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In Tunisia, olive growing and olive oil production represent a key element of the agricultural and economic sectors. Furthermore, olive producing areas are mostly located in semi-arid and arid regions with low water availability. On the other hand, olive oil industry generates high liquid effluent volumes (olive mill wastewater (OMW)) that represent a major environmental concern, and therefore must be appropriately managed. Accordingly, spreading OMW on agricultural lands in water scare areas may help to sustain dry lands productivity. In this study, we investigated the long-term effects of OMW spreading to an olive orchard in a semi-arid region. Physicochemical and biological properties of soil as well as olive oil quality were monitored. OMW was applied, after the end of the olive milling season, at annual dose of 50 m3 ha−1 y−1 every 2 years. The findings revealed that the OMW application increased soil water content. Moreover, OMW positively affected soil fertility, and increased, soil organic matter and biological activity. The overall results of this study indicate that OMW spreading at doses of 50 m3 ha−1 y−1 in a semi-arid region improves soil physicochemical properties and does not have a negative impact on olive oil quality. Additionally, direct spreading of OMW, if applied every 2 years, could be a sustainable practice in olive orchards under semi-arid environments. [ABSTRACT FROM AUTHOR]

The scheduling literature is extensive, but much of this work is theoretical and does not capture the complexity of real world systems. Capital goods companies produce products with deep and complex product structures, each of which requires the coordination of jobbing, batch, flow and assembly processes. Many components require numerous operations on multiple machines. Integrated scheduling problems simultaneously consider two or more simultaneous decisions. Previous production scheduling research in the capital goods industry has neglected maintenance scheduling and used metaheuristics with stochastic search that cannot guarantee an optimal solution. This paper presents a novel mixed integer linear programming model for simultaneously solving the integrated production and preventive maintenance scheduling problem in the capital goods industry, which was tested using data from a collaborating company. The objective was to minimise total costs including: tardiness and earliness penalty costs; component and assembly holding costs; preventive maintenance costs; and set-up, production, transfer and production idle time costs. Thus, the objective function and problem formulation were more extensive than previous research. The tool was successfully tested using data obtained from a collaborating company. It was found that the company's total cost could be reduced by up to 63.5%. [ABSTRACT FROM AUTHOR]

Behçet Disease is a relapsing and remitting variable vessel vasculitis characterized by recurrent mucocutaneous ulcers that can involve almost every organ system in the body. Indeed, the presence of recurrent oral or genital ulcers with other auto-inflammatory symptoms should raise suspicion for this elusive disease. It is unique among the vasculitides in that it can affect vessels of small, medium, and large size and tends to involve venous rather than arterial circulation, and its effects on the pulmonary venous circulation are particularly notable for their role in disease mortality. Classically seen in Mediterranean, Middle-Eastern, and eastern Asian countries, and relatively rare in the United States, prevalence has been increasing, prompting an increased need for internists to be aware of Behcet's clinical presentation and treatment. As early recognition and diagnosis of the disease is key to successful treatment and better prognosis, this review provides a brief summary of the current etiological theories, important clinical manifestations, and treatments including newer biologic alternatives. [ABSTRACT FROM AUTHOR]

Roads are an important role in the transportation and the economy. Therefore, roads should be constructed under geometric standards to increase service life and maximize safety. However, landslides occurring around the road, especially in mountainous regions, may cause deformation on the road surface. Generally, landslide areas can be detected by measuring in more than one period. The proposed methodology investigates the landslide effect in a single period and consists of the following steps. First, a UAV collects data to generate a 3 D model. Then, an appropriate road project is designed according to the road geometric standards and 3 D model. Finally, landslides are successfully determined by comparing the appropriate road design and the current state of the road. It is found that there are road subsidence and rising areas up to 20 cm. As a result, it was determined the landslide had significant effects on the road surface with single-period UAV data. [ABSTRACT FROM AUTHOR]

