Complete Genome Sequence of the Avian-Pathogenic Escherichia coli Strain APEC O18.

Avian-pathogenic Escherichia coli (APEC) is the causative agent of colibacillosis, a disease that affects all facets of poultry production worldwide, resulting in multimillion dollar losses annually. Here, we report the genome sequence of an APEC O18 sequence type 95 (ST95) strain associated with disease in a chicken.

Cell coupling mediated by connexin 26 selectively contributes to reduced adhesivity and increased migration.

Gap junction proteins (connexins) have crucial effects on cell motility in many systems, from migration of neural crest cells to promotion of metastatic invasiveness. Here, we show that expression of Cx26 (also known as GJB2) in HeLa cells specifically enhances cell motility in scrape wounding and sparse culture models. This effect is dependent on gap junction channels and is isotype specific [Cx26 enhances motility, whereas Cx43 (also known as GJA1) does not and Cx32 (also known as GJB1) has an intermediate effect].

Ubiquitin-specific Protease-7 Inhibition Impairs Tip60-dependent Foxp3+ T-regulatory Cell Function and Promotes Antitumor Immunity.

Foxp3+ T-regulatory (Treg) cells are known to suppress protective host immune responses to a wide variety of solid tumors, but their therapeutic targeting is largely restricted to their transient depletion or "secondary" modulation, e.g. using anti-CTLA-4 monoclonal antibody.

Extended-spectrum ß-Lactamase-producing Enterobacteriaceae as a Common Cause of Urinary Tract Infections in Sri Lanka.

Background: Extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-PE) are increasingly reported as pathogens in urinary tract infections (UTIs). However, in Sri Lanka, the clinical and molecular epidemiology of ESBL-PE implicated in UTIs has not been well described.

Materials And Methods: We conducted prospective, laboratory-based surveillance from October to December 2013 at a tertiary care hospital in southern Sri Lanka and enrolled patients ≥1 year of age with clinically relevant UTIs due to ESBL-PE.

Pediatric Blunt Neck Trauma Causing Esophageal and Complete Tracheal Transection.

Background: Blunt injuries to the cervical trachea remain rare but present unique and challenging clinical scenarios for prehospital providers. These injuries depend on prehospital providers either definitively securing the injured airway or bridging the patient to a treatment facility that can mobilize the necessary resources.

Case Summary: The case presented here involves a clothesline injury to a pediatric patient that resulted in complete tracheal transection and partial esophageal transection.

Economic and clinical burden of opioid-induced nausea and vomiting.

Opioids are the standard of care for treating moderate-to-severe pain; however, their efficacy can be limited by adverse events (AEs), including nausea and vomiting. Opioid-induced nausea and vomiting (OINV) is an inherent adverse effect of opioid treatment, exerting effects centrally and peripherally. Opioid-related AEs can impact treatment adherence and discontinuation, which can result in inadequate pain management.

Blood Measurement of Carcinoembryonic Antigen Level for Detecting Recurrence of Colorectal Cancer.

Clinical Question: What is the trade-off between sensitivity and specificity at specific carcinoembryonic antigen (CEA) thresholds for detecting recurrent colorectal cancer?

Bottom Line: To detect colorectal cancer recurrence, the sensitivity of CEA ranges from 68% for a threshold of 10 µg/L to 82% for a threshold of 2.5 µg/L and the specificity ranges from 97% for a threshold of 10 µg/L to 80% for a threshold of 2.5 µg/L.

Pilot Trial of Intravenous Lipid Emulsion Treatment for Severe Nifedipine-Induced Shock.

Animal studies and human case reports show promise in using lipid rescue to treat refractory calcium channel antagonist toxicity. However, the majority of research and clinical experience has focused on non-dihydropyridine agents. Thus, we sought to investigate the value of lipid emulsion (ILE) therapy for dihydropyridine-induced shock.

Variation in Direct Access to Tests to Investigate Cancer: A Survey of English General Practitioners.

Background: The 2015 NICE guidelines for suspected cancer recommend that English General Practitioners have direct access to diagnostic tests to investigate symptoms of cancer that do not meet the criteria for urgent referral. We aimed to identify the proportion of GPs in England with direct access to these tests.

Methods: We recruited 533 English GPs through a national clinical research network to complete an online survey about direct access to laboratory, radiology, and endoscopy tests in the three months leading up to the release of the 2015 NICE guidance.

Extranodal Lymphoma of the Breast.

Extranodal lymphoma represents fewer than 0.5% of all breast malignancies. Secondary involvement of the breast with lymphoma is more common than primary breast lymphoma.

A Genomic Signature of Influenza Infection Shows Potential for Presymptomatic Detection, Guiding Early Therapy, and Monitoring Clinical Responses.

Early, presymptomatic intervention with oseltamivir (corresponding to the onset of a published host-based genomic signature of influenza infection) resulted in decreased overall influenza symptoms (aggregate symptom scores of 23.5 vs 46.3), more rapid resolution of clinical disease (20 hours earlier), reduced viral shedding (total median tissue culture infectious dose [TCID50] 7.

9th GCC closed forum: CAPA in regulated bioanalysis; method robustness, biosimilars, preclinical method validation, endogenous biomarkers, whole blood stability, regulatory audit experiences and electronic laboratory notebooks.

The 9th GCCClosed Forum was held just prior to the 2015 Workshop on Recent Issues in Bioanalysis (WRIB) in Miami, FL, USA on 13 April 2015. In attendance were 58 senior-level participants, from eight countries, representing 38 CRO companies offering bioanalytical services. The objective of this meeting was for CRO bioanalytical representatives to meet and discuss scientific and regulatory issues specific to bioanalysis.

