Clinical spectrum of patients diagnosed with childhood mastocytosis: a retrospective single center experience.

Summary: Background. Pediatric cutaneous mastocytosis patients diagnosed and followed up by our specialist were enrolled in this study, and clinical and laboratory evaluations were retrospectively analyzed from patients' archived files. Methods. Patients, who applied to the Division of Pediatric Allergy And Immunology Unit of a University Training and Research Hospital between 01.01.2010 and 28.04.2021, were enrolled in this study. Results. Of the 33 patients included in the study, 11 (33.3%) were female and 22 (67.7%) were male. The median age of onset of the patient's complaints was 7 (0-60) months. The median age at diagnosis was 11 (2-64) months. Their complaints' median regression age was 54 (6-192) months. Resistant clinical findings were followed in 13 (39.4%) patients. Itching, redness, gastrointestinal symptoms, and maculopapular eruption were the most common complaints. The rashes were mostly polymorphic and larger than 1 cm. Heat was the most common trigger. Darier's sign was positive in 97% of the patients. Antihistamines were the most commonly used drug for prophylaxis and treatment. The autoinjector prescription rate was 24.2%. Conclusions. Quality of life was mildly affected in 48,5% of the patients based on the CDLQI scores. Thus, patients should be followed up through adolescence for the development of systemic signs and symptoms.

The ameliorative effects of Nigella sativa, thymoquinone, and bentonite against aflatoxicosis in broilers via AFAR and Nrf2 signalling pathways, and down-regulation of caspase-3.

1. Aflatoxins (AFs) are metabolites which especially have toxic effects on proteins, and are detoxified by the aflatoxin-B1 aldehyde reductase (AFAR) pathway. In this pathway, the aldo-keto reductase family 7, member A2 (AKR7A2) enzyme, which is controlled by nucleic-related erythroid factor 2 (Nrf2), plays an active role. However, data on the efficacy of this critical pathway in broilers is limited.2. The aim of the following study was to investigate the changes in the expression levels of AKR7A2, Nrf2, and caspase-3, and the effects of Nigella sativa seeds (NS), thymoquinone (TMQ), and bentonite (BNT) in broilers exposed to AFs.3. One-hundred broilers were divided into ten groups (control (CNT); AF; NS; TMQ; BNT; AF+TMQ; AF+NS; AF+BNT; AF+BNT+NS; AF+BNT+TMQ) and fed for 28 d. AF, TMQ, NS and BNT were added to diets at levels of 2 mg/kg, 300 mg/kg, 50 g/kg and 10 g/kg respectively.4. The addition of AF to the diet decreased AKR7A2 and Nrf2 levels dramatically, but increased caspase-3 (P < 0.01). TMQ, NS and BNT additions to the diet eliminated all negative effects caused by AF (P < 0.01); and AKR7A2 and Nrf2 were further raised in TMQ and NS groups when compared to the control group. TMQ and NS showed a positive effect on detoxification parameters when given together with BNT.5. Supplementation with NS and TMQ enhanced AF detoxification via the AFAR pathway, by increasing AKR7A2 and Nrf2 levels, in addition to reducing hepatocyte apoptosis.

An effective artificial testing model to reliability experiments for electronic apex locator devices used in endodontic practice.

Background and Aim: This experimental study aimed to investigate the reliability of using electronic apex locator devices to determine the working length of artificial root canals. Materials and Methods: The experiments were performed using resin endoblocks and mandibular canine teeth (n = 20/group). After the same working length of root canal samples was provided, the teeth and artificial root canals were embedded in an alginate mold. The measurements with Root ZX® and Propex Pixi® apex locators were performed and recorded. The data were analyzed using SPSS software (SPSS V23; IBM Corp., Armonk, New York, USA) and the variance was set at P < 0.05. Results: There was no significant difference between the groups; mean distance from the actual working length using different apex locators (P = 0.633, P = 0.474), and endpoint positioning distributions (P = 0.591). Conclusion: The results indicate that the artificial model could be a laboratory method of determining the accuracy of apex locators and efficient calibration of devices before their clinical use.

Evaluation of retinal and choroidal thicknesses in patients with diabetes mellitus without diabetic retinopathy: A comparative study.

