Racial differences in health-related quality of life and functional ability in patients with gout.

Objective: To compare the health-related quality of life (HRQOL) and the functional ability by race in patients with gout.

Methods: In a 9-month prospective cohort multicentre study, patients with gout self-reported race, dichotomized as Caucasian or African American (others excluded). We calculated HRQOL/function scores adjusted for age, study site and college education for Short Form-36 (SF-36; generic HRQOL), Gout Impact Scale (GIS; disease-specific HRQOL) and HAQ-disability index (HAQ-DI; functional ability).

Structure-Activity Relationships of Small Molecule Autotaxin Inhibitors with a Discrete Binding Mode.

Autotaxin (ATX) is a secreted enzyme responsible for the hydrolysis of lysophosphatidylcholine (LPC) to the bioactive lysophosphatidic acid (LPA) and choline. The ATX-LPA signaling pathway is implicated in cell survival, migration, and proliferation; thus, the inhibition of ATX is a recognized therapeutic target for a number of diseases including fibrotic diseases, cancer, and inflammation, among others. Many of the developed synthetic inhibitors for ATX have resembled the lipid chemotype of the native ligand; however, a small number of inhibitors have been described that deviate from this common scaffold.

Inflammasome-Independent NLRP3 Restriction of a Protective Early Neutrophil Response to Pulmonary Tularemia.

Francisella tularensis (Ft) causes a frequently fatal, acute necrotic pneumonia in humans and animals. Following lethal Ft infection in mice, infiltration of the lungs by predominantly immature myeloid cells and subsequent myeloid cell death drive pathogenesis and host mortality. However, following sub-lethal Ft challenge, more mature myeloid cells are elicited and are protective.

Enriching s U-RNA Using Methane Thiosulfonate (MTS) Chemistry.

Metabolic labeling of cellular RNA is a useful approach to study RNA biology. 4-Thiouridine (s U) is a convenient nucleoside for metabolic labeling because it is cell permeable and is incorporated into newly transcribed RNA, and the sulfur moiety provides a handle for biochemical purification. However, a critical step in the purification of s U-RNA is the efficiency of the chemistry used to enrich s U-RNA.

The Role of Substance P in Pulmonary Clearance of Bacteria in Comparative Injury Models.

Neural input to the immune system can alter its ability to clear pathogens effectively. Patients suffering mild traumatic brain injury (mTBI) have shown reduced rates of pneumonia and a murine model replicated these findings, with better overall survival of TBI mice compared with sham-injured mice. To further investigate the mechanism of improved host response in TBI mice, this study developed and characterized a mild tail trauma model of similar severity to mild TBI.

Graft Loss and CLAD-Onset Is Hastened by Viral Pneumonia After Lung Transplantation.

Background: Community-acquired respiratory virus (CARV) infections occur frequently after lung transplantation and may adversely impact outcomes. We hypothesized that while asymptomatic carriage would not increase the risk of chronic lung allograft dysfunction (CLAD) and graft loss, severe infection would.

Methods: All lung transplant cases between January 2000 and July 2013 performed at our center were reviewed for respiratory viral samples.

Shorter Duration of Post-Operative Antibiotics for Cecal Ligation and Puncture Does Not Increase Inflammation or Mortality.

Antimicrobial therapy for sepsis has beneficial effects, but prolonged use fosters emergence of resistant microorganisms, increases cost, and secondary infections. We tested whether 3 days versus 5 days of antibiotics in the murine model of cecal ligation and puncture (CLP) negatively influences outcomes. Following CLP mice were randomized to receive the antibiotic imipenem-cilastatin (25mg/kg) in dextrose 5% in Lactated Ringer's solution every 12 hours for either three or five days.

Antagonism of the Neurokinin-1 Receptor Improves Survival in a Mouse Model of Sepsis by Decreasing Inflammation and Increasing Early Cardiovascular Function.

Objectives: Sepsis remains a serious clinical problem despite intensive research efforts and numerous attempts to improve outcome by modifying the inflammatory response. Substance P, the principal ligand for the neurokinin-1 receptor, is a potent proinflammatory mediator that exacerbates inflammatory responses and cardiovascular variables in sepsis.

Design: The current study examined whether inhibition of the neurokinin-1 receptor with a specific antagonist (CJ-12,255) would improve survival in the cecal ligation and puncture model of sepsis in adult female outbred mice.

Culturally capable and culturally safe: Caseload care for Indigenous women by Indigenous midwifery students.

