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2.
Artigo em Inglês | MEDLINE | ID: mdl-31625617

RESUMO

The Raphe Pallidus (RPa) is a region of the brainstem that was shown to modulate the sympathetic outflow to many tissues and organs involved in thermoregulation and energy expenditure. In rodents, the pharmacological activation of RPa neurons was shown to increase the activity of the brown adipose tissue, heart rate, and expired CO2 , whereas their inhibition was shown to induce cutaneous vasodilation and a state of hypothermia that, when prolonged, leads to a state resembling torpor referred to as synthetic torpor. If translatable to humans, this synthetic torpor-inducing procedure would be advantageous in many clinical settings. A first step to explore such translatability, has been to verify whether the neurons within the RPa play the same role described for rodents in a larger mammal such as the pig. In the present study, we show that the physiological responses inducible by the pharmacological stimulation of RPa neurons are very similar to those observed in rodents. Injection of the GABAA agonist GABAzine in the RPa induced an increase in heart rate (from 99 to 174 bpm), systolic (from 87 to 170 mmHg) and diastolic (from 51 to 98 mmHg arterial pressure, and end tidal CO2 (from 49 to 62 mmhg). All these changes were reversed by the injection in the same area of the GABAA agonist muscimol. These results support the possibility for RPa neurons to be a key target in the research for a safe and effective procedure for the induction of synthetic torpor in humans.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31274159

RESUMO

OBJECTIVES: SS is an autoimmune condition characterized by systemic B-cell activation, autoantibody production and ectopic germinal centres' formation within the salivary gland (SG). The extent of SG infiltrate has been proposed as a biomarker of disease severity. Plasma levels of CXCL13 correlate with germinal centres' activity in animal models and disease severity in SS, suggesting its potential use as a surrogate serum marker to monitor local B-cell activation. The aim of this study was to evaluate the potential role of CXCL13 as a biomarker of SG pathology in two independent SS cohorts. METHODS: 109 patients with SS were recruited at Sapienza University of Rome (Italy) (n = 60), or at Queen Elizabeth Hospital in Birmingham and Barts Health NHS Trust in London (n = 49). Both sera and matched minor SG biopsy were available. Sicca (n = 57) and healthy subjects' (n = 19) sera were used as control. RESULTS: CXCL13 serum level was higher in SS patients compared with controls. Correlations between its serum levels and a series of histomorphological parameters, including size of the aggregates and the presence germinal centres', were observed. CONCLUSION: Our data foster the use of CXCL13 to monitor the extent of local pathology in SS and its validation in longitudinal clinical studies.

4.
Proc Natl Acad Sci U S A ; 116(27): 13490-13497, 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31213547

RESUMO

Resident fibroblasts at sites of infection, chronic inflammation, or cancer undergo phenotypic and functional changes to support leukocyte migration and, in some cases, aggregation into tertiary lymphoid structures (TLS). The molecular programming that shapes these changes and the functional requirements of this population in TLS development are unclear. Here, we demonstrate that external triggers at mucosal sites are able to induce the progressive differentiation of a population of podoplanin (pdpn)-positive stromal cells into a network of immunofibroblasts that are able to support the earliest phases of TLS establishment. This program of events, that precedes lymphocyte infiltration in the tissue, is mediated by paracrine and autocrine signals mainly regulated by IL13. This initial fibroblast network is expanded and stabilized, once lymphocytes are recruited, by the local production of the cytokines IL22 and lymphotoxin. Interfering with this regulated program of events or depleting the immunofibroblasts in vivo results in abrogation of local pathology, demonstrating the functional role of immunofibroblasts in supporting TLS maintenance in the tissue and suggesting novel therapeutic targets in TLS-associated diseases.

5.
Nature ; 570(7760): 246-251, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31142839

RESUMO

The identification of lymphocyte subsets with non-overlapping effector functions has been pivotal to the development of targeted therapies in immune-mediated inflammatory diseases (IMIDs)1,2. However, it remains unclear whether fibroblast subclasses with non-overlapping functions also exist and are responsible for the wide variety of tissue-driven processes observed in IMIDs, such as inflammation and damage3-5. Here we identify and describe the biology of distinct subsets of fibroblasts responsible for mediating either inflammation or tissue damage in arthritis. We show that deletion of fibroblast activation protein-α (FAPα)+ fibroblasts suppressed both inflammation and bone erosions in mouse models of resolving and persistent arthritis. Single-cell transcriptional analysis identified two distinct fibroblast subsets within the FAPα+ population: FAPα+THY1+ immune effector fibroblasts located in the synovial sub-lining, and FAPα+THY1- destructive fibroblasts restricted to the synovial lining layer. When adoptively transferred into the joint, FAPα+THY1- fibroblasts selectively mediate bone and cartilage damage with little effect on inflammation, whereas transfer of FAPα+ THY1+ fibroblasts resulted in a more severe and persistent inflammatory arthritis, with minimal effect on bone and cartilage. Our findings describing anatomically discrete, functionally distinct fibroblast subsets with non-overlapping functions have important implications for cell-based therapies aimed at modulating inflammation and tissue damage.

