Search

Pancreatic cancer is highly aggressive and at the time of diagnosis, 80% of patients are in the metastatic stage. Personalize d therapy guided by genomic biomarkers for pancreatic cancer has only recently begun to be investigated.This study aimed to comprehensively identify possible activating and pathological mutations in metastatic pancreatic cancer with NGS of liquid biopsies and to investigate miRNAs and mutations as therapeutic targets as we evaluated their relationships and effect on prognoses Seventeen patients and 20 healthy volunteers were included in the study. Blood samples were taken from the patients, cell free DNA was isolated from the serum, and mutation profiles were analyzed by NGS. Serum miRNA levels were analyzed by isolating circulating miRNA from the same samples from all groups. In patients with G288G synonymous mutants in the HNF1A gene compared to non-mutant patients, miR-17, miR-24, and miR-150 levels were found to be statistically significantly lower;The miR-17 and miR-146a levels of patients with a TP53 gene Pro72Arg mutation were found to be statistically significantly higher than that of the non-mutant group Survival was lower with the c.2472 C>T mutation located in exon 18 of the PDGFRA gene; higher in patients with P72R mutations in the TP53 gene and those with miRNA 17 and 146 upregulation carrying this mutation. This study is clinically meaningful in revealing possible pathogenic mutations detected in tumor cells circulating in metastatic pancreatic cancer, both in terms of prognostic value and whether the information can be used to target treatment, including gene therapy. © 2023, Yuzuncu Yil Universitesi Tip Fakultesi. All rights reserved.

Background: Although the role of miR-21-5p in some kidney diseases is relatively documented, the relationship of miR-21-5p with markers of bone metabolism and inflammation in patients receiving hemodialysis (HD) remains unclear. Here, we aim to explore the relationship of miR-21-5p with routine biochemical parameters, mineral bone disorders, and inflammatory markers in HD patients. Methods: Serum miR-21-5p expressions from 60 HD patients and 20 healthy controls were analyzed with qPCR. Bone metabolism-related parameters such as receptor activator of nuclear factor-kappa B ligand (RANKL), osteocalcin, calcium, phosphorus, and parathormone; inflammation-related markers such as tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, IL-10, and C-reactive protein (CRP); and oxidative stress markers such as total antioxidant status (TAS) and total oxidant status (TOS) were measured in serum samples of HD patients. Results: We showed for the first time that miR-21-5p expressions were increased in patients receiving HD. In addition, miR-21-5p expressions showed a significantly positive correlation with bone metabolism markers, i.e. RANKL, osteocalcin, phosphorus, and parathormone, and inflammation markers, i.e. TNF-α, IL-6, and CRP. We detected that areas under the receiver operating characteristic curve for miR-21-5p, RANKL, osteocalcin, TNF-a, IL-6, and oxidative stress index in HD patients were 0.9317, 0.7742, 0.9038, 0.7319, 0.7063, and 0.7738, respectively. Conclusion: Elevated miR-21-5p expressions are associated with routine biochemical and inflammatory markers in HD patients, suggesting that miR-21-5p might have diagnostic and/or therapeutic importance in the treatment of chronic kidney diseases. © 2023 Elsevier Inc.

Background: Colorectal cancer (CRC) is one of the most common types of cancer worldwide. A number of dysregulated microRNAs (miRNAs) have been linked to CRC progression and treatment response and are thought to be promising prognostic biomarkers for this cancer. microRNA-330 (miR-330-5p) has been reported to inhibit cell proliferation through suppressing thymidylate synthase (TYMS). In the current study, miR-330-5p, TYMS, and their interactions were investigated to evaluate their therapeutic and diagnostic value for CRC treatment. Methods: The expression levels of miR-330-5p and TYMS were evaluated in silico using TCGA datasets for CRC. Data validation was performed on a set of internal samples (100 pairs of CRC tumor specimens and adjacent non-cancerous samples) utilizing real-time PCR assay. The linkage between clinicopathological parameters and expression levels was also investigated. Results: TCGA results indicated that miR-330-5p and TYMS were significantly upregulated and downregulated in the CRC, respectively. Real-time PCR results confirmed that the expression of miR-330-5p was significantly upregulated in tumor tissues relative to marginal tissues (P = 0.0005), whereas TYMS expression was significantly downregulated (P = 0.0001). The transcript level of miR-330-5p was associated with tumor stage and lymph node metastases. Conclusion: The microRNA-330 inhibited cell proliferation by suppressing thymidylate synthase (TYMS) in colorectal cancer. Therefore, suggesting that they are valuable factors for further studies of alternative treatment and diagnostic methods. © 2021, Springer Science+Business Media, LLC, part of Springer Nature., This study was supported by a grant from the research deputy of the Department of Tuberculosis and Lung Diseases Research Center, University Tabriz University of Medical Sciences, Tabriz, Iran.

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has required changes in the management of pediatric cardiac surgery. We would like to share the patient treatment and surgical management strategies employed in our Pediatric Cardiovascular Surgery Clinic during the COVID-19 pandemic. Methods: A total of 112 patients were followed up in our clinic between 11.03.2020 and 02.07.2020. Their mean age was 1,118 (4-5,740) days. Management and treatment were performed by our pediatric heart team (pediatric cardiac anesthetists, general pediatricians, pediatric cardiologists, pediatric cardiac surgeons, and an infectious diseases specialist). We prepared new protocols and a surveillance system specific to the pandemic to prevent in-hospital transmission and reduce postoperative mortality and morbidity; our operations were performed according to these protocols. All decisions pertaining to the operation timing and treatment strategy of our COVID-19-positive patients were made by the same team. Results: During the study period, a total of 112 patients, 69 boys and 43 girls, were hospitalized in our clinic. A total of 333 COVID-19 real-time polymerase chain reaction tests were performed on patients and accompanying persons; positive results were found in three patients and two accompanying individuals. Conclusion: By employing new protocols and a surveillance system throughout the healthcare system, we think that early diagnosis and treatment of the pediatric congenital heart disease population, which is susceptible to infections, can continue unperturbed. This and similar approaches can increase postoperative success and prevent transmission in the pediatric population - which are frequently COVID-19 asymptomatic.

Background Despite the notable advances in modern surgery and radiotherapy,no significant increase in the five year survival rate of oral squamous cell carcinoma has been reported. Collecting evidence demonstrates that miR 153 and miR 455-5p play a key role in growth and progression of oral cancer. Early detection of OSCC is important for enhancing patient quality of life and clinical treatment.For this reason, biomarkers or tumour markers offer an opportunity to intervene and avoid development of oral cancer. Methods A total of 50 blood samples from patients from both genders (25 OSCC and 25 healthy people/control groups) were obtained to determine the expression of miR153 and miR455-5p using Real time Polymerase chain reaction and t test. Results In general by using the formula Δ ct, it is evident that the miR 153 expression in peripheral blood is lower in patients than in healthy individuals (1.97) while the miR 455-5p expression in peripheral blood is higher in patients than in healthy individuals (2.56). Conclusion We conclude that miR153 and miR 455-5p expression in serum can function as a diagnostic screening test for the early detection of oral squamous cell carcinoma. .

Genetic mutations in FUS, a DNA/RNA-binding protein, are associated with inherited forms of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). A novel transgenic FUS[1-359]-tg mouse line recapitulates core hallmarks of human ALS in the spinal cord, including neuroinflammation and neurodegeneration, ensuing muscle atrophy and paralysis, as well as brain pathomorphological signs of FTLD. However, a question whether FUS[1-359]-tg mouse displays behavioural and brain pro-inflammatory changes characteristic for the FTLD syndrome was not addressed. Here, we studied emotional, social and cognitive behaviours, brain markers of inflammation and plasticity of pre-symptomatic FUS[1-359]-tg male mice, a potential FTLD model. These animals displayed aberrant behaviours and altered brain expression of inflammatory markers and related pathways that are reminiscent to the FTLD-like syndrome. FTLD-related behavioural and molecular Journal of Cellular and Molecular Medicine features were studied in the pre-symptomatic FUS[1-359]-tg mice that received standard or new ALS treatments, which have been reported to counteract the ALS-like syndrome in the mutants. We used anti-ALS drug riluzole (8 mg/kg/d), or anti-inflammatory drug, a selective blocker of cyclooxygenase-2 (celecoxib, 30 mg/kg/d) for 3 weeks, or a single intracerebroventricular (i.c.v.) infusion of human stem cells (Neuro-Cells, 500 000-CD34+), which showed anti-inflammatory properties. Signs of elevated anxiety, depressive-like behaviour, cognitive deficits and abnormal social behaviour were less marked in FUS-tg–treated animals. Applied treatments have normalized protein expression of interleukin-1β (IL-1β) in the prefrontal cortex and the hippocampus, and of Iba-1 and GSK-3β in the hippocampus. Thus, the pre-symptomatic FUS[1-359]-tg mice demonstrate FTLD-like abnormalities that are attenuated by standard and new ALS treatments, including Neuro-Cell preparation. © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd We thank Thomas Ricker and Alexander Trofimov for their valuable technical contribution, RSF-18-15-00357 and Neuroplast-BV (Maastricht, Netherlands) for a supply of FUS[1-359]-tg mice and ?Neuro-Cells', respectively, RFBR-18-015-00450 for a help with in vitro work and ?5-100' Russian Excellence Program for a support.

