Association of Single Nucleotide Polymorphisms in Cytotoxic T-Lymphocyte Antigen 4 and Susceptibility to Autoimmune Type 1 Diabetes in Tunisians

In addition to HLA and insulin genes, the costimulatory molecule CTLA-4 gene is a confirmed type 1 diabetes (T1D) susceptibility gene. Previous studies investigated the association of CTLA-4 genetic variants with the risk of T1D, but with inconclusive findings. Here, we tested the contributions of common CTLA-4 gene variants to T1D susceptibility in Tunisian patients and control subjects. The study subjects comprised 228 T1D patients (47.8% females) and 193 unrelated healthy controls (45.6% females). Genotyping for CTLA-4 CT60A/G (rs3087243), +49A/G (rs231775), and −318C/T (rs5742909) was performed by PCR-restriction fragment length polymorphism (RFLP) analysis. The minor-allele frequencies (MAF) for the three CTLA-4 variants were significantly higher in T1D patients, and significantly higher frequencies of homozygous +49G/G and homozygous CT60G/G genotypes were seen in patients, which was confirmed by univariate regression analysis (taking the homozygous wild type as a reference). Of the eight possible three-locus CTLA-4 haplotypes (+49A/G, −318C/T, and CT60A/G) identified, multivariate regression analysis confirmed the positive association of ACG (odds ratio [OR], 1.93; 95% confidence interval [CI], 1.26 to 2.94), GCG (OR, 2.40; 95% CI, 1.11 to 5.21), and GTA (OR, 4.67; 95% CI, 1.52 to 14.39) haplotypes with T1D, after confounding variables were adjusted for. Our results indicate that CTLA-4 gene variants are associated with increased T1D susceptibility in Tunisian patients, further supporting a central role for altered T-cell costimulation in T1D pathogenesis.Type 1 (insulin-dependent) diabetes (T1D) is the most prevalent form of diabetes in children and young adults and results from autoimmune CD4⁺ and CD8⁺ T-cell-directed destruction of insulin-producing pancreatic β islet cells in genetically susceptible individuals (3, 12), leading to irreversible hyperglycemia and related complications (13). There is a strong genetic component to T1D pathogenesis, evidenced by its clustering in families and by the contributions of a number of susceptibility gene variants to its pathogenesis (10, 12, 29). They include the human leukocyte antigen (HLA) locus, in particular the class II region (DR and DQ), which accounts for 40 to 50% of T1D familial clustering (1, 12, 18), and non-HLA susceptibility loci, several of which were mapped by genome-scanning (11, 29) and/or candidate gene (7, 18, 31) approaches. They include insulin promoter gene variants, which reportedly may modulate immunological tolerance by controlling the expansion of the autoreactive cell pool (26), and the T-cell costimulator cytotoxic T-lymphocyte antigen 4 (CTLA-4) transmembrane glycoprotein, which plays a key role in the fine tuning of T-cell immunity (9, 32, 33).CTLA-4 is a 40-kDa transmembrane glycoprotein expressed on resting and activated T cells and nonlymphoid cells (33), and along with the related CD28 costimulatory molecule, it regulates T-cell activation (and is itself primarily mediated by engagement of the T-cell receptor [TCR]) but does recognize major histocompatibility complex (MHC)-bound antigenic peptides (9, 33). CTLA-4 negatively regulates T-cell activation and effector function, in part by inhibiting Th1 (interleukin 2 [IL-2] and gamma interferon [IFN-γ]) cytokine production and IL-2 receptor α-chain (p55; Tac) expression by engaging antigen-presenting cell (APC)-bound B7.1 (CD80) and B7.2 (CD86) ligands (9, 33). Functionally, CTLA-4 attenuates T-cell signaling by interference with intracellular signal transduction events, including TCR signaling, and reduced CTLA-4 expression and/or activity results in uncontrolled T-cell-associated autoimmunity and lymphoproliferative disease (9, 21). In this regard, it was shown that CTLA-4 polymorphisms significantly influence the risk of autoimmune diseases, including Graves'' disease, systemic lupus erythematosus, autoimmune hypothyroidism, celiac disease, and type 1 diabetes (15, 21, 32).First observed in Italian subjects (25), and confirmed subsequently by case control and family studies, CTLA-4 polymorphic variants were linked with T1D pathogenesis (14, 20, 31, 32). While this association was detected in different ethnic groups (14, 23, 30), it appears more likely to be Caucasian selective (10, 29, 33) and absent from non-Caucasians (5, 6, 8, 19, 22). A recent report from the Type I Diabetes Genetics Consortium bearing on 2,300 affected sib pair families demonstrated that among the 24 single nucleotide polymorphisms (SNPs) genotyped in the CTLA-4 region, only the +49A/G and CT60 SNPs were replicated in the nine combined collections (27). In the present study, we investigated the association of three common CTLA-4 SNPs (−318C/T; +49A/G, and CT60A/G) and the corresponding haplotypes with T1D in Tunisian Arab patients.     

