Methicillin-resistant Staphylococcus aureus adaptation to human keratinocytes.

Unlabelled: Skin is the most common site of Staphylococcus aureus infection. While most of these infections are self-limited, recurrent infections are common. Keratinocytes and recruited immune cells participate in skin defense against infection.

Adalimumab-Induced Cutaneous Lupus Erythematosus in a 16-Year-Old Girl with Juvenile Idiopathic Arthritis.

Tumor necrosis factor α (TNF-α) antagonists are used in the treatment of numerous autoimmune conditions. Adalimumab is the first monoclonal antibody to TNF-α and is used to treat juvenile idiopathic arthritis. A growing body of literature associates anti-TNF-α therapies with several adverse dermatologic manifestations, including drug-induced lupus erythematosus (LE).

Oncolytic reovirus enhances rituximab-mediated antibody-dependent cellular cytotoxicity against chronic lymphocytic leukaemia.

The naturally occurring oncolytic virus (OV), reovirus, replicates in cancer cells causing direct cytotoxicity, and can activate innate and adaptive immune responses to facilitate tumour clearance. Reovirus is safe, well tolerated and currently in clinical testing for the treatment of multiple myeloma, in combination with dexamethasone/carfilzomib. Activation of natural killer (NK) cells has been observed after systemic delivery of reovirus to cancer patients; however, the ability of OV to potentiate NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC) is unexplored.

Müller glia activation in response to inherited retinal degeneration is highly varied and disease-specific.

Despite different aetiologies, most inherited retinal disorders culminate in photoreceptor loss, which induces concomitant changes in the neural retina, one of the most striking being reactive gliosis by Müller cells. It is typically assumed that photoreceptor loss leads to an upregulation of glial fibrilliary acidic protein (Gfap) and other intermediate filament proteins, together with other gliosis-related changes, including loss of integrity of the outer limiting membrane (OLM) and deposition of proteoglycans. However, this is based on a mix of both injury-induced and genetic causes of photoreceptor loss.

Changes in inpatients' experiences of hospital care in England over a 12-year period: a secondary analysis of national survey data.

Objectives: Adult inpatient surveys generate approximately 70,000 responses per year about patients' experiences of National Health Service hospital care in England. We examine historical data to assess change between 2002 and 2013 and consider the factors that may have stimulated any change.

Methods: Archived national data from National Health Service Inpatient Surveys between 2002 and 2013 (comprising 840,077 patient responders) were obtained.

A comparison of drugs and procedures of care in the Italian hospice and hospital settings: the final three days of life for cancer patients.

Background: A palliative approach at the end of life typically involves forgoing certain drugs and procedures and starting others - weighing burden against potential benefit. An assessment of the palliative approach may be undertaken by investigating which drugs and procedures are used in the dying phase, and at what frequencies.

Methods: Drugs were classified as potentially (in)appropriate based on expert classification.

EGR2 is critical for peripheral naïve T-cell differentiation and the T-cell response to influenza.

Early growth response 2 (EGR2) transcription factor negatively regulates T-cell activation, in contrast to the positive regulation of this process by EGR1. Here, we unexpectedly found that EGR2 promotes peripheral naïve T-cell differentiation, with delayed T-cell receptor-induced proliferation in naïve T cells from Egr2 conditional knockout (CKO) mice and decreased production of IFN-γ, IL-4, IL-9, and IL-17A in cells subjected to T-helper differentiation. Moreover, genes that promote T-cell activation, including Tbx21 and Notch1, had decreased expression in Egr2 CKO T cells and are direct EGR2 target genes.

Interplay between regulatory T cells and PD-1 in modulating T cell exhaustion and viral control during chronic LCMV infection.

Regulatory T (T reg) cells are critical for preventing autoimmunity mediated by self-reactive T cells, but their role in modulating immune responses during chronic viral infection is not well defined. To address this question and to investigate a role for T reg cells in exhaustion of virus-specific CD8 T cells, we depleted T reg cells in mice chronically infected with lymphocytic choriomeningitis virus (LCMV). T reg cell ablation resulted in 10-100-fold expansion of functional LCMV-specific CD8 T cells.

