Browsing by Author "Mutlu, Derya"

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Comparison of two commercial quantitative cytomegalovirus (CMV) polymerase chain reaction tests calibrated by world health organization international CMV standard
(Ankara Mikrobiyoloji, 2020-04-01) Çolak, Dilek; Sağlık, İmran; Can Sarınoğlu, Rabia; Mutlu, Derya; Peker, Bilal Olcay; Erman Daloğlu, Aylin; Parkan, Ömur Mustafa; Koyuncu Özyurt, Özlem; SAĞLIK, İMRAN; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Mikrobiyoloji Anabilim Dalı; 0000-0003-0864-4989; GCM-3391-2022
Cytomegalovirus (CMV) viral load quantitation is important in diagnosis, follow-up, and monitoring of antiviral therapy in transplanted patients. In this study, it was aimed to compare the results of the two commercial World Health Organization (WHO) International CMV standard calibrated polymerase chain reaction tests, CMV Cobas Ampliprep/Cobas Taqman (CMV-CAP/CTM) (Roche, Germany) and Artus CMV QIASymphony-Rotorgene (CMV-QS-RGQ) (Qiagen, Germany). Both tests were performed simultaneously on 244 plasma samples. The results were measured in copies/ml and converted to IU/ml by multiplying with 0.91 for CMV-CAP/CTM and 1.64 for CMV-QS-RGQ, as specified by the manufacturers. CMV DNA was detected in 174 (71.3%) and was not detected in 52 (21.3%) of the samples and eighteen (7.4%) samples had discordant results by both of the tests. In 16 out of 18 samples with discordance, the viral load was below the dynamic measuring ranges of both tests. In one sample, CMV DNA could not be detected by CMV-CAP/CTM but detected by CMV-QS-RGQ with 497 copies/ml, and 334 copies/ ml CMV DNA was detected by CMV-CAP/CTM in another sample where it could not be detected by CMV-QS-RGQ. A high degree of agreement was found between the qualitative results of the both tests (kappa=0.80, p<0.001). For quantitative results in the dynamic measuring range of both assays (n=129), the median viral load values measured by CMV-CAP/CTM and CMV-QS-RGQ were 1140 copies/ml (range: 151-254000) and 1826 copies/ml (range: 189-551521). When the results were converted to IU/ml, the median viral load values measured by CMV-CAP/CTM and CMV-QS-RGQ were 1037 IU/ml (range: 137-231140) and 2993 IU/ml (range: 310-904133), respectively. There was a very strong correlation (r=0.94, p<0.001; r=0.94, p<0.001, respectively) between the log 10 values of the quantitative results in the dynamic measuring ranges (n= 129) as copies/ml and IU/ml of both tests. CMV-QS-RGQ values corresponding to 150, 1000, 3000 copies/ml in CMV-CAP/CTM were as 94.5, 1571, 323.5 copies/ml and CMV-QS-RGQ values corresponding to 137, 910, 2730 IU/ml in CMV CAP/CTM were as 154, 2557.6, 6965.9 IU/ml, respectively. A variation of 0.45 log(10) was determined between these values. In a total of 131 samples; 129 of them with the result of both tests in the dynamic measuring range and two of them which CMV DNA was not detected in one of the tests; it was found that 112 (85.5%) results for copy/ml, 73 (56%) results for IU/ml were within the measurement difference of +/- 0.5 log(10) and 19 (14.5%) results for copy/ml and 58 (44%) results for IU/ml were greater than +/- 0.5 log(10). Bland-Altman analysis showed that CMV-CAP/CTM test made lower measurements than CMV-QS-RGQ and the average difference for copy/ml and IU/ml results were 0.22 log(10) copies/ml and 0.47 log(10) IU/ml. In conclusion; when the results were converted to IU/ml, the number of samples with an acceptable measurement difference between the two test results (<= 0.5 log(10)) decreased and the number of samples with a measurement difference > 0.5 log(10) increased and the difference was found as statistically significant (p<0.001).Calibrating the Roche CMV CAP/CTM and Artus CMV-QS-RGQ tests with the WHO international CMV standard did not increase comparability between quantitative results in plasma samples, on the contrary, it was found that when the results were converted to IU/ml, a measurement difference indicating biologically significant viral replication was detected between the two test results.