MicroRNAs are non-protein coding RNAs that have recently been revealed to be effective in cancer biogenesis which effect post-transcriptional gene modification. The incidence of childhood hematologic cancers is increasing. Therefore, this study aimed to investigate the relationship between miRNA expression and its prognosis in childhood leukemias. Twenty-one patients and 5 healthy control subjects were included in the study. Out of 26 subjects, 15 were patients diagnosed with acute lymphoblastic leukemia (ALL), 6 were patients diagnosed with acute myeloblastic leukemia (AML) and 5 were healthy control subjects. Peripheral venous samples were col-lected from the patients before and 1 month after chemotherapy and their miRNA analyses were performed. Decreased expressions of let-7b, miR-31, miR-128-1, miR-218, miR-331, miR-372, miR-375, miR-422, miR-451 and miR-520 were found in patients with AL compared to the healthy control subjects. While the expression of miR-375 decreased in patients with ALL, the expressions of miR-21, miR-222, miR-30, miR-145, miR-146a and miR-155 increased. While the expression of miR-155 increased in patients with AML, the expressions of miR-10, miR-23, miR-218, miR-422 and miR-451 decreased. It was also found that while the expressions of miR-204,miR-7,miR-10, miR-30, miR-155, miR-192, miR-422, miR-451,miR-520, miR-548, miR-375, miR-1, miR-23 and miR-146a increased in patients with leukemia after the treatment, the expressions of let-7b and miR-132 decreased. A positive correlation was found between leukocyte count of patients with leukemia before the treatment and the expressions of miR-128-1 and miR-331 among miRNAs that changed after the treatment. MiRNAs play role in the pathogenesis, treatment response, relapse and prognosis of hematologic malignancies. © 2020, UHOD - Uluslararasi Hematoloji Onkoloji Dergisi. All rights reserved.

In March 2015, a patient in Colombia with HIV/AIDS was hospitalized for disseminated ulcers after milking cows that had vesicular lesions on their udders. Vaccinia virus was detected, and the case met criteria for progressive vaccinia acquired by zoonotic transmission. Adherence to an optimized antiretroviral regimen resulted in recovery. © 2020 Centers for Disease Control and Prevention (CDC). All rights reserved.

Background: Let-7f has essential impacts on biological processes; however, its biological and molecular functions in lung cancer pathogenesis have yet been remained unclear. We aimed to investigate the expression level of let-7f and its candidate target genes both in lung cancer tissues and A549 cell line. Methods: Bioinformatics databases were first used to select candidate target genes of let-7f. Then the relative gene and protein expressions of let-7f and its target genes, including HMGA2, ARID3B, SMARCAD1, and FZD3, were measured in lung tissues of NSCLC patients and A549 cell line using qRT-PCR and Western blotting. The electroporation method was used to transfect A549 cells with let-7f mimic and microRNA inhibitor. The impact of let-7f transfection on the viability of A549 cells was assessed using MTT assay. The expression data of studied genes were analyzed statistically Results: Results indicated significant downregulated expression level of let-7f-5p (p = 0.0013) and upregulated level of the HMGA2 and FZD3 in NSCLC cases (p < 0.05). In A549 cells, after transfection with let-7f mimic, the expression of both mRNA and protein levels of HMGA2, ARID3B, SMARCAD1, and FZD3 decreased. Also, the overexpression of let-7f significantly inhibited the A549 cell proliferation and viability (p = 0.017). Conclusion: Our findings exhibited the high value of let-7f and HMGA2 as biomarkers for NSCLC. The let-7f, as a major tumor suppressor regulatory factor via direct targeting genes (e.g. HMGA2), inhibits lung cancer cell viability and proliferation and could serve as a marker for the early diagnostic of NSCLC. © 2022, Pasteur Institute of Iran. All rights reserved., Ministry of Health and Medical Education, MOHME; Tabriz University of Medical Sciences, TUOMS, This study was supported by the Non-Communicable Center of the Ministry of Health and Medical Education, and Tuberculosis and Lung Disease Center of Tabriz University of Medical Sciences (Tabriz, Iran. of Medical Sciences.

The literature on neonates with SARS-CoV-2 is mainly concerned with perinatal cases, and scanty data are available about environmentally infected neonates. To fill knowledge gaps on the course and prognosis of neonatal cases, we analyzed 1-year data from the Turkish Neonatal Society in this prospective cohort study of neonates with postnatal transmission. Data from 44 neonatal intensive care units (NICUs), of neonates with positive RT-PCR results at days 5–28 of life, were extracted from the online registry system and analyzed. Of 176 cases, most were term infants with normal birth weight. Fever was the most common symptom (64.2%), followed by feeding intolerance (25.6%), and cough (21.6%). The median length of hospitalization was 9 days, with approximately one quarter of infants receiving some type of ventilatory support. Myocarditis (5.7%) was the most common complication during follow-up. Among the clinical findings, cough (odds ratio [OR]: 9.52, 95% confidence interval [CI]: 4.17–21.71), tachypnea (OR: 26.5, 95% CI: 9.59–73.19), and chest retractions (OR: 27.5, 95% CI: 5.96–126.96) were associated with more severe clinical disease. Also, there were significant differences in the C-reactive protein level, prothrombin time (PT), partial thromboplastin time, international normalized ratio, and days in the NICU (p = 0.002, p = 0.012, p = 0.034, p = 0.008, and p < 0.001, respectively) between patients with mild-moderate and severe-critical presentations. A PT above 14 s was a significant predictor of severe/critical cases, with a sensitivity of 64% and specificity of 73%. Conclusions: Our data showed that late-onset COVID-19 infection in neonates who need hospitalization can be severe, showing associations with high rates of ventilatory support and myocarditis. Cough, tachypnea, and retractions on admission suggest a severe disease course. Trial registration: ClinicalTrials.gov identifier: NCT04401540.What is Known:• Neonatal cases of COVID-19 infection are mainly reported as perinatal COVID-19 cases.• Neonates with perinatal transmission have a mild course and favorable prognosis.What is New:• Among symptomatic neonates with late-onset COVID-19 infection, fever was the most common symptom, and almost one quarter of hospitalized cases needed some type of respiratory support. Myocarditis was the most common complication.• The presence of cough, tachypnea, retractions, and a PT above 14 s were associated with an increased risk of severe COVID-19. © 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Elevated expression of lysine demethylase 6A (KDM6A) and lysine demethylase 6B (KDM6B) has been reported in prostate cancer (PCa). However, the mechanism underlying the specific role of KDM6A/B in PCa is still fragmentary. Here, we report novel KDM6A/B downstream targets involved in controlling PCa cell proliferation. KDM6A and KDM6B mRNAs were higher in prostate adenocarcinoma, lymph node metastatic site (LNCaP) but not in prostate adenocarcinoma, bone metastatic site (PC3) and prostate adenocarcinoma, brain metastatic site (DU145) cells. Higher KDM6A mRNA was confirmed at the protein level. A metastasis associated gene focused oligonucleotide array was performed to identify KDM6A/B dependent genes in LNCaP cells treated with a KDM6 family selective inhibitor, ethyl-3-(6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-ylamino)propanoate (GSK-J4). This identified five genes [V-myc myelocytomatosis viral oncogene homolog (avian) (c-MYC), neurofibromin 2 (merlin) (NF2), C-terminal binding protein 1 (CTBP1), EPH receptor B2 (EPHB2), and plasminogen activator urokinase receptor (PLAUR)] that were decreased more than 50% by GSK-J4, and c-MYC was the most downregulated gene. Array data were validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR), which detected a reduction in c-MYC steady state mRNA and prespliced mRNA, indicative of transcriptional repression of c-MYC gene expression. Furthermore, c-MYC protein was also decreased by GSK-J4. Importantly, GSK-J4 reduced mRNA and protein levels of c-MYC target gene, cyclinD1 (CCND1). Silencing of KDM6A/B with small interfering RNA (siRNA) confirmed that expression of both c-MYC and CCND1 are dependent on KDM6B. Phosphorylated retinoblastoma (pRb), a marker of G1 to S-phase transition, was decreased by GSK-J4 and KDM6B silencing. GSK-J4 treatment resulted in a decrease in cell proliferation and cell number, detected by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sul-fophenyl)-2H-tetrazolium, inner salt (MTS) assay and conventional cell counting, respectively. Consequently, we conclude that KDM6B controlling c-MYC, CCND1, and pRb contribute regulation of PCa cell proliferation, which represents KDM6B as a promising epigenetic target for the treatment of advanced PCa. Copyright © 2022 by The American Society for Pharmacology and Experimental Therapeutics., 118S151; Türkiye Bilimsel ve Teknolojik Araştirma Kurumu, TÜBITAK, This work is supported by The Scientific and Technological Research Council of Turkey (TUBITAK) [Grant 118S151]. The author has no actual or perceived conflict of interest with the contents of this article. https://dx.doi.org/10.1124/molpharm.121.000372.

