Immunogenicity and safety of the CoronaVac and BNT162b2 Covid-19 vaccine in patients with inflammatory rheumatic diseases and healthy adults: comparison of different vaccines.

OBJECTIVES: To determine the seroconversion (SC) rate after CoronaVac and BNT162b2 vaccines in adults with inflammatory rheumatic disease (IRD). METHODS: Patients who were followed up with IRD and who received two doses of either CoronaVac or BNT162b2 vaccines were included in this prospective observational single-center study. Subjects with two doses of CoronaVac or BNT162b2 without known IRD were included in the healthy controls. The blood samples were taken at a minimum of two and a maximum of 12 weeks after the second dose of vaccine. RESULTS: A total of 81 patients with IRD (61 CoronaVac, 20 BNT162b2) and 100 healthy controls (70 CoronaVac, 30 BNT162b2) were included. The SC rate was slightly lower among patients with IRD versus controls (84 vs 97%, p = 0.002). The SC rate was 100% in all participants who received BNT162b2 both in the patient and control group. The IgG antibody level after CoronaVac in the patient group was significantly lower than both the BNT162b2 (p = 0.031) and the healthy group (p < 0.001). Among patients with IRD, those on rituximab (RTX) (12/81,14.8%) had significantly less SC rate (5/12, 41.7%). The median neutralizing antibody titers were significantly higher in patients with BNT162b2 compared with CoronaVac (1.97 vs. 16.34, p < 0.001). CONCLUSIONS: This study showed that all patients with BNT162b2 vaccine developed immunogenicity in patients with IRD, while there was a decreased antibody response with CoronaVac vaccine compared to that of BNT162b2. In particular, RTX significantly reduces the SC rate.

Genomic characterization of SARS-CoV-2 isolates from patients in Turkey reveals the presence of novel mutations in spike and nsp12 proteins.

Novel mutations have been emerging in the genome of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2); consequently, the evolving of more virulent and treatment resistance strains have the potential to increase transmissibility and mortality rates. The characterization of full-length SARS-CoV-2 genomes is critical for understanding the origin and transmission pathways of the virus, as well as identifying mutations that affect the transmissibility and pathogenicity of the virus. We present an analysis of the mutation pattern and clade distribution of full-length SARS-CoV-2 genome sequences obtained from specimens tested at Gazi University Medical Virology Laboratory. Viral RNA was extracted from nasopharyngeal specimens. Next-generation sequencing libraries were prepared and sequenced on Illumina iSeq 100 platform. Raw sequencing data were processed to obtain full-length genome sequences and variant calling was performed to analyze amino acid changes. Clade distribution was determined to understand the phylogenetic background in relation to global data. A total of 293 distinct mutations were identified, of which 152 missense, 124 synonymous, 12 noncoding, and 5 deletions. The most frequent mutations were P323L (nsp12), D614G (ORF2/S), and 2421C>T (5'-untranslated region) found simultaneously in all sequences. Novel mutations were found in nsp12 (V111A, H133R, Y453C, M626K) and ORF2/S (R995G, V1068L). Nine different Pangolin lineages were detected. The most frequently assigned lineage was B.1.1 (17 sequences), followed by B.1 (7 sequences) and B.1.1.36 (3 sequences). Sequence information is essential for revealing genomic diversity. Mutations might have significant functional implications and analysis of these mutations provides valuable information for therapeutic and vaccine development studies. Our findings point to the introduction of the virus into Turkey through various sources and the subsequent spread of several key variants.

[Investigation of the Relationship Between IL28B Polymorphisms and Plasma IL28B Levels in Patients with Chronic Hepatitis B or C]. / Kronik Hepatit B veya C Hastalarinda IL28B Polimorfizmleri ve Plazma IL28B Düzeyleri Arasindaki Iliskinin Arastirilmasi.

