Anti Bullying Procedures for Primary and Post Primary Schools - Appendix 2 Practical tips for building a positive school culture and climate

Anti Bullying Procedures for Primary and Post Primary Schools - Appendix 2 Practical tips for building a positive school culture and climate. Provided by the Department of Education and Skills, Ireland.

Anti Bullying Procedures for Primary and Post Primary Schools - Appendix 3 Template for recording bullying behaviour

Anti Bullying Procedures for Primary and Post Primary Schools - Appendix 3 Template for recording bullying behaviour. Provided by the Department of Education and Skills, Ireland.

Anti Bullying Procedures for Primary and Post Primary Schools - Appendix 4 Checklist for annual review of the anti-bullying policy and its implementation

The Board of Management (the Board) must undertake an annual review of the school’s anti-bullying policy and its implementation. The following checklist must be used for this purpose. The checklist is an aid to conducting this review and is not intended as an exhaustive list. In order to complete the checklist, an examination and review involving both quantitative and qualitative analysis, as appropriate across the various elements of the implementation of the school’s anti-bullying policy will be required.

Hepatitis B virus screening in contacts of blood donors with antibodies against core protein (anti-HBc), but without surface antigen (HBsAg)

To increase blood safety Brazil introduced screening for anti-HBc among blood donors in 1993. There was a decrease in the hepatitis B virus (HBV) transmission, but this measure identified a great number of HBsAg-negative, anti-HBc-positive donors. Surveillance policy determines that contacts of HBV carriers should be screened to HBV markers, but there is no recommendation about how to guide contacts of HBsAg-negative, anti-HBc-positive donors. Aiming to evaluate whether the contacts of this group are at greater risk for HBV infection, a cross-sectional study was performed to compare prevalence of HBV infection between contacts of HBsAg-positive blood donors (group I) and contacts of HBsAg-negative, anti-HBc-positive donors (group II). Contacts were submitted to a questionnaire and blood tests for HBV markers. In group I (n = 143), 53 (37.1%) were anti-HBc-positive and 11 (7.7%) were HBsAg-positive. In group II (n = 111), there were 9 and 0.9%, respectively. HBV exposure was associated with group I, sexual activity, blood transfusion, being one of the donor's parents, and living for more than ten years with the donor. Regarding the families as sample units, it was more common to find at least one member with HBV markers (p < 0.05) among the families of group I compared to group II. Contacts of HBsAg-negative, anti-HBc-positive individuals presented a much lower risk of having already been exposed to HBV and there is no need to screen them for HBV in low to moderate prevalence populations.

Schistosoma mansoni major egg antigen Smp40: molecular modeling and potential immunoreactivity for anti-pathology vaccine development

The pathogenesis of Schistosoma mansoni infection is largely determined by host T-cell mediated immune responses such as the granulomatous response to tissue deposited eggs and subsequent fibrosis. The major egg antigens have a valuable role in desensitizing the CD4+ Th cells that mediate granuloma formation, which may prevent or ameliorate clinical signs of schistosomiasis.S. mansoni major egg antigen Smp40 was expressed and completely purified. It was found that the expressed Smp40 reacts specifically with anti-Smp40 monoclonal antibody in Western blotting. Three-dimensional structure was elucidated based on the similarity of Smp40 with the small heat shock protein coded in the protein database as 1SHS as a template in the molecular modeling. It was figured out that the C-terminal of the Smp40 protein (residues 130 onward) contains two alpha crystallin domains. The fold consists of eight beta strands sandwiched in two sheets forming Greek key. The purified Smp40 was used for in vitro stimulation of peripheral blood mononuclear cells from patients infected with S. mansoni using phytohemagglutinin mitogen as a positive control. The obtained results showed that there is no statistical difference in interferon-g, interleukin (IL)-4 and IL-13 levels obtained with Smp40 stimulation compared with the control group (P > 0.05 for each). On the other hand, there were significant differences after Smp40 stimulation in IL-5 (P = 0.006) and IL-10 levels (P < 0.001) compared with the control group. Gaining the knowledge by reviewing the literature, it was found that the overall pattern of cytokine profile obtained with Smp40 stimulation is reported to be associated with reduced collagen deposition, decreased fibrosis, and granuloma formation inhibition. This may reflect its future prospect as a leading anti-pathology schistosomal vaccine candidate.

Caspase-induced inactivation of the anti-apoptotic TRAF1 during Fas ligand-mediated apoptosis.

