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Toscana virus ( TOSV), West Nile virus ( WNV) and tickborne encephalitis virus ( TBEV) are among major viral pathogens causing febrile disease and meningitis/encephalitis. The impact of these viruses was investigated at a referral centre in Ankara Province, Central Anatolia in 2012, where previous reports suggested virus circulation but with scarce information on clinical cases and vector activity. Serum and/or cerebrospinal fluid samples from 94 individuals were evaluated, in addition to field-collected arthropod specimens that included 767 sandflies and 239 mosquitoes. Viral nucleic acids in clinical samples and arthropods were sought via specific and generic nested/real-time PCRs, and antibody responses in clinical samples were investigated via commercial indirect immunofluorescence tests ( IIFTs) and virus neutralization. A WNV antigen assay was also employed for mosquitoes. WNV neuroinvasive disease has been identified in a 63-year-old male via RNA detection, and the WNV strain was characterized as lineage 1. TOSV infections were diagnosed in six individuals (6.3%) via RNA or IgM detection. Partial sequences in a 23-year-old female, presented with fever and transient pancytopenia, were characterized as TOSV genotype A. Febrile disease with arthralgia and/or peripheral cranial nerve involvement was noted in cases with TOSV infections. Previous WNV and TOSV exposures have been observed in 5.3% and 2.1% of the subjects, respectively. No confirmed TBEV exposure could be identified. Morphological identification of the field-collected mosquitoes revealed Culex pipiens sensu lato (74.4%), Anopheles maculipennis (20.9%), An. claviger (2.1%) and others. Sandfly species were determined as Phlebotomus papatasi (36.2%), P. halepensis (27.3%), P. major s. l. (19.3%), P. sergenti (8.9%), P. perfiliewi (4.4%), P. simici (2.6%) and others. Viral infections in arthropods could not be demonstrated. TOSV genotype A and WNV lineage 1 activity have been demonstrated as well as serologically proven exposure in patients. Presence of sandfly and mosquito species capable of virus transmission has also been revealed. [ABSTRACT FROM AUTHOR]

Summary Toscana virus (TOSV), a sandfly fever virus serotype of medical and public health importance, is a major pathogen involved in aseptic meningtis occurring in Mediterranean countries and poses a threat to the residents as well as travellers. Limited data on TOSV activity are present from Turkey despite being located in the endemic zone. We aimed to identify TOSV exposure in 1115 healthy blood donors at the Hacettepe University Hospital Blood Bank in Ankara, Turkey, using commercial indirect fluorescence assays (IFAs) and virus neutralization test (VNT) for antibody detection and specificity confirmation. A total of 199 samples (17.8%) were positive for anti-TOSV that include IgG reactivity in 10.4%, IgM reactivity in 8.2% and IgM + IgG reactivity in 0.7% of the sera. Anti-TOSV specificity could be confirmed via VNT in 56% of the IgG- and 43.6% of the IgM-positive sera, making up a total of 58 samples (5.2%). Risk factors associated with TOSV IgG reactivity were male gender, residing in rural areas, frequent sighting of mosquitoes/sandflies and working outdoors. TOSV-specific antibody prevalence increased significantly with age. Evidence of exposure to other sandfly fever viruses was noted. These data reveal that mild or asymptomatic infections with TOSV are frequent in central and northern Anatolia. TOSV exposure has also been identified in residents of 9 provinces in southern/southeastern Anatolia for the first time. [ABSTRACT FROM AUTHOR]

Introduction: The study is based on application of recently proposed International Academy of cytology (IAC) Yokohama system of Breast cytology. Aim: The main objectives of the study were to categorise the Breast Fine Needle Aspiration Biopsy (FNAB) samples according to this new system of reporting and to assess the Risk of malignancy (ROM) for each category as well as the diagnostic yield of the Breast FNAB. Materials and Methods: A Total of 470 FNAB cytology specimens from January 2017 to December 2018 were obtained. These were studied and reclassified according to newly proposed IAC Yokohama system of reporting. The ROM was determined. The sensitivity, specificity, Positive Predictive Value (PPV), Negative Predictive Value (NPV) and diagnostic yield of Breast FNAB were calculated accordingly. Results: The Breast FNAB samples were distributed as follows: insufficient material 5%, benign 71%, Atypical probably benign 1%, suspicious for malignancy 2% and malignant 21%. Of the 470 cases, 179 cases had histopathological correlation. The respective ROM for each category was 0% for category 1 (insufficient), 4% for category 2 (benign), 66% for category 3 (atypical), 83% for category 4 (suspicious for malignancy) and 99% for category 5 (Malignant). The sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy were respectively 94.59%, 98.9%, 98.59, 95.74% and 96.97%. Conclusion: Categorisation of the Breast FNAB cytology according to IAC Yokohama system of reporting helps pathologist in the diagnostic clarity and guides clinician in the appropriate patient management. IAC Yokohama system of reporting breast cytopathology serves as a common language to pathologist and clinician.

[This corrects the article DOI: 10.1371/journal.pone.0206389.].

Introduction: Dengue fever is the most common arthropod borne disease and major public health concerns in India. The clinical presentation of this disease is difficult to distinguish from other febrile illnesses like malaria and typhus fever. Correlation of haematological parameters helps to differentiate these diseases in early stage. Aim: The present study aimed to identify the haematological features useful for discriminating dengue from other febrile illnesses and to evaluate the accuracy of these haematological parameters. Materials and Methods: A retrospective study was done to differentiate between dengue and other febrile illnesses between January 2017 to July 2017 at Sri Dharmasthala Manjunatheshwara College of Medical Sciences and Hospital, Dharwad Karnataka. Data regarding haematological parameters were collected in 170 cases classified as dengue (D) and 170 cases classified as non dengue (ND) based on laboratory tests. Results: The following parameters were significantly lower in patients with DF as compared to non dengue patients (p-value less than 0.05); WBC, Platelets, Neutrophils, Eosinophils. The following parameters were significantly higher in patients with DF as compared to non dengue cases (p

Changes in levels of cytokines and chemokines have been proposed as possible biomarkers of tissue injury, including liver injury due to drugs. Recently, in acute drug-induced liver injury (DILI), we showed that 19 of 27 immune analytes were differentially expressed and that disparate patterns of immune responses were evident. Lower values of serum albumin (< 2.8 g/dL) and lower levels of only four analytes, namely, IL-9, IL-17, PDGF-bb, and RANTES, were highly predictive of early death [accuracy = 96%]. The goals of this study were to assess levels of the same 27 immune analytes in larger numbers of subjects to learn whether the earlier findings would be confirmed in new and larger cohorts of subjects, compared with a new cohort of healthy controls. We studied 127 subjects with acute DILI enrolled into the US DILIN. We also studied 118 subjects with severe acute liver injury of diverse etiologies, enrolled into the ALF SG registry of subjects. Controls comprised 63 de-identified subjects with no history of liver disease and normal liver tests. Analytes associated with poor outcomes [death before 6 months, n = 32 of the total of 232 non-acetaminophen (Apap) subjects], were lower serum albumin [2.6 vs 3.0 g/dL] and RANTES [6,458 vs 8,999 pg/mL] but higher levels of IL-6 [41 vs 18], IL-8 [78 vs 48], and MELD scores [30 vs 24]. Similar patterns were observed for outcome of death/liver transplant within 6 months. A model that included only serum albumin < 2.8 g/dL and RANTES below its median value of 11,349 had 83% (or 81%) accuracy for predicting early death (or early death/liver transplant) in 127 subjects from DILIN. No patterns of serum immune analytes were reflective of the etiologies of acute liver failure, but there were cytokine patterns that predicted prognosis in both acute DILI and ALF.

