Promoting creativity in early childhood education.

This study aims to find out the opinions and experience of teachers and teacher candidates on promoting creativity and creative thinking in the early childhood stage within the scope of the current preschool educational program. The method of the study is the basic qualitative research design. The study group consists of 25 preschool teachers employed in the province of Alanya in the city of Antalya, and 25 preschool teacher candidates who were students in their 3rd and 4th year at Akdeniz University, Faculty of Education, Department of Preschool Education. Open-ended questionnaire form was used for getting the opinions of teachers and teacher candidates. The data was analyzed within the principles of content analysis. According to the results of the study, statements on the prominence of creative thinking mainly emphasized the child being able to express her/his emotions and thoughts effectively, developing the child's problem-solving skills, forming cause- effect relationships, and being able to create a different point of view towards events and situations. As for developing creative thinking, the opinions that come to the forefront are going on trips with the children, conducting art activities, focusing on drama activities, conducting science and maths activities based on research, and motivating children to create authentic products with different materials. On the whole, teachers and teacher candidates expressed that the present preschool educational program has positive contributions to promoting creative thinking in children.

Extracellular Vesicle-Based Detection of Pancreatic Cancer.

Due to a grim prognosis, there is an urgent need to detect pancreatic ductal adenocarcinoma (PDAC) prior to metastasis. However, reliable diagnostic imaging methods or biomarkers for PDAC or its precursor lesions are still scarce. ADAM8, a metalloprotease-disintegrin, is highly expressed in PDAC tissue and negatively correlates with patient survival. The aim of our study was to determine the ability of ADAM8-positive extracellular vesicles (EVs) and cargo microRNAs (miRNAs) to discriminate precursor lesions or PDAC from healthy controls. In order to investigate enrichment of ADAM8 on EVs, these were isolated from serum of patients with PDAC (n = 52), precursor lesions (n = 7) and healthy individuals (n = 20). Nanoparticle Tracking Analysis and electron microscopy indicated successful preparation of EVs that were analyzed for ADAM8 by FACS. Additionally, EV cargo analyses of miRNAs from the same serum samples revealed the presence of miR-720 and miR-451 by qPCR and was validated in 20 additional PDAC samples. Statistical analyses included Wilcoxon rank test and ROC curves. FACS analysis detected significant enrichment of ADAM8 in EVs from patients with PDAC or precursor lesions compared to healthy individuals (p = 0.0005). ADAM8-dependent co-variates, miR-451 and miR-720 were also diagnostic, as patients with PDAC had significantly higher serum levels of miR-451 and lower serum levels of miR-720 than healthy controls and reached high sensitivity and specificity (AUC = 0.93 and 1.00, respectively) to discriminate PDAC from healthy control. Thus, detection of ADAM8-positive EVs and related cargo miR-720 and miR-451 may constitute a specific biomarker set for screening individuals at risk for PDAC.

PRMT1 promotes the tumor suppressor function of p14ARF and is indicative for pancreatic cancer prognosis.

The p14ARF protein is a well-known regulator of p53-dependent and p53-independent tumor-suppressive activities. In unstressed cells, p14ARF is predominantly sequestered in the nucleoli, bound to its nucleolar interaction partner NPM. Upon genotoxic stress, p14ARF undergoes an immediate redistribution to the nucleo- and cytoplasm, where it promotes activation of cell cycle arrest and apoptosis. Here, we identify p14ARF as a novel interaction partner and substrate of PRMT1 (protein arginine methyltransferase 1). PRMT1 methylates several arginine residues in the C-terminal nuclear/nucleolar localization sequence (NLS/NoLS) of p14ARF . In the absence of cellular stress, these arginines are crucial for nucleolar localization of p14ARF . Genotoxic stress causes augmented interaction between PRMT1 and p14ARF , accompanied by arginine methylation of p14ARF . PRMT1-dependent NLS/NoLS methylation promotes the release of p14ARF from NPM and nucleolar sequestration, subsequently leading to p53-independent apoptosis. This PRMT1-p14ARF cooperation is cancer-relevant and indicative for PDAC (pancreatic ductal adenocarcinoma) prognosis and chemotherapy response of pancreatic tumor cells. Our data reveal that PRMT1-mediated arginine methylation is an important trigger for p14ARF 's stress-induced tumor-suppressive function.

Cohort Analysis of ADAM8 Expression in the PDAC Tumor Stroma.

