Search

Being one of the leading causes of cancer deaths worldwide and their resistance to conventional treatment methods, made gastrointestinal stromal tumors (GISTs) one of the hot topics in medical research areas in the past decade. To investigate molecular alterations underlying the tumor is of great importance to be able to develop new, targeted treatment options. In this study, GIST samples obtained from 40 Turkish patients were analyzed for actionable epidermal growth factor receptor (EGFR) mutations that are related to treatment regimes in non small cell lung cancer (NSCLC) to understand whether EGFR expression is altered in GISTs. Established alterations in EGFR can make the use of tyrosine kinase inhibitors possible, which are currently used in cancer therapy, especially in NSCLC. Our results indicated that EGFR mutations are rare in GISTs. Further research is needed to sequence whole coding regions of the gene to investigate new actionable mutations in EGFR in an increased sample size.

Ahmet Umit Sabancı,1,* Perihan Erkan Alkan,2,* Cem Mujde,3,* Hivda Ulbeği Polat,4,* Cemre Ornek Erguzeloglu,5,* Atil Bisgin,3,6,* Cuneyt Ozakin,7,* Sehime G Temel5,8,9,* 1Bursa Çekirge State Hospital, Orthopedics and Traumatology Clinic, Bursa, Turkey; 2Bursa Uludağ University, Vocational School of Health Services, Medical Laboratory Technician Department, Bursa, Turkey; 3Çukurova University AGENTEM (Adana Genetic Diseases and Treatment Center), Adana, Turkey; 4TUBITAK, Marmara Research Center, Genetic Engineering and Biotechnology Institute, Gebze, Kocaeli, Turkey; 5Bursa Uludag University, Institute of Health Sciences, Department of Translational Medicine, Bursa, Turkey; 6Çukurova University, Faculty of Medicine, Department of Medical Genetics, Adana, Turkey; 7Bursa Uludağ University, Faculty of Medicine, Department of Infectious Diseases and Microbiology, Bursa, Turkey; 8Bursa Uludağ University, Faculty of Medicine, Department of Medical Genetics, Bursa, Turkey; 9Bursa Uludag University, Health Sciences Institute, Department of Translational Medicine, Bursa, Turkey*These authors contributed equally to this workCorrespondence: Cuneyt OzakinBursa Uludağ University, Faculty of Medicine, Department of Infectious Diseases and Microbiology, Bursa, TurkeyEmail ozakin@uludag.edu.trSehime G TemelBursa Uludağ University, Faculty of Medicine, Department of Medical Genetics, Bursa, TurkeyEmail sehime@uludag.edu.trPurpose: SARS-CoV-2-infected individuals may be asymptomatic, and therefore, the virus is highly contagious. We aimed to develop an agent to control viral replication in the upper respiratory tract and to prevent progression of the disease into the lower airways as well as inter-individual transmission. For this purpose, we investigated the antibacterial and antiviral activities of our novel nanobubble ozonated hyaluronic acid-decorated liposomal (NOHAL) solution, developed by using nanotechnology.Methods: The MIC levels of NOHAL solution were determined on blood agar cultures of Staphylococcus aureus (ATCC 6538), Streptococcuspneumoniae (ATCC 49619) and Escherichia coli (ATCC 25922). The in vitro anti-viral activity of NOHAL solution was studied using recombinant SARS-CoV-2 copies of the original virus, grown in Vero cells generated by reverse genetic technology. Human primary lung epithelial cells obtained by bronchoscopy or lung resection were used for cell viability tests using flow cytometry analysis. The cytotoxicity testing was performed using the BALB/c 3T3 (CCL-163) cell line. Skin, oral, nasal and ocular irritation tests were performed using New Zealand albino rabbits, Syrian hamsters, BALB c mice and New Zealand albino rabbits of both sexes.Results: Bacterial growth was prevented by NOHAL solution in a time-/dose-dependent manner. In vivo or in vitro experiments did not show any toxicity of NOHAL solution. No cytotoxicity was recorded on cell viability. No skin, oral, nasal or ocular toxicities were recorded. In addition, in a SARS-CoV-2 mouse infection model, NOHAL solution diminished the viral RNA levels effectively in nasopharyngeal and lung samples after its prophylactic intranasal application.Conclusion: NOHAL solution has the potential to reduce or prevent the spread of SARS-CoV-2 through the nose and/or oral cavity. The clinical efficacy of this solution needs to be tested in order to determine its efficacy in the early phase of COVID-19.Keywords: nanobubble, ozone, hyaluronic acid, liposome, anti-microbial, anti-viral