Feasibility of assessing quality of care at the end of life in two cluster trials using an after-death approach with multiple assessments.

Background: In 2009 two randomised cluster trials took place to assess the introduction of the Italian Version of the Liverpool Care Pathway in hospitals and hospices. Before and after data were gathered. The primary aim of this study is to evaluate the feasibility of using a combination of assessment methods aimed at different proxy respondents to create a means of measuring quality of care at the end of life.

A survey comparison of rural versus urban residents and household preparedness.

The purpose of this study was to (a) determine how effective the state's campaign has been in informing rural and urban residents who are reliant on electronic medical equipment about the campaign and (b) determine how effective the state campaign has been in informing medical suppliers about the campaign. Approximately 2,000 residents were interviewed about their understanding of the emergency preparedness campaign. Results indicate that approximately 74% of the rural residents and 82% or the urban residents using electronic medical equipment were unaware of the state's disaster preparedness program.

Thymic stromal lymphopoietin and interleukin-4 mediate the pathogenesis of halothane-induced liver injury in mice.

Unlabelled: Liver eosinophilia has been associated with incidences of drug-induced liver injury (DILI) for more than 50 years, although its role in this disease has remained largely unknown. In this regard, it was recently shown that eosinophils played a pathogenic role in a mouse model of halothane-induced liver injury (HILI). However, the signaling events that drove hepatic expression of eosinophil-associated chemokines, eotaxins, eosinophil infiltration, and subsequent HILI were unclear.

It takes patience and persistence to get negative feedback about patients' experiences: a secondary analysis of national inpatient survey data.

Background: Patient experience surveys are increasingly used to gain information about the quality of healthcare. This paper investigates whether patients who respond before and after reminders to a large national survey of inpatient experience differ in systematic ways in how they evaluate the care they received.

Methods: The English national inpatient survey of 2009 obtained data from just under 70,000 patients.

Prelimbic and infralimbic cortical regions differentially encode cocaine-associated stimuli and cocaine-seeking before and following abstinence.

Cocaine stimuli often trigger relapse of drug-taking, even following periods of prolonged abstinence. Here, electrophysiological recordings were made in rats (n = 29) to determine how neurons in the prelimbic (PrL) or infralimbic (IL) regions of the medial prefrontal cortex (mPFC) encode cocaine-associated stimuli and cocaine-seeking, and whether this processing is differentially altered after 1 month of cocaine abstinence. After self-administration training, neurons (n = 308) in the mPFC were recorded during a single test session conducted either the next day or 1 month later.

Nurse staffing, medical staffing and mortality in Intensive Care: An observational study.

Objectives: To investigate whether the size of the workforce (nurses, doctors and support staff) has an impact on the survival chances of critically ill patients both in the intensive care unit (ICU) and in the hospital.

Background: Investigations of intensive care outcomes suggest that some of the variation in patient survival rates might be related to staffing levels and workload, but the evidence is still equivocal.

Data: Information about patients, including the outcome of care (whether the patient lived or died) came from the Intensive Care National Audit & Research Centre (ICNARC) Case Mix Programme.

Effects of respiratory exchange ratio on the prognostic value of peak oxygen consumption and ventilatory efficiency in patients with systolic heart failure.

Objectives: The purpose of this analysis was to evaluate the prognostic characteristics of peak oxygen consumption (Vo2) and the minute ventilation/carbon dioxide (VE/Vco2) slope of different peak respiratory exchange ratios (RERs) obtained from cardiopulmonary exercise testing in patients with heart failure (HF).

Background: For patients with HF, peak Vo2 and the VE/Vco2 slope are used for assessing prognosis. Peak Vo2 is assessed in association with peak RER ≥1.

Vemurafenib-induced neutrophilic panniculitis in a child with a brainstem glioma.

Neutrophilic panniculitis is a rare adverse effect of therapy with selective BRAF inhibitors. We report a case of neutrophilic panniculitis in a 15-year-old girl receiving treatment with vemurafenib for a brainstem glioma. Clinicians should be aware of this rare but important side effect of vemurafenib.

Opposing actions of IL-2 and IL-21 on Th9 differentiation correlate with their differential regulation of BCL6 expression.