Background: One of the most important complications of diabetes mellitus (DM) is vision loss due to diabetic retinopathy (DR). Optical coherence tomography (OCT) provides visualization of early structural abnormalities of the retina and choroid. Aim: To compare retinal thickness (RT) and choroidal thickness (CT) between patients with DM without DR and healthy controls. Patients and Methods: Diabetic patients without DR were divided into two groups according to serum glycosylated hemoglobin (HbA1c) levels. Group 1: HbA1c ≤7.5 (n = 25) and group 2: HbA1c >7.5 (n = 23). The 3rd group was the healthy control group (n = 25). CT and RT measured by OCT were compared between the three groups. Results: CT in the subfoveal, temporal, and nasal quadrants was significantly higher in the healthy control group than in groups 1 and 2. Subfoveal and temporal quadrant CT in group 2 were significantly thinner than those in group 1. The average RT (ART) was thinner in group 1 than in the other groups, but there was no difference between the control group and group 2. Conclusions: This study showed that CT and ART decreased in diabetic patients without DR.

Postoperative pain after glide path preparation using manual, reciprocating and continuous rotary instruments: a randomized clinical trial.

AIM: To compare the incidence, intensity and prediction of postoperative pain after glide path preparation with manual, continuous rotary and a novel reciprocating glide path instrument. METHODOLOGY: The study included 240 patients, who were treated by four specialists according to a planned treatment protocol. Following access cavity preparation and prior to glide path preparation, the subjects were randomly assigned to one of the three groups according to the glide path instrument by choosing a sealed envelope containing the group name: R-Pilot (VDW, Munich, Germany), ProGlider (Dentsply Sirona, Ballaigues, Switzerland) and stainless steel K-files (Dentsply Sirona; n = 80). Following glide path preparation, the teeth underwent standardized single visit root canal treatment procedures. The root canals were chemomechanically prepared using the ProTaper Next rotary system (Dentsply Sirona) under copious irrigation with 5.25% NaOCl. Final irrigation was performed with 17% EDTA and distilled water. Root fillings were placed using an epoxy resin sealer and gutta-percha with a cold lateral compaction technique. After coronal restorations were placed, the patients were discharged with a questionnaire about the incidence and intensity of pain at 6, 12, 18, 24, 48 and 72 h postoperatively. The data were analysed using chi-square, anova and Tukey tests and logistic regression analysis. RESULTS: The presence of preoperative pain (OR ranged between 3.5 and 14.3) and the glide path preparation techniques (OR between 2.2 and 4.1) were associated with significant effects on the incidence of postoperative pain when comparing manual versus engine-driven glide path preparation (P < 0.05). Patients in the R-Pilot (Mean VAS ranged between 1.57-0.21) and ProGlider (1.97-0.28) groups reported significantly less postoperative pain scores than those in the manual group (2.82-1.32; P < 0.05). There was no significant difference between R-Pilot and ProGlider groups regarding the postoperative pain scores (P > 0.05). CONCLUSION: Preparation of glide paths with rotating or reciprocating NiTi instruments was associated with less postoperative pain levels and incidence compared to manual glide path preparation with no significant difference between rotating and reciprocating instruments. Preoperative pain was the most significant predictor for the occurrence of postoperative pain.

THE IN VITRO CYTOTOXICITY, GENOTOXICITY AND OXIDATIVE DAMAGE POTENTIAL OF THE ORAL DIPEPTIDYL PEPTIDASE-4 INHIBITOR, LINAGLIPTIN, ON CULTURED HUMAN MONONUCLEAR BLOOD CELLS.

