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MicroRNAs (miRs) modulate the expression of target genes in the signal pathway on transcriptome level. The present study investigated the 'epigenetic-based miRNA (epi-miRNA)-mRNA' regulatory network of miR-34b, miR-34c, miR-148a, miR-152, miR-200a and miR-200b epi-miRNAs and their target genes, DNA methyltransferase (DNMT1, 3a and 3b), phosphate and tensin homolog (PTEN) and NK3 Homeobox 1 (NKX3.1), in prostate cancer (PCa) using reverse transcription-quantitative PCR. The expression level of NKX3.1 were not significantly different between the PCa, Met-PCa and control groups. However, in the PCa and Met-PCa groups, the expression level of DNMT1 was upregulated, while DNMT3a, DNMT3b and PTEN were downregulated. Overexpression of DNMT1 (similar to 5 and similar to 6-fold increase in the PCa and Met-PCa groups respectively) was accompanied by a decreased expression in PTEN, indicating a potential negative association. Both groups indicated that a high level of DNMT1 is associated with the aggressiveness of cancer, and there is a a directly proportional relationship between this gene and PSA, GS and TNM staging. A significant similar to 2 to similar to 5-fold decrease in the expression levels of DNMT3a and DNMT3b was found in both groups. In the PCa group, significant associations were identified between miR-34b and DNMT1/DNMT3b; between miR-34c/miR-148a and all target genes; between miR-152 and DNMT1/DNMT3b and PTEN; and between miR-200a/b and DNMT1. In the Met-PCa group, miR-148a, miR-152 and miR-200b exhibited a significant association with all target genes. A significant negative association was identified between PTEN and DNMT1 in the Met-PCa group. It was also revealed that that miR-148a, miR-152 and miR-200b increased the expression of DNMT1 and suppressed PTEN. Furthermore, the 'epi-miRNA-mRNA' bidirectional feedback loop was emphasised and the methylation pattern in PCa anti-cancer therapeutics was highlighted.

Purpose: In Turkey, pneumococcal conjugate vaccine (PCV) was introduced to the national immunization program as PCV7 in 2008, and was replaced with PCV13 in 2011. The aim of the study was to demonstrate the pneumococcal carriage rate and the serotype distribution in healthy children under 5 years in Turkey who were vaccinated with PCV13. Methods: We conducted a cross-sectional study including the collection of questionnaire data and nasopharyngeal (NP) specimens among children aged, Pfizer [WI229479], The study was supported by Pfizer [grant number WI229479].

WOS: 000513186600001, PubMed: 32028863, Neisseria meningitidis (N. meningitidis) is regarded as the leading cause of bacterial meningitis in many regions of the world. The empiric antimicrobial treatment is mainly based on antimicrobial resistance and patient characteristics. We aimed to analyze susceptibility patterns of N. meningitidis strains isolated in Turkey. Invasive meningococci collected in a multicenter, hospital-based, epidemiological surveillance study of pediatric (0-18 years of age) bacterial meningitis cases between 2013 and 2018 were studied. Five isolates (8.7%) displayed resistance to penicillin-G, while 13 isolates (22.8%) had intermediate susceptibility. All isolates were cefotaxime and rifampin susceptible. The data shows appropriateness of third-generation cephalosporins in empirical use for meningococcal infections in children. Since Turkey is located in a transition zone geographically, surveillance reports are very crucial.

WOS: 000462484500020, PubMed: 30869496, Streptococcus pneumoniae is the most common cause of complicated pneumonia. Pneumococcal necrotizing pneumonia (PNP) is a rare and serotype related complication. Serotypes 1, 3, 14, 15, 19A and 33 were the most reported serotypes in children with PNP before immunization. Despite widespread vaccination, S. pneumoniae is still cause of invasive diseases. We reported a child, fully immunized with 13-valent conjugated pneumococcal vaccine (PCV13) who was diagnosed PNP due to serotype 3. Breakthrough invasive infection caused by S. pneumoniae must be considered in mind despite fully vaccination.

Invasive pneumococcal infections among children are a serious public health problem in many countries, including Turkey. Pneumococcal conjugate vaccine has been included in Turkey's National Immunization Programme since 2009. We report the first two pediatric cases of invasive pneumococcal infection due to non-vaccine serotype 15A after pneumococcal conjugate vaccine implementation in Turkey. It is essential to monitor the countries' own local seroepidemiologic data for detecting selective pressure of non-vaccine serotypes of S. pneumonia.