In our day-to-day life, synchronizing vision and language aspects plays a crucial role in solving various real-time challenges. Image captioning is one of them, and it aims to recognise objects, activities, and their relationships in order to provide a syntactically and semantically correct visual description. There are existing works of image captioning in various directions, such as news, fashion, art, and medical domains. The core architectural idea of image captioning is based on merging CNN, RNN, and transformer models. In practice, there are many conceivable combinations, and brute forcing all of them would take a long time. As we know, there is no work on interpreting image captioning models across various usecases. In this research article, we examine and analyze different image captioning models used across various domains, and multiple insights are extracted to determine the best combinational architecture for a new application without ignoring contextual semantics. We examined numerous designs and determined that LSTM is best for image captioning across several domains. [ABSTRACT FROM AUTHOR]

Recent patient studies have shown that gluten-free diet is less effective in treating celiac disease than previously believed, and additionally patients remain vulnerable to gluten-induced acute symptoms and systemic cytokine release. Safe and effective pharmacological adjuncts to gluten-free diet are in preclinical and clinical development. Clear understanding of the pathogenesis of celiac disease is critical for drug target identification, establishing efficacy endpoints and to develop noninvasive biomarkers suitable to monitor and potentially diagnose celiac disease. The role and clinical effects of CD4+ T cells directed against deamidated gluten in the context of an 'adaptive immune paradigm' are reviewed. Alternative hypotheses of gluten toxicity are discussed and contrasted. In the context of recent patient studies, implications of the adaptive immune paradigm for future strategies to prevent, diagnose, and treat celiac disease are outlined. Effective therapeutics for celiac disease are likely to be approved and necessitate a variety of new clinical instruments and tests to stratify patient need, monitor remission, and confirm diagnosis in uncertain cases. Sensitive assessments of CD4+ T cells specific for deamidated gluten are likely to play a central role in clinical management, and to facilitate research and pharmaceutical development. [ABSTRACT FROM AUTHOR]

Electrochemical water splitting is a well-sought method for the production of renewable energy due to its low cost, high efficiency, ease of operation, availability of a variety of catalysts, and green approach. In this research, an amine-functionalized Ce-MOF loaded on nickel foam (NF) presented as Ce-MOF-NH2/NF electrocatalyst is prepared by a simple hydrothermal method. Prepared material is characterized by X-ray diffraction (XRD), energy-dispersive spectroscopy (EDS), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and atomic force microscopy (AFM) to confirm morphological and structural properties. The synthesized catalyst is used for electrochemical OER in a 1M KOH solution. Ce-MOF-NH2/NF demonstrated onset potential, Tafel slope, and overpotential of 1.49 V, 69 mV/dec, and 328 mV, respectively. For comparison, Ce-MOF is also prepared and employed for OER under the same conditions and it exhibited onset potential, Tafel slope, and overpotential 1.5 V, 89 mV/dec, and 348 mV, indicating the superior performance of functionalized MOF. The obtained results reveal the promising overpotential of the Ce-MOF-NH2/NF -based electrocatalyst for green energy production via electrochemical water splitting. [ABSTRACT FROM AUTHOR]

While the epidermis is the frontline defense against infections and indeed, it is a peripheral lymphoid organ, the same immunological mechanisms may initiate and sustain pathological conditions. Indeed, a deregulated action against exogenous pathogens could activate a T cell response in atopic dermatitis, hidradenitis suppurativa and vitiligo. Atopic dermatitis (AD) is a chronic inflammatory skin condition with a complex pathophysiology. Although T helper 2 immunity dysregulation is thought to be the main cause of AD etiopathogenesis, the triggering mechanism is not well understood, and the treatment is often difficult. As the AD, hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with a dramatic impact on the quality of life of the affected patients. The exact pathophysiology of HS is still unclear, but many evidences report a follicular obstruction and subsequent inflammation with TNF-α, interleukin (IL)-1β, IL-10, and IL-17 involvement. Vitiligo is an autoimmune epidermal disorder which consists of melanocytes destruction and skin depigmentation. Melanocytes destruction is mainly due to their increased oxidative-stress sensitivity with a consequent activation of innate first and adaptative immunity (CD8+ T cells) later. The understanding of the triggering mechanisms of AD, HS and Vitiligo is pivotal to outline novel therapies aimed at regaining the physiological immune homeostasis of healthy skin. The aim of this review is to provide new insight on the pathogenesis of these skin diseases and to highlight on the new therapeutic approaches adopted in the treatment of AD, HS and Vitiligo. [ABSTRACT FROM AUTHOR]