BACKGROUND: Linagliptin (LNG) is a selective dipeptidyl peptidase-4 (DPP-4) inhibitor that ameliorates blood glucose control of patients with type 2 diabetes, without developing hypoglycemic risk and weight gain with a good clinical and biological tolerance profile. To the best of our knowledge, its cytotoxic, genotoxic and oxidative effects have never been studied on any cell line. AIM: To evaluate the in vitro cytotoxic, genotoxic damage potential and antioxidant/oxidant activity of LNG in cultured peripheral blood mononuclear cells (PBMC). MATERIAL AND METHODS: After exposure to different doses (from 0.5 to 500 mg/L) of LNG, cell viability was measured by the MTT (3,(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and lactate dehydrogenase (LDH) leakage tests. The antioxidant activity was assessed by the total antioxidant capacity (TAC) and total oxidative stress (TOS) assays. To evaluate the genotoxic damage potential, chromosomal aberration (CA) frequencies and 8-oxo-2'-deoxyguanosine (8-oxo-dG) levels were determined. RESULTS: Treatment with LNG did not cause statistically significant decreases of cell viability at lower concentrations than 100 mg/L as compared to untreated cultures. However, LNG exhibited cytotoxic action at 250 and 500 mg/L. Also, IC20 and IC50 values of LNG were determined as 8.827 and 70.307 mg/L, respectively. In addition, the oxidative analysis revealed that LNG supported antioxidant capacity at concentrations of 2.5, 5, 10, 25, 50 and 100 mg/L without generating oxidative stress. Besides, the results of CA and 8-oxo-dG assays showed in vitro non-genotoxic feature of LNG. As a conclusion, our findings clearly revealed that LNG had no cytotoxic and genotoxic actions, but exhibited antioxidative activity. In conclusion, therefore it is suggested that LNG use in diabetic patients is safe and provides protection against diabetic vascular and oxidative complications.

Organic chromium modifies the expression of orexin and glucose transporters of ovarian in heat-stressed laying hens.

In this study, the effect of the supplemental organic chromium (Cr) forms on the expression of ovarian orexin(hypocretin), glucose transporters (GLUTs), heat shock proteins (HSPs) andnuclear factor-kappaB (NF-κB)were investigated in laying hens (HS). Laying hens (n=1800; 16-wk-old; Lohmann LSL-Lite) were allocated to 6 random groups according to a 2 × 3 factorial trial scheme with two different environmental temperatures [Thermoneutral (TN groups; at either 22±2 °C 24 h/d)  and heat stress (HS groups; at 34±2 °C for 8 h/d, 08:00 to 17:00 h, followed by 22°C for 16 h for a period of 12 wks)], andhens reared under both environmental conditions were fed either a basal diet or the basal diet supplemented with 1.600 mg of chromium-picolinate (CrPic, 12.43% Cr) and 0.788 mg of chromium-histidinate (CrHis, 25.22% Cr) per kg of diet, delivering 200 µg elemental Cr per kg diet. HS groups showed decreased levels of orexin and GLUTs(GLUT1, GLUT4), and increased NFκB, HSP60, HSP70 and HSP90 levels compared to the TN groups in ovarian tissue of hens (P < 0.0001 for all).However, dietary chromium supplementation (CrPic-CrHis) increasedorexin and GLUTs levels and significantly reduced the NF-κB and HSPs levels making them closer to those of thermoneutral group (P < 0.0001).In conclusion, CrPic and CrHis showed supported the relief and treatment of stress complications.

SYNE1 related cerebellar ataxia presents with variable phenotypes in a consanguineous family from Turkey.

SYNE1 related autosomal recessive cerebellar ataxia type 1 (ARCA1) is a late-onset cerebellar ataxia with slow progression originally demonstrated in French-Canadian populations of Quebec, Canada. Nevertheless, recent studies on SYNE1 ataxia have conveyed the condition from a geographically limited pure cerebellar recessive ataxia to a complex multisystem phenotype that is relatively common on the global scale. To determine the underlying genetic cause of the ataxia phenotype in a consanguineous family from Turkey presenting with very slow progressive cerebellar symptoms including dysarthria, dysmetria, and gait ataxia, we performed SNP-based linkage analysis in the family along with whole exome sequencing (WES) in two affected siblings. We identified a homozygous variant in SYNE1 (NM_033071.3: c.13086delC; p.His4362GlnfsX2) in all four affected siblings. This variant presented herein has originally been associated with only pure ataxia in a single case. We thus present segregation and phenotypic manifestations of this variant in four affected family members and further extend the pure ataxia phenotype with upper motor neuron involvement and peripheral neuropathy. Our findings in turn established a precise molecular diagnosis in this family, demonstrating the use of WES combined with linkage analysis in families as a powerful tool for establishing a quick and precise genetic diagnosis of complex neurological phenotypes.

Possible association between germline methylenetetrahydrofolate reductase gene polymorphisms and psoriasis risk in a Turkish population.

