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    PublicationOpen Access
    A combined VBM and DTI study of schizophrenia: bilateral decreased insula volume and cerebral white matter disintegrity corresponding to subinsular white matter projections unlinked to clinical symptomatology
    (Aves, 2017) Ulaşoğlu-Yıldız, Çiğdem; Aslan, Selçuk; Talı, Erhan Turgut; N/A; N/A; Onay, Aslıhan; Eser, Hale Yapıcı; Faculty Member; School of Medicine; N/A; 134359
    PURPOSE: Grey matter and white matter changes within the brain are well defined in schizophrenia. However, most studies focused on either grey matter changes or white matter integrity separately; only in limited number of studies these changes were interpreted in the same frame. In addition, the relationship of these findings with clinical variables is not clearly established. Here, we aimed to investigate the grey matter and white matter changes in schizophrenia patients and exhibit the relation of these imaging findings with clinical variables. METHODS: A total of 20 schizophrenia patients and 16 matched healthy controls underwent magnetic resonance imaging to investigate the grey matter and white matter alterations that occur in schizophrenia patients using voxel-based morphometry (VBM) and whole brain voxel-wise analysis of diffusion tensor imaging (DTI) parameters with SPM8, respectively. While the preprocessing steps ofVBM were performed with the default parameters of VBM8 toolbox, the preprocessing steps of DTI were carried out using FSL. Additionally, VBM results were correlated with clinical variables. RESULTS: Bilateral insula showed decreased grey matter volume in schizophrenia patients compared with healthy controls (P < 0.01). The opposite contrast did not show a significant difference. Psychiatric scores, duration of illness, and age were not correlated with the decreased grey matter volume of insula in schizophrenia patients. DTI analysis revealed a significant increase in mean, radial, and axial diffusivity, mainly of the fibers of bilateral anterior thalamic radiation and superior longitudinal fasciculus with left predominance, which intersected with bilateral subinsular white matter (P < 0.05). CONCLUSION: Our findings suggest that insula may be the main affected brain region in schizophrenia, which is also well supported by the literature. Our results were independent of disease duration and schizophrenia symptoms. White matter alterations were observed within bilateral anterior thalamic radiation and superior longitudinal fasciculus that intersects with subinsular white matter. Studies with larger sample sizes and more detailed clinical assessments are required to understand the function of insula in the neurobiology of schizophrenia.
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    A fredholm alternative-like result on power bounded operators
    (Scientific Technical Research Council Turkey-Tubitak, 2011) Yavuz, Onur; Department of Mathematics; Ülger, Ali; Faculty Member; Department of Mathematics; College of Sciences; N/A
    Let X be a complex Banach space and T:X\rightarrow X be a power bounded operator, i.e., \sup_{n \geq 0}\ T^n\
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    A possibly fatal outcome of oral contraceptive therapy: estrogen triggered hereditary angioedema attack in an adolescent
    (Galenos Yayınevi, 2021) Demirkol, Demet; Birben, Esra; Soyer, Özge; N/A; Balkancı, Uğur Berkay; Yeşiltepe Mutlu, Rahime Gül; Yılmaz, Özlem; Saçkesen, Cansın; Undergraduate Student; Faculty Member; Doctor; Faculty Member; School of Medicine; School of Medicine; N/A; School of Medicine; Koç University Hospital; Koc University Hospital; N/A; 153511; 140706; 182537
    Hereditary angioedema (HAE) is characterized by recurrent angioedema attacks with no urticaria. This disease has a high mortality due to asphyxia. Level of complement 4 (C4), C1 esterase inhibitor (C1-INH) level and function, and genetic mutations determine different endotypes of HAE. Clinical presentation and the triggers of vasogenic edema may change according to the endotypes. An adolescent girl with oligomenorrhea, obesity, hirsutism, and acanthosis nigricans was diagnosed with polycystic ovary syndrome (PCOS) and prescribed ethinyl estradiol & cyproterone acetate containing oral contraceptive (OC). On the 16th day of treatment, she developed angioedema on the face, neck, and chest leading to dyspnea. Adrenaline, antihistamine, and corticosteroid treatments were ineffective. In the family history, the patient's mother and two cousins had angioedema attacks. C1-INH concentrate was administered with a diagnosis of HAE. C4, and C1-INH level and activity were normal. Genetic analysis identified a mutation of Factor XII (F12) gene, and the diagnosis of Factor 12 (F12)-related HAE was made. OC treatment discontinued. She has had no additional angioedema attacks in the follow-up period of two years. OC containing estrogen may induce the life-threatening first attack of F12-related HAE even in children. Recurring angioedema attacks in the family should be asked before prescribing estrogen-containing OC pills.