Background: Acute appendicitis is the most common surgical emergency. Obstruction of the lumen by fecolith is the usual cause of acute appendicitis.The aim of the study was to analyze clinical presentation of acute appendicitis and its histopathological correlation. Materials and Methods: A retrospective study of acute appendicitis was done in the Department of Surgery of Helping Hands Community Hospital from January 2009 to December 2010. Three hundred forty five patients out of 415 patients with clinical diagnosis of appendicitis underwent operative treatment. The histopathological reports were reviewed and correlated with clinical diagnosis. Results: Out of 345 patients who underwent operative procedure 98% (n= 338) came with chief complaint of pain in the periumbilical region migrating to the right iliac fossa. The mean age of presentation was 42 years. Increased leucocyte count was seen in only 65% cases. Acute appendicitis was more commonly seen in male patients (214 cases, 62%). The most common per operative finding was acutely inflammed appendix (84%) followed by perforated appendix (7.5%), gangrenous appendix (3.5%) and appendicular lump (1.5%). However, histopathological diagnoses were acute appendicitis (91.9%), resolving appendicitis (3.5%), lymphoid hyperplasia (2.6%), mucocele (0.3%) and carcinoid (0.3%). Normal histology was seen in 1.4% cases. Conclusion: Though there are other causes of acute abdomen, acute appendicitis still stands first amongst all the emergencies. Histopathological examination of appendectomy specimen should not be omitted in order to see the incidence negative appendectomy rate and to avoid complications relating to malignant conditions. Keywords: Acute appendicitis; Appendectomy; Appendicular perforation; Histopathology DOI: http://dx.doi.org/10.3126/jpn.v1i2.5402 JPN 2011; 1(2): 104-107

The primary cone-beam computed tomography (CBCT) imaging beam scatters inside the patient and produces a contaminating photon fluence that is registered by the detector. Scattered photons cause artifacts in the image reconstruction, and are partially responsible for the inferior image quality compared to diagnostic fan-beam CT. In this work, a deep convolutional autoencoder (DCAE) and projection-based scatter removal algorithm were constructed for the ImagingRing TM system on rails (IRr), which allows for non-isocentric acquisitions around virtual rotation centers with its independently rotatable source and detector arms. A Monte Carlo model was developed to simulate (i) a non-isocentric training dataset of ≈1200 projection pairs (primary + scatter) from 27 digital head-and-neck cancer patients around five different virtual rotation centers (DCAE NONISO ), and (ii) an isocentric dataset existing of ≈1200 projection pairs around the physical rotation center (DCAE ISO ). The scatter removal performance of both DCAE networks was investigated in two digital anthropomorphic phantom simulations and due to superior performance only the DCAE NONISO was applied on eight real patient acquisitions. Measures for the quantitative error, the signal-to-noise ratio, and the similarity were evaluated for two simulated digital head-and-neck patients, and the contrast-to-noise ratio (CNR) was investigated between muscle and adipose tissue in the real patient image reconstructions. Image quality metrics were compared between the uncorrected data, the currently implemented heuristic scatter correction data, and the DCAE corrected image reconstruction. The DCAE NONISO corrected image reconstructions of two digital patient simulations showed superior image quality metrics compared to the uncorrected and corrected image reconstructions using a heuristic scatter removal. The proposed DCAE NONISO scatter correction in this study was successfully demonstrated in real non-isocentric patient CBCT acquisitions and achieved statistically significant higher CNRs compared to the uncorrected or the heuristic corrected image data. This paper presents for the first time a projection-based scatter removal algorithm for isocentric and non-isocentric CBCT imaging using a deep convolutional autoencoder trained on Monte Carlo composed datasets. The algorithm was successfully applied to real patient data.

Background: This paper investigates the benefits of data filtering via complex dual wavelet transform for metal artifact reduction (MAR). The advantage of using complex dual wavelet basis for MAR was studied on simulated dental computed tomography (CT) data for its efficiency in terms of noise suppression and removal of secondary artifacts. Dual-tree complex wavelet transform (DT-CWT) was selected due to its enhanced directional analysis of image details compared to the ordinary wavelet transform. DT-CWT was used for multiresolution decomposition within a modified total variation (TV) regularized inversion algorithm., Methods: In this study, we have tested the multiresolution TV (MRTV) approach with DT-CWT on a 2D polychromatic jaw phantom model with Gaussian and Poisson noise. High noise and sparse measurement settings were used to assess the performance of DT-CWT. The results were compared to the outcome of the single-resolution reconstruction and filtered back-projection (FBP) techniques as well as reconstructions with Haar wavelet basis., Results: The results indicate that filtering of wavelet coefficients with DT-CWT effectively removes the noise without introducing new artifacts after inpainting. Furthermore, adoption of multiple resolution levels yield to a more robust algorithm compared to varying the regularization strength., Conclusions: The multiresolution reconstruction with DT-CWT is also more robust when reconstructing the data with sparse projections compared to the single-resolution approach and Haar wavelets.

Objectives: As the primary cause of disability worldwide, depression is a significant contributor to global morbidity and mortality and often disproportionately affects older adults. Several studies have demonstrated a link between urban residence and depression, but few studies have examined this association among older adult populations, and even fewer have studied it within an African context. Given that African societies are aging and urbanizing at rapid rates, this study aimed to assess the relationship between urbanicity and depression within older adult populations in two African countries., Method: Data were drawn from the Ghana and South Africa samples of the World Health Organization Study on Global AGEing and Adult Health (SAGE) wave 1 (2007-2008). Depression over the past 12 months was measured using self-reported treatment and depressive symptoms based on ICD-10 criteria in 4209 Ghanaian and 3148 South African adults aged 50 years and older residing in their current location for over one year., Results: The 12-month prevalence of depression was 7.5% and 4.0% in Ghana and South Africa, respectively; 41.1% and 65.6%, respectively, lived in urban areas. Comparing urban to rural residents, the adjusted odds ratio (OR) for depression in multivariable analysis was 1.13 (95% CI: 0.71-1.79) in South Africa and 0.85 (95% CI: 0.55-1.31) in Ghana., Conclusion: Results do not support a significant urban-rural difference in 12-month depression among Ghanaian or South African SAGE participants. Mental health resources in rural areas should therefore be enhanced in these countries for more equitable distributions between the two settings given similar need.

