187 research outputs found
Effects of stress on neural processing of combat-related stimuli in deployed soldiers: An fMRI study
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Immature B cells preferentially switch to IgE with increased direct SĪ¼ to SĪµ recombination
Immunoglobulin heavy chain (IgH) class-switch recombination (CSR) replaces initially expressed CĪ¼ (IgM) constant regions (C(H)) exons with downstream C(H) exons. Stimulation of B cells with anti-CD40 plus interleukin-4 induces CSR from CĪ¼ to CĪ³1 (IgG1) and CĪµ (IgE), the latter of which contributes to the pathogenesis of atopic diseases. Although CĪµ CSR can occur directly from CĪ¼, most mature peripheral B cells undergo CSR to CĪµ indirectly, namely from CĪ¼ to CĪ³1, and subsequently to CĪµ. Physiological mechanisms that influence CSR to CĪ³1 versus CĪµ are incompletely understood. In this study, we report a role for B cell developmental maturity in IgE CSR. Based in part on a novel flow cytometric IgE CSR assay, we show that immature B cells preferentially switch to IgE versus IgG1 through a mechanism involving increased direct CSR from CĪ¼ to CĪµ. Our findings suggest that IgE dysregulation in certain immunodeficiencies may be related to impaired B cell maturation
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Microbial colonization influences early B-lineage development in the gut lamina propria
The RAG1/RAG2 endonuclease ("RAG") initiates the V(D)J recombination reaction that assembles Ig heavy (IgH) and light (IgL) chain variable region exons from germline gene segments to generate primary antibody repertoires1. IgH V(D)J assembly occurs in progenitor (pro-) B cells followed by that of IgL in precursor (pre-) B cells. Expression of IgH Ī¼ and IgL (IgĪŗ or IgĪ») chains generates IgM, which is expressed on immature B cells as the B cell antigen-binding receptor ("BCR"). Rag expression can continue in immature B cells2, allowing continued IgĪŗ V(D)J recombination that replaces the initial VĪŗJĪŗ exon with one that generates a new specificity3ā5. This āreceptor editingā process, which also can lead to IgĪ» V(D)J recombination and expression3,6,7, provides a mechanism whereby antigen-encounter at the Rag-expressing immature B cell stage helps shape pre-immune BCR repertoires. As the major site of post-natal B cell development, the bone marrow is the principal location of primary Ig repertoire diversification in mice. Here, we report that early B cell development also occurs within the mouse intestinal lamina propria (LP), where the associated V(D)J recombination/receptor editing processes modulate primary LP Ig repertoires. At weanling age in normally housed mice, the LP contains a population of Rag-expressing B lineage cells that harbor intermediates indicative of ongoing V(D)J recombination and which contain cells with pro-B, pre-B, and editing phenotypes. Consistent with LP-specific receptor editing, Rag-expressing LP B-lineage cells have similar VH repertoires, but significantly different VĪŗ repertoires, compared to those of Rag2-expressing BM counterparts. Moreover, colonization of germ-free mice leads to an increased ratio of IgĪ»-expressing versus IgĪŗ-expressing B cells specifically in the LP. We conclude that B cell development occurs in the intestinal mucosa, where it is regulated by extra-cellular signals from commensal microbes that influence gut Ig repertoires
Memantine augmentation in clozapine-refractory schizophrenia: a randomized, double-blind, placebo-controlled crossover study
Cost-effectiveness of an integrated 'fast track' rehabilitation service for multi-trauma patients involving dedicated early rehabilitation intervention programs: design of a prospective, multi-centre, non-randomised clinical trial
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79649.pdf (publisher's version ) (Open Access)ABSTRACT: BACKGROUND: In conventional multi-trauma care service (CTCS), patients are admitted to hospital via the accident & emergency room. After surgery they are transferred to the IC-unit followed by the general surgery ward. Ensuing treatment takes place in a hospital's outpatient clinic, a rehabilitation centre, a nursing home or the community. Typically, each of the CTCS partners may have its own more or less autonomous treatment perspective. Clinical evidence, however, suggests that an integrated multi-trauma rehabilitation approach ('Supported Fast-track multi-Trauma Rehabilitation Service': SFTRS), featuring: 1) earlier transfer to a specialised trauma rehabilitation unit; 2) earlier start of 'non-weight-bearing' training and multidisciplinary treatment; 3) well-documented treatment protocols; 4) early individual goal-setting; 5) co-ordination of treatment between trauma surgeon and physiatrist, and 6) shorter lengths-of-stay, may be more (cost-)effective.This paper describes the design of a prospective cohort study evaluating the (cost-) effectiveness of SFTRS relative to CTCS. METHODS/DESIGN: The study population includes multi-trauma patients, admitted to one of the participating hospitals, with an Injury Severity Scale score > = 16, complex multiple injuries in several extremities or complex pelvic and/or acetabulum fractures. In a prospective cohort study CTCS and SFTRS will be contrasted. The inclusion period is 19 months. The duration of follow-up is 12 months, with measurements taken at baseline, and at 3,6,9 and 12 months post-injury.Primary outcome measures are 'quality of life' (SF-36) and 'functional health status' (Functional Independence Measure). Secondary outcome measures are the Hospital Anxiety & Depression Scale, the Mini-Mental State Examination as an indicator of cognitive functioning, and the Canadian Occupational Performance Measure measuring the extent to which individual ADL treatment goals are met. Costs will be assessed using the PROductivity and DISease Questionnaire and a cost questionnaire. DISCUSSION: The study will yield results on the efficiency of an adapted care service for multi-trauma patients (SFTRS) featuring earlier (and condensed) involvement of specialised rehabilitation treatment. Results will show whether improved SFTRS logistics, combined with shorter stays in hospital and rehabilitation clinic and specialised early rehabilitation training modules are more (cost-) effective, relative to CTCS. TRIAL REGISTRATION: Current Controlled Trials register (ISRCTN68246661) and Netherlands Trial Register (NTR139)
Towards a comprehensive estimate of national spending on prevention
Background
Comprehensive information about national spending on prevention is crucial for health policy development and evaluation. This study provides a comprehensive overview of prevention spending in the Netherlands, including those activities beyond the national health accounts.
Methods
National spending on health-related primary and secondary preventive activities was examined by funding source with the use of national statistics, government reports, sector reports, and data from individual health associations and corporations, public services, occupational health services, and personal prevention. Costs were broken down by diseases, age groups and gender using population-attributable risks and other key variables.
Results
Total expenditures on prevention were ā¬12.5 billion or ā¬769 per capita in the Netherlands in 2003, of which 20% was included in the national health accounts. 82% was spent on health protection, 16% on disease prevention, and 2% on health promotion activities. Most of the spending was aimed at the prevention of infectious diseases (34%) and acute physical injuries (29%). Per capita spending on prevention increased steeply by age.
Conclusion
Total expenditure on health-related prevention is much higher than normally reported due to the inclusion of health protection activities beyond the national health accounts. The allocative efficiency of prevention spending, particularly the high costs of health protection and the low costs of health promotion activities, should be addressed with information on their relative cost effectiveness
Receptor-Mediated Gonadotropin Action in Ovary
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66088/1/j.1432-1033.1981.tb05481.x.pd
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