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    PublicationOpen Access
    An evaluation of glucagon injection anxiety and its association with the fear of hypoglycemia among the parents of children with type 1 diabetes
    (Galenos Yayınevi, 2021) Muradoğlu, Serra Küpçüoğlu; Gökçe, Tuğba; Can, Ecem; Yeşiltepe Mutlu, Rahime Gül; Hatun, Şükrü; Faculty Member; School of Medicine; Graduate School of Health Sciences; Koç University Hospital; N/A; N/A; N/A; 153511; 153504
    Objective: Hypoglycemia is a common acute complication of type 1 diabetes (T1D), which may cause seizure, loss of consciousness, and temporary motor or sensory impairment. Glucagon administration is an effective way of treating severe hypoglycemia, especially in a free-living setting. Nonetheless, families have difficulties in managing severe hypoglycemia due to their anxiety and challenges with current glucagon administration techniques. The aim of the current study was to explore the associations between parental fear of hypoglycemia (FoH) and their general anxiety level, and in particular, their attitudes towards and thoughts on glucagon administration. Methods: Parents of children with T1D completed questionnaires assessing background and clinical information, FoH, generalized anxiety disorder (GAD) and parental anxiety for glucagon administration (PAGA). Results: sixty-eight parents participated. Positive correlations were found between parental GAD-7 score and both FoH and the number of night-time blood glucose measurements and there was a negative correlation with the child's age. Parents mean self-evaluation score of their competence in glucagon administration was 6 (standard deviation +/- 2.9) on a scale of 0 to 10. Unsurprisingly, this score was negatively correlated with the PAGA scores. There was no significant difference between children using continuous glucose monitoring system and self-monitoring of blood glucose in terms of parental FoH, anxiety and misconceptions about glucagon administration. Conclusion: the results showed that parents of children with T1D had anxiety and fear connected with hypoglycemia and glucagon administration. Structured and practical training should be implemented to increase parents' self-confidence including annual refresher training for home glucagon administration.
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    PublicationOpen Access
    An integrated analysis of capacity allocation and patient scheduling in presence of seasonal walk-ins
    (Springer, 2018) Çayırlı, Tuğba; Dursun, Pınar; Department of Business Administration; Güneş, Evrim Didem; Faculty Member; Department of Business Administration; College of Administrative Sciences and Economics; 51391
    This study analyzes two decision levels in appointment system design in the context of clinics that face seasonal demand for scheduled and walk-in patients. The macro-level problem addresses access rules dealing with capacity allocation decisions in terms of how many slots to reserve for walk-ins and scheduled patients given fixed daily capacity for the clinic session. The micro-level problem addresses scheduling rules determining the specific time slots for scheduled arrivals. A fully-integrated simulation model is developed where daily demand actualized at the macro level becomes an input to the micro model that simulates the in-clinic dynamics, such as the arrivals of walk-ins and scheduled patients, as well as stochastic service times. The proposed integrated approach is shown to improve decision-making by considering patient lead times (i.e., indirect wait), direct wait times, and clinic overtime as relevant measures of performance. The traditional methods for evaluating appointment system performance are extended to incorporate multiple trade-offs. This allows combining both direct wait and indirect wait that are generally addressed separately due to time scale differences (minutes vs. days). The results confirm the benefits of addressing both decision levels in appointment system design simultaneously. We investigate how environmental factors affect the performance and the choice of appointment systems. The most critical environmental factors emerge as the demand load, seasonality level, and percentage of walk-ins, listed in the decreasing order of importance.
