Publications with Fulltext
Permanent URI for this collectionhttps://hdl.handle.net/20.500.14288/6
Browse
652 results
Search Results
Publication Open Access DNA methylation profiling identifies novel markers of progression in hepatitis B-related chronic liver disease(BioMed Central, 2016) Vatansever, Sezgin; Hardy, Timothy; Sarı, Aysegül Akder; Çakalağaoğlu, Fulya; Avcı, Arzu; Zeybel, Gemma Louise; Bashton, Matthew; Mathers, John C.; Ünsal, Belkis; Mann, Jelena; N/A; Department of Molecular Biology and Genetics; Zeybel, Müjdat; Karahüseyinoğlu, Serçin; Faculty Member; Faculty Member; Department of Molecular Biology and Genetics; School of Medicine; 214694; 110772Background: Chronic hepatitis B infection is characterized by hepatic immune and inflammatory response with considerable variation in the rates of progression to cirrhosis. Genetic variants and environmental cues influence predisposition to the development of chronic liver disease; however, it remains unknown if aberrant DNA methylation is associated with fibrosis progression in chronic hepatitis B. Results: To identify epigenetic marks associated with inflammatory and fibrotic processes of the hepatitis B-induced chronic liver disease, we carried out hepatic genome-wide methylation profiling using Illumina Infinium beadarrays comparing mild and severe fibrotic disease in a discovery cohort of 29 patients. We obtained 310 differentially methylated regions and selected four loci comprising three genes from the top differentially methylated regions: hypermethylation of HOXA2 and HDAC4 along with hypomethylation of PPP1R18 were significantly linked to severe fibrosis. We replicated the prominent methylation marks in an independent cohort of 102 patients by bisulfite modification and pyrosequencing. The timing and causal relationship of epigenetic modifications with disease severity was further investigated using a cohort of patients with serial biopsies. Conclusions: Our findings suggest a linkage of widespread epigenetic dysregulation with disease progression in chronic hepatitis B infection. Cpg methylation at novel genes sheds light on new molecular pathways, which can be potentially exploited as a biomarker or targeted to attenuate inflammation and fibrosis.Publication Open Access Liver transplantation in hepatic myelopathy(Kare Yayıncılık, 2022) Acar, Sencan; Dinçkan, Ayhan; Akyıldız, Murat; Faculty Member; School of Medicine; 123080Hepatic myelopathy (HMy) is a rare neurological complication of liver cirrhosis that involves spastic paraplegia caused by lateral cord demyelination especially due to the accumulation of some metabolites such as ammonia and manganese. We report a young adult woman presenting with spasticity and paraparesis in extremities after intrahepatic portosystemic shunting (TIPS) application and underwent deceased liver transplantation (LT). A 39-year-old woman underwent deceased LT because of cryptogenic liver cirrhosis. She underwent a TIPS procedure 5 years ago. After that, hepatic encephalopathy and spasticity appeared. She was on the waiting list for 3 years. Neurological findings after LT significantly decreased, but did not return to normal. After the emergence of neurological findings, the earlier LT can provide improvement in neurological findings.Publication Open Access Pneumonia in HIV-infected patients(Aves, 2016) Önür, Seda Tural; Dalar, Levent; Yalçın, Arzu Didem; İliaz, Sinem; Doctor; Koç University Hospital; 168584Acquired immune deficiency syndrome (AIDS) is an immune system disease caused by the human immunodeficiency virus (HIV). The purpose of this review is to investigate the correlation between an immune system destroyed by HIV and the frequency of pneumonia. Observational studies show that respiratory diseases are among the most common infections observed in HIV-infected patients. In addition, pneumonia is the leading cause of morbidity and mortality in HIV-infected patients. According to articles in literature, in addition to antiretroviral therapy (ART) or highly active antiretroviral therapy (HAART), the use of prophylaxis provides favorable results for the treatment of pneumonia. Here we conduct a systematic literature review to determine the pathogenesis and causative agents of bacterial pneumonia, tuberculosis (TB), nontuberculous mycobacterial disease, fungal pneumonia, Pneumocystis pneumonia, viral pneumonia and parasitic infections and the prophylaxis in addition to ART and HAART for treatment. Pneumococcus-based polysaccharide vaccine is recommended to avoid some type of specific bacterial pneumonia.Publication Open Access REM-predominant obstructive sleep apnea in patients with coronary artery disease(Multidisciplinary Digital Publishing Institute (MDPI), 2022) Newitt, Jennifer; Strollo, Patrick J., Jr.; Balcan, Mehmet Baran; Çelik, Yeliz; Peker, Yüksel; Researcher; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; Koç University Hospital; N/A; N/A; 234103Obstructive sleep apnea (OSA) is common in adults with coronary artery disease (CAD). OSA that occurs predominantly during rapid-eye movement (REM) sleep has been identified as a specific phenotype (REM-predominant OSA) in sleep clinic cohorts. We aimed to examine the association of REM-predominant OSA with excessive sleepiness, functional outcomes, mood, and quality of life in a CAD cohort, of whom 286 OSA patients with total sleep time >= 240 min, and REM sleep >= 30 min, were included. REM-predominant OSA was defined as a REM-apnea-hypopnea-index (AHI) /non-REM (NREM) AHI >= 2. In all, 73 (25.5%) had REM-predominant OSA. They were more likely to be female (26.0% vs. 9.9%; p = 0.001), and more obese (42.5% vs. 24.4%; p = 0.003) but had less severe OSA in terms of AHI (median 22.6/h vs. 36.6/h; p < 0.001) compared to the patients with non-stage specific OSA. In adjusted logistic regression models, female sex (odds ratio [OR] 4.64, 95% confidence interval [CI] 1.85-11.64), body-mass-index (BMI; OR 1.17; 95% CI 1.07-1.28) and AHI (OR 0.93, 95% CI 0.91-0.95) were associated with REM-predominant OSA. In univariate linear regression models, there was a dose-response relationship between REM-AHI and Zung Self-rated Depression Scale but not excessive sleepiness, functional outcomes, and anxiety scores. Among the Short Form-36 subdomains, Vitality, Mental Health, and Mental Component Summary (MCS) scores were inversely correlated with REM-AHI. In multivariate linear models, only MCS remained significantly associated with REM-AHI after adjustment for age, BMI, and sex (beta-coefficient -2.20, %95 CI [-0.56, -0.03]; p = 0.028). To conclude, female sex and BMI were related to REM-predominant OSA in this revascularized cohort. MCS was inversely associated with REM-AHI in the multivariate model.Publication Open Access Effectiveness of posterior structures in the development of proximal junctional kyphosis following posterior instrumentation: a biomechanical study in a sheep spine model(Elsevier, 2019) Akgül, Turgut; Sarıyılmaz, Kerim; Özkunt, Okan; Dikici, Fatih; Yazıcıoğlu, Önder; N/A; Korkmaz, Murat; Doctor; School of MedicineIntroduction: proximal junctional kyphosis – PJK has been defined by a 10 or greater increase in kyphosis at the proximal junction as measured by the Cobb angle from the caudal endplate of the uppermost instrumented vertebrae (UIV) to the cephalad endplate of the vertebrae 1 segments cranial to the UIV. In this biomechanical study, it is aimed to evaluate effects of interspinosus ligament complex distruption and facet joint degeneration on PJK development. Materials and methods: posterior instrumentation applied between T2 – T7 vertebrae using pedicle screws to randomly selected 21 sheeps, divided into 3 groups. First group selected as control group (CG), of which posterior soft tissue and facet joints are protected. In second group (spinosus group, SG) interspinosus ligament complex which 1 segment cranial to UIV has been transected, and third group (faset group-FG) was applied facet joint excision. 25 N, 50 N, 100 N, 150 N and 200 N forces applied at frequency of 5 Hertz as 100 cycles axial to the samples. Then, 250 N, 275 N and 300 N forces applied static axially. Interspinosus distance, kyphosis angle and discus heights was measured in radiological evaluation. Abnormal PJK was defined by a proximal junctional angle greater than 100 and at least 100 greater than the corresponding preoperative measurement. Results: in CG group, average interspinosus distance was 6,6 ± 1.54 mm and kyphosis angle was 2,2 ± 0.46° before biomechanical testing, and they were measured as 9,4 ± 1.21 mm and 3,3 ±0.44° respectively after forces applied to samples. In SG group, average interspinosus distance was 6,2 ± 1.72 mm and kyphosis angle was 2,7 ± 1.01° before experiment, and they were measured as 20,8 ± 5.66 mm and 15,1 ± 2.34° respectively after forces applied to samples. In FG group, average interspinosus distance was 4,8 ± 1.15 mm and kyphosis angle was −1 ± 4.14° before experiment, and they were measured as 11,1 ±1.96mm and 11 ± 2.87° respectively after forces applied to samples. In comparison to group CG, statistically significant junctional kyphosis was seen on both FG and SG group after statistical analysis. (p < 0.05). PJK was seen statistically significant more on SG group than FG group. (p < 0.05). Not any statistically significant difference was seen on measurement of disk distances among three groups. (p > 0.05) Conclusions: protecting interspinosus ligament complex and facet joint unity during posterior surgical treatment for spine deformation is vital to prevent PJK development. Based on our literature review, this is the first biomechanical study that reveals interspinosus ligament complex are more effective on preventing PJK development than facet joints.Publication Open Access Quadrant and dermatomal analysis of sensorial block in ultrasound-guided erector spinae plane block(Aves, 2022) Selvi, Onur; Tulgar, Serkan; Şerifsoy, Talat