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The association between hypertensive retinopathy and left atrial (LA) impairment is unknown. Accordingly, it was aimed to investigate the possible relationship between hypertensive retinopathy and LA phasic functions by means of two-dimensional speckle-tracking echocardiography (2D-STE).A total of 124 hypertensive patients and 27 control subjects were included in the study. LA reservoir strain (LAHypertensive patients (with and without retinopathy) displayed an obvious reduction in the LA reservoir strain (LAImpaired LA reservoir and conduit strain may be used to predict hypertensive patients at higher risk of developing hypertensive retinopathy, and to determine which patients should be followed more closely for hypertensive retinopathy.

It is challenging to determine whether Bacillus species other than Bacillus anthracis cause infections. Pseudo and true outbreaks of Bacillus spp. have been noted. Here, we present a molecular analysis of a Bacillus spp. pseudo-outbreak caused by contaminated culture tubes containing Stuart medium.Between January and March 2015, a high percentage of Bacillus spp. was isolated from the wound samples of inpatients at the Karabuk University Hospital, and an outbreak was suspected. Environmental and staff nasal samples were cultured aerobically, and Bacillus spp. were isolated from some of them. However, the isolation of Bacillus spp. in throat cultures of outpatients suggested contamination caused by culture tubes containing Stuart medium. We examined two lots of culture tubes used in the hospital. Although the culture tubes' expiry date and storage conditions were suitable, Bacillus spp. grew in one of these lots. A total of 47 Bacillus spp. isolated during this period were identified, and the clonal relationship among the isolates was investigated by arbitrarily primed polymerase chain reaction.Twenty-seven strains were identified as Bacillus megaterium and 20 as Bacillus firmus. Of the four strains isolated from the Stuart medium, two were identified as B. firmus and the other two were B. megaterium. Two B. firmus strains isolated from the Stuart medium and two B. firmus strains obtained from the coronary intensive care environmental samples were matched and clustered within the same genotype. We recalled all culture tubes containing Stuart medium. After another brand's culture tubes were distributed, no growth was observed. It was then understood that the pseudo-outbreak source was contaminated culture tubes containing Stuart medium.Microbiological controls of medical materials and equipment should be regularly checked to prevent outbreaks (true or pseudo).

The most common gynecologic cancers detected in women in Turkey are uterine cancer, ovarian cancer, and cervical cancer. These data reported that a mean of 3800 individuals were diagnosed with uterine cancer, 2790 were diagnosed with ovarian cancer, and 1950 were diagnosed with cervical cancer, and 400 individuals were diagnosed with other gynecologic cancers each year in Turkey. A mean of 14.270 individuals were detected to have been diagnosed with gynecologic cancers each year in the United States of America(USA). Ovarian cancer treatment is generally composed of chemotherapy, and surgery. In general, chemotherapy is administered after surgery. The identification of the molecular pathogenesis of ovarian cancer, and discovery of new moleculer biomarkers which facilitate the ovarian cancer treatment are required for an effective ovarian cancer treatment in clinics. miRNAs are reported to be the possible biologic indicators for various cancer types. We aimed to investigate 2 miRNAs which were suggested to have effect in ovarian cancer in our (previous)monozygotic twin study from miR-1260 microRNA family whose association with ovarian cancer yet has not been reported in the literature. We investigated the expression levels of miR-1260a, and miR-1260b miRNAs, in the peripheral blood lymphocytes of 150 familial and sporadic ovarian cancer patients, and of 100 healthy individuals of the control group who were matched for age, sex, and ethnicity with the patient group, and investigated their possible property of being a biologic indicator for ovarian cancer. The expression results of ovarian cancer patients were evaluated by comparison of the results of the control group in the study. The expression levels of miR-1260a, and miR-1260b in ovarian cancer patients were found highly increased compared with the levels in the control group. miR-1260a expression level in ovarian cancer patients was detected to have increased approximately 17 fold compared with the control group, and miR-1260b expression level in ovarian cancer patients was detected to have increased approximately 33 fold compared with the levels in the control group. The String Analyses showed that the miR-1260a was associated with the ribosomal protein family which was known to be effective in the translation stage of cell and that miR-1260b was associated with CHEK2 protein which was a member of the serine/threonine-protein kinase family. It should be investigated for larger cohorts in benign ovarian diseases and in different stages of patients receiving ovarian cancer treatment whether these two molecules are a noninvasive biomarker and therapeutic target to be used especially in the early diagnosis and prognosis of ovarian cancer in future.