Health-related quality of life of school- age children with rheumatic Fever

Background: Rheumatic fever (RF) is a major public health problem and it is an important cause of acquired cardiovascular disease in childhood and adolescence. The goal of effective management of rheumatic fever is to allow children with RF to function with minimal restrictions and enjoy a good quality of life(QOL) throughout their lives. The aim of this study was to identify the health-related quality of life of school- age children with rheumatic fever. Materials and Methods: A convenient sample of 100 school-age children with rheumatic fever and their mothers were selected from outpatient clinic and inpatient pediatric cardiac departments of EL-Shatby Children University Hospital, Alexandria, Egypt. Data was collected from children in the previously mentioned settings who fulfil the following criteria, the children's age ranged from 8 to 12 years & free from any associated disease. Two tools were used in Clinical Data of Rheumatic School-Age Children Questionnaire that was developed by the researcher and Pediatric Quality of Life Inventory scale (Peds QL). Results: The majority (78.3%) of school-age children with rheumatic fever had a neutral HRQOL and less than a quarter of them had high HRQOL. Only small percent (8.7%) of studied subjects had poor HRQOL. Children's parents' reports confirmed such results, where there were a significant positive correlations between children reports and their parents reports in the majority of studied items of HRQOL regarding rheumatic fever. Conclusion and Recommendations: Health education program for school-age children who had rheumatic fever and their parents towards the different measures of high HRQOL is recommended to help those children to improve their quality of life.     

Investigation of Potential Use of Soybean Protein Isolate–Chinese Bayberry Tannin Extract Cross-Linked Films in Packaging Applications

The possibility of using commercial bayberry tannin (BT) from a Chinese source as a cross-linker and functional additive to develop soybean protein isolate (SPI)-based films was explored in this study by using the solvent casting method. In particular, the impacts of BT loading on the tensile strength, microstructure, thermal stability, water resistance and antioxidant capacity were fully investigated. The results reveal that SPI incorporated with BT yielded a phenolic–protein hybrid whose relevant films exhibited an improvement in tensile strength of around two times greater compared with native SPI as a result of the formed interactions and covalent cross-links, which could be proven using FTIR spectroscopy. The introduction of BT also led to the compact microstructure of SPI–BT films and enhanced the thermal stability, while the water vapor permeability was reduced compared with the control SPI film, especially at high loading content of tannin. Additionally, the use of BT significantly promoted the antioxidant capacity of the SPI-based films according to DPPH radical scavenging assay results. On this basis, Chinese bayberry tannin is considered a promising natural cross-linker and multifunctional additive that can be dedicated to developing protein-derived films with antioxidant activity for food packaging applications.     

The pathogenesis of accelerated fibrinolysis in hepatosplenic schistosomiasis.

Seventy patients with different stages of hepatosplenic schistosomiasis and 18 non-bilharzial normal controls were studied. Plasminogen, plasminogen activators (PA), tissue-type plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA), alpha 2-antiplasmin (alpha 2-AP), plasminogen activator inhibitor (PAI), fibrinogen/fibrin degradation products (FDP) and D-dimer were determined to elucidate the role of plasminogen activators and inhibitors in the pathogenesis of accelerated fibrinolysis in schistosomiasis. There was a progressive increase in the levels of PA, t-PA, u-PA, FDP and D-dimer indicating enhanced fibrinolytic activity with advancing disease. In addition, there was progressive decrease of plasminogen, alpha 2-AP and PAI levels which might be due to decreased hepatic synthesis and/or increased peripheral consumption. These findings suggest that the pathogenesis of accelerated fibrinolysis in schistosomiasis is multifactorial, but may be due to the progressive increase in the levels of plasminogen activators. In addition, the increase of FDP and D-dimer levels are evidence of secondary fibrinolysis following thrombin generation.     

