Body shape phenotypes of multiple anthropometric traits and cancer risk: a multi-national cohort study

Background - Classical anthropometric traits may fail to fully represent the relationship of weight, adiposity, and height with cancer risk. We investigated the associations of body shape phenotypes with the risk of overall and site-specific cancers. Methods - We derived four distinct body shape phenotypes from principal component (PC) analysis on height, weight, body mass index (BMI), waist (WC) and hip circumferences (HC), and waist-to-hip ratio (WHR). The study included 340,152 men and women from 9 European countries, aged mostly 35–65 years at recruitment (1990–2000) in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Cox proportional hazards regression was used to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). Results - After a median follow-up of 15.3 years, 47,110 incident cancer cases were recorded. PC1 (overall adiposity) was positively associated with the risk of overall cancer, with a HR per 1 standard deviation (SD) increment equal to 1.07 (95% confidence interval 1.05 to 1.08). Positive associations were observed with 10 cancer types, with HRs (per 1 SD) ranging from 1.36 (1.30–1.42) for endometrial cancer to 1.08 (1.03–1.13) for rectal cancer. PC2 (tall stature with low WHR) was positively associated with the risk of overall cancer (1.03; 1.02–1.04) and five cancer types which were not associated with PC1. PC3 (tall stature with high WHR) was positively associated with the risk of overall cancer (1.04; 1.03–1.05) and 12 cancer types. PC4 (high BMI and weight with low WC and HC) was not associated with overall risk of cancer (1.00; 0.99–1.01). Conclusions - In this multi-national study, distinct body shape phenotypes were positively associated with the incidence of 17 different cancers and overall cancer

Expanding the clinical and immunological phenotypes of PAX1-deficient SCID and CID patients

Paired box 1 (PAX1) deficiency has been reported in a small number of patients diagnosed with otofaciocervical syndrome type 2 (OFCS2). We described six new patients who demonstrated variable clinical penetrance. Reduced transcriptional activity of pathogenic variants confirmed partial or complete PAX1 deficiency. Thymic aplasia and hypoplasia were associated with impaired T cell immunity. Corrective treatment was required in 4/6 patients. Hematopoietic stem cell transplantation resulted in poor immune reconstitution with absent naïve T cells, contrasting with the superior recovery of T cell immunity after thymus transplantation. Normal ex vivo differentiation of PAX1-deficient CD34+ cells into mature T cells demonstrated the absence of a hematopoietic cell-intrinsic defect. New overlapping features with DiGeorge syndrome included primary hypoparathyroidism (n = 5) and congenital heart defects (n = 2), in line with PAX1 expression during early embryogenesis. Our results highlight new features of PAX1 deficiency, which are relevant to improving early diagnosis and identifying patients requiring corrective treatment

THE EFFECT OF FACTOR II , FACTOR V , METHYLENETETRAHYDROFOLATE REDUCTASE GENE MUTATIONS ON THE ETIOLOGY OF SPONTANEOUS ABORTIONS WHICH HAVE NORMAL KARYOTYPE

Gelişmiş ülkelerde her 10 gebelikten biri erken gebelik kaybı, her 200 gebelikten biri geç gebelik kaybı ile sonuçlanmaktadır. Koagülasyon faktörlerinden kaynaklanan hemostatik hataların, plasental yatak damarlarında tıkanıklığa yol açabilmesinden yola çıkılarak, düşük oluşumuna neden olabileceği düşünülmektedir. Bu yüzden trombofililer obstetrik açıdan önemli patolojilerdir. Bu çalışma ile ülkemizde ilk defa kendiliğinden oluşan düşüklerin etiyolojisinde kromozomal komponentin yanı sıra ebeveynler ve düşük materyali DNA'sında maternal hücre kontaminasyonu ekarte edildikten sonra Faktör V (Leiden), Faktör II (G20210A) ve Metilentetrahidrofolat redüktaz (C677T) mutasyonlarının araştırılması sağlanacaktır. Literatürde, bahsedilen bu üç gene ait ailelerde yapılan mutasyon çalışmalarına rastlanmakla beraber, düşük materyali dokusundan yapılan çalışmalar son derece sınırlıdır. Bu çalışmaya Gazi Üniversitesi Tıp Fakültesi Kadın Hastalıkları ve Doğum Anabilim Dalı'na açıklanamayan kendiliğinden düşük oluşumu ile başvuran 70 hasta ile başlanmıştır. Yapılan uzun dönem doku kültürleri sonrasında 26'sında (%37,1) kromozom anomalileri belirlenmiş olup düşük oluşumunun nedeni açıklandığı için çalışma grubu dışında bırakılmıştır. 46, XX kromozom kuruluşu belirlenen 38 olguda ise maternal hücre kontaminasyonunu ekarte etmek amacıyla uygulanan moleküler teknikler doğrultusunda 34'ünün (%89,4) hücrelerinin anneye ait olduğu belirlenmiştir. Bu sonuçlar doğrultusunda doku kültürü sonucunda düşük materyalini yansıtan; 46,XY normal karyotipi belirlenen 6 olgu ve maternal hücre kontaminasyonu ekarte edilen 4 olgu ve ebeveynlerinden mutasyon taraması yapılmıştır. Bu çalışmada az sayıda düşük materyalinde trombofili çalışması gerçekleştirilebilmesine karşın, doğru bir algoritma sonrası elde edilen veriler kesin olarak gebelik kaybını yansıttığı için son derece değerlidir.In developed countries early pregnancy loss occurs in 10 % of pregnant women, late pregnancy loss occurs in 5 ‰ of these women. As haemostatic errors, happening due to coagulation factors, are able to close the placental vessels, they may cause to occur spontaneous abortion. Because of this thrombophilias are very important pathologies. In this study Factor II (G20210A), Factor V (Leiden), Methylenetetrahydrofolate reductase (C677T) gene mutations are invastigated in the DNA of both parents and fetus after eleminating abnormal chromosome settings in the fetus and maternal cell contamination in fetal DNA. We came across some studies on these gene mutations in the literature but investigations on fetal DNA are very limited. This study started with 70 patients who enrolled to Gazi University Medical Faculty Obstetrics and Gynaecology department because of spontaneous abortion. After long-term tissue culturing, in 26 abort material (37,1%) chromosome abnormalities are detected and this group is excluded from the study as it explains the reason for abortion. 46,XX chromosome setting is detected in 38 material so that moleculer studyings for maternal cell contamination are done. It is seen that in 34 patients (89,4%) the cells are belong to mother. According to this results 6 materials having 46,XY karyotype and 4 materials having 46,XX karyotype are scanned for mutations. In this study, although restrictred number of DNAs' thrombophily mutations could be performed, as the data reflect the true components of the pregnancy losses through a efficient algorithm, they are very valuable