WOS: 000401516100041, PubMed ID: 28140784, The serogroup epidemiology of invasive meningococcal disease (IMD), which varies considerably by geographic region and immunization schedule, changes continuously. Meningococcal carriage data are crucial for assessing IMD epidemiology and designing f potential vaccination strategies. Meningococcal seroepidemiology in Turkey differs from that in other countries: serogroups W and B are the predominant strains for IMD during childhood, whereas no serogroup C cases were identified over the last 10 y and no adolescent peak for IMD was found. There is a lack of data on meningococcal carriage that represents the whole population. The aims of this multicenter study (12 cities in Turkey) were to evaluate the prevalence of Neisseria meningitidis carriage, the serogroup distribution and the related risk factors (educational status, living in a dormitory or student house, being a household contact with Hajj pilgrims, smoking, completion of military service, attending bars/clubs) in 1518 adolescents and young adults aged 10-24 y. The presence of N. meningitidis DNA was tested, and a serogroup analysis was performed using polymerase chain reaction. The overall meningococcal carriage rate was 6.3% (n = 96) in the study population. A serogroup distribution of the 96 N. meningitidis strains isolated from the nasopharyngeal specimens revealed serogroup A in 5 specimens (5.2%), serogroup B in 9 specimens (9.4%), serogroup W in 64 specimens (66.6%), and serogroup Y in 4 specimens (4.2%); 14 were classified as non-grouped (14.4%). No serogroup C cases were detected. The nasopharyngeal meningococcal carriage rate was 5% in the 10-14 age group, 6.4% in the 15-17 age-group, and 4.7% in the 18-20 age group; the highest carriage rate was found in the 21-24 age group (9.1%), which was significantly higher than those of the other age groups (p < 0.05). The highest carriage rate was found in 17-year-old adolescents (11%). The carriage rate was higher among the participants who had had close contact with Hajj/Umrah pilgrims (p < 0.01) or a history of upper respiratory tract infections over the past 3 months (p < 0.05). The nasopharyngeal carriage rate was 6.3% among adolescents and young adults in Turkey and was similar to the recent rates observed in the same age groups in other countries. The most prevalent serogroup was W, and no serogroup C cases were found. In conclusion, the present study found that meningococcal carriage reaches its peak level by age 17, the highest carriage rate was found in 21-to 24-year-olds and the majority of the carriage cases were due to serogroup W. Adolescents and young adult carriers seem to be a potential reservoir for the disease, and further immunization strategies, including adolescent immunization, may play a role in the control of IMD., Scientific Research Projects of the Eskisehir Osmangazi University [2014/455], The study was fully financed by the Scientific Research Projects of the Eskisehir Osmangazi University (2014/455).

The aim of the present study was to analyze the molecular mechanisms involved in blocking the signaling pathway and the effects of this on the progression of prostate cancer (CaP) cells in vitro. LNCaP human CaP cell line was stimulated with interleukin-6 (IL-6) in the presence/absence of Janus kinase (JAK) 2 (AG490), signal transducer and activator of transcription 3 [(STAT3) S3I-201] inhibitors and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Cytotoxic activity, the activation of phosphorylated (p)-STAT3 protein, caspase (CASP) 3 activity at protein level, vascular endothelial growth factor (VEGF) A, VEGFC, vascular endothelial growth factor receptor 2, STAT3, matrix metalloproteinase-2, myeloid cell leukemia sequence 1 (MCL-1), CASP8 and CASP9 messenger RNA (mRNA) levels were determined. Morphology and apoptosis were confirmed by DAPI staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. IL-6 rapidly induced the phosphorylation of STAT3 in a dose- and time-dependent manner with a peak expression at 3 h at a concentration of 25 ng/ml. In addition, AG490 (50 μM) and S3I-201 (300 μM) inhibited STAT3 activation. Western blotting results revealed that p-STAT3 protein expression decreased significantly with AG490 and S3I-201 treatment in LNCaP cells. AG490 and S3I-201 induced the downregulation of VEGFA, MCL-1 and STAT3 and the upregulation of CASP8 and CASP9 mRNA transcription levels. In addition, the inhibitors increased the level of CASP3 protein. Combinations of AG490- and S3I-201-TRAIL did not result in an increase in this effect. Parallel results were found by DAPI staining and TUNEL assay. To the best of our knowledge, this is the first study to investigate the possible clinical use of AG490 or S3I-201, together with the reduced use of chemotherapeutic agents with high cytotoxicity, for their ability to exert an apoptotic effect, targeting the JAK/STAT3 pathway.