Background Mucopolysaccharidosis IVA (MPS IVA, also called Morquio A syndrome) is caused by a deficiency of N‐acetylglucosamine‐6‐sulfate sulfatase (GALNS) and results in skeletal dysplasia symptoms such as short stature and abnormal gait. Treatments include enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT), but the effects are limited depending on the age of initiation and clinical phenotype. Thus, this study aims to assess the effects of treatments on MPS IVA patients compared to untreated MPS IVA patients and an age‐matched control group. Methods We used activity of daily living (ADL) survey with 4 sections: “movement,” “movement with cognition,” “cognition,” and “other MPS symptoms.” Lower scores indicate more assistance required. This study included 161 patients, 270 total surveys, and 70 patients with longitudinal data. Results We describe 134 severe patients and 25 attenuated patients. ERT and HSCT treatment improved only the “other MPS symptoms” section in severe patients. There were no differences between ERT and HSCT severe patient scores. A 19‐year‐old male patient, who had robust physical training, provided a significant increase in “movement” without treatment, suggesting the importance of exercise. Conclusion Overall, this ADL questionnaire has demonstrated validation and reliability in assessing the MPS IVA patients and therapeutic efficacy., We have evaluated activity of daily living in mucopolysaccharidosis IVA patients from 161 patients. This is the first manuscript to evaluate therapeutic efficacy in both HSCT and ERT.

The most prevalent malignant bone tumor, osteosarcoma, affects the growth plates of long bones in adolescents and young adults. Standard chemotherapeutic methods showed poor response rates in patients with recurrent and metastatic phases. Therefore, it is critical to develop novel and efficient targeted therapies to address relapse cases. In this regard, RNA interference technologies are encouraging options in cancer treatment, in which small interfering RNAs regulate the gene expression following RNA interference pathways. The determination of target tissue is as important as the selection of tissue-specific promoters. Moreover, small interfering RNAs should be delivered effectively into the cytoplasm. Lentiviral vectors could encapsulate and deliver the desired gene into the cell and integrate it into the genome, providing long-term regulation of targeted genes. Silencing overexpressed genes promote the tumor cells to lose invasiveness, prevents their proliferation, and triggers their apoptosis. The uniqueness of cancer cells among patients requires novel therapeutic methods that treat patients based on their unique mutations. Several studies showed the effectiveness of different approaches such as microRNA, drug- or chemotherapy-related methods in treating the disease; however, identifying various targets was challenging to understanding disease progression. In this regard, the patient-specific abnormal gene might be targeted using genomics and molecular advancements such as RNA interference approaches. Here, we review potential therapeutic targets for the RNA interference approach, which is applicable as a therapeutic option for osteosarcoma patients, and we point out how the small interfering RNA method becomes a promising approach for the unmet challenge.

BRCA1/2 gene testing is a difficult, expensive, and time-consuming test which requires excessive work load. The identification of the BRCA1/2 gene mutations is significantly important in the selection of treatment and the risk of secondary cancer. We aimed to develop an algorithm considering all the clinical, demographic, and genetic features of patients for identifying the BRCA1/2 negativity in the present study. An experimental dataset was created with the collection of the all clinical, demographic, and genetic features of breast cancer patients for 20 years. This dataset consisted of 125 features of 2070 high-risk breast cancer patients. All data were numeralized and normalized for detection of the BRCA1/2 negativity in the machine learning algorithm. The performance of the algorithm was identified by studying the machine learning model with the test data. k nearest neighbours (KNN) and decision tree (DT) accuracy rates of 9 features involving Dataset 2 were found to be the most effective. The removal of the unnecessary data in the dataset by reducing the number of features was shown to increase the accuracy rate of algorithm compared with the DT. BRCA1/2 negativity was identified without performing the BRCA1/2 gene test with 92.88% accuracy within minutes in high-risk breast cancer patients with this algorithm, and the test associated result waiting stress, time, and money loss were prevented. That algorithm is suggested be useful in fast performing of the treatment plans of patients and accurately in addition to speeding up the clinical practice. Scientific Research Projects Coordination Unit of Istanbul UniversityIstanbul University [TSA-2019-34244] This study was funded by the Scientific Research Projects Coordination Unit of Istanbul University (project number: TSA-2019-34244).