Introduction: Dysregulation of melanocyte function is associated with vitiligo, an idiopathic autoimmune hypopigmentary skin disorder, caused by the selective destruction of melanocytes. Cytokines, the key mediators of immune response, which are pivotal in maintaining immune homeostasis, are crucial in vitiligo pathogenesis. Several studies indicate that there is an imbalance between pro- and anti-inflammatory cytokines in the skin and serum of vitiligo patients. Areas covered: In this comprehensive review, we have summarized the correlation of cytokine imbalance and vitiligo pathogenesis, its role in melanocyte biology, and its impact on vitiligo treatment. We have integrated various published reports on the levels of major cytokines from skin and serum samples of vitiligo patients. We have also discussed the role of endoplasmic reticulum and oxidative stress on cytokine imbalance and vice versa leading to destruction of melanocytes. Expert commentary: The review reflects that dysregulation of cytokines is multifactorial, ranging from genetic predisposition to altered protein expression relevant to vitiligo pathogenesis. We emphasize that cytokine imbalance in systemic and skin microenvironment plays a crucial role in vitiligo pathogenesis and has promising potential as therapeutic targets for vitiligo. [ABSTRACT FROM AUTHOR]

Behçet’s disease (BD) is a chronic autoimmune condition primarily prevalent in populations along the Mediterranean Sea. The exact etiology of BD has not been fully explained yet, but the disease occurrence is associated with a genetic factor, human leukocyte antigen (HLA)-B51 antigen. Among the various immunodysfunctions that are found in BD, patients are increased neutrophil motility and superoxide production, as well as elevated production of tumor necrosis factor (TNF)-α and decreased production of interleukin (IL)-10. Elevated levels of inflammatory cytokines like IL-1 and IL-17 in BD have been found associated with aberrant expression of microRNA. Gene polymorphisms in BD patients have been observed in molecules involved in responses to pathogens that can ultimately modulate the host antimicrobial response. Moreover, several single nucleotide polymorphisms (SNPs) have been reported in genes encoding chemokines and adhesion molecules; many of these changes manifest as increases in vascular inflammation and vascular damage. Lastly, genetic and epigenetic changes have been suggested as involved in the pathogenesis of BD. Modifications in DNA methylation have been found in BD patient monocytes and lymphocytes, leading to adverse function of these cells. This review presents a comprehensive compilation of the literature with regard to the immunodysfunction underlying BD, as well as of the genetics, newly described clinical specifications and novel treatment strategies using immunomodulants based on the current understanding of BD. [ABSTRACT FROM PUBLISHER]

In Italy, the law no 574 of 1996 permits and regulates the disposal of olive mill wastewater (OMW), the liquid by-product obtained in oil mill when olive fruits are processed to extract virgin olive oil, by its controlled spreading on cultivated soil. With the aim to verify the long-term effects of the practice on olive production, oil quality, and physical–chemical and microbiological characteristics of soil, different amounts of OMW were spread in February, for 9 years consecutively, on soil cultivated with olive trees. The results obtained confirmed that the controlled spreading of OMW is not harmful for the plant production. On the contrary, OMW spread on olive grove is useful for the fertility of soil and the growth of microflora for the important supply of nitrogen (N), phosphorus (P), potassium (K), and, above all, of organic matter. The evaluated biological properties indicated that OMW spreading stimulates the growth of soil fungal and fungus-like communities and aerobic N2fix micro-organisms. With regard to the oil quality, the data indicate that no significant differences were ascertained on the analyzed parameters. [ABSTRACT FROM PUBLISHER]