Some single nucleotide polymorphisms (SNPs) of the gene encoding interleukin 28B (IL28B) may increase susceptibility to infection and chronicity in humans with hepatitis B and C viruses. In our study, we aimed to investigate the prevalence of rs12979860, rs8099917 and rs12980275 SNPs in IL28B in patients with hepatitis B (HBV) or hepatitis C Virus (HCV) infection and to determine the relationship of these polymorphisms with plasma IL28B levels. For this purpose, 64 HBV-infected and 66 HCV-infected patients and 70 healthy individuals were included in the study. The SNPs were investigated by real time PCR (Polimerase Chain Reaction, Rt-PCR) using TaqMan SNP Genotyping Assay. The plasma levels of IL28B were detected by 'Enzyme Linked Immunosorbent Assay (ELISA)'. The frequencies of the rs12980275AG genotype and G allele (p= 0.003 and p= 0.04, respectively), and the rs12979860CT genotype and T allele (p= 0.01 and p= 0.04, respectively) were lower in HBV-infected patients. In HCV-infected patients, the rs8099917TG genotype and G allele frequencies (p= 0.04) were higher and the TGG haplotype showed a statistically significant difference (p= 0.04). The mean of IL28B plasma levels were higher in the control group than the HBV or HCV-infected patient groups (p= 0.001 and p= 0.01, respectively). However, HBV-infected patients with the rs12980275AG genotype showed a significant difference in plasma IL28B levels compared to the other genotypes (p= 0.0001) and these patients had lower viral loads (<105 IU/ml). According to the results of the study, it can be stated that rs12979860CT and rs12980275AG genotypes may play a role in preventing the chronicity of HBV infection, while rs8099917TG genotype may contribute to the transformation of HCV infection into chronic infection. In this study, it was observed that the presence of the G allele for the rs8099917 polymorphism could be evaluated as a risk allele for chronic HCV infection and that the TGG haplotype could have a strong predictive effect on increasing susceptibility to chronic HCV infection. It is recommended to evaluate the genotypic distribution of IL28B before treatment because of its prognostic significance in HBV or HCV infected patients. In HBV infection, the rs12980275AG genotype which is thought to have a protective effect by limiting viral replication with increased plasma IL28B levels, can be used as a good prognostic factor. These polymorphisms could be used as biomarkers to predict the clinical consequences of the patients infected with HBV or HCV, to take precautions to prevent the chronicity of the infection and its complications, and to develop new molecular targeted therapies with further research.

[Investigation of HTLV-I/II Seroprevalance of Patients with HIV Positivity being Monitored by Real-Time RT-PCR]. / HIV Pozitifligi Gerçek Zamanli RT-PCR ile Takip Edilen Hastalarin HTLV-I/II Seroprevalansinin Arastirilmasi.

Human T-lymphotropic virus-I/II (HTLV-I/II) and human immun viruses (HIVs), that have similar genomic characteristics also share the same transmission routes and infect T lymphocytes. Regarding this epidemiological similarity, HIV and HTLV infections can be seen together. HIV and HTLV-I/II coinfection occurs with variable frequencies in different populations and geographic regions. There are not any population-based studies carried out defining the number of individuals coinfected with HIV and HTLV-I/II in Turkey. The aim of this study was to determine the seropositivity rates of HTLV-I/II in patients whose HIV viral load was monitored in Gazi University Faculty of Medicine Medical Virology Laboratory Forty-seven HIV positive cases followed-up in Medical Virology Laboratory for HIV viral load monitoring between May 2017-January 2019 were included in the study. HIV seropositivity of the samples was confirmed by the chemiluminescence microparticle immunoassay method. HIV viral load values of the samples were evaluated by real-time reverse transcriptase polymerase chain reaction. The samples were screened for antibodies against HTLV-I/II using chemiluminescent microparticle immunoassay. The study population range was between 19 to 60 years of age. Among the study population, 39 (83%) patients were male and 8 (17%) patients were female. Of 47 samples, 18 samples (38.3%) had viral load of <1000 copies/ml, 10 samples (21.3%) had viral load of 1000-10000 copies/ml, 19 samples (40.4%) had viral load of ≥10000 copies/ml. HTLV serology was negative in all samples included in the study. CD4+ results were available for 42 patients and the CD4+ results of five patients could not be studied. Co-infection with different retroviruses is a well-known fact which should be thoroughly examined. HTLV-I co-infection leads to faster progression of the disease in HIV-1 positive patients. Although it is known that the co-infection has a significant effect on the progression of the disease, there are very few centers in the world and in our country that routinely perform HTLV testing in HIV-positive patients. We think that in order to evaluate the clinical and microbiological importance of the coinfection of retroviruses with each other and to determine the frequency of these infections together, there is a need for studies involving a larger number of patients, including detailed clinical backgrounds of individuals, and that the importance of this issue should be realized at the same time.

Retrospective analysis of the association of the expression and single nucleotide polymorphisms (SNPs) of the TLR4, PTX3 and Dectin-1 (CLEC/A) genes with development of invasive aspergillosis among haematopoietic stem cell transplant recipients with oncohaematological disorders.

