Germline Pathogenic Variants Identified by Targeted Next-Generation Sequencing of Susceptibility Genes in Pheochromocytoma and Paraganglioma

The aim of this study was to evaluate germline variant frequencies of pheochromocytoma and paraganglioma targeted susceptibility genes with next-generation sequencing method. Germline DNA from 75 cases were evaluated with targeted next-generation sequencing on an Illumina NextSeq550 instrument. KIF1B, RET, SDHB, SDHD, TMEM127, and VHL genes were included in the study, and Sanger sequencing was used for verifying the variants. The pathogenic/likely pathogenic variants were in the VHL, RET, SDHB, and SDHD genes, and the diagnosis rate was 24% in this study. Three different novel pathogenic variants were determined in five cases. This is the first study from Turkey, evaluating germline susceptibility genes of pheochromocytoma and paraganglioma with a detection rate of 24% and three novel variants. All patients with pheochromocytoma and paraganglioma need clinical genetic testing with expanded targeted gene panels for higher diagnosis rates

Investigation of the radioprotective effects of myricetin with micronucleus assay in vitro conditions

Yüksek Lisans TeziGünümüzde radyasyon, birçok hastalığın tanı ve tedavisinde kullanılmaktadır. Ancak sağaltım amacıyla da olsa, uygulanan radyasyon, genetik materyalde doza bağlı olarak hasarlar meydana getirebilmektedir. Hasarlar ya doğrudan radyasyonun DNA'yı hasarlaması ya da dolaylı yoldan ortamdaki su molekülleri ile etkileşerek serbest radikaller oluşturmasıyla meydana gelir. Oluşan hasarların bazıları farklı DNA tamir mekanizmaları ile onarılabildiği gibi bazıları onarılamayacak seviyede olabilir. Bu nedenle radyasyon hasarını azaltmak amacıyla hastalara bazı koruyucu ajanlar verilmektedir. Bu koruyucu ajanlar radyasyonun verilen dozunu düşürerek tedavi sürecinde istenmeyen bir etki oluşturabilse de sağlam dokuların radyasyon hasarından korunabilmesi için kullanılmalarının gerekli olduğu durumlar vardır. Myricetin, bitkisel kaynaklı doğal bir flavonoid olup antioksidan özelliği olduğu bilinen bir maddedir. Bu nedenle radyasyon sonucu oluşan serbest radikalleri kendine bağlayarak DNA'da oluşacak oksidatif hasarı engelleyebileceği beklenmektedir. DNA'da oluşan hasarları belirlemek için, farklı dozimetrik yöntemler kullanılmaktadır. Mikronukleus (MN) analiz yöntemi de, oluşan DNA hasarının belirlenmesinde ve DNA hasarına karşı hücrede oluşan yanıtın incelenmesinde kullanılan bir tekniktir. MN'lar, binukleat (BN) hücreler ile aynı sitoplazma içinde bulunan, hücre bölünmesi sırasında mitotik iğdeki hatalar nedeniyle kutuplara çekilemeyen kromozomlardan ve/veya kromozom parçalarından oluşmaktadır. Radyasyonun oluşturduğu hasarlar da MN analizi ile incelenebilmektedir. Bu çalışmada, yapısında bulunan OH ekleri sayesinde güçlü bir antioksidan olarak bilinen myricetinin farklı radyasyon dozlarında, radyasyon öncesi ya da sonrasında kullanılmasının MN sıklığı üzerine etkileri incelendi. Farklı konsantrasyonlardaki myricetinin 2 Gray (Gy) ve 4 Gy radyasyon öncesi ve sonrasında MN sıklığı üzerine etkileri değerlendirildi. Farklı radyasyon dozlarında, 100 µM ve 200 µM konsantrasyonlarında uygulanan myricetinin MN sıklığını azalttığı görüldü. Radyasyon öncesi ve sonrasında uygulanan myricetin ise MN sıklığında istatistiksel olarak anlamlı bir fark oluşturmadı (P>0.05). Uygulanan myricetin konsantrasyonlarında radyasyon dozunun azaldığı ancak bu azalmanın gruplar arasında anlamlı bir fark oluşturmadığı bulundu. Radyasyon öncesi ve sonrası arasında fark bulunmadığı için myricetinin antioksidan etkisinden daha çok, DNA tamirini uyararak etki ettiği ya da radyasyon sonucu hücrede oluşan hasar miktarına göre hücreyi apoptoza götürdüğü düşünüldü. Birden fazla MN taşıyan BN hücrelerin sayısı azalırken, kromozom aberasyon taşımayan hücrelerin sayısı değişmedi. Bu çalışmanın sonucu olarak, kanser hastalarında myricetinin radyoterapi tedavisine ek olarak kullanılabilmesi için daha ileri çalışmaların yapılması gerektiği önerilmektedir.Anahtar Kelimeler: Myricetin, mikronukleus, DNA hasarı, radyoprotektif etkiAbstractNowadays the radiation is used in the diagnosis and treatment of many diseases However, even for medical purposes, the radiation is able to cause damage in genetic material of the cell depending on its dose. Damages occur either direct effect of radiation to DNA, or indirect hazardous effect of free radicals generated from interaction of the radiation-water molecules in the environment. Some of damages can be repaired by some different DNA repair mechanisms but some of them may be unrepairable level. That's why, some protective agents have been given to patients in order to reduce radiation damage. Although these protective agents have some undesirable effects in the treatment process such as reducing the given radiation dose, there are many situations to use of protective agents that necessary to preserve healthy tissues from radiation damage. Myricetin is a plant-derived natural flavonoid that's known as an antioxidant featured substance. Therefore, it is expected that myricetin may inhibit the oxidative damage by binding the free radicals produced by radiation. To determine the damage in DNA, different methods have been used in dosimeter. Micronuclei (MN) analysis method is a preferred technique for determining of DNA damage and response against to DNA damage in the cells and Micronuclei are composed of chromosomes and/or chromo pieces which cannot pulled away to the poles due to mitotic yarns errors and located in same cytoplasm with BN. Damages produced by ionizing radiation can be investigated by MN analysis method. In this study, the effects of myricetin, a powerful antioxidant containing OH adducts in its structure, on frequency of MN, was investigated in different radiation doses in before and after radiation treatment. Effects of different concentratios of myricetin on frequency of MN were evaluated in pre and post-treatment of 2 Gy and 4 Gy radiation doses. In different radiation doses, applied myricetin in 100 µM and 200 µM concentratios, decreased frequency of MN. Myricetin that applied before and after radiation treatment did not make a statistically significant difference in MN frequency (P >0.05). It was found that radiation doses were reduced by applied myricetin doses in different concentrations but no significant differences between the groups were observed. Since there is no difference between pre-and post-irradiation, instead of antioxidant effect, myricetin was thought working via inducing DNA repair or by triggering apoptosis by the amount of damage in the cell. Number of BN cells with more than one MN decreased, but the number of cells not bearing chromosome aberrations did not change. As a result of this study, it is suggested that there is need to further studies to be able to use myricetin in addition to radiotherapy in patients with cancer.Keywords: Myricetin, micronucleus DNA damage, radioprotective effec

