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.
View Article and Find Full Text PDFAims: 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.
Eur Heart J Qual Care Clin Outcomes
July 2018
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.
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.
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.
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.
View Article and Find Full Text PDFIron‑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.
View Article and Find Full Text PDFPlants 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.
View Article and Find Full Text PDFAs 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.
View Article and Find Full Text PDFObjectives: 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.
View Article and Find Full Text PDFArtificial 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.
View Article and Find Full Text PDFBackground: 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 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.
View Article and Find Full Text PDFWest 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.
View Article and Find Full Text PDFNew 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.
View Article and Find Full Text PDFIn 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.
View Article and Find Full Text PDFIron-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.
View Article and Find Full Text PDFBackground: 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.
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.
View Article and Find Full Text PDFCurr Opin Chem Biol
April 2018
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.
View Article and Find Full Text PDFBackground: 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.