OBJECTIVES: Several studies described single nucleotide polymorphisms (SNPs) on pattern recognition receptor (PRR) such as toll-like receptors (TLRs), dendritic cell-associated C-type lectin-1 (Dectin-1/CLEC7A) genes of patients with invasive fungal infections (IFIs) caused by Candida and Aspergillus. We screened TLR4, Dectin-1 and PTX3 polymorphisms in a Turkish population with invasive aspergillosis (IA) underlying haematological malignancies. METHODS: In this case-control study, a cohort of 59 patients with haematological malignancies were included. There were 26 IA patients assigned by the EORTC-MSG criteria and 33 patients with no evidence of fungal disease. DNA and RNA were isolated from frozen bone marrow and serum samples. RNA levels and polymorphisms of TLR4 (rs4986790, rs4986791), Dectin-1 (rs16910526, rs7309123) and PTX3 (rs2305619, rs3816527) were determined. The odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated by unconditional logistic regression analysis. RESULTS AND CONCLUSIONS: TLR4, PTX3 and Dectin-1 genes were downregulated in aspergillosis cohort under similar haematological conditions. TLR4 expression was 0.0626 ± 0.032 in controls when compared to IA patients as 0.0077 ± 0.014, and the difference was significant (P = .026). There was a difference in also the PTX3 gene among IA (0.0043 ± 0.004) and control (0.5265 ± 0.0043) groups (P = .035). The Dectin-1 (CLEC/A) expression was downregulated in IA group (0.1887 ± 0.072 & 0.0655 ± 0.010) but not statistically significant (P > .05). Conditional logistic regression analyses indicated that the GT genotype of rs16910526 polymorphism in Dectin-1 gene was associated with lower risk of IA (odds ratio = 3.635, 95% confidence interval = 0.690-3.138, P = .04).

The Prevalence of Mixed Genotype Infections in Turkish Patients with Hepatitis C: a Multicentered Assessment.

BACKGROUND: HCV virus infections are one of the major health problems in the world that can cause cirrhosis and liver cancer at a higher rate than other hepatitis data. The aim of this study was to determine the prevalence of mixed infections with different HCV genotypes in Turkey and also to evaluate the current HCV genotype and sub-type distributions by a multicentered assessment. METHODS: The HCV genotype data of 17,578 hepatitis C patients collected from 23 centers from different geographic regions covering all Turkey were collected. The data included information about the HCV genotypes in the last 10 years (between 2007 and 2016), demographic properties of the patients and the methods/systems used to determine the genotypes. RESULTS: Two hundred twenty-eight of the patients (1.3%) had mixed genotype. The most common mixed genotype combination was 1b + 4 (0.83%) followed by 1a + 1b (0.26%). Genotype distribution varies according to geographical regions. However, genotype 1 (82.92%) was the most common genotype in all regions and all years. This was followed by genotype 3 (7.07%) and genotype 4 (5.43%). A variety of methods were used by the centers including sequencing, pyrosequencing, real-time PCR, in-house RFLP, reverse hybridization (LIPA), and hybridization. CONCLUSIONS: Infection with mixed HCV genotypes in Turkey is uncommon. Genotype distribution varies according to geographic regions; the most common genotype 1 is encountered all over the country, while genotypes 3 and 4 are only in some of the centers. Since there is limited information about mixed HCV infection, further investigations are needed to determine the clinical importance of mixed HCV infection.

Circulating Th17 cytokine levels are altered in Hashimoto's thyroiditis.

The disrupted autoimmune response in Hashimoto's thyroiditis (HT) has long been considered to be dominantly T helper type 1 (Th1) mediated. Recent advances in the field of immunology have introduced a new class of effector T cells, named 'Th17', which plays important roles in autoimmune disorders once thought to be merely Th1 mediated. We aimed to examine the levels of major Th17 cytokines in patients with HT in this study. We studied serum interleukin 17 (IL-17) and interleukin 23 (IL-23) levels in 46 newly diagnosed, untreated patients with HT (40 women and 6 men, aged 40.0 ± 11.8 years) divided into euthyroid (n=22) and hypothyroid (n=24) groups and compared them with age and sex matched 26 healthy euthyroid controls without HT (21 women and 5 men; aged 36.0 ± 12.9 years). Serum IL-17 and IL-23 levels were significantly different among euthyroid and hypothyroid HT patients and controls, with highest levels obtained in the euthyroid HT group (p=0.041 for IL-17 and p<0.001 for IL-23). TSH was negatively and FT4 was positively correlated with IL-17 (p=0.016 for TSH and p=0.004 for FT4) and IL-23 (p<0.001 for TSH and p=0.003 for FT4) levels. There were no correlations between thyroid volumes calculated on thyroid ultrasonography and IL-17 (p=0.630) or IL-23 (p=0.321) levels. In conclusion, the levels of IL-17, one of the major effector cytokines of the Th17 system, and IL-23, which had been implicated in the generation, survival and expansion of Th17 cells, are altered in HT. How thyroid hormone status and the course of disease affect Th17 system in chronic autoimmune thyroiditis needs to be determined with further studies.