Behçet’s disease (BD) is an inflammatory multisystemic disorder associated with orogenital ulcers, uveitis and skin lesions with unpredictable episodes of exacerbations and remissions. Even though several immunological and environmental factors contribute to BD progression, its ethiopathogenesis remains uncertain and elusive. Considered as one of the potent environmental factors that can increase prevalence of some autoimmune and inflammatory disorders, vitamin D deficiency has been linked to several diseases as BD. The aim of this study is to assess vitamin D status in Algerian BD patients and its relationship with disease activity. Immunomodulatory effect of this vitamin on nitric oxide (NO), inflammatory mediator, was also undertaken. Serum 25(OH) vitamin D levels were measured in healthy controls (HC), active and inactive BD patients with an electrochemiluminescence method. After treatment of HCs’ and patients’ peripheral blood mononuclear cells with different concentrations of vitamin D3, NO production was evaluated with Griess method, while inducible nitric oxide synthase (iNOS) and NF-κB expression with immunofluorescence test. A high decrease of vitamin D levels was noted in active BD patients compared to those of inactive stage and HC. However, a higher NO production was observed during active stage of BD compared to inactive one. In inactive BD, vitamin D levels correlates negatively with NO. Interestingly, vitamin D3 inhibitsex vivoNO production, iNOS and NF-κB expression in BD patients. In conclusion, vitamin D deficiency was associated with active BD. This vitamin down-modulates NO production in BD patients, suggesting that it may be considered as promising therapy modulating inflammation during BD. [ABSTRACT FROM AUTHOR]

Background: Behçet’s disease (BD) is a rare, chronic autoinflammatory disorder of unknown origin. Natural killer (NK) cells are one of the major immunoregulatory cell groups of the innate immune system, but their role in BD pathogenesis is not well documented. Objectives: We aimed to investigate the role of NK cell subsets and their cytokine secretion and cytotoxic activity in patients with BD. Patients and methods: The study group consisted of BD patients who had only mucocutaneous involvement, and they were compared with healthy subjects. BD patients were divided into two groups according to their frequencies of oral ulcerations. NK cell cytotoxicity was determined using CD107a expression and a CFSE-based cytotoxicity test. Expression of NK cell receptors and surface markers and the intracellular IL-5, IL-10, IL-17, and IFN-γ levels in CD16+NK cells were assessed by flow cytometry. Results: Although the cytokine secretion pattern was different, no difference was obtained in cytotoxic activity, expression of activatory receptors, or degranulation of NK cells. Conclusion: Increases in NK1/NK2 ratio and CD16+IFN-γ+NK1 cells might support the idea of a biased IFN-γ dominant immune response in the mucocutaneous involvement of BD pathogenesis. Although the cytokine secretion pattern was different, no difference was obtained in cytotoxic activity, expression of activatory receptors, or degranulation of NK cells. [ABSTRACT FROM AUTHOR]

Objective.The development of gliadin-specific antibody and T-cell responses were longitudinally monitored in young children with genetic risk for celiac disease (CD).Material and methods.291 newborn children positive for HLA-DQB1*02 and -DQA1*05 alleles were followed until 3–4 years of age by screening for tissue transglutaminase autoantibodies (tTGA) by using a commercial ELISA-based kit and antibodies to deamidated gliadin peptide (anti-DGP) by an immunofluorometric assay. Eighty-five of the children were also followed for peripheral blood gliadin-specific CD4+T-cell responses by using a carboxyfluorescein diacetate succinimidyl ester-basedin vitroproliferation assay.Results.The cumulative incidence of tTGA seropositivity during the follow-up was 6.5%. CD was diagnosed in nine of the tTGA-positive children (3.1%) by duodenal biopsy at a median 3.5 years of age. All of the children with confirmed CD were both IgA and IgG anti-DGP positive at the time of tTGA seroconversion and in over half of the cases IgG anti-DGP positivity even preceded tTGA seroconversion. Peripheral blood T-cell responses to deamidated and native gliadin were detected in 40.5% and 22.2% of the children at the age of 9 months and these frequencies decreased during the follow-up to the levels of 22.2% and 8.9%, respectively.Conclusions.Anti-DGP antibodies may precede tTGA seroconversion and thus frequent monitoring of both tTGA and anti-DGP antibodies may allow earlier detection of CD in genetically susceptible children. Peripheral blood gliadin-specific T-cell responses are relatively common in HLA-DQ2-positive children and are not directly associated with the development of CD. [ABSTRACT FROM PUBLISHER]