Central Odontogenic Fibroma with Giant Cell Granuloma-Like Lesion: A Report of an Additional Case and Review of Literature

Central odontogenic fibroma is a rare benign odontogenic tumor that relies on clinical–radiographic–histological correlation to reach its diagnosis, especially its rare variants. Of these rare types is the coexistence of giant cell granuloma-like lesion, with the characteristic odontogenic epithelial rests. The presented case is a 33 years old female complaining of asymptomatic mandibular bony swelling. Radiographically, the lesion is unilocular radiolucent, without root resorption. Histological examination revealed the presence of multinucleated giant cells within the diagnosed central odontogenic fibroma. Immunohistochemical staining highlighted the presence of both components.     

Image-Guided Percutaneous Bleomycin and Bevacizumab Sclerotherapy of Orbital Lymphatic Malformations in Children

CardioVascular and Interventional Radiology - To evaluate the effectiveness and safety of image-guided percutaneous sclerotherapy using bleomycin for macrocystic and bevacizumab (Avastin™)...     

Evaluation of the diagnostic efficacy of enzyme colorimetric assay compared to tandem mass spectrometer in neonatal screening for phenylketonuria

The present study aims at evaluating the diagnostic efficacy of an enzyme-based colorimetric method (Enzolve’s kit) for quantitative determination of phenylalanine in comparison to the gold standard tandem mass spectrometer (MS/MS). This study was conducted on 155 neonates aged 3–7?days attending the neurometabolic clinic of Cairo University Children Hospital as a part of the neonatal screening program. Samples of patients were selected according to their phenylalanine levels obtained by MS/MS. Group 1 included 49 normal neonates with phenylalanine level <150?μmol/L. Group 2 included 106 phenylketonuria (PKU)-affected neonates with phenylalanine level >150?μmol/L selected to cover the analytical range of the commercial kit. Blood samples on filter paper cards were reassayed by an enzyme-based colorimetric test kit. On correlating the phenylalanine level assayed using enzyme-based colorimetric technique using Enzolve kit and MS/MS technique, r?=?0.83 and P?<?0.01 were found. Also it yielded a regression equation; phenylalanine level assayed using Enzolve kit?=?(30.6?+?0.98?×?phenylalanine level assayed using MS/MS). Upon detecting positive PKU cases using Enzolve’s kit at a phenylalanine cutoff level of 127?μmol/L and by MS/MS technique at a cutoff level of 150?μmol/L, a statistically significantly association (P?=?0.000) and an agreement with kappa of 0.64 (P?=?0.000) were produced. On constructing ROC curve for assay of phenylalanine using Enzolve’s kit, an area under the curve of 0.963 was found. The Enzolve kit is a simple ,cost-effective, rapid with an accepted overall accuracy test that can be used preliminary to the use of the more sophisticated and expensive MS/MS in screening as well as monitoring patients with PKU.     

Emergency laparoscopic-assisted gastrotomy for the treatment of an iron bezoar

Iron ingestion accounts for approximately 3% of calls to poison control centers. The profound local and systemic effects of an iron overdose have an associated mortality rate of 5%. Laparotomy and gastrotomy has been reported as a life-saving maneuver to extract the retained iron aggregates that are notoriously resistant to, removal by conventional emesis or lavage techniques. In this paper, we describe, for the first time, the use of laparoscopic-assisted gastrotomy in the treatment of an iron overdose. A 14-year-old girl attempted suicide by means of a polydrug drug overdose, which included ferrous fumarate, at a calculated potentially lethal dose of 70 mg/kg. A gastric iron bezoar was seen on plain radiograph. The regional poison control center recommended surgical removal of the retained iron tablets. Upper endoscopy confirmed the retention of iron and showed its dense adherence to the gastric mucosa. A 5-mm laparoscope was introduced at the umbilicus, and the stomach was grasped by an instrument introduced through a left-upper quadrant incision. The incision was then enlarged to allow the formation of a gastrotomy. The iron bezoar was removed with the aid of digital disimpaction and copious saline irrigation. The patient made a rapid postoperative recovery prior to undergoing psychiatric treatment. We conclude that laparoscopic-assisted gastrotomy is a simple and safe option in the acute management of a retained iron bezoar.