Pyruvate kinase (PK) is a key enzyme of anaerobic glycolysis. The genetic heterogeneity of PK deficiency (PKD) is high, and over 400 unique variants have been identified. Twenty-nine patients who had been diagnosed as PKD genetically in seven distinct paediatric haematology departments were evaluated. Fifteen of 23 patients (65.2%) had low PK levels. The PK:hexokinase ratio had 100% sensitivity for PKD diagnosis, superior to PK enzyme assay. Two novel intronic variants (c.695-1G>A and c.694+43C>T) have been described. PKD should be suspected in patients with chronic non-spherocytic haemolytic anaemia, even if enzyme levels are falsely normal. Total PKLR gene sequencing is necessary for the characterization of patients with PKD and for genetic counselling., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

The novel coronavirus (SARS-CoV-2) outbreak has spread worldwide, and the World Health Organization (WHO) declared a global pandemic in March 2020. The transmission mechanism of SARS-CoV-2 in indoor environments has begun to be investigated in all aspects. In this regard, many numerical studies on social distancing and the protection of surgical masks against infection risk have neglected the evaporation of the particles. Meanwhile, a 1.83 m (6 feet) social distancing rule has been recommended to reduce the infection risk. However, it should be noted that most of the studies were conducted in static air conditions. Air movement in indoor environments is chaotic, and it is not easy to track all droplets in a ventilated room experimentally. Computational Fluid Dynamics (CFD) enables the tracking of all particles in a ventilated environment. This study numerically investigated the airborne transmission of infectious droplets in a hospital examination room cooled by a split-type air conditioner with the CFD method. Different inlet velocities (1, 2, 3 m/s) were considered and investigated separately. Besides, the hospital examination room is a model of one of the Bursa Uludag University Hospital examination rooms. The patient, doctor, and some furniture are modeled in the room. Particle diameters considered ranged from 2 to 2000 μm. The evaporation of the droplets is not neglected, and the predictions of particle tracks are shown. As a result, locations with a high infection risk were identified, and the findings that could guide the design/redesign of the hospital examination rooms were evaluated., (© The Author(s) 2024.)

Objective: 22q11.2 deletion syndrome (22q11.2 DS) is the most common chromosomal microdeletion disorder. Associated problems in 22q11.2 DS may include cardiac abnormalities, immune dysfunction, facial dysmorphism, with endocrine, genitourinary and gastrointestinal problems, and developmental delay. The aim of this study was to evaluate and present all endocrinological findings of patients with 22q11.2 DS from a single center., Methods: All participants had confirmed 22q11.2 DS by fluorescence in situ hybridization with hypoparathyroidism. Data were retrieved by retrospective review of patient records., Results: A total of 17 patients were reviewed. On physical examination, all patients had similar dysmorphic features. The median age at diagnosis was 45 days (1 day-13 years). Most cases (64.7%, 11/17) were diagnosed with hypoparathyroidism incidentally after routine tests. At the time of diagnosis, mean calcium was 7.04±0.80 mg/dL, phosphorus was 6.2±1.1 mg/dL, and median parathyroid hormone (PTH) was 11.5 (3.7-47.6) ng/L. Transient hypoparathyroidism was detected in five cases (29.4%). There was no significant difference between patients with permanent or transient hypoparathyroidism regarding gender, age at diagnosis, calcium, phosphorus, and PTH levels. However, vitamin D levels were significantly lower in the transient group (p=0.036). During follow-up, short stature, obesity, and type 2 diabetes mellitus were absent. Thyroid autoantibodies were detected in two patients with normal thyroid function tests. Despite there being no pathological short stature, final stature was shorter than the general population (mean height standard deviation score: -0.94±0.83)., Conclusion: Hypocalcemia may be detected during acute illness in some cases where hypocalcemia appears at later ages. There was no significant difference between permanent and transient hypoparathyroidism cases in terms of PTH level. Recognition of the more specific facial findings is important to trigger investigation of genetic variants, additional anomalies, and for follow-up.