Interleukin 9 (IL-9) is a γc-family cytokine that is highly produced by T-helper 9 (Th9) cells and regulates a range of immune responses, including allergic inflammation. Here we show that IL-2-JAK3-STAT5 signaling is required for Th9 differentiation, with critical STAT5 binding sites in the Il9 (the gene encoding IL-9) promoter. IL-2 also inhibited B cell lymphoma 6 (BCL6) expression, and overexpression of BCL6 impaired Th9 differentiation.

Viral warfare! Front-line defence and arming the immune system against cancer using oncolytic vaccinia and other viruses.

Background: Despite mankind's many achievements, we are yet to find a cure for cancer. We are now approaching a new era which recognises the promise of harnessing the immune system for anti-cancer therapy. Pathogens have been implicated for decades as potential anti-cancer agents, but implementation into clinical therapy has been plagued with significant drawbacks.

Is there a relationship between pain and psychological concerns related to falling in community dwelling older adults? A systematic review.

Purpose: To systematically review and synthesise the research evidence linking pain to psychological concerns about falling in community dwelling older adults.

Methods: A systematic review was conducted in accordance with the preferred reporting items of systematic reviews and meta-analysis statement (PRISMA). Major electronic databases were searched from inception until June 2013.

A multicenter study of initiation of antiretroviral therapy and transmitted drug resistance in antiretroviral-naive adolescents and young adults with HIV in New York City.

Background: In December 2009, the Department of Health and Human Services guidelines for initiation of antiretroviral therapy (ART) changed to include patients with CD4 counts between 350 and 500 cells/µL. The aims of this study were to assess uptake of this recommendation in ART-naive youth with human immunodeficiency virus (HIV) and to describe the epidemiology of transmitted genotypic drug resistance mutations (DRMs) in this population.

Methods: A multicenter, retrospective cohort study of ART initiation in ART-naive youth was performed.

Comparison of the EPOC and i-STAT analysers for canine blood gas and electrolyte analysis.

Objectives: A prospective study to evaluate agreement and precision of a new point-of-care portable analyser, the EPOC analyser, compared with the i-STAT analyser in canine blood.

Methods: Blood samples (68 venous and 32 arterial) were obtained from 63 client-owned dogs for clinical reasons and surplus blood was used to analyse agreement between the EPOC and i-STAT analysers. Precision of the EPOC analyser was also assessed by repeat analysis of 20 samples.

A neural network approach to predicting outcomes in heart failure using cardiopulmonary exercise testing.

Objectives: To determine the utility of an artificial neural network (ANN) in predicting cardiovascular (CV) death in patients with heart failure (HF).

Background: ANNs use weighted inputs in multiple layers of mathematical connections in order to predict outcomes from multiple risk markers. This approach has not been applied in the context of cardiopulmonary exercise testing (CPX) to predict risk in patients with HF.

Generalized verrucosis in a patient with GATA2 deficiency.

Generalized verrucosis is a characteristic of several genetic and immunodeficiency disorders including epidermodysplasia verruciformis; warts, hypogammaglobulinaemia, infections and myelokathexis (WHIM) syndrome; warts, immunodeficiency, lymphoedema and anogenital dysplasia (WILD) syndrome; severe combined immune deficiency and HIV, among others. In recent years, it has been consistently recognized in patients with GATA2 deficiency, a novel immunodeficiency syndrome characterized by monocytopenia, B-cell and natural killer-cell lymphopenia, and a tendency to develop myeloid leukaemias and disseminated mycobacterial, human papillomavirus (HPV) and opportunistic fungal infections. Mutations in GATA2 cause haploinsufficiency and track in families as an autosomal dominant immunodeficiency.

TSLP: A Key Regulator of Asthma Pathogenesis.

Asthma is a complex disorder of the airways that is characterized by T helper type 2 (Th2) inflammation. The pleiotrophic cytokine TSLP has emerged as an important player involved in orchestrating the inflammation seen in asthma and other atopic diseases. Early research elucidated the role of TSLP on CD4 T cells, and recent work has revealed the impact of TSLP on multiple cell types.