Evidence for eosinophil and IL-17 mediated inflammation in allergic rhinitis.

Background: The aim was to determine the level of inflammatory cytokines, eosinophil cationic protein and IgE in allergic rhinitis (AR) patients. Subjects and methods: Blood samples were taken from 88 AR patients and 88 healthy controls (HC). Each sample was analysed for eosinophil counts by flow cytometry, IgE by ECLIA, ECP, IL-17, and IL-33 by using ELISA test. Results: There was no significant difference between AR patients and the control group in age and gender. Levels of eosinophils, IgE, ECP, IL-17, IL-33 and the total symptom scores were significantly higher in AR patients than the HC (P = 0.0001). Serum ECP correlated with IL-17 (P = 0.041, r = 0.42), IL-33 (P = 0.0001, r = 080), and IgE levels (P = 0.017, r = 0.45) in the R patients. There was no correlation between IL-17 and IL-33. There was a correlation between symptom scores and eosinophils (P = 0.026, r = 0.52), and IgE (P = 0.001, r = 0.60) in the patients. No correlation was observed between symptom scores and ECP, IL-17, and IL-33 in the AR patient. Conclusions: Patients with AR have significant higher serum levels of ECP, IL-17, and IL-33 than healthy controls. This indicates that these markers could be used to in order to diagnose AR and to monitor disease. Inhibitory molecules to IL-17 and IL-33 may be considered as novel treatment strategies

Systemic lupus erythematosus and diffuse alveolar hemorrhage, etiology and novel treatment strategies.

Diffuse alveolar hemorrhage is a severe respiratory complication of systemic lupus erythematosus. The illness develops over hours to a few days and is the systemic lupus erythematosus-associated syndrome with highest mortality. Although no specific symptoms have been identified, a number of features are associated with diffuse alveolar hemorrhage, with a drop in blood hemoglobin the most prominent. Dyspnea, blood-stained sputum, diffuse infiltrates identified by chest imaging, elevated single breath-diffusing capacity for monoxide, thrombocytopenia and C3 hypocomplementemia are other commonly reported signs of diffuse alveolar hemorrhage. The etiology is not completely understood but many patients develop diffuse alveolar hemorrhage concomitant with lupus nephritis, suggesting immune complex-driven pathology. Biopsy studies have identified both cases with capillaritis and a bland non-inflammatory phenotype. An animal model of diffuse alveolar hemorrhage has indicated requirement of B lymphocytes and complement receptor-mediated apoptotic body phagocytosis by monocytes as part of the pathogenesis. This review will discuss considerations when diagnosing the condition and available therapies. Infections and other causes of hemorrhage have to be excluded as these require different treatment strategies. Methylprednisolone and cyclophosphamide remain the most commonly used therapies. Plasmapheresis and rituximab are other beneficial treatment options. A few studies have also considered intrapulmonary Factor VII therapy, extracorporeal membrane oxygenation and mesenchymal stem cell therapy. There is an unmet need of better definition of diffuse alveolar hemorrhages etiology and pathology for development of improved treatment strategies

Autoantibody profiles in autoimmune hepatitis and chronic hepatitis C identifies similarities in patients with severe disease

Bror Hjerpstedts Foundation, Sweden

CAR T cells targeting tumor endothelial marker CLEC14A inhibit tumor growth

Engineering T cells to express chimeric antigen receptors (CARs) specific for antigens on hematological cancers has yielded remarkable clinical responses, but with solid tumors, benefit has been more limited. This may reflect lack of suitable target antigens, immune evasion mechanisms in malignant cells, and/or lack of T cell infiltration into tumors. An alternative approach, to circumvent these problems, is targeting the tumor vasculature rather than the malignant cells directly. CLEC14A is a glycoprotein selectively overexpressed on the vasculature of many solid human cancers and is, therefore, of considerable interest as a target antigen. Here, we generated CARs from 2 CLEC14A-specific antibodies and expressed them in T cells. In vitro studies demonstrated that, when exposed to their target antigen, these engineered T cells proliferate, release IFN-γ, and mediate cytotoxicity. Infusing CAR engineered T cells into healthy mice showed no signs of toxicity, yet these T cells targeted tumor tissue and significantly inhibited tumor growth in 3 mouse models of cancer (Rip-Tag2, mPDAC, and Lewis lung carcinoma). Reduced tumor burden also correlated with significant loss of CLEC14A expression and reduced vascular density within malignant tissues. These data suggest the tumor vasculature can be safely and effectively targeted with CLEC14A-specific CAR T cells, offering a potent and widely applicable therapy for cancer

Lament as Transitional Justice

Works of human rights literature help to ground the formal rights system in an informal rights ethos. Writers have developed four major modes of human rights literature: protest, testimony, lament, and laughter. Through interpretations of poetry in Carolyn Forché’s anthology, Against Forgetting, and novels from Rwanda, the United States, and Bosnia, I focus on the mode of lament, the literature of mourning. Lament is a social and ritualized form, the purposes of which are congruent with the aims of transitional justice institutions. Both laments and truth commissions employ grieving narratives to help survivors of human rights trauma bequeath to the ghosts of the past the justice of a monument while renewing the survivors’ capacity for rebuilding civil society in the future. Human rights scholars need a broader, extra-juridical meaning for “transitional justice” if we hope to capture its power

Interleukin-17D and Nrf2 mediate initial innate immune cell recruitment and restrict MCMV infection.