Objective: The potential role of procalcitonin (PCT) in the diagnosis of catheter-related bloodstream infection (CRBSIs) is still unclear and requires further research. The diagnostic value of serum PCT for the diagnosis of CRBSI in children is evaluated here. Method: This study was conducted between October 2013 and November 2014, and included patients with suspected CRBSI from 1 month to 18 years of age who were febrile, with no focus of infection, and had a central venous catheter. Levels of PCT and other serum markers were measured, and their utility as CRBSI markers was assessed. Additionally, the clinical performance of a new, automated, rapid, and quantitative assay for the detection of PCT was tested. Results: Among the 49 patients, 24 were diagnosed with CRBSI. The PCT-Kryptor and PCT-RTA values were significantly higher in proven CRBSI compared to those in unproven CRBSI (p = 0.03 and p = 0.03, respectively). There were no differences in white blood cell count and C-reactive protein (CRP) levels between proven CRBSI and unproven CRBSI. Among the 24 patients with CRBSI, CRP was significantly higher among those with Gram-negative bacterial infection than in those with Gram-positive bacterial infections. PCT-Kryptor was also significantly higher among patients with Gram-negative bacterial infection than in those with Gram-positive bacterial infections (p = 0.01 and p = 0.02, respectively). Conclusions: The authors suggest that PCT could be a helpful rapid diagnostic marker in children with suspected CRBSIs. Resumo: Objetivo: O possível papel da procalcitonina (PCT) no diagnóstico de infecções de corrente sanguínea relacionadas a cateter (ICSRCs) ainda não está claro e precisa ser mais pesquisado. O valor diagnóstico da PCT sérica para o diagnóstico de ICSRC em crianças é avaliado neste estudo. Método: Este estudo foi feito entre outubro de 2013 e novembro de 2014 e incluiu pacientes com suspeita de ICSRC de um mês a 18 anos de idade que estavam febris, não tinham foco de infecção e tinham cateter venoso central. Foram medidos os níveis de PCT e de outros marcadores séricos, cuja utilidade como marcadores de ICSRC foi avaliada. Adicionalmente, foi testado o desempenho clínico de um novo ensaio quantitativo automatizado e rápido para a detecção de PCT. Resultados: Dentre 49 pacientes, 24 foram diagnosticados com ICSRC. Os valores de PCT-Kryptor e PCT-RTA foram significativamente maiores em ICSRCs comprovadas do que em ICSRCs não comprovadas (p = 0,03 e p = 0,03, respectivamente). Não houve diferença na contagem de glóbulos brancos e nos níveis de proteína C reativa (PCR) entre ICSRCs comprovadas e ICSRCs não comprovadas. Dentre os 24 pacientes com ICSRC, a PCR era significativamente maior entre aqueles com infecção bacteriana gram-negativa do que naqueles com infecção bacteriana gram-positiva. O PCT-Kryptor também foi significativamente maior entre pacientes com infecção por bactérias gram-negativas do que naqueles com infecção por bactérias gram-positivas (p = 0,01 e p = 0,02, respectivamente). Conclusões: Sugerimos que a PCT pode ser um marcador de diagnóstico rápido útil em crianças com suspeita de ICSRCs. Keywords: Biomarkers, Bloodstream infection, Children, C-reactive protein, Procalcitonin, Palavras-chave: Biomarcadores, Infecção da corrente sanguínea, Crianças, Proteína C reativa, Procalcitonina

WOS: 000305386800011, PubMed ID: 22711352, The age-specific human papillomavirus (HPV) seroprevalence and HPV type distribution in women with normal cervical cytology were studied. Cervical smear samples obtained using liquid-based smears from 582 clinically healthy women aged between 15 and 68 years from five centers from four different regions of Turkey, were studied between February 2010 and January 2011. Overall, 530 of the women with normal cytology were included and the samples were analyzed for the presence of HPV by AmpliTaq. Positive samples were typed further for 37 different HPV genotypes by a line blot assay. HPV was positive in 17.9% of the women. HPV prevalence was highest in the age group of 2529 years (31.8%), and decreased with increasing age. HPV 16 was the most common type (3.6%) followed by type 6 (2.6%) and type 45 (2.2%). Types 11 and 18 were rare (0.6% and 0.4%, respectively). Among the risk factors, number of sexual partners and parity were positively correlated with HPV positivity. In the present study, a large number of sex partners and high parity increased the risk for HPV infection. The age-specific distribution of HPV in women with normal Pap smears did not show a U-shaped curve in contrast to European countries and the USA. J. Med. Virol. 84: 12421247, 2012. (C) 2012 Wiley Periodicals, Inc.