Background: Evidence is emerging of the benefits to students of providing continuity of midwifery care as a learning strategy in midwifery education, however little is known about the value of this strategy for midwifery students.

Aim: To explore Indigenous students' perceptions of providing continuity of midwifery care to Indigenous women whilst undertaking a Bachelor of Midwifery.

Methods: Indigenous Bachelor of Midwifery students' experiences of providing continuity of midwifery care to Indigenous childbearing women were explored within an Indigenous research approach using a narrative inquiry framework.

FcγR mediates TLR2- and Syk-dependent NLRP3 inflammasome activation by inactivated Francisella tularensis LVS immune complexes.

IgG (mAb)-opsonized, inactivated Francisella tularensis LVS (iFt-mAb) enhances TLR2-dependent IL-6 production by macrophages via Fcγ receptors (FcγR). In mice, vaccination with iFt-mAb provides IgA-dependent protection against lethal challenge with Ft LVS. Because inflammasome maturation of IL-1β is thought important for antibody-mediated immunity, we considered the possibility that iFt-mAb elicits an FcγR-dependent myeloid cell inflammasome response.

Navigating highly homologous genes in a molecular diagnostic setting: a resource for clinical next-generation sequencing.

Purpose: Next-generation sequencing (NGS) is now routinely used to interrogate large sets of genes in a diagnostic setting. Regions of high sequence homology continue to be a major challenge for short-read technologies and can lead to false-positive and false-negative diagnostic errors. At the scale of whole-exome sequencing (WES), laboratories may be limited in their knowledge of genes and regions that pose technical hurdles due to high homology.

Lung Transplant Outcomes in Systemic Sclerosis with Significant Esophageal Dysfunction. A Comprehensive Single-Center Experience.

Rationale: Consideration of lung transplantation in patients with systemic sclerosis (SSc) remains guarded, often due to the concern for esophageal dysfunction and the associated potential for allograft injury and suboptimal post-lung transplantation outcomes.

Objectives: The purpose of this study was to systematically report our single-center experience regarding lung transplantation in the setting of SSc, with a particular focus on esophageal dysfunction.

Methods: We retrospectively reviewed all lung transplants at our center from January 1, 2000 through August 31, 2012 (n = 562), comparing the SSc group (n = 35) to the following lung transplant diagnostic subsets: all non-SSc (n = 527), non-SSc diffuse fibrotic lung disease (n = 264), and a non-SSc matched group (n = 109).

In Vitro Activity of Delafloxacin against Clinical Neisseria gonorrhoeae Isolates and Selection of Gonococcal Delafloxacin Resistance.

We evaluated the in vitro activity of delafloxacin against a panel of 117 Neisseria gonorrhoeae strains, including 110 clinical isolates collected from 2012 to 2015 and seven reference strains, compared with the activities of seven antimicrobials currently or previously recommended for treatment of gonorrhea. We examined the potential for delafloxacin to select for resistant mutants in ciprofloxacin-susceptible and ciprofloxacin-resistant N. gonorrhoeae We characterized mutations in the gyrA, gyrB, parC, and parE genes and the multidrug-resistant efflux pumps (MtrC-MtrD-MtrE and NorM) by PCR and sequencing and by whole-genome sequencing.

Characterisation of graphene fibres and graphene coated fibres using capacitively coupled contactless conductivity detector.

The use of capacitively coupled contactless conductivity detection (C(4)D) for the characterisation of thin conductive graphene fibres, graphene composite fibres, and graphene coated fibrous materials is demonstrated for the first time. Within a few seconds, the non-destructive C(4)D detector provides a profile of the longetudinal physical homogeneity of the fibre, as well as extra information regarding fibre mophology and composition. In addition to the theoretical considerations related to the factors affect the output signal, this work evaluates the properties of graphene fibres using scanning C(4)D following the manufacturing process of wet-spinning.

Performance of Gout Impact Scale in a longitudinal observational study of patients with gout.

Objective: The aim was to evaluate the reliability, validity and responsiveness to change of the Gout Impact Scale (GIS), a disease-specific measure of patient-reported outcomes, in a multicentre longitudinal prospective cohort of gout patients.

Methods: Subjects completed the GIS, a 24-item instrument with five scales: Concern Overall, Medication Side Effects, Unmet Treatment Need, Well-Being during Attack, and Concern Over Attack. The total GIS score was calculated by averaging the GIS scale scores.