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    PublicationOpen Access
    Are the criteria always right? Assessment of hepatocellular carcinoma cases in living donor liver transplantation at a high-volume center
    (TÜBİTAK, 2021) Yankol, Y.; Hoş, G.; Çakaloğlu, Y.; Acarlı, K. S.; Kanmaz, Turan; Mecit, Nesimi; Faculty Member; School of Medicine; Koç University Hospital
    Background/aim: with the increased experience in living donor liver transplantation (LDLT), it has been adopted for the treatment of hepatocellular carcinoma (HCC), with emerging discussions of criteria beyond tumor size and number. In contrast to deceased donor liver transplantation (DDLT), recipient selection for LDLT is not limited by organ allocation systems. We discuss herein the assessment, criteria, and experience with liver transplantation (LT) in HCC cases at a high-volume LDLT center. Material and methods: between August 2006 and December 2017, 191 adult LT HCC recipients with at least one-year follow-up were retrospectively analyzed. Results: in 191 patients, one-, three-and five-year survival rates were 87.2%, 81.6%, and 76.2%, respectively, including early postoperative mortality. In 174 patients with long-term follow-up, one-, three-and five-year disease-free survival rates were 91.6%, 87.7%, and 84.4%, respectively. When multivariate analysis was utilized, tumor differentiation was the only factor which statistically affected survival (p = 0.025). Conclusion: LDLT allows us to push the limits forward and the question ""Are the criteria always right?"" is always on the table. We can conclude that, with the advantage of LDLT, every HCC patient deserves a case-by-case basis discussion for LT under scientific literature support. In borderline cases, tumor biopsy might help determine the decision for LT.
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    Artifact-removed quantitative analysis of choriocapillaris flow voids
    (Galenos Publ House, 2023) M. Giray ERSÖZ; Serra ARF; Murat KARAÇORLU; Mumin HOCAOĞLU; Işıl SAYMAN MUSLUBAŞ; N/A; Yıldız, Erdost; Koç University Research Center for Translational Medicine (KUTTAM); Graduate School of Health Sciences
    Amaç: Vitreus opasiteleri, retina pigment epiteli altı sıvı ve birikintileri ve subretinal sıvı (SRS) nedeniyle oluşan artefaktları dış retinanın en-face optik koherens tomografi (OKT) görüntüsünün eşiklenmesi yoluyla çıkarabilen yeni bir OKT-anjiyografi (OKTA) görüntü işleme stratejisiyle koryokapillaris akım boşluklarını (AB) araştırmak. Gereç ve Yöntem: Drusenli hastaların ve aktif santral seröz koryoretinopatili (SSKR) hastaların tıbbi kayıtlarını retrospektif olarak inceledik. Önerilen strateji kullanılarak elde edilen AB sayısı (ABs), ortalama alanı (ABa) ve maksimum alanı (ABmaks) ve perfüze olmayan koryokapillaris alanının yüzdesi (POKAY), sadece yüzeyel kapiller pleksus (YKP) nedeniyle oluşan artefaktların çıkarılmasıyla elde edilenlerle karşılaştırıldı. Bulgular: SRS grubuna aktif SSKR’li 21 göz, drusen grubuna ise non-eksüdatif yaşa bağlı maküla dejenerasyonlu 29 göz dahil edildi. İki grupta da algoritmamız kullanılarak elde edilen ABs, ABa, ABmaks ve POKAY, sadece YKP nedeniyle oluşan artefaktların çıkarılmasıyla elde edilenlerden anlamlı olarak düşüktü (tüm p’ler<0.05). Algoritma ayrıca vitreus opasitelerine bağlı artefaktların %96,9’unu ve seröz pigment epitel dekolmanlarına bağlı tüm artefaktları çıkarabildi. Sonuç: Retina pigment epiteli anormallikleri ve SRS olan gözlerde artefaktlar nedeniyle koryokapillarisin OKTA görüntülerinde non-perfüzyon alanları olduğundan fazlaymış gibi değerlendirilebilir. Koryokapillaris OKTA görüntülerindeki bu artefakt alanları, dış retina en-face OKT taramalarının eşiklenmiş görüntüleri kullanılarak çıkarılabilir. Yeni artefakt çıkarma stratejimiz, SRS, drusen, drusen benzeri birikintiler ve pigment epitel dekolmanı olan gözlerde koryokapillaris AB’nin değerlendirilmesi için kullanılabilir./Abstract Objectives: To investigate choriocapillaris flow voids (FV) with a new optical coherence tomography angiography (OCTA) image processing strategy that can eliminate artifacts caused by vitreous opacities, sub-retinal pigment epithelium fluid and deposits, and subretinal fluid (SRF) by thresholding the en-face OCT image of the outer retina. Materials and Methods: We retrospectively reviewed medical records of patients with drusen and patients with active central serous chorioretinopathy (CSC). FV number (FVn), average area (FVav), and maximum area (FVmax) and the percentage of nonperfused choriocapillaris area (PNPCA) obtained using the proposed strategy were compared with those obtained by removing only artifacts caused by the superficial capillary plexus (SCP). Results: The SRF group included 21 eyes with active CSC and the drusen group included 29 eyes with nonexudative age-related macular degeneration. FVav, FVmax, FVn, and PNPCA obtained using the algorithm were significantly lower than those obtained by removing only SCP-related artefacts in both groups (all p<0.05). The algorithm was also able to remove 96.9% of artifacts secondary to vitreous opacities and all artifacts secondary to serous pigment epithelial detachments.
