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Background Since 2011, the therapeutic landscape of melanoma has changed dramatically because of the adoption of immune checkpoint inhibitor and targeted therapies. The authors sought to quantify the effects of these changes on short-term treatment costs by comparing the first-year cancer-attributable costs in novel (2011-2015) and historical (2004-2010) treatment eras. Methods The authors estimated the first-year cancer-attributable and out-of-pocket (OOP) costs by cancer stage at diagnosis by using a case-control approach. Patients aged ≥67 years with melanoma results were used to calculate the total direct costs of treatment during the first year after the diagnosis of melanoma in the US Medicare population older than 65 years. Costs were reported in 2018 dollars. Results Costs increased with the stage at diagnosis. Average first-year cancer-attributable costs per patient for stage IV patients increased significantly by 61.7% from $45,952 to $74,297 after the adoption of novel treatments. Per-patient OOP responsibility decreased by almost 30.8% across all stages of cancer but increased by 16.5% for stage IV patients from 2004 ($7646) to 2015 ($8911). The total direct cost of treatment for persons with melanoma older than 65 years increased by $16.03 million (4.93%) from $324.68 million in 2010 to $340.71 million in 2015. The largest increase in yearly total cost, $23.64 million (56.53%), was observed among stage IV patients. Conclusions The direct cost of melanoma increased significantly in the Medicare population, particularly for advanced-stage disease. Prevention and early detection initiatives may reduce the economic burden of melanoma.

BACKGROUND There has been no study evaluating the psychopathology in breastfeeding mothers of infants with food allergy (FA). OBJECTIVE The aim of the study was to investigate the relationship between dietary elimination and maternal psychopathology, specifically anxiety, depression, and mother-to-infant bonding, in breastfeeding mothers of infants with food allergy. METHODS Breastfeeding mothers following an elimination diet due to FA in their children aged 1-to-12 months were compared with the healthy controls. The physician-diagnosed FA group was divided into IgE-, non-IgE-mediated, and infants with some minor symptoms which were not enough to make the diagnosis of FA were classified as Indecisive symptoms for FA group. Mothers completed standardized questionnaires including Symptom Checklist 90R, Beck Depression/Anxiety Inventories (BDI/BAI), Postpartum Bonding Questionnaire (Bonding). RESULTS Of 179 mother and infants, 64 were healthy, 89 were FA, 16 were indecisive symptoms for FA. The mean age of the mothers and infants were 31.1 ± 4.7 years and 6.3 ± 3.6 months, respectively. The physician-diagnosed FA groups had higher scores for anxiety (p = .008), anger (p = .042), depression (p

There is conflicting data regarding the role of transforming growth factor-β1 (TGF-β1) in the pathogenesis of airway hyper-reactivity and asthma exacerbation.To investigate the role of exhaled-TGF-β1 in exercise-induced bronchospasm (EIB) in asthmatic and nonasthmatic healthy children, and in asthma exacerbation and asthma control.The exhaled-TGF-β1 levels of 56 stable asthmatic children and 15 nonasthmatic healthy children were evaluated before and 30 min after an exercise challenge. The exhaled-TGF-β1 levels of 20 additional children with asthma exacerbation were evaluated.While no significant difference in the exhaled-TGF-β1 levels was found at the baseline, exhaled-TGF-β1 levels after the exercise challenge were significantly higher in the non-EIB (Our results suggest that TGF-β1 may play a role in suppressing airway reactivity and its deficiency is associated with asthma exacerbation.

Background: There has been no trial evaluating the psychopathology in breastfeeding mothers of infants with food allergy (FA). Objective: To investigate the effect of dietary elimination on maternal psychopathology, specifically stress/anxiety and mother-to-infant bonding and explore the importance of sociodemographic features on these variables. Methods: Breastfeeding mothers following an elimination diet due to FA in their children aged 1-to-12 months were compared with the healthy controls. Physician-diagnosed FA group were divided into IgE-, non-IgE-mediated and infants with some minor symptoms which were not enough to make the diagnosis of FA were classified as Indecisive symptoms for FA group. Mothers completed standardized questionnaires including Symptom Checklist 90R, Beck Depression/Anxiety Inventories (BDI/BAI), Postpartum Bonding Questionnaire (Bonding). Results: Of 179 mother-infants, 64 were healthy, 89 were FA, 16 were indecisive symptoms for FA. The mean age of the mothers and infants were 31.1±4.7 years and 6.3±3.6 months. The physician diagnosed FA groups had higher scores for anxiety (p=0.008), anger (p=0.042), depression (p

Spontaneous combustion of coal is a complex underground mining disaster, which mainly threats mine safety and efficiency. Several factors usually cause spontaneous combustion of coal, such as gas concentration, ventilation and coal properties. In this study, spontaneous combustion tendencies of coal mines were predicted considering the effective parameters for an underground coal mine in Turkey. Multinomial logistic regression, a multivariate statistical technique, was applied. Gas concentrations (CH4, CO, O2) and air velocity were defined as factors affecting spontaneous coal combustion. Fire hazard levels of the coal mines were determined as ‘normal situation’ and ‘potential combustion’. It was observed that CH4 and CO variables and CH4 × CO interaction were effective in the formation of clusters. The results indicate that Mine I is more liable to spontaneous combustion than Mine II and Mine III. At the same time, the effects of variations in factors are examined in the study.

In this study, a new hybrid-clustering algorithm is proposed for model-based clustering of multivariate data. In order to dimension reduction with variable selection in multivariate data, heterogeneous (mixture) structures in the variables are determined according to the univariate Gaussian mixture models (GMM). Component numbers of variables in heterogeneous data are determined comparatively based on univariate Gaussian mixture distribution and k-means algorithms. Based on the number of components (subgroup) in the variables, the number, orientations and structure of the clusters are determined by the mixture models created. The number of candidate mixture models that can be determined by the soft calculation method developed for model-based determination of cluster structures consisting of mixture distributions is determined. Information criteria are used to select the best model that fits the data among candidate mixture models. In selecting the best model, information criteria based on likelihood function, such as AIC (Akaike Information Criteria) and BIC (Bayesian Information Criteria) are used.

Background: Benefit–harm tradeoffs of melanoma screening depend on disease risk and treatment efficacy. We developed a model to project outcomes of screening for melanoma in populations with different risks under historic and novel systemic treatments. Methods: Computer simulation model of a screening program with specified impact on overall and advanced-stage incidence. Inputs included meta-analyses of treatment trials, cancer registry data, and a melanoma risk prediction study Results: Assuming 50% reduction in advanced stage under screening, the model projected 59 and 38 lives saved per 100,000 men under historic and novel treatments, respectively. With 10% increase in stage I, the model projects 2.9 and 4.7 overdiagnosed cases per life saved and number needed to be screened (NNS) equal to 1695 and 2632 under historical and novel treatments. When screening was performed only for the 20% of individuals with highest predicted risk, 34 and 22 lives per 100,000 were saved under historic and novel treatments. Similar results were obtained for women, but lives saved were lower. Conclusions: Melanoma early detection programs must shift a substantial fraction of cases from advanced to localized stage to be sustainable. Advances in systemic therapies for melanoma might noticeably reduce benefits of screening, but restricting screening to individuals at highest risk will likely reduce intervention efforts and harms while preserving >50% of the benefit of nontargeted screening. Impact: Our accessible modeling framework will help to guide population melanoma screening programs in an era of novel treatments for advanced disease.

In this study, a new algorithm was developed for clustering multivariate big data. Normal mixture distributions are used to determine the partitions of variables. Normal mixture models obtained from the partitions of variables are generated using Genetic Algorithms (GA). Each partition in the variables corresponds to a clustering center in the normal mixture model. The best model that fits the data structure from normal mixture models is obtained by using the information criteria obtained from normal mixture distributions.