Background: Parasitic infections, particularly those caused by protozoa, represent a considerable public health problem in developing countries. Blastocystis, Giardia duodenalis, Cryptosporidium spp. and the Entamoeba complex (Entamoeba histolytica, Entamoeba dispar and Entamoeba moshkovskii) are the most common etiological causes of intestinal parasitic infections. Methods: We carried out a descriptive cross-sectional study in school-age children attending a daycare institution in commune eight of Popayán, Cauca (Southwest Colombia). A total of 266 fecal samples were collected (258 from children and eight from pets). Blastocystis, G. duodenalis, Cryptosporidium spp. and the Entamoeba complex were identified by microscopy, quantitative real-time PCR (qPCR) and conventional PCR. The concordance of qPCR and microscopy was assessed using the Kappa index. Molecular characterization was conducted to identify Blastocystis subtypes (18S), G. duodenalis assemblages (tpi and gdh) and Cryptosporidium species/subtypes (18S and GP60). Potential associations between intestinal parasitism and sociodemographic factors were examined using bivariate analyses. Results: A total of 258 fecal samples from children were analyzed by microscopy and 255 samples were analyzed by qPCR. The prevalence of Blastocystis was between 25.19% (microscopy) and 39.22% (qPCR), that of G. duodenalis was between 8.14% (microscopy) and 10.59% (qPCR), that of Cryptosporidium spp. was estimated at 9.8% (qPCR), and that of the Entamoeba complex was between 0.39% (conventional PCR) and 0.78% (microscopy). The concordance between microscopy and qPCR was very low. Blastocystis ST1 (alleles 4, 8, and 80), ST2 (alleles 11, 12, and 15), ST3 (alleles 31, 34, 36, 38,57, and 151), and ST4 (alleles 42 and 91), G. duodenalis assemblages AII, BIII, BIV and D, C. parvum subtype IIa and C. hominis subtype IbA9G3R2 were identified. The only identified member of the Entamoeba complex corresponded to E. histolytica. No statistically significant association was identified between parasitic infection and any sociodemographic variable. Conclusion: This study revealed the usefulness of molecular methods to depict the transmission dynamics of parasitic protozoa in southwest Colombia. The presence of some of these protozoa in domestic animals may be involved in their transmission. © 2019 The Author(s).

Schizophrenia and schizoaffective disorder are chronic and debilitating psychiatric disorders. The present study was designed to determine DNA damage in patients with schizophrenia and schizoaffective disorder to assess the roles of oxidative metabolism and DNA repair mechanisms in this process, to assess the contribution of drugs, and thus to demonstrate the differences between schizophrenia and schizoaffective disorder. Thirty schizophrenia and 30 schizoaffective disorder patients, each having at least five years of disease history, aged between 18 and 60 years with no physical or neurological diseases, and 30 healthy volunteers participated in the study. Psychometric scales were applied, and 5 ml of blood was taken from all participants. The DNA damage was measured in lymphocytes by the comet assay method; the total oxidative parameters by ELISA; OGG1 and NEIL1 gene expressions by real-time PCR; and the role of drugs by in vitro assays. The most important finding in this study was that patients with schizophrenia had significantly greater DNA damage than schizoaffective disorder patients and the controls. This study also provides evidence of high oxidative stress statuses and inadequate DNA repair capacities in patients with schizophrenia. Moreover, psychotropic drugs did not induce any DNA damage to the lymphocytes according to in vitro analyses. The use of clozapine and adequate repair processes of the patients were the decisive factors in the prevention of DNA damage. The results of this study provide a reexamination of schizoaffective disorder within the schizophrenia spectrum and indicate that schizoaffective disorder may be considered a different diagnostic category. © 2018 Elsevier B.V.

Background: Aberrant expression of long noncoding RNAs (lncRNAs) is associated with the progression of human cancers, including gastric cancer (GC). The function of lncRNA DLGAP1-AS2, as an oncogene, has been identified in glioma, hepatocellular carcinoma, and cholangiocarcinoma but not in other malignancies. Therefore, this study was aimed to explore the association of DLGAP1-AS2 with gastric tumorigenesis and beyond.Methods and Results: The expression level of DLGAP1-AS2 was prevaluated in GC datasets from Gene Expression Omnibus (GEO). Moreover, qRT-PCR experiment was performed on 25 paired GC and adjacent normal tissue samples. The Cancer Genome Atlas (TCGA) data were also analyzed for further validations. Consistent with data obtained from GEO datasets, qRT-PCR results revealed that DLGAP1-AS2 was significantly (p < 0.0032) upregulated in GC specimens compared to normal samples, which was additionally confirmed using TCGA analysis (p). DLGAP1-AS2 expression level was also correlated with age (p =0.0008), lymphatic and vascular invasion (p =0.0415) in internal samples. Also, a significant correlation was found between DLGAP1-AS2 and YAP1 expression, as its valid downstream target, in GC samples. Besides, analysis of other prevalent tumor entities using TCGA illustrated the significant overexpression of DLGAP1-AS2 in lung, colorectal, and prostate cancers, further indicating its promise as an oncogene. Moreover, ROC curve analysis showed the high accuracy of the DLGAP1-AS2 expression pattern as a diagnostic biomarker for gastric and colorectal cancers. Conclusion: Our findings indicated that DLGAP1-AS2 might display oncogenic property in gastric tumorigenesis and be suggested as a therapeutic and diagnostic target.

Baykan, Özgür (Balikesir Author), Objectives: It has been shown that the dys-regulation of tyrosine kinase Axl receptor and its ligand growth arrest-specific gene (Gas6) are associated with poor prognosis in various types of tumors but there is not enough study about their importance in bladder cancer (BC). We evaluated the relation of Gas6 gene expression and tyrosine-kinase Axl and Sky (Tyro 3) receptors with tumor stage and grade in patients with BC. Material and Methods: The study group consists of 55 patients whose transurethral resection of bladder (TUR-B) has been performed due to RC and the control group consists of 12 patients with normal bladder mucosa. In tissues mRNAs of Gas6, Axl, and Sky receptors were examined by quantitative (Real-Time) PCR (qPCR). Protein expression was measured by immunohistochemistry. Plasma Gas6 protein levels were compared with control group by ELISA method. Results: Patients with BC were grouped as Ta low (n=17), Ta high (n=5), T1 low (n=9), T1 high (n=8) and T2 (n=16) according to their TUR-B pathologies. The qPCR analysis showed that the expression of Gas6 gene and AxI receptor is higher in the tumor-positive group and the immune-histochemical showed that the bladder samples of the tumor-positive group stained significantly positive. When the patients are grouped according to the TUR-B pathologies, a statistical significant difference was observed among groups in the qPCR analysis ratios of Gas6 gene and Axl receptor by (p < 0.05) but no significance was found for Sky receptor (p > 0.05). When Gas6 protein levels in plasma samples were compared by ELISA method, a statistical significance was determined among groups (p = 0.001). Conclusions: Our findings indicate that mRNAs of Gas6 and Axl receptor are closely related to tumor stage and grade in patients with BC. Further studies are needed for understanding the role of Gas6 and its receptors on the neoplastic transformation in terms of novel biomarkers and potential therapeutic targets., Marmara University SAG-C-TUP-130612-0208

19 páginas, 4 figuras, 2 tablas., World Health Organization goals against soil-transmitted helminthiases (STH) are pointing towards seeking their elimination as a public health problem: reducing to less than 2% the proportion of moderate and heavy infections. Some regions are reaching WHO goals, but transmission could rebound if strategies are discontinued without an epidemiological evaluation. For that, sensitive diagnostic methods to detect low intensity infections and localization of ongoing transmission are crucial. In this work, we estimated and compared the STH infection as obtained by different diagnostic methods in a low intensity setting. We conducted a cross-sectional study enrolling 792 participants from a district in Mozambique. Two stool samples from two consecutive days were collected from each participant. Samples were analysed by Telemann, Kato-Katz and qPCR for STH detection. We evaluated diagnostic sensitivity using a composite reference standard. By geostatistical methods, we estimated neighbourhood prevalence of at least one STH infection for each diagnostic method. We used environmental, demographical and socioeconomical indicators to account for any existing spatial heterogeneity in infection. qPCR was the most sensitive technique compared to composite reference standard: 92% (CI: 83%– 97%) for A. lumbricoides, 95% (CI: 88%– 98%) for T. trichiura and 95% (CI: 91%– 97%) for hookworm. qPCR also estimated the highest neighbourhood prevalences for at least one STH infection in a low intensity setting. While 10% of the neighbourhoods showed a prevalence above 20% when estimating with single Kato-Katz from one stool and Telemann from one stool, 86% of the neighbourhoods had a prevalence above 20% when estimating with qPCR. In low intensity settings STH estimated prevalence of infection may be underestimated if based on Kato-Katz. qPCR diagnosis outperformed the microscopy methods. Thus, implementation of qPCR based predictive maps at STH control and elimination programmes would disclose hidden transmission and facilitate targeted interventions for transmission interruption., BGP and JM received financial support for this study from Mundo Sano Foundation (www.mundosano.org). JG was personally supported at the beginning of the work by the Ramón Areces Foundation and is now funded by the Spanish ‘Juan de la Cierva’ Programme, Ministry of Economy and Competitiveness (FJC-2018-38305). MMV is personally supported by the Spanish ‘Ramón y Cajal’ Programme, Ministry of Economy and Competitiveness (RYC-2015-18368). MCP is personally supported by Junta de Castilla y León and Fondo Social Europeo (LE-135-19). ISGlobal is a member of the CERCA Programme, Generalitat de Catalunya. CISM is supported by the Government of Mozambique and the Spanish Agency for International Development (AECID). Prof. Dr. P.C. Flu Foundation also founded this project. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

The analysis of semen microbiota is difficult due to the lack of established criteria for interpretation of microbiological tests. The aim of the study was to determine the stable clusters of semen microbiota analyzed by real-time PCR in samples with normozoospermia. Semen samples of 227 men with normal spermiograms were included in the study. The quantity of total bacterial DNA and at least one group of microorganisms was more than 103 GE/ml in 107 (41.7%) samples. Four stable microbiota clusters with the prevalence of a specific microorganism group were distinguished in these samples: obligate anaerobes (OA) cluster (proportion in the centroid - 81.1%); Lactobacillus spp. cluster (proportion in the centroid - 64.3%); gram-positive facultative anaerobes (GPFA) cluster (proportion in the centroid - 92.5%); Enterobacteriaceae/Enterococcoccus (EE) cluster (proportion in the centroid - 80.8%). The clusters were ranked by frequency of occurrence: OA cluster was the most prevalent (43 (40.2%) of 107), second-most frequent were GPFA-cluster (27 (25.2%)) and Lactobacillus-cluster (22 (20.6%)). EE-dominated cluster was found in 15 (14.0%) cases. © 2021 Pirogov Russian National Research Medical University. All rights reserved. The authors would like to thank VN Khayutin, director of "Garmonia" Medical Center, for allowing them to conduct the study in the clinic's laboratory department.