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    Bringing packed red blood cells to the point of combat injury: are we there yet?
    (Galenos Yayınevi, 2018) Unlu, Aytekin; Yilmaz, Soner; Uyanik, Metin; Petrone, Patrizio; Cetinkaya, Riza Aytac; Eker, Ibrahim; Urkan, Murat; Ozgurtas, Taner; Avci, Ismail Yasar; Zeybek, Nazif; Yalçın, Özlem; Aksu, Ali Cenk; Faculty Member; PhD Student; School of Medicine; Graduate School of Health Sciences; 218440; N/A
    Objective: Hemorrhage is the leading cause of injury-related prehospital mortality. We investigated worst-case scenarios and possible requirements of the Turkish military. As we plan to use blood resources during casualty transport, the impact of transport-related mechanical stress on packed red blood cells (PRBCs) was analyzed. Materials and Methods: The in vitro experiment was performed in the environmental test laboratories of ASELSAN((R)). Operational vibrations of potential casualty transport mediums such as Sikorsky helicopters, Kirpi((R)) armored vehicles, and the NATO vibration standard MIL-STD-810G software program were recorded. The most powerful mechanical stress, which was created by the NATO standard, was applied to 15 units of fresh (<= 7 days) and 10 units of old (>7 days) PRBCs in a blood cooler box. The vibrations were simulated with a TDS v895 Medium-Force Shaker Device. On-site blood samples were analyzed at 0, 6, and 24 h for biochemical and biomechanical analyses. Results: The mean (+/- standard deviation) age of fresh and old PRBCs was 4.9 +/- 2.2 and 32.8 +/- 11.8 days, respectively. Six-hour mechanical damage of fresh PRBCs was demonstrated by increased erythrocyte fragmentation rates (p=0.015), hemolysis rates (p=0.003), and supernatant potassium levels (p=0.003) and decreased hematocrit levels (p=0.015). Old PRBC hemolysis rates (p=0.015), supernatant potassium levels (p=0.015), and supernatant hemoglobin (p=0.015) were increased and hematocrit levels were decreased (p=0.015) within 6 h. Two (13%) units of fresh PRBCs and none of the old PRBCs were eligible for transfusion after 6 h of meehanical stress. Conclusion: When an austere combat environment was simulated for 24 h, fresh and old PRBC hemolysis rates were above the quality criteria. Currently, the technology to overcome this mechanical damage does not seem to exist. In light of the above data, a new national project is being performed. / Amaç: Kan kayıpları, hastane öncesi dönemdeki yaralanmalara bağlı ölümlerin en sık sebebidir. Türk ordusu için en kötü senaryoları ve olası ihtiyaçları araştırdık. Çatışma alanından nakil esnasında kan kaynaklarını kullanmayı planladığımız için nakil işleminden kaynaklı mekanik stresin eritrosit konsantreleri üzerine etkisini analiz edilmiştir. Gereç ve Yöntemler: İn vitro çalışmalar ASELSAN®’ın dış ortam test laboratuvarlarında gerçekleştirildi. Çatışma alanında kan taşıma işleminde kullanılması muhtemel olan Sikorsky helikopteri ve Kirpi® araçlarının operasyonel vibrasyonları ve NATO MIL-STD-810G titreşim standart yazılımı kayıt altına alındı. NATO standardının en güçlü titreşime neden olduğu hesaplandı. Kan saklama çantası içindeki 15 ünite taze (≤7 gün) ve 10 ünite taze olmayan eritrosit konsantresi (>7 gün), NATO standardı olan mekanik strese maruz bırakıldı. Titreşim TDS v895 Medium-Force Shaker cihazı tarafından simüle edildi. Simülasyonun 0., 6. ve 24. saatinde biyokimyasal ve biyomekanik analiz için kan örnekleri alındı. Bulgular: Taze