Complete Genomic Sequence of an Avian Pathogenic Escherichia coli Strain of Serotype O7:HNT.

Avian pathogenic Escherichia coli (APEC) is associated with colibacillosis in poultry. Here, we present the first complete sequence of an APEC strain of the O7:HNT serotype and ST73 sequence type, isolated from a broiler with cellulitis. Complete genomes of APEC with distinct genetic backgrounds may be useful for comparative analysis.

Genetic Characterization of ExPEC-Like Virulence Plasmids among a Subset of NMEC.

Neonatal Meningitis Escherichia coli (NMEC) is one of the most common causes of neonatal bacterial meningitis in the US and elsewhere resulting in mortality or neurologic deficits in survivors. Large plasmids have been shown experimentally to increase the virulence of NMEC in the rat model of neonatal meningitis. Here, 9 ExPEC-like plasmids were isolated from NMEC and sequenced to identify the core and accessory plasmid genes of ExPEC-like virulence plasmids in NMEC and create an expanded plasmid phylogeny.

Transcriptomic Analysis of the Host Response and Innate Resilience to Enterotoxigenic Escherichia coli Infection in Humans.

Background: Enterotoxigenic Escherichia coli (ETEC) is a globally prevalent cause of diarrhea. Though usually self-limited, it can be severe and debilitating. Little is known about the host transcriptional response to infection.

International variation in adherence to referral guidelines for suspected cancer: a secondary analysis of survey data.

Background: Variation in cancer survival persists between comparable nations and appears to be due, in part, to primary care practitioners (PCPs) having different thresholds for acting definitively in response to cancer-related symptoms.

Aim: To explore whether cancer guidelines, and adherence to them, differ between jurisdictions and impacts on PCPs' propensity to take definitive action on cancer-related symptoms.

Design And Setting: A secondary analysis of survey data from six countries (10 jurisdictions) participating in the International Cancer Benchmarking Partnership.

Blood CEA levels for detecting recurrent colorectal cancer.

Background: Testing for carcino-embryonic antigen (CEA) in the blood is a recommended part of follow-up to detect recurrence of colorectal cancer following primary curative treatment. There is substantial clinical variation in the cut-off level applied to trigger further investigation.

Objectives: To determine the diagnostic performance of different blood CEA levels in identifying people with colorectal cancer recurrence in order to inform clinical practice.

2015 White Paper on recent issues in bioanalysis: focus on new technologies and biomarkers (Part 1 - small molecules by LCMS).

The 2015 9th Workshop on Recent Issues in Bioanalysis (9th WRIB) took place in Miami, Florida with participation of over 600 professionals from pharmaceutical and biopharmaceutical companies, biotechnology companies, contract research organizations and regulatory agencies worldwide. It is once again a 5-day week long event - a full immersion bioanalytical week - specifically designed to facilitate sharing, reviewing, discussing and agreeing on approaches to address the most current issues of interest in bioanalysis. The topics covered included both small and large molecules, and involved LCMS, hybrid LBA/LCMS, LBA approaches including the focus on biomarkers and immunogenicity.

Differential evolution of peripheral cytokine levels in symptomatic and asymptomatic responses to experimental influenza virus challenge.

Exposure to influenza virus triggers a complex cascade of events in the human host. In order to understand more clearly the evolution of this intricate response over time, human volunteers were inoculated with influenza A/Wisconsin/67/2005 (H3N2), and then had serial peripheral blood samples drawn and tested for the presence of 25 major human cytokines. Nine of 17 (53%) inoculated subjects developed symptomatic influenza infection.

Pneumococcal Carriage and Vaccine Coverage in Retirement Community Residents.

Objectives: To evaluate pneumococcal immunization in older adults living in retirement communities and to measure nasopharyngeal carriage of Streptococcus pneumoniae to better assess the potential for herd protection from the 13-valent pneumococcal conjugate vaccine (PCV-13) in these settings.

Design: Cross-sectional observational study of adults aged 65 and older living in retirement communities to determine coverage with 23-valent pneumococcal vaccine (PPSV-23), coverage with PCV-13 in immuncompromised individuals according to 2012 Advisory Committee on Immunization Practices (ACIP) guidelines, and nasopharyngeal carriage of S. pneumoniae.

Serotype O18 avian pathogenic and neonatal meningitis Escherichia coli strains employ similar pathogenic strategies for the onset of meningitis.

Neonatal meningitis Escherichia coli K1 (NMEC) are thought to be transmitted from mothers to newborns during delivery or by nosocomial infections. However, the source of E. coli K1 causing these infections is not clear.

The contribution of Chlamydia-specific CD8⁺ T cells to upper genital tract pathology.

Genital chlamydial infections lead to severe upper reproductive tract pathology in a subset of untreated women. We demonstrated previously that tumor necrosis factor (TNF)-α-producing CD8(+) T cells contribute significantly to chlamydial upper genital tract pathology in female mice. In addition, we observed that minimal chlamydial oviduct pathology develops in OT-1 transgenic (OT-1) mice, wherein the CD8(+) T-cell repertoire is restricted to recognition of the ovalbumin peptide Ova(257-264), suggesting that non-Chlamydia-specific CD8(+) T cells may not be responsible for chlamydial pathogenesis.

A Randomized, Placebo-controlled Trial of Digestive Enzymes in Children with Autism Spectrum Disorders.

Objective: There is growing evidence for a gut-brain connection associated with autism spectrum disorders (ASDs). This suggests a potential benefit from introduced digestive enzymes for children with ASD.

Methods: We performed a double-blind, randomized clinical trial on 101 children with ASD (82 boys and 19 girls) aged from 3 to 9 years.