A new method for semi-supervised classification of remotely-sensed multispectral image data is developed in this study. It consists of unsupervised-clustering for data labelling and supervised-classification of clusters in multispectral image data (MID) using spectral signatures. Mixture model clustering, based on model selection, is proposed for finding the number and determining the structures of clusters in MID. The best mixture model, for the best clustering of data, finds the number and determines the structure of clusters in MID. The number of elements in the best mixture model fits to the number of clusters in MID. The elements of the best mixture model fits to the structure of clusters in MID. Clusters in MID is supervised-classified using spectral signatures. Euclidean distance is used as the discrimination function for the supervised-classification method. The values of Euclidean distances are used as decision rule for the supervised-classification method.

BACKGROUND This study aimed to evaluate the ratio of C-reactive protein (CRP) to albumin, inflammatory markers, and parameters from the complete blood count (CBC) in patients with Takayasu arteritis and the association with disease activity. MATERIAL AND METHODS A retrospective study included thirty-two patients with Takayasu arteritis and 32 healthy controls. Clinical and demographic characteristics of patients with Takayasu arteritis were recorded at baseline, before medication and on remission. Similar data were obtained for the controls at recruitment. Remission was defined as more than six months of stable disease without new vascular lesions in patients who previously had active disease. Kerr's criteria were used to define active Takayasu arteritis. RESULTS In patients with Takayasu arteritis, the erythrocyte sedimentation rate (ESR), CRP, CRP/albumin ratio, red cell distribution width (RDW), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and monocyte-lymphocyte ratio (MLR) were significantly higher, and albumin and MPV were significantly lower compared with controls. The ESR, CRP, CRP/albumin ratio, NLR, PLR, and MLR were decreased in remission, whereas MPV was increased. CRP and the CRP/albumin ratio were positively correlated and albumin and MPV were negatively correlated with disease activity. The CRP/albumin ratio had the highest correlation with disease activity in Takayasu arteritis. The CRP/albumin ratio, RDW, NLR, PLR, and MLR were positively correlated with CRP and ESR. CONCLUSIONS The CRP/albumin ratio, RDW, NLR, PLR, MLR, and MPV were markers of remission of active disease, and the CRP/albumin ratio, total albumin, and MPV were markers of disease activity in Takayasu arteritis.

Contemporary developments in computer vision and artificial intelligence show promise to greatly improve the lives of those with disabilities. In this paper, we propose one such development: a wearable object recognition device in the form of eyewear. Our device is specialized to recognize items from the produce section of a grocery store, but serves as a proof of concept for any similar object recognition wearable. It is user friendly, featuring buttons that are pressed to capture images with the built-in camera. A convolutional neural network (CNN) is used to train the object recognition system. After the object is recognized, a text-to-speech system is utilized to inform the user which object they are holding in addition to the price of the product. With accuracy rates of 99.35%, our product has proven to successfully identify objects with greater correctness than existing models.

The anti-inflammatory effect of high-dose inhaled corticosteroids (ICS) in children with asthma exacerbation is unknown. We aimed to investigate the efficacy of single-high dose ICS versus oral prednisone treatment followed by a course of six day high-dose ICS or oral prednisone (P) treatment on the concentrations of Cys-LTs and 8-isoprostane levels in the exhaled breath condensate (EBC) of children with asthma exacerbation.Ninety-four children with moderate-severe asthma exacerbation were evaluated with asthma scores, peak expiratory flow rate (PEF), forced expiratory volume in first second (FEV1) and exhaled Cys-LT and 8-isoprostane levels before and after treatment. EBC was collected from 52 patients before and four hours after treatment with inhaled fluticasone propionate (FP) (4000 μg) or P and after six days of treatment with FP-1000 μg/day or P. Cys-LTs and 8-isoprostane concentrations were determined using a specific immunoassay kit.Both single high-dose FP (n=59) and p (n=35) treatment resulted in a significant improvement in asthma score (p0.0001), PEF (p0.0001), and FEV1 (p0.0001). Cys-LT concentration in the EBC decreased significantly both after the initial treatment (p=0.001), and at the end of the six-day period in the FP group (p0.0001). 8-Isoprostane concentration was lower only after six days of treatment with FP-1000 μg/day in the FP group (p=0.023). There was a significant decrease in exhaled Cys-LTs after four hours (p=0.012) and six days of P treatment (p=0.018) in children with asthma exacerbation.High-dose ICS treatment may be useful in the treatment of children with asthma exacerbation. The effects start as early as after four hours. The suppression of Cys-LTs production contributes to the early effects. Suppression of both Cys-LTs and oxidants may favourably contribute to the effects observed later.

BACKGROUND AND OBJECTIVES There are controversial results in the literature regarding urinary electrolytes, especially potassium, in enuretic children. KCNJ10 channel protein, a member of the Kir 4.1 family is expressed in renal distal tubules and has an important function in renal ion transport. We investigated whether KCNJ10 gene polymorphisms are associated with clinical and laboratory findings of a group of Turkish children with monosymptomatic primary nocturnal enuresis (MNE). METHOD Ninety-seven MNE children and 100 healthy controls were tested for three single nucleotide polymorphisms (SNPs) in the KCNJ10 gene. The transversions in SNPs were G to A for intron 1(SNP1), G to A for exon 2 (SNP2), and T to C transition for promoter (SNP3). All SNPs were genotyped by PCR-restriction fragment length polymorphism. RESULTS SNP3 in promoter of KCNJ10 gene showed strong association with MNE children for distribution of genotype and allele frequency, while SNP1 in intron 1 and SNP2 in exon 2 were noninformative. The distribution of TT, TC, and CC genotypes for SNP3 was 66%, 26.8% and 7.2% respectively in MNE compared with 38%, 59% and 3% respectively in controls (p < 0.0001). In enuretic children, TT genotype was higher and there was an increased potassium excretion in children with TT genotype (P < 0.05). CONCLUSION We conclude that KCNJ10 gene promoter polymorphism may have a role on potassium excretion in Turkish MNE children. This is the first study in literature evaluating KCNJ10 gene polymorphism in this patient population. Future studies investigating the other SNPs, mutations or altered regulation of Kir4.1 in larger samples would help clarify the role (s) of KCNJ10 gene in enuresis.