6.
Artigo em Inglês | MEDLINE | ID: mdl-30945742

RESUMO

Primary SS (pSS) is a chronic autoimmune condition characterized by infiltration of the exocrine glands and systemic B cell hyperactivation. This glandular infiltration is associated with loss of glandular function, with pSS patients primarily presenting with severe dryness of the eyes and mouth. Within the affected glands, the infiltrating lymphocytes are organized in tertiary lymphoid structures. Tertiary lymphoid structures subvert normal tissue architecture and impact on organ function, by promoting the activation and maintenance of autoreactive lymphocytes. This review summarizes the current knowledge about the role of stromal cells (including endothelium, epithelium, nerves and fibroblasts) in the pathogenesis of pSS, in particular the interactions taking place between stromal cells and infiltrating lymphocytes. We will provide evidences pointing towards the driving role of stromal cells in the orchestration of the local inflammatory milieu, thus highlighting the need for therapies aimed at targeting this compartment alongside classical immunosuppression in pSS.

7.
Molecules ; 24(6)2019 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-30893764

RESUMO

The growing interest towards essential oils stems from their biological capabilities that include antibacterial and antioxidant effects. Such properties may be extremely useful in the reproductive field; nonetheless essential oils show toxic effects that can lead to cell disruption. The present study aimed to evaluate and compare the effects of tea tree oil (TTO) and its principal component terpinen-4-ol (TER) on the morpho-functional parameters of swine spermatozoa. Experimental samples were prepared by suspending 15 × 107 spermatozoa in 5 mL of medium with different concentrations of the above-mentioned compounds: from 0.2 to 2 mg/mL at an interval of 0.2 for TTO, while TER concentrations were adjusted according to its presence in TTO (41.5%). After 3 h incubation at 16 °C, samples were analyzed for pH, viability, acrosome status, and objective motility. The results highlighted a concentration-dependent effect of TTO with total motility as the most sensitive parameter. TER was better tolerated, and the most sensitive parameters were related to membrane integrity, suggesting a different pattern of interaction. The study confirms the importance of evaluating the effects of natural compounds on spermatozoa before exploiting their beneficial effects. Spermatozoa seem to be good candidates for preliminary toxicological screenings in the light of their peculiar properties.


Assuntos
Melaleuca/química , Espermatozoides/efeitos dos fármacos , Óleo de Melaleuca/farmacologia , Terpenos/farmacologia , Animais , Masculino , Suínos , Terpenos/química
8.
Invest Ophthalmol Vis Sci ; 60(2): 741-747, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30793206

RESUMO

Purpose: Qualitative and quantitative analysis of vitreous humor (VH) is important to discriminate between physiological and pathological conditions and may be particularly helpful when using animal models for ophthalmologic research. The aim of the present study was to investigate the physiological qualitative/quantitative composition of the VH of the standard pig using a metabolomics approach based on 1H nuclear magnetic resonance (NMR) spectroscopy. A secondary aim was the characterization of the VH of the porcine model of photoreceptor degeneration induced with iodoacetic acid (IAA), widely used in the biomedical field, and comparison with the physiological one. Methods: VH samples were collected from 30 pigs (17 in the physiological condition and 13 treated with IAA) upon vitrectomy and analyzed by means of 1H NMR spectroscopy for characterization. Results: On all analyzed samples, 40 molecules could be identified and quantified, with lactate being the most abundant in both physiological and photoreceptor degeneration conditions. Upon comparison, only 17 molecules showed statistical differences: In the IAA group, glucose and glutamine increased, while lactate, 4-amynobutyrate, hypoxanthine, dicarboxylic acids (succinate and fumarate), amino acids with their derivatives (creatine, alanine, valine, lysine, leucine, glycine, taurine, and isoleucine), and choline with its precursor sn-glycero-3-phosphocholine decreased. Conclusions: The results validate the metabolic impairment determined by glycolysis inhibition upon systemic IAA administration. In conclusion, this work represents the first characterization of the porcine VH metabolome in physiological conditions and provides additional information for the characterization and refinement of the IAA-induced photoreceptor degeneration model.