T cell receptor excision circles (TRECs) and kappa-deleting excision circles (KRECs) are DNA fragments potentially indicative of T and B cell development, respectively. Recent thymic emigrants (RTEs) are a subset of peripheral cells that may also represent thymic function. Here, we investigated TREC/KREC copy numbers by quantitative real-time PCR in the peripheral blood of patients with primary immunodeficiencies (PIDs, n = 145) and that of healthy controls (HCs, n = 86) and assessed the correlation between RTEs and TREC copy numbers. We found that TREC copy numbers were significantly lower in children and adults with PIDs (P < .0001 and P < .002, respectively) as compared with their respective age-matched HCs. A moderate correlation was observed between TREC copies and RTE numbers among children with PID (r = .5114, P < .01), whereas no significant correlation was detected between RTE values and TREC content in the HCs (r = .0205, P = .9208). Additionally, we determined TREC and KREC copy numbers in DNA isolated from the Guthrie cards of 200 newborns and showed that this method is applicable to DNA isolated from both peripheral blood samples and dried blood spots, with the two sample types showing comparable TREC and KREC values. We further showed that RTE values are not always reliable markers of T cell output. Although additional confirmatory studies with larger cohorts are needed, our results provide thresholds for TREC/KREC copy numbers for different age groups., (© 2022 The Scandinavian Foundation for Immunology.)

Objectives: Vitamin D is a fat-soluble, prohormone vitamin that is important especially for bone mineralization and skeletal health. In recent years, vitamin D deficiency appeared as a worldwide problem, affecting many people in different ways including the Northern Cypriot population. The deficiency might be caused by the lack of exposure to sunlight, diet low in vitamin D, sedentary lifestyle, and also due to some genetic variations in the vitamin D receptor (VDR) gene., Methods: In this study, four common VDR polymorphisms and associations with vitamin D deficiency in the Turkish Cypriot population between ages 18-40 and working in office conditions was studied by PCR- RFLP analysis., Results: rs2228570 C>T variant was shown to be significantly associated with low serum vitamin D levels in the studied population., Conclusion: Together with the effect of rs2228570 C>T variant in the VDR gene, it is thought that the lifestyle changes in the Turkish Cypriot population might have caused the increased frequency of vitamin D deficiency in the young professionals.

Male infertility affects ∼7% of men, but its causes remain poorly understood. The most severe form is non-obstructive azoospermia (NOA), which is, in part, caused by an arrest at meiosis. So far, only a few validated disease-associated genes have been reported. To address this gap, we performed whole-exome sequencing in 58 men with unexplained meiotic arrest and identified the same homozygous frameshift variant c.676dup (p.Trp226LeufsTer4) in M1AP, encoding meiosis 1 associated protein, in three unrelated men. This variant most likely results in a truncated protein as shown in vitro by heterologous expression of mutant M1AP. Next, we screened four large cohorts of infertile men and identified three additional individuals carrying homozygous c.676dup and three carrying combinations of this and other likely causal variants in M1AP. Moreover, a homozygous missense variant, c.1166C>T (p.Pro389Leu), segregated with infertility in five men from a consanguineous Turkish family. The common phenotype between all affected men was NOA, but occasionally spermatids and rarely a few spermatozoa in the semen were observed. A similar phenotype has been described for mice with disruption of M1ap. Collectively, these findings demonstrate that mutations in M1AP are a relatively frequent cause of autosomal recessive severe spermatogenic failure and male infertility with strong clinical validity., (Copyright © 2020 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Peeling skin syndrome is a heterogeneous group of rare disorders. Peeling skin, leukonychia, acral punctate keratoses, cheilitis and knuckle pads (PLACK syndrome, OMIM616295) is a newly described form of PSS with an autosomal recessive mode of inheritance. We report a 5.5-year-old boy with features of PLACK syndrome. Additionally, he had mild cerebral atrophy and mild muscle involvements. Whole exome sequencing was performed in genomic DNA of this individual and subsequent analysis revealed a homozygous c.544G > T (p.Glu182*) nonsense mutation in the CAST gene encoding calpastatin. Sanger sequencing confirmed this variant and demonstrated that his affected aunt was also homozygous. Real-time qRT-PCR and immunoblot analysis showed reduced calpastatin expression in skin fibroblasts derived from both affected individuals compared to heterozygous family members. In vitro calpastatin activity assays also showed decreased activity in affected individuals. This study further supports a key role for calpastatin in the tight regulation of proteolytic pathways within the skin.