The aim of this paper is to advance electroencephalography (EEG) source analysis using finite element method (FEM) head volume conductor models that go beyond the standard three compartment (skin, skull, brain) approach and take brain tissue inhomogeneity (gray and white matter and cerebrospinal fluid) into account. The new approach should enable accurate EEG forward modeling in the thin human cortical structures and, more specifically, in the especially thin cortices in children brain research or in pathological applications. The source model should thus be focal enough to be usable in the thin cortices, but should on the other side be more realistic than the current standard mathematical point dipole. Furthermore, it should be numerically accurate and computationally fast. We propose to achieve the best balance between these demands with a current preserving (divergence conforming) dipolar source model. We develop and investigate a varying number of current preserving source basis elements n (n=1,…,n=5). For validation, we conducted numerical experiments within a multi-layered spherical domain, where an analytical solution exists. We show that the accuracy increases along with the number of basis elements, while focality decreases. The results suggest that the best balance between accuracy and focality in thin cortices is achieved with n=4 (or in extreme cases even n=3) basis functions, while in thicker cortices n=5 is recommended to obtain the highest accuracy. We also compare the current preserving approach to two further FEM source modeling techniques, namely partial integration and St. Venant, and show that the best current preserving source model outperforms the competing methods with regard to overall balance. For all tested approaches, FEM transfer matrices enable high computational speed. We implemented the new EEG forward modeling approaches into the open source duneuro library for forward modeling in bioelectromagnetism to enable its broader use by the brain research community. This library is build upon the DUNE framework for parallel finite elements simulations and integrates with high-level toolboxes like FieldTrip. Additionally, an inversion test has been implemented using the realistic head model to demonstrate and compare the differences between the aforementioned source models., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Recombination (R) rate and linkage disequilibrium (LD) analyses are the basis for plant breeding. These vary by breeding system, by generation of inbreeding or outcrossing and by region in the chromosome. Common bean (Phaseolus vulgaris L.) is a favored food legume with a small sequenced genome (514 Mb) and n = 11 chromosomes. The goal of this study was to describe R and LD in the common bean genome using a 768-marker array of single nucleotide polymorphisms (SNP) based on Trans-legume Orthologous Group (TOG) genes along with an advanced-generation Recombinant Inbred Line reference mapping population (BAT93 x Jalo EEP558) and an internationally available diversity panel. A whole genome genetic map was created that covered all eleven linkage groups (LG). The LGs were linked to the physical map by sequence data of the TOGs compared to each chromosome sequence of common bean. The genetic map length in total was smaller than for previous maps reflecting the precision of allele calling and mapping with SNP technology as well as the use of gene-based markers. A total of 91.4% of TOG markers had singleton hits with annotated Pv genes and all mapped outside of regions of resistance gene clusters. LD levels were found to be stronger within the Mesoamerican genepool and decay more rapidly within the Andean genepool. The recombination rate across the genome was 2.13 cM / Mb but R was found to be highly repressed around centromeres and frequent outside peri-centromeric regions. These results have important implications for association and genetic mapping or crop improvement in common bean.

The present study examined the role of executive control functions (ECF) in adaptive risk-taking during adolescence. Healthy individuals aged 8-25 were administered ECF measures and the Balloon Analogue Risk Task (BART), a computerized measure of risk-taking propensity. Findings demonstrated that adolescents who executed a more consistent response strategy evidenced better performance on the BART. Greater working memory (WM) predicted lower response variability and WM capacity mediated the relationship between age and variability. Results suggest that intra-individual response variability may index adaptive risk-taking and that the development of ECF, specifically WM, may play an integral role in adaptive decision making during adolescence and young adulthood.

Superantigens (SAgs) are microbial proteins produced by various microorganisms that elicit excessive and strong stimulation of T cells via an unconventional mechanism. They cause polyclonal activation of T cells in a non-specific manner, by binding to a particular variable-beta (Vβ) chain of T-cell receptor (TCR) and MHC class II molecule, in unprocessed form and outside of peptide-binding cleft, forming a bridge between the antigen presenting cell and the T cell. SAgs are classified into three groups, namely 1) exogenous (soluble proteins and exotoxins secreted by microorganisms), 2) endogenous (transmembrane proteins encoded by viruses which are integrated into the genome) and 3) B-cell SAgs (proteins which stimulate predominantly B cells). The best characterized and mostly studied SAgs are staphylococcal and streptococcal exotoxins, however it is well-known that many other microorganisms also possess SAg activities. Despite the presence of several viruses that cause severe infections in humans, the number of viruses that have proteins identified with SAg property in their pathogenesis, is relatively low. To date, the defined viruses that encoded SAgs are as follows; mouse mammary tumor virus (MMTV) (Marrack, et al. 1991), rabies virus (Lafon, et al. 1992), Epstein-Barr virus (EBV) (Sutkowski, et al. 1996), human endogenous retrovirus (HERV) (Conrad, et al. 1997), human immunodeficiency virus (HIV) (Posnett, et al. 1995; Torres, et al. 1996; Townsley-Fuchs, et al. 1997) and Ebola virus (Leroy, et al. 2011). SAgs were first described in the MMTV, a polymorphic B-type retrovirus that is either contained in the genome as an endogenous provirus (germline transmission) or exogenous infectious virus that transmits vertically via breast milk. Both MMTV forms encode SAgs. The SAg-mediated massive T cell activation is required for the spread of exogenous MMTV from intestines to mammary glands, facilitating the transmission of infectious virus. On the other hand, expression of endogenous SAgs leads to thymic deletion of responding T cells (bearing Vβ6-9+ TCR) due to self-tolerance induction during the fetal life, and protects the host against future exogenous MMTV infections. The SAg of rabies virus is the N protein found in nucleocapsid structure and stimulates Vβ8+TCR-bearing T cells. The SAg-induced polyclonal activation of T cells leads to turn-off the specific immune response, to enhance the immunopathogenesis and facilitates viral transmission from the initial site of infection (the muscle tissue) to the nerve endings. In case of EBV-associated SAg that activates Vβ13+TCR-bearing T cells, it was detected that the SAg activity was not encoded by EBV itself, but instead was due to the transactivation of HERV-K18 by EBV latent membrane proteins, whose env gene encodes the SAg (Sutkowski, et al. 2001). It has been denoted that EBV-induced SAg expression plays a role in the long-term persistence and latency of virus in memory B cells, in the development of autoimmune diseases and in the oncogenesis mechanisms. The proteins which are identified as SAgs of HIV are Nef and gp120. It is believed that, the massive activation of CD4+ T cells (selectively with Vβ-12+, Vβ-5.3+ and Vβ-18+ TCRs) in early stages of infection and clonal deletion, anergy and apoptosis of bystander T cells in the late stages may be due to SAg property of Nef protein, as well as the other mechanisms. However there are some studies indicating that Nef does not act as a SAg (Lapatschek, et al. 2001). HIV gp120 glycoprotein is a B-cell SAg that binds to VH3-expressing B cell receptors and causes polyclonal B cell activation. In addition, binding of gp120 to IgE on the surface of basophiles and mast cells causes activation of those cells, secretion of high level proinflammatory mediators leading to allergic reactions and tissue damage. In a recent study, the depletion (anergy or deletion) of T cell populations bearing Vβ12+, Vβ13+ and Vβ17+ TCR have been shown, in patients infected with Zaire Ebola virus, whatever the clinical outcome (death or recovery), these results also suggest the presence of SAg activity. In this review article, following a brief description of the general characteristics of SAgs, virus-encoded SAgs and their roles in the diseases have been discussed.

An increased incidence of chronic kidney disease (CKD) after West Nile Virus (WNV) infections has been suggested but the association of WNV infections with renal damage remain inconclusive. This study was undertaken to characterize WNV infections in individuals with acute kidney injury (AKI) and CKD, and to evaluate hemodialysis as a probable transmission route. A total of 463 plasma and urine samples were collected from 45 AKI and 77 CKD patients. Nested and real-time polymerase chain reaction (PCR) assays were employed for viral RNA detection. Specific immunoglobulins were investigated via immunofluorescence and plaque reduction neutralization assays. Consecutive pre and post-dialysis samples were evaluated in CKD cases. WNV RNA and specific immunoglobulins were detected in 7 (5.7%) and 5 (4.1%) individuals, respectively. The AKI patients with WNV RNA in blood and urine had underlying diseases requiring immunosuppressive therapy and demonstrated moderate to high viral loads. No clinical symptom related to WNV infection were observed in CKD cases with detectable viral nucleic acids. All WNV sequences were characterized as lineage 1 clade 1a and several amino acid substitutions with unknown impact were noted. Detailed epidemiologic investigation of WNV RNA positive CKD cases revealed probable vector-borne virus exposure, without the evidence for transmission via hemodialysis., (© 2015 Wiley Periodicals, Inc.)

