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    PublicationOpen Access
    Dimerization of pyrrole
    (TÜBİTAK, 1998) Yurtsever, Mine; Department of Chemistry; Department of Chemistry; Yurtsever, İsmail Ersin; Faculty Member; College of Sciences; 7129
    Accurate ab-inito quantum mechanical calculations of pyrrole dimers are reported. The thermodynamical stabilities of dimers with alpha - alpha, alpha -beta, and beta - beta type linkages are compared in order to predict the possibilities of branching in polypyrroles. Calculations employing large basis sets and including electron correlation effects predict the alpha - alpha dimers as the most stable form. However, an alpha - beta type bonding requires only 1.5-2.0 kcal/mol, and the energy necessary to introduce a beta - beta type bond is 3.6-4.0 kcal/mol. These values show that a high degree of branching is possible even at room temperatures.
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    PublicationOpen Access
    Recommendations for hepatitis B immunoglobulin and antiviral prophylaxis against hepatitis B recurrence after liver transplantation
    (Aves, 2021) Akarsu, Mesut; Önem, Soner; Turan, İlker; Adalı, Gupse; Akdoğan, Meral; Aladağ, Murat; Balaban, Yasemin; Danış, Nilay; Dayangaç, Murat; Gökcan, Hale; Sertesen, Elif; Gürakar, Merve; Harputluoğlu, Murat; Kabacam, Gökhan; Karademir, Sedat; Kıyıcı, Murat; İdilman, Ramazan; Karasu, Zeki; Akyıldız, Murat; Gençdal, Genco; Faculty Member; Doctor; School of Medicine; Koç University Hospital; 123080; N/A
    The combination of hepatitis B immunoglobulin and potent nucleos(t)ide analogs after liver transplantation is considered as the standard of care for prophylaxis against hepatitis B virus recurrence. However, the recommended doses, route of administration, and duration of HBIG administration remain unclear. Moreover, hepatitis B immunoglobulin-free prophylaxis with potent nucleos(t)ide analogs has shown promising disease outcomes in preventing hepatitis B virus recurrence. The current recommendations, produced by the Turkish Association for the Study of the Liver, Acute Liver Failure and Liver Transplantation Special Interest Group, suggest a reduced need for hepatitis B immunoglobulin administration with effective long-term suppression of hepatitis B virus replication using potent nucleos(t)ide analogs after liver transplantation.
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    PublicationOpen Access
    Clinical efficacy, safety, tolerability, and survival outcome of long-term inhaled iloprost treatment in the management of pulmonary arterial hypertension: data from prospective multicenter observational OPTION study
    (Aves, 2021) Küçükoğlu, Mehmet Serdar; Hanta, İsmail; Akdeniz, Bahri; Güllülü, Sümeyye; Atahan, Ersan; Sayın, Tamer; Okumuş, Gülfer; Önen, Zeynep Pınar; Yokuşoğlu, Mehmet; Baygül, Arzu Eden; Faculty Member; School of Medicine; 272290
    Objective: to evaluate clinical efficacy, safety and tolerability of long-term inhaled iloprost treatment in the daily practice for the management of pulmonary arterial hypertension (PAH). Methods: a total of 115 patients with PAH on inhaled iloprost treatment were included. New York Heart Association (NYHA) functional class, brain natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, and 6-minute walk distance (6MWD) were recorded at baseline and at 3rd to 24th month visits. Safety and tolerability of iloprost treatment were also evaluated during follow-up, as were the survival, clinical worsening, and the related risk factors. Results: the treatment was associated with an increase in the percentage NYHA functional class II (from 0.0% at enrolment to 36.2% at 24th month visit) patients but no significant difference was noted in 6MWD values. Clinical worsening was observed in 63.5% patients, while survival rate was 69.6%. NT-proBNP levels were significantly higher in non-survivors than in survivors (p=0.042). Cox regression analysis revealed the association of female sex [odds ratio (OR)=0.318; 95% confidence interval (CI), 0.128-0.792; p=0.014] and scleroderma-related PAH (OR=0.347; 95% CI, 0.140-0.860; p=0.022) with significantly lower risk (3.14 fold and 2.88 fold, respectively) of mortality. Conclusion: our findings indicate favorable efficacy, safety, and tolerability of long-term iloprost treatment in the management of PAH, whereas improved NYHA functional class was not accompanied with a significant change in 6MWD values. Patient age was a risk factor for clinical worsening, while female sex, scleroderma subtype, and lower NT-proBNP levels were associated with significantly lower mortality risk.