Distribution of hepatitis c virus (hcv) genotypes among intravenous drug and non-drug user patients
(Ankara Microbiology, 2021-01-01) Erman Daloglu, Aylin; Parkan, Omur Mustafa; Erdogan, Ali; Peker, Bilal Olcay; Can Sarinoglu, Rabia; Saglik, Imran; Inan, Dilara; Kuloglu, Mehmet Murat; Mutlu, Derya; Ongut, Gozde; Colak, Dilek; Saglik, Imran; SAĞLIK, İMRAN; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Mikrobiyoloji Anabilim Dalı.; 0000-0003-0120-3830; 0000-0002-1071-4985; 0000-0003-0329-6778; 0000-0001-8735-2962; 0000-0001-9222-8659; 0000-0003-0864-4989; 0000-0002-6786-137X; U-8647-2019; AAX-1743-2021; AAD-7444-2022; C-7162-2016; D-7990-2018; C-9377-2018
Genotype distribution of hepatitis C virus (HCV) can vary over the years between different patient groups and regions. The prevalence of intravenous drug users (IVDU) is known to increase in our country, yet there are a limited number of studies investigating the distribution of HCV genotypes in this group. These data are essential for monitorization of the changes in HCV epidemiology. The present study aimed to evaluate the five-year results of HCV genotyping among patients infected with HCV related to IVDU and unrelated to drug use. Plasma samples of 720 patients (HCV antibody, HCV RNA positive), which were sent to our laboratory for HCV genotyping between January 2014-March 2019 were analyzed. HCV RNA extraction from plasma samples was performed in the automated-extraction system of EZ1 advanced (Qiagen, Germany) using the EZ1 virus mini kit v2.0 (Qiagen, Germany). Amplicons were obtained by amplifying the 5'NCR and core gene region in the Rotorgene 6000 real-time PCR (Qiagen, Germany) device with the HCV RNA real-time quantitative 2.0 (NLM, Italy) kit. For the genotyping, a commercial line probe assay (LIPA) based on in vitro reverse hybridization GEN-C2.0 kit (NLM, Italy) which can distinguish 1, 2, 3, 4, 6 genotypes and 1a, 1b, 2a/c, 2b, 3a, 3b, 3c, 3k, 4a, 4b, 4c/d, 4e, 4f, 4h, 5a, 6a/b, 6g, 6f/q, 6m, 7a subtypes of HCV, based on variations in the 5'-NCR and core regions was used. HCV genotype distribution of 266 IVDU (93.2%: male; median age: 25 +/- 6.82) and 454 non-drug users (51.3%: male; median age: 56.5 +/- 16.06) were examined. In order of frequency in the group with IVDU; genotype 1a, 3a, 1b, 4c/d, 2b, 4, 3 were observed and genotype 1, 2a/c and mixed genotype (1+3a) were detected in one patient. In the group without IVDU, in order of frequency; genotype 1b, 1a, 3a, 1, 2a/c, 4 were observed and genotype 2b, 4c/d, 5a, 6a/b, 6 and mixed genotype (3+4) were detected in one patient. Genotypes la and 3a were significantly higher in the IVDU group (p< 0.00001, p< 0.00001), while 1b was significantly higher in patients without IVDU (p< 0.00001). Genotypes 1a and 3a were more common in young men (p< 0.00001, p= 0.000163), while 1b was higher in middle-aged women (p< 0.00001). The incidence of genotypes 1b (p= 0.021) and 3a (p= 0.012) was higher in foreign nationals than the Turkish patients. When the HCV genotype distribution was examined by years, it was observed that the percentages of genotype 1b and la were decreasing, while the percentage of genotype 3a was increasing. As a result, in this study, HCV genotype distribution among IVDU was observed to be different from the general population without IVDU. It was found that genotypes la and 3a were more common in the IVDU group. As in the other regions of our country, genotype 1b was found most frequently in the general population. Genotype 3a increases significantly compared to years. In our study, the determination of genotypes existing in different parts of the world may be due to the foreign nationals living in our city and our region is a tourism center. It is also necessary to investigate whether there is an increase in IVDU over the years.
Follow-up of human adenovirus viral load in pediatric hematopoietic stem cell transplant recipients
(Wiley, 2021-01-16) Peker, Bilal Olcay; Kıntrup, Gülen Tüysüz; Sağlık, İmran; Sarinoğlu, Rabia Can; Güler, Elif; Mutlu, Derya; Küpesiz, Osman Alphan; Çolak, Dilek; SAĞLIK, İMRAN; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Mikrobiyoloji Anabilim Dalı.; 0000-0003-0864-4989; A-4970-2019; GCM-3391-2022
Background: The spectrum of human adenovirus (HAdV)-related disease is broad, and the virus acts on many organs and systems in hematopoietic stem cell transplantation (HSCT) recipients. We aimed to evaluate the effect of HAdV-DNA positivity with clinical and laboratory findings 4 months after HSCT.Methods and results: We retrospectively investigated HAdV-DNA in 153 HSCT recipients (<= 18 years) by quantitative real-time polymerase chain reaction (RealStar; Altona Diagnostics). The results of samples from January 2014 to December 2017 are included. HAdV-DNA was positive for at least one sample type in 50 (32.67%) patients. HAdV-DNA positivity rate was 8.92% (N: 145/1625), 40.25% (N: 64/159), and 25% (N: 2/8) for plasma, stool, and urine samples, respectively. HAdV-DNA was positive in the plasma of 38 (24.83%) patients at a median 16 (range: 1-58 days) days after HSCT. The mortality rate was 23.68% and 6.95% in plasma HAdV-positive and HAdV-negative patients (p = .014). Moreover, HAdV-DNA positivity had an impact on overall survival for allogeneic-HSCT (p = .013), with the cumulative effect including graft-versus-host disease state in multivariate analysis (p = .014).Conclusions: Plasma HAdV-DNA positivity is a potential influencer that decreases survival in the early post-transplant period. Due to the high mortality rates, close monitoring is required of HAdV infections after HSCT with sensitive methods, especially at the early stage.
