Unified modeling of familial mediterranean fever and cryopyrin associated periodic syndromes

Familial mediterranean fever (FMF) and Cryopyrin associated periodic syndromes (CAPS) are two prototypical hereditary autoinflammatory diseases, characterized by recurrent episodes of fever and inflammation as a result of mutations in MEFV and NLRP3 genes encoding Pyrin and Cryopyrin proteins, respectively. Pyrin and Cryopyrin play key roles in the multiprotein inflammasome complex assembly, which regulates activity of an enzyme, Caspase 1, and its target cytokine, IL-1 beta. Overproduction of IL-1 beta by Caspase 1 is the main cause of episodic fever and inflammatory findings in FMF and CAPS. We present a unifying dynamical model for FMF and CAPS in the form of coupled nonlinear ordinary differential equations. The model is composed of two subsystems, which capture the interactions and dynamics of the key molecular players and the insults on the immune system. One of the subsystems, which contains a coupled positive-negative feedback motif, captures the dynamics of inflammation formation and regulation. We perform a comprehensive bifurcation analysis of the model and show that it exhibits three modes, capturing the Healthy, FMF, and CAPS cases. The mutations in Pyrin and Cryopyrin are reflected in the values of three parameters in the model. We present extensive simulation results for the model that match clinical observations

The evaluation of the Myxovirus Resistance 1 protein in serum and saliva to monitor disease activation in primary Sjögren’s syndrome

OBJECTIVE: Primary Sjo¨ gren’s syndrome (pSjS) is a chronic autoimmune disease that causes dry eye and mouth. No laboratory parameters to monitor the activation of this disease have been identified. Therefore, any possible relationships between salivary and blood myxovirus resistance 1 (MX1) and pSjS must be prospectively studied. METHODS: Thirty female patients with pSjS, 30 women with rheumatoid arthritis (RA) without secondary Sjo¨ gren’s syndrome (SjS) and 28 healthy control women were enrolled in this investigation. Analyses of MX1 by the enzyme-linked immunosorbent assay (ELISA) method, SS-A (Ro) and SS-B (La) tests by the strip immunoblot method, anti-nuclear antibody (ANA) tests by immunofluorescence and the measurement of serum rheumatoid factor (RF), C3, C4, immunoglobulin A (IgA), immunoglobulin M (IgM), and immunoglobulin G (IgG) were performed. RESULTS: The serum level of MX1 in patients without Raynaud phenomenon was higher than in those with Raynaud phenomenon (p:0.029, po0.05, statistically significant). There was a statistically significant positive association between hemoglobin levels and MX1 serum levels. No statistically significant association was found among the other parameters. Low MX1 levels were shown to be associated with both a low disease activity score based on the European League Against Rheumatism (EULAR) Sjo¨ gren’s Syndrome Disease Activity Index (ESSDAI) and hydroxychloroquine use in all patients. CONCLUSION: MX1 levels have a considerable impact on the assessment of the disease activity in SjS. We believe that more-comprehensive studies should be performed on patients with pSjS who do not use hydroxychloroquine to prove this relationship and that MX1 levels should be used as a routine marker for the assessment of pSjS disease activity. Further studies are needed to create awareness of the role that MX1 has in the diagnosis of pSjS, which may help to uncover novel pathways for new therapeutic modalities

Researches of Yield and Quality Characteristics of Lavandin (Lavandula X Ä°ntermedia Emeric Ex Loisel) Under Continental Type of Climate

This study was carried out in Lavandin (Lavandula x intermedia Emeric ex Loisel) planted in the farmers' land in Kayseri, Turkey in 2015-2017. Kayseri is a region with a continental climate in Turkey's Central Anatolia Region. In this study, dry flower weight, essential oil content, essential oil yield, and essential oil components were investigated in demonstrations established in 14 locations in Kayseri. Accordingly, in Lavandin, with dry flower weight of 30-127 kg ha-1, the essential oil content was 2.72-9.00% and the essential oil yield was found between 17-77 lt ha-1. A total of 37 components were identified in the essential oil analysis including linalool (37.59-50.48%), linalyl acetate (1.10-40.23%), 1.8 cineole (2.09-17.72%), and camphor (4.13-9.21%). In Lavandin (Lavandula x intermedia Emeric ex Loisel) cultivation studies in the Kayseri, altitude below 1350-1400 m positive results were obtained in the region