Hepatitis E virus (HEV), classified in Hepeviridae family, Hepevirus genus, is a non-enveloped virus with icosahedral capsid containing single-stranded positive sense RNA genome. HEV infections may be asymptomatic especially in children, however it may present as fulminant hepatitis in pregnant women, as well as chronic hepatitis in immunocompromised patients. There are four well-known genotypes of HEV that infect humans and many mammalian species. Genotype 1 and 2 are frequently responsible for water-borne infections transmitted by fecal-oral way in developing countries, while genotype 3 and 4 cause zoonotic infections in developed countries. Turkey is considered as an endemic country with a total seroprevalence rate of 6.3% for normal population, showing significant variation (0-73%) according to the regions and study groups. The aims of this study were to investigate the HEV seropositivity in cases admitted to Hacettepe University Medical Faculty Hospital (HUMFH), to evaluate the results according to the demographic features of patients, and to determine the current HEV seroprevalence in our region, contributing seroepidemiological data in Turkey. A total of 1043 serum samples (514 female, 529 male; age range: 1-90 years, mean age: 38.03) obtained from 327 blood donors (32 female, 295 male; age range: 19-59 years, mean age: 31.1) who were admitted to HUMFH Blood Center, and 716 sera (482 female, 234 male; age range: 1-90 years, mean age: 41.7) that were sent to HUMFH Central Laboratory from various outpatient/inpatient clinics, between November 2012 to November 2013, were included in the study. The presence of HEV-IgG antibodies in serum samples was detected by a commercial ELISA method (Euroimmun, Germany), and the presence of HEV-IgM antibodies was also investigated in the sera with IgG-positive results. The overall HEV-IgG seropositivity rate was determined as 4.4% (46/1043), and the seropositivity rates for blood donors and in/outpatients were as 0.92% (3/327) and 6.0% (43/716), respectively. HEV-IgM antibody was not detected in any of the cases. The HEV-IgG seropositivity was 3.2% among male, and 5.6% among female, yielding no statistically significant difference between the gender (p= 0.056). HEV-IgG antibodies were detected in none (0/118) of the pediatric age group (0-18 years), while the seropositivity rates were 1.9% (14/731) and 16.5% (32/194) in 19-55 and ≥ 56 years-old groups, respectively. The difference between the age groups was statistically significant (p< 0.001), indicating the age-related pattern of HEV exposure. In conclusion, the total HEV seroprevalence rate found as 4.4% in our study, is comparable to the average results reported from Turkey. Our data is also in agreement with the result of a previous report (3.8%) that performed from Ankara province in 2002 with similar study groups, emphasizing that there was no significant changes for HEV exposure have occured over more than the last decade in Ankara, Cental Anatolia, Turkey.

Introduction: Increased thromboembolic disorders and chemotherapy-induced thromboembolic events are well known phenomena in patients with breast cancer. Antithrombin III (AT III) inactivates thrombin, resulting in increased thrombin-antithrombin (TAT) levels. Activated factor X cleaves prothrombin and thrombin, resulting in increased levels of prothrombin fragment 1+2 (F 1+2). Increased TAT and F 1+2 levels show coagulation activation. The aim of this study was to examine plasma levels of TAT and F 1+2 and the effect of anthracycline-based chemotherapy on plasma TAT and F 1+2 in patients with operable breast cancer., Materials and Methods: Seventy patients and 30 age-matched healthy controls were enrolled. Levels of TAT and F 1+2 were investigated before and after adjuvant chemotherapy. Basal levels (pre-chemotherapy) of TAT and F 1+2 in patients were compared with those in healthy controls and patient levels after 3 cycles of chemotherapy. Levels of TAT and F 1+2 were determined using the ELISA method., Results: TAT and d-dimer levels were significantly higher in patients, (P: 0.02 and P<0.001, respectively). Post-chemotherapy F 1+2 levels were higher than basal levels (P: 0.02). F 1+2 levels were higher in patients, although the difference was not statistically significant (P: 0.52). There was no difference between basal and post-chemotherapy TAT levels., Discussion: In conclusion, while higher post-chemotherapy F 1+2 levels suggest that the cumulative effect of chemotherapy increases the risk of thrombosis, TAT and d-dimer levels indicate that the effect of the cancer further increases the risk of thrombosis in patients with operable breast cancer., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Objective: To investigate the effects of tyrphostin AG 556, a tyrosine kinase inhibitor (TKI) in an experimental model of testicular ischemia-reperfusion (I/R) injury., Material and Methods: Twenty-four adult male rats were randomly divided into four groups (n = 6): sham, torsion/detorsion (T/D), T/D + dimethylsulfoxide (DMSO) (vehicle group), and T/D + DMSO + tyrphostin AG 556. Testicular torsion was achieved by rotating the left testis 720° clockwise for 4 h. Thirty minutes before detorsion, 3 mg/kg tyrphostin AG 556 was injected transperitoneally in the AG 556 group and DMSO was injected transperitoneally in the DMSO group. After 2 h of reperfusion arterial blood samples were collected for biochemical analysis for malondialdehyde (MDA), ischemia modified albumin (IMA), SCUBE1 (signal peptide-CUB [complement C1r/C1s, Uegf, and Bmp1] and EGF [epidermal growth factor] like domain-containing protein 1), total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI) parameters, and ipsilateral orchiectomies were performed for histopathological examination based on the semi-quantitative Johnsen's mean testicular biopsy score (MTBS) in all groups., Results: Tyrphostin AG 556 exhibited a protective effect against I/R injury in testicular torsion. Of the biochemical parameters evaluated as a result of testicular I/R, IMA, MDA, and TOS levels were significantly elevated. There was no significant difference in terms of these biochemical parameters between the sham and AG 556 groups. Significant histopathological injury was determined by comparing the T/D and sham groups. According to histopathological injury scores, significant differences were determined between T/D and AG 556 groups and between AG 556 and sham groups. AG 556 had a superior improving effect on Johnsen's scores than DMSO., Conclusions: Our results suggest that the use of tyrphostin AG 556 prior to testicular reperfusion has a protective effect against testicular I/R injury., (Copyright © 2013 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Naturally-occurring mutations associated with resistance to nucleoside/nucleotide analogues (NA) can be detected in a group of treatment-naive individuals chronically infected with hepatitis B virus (HBV). Genotypic resistance testing prior to the initiation of NA therapy may facilitate the selection of optimal drug regime and help to prevent early emergence of clinical resistance. In this study, presence of resistance mutations in treatment-naive individuals with chronic hepatitis B (CHB) was investigated in Hacettepe University Hospital, a referral center in Ankara province, Turkey. A total of 42 patients (17 female, 25 male; age range: 18-62 years) diagnosed as CHB were enrolled in the study with informed consent. All of the patients were negative for hepatitis C and D viruses and human immunodeficiency virus coinfections, and none had a history of interferon or NA treatment. HBV viral load, HBV markers and hepatic enzymes in patients were determined via standardized commercial assays. For the detection of NA resistance mutations, a partial sequence of approximately 250 nucleotides, harboring the frequently-observed sites for NA resistance was amplified via nested PCR and characterized by direct sequencing of the amplicons. The sequences were handled and interpreted for the presence of mutations via various softwares and a web-based virtual phenotyping tool. Well-characterized sequences were obtained in 30 out of 42 samples (71.4%). All circulating HBV strains were observed as genotype D. Nucleotide variations were detected in 19 individuals (63.5%) that comprise silent mutations without amino acid substitution in 8 (26.6%), mutations with undetermined significance in 7 (23.3%) and mutations associated with NA resistance in 3 (10%) patients. Mutations conferring resistance to entecavir + lamivudine (S202G, M204V, L180M, T184N) were identified in one patient whereas L180P, A181Q and A194V substitutions associated with probable lamivudin + adefovir and tenofovir resistance, respectively, were detected in other patients. All patients with resistance mutations were HBsAg and HBeAg positive, anti-HBe negative and had viral loads exceeding 3 x 10(7) IU/ml. In two patients, the route for HBV transmission was vertical. Since no follow-up samples were available from individuals with resistance mutations, alterations in serological markers, viral load and mutation patterns could not be monitored. In conclusion, the presence of NA resistance mutations were revealed in treatment-naive CHB cases in a referral hospital in Turkey. The impact and cost-effectivity of detecting naturally-occurring resistance mutations for clinical follow-up prior to the antiviral therapy need to be elucidated by prospective studies.