The brominated flame retardants (BFRs), 1,2-dibromo-4-(1,2 dibromoethyl)cyclohexane (TBECH) and 2,3-dibromopropyl-2,4,6-tribromophenyl ether (DPTE) bind to the androgen receptor (AR). in vitro bioassays have shown that TBECH is a potent androgen agonist while DPTE is a potent AR antagonist. Both TBECH and DPTE alter gene expression associated with AR regulation. However, it remains to be determined if TBECH and DPTE can affect the prostate. For this reason, we exposed CD1 mice to a 1:1 mixture of TBECH diastereomers alpha and beta, a 1:1 mixture of gamma and delta, and to DPTE, and tested their effects on prostate growth, histology and gene expression profiles. Castrated mice were used to study the androgenic effects of TBECH alpha beta and TBECH gamma delta while the antagonistic effects of DPTE were studied in non-castrated mice. We observed that testosterone and TBECH gamma delta increased body and prostate weights while TBECH alpha beta affected neither of them; and that DPTE had no effect on body weight but reduced prostate weight drastically. Histomorphometric analysis of the prostate revealed epithelial and glandular alterations in the TBECH gamma delta group comparable to those in testosterone group while alterations in the TBECH alpha beta group were less pronounced. DPTE displayed androgen antagonist activity reminiscent of castration. The transcription profile of the prostate was altered by castration and exposure to testosterone and to TBECH gamma delta reversed several of these changes. Testosterone and TBECH gamma delta also regulated the expression of several androgen responsive genes implicated in prostate growth and cancer. While DPTE resulted in a drastic reduction in prostate weight, it only affected a small number of genes. The results indicate that TBECH gamma delta and DPTE are of high human health concern as they may contribute to changes in prostate growth, histology and function

The coronavirus disease 2019 (COVID-19) pandemic has created a global health- and economic crisis. Lifting confinement restriction and resuming to normality depends greatly on COVID-19 immunity screening. Detection of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which causes COVID-19 by serological methods is important to diagnose a current or resolved infection. In this study, we applied a rapid COVID-19 IgM/IgG antibody test and performed serology assessment of antibody response to SARS-CoV-2. In PCR-confirmed COVID-19 patients (n=45), the total antibody detection rate is 92% in hospitalized patients and 79% in non-hospitalized patients. We also studied antibody response in relation to time after symptom onset and disease severity, and observed an increase in antibody reactivity and distinct distribution patterns of IgM and IgG following disease progression. The total IgM and IgG detection is 63% in patients with < 2 weeks from disease onset; 85% in non-hospitalized patients with > 2 weeks disease duration; and 91% in hospitalized patients with > 2 weeks disease duration. We also compared different blood sample types and suggest a potentially higher sensitivity by serum/plasma comparing with whole blood measurement. To study the specificity of the test, we used 69 sera/plasma samples collected between 2016-2018 prior to the COVID-19 pandemic, and obtained a test specificity of 97%. In summary, our study provides a comprehensive validation of the rapid COVID-19 IgM/IgG serology test, and mapped antibody detection patterns in association with disease progress and hospitalization. Our study supports that the rapid COVID-19 IgM/IgG test may be applied to assess the COVID-19 status both at the individual and at a population level.

Traumatic brain injury (TBI) often causes massive brain cell death accompanied by the accumulation of toxic factors in interstitial and cerebrospinal fluids. The persistence of the damaged brain area is not transient and may occur within days and weeks. Chaperone Hsp70 is known for its cytoprotective and antiapoptotic activity, and thus, a therapeutic approach based on chemically induced Hsp70 expression may become a promising approach to lower post-traumatic complications. To simulate the processes of secondary damage, we used an animal model of TBI and a cell model based on the cultivation of target cells in the presence of cerebrospinal fluid (CSF) from injured rats. Here we present a novel low molecular weight substance, PQ-29, which induces the synthesis of Hsp70 and empowers the resistance of rat C6 glioma cells to the cytotoxic effect of rat cerebrospinal fluid taken from rats subjected to TBI. In an animal model of TBI, PQ-29 elevated the Hsp70 level in brain cells and significantly slowed the process of the apoptosis in acceptor cells in response to cerebrospinal fluid action. The compound was also shown to rescue the motor function of traumatized rats, thus proving its potential application in rehabilitation therapy after TBI. © 2020 by the authors. Licensee MDPI, Basel, Switzerland. Ministry of Education and Science of the Russian Federation, Minobrnauka: 0124-2019-002 Russian Foundation for Basic Research, RFBR: 20-33-70102 Russian Science Foundation, RSF: 18-74-10087 Funding: This research was funded by Russian Science Foundation, research project #18-74-10087 (V.F.L., E.A.D., M.A.M., E.R.M.), Russian Foundation for Basic Research, research project #20-33-70102 (I.A.U., O.N.C., V.N.C, M.?.T., I.V.G.), and by The Ministry of Education and Science of Russian Federation № 0124-2019-002 (R.V.S., N.D.A., B.A.M.).

To this day semen microbiota is still poorly understood, and clinical significance of detecting specific microorganism groups has not been clearly determined. The aim of this work was to conduct cluster analysis of semen microbiota detected using real-time PCR. 634 semen samples of reproductive age men were analyzed using the Androflor kit. Microbial DNA in the quantity of no less than 103 GE/ml was detected in 460 samples (72.5%). From 1 to 14 microorganism groups were detected in 350 samples (55.2%) in the quantities that exceeded the threshold values (the detection rate of specific groups: 3.3–21.0%). In these 350 samples 4 stable microbiota clusters were determined. Each of the clusters was characterized by the prevalence of a specific microorganism group: obligate anaerobes (cluster 1; n = 172; detection rate — 49.1%), Lactobacillus spp. (cluster 2; n = 78; detection rate — 22.3%), gram-positive facultative anaerobes (cluster 3; n = 62; detection rate — 17.7%), Enterobacteriaceae / Enterococcus (cluster 4; n = 62; detection rate — 10.9%). Cluster 1 was less stable and was characterized by the larger species diversity compared to other clusters. © 2020 Pirogov Russian National Research Medical University. All rights reserved.

This study aimed to determine the association of fatty acid transporter plasma solublecluster of differentiation 36 (sCD36) with subclinical carotid atherosclerosis (SCA). A cross-sectionalstudy was conducted in 1023 subjects, 225 with type 1 diabetes (T1D), 276 with type 2 diabetes (T2D)and 522 who were nondiabetic. Carotid atherosclerotic plaque (CAP) presence was determined usingB-mode carotid ultrasound imaging. sCD36 were analysed by ELISA, and CD36 surface receptor andmRNA expression were measured by flow cytometry and real-time PCR. Logistic regression modelswere used to evaluate sCD36 as a biomarker of SCA. Up to 376 (36.75%) participants had at least oneCAP, 76 T1D, 164 T2D and 136 without diabetes, while the remaining 647 (63.25%) did not have anyCAP. There were no differences in sCD36 between patients with and without CAP in T1D (p=0.287)or T2D (p=0.513). Although nondiabetic subjects with plaques had lower sCD36 levels than thosewithout (p=0.023), the multivariate models revealed no association of sCD36 with CAP in any of thethree study groups. No differences were found in surface CD36 or CD36 mRNA expression between the patients with and without CAP. sCD36 is not associated with SCA in type 1 or type 2 diabetic orin nondiabetic subjects. This research was supported by grants from the European Foundation for the study of diabetes (2014-EFSD-00914) and European Regional Development Fund (ERDF). CIBER for Diabetes and Associated Metabolic Diseases (CIBERDEM), CIBER on Liver and Digestive Diseases (CIBEREHD), and CIBER on Physiopathology ofObesity and Nutrition (CIBEROBN) are initiatives of the Carlos III National Institute of Health, Spain.

Despite many advances in assisted reproductive technology (ART), the most viable embryo selection remains a challenge for infertility treatment. This study was designed to investigate whether intrafollicular circulating cell-free DNA (cfDNA) fragments and Melatonin levels predict embryo quality in patients undergoing IVF treatment. A total of eight hundred and ninety-five follicular fluid (ff) samples were collected from 325 infertile patients undergoing IVF treatment. Patients were enrolled from August 2017 to December 2018 in the infertility center of a tertiary care hospital. A clear non-hematic follicular fluid was aspirated after the removal of eggs from the dominant follicles (>18 mm) of each patient. Melatonin and E-2 levels in each follicular sample were estimated by immune-chemiluminescence using commercially available kits. ALU-qPCR evaluated cfDNA levels in individual follicular fluid samples. Our study presented a significant and negative relationship between intra-follicular cfDNA and melatonin concentration (-0.541: P = 25%) than embryos with low fragmentation rate (, Lahore institute of Fertility and Endocrinology, Hammed Latif Hospital, Lahore institute of Fertility and Endocrinology, Hammed Latif Hospital.

