Tamoxifen induces apoptotic neutrophil efferocytosis in horses.

Macrophages and neutrophils are important cellular components in the process of acute inflammation and its subsequent resolution, and evidence increasingly suggests that they play important functions during the resolution of chronic, adaptive inflammatory processes. Exacerbated neutrophil activity can be harmful to surrounding tissues; this is important in a range of diseases, including allergic asthma and chronic obstructive pulmonary disease in humans, and equine asthma (also known as recurrent airway obstruction (RAO). Tamoxifen (TX) is a non-steroidal estrogen receptor modulator with effects on cell growth and survival.

Corrigendum: Surgical Rates for Crohn's Disease Are Decreasing: A Population-Based Time Trend Analysis and Validation Study.

This corrects the article DOI: 10.1038/ajg.2017.

The Microbiome of Potentially Malignant Oral Leukoplakia Exhibits Enrichment for , and Species.

Oral leukoplakia presents as a white patch on the oral mucosa and is recognized as having significant malignant potential. Although colonization of these patches with is common, little is known about the bacterial microbiota of these patches. In the current study we analyzed the microbiome of oral leukoplakia in 36 patients compared to healthy mucosal tissue from the same patients and healthy control subjects to determine if specific microbial enrichments could be identified early in the malignant process that could play a role in the progression of the disease.

Aspergillus fumigatus-sensitive IgE is associated with bronchial hypersensitivity in a murine model of neutrophilic airway inflammation.

Neutrophils are the predominant inflammatory cells that infiltrate airways during acute exacerbation of asthma. The importance of A. fumigatus sensitization, and IgE response in the airways in patients with acute asthma is unclear.

The TOR-Activating GTPases Gtr1 and Rhb1 Coregulate Starvation Responses and Biofilm Formation.

Target of rapamycin complex 1 (TORC1) is an essential regulator of metabolism in eukaryotic cells and in the fungal pathogen regulates morphogenesis and nitrogen acquisition. Gtr1 encodes a highly conserved GTPase that in regulates nitrogen sensing and TORC1 activation. Here, we characterize the role of in TORC1 activation and compare it with the previously characterized GTPase Rhb1.

Systematic Review and Meta-Analysis on the Efficacy of Chemotherapy with Transurethral Resection of Bladder Tumors as Definitive Therapy for Muscle Invasive Bladder Cancer.

Background: Bladder-sparing treatment of muscle invasive bladder cancer (MIBC) with systemic chemotherapy plus transurethral resection of bladder tumors (TURBT) is increasingly seen in the literature -both in case series and subanalyses of patients who opt out of or are unfit for radical cystectomy (RC). Survival outcomes among these patients are often impressive, but these are typically small retrospective studies from single institutions and therefore of limited clinical value.

Objectives: Our aim is to summarize the literature regarding definitive treatment of MIBC with systemic chemotherapy plus TURBT and provide a meta-analysis of survival outcomes for patients who received this treatment.

Comparison of Outcomes of antibiotic Drugs and Appendectomy (CODA) trial: a protocol for the pragmatic randomised study of appendicitis treatment.

Introduction: Several European studies suggest that some patients with appendicitis can be treated safely with antibiotics. A portion of patients eventually undergo appendectomy within a year, with 10%-15% failing to respond in the initial period and a similar additional proportion with suspected recurrent episodes requiring appendectomy. Nearly all patients with appendicitis in the USA are still treated with surgery.

Surgical Rates for Crohn's Disease are Decreasing: A Population-Based Time Trend Analysis and Validation Study.

Objectives: Temporal changes for intestinal resections for Crohn's disease (CD) are controversial. We validated administrative database codes for CD diagnosis and surgery in hospitalized patients and then evaluated temporal trends in CD surgical resection rates.

Methods: First, we validated International Classification of Disease (ICD)-10-CM coding for CD diagnosis in hospitalized patients and Canadian Classification of Health Intervention coding for surgical resections.