Assuntos
Oftalmopatias/metabolismo , Espectroscopia de Prótons por Ressonância Magnética , Degeneração Retiniana/metabolismo , Corpo Vítreo/metabolismo , Aminoácidos/metabolismo , Animais , Feminino , Ácido Iodoacético/toxicidade , Masculino , Metaboloma , Metabolômica/métodos , Modelos Animais , Células Fotorreceptoras de Vertebrados/efeitos dos fármacos , Degeneração Retiniana/induzido quimicamente , Sus scrofa , Vitrectomia
9.
Clin Nutr ; 38(6): 2645-2651, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30567626

RESUMO

OBJECTIVE: To explore the possible mechanisms behind the lower glycemic response observed when extra-virgin olive oil (EVOO) is added to a high-glycemic index meal in patients with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: According to a randomized cross-over design, eleven T1D patients (6 women, 5 men) on insulin pump consumed in the metabolic ward, one week apart, three high-glycemic index meals differing only for amount and quality of fat: high-monounsaturated fat (EVOO), high-saturated fat (Butter), and low-fat (LF). Before and after the meals, blood glucose (continuous glucose monitoring), gastric emptying rate (ultrasound technique), and plasma concentrations of glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide GIP (ELISA), glucagon (RIA), and lipids (colorimetric assays) were evaluated. RESULTS: Blood glucose iAUC (mmol/lx360 min) was lower after the EVOO (690 ± 431) than after the Butter (1320 ± 600) and LF meals (1007 ± 990) (M ± SD, p = 0.041 by repeated measures ANOVA). Gastric antrum volume was significantly larger in the early (60-90 min) postprandial phase (106 ± 21 vs. 90 ± 16 ml, p = 0.048) and significantly smaller in the late phase (330-360 min) (46 ± 10 vs. 57 ± 22 ml, p = 0.045) after the EVOO than after Butter meal. EVOO significantly increased postprandial GLP-1 iAUC (261 ± 311) compared to Butter (189 ± 349) (pmol/Lx180 min, p = 0.009). Postprandial GIP and glucagon responses were not significantly different between EVOO and Butter. Postprandial triglyceride iAUC was significantly higher after EVOO (100 ± 53) than after Butter (65 ± 60) (mmol/l × 360 min, p = 0.048). CONCLUSIONS: Changes in gastric emptying and GLP-1 secretion and reduced glucose absorption through glucose-lipid competition may contribute to lower glycemia after a high-glycemic index meal with EVOO in T1D patients. CLINICAL TRIALS NUMBER: NCT02330939.

10.
Nutrients ; 11(1)2018 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-30577558

RESUMO

Einkorn wheat (Triticum monococcum) is characterized by high content of proteins, bioactive compounds, such as polyunsaturated fatty acids, fructans, tocols, carotenoids, alkylresorcinols, and phytosterols, and lower α-, ß-amylase and lipoxygenase activities compared to polyploid wheat. These features make einkorn flour a good candidate to provide healthier foods. In the present study, we investigated the effects of einkorn bread (EB) on the intestinal physiology and metabolism of the pig model by characterizing the glycemic and insulinemic response, and the microbiota and metabolome profiles. Sixteen commercial hybrid pigs were enrolled in the study; four pigs were used to characterize postprandial glycemic and insulinemic responses and twelve pigs underwent a 30-day dietary intervention to assess microbiota and metabolome changes after EB or standard wheat bread (WB) consumption. The postprandial insulin rise after an EB meal was characterized by a lower absolute level, and, as also observed for glucose, by a biphasic shape in contrast to that in response to a WB meal. The consumption of EB led to enrichment in short-chain fatty acid producers (e.g., Blautia, Faecalibacterium, and Oscillospira) in the gut microbiota and to higher metabolic diversity with lower content of succinate, probably related to improved absorption and therefore promoting intestinal gluconeogenesis. The observed changes, at both a compositional and metabolic scale, strongly suggest that EB consumption may support a health-promoting configuration of the intestinal ecosystem.