Three clusters of Chryseobacterium meningosepticum infections in a tertiary health center in July 2006 and January 2007 involving 8 newborns and 5 older children were investigated. The index patient was from the neonatal intensive care unit, and the older patients were from other pediatric wards. Cultures were obtained from the environment and from health care workers' hands as part of an outbreak investigation. C meningosepticum was isolated from hand cultures obtained from a senior resident and from environmental cultures obtained from powdered infant formula, an electrical button, a computer keyboard, phone, a doorknob, and an Ambu bag. Antibiogram typing and enterobacterial repetitive intergenic consensus sequence polymerase chain reaction indicated that all of the isolates were epidemiologically related. Nine patients improved on antimicrobial treatment, and 4 premature infants died after the infection. C meningosepticum is a well-known etiologic agent for nosocomial infections involving newborns and immunocompromised patients. Wet and dry environmental surfaces and equipment may act as a source or play a role in disseminating the microorganism. Outbreaks may be controlled with strong emphasis on infection control measures.

Background: Acute otitis media (AOM) is one of the most common childhood diseases requiring antimicrobial prescription drugs in pre-school children. In this study, we sought to describe the bacterial etiology of pediatric cases of AOM in Turkey. Materials and Methods: This prospective, multi-center, tympanocentesis-based epidemiological study was performed during 2010-2012in children aged between3 months and 6 years. All isolates were cultured and sero grouped by the Quellung reaction. Results: During 2010-2012, 38 cases fulfilled the study inclusion criteria. Overall, 45% of samples were culture positive for bacterial pathogens Streptococcus pneumonia (13.1%) was the leading cause of bacterial AOM followed by Streptococcus pyogenes (10.5%) and H. influenza (7.9%). Serotype-3 was detected in two of the samples, and serotypes 9V, 19, and 19A were isolated from one patient each. S. pneumoniae was detected in 36% (4/11) of otorrhea samples. All H. influenzae-positive samples were collected by tympanocentesis. All H. influenzae isolates were identified as non-typeable. The pneumococcal serotype coverage rates for PCV-7, PVC-10 and PCV-13 were 20% (1/5), 20% (1/5), and 80% (4/5), respectively. PHiD-CV (PCV-7 types plus 1, 5, and 7F) targets non-typeable H. influenza, and 4 of 38 (11%) of the pathogens causing episodes of AOM were also covered. Conclusion and Recommendation: In Turkey, S.pneumonia remains the most common pathogen in children with AOM. Both S. pneumonia and non-typeable H. influenzae represent important targets for vaccination strategies to reduce AOM in children. Based on our results, conjugated pneumococcal vaccines may have potential impact to decrease the burden of AOM. © 2013 Ceyhan M, et al.

WOS: 000348316800043, PubMed: 25483487, Successful vaccination policies for protection from bacterial meningitis are dependent on determination of the etiology of bacterial meningitis. Cerebrospinal fluid (CSF) samples were obtained prospectively from children from 1 month to, Novartis Vaccines and Diagnostics; GlaxoSmithKlineGlaxoSmithKline, The study was supported by Novartis Vaccines and Diagnostics (for 5 years) and by GlaxoSmithKline (for 2 years). The authors declare that they have no other conflicts of interest.