Celiac disease (CD) is a chronic, small intestinal, immune-mediated enteropathy triggered by exposure to dietary gluten in genetically susceptible individuals. Currently, lifelong adherence to a gluten-free diet (GFD) is the only available treatment. However, GFD alone is not sufficient to relieve symptoms, control small intestinal inflammation and prevent long-term complications in many patients. The GFD has its challenges including issues related to adherence, lifestyle restrictions and cost. As a result, there is growing interest in and a need for non-dietary therapies to manage this condition. In recent years, different targets in the immune-mediated cascade of CD have been identified in clinical and pre-clinical trials for potential therapies. This review will discuss the latest non-dietary therapies in CD, including endopeptidases, modulators of enterocyte tight junctions and agents involved in gluten tolerization and immunomodulation. We will also discuss the potential implications of approved therapeutics on CD clinical practice. [ABSTRACT FROM AUTHOR]

A small subset of celiac disease (CD) patients becomes refractory to a gluten-free diet with persistent malabsorption and intestinal villous atrophy. Diagnosis of this condition defined as refractory celiac disease (RCD) is made after exclusion of other small bowel diseases with villous atrophy. RCD has been subdivided into two subgroups according to the normal or abnormal phenotype of intraepithelial lymphocytes. Whereas normal RCD is hardly distinguishable from active CD, abnormal RCD has a severe clinical presentation and a very poor prognosis. We precisely describe below the different types of RCD and propose diagnostic and therapeutic guidelines for its clinical management. [ABSTRACT FROM AUTHOR]

Uveitis, recurrent oral and genital ulcerations associated with skin lesions are the major symptoms of a chronic multisystemic inflammatory disorder known as Behçet's disease (BD). High prevalence of this dreaded disease has been observed in the Mediterranean basin, including Algeria and along the Silk Road. Although the etiologic agent of this disease remains uncertain, many hypotheses have been advanced in its pathogenesis. Our team has previously reported high levels of nitric oxide (NO) in sera of BD patients, suggesting its deleterious effect during chronic inflammation. In our current study, the aim is to investigate the ex vivo immunomodulatory effect of all-trans-retinoic acid (ATRA) on NO pathway in Algerian BD patients. First, peripheral blood mononuclear cells isolated from active and inactive BD patients and healthy controls were cultured with different concentrations of ATRA. NO production was estimated with the Griess method. To elucidate the underlying mechanisms of ATRA effect on NO production, we analyze inducible nitric oxide synthase expression and nuclear factor-κB (NF-κB) activity by immunofluorescence test. Our results revealed a higher production of NO in active BD compared with the inactive stage and healthy controls. We observed that ATRA inhibits NO production in BD both in active and inactive stages and inhibits NF-κB translocation. In conclusion, we report a relationship between NO production and the disease activity. ATRA down-regulates NO production in BD patients. This immunomodulatory effect seems to be mediated through NF-κB pathway. All these findings suggest that ATRA could be considered as a promising therapy for BD. [ABSTRACT FROM AUTHOR]