The relationship between the clinical course of SARS-CoV-2 infections and ACE2 and TMPRSS2 expression and polymorphisms.

BACKGROUND: The viral spike (S) protein and host ACE2 and TMPRSS2 genetic variations may act as a barrier to viral infections or determine susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. OBJECTIVES: We investigated the relationship between the expression patterns and polymorphisms of the ACE2 and TMPRSS2 receptor genes associated with coronavirus disease 2019 (COVID-19) and the clinical course of SARS-CoV-2 infections. MATERIAL AND METHODS: We examined 147 COVID-19 patients (41 asymptomatic, 53 symptomatic and 53 cases treated in the intensive care unit (ICU)) and 33 healthy controls. The ACE2 and TMPRSS2 expression was determined using the One-Run RT-qPCR kit. Genotypic distributions of single nucleotide polymorphisms (SNPs) of ACE2 and TMPRSS2 were obtained using reverse transcription quantitative polymerase chain reaction (RT-qPCR). RESULTS: The expressions of ACE2 and TMPRSS2 were different between SARS-CoV-2-positive and -negative groups. The ACE2 rs714205GG genotype and G-allele showed significant differences in the asymptomatic SARS-CoV-2-positive group. A significant correlation was found between the expression of TMPRSS2 rs8134378GA, rs2070788GA, rs7364083GA, and rs9974589AC genotypes and SARS-CoV-2 positivity. The rs1978124 C-allele and rs8134378 A-allele expressions were significant in the symptomatic SARS-CoV-2-positive group. The TMPRSS2 rs2070788GA expression was different in all patient groups compared to the control group. There was a difference between SARS-CoV-2-positive and -negative groups regarding the CTTA haplotype formed by ACE2 variants. The AGCAG and AGAAG haplotypes formed by the TMPRSS2 variants were more common in the asymptomatic patient group than in other patient groups. CONCLUSIONS: Identifying the relationship between host genetic variants and COVID-19 susceptibility will contribute to further studies, enabling new vaccines and potential therapeutic approaches to be discovered.

MicroRNA expression profile of alveolar epithelial cells infected with Aspergillus fumigatus.

There are limited number of studies investigating the role of microRNAs (miRNAs) in Aspergillus infections. In this study, we designed an in vitro aspergillosis model to identify differentially expressed Aspergillus-related miRNAs. For this purpose, carcinoma cell lines "A549" and "Calu-3" were infected with Aspergillus fumigatus. Total miRNA was isolated at 0, 1, 6, and 24 h post-infection. Quantitative real-time PCR assay was conducted to screen 31 human miRNAs that were possibly related to aspergillosis. Up- and downregulated miRNAs were detected in the infected cells. Highest level of miRNA expression was detected at 6 h post-infection. miR-21, hsa-miR-186-5p, hsa-miR-490-5p, miR-26a-5p, miR-26b-5p, hsa-miR-424-5p, hsa-miR-548d-3p, hsa-miR-196a-5p, miR-150-5p, miR-17-5p, and hsa-miR-99b-5p were found to be significantly upregulated (p < 0.001) at 6 h after A. fumigatus infection compared with the controls. Among the screened miRNAs, hsa-miR-145-5p (p < 0.001); hsa-miR-583 and hsa-miR-3978 (p < 0.01); and miR-21-5p, hsa-miR-4488, and hsa-miR-4454 (p < 0.05) were found to be downregulated compared with the controls. In conclusion, screening the identified miRNAs may reveal the personal predisposition to aspergillosis, which might be valuable from the perspective of personalized medicine.

[Investigation of BK and JC virus DNA positivities by real-time polymerase chain reaction in the clinical samples of patients with high risk]. / Yüksek Risk Altindaki Hastalarin Klinik Örneklerinde BK ve JC Virus DNA Pozitifliginin Gerçek Zamanli Polimeraz Zincir Reaksiyonu ile Arastirilmasi