WOS: 000320857300004, PubMed ID: 23637041, Streptococcus pneumoniae is the most common etiological cause of complicated pneumonia, including empyema. In this study, we investigated the serotypes of S. pneumoniae that cause empyema in children. One hundred fifty-six children who were diagnosed with pneumonia complicated with empyema in 13 hospitals in seven geographic regions of Turkey between 2010 and 2012 were included in this study. Pleural fluid samples were collected by thoracentesis and tested for 14 serotypes/serogroups using a Bio-Plex multiplex antigen detection assay. The serotypes of S. pneumoniae were specified in 33 of 156 samples. The mean age +/- the standard deviation of the 33 patients was 6.17 +/- 3.54 years (range, 0.6 to 15 years). All of the children were unvaccinated according to the vaccination reports. Eighteen of the children were male, and 15 were female. The serotypes of the non-7-valent pneumococcal conjugated vaccine (non-PCV-7), serotype 1, serotype 5, and serotype 3, were detected in eight (14.5%), seven (12.7%), and five (9.1%) of the samples, respectively. Serotypes 1 and 5 were codetected in two samples. The remaining non-PCV- 7 serotypes were 8 (n = 3), 18 (n = 1), 19A (n = 1), and 7F/A (n = 1). PCV-7 serotypes 6B, 9V, 14, 19F, and 23F were detected in nine (16.3%) of the samples. The potential serotype coverages of PCV-7, PCV-10, and PCV-13 were 16.3%, 45.4%, and 60%, respectively. Pediatric parapneumonic empyema continues to be an important health problem despite the introduction of conjugated pneumococcal vaccines. Active surveillance studies are needed to monitor the change in S. pneumoniae serotypes that cause empyema in order to have a better selection of pneumococcal vaccines., GlaxoSmithKlineGlaxoSmithKline, The study was supported by GlaxoSmithKline.

Background: Despite high vaccination coverage, pertussis continues to be a great public health problem. Adults and adolescents are source of infection for infants who are too young to be completely vaccinated. The aim of the study is detect if there is a household transmission of pertussis. Methods: Presence of Bordetella pertussis among the household contacts of the children who had had the positive result for Bordetella pertussis by real-time polymerase chain reaction was detected. Results: Of the 173 infants with clinical suspicion of pertussis, 48 (27.7%) turned out to be positive by PCR. The mothers of 19 (41.3% of all tested mothers) of them were also PCR positive for B. pertussis, being the family member most frequently infected. Conclusion: Despite high coverage of pertussis vaccination in Turkey, pertussis is prevalent both in incompletely protected infants and older children. High rate of presence of the bacteria in the household contacts depicts the importance of further pertussis booster vaccination in adolescents, adults and the targeted vaccination of the adults having close contacts with infants (cocoon strategy). © 2013 Tamburaci{dotless} Uslu ZD, et al.

Invasive meningococcal disease is a recognized public health problem worldwide, with a dynamic and changeable epidemiology. In Turkey, the second most common pathogenic meningococcal serogroup (after serogroup B) is W-135, including an epidemic in 2005, which has been strongly associated with Hajj pilgrims and their close contacts. In two studies conducted in 2010, we assessed meningococcal carriage in intending Turkish pilgrims to the Hajj when they attended to receive a plain polysaccharide vaccine against serogroups A, C, W-135, and Y and, upon their return, to determine the acquisition of meningococcal carriage by the pilgrims themselves and subsequently their household contacts. Nasopharyngeal swabs were obtained from pilgrims before the Hajj and upon their return. Swabs were then obtained from 39 household contacts of pilgrims who were shown to have acquired carriage during the Hajj. Of the 472 pilgrims before the Hajj, 63 (13%) were positive for meningococcal carriage, of which 52 cases (83%) were serogroup W-135. In the 296 pilgrims tested after the Hajj, 81 (27%) were positive for meningococcal carriage, including 74 (91%) with W-135. In 11 family members of pilgrims who acquired W-135 carriage at the Hajj, 10 (91%) had acquired carriage of serogroup W-135. This study illustrates the acquisition of meningococcal carriage, predominantly of serogroup W-135 by pilgrims attending the Hajj, and the transmission of this carriage to their family members on their return, explaining the source of W-135 meningococcal disease in Turkey.

Bulgular: Sisplatinin 72 saatte doza bagli sitotoksik etki gosterdigi ve uygun apoptotik dozunun yine bu saat icin 50μM oldugu tespit edilmistir. Arastirilan uc genin mRNA duzeylerinin, 5μM sisplatin uygulandiginda kontrole gore istatistiksel olarak anlamli artis gosterdigi belirlenmistir (p 0.05), ancak ayni doz ve surede CASP3 mRNA duzeyinin 2.2 kat, CASP8 mRNA duzeyinin 3.0 kat arttigi bulunmustur (p