BACKGROUND: Psoriasis is a common chronic inflammatory skin disease caused by genetic and epigenetic factors. There are conflicting results in the literature about the association between psoriasis and the methylenetetrahydrofolate reductase gene (MTHFR), ranging from strong linkage to no association. AIM: To investigate the association between the germline MTHFR polymorphisms C677T and A1298C with psoriasis risk in a Turkish population. METHODS: The study enrolled 84 patients with psoriasis and 212 healthy controls (HCs) without any history of psoriasis. DNA was extracted from peripheral blood samples of patients and HCs, and real-time PCR was used for genotyping. Results were compared by Pearson χ² test and multiple logistic regression models. RESULTS: The frequency of both the MTHFR 677TT and A1298C (homozygous) genotypes was statistically significantly different from HCs. Point mutations were detected in all patients with early-onset psoriasis (before the age of 20 years). The T allele of MTHFR 677 and the C allele of MTHFR 1298 increased psoriasis risk by 12.4- and 17.0-fold, respectively, in patients compared with HCs. CONCLUSION: A possible association was detected betweengermline MTHFR 677 C>T and 1298 A>C genotypes and psoriasis risk in a Turkish population. These results need to be confirmed in further studies with larger sample sizes.

Vitamin D Receptor Gene BSMI, FOKI, APAI, and TAQI Polymorphisms and the Risk of Atopic Dermatitis.

BACKGROUND AND OBJECTIVE: The association between vitamin D receptor (VDR) gene polymorphisms and the risk of skin diseases has been widely studied, yet there is only one study on atopic dermatitis. In this study, we aimed to investigate the association between 4 VDR polymorphisms and atopic dermatitis. PATIENTS AND METHODS: This cross-sectional case control study was performed between March 2013 and April 2014 at the University Hospital in Çanakkale, Turkey. Peripheral blood samples were collected in EDTA tubes. DNA extraction was performed using the spin column procedure. The VDR polymorphisms FokI (rs2228570), BsmI (rs1544410), ApaI (rs7975232), and TaqI (rs731236) were determined by polymerase chain reaction-restriction fragment length polymorphism analysis in 42 atopic dermatitis patients and 96 healthy individuals from a Turkish population. RESULTS: The VDR rs1544410 polymorphism increased the risk of atopic dermatitis in our Turkish population [OR, 12.2; 95%CI, 0.44-336; P=.05]. The FoqI, TaqI, and ApaI polymorphisms were not significantly associated with atopic dermatitis susceptibility. CONCLUSION: The VDR Fok1, TaqI, and ApaI gene polymorphisms were not associated with the risk of atopic dermatitis in the Turkish population but the BsmI polymorphism was found to increase risk.

A randomised controlled study comparing valethamate bromide and placebo in shortening the duration of active labour.

The aim of this study is to compare the efficacy and safety of valethamate bromide and placebo against placebo in shortening the duration of active labour. A prospective randomised trial of 158 low-risk women in spontaneous labour was conducted. After evaluation of the patients according to exclusion criteria 30 women were given valethamate bromide (Group 1) and 32 women were given placebo (Group 2). Labour duration was the main outcome measure. The duration of the active phase after starting the treatment was similar in the two groups at 225 and 219 min, respectively. However, differences were not significant between the 2 groups. Side effects such as tachycardia, flushing of the face and dryness of mouth were noted with valethamate bromide administration. In conclusion, valethamate bromide did not significantly shortened the duration of active labour in nulliparous women with a singleton pregnancy at term.

The comparison of EMG-biofeedback and extracorporeal magnetic innervation treatments in women with urinary incontinence.

PURPOSE: This study aimed to compare the effectiveness of EMG-biofeedback (EMG-BF), extracorporeal magnetic innervation (ExMI), and pelvic floor muscle training (PFMT) treatments on women with stress urinary incontinence (SUI). Materials and Meth- ods: The study included 67 women with SUI. Pelvic floor muscles (PFMs) were evaluated with electromyography and the quality of life (QoL) with Incontinence Quality of Life (I-QoL) questionnaire; afterwards, the subjects were divided into three groups; EMG-BF group (n=23), ExMI group (n=20), and PFMT group (n=24). EMG-BF group and ExMI group were given training in urogynecologi- cal physiotherapy clinic. PFMT group were given eight-week home exercises. Each group was assessed before training and after eight weeks. RESULTS: All three groups showed a significant improvement in EMG activity values and average QoL scores. The greatest im- provement was observed in the EMG-BF training group for QoL scores. CONCLUSIONS: This study demonstrated that all of the three methods performed with the purpose of increasing PFM strength were effective. The increase in PFM strength reduces incontinence associated symptoms and thus improves Qol.