ve taze olmayan eritrosit konsantreleri sırasıyla ortalama 4,9 [standart deviasyon (SD) ±2,2] ve 32,8 (SD ±11,8) günlüktü. Taze eritrosit konsantrelerinde 6. saatte gelişen mekanik hasar; artmış eritrosit fragmentasyonu (p=0,015), hemoliz oranı (p=0,003) ve supernatant potasyum (p=0,015) düzeyleri ile gösterildi. Taze olmayan eritrosit konsantrelerinin 6. saatte hemoliz oranı (p=0,015) ve supernatant potasyum düzeyi (p=0,015) yükselirken, hematokrit değerleri (p=0,015) düştü. İlk 6 saat içerisinde taze eritrosit konsantrelerinin 2’si (%13) transfüze edilebilir kalitede kalırken, taze olmayanların ise hiçbirisi uygun değildi. Sonuç: Taze ve taze olmayan eritrosit konsantrelerinin hemoliz oranları, bu ürünleri muharebe sahasında taşıdığımızda, çoğunun kullanılamaz hale geleceğini göstermektedir. Halihazırda eritrositler üzerinde oluşan mekanik hasarlanmanın önüne geçebilecek bir teknoloji bulunmamaktadır. Yukarıdaki verilerin ışığı altında yeni bir ulusal proje gerçekleştirilmektedir.
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    Bud14 function is crucial for spindle pole body size maintenance
    (TUBITAK, 2024) Department of Molecular Biology and Genetics; Girgin, Sevilay Münire; Çaydaşı, Ayşe Koca; Department of Molecular Biology and Genetics; College of Sciences; Graduate School of Sciences and Engineering
    Background/aim: Spindle pole bodies (SPB), the functional equivalent of centrosomes in yeast, duplicate through generation of a new SPB next to the old one. However, SPBs are dynamic structures that can grow and exchange, and mechanisms that regulate SPB size remain largely unknown. This study aims to elucidate the role of Bud14 in SPB size maintenance in Saccharomyces cerevisiae. Materials and methods: We employed quantitative fluorescence microscopy to assess the relative and absolute amounts of SPB structural proteins at SPBs of wildtype cells and in cells lacking BUD14 (bud14∆). Quantifications were performed using asynchronous cell cultures, as well as cultures synchronously progressing through the cell cycle and upon different cell cycle arrests. We also utilized mutants that allow the separation of Bud14 functions. Results: Our results indicate that higher levels of SPB inner, outer, and central plaque proteins are present at the SPBs of bud14∆ cells compared to wildtype cells during anaphase, as well as during nocodazole-induced M-phase arrest. However, during α-factor mediated G1 arrest, inner and outer plaque proteins responded differently to the absence of BUD14. A Bud14 mutant that cannot interact with the Protein Phosphatase 1 (Glc7) phenocopied bud14∆ in terms of SPB-bound levels of the inner plaque protein Spc110, whereas disruption of Bud14-Kel1-Kel2 complex did not alter Spc110 levels at SPBs. In cells synchronously released from α-factor arrest, lack of Bud14-Glc7 caused increase of Spc110 at the SPBs at early stages of the cell cycle. Conclusion: We identified Bud14 as a critical protein for SPB size maintenance. The interaction of Bud14 with Glc7, but not with the Kelch proteins, is indispensable for restricting levels of Spc110 incorporated into the SPBs. © TÜBİTAK.
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    Charcot-Leiden crystals in acute myeloid leukemia with bone marrow necrosis
    (Galenos Publishing House, 2023) Yeldir, Nese; N/A; Tan, Taner; Akay, Olga Meltem; School of Medicine; Koç University Hospital
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