Primary mutations conferring hepatitis B virus (HBV) antiviral resistance and associated secondary/compensatory mutations were investigated in this study by DNA sequencing (SEQ) and two commercial Line Probe Assays (LiPAs) (Inno-Lipa HBV DRv2 and Inno-Lipa HBV DRv3, Innogenetics, Belgium). A total of 71 subjects under follow-up for chronic hepatitis B and receiving lamivudine (LVD) therapy for one year or longer at the Hacettepe University Faculty of Medicine, Department of Internal Medicine, Gastroenterology Unit were included in the study with informed consent. Male to female ratio and mean age was noted as 47/24 and 43 ± 15.8 (age range: 13-71) years, respectively. Twenty samples with low HBV DNA levels (mean: 204.6 IU/ml) could not be interpreted by SEQ due to insufficient amplification. All samples with a positive consensus PCR were further analysed via LiPAs, as directed by the manufacturer. Thus a total of 51 and 56 samples could be evaluated via SEQ and LiPA assays, respectively. In 13 of the 51 (25.5%) samples by SEQ and in 9 of 56 (16%) samples by LiPAs, primary and compensatory mutations associated with resistance were identified. Multiple mutations that comprise L180M + M204I in four and L180M + M204V in one sample and single mutations (M204I) in three samples were identified by SEQ. In one sample which had multiple mutations associated with LVD resistance single mutations (S202G, N236T) associated with entecavir resistance and in two other such samples mutations associated with adefovir resistance were detected by SEQ. Also, in three samples amino acid substitution at position rt215 (QÆS) as alone and in one sample with multiple mutations were observed via SEQ. In five of nine samples primary and compensatory multiple mutations (L180M + M204I in one sample, L80I + L180M + M204I in two samples, L80I/V + M204I in one sample) and primary single mutations associated with LVD resistance (M204I/V) in four samples were detected by Inno-Lipa HBV DRv2. Two different mutations (G202, ILFM184) were observed in two samples with multiple mutations associated LVD resistance via Inno-Lipa HBV DRv3. However, mutation at position rt184 was evaluated as a weak positive. Any mutation associated with adefovir resistance was not detected by LiPA. As a result, SEQ and LiPAs displayed comparable performances for the detection of HBV drug resistance mutations. We suggested that for the evaluation of discordant results, it should be better to test consecutive serum samples.

Background: West Nile fever is an important zoonotic infection caused by West Nile virus (WNV), a member of the Flaviviridae. Previous serological data from Turkey suggest widespread WNV circulation. This report includes cases of human and equine WNV infections occurring concurrently, and manifesting as central nervous system infections, in two neighboring provinces of Central Anatolia, Turkey. A partial phylogenetic analysis of the causative virus is given for the first time., Methods: The cases were reported in February (horses) and March (human). Symptoms of the disease were similar in the two species, characterized by neurological manifestations suggesting meningoencephalitis. Real-time/nested PCRs and commercial immunoassays and a plaque reduction neutralization assay were employed for the detection of viral RNA and specific antibodies, respectively., Results: WNV RNAs were detected in buffy coat (horses) and cerebrospinal fluid (human) samples. Partial nucleotide sequences of the E-gene coding region revealed that the strains are closely related to viruses of lineage 1, clade 1a. Accompanying equine serosurveillance demonstrated WNV-specific antibodies in 31.6% of the samples., Conclusions: This is the first report of acute WNV infections caused by lineage 1 strains from Turkey, in concordance with previous reports from some European and North African countries., (Copyright © 2013 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Polyomaviruses, classified in Polyomaviridae family, are non-enveloped small (40-45 nm) viruses with icosahedral symmetry and circular double-stranded DNA genome. Polyomaviruses can infect a variety of vertebrates including birds, rodents, cattle, monkeys and humans. The characteristics such as establishment of latent infections, reactivations during immunosuppression and oncogenic potencies render the human polyomaviruses (HPyVs) of considerable importance for public health. The first polyomavirus (Mouse polyomavirus) has been identified in 1953 as filterable tumor-causing agents in mice, followed by Simian vacuolating virus (SV40) isolated from rhesus monkey kidney cells that had been used for poliovirus vaccine preparation in 1960. Due to the known transforming capacity of SV40, it was initially thought that the incidence of cancer could increase following the administration of SV40-contaminated polio vaccines, however advanced studies yielded inconsistent results, without any evidence to conclude whether or not the contaminated polio vaccine caused cancer. Several studies have reported the detection of SV40 genome in some of the human tumors, as well as in the clinical samples of healthy subjects. In addition SV40 seropositivity was reported in human populations although in low rates (2-10%). These data have raised the possibility that SV40 infects humans and circulates in human populations unrelated to being exposed to the vaccine. The discovery of the first human polyomaviruses was in 1971 independently from each other, one was BK virus (BKPyV) isolated from the urine sample of a renal transplant patient, and the other was JC virus (JCPyV) isolated from the brain tissue of a patient with progressive multifocal leukoencephalopathy, and both were named after the patients' initials. BK and JC viruses were the only well-known human polyomaviruses throughout 36 years, however drammatical increase in number of newly identified human polyomaviruses was recorded in the last six years due to the use of sophisticated molecular methods and new-generation sequencing technologies. In 2007, two new HPyVs were identified independently from nasopharyngeal aspirates of children with acute respiratory tract infections; one was KI (Karolinska Institute) and the other was WU (Washington University) polyomaviruses, named after the initials of institutes which they were first described. In 2008, the fifth HPyV namely Merkel cell polyomavirus (MCPyV) was isolated from the skin tumor sample of a patient with Merkel cell carcinoma. In 2010, three other novel human polyomaviruses were discovered, two were from skin samples of healthy subjects (HPyV-6 and HPyV-7), and one (Trichodysplasia Spinulosa-associated virus; TSPyV) from keratotic spicule sample of a heart-transplanted patient. Another new HPyV was identified in 2011 named HPyV-9, from the blood and urine samples of an asymptomatic patient with kidney transplant. Most recently, three new HPyVs have been sequentially discovered during the last quarter of 2012. The 10th HPyV (HPyV10) was identified in condyloma samples of an immunocompromised patient with WHIM syndrome (Wart, Hypogammaglobulinemia, Infections, Myelokathexis), 11th virus was isolated from stool sample of a healthy child from Malawi (Malawi polyomavirus; MWPyV), and 12th was described from fecal sample of a diarrheal child from Mexico (Mexico polyomavirus; MXPyV). The whole genome sequence analysis of HPyV10, MWPyV and MXPyV pointed out that they are closely related viruses. The last novel polyomavirus, namely Saint Louis polyomavirus (STLPyV) has been reported in a study published on February 2013, identified from the stool sample of a healthy child. Seroepidemiological studies indicated that most of the novel HPyVs are highly prevalent (average rate: 40-80%) worldwide and likely acquired asymptomatically during childhood, similar to the old ones, BKPyV and JCPyV. However data about HPyV10, MWPyV, MXPyV and STLPyV are not enough as they have been discovered most recently. Similarly, little is known about the pathogenesis, route of infection and the relationship with clinical diseases of novel HPyVs except MCPyV and TSPyV which are known to be responsible for Merkel cell carcinoma and trichodysplasia spinulosa, respectively. The expanding repertoire of human polyomaviruses made us think that many others will be uncovered in the future thanking to the advances in molecular methods. In this review, recent developments subjecting new human polyomaviruses have been summarized.