The activation of the transcription factor NF-kappaB often results in protection against apoptosis. In particular, pro-apoptotic tumor necrosis factor (TNF) signals are blocked by proteins that are induced by NF-kappaB such as TNFR-associated factor 1 (TRAF1). Here we show that TRAF1 is cleaved after Asp-163 when cells are induced to undergo apoptosis by Fas ligand (FasL). The C-terminal cleavage product blocks the induction of NF-kappaB by TNF and therefore functions as a dominant negative (DN) form of TRAF1. Our results suggest that the generation of DN-TRAF1 is part of a pro-apoptotic amplification system to assure rapid cell death.

Imaging of inflammatory and infectious lesions after injection of radioiodinated monoclonal anti-granulocytes antibodies.

Successful detection of inflammatory lesions by planar scintigraphy and SPECT after injection of iodine-123 labelled monoclonal antibodies directed against human granulocytes (123I-Mabgc) is demonstrated. This new tracer has been compared with indium-111 labelled white blood cells (111In-WBC) in selected patients with proven infectious lesions. Scans were equally positive in all cases, but the methodical advantages of the new marker were obvious, namely, there is no need for cell separation and the images of inflammatory lesions were better defined. In addition, SPECT could be performed with 123I-Mabgc and allowed a better anatomic localization and a three-dimensional description of the lesions. No adverse reactions have been seen. It is concluded, therefore, that 123I-Mabgc is a promising agent for the detection of acute focal inflammatory lesions which may, with advantages, replace 111In-WBC.

THE CXCR7/CXCR4/CXCL12 AXIS IN HUMAN NEUROBLASTOMA: INVOLVEMENT IN MALIGNANT PROGRESSION

Le neuroblastome (NB) est la tumeur maligne solide extra-crânienne la plus fréquente chez le jeune enfant. L'évolution clinique est très hétérogène, et les NBs de haut risque échappent encore aux traitements les plus agressifs. Diverses études ont montré que les chimiokines et leurs récepteurs, particulièrement l'axe CXCR4/CXCL12, sont impliqués dans la progression tumorale. Dans le NB, l'expression de CXCR4 est corrélée à un pronostic défavorable. De récentes études ont identifié l'expression d'un autre récepteur, CXCR7, présentant une forte affinité pour le ligand CXCL12. Cependant, son implication potentielle dans l'agressivité des NBs reste encore inconnue. Notre étude a pour objectif d'analyser le rôle de CXCR7 dans le comportement malin du NB, et son influence sur la fonctionnalité de l'axe CXCR4/CXCL12. Les profils d'expression de CXCR7 et CXCL12 ont d'abord été évalués sur un large échantillonnage de tissus de NB, incluant des tissus de tumeurs primaires et de métastases, provenant de 156 patients. CXCL12 est fortement détecté dans les vaisseaux et le stroma des tumeurs. Contrairement à CXCR4, CXCR7 n'est que très faiblement exprimé par les tumeurs indifférenciées. Néanmoins, l'expression de CXCR7 augmente dans les tumeurs matures, et se trouve spécifiquement associée aux cellules neurales différentiées, telles que les cellules ganglionnaires. L'expression de CXCR7 est faiblement détectée dans un nombre réduit de lignées de NB, mais peut-être induite suite à des traitements avec des agents de différenciation in vitro. La surexpression de CXCR7, CXCR4 et une combinaison des deux récepteurs dans les lignées IGR-NB8 et SH-SY5Y a permis l'analyse de leur fonction respective. En réponse à leur ligand commun, chaque récepteur induit l'activation de la voie ERK 1/2, mais pas celle de la voie Akt. Contrairement à CXCR4, l'expression exogène de CXCR7 réduit fortement la prolifération des cellules de NB in vitro, et in vivo dans un modèle d'injection sous-cutanée de. souris immunodéprimées. CXCR7 altère également la migration des cellules induite par l'axe CXCR4/CXCL12. De plus, l'utilisation d'un modèle orthotopique murin a démontré que la croissance tumorale induite par CXCR4 peut être fortement retardée lorsque les deux récepteurs sont co-exprimés dans les cellules de NB. Aucune induction de métastases n'a pu être observée dans ce modèle. Cette étude a permis d'identifier un profil d'expression opposé et des rôles distincts pour CXCR7 et CXCR4 dans le NB. En effet, contrairement à CXCR4, CXCR7 présente des propriétés non tumorigéniques et peut être associé au processus de différenciation du NB. De plus, nos analyses suggèrent que CXCR7 peut réguler les mécanismes induits par CXCR4. Ces données ouvrent donc de nouvelles perspectives de recherche quant au rôle de l'axe CXCR7/CXCR4/CXCL12 dans la biologie des NBs. - Neuroblastoma (NB) is a typical childhood and heterogeneous neoplasm for which efficient targeted therapy for high-risk tumours is not yet identified. The chemokine CXCL12, and its receptors CXCR4 and CXCR7 have been involved in tumour progression and dissemination in various cancer models. In the context of NB, CXCR4 expression is associated to undifferentiated tumours and poor prognosis, while the role of CXCR7, the recently identified second CXCL12 receptor, has not yet been elucidated. In this report, CXCR7 and CXCL12 expression were evaluated using a tissue micro-array (TMA) including 156 primary and 56 metastatic NB tissues. CXCL12 was found to be highly associated to NB vascular and stromal structures. In opposite to the CXCR4 expression pattern, the neural-associated CXCR7 expression was extremely low in undifferentiated tumours, while its expression increased in maturated tissues and was specifically associated to the differentiated neural tumour cells. As determined by RT-PCR, CXCR7 expression was only found in a minority of NB cell lines. Moreover, its expression in two CXCR7-negative NB cell lines was further induce upon treatment with differentiation agents in vitro. The relative roles of the two CXCL12 receptors was further assessed by overexpressing individual CXCR7 or CXCR4 receptors, or a combination of both, in the IGR-NB8 and SH-SY5Y NB cell lines. In vitro functional analyses indicated that, in response to their common ligand, both receptors induced activation of ERK 1/2 cascade, but not Akt signaling pathway. CXCR7 strongly reduced in vitro growth, in contrast to CXCR4. Sub-cutaneous implantations of CXCR7-expressing NB cells showed that CXCR7 also drastically reduced in vivo growth. Moreover, CXCR7 impaired CXCR4-mediated chemotaxis, and altered CXCR4-mediated growth when CXCR4/CXCR7-expressing NB cells were engrafted orthotopically in mouse adrenal gland, a CXCL12-producing environment. In such model, CXCR7 alone, or in association with CXCR4, did not induce NB cell metastatic dissemination. In conclusion, the CXCL12 receptors, CXCR7 and CXCR4, revealed opposite expression patterns and distinct functional roles in NB. While CXCR4 favours NB growth and chemotaxis, CXCR7 elicits anti-tumorigenic properties and may be associated with NB differentiation. Importantly, CXCR7 may act as a negative modulator of CXCR4 signaling, further opening new research perspectives for the role of the global CXCR7/CXCR4/CXCL12 axis in NB.