Background Ovarian cancer is the second most common gynecologic cancer with high mortality rate and generally diagnosed in advanced stages. The 5-year disease-free survival is below 40%. MicroRNAs, subset of the non-coding RNA molecules, regulate the translation in post transcriptional level by binding to specific mRNAs to promote or degrade the target oncogenes or tumor suppressor genes. Abnormal expression of miRNAs were found in numerous human cancer, including ovarian cancer. Investigating the miRNAs derived from the peripheral blood samples can be used as a marker in the diagnose, treatment and prognosis of ovarian cancer. We aimed to find biological markers for early diagnosis of ovarian cancer by investigating BRCA1 gene mutation carrier monozygotic discordant twins and their high risk healthy family individual’s miRNAs. Methods The study was conducted on monozygotic twins discordant for ovarian cancer, and the liquid biopsy exploration of miRNAs was performed on mononuclear cells that were isolated from the peripheral blood samples. The miRNA expression profile changes in the study were found by using microarray analysis. miRNA isolation procedure performed from the lymphocyte in accordance with the kit protocol. The presence and quality of the isolated miRNAs screened by electrophoresis. Raw data logarithmic analysis was studied by identifying the threshold, normalization, correlation, mean and median values. Target proteins were detected for each miRNA by using different algorithms. Results After the comparison of monozygotic discordant twins for epithelial ovarian carcinoma upregulation of the 4 miRNAs, miR-6131, miR-1305, miR-197-3p, miR-3651 and downregulation of 4 miRNAs, miR-3135b, miR-4430, miR-664b-5p, miR-766-3p were found statically significant. Conclusions The detected 99 miRNAs out of 2549 miRNAs might be used in the clinic as new biological indicators in the diagnosis and follow up of epithelial ovarian cancer with complementary studies. The miRNA expression profiles were identified to be statistically significant in the evaluation of ovarian cancer etiology, BRCA1 mutation status, and ovarian cancer risk in accordance with the obtained data. There is a need for validation of the miRNAs which were particularly detected between monozygotic twins and its association with ovarian cancer was emphasized in our study in wider cohorts including ovarian cancer patients, and healthy individuals.

MicroRNAs (miRNAs) have major roles in nearly all cellular process including gene expression, and may behave as oncogene or tumor suppressor gene by binding to complementary sequences in the target mRNA. The circulating microRNA-15a (miRNA-15a) and microRNA-16-1 (miRNA-16-1) of 15 healthy adults and of 40 untreated patients diagnosed with diffuse large B-cell lymphoma (DLBC) were recruited to investigate the expression levels. The expression levels of miRNA-15a, and miRNA-16-1 genes of the untreated DLBCL patients, and healthy individuals with matched age, sex and ethnicity were examined. MicroRNA expression profiles obtained from peripheral blood were investigated. The samples were collected from 40 patients diagnosed with DLBC patients, and from 15 healthy controls. Two miRNAs were selected, and expression profile was examined using a quantitative real-time polymerase chain reaction (qPCR) based on the previous studies. Statistically significant expression level differences (p 0.05) were detected for miRNA-16-1 in DLBCL patients and healthy control groups. miRNA-16-1 gene expression level was found approximately ninefold higher in the patient group compared to the controls; however, no statistical difference was detected in the expression profile of miRNA-15a between the both groups. On the other hand, the decreased gene expression in miRNA16-1 was observed in 88.3% of DLBCL patients. These results suggested that there was no statistically significant decrease in the miRNA-15a gene expression in DLBCL patients (p 0.05). On the contrary to the literature, miRNA-16-1 expression level was suppressed in DLBCL group in our study, however no whole gene silencing was performed. MicroRNA-16-1 might be suggested to behave as a tumor suppressor in DLBCL in our study.

Introduction: Acinetobacter baumannii is an opportunistic pathogen that causes nosocomial infections with high mortality. Treatment options are limited owing to its resistance to numerous antibiotics. Here, we sought to determine the antibiotic susceptibilities of A. baumannii isolates, investigate clonal relationship among the strains, and determine the frequency of beta-lactamase resistance genes. Methodology: The identification and antibiotic susceptibilities of 69 A. baumannii strains were determined using a BD-Phoenix automated system. The presence of blaOXA-2, blaOXA-10, blaOXA-23, blaOXA-24/40, blaOXA-51, blaOXA-58, blaTEM, blaSHV, blaIMP, blaVIM, and blaGIM genes were investigated using polymerase chain reaction (PCR), and clonal relatioships among the isolates were determined using pulsed-field gel electrophoresis (PFGE). Results: All strains were resistant to ampicillin–sulbactam, gentamicin, cefepime, ciprofloxacin, and ceftriaxone. While 65 of the 69 strains (94.2%) were resistant to piperacillin-tazobactam, amikacin, imipenem, and meropenem, all strains were susceptible to tigecycline and colistin. The frequencies of blaOXA-51, blaOXA-23, blaTEM, blaOXA-2, blaVIM, and blaSHV were 100%, 94.2%, 53.6%, 21.7%, 14.5%, and 2.9%, respectively. Based on PFGE results, 56 of the 69 strains were clonally related, and the clustering rate was 81.2%. No common outbreak isolate was detected. Conclusions: The most prevalent OXA genes were blaOXA-51, blaOXA-23, and blaOXA-2. Furthermore, blaTEM, blaSHV, and blaVIM, which are common in Enterobacterales and Pseudomonas spp, were detected, suggesting horizontal gene transfer had occurred between bacteria. No single clone outbreak was detected by PFGE. However, multiclonal spread and the high clustering rate suggest cross-contamination. Therefore, in future, more effective infection control measures must be implemented.