Objectives: Flavi- and Phleboviruses associated with central nervous system (CNS) infections including West Nile Virus (WNV), Tick-borne Encephalitis Virus (TBEV) and Toscana Virus (TOSV) cause significant morbidity and mortality in humans. In this study, the impact of these agents have been investigated in CNS infections at referral hospitals in two provinces in Turkey, where circulation of these viruses have previously been recognized., Methods: In the study, 258 samples from 126 individuals from Ankara and 113 samples from 108 individuals from Izmir provinces collected in 2010 were included. Viral RNAs were investigated by multiple genus and strain specific primers. Commercial serological assays were employed in screening and reactive results were evaluated with additional assays and by plaque reduction neutralization assay., Results: Two cases of WNV CNS infections, 14 cases of TOSV infections and one TBEV-exposed individual were identified via serological testing. WNV infections in 61 and 56-year old individuals from Ankara presented with fever and encephalitis without skin rash and residual neurologic damage. TOSV-associated cases from both provinces mainly displayed signs of meningitis. TOSV exposure was documented for the first time from Izmir., Conclusions: WNV, TBEV and TOSV infections must be considered in cases of meningoencephalitis of unknown etiology in Turkey., (Copyright © 2012 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

We present a case of viral encephalitis due to Sandfly Fever Turkey Virus (SFTV), a novel phlebovirus genetically related to but distinct from Sandfly Fever Sicilian Virus (SFSV), recently identified in a 63-year-old female, via consensus PCR and sequencing. SFTV was initially characterized in 2010 in samples from outbreaks of febrile diseases occurred during 2007-2008 and to the best of our knowledge, this is the first report of an SFTV-related central nervous system (CNS) infection., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Introduction: Sandfly fever virus (SFV) serotypes sandfly fever Naples virus, sandfly fever Sicilian virus, and sandfly fever Cyprus virus cause febrile diseases, whereas Toscana virus (TOSV) is responsible for aseptic meningoencephalitis. Diagnosis and surveillance of TOSV depend heavily on virus serology, and various commercial assays utilizing various antigen sources and formats have been available. The aim of this study was to perform comparative evaluation of commercially available serological assays for anti-TOSV immunoglobulins., Materials and Methods: A collection of 120 sera from healthy blood donors from an endemic region, previously identified to be reactive for antibodies against various SFV serotypes by indirect immunofluorescence test (IIFT), was reevaluated for IgG/IgM via IIFT, enzyme-linked immunosorbent assay, and an immunoblot assay manufactured by Euroimmun, Diesse, and Mikrogen, respectively. Virus neutralization test (VNT) was performed for 99 sera using standard TOSV, sandfly fever Sicilian virus, and sandfly fever Naples virus strains., Results: A total of 89 samples (74.2%) were reactive for TOSV IgG in at least one of the commercial assays, and 31 samples (31.3%) were reactive in VNT for various SFV serotypes. Average percentage agreements among commercial assays and between VNT and the commercial assays were noted as 57.8% and 62.6%, respectively. No significant correlation between assay results and VNT titers was observed. SFV IgM antibodies were detected in a total of eight samples (6.7%) via IIFT, which were nonreactive in enzyme-linked immunosorbent assay and VNT., Discussion: Commercial diagnostic immunoassays displayed slight to fair agreement for TOSV IgG as assessed via kappa and percentage agreement values. The results could only be confirmed via virus neutralization in a portion of the samples, and overall agreement between the commercial assays and VNT was slight. Commercial assays such as immunoblot can be used in addition to VNT for confirmation of TOSV exposure.

West Nile virus (WNV), a member of Flaviviridae family, is an enveloped, icosahedral, single-stranded positive-sense RNA virus. WNV is transmitted to humans by infected mosquitoe (especially Culex spp.) bites and cause a variety of clinical outcomes, ranging from asymptomatic infection to severe meningoencephalitis. The aims of this study were to determine and confirm the WNV seroprevalence in a chosen healthy population and to provide epidemiological data for Turkey about the recent status of the infection at our region. A total of 1200 serum samples collected from blood donors (400 were female, 800 were male; age range: 18-61 years, mean age: 37.8) who were admitted to Hacettepe University Hospital Blood Donation Center between April to December 2009, were included to the study. The presence of WNV IgG antibodies were screened by ELISA (Euroimmun, Germany), and the positive samples have been further investigated by WNV IgG avidity test in order to estimate the time of encounter to the virus. Indirect immunofluorescence antibody (IFA) test (Euroimmun, Germany) and plaque reduction neutralization test (PRNT) which is accepted as the reference method, were performed for the confirmation of WNV IgG positive results. Nineteen (1.6%) of the samples yielded WNV IgG positivity with ELISA, and all of which were IgGs with high avidities (Avidity index values were between 67.8-99.2%). Eight of 19 (42.1%) WNV ELISA IgG positive donors, had risk factors such as joining outdoor activities, contact with mosquitos and ticks and consuming raw milk and milk products. Of 19 samples that were taken into confirmation tests, 15 (78.9%) were found positive with IFA, and 10 (52.6%) were found positive with PRNT. WNV antibody positivity of 10 samples were then confirmed by PRNT, however eight samples which were found positive with both ELISA and IFA yielded negative results with PRNT. This data might indicate that ELISA and IFA methods in which virus-infected cells were used as substrates, have detected non-neutralizing antibodies against viral nucleocapsid antigens rather than the neutralizing antibodies detected against envelope glycoproteins by PRNT method. One sample which yielded low positive result only by ELISA test has been evaluated as a specificity issue of the test. As a result, the positivity rate (19/1200; 1.6%) of WNV IgG detected by ELISA in blood donors, has been confirmed as 0.8% (10/1200) by a gold standard method, PRNT. The data of this study indicated that the prevalence of WNV infections, although low in our region, deserves attention to be considered in surveillance and control programs related to WNV in Turkey.

Introduction: West Nile virus (WNV) is a reemerging flavivirus that has displayed a drastic change in epidemiology in the last decade. Data on WNV activity in Turkey are currently limited. This study investigated WNV exposure in blood donors from Central Anatolia, Turkey., Materials and Methods: A total of 2516 sera, collected from blood donors at four major branches of the Turkish Red Crescent Middle Anatolia Regional Blood Center, were evaluated by a commercial WNV immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA). Positive and borderline samples were investigated further by a WNV IgG indirect immunofluorescence test (IIFT), IgG ELISAs for tick-borne encephalitis virus and dengue virus, an IgG IIFT for yellow fever virus, and a multi-Flavivirus biochip IgG IIFT. WNV antibody specificity and titer values were determined by plaque reduction neutralization assay. IgG avidity and IgM were determined for confirmed samples. IgM-positive samples were also evaluated by a real-time reverse transcription polymerase chain reaction assay., Results: Twenty-five samples (25/2516; 0.99%) were found reactive in the WNV ELISA/IIFT assays, and 14 could be confirmed by the plaque reduction neutralization assay (14/2516; 0.56%). All IgGs were of high avidity, and four samples (4/14; 28.6%), which were negative for viral RNA, were IgM positive. Although samples with neutralizing WNV IgGs had strong fluorescence intensity in IIFTs, no correlation between antibody titer values and IIFT intensity or quantitative ELISA results could be found. Three WNV nonreactive samples were positive in the dengue IgG ELISA test; one of these also displayed positive results for dengue virus in the mosaic biochip IIFT and reactivity in yellow fever virus IIFT., Discussion: WNV exposure is confirmed in 0.56% of the tested healthy blood donors in Central Anatolia, with evidence for dengue/yellow fever and/or other flaviviral infections. This study is the first to document WNV exposure in individuals from Konya, Yozgat, and Sivas provinces in Central Anatolia, and it also establishes viral activity in Ankara, the capital of Turkey.