Small Frontal Gray Matter Volume in First-Episode Depression Patients

WOS: 000281709900001PubMed ID: 20818506Objective: Brain imaging studies have shown that depressed individuals suffer from inadequate frontal lobefunctions vis a vis smaller frontal lobes. The effects of depression's recurrent nature and long-term antidepressant treatment are not definitely known. This study aimed to examine frontal lobe volume at the onset of clinical depression by including first-episode drug-naive depressed patients. Method: The study included 23 first-episode drug-free major depression patients diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) and 28 healthy age- and sex-matched controls. Cranial magnetic resonance (MR) images were obtained in both groups using a 1.5 Tesla device. Gray and white matter volumes in the frontal lobes were measured using the Medical Image Processing Analysis and Visualization (MIPAV) computer program. Results: Frontal gray matter volume in the patients was lower than that in the control group. White matter and total intracranial volume did not differ between the 2 groups. Small gray matter volume was not correlated with the duration or severity of illness. Conclusion: The results of this study indicate that frontal lobe gray matter volume is low in first-episode depressed patients and is independent of both illness severity and duration. This result suggests that the observed changes in the frontal lobe could have occurred before the clinical symptoms of depression were observed

Personality change after ‘flow diverter implantation’ for intracranial aneurysm in a patient with stroke: A case report

Objective: This study aimed to present a patient with psychiatric symptoms that occur after flow diverter stent placement in a posterior communicating artery (PComA) aneurysm in a patient. Design: A case study. Method: We performed cranial magnetic resonance imaging (MRI), magnetic resonance angiography, computed tomography angiography, neuropsychological tests, Levenson Self-Report Psychopathy Scale (LSRP), and a 25-item version of the Wender Utah Rating Scale (WURS-25). The patient’s recent MRI was compared with previous MRIs. Neuropsychological testing consisted of a clinical interview, clinical assessment of frontal lobe syndrome, and tests evaluating the prefrontal cortex functions (Wisconsin Card Sorting Test-128 card version and Iowa Gambling Test). Results: Our results showed that the patient’s personality change and psychiatric symptoms occurred after the stent placement. Symptoms were still present at evaluation two and a half years after stent placement. Conclusion: The study demonstrates personality changes and psychiatric symptoms that might occur as complications following the placement of a flow diverter for incidentally detected aneurysm