Both uterine serous carcinoma (USC) and ovarian serous carcinoma (OSC) are presented at advanced stage at the first admittion and dissseminated disease makes the anatomical site of the tumor origin imposible. CA125 and p53 are reliable markers that are useful for differentiating both uterine serous and ovarian serous carcinoma from their most common subtypes (endometrioid type carcinoma of ovary and uterus) but so far there is no histopathologic marker that differentiates USC from OSC. On the other hand, Trastuzumab (Herceptin) increases progression-free survival among USC patients, but not OSC patients and makes the histopathologically assigning the origin of the tumor important. So, the aim of this study was to evaluate the immunohistopathological discriminative value of the human epididymis secretory protein 4 (HE4) between OSC and USC patients. Patients with a diagnosis of OSC and UTC were enrolled. HE4 expression was evaluated by immunohistochemistry. The results were compared between groups. Of the tumor tissues studied, HE4 immunostaining was seen in the majority of ovarian serous carcinoma cases (89.65%), while endomatrial serous carcinoma cases were devoid of HE4 immunostaining. HE4 immunostaining was seen in 39.1% uterin serous carcinoma cases and this difference was statistically significant (p = 0.001). Our study demonstrated for the first time the potential of HE4 expression to predict the anatomical site of tumor origin. HE4 is a novel tumor marker that differentiates USC from OSC.

Patient: Female, 74 Final Diagnosis: Toxic epidermal necrolysis Symptoms: Bullous hemorrhagic lesions Medication: Levoflaxosine Clinical Procedure: Omalizumab therapy Specialty: Allergology Objective: Rare disease Background: Toxic epidermal necrolysis (TEN) is characterized by widespread erythematous and bullous lesions on the skin. Nowadays, considerable progress has been made in the understanding of its pathogenesis. Immunologically it is similar to graft-versus-host disease. Therefore, we may propose that TEN is a disorder of cell-mediated immunity. Case Report: Our patient was a 74-year-old white female who had pneumonia and was positive for hepatitis C virus (HCV), and who had been on levofloxacin therapy. After the first levofloxacin dose, erythematous dusky red macules occurred on her extremities and trunk, and on the following day, confluent purpuric lesions tended to run together over 85% of her body. Her biopsy results indicated TEN. Laboratory testing for serum ECP (eosinophil cationic peptide) and serum immunoglobulin (Ig) levels were performed, and blister fluid was investigated. The patient responded positively to omalizumab treatment and after treatment laboratory tests revealed decreased high sensitive CRP, ECP, IgG1, IgG2, IgG3, IgG4, IgA, and IgM levels. Conclusions: To the best of our knowledge, this is the first case of a patient with HCV who developed cutaneous adverse drug reaction on levofloxacin medication and recovered with omalizumab treatment. This is the first documentation of omalizumab treatment of a TEN patient.

The term "asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome" (ACOS) has been applied to the condition, in which a person has clinical features of both asthma and COPD.The patients (N = 10) were presented to our clinic with low lung function, limited reversibility of airway obstruction, hyperinflation, abnormal body composition, dyspnea and episodic wheezing. Based on the clinical and laboratory findings, the patients were diagnosed with ACOS. Patients' serum IL-2 (sIL-2), sIL-4 sIL-6, sIL-10, sIL-17, sTNF-α and sIFN-γ levels were investigated as an apoptotic marker and a marker for inflammation.Having undergone omalizumab treatment and a long-term (12 months) later, patients had a decreased IgE, fractional exhaled nitric oxide concentrations (FENO), eosinophil, neutrophils, macrophages, eosinophil cationic peptide (ECP) and sIL-4 levels.To our knowledge, this is the first documentation of omalizumab use in ACOS. We demonstrated decreased IL-4, allergic pulmonary symptoms (dyspnea, wheezing, bronchial hyper responsiveness) and migraine attacks in the patients.

Kebudi, Rejin/0000-0003-4344-8174; ERDOGAN, OZGE SUKRUOGLU/0000-0002-0893-1251; KURU TURKCAN, GOZDE/0000-0001-5974-4731; TUNCER, SEREF BUGRA/0000-0001-8023-3223; celik, betul/0000-0001-7923-275X; Akdeniz Odemis, Demet/0000-0002-2271-8481 WOS:000480287200055 PubMed ID: 31207142 Background Retinoblastoma (Rb) is the most prevalent intraocular pediatric malignancy of the retina. Significant genetic factors are known to have a role in the development of Rb. Methods Here, we report the mutation status of 4813 clinically significant genes in six patients with noncarrier of RB1 gene mutation and having normal RB1 promoter methylation from three families having higher risk for developing Rb in the study. Results A total of 27 variants were detected in the study. Heterozygous missense variants c.1162G > A (p.Gly388Arg) in the FGFR4 gene; c.559C > T (p.Pro187Ser) in the NQO1 gene were identified. The family based evaluation of the variants showed that the variant, c.714T > G (p.Tyr238Ter), in the CLEC7A gene in first family; the variant, c.55C > T (p.Arg19Ter), in the APOC3 gene and the variant, c.1171C > T (p.Gln391Ter), in the MUTYH gene in second family; and the variant, c.211G > A (p.Gly71Arg), in the UGT1A1 gene in the third family, were found statistically significant (p < 0.05). Conclusion This study might be an important report on emphazing the mutational status of other genes in patients without RB1 gene mutations and having high risk for developing Rb. The study also indicates the interaction between the retinoic acid pathway and Rb oncogenesis for the first time. Bilimsel Arastirma Projeleri Birimi, Istanbul Universitesi [21460] Bilimsel Arastirma Projeleri Birimi, Istanbul Universitesi, Grant/Award Number: Project number: 21460