Ercan; Lance, Robert; Thomas, David Terence; Gürkan, Yavuz; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; 154129Objective: as a novel procedure now gaining popularity, erector spinae plane block has been the subject of many studies. However, dermatomal coverage of the sensory block caused by erector spinae plane block has been rarely studied. The goal of this study is to evaluate the sensory block resulting from erector spinae plane block applied at the T9 vertebral level. Materials and methods: this observational, prospective, blinded study was conducted on 50 adult patients undergoing laparoscopic abdominal surgery. All patients underwent bilateral erector spinae plane block at the T9 level after completion of the surgery while under general anesthesia. In order to further evaluate the sensory blockade, we divided the hemiabdomen-hemithorax region into 4 quadrants: dorsal-medial, dorsallaterel, ventral-lateral, and ventral-medial. The sensorial evaluation was performed using the pinprick test, 2 hours following the application of erector spinae plane block. Results: a total of 28 female and 22 male patients were examined in this study. Complete failure of the block was recorded in 7 patients, with no thoracic/lumbar segmental or quadrant involvement. Successful sensory block was achieved in 67% of the dorsolateral quadrants, 58% of the dorsomedial quadrants, 69% of the ventrolateral quadrants, and 55% of the ventromedial quadrants. Conclusion: cutaneous sensory block of erector spinae plane block at T9 vertebral level revealed variable results and low failure rates. Administration of erector spinae plane block for postoperative analgesia in thoracoabdominal surgeries requires further randomized controlled trials to confirm its effectiveness and convenience.Publication Open Access Isolated omental metastasis of renal cell carcinoma after extraperitoneal open partial nephrectomy : a case report(Elsevier, 2016) Sağlıcan, Yeşim; N/A; N/A; N/A; N/A; Acar, Ömer; Sağ, Alan Alper; Falay, Fikri Okan; Selçukbiricik, Fatih; Tabak, Levent; Esen, Tarık; Faculty Member; Faculty Member; Teaching Faculty; Faculty Member; Faculty Member; Faculty Member; School of Medicine; 237530; N/A; N/A; N/A; N/A; N/A; 50536INTRODUCTION: Metachronous metastatic spread of clinically localized renal cell carcinoma (RCC) affects almost 1/3 of the patients. They occur most frequently in lung, liver, bone and brain. Isolated omental metastasis of RCC has not been reported so far. CASE PRESENTATION: A 62-year-old patient previously diagnosed and treated due to pulmonary sarcoidosis has developed an omental metastatic lesion 13 years after having undergone open extraperitoneal partial nephrectomy for T1 clear-cell RCC. Constitutional symptoms and imaging findings that were attributed to the presence of a sarcomatoid paraneoplastic syndrome triggered by the development this metastatic focus complicated the diagnostic work-up. Biopsy of the [18F]-fluorodeoxyglucose (+) lesions confirmed the diagnosis of metastatic RCC and the patient was managed by the resection of the omental mass via near-total omentectomy followed by targeted therapy with a tyrosine kinase inhibitor. DISCUSSION: Late recurrence of RCC has been reported to occur in 10-20% of the patients within 20 years. Therefore lifelong follow up of RCC has been advocated by some authors. Diffuse peritoneal metastases have been reported in certain RCC subtypes with adverse histopathological features. However, isolated omental metastasis without any sign of peritoneal involvement is an extremely rare condition. CONCLUSION: To our knowledge, this is the first reported case of metachronously developed, isolated omental metastasis of an initially T1 clear-cell RCC. Constitutional symptoms, despite a long interval since nephrectomy, should raise the possibility of a paraneoplastic syndrome being associated with metastatic RCC. Morphological and molecular imaging studies together with histopathological documentation will be diagnosticPublication Open Access The MHC class I MICA gene is a histocompatibility antigen in kidney transplantation(Springer Nature, 2022) Carapito, Raphael; Aouadi, Ismail; Verniquet, Martin; Untrau, Meiggie; Pichot, Angelique; Beaudrey, Thomas; Bassand, Xavier; Meyer, Sebastien; Faucher, Loic; Posson, Juliane; Morlon, Aurore; Kotova, Irina; Delbos, Florent; Walencik, Alexandre; Aarnink, Alice; Kennel, Anne; Suberbielle, Caroline; Taupin, Jean-Luc; Matern, Benedict M.; Spierings, Eric; Congy-Jolivet, Nicolas; Essaydi, Arnaud; Perrin, Peggy; Blancher, Antoine; Charron, Dominique; Cereb, Nezih; Maumy-Bertrand, Myriam; Bertrand, Frederic; Garrigue, Valerie; Pernin, Vincent; Weekers, Laurent; Naesens, Maarten; Kamar, Nassim; Legendre, Christophe; Glotz, Denis; Caillard, Sophie; Ladriere, Marc; Giral, Magali; Anglicheau, Dany; Bahram, Seiamak; Süsal, Caner; Other; School of MedicineThe identity of histocompatibility loci, besides human leukocyte