The mortality rate for the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is increasing worldwide with each passing day. The risk factors for mortality include advanced age and comorbidities. It is still uncertain whether biological agents pose a risk for the progression of SARS-CoV-2. Although there are studies suggesting the use of biological agents in the literature, there are also studies suggesting the discontinuation of biological agents during SARS-CoV-2. In this study, we aimed to determine whether anti-tumor necrosis factor (anti-TNF-α agents) therapy, which is one of the biological agents commonly used in rheumatology clinics, has an effect on the clinical course of SARS-CoV-2 infection, and to review the literature. We searched the MEDLINE/PubMed and SCOPUS databases until the date of August 15, 2020, using the following keywords: SARS-CoV-2 and anti-TNF-α agents. We reviewed abstracts and retrieved the relevant articles. We reported the clinical manifestation and disease course of SARS-CoV-2 pneumonia in three patients with ankylosing spondylitis who were receiving anti-TNF-α agents. All patients in our case series had a mild course similar to the most cases reported in the literature. © 2020 Indian Journal of Rheumatology | Published by Wolters Kluwer - Medknow.

The accuracy of risk prediction for coronary artery disease can be improved with the use of novel molecular or genetic biomarkers. In this study, we investigated the difference of five selected microRNAs (miR or miRNA) in patients with coronary artery disease (CAD) and controls, assessed by coronary angiography. The study population consisted of 85 subjects, aged between 18 and 75 years and underwent invasive coronary angiography. Subjects with more than 30% stenosis in at least one coronary artery, patients with a history of prior percutaneous coronary intervention or coronary by-pass surgery were allocated to the patient group; whereas the subjects without at least 30% stenosis consisted the control group. Groups were similar in age, presence of hypertension, and smoking status. However, the proportion of males and subjects taking angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, beta blockers, nitrates, and statins were higher in the patient group. miR-221 and miR-155 were downregulated (P = .02 and .001, respectively), while miR-21 levels were significantly increased (P = .003) in the patient group compared to controls. Changes in miR-145 and miR-126 did not reach statistical significance (P > .05). miRNA- 21, miR-155, and miR-221 were differentially expressed between the patients and controls. miRNAs are promising biomarkers for CAD diagnosis, however, this requires further research with larger groups. C1 [Sanlialp, Musa] Tavas State Hosp, Dept Cardiol, Denizli, Turkey. [Dodurga, Yavuz; Secme, Mucahit] Pamukkale Univ, Sch Med, Dept Med Biol & Genet, Denizli, Turkey. [Uludag, Burcu] Dr Suat Seren Chest Hosp, Dept Cardiol, Izmir, Turkey. [Alihanoglu, Yusuf, I] Denizli Cerrahi Hosp, Dept Cardiol, Denizli, Turkey. [Enli, Yasar; Bostanci, Hayrani Eren] Pamukkale Univ, Fac Med, Dept Biochem, Denizli, Turkey. [Sanlialp, Sara Cetin] Servergazi State Hosp, Dept Cardiol, Denizli, Turkey. [Tok, Ozge Ozden] Bahcelievler Mem Hosp, Dept Cardiol, Istanbul, Turkey. [Kaftan, Asuman; Kilic, Ismail Dogu] Pamukkale Univ Hosp, Dept Cardiol, TR-20160 Denizli, Turkey.

Microcephalic primordial dwarfism (MPD) is a group of autosomal recessive inherited single-gene disorders with intrauterine and postnatal global growth failure. Seckel syndrome is the most common form of the MPD. Ten genes are known with Seckel syndrome. Using genome-wide SNP genotyping and homozygosity mapping we mapped a Seckel syndrome gene to chromosomal region 4q28.1-q28.3 in a Turkish family. Direct sequencing of PLK4 (polo-like kinase 4) revealed a homozygous splicing acceptor site transition (c.31-3 A>G) that results in a premature translation termination (p.[=,Asp11Profs*14]) causing deletion of all known functional domains of the protein. PLK4 is a master regulator of centriole biogenesis and its deficiency has recently been associated with Seckel syndrome. However, the role of PLK4 in genomic stability and the DNA damage response is unclear. Evaluation of the PLK4-Seckel fibroblasts obtained from patient revealed the expected impaired centriole biogenesis, disrupted mitotic morphology, G 2 /M delay, and extended cell doubling time. Analysis of the PLK4-Seckel cells indicated that PLK4 is also essential for genomic stability and DNA damage response. These findings provide mechanistic insight into the pathogenesis of the severe growth failure associated with PLK4-deficiency. © 2017 European Society of Human Genetics All rights reserved.

Introduction: Hyperprolactinemia is a common serious side effect of antipsychotic medications that are currently used in the treatment of patients with schizophrenia. Pharmacogenetic approaches offer the possibility of identifying patient-specific biomarkers for predicting the risk of this side effect. We investigated a possible relationship between variants (SNPs) in genes for cytochrome 2D6 (CYP2D6), dopamine-2 receptor (DRD2) and serotonin-2C receptor (HTR2C) and antipsychotic drug-induced hyperprolactinemia in patients with schizophrenia. Methods: Overall, 128 Russian patients with paranoid schizophrenia (61F/67M, aged 18-65 y) were included. Serum prolactin concentration was measured with ELISA. DNA analysis and genotyping of CYP2D6 (rs3892097), DRD2 (rs6275) and HTR2C (rs6318) genes was done with StepOnePlus Real-Time PCR System using TaqMan® SNP Genotyping Assays (Applied Biosystems, USA). Results: Our study showed an association of the CYP2D6 (rs3892097) and HTR2C (rs6318) gene polymorphism with hyperprolactinemia in patients with schizophrenia on the background of therapy. No associations were identified between the DRD2 (rs6275) gene polymorphism and the risk of antipsychotic-induced hyperprolactinemia in patients with schizophrenia. Conclusion: Our study confirms a contribution of genetic factors to the antipsychoticinduced hyperprolactinemia in patients with schizophrenia. Further studies are required to unravel the genetic predictors of antipsychotic-induced side effects and to develop the personalized treatment strategies for patients with schizophrenia.

Introduction: Hyperprolactinemia is a common serious side effect of antipsychotic medications that are currently used in the treatment of patients with schizophrenia. Pharmacogenetic approaches offer the possibility of identifying patient-specific biomarkers for predicting the risk of this side effect. We investigated a possible relationship between variants (SNPs) in genes for cytochrome 2D6 (CYP2D6), dopamine-2 receptor (DRD2) and serotonin-2C receptor (HTR2C) and antipsychotic drug-induced hyperprolactinemia in patients with schizophrenia. Methods: Overall, 128 Russian patients with paranoid schizophrenia (61F/67M, aged 18-65 y) were included. Serum prolactin concentration was measured with ELISA. DNA analysis and genotyping of CYP2D6 (rs3892097), DRD2 (rs6275) and HTR2C (rs6318) genes was done with StepOnePlus Real-Time PCR System using TaqMan® SNP Genotyping Assays (Applied Biosystems, USA). Results: Our study showed an association of the CYP2D6 (rs3892097) and HTR2C (rs6318) gene polymorphism with hyperprolactinemia in patients with schizophrenia on the background of therapy. No associations were identified between the DRD2 (rs6275) gene polymorphism and the risk of antipsychotic-induced hyperprolactinemia in patients with schizophrenia. Conclusion: Our study confirms a contribution of genetic factors to the antipsychoticinduced hyperprolactinemia in patients with schizophrenia. Further studies are required to unravel the genetic predictors of antipsychotic-induced side effects and to develop the personalized treatment strategies for patients with schizophrenia.

WOS: 000531077200005, PubMed ID: 32315829, Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used pharmaceuticals to treat pain, fever and inflammation. NSAIDs are also known to have many side effects including adverse effects on reproduction in both humans and animals. As NSAIDs usage is not regulated they are frequently detected at high concentrations in the environment. In order to understand the effect of NSAIDs on zebrafish sex differentiation, we used seven different NSAIDs which were either Cox-1 selective, Cox-1 biased, non-selective or COX-2 selective. We show that at higher concentration, NSAIDs are toxic to zebrafish embryo as they lead to mortality and hatching delay. Gene expression analysis following short term exposure of NSAIDs led to downregulation of female specific genes including zp2, vtg2 foxl2 and wnt4. Long term exposure of larvae to environmentally relevant concentrations of Cox-2 selective and non-selective NSAIDs resulted in male-biased sex ratio which confirmed the qRT-PCR analysis. However, the Cox-1 selective acetylsalicylic acid and the Cox-1 biased ketoprofen did not alter sex ratio. The observed male-biased sex ratio could also be due to induction of apoptosis process as the genes including p21 and casp8 were significantly upregulated following exposure to the Cox-2 selective and the nonselective NSAIDs. The present study indicates that NSAIDs alter sex differentiation in zebrafish, primarily through inhibition of Cox-2. This study clearly demonstrates that the use of NSAIDs and their release into the aquatic environment should be carefully monitored to avoid adverse effects to the aquatic organisms., Swedish Research CouncilSwedish Research Council [201504600]; Knowledge Foundation Sweden [20150084]; Orebro University, This study was financed by the Swedish Research Council (201504600), the Knowledge Foundation Sweden (20150084), and Orebro University.

Chronic mountain sickness (CMS) is a pathological condition resulting from chronic exposure to high-altitude hypoxia. While its prevalence is high in native Andeans (>10%), little is known about the genetic architecture of this disease. Here, we performed the largest genome-wide association study (GWAS) of CMS (166 CMS patients and 146 controls living at 4,380 m in Peru) to detect genetic variants associated with CMS. We highlighted four new candidate loci, including the first CMS-associated variant reaching GWAS statistical significance (rs7304081; P = 4.58 × 10−9). By looking at differentially expressed genes between CMS patients and controls around these four loci, we suggested AEBP2, CAST, and MCTP2 as candidate CMS causal genes. None of the candidate loci were under strong natural selection, consistent with the observation that CMS affects fitness mainly after the reproductive years. Overall, our results reveal new insights on the genetic architecture of CMS and do not provide evidence that CMS-associated variants are linked to a strong ongoing adaptation to high altitude.