Studies on sCD200 (OX-2), 25-hydroxyvitamin-D (25(OH)D), homocysteine (hcy), eosinophil cationic peptide (ECP), d-dimer, CXCL8 and fractional exhale nitric oxide concentrations in allergic patients in Mediterranean regions under various climatic conditions have not been performed. In this report, blood samples were taken in May and June during times of high air pollination. This study was performed to compare serum biomolecule concentrations in allergic patients and matched controls and to evaluate the characteristics of allergic disease.The study participants (n = 129) included 25 healthy individuals (controls) and 104 allergic patients. Consecutive patients with managed allergic disease (Group II, III, IV and V) above the age of 18 years were included.In the control group, there was a significant positive correlation between ECP level and body mass index (BMI). Positive correlations among ECP, IgE and OX-2 levels were detected in Group IV. In Group V patients, positive correlations between age and IgE and between BMI and 25(OH)D were identified. Statistical analysis revealed positive correlations among basophil, eosinophil and OX-2 levels, and a negative correlation between ECP and age in Group V.Overall, these data suggest that hcy, 25(OH)D and OX-2 may be useful biomarkers for conventional clinical measurements.

BACKGROUND CD200 (OX-2) is a novel immune-effective molecule, existing in a cell membrane-bound form, as well as in a soluble form in serum (s OX-2), which acts to regulate inflammatory and acquired immune responses. MATERIAL AND METHODS We planned this study to evaluate the sOX-2 levels of type 2 diabetic foot (group B), and compare it with that of healthy controls (group A). The patient group had the following values: DM period: 27.9±10.3 year [mean ±SD], HbA1c: 9.52±2.44% [mean ±SD]. RESULTS Blood samples for sCD200 measurement were always taken in the morning between 8 and 10 A.M.. The results were reported as means of duplicate measurements. Concentrations of sOX-2 in the serum samples were quantified using an ELISA kit. Serum hs-CRP levels were measured using an hs-CRP assay kit. The sOX-2 level in group B was 173.8±3.1 and in group A was 70.52±1.2 [p

D-dimer (DD), a fibrin degradation product formed during the lysis of a thrombus, is also detected in high levels in patients with active chronic urticaria (CU). Severe persistent allergic asthma (SPA) is associated with a procoagulant state in the bronchoalveolar space, further aggravated by impaired local activities of the anticoagulant protein C/protein S, antithrombin III system and fibrinolysis. This was demonstrated as massive fibrin depositions found in the alveoli of a SPA patient who died from a SPA attack and who did not respond to treatment.For this reason, we investigated the effect of omalizumab both in bronchial and systemic vascular areas and evaluated SPA (group I) and CU (group II) patients before and after therapy period.Blood samples were taken before treatment (A), on 4th month (B), on 8th month (C) and on 12th month (D) post treatment in both groups.We compared DD levels between groups: the significant DD difference was observed between group-IA and group-IC (p = 0.031); between group-IA and group-ID (p = 0.003); between group-IB and group-ID (p = 0.049) and between group IIA-1 and group-IID (p = 0.015). In the IIA-1 group, there was a significant positive correlation between DD and age (p = 0.008, r = 0.848).In conclusion, mediators and cells classically involved in procoagulant and anticoagulant pathways together play a role in SPA and CU pathophysiology, where omalizumab has its effect.

