Genome-wide profiling of circulatory microRNAs associated with cognition and dementia.

Introduction: MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression. Their role in the pathophysiology of dementia and potential as biomarkers remains undetermined.

Methods: We conducted a single- (one-by-one) and multi-marker (joint) analysis to identify well-expressed circulating miRNAs in plasma (total = 591) associated with general cognition and incident dementia, for 1615 participants of the population-based Rotterdam Study.

Multi-Omics Analysis Reveals MicroRNAs Associated With Cardiometabolic Traits.

MicroRNAs (miRNAs) are non-coding RNA molecules that regulate gene expression. Extensive research has explored the role of miRNAs in the risk for type 2 diabetes (T2D) and coronary heart disease (CHD) using single-omics data, but much less by leveraging population-based omics data. Here we aimed to conduct a multi-omics analysis to identify miRNAs associated with cardiometabolic risk factors and diseases.

Screening and Stepped Care Targeting Psychological Distress in Patients With Metastatic Colorectal Cancer: The TES Cluster Randomized Trial.

Background: This study evaluated the effectiveness of a screening and stepped care program (the TES program) in reducing psychological distress compared with care as usual (CAU) in patients with metastatic colorectal cancer starting with first-line systemic palliative treatment.

Patients And Methods: In this cluster randomized trial, 16 hospitals were assigned to the TES program or CAU. Patients in the TES arm were screened for psychological distress with the Hospital Anxiety and Depression Scale and the Distress Thermometer/Problem List (at baseline and 10 and 18 weeks).

A retrospective cohort study of racing performance in Quarter Horses undergoing prosthetic laryngoplasty for treatment of recurrent laryngeal neuropathy.

OBJECTIVE To determine effects of prosthetic laryngoplasty on return to racing, performance index, and career longevity in racing Quarter Horses with recurrent laryngeal neuropathy (RLN) and to evaluate performance variables for horses with RLN undergoing prosthetic laryngoplasty, compared with a control horse population. DESIGN Multicenter, retrospective cohort study. ANIMALS 162 racing Quarter Horses with RLN treated with prosthetic laryngoplasty (case horses) and 324 racing Quarter Horse without RLN (control horses).

Viral testing of 18 consecutive cases of equine serum hepatitis: A prospective study (2014-2018).

Background: Three flaviviruses (equine pegivirus [EPgV]; Theiler's disease-associated virus [TDAV]; non-primate hepacivirus [NPHV]) and equine parvovirus (EqPV-H) are present in equine blood products; the TDAV, NPHV, and EqPV-H have been suggested as potential causes of serum hepatitis.

Objective: To determine the prevalence of these viruses in horses with equine serum hepatitis.

Animals: Eighteen horses diagnosed with serum hepatitis, enrolled from US referral hospitals.

Structural basis for recognition of the central conserved region of RSV G by neutralizing human antibodies.

Respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract infections in infants and the elderly, and yet there remains no effective treatment or vaccine. The surface of the virion is decorated with the fusion glycoprotein (RSV F) and the attachment glycoprotein (RSV G), which binds to CX3CR1 on human airway epithelial cells to mediate viral attachment and subsequent infection. RSV G is a major target of the humoral immune response, and antibodies that target the central conserved region of G have been shown to neutralize both subtypes of RSV and to protect against severe RSV disease in animal models.

Incidence of post-anesthetic colic in non-fasted adult equine patients.

The purpose of this study was to determine the incidence of post-anesthetic colic in non-fasted adult horses undergoing isoflurane inhalant anesthesia for an elective, non-abdominal procedure at a single referral center. Medical records were searched from May 1, 2012 to May 31, 2014. Inclusion criteria included non-fasted patients ≥ 2 years of age that were anesthetized for an elective, non-abdominal procedure.

Translation and linguistic validation of the FACT-EGFRI-18 quality of life instrument from English into Dutch.