Feasibility and Reliability of Pediatric Early Warning Score in the Emergency Department.

Pediatric early warning scores in an emergency department may be used in routine patient evaluation of illness severity and resource allocation, thereby positively impacting quality and safety in pediatric care. This prospective nursing study assessed the feasibility and reliability of pediatric early warning scores in a busy, inner-city, level 1 trauma center pediatric emergency department. The pediatric early warning scores demonstrated high interrater reliability (degree of agreement among scorers) (intraclass correlation coefficient = 0.

Electrokinetic Properties of Lubricin Antiadhesive Coatings in Microfluidic Systems.

Lubricin is a glycoprotein found in articular joints which has long been recognized as being an important biological boundary lubricant molecule and, more recently, an impressive antiadhesive that readily self-assembles into a well ordered, polymer brush layer on virtually any substrate. The lubricin molecule possesses an overabundance of anionic charge, a property that is atypical among antiadhesive molecules, that enables its use as a coating for applications involving electrokinetic processes such as electrophoresis and electroosmosis. Coating the surfaces of silica and polymeric microfluidic devices with self-assembled lubricin coatings affords a unique combination of excellent fouling resistance and high charge density that enables notoriously "sticky" biomolecules such as proteins to be used and controlled electrokinetically in the device without complications arising from nonspecific adsorption.

A randomized, double-blind, Phase 2 study to evaluate subjective and objective outcomes in patients with acute bacterial skin and skin structure infections treated with delafloxacin, linezolid or vancomycin.

Objectives: Delafloxacin is an investigational anionic fluoroquinolone being developed to treat infections caused by Gram-positive and -negative organisms. This clinical trial evaluated the efficacy and safety of delafloxacin in the treatment of acute bacterial skin and skin structure infections (ABSSSIs).

Methods: In a double-blind, Phase 2 trial, 256 patients were randomized (1 : 1 : 1) to 300 mg of delafloxacin, 600 mg of linezolid or 15 mg/kg vancomycin (actual body weight), each administered intravenously twice daily for 5-14 days.

Toward real-time remote processing of laparoscopic video.

Laparoscopic surgery is a minimally invasive surgical technique where surgeons insert a small video camera into the patient's body to visualize internal organs and use small tools to perform surgical procedures. However, the benefit of small incisions has a drawback of limited visualization of subsurface tissues, which can lead to navigational challenges in the delivering of therapy. Image-guided surgery uses the images to map subsurface structures and can reduce the limitations of laparoscopic surgery.

Identifying three-dimensional structures of autophosphorylation complexes in crystals of protein kinases.

Protein kinase autophosphorylation is a common regulatory mechanism in cell signaling pathways. Crystal structures of several homomeric protein kinase complexes have a serine, threonine, or tyrosine autophosphorylation site of one kinase monomer located in the active site of another monomer, a structural complex that we call an "autophosphorylation complex." We developed and applied a structural bioinformatics method to identify all such autophosphorylation complexes in x-ray crystallographic structures in the Protein Data Bank (PDB).

Initiating an online asthma management program in urban emergency departments: the recruitment experience.

Background: The emergency department could represent a means of identifying patients with asthma who could benefit from asthma interventions.

Objective: To assess the initiation of a Web-based tailored asthma intervention in the emergency department of 2 urban tertiary care hospitals.

Methods: In addition to awareness strategies for emergency department staff (eg, attending nursing huddles, division meetings, etc), recruitment experiences are described for 2 strategies: (1) recruitment during an emergency department visit for acute asthma and (2) recruitment from patient listings (mail or telephone).

Targeted Droplet-Digital PCR as a Tool for Novel Deletion Discovery at the DFNB1 Locus.

Pathogenic variants at the DFNB1 locus encompassing the GJB2 and GJB6 genes account for 50% of autosomal-recessive, congenital nonsyndromic hearing loss in the United States. Most cases are caused by sequence variants within the GJB2 gene, but a significant number of DFNB1 patients carry a large deletion (GJB6-D13S1830) in trans with a GJB2 variant. This deletion lies upstream of GJB2 and was shown to reduce GJB2 expression by disrupting unidentified regulatory elements.

Almost half of women with endometrial cancer or hyperplasia do not know that obesity affects their cancer risk.

• A group of low income, largely Hispanic women demonstrated poor knowledge of the adverse reproductive effects of obesity. • 53.5% of endometrial cancer/hyperplasia patients identified obesity as a risk factor for endometrial cancer.