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    PublicationOpen Access
    Reduced serum sRANKL and sTREM2 levels in high-grade gliomas: association with prognosis
    (Turkish Neuropsychiatry Association / Türk Nöropsikiyatri Derneği, 2021) Efendioğlu, Mustafa; Şanlı, Elif; Balak, Naci; Türkoğlu, Çağla Ceren; School of Medicine
    Introduction: high-grade gliomas (HGG), including Glioblastoma multiforme (GBM), account for the majority of primary brain tumors. Nevertheless, prognostic and diagnostic biomarkers are quite limited for HGG. The objective of this study was to investigate the prognostic value of sRANKL and sTREM2 levels in HGG patients. Methods: twelve consecutive patients with HGG, 14 patients with non-glial tumors (non-GT) and 20 age and gender-matched healthy controls were recruited. Overall survival duration of the patients was recorded. Pre-operative serum levels of sRANKL and sTREM2 were measured by ELISA. Tumors of HGG patients were analyzed by immunohistochemical staining for p53 and Ki67 and percentage scores were calculated. Results: patients with HGG and non-GT showed lower serum sRANKL and sTREM2 levels than healthy individuals. Levels of sRANKL were inversely correlated with the overall survival of patients (p=0.002, R=0.787), while sTREM2 levels were inversely correlated with p53 score (p=0.018, R=-0.666) but not survival. Conclusion: brain tumor patients show suppressed levels of filial activity biomarkers in the peripheral circulation. Serum sRANKL levels may serve as a potential prognostic biomarker for HGG. / Amaç: glioblastoma multiforme (GBM) dâhil olmak üzere yüksek dereceli gliomalar (YDG), birincil beyin tümörlerinin çoğunluğunu oluşturur. Bununla birlikte, tanısal ve prognostik biyobelirteçler YDG için oldukça sınırlıdır. Bu çalışmanın amacı, YDG hastalarında sRANKL vesTREM2 düzeylerinin prognostik değerini araştırmaktır. Yöntem: çalışmaya 12 YDG hastası, 14 tümörü glial (GT) kaynaklı olmayan hasta ile 20 yaş ve cinsiyet uyumlu sağlıklı kontrol dâhil edildi. Hastaların genel sağkalım süreleri kaydedildi. sRANKL ve sTREM2’ninoperasyon öncesi serum seviyeleri ELISA yöntemi ile ölçüldü. YDG hastalarının tümörleri p53 ve Ki67 için immünohistokimyasal boyama ile analiz edilerek yüzde skorları hesaplandı. Bulgular: YDG’si olan ve GT olmayan hastalar, sağlıklı bireylere göre daha düşük serum sRANKL ve sTREM2 seviyeleri gösterdi. sRANKL seviyeleri hastaların genel sağkalımı ile ters orantılıyken (p=0,002, R=-0,787),sTREM2 seviyelerinin ise p53 skoru ile ters orantılı olduğu saptandı(p=0,018, R=-0,666).Sonuç: beyin tümörü bulunan hastalarda, periferik dolaşımdaki glial aktivite biyobelirteçlerinin seviyeleri gösterilmiştir. Serum sRANKL seviyeleri, YDG hastaları için potansiyel bir prognostik biyobelirteç olabilir.
