cancer of the Prostate Strategic Urologic Research Endeavor.