Regulatory B Cells: The New “It” Cell

Regulatory B cells (B_reg) are a subpopulation of B cells that play a suppressive role in the immune system. The mechanism of how these immune cells perform their effects has been explored by experiments in mice and in humans. Intracellular staining for interleukin 10 continues to be a consistent and reproducible method of identifying B_reg in mouse and human studies. The lack of B_reg is associated with a worsening of several autoimmune diseases such as collagen-induced arthritis, systemic lupus erythematosus, and experimental autoimmune encephalomyelitis in murine studies. The purpose of this review is to provide a concise summary of the role of B_reg in the immune system, including the most recently studied cell surface markers associated with B_reg, and to describe the role of B_reg in the etiology of several autoimmune diseases, the current understanding of B_reg development, their role in the development of autoimmune diseases, and their role in inducing tolerance after transplantation.     

Supporting older people following out of hours discharge from the Emergency Department: An integrative review of the literature

Background

For many older people the emergency department (ED) is an important but sometimes difficult step in their healthcare journey. They often attend the ED with co and multi morbidities. Discharge home at evenings and weekends when post-discharge support services are limited can result in a delay or failure to follow through on their discharge plan leading to adverse health outcomes and in some cases, readmission to ED.

Objective

The aim of this integrative review was to identify and appraise the support available to older people following discharge from the ED out of hours (OOH).

Methods

For this review, out of hours referred to those times after 17.30 until 08.00 a.m. on Mondays to Fridays, all hours on weekends and public holidays. Whittemore and Knafl's (Journal of Advanced Nursing, 2005;52:546), framework was used to guide all stages of the review process. Articles were retrieved following a rigorous search of published works using various databases, the grey literature and hand search of the reference lists of the studies included.

Results

In total 31 articles were included in the review. These comprised systematic reviews, randomised control studies, cohort studies and surveys. Main themes identified included processes that enable support, support provision by health and social care professionals and telephone follow-up. Results identified a significant dearth of out of hours discharge research and a strong recommendation for more concise and thorough research in this important area of care transition.

Conclusion

Older person discharge home from the ED presents an associated risk as previous research has identified frequent readmission and periods of ill health and dependency. Out of hours discharge can be even more problematic when it may be difficult to arrange support services and ensure continuity of care. Further work in this area is required, taking cognisance of the findings and recommendations identified in this review.     

Complications,revision fusions,readmissions, and utilization over a 1-year period after bone morphogenetic protein use during primary cervical spine fusions

Background contextNationwide estimates examining bone morphogenetic protein (BMP) use with cervical spine fusions have been limited to perioperative outcomes.PurposeTo determine the 1-year risk of complications, cervical revision fusions, hospital readmissions, and health care services utilization.Study designA retrospective cohort study from 2002 to 2009 using a nationwide claims database.Patient sampleThere were 61,937 primary cervical spine fusions of which 1,677 received BMP.Outcome measuresComplications, revision fusions, 30-day hospital readmission, and health care utilization.MethodsData for these analyses come from the Thomson Reuters MarketScan Commercial Claims and Encounters Database 2010. Patients were aged 18 to 64 years, receiving and not receiving BMP with a primary (C2–C7) cervical spine fusion. All outcomes were defined by International Classification of Diseases, 9th edition Clinical Modification and Current Procedural and Terminology, 4th edition codes. Complications were analyzed as any complication and stratified by nervous system, wound, and dysphagia or hoarseness. Cervical revision fusions were determined in the 1-year follow-up. Hospital readmission discharge records defined 30-day hospital readmission and reason for the readmission. The utilization of at least one health care service of cervical spine imaging, epidural usage or rehabilitation service was examined. Poisson regression models were used to estimate the relative risk and 95% confidence interval (CI). Linear regression was used to determine the time to hospital readmission. Results were stratified by anterior or posterior and circumferential approaches.ResultsPatients receiving BMP were 29% more likely to have a complication (adjusted relative risk [aRR]=1.29 [95% CI, 1.14–1.46]) and a nervous system complication (aRR=1.42 [95% CI, 1.10–1.83]). Cervical revision fusions were more likely among patients receiving BMP (aRR=1.69 [95% CI, 1.35–2.13]). The risk of 30-day readmission was greater with BMP use (aRR=1.37 [95% CI, 1.07–1.73]) and readmission occurred 27.4% sooner on an average. Patients receiving BMP were more likely to receive computed tomography scans (aRR=1.34 [95% CI, 1.06–1.70]) and epidurals with anterior surgical approaches (aRR=1.29 [95% CI, 1.00–1.65]).ConclusionsThese findings question both the safety and effectiveness of off-label BMP use in primary cervical spine fusions.     

Dissecting virulence: systematic and functional analyses of a pathogenicity island

Bacterial pathogenicity islands (PAI) often encode both effector molecules responsible for disease and secretion systems that deliver these effectors to host cells. Human enterohemorrhagic Escherichia coli (EHEC), enteropathogenic E. coli, and the mouse pathogen Citrobacter rodentium (CR) possess the locus of enterocyte effacement (LEE) PAI. We systematically mutagenized all 41 CR LEE genes and functionally characterized these mutants in vitro and in a murine infection model. We identified 33 virulence factors, including two virulence regulators and a hierarchical switch for type III secretion. In addition, 7 potential type III effectors encoded outside the LEE were identified by using a proteomics approach. These non-LEE effectors are encoded by three uncharacterized PAIs in EHEC O157, suggesting that these PAIs act cooperatively with the LEE in pathogenesis. Our findings provide significant insights into bacterial virulence mechanisms and disease.     

Oxidative metabolism of the human eosinophil

We have compared the oxidative metabolism of human eosinophils (80%-90% purity) to that of neutrophils. Hexose monophosphate (HMP) shunt activity of eosinophils was higher than that of neutrophils under either resting or phagocytizing conditions. Eosinophil HMP shunt activity also was stimulated by phorbol myristate acetate, a membrane- active agent. Eosinophils showed a marked incorporation of 125I into trichloroacetic acid-insoluble material under resting conditions, which increased markedly during phagocytosis. Eosinophils likewise showed a greater reduction of nitroblue tetrazolium dye during phagocytosis than did neutrophils. Measurement of other parameters of oxidative metabolism indicated that eosinophils generated superoxide anion following phagocytosis and also elicited a burst of chemiluminescence similar to that observed during phagocytosis by neutrophils. Measurement of NADPH oxidase activity demonstrated that this enzyme was 3-6 times more active in fractions isolated from eosinophils than in corresponding fractions isolated from neutrophils; this was observed over a range of substrate concentrations. The eosinophil enzyme sedimented differently than the neutrophil enzyme with differential centrifugation; neither showed sedimentation characteristics of peroxidase. These data indicate that eosinophils possess a similar, although in some ways more potent, oxidative burst than neutrophils and are consistent with a role for NADPH oxidase in the initiation of that burst.     

Characterization of N-acetyltransferase 1 and 2 polymorphisms and haplotype analysis for inflammatory bowel disease and sporadic colorectal carcinoma

Background  

N-acetyltransferase 1 (NAT1) and 2 (NAT2) are polymorphic isoenzymes responsible for the metabolism of numerous drugs and carcinogens. Acetylation catalyzed by NAT1 and NAT2 are important in metabolic activation of arylamines to electrophilic intermediates that initiate carcinogenesis. Inflammatory bowel diseases (IBD) consist of Crohn's disease (CD) and ulcerative colitis (UC), both are associated with increased colorectal cancer (CRC) risk. We hypothesized that NAT1 and/or NAT2 polymorphisms contribute to the increased cancer evident in IBD.