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    PublicationOpen Access
    Screening for hepatic fibrosis and steatosis in Turkish patients with type 2 diabetes mellitus: a transient elastography study
    (Aves, 2019) Demir, Meryem; Yılmaz, Yusuf; N/A; Deyneli, Oğuzhan; Faculty Member; School of Medicine
    Background/aims: non-alcoholic fatty liver disease is highly prevalent in patients with type 2 diabetes mellitus (T2DM). The aim of the present study was to investigate the potential usefulness of transient elastography (TE), which is a technique that allows measuring both fibrosis and liver fat content simultaneously, as a screening tool for hepatic involvement in Turkish patients with T2DM. Materials and methods: we obtained liver stiffness measurements (LSMs, as a measure of fibrosis) and controlled attenuation parameter (CAP, as a marker of steatosis) in 124 (46 males and 78 females; mean body mass index (BMI): 33.2 +/- 6.6 kg/m(2)) Turkish patients with T2DM. The prevalence rates of overweight, obesity, and metabolic syndrome in our sample were 28.2%, 64.5%, and 77.4%, respectively. Probe-specific LSM cut-off values were used to define advanced fibrosis (>= F3) and cirrhosis (F4) (M probe: F3=9.6-11.4 kPa, F4 >= 11.5 kPa and XL probe: F3=9.3-10.9 kPa, F4 >= 11.0 kPa). Mild, moderate, and severe steatosis were defined as CAP 222-232 dB/m, CAP 233-289 dB/m, and CAP >= 290 dB/m, respectively. Results: advanced fibrosis and cirrhosis were identified in 21 (16.9%) and 10 (8.0%) patients, respectively. TE-defined hepatic steatosis (CAP>222 dB/m) was detected in 117 (94.3%) patients. Mild, moderate, and severe steatosis were identified in 0, 29, and 88 patients, respectively. Conclusion: TE is a useful non-invasive imaging modality to screen for liver involvement in Turkish patients with T2DM. High rates of TE-defined fibrosis and steatosis in our sample reflect the presence of an elevated mean BMI.
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    PublicationOpen Access
    Neurocognitive functions in bipolar disorder in relation to comorbid ADHD
    (Turkish Neuropsychiatry Association / Türk Nöropsikiyatri Derneği, 2021) Arat Çelik, Hidayet Ece; Hıdıroğlu Ongun, Ceren; Erdoğan, Ayşe; Tan, Devran; Gümüşkesen, Peren; Bağcı, Başak; Özerdem, Ayşegül; Ceylan, Deniz; Faculty Member; School of Medicine; Koç University Hospital; 137755
    Introduction: bipolar disorder (BD) and attention deficit hyperactivity disorder (ADHD) often co-occur in adult population. Both conditions present various neurocognitive and behavioral problems. We aimed to examine neurocognitive functions in adult patients with comorbid BD and ADHD (BD+ADHD) in comparison to patients with only BD, only ADHD and healthy controls (HCs). Method: an extensive cognitive battery which evaluates verbal learning and memory, visual memory, processing speed, attention, executive functions, working memory and verbal fluency, was used to assess neurocognitive functions respectively in adult (age 18-65 years) patients with BD (n=37), ADHD (n=43), BD+ADHD (n=20) in comparison to HCs (n=51). The Multivariate Analysis of Covariance models, where age, level of education and total BIS-11 scores were included as covariates, were used for comparing neurocognitive scores among groups. Results: both BD and BD+ADHD groups showed significantly poorer performance than HCs in processing speed, attention, executive functions, and verbal fluency domains. The BD group had additional significant deficits in executive functions, verbal learning and memory domains. There were no significant differences between BD and BD+ADHD groups with regards to verbal learning and memory, visual memory, processing speed, attention, executive functions, working memory and verbal fluency domains. Patients with only ADHD showed significantly poorer performance than HCs in verbal fluency domain. Conclusions: our results show similarities in the neurocognitive functions of adults with BD and BD+ADHD across a wide