Dengue virus (DENV) and yellow fever virus (YFV) are two of the globally prevalent vector-borne flaviviruses. Data on these viruses from Turkey is limited to a single study originating from the western, Aegean region of Turkey, where evidence for DENV exposure had been confirmed in residents and presence of hemagglutination inhibiting antibodies against YFV had been revealed. The aim of this study was to investigate the rates of seropositivity of DENV and YFV in blood donors from Central/Northern Anatolia, Turkey, for the demonstration of possible human exposure. Serum samples were collected by the Turkish Red Crescent Middle Anatolia Regional Blood Center from donation sites at Ankara, Konya, Eskişehir and Zonguldak provinces and included in the study after informed consent. Ankara is the capital and second most-populated city in Turkey. All samples were previously evaluated for West Nile and tick-borne encephalitis virus antibodies and found to be negative. A total of 2435 and 1502 sera have been evaluated for IgG antibodies against DENV and YFV, respectively. Commercial enzymelinked immunosorbent assays (ELISAs) and indirect immunofluorescence tests (IIFTs) were applied (Euroimmun, Germany) for DENV/YFV IgG surveillance. DENV IgG reactive sera were further evaluated for IgM by ELISA and a commercial mosaic IIFT to determine DENV subtypes. IgM positive samples were also analyzed by a commercial NS1 antigen detection assay (Bio-Rad Laboratories, France). YFV IgG reactive samples were evaluated by IIFT for IgM and via mosaic IIFT and antibody specificity were confirmed by plaque reduction neutralization test (PRNT). Anti-DENV IgGs were demonstrated in repeated assays in 0.9% (21/2435) of the sera. In two samples with borderline IgG results, presence of DENV IgM was detected, one of which was also borderline positive for DENV NS1 antigen. In 14.3% (3/21) of the IgG reactive sera, mosaic IIFT was evaluated as positive and displayed prominent reactivity for DENV-2 in all samples. From five donors with DENV reactivity, new samples were obtained after at least six months which revealed the continuing presence of DENV IgG activity in four. One sample which was initially positive for IgM, borderline for NS1 antigen and borderline for IgG was observed to be positive for IgG and negative for IgM in redonation. IIFT results in three redonation samples also indicated reactivity for DENV-1 and DENV-2 subtypes. Anti-YFV IgGs were detected in 0.6% (9/1502) of the sera. YFV IgM could not be demonstrated in any of the IgG reactive samples and PRNT was evaluated as negative. In conclusion, evidence for DENV exposure, presumably to DENV-2, was identified in residents from Central Anatolian provinces of Ankara and Konya for the first time, however, seroreactivity detected against YFV could not be confirmed by PRNT. These findings indicated that DENV or an antigenically-similar flavivirus was probably present in the study region and sporadic human exposure might have occurred.

Arthropod-borne viral infections have recently gained considerable attention and importance as re-emerging infections in a global scale. West Nile Virus (WNV), a member of Flaviviridae, is an enveloped positive strand RNA virus that is usually transmitted to humans by the bite of Culicine mosquitoes. Although the majority of the human infections are asymptomatic, WNV may also cause febrile and neuro-invasive diseases. Seroprevalence data from Turkey indicate that WNV activity is present in Central Anatolia. In this study performed at Hacettepe University Hospital, paired serum and cerebrospinal fluid (CSF) samples from 87 adult patients with the preliminary diagnosis of aseptic meningitis/encephalitis of unknown etiology were evaluated retrospectively to identify WNV-related syndromes. Bacterial, fungal and mycobacterial cultures yielded negative results and Mycobacterium tuberculosis and Herpes simplex virus nucleic acid tests were also negative for the selected patients. Commercial enzyme-linked immunosorbent assay (ELISA)s and indirect immunofluorescence test (IIFT)s were employed for WNV IgM and IgG antibody detection (Anti-WNV Virus IgG/IgM ELISA, Anti-WNV Virus IgG/IgM IIFT; Euroimmun, Germany). Additional ELISA/IIFT assays were further performed for WNV antibody reactive samples to identify cross-reactions and/or infections with other flaviviruses and phleboviruses. All WNV antibody positive samples were also evaluated by a WNV real-time reverse-transcription polymerase chain reaction (RT-PCR) assay. WNV IgM and IgG antibodies were detected in %9.2 (8/87) and 3.4% (3/87) of the serum samples, respectively. All IgG reactive samples were negative for IgM. All sera with WNV antibody reactivity (n = 11) and the corresponding CSF samples were negative for viral RNA via RT-PCR. In 5 of the 8 WNV IgM positive subjects, sandfly fever virus IgM antibodies were detected, which was also accompanied by Dengue virus IgM positivity in one sample. In another case, intrathecal antibody synthesis against measles virus was demonstrated. Two cases (2/87; 2.3%) with WNV IgM positivity as the only serologic marker were identified as probable WNV infections and clinical features were discussed. In conclusion, in order to fully understand the impact of WNV and/or other flavivirus infections in Turkey, epidemiology and ecological features of these agents need to established.

Objectives: Lactoferrin (LF) is an iron binding protein and stored in the specific granules of granulocytes. It is released by degranulation following granulocyte activation. A positive correlation was previously reported between periodontitis and LF titers of gingival crevicular fluid (GCF) and blood. The purpose of this study was to examine alterations of GCF and blood levels of LF (LF-GCF and LF-BL, respectively), employing the experimental gingivitis model., Methods: Twelve systemically healthy volunteers, aged 19-21, were selected. Pre-experimental phase of hygiene was followed by a 14-day experimental gingivitis phase in which subjects refrained from all oral hygiene procedures. After that subjects resumed optimal plaque control for 21 days of recovery period. At days 0 (baseline), 14 and 35 gingival crevicular fluid (GCF) and blood samples were collected and plaque index (PI), gingival index (GI), bleeding on probing (BOP) and probing pocket depth scores were recorded. LF levels were measured with commercial enzyme-linked immunosorbent assay (ELISA) kit., Results: PI, GI, BOP and LF-GCF increased significantly after 14 days of experimental gingivitis period and decreased significantly after reinstitution of oral hygiene measures (P<.05). LF-BL appeared to follow the same pattern. Significant negative correlation was detected between the level of LF-BL and BOP at day 14 (P<.05), whereas significant positive correlation was noticed between LF-BL and clinical scores PI, GI and BOP at day 35 (P<.05)., Conclusions: LF-BL followed the same pattern with LF-GCF and clinical scores during the experimental gingivitis and recovery periods, although alterations of the LF-BL appeared statistically insignificant.