Pancreatic ductal adenocarcinoma (PDAC) is a cancer type with one of the highest mortalities. The metalloprotease-disintegrin ADAM8 is highly expressed in pancreatic cancer cells and is correlated with an unfavorable patient prognosis. However, no information is available on ADAM8 expression in cells of the tumor microenvironment. We used immunohistochemistry (IHC) to describe the stromal cell types expressing ADAM8 in PDAC patients using a cohort of 72 PDAC patients. We found ADAM8 expressed significantly in macrophages (6%), natural killer cells (40%), and neutrophils (63%), which showed the highest percentage of ADAM8 expressing stromal cells. We quantified the amount of ADAM8+ neutrophils in post-capillary venules in PDAC sections by IHC. Notably, the amount of ADAM8+ neutrophils could be correlated with post-operative patient survival times. In contrast, neither the total neutrophil count in peripheral blood nor the neutrophil-to-lymphocyte ratio showed a comparable correlation. We conclude from our data that ADAM8 is, in addition to high expression levels in tumor cells, present in tumor-associated stromal macrophages, NK cells, and neutrophils and, in addition to functional implications, the ADAM8-expressing neutrophil density in post-capillary venules is a diagnostic parameter for PDAC patients when the numbers of ADAM8+ neutrophils are quantified.

[The importance of non-lipid risk factors: a review focusing on C-reactive protein]. / Lipit disi risk faktörlerinin aterosklerozda önemi: C-reaktif protein odakli bir degerlendirme.

Identification of individuals at risk before the development of atherosclerosis-related diseases is important for preventive cardiology. Current risk calculators are not sufficient to effectively discriminate high-risk individuals from those having a low cardiovascular risk. It is obvious that new risk factors are needed to be used either alone or in conjunction with the current risk calculators to increase the accuracy of this discrimination. C-reactive protein (CRP) seems to be a good candidate as a biomarker, since it has been widely analyzed in prospective cohort studies and clinical trials. In this review, the value of CRP as a risk factor in atherosclerotic heart disease is discussed.

[Atorvastatin in secondary prevention]. / Ikincil korunmada atorvastatin.

During the 10 years of atorvastatin availability in the Turkish market, the physicians have had the opportunity to observe the accumulation of data related to its beneficial effect on clinical endpoints. The scope of this review is limited to the trials concerning the role of atorvastatin in secondary prevention. In GREACE and ALLIANCE studies, the benefit of atorvastatin was demonstrated in patients with coronary heart disease in real-world setting. TNT was the first trial which showed that aggressive lipid lowering therapy was more protective than a moderate one in patients with stable coronary artery disease. In the MIRACL trial, 80 mg atorvastatin was compared with placebo and found effective in preventing ischemic events in patients with non-ST elevation acute coronary syndromes. PROVE-IT proved that aggressive lipid lowering therapy with atorvastatin 80 mg was much more effective than moderate therapy (pravastatin 40 mg) in patients with all types of acute coronary syndromes. AVERT was the first statin trial to show that aggressive therapy with atorvastatin was at least as effective as angioplasty in patients with stable coronary artery disease. The SPARCL trial demonstrated the efficacy of atorvastatin in secondary prevention of patients with stroke.

Co-opting macrophage traits in cancer progression: a consequence of tumor cell fusion?

Tumor-associated macrophages (TAMs) play multiple roles in tumor initiation and progression. Tumors frequently appear in areas of chronic inflammation. This is likely aided by the mutagenic actions of macrophages. Tumor growth and progression is supported by macrophage-induced neoangiogenesis and stroma production, and macrophages produce tumor-stimulating growth factors. In most cancers a high density of TAMs predicts poor outcome. But not only do cancer cells depend upon macrophages for growth and invasion, they also co-opt macrophage traits. These include a wide diversity of molecules and pathways regulating adhesion, matrix alterations, neoangiogenesis, motility, chemotaxis, immune signaling pathways and even multidrug resistance proteins. Evidence is presented that these traits could be generated through macrophage-tumor cell fusion. Fusion has been reported in numerous animal tumor models and was recently documented in 2 human cases. Fusion could also account for the high degree of aneuploidy and plasticity in cancer, and for immune evasion. One common trait of myeloid-tumor fusion is the high expression of Beta1,6-branched N-glycans, used by macrophages in systemic migration. Beta1,6-branched oligosaccharides have long been associated with metastasis in animal models and were recently found to be common in a wide diversity of human cancers. We suggest that Beta1,6-branched oligosaccharides in human cancer may reflect widespread tumor cell fusion. Viewing the cancer cell as a myeloid hybrid provides new approaches towards understanding and treating this complex disease.

RET/papillary thyroid cancer rearrangement in nonneoplastic thyrocytes: follicular cells of Hashimoto's thyroiditis share low-level recombination events with a subset of papillary carcinoma.