Investigation of ganciclovir resistance in cytomegalovirus isolates by phenotypic and genotypic methods
(Ankara Mikrobiyoloji, 2023-07-01) Sarınoğlu, Rabia Can; Çolak, Dilek; Küpesiz, Osman Alphan; Kuşkuçu, Mert Ahmet; Yalçın, Koray; Saglık, İmran; Mutlu, Derya; Midilli, Kenan; Peker, Bilal Olcay; Özhak, Betil; Özkul, Aykut; Foldes, Kataline; SAĞLIK, İMRAN; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Mikrobiyoloji Anabilim Dalı; 0000-0003-0864-4989; A-4970-2019
Ganciclovir-resistant cytomegalovirus (CMV) strains are reported following long-term antiviral agent use, especially for immune-suppressive patients. In this study, it was aimed to investigate the mutations in the UL97 gene of CMV, which causes ganciclovir (GCV) resistance by genotypic and phenotypic methods in patients who developed CMV infection following hematopoietic cell (HCT) or solid organ transplantation (SOT). Thirty patients who had HCT or SOT in Mediterranean University Hospital and developed CMV infection during routine follow-up with a viral load of CMV over 1000 copies/mL were included in the study. CMV DNA was analyzed by an automated system (Cobas Ampliprep/COBAS TaqMan CMV Test, Roche Diagnostics, Germany) quantitatively. DNA sequence analysis of the regions including codons 420-664 in the UL97 gene region was done by the Sanger sequencing method to detect mutations causing antiviral resistance and compared with defined mutations. In order to investigate antiviral resistance by phenotypic methods, heparinized blood samples of the patients were collected, 'buffy coat (leukocyte layer)' was inoculated into MRC-5 cells by centrifugation method and CMV growth in these cells was controlled with monoclonal antibodies when growth was detected, virus titer was determined and plaque reduction test was applied as recommended. It was determined that 22 of the 30 patients were HCT recipients and eight were SOT (five kidney, three liver) recipients. When the CMV serology pattern of the patients was evaluated before transplantation, 29 (96.7%) patients were found to be seropositive and one (3.3%) patient was found to be seronegative. Totally, nine CMV UL97 mutations were detected in seven (23.3%) pediatric patients who had HCT, including six seropositive and one seronegative case. In addition, one mutation (D605E) not known to cause GCV resistance was detected in a seronegative recipient and three previously unidentified mutations were detected (1474T, F499S, V559A) in a seronegative recipient. Five of the mutations defined were UL97 mutations with a defined clinical resistance against GCV in each of the five recipients (C603W, C592G, H520Q, M460V, A594T). In the plaque reduction test using 3 mu M, 12 mu M, 48 mu M and 96 mu M concentrations of GCV in CMV strains, the IC50 value was determined to be >= 8 mu M for the five CMV strains, and the phenotypic presence of GCV resistance was shown. Clinical resistance associated with CMV UL97 mutation was detected in five (22.7%) of 22 patients who had HCT. GCV resistance was also demonstrated in these patients by phenotypic methods. No UL97 mutation was detected in the patients who had SOT.
Synergizing electrical, mechanical, and radiation shielding properties of dendritic copper filled epoxy polymer composites
(Pergamon-elsevier Science Ltd, 2023-11-18) Mutlu, Derya; Karagöz, İdris; Sepetçioğlu, Harun; Tarım, Urkiye Akar; AKAR TARIM, ÜRKİYE; Gürler, Orhan; GÜRLER, ORHAN; Bursa Uludağ Üniversitesi/Fen Edebiyat Fakültesi/Psikoloji Anabilim Dalı.; AAX-9870-2021
The study examined the properties of epoxy composites with dendritic copper (Cu) particles through various tests, including FTIR, DSC, TGA, electrical conductivity, and mechanical tests. The addition of Cu particles to the composites improved their electrical conductivity and mechanical properties, particularly tensile strength and flexural modulus. The Tg temperature of the composites could be adjusted by varying the Cu particle ratio. Notably, in the study, we prepared composites with varying Cu particle concentrations, specifically at ratios of 1%, 2%, 3%, 4%, 5%, and 6%, and observed distinct effects on the properties of the epoxy-Cu composites. Although there was no chemical bonding between the epoxy and Cu particles, the Cu additive acted as a pinning agent, restricting the movement of the polymer chains. This suggests that incorporating small amounts of Cu into epoxy composites can enhance their properties, making them suitable for applications in the electrical and electronics industry. Additionally, we evaluated the shielding properties of selected epoxy-based composites incorporating copper powder against gamma radiation with energies of 59.5 keV, 661.6 keV, and 1332.5 keV, and also investigated the composites' ability to attenuate gamma rays, recommending specific composites (ECU6, ECU1, and ECU2) for different energy levels of gamma rays. SEM examinations showed that the addition of Cu particles significantly altered the microstructure and mechanical properties of the composites, resulting in an irregular and rough fracture surface and decreased structural integrity.