Background UC-II contains a patented form of undenatured type II collagen derived from chicken sternum. Previous preclinical and clinical studies support the safety and efficacy of UC-II in modulating joint discomfort in osteoarthritis and rheumatoid arthritis. The purpose of this study was to assess the efficacy and tolerability of UC-II in moderating joint function and joint pain due to strenuous exercise in healthy subjects. Methods This randomized, double-blind, placebo-controlled study was conducted in healthy subjects who had no prior history of arthritic disease or joint pain at rest but experienced joint discomfort with physical activity. Fifty-five subjects, who reported knee pain after participating in a standardized stepmill performance test, were randomized to the placebo (n = 28) or the UC-II (40 mg daily, n = 27) cohort for 120 days. Joint function was assessed by measuring knee flexion and knee extension as well as time to experiencing and recovering from joint pain following strenuous stepmill exertion. Results After 120 days of supplementation, subjects in the UC-II group exhibited a statistically significant improvement in average knee extension compared to placebo (81.0 ± 1.3° vs 74.0 ± 2.2°; p = 0.011) and to baseline (81.0 ± 1.3° vs 73.2 ± 1.9°; p = 0.002). The UC-II cohort also demonstrated a statistically significant change in average knee extension at day 90 (78.8 ± 1.9° vs 73.2 ± 1.9°; p = 0.045) versus baseline. No significant change in knee extension was observed in the placebo group at any time. It was also noted that the UC-II group exercised longer before experiencing any initial joint discomfort at day 120 (2.8 ± 0.5 min, p = 0.019), compared to baseline (1.4 ± 0.2 min). By contrast, no significant changes were seen in the placebo group. No product related adverse events were observed during the study. At study conclusion, five individuals in the UC-II cohort reported no pain during or after the stepmill protocol (p = 0.031, within visit) as compared to one subject in the placebo group. Conclusions Daily supplementation with 40 mg of UC-II was well tolerated and led to improved knee joint extension in healthy subjects. UC-II also demonstrated the potential to lengthen the period of pain free strenuous exertion and alleviate the joint pain that occasionally arises from such activities. [ABSTRACT FROM AUTHOR]

Given the availability and ample choice of methods, processes, tools and environments for sharing knowledge on the web - 20 years of research has yielded a vast body of literature - it is surprising that the adoption of knowledge sharing artefacts designed to optimise knowledge exchange on the web is still limited. In related work, a systematic review of publicly funded systems engineering (SE) research in the United Kingdom is undertaken, the outcomes of which contribute to motivating the ongoing search for simple standardised shared knowledge representations and formalisation mechanisms. This paper defines knowledge objects (KOs) as identified in the literature, and explores their role as a possible codification method for facilitating and reducing the costs associated with knowledge sharing of system knowledge. The paper suggests that KO architectures should aim to integrate various knowledge types, and provides two KO outlines, system knowledge object (SKO) and systems engineering knowledge object (SEKO), together with suggestions for future work. [ABSTRACT FROM AUTHOR]

Objective. Most of the recent studies suggest that oats are well tolerated by celiac disease (CD) patients. However, it is still possible that different oat cultivars may display different biological properties relevant for CD pathogenesis. We aimed to investigate biological and immunological properties of two oat varieties, Avena genziana and Avena potenza, in relation to their safety for CD patients. Material and Methods. Phosphorylation of extracellular signal-regulated kinase (ERK) and trans-epithelial electrical resistance (TEER) were evaluated in CaCo-2 cells treated with peptic-tryptic (PT) digests from the two oats and from gliadin (PTG). With the same PT-digests, duodenal biopsies from 22 CD patients were treated in vitro for 24 h and density of CD25++ cells in lamina propria and of intraepithelial CD3++ T cells was measured, as well as crypt cell proliferation and epithelial expression of interleukin 15. Finally, interferon γ (IFN-γ) production was measured as evidence of gliadin-specific T-cell activation by PT-digests. Results. In contrast to PTG, oats PT-digests were not able to induce significant increase in ERK phosphorylation and decrease in TEER in CaCo-2 cells. In the organ culture system, oats PT-digests, unlike PTG, did not induce significant increase in crypt enterocyte proliferation, increase in interleukin 15 expression or in lamina propria CD25++ cells. Nevertheless Avena potenza increased intraepithelial T-cell density, while Avena genziana-induced IFN-γ production in 3/8 CD intestinal T cell lines. Conclusions. Our data show that Avena genziana and Avena potenza do not display in vitro activities related to CD pathogenesis. Some T-cell reactivity could be below the threshold for clinical relevance. [ABSTRACT FROM AUTHOR]

Several animal models have been recently developed to recapitulate various components of the complex process that is celiac disease. In addition to the increasing diversity of murine models there are now monkey models of celiac disease. Mouse strains and protocols have been developed that are now just beginning to address the complex interactions among the innate and adaptive immune responses to gluten, as well as gluten-dependent autoimmunity in celiac disease. The most important conclusion that these models have provided us with so far is that while all three components (innate gluten sensitivity, adaptive gluten sensitivity, and autoimmunity) are independent phenomena, all are necessary for celiac disease to develop. [ABSTRACT FROM AUTHOR]