Assuntos
Glicemia/metabolismo , Pão , Microbioma Gastrointestinal/fisiologia , Insulina/sangue , Metaboloma/fisiologia , Triticum , Animais , Ingestão de Alimentos/fisiologia , Farinha/análise , Período Pós-Prandial , Suínos
11.
Ann Rheum Dis ; 2018 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-30472652

RESUMO

BACKGROUND: The phosphatidylinositol 3-kinase delta isoform (PI3Kδ) belongs to an intracellular lipid kinase family that regulate lymphocyte metabolism, survival, proliferation, apoptosis and migration and has been successfully targeted in B-cell malignancies. Primary Sjögren's syndrome (pSS) is a chronic immune-mediated inflammatory disease characterised by exocrine gland lymphocytic infiltration and B-cell hyperactivation which results in systemic manifestations, autoantibody production and loss of glandular function. Given the central role of B cells in pSS pathogenesis, we investigated PI3Kδ pathway activation in pSS and the functional consequences of blocking PI3Kδ in a murine model of focal sialoadenitis that mimics some features of pSS. METHODS AND RESULTS: Target validation assays showed significant expression of phosphorylated ribosomal protein S6 (pS6), a downstream mediator of the phosphatidylinositol 3-kinase delta (PI3Kδ) pathway, within pSS salivary glands. pS6 distribution was found to co-localise with T/B cell markers within pSS aggregates and the CD138+ plasma cells infiltrating the glands. In vivo blockade of PI3Kδ activity with seletalisib, a PI3Kδ-selective inhibitor, in a murine model of focal sialoadenitis decreased accumulation of lymphocytes and plasma cells within the glands of treated mice in the prophylactic and therapeutic regimes. Additionally, production of lymphoid chemokines and cytokines associated with ectopic lymphoneogenesis and, remarkably, saliva flow and autoantibody production, were significantly affected by treatment with seletalisib. CONCLUSION: These data demonstrate activation of PI3Kδ pathway within the glands of patients with pSS and its contribution to disease pathogenesis in a model of disease, supporting the exploration of the therapeutic potential of PI3Kδ pathway inhibition in this condition.

12.
Front Immunol ; 9: 1952, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30258435

RESUMO

Tertiary lymphoid structures (TLS) are frequently observed in target organs of autoimmune diseases. TLS present features of secondary lymphoid organs such as segregated T and B cell zones, presence of follicular dendritic cell networks, high endothelial venules and specialized lymphoid fibroblasts and display the mechanisms to support local adaptive immune responses toward locally displayed antigens. TLS detection in the tissue is often associated with poor prognosis of disease, auto-antibody production and malignancy development. This review focuses on the contribution of TLS toward the persistence of the inflammatory drive, the survival of autoreactive lymphocyte clones and post-translational modifications, responsible for the pathogenicity of locally formed autoantibodies, during autoimmune disease development.

13.
PLoS Biol ; 16(9): e2005046, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30180168

RESUMO

The microenvironment of lymphoid organs can aid healthy immune function through provision of both structural and molecular support. In mice, fibroblastic reticular cells (FRCs) create an essential T-cell support structure within lymph nodes, while human FRCs are largely unstudied. Here, we show that FRCs create a regulatory checkpoint in human peripheral T-cell activation through 4 mechanisms simultaneously utilised. Human tonsil and lymph node-derived FRCs constrained the proliferation of both naïve and pre-activated T cells, skewing their differentiation away from a central memory T-cell phenotype. FRCs acted unilaterally without requiring T-cell feedback, imposing suppression via indoleamine-2,3-dioxygenase, adenosine 2A Receptor, prostaglandin E2, and transforming growth factor beta receptor (TGFßR). Each mechanistic pathway was druggable, and a cocktail of inhibitors, targeting all 4 mechanisms, entirely reversed the suppressive effect of FRCs. T cells were not permanently anergised by FRCs, and studies using chimeric antigen receptor (CAR) T cells showed that immunotherapeutic T cells retained effector functions in the presence of FRCs. Since mice were not suitable as a proof-of-concept model, we instead developed a novel human tissue-based in situ assay. Human T cells stimulated using standard methods within fresh tonsil slices did not proliferate except in the presence of inhibitors described above. Collectively, we define a 4-part molecular mechanism by which FRCs regulate the T-cell response to strongly activating events in secondary lymphoid organs while permitting activated and CAR T cells to utilise effector functions. Our results define 4 feasible strategies, used alone or in combinations, to boost primary T-cell responses to infection or cancer by pharmacologically targeting FRCs.