Background The changes and correlations of TRAIL (TNF-related apoptosis-inducing-ligand) and CXCL8 (IL8) prior to treatment and three months following therapy as well as the corresponding Positron emission tomography (PET/CT) (SUVmax: standardized uptake maximum values) results were evaluated. Material/Methods The measurements were taken before and after treatment for comparison purposes. The study population comprised 29 patients with Metastatic Colorectal cancer (MCRC), undergoing PET/CT scanning prior to treatment. Results There were significant changes prior to treatment and three months later for sTRAIL (p=0.0080) and CXCL8 (p=0.0001)values. Generally, sTRAIL values were increasing during therapy, while a decrease was observed for CXCL8. Correlation analysis was applied to the data and revealed significant correlations for the SUVmax in the primary tumor prior to treatment and CXCL8 prior to therapy (p=0.0303). Furthermore, significant correlations were observed for the SUVmax and sTRAIL (p=0.0237) as well as CXCL8 (p=0.0002) three months after treatment initiation. CXCL8 prior to treatment was also correlated with the SUV three months after onset of treatment (p=0.0072). A significant correlation was noted for one combination of two variables, the SUVmax in the metastases and CXCL8 prior to treatment (p=0.0175). These results are supported when we group the SUVmax in the metastases following treatment into two groups with SUVmax 5. Conclusions This study provides evidence that proteomics patterns of sTRAIL and CXCL8 predict tumor response und survival in MCRC patients treated with bevacizumab and within a high concordance of FDG-PET/CT findings.

WOS:000393254100009 PubMed: 27169944 In this study, associations between IL-4, IL-6, and macrophage migration inhibitory factor (MIF) polymorphisms and susceptibility to brucellosis were investigated. Consecutive adult patients with no known treatment against brucellosis and who did not have any other autoimmune and/or chronic disorders, were included in this study (n = 120, Group I). Age and sex-matched controls who had no other autoimmune and/or chronic disorders were also included (n = 120, healthy volunteers, Group II). The IL4_P2P2 genotype, IL4_P1 allele, and IL4_variable number of tandem repeats (VNTR)_IL6-174CG compound genotype were found to be more frequent in the patient group than in control subjects. There were significant differences between the patients and controls with respect to the frequencies of the IL4_P2P2 genotype (77.5% versus 87.5%; p = 0.001; OR, 0.36; 95% confidence interval [CI], 0.21-0.62) and the IL4_P1 allele (12.1% versus 6.7%; p = 0.030; OR, 0.92; CI, 1.02-3.64). The IL4-VNTR_IL6-174CG compound genotype was also present at a significantly higher frequency in the patient group than in control subjects (11.7% versus 4.2%; p = 0.027, OR, 3.04; CI, 1.06-8.68). No statistically significant differences in the frequencies of the IL-6-174, MIF-173, IL-4_P1P1, and IL4_P2P1 genotypes were observed between patients and control subjects. The IL4_VNTR P1 allele, P2P2 genotypes, and IL4-VNTR_IL6-174CG P2P1-GG genotypes are common in southern Turkey, and carriers of these polymorphisms are susceptible to brucellosis.

Thyroid fine-needle aspiration (FNA) is used to assess appropriate management of nodular thyroid lesions safely, but Bethesda category III (atypia of undetermined significance/follicular lesion of undetermined significance) and category IV (follicular neoplasm/suspicious for follicular neoplasm) lesions are problematic. This study aimed to evaluate the Afirma Gene Expression Classifier (GEC) results for lesions in those categories.Medical records of patients with thyroid FNA and GEC results were obtained from archived material. Results were compared to thyroidectomy histologic diagnoses.Among 66 patients with FNA results (47 women and 19 men aged 26-89 years [mean, 59.4 years]), surgical reports were available for 38. Afirma GEC results were "nondiagnostic" for 10 of 66 (15.2%), "benign" for 22 (33.3%), and "suspicious" for 34 (51.5%). Surgical diagnosis was available for 38 of 66 patients (57.6%); GEC results for 6 (15.8%) of these were "nondiagnostic," 27 (71.0%) were "suspicious," and 5 (13.2%) were "benign." One of 6 (16.7%) samples with "nondiagnostic" results, 1 of 5 (20%) with "benign" results, and 15 of 27 (55.6%) with "suspicious" results were malignant on histology. Papillary carcinoma was the most common tumor type (15 of 38; 39.5%).Afirma GEC results minimize the number of unnecessary operations. Afirma GEC testing may be reserved for FNAs with a category III diagnosis on follow-up cytologic examination. We recommend a conservative approach for "suspicious" Afirma GEC results if Hürthle cells are seen with FNA.

The purpose of this study was to evaluate the soluble Apo-2L (sApo-2L) levels in the ascitic fluid and to study its potential in detecting malignant ascites and soluble CD200 (sCD200,sOX-2) levels so as to predict its clinical usage for detecting stage 4 metastatic endometrial, ovarian and breast cancer in serum samples.Ascitic fluid from 53 and blood from 25 subjects without known malignancy on admission were collected. There were 14 breast cancer (BC), 17 ovarian cancer (OC) and 19 endometrial cancer (EC) patients diagnosed later on. Blood samples for sApo-2L, sCD200, liver function tests and CEA, CA-19.9 and CA-125 were always taken and assayed in the morning.Significantly low levels of sApo-2L were observed in peritoneal fluid from OC and EC patients compared to benign peritoneal fluid from control individuals. Positive correlation was observed between sApo-2L and aspartate aminotransferase (AST) in benign peritoneal fluid and sCD200, and creatinine and sCD200 and platelets in OC patients; also, sCD200 and CEA in EC patients and sCD200 and blood urea nitrogen (BUN) in healthy subjects.Our data indicate that low proteomics pattern of sApo-2L but not sCD200 is a good biochemical marker. Further decline in the level of sApo-2L was seen in EC compared to OC. Since higher levels of sApo-2L were seen with higher levels of AST, the liver might be involved in its metabolism. The positive correlation detected between sCD200 and creatinine, platelets, CEA and BUN needs to be elucidated.