Aim: Ankylosing spondylitis (AS) is a chronic disease featuring axial changes, peripheral arthritis and systemic involvement. AS is not only characterized by the strongest genetic contribution for any complex rheumatological disease but is also influenced by environmental and immunological factors. Various proinflammatory cytokines such as tumor necrosis factor (TNF), interleukin- (IL-) 1, IL-6, IL17/28 are probably involved in AS pathogenesis. Recent years IL -23 / IL-17 pathway in the disease pathogenesis has been shown. Bilirubin (Bb) was known to be the end product of hem catabolic pathway, but it was the subject of various studies with antioxidant, anti-inflammatory and immunomodulatory properties in the last decade. Here, the clinic importance of serum Bb parameters in AS patients has been analyzed.Methods: The study designed as case-control. One hundred (N=100) patients with axial AS diagnosed by 2010 Assesment in Ankylosing Spondylitis International Society (ASAS) Classification Criteria were included to the study. Control group was consisted of 75 patients of similar age, gender and BMI. Participants' age, gender, body mass index (BMI), disease acitivity scores and laboratory data were recorded from the hospital data. Disease activity evaluated by Bath Ankylosing spondylitis disease activity index (BASDAI), Bath Ankylosing spondylitis functional index (BASFI) and Ankylosing spondylitis disease activity score-C-reactive protein (ASDAS_CRP). For these three scores, automatic calculation formulas were used on Internet. ASDAS_CRP>3.5 were accepted as cut-off value for high disease activity. Serum direct Bb, indirect Bb, total Bb, aspartat aminotransferase (AST), alanin aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), gamma glutamyl transferase (GGT), amylase, lipase, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) values were recorded from the hospital records.Results: The study included 100 AS patients at mean age of 37.9 ± 12 years, 75 controls at mean age of 39.2 ± 5.2 years. There was no significant difference between the two groups in terms of age (p = 0.12), gender (p = 0.32), and BMI (p = 0.067). In the AS group, ESR (p< 0.001), CRP (p < 0.001), uric acid (p 3.5, direct Bb (p = 0.020), total Bb (p = 0.029) and AST (p = 0.004) were significantly lower in high activity group (N = 25) and ESR (p = 0.000) was significantly higher.Conclusion: The direct Bb in patients with AS were found significantly low and negatively correlated with disease activity, this supports the role of oxidative stress in AS disease pathogenesis. Bb can be used as a biomarker in diagnosis and follow up in AS disease., Amaç: Ankilozan spondilit (AS) aksiyal değişiklikler, periferik artrit ve sistemik tutulum içeren kronik bir hastalıktır. AS herhangi bir komplike romatizmal hastalık gibi sadece en güçlü genetik katkı ile karakterize edilmez, aynı zamanda çevresel ve immünolojik faktörlerden de etkilenir. Tümör nekroz faktörü (TNF), interlökin- (IL-) 1, IL-6, IL17 / 28 gibi çeşitli proinflamatuar sitokinler muhtemelen AS patogenezinde rol oynar. Son yıllarda hastalık patogenezinde IL-23 / IL-17 yolu gösterilmiştir. Bilirubin (Bb) hem katabolik yolun son ürünüdür hem de son on yılda antioksidan, antienflamatuar ve immünmodülatör özellikleri olan çeşitli çalışmaların konusu olmuştur. Burada AS hastalarında serum Bb parametrelerinin klinik önemi analiz edilmiştir.Yöntemler: Çalışma vaka-kontrol olarak planlandı. Uluslar arası Ankilozan Spondilit Topluluğu 2010 Sınıflandırma Kriterleri'ne göre (ASAS) aksiyal AS tanısı almış 100 hasta (N = 100) çalışmaya dahil edildi. Kontrol grubu benzer yaş, cinsiyet ve VKİ olan 75 kişiden oluşmaktaydı. Katılımcıların yaş, cinsiyet, vücut kitle indeksi (BMI), hastalık skoru puanları ve laboratuvar verileri hastane verilerinden kaydedildi. Hastalık aktivitesi Bath Ankilozan Spondilit Hastalığı Aktivite İndeksi (BASDAI), Bath Ankilozan Spondilit Fonksiyonel İndeks (BASFI) ve Ankilozan Spondilit Hastalığı Aktivite skoru-C-reaktif protein (ASDAS_CRP) ile değerlendirildi. Bu üç puan için, internette otomatik hesaplama formülleri kullanıldı. ASDAS_CRP> 3,5 yüksek hastalık aktivitesi için eşik değer olarak kabul edildi. Serum direkt Bb, indirekt Bb, total Bb, aspartat aminotransferaz (AST), alanin aminotransferaz (ALT), alkalen fosfataz (ALP), laktat dehidrojenaz (LDH), gama glutamil transferaz (GGT), amilaz, lipaz, eritrosit sedimentasyon hızı (ESR) ve C-reaktif protein (CRP) değerleri hastane kayıtlarından kaydedildi.Bulgular: Çalışmaya yaş ortalaması 37,9 ± 12 yıl olan 100 AS hastası, yaş ortalaması 39,2 ± 5,2 yıl olan 75 kontrol alındı. İki grup arasında yaş (p = 0.12), cinsiyet (p = 0.32) ve VKİ (p = 0.067) açısından anlamlı fark yoktu. AS grubunda ESR (p < 0.001), CRP (p< 0.001), Bb (p = 0.016) anlamlı düşük; ürik asit (p< 0.001) kontrollerden anlamlı olarak yüksek bulundu.Korelasyon analizinde, Bb parametreleri ve hastalık aktivite parametreleri birbirleriyle negatif korelasyon göstermiştir. ASDAS_CRP> 3,5'e göre gruplandırıldığında, direkt Bb (p = 0,020), total Bb (p = 0,029) ve AST (p = 0,004) yüksek aktivite grubunda (N = 25) anlamlı düşük; ESR (p

Background/Aims: Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, which catalyzes the formation of reactive oxygen species (ROS) in phagocytic cells, has five subunits: p67phox ("phox"refers to "phagocyte oxidase"), p47phox, p40phox, p22phox, and gp91phox (catalytic subunit). Oxidative stress resulting from the accumulation of ROS and/or defective removal of ROS by antioxidants has detrimental effects on cellular functions and may contribute to chronic inflammation. Disruption of the colonic mucosa due to the dysregulation of antioxidants or transformation enzymes may play a role in the pathogenesis of ulcerative colitis (UC) and influence the clinical features of this disease. In this study, we examined the expression of the gene encoding NADPH oxidase subunit p22phox cytochrome b-245, alphapolypeptidein the colonic mucosa to test its possible contribution in the pathogenesis of UC.Materials and Methods: Expression levels of mRNA in the inflamed and non-inflamed colonic mucosa (determined using colonoscopy)of 22 patients with UC and in the normal mucosa of 22 healthy controls were analyzed using real-time polymerase chain reaction.Results: Expression levels of mRNA were not significantly different between patients with inflamed and non-inflamed colonic mucosa (p>0.05) and betweenpatients with inflamed colonicmucosa and healthy controls (p>0.05). Conclusion: Although our data suggest that expression of the gene encoding p22phox is not associated with chronic inflammation in patients with UC, other mechanisms can affect oxidative stress in these patients.

Background Corticosteroids are used in the treatment of asthma. The aim of this study was to determine the efficacy of anti-IgE and anti-TNF alpha as asthma treatments. Methods A mouse model of chronic asthma was developed. The fluticasone group was exposed to fluticasone and the anti-IgE and anti-TNF groups were administered anti-IgE or anti-TNF. IL-4, and IgE levels were measured, and histological analysis, pathological analysis and miRNA-126, miRNA-133a analyses were applied. Results The cell concentration in the BAL fluid decreased in all the treatment groups. The rate of perivascular and peribronchial cell infiltration decreased in the lung in the high-dose anti-IgE and anti-TNF groups. Smooth muscle thickness decreased in the lung tissue in the low-dose anti-IgE and anti-TNF groups. Bronchial wall thickness decreased in the lung tissue in the fluticasone + anti-IgE group. The IL-4 level in BAL fluid decreased in the high-dose anti-IgE, fluticasone + anti-IgE and anti-TNF groups. IgE levels increased in the BAL fluid in the high-dose anti-IgE and anti-TNF groups. The lymphocyte level increased in the BAL fluid in the high-dose anti-IgE group. The macrophage level decreased in the BAL fluid in the anti-TNF group. The relative expression of miRNA-126 increased in all groups. The relative expression of miRNA-133a decreased in the placebo and fluticasone groups. The relative expression of miRNA-133a increased in the low-dose anti-IgE, high-dose anti-IgE, fluticasone + anti-IgE and anti-TNF groups. Conclusions The results showed that anti-IgE is successful as a treatment. Fluticasone + anti-IgE and anti-TNF were seen to be superior to other therapeutic modalities when used for prophylaxis.