Background There are no data regarding the prevalence of malignancies in patients with primary immunodeficiency (PID) in Turkey. Along with the prevalence of malignancy, we aimed to present the types of malignancy and define the underlying immune deficiency of the patients. Method Between the years 1992 and 2018, from five tertiary immunology clinics, fifty-nine patients with PID who developed malignancy were included. All patients were evaluated for demographics, clinical features, and prognosis. Results The prevalence of malignancy in our cohort was detected as 0.9% (59/6392). The male-to-female ratio was 1.8 (38/21), and the median age of patients was 14 years (range: 1.5-51). The median age at diagnosis of malignancy was 10 years (range: 1.5-51). Ataxia-telangiectasia was the most frequent PID in patients with malignancy (n = 19, 32.2%), and non-Hodgkin lymphoma was the most common malignancy (n = 32, 51.6%). The rate of malignancy in DOCK8 deficiency (n = 7/43, 16.3%) was higher than AT (n = 19/193, 9.8%), Wiskott-Aldrich syndrome (n = 2/22, 9.1%), and common variable immunodeficiency (n = 11/205, 5.4%). EBV quantitative PCR was positive in 16 out of 53 patients (30.2%). Three patients had secondary malignancies. Remission was achieved in 26 patients (44.1%). However, 31 patients (52.5%) died. Two patients (3.4%) are still on chemotherapy. Conclusion This study is the largest cohort investigating the association of malignancy in patients with PID in Turkey. While lymphoid malignancies were the most common malignancy and observed more frequently in AT patients, the risk for malignancy was higher in patients with DOCK8 deficiency compared to AT.

Background/Aims: Kefir is a kind of fermented probiotic dairy product. The objective of the present study was to investigate the effects of kefir consumption on the fecal microflora and symptoms of patients with inflammatory bowel disease (IBD). Materials and Methods: Kefir was serially diluted and inoculated into de Man, Rogosa, and Sharpe agar and incubated at 37 degrees C for 48 to 72 h under anaerobic conditions. This was a single-center, prospective, open-label randomized controlled trial. Forty-five patients with IBD were classified into two groups: 25 for treatment and 20 for control. A 400 mL/day kefir was administered to the patients for 4 weeks day and night. Their stool Lactobacillus, Lactobacillus kefiri, content was quantitated by real-time quantitative polymerase chain reaction before and after consumption. Abdominal pain, bloating, stool frequency, stool consistency, and feeling good scores were recorded in diaries daily by the patients. Results: A 5x10(7) CFU/mL count of lactic acid bacteria colony forming units was found in a kefir sample as the total average count. Lactobacillus bacterial load of feces of all subjects in the treatment group was between 10(4) and 10(9) CFU/g, and the first and last measurements were statistically significant (p=0.001 in ulcerative colitis and p=0.005 in Crohn's disease (CD)). The L. kefiri bacterial load in the stool of 17 subjects was measured as between 10(4) and 10(6) CFU/g. For patients with CD, there was a significant decrease in erythrocyte sedimentation rate and C-reactive protein, whereas hemoglobin increased, and for the last 2 weeks, bloating scores were significantly reduced (p=0.012), and feeling good scores increased (p=0.032). Conclusion: According to our data, kefir consumption may modulate gut microbiota, and regular consumption of kefir may improve the patient's quality of life in the short term.

The aim of this study was to determine whether plasma concentrations of sCD36 (soluble CD36) are associated with the presence of type 1 or type 2 diabetes. Plasma levels of sCD36 were analysed in 1023 subjects (225 type 1 diabetes (T1D) patients, 276 type 2 diabetes (T2D) patients, and 522 non-diabetic control subjects) using an enzyme-linked immunosorbent assay (ELISA). Multinomial and logistic regression models were performed to evaluate associations with sCD36 and its association with diabetes types. There were no significant differences in sCD36 (p = 0.144) among study groups, neither in head-to-head comparisons: non-diabetic versus T1D subjects (p = 0.180), non-diabetic versus T2D subjects (p = 0.583), and T1D versus T2D patients (p = 0.151). In the multinomial model, lower sCD36 concentrations were associated with older age (p &lt, 0.001), tobacco exposure (p = 0.006), T2D (p = 0.020), and a higher-platelets count (p = 0.004). However, in logistic regression models of diabetes, sCD36 showed only a weak association with T2D. The current findings show a weak association of circulating sCD36 with type 2 diabetes and no association with T1D.

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder. Its etiology is not clearly understood yet, but neurobiological, genetic and environmental factors are shown to play a role. The relationship between ADHD and miRNAs has been studied quite recently, and few studies have been conducted up to now. In this study, peripheral blood expression levels of miR-5692b, miR-let-7d, miR-124-3p, miR-4447 and miR-107 of 30 children and adolescents with combined type ADHD were compared to 30 healthy controls to understand the roles of these miRNAs in the ADHD etiopathogenesis. Compared to controls, levels of miR-5692b (p = 0.006) were found higher and levels of miR-let-7d (p = 0.017) were found lower in the ADHD group. There was no significant difference in terms of miR-124-3p, miR-4447, and miR-107 levels between the groups. In conclusion, our findings support other studies suggesting the importance of miRNAs in the pathogenesis of ADHD. Regarding the regulatory role of miRNAs in gene regulation, their contribution to etiopathogenesis and heterogeneity of ADHD should be investigated further. © 2019 Elsevier Ltd

Introduction: In the diagnosis of hepatitis C virus (HCV) infection, the first step is screening for anti-HCV antibodies, and positive results are generally confirmed with nucleic acid amplification tests. Recent studies have reported that more compatible results have been obtained with the HCV RNA test using signal to cut-off (S/Co) values >1, which are the routine reactivity threshold for the anti-HCV enzyme immunoassay (EIA) test. The aim of this study was to determine the most appropriate S/Co value for the anti-HCV test, predicting HCV infection. Methodology: Comparisons were made between results of 559 patients who underwent anti-HCV with ECLIA method and HCV RNA tests with real-time polymerase chain reaction (PCR) method. By accepting the HCV-RNA test as the gold standard for HCV infection, the sensitivity, specificity and predictive values of the ECLIA test were determined and statistical "receiver operating characteristic" (ROC) analysis was applied to determine the most appropriate threshold. Results: Between January 2013 and April 2018, a total of 81,203 serum samples were examined. Of 559 anti-HCV positive patients, HCV RNA positivity was determined in 214 (38.2%). According to the ROC analysis results, the most appropriate S/Co value was determined as 12.27, at which sensitivity was 94.4 %, and specificity 97.4%. The positive and negative predictive values were calculated at the high rate of 95.7% and 96.6% respectively. Conclusions: The results of this study investigating the anti-HCV reactivity values which could be used in the diagnosis of HCV infection determined the most appropriate value to be 12.27. C1 [Kirisci, Ozlem] Necip Fazil City Hosp, Med Microbiol Dept, Kahramanmaras, Turkey. [Caliskan, Ahmet] Pamukkale Univ, Fac Med, Dept Med Microbiol, Denizli, Turkey.

Background: The genotype determination is of importance in the clinical management of hepatitis C virus (HCV) infection. Objectives: The aim of this study was to evaluate the distribution of genotypes in HCV patients in the Kahramanmaras region, Turkey, and determine if the genotype rates of Syrian refugee patients with hepatitis C are different from the population they migrated to. Methods: Blood samples sent to the microbiology laboratory between September 2014andFebruary 2018 were examined with genotyping using a real-time PCR reagent kit. Results: The results of 274 patients who were HCV genotype-assigned were obtained from the hospital electronic information system. Of 230 Turkish HCV patients, 121 (52.8%) were identified as genotype 3, 100 (43.3%) as genotype 1, five (2.2%) as genotype 2, and four (1.7%) as genotype 4. Of the 44 Syrian refugee patients, 24 (54.5%) were identified as genotype 1, 18 (40.9%) as genotype 4, one (2.3%) as genotype 2, and one (2.3%) as genotype 3. Conclusions: Predominant genotype 3 with the prevalence of 52.8% was seen to be more frequent in the current study region than in other regions of Turkey, demonstrating the highest rate of genotype 3 infection in Turkey to date. In Syria, the predominant HCV genotype is genotype 4 with a 57% prevalence, followed by genotype 1 with 29%. In the Syrian refugees, however, the current study showed genotype 1 was more frequent than genotype 4 (54.5% vs. 40.9%). This suggests that HCV genotypes may be affected by situations such as war and migration. © 2019 Author(s). All rights reserved.

DOGAN, GOKSEL/0000-0002-4583-3140; CINAR KUL, Bengi/0000-0002-8955-0097, WOS: 000510017700006, PubMed: 31504752, In vitro culture under atmospheric oxygen puts embryos under oxidative stress and impairs preimplantation development. However, to what extent this process alters the redox balance in the perinatal period remains largely unknown. the aim of the present study was to examine if the redox balance is altered in the lung tissue of fetuses generated through transfer of mouse embryos exposed to atmospheric oxygen at different stages of development and to determine if this has any effect on lung morphogenesis and gene expression. Two experimental groups (EGs) were generated by transferring in vitro- and in vivo-derived blastocysts to pseudo-pregnant females. in vivo-developed fetuses served as control. Enzymatic/nonenzymatic antioxidants, malondialdehyde (MDA) levels, total antioxidant capacity, stage of lung development and gene expression were evaluated on day 18 of pregnancy. Weight of fetuses was significantly less in both experimental cohorts (ANOVA, P < 0.001 versus control), associated with delayed lung development, higher amounts of MDA (ANOVA, P < 0.001 versus control) and altered expression of several genes in oxidative stress/damage pathways. Evidence gathered in the present study indicates that pre-implantation stress caused by culture under atmospheric oxygen, even for a short period of time, leads to fetal growth restriction, impaired lung development and redox balance along with dysregulation of several genes in oxidative stress response. Absence of an EG in which in vitro embryo culture was performed at 5% oxygen and the use of genetically heterogeneous F2 fetuses are the limitations of the study. in any case, the long-term impact of such dramatic changes in the developmental programming of resulting fetuses warrants further investigations., Scientific and Technological Research Council of Turkey (TUB.ITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [112O259], This work was funded by the Scientific and Technological Research Council of Turkey (TUB.ITAK, Project no: 112O259).