Prevalence and mutations of ß-thalassemia trait and abnormal hemoglobins in premarital screening in Çanakkale province, Turkey.

The prevalence of ß-thalassemia (ß-thal) carriers in Turkey varies according to region but in general it is 2.0%. Çanakkale is a city in the Aegean region of Turkey but no study about ß-thal frequency in Çanakkale has been published to date. In this study, we aimed to investigate the frequency of ß-thal mutations in this province. A total of 4452 couples (8904 individuals) applied for premarital thalassemia scans at the Çanakkale State Health Directorate Laboratory between January 2008 and June 2012 and scanning was done with high performance liquid chromatography (HPLC). Of 125 ß-thal carriers seen at the Medical Genetics Clinic, Çanakkale Onsekiz Mart University, Çanakkale, Turkey, for genetic counseling, 46 participated in the study. The remaining 79 patients could not be reached. The prevalence for ß-thal carriers in Çanakkale was identified as 1.4% (125/8904). One couple were both ß-thal carriers. ß-Globin gene analysis of 46 carriers found the total frequency of the three most common mutations was 45.6%. These mutations were found to be HBB: c.93-21G>A [IVS-I-110 (G>A)], 26.08% (12/46); HBB: c.17_ 18delCT [codon 5 (‒CT)], 10.85% (5/46); HBB: c.20delA [codon 6 (‒A)] 8.69% (4/46). This is the first report on the frequency and mutation profiles of ß-thal for Çanakkale. The incidence of ß-thal carriers in Çanakkale is below the average for Turkey. The most frequently observed mutation profile and rate of ß-thal in our region is different from the other regions of Turkey.

The MEFV gene pathogenic variants and phenotype-genotype correlation in children with familial Mediterranean fever in the Çanakkale population.

The aim of the current study was to determine the frequency of the Mediterranean fever (MEFV) gene pathogenic variants in 60 children diagnosed with familial Mediterranean fever (FMF) and to compare the phenotype-genotype correlation. Genomic DNA was isolated by the spin-column method from peripheral blood samples (collected in vacutainers containing EDTA) and buccal smears. The MEFV gene profiles for the current FMF cohort were genotyped by pyrosequencing and direct Sanger sequencing techniques for the target pathogenic variants. The most prominent clinical symptoms were abdominal pain (53.4%), fever (23.4%) and arthritis (23.3%). Eighteen different pathogenic variants were identified and the most frequent were p.Met694Val (20.0%), p.Glu148Gln (13.3%), p.Met680 Ile (11.7%) and p.Arg202Gln (11.7%). Abdominal pain, fever and arthritis were the most common presenting clinical characteristics. Results showed that not only clinical characteristics, but also genotyping of the MEFV gene is needed to establish the correct diagnosis of FMF in children and other family members.

Association between FokI, ApaI and TaqI RFLP polymorphisms in VDR gene and Hashimoto's thyroiditis: preliminary data from female patients in Serbia.

Hashimoto's thyroiditis (HT) is the most prevalent autoimmune thyroid disorder caused by an interaction between genes and environmental triggers. Intrathyroid lymphocytic infiltration may lead to progressive destruction of thyroid tissue and consequently to hypothyroidism. Many studies in different populations have shown association between vitamin D receptor (VDR) gene polymorphisms and various autoimmune diseases, including HT. The study included 44 female patients (mean age ± standard deviation 38 ± 5.4) with Hashimoto's thyroiditis and 32 healthy age-matched, sex-matched and geographically matched controls without personal history of autoimmune and endocrine diseases. Genomic DNA was isolated from peripheral blood-EDTA, and the target VDR gene was genotyped by PCR-RFLP technique after VDR-FokI (rs2228570), VDR-ApaI (rs7975232) and VDR-TaqI (rs731236) restriction enzymes digestion. We used spss 20.0 integrated software for data analysis and found a significant difference in the genotype distribution of VDR-FokI polymorphism between patients with HT and controls (P = 0.009). For ApaI and TaqI, we observed a higher frequency of variant allele in patients with HT, which was not significantly different compared to control women (P > 0.05). The current first and preliminary results identified the association between VDR-FokI gene polymorphism and Hashimoto's thyroiditis in Serbian population. Results need to be supported by further investigations that define haplotype patterns for VDR gene polymorphisms in a larger group of HT patients of both sexes.