MicroRNAs (miRNAs) are important factors during tumorigenesis by affecting posttranscriptional gene expression. miRNA 204 (miR-204) is a miRNA frequently investigated in different types of cancers. According to literature, autophagy has dual roles in cancer, acting as both a tumor suppressor and cell survival agent. Also, the current data suggests that autophagy is activated in human colorectal cancer cells and enhances the aggressiveness of human colorectal cancer cells. So, our aim is to investigate potential effect of miR-204-5p on colorectal cancer by associating its expression with autophagy-related targets of miR-204-5p. This is the first miRNA study conducted on patients with colorectal cancer and healthy subjects and also to search the relation of miR-204-5p with clinicopathological factors and survival. Sixty-six patients with colorectal cancer and healthy subjects without any known chronic disease were enrolled into our study. Total miRNA was isolated from paraffin-embedded tissues of all patients' cancerous and normal tissues, and healthy subjects. cDNAs were obtained from this miRNAs by reverse transcriptase method, and miR-204-5p relative expression levels were detected by qRT-PCR method. Patients were divided into two groups according to median relative expression levels of miR-204-5p, as low- and high-expression group. Relation of miR-204-5p with clinicopathological factors and overall survival was also investigated. Medians of miR-204-5p relative expression levels in cancerous and normal tissues of patients were found as 0.00235 and 0.00376, respectively. The difference between two groups was not statistically significant (p = 0.11). Nonetheless, median of miR-204-5p relative expression levels in healthy subjects were found as 0.00135, and the difference between patient with cancer and healthy subjects and between normal tissues of patients and healthy subjects were statistically significant (p = 0.021 and p = 0.0005, respectively). There were 32 patients (48.5 %) showing high expression and 34 patients (51.5 %) showing low expression according to miR-204-5p relative expression levels. There were no statistically significant relation between clinicopathologic features and miR-204-5p relative expression levels. We also investigated the relation between miR-204-5p relative expression levels and overall survival, and no statistically significant relation was found between them (p = 0.462). The absence of any significant difference between tumor and non-tumor samples, low sample size, and performance at just one center are the limitations of our study. In opposition to literature, miR-204-5p is overexpressed in colorectal cancer patients as compared with healthy subjects and this situation is not associated with clinicopathological factors and overall survival. This may be explained by the fact that miR-204-5p increases in colorectal cancer cases in order to inhibit increased activity of LC3B-II in autophagy and Bcl2 against apoptosis posttranscriptionally and to take role as tumor suppressor.

There is an increased airway inflammation in the pathogenesis of chronic obstructive pulmonary disease (COPD), and it has been suggested that there may also be problem in the apoptosis and renewal of cells. However, there are limited human airway cell studies, in particular those from larger airways such as bronchi. We cultured primary human bronchial epithelial cells (HBECs) from bronchial explants of smokers (n = 6) without COPD and smokers with COPD (n = 8). Apoptosis was studied by fluorescence activated cell sorting. qRT-PCR was used to assess mRNA expression for proteins involving apoptosis including p21(CIP1/WAF1), p53, caspase-8 and caspase-9. Although there was no difference in the rate of viable cells between cells from smokers and COPDs, the level of early apoptotic cells was significantly increased in COPD cells [mean ± standard error of mean (SEM) = 4.86 ± 3.2 %, p = 0.015] as compared to smokers (mean ± SEM = 2.71 ± 1.62 %). In contrast, the rate of late apoptotic cells was significantly decreased in COPD cells (mean ± SEM = 9.82 ± 5.71 %) comparing to smokers (mean ± SEM = 15.21 ± 5.08 %, p = 0.003). Although expression of mRNA for p21(CIP1/WAF1) and caspase-9 was similar in both groups, p53 and caspase-8 mRNA expression was significantly greater in COPD cells. These findings suggest that HBEC apoptosis is increased in COPD, and that this involves p53 and caspase-8 pathways.

Breast cancer (BC) is the most frequent cancer type in women, and the mortality rate is high especially in metastatic disease. Ion channels such as the transient receptor potential (TRP) channels correlate with malignant growth and cancer progression. Hence, some authors have suggested that the expression levels of TRP channels may be used as a marker in the diagnosis and predicting the prognosis of BC. Also, in some recent studies, targeting TRP channels are suggested as a novel treatment strategy in BC. The aim of this study was to investigate the effect of two Rho-kinase (ROCK) inhibitors, fasudil and Y-27632, on the expression levels of TRP channel genes in breast cancer cell lines (ZR-75-1, MCF7, and MDA-MB-231) and breast epithelial cell line (hTERT-HME1). The expression levels of TRP genes were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). We found that fasudil had reduced the TRPC1, TRPV2 expression levels in the ZR-75-1, MCF7, and MDA-MB-231 cell lines. On the other hand, fasudil and Y-27632 had reduced TRPM6 expression levels in all cell lines. Y-27632 increased the expression levels of TRPC7 in all cell lines. In conclusion, this is the first study demonstrating that the inhibition of ROCK pathway changes the expression levels of some TRP genes. Also, our study has firstly shown that the expression levels of the TRP genes which are suggested as a diagnostic and prognostic biomarker in BC, were changed with the treatment of fasudil and Y-27632.

A genetic algorithm for mixture model clustering using variable data segmentation and model selection is proposed in this study. Principle of the method is demonstrated on mixture model clustering of Ruspini data set. The segment numbers of the variables in the data set were determined and the variables were converted into categorical variables. It is shown that variable data segmentation forms the number and structure of cluster centers in data. Genetic Algorithms were used to determine the number of finite mixture models. The number of total mixture models and possible candidate mixture models among them are calculated using cluster centers formed by variable data segmentation in data set. Mixture of normal distributions is used in mixture model clustering. Maximum likelihood, AIC and BIC values were obtained by using the parameters in the data for each candidate mixture model. Candidate mixture models are established, to determine the number and structure of clusters, using sample means and variance-covariance matrices for data set. The best mixture model for model based clustering of data is selected according to information criteria among possible candidate mixture models. The number of components in the best mixture model corresponds to the number of clusters, and the components of the best mixture model correspond to the structure of clusters in data set.

OBJECTIVE: Nitric oxide is produced by endothelial nitric oxide synthase, and its production can be influenced by polymorphisms of the endothelial nitric oxide synthase gene. Because candidate genes responsible for susceptibility to ankylosing spondylitis are mostly unknown and available data suggest that there may be problems related to the nitric oxide pathway, such as endothelial dysfunction and increased asymmetric dimethylarginine, this study aimed to assess the association of common endothelial nitric oxide synthase gene polymorphisms with ankylosing spondylitis. METHODS: One hundred ninety-four unrelated Turkish ankylosing spondylitis patients and 113 healthy without apparent cardiovascular disease, hypertension or diabetes mellitus were included. All individuals were genotyped by PCR-RFLP for two single-nucleotide polymorphisms, namely 786T>;C (rs2070744, promoter region) and 786 Glu298Asp (rs1799983, exon 7). Variable numbers of tandem repeat polymorphisms in intron 4 were also studied and investigated by direct electrophoresis on agarose gel following polymerase chain reaction analysis. The Bath ankylosing spondylitis metrology index of the patients was calculated, and human leukocyte antigen B27 was studied. RESULTS: All studied polymorphisms satisfied Hardy-Weinberg equilibrium. Sex distributions were similar between the patient and control groups. No significant differences were found in the distributions of allele and genotype frequencies of the studied endothelial nitric oxide synthase polymorphisms between patients and controls. There were no correlations between endothelial nitric oxide synthase polymorphisms, disease duration, Bath ankylosing spondylitis metrology index or human leukocyte antigen B27. CONCLUSION: The results presented in this study do not support a major role of common endothelial nitric oxide synthase polymorphisms in Turkish ankylosing spondylitis patients.

Although studies have reported an association between air pollutants and increased allergic airway diseases, such as allergic rhinitis and nasal polyposis, the underlying mechanisms are not fully understood. A limited number of studies have suggested that diesel exhaust particles (DEP) play a role in atopy and the pathogenesis of allergic upper airway diseases. The aim of this study was to investigate the effect of DEP on inflammatory cytokine release, and mRNA expression of transcription factors such as JNK and NF-β in primary nasal epithelial cells (NECs), in vitro.NECs from non-atopic, non-rhinitic subjects (controls) and patients with allergic rhinitis and nasal polyps were cultured and incubated with 0-100μg/ml DEP for 24h. ELISA and RT-PCR were used to assess the release of IL-8, GM-CSF, and RANTES, and mRNA expression for JNK and NF-κB, respectively.Compared to control cells, NECs from subjects with atopic polyps released significantly greater amounts of IL-8 (median=887 vs. 176.6pg/μg cellular protein; p0.0001) and RANTES (median=0.191 vs. 0.02pg/μg cellular protein; p0.001). While 50μg/ml DEP induced release of RANTES in NECs from patients with allergic rhinitis, 100μg/ml DEP decreased IL-8 levels in NECs from both control and allergic rhinitic subjects. DEP did not affect mRNA expression for JNK and NF-κB from NECs of subjects with polyps.NECs from subjects with various pathologies may respond differently to DEP.