R7V is a seven-aminoacid peptide epitope derived from cellular beta-2 microglobulin, present on human immunodeficiency virus (HIV) virion surface in patients with HIV infection. Antibodies against R7V peptide have the property of neutralizing all strains of HIV, unrelated to genotype, phenotype, or geographical origin of the virus, even in the presence of anti-retroviral drug resistance. Patients that mount an anti-R7V antibody response have been shown to be slow or non-progressors and this epitope has been considered for vaccine and/or therapeutic uses. In this study, HIV-infected patients under highly active anti-retroviral therapy (HAART) at Hacettepe University Faculty of Medicine, Department of Internal Medicine, Division of Infectious Diseases, were evaluated for the presence of anti-R7V antibodies. Thirty-three HIV positive patients and 10 healthy controls were enrolled to the study. For HIV-infected patients, determination of viral load and CD4+ T lymphocyte counts were performed by a commercial real-time PCR assay and flow cytometry, respectively. Anti-R7V antibodies were detected from serum samples by a commercial ELISA (Anti-R7V ELISA, Ivagen, France) test. Three HIV infected patients (3/33, 9.1%) displayed anti-R7V antibodies whereas the remaining 30 (90.9%) patients and all controls were interpreted as negative. No statistically significant difference was detected for HIV-RNA levels and CD4+ T lymphocyte counts between anti-R7V positive and negative patients (p= 0.871 and p= 0.287, respectively). These results indicate the presence of anti-R7V antibodies in our study population with HIV infection. No correlation with the presence of anti-R7V and disease progression were displayed in this study. Clinical impact of anti-R7V antibody assays for the management of HIV-infected patients will be revealed in the near future with the help of advanced studies.

Ganciclovir treatment in children with cytomegalovirus (CMV) infection is still controversial and only indicated in selected cases. The aim of thi study was to evaluate clinical and demographic features of CMV hepatitis in immunocompetent children and to determine the effect of ganciclovir treatment in these patients retrospectively. The study was carried out in a group o 29 children with CMV hepatitis. All the patients were investigated for signs of infection, inborn errors of metabolism, genetic diseases, extrahepatic biliary atresia and other causes of hepatitis. Two patients with congenital CMV infection and two patients with biliary atresia were excluded from the study group. The patients included in the study were divided into two groups: non-cholestatic hepatitis (n=16) as Group I and cholestatic hepatitis (n=9) as Group II. Four (25%) patients in the non-cholestatic group and four (44.4 in the cholestatic group were treated with ganciclovir for a median of 21 days. The mean age was 9.6+/- 10.9 months (median age 6 months) in Group I, while cholestatic hepatitis patients in Group II were significantly younger, with a mean age of 2.7+/-0.9 months (p<0.01). The most prominent symptoms at admission were diarrhea and vomiting (25%) in Group I. In Group I, all cases (100%) and in Group II, three of four cases (75%) treated with ganciclovir had recovery from acute CMV hepatitis. In the non-cholestatic group, no relapses were observed while one patient in the cholestatic group relapsed and progressed into chronic liver disease. Patients who received supportive treatment showed a marked decrease in GGT, ALT, AST and bilirubin levels spontaneously and no relapses of hepatitis were observed in at least one year of follow-up. Although ganciclovir therapy is not indicated particularly in immunocompetent cases, since most were self-limited infections, in case of progressive and persistent hepatitis, such as in our cases, ganciclovir was a treatment option; no side effect due to ganciclovir therapy was observed in our cases. Although ganciclovir seems to be effective in progressive CMV hepatitis, multicenter randomized studies in a large study group are necessar to determine the efficacy and indications for ganciclovir treatment.

The most dramatic example of defining the pathogenicity of influenza virus A/H5N1 strains is the higher fatality rate of avian influenza epidemic (>50%) occured in Southeast Asia in 1997 comparing to the pandemic caused by influenza virus A/H1N1 in 1918 (5-10%) which was recorded as the most destructive pandemic in the world. When considering the fatal/total case numbers (208/340) reported by World Health Organization in respect of December 14th, 2007, the mortality rate has now reached to 61 percent. Recent studies have shown that the high fatality rate of avian influenza virus infections is a consequence of an overactive inflammatory response and the severity of infection is closely related with virus-induced cytokine dysregulation. The most important feature of A/H5N1 immunopathogenesis is the appearence of hypercytokinemia ("cytokine storm") which is characterized by the extreme (exaggerated) production and secretion of large numbers and excessive levels of pro-inflammatory cytokines. This phenomenon is blamed on the emergence of lethal clinical symptoms such as extensive pulmonary oedema, acute bronchopneumoniae, alveolar haemorrhage, reactive haemophagocytosis, and acute respiratory distress syndrome, associated with necrosis and tissue destruction. Numerous in vitro, in vivo and clinical studies have pointed out that A/H5N1 viruses are very strong inducers of various cytokines and chemokines [Tumor Necrosis Factor (TNF)-alpha, Interferon (IFN)-gamma, IFN-alpha/beta, Interleukin (IL)-6, IL-1, MIP-1 (Macrophage Inflammatory Protein), MIG (Monokine Induced by IFN-gamma), IP-10 (Interferon-gamma-Inducible Protein), MCP-1 (Monocyte Chemoattractant Protein), RANTES (Regulated on Activation Normal T-cell Expressed and Secreted), IL-8], in both humans and animals. The privileged cells of cytokine storm are macrophages and CD8+ T-lymphocytes, while the primary contributor cytokines are TNF-alpha, IL-6 and IFN-gamma. It has been detected that, mutations of some viral genes (NS1, PB2, HA and NA) are responsible for the cytokine storm, by increasing the viral replication rate, expending the tissue tropism, facilitating the systemic invasion and emerging of resistance against the host antiviral response. It has been shown that Glu92 and Ala149 mutations, and carboxyl-terminal ESEV/EPEV motif of NS1 protein have been implicated as determinants of virulence for A/H5N1 strains. In addition, Lys627 mutation in PB2 protein, polybasic aminoacid mutations in the cleavage region of hemagglutinin (HA) polyprotein, and glycosylation and sialylation mutations in HA and neuraminidase (NA) proteins were found to enhance the immune-mediated patology of highly virulent A/H5N1 strains. In this review article, the immunopathogenesis of influenza infection and the mechanisms of cytokine storm caused by influenza A/H5N1 viruses have been discussed under the light of recent literature.

West Nile virus (WNV) and tick-borne encephalitis virus (TBEV) are among the medically important Flaviviruses that cause significant morbidity and mortality in humans. In this study, seroprevalence of WNV and TBEV in sera from two state medical hospitals from the southeastern part of Turkey was investigated. One hundred eighty-one serum samples were evaluated for WNV immunoglobulin G (IgG) by an indirect immunofluorescence test (IIFT) and for IgG antibodies against TBEV by a commercial enzyme-linked immunosorbent assay (ELISA) kit with enhanced sensitivity and specificity. Sera positive for WNV IgG were further analyzed by plaque reduction neutralization assay (PRNA). TBEV IgM was also investigated by ELISA in all seroreactive samples. Of 181 sera, 29 (16%) were positive for WNV IgG by IIFT and 17 of 179 (9.5%) were confirmed by PRNA. Nineteen of 181 (10.5%) sera were detected to have TBEV IgG. Mean titer of TBEV IgG was 43.0 RU/mL (median, 33.9 RU/mL; cutoff: 20 RU/mL). Four samples with WNV IgG antibodies were also positive for TBEV IgG antibodies. TBEV IgM was detected in 9 of 39 (23%) of all seroreactive sera, where IgM positivity were accompanied by IgG for 6 samples. These results suggest the presence of possible human WNV and TBEV infections in southeastern Turkey where vector activity have previously been detected.