range of cognitive domains. The findings point to the need for further exploration of diverging and converging neurodevelopmental trajectories of BD and ADHD. / Amaç: bipolar bozukluk (BB) ve dikkat eksikliği hiperaktivite bozukluğu (DEHB) yetişkinlerde sıklıkla bir arada görülmektedir. Her iki durumda da nörobilişsel ve davranışsal problemler bulunmaktadır. Bu çalışmada DEHB ek tanısı olan erişkin BB (BB+DEHB) tanılı bireylerin nörobilişsel işlevlerinin yalnız BB tanılı bireyler, yalnız DEHB tanılı bireyler ve sağlıklı kontrollerle (SK) karşılaştırılması amaçlanmıştır. Yöntem: nörobilişsel işlevlerin değerlendirilmesi amacıyla erişkin (18–65 yaş arası) BB tanılı bireylere (s=37), DEHB tanılı bireylere (s=43),BB+DEHB (s=20) tanılı bireylere ve sağlıklı kontrollere (s=51) sözel öğrenme ve bellek, görsel bellek, işlem hızı, dikkat, yürütücü işlevler, işleyen bellek ve sözel akıcılık işlevlerinin ölçüldüğü geniş bir nörobilişsel batarya uygulanmıştır. Nörobilişsel testler gruplar arasında, yaş, eğitim seviyesi ve toplam BIS puanları eş değişken olarak alınarak, çok faktörlü kovaryans analizi modeli kullanılarak değerlendirilmiştir. Bulgular: BB ve BB+DEHB grupları işlem hızı, dikkat, yürütücü işlev ve sözel akıcılık alanlarında, sağlıklı kontrollere göre anlamlı olarak düşük performans göstermiştir. BB grubu ek olarak yürütücü işlev, sözel öğrenme ve bellek alanlarında bozukluklar göstermiştir. BB veBB+DEHB grupları arasında sözel öğrenme ve bellek, görsel bellek, işlem hızı, dikkat, yürütücü işlevler, işleyen bellek ve sözel akıcılık alanlarında anlamlı farklılık saptanmamıştır. DEHB grubu sözel akıcılık alanında sağlıklı kontrollere göre anlamlı olarak kötü performans sergilemiştir. Sonuç: bulgularımız erişkin BB ve BB+DEHB tanılı bireylerin nörobilişsel işlevler açısından büyük oranda benzerlikler gösterdiğini ortaya koymaktadır. Bulgular BB ve DEHB’nin nörogelişimsel açıdan benzer ve farklı yönlerinin ortaya konması için daha çok çalışmaya ihtiyaç olduğunu göstermektedir.
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    PublicationOpen Access
    Impact of autoimmune demyelinating brain disease sera on pericyte survival
    (Turkish Neuropsychiatry Association / Türk Nöropsikiyatri Derneği, 2021) Ulusoy, Canan; Yılmaz, Vuslat; Küçükali, Cem İsmail; Karaaslan, Zerrin; Kürtüncü, Murat; Türkoğlu, Recai; Tüzün, Erdem; Şekerdağ, Emine; Gökyüzü, Aysu Bilge; Atak, Dila; Vural, Atay; Özdemir, Yasemin Gürsoy; PhD Student; Researcher; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Health Sciences; School of Medicine; N/A; N/A; N/A; 182369; 170592
    Introduction: multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) characterized by demyelination and brain pericyte dysfunction might be involved in MS pathogenesis Our aim was to evaluate whether the factors in serum affect pericyte survival. Method: C57BL/6 female mice were immunized with myelin oligodendrocyte glycoprotein (MOG) to induce experimental autoimmune encephalomyelitis (EAE). To confirm the animal model, the sera level of anti-MOG antibody in mice and platelet-derived growth factor-BB (PDGF-BB) in patients was measured by ELISA. Human brain vascular pericytes (HBVP) cell lines were incubated with sera of EAE mice and primer progressive MS (PPMS), seconder progressive MS (SPMS) and relapsing-remitting MS (RRMS) patients. The viability of HBVP is measured with Annexin V-FITC/propidium iodide staining with flow cytometry. Results: annexin V-FITC/propidium iodide staining with flow cytometry showed increased ratios of early apoptosis and decreased survival following incubation with sera of EAE and progressive MS. Levels of platelet-derived growth factor-BB were identical in serum and cerebrospinal fluids of patients with different forms of MS. Conclusion: our results suggest that serum factors might contribute to progressive MS pathogenesis via pericyte dysfunction. / Amaç: multipl skleroz (MS) merkezi sinir sisteminin (MSS) otoimmün demiyelinizan hastalığıdır. Son yıllardaki bulgular