Background: Psoriasis is a chronic, inflammatory skin disease. The etiology of the disease is unknown. It is a polygenic and multifactorial disease, which interacts with genetic and environmental factors. Genetic factors (polymorphism/mutation) can alter the immune system and normal physiologically functioning keratinocytes to pathological or predisposition levels. Aims: We aimed to investigate psoriasis at a different and novel window by searching for vascular and immunological variations and intersections in psoriasis. We investigated the main vascular and hypoxic controlling factors, which are vascular endothelial growth factor (VEGF) and hypoxia inducible factor 1 alpha (HIF-1α), as well as immunological and serotonergic factors, such as TNF-α, IL-10, and 5HT2A, which could connect each other to the pathogenesis of psoriasis. Subjects and Methods: Nine single nucleotide polymorphisms (SNPs) in five genes were genotyped by mini-array format in 300 subjects: VEGF (rs2010963, rs833061, and rs1570360), HIF-1α (rs11549465), TNF-α (rs361525, rs1799964, and rs1800629), IL-10 (rs1800896), and 5HT2A (rs6311). Results: An association was found between rs1800629 (TNF-α) and Type I psoriasis, and rs833061 (VEGF) and Type II psoriasis. Haplotype analysis suggests that the coexistence of the polymorphisms rs1799964 (TNF-α), rs2010963 (VEGF), rs833061 (VEGF), and rs6311 (5HT2A) may be a protective factor for psoriasis. Conclusion: Our results suggest that the vascular component of the studied vasculo-immunologic variation is more relevant in the pathogenesis of psoriasis. © 2019 Indian Journal of Dermatology | Published by Wolters Kluwer - Medknow.

EgeUn###, 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 subtype 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. © 2019 Verlag Klinisches Labor GmbH. All rights reserved.

Human immunodeficiency virus (HIV) disease progression is associated with a marked change in the level of plasma cytokines. The study reported here investigated the level of mRNA expression of different cytokines: Tumour necrosis factor-alpha (TNF-α), interferon (INF)-gamma, interleukin-10 (IL-10) and IL-21 in the peripheral blood mononuclear cell among the antiretroviral therapy naive subtype C HIV-1 infected individuals and normal healthy controls by real time polymerase chain reaction. The mRNA expressions of all the 4 cytokines in HIV-1 infected individuals were significantly higher compared to healthy controls (P value range 0.0004–0.01). The mean level of IL-10, INF-gamma and TNF-α were higher in HIV infected individuals with low CD4 counts (

Background: Faced with the resurgence of malaria, malaria surveillance in the Peruvian Amazon incorporated consecutive active case detection (ACD) interventions using light microscopy (LM) as reactive measure in communities with an unusual high number of cases during high transmission season (HTS). We assessed the effectiveness in malaria detection of this local ACD-based strategy. Methods: A cohort study was conducted in June&ndash, July 2015 in Mazan, Loreto. Four consecutive ACD interventions at intervals of 10 days were conducted in four riverine communities (Gamitanacocha, Primero de Enero, Libertad and Urco Mira&ntilde, o). In each intervention, all inhabitants were visited at home, and finger-prick blood samples collected for immediate diagnosis by LM and on filter paper for later analysis by quantitative real-time polymerase chain reaction (qPCR). Effectiveness was calculated by dividing the number of malaria infections detected using LM by the number of malaria infections detected by delayed qPCR. Results: Most community inhabitants (88.1%, 822/933) were present in at least one of the four ACD interventions. A total of 451 infections were detected by qPCR in 446 participants (54.3% of total participants), five individuals had two infections. Plasmodium vivax was the predominant species (79.8%), followed by P. falciparum (15.3%) and P. vivax-P. falciparum co-infections (4.9%). Most qPCR-positive infections were asymptomatic (255/448, 56.9%). The ACD-strategy using LM had an effectiveness of 22.8% (detection of 103 of the total qPCR-positive infections). Children aged 5&ndash, 14 years, and farming as main economic activity were associated with P. vivax infections. Conclusions: Although the ACD-strategy using LM increased the opportunity of detecting and treating malaria infections during HTS, the number of detected infections was considerably lower than the real burden of infections (those detected by qPCR).

We present here a longitudinal study determining the effects of two 3 week-periods of high intensity high volume interval training (HIHVT) (90 intervals of 6 s cycling at 250% maximum power, Pmax/24 s) on a cycle ergometer. HIHVT was evaluated by comparing performance tests before and after the entire training (baseline, BSL, and endpoint, END) and between the two training sets (intermediate, INT). The mRNA expression levels of myosin heavy chain (MHC) isoforms and markers of energy metabolism were analyzed in M. vastus lateralis biopsies by quantitative real-time PCR. In incremental tests peak power (Ppeak) was increased, whereas V·O2 peak was unaltered. Prolonged time-to-exhaustion was found in endurance tests with 65 and 80% Pmax at INT and END. No changes in blood levels of lipid metabolites were detected. Training-induced decreases of hematocrit indicate hypervolemia. A shift from slow MHCI/β to fast MHCIIa mRNA expression occurred after the first and second training set. The mRNA expression of peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α), a master regulator of oxidative energy metabolism, decreased after the second training set. In agreement, a significant decrease was also found for citrate synthase mRNA after the second training set, indicating reduced oxidative capacity. However, mRNA expression levels of glycolytic marker enzyme glyceraldehyde-3-phosphate dehydrogenase did not change after the first and second training set. HIHVT induced a nearly complete slow-to-fast fiber type transformation on the mRNA level, which, however, cannot account for the improvements of performance parameters. The latter might be explained by the well-known effects of hypervolemia on exercise performance.

WOS: 000429311800001, Background: Hepatitis B virus (HBV) has a high mutation rate due to its unusual replication strategy leading to the production of a large number of virions with single and double mutations. The mutations, in turn, are associated with the development of drug resistance to nucleos(t)ide analogs (NUCs) in patients before and during NUCs therapy. Objectives: The current study aimed at investigating the molecular characterization of HBV in Turkish patients with chronic hepatitis B (CHB) infection. Methods: Polymerase chain reaction (PCR) amplification and direct sequencing procedures were used to analyze mutations. The detected drug resistance mutations were divided into the nucleos(t) ide analogs primary, partial, and compensatory resistance groups. The amino acid substitutions of hepatitis B surface antigen (HBsAg) were categorized into antiviral drug - associated potential vaccine-escape mutations (ADAPVEMs) and typical HBsAg amino acid substitutions, which included hepatitis B hyperimmunoglobulin (HBIg) - selected escape mutation, vaccine escape mutation, hepatitis B misdiagnosis, and immune - selected amino acid substitutions. Results: The number of patients included in the study was 528 out of which 271 (51.3%) were treatment - naive and 351 (66.3%) were hepatitis B e antigen (HBeAg) - negative. Moreover, 325 (61.6%) were males with a mean age of 38 years (range: 18 - 69). Primary, partial, and compensatory resistance to NUCs was reported in 174 (32.9%) patients. Six different ADAPVEM motifs were determined in both treatment - naive and treatment - experienced patients, namely, sF161L/rtI169X, sE164D/rtV173L, sL172L/rtA181T, sL173F/rtA181V, sS195M/rtM204V, and sS196L/rtM204I. The prevalence of ADAPVEMs and typical HBsAg escape mutations was 5.3% (n = 28) and 34.8% (n = 184), respectively. Conclusions: The analysis of drug resistance should constitute a fundamental part of the follow - up period of patients with CHB undergone treatment with NUCs. The surveillance of development of drug resistance mutations, while receiving treatment for hepatitis B is of paramount importance to monitor and control the emerging resistance.

Objective To show experimentally induced renal stone disease and to evaluate secondary inflammatory responses in vivo, and to characterize changes in the expression of Toll-like receptor (TLR) subtypes in this model. Methods Twenty 5- to 6-week-old male Wistar rats were divided into control and hyperoxaluria groups (n = 10 per group) and were supplied with normal water or 1% ethylene glycol, respectively, for 16 weeks. The animals were then placed in metabolic cages, and urine was collected for a 24-hour urine oxalate level evaluation. Following sacrifice, rats were subjected to bilateral nephrectomy and both kidneys were histopathologically evaluated. A 1-mm3 biopsy section from the right kidney of each rat was subjected to real-time polymerase chain reaction of the TLR expression. Results At the end of week 16, the hyperoxaluria group had a higher mean 24-hour urine oxalate level (1.91) than the control group (0.29) (P

Background Acute febrile illness (AFI) represent a significant health challenge in the Peruvian Amazon basin population due to their diverse etiologies and the unavailability of specific on-site diagnostic methods, resulting in underreporting of cases. In Peru, one of the most endemic regions to dengue and leptospirosis is Madre de Dios, a region also endemic to emergent bacterial etiologic agents of AFI, such as bartonellosis and rickettsiosis, whose prevalence is usually underreported. We aimed to molecularly identify the presence of Leptospira spp., Bartonella bacilliformis, and Rickettsia spp. by Polymerase Chain Reaction in serum samples from patients with AFI from Puerto Maldonado-Madre de Dios in Peru. Methods Serum samples from patients with acute febrile illness were analyzed by real-time PCR for detecting the presence of Bartonella bacilliformis, Leptospira spp. and Rickettsia spp. Results Bartonella bacilliformis was the most prevalent bacteria identified in 21.6% (30/139) of the samples, followed by Leptospira spp. in 11.5% (16/139) and Rickettsia spp. in 6.5% (9/139) of the samples. No co-infections were observed between these bacteria. The most frequent symptoms associated with fever among all groups, were headaches, myalgias, and arthralgias. We found no statistically significant differences in the clinical presentation between patients infected with each bacterium. Conclusions In a previous study, we shown the presence of dengue, chikungunya, Zika and oropouche virus. We were able to identify these pathogens in 29.5% of all the samples, with chikungunya and OROV as the most frequently found in 9.4 and 8.6% of all the samples, respectively. In this study we show that B. bacilliformis (21.6%), Leptospira spp. (11.5%) and Rickettsia spp. (6.5%) accounted for the main etiologies of AFI in samples from Puerto Maldonado-Madre de Dios, Perú. Our analysis of their clinical presentation, further shows the importance of implementing more sensitive and specific on-site diagnostic tools in the national surveillance programs.This study confirms that the un-specificity of signs and symptoms is not only associated with arboviral infections, but also with the clinical presentation of endemic bacterial infections.