Subgroup Analysis of Antibiotic Treatment for Skin Abscesses.

Study Objective: Two large randomized trials recently demonstrated efficacy of methicillin-resistant Staphylococcus aureus (MRSA)-active antibiotics for drained skin abscesses. We determine whether outcome advantages observed in one trial exist across lesion sizes and among subgroups with and without guideline-recommended antibiotic indications.

Methods: We conducted a planned subgroup analysis of a double-blind, randomized trial at 5 US emergency departments, demonstrating superiority of trimethoprim-sulfamethoxazole (320/1,600 mg twice daily for 7 days) compared with placebo for patients older than 12 years with a drained skin abscess.

Screening for Behavioral Health Conditions in Primary Care Settings: A Systematic Review of the Literature.

Background: Mounting evidence indicates that early recognition and treatment of behavioral health disorders can prevent complications, improve quality of life, and help reduce health care costs. The aim of this systematic literature review was to identify and evaluate publicly available, psychometrically tested tools that primary care physicians (PCPs) can use to screen adult patients for common mental and substance use disorders such as depression, anxiety, and alcohol use disorders.

Methods: We followed the Institute of Medicine (IOM) systematic review guidelines and searched PubMed, PsycINFO, Applied Social Sciences Index and Abstracts, Cumulative Index to Nursing and Allied Health Literature, and Health and Psychosocial Instruments databases to identify literature addressing tools for screening of behavioral health conditions.

How does role transition affect the experience of trainee Advanced Clinical Practitioners: Qualitative evidence synthesis.

Background: Advanced Clinical Practitioners have been developed to address current and future gaps in the medical workforce. Insight into problems associated with Advanced Clinical Practitioner transition may help present and future trainees adapt to their changing and demanding health environment.

Aims: To identify potential problems experienced by trainee Advanced Clinical Practitioners during transition and what the implications might be for workforce planning.

MRI assessment of the postprandial gastrointestinal motility and peptide response in healthy humans.

Background: Feeding triggers inter-related gastrointestinal (GI) motor, peptide and appetite responses. These are rarely studied together due to methodological limitations. Recent MRI advances allow pan-intestinal, non-invasive assessment of motility in the undisturbed gut.

A competent catalytic active site is necessary for substrate induced dimer assembly in triosephosphate isomerase.

The protozoan parasite Trichomonas vaginalis contains two nearly identical triosephosphate isomerases (TvTIMs) that dissociate into stable monomers and dimerize upon substrate binding. Herein, we compare the role of the "ball and socket" and loop 3 interactions in substrate assisted dimer assembly in both TvTIMs. We found that point mutants at the "ball" are only 39 and 29-fold less catalytically active than their corresponding wild-type counterparts, whereas Δloop 3 deletions are 1502 and 9400-fold less active.

Site-Specific Phosphorylation of PSD-95 PDZ Domains Reveals Fine-Tuned Regulation of Protein-Protein Interactions.

The postsynaptic density protein of 95 kDa (PSD-95) is a key scaffolding protein that controls signaling at synapses in the brain through interactions of its PDZ domains with the C-termini of receptors, ion channels, and enzymes. PSD-95 is highly regulated by phosphorylation. To explore the effect of phosphorylation on PSD-95, we used semisynthetic strategies to introduce phosphorylated amino acids at four positions within the PDZ domains and examined the effects on interactions with a large set of binding partners.

A Qualitative Study Examining Experiences and Dilemmas in Concealment and Disclosure of People Living With Serious Mental Illness.

People with mental illnesses face the dilemma of whether to disclose or conceal their diagnosis, but this dilemma was scarcely researched. To gain in-depth understanding of this dilemma, we interviewed 29 individuals with mental illnesses: 16 with major depression/bipolar disorders and 13 with schizophrenia. Using a phenomenological design, we analyzed individuals' experiences, decision-making processes, and views of gains and costs regarding concealment and disclosure of mental illness.

Phosphate is the third nutrient monitored by TOR in and provides a target for fungal-specific indirect TOR inhibition.