beyin perisit disfonksiyonunun MS patogenezinde yol oynayabileceğini göstermiştir. Bu çalışmada amacımız MS’nin perisit sağkalımına etkilerini ortaya koymaktır. Yöntem: MS hayvan modeli olan deneysel otoimmün ensefalomiyelit (DOE) modelini oluşturmak için, 8–10 haftalık C57BL/6 dişi fareler miyelin oligodendrosit glikoprotein (MOG) ile immünize edildi. Deneysel hayvan modelinin başarılı bir şekilde oluştuğunu doğrulamak için fareler klinik olarak gözlemlendi ve kanları alınarak serumlarında anti-MOG antikoru taraması yapıldı. Hücre kültürü ortamında, insan beyin damarsal perisit (İBDP) ile DOE fare ve insan MS hastası serumları (yineleyici MS, sekonder progresif MS ve primer progresif MS hastaları dâhil edilmiştir.) Yirmi dört saat inkübe edildi. Perisitlerin hücresel canlılık durumu Annexin V-FITC/ propidiyum iyodid (PI) ile akım sitometrisinde değerlendirildi. Ayrıca MS hastaları serumunda perisitlerin fonksiyonu için önemli olan trombosit kaynaklı büyüme faktörü düzeyi ELISA yöntemi ile ölçüldü. Bulgular: DOE ve progresif tip MS serumları ile inkübe olan perisitlerin diğer gruplara göre anlamlı derecede yüksek oranlarda erken apoptoza girdiği ve buna bağlı olarak canlılık yüzdelerinin düştüğü görülmüştür. Farklı MS tiplerine sahip hasta ve sağlıklı kontrollerin serum ve beyin omurilik sıvılarındaki trombosit-kaynaklı büyüme faktörü seviyeleri açısından anlamlı bir fark bulunmadı. Sonuç: elde ettiğimiz bulgular progresif tip MS hastalarının serumlarındaki birtakım faktörlerin perisit disfonksiyonuna sebep olarak MS patogenezine katkı yaptığını düşündürmektedir.
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    PublicationOpen Access
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    PublicationOpen Access
    Quantitative comparison of a laterally misplaced pedicle screw with a re-directed screw. How much pull-out strength is lost?
    (Elsevier, 2018) Şanyılmaz, Kerim; Özkunt, Okan; Gemalmaz, Halil Can; Akgül, Turgut; Sungur, Mustafa; Dikici, Fatih; Baydoğan, Murat; Korkmaz, Murat; Doctor; Koç University Hospital
    Objective: redirecting of a laterally misplaced pedicle screw into the accurate position decreases the pull-out strength due to the reinsertion, lateral wall cortical perforation and widening of the pedicle hole. Thus, this biomechanical study was performed to quantitatively analyze the pullout strength of a redirected laterally misplaced pedicle screw into the accurate position. Methods: thirty pedicules of 15 bovine vertebrae were separated to 3 groups, according to the screw placement method: 1) standard flawless trajectory; 2) trajectory with lateral pedicle wall perforation; 3) trajectory with lateral wall perforation redirected to the standard trajectory. Samples were placed on a universal testing machine and pullout loads were measured. Kruskal-Wallis test was utilized within 95% confidence interval and p value <0.05 to test for the statistical significance. Results: the mean pullout strength was 2891 +/- 654,2 N(1383-3814,5) in Group 1; 817,8 +/- 227,6 N(308,6-1144,9) in Group 2 and 2081,1 +/- 487,7 N(1583,5-2962,5) in Group 3. The results found out to be statistically significant (p<0.05). Inter-group comparisons revealed that lateral pedicle wall perforation significantly decreases the pullout strength (p<0.05) and redirection of the screw increases the strength (p<0.05), however it was still weaker than the screws with flawless standard trajectory but this was not statistically significant (p>0.05). Conclusion: The results of this study confirm that pullout strength of pedicle screw decreases by approximately 71% when the lateral wall is perforated and decreases 28% after redirection to the accurate position.
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    PublicationOpen Access
    The usefulness of cardiac magnetic resonance in prevention of sudden cardiac death after myocardial infarction: Author's reply
    (Kare Yayıncılık, 2015) Yalın, Kıvanç; Gölcük, Şükriye Ebru; Doctor; Koç University Hospital