Purpose: The Functional Assessment of Cancer Therapy-Epidermal Growth Factor Receptor Inhibitor 18 (FACT-EGFRI-18) is a patient-reported outcomes questionnaire developed to assess the effect of EGFRI on patients. The FACT-EGFR-18 was translated into Dutch and evaluated in order to document that the translation adequately captures the concepts of the original English-language version of the questionnaire and is readily understood by subjects in the target population.

Method: Translation of the FACT-EGFRI-18 from English to Dutch was accomplished by employing the Functional Assessment of Chronic Illness Therapy (FACIT) multilingual translation methodology.

Clinical outcome of collateral ligament injuries of the tarsus.

The significance of collateral ligament desmitis of the tarsocrural joint is often clinically underestimated, because it is an uncommon injury with a guarded prognosis for athletic soundness. The objective of this study was to describe the clinical presentation, treatment, and outcome of 12 horses with collateral ligament desmitis, along with tarsocrural joint synovitis secondary to hemarthrosis. Criteria for inclusion in this study included clinical signs of tarsocrural joint synovitis and sonographic evidence of collateral ligament desmitis.

Highly conserved protective epitopes on influenza B viruses.

Identification of broadly neutralizing antibodies against influenza A viruses has raised hopes for the development of monoclonal antibody-based immunotherapy and "universal" vaccines for influenza. However, a substantial part of the annual flu burden is caused by two cocirculating, antigenically distinct lineages of influenza B viruses. Here, we report human monoclonal antibodies, CR8033, CR8071, and CR9114, that protect mice against lethal challenge from both lineages.

Oral adverse events associated with tyrosine kinase and mammalian target of rapamycin inhibitors in renal cell carcinoma: a structured literature review.

Background: Oral adverse events (OAEs) associated with multitargeted tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin inhibitors (mTORIs) are underestimated but frequent and novel presentations of mucosal manifestations. Because optimal antitumor activity requires maintaining the optimal dose, it is essential to avoid unintended treatment delays or interruptions.

Methods: We review the reported prevalence and appearance of OAEs with TKIs and mTORIs and the current oral assessment tools commonly used in clinical trials.

A highly conserved neutralizing epitope on group 2 influenza A viruses.

Current flu vaccines provide only limited coverage against seasonal strains of influenza viruses. The identification of V(H)1-69 antibodies that broadly neutralize almost all influenza A group 1 viruses constituted a breakthrough in the influenza field. Here, we report the isolation and characterization of a human monoclonal antibody CR8020 with broad neutralizing activity against most group 2 viruses, including H3N2 and H7N7, which cause severe human infection.

New class of monoclonal antibodies against severe influenza: prophylactic and therapeutic efficacy in ferrets.

Background: The urgent medical need for innovative approaches to control influenza is emphasized by the widespread resistance of circulating subtype H1N1 viruses to the leading antiviral drug oseltamivir, the pandemic threat posed by the occurrences of human infections with highly pathogenic avian H5N1 viruses, and indeed the evolving swine-origin H1N1 influenza pandemic. A recently discovered class of human monoclonal antibodies with the ability to neutralize a broad spectrum of influenza viruses (including H1, H2, H5, H6 and H9 subtypes) has the potential to prevent and treat influenza in humans. Here we report the latest efficacy data for a representative antibody of this novel class.

Pre- and postexposure use of human monoclonal antibody against H5N1 and H1N1 influenza virus in mice: viable alternative to oseltamivir.

New strategies to prevent and treat influenza virus infections are urgently needed. A recently discovered class of monoclonal antibodies (mAbs) neutralizing an unprecedented spectrum of influenza virus subtypes may have the potential for future use in humans. Here, we assess the efficacies of CR6261, which is representative of this novel class of mAbs, and oseltamivir in mice.

Partial resection of the plica salpingopharyngeus for the treatment of three foals with bilateral tympany of the auditory tube diverticulum (guttural pouch).

