Sustained meningeal lymphatic vessel atrophy or expansion does not alter Alzheimer's disease-related amyloid pathology.

Discovery of meningeal lymphatic vessels (LVs) in the dura mater, also known as dural LVs (dLVs) that depend on vascular endothelial growth factor C expression, has raised interest in their possible involvement in Alzheimer's disease (AD). Here we find that in the APdE9 and 5xFAD mouse models of AD, dural amyloid-β (Aβ) is confined to blood vessels and dLV morphology or function is not altered. The induction of sustained dLV atrophy or hyperplasia in the AD mice by blocking or overexpressing vascular endothelial growth factor C, impaired or improved, respectively, macromolecular cerebrospinal fluid (CSF) drainage to cervical lymph nodes.

ciRS-7 and miR-7 regulate ischemia-induced neuronal death via glutamatergic signaling.

Brain functionality relies on finely tuned regulation of gene expression by networks of non-coding RNAs (ncRNAs) such as the one composed by the circular RNA ciRS-7 (also known as CDR1as), the microRNA miR-7, and the long ncRNA Cyrano. We describe ischemia-induced alterations in the ncRNA network both in vitro and in vivo and in transgenic mice lacking ciRS-7 or miR-7. Our data show that cortical neurons downregulate ciRS-7 and Cyrano and upregulate miR-7 expression during ischemia.

Control of protein synthesis through mRNA pseudouridylation by dyskerin.

Posttranscriptional modifications of mRNA have emerged as regulators of gene expression. Although pseudouridylation is the most abundant, its biological role remains poorly understood. Here, we demonstrate that the pseudouridine synthase dyskerin associates with RNA polymerase II, binds to thousands of mRNAs, and is responsible for their pseudouridylation, an action that occurs in chromatin and does not appear to require a guide RNA with full complementarity.

Neutralization of the Positive Charges on Histone Tails by RNA Promotes an Open Chromatin Structure.

RNA associates extensively with chromatin and can influence its structure; however, the potential role of the negative charges of RNA on chromatin structure remains unknown. Here, we demonstrate that RNA prevents precipitation of histones and can attenuate electrostatic interactions between histones and DNA, thereby loosening up the chromatin structure. This effect is independent of the sequence of RNA but dependent on its single-stranded nature, length, concentration, and negative charge.

Point-of-care-based protocol with first-line therapy with coagulation factor concentrates is associated with decrease allogenic blood transfusion and costs in cardiovascular surgery: an Italian single-center experience.

Background: Transfusion in patients having cardiac surgery has been associated with increased morbidity, mortality, and costs. This analysis assessed the impact of a rotational thromboelastometry (ROTEM®)- and functional platelet assessment (Multiplate®)-based protocol for bleeding management on perioperative outcomes and costs in patients undergoing cardiac surgery.

Methods: This retrospective analysis of the records of all patients who underwent cardiac surgery at the Hesperia Hospital, Modena, Italy, from December 2012 to December 2013 compared outcomes and costs of bleeding management for the two 6-month periods before/after introduction of the ROTEM- and Multiplate-based protocol.

Benefits and medium-term outcome of the Sorin Pericarbon Freedom stentless aortic prosthesis in cases of acute bacterial endocarditis.

Objectives: The aim of this study is to evaluate the ease of use and the advantages of Sorin Pericarbon Freedom (SPF) stentless valve in cases of acute bacterial endocarditis and to check the intermediate-term results after the implant of SPF with respect to resistance to infection, valve deterioration and durability.

Methods: Between June 2003 and February 2015, 26 patients with active aortic valve bacterial endocarditis underwent aortic valve replacement with SPF pericardial stentless aortic prosthesis. The mean age was 57 ± 18 years; 73% of the patients were in preoperative NYHA class III and VI.

Effectiveness of sepsis bundle application in cirrhotic patients with septic shock: a single-center experience.

Purpose: To evaluate the effect of adherence to evidence-based guidelines of the Surviving Sepsis Campaign (SSC) on the outcome of cirrhotic patients with septic shock admitted to the intensive care unit.

Methods: This prospective observational cohort study included 38 patients with documented liver cirrhosis and septic shock admitted to a multidisciplinary intensive care unit at a University Hospital from January 2005 to June 2009. In each patient, the compliance to 4 resuscitation (ie, 6-hour bundle) and to 3 management (i.