14.
Methods Mol Biol ; 1845: 17-30, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30141005

RESUMO

Inflammatory immune cells recruited at the site of chronic inflammation form structures that resemble secondary lymphoid organs (SLO). These are characterized by segregated areas of prevalent T- or B-cell aggregation, differentiation of high endothelial venules, and local activation of resident stromal cells, including lymphatic endothelial cells. B-cell proliferation and affinity maturation toward locally displayed autoantigens have been demonstrated at these sites, known as tertiary lymphoid structures (TLS). TLS formation during chronic inflammation has been associated with local disease persistence and progression, as well as increased systemic manifestations. While bearing a similar histological structure to SLO, the signals that regulate TLS and SLO formation can diverge and a series of pro-inflammatory cytokines have been ascribed as responsible for TLS formation at different anatomical sites. Moreover, for a long time the structural compartment that regulates TLS homeostasis, including survival and recirculation of leucocytes has been neglected. In this chapter, we summarize the novel data available on TLS formation, structural organization, and the functional and anatomical links connecting TLS and SLOs.

15.
J Autoimmun ; 94: 143-155, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30119881

RESUMO

IL-12 is a pro-inflammatory cytokine that induces the production of interferon-γ (IFNγ) and favours the differentiation of T helper 1 (Th1) cells. In the presence of IL-12 human Treg cells acquire a Th1-like phenotype with reduced suppressive activity in vitro. Primary biliary cholangitis (PBC) is an autoimmune cholestatic liver disease characterised by high Th1 and Th17 infiltrating cells, reduced frequencies of Treg cells, and a genetic association with IL-12 signalling. Herein, we sought to evaluate the IL-12 signalling pathway in PBC pathology, by studying human samples from patients with PBC, alongside those with primary Sjögren's syndrome (pSS)(autoimmune disease with IL-12 signalling gene association), primary sclerosing cholangitis (PSC) (cholestatic liver disease without IL-12 gene association) and healthy individuals. Our data revealed that TLR stimulation of PBC (n = 17) and pSS monocytes (n = 6) resulted in significant induction of IL12A mRNA (p < 0.05, p < 0.01, respectively) compared to PSC monocytes (n = 13) and at similar levels to HC monocytes (n = 8). PSC monocytes expressed significantly less IL-12p70 (108 pg/ml, mean) and IL-23 (358 pg/ml) compared to HC (458 pg/ml and 951 pg/ml, respectively) (p < 0.01, p < 0.05). Treg cells from patients with PBC (n = 16) and pSS (n = 3) but not PSC (n = 10) and HC (n = 8) responded to low dose (10 ng/ml) IL-12 stimulation by significant upregulation of IFNγ (mean 277 and 254 pg/ml, respectively) compared to PSC and HC Treg cells (mean 22 and 77 pg/ml, respectively)(p < 0.05). This effect was mediated by the rapid and strong phosphorylation of STAT4 on Treg cells from patients with PBC and pSS (p < 0.05) but not PSC and HC. In the liver of patients with PBC (n = 7) a significantly higher proportion of IL-12Rß2+Tregs (16% on average) was detected (p < 0.05) compared to other liver disease controls (5%)(n = 18) which also showed ex vivo high IFNG and TBET expression. CONCLUSION: Our data show an increased sensitivity of PBC and pSS Treg cells to low dose IL-12 stimulation, providing ongoing support for the importance of the IL12-IL-12Rß2-STAT4 pathway on Treg cells in disease pathogenesis and potentially treatment.

16.
Animals (Basel) ; 8(7)2018 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-29986391

RESUMO

The roe deer is a seasonally breeding species with a reproductive cycle regulated by endogenous rhythms and photoperiod-sensitivity. Sexually mature bucks show hormonal and testicular activation during the reproductive season, with a peak in the rut period, and following gradual involution. Hair is a good matrix for non-invasive endocrinological analyses that provide long-term information without being influenced by the hormones’ pulsating release patterns in blood. The aim of the work was to quantify hair concentrations of testosterone and cortisol in wild roe deer bucks hunted during the pre- and post-rut period, using a radioimmunoassay methodology, and to look for differences between the two periods. The secondary objective was the evaluation of possible correlations of such hair concentrations with blood and morphometric parameters of the testes. Both hormones showed statistical differences, with opposing trends, when comparing the two periods: testosterone increased while cortisol decreased. The correlation analysis was in agreement with existing literature regarding metabolism/actions of these hormones and testicular morphometric parameters. This study represents the first report of the use of radioimmunoassay techniques to quantify testosterone and cortisol in roe deer hair, and may provide interesting insights into their reproductive physiology.