NADPH oxidase P22PHOX gene expression in ulcerative colitis

Background/Aims: Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, which catalyzes the formation of reactive oxygen species (ROS) in phagocytic cells, has five subunits: p67phox ("phox"refers to "phagocyte oxidase"), p47phox, p40phox, p22phox, and gp91phox (catalytic subunit). Oxidative stress resulting from the accumulation of ROS and/or defective removal of ROS by antioxidants has detrimental effects on cellular functions and may contribute to chronic inflammation. Disruption of the colonic mucosa due to the dysregulation of antioxidants or transformation enzymes may play a role in the pathogenesis of ulcerative colitis (UC) and influence the clinical features of this disease. In this study, we examined the expression of the gene encoding NADPH oxidase subunit p22phox cytochrome b-245, alphapolypeptidein the colonic mucosa to test its possible contribution in the pathogenesis of UC.Materials and Methods: Expression levels of mRNA in the inflamed and non-inflamed colonic mucosa (determined using colonoscopy)of 22 patients with UC and in the normal mucosa of 22 healthy controls were analyzed using real-time polymerase chain reaction.Results: Expression levels of mRNA were not significantly different between patients with inflamed and non-inflamed colonic mucosa (p>0.05) and betweenpatients with inflamed colonicmucosa and healthy controls (p>0.05). Conclusion: Although our data suggest that expression of the gene encoding p22phox is not associated with chronic inflammation in patients with UC, other mechanisms can affect oxidative stress in these patients.Background/Aims: Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, which catalyzes the formation of reactive oxygen species (ROS) in phagocytic cells, has five subunits: p67phox ("phox"refers to "phagocyte oxidase"), p47phox, p40phox, p22phox, and gp91phox (catalytic subunit). Oxidative stress resulting from the accumulation of ROS and/or defective removal of ROS by antioxidants has detrimental effects on cellular functions and may contribute to chronic inflammation. Disruption of the colonic mucosa due to the dysregulation of antioxidants or transformation enzymes may play a role in the pathogenesis of ulcerative colitis (UC) and influence the clinical features of this disease. In this study, we examined the expression of the gene encoding NADPH oxidase subunit p22phox cytochrome b-245, alphapolypeptidein the colonic mucosa to test its possible contribution in the pathogenesis of UC.Materials and Methods: Expression levels of mRNA in the inflamed and non-inflamed colonic mucosa (determined using colonoscopy)of 22 patients with UC and in the normal mucosa of 22 healthy controls were analyzed using real-time polymerase chain reaction.Results: Expression levels of mRNA were not significantly different between patients with inflamed and non-inflamed colonic mucosa (p>0.05) and betweenpatients with inflamed colonicmucosa and healthy controls (p>0.05). Conclusion: Although our data suggest that expression of the gene encoding p22phox is not associated with chronic inflammation in patients with UC, other mechanisms can affect oxidative stress in these patients

Irak-Türkiye ham petrol boru hattı projesi

Ankara : İhsan Doğramacı Bilkent Üniversitesi İktisadi, İdari ve Sosyal Bilimler Fakültesi, Tarih Bölümü, 2018.This work is a student project of the Department of History, Faculty of Economics, Administrative and Social Sciences, İhsan Doğramacı Bilkent University.The History of Turkey course (HIST200) is a requirement for all Bilkent undergraduates. It is designed to encourage students to work in groups on projects concerning any topic of their choice that relates to the history of Turkey. It is designed as an interactive course with an emphasis on research and the objective of investigating events, chronologically short historical periods, as well as historic representations. Students from all departments prepare and present final projects for examination by a committee, with 10 projects chosen to receive awards.Includes bibliographical references (pages 17-20).by Süha Ünsal