Innate immune cells quickly infiltrate the site of pathogen entry and not only stave off infection but also initiate antigen presentation and promote adaptive immunity. The recruitment of innate leukocytes has been well studied in the context of extracellular bacterial and fungal infection but less during viral infections. We have recently shown that the understudied cytokine Interleukin (IL)-17D can mediate neutrophil, natural killer (NK) cell and monocyte infiltration in sterile inflammation and cancer. Herein, we show that early immune cell accumulation at the peritoneal site of infection by mouse cytomegalovirus (MCMV) is mediated by IL-17D. Mice deficient in IL-17D or the transcription factor Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), an inducer of IL-17D, featured an early decreased number of innate immune cells at the point of viral entry and were more susceptible to MCMV infection. Interestingly, we were able to artificially induce innate leukocyte infiltration by applying the Nrf2 activator tert-butylhydroquinone (tBHQ), which rendered mice less susceptible to MCMV infection. Our results implicate the Nrf2/IL-17D axis as a sensor of viral infection and suggest therapeutic benefit in boosting this pathway to promote innate antiviral responses

Survey of attitudes, materials and methods employed in endodontic treatment by general dental practitioners in North Jordan

BACKGROUND: General dental practitioners provide the majority of endodontic treatment in Jordan. The aim of this study was to gather information on the methods, materials and attitudes employed in root canal treatment by dentists in North Jordan, in order to evaluate and improve the quality of current practice. METHODS: A questionnaire was posted to all registered general dental practitioners working in private practice in Irbid Governate in North Jordan (n = 181). The questionnaire included information on methods, materials and techniques used in endodontic treatment. RESULTS: Reply rate was 72% (n = 131). The results demonstrated that only five dentists used rubber dam occasionally and not routinely. The majority used cotton rolls for isolation solely or in combination with a high volume saliva ejector (n = 116). The most widely used irrigants were sodium hypochlorite and hydrogen peroxide, which were used by 32.9% (n = 43) and 33.6% (n = 44) of the respondents, respectively. Forty eight percent of the respondents (n = 61) used the cold lateral condensation technique for canal obturation, 31.3% (n = 41) used single cone, 9.9% (n = 13) used vertical condensation and 12.2% (n = 16) used paste or cement only for the obturation. The majority used zinc oxide eugenol as a sealer (72.5%). All, but one, respondents used hand instruments for canal preparation and the technique of choice was step back (52.7%). More than 50% (n = 70) of the dentists took one radiograph for determining the working length, whilst 22.9% (n = 30) did not take any radiograph at all. Most practitioners performed treatment in three visits for teeth with two or more root canals, and in two visits for teeth with a single root canal. CONCLUSIONS: This study indicates that dentists practicing in North Jordan do not comply with international quality standards and do not use recently introduced techniques. Many clinicians never take a radiograph for determining the working length and never used rubber dam or intra-canal medicaments

Extrusion of Endodontic Filling Materials: Medico-Legal Aspects. Two Cases

The Authors describe two cases of alleged malpractice due to overfilling. The aim of this article is to underline some medico-legal aspects regarding the quantity of extruded material which may be considered acceptable and the consequent damage to the patient

Alumina-on-alumina total hip replacement for femoral neck fracture in healthy patients

<p>Abstract</p> <p>Background</p> <p>Total hip replacement is considered the best option for treatment of displaced intracapsular fractures of the femoral neck (FFN). The size of the femoral head is an important factor that influences the outcome of a total hip arthroplasty (THA): implants with a 28 mm femoral head are more prone to dislocate than implants with a 32 mm head. Obviously, a large head coupled to a polyethylene inlay can lead to more wear, osteolysis and failure of the implant. Ceramic induces less friction and minimal wear even with larger heads.</p> <p>Methods</p> <p>A total of 35 THAs were performed for displaced intracapsular FFN, using a 32 mm alumina-alumina coupling.</p> <p>Results</p> <p>At a mean follow-up of 80 months, 33 have been clinically and radiologically reviewed. None of the implants needed revision for any reason, none of the cups were considered to have failed, no dislocations nor breakage of the ceramic components were recorded. One anatomic cementless stem was radiologically loose.</p> <p>Conclusions</p> <p>On the basis of our experience, we suggest that ceramic-on-ceramic coupling offers minimal friction and wear even with large heads.</p