Human polyomaviruses, namely BK (BKV) and JC (JCV) viruses are small DNA viruses that cause latent infections worldwide. Primary infections are usually acquired in the early periods of life and are generally asymptomatic. However BKV/JCV infections may cause severe clinical conditions in immunosuppressive patients such as bone marrow and solid organ transplantation or cancer patients. The aim of this retrospective study was to investigate the presence of BKV and JCV nucleic acids by real-time polymerase chain reaction (RT-PCR) in the clinical samples of patients with high risk. A total of 268 (62 blood, 206 urine) samples obtained from 115 immunocompromised patients hospitalized in Gazi University Hospital between July 2007 to January 2009, were included to the study. Viral nucleic acids were extracted from the samples with High Pure PCR Template Preparation Kit (Roche, Germany). By using amplification mix (TIB Molbiol GmbH, Germany) that included primers targeting 174 (JCV) and 219 (BKV) base pair fragments of the small t antigen, and hybridization probes (Roche, Germany), nucleic acids were amplified with LightCycler (Roche Applied Science, Germany) system. As a result, total polyomavirus DNA positivity rate was found as 33.2% (89/268). When BKV and JCV DNA positivities were evaluated according to the samples, 25.2% (53/206) of urine samples yielded positive results for BKV, 14.5% (30/206) for JCV and 2.4% (5/206) for both BKV and JCV. Only one of the blood samples (1/62; 1.6%) were found positive by means of BKV DNA, while none of the blood samples were positive for JCV DNA. The distribution of BKV and JCV DNA positivity rates according to the inpatient clinics were as follows, respectively; 24.3% and 9.5% for pediatric nephrology, 9.6% and 8.2% for renal transplantation unit, 13.5% and 18.9% for adult nephrology, 30.8% and 15.4% for bone marrow transplantation unit, 22.9% and 8.6% for pediatric clinics. In samples from pediatric hematology patients, BKV positivity was 36.4% (4/11), while there were no JCV positivity. However, in hematology patients, while JCV was positive in one of the three samples, no BKV positivity was detected.BKV was seen in three of six samples obtained from patients in the intensive care unit. JCV was positive in both of the two samples obtained from patients in pediatric endocrinology. The only patient that had BKV DNA in blood sample was a renal transplant patient. BKV + JCV DNAs were positive together in only five (1.9%) of the urine samples. In 24% (22/89) of the samples, BKV DNA was found ≥ 107 copies/ml, in 2.2% (2/89) JCV DNA was ≥ 107 copies/ml, whereas in 2.2% (2/89) of samples both BKV and JCV DNA was ≥ 107 copies/ml. All of those samples with high DNA levels were urine. The data of this study led to the establishment of a collaborative algorithm between the laboratory and clinics in our hospital for the diagnosis and follow-up of the patients in terms of BKV/JCV infections. In conclusion, since BKV/JCV reactivations and infections are crutial in immunosuppressive patients, especially medical centers specialized in bone marrow and renal transplantation, diagnostic and monitoring procedures related to those infections should be programmed.

[Investigation of interleukin-10, tumor necrosis factor-alpha and interferon-gamma expression in experimental model of pulmonary aspergillosis]. / Deneysel Pulmoner Aspergilloz Modelinde Interlökin-10, Tümör Nekroz Faktörü-alfa ve Interferon-gama Ifadelenmesinin Arastirilmasi

Pulmonary aspergillosis which is an important opportunistic infection in neutropenic patients, is usually caused by Aspergillus fumigatus. Since the pathogenesis of disease is not well understood, the main proposed mechanism is thought to be cell-mediated immunity and cytokine response. The aim of this study was to investigate the local production of cytokines in the lung tissues of rats with experimentally developed aspergillosis, by reverse transcriptase-polymerase chain reaction (RT-PCR). A total of 33 Wistar albino type rats were included in the study with the consent of Experimental Animal Ethics Committee. Twenty-five of the rats were infected with A.fumigatus by intratracheal way, while 8 animals were used as controls. The presence of A.fumigatus in the lung tissues of infected rats was confirmed with the use of quantitative culture and histologic staining methods. RNA isolation from the lung tissue samples of both groups were performed by a commercial kit (Qiagen, Germany). After obtaining complementary DNAs from the genomic RNAs, in-house qualitative and quantitative (real-time) PCR methods were used to amplify the target regions for interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-?) and interferon-gamma (IFN-?) by using specific primers (Tib Molbiol, Germany). Mean mRNA levels achieved by real-time PCR for IL-10, TNF-? and IFN-? in aspergillosis group were 6.5 x 106 copies/ml, 7.9 x 105 copies/ml and 2.2 x 103 copies/ml, respectively, while those values in control group were 4.3 x 102 copies/ml, 5.6 x 103 copies/ml and 1.3 x 102 copies/ml, respectively. Our data indicated that rat model of aspergillosis was associated with significantly increased expression of mRNA encoding IL-10 and TNF-? than controls (p< 0.05), however there was no statistically significant difference between the groups with respect to IFN-? expression (p= 0.53). In conclusion, the production of proinflammatory cytokines which mediate the influx of phagocytic cells might account for the localization of Aspergillus infection to the upper respiratory tract. The up-regulation of the expression of the immunomodulatory cytokine TNF-? and IL-10 in lung tissue from infected rats might be important to limit the extent of local tissue destruction, but might also account for the fact that infected rats are generally unable to clear the infection spontaneously.