Objective: Recent genome-wide association studies have established that polymorphisms within CDKN2B-AS1 of chr9p21.3 locus increased susceptibility to coronary artery disease (CAD) or myocardial infarction. Common variants of CDKN2B-AS1 (including rs4977574 A>G and rs1333040 C>T) are determined to be directly associated with CADs in many populations worldwide and suggested biomarkers for the early detection of CAD. There is a lack of investigation for the association between CDKN2B-AS1 rs4977574 A>G and rs1333040 C>T genetic modifiers and CAD in a Turkish Cypriot population. The aim of the present study was to investigate the potential effects of these variants on susceptibility to developing CAD in a Turkish Cypriot population and their contribution to lipid metabolism., Methods: Seventy-one patients with angiography-confirmed CAD were recruited to the CAD group, whereas 153 voluntary subjects without CAD symptoms were enrolled to the control group. Genotyping for the CDKN2B-AS1 gene polymorphisms was performed by polymerase chain reaction, followed by restriction fragment length polymorphism analysis., Results: There is no statistical significant association observed between rs4977574 and rs1333040 single-nucleotide polymorphisms and two studied groups [odds ratio (OR): 0.763, p=0.185, 95% confidence interval (CI): 0.511-1.139 and OR: 1.060, p=0.802, 95% CI: 0.672-1.671, respectively]. However, rs2977574 G and rs1333040 T alleles-the risk alleles-were found to be associated with higher level of serum total cholesterol and lower level of high-density lipoprotein-cholesterol in the CAD group (p=0.019, p=0.006 and p=0.022, p=0.031, respectively). To our knowledge, this is the first study that establishes the effect of rs1333040 on lipid metabolism., Conclusion: The presence of rs4977574 G and rs1333040 T alleles and interaction may exist as environmental factors associated with lipid metabolism and might be responsible for the development of CAD in a Turkish Cypriot population.

Long QT syndrome is one of the most common cardiac ion channel diseases, but its morbidity and mortality rate can be lessened with an early diagnosis and proper treatment. This cardiac ventricular repolarization abnormality is characterized by a prolonged QT interval and a propensity for ventricular tachycardia (VT) of the torsades de pointes type. The long QT syndrome represents a high risk for presyncope, syncope, cardiac arrest, and sudden death. Jervell and Lange-Nielsen syndrome (JLNS) is a recessively inherited form of long QT syndrome characterized by profound sensorineural deafness and prolongation of the QT interval. Findings have shown that JLNS occurs due to homozygous and compound heterozygous pathogenic variants in KCNQ1 or KCNE1. A 3.5-year-old girl presented to the hospital with recurrent syncope, seizures, and congenital sensorineural deafness. Her electrocardiogram showed a markedly prolonged QT interval, and she had a diagnosis of JLNS. The sequence analysis of the proband showed the presence of a pathogenic homozygous missense variant (c.728G>A, p.Arg243His). Heterozygous mutations of KCNQ1 were identified in her mother, father, and sister, demonstrating true homozygosity. Even with high-dose beta-blocker therapy, the patient had two VT attacks, so an implantable cardioverter defibrillator was fitted. The authors suggest early genetic diagnosis for proper management of the disease in the proband and genetic counseling for both the proband and the girl's extended family.