Anti-leishmania effector functions of CD4+ Th1 cells and early events instructing Th2 cell development and susceptibility to Leishmania major in BALB/c mice.

Resistance and susceptibility to infection with the intracellular parasite, Leishmania major, are mediated by parasite-specific CD4+ Th1 and Th2 cells, respectively. It is well established that the protective effect of parasite-specific CD4+ Th1 cells is largely dependent upon the IFN-gamma produced. However, recent results indicate that the effect of Th1 cells on resolution of lesions induced by L. major in genetically resistant mice also requires a functional Fas-FasL pathway of cytotoxicity. In contrast to resistant mice, susceptible BALB/c mice develop aberrant Th2 responses following infection with L. major and consequently suffer progressive disease. These outcomes clearly depends upon the production of interleukin 4 (IL-4) early after infection. We have shown that a burst of IL-4 mRNA, peaking in draining lymph nodes of BALB/c mice 16 hrs after infection, occurs within CD4+ T cells that express V beta 4-V alpha 8 T cell receptors. In contrast to control and V beta 6-deficient mice, V beta 4-deficient BALB/c mice were resistant to infection, demonstrating the role of these cells in Th2 development. The early IL-4 response was absent in these mice, and Th1 responses occurred following infection. The LACK antigen of L. major induced comparable IL-4 production in V beta 4-V alpha 8 CD4+ T cells. Thus, the IL-4 required for Th2 development and susceptibility to L. major is produced by a restricted population of V beta 4-V alpha 8 CD4+ T cells after cognate interaction with a single antigen from this complex parasite. The IL-4 produced rapidly by these CD4+ T cells induces within 48 hours a state of unresponsiveness to IL-12 among parasite-specific CD4+ T cell precursors by downregulating the IL-12 receptor beta 2 chain expression.