Task-oriented circuit training combined with aerobic training improves motor performance and balance in people with Parkinson's Disease.

Goal-based training such as task practice combined with aerobic training (AT) has been suggested to improve motor performance and neuroplasticity for people with Parkinson's Disease (PwPD); however, its effect on clinical outcomes is unclear. Therefore, the main aim was to investigate the effects of task-oriented circuit training combined with AT (TOCT-AT) on balance and gait in PwPD. The secondary aim was to investigate the effects of TOCT-AT on functional mobility, balance confidence, disease severity, and quality of life. Twenty-six PwPD were randomly assigned to either to the experimental group (n = 14) or the control group (n = 12). The control group received AT, while the experimental group received TOCT-AT three times a week for 8 weeks. The main outcomes were the Berg Balance Scale (BBS), Postural Stability Test (PST), Limits of Stability Test (LOS), Pull Test (PT), Six Minute Walk Test (6MWT), Timed Up and Go Test (TUG), Activities-specific Balance Confidence Scale (ABC), Unified Parkinson's Disease Rating Scale (UPDRS), and eight-item Parkinson's Disease Questionnaire (PDQ-8) were secondary outcomes. After intervention, between-group comparisons showed that the experimental group significantly improved more than the control group in all outcomes (p < 0.05). Additionally, both groups significantly improved in BBS, 6MWT, TUG, ABC, UPDRS-II, UPDRS-III, UPDRS total, and PDQ-8 (p < 0.05), while only the experimental group significantly improved in PST, LOS, and PT (p < 0.001). This study suggest that TOCT-AT could improve balance and gait performance, which could also be positively translated into functional mobility, balance confidence, disease severity, and quality of life in PwPD.

Effects of task-oriented training combined with aerobic training on serum BDNF, GDNF, IGF-1, VEGF, TNF-α, and IL-1ß levels in people with Parkinson's disease: A randomized controlled study.

INTRODUCTION: Parkinson's disease (PD) is a chronic neurodegenerative disease characterized by the death of dopaminergic neurons in the substantia nigra pars compacta. Exercise training, which is incorporated both goal-based training such as task-oriented training (TOT) and aerobic training (AT), has been suggested to induce neuroprotection. However, molecular mechanisms which may underlie exercise-induced neuroprotection are still largely unknown. Thus, the aim of the present study was to investigate the effects of TOT combined with AT (TOT-AT) on serum brain-derived neurotrophic factor (BDNF), glial cell-derived growth factor (GDNF), insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß) levels in people with PD (PwPD). METHODS: Forty PwPD were randomized into 8-week of either exercise group (n = 20) or control group (n = 20). The exercise group received TOT-AT while the control group received only AT. Serum BDNF, GDNF, IGF-1, VEGF, TNF-α, and IL-1ß levels determined with ELISA were assessed at baseline and after training. RESULTS: A total of 29 PwPD completed this study. Our results showed no significant change in the serum BDNF, GDNF, IGF-1, VEGF, TNF-α, and IL-1ß levels in both groups. After the intervention period, no significant difference was observed between the groups regarding the serum BDNF, GDNF, IGF-1, VEGF, TNF-α, and IL-1ß levels. CONCLUSION: TOT-AT could not be an effective exercise method for changing serum concentrations of BDNF, GDNF, IGF-1, VEGF, TNF-α, and IL-1ß in the rehabilitation of PD.

Determination and Role of Epstein-Barr Virus in Patients With Lymphoproliferative Disorders.