WOS: 000442483900002 PubMed ID: 30132448 Background: We aimed to determine the effects of exercise followed by detraining on systolic blood pressure (SBP), heme oxygenase 2 (HO-2) expression, and carboxyhemoglobin (COHb) concentration in spontaneously hypertensive rats (SHR) to explain the role of carbon monoxide (CO) in this process. Material/Methods: Animals were randomized into exercised and detrained groups. Corresponding sedentary rats were grouped as Time 1-2. Swimming of 60 min/5 days/week for 10 weeks was applied. Detraining rats discontinued training for an additional 5 weeks. Gene and protein expressions were determined by real-time PCR and immunohistochemistry. Results: Aorta HO-2 histological scores (HSCORE) of hypertensive rats were lower, while SBP was higher. Swimming caused enhancement of HO-2 immunostaining in aorta endothelium and adventitia of SHR. Exercise induced elevation of blood COHb index in SHR. Synchronous BP lowering effect of exercise was observed. HO-2 mRNA expression, HSCORE, and blood COHb index were unaltered during detraining, while SBP was still low in SHR. Conclusions: CO synthesized by HO-2 at least partly plays a role in SBP regulation in the SHR-and BP-lowering effect of exercise. Regular exercise with short-term pauses may be advised to both hypertensives and individuals who are at risk. Pamukkale University Scientific Research Projects Coordination UnitPamukkale University [2012ARS002, 2013SBE002, 2016HZLDP018, 2018KRM002-201] This study is part of a PhD thesis and was supported by Pamukkale University Scientific Research Projects Coordination Unit through project numbers 2012ARS002, 2013SBE002, 2016HZLDP018 and 2018KRM002-201

Balamuthia mandrillaris, a free-living ameba, causes rare but frequently fatal granulomatous amebic encephalitis (GAE). Few patients have survived after receiving experimental drug combinations, with or without brain lesion excisions. Some GAE survivors have been treated with a multi-drug regimen including miltefosine, an investigational anti-leishmanial agent with in vitro amebacidal activity. Miltefosine dosing for GAE has been based on leishmaniasis dosing because no data exist in humans concerning its pharmacologic distribution in the central nervous system. We describe results of limited cerebrospinal fluid (CSF) and serum drug level testing performed during clinical management of a child with fatal GAE who was treated with a multiple drug regimen including miltefosine. Brain biopsy specimens, CSF, and sera were tested for B. mandrillaris using multiple techniques, including culture, real-time polymerase chain reaction, immunohistochemical techniques, and serology. CSF and serum miltefosine levels were determined using a liquid chromatography method coupled to tandem mass spectrometry. The CSF miltefosine concentration on hospital admission day 12 was 0.4 μg/mL. The serum miltefosine concentration on day 37, about 80 h post-miltefosine treatment, was 15.3 μg/mL. These are the first results confirming some blood–brain barrier penetration by miltefosine in a human, although with low-level CSF accumulation. Further evaluation of brain parenchyma penetration is required to determine optimal miltefosine dosing for Balamuthia GAE, balanced with the drug’s toxicity profile. Additionally, the Balamuthia isolate was evaluated by real-time polymerase chain reaction (PCR), demonstrating genetic variability in 18S ribosomal RNA (18S rRNA) sequences and possibly signaling the first identification of multiple Balamuthia strains with varying pathogenicities.

Simavli, Huseyin/0000-0003-1657-9099 WOS: 000356948400021 PubMed: 25957764 The aim of this study was to determine serum and aqueous xanthine oxidase (XO) levels, and mRNA expression in anterior lens epithelial cells in pseudoexfoliation (PEX). In this prospective study, serum, aqueous and anterior lens capsules were taken from 21 patients with PEX and 23 normal subjects who had undergone routine cataract surgery. Serum and aqueous XO levels were analyzed using the colorimetric method. mRNA expression of XO in anterior lens epithelial cells was evaluated using reverse transcription polymerase chain reaction analysis. Serum XO levels (means +/- standard deviations) were 207.0 +/- 86.1 IU/mL and 240.6 +/- 114.1 IU/mL in the normal and PEX groups, respectively (p = 0.310). Aqueous XO levels (means +/- standard deviations) were 65.5 +/- 54.3 IU/mL in the normal group and 130.5 +/- 117.4 IU/mL in the PEX group (p = 0.028). There was a 2.9 fold decrease in mRNA expression in anterior lens epithelial cells of PEX, which is significantly lower than the normal group (p = 0.01). Higher aqueous XO levels lacking associated different serum XO suggests higher oxidative stress in the aqueous. Higher aqueous XO levels in PEX with decreased mRNA expression in anterior lens epithelial cells indicate possible overexpression of XO in other structures related to the aqueous.

Chagas disease is an endemic zoonosis in Latin America and caused by the parasite Trypanosoma cruzi. This kinetoplastid displays remarkable genetic variability, allowing its classification into six Discrete Typing Units (DTUs) from TcI to TcVI. T. cruzi I presents the broadest geographical distribution in the continent and has been associated to severe forms of cardiomyopathies. Recently, a particular genotype associated to human infections has been reported and named as TcIDOM (previously named TcIa-b). This genotype shows to be clonal and adapted to the domestic cycle but so far no studies have determined the biological properties of domestic (TcIDOM) and sylvatic TcI strains (previously named TcIc-e). Hence, the aim of this study was to untangle the biological features of these genotypes in murine models. We infected ICR-CD1 mice with five TcI strains (two domestic, two sylvatic and one natural mixture) and determined the course of infection during 91days (acute and chronic phase of the disease) in terms of parasitemia, tissue tropism, immune response (IgG titers) and tissue invasion by means of histopathology studies. Statistically significant differences were observed in terms of parasitemia curves and prepatent period between domestic (TcIDOM) and sylvatic strains. There were no differences in terms of IgG antibodies response across the mice infected with the five strains. Regarding the histopathology, our results indicate that domestic strains present higher parasitemias and low levels of histopathological damage. In contrast, sylvatic strains showed lower parasitemias and high levels of histopathological damage. These results highlight the sympatric and behavioral differences of domestic and sylvatic TcI strains; the clinical and epidemiological implications are herein discussed. © 2014 Elsevier B.V.

Objectives: Caspase-1 (casp1), a key protease involved in the systemic inflammatory response syndrome (SIRS), controls the brain expression of a set of eight genes: Nos2 and Ptgs2 (nitric oxide synthase 2 and prostaglandin-endoperoxide synthase 2, two inducible enzymes), Cxcl1 and Cxcl10 (C-X-C motif chemokine ligand 1 and ligand 10), Tgtp and Gbp2 (T cell-specific GTPase 1 and guanylate-binding protein 2, two GTPases), Adamts1 (a disintegrin-like and metallopeptidase with thrombospondin type 1 motif, 1, a metalloprotease) and Il1rn (interleukin-1 receptor antagonist). Our objective was to ascertain whether casp1 also controlled the peripheral expression of these genes and, if so, to compare their central versus peripheral patterns of gene expression in immune and endocrine tissues during SIRS. Methods: Wild-type (wt) and casp1 knockout (casp1-/-) mice were injected with either saline or a high dose of endotoxin/lipopolysaccharide (LPS; 800 μg/mice i.p.). Saline-injected mice were immediately euthanized after injection, whereas LPS-injected mice were sacrificed 6 and 12 h after LPS administration. Hippocampal, splenic and adrenal gene expressions were determined by real-time PCR. Results: Overall, casp1-/- mice showed a lower inflammatory response than wt mice. The expression levels of powerful proinflammatory factors such as Nos2 and Ptgs2 was reduced in casp1-/- mice. Moreover, a hierarchical clustering analysis aimed at studying patterns of gene coexpression revealed large alterations in the hippocampal pattern of casp1-/- mice. Surprisingly, the expression of Adamts1 was increased in the hippocampus and adrenals of casp1-/- mice. Conclusions: The resilience of casp1-/- mice to SIRS lethality is associated with a lower inflammatory response, loss of hippocampal gene coexpression patterns, and increased hippocampal Adamts1 gene expression. The latter might be beneficial for casp1-/- mice, since ADAMTS1 is likely to play a role in neuronal plasticity. The mechanisms described here may help the development of either novel biomarkers or therapeutic targets against SIRS/sepsis.