Introduction: In busy emergency departments, errors made during the pre-analytical phase can cause delayed diagnosis and treatment, and prolonged follow-up periods. The most common error in the pre-analytical phase is hemolysis in blood samples. In this study, we aimed to assess the effectiveness of the Luer-Lok (BD Vacutainer®) method of taking samples in avoiding hemolysis. Materials and Methods: The study was conducted at the emergency department of a tertiary healthcare facility on patients that register at level 1 or 2 of the Emergency Severity Index triage algorithm. Three sets of prospective observations were made, each lasting for five days. In the first period, hemolysis rates were determined. Following a training course on appropriate blood sampling techniques during the second period, hemolysis rates were determined again while Luer-Lok (BD Vacutainer®) was being used. Taking and processing of samples were carried out by the same personnel throughout the study. Assessment of hemolysis was performed by those that were blind to sampling. All the samples were analyzed at the laboratory located inside the emergency department. Results: In total, 2,027 blood samples were sent to the emergency laboratory for analysis. The hemolysis rate was 8.1% in the first period, 5.5% in the second and 1.4% in the third. The difference in rates between the first and second periods was not statistically significant (p=0.0793). The hemolysis rate in the third period was significantly lower compared to the other two periods (p=0.0001). Conclusion: Using Luer-Lok (BD Vacutainer®) may be effective in reducing hemolysis rates in busy emergency departments.

To evaluate possible role of the UTS2 gene polymorphisms (Thr21Met and Ser89Asn) in the genetic susceptibility to diabetic retinopathy (DR) in a Turkish population.Total number of 280 patients with DR (nonproliferative DR 170 and proliferative DR 110), 291 nondiabetic healthy controls, and 113 diabetic controls (without DR) were included to this study. The detection of UTS2 gene polymorphisms was achieved with PCR-RFLP technique. The Discovery Studio 2.1 program was used for molecular modeling analysis.Thr21Met (T21M) and Ser89Asn (S89N) polymorphisms of the UTS2 gene were associated with the risk of developing diabetes and DR. M21M genotype frequencies were high in PDR (8.9% in diabetic control vs. 54.6% in PDR, P = 0.0092) group. Increases in 21M allele frequency (52.7% in diabetic control vs. 76.4% in PDR, P0.0001) frequency in PDR group were detected. However, there were no changes in genotype and allele frequencies for T21M in NPDR group. There were decreases in the S89N genotype (23.9% in diabetic control vs. 13.5%) and 89N allele frequencies (11.9% in diabetic control vs. 6.8%) in NPDR group. However, S89S genotype (76.1% in diabetic control vs. 86.4%) and 89S allele frequencies (88.1% in diabetic control vs. 93.2%) were high in NPDR group. Three haplotypes (MN, MS and TS) were associated with NPDR patients (P0.001), but only MN (P0.001) and TS haplotypes (P = 0.018) were associated in PDR group. Molecular modeling analysis showed that these two polymorphisms changed the 3D structure of UTS2, and provided interactions with neighboring residues.The associations between Thr21Met and Ser89Asn polymorphisms in the UTS2 gene and DR strongly suggest that these SNPs may be an important a risk factor for the development of DR in Caucasians, and could be candidate markers for earlier diagnosis and targets for DR therapy.

SummaryThe differential diagnosis of pleural effusion often requires invasive procedures. Up to 25 percent of pleural effusions can remain undiagnosed with an unclear pathogenesis. Therefore new biological markers may increase diagnostic yield and provide better understanding of pathogenesis of pleural effusion. We hypothesized that new ischemia biomarker, “ischemia modified albumin (IMA)” would help in both the differentiation of the underlying etiologies and provide a better understanding of pathogenesis of pleural effusions. This study was done between December 2009 and September 2010 in the Department of Pulmonary Diseases of Gaziantep University Hospital. One hundred and sixteen subjects with pleural effusion were included. Pleural and blood IMA levels were measured by ELISA. The underlying etiologies of pleural effusions were as follows: transudates (n = 50), malignancy (n = 32), tuberculosis (n = 12), pulmonary thromboembolism (n = 6), pneumonia (n = 16). The median pleural IMA levels were significantly different between the groups (p

A comprehensive model, previously developed and tested for prediction of behavior of continuous fluidized bed combustors is extended to incorporate NOx formation and reduction reactions and applied to the simulation of Middle East Technical University (METU) 0.3 MWt Atmospheric Bubbling Fluidized Bed Combustor (ABFBC) burning lignites with high Volatile Matter/Fixed Carbon (VM/FC) ratios in their own ashes. Favorable comparisons are obtained between the predicted and measured temperatures and concentrations of gaseous species along the combustor. Results show that determination of partitioning of coal nitrogen into char-N and volatile-N, char combustion rate, and amount of volatile nitrogen released along the combustor are found to be the most important parameters that affect NO formation and reduction in bubbling fluidized bed combustors.

Studies suggest steroid resistance in COPD patients.We cultured primary BECs from non-smokers (NS), smokers (S) and patients with COPD and incubated with dexamethasone (DEX, 0.1-100nM), N-acetylcysteine (NAC, 3.3-10mM), or c-jun N-terminal kinase inhibitor (SP600125; 3.3-33µM) under unstimulated and stimulated condition by 1ng/ml interleukin (IL)-1β.IL-6, IL-8 and granulocyte macrophage-colony stimulating factor (GM-CSF) levels,mRNA expression was assessed.DEX inhibited release of GM-CSF from un-stimulated COPD BECs (median= 1.047ng/ml) at 1nM, 100nM, and from stimulated cells (median=21.6ng/ml), at 1nM (median=15ng/ml; p

MTHFR (Methylenetatrahydrofolate reductase) is one of the most important enzymes because of its function about folate metabolism and DNA synthesis nucleotide polymorphism in the gene encoding the enzyme, have been associated with many diseases including prostate cancer. We aimed to evaluate the association between the polymorphism and prostate cancer by comparing the results between patients and controls, MTHFR (Metilentetrahidrofolatredüktaz), folat metabolizması ve DNA sentez yolağındaki kilit rolü sebebiyle en önemli enzimlerden biridir. Enzimi kodlayan gendeki C677T tek nükleotid polimorfizmi, prostat kanseri de dahil olmak üzere birçok hastalıkla ilişkilendirilmiştir. Çalışmanın amacı, ilgili polimorfizmin, prostat kanseri teşhisi konmuş hasta ve sağlıklı kontrol bireyler arasında kıyaslanarak, hastalık ile ilişkisinin değerlendirilmesidir. Çalışmaya, 20 prostat kanseri teşhisi konmuş hasta ve herhangi bir patolojisi saptanmamış 20 sağlıklı birey dahil edilmiştir. İlk olarak, bu bireylerden alınan kan örneklerinden DNA’ları izole edildi. İlgili polimorfizmin bulunduğu bölge Polimeraz Zincir Reaksiyonu (PCR) ile çoğaltıldıktan sonra, uygun restriksiyon enzimi aracılığıyla, Restriksiyon Parça Uzunluk Polimorfizmi (RFLP) yöntemi ile kesildi. Daha sonra Poliakrilamid Jel Elektroforezi tekniği ile örnekler yürütüldü ve jel görüntülenerek oluşan bantlar yorumlandı.Sonuçlar, MTHFR C677T polimorfizm genotipleri açısından değerlendirildiğinde, çalışmaya dâhil ettiğimiz hasta bireylerin %60’inde CC (homozigot normal), %40’inde CT (heterozigot mutant); sağlıklı bireylerin ise %60’ında CC, %35’inde CT ve %5’inde TT (homozigot mutant) genotipi olduğu tespit edilmiştir.Sonuç olarak, MTHFR 677TT genotipinin prostat kanseri için koruyucu etki gösterdiği tespit edilmiştir.Anahtar Kelimeler: MTHFR C677T, prostat kanseri, polimorfizm.

