SMAD4 haploinsufficiency in small intestinal neuroendocrine tumors

Background: Patients with small intestinal neuroendocrine tumors (SINETs) frequently present with lymph node and liver metastases at the time of diagnosis, but the molecular changes that lead to the progression of these tumors are largely unknown. Sequencing studies have only identified recurrent point mutations at low frequencies with CDKN1B being the most common harboring heterozygous mutations in less than 10% of all tumors. Although SINETs are genetically stable tumors with a low frequency of point mutations and indels, they often harbor recurrent hemizygous copy number alterations (CNAs) yet the functional implications of these CNA are unclear. Methods: Utilizing comparative genomic hybridization (CGH) arrays we analyzed the CNA profile of 131 SINETs from 117 patients. Two tumor suppressor genes and corresponding proteins i.e. SMAD4, and CDKN1B, were further characterized using a tissue microarray (TMA) with 846 SINETs. Immunohistochemistry (IHC) was used to quantify protein expression in TMA samples and this was correlated with chromosome number evaluated with fluorescent in-situ hybridization (FISH). Intestinal tissue from a Smad4+/− mouse model was used to detect entero-endocrine cell hyperplasia with IHC. Results: Analyzing the CGH arrays we found loss of chromosome 18q and SMAD4 in 71% of SINETs and that focal loss of chromosome 12 affecting the CDKN1B was present in 9.4% of SINETs. No homozygous loss of chromosome 18 was detected. Hemizygous loss of SMAD4, but not CDKN1B, significantly correlated with reduced protein levels but hemizygous loss of SMAD4 did not induce entero-endocrine cell hyperplasia in the Smad4+/− mouse model. In addition, patients with low SMAD4 protein expression in primary tumors more often presented with metastatic disease. Conclusions: Hemizygous loss of chromosome 18q and the SMAD4 gene is the most common genetic event in SINETs and our results suggests that this could influence SMAD4 protein expression and spread of metastases. Although SMAD4 haploinsufficiency alone did not induce tumor initiation, loss of chromosome 18 could represent an evolutionary advantage in SINETs explaining the high prevalence of this aberration. Functional consequences of reduced SMAD4 protein levels could hypothetically be a potential mechanism as to why loss of chromosome 18 appears to be clonally selected in SINETs

Mean platelet volume could be a promising biomarker to monitor dietary compliance in celiac disease

Background. Celiac disease (CD) is an autoimmune disease that develops in patients with a genetic predisposition, incurring a susceptibility to gluten-containing foods such as barley, wheat, and rye. The elimination of gluten from the diet is the main therapeutic approach and usually leads to clinical and laboratory improvement. There are no ideal markers that objectively assess dietary compliance in CD patients. Materials and methods. Sixty newly diagnosed CD patients (male/female: 43/17) and 40 healthy subjects (male/female: 23/17) were enrolled in this study. The diagnosis of CD was established by both histological findings of duodenum biopsy (total villous atrophy and lymphocytic infiltration) and positive antibodies against endomysium or gliadin. Results. A significantly higher mean platelet volume (MPV) was observed in the CD group compared with healthy subjects (8.45 +/- 0.96 fL versus 7.93 +/- 0.63 fL; p = 0.004). After introduction of a gluten-free diet, the MPV of CD patients in the dietary adherent group was significantly lower than that of the non-adherent group (8.09 +/- 0.6 fL versus 8.9 +/- 1.08 fL; p = 0.001). Overall dietary adherence rate was 71.6% (43/60 CD patients). In the dietary compliant group, initiation of gluten-free diet was associated with a significant decrease in MPV from base-line values (8.56 fL versus 8.25 fL; p = 0.008). In the non-adherent group, MPV on 3-month follow-up was higher than at base-line (8.05 fL versus 8.91 fL; p = 0.001). Conclusion. MPV could be a promising and easily available biomarker for monitoring of dietary adherence in CD patients at a low cost in comparison with other modalities.WoSScopu

A population-based survey of Chronic REnal Disease In Turkey—the CREDIT study

Background. Chronic kidney disease (CKD) is a growing health problem worldwide that leads to end-stage kidney failure and cardiovascular complications. We aimed to determine the prevalence of CKD in Turkey, and to evaluate relationships between CKD and cardiovascular risk factors in a population-based survey

A physarum-inspired approach to supply chain network design

A supply chain is a system which moves products from a supplier to customers, which plays a very important role in all economic activities. This paper proposes a novel algorithm for a supply chain network design inspired by biological principles of nutrients’ distribution in protoplasmic networks of slime mould Physarum polycephalum. The algorithm handles supply networks where capacity investments and product flows are decision variables, and the networks are required to satisfy product demands. Two features of the slime mould are adopted in our algorithm. The first is the continuity of flux during the iterative process, which is used in real-time updating of the costs associated with the supply links. The second feature is adaptivity. The supply chain can converge to an equilibrium state when costs are changed. Numerical examples are provided to illustrate the practicality and flexibility of the proposed method algorithm

The Relationship between quality of life and social support in homosexuals living in Izmir Turkey

[No abstract available

Radar fingerprint extraction via variational mode decomposition [Varyasyonel Kip Ayriştirici ile Radar Parmak İzi ÇikarIffi]

In iMs paper, a novel method for extracting radar fingerprint using the unintentional modulation on radar signals is proposed. Proposed technique decomposes the unintentional modulations into its components using Variational Mode Decomposition (VMD) technique. Then, features that characterize each component are calculated. Simulations using real radar data show that proposed technique can classify radars in the dataset with high performance. © 2017 IEEE

A comparison of contribution of informed consent forms with long or short texts with regard to obtaining knowledge by volunteers: A pilot study [Tıbbi bilgi alma baglamında uzun ve kısa metinli bilgilendirilmiş onam formlarının gönüllülerin bilgilenme düzeyine katkısının karşılaştırılması: Bir pilot çalışma]

AIM: The objective is to determine which of the two texts giving information about the same issue and one of which id short and one of which is long is more effective in enlightening readers having no pre-knowledge of medical science and whether there is coherence between the scores obtained from the texts. METHOD: The sampling of the research planned as experimental is constituted by 66 volunteer female students who are 1st year students at the faculty of agriculture. The group was randomly divided into two and the first group was given the short text and the other one the long text. Then the question from was applied in order to find out how much of the information in the form they learnt. Each true answer given to the questions was scored as 1, and each wrong answer was secored as 0; therefore a total grade was obtained. For data analysis, Mann Whitney-U and t Tests analysis methods have been used. Score averages have been compared using Chi-square statistics and calculated using Odds ratio (OR). Consistency between the average scores of the