For measurement value logging of board angle values during balance training, it is necessary to develop a measurement system. This study will provide data for a balance study using the smartcard. The data acquisition comes automatically. An individually training plan for each proband is necessary. To store the proband identification a smartcard with an I2C data bus protocol and an E2PROM memory system is used. For reading the smartcard data a smartcard reader is connected via universal serial bus (USB) to a notebook. The data acquisition and smartcard read programme is designed with Microsoft® Visual C#. A training plan file contains the individual training plan for each proband. The data of the test persons are saved in a proband directory. Each event is automatically saved as a log-file for the exact documentation. This system makes study development easy and time-saving. [ABSTRACT FROM AUTHOR]

Interleukin (IL)-15 and CD30 may be associated with the ongoing intestinal immunologic activation in celiac disease (CD). We studied duodenal biopsies and blood samples of patients with active CD (Cel) and controls in order to determine the regulatory role proposed for CD30+ T cells in this Th1-driven disease and the potential influences of IL-15 on CD30 expression. We detected that a CD30+ T-cell subpopulation persists longer in Cel after a 5 day incubation with anti-CD3 antibody than in controls ( p = 0.0063). CD30 upregulation by IL-15 in T blasts was greater in Cel than in controls ( p = 0.0062). At the mucosal compartment, the CD30 antigen was examined by immunohistochemistry and quantified on isolated lamina propria (LP) and epithelial T cells by flow cytometry. For Cel and controls, similar mean percentages of CD3+CD30+ intraepithelial T cells (5.88 vs. 5.51, p = ns) and LP T cells (7.38 vs. 7.49, p = ns) were observed at baseline and after in vitro gliadin challenge of duodenal biopsy samples. Our study demonstrates the occurrence of potentially important alterations of the immune response at the peripheral compartment. Our findings also allow us to speculate that a negative effect of soluble mediators at the mucosal compartment might counteract the latent influence of IL-15 on CD30 expression precluding a more severe course of active CD. [ABSTRACT FROM AUTHOR]

Objective: We analysed the production of soluble tumour necrosis factor receptors sTNFR1 and sTNFR2 at sites of inflammation and measured their plasma concentrations to evaluate them as biological markers of disease activity. Methods: Plasma samples of 35 patients with Behçet's disease (BD) were collected prospectively at monthly intervals and grouped for inactive disease, active BD without arthritis, and active BD with arthritis. sTNFR1 and sTNFR2 concentrations were measured using immunoassays and compared with other biological disease activity parameters. Plasma sTNFR levels were compared to synovial fluid (SF) levels in seven patients. Sixteen tissue samples of mucocutaneous lesions were stained for TNFR2 expression by immunohistochemistry. Results: sTNFR1 and sTNFR2 were found at increased plasma concentrations in active BD, with the highest concentration in active BD with arthritis (p<0.001). Concentrations of both sTNFRs were at least three times higher in SF of arthritic joints than in the corresponding plasma samples (p = 0.025). A change of more than 1 ng/mL of sTNFR2 plasma concentrations correlated with a concordant change in arthritic activity (96% confidence interval). Sensitivity to change was superior to that of sTNFR1, and other biological disease activity parameters such as erythrocyte sedimentation rate (ESR), immunoglobulin (Ig)G, IgA, and interleukin (IL)-10 plasma concentrations. A strong staining for TNFR2 was found in mucocutaneous lesions, where mast cells were identified as the major source for this receptor. Conclusions: This longitudinal study demonstrates that sTNFR2 plasma concentrations are closely linked with active BD, and especially with arthritis. Taken together with the expression of TNFR molecules in mast cells of mucocutaneous lesions, our results indicate a fundamental role for the TNF/TNFR pathway in BD. [ABSTRACT FROM AUTHOR]