CONTEXT: RET/papillary thyroid cancer (PTC) is a marker for papillary thyroid carcinoma, but its specificity has been questioned because of the disputed identification of RET/PTC in Hashimoto's thyroiditis (HT), oncocytic tumors, and other thyroid lesions. OBJECTIVE: The objective of this study was to determine 1) whether RET/PTC occurs in nonneoplastic follicular cells of HT, and 2) its recombination rate in thyroid tumors. DESIGN/PATIENTS: Forty-three samples from 31 cases of HT were examined using interphase fluorescence in situ hybridization (FISH) with RET probes spanning the breakpoint region; real-time RT-PCR to quantify RET/PTC1, RET/PTC3, and c-RET transcripts; and RT-PCR after laser capture microdissection to enrich samples for follicular cells. The results were compared with those similarly obtained in 34 papillary carcinomas, eight thyroid oncocytic tumors, and 21 normal thyroids. RESULTS: Normal samples showed no RET rearrangement. Sixty-eight percent (15 of 22) of HT were positive by FISH; in all thyroiditis, signals were localized to rare nonneoplastic follicular cells; low-level RET/PTC was identified in 17% (five of 29) of thyroiditis cases by real-time RT-PCR and in an additional six of 11 real-time negative cases after increasing sensitivity with laser capture microdissection. Low RET/PTC1 levels were detected in 26% (nine of 34) of papillary carcinomas with an expression pattern and proportion of FISH-positive cells similar to those of the thyroiditis. Forty-seven percent (16 of 34) of papillary carcinomas and one oncocytic carcinoma expressed high RET/PTC1 mRNA levels. CONCLUSIONS: Low-level RET/PTC recombination occurs in nonneoplastic follicular cells in HT and in a subset of papillary thyroid carcinomas. RET/PTC expression variability should be taken into account for the molecular diagnosis of thyroid lesions. Overlapping molecular mechanisms may govern early stages of tumor development and inflammation in the thyroid.

Natural killer cell lymphoma/leukemia with homozygous loss of p27/kip1.

We describe a case of natural killer (NK) cell lymphoma/leukemia with only an interstitial deletion in the short arm of chromosome 12 as the primary event. Fluorescence in situ hybridization revealed that the ETV6 locus (12p13) and subtelomeric sequences are not deleted in the process. The p27/kip1 locus (12p12-13), a candidate tumor suppressor gene, was deleted on the abnormal chromosome. Sequence analysis detected an adenine nucleotide deletion in the third codon of exon 1 leading to frameshift and premature termination at codon 41 of the retained copy of p27/kip1. To the best of our knowledge, this is the first report in literature on a NK cell lymphoma/leukemia with complete loss of p27/kip1.

Perivascular epithelioid cell tumor (PEComa) of the uterine cervix associated with intraabdominal "PEComatosis": A clinicopathological study with comparative genomic hybridization analysis.

BACKGROUND: The World Health Organization recently recognized a family of neoplasms showing at least partial morphological or immunohistochemical evidence of a putative perivascular epithelioid cell (PEC) differentiation. These tumors include angiomyolipoma (AML), clear cell "sugar" tumors of the lung (CCST), lymphangioleiomyomatosis (LAM), clear cell myomelanocytic tumors of the falciform ligament and distinctive clear cell tumors at various other anatomic sites. CASE PRESENTATION & METHODS: A 41-year old gravida-1 para-1 with tuberous sclerosis presented with an incidentally identified 2.2 cm mass. The morphology and immunohistochemical profile was consistent with PEComa. Distinct aggregates of HMB-45 epithelioid cells were present in an occasionally distinctive perivascular distribution in the myometrium, small bowel lamina propria and ovarian hila. These distinctive aggregates, for which we propose the designation "PEComatosis" based on their intraabdominal distribution, did not display cytological atypia, mitotic activity or necrosis. CGH and DNA ploidy analysis showed a balanced chromosomal profile and diploid nuclei, respectively. There was no recurrence or metastases at 35 months' follow-up. Fifty-one previously reported cases of non-AML, LAM and CCST PEComas [perivascular epithelioid cell tumors- not otherwise specified (PEComa-NOS)] are reviewed. CONCLUSIONS: The lesions may be a reflection of tumor multicentricity, in which each may be a potential nidus for the development of future more well-developed tumors. Alternatively, they may be a manifestation of a poorly understood "field effect", in which there is an increased propensity to develop tumors of this type throughout the abdomen. Finally, and least likely in our opinion, they may represent tumor spread from its primary site.