17.
J Am Assoc Lab Anim Sci ; 57(4): 350-356, 2018 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-29966544

RESUMO

Swine (Sus scrofa) are often the 'gold standard' laboratory animal for ophthalmology research due to the anatomic and physiologic similarities between the porcine and human eye and retina. Despite the importance of this model, few tools for behavioral vision assessment in pigs are available. The aim of this study was to identify and validate a feasible and reproducible behavioral test to assess vision in a pig model of photoreceptor degeneration. In addition, a robust behavioral test will reduce stress and enhance enrichment by allowing animals opportunities for environmental exploration and by reducing the number of invasive experimental procedures. Two distinct behavioral approaches were tested: the obstacle-course test and temperament test. In the obstacle-course test, pigs were challenged (after an initial training period) to navigate a 10-object obstacle course; time and the number of collisions with the objects were recorded. In the temperament test, the time needed for pigs to complete 3 different tasks (human-approach, novel-object, and open-door tests) was recorded. The obstacle-course test revealed significant differences in time and number of collisions between swine with vision impairment and control animals, and the training period proved to be pivotal to avoid bias due to individual animal characteristics. In contrast, the temperament test was not altered by vision impairment but was validated to measure stress and behavioral alterations in laboratory pigs undergoing experimental procedures, thus achieving marked refinement of the study.

18.
Ig Sanita Pubbl ; 74(2): 153-167, 2018 Mar-Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29936524

RESUMO

BACKGROUND: Interruptions during nurses' work may lead to errors. Little research has been undertaken to date on interruptions in nursing care in surgical settings, specifically with regard to interruptions where other staff was the source of the interruption. OBJECTIVES: To describe the frequency and characteristics of interruptions to nursing work caused by other staff members and to identify predictors according to the source of interruption. METHODS: We conducted a multi-centre observational study in five surgical units admitting urgent and elective cases, in public hospitals in northern Italy. Registered nurses (RN) met inclusion criteria if, at the time of the study, they were (a) working full-time at the study hospital, (b) working since at least three years in the surgical unit, and (c) working either during morning or afternoon shifts. A random sample of 50 RNs was observed during morning and afternoon shifts for a total of 360 hours. Data on interruptions (e.g. duration of the interruption), individual nurses' characteristics (e.g. years of clinical experience), and work setting (e.g. hospital size) were collected and subjected to logistic regression analysis. RESULTS: The mean frequency of interruptions either caused by staff members or other sources was respectively 2.7/hour and 2.9/ hour. Interruptions caused by staff members were shorter than those due to other sources (25.6s vs 39.4s; p=<0.001), just over half occurred during the morning shift and most took place either in the corridors (37%) or in nurses' rooms (36%). Having more years of experience in a surgical unit and having a higher number of nurses available during the shift were protective against interruptions whereas being a graduate RN, taking care of a higher number of patients and working in a large hospital increased the risk of being interrupted by staff members. CONCLUSIONS: Strategies for multi-professional cooperation which minimise interruptions and protect younger graduate nurses are needed.

20.
Artigo em Inglês | MEDLINE | ID: mdl-29608774

RESUMO

Objectives: B-cell activating factor (BAFF), ß-2 microglobulin (ß2M) and serum free light chains (FLCs) are elevated in primary SS (pSS) and associated with disease activity. We aimed to investigate their association with the individual disease activity domains of the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) in a large well-characterized pSS cohort. Methods: Sera from pSS patients enrolled in the UK Primary Sjögren's Syndrome Registry (UKPSSR) (n = 553) and healthy controls (n = 286) were analysed for FLC (κ and λ), BAFF and ß2 M. Pearson correlation coefficients were calculated for patient clinical characteristics, including salivary flow, Schirmer's test, EULAR Sjögren's Syndrome Patient Reported Index and serum IgG levels. Poisson regression was performed to identify independent predictors of total ESSDAI and ClinESSDAI (validated ESSDAI minus the biological domain) scores and their domains. Results: Levels of BAFF, ß2M and FLCs were higher in pSS patients compared to controls. All three biomarkers associated significantly with the ESSDAI and the ClinESSDAI. BAFF associated with the peripheral nervous system domain of the ESSDAI, whereas ß2M and FLCs associated with the cutaneous, biological and renal domains. Multivariate analysis showed BAFF, ß2M and their interaction to be independent predictors of ESSDAI/ClinESSDAI. FLCs were also shown to associate with the ESSDAI/ClinESSDAI but not independent of serum IgG. Conclusion: All biomarkers were associated with total ESSDAI scores but with differing domain associations. These findings should encourage further investigation of these biomarkers in longitudinal studies and against other disease activity measures.

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