Objective: Although the pathogenesis of Behcet's disease (BD) is unknown, immune dysfunction appears to be involved. To improve understanding of the role of T cells and cytokines in BD, the current study analysed the localization and extent of expression of T cell subsets, cytokines, chemokines, and chemokine receptors in oral ulcers from BD patients and for comparison in oral ulcers from patients with recurrent aphthous stomatitis (RAS), as well as in healthy oral mucosa.Methods: Biopsies from oral ulcers of 25 BD patients and 19 RAS patients and oral mucosa from six healthy volunteers were immunoperoxidase stained.Results: Both CD4- and CD8-positive T cells were present in the oral ulcers of BD and RAS patients. The T helper (Th)1 cytokines interleukin (IL)-12, interferon (IFN)-gamma, and tumour necrosis factor (TNF)alpha and the Th1-associated chemokine receptors CCR5 and CXCR3 were increased in both patient groups as compared to normal controls, indicating the involvement of a Th1 immune response in the immunopathology of both BD and RAS. However, the Th2 cytokine IL-4 was only observed in oral ulcers of BD patients but not in RAS patients.Conclusion: This is the first study that shows the presence of pro-inflammatory cytokines, as well as Th1-associated chemokine receptors, in the oral ulcers of BD patients, as well as RAS patients, at a protein level. However, the expression of the Th2 cytokine IL-4 within the oral lesions of only BD patients is suggestive of a more complex antigenic stimuli in BD patients compared with RAS patients. [ABSTRACT FROM AUTHOR]

The physiological immune response in the intestine against dietary proteins and commensal flora is characterized by regulatory mechanisms (tolerance) that prevent harmful consequences. Intestinal dendritic cells (DCs) have a central role in the development of immunosuppressive regulatory T cells owing to their ability to produce TGF-β and retinoic acid (RA). However, the article under evaluation shows an unexpected effect of RA -- that of promoting a proinflammatory phenotype in intestinal DCs involved in the generation of inflammatory immune responses to dietary antigens. By using a double transgenic murine model that resembles human celiac disease, it was demonstrated that RA synergizes with IL-15 in promoting the breakdown of gluten tolerance and the development of enteropathy. The tissue microenvironment modulates DC function, and immune therapies that are based on RA aiming to restore oral tolerance should be used with caution because the presence of IL-15 (and/or other proinflammatory cytokines) may have undesirable effects. [ABSTRACT FROM AUTHOR]

We have previously shown that the development of a major histocompatibility complex class I (MHC-I)-deficient tumor was favored in protein kinase C-θ knockout (PKC-θ−/−) mice compared to that occurring in wild-type mice. This phenomenon was associated with scarce recruitment of natural killer (NK) cells to the tumor site, as well as impaired NK cell activation and reduced cytotoxicityex vivo. Poly-inosinic:cytidylic acid (poly I:C) treatment activated PKC-θ in NK cells depending on the presence of a soluble factor produced by a different splenocyte subset. In the present work, we sought to analyze whether interleukin-15 (IL-15) and/or interferon-α (IFNα) mediate PKC-θ-dependent antitumor NK cell function. We found that IL-15 improves NK cell viability, granzyme B expression, degranulation capacity and interferon-γ (IFNγ) secretion independently of PKC-θ. In contrast, we found that IFNα improves the degranulation capability of NK cells against target cancer cells in a PKC-θ-dependent fashion bothex vivoandin vivo. Furthermore, IFNα induces PKC-θ auto-phosphorylation in NK cells, in a signal transduction pathway involving both phosphatidylinositol-3-kinase (PI3K) and phospholipase-C (PLC) activation. PKC-θ dependence was further implicated in IFNα-induced transcriptional upregulation of chemokine (C-X-C motif) ligand 10 (CXCL10), a signal transducer and activator of transcription-1 (STAT-1)-dependent target of IFNα. The absence of PKC-θ did not affect IFNα-induced STAT-1 Tyr701 phosphorylation but affected the increase in STAT-1 phosphorylation on Ser727, attenuating CXCL10 secretion. This connection between IFNα and PKC-θ in NK cells may be exploited in NK cell-based tumor immunotherapy. [ABSTRACT FROM PUBLISHER]

Presents a letter to the editor of the "Scandinavian Journal of Gastroenterology" reacting to the paper "Duodenal intraepithelial lymphocyte-count revisited," by Veress et al.