antigen (HLA), remains elusive. The major histocompatibility complex (MHC) class I MICA gene is a candidate histocompatibility locus. Here, we investigate its role in a French multicenter cohort of 1,356 kidney transplants. MICA mismatches were associated with decreased graft survival (hazard ratio (HR), 2.12; 95% confidence interval (CI): 1.45-3.11; P < 0.001). Both before and after transplantation anti-MICA donor-specific antibodies (DSA) were strongly associated with increased antibody-mediated rejection (ABMR) (HR, 3.79; 95% CI: 1.94-7.39; P < 0.001; HR, 9.92; 95% CI: 7.43-13.20; P < 0.001, respectively). This effect was synergetic with that of anti-HLA DSA before and after transplantation (HR, 25.68; 95% CI: 3.31-199.41; P = 0.002; HR, 82.67; 95% CI: 33.67-202.97; P < 0.001, respectively). De novo-developed anti-MICA DSA were the most harmful because they were also associated with reduced graft survival (HR, 1.29; 95% CI: 1.05-1.58; P = 0.014). Finally, the damaging effect of anti-MICA DSA on graft survival was confirmed in an independent cohort of 168 patients with ABMR (HR, 1.71; 95% CI: 1.02-2.86; P = 0.041). In conclusion, assessment of MICA matching and immunization for the identification of patients at high risk for transplant rejection and loss is warranted.Publication Open Access High-throughput automated phenotyping of two genetic mouse models of huntington's disease(Public Library of Science, 2013) Oakeshott, Stephen; Shamy, Jul Lea T; El-Khodor, Bassem Fouad; Filippov, Igor V.; Mushlin, Richard A.; Port, Russell G.; Connor, David; Paintdakhi, Ahmad; Menalled, Liliana B.; Ramboz, Sylvie; Howland, David S.; Kwak, Seung; Brunner, Dani; Department of Psychology; Balcı, Fuat; Faculty Member; Department of Psychology; College of Social Sciences and Humanities; 51269Phenotyping with traditional behavioral assays constitutes a major bottleneck in the primary screening, characterization, and validation of genetic mouse modelsof disease, leading to downstream delays in drug discovery efforts. We present a novel and comprehensive one-stop approach to phenotyping, the PhenoCube™. This system simultaneously captures the cognitive performance, motor activity, and circadian patterns of group-housed mice by use of home-cage operant conditioning modules (IntelliCage) and custom-built computer vision software. We evaluated two different mouse models of Huntington's Disease (HD), the R6/2 and the BACHD in the PhenoCube™ system. Our results demonstrated that this system can efficiently capture and track alterations in both cognitive performance and locomotor activity patterns associated with these disease models. This work extends our prior demonstration that PhenoCube™ can characterize circadian dysfunction in BACHD mice and shows that this system, with the experimental protocols used, is a sensitive and efficient tool for a first pass high-throughput screening of mouse disease models in general and mouse models of neurodegeneration in particularPublication Open Access Fear of happiness among college students: the role of gender, childhood psychological trauma, and dissociation(Medknow Publications, 2019) Türk, Tuğba; Öztürk, Erdinç; N/A; Şar, Vedat; Faculty Member; School of Medicine; 8542Aims: this study aimed to evaluate the fear of happiness among college students and its relationship to gender, childhood psychological trauma, and dissociation. Setting and Design: College students were addressed as study population, and a relational screening method was implemented. Materials and Methods: among 184 participants, 93 (50.5%) were women. The Fear of Happiness Scale (FHS), the Childhood Trauma Questionnaire (CTQ), and the Dissociative Experiences Scale (DES) were administered to all participants. Statistical Analysis Used: MannuWhitney-U and Student's t-tests were implemented for comparison of groups. Pearson correlation and stepwise multiple regression analyses were conducted to identify associations between variables. Results: there were no differences on DES, FHS, and CTQ total scores between genders. DES was associated with CTQ total scores in both genders. Women had higher scores than men on childhood emotional abuse and fear of "cheerfulness ends up with bad faith." Compared to nonmembers, female dissociative taxon members had higher scores on all childhood trauma types except sexual abuse, and on all types of fear of happiness except "good fortune ends up with disaster" which was the only type of fear significantly elevated among male dissociative taxon members. A stepwise regression analysis revealed that depersonalization, childhood emotional neglect, and physical abuse predicted fear of happiness among women which was predicted by absorption among men. Conclusions: there is a relationship between childhood psychological trauma, dissociation, and fear of happiness. Women seem to be more vulnerable in this path of obsessional thinking which affects different realms in male and female genders.