Screening of 23 candidate genes by next-generation sequencing of patients with permanent congenital hypothyroidism: novel variants in TG, TSHR, DUOX2, FOXE1, and SLC26A7.

PURPOSE: To date, many genes have been associated with congenital hypothyroidism (CH). Our aim was to identify the mutational spectrum of 23 causative genes in Turkish patients with permanent CH, including thyroid dysgenesis (TD) and dyshormonogenesis (TDH) cases. METHODS: A total of 134 patients with permanent CH (130 primary, 4 central) were included. To identify the genetic etiology, we screened 23 candidate genes associated with CH by next-generation sequencing. For confirmation and to detect the status of the specific familial variant in relatives, Sanger sequencing was also performed. RESULTS: Possible pathogenic variants were found in 5.2% of patients with TD and in 64.0% of the patients with normal-sized thyroid or goiter. In all patients, variants were most frequently found in TSHR, followed by TPO and TG. The same homozygous TSHB variant (c.162 + 5G > A) was identified in four patients with central CH. In addition, we detected novel variants in the TSHR, TG, SLC26A7, FOXE1, and DUOX2. CONCLUSION: Genetic causes were determined in the majority of CH patients with TDH, however, despite advances in genetics, we were unable to identify the genetic etiology of most CH patients with TD, suggesting the effect of unknown genes or environmental factors. The previous studies and our findings suggest that TSHR and TPO mutations is the main genetic defect of CH in the Turkish population.

Effect of Dephytinization by Fermentation and Hydrothermal Autoclaving Treatments on the Antioxidant Activity, Dietary Fiber, and Phenolic Content of Oat Bran.

Fermentation and hydrothermal methods were tested to reduce the phytic acid (PA) content of oat bran, and the effects of these methods on the dietary fiber (DF) and total phenolic (TP) contents as well as the antioxidant activity (AA) were also investigated. Fermentation with 6% yeast and for 6 h resulted in 88.2% reduction in PA content, while it only resulted in 32.5% reduction in the sample incubated for 6 h without yeast addition. The PA loss in autoclaved oat bran sample (1.5 h, pH 4.0) was 95.2% while it was 41.8% at most in the sample autoclaved without pH adjustment. In both methods, soluble, insoluble, and total DF contents of samples were remarkably higher than the control samples. Also for TP in the oat bran samples, both processes led to 17% and 39% increases, respectively, while AA values were 8% and 15%, respectively. Among all samples, the autoclaving process resulted in the lowest PA and the greatest amount of bioactive compounds.

High-rate sulphidogenic fluidised-bed treatment of metal-containing wastewater at high temperature.

The applicability of fluidised-bed reactor (FBR) based sulphate reducing bioprocess was investigated for the treatment of iron containing (40-90 mg/L) acidic wastewater at 65 degrees C. The FBR was inoculated with sulphate-reducing bacteria (SRB) originally enriched from a hot mining environment. Ethanol or acetate was supplemented as carbon and electron source for the SRB. A rapid startup with 99.9, 46 and 29% ethanol, sulphate and acetate removals, in respective order, was observed even after 6 days. Iron was almost completely removed with a rate of 90 mg/L.d. The feed pH was decreased gradually from its initial value of 6 to around 3.7 during 100 days of operation. The wastewater pH of 4.3-4.4 was neutralised by the alkalinity produced in acetate oxidation and the average effluent pH was 7.8 +/- 0.8. Although ethanol removal was complete, acetate accumulated. Later the FBR was fed with acetate only. Although acetate was present in the reactor for 295 days, its oxidation rates did not improve, which may be due to low growth rate and poor attachment ability of acetate oxidising SRB. Hence, the oxidation of acetate is the rate limiting step in the sulphidogenic ethanol oxidation by the thermophilic SRB.

Effects of wheat maturation stage and cooking method on dietary fiber and phytic acid contents of firik, a wheat-based local food.

Samples of two durum wheat cultivars (cvs. Duraking and Ege 88) at different maturation stages (13, 16, 19, 22, 25 days post anthesis) were processed into firik (a wheat-based specialty food) using two different cooking methods: roasting (scorching) on flames and boiling at atmospheric pressure. Both the acid detergent and neutral detergent fiber contents of the firiks produced from two durum wheat samples decreased significantly (p < 0.01) with maturation. Total P contents of the firiks of both cultivars produced by both methods showed a significant downward trend within the period of maturation while their phytic acid contents showed a significant upward trend (p < 0.01). It was possible to obtain a reduced phytic acid, high fiber product from the wheats harvested at early stages of maturation (13 and 16 days after anthesis).

Efficacy of interferon therapy on serum fibronectin levels in children with chronic hepatitis B infection.