Case Description: 3 foals were referred for treatment of tympany of the auditory tube diverticulum (guttural pouch).

Clinical Findings: Bilateral guttural pouch tympany was diagnosed in all 3 foals on the basis of clinical signs and results of radiographic and endoscopic evaluations and gutturocentesis. In each foal, previous medical or surgical interventions or both had failed to correct the problem.

Intracorporeal suture closure of the internal inguinal and vaginal rings in foals and horses.

Objective: To report a technique for repair or prevention of inguinal hernia in horses using intracorporeal suture closure of the internal inguinal and vaginal rings.

Study Design: Case series.

Animals: Foals (n=6) and geldings (n=2).

A sensitive cell-based assay for the detection of residual infectious West Nile virus.

Ensuring complete viral inactivation is critical for the safety of vaccines based on an inactivated virus. Detection of residual infectious virus is dependent on sensitivity of the assay, sample volume analyzed and the absence of interference with viral infection. Here we describe the development and qualification of a sensitive cell-based assay for the detection of residual infectious West Nile Virus (WNV).

The prevalence of laryngeal disease in a large population of competition draft horses.

Objectives: (1) To determine the effect of age, height, weight, breed, sex, and specific use on the prevalence of idiopathic left laryngeal hemiplegia (ILH) in a population of draft performance horses; (2) to determine the association between tracheal mucus and laryngeal dysfunction, and the prevalence of exercise-induced pulmonary hemorrhage (EIPH) in a population of draft performance horses.

Study Design: Cross-sectional.

Animals: Draft horses competing at the 2005 Michigan Great Lakes Draft Horse Show.

Long-term intravenous treatment of Pompe disease with recombinant human alpha-glucosidase from milk.

Objective: Recent reports warn that the worldwide cell culture capacity is insufficient to fulfill the increasing demand for human protein drugs. Production in milk of transgenic animals is an attractive alternative. Kilogram quantities of product per year can be obtained at relatively low costs, even in small animals such as rabbits.

Pharmacokinetic profile of a modified release formulation of trimetazidine (TMZ MR 35 mg) in the elderly and patients with renal failure.

Objectives - To study the effect of age and renal function on the pharmacokinetic profile of a modified release tablet of trimetazidine (TMZ MR 35 mg) administered twice daily.Methods- Study 1: Twelve healthy elderly subjects (CL(creat) 72+/-8 ml/min, 72+/-4 years mean+/-SD) and eight young volunteers (CL(creat) 134+/-18 ml/min, 25+/-8 years) received TMZ MR 35 mg b.i.

An optimized methodology for combined phenotyping and genotyping on CYP2D6 and CYP2C19.

A method for simultaneous phenotyping and genotyping for CYP2D6 and CYP2C19 was tested. Six healthy volunteers were selected (three extensive and three poor metabolisers for CYP2D6). CYP2D6 was probed with dextromethorphan and metoprolol and CYP2C19 was probed with omeprazole.

Human acid alpha-glucosidase from rabbit milk has therapeutic effect in mice with glycogen storage disease type II.

Pompe's disease or glycogen storage disease type II (GSDII) belongs to the family of inherited lysosomal storage diseases. The underlying deficiency of acid alpha-glucosidase leads in different degrees of severity to glycogen storage in heart, skeletal and smooth muscle. There is currently no treatment for this fatal disease, but the applicability of enzyme replacement therapy is under investigation.

High-throughput solid-phase extraction for the determination of cimetidine in human plasma.

For the implementation and validation of an automated 'high-throughput' solid-phase extraction (SPE) system, using microtiter solid-phase technology and a pipetting robot, a SPE method previously validated manually for cimetidine in human plasma was adapted. Sample cleanup was performed by means of SPE using Microlute extraction plates in the 96-well format, each well filled with 50 mg of Varian C18 sorbent. Separation was performed by reversed-phase high-performance liquid chromatography (HPLC) with UV detection at 234 nm.