5,10-Methlenetetrahydrofolate reductase (MTHFR) is one of the most important enzymes for folic acid metabolism. This protein\'s gene is mapped on chromosome 1, which is located at the end of the short arm (1p36.3). MTHFR enzyme plays a key role in cell metabolism including folic acid and nucleotide synthesis (DNA, RNA). Polymorphism is also a factor in biodiversity, and is different according to ethnic heritage and racial. The 677 C>T is also MTHFR polymorphisms that decrease MTHFR enzyme activity. The aim of this study is to compile studies are associated with MTHFR C677T polymorphism. PUBMED, Turk Biochemistry and Jornal of Clinical & Experimental Investigations were searched to develop an investigatory pursuit strategy. MTHFR, Turkish population, 677 C>T and polymorphisms were key words including “MTHFR”, “Türk popülasyonu: Turkish population”, “677 C>T” “polimorfizm: polymorphism” used to focus the search. The literature review included all published relevant Turkish population and MTHFR polymorphisms for that all of study. The data of selected polymorphism for Turkish population was listed in tables for easy access and retrieval., 5,10-Metilentetrahidrofolat redüktaz (MTHFR) folik asit metabolizması için en önemli enzimlerden biridir. Bu proteinin geni 1 numaralı kromozomun kısa kolunda (1p36.3) haritalanmıştır. MTHFR enzimi, folik asit, nükleotid sentezi (DNA, RNA) gibi pek çok reaksiyonu içeren hücre metabolizmasında, kilit rol oynar. Polimorfizmler etnik kökene ve ırklara göre farklılık gösteren ve biyoçeşitlilikte rol oynayan bir faktördür. MTHFR 677 C>T polimorfizmi enzim aktivitesini azaltan bir polimorfizmdir. Çalışmanın amacı, Türkiye\'de MTHFR C677T polimorfizmi ile ilgili olan çalışmaları derlemektir. Bu nedenle, Türkiye\'de yapılmış MTHFR 677 C>T polimorfizmi ile ilgili PUBMED, Türk Biyokimya ve Klinik & Deneysel Araştırmalar dergisinde yayınlanmış bütün çalışmalar derlenmiştir. Araştırma yapılırken “MTHFR”, “Türk popülasyonu: Turkish population”, “677 C>T” “polimorfizm: polymorphism” anahtar kelimeleri kullanılmıştır. Bu çalışmalar, belli başlı hastalık gruplarına göre sınıflandırılmış ve tablolar halinde okuyucunun değerlendirmesine sunulmuştur.

Thymoquinone, one of the essential oil in the structure of cumin, is used for alternative therapy for many diseases from past to present. It was shown to have anti-carcinogenic and anti-inflammatory effects, as well as positive effects on fibrosis. However, there is no study on the effect of thymoquinone on cancer and fibrosis mechanism in bronchial epithelium cell line BEAS-2B. In our study, the effect of thymoquinone on cell viability and transforming growth factor-beta 1 (TGF-β1) level, which has an important role in the regulation of many biological processes including cancer and fibrosis-associated signal transduction, was evaluated. BEAS-2B cells were exposed to thymoquinone at 0–80 μmol/L concentrations for 24-, 48- and 72-hour durations. Cell viability was evaluated with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test. TGF-β1 level was determined with enzyme-linked immunosorbent assay (ELISA) method from the collected supernatant. Cell viability was found to be increased at all concentrations and durations (10–80 μmol/L; 24, 48 and 72 h) according to the control group (0 μmol/L; thymoquinone in ethanol) (p < 0.0001). Moreover, thymoquinone was found to increase the level of TGF-β1 only at 80 μmol/L concentration and 24-hour exposure period (0 μmol/L, 53.41 ± 18.44 pgr/ml TGF-β1; 80 μmol/L, 174.5 ± 80.03 pgr/ml TGF-β1). As a result, thymoquinone was found to increase cell proliferation and encourage TGF-β1 release.

There is very little work on the expression of TRPM6/7 in ischemia reperfusion models. In previous studies, after ischemia, reperfusion had been kept limited to 24 h, yet in our study, expressions of these channels were elucidated after its modification to 48 h to establish what kind of changes renal tissues undergo. For the current study, 20 Wistar albino rats were divided into two groups equally. Group I: control group, Group II = I/R group (60 min ischemia + 48 h reperfusion). For the mRNA analysis, right kidneys of I/R group was used as a reference in order to eliminate genetic differences. The left renal artery (I/R generated part) of I/R area was removed from all rats in the second group. Likewise, normal tissues of right renal artery were removed from all rats. Histopathologic scoring of the tissue samples were achieved semi-quantitatively according to normal tissue composition. Consequently, both TRPM6 and TRPM7 expression levels were decreased in all groups according to control groups, yet results were not counted as significant (p > 0.05). Additionally, correlation analysis confirmed these results. Also, I/R performed kidneys had more tissue damage compared to control group. To conclude, our study results suggest that TRPM6/7 expressions may be increased and after 48 h of reperfusion expression levels of these two stored to normal levels. At the same time, damages have occurred in renal tissues after ischemia. These damages were considered to be resulted from the oxidative effects as previously reported.

This study describes the partitioning of 20 trace elements (As, B, Ba, Cd, Co, Cr, Cu, Hg, Li, Mn, Mo, Ni, P, Pb, Sb, Se, Sn, Tl, V, Zn) and eight major and minor elements (Al, Ca, Fe, K, Mg, Na, Si, Ti) during the combustion of high ash content lignite. The experiments were carried out in the 0.3 MW t Middle East Technical University (METU) atmospheric bubbling fluidized bed combustor (ABFBC) test rig with and without limestone addition. Inert bed material utilized in the experiments was bed ash obtained previously from the combustion of the same lignite without limestone addition in the same test rig. Concentrations of trace elements in coal, limestone, bottom ash, cyclone ash and filter ash were determined by inductively coupled plasma optical emission spectroscopy (ICP-OES). Partitioning of major and minor elements are influenced by the ash split between the bottom ash and fly ash and that the major proportion of most of the trace elements (As, Ba, Cr, Hg, Li, Mo, Ni, Sn, V, Zn) are recovered in fly ash. Limestone addition shifts the partitioning of Ba, Cr, Mo, Ni, Sn, V, Zn from bottom ash to fly ash.

The behavior of 20 trace elements (As, B, Ba, Cd, Co, Cr, Cu, Hg, Li, Mn, Mo, Ni, P, Pb, Sb, Se, Sn, Tl, V, Zn) and 8 major and minor elements (Al, Ca, Fe, K, Mg, Na, Si, Ti) during the combustion of high ash content lignite with and without limestone addition have been investigated in the 0.3 MWt Middle East Technical University (METU) Atmospheric Bubbling Fluidized Bed Combustor (ABFBC) Test Rig. Experiments were performed without fines recycle. Inert bed material utilized in the experiments was bed ash obtained previously from the combustion of the same lignite without limestone addition in the same test rig. Concentrations of trace elements in coal, limestone, bottom ash, cyclone ash and filter ash were determined by Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES). Measurements show that the distribution of major and minor elements follows the ash split between the bottom ash and fly ash and that the major proportion of most of the trace elements (As, Ba, Cr, Hg, Li, Mo, Ni, Sn, V, Zn) are recovered in fly ash. Comparisons between the trace element partitioning of the runs with and without limestone addition reveal that addition of limestone shifts the partitioning of Ba, Cr, Hg, Mo, Ni, Sn, V, Zn from bottom ash to fly ash.Copyright © 2005 by ASME

Synovial fibrosis is one of the main outcomes of osteoarthritis. Some authors have reported that urotensin-II (U-II) may cause pathologic fibrosis in cardiovascular system, lung and liver. However there are no previous reports available in the literature about its relationship with the synovial fibrosis in osteoarthritis. The aim of this study was to compare the U-II levels in knee synovial fluids obtained from osteoarthritic and non-osteoarthritic patients. Two groups were created, the osteoarthritis group and non-osteoarthritic control group. The control group was consisted of patients who underwent arthroscopic surgery for other reasons than cartilage disorders. In the osteoarthritis group all patients had grade 4 primer degenerative osteoarthritis and were treated with total knee arthroplasty. Minimum 1 mL knee synovial fluids were obtained during operation. Levels of U-II were measured by using ELISA kit U-II levels were significantly higher in the osteoarthritic group than that in the control group. No correlation was found between U-II levels and age. In conclusion, the significantly high U-II levels in the knee synovial fluid of osteoarthritic patients supported our hypothesis that “U-II may be associated with the synovial fibrosis in osteoarthritis”.