Pro-inflammatory factors regulated by TRAIL in vivo may lead to the development of novel therapeutic strategies for diseases as diverse as infection, autoimmunity and allergy. In this study we aimed to investigate the relationship between IFN treatment response, HCV viral load and sApo 2L levels. Eleven HCV-treatment naive HCV-infected patients were treated with pegIFN alfa-2a. Intensive serum circulating Apo 2L levels were monitored at study visits on day 0 (pretreatment), and in weeks 4, 6 and 12. HCV-RNA and sApo 2L levels decreased gradually with PegIF-alfa 2 treatment and the differences were significant between day 0 and week 4 (p 0.001, p 0.005 and p 0.01, p 0.005 respectively); between day 0 and week 12 (p 0.001, p 0.005 and p 0.001, p 0.000 respectively); between weeks 6 and 12 (p 0.01, p 0.05 and p 0.01, p 0.05 respectively). We suggest that decreased levels of circulating Apo 2L may reflect its increased binding to its ligand expressed on hepatocytes or lymphocytes under the influence of PegIFN treatment.

Radial scars (RSs) or complex sclerosing lesions (CSLs) of the breast are benign radiologic and histologic entities. With the introduction of population-based screening programs, their incidence has increased to 0.03% to 0.09% of all core needle biopsies (CNBs). They can pose diagnostic difficulty because their radiologic and histologic appearances mimic carcinoma. We retrospectively searched for and reviewed all cases of RS/CSL diagnosed on image-guided CNB from January 1, 1994, to August 31, 2013, at a single institution. We also assessed the pathologic reports from excisional biopsies to identify cases upstaged to atypia or neoplasm. After exclusions, 100 CNBs were identified from 97 women, which showed RS/CSL without concomitant atypia. Mean age of the women was 52.9 years. Thirty-five women (38/100 CNBs, 38%) had follow-up excision. The median size of the excised RS/CSLs was 1.2 cm; 69% were larger than 1.0 cm. Almost all excised cases (92%) showed radiologic and pathologic concordance, and 79% were designated as suspicious for malignancy (Breast Imaging Reporting and Data System level 4). The most common findings of 38 follow-up excisional biopsies were residual RS (22 [58%]), atypical lobular hyperplasia (5 [13%]), and no residual lesion (5 [13%]). Eleven excisional biopsies (29%) were upstaged to invasive or in situ carcinoma or to atypical hyperplasia. Follow-up excisional biopsy is warranted for RS/CSLs, specifically those larger than 1.0 cm with worrisome radiographic findings or with radiologic and pathologic discordance. Approximately 29% of cases were upstaged to in situ or invasive carcinomas or other high-risk lesions in our study.

Classical anti-mitotic drugs have failed to translate their preclinical efficacy into clinical response in human trials. Their clinical failure has challenged the notion that tumor cells divide frequently at rates comparable to those of cancer cells in vitro and in xenograft models. Given the preponderance of interphase cells in clinical tumors, we asked whether targeting amplified centrosomes, which cancer cells carefully preserve in a tightly clustered conformation throughout interphase, presents a superior chemotherapeutic strategy that sabotages interphase-specific cellular activities, such as migration. Herein we have utilized supercentrosomal N1E-115 murine neuroblastoma cells as a test-bed to study interphase centrosome declustering induced by putative declustering agents, such as Reduced-9-bromonoscapine (RedBr-Nos), Griseofulvin and PJ-34. We found tight ‘supercentrosomal’ clusters in the interphase and mitosis of ~80% of patients’ tumor cells with excess centrosomes. RedBr-Nos was the strongest declustering agent with a declustering index of 0.36 and completely dispersed interphase centrosome clusters in N1E-115 cells. Interphase centrosome declustering caused inhibition of neurite formation, impairment of cell polarization and Golgi organization, disrupted cellular protrusions and focal adhesion contacts—factors that are crucial prerequisites for directional migration. Thus our data illustrate an interphase-specific potential anti-migratory role of centrosome-declustering agents in addition to their previously acknowledged ability to induce spindle multipolarity and mitotic catastrophe. Centrosome-declustering agents counter centrosome clustering to inhibit directional cell migration in interphase cells and set up multipolar mitotic catastrophe, suggesting that disbanding the nuclear–centrosome–Golgi axis is a potential anti-metastasis strategy.