Bir Türk Popülasyonunda Genom Çapında İlişkilendirme Çalışmalarından Kaynaklanan Polimorfizmler ile Farklılaşmış Tiroid Kanseri Riski Arasındaki İlişkinin İncelenmesi]

Background: Thyroid cancer is the most common malignancy of endocrine system. Genome Wide Association Studies (GWAS) revealed a number of common variants associated with thyroid cancer risk. In this study, we aimed to investigate the association of these known variants with thyroid cancer risk in a Turkish population living in Trakya region. Methods: The study included 97 cases of differentiated thyroid cancer and 379 healthy controls. Real-Time Polymerase Chain Reaction (RT-PCR) method was used for the genotyping of rs965513, rs944289, rs966423 rs2439302 polymorphisms. Results: There was no statistically significant difference between patients and controls in terms of SNP genotype and allele frequencies. The distribution of cumulative genetic risk scores between patients and controls was also not significantly different. In the multiple logistic regression analysis (MLR), it was observed that the relationship of rs2439302 polymorphism GG genotype with thyroid cancer risk has a trend to be significant ((p = 0.067, 95%CI: 2.947 (0.928-9.357)). Conclusion: We suggest that the confirmation of the association of common variants with thyroid cancer in different populations will contribute to make a consensus on global risk alleles. The marginal significance of the association of rs2439302 with thyroid carcinoma risk shown in our study supports the need for functional studies on the role of this polymorphism in thyroid carcinoma.Trakya University Scientific Research Projects UnitTrakya University [TuBAP 2016/132]This study has been financially supported by the Trakya University Scientific Research Projects Unit (TuBAP 2016/132)

ARTICLE IN PRESS Th e Disrupted Connection Between Cerebral Hemispheres in Schizophrenia Patients: A Diff usion Tensor Imaging Study •

SUMMARY Aim: In schizophrenia, the disruption of the communication between two brain hemispheres has not been shown clearly in the anatomical aspect despite other studies with different modalities suggested so. In this study, the structural integrity and the variables affecting the structural integrity of the corpus callosum, which is the main connection between two hemispheres, was investigated via diffusion tensor imaging (DTI). Methods: The participants were evaluated by SCID-I and symptoms of the patients were assessed with PANSS. DT images of 25 schizophrenia patients and 17 healthy volunteers were acquired via 1.5 T MR. Fractioned Anisotropy (FA) values of two groups, measured on the DT images, were compared. Results: It was found that fractioned anisotropy (FA) values were lower in the genu of the patients than the healthy controls; however, there was no difference between the FA values of the patients and the controls in the splenium. Moreover, a significant negative correlation between the splenium FA values and the antipsychotic medication doses; and a trend level negative correlation of splenium FA and PANSS scores were found. Conclusion: Corpus callosum is the most important structure that connects two frontal lobes. The hypothesis that posits the fundamental role of the disconnection of frontal lobes in schizophrenia is supported by the findings of this study

Emotional context effect on recognition of varying facial emotion expression intensities in depression

Background: Previous research has indicated that Major Depressive Disorder (MDD) patients have deficits in the process of facial emotion recognition. In most of these studies, isolated emotional faces were used, and the effect of the surrounding context of the face was neglected. We aimed to investigate how context emotion (sad or happy) affects facial emotion recognition and whether this effect is different in depressive individuals compared to the control group. Methods: Happy, sad, neutral facial expressions with congruent and incongruent visual contexts were presented to 51 MDD patients and 42 matched healthy controls. Emotional facial expressions are presented as morphs gradually expressing happiness or sadness with 40% and 80% intensity levels. Mean reaction time, mean accuracy rate, and mean emotion intensity rating score was calculated for each condition. Results: The performances on facial emotion intensity rating and accuracy rate were similar between MDD patients and controls. MDD patients were slower to recognize all facial emotions and to recognize facial emotions with emotionally incongruent backgrounds compared to congruent ones. Limitations: Antidepressant therapy of patients might have affected our results. Conclusions: Emotional contextual features have an important role in facial emotion recognition but this effect is independent of depression. Longer reaction time in depression may be related to some cognitive impairments