Exhaled breath condensate (EBC) is a completely non-invasive method for the collection of airway secretions to measure intense inflammation in the airways of asthmatics. It has been shown that the childhood asthma control test (c-ACT) is a good tool for use in the evaluation of asthmatics. Whether the c-ACT score and asthma control level correlate with the airway inflammation is not well known. We aimed to evaluate the relationship between exhaled cysteinyl leukotrienes (Cys-LTs) and 8-isoprostane levels and asthma severity, asthma control level and c-ACT score in asthmatic children.Thirty asthmatic children were evaluated with c-ACT score and pulmonary function tests. Asthma severity and asthma control level were assessed according to GINA. EBC was collected and Cys-LTs and 8-isoprostane concentrations were determined using a specific immunoassay kit.Exhaled 8-isoprostane level in patients with moderate persistent asthma [114 (55-146)pg/ml] was higher than in the mild persistent group [52 (21-91)pg/ml] (p=0.05, Mann-Whitney U [MWU]). EBC 8-isoprostane in children with 1-4 asthma exacerbations/year [52 (16-80)pg/ml] was significantly lower than in children with4 asthma exacerbations/year [114 (57-129)pg/ml] (p0.05, MWU). No significant relation was determined between exhaled 8-isoprostane and Cys-LTs levels and c-ACT score and asthma control level. Exhaled 8-isoprostane correlated negatively with bronchodilator response (p=0.015, r=-0.45).Exhaled 8-isoprostane, as an oxidative stress specifier, was found to be increased in relation with asthma exacerbation frequency and oxidative stress increases with the severity of asthma. In contrast to asthma severity level, c-ACT score and asthma control level may not reflect airway inflammation.

Despite the universality and clinical significance of exercise-induced bronchospasm (EIB), the mechanisms responsible for it are incompletely understood.To investigate the role of exhaled RANTES (regulated on activation, normal T-cell expressed and secreted) and interleukin (IL) 4 in EIB in children with asthma.Fifty-six children with asthma were evaluated with exercise challenge and exhaled RANTES and IL-4 levels. Exhaled breath condensate was collected before and 30 minutes after exercise challenge. RANTES and IL-4 concentrations were determined using a specific immunoassay kit.A significant increase was found in RANTES levels after exercise challenge in the asthmatic children (P.001). A statistically significant increase in RANTES levels was noted after exercise challenge in both the asthmatic children with EIB (n=25, P=.007) and in the non-EIB asthmatic group (n=31, P=.005). Our study revealed that exhaled RANTES level correlates significantly well with percentage of forced expiratory volume in 1 second (FEV1), exacerbation frequency, serum IgE, and body mass index. No statistically significant increase was found in IL-4 levels after exercise challenge. The maximal postexercise decrease in FEV1 strongly correlated with total eosinophil count (P.001, r = -0.61) and baseline ratio of FEV1 to forced vital capacity (FVC) (P=.002, r=0.40). Results from multivariate regression analysis adjusted for age, sex, and atopy as covariates showed that eosinophil count and FEV1/FVC ratio were significantly associated with EIB.We found that exercise challenge, leading to hyperosmolar stimulus, may increase exhaled RANTES levels in children with asthma. In addition, exhaled RANTES levels correlate well with serum IgE, severity of asthma, FEV1/FVC ratio, and body mass index. RANTES and IL-4 may not be independent predictors for EIB. Furthermore, eosinophil count and FEV1/FVC ratio may predict the presence and severity of EIB in asthmatic children.

Amac: Son y›llarda, topikal isosorbid dinitrat uygulamas›n›n internal anal sfinkterde gevfleme ile kronik anal fissurde iyileflmeye neden olabileceini bildiren cok say›da cal›flma bildirilmifltir. Ancak uygulanacak ilaclar›n dozlar› ve sureleri hakk›nda fikir bir- lii yoktur. Ayr›ca nitratl› bilefliklerle tedavi edilmifl kronik anal fissurlu hastalar›n uzun donem sonuclar› bilinmemektedir. Bu cal›flmada isosorbid dinitrat›n farkl› dozlar›n›n kronik anal fissur uzerindeki etkilerini ve uzun donem sonuclar›n› incelemeyi amaclad›k. Yontem: Kronik anal fissur tan›s› konulan ard›fl›k 75 hasta 3 gruba bolundu. I. gruba (n=15) sadece semptomatik te- davi verildi. II. ve III. gruplara (n=30) ise s›ras›yla %5 ve %10 topikal isosorbid dinitrat uyguland›. 20 gun aral›klarla 3 kontrol yap›ld›. Tedaviye yan›t al›nan 44 hasta ile 5 y›l sonra telefonda gorufluldu. Bulgular: Tedavinin 20. gununde %10 isosorbid dinit- rat grubunda salanan tam iyileflme oran›, %5 isosorbid dinitrat grubundakinden belirgin olarak daha fazlayd› (%53.3 vs. %26.7, p 0.05). Befl y›l sonra, tedaviden fayda goren hastalar›n %52.3'unde semptomlar›n nuk- settii saptand›. Sonuc: Topikal isosorbid dinitrat uygulamas› kronik anal fissurun tedavisinde internal anal sfinkteri korumaya yonelik iyi bir alternatiftir. Ancak uzun donemde nuks oranlar› yuksektir. Anahtar kelimeler: Kronik anal fissur, isosorbid dinitrat, internal anal sfinkter Background/aims: In recent years, numerous studies have reported that the application of topical isosorbide dinitrate can cause fissure recovery with the relaxation of the internal anal sphincter. However, there is no consensus about the dose or duration of the drugs to be applied. In addition, long-term results of the patients with chronic anal fissure treated with nitrate-containing compo- unds are unknown. In this study, the goal was to investigate the effects of various doses of isosorbide dinitrate on chronic anal fis- sure and their long-term effects. Methods: Seventy-five sequential patients with chronic anal fissure were divided into three groups. Only symptomatic treatments were applied to patients in the first group (n=15). The patients in second and third groups (n=30 each) were treated with topical isosorbide dinitrate 5% and 10%, respectively. The patients were examined three times at 20-day intervals. Five years later, 44 patients who were responsive to treatment were contacted by telephone. Results: The rate of full response in the 10% isosorbide dinitrate group was statistically higher than of the 5% isosorbide dinitrate group on the 20 th day (53.3% vs. 26.7%, p 0.05). Five years later, 52.3% of patients who were responsive to treatment had a symptomatic relapse. Conclusions: Topical isosorbide dinitrate is a good alternative therapy to protect internal anal sphincter in the treatment of chronic anal fissure. However, the recurrence rates are high in the long-term.