The Target of Rapamycin (TOR) pathway regulates morphogenesis and responses to host cells in the fungal pathogen Eukaryotic Target of Rapamycin complex 1 (TORC1) induces growth and proliferation in response to nitrogen and carbon source availability. Our unbiased genetic approach seeking unknown components of TORC1 signaling in revealed that the phosphate transporter Pho84 is required for normal TORC1 activity. We found that mutants in are hypersensitive to rapamycin and in response to phosphate feeding, generate less phosphorylated ribosomal protein S6 (P-S6) than the WT.

The enzyme: Renalase.

Within the last two years catalytic substrates for renalase have been identified, some 10 years after its initial discovery. 2- and 6-dihydronicotinamide (2- and 6-DHNAD) isomers of β-NAD(P)H (4-dihydroNAD(P)) are rapidly oxidized by renalase to form β-NAD(P). The two electrons liberated are then passed to molecular oxygen by the renalase FAD cofactor forming hydrogen peroxide.

Effect of Cephalexin Plus Trimethoprim-Sulfamethoxazole vs Cephalexin Alone on Clinical Cure of Uncomplicated Cellulitis: A Randomized Clinical Trial.

Importance: Emergency department visits for skin infections in the United States have increased with the emergence of methicillin-resistant Staphylococcus aureus (MRSA). For cellulitis without purulent drainage, β-hemolytic streptococci are presumed to be the predominant pathogens. It is unknown if antimicrobial regimens possessing in vitro MRSA activity provide improved outcomes compared with treatments lacking MRSA activity.

Combination of corticosteroids and 5-aminosalicylates or corticosteroids alone for patients with moderate-severe active ulcerative colitis: A global survey of physicians' practice.

Aim: To examine treatment decisions of gastroenterologists regarding the choice of prescribing 5-aminosalycilates (5ASA) with corticosteroids (CS) versus corticosteroids alone for patients with active ulcerative colitis (UC).

Methods: A cross-sectional questionnaire exploring physicians' attitude toward 5ASA + CS combination therapy CS alone was developed and validated. The questionnaire was distributed to gastroenterology experts in twelve countries in five continents.

Literature review: impacts of socioeconomic status on the risk of inflammatory bowel disease and its outcomes.

The relationship between socioeconomic status (SES) and inflammatory bowel disease (IBD) is controversial. To date, research has focused on effects on incidence and prevalence, disease management and clinical outcomes; however, conclusions remain uncertain. This review examines current evidence, identifies what remains to be understood and explores the practical implications this has for today.

Modulatory role of regulatory T cells in a murine model of severe equine asthma.

Background: It is accepted that T regulatory cells (Treg) control different types of immune responses. In connection with this role, we have recently described an important increase in CD4+, CD25, Foxp3+ lymphocytes in the airway system of horses coursing with an exacerbation of severe equine asthma (EA). To explore the potential role of this population in the resolution of EA inflammation, we used a murine experimental model in which airway neutrophilic inflammation, which is similar to that observed in EA, is induced in mice by continual exposure to Aspergillus fumigatus contaminated hay.

The Pattern of Underlying Cause of Death in Patients with Inflammatory Bowel Disease in England: A Record Linkage Study.

Background And Aims: Numerous studies have established that mortality risk in inflammatory bowel disease [IBD] patients is higher than in the general population, but the causes of death have seldom been examined. We aimed to describe causes of death in IBD.

Methods: A matched cohort study using UK general practice data from Clinical Practice Research Datalink linked to death registration records.

New insight on intergenerational attachment from a relationship-based analysis.

Research on attachment transmission has focused on variable-centered analyses, where hypotheses are tested by examining linear associations between variables. The purpose of this study was to apply a relationship-centered approach to data analysis, where adult states of mind, maternal sensitivity, and infant attachment were conceived as being three components of a single, intergenerational relationship. These variables were assessed in 90 adolescent and 99 adult mother-infant dyads when infants were 12 months old.