INTRODUCTION: Epstein-Barr virus (EBV) is associated with different types of human malignancies, including Burkitt lymphoma, nasopharyngeal carcinoma, and lymphomas. We retrospectively investigated the presence of EBV-DNA by real-time PCR in clinical samples of patients diagnosed as having hematologic malignancies while investigating the cause of lymphoproliferative disorders, and investigated its relationship to clinical manifestations. PATIENTS AND METHODS: Fifty clinical samples sent to Gazi University's hematology clinics between November 2013 and March 2018 were included. EBV-DNA was investigated by real-time PCR method, and EBV-IgM and EBV-IgG antibodies were investigated by ELISA. RESULTS: Fifty serum samples were investigated, and 10% (5/50) EBV-DNA positivity was determined in patients. Of the 5 patients with EBV-DNA positivity, 2 had acute lymphoblastic leukemia, 1 lymphoma, 1 T-cell lymphoma, and 1 B-cell lymphoma. Concomitant EBV-DNA and viral capsid antigen (VCA)-IgM positivity was not detected. The VCA-lgM test results of the all EBV-DNA-positive patients were negative and VCA-IgG positive (except for 1 patient). Regarding virus load, of the 5 samples, 2, 1, 1, and 1 of the samples had a virus load of 102, 103, 104, and 105 copies/mL, respectively. CONCLUSION: EBV infection is threatening in patients with hematologic malignancies and are diagnosed by serologic and molecular methods. As a result of the study, we suggest that the detection of EBV-DNA by real-time PCR in patients being admitted with lymphoproliferative diseases and diagnosed as acute lymphoblastic leukemia and lymphomas may be useful in follow-up and treatment.

High incidence of Candida parapsilosis candidaemia in non-neutropenic critically ill patients: epidemiology and antifungal susceptibility.

The epidemiological and antifungal susceptibility data for 35 episodes of candidemia in intensive care units (ICU) in 2007 were evaluated by prospective active surveillance. The incidence of fungaemia was 39.1 cases per 1000 ICU admissions and 2.85 cases per 1000 patient-days. The crude mortality was 65.7%; 70.8% of the fatalities occurred within 7 days of admission to the ICU. Only 2 species were isolated, Candida parapsilosis (77.1%) and Candida albicans (22.9%). There was no association between mortality and patient characteristics, prior antifungal usage, Candida subspecies or antifungal resistance (p > 0.05). Of the isolates, 5.7% were resistant to fluconazole and caspofungin, and 3.4% to voriconazole and amphotericin B. In molecular analysis of the isolates, 2 clusters of C. parapsilosis in the neurology and anaesthesiology ICUs were detected by randomly amplified polymorphic DNA (RAPD), suggesting a nosocomial transmission. In conclusion, a high incidence and high mortality rate of C. parapsilosis candidaemia were found in the ICUs. An excessive use of invasive procedures, total parenteral nutrition and broad-spectrum antibiotics in the ICUs, combined with a lack of proper infection control measures, may possibly explain the high incidence of C. parapsilosis candidaemia in our hospital.

Nosocomial transmission of Candida pelliculosa fungemia in a pediatric intensive care unit and review of the literature.

Horizontal transmission of Candida species in the hospital environment and the fungemia rates have increased in the past decade. We describe a nosocomial cluster of fungemia caused by Candida pelliculosa (teleomorph Pichia anomala) in four infants hospitalized in the pediatric intensive care unit. Candida isolates had strictly related fingerprints, as generated by randomly amplified polymorphic DNA analysis using five different primer sets. The four babies were all treated successfully and recovered. All of the isolates were susceptible to the antifungals tested including amphotericin B, flucytosine, fluconazole, miconazole, micafungin, itraconazole, and voriconazole. Infection control procedures were adapted in the unit and no relapse was detected. In addition, 30 publications presenting 450 pediatric and 28 adult cases are reviewed.

[Investigation of West Nile virus seroprevalence in healthy blood donors]. / Saglikli kan vericilerinde Bati Nil virusu seroprevalansinin arastirilmasi

West Nile virus (WNV) which is a flavivirus transmitted by mosquitos, may lead to asymptomatic infection, mild febrile illness or encephalitis. Many sporadic cases and major outbreaks of West Nile fever have been reported worldwide, however, WNV infections have not been well documented in Turkey. The aim of the present study was to determine the prevalence of past WNV infections in a population of blood donors. Blood samples were collected from donors with their informed consent. Samples were processed and tested for WNV IgG by enzyme-linked immunosorbent assay (ELISA) (Euroimmun, Germany) according to the manufacturer's guidelines. Demographic data of the donors were recorded. A total of 2821 serum samples were tested. Among them, 28 samples were found to be WNV IgG positive (0.9%) and 41 of them were indeterminate (1.4%). Thus a total of 69 objects were considered to have encountered WNV (2.4%). All of the IgG positive samples (n= 69) and randomly-selected negative samples (n= 60) were re-analysed for the presence of viral RNA by a commercial real-time reverse transcriptase PCR (LightMix® Kit West Nile Virus, TIBMolbiol, Germany). West Nile virus RNA was not found in any of the samples. In conclusion, our data have supported the results of other studies indicating the presence of WNV infection in Turkey. Further larger scale studies are necessary to evaluate the possible risks of WNV infections in our country in terms of blood banking.