Cross-immunoreactivity between anti-potato apyrase antibodies and mammalian ATP diphosphohydrolases: potential use of the vegetal protein in experimental schistosomiasis

We have previously showed that Schistosoma mansoni ATP-diphosphohydrolase and Solanum tuberosum potato apyrase share epitopes and the vegetable protein has immunostimulatory properties. Here, it was verified the in situ cross-immunoreactivity between mice NTPDases and anti-potato apyrase antibodies produced in rabbits, using confocal microscopy. Liver samples were taken from Swiss Webster mouse 8 weeks after infection with S. mansoni cercariae, and anti-potato apyrase and TRITC-conjugated anti-rabbit IgG antibody were tested on cryostat sections. The results showed that S. mansoni egg ATP diphosphohydrolase isoforms, developed by anti-potato apyrase, are expressed in miracidial and egg structures, and not in granulomatous cells and hepatic structures (hepatocytes, bile ducts, and blood vessels). Therefore, purified potato apyrase when inoculated in rabbit generates polyclonal sera containing anti-apyrase antibodies that are capable of recognizing specifically S. mansoni ATP diphosphohydrolase epitopes, but not proteins from mammalian tissues, suggesting that autoantibodies are not induced during potato apyrase immunization. A phylogenetic tree obtained for the NTPDase family showed that potato apyrase had lower homology with mammalian NTPDases 1-4, 7, and 8. Further analysis of potato apyrase epitopes could implement their potential use in schistosomiasis experimental models.

Evaluation of MRSA-Screen, a simple anti-PBP 2a slide latex agglutination kit, for rapid detection of methicillin resistance in Staphylococcus aureus.

The MRSA-Screen test (Denka Seiken Co., Ltd., Tokyo, Japan), consisting of a slide latex agglutination kit that detects PBP 2a with a monoclonal antibody, was blindly compared to the oxacillin disk diffusion test, the oxacillin-salt agar screen, and PCR of the mecA gene for the detection of methicillin resistance in Staphylococcus aureus. A total of 120 methicillin-susceptible S. aureus (MSSA) and 80 methicillin-resistant S. aureus (MRSA) isolates, defined by the absence or presence of the mecA gene, respectively, were tested. The MRSA-Screen test, the oxacillin disk diffusion test, and the oxacillin-salt agar screening test showed sensitivities of 100, 61.3, and 82.5% and specificities of 99.2, 96.7, and 98.3%, respectively. We conclude that the MRSA-Screen is a very accurate, reliable, and fast test (15 min) for differentiation of MRSA from MSSA colonies on agar plates.

Analgesic and anti-inflammatory activity of the aqueous extract of Rheedia longifolia Planch & Triana

Rheedia longifolia Planch et Triana belongs to the Clusiaceae family. This plant is widely distributed in Brazil, but its chemical and pharmacological properties have not yet been studied. We report here that leaves aqueous extract of R. longifolia (LAE) shows analgesic and anti-inflammatory effects. Oral or intraperitoneal administration of this extract dose-dependently inhibited the abdominal constrictions induced by acetic acid in mice. The analgesic effect and the duration of action were similar to those observed with sodium diclofenac, a classical non-steroidal analgesic. In addition to the effect seen in the abdominal constriction model, LAE was also able to inhibit the hyperalgesia induced by lipopolysaccharide from gram-negative bacteria (LPS) in rats. We also found that R. longifolia LAE inhibited an inflammatory reaction induced by LPS in the pleural cavity of mice. Acute toxicity was evaluated in mice treated with the extract for seven days with 50 mg/kg/day. Neither death, nor alterations in weight, blood leukocyte counts or hematocrit were noted. Our results suggest that aqueous extract from R. longifolia leaves has analgesic and anti-inflammatory activity with minimal toxicity and are therefore endowed with a potential for pharmacological control of pain and inflammation.

Anti-TNF Therapy in the Treatment of Psoriasis in a Patient with Acute-on-Chronic Pancreatitis.

Background: Psoriasis is accepted as a multisystemic disease with several important systemic manifestations. Thus, underlying comorbidities have to be taken into account in the choice of treatment. Objective: To explore the role of anti-TNF therapy in the treatment of psoriasis in a patient with acute-on-chronic pancreatitis. Methods: Here, we present the case of a 75-year-old patient with severe psoriasis also suffering from chronic alcohol-induced pancreatitis with recurrent acute flares. A recent life-threatening episode of acute pancreatitis and ischemic liver precluded the reintroduction of methotrexate. Cyclosporine was also excluded as it has been reported to induce acute pancreatitis. Thus, an anti-TNF treatment was initiated in close collaboration with a gastroenterologist. Results: A year after starting anti-TNF therapy the patient continues to show complete clinical remission of his psoriasis. No side effects, particularly no bacterial infections, were reported. No relapses of the patient's underlying chronic pancreatitis were observed throughout the entire treatment with regular clinical and laboratory monitoring, suggesting that chronic pancreatitis is not per se a contraindication for anti-TNF therapy. Conclusion: This case study opens the way for further questioning on the role of TNF in the pathogenesis of chronic and acute pancreatitis and the use of anti-TNF therapy in its treatment. © 2013 S. Karger AG, Basel.