Objective.Systemic sclerosis (SSc) is an autoimmune chronic fibrotic disorder. Urotensin II (U-II) is predominantly a vasoactive peptide with fibrotic and prothrombotic features. Like endothelin-1 (ET-1), U-II could play an important role in SSc pathogenesis. We evaluated the possible role of the U-II gene polymorphisms (Thr21Met and Ser89Asn) in the genetic susceptibility to SSc in a Turkish population.Methods.A total of 189 patients with SSc and 205 healthy controls were enrolled in our study. We analyzed the genotype and allele frequencies of the U-II (UTS2) gene polymorphisms Thr21Met and Ser89Asn in patients with SSc and in controls.Results.We found that the Thr21Met polymorphism of the UTS2 gene was markedly associated with the risk of developing SSc (p < 0.0001), but there was no relationship between the Ser89Asn polymorphism and SSc (p > 0.05). Two haplotypes (MS and TS) were markedly associated with SSc (p < 0.05). There were significant associations between the genotype and allele frequencies of UTS2 gene Thr21Met polymorphism and cases with diffuse or limited SSc, systemic or lung involvement, finger flexion deformity, pitting scars at the fingertips, positive anticentromere, or positive antitopoisomerase 1 antibody groups.Conclusion.Our study shows the association between Thr21Met, but not Ser89Asn, in the UTS2 gene and SSc. The results strongly suggest that this single-nucleotide polymorphism may be an important risk factor in the development of SSc, and a powerful indicator of severe skin and lung involvement in patients with SSc.

Fine-needle aspiration biopsy (FNA) is currently the best initial diagnostic test for evaluation of a thyroid nodule. FNA cytology cannot discriminate between benign and malignant thyroid nodules in up to 30% of thyroid nodules. Therefore, an adjunct to FNA is needed to clarify these lesions as benign or malignant. Using differential display-polymerase chain reaction method, the gene expression differences between follicular and classic variants of papillary thyroid carcinoma (PTC) and benign thyroid nodules were evaluated in a group of 42 patients. Computational gene function analyses via Cytoscape, FuncBASE, and GeneMANIA led us to a functional network of 17 genes in which a core sub-network of five genes coexists. Although the exact mechanisms underlying in thyroid cancer biogenesis are not currently known, our data suggest that the pattern of transformation from healthy cells to cancer cells of PTC is different in follicular variant than in classic variant.

This chapter overviews direct co-firing applications of agricultural and forestry residues with coal in fluidized bed combustion (FBC) systems, which is the most promising technology due to its fuel flexibility and high efficiency. Similarities and differences in characteristics of biomass and coal are summarized. Issues on operational problems and their possible solutions in FBC systems firing biomass only are identified. Among the available solutions to these problems, co-firing biomass with coal is the most effective and simple option. Experiences obtained from several biomass/coal blends in FBC systems, ranging from laboratory rigs to large-scale utility boilers, are presented to emphasize the impact of co-firing on combustion efficiency, emissions and ash-related operational problems. Keywords: ash; biomass; coal; co-firing; fluidized bed combustion

Bikunin is an inhibitor of kidney stone formation synthesized in the liver together with α(1)-microglobulin from the α(1)-microglobulin/bikunin precursor (AMBP) gene. The aim of this study was to investigate the possible association between bikunin/AMBP gene polymorphisms and urinary stone formation.To analyse the DNA, blood samples were taken from 75 kidney stone formers who had a familial stone history, 35 sporadic stone formers and 101 healthy individuals. Four exons of bikunin gene and five parts of the promoter region of the AMBP gene were screened using single-strand conformation polymorphism and nucleotide sequence analysis.The Init-2 region of the promoter of AMBP gene had polymorphisms at positions -218 and -189 nt giving three different genotypes having 1,3, 2,4 and 1,2,3,4 alleles with frequencies of 17.06%, 60.19% and 22.75%, respectively, in all groups. Therefore, the Init-2 region appears to be polymorphic. As a result, the 1,3 allele has -218G and -189T complying with the reference database sequence, the 2,4 allele has -218G and T-189C substitution and the allele 1,2,3,4 genotype has substitutions at positions G-218C and T-189C.There were no significant differences in allele distribution between patients and controls. These common alleles exist in the Turkish population independent of stone formation. These results are the first to demonstrate the existence of bikunin and AMBP promoter polymorphism. Although the Init-2 region of the AMBP gene is the binding site for various transcription factors, the results showed no association between these observed genotypes and stone-forming phenotypes.

This study describes the partitioning of 18 trace elements (As, Ba, Cd, Co, Cr, Cu, Li, Mn, Mo, Ni, P, Pb, Sb, Se, Sn, Tl, V, Zn) and 9 major and minor elements (Al, Ca, Fe, K, Mg, Na, S, Si, Ti) during co-firing of olive residue, hazelnut shell and cotton residue with high sulfur and ash content lignite in 0.3 MWt Middle East Technical University (METU) Atmospheric Bubbling Fluidized Bed Combustor (ABFBC) test rig with limestone addition. Concentrations of trace elements in coal, biomass, limestone, bottom ash, cyclone ash and filter ash were determined by inductively coupled plasma optical emission and mass spectroscopy (ICP-OES and ICP-MS). Partitioning of major and minor elements are influenced by the ash split between the bottom ash and fly ash and that the major proportion of most of the trace elements (As, Ba, Co, Cr, Cu, Li, Mn, Mo, Ni, Pb, Tl, V and Zn) are recovered in fly ash when firing lignite only. Co-firing lignite with biomass enhances partitioning of these elements to fly ash. Co-firing also shifts the partitioning of Cd, P, Sb and Sn from bottom to fly ash. (C) 2008 Elsevier B.V. All rights reserved.

Combustion and emission behavior of 100 % steam coal (SET 1) and a mixture of 80 % by weight steam coal and 20 % by weight local lignite, characterized by high sulfur and ash contents, (SET 2) were investigated in the 0.3 MWt Middle East Technical University (METU) Atmospheric Bubbling Fluidized Bed Combustor (ABFBC) Test Rig. Experiments were performed with limestone addition at various Ca/S molar ratios with fines recycle. In both sets of experiments, parameters other than Ca/S molar ratio were held as nearly constant as possible. On-line measurements of O2 , CO2 , CO, SO2 , NOx emissions were carried out. Comparisons between the emissions show that lower NOx and SO2 emissions are obtained from combustion of steam coal/lignite mixture compared to those from steam coal only despite higher sulfur and almost equal nitrogen contents of the mixture. Calculated combustion efficiencies were found to be around 98 and 96 % for SET 1 and SET 2, respectively. As for the sulfur retention efficiencies, up to three times higher efficiencies were achieved when steam coal is co-fired with high sulfur lignite.Copyright © 2005 by ASME

Background. Peritoneal adhesions are pathological fibrotic bands developing after mesothelial damage. Transforming growth factor beta-1 (TGF-1) has mitogenic activities for macrophages and fibroblasts. Overexpression of TGF-1 has been implicated in the pathogenesis of several fibrotic disorders. Angiotensin II increases the expression of the TGF-1 in fibroblasts. The aim of the study was to investigate the effect of angiotensin converting enzyme inhibitor (ACE) on intraperitoneal adhesions. Materials and methods. Thirty male Wistar albino rats were divided into two groups. In the first procedure, laparotomy was performed through a 3-cm midline incision. Ileum was divided above 10 cm from ileocecal valve and a single-layer ileoileal anastomosis was performed. Although no treatment was given to rats in group 1, lisinopril (an ACE inhibitor) was given to rats in group 2 for postoperative 7 days in drinking water. Estimated amount of supplied lisinopril was 6.5 mg/kg/day. On postoperative 8th day, relaparotomy was performed and adhesions were evaluated. At the same time, blood samples were taken for TGF-1 measurements. Results. Adhesion severity was significantly less in the ACE inhibitor group (P < 0.001). While mean TGF-1 level was 860.3 108.1 pg/dl (mean SD) in control group, it was 335.8 52.4 pg/dl in ACE inhibitor group (P < 0.001). There was a significant correlation between serum TGF-1 levels and grade of adhesions (r 0.948). Conclusion. It was concluded that ACE inhibitors might be useful for preventing peritoneal adhesions.

e14603 Background: Increasingly more evidence support the role of the micrornas in tumorgenesis. miR-211 is a microrna that acts as a tumor suppressor at a posttranlational level in colorectal canc...