BACKGROUND: Fibronectin (FN) is a glycoprotein, the major sources of which are hepatocytes, Kupffer cells and endothelial cells. It has many biological functions including adhesion between cells, immunity, blood coagulation and platelet aggregation. Serum FN levels are generally decreased in pathological blood coagulation and inflammation. In the present study, we evaluated the serum levels of FN in patients with chronic hepatitis B virus (HBV) infection treated with interferon-alpha 2b. METHODS: We studied serum levels of FN in a prospective trial between October 1995 and May 1997. The study included 16 patients with chronic HBV infection before and after interferon therapy, in a period of 6 months, and 17 healthy controls. In total, we had 40 patients with chronic HBV infection. We studied these 16 patients (40%) who recovered with interferon therapy. We could not study the other 24 patients because we did not have enough of the reagents for studying FN. RESULTS: Chronic hepatitis B infection was diagnosed serologically and histopathologically. In mean age and sex, no statistically significant differences were found between patients and healthy subjects. The serum FN concentration before treatment with interferon therapy appeared significantly lower in HBV patients than in healthy control subjects (P = 0.026 using the Mann-Whitney confidence interval and test). After treatment with interferon, serum levels of FN were significantly higher than levels obtained before interferon therapy (P = 0.004 using the Wilcoxon Test). CONCLUSIONS: These results suggest that a decreased level of serum FN in patients with chronic hepatitis before interferon treatment is related to hepatic injury and inflammation. Because of inflammation, the serum FN level is decreased due to the consumption of FN. Increased levels of serum FN in patients having interferon therapy is important and is related to the effects of interferon including antiviral, antiproliferative, anti-inflammatory and immunoregulatory properties in patients with chronic HBV infection. A Japanese study showed a correlation between development of hepatic fibrosis and decrease of plasma FN concentration in adult patients with chronic liver disease. Therefore, the serum level of FN may be a useful marker of hepatic fibrosis in chronic liver disease and interferon may be an important drug for prevention of liver fibrosis. Fibronectin may be also a useful marker in predicting IFN response.

The Ege Stroke Registry: a hospital-based study in the Aegean region, Izmir, Turkey. Analysis of 2,000 stroke patients.

We present the profile of risk factors, etiologic and clinical data of 2,000 consecutive patients with first-ever-in-a-lifetime stroke (cerebral infarction, cerebral hemorrhage and subarachnoid hemorrhage), admitted to the Ege University Hospital between January 1, 1991, and September 31, 1995. This hospital-based registry is the first systematic epidemiologic report on the stroke profile of Turkish people The Ege University Stroke Unit is the only tertiary medical care facility which is organized for patients with different stroke subtypes in Izmir, Turkey. A prospective hospital-based registry using systematic computer coding of data of all stroke patients has been used since January 1991. All patients were evaluated by clinical examination, CT and/or MRI, color duplex and specific cardiac investigations. They were followed up for at least 6 months. The mean age was 62.3 +/- 12 years, and 44.4% were females. Ischemic stroke was found in 77%, primary intracerebral hemorrhage in 19% and subarachnoid hemorrhage in 4%. The major risk factor of ischemic stroke was hypertension (63%), followed by hypercholesterolemia (37%), diabetes mellitus (35%), ischemic heart disease (23%), atrial fibrillation (20%) and smoking (17%). The main cause of primary intracerebral hemorrhage was hypertension (88%), and the principal localization was the thalamus (38%), followed by putamen (28%), lobar(16%), pons(6%), cerebellar(4%), primary intraventricular hemorrhage (4%) and multiple hemorrhages (2%). The over- all 30-day case-fatality rate was 19.7% and the higher mortality rate was found in patients with primary intracerebral hemorrhage (29%) than in those with ischemic stroke (17%). The Ege Stroke Registry allows to estimate the stroke-related problems in patients admitted to a stroke unit and to evaluate the risk factors, etiology and clinical manifestations of stroke in Turkey.

Comparative efficacy of cefixime and ampicillin-sulbactam in shigellosis in children.

Shigellosis is still an important health problem in developing and underdeveloped countries as it is resistance to commonly used antibiotics including ampicillin, trimethoprim-sulfamethoxazole, chloramphenicol and tetracycline. Between May 1996 and October 1996, in a prospective randomized double-blind trial, cefixime was compared with ampicillin-sulbactam, both given orally for a period of 5 days, for the treatment of 80 children with acute bloody diarrhea. Forty patients were treated with a single-dose (8 mg/kg per day) of cefixime and the other 40 patients were given three doses of 100 mg/kg per day of ampicillin-sulbactam. After identification of Shigella organisms in stool specimens, nine patients in the cefixime receiving group and six patients in the ampicillin-sulbactam receiving group were excluded from the study. Differences in average age, sex and weight between the cefixime and ampicillin-sulbactam group were statistically meaningless (P > 0.05). Fever and bloody diarrhea were universal features. The efficacy of cefixime was found to be better than ampicillin-sulbactam. Patients given cefixime had a shorter duration of fever (P < 0.01), shorter duration to disappearance of blood in the stool (P < 0.01), reduced time with diarrhea (P < 0.01) and reduced hospitalization time during the 5 study days (P < 0.01) than patients given ampicillin-sulbactam. No adverse effects were observed in the two study groups. This controlled trial showed good efficacy with cefixime compared to ampicillin-sulbactam in the treatment of shigellosis. Single-dose daily oral therapy with cefixime also showed good tolerability. Cefixime should be considered as an alternative drug of choice for shigellosis in children.