Our objective was to evaluate the diagnostic yield of rapid on-site evaluation (ROSE) on the differential diagnosis of non–small cell lung carcinoma, not otherwise specified (NSCLC-NOS). Biopsied cases diagnosed as NSCLC-NOS with ROSE during 2004 through 2008 were retrieved. Diagnostic confirmation was done with immunohistochemistry (IHC) involving thyroid transcription factor-1 and p63 immunostains. For the study, 106 cases were available. The final diagnoses rendered were squamous cell carcinoma (SqCC) (n = 39) and adenocarcinoma (AC) (n = 67). Cytologic, histologic, and IHC concordance for these diagnoses occurred in 75 cases (70.8 %), of which 56 (52.8 %) were AC and 19 (17.9 %) were SqCC. Cytologic, histologic, and IHC discordance was found in 31 cases (29.2 %). Of these 31 cases, 11 NSCLC-NOS diagnoses histologically corresponded to 1 SqCC plus 4 ACs, and 4 favor SqCC plus 2 ACs; the former 5 NSCLC-NOS cases classified correctly through cytology, as well as IHC. However, IHC was not available for the latter 6 NSCLC-NOS cases that were also classified correctly through cytology. In addition, only 3 NSCLC-NOS diagnoses cytologically corresponded to 3 favor SqCC histologically, in which IHC was not available, and for 2 cases that both corresponded to favor SqCC and favor AC histologically and cytologically. In the other 15 cases, histology labeled 4 cases NSCLC-NOS and misclassified 2 cases; cytology labeled 1 case NSCLC-NOS and misclassified 13 cases. ROSE has high diagnostic yield over subclassification of NSCLC-NOS. We recommend allocating a cytotechnologist for specimen adequacy and a cytopathologist for cytologic diagnosis.

This study seeks to define the glomerular changes that are associated with human BK virus nephropathy (BKVN). It is based on histopathologic review of 124 biopsies showing light-microscopic changes of viral nephropathy. The diagnosis of BKVN was confirmed by immunohistochemistry or by in situ hybridization. Histological lesions were scored by the Banff 97 criteria for renal allograft pathology and were correlated with clinical parameters. Viral cytopathic effect in the parietal Bowman's capsular epithelium was seen in 21/124 (17%) biopsies. Immunohistochemistry showed infection of Bowman's capsular epithelium in an additional 15/124 (12%) biopsies. Crescents were found in 15/124 (12%) samples. Glomerulitis exceeding grade Banff g1 was only occasionally shown (4/124 = 3% biopsies). Other pathologic lesions documented include mild increase in mesangial matrix in 23% biopsies, aneurysmal dilatation of glomerular capillaries in 28%, ischemic glomerulopathy in 62%, and chronic transplant glomerulopathy graded as mild (cg1) in 62% of biopsies and as moderate (cg2) in 2/124 (1.9%) biopsies. These findings show that infection of the glomerular epithelium cells can occur in a subset of patients with BKVN, most often in biopsies with high viral load in the tubular epithelium. Isolated crescents can occur in BKVN biopsies, but rapidly progressive glomerulonephritis is not observed. Two biopsies showed electron-dense deposits on ultrastructural examination, but a cause and effect relationship to BK virus infection could not be established.

Our initial cases of polyoma virus allograft nephropathy (PVAN) received pulse steroids due to anxiety about concomitant acute rejection triggered by the presence of tubulitis. However, our current policy is to reduce immunosuppression in all cases. The aim of this study was to determine whether clinical follow-up in these patient categories shows any differences in: (a) histologic viral load, (b) grade of tubulitis, and (c) graft function. Reduced viral load assessed within 8 weeks was seen in 4/20 (20.0%) biopsies treated initially by increased immunosuppression, compared to 15/19 (83.3%) biopsies treated with reduced immunosuppression (p = 0.001, Fisher's exact test). Yet, >70% reversal of the rise in serum creatinine occurred in only 3/19 (15.8%) and 1/19 (5.3%) patients, respectively, in these two groups. Improved tubulitis was seen in 11/20 (55%) of biopsies treated with steroids, despite the lack of beneficial effect on serum creatinine in 12/19 (63.1%) instances. In biopsies not treated with any change in immunosuppression, the serum creatinine remained stable in 1/5 (20%) and worsened in 4/5 (80%) biopsies. These data demonstrate that in biopsies with PVAN and tubulitis, reduced immunosuppression is more effective in lowering viral load than steroid therapy. Lack of parallelism between viral load, tubulitis grade, and serum creatinine illustrates a complex interplay of viral and alloimmune factors leading to graft injury.