Oral health-related quality of life of preschool-aged Turkish children with congenital heart disease

Background. Dental caries and poor oral hygiene can affect the quality of life (QoL) of patients with con -genital heart disease (CHD). Information about the oral health-related quality of life (OHRQoL) of Turkish preschool children with CHD is scarce.Objectives. The aim of the present study was to assess the OHRQoL, and the presence of caries, plaque and gingivitis in Turkish preschool children with CHD as compared to children without CHD (control group).Material and methods. Children aged 3-6 years with CHD (n = 75) and a control group (n = 75) were included in the study. Examinations were conducted using the plaque index (PI), the gingival index (GI) and the World Health Organization (WHO) caries diagnostic criteria. The Early Childhood Oral Health Impact Scale (ECOHIS) questionnaire was completed by the children's families.Results.The amount of caries and plaque, as well as the number of missing teeth were higher in children with CHD. The OHRQoL was lower in children with CHD. However, the differences between the 2 groups were not statistically significant (p > 0.05). The number of filled teeth was significantly higher in the con-trol group (p < 0.05).Conclusions. According to the findings of the present study, the high amount of caries and plaque in both groups demonstrates that caries continues to be a major public health problem. Although there was no significant difference in terms of QoL scale scores between the 2 groups, the study showed that OHRQoL was lower in children with CHD

Gastrointestinal Stromal Tumors with Unusual Localization: Report of Three Cases with a Brief Literature Review

The most common tumors derived from the mesenchyme of the gastrointestinal system are stromal tumors. These tumors are typically seen in the stomach and small intestine and less frequently in the colon, rectum and esophagus and are very rarely located outside the gastrointestinal system. Cure is provided with complete surgical resection with resection borders free of tumor. Tumor size, mitotic index, localization, CD117 and CD34 negativity in immunohistochemical studies, mucosal ulceration and presence of necrosis help to predict recurrence of the illness and patient survival. In high-risk gastrointestinal stromal tumors (GISTs) there is an increased rate of recurrence and shortened survival despite complete surgical resection. Thus patients with a high-risk GIST should be given adjuvant therapy with imatinib mesylate. Sunitinib maleate is another FDA-approved agent only for cases who cannot tolerate imatinib or who are resistant to it. Herein we present three cases with GISTs in different locations of the gastrointestinal system with a review of the relevant literature

Genetic Analysis of MEFV Gene Pyrin Domain in Patients With Behçet's Disease

Objectives. Behçet's disease (BD) is a systemic vasculitis with recurrent oral and genital ulcers and uveitis. MEFV gene, which is the main factor in familial Mediterranean fever (FMF), is also reported to be a susceptibility gene for BD. The pyrin domain of MEFV gene is a member of death-domain superfamily and has been proposed to regulate inflammatory signaling in myeloid cells. This study was designed to determine if mutations in pyrin domain of MEFV gene are involved in BD. Methods. We analyzed the pyrin domain of MEFV gene in 54 Turkish patients with BD by PCR-analysis and direct sequencing. Results. Neither deletion or insertion mutations nor point mutations in pyrin domain were found in any patient. Conclusion. Although pyrin gene mutations have been reported in patients with BD, pyrin domain is not mutated. However, alterations in other regions of MEFV gene and interaction between pyrin domains are needed to be further investigated

Solving challenging grid puzzles with answer set programming

We study four challenging grid puzzles, Nurikabe, Heyawake, Masyu, Bag Puzzle, interesting for answer set programming (ASP) from the viewpoints of representation and computation: they show expressivity of ASP, they are good examples of a representation methodology, and they form a useful suite of benchmarks for evaluating/improving computational methods for nontight programs