[In vitro synergistic effect of moxifloxacin and amphotericin B combination against Candida strains]. / Moksifloksasin ve amfoterisin b kombinasyonunun Candida türleri uzerine in vitro sinerjistik etkisi.

Contradictory results such as synergy or indifferent effect, have been reported about the interactions between quinolones and antifungal drugs in different studies. The aim of this study was to investigate the in vitro susceptibilities of Candida spp. to moxifloxacin (MOX) alone and MOX + amphotericin B (AmB) combination. A total of 20 strains were included to the study, of which 19 were clinical isolates (10 Candida albicans, 4 Candida glabrata, 2 Candida parapsilosis, 1 Candida tropicalis, 1 Candida pelliculosa ve 1 Candida sake) and 1 was a standard strain (C. albicans ATCC 90028). In vitro susceptibilities of the strains to MOX with AmB were investigated by broth microdilution method according to the recommendations of the Clinical and Laboratory Standards Institute (CLSI), and in vitro interaction of these drugs were determined by a chequerboard titration method. Minimal inhibitory concentration (MIC) values of Candida spp. for MOX were found > or = 400 microg/ml indicating that MOX, by itself has no antifungal activity. AmB MIC values were found 1 microg/ml in 11 of the clinical isolates, and < or = 0.5 microg/ml in the other 8 clinical isolates and 1 standard strain. The inhibitor activity of AmB was slightly enhanced when combined with MOX, there being a decrease of 1-4 fold dilutions in the AmB MICs against all isolates tested. Synergistic effect between MOX and AmB, defined as a fractional inhibitory concentration (FIC) index as < or = 0.5, was observed in 90% (18/20; all were clinical isolates) of the strains, whereas indifferent effect (FIC = 1) was detected in 10% (2/20; 1 was clinical and 1 was standard strain) of the strains. Antagonistic effect was not observed for this combination even at 48th hours. It was concluded that these preliminary results should be confirmed by large-scaled in vitro and in vivo studies to evaluate MOX + AmB combination as a therapeutic option for the treatment of Candida infections.

Effects of Saccharomyces boulardii on cytokine secretion from intraepithelial lymphocytes infected by Escherichia coli and Candida albicans.

Saccharomyces boulardii (S. boulardii) is a probiotic and used in the prevention or treatment of diarrhoea. Saccharomyces boulardii has many mechanisms to protect the host against diarrhoeal pathogens. It might modulate the immune system. In this study, the influence of S. boulardii on the secretion of cytokines from intraepithelial lymphocytes (IELs) infected with Escherichia coli (E. coli) and Candida albicans (C. albicans) was investigated in vitro. Cytokine levels were determined by enzyme-linked immunosorbent assay. The secretion of proinflammatory cytokines such as interleukin (IL)-1beta was decreased in the infected IELs incubated with S. boulardii, but different from it, anti-inflammatory cytokine levels such as IL-4 and IL-10, however, were found to be higher. These findings demonstrated that S. boulardii may have protective effects against diarrhoeal pathogens by reducing the proinflammatory response.

Determination of the expression of lymphocyte surface markers and cytokine levels in a mouse model of Plasmodium berghei.

This study aimed to determine the changes in lymphocyte surface markers and cytokine profiles during a malarial infection in a mouse model of malaria. Mononuclear cells obtained from the spleens of the mice infected with Plasmodium berghei (P. berghei) were stained with anti-mouse CD3, anti-mouse CD4, anti-mouse CD8, anti-mouse CD19, anti-mouse CD152, anti-mouse pan natural killer (NK), anti-mouse CD80 monoclonal antibodies and expression of surface markers was evaluated by flow cytometry. In the serum samples of the mice, the levels of tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), transforming growth factor-1beta (TGF-1beta), and interleukin (IL)-4, IL-10, and IL-12 cytokines were determined by ELISA method. The expressions of all the surface markers of lymphocyte evaluated were statistically significantly lower in the infected mice than in the healthy control mice (p < 0.05). However, except for the level of TGF-1beta, the levels of all the other cytokines evaluated were statistically significantly higher in the infected group than in the control group (p < 0.001). No significant differences were determined between the TGF-1beta levels of the study and control groups (p > 0.05). In this study, T, B, and NK lymphocyte responses were inhibited and cytokine profiles changed in the course of malarial infection. Thus, interventions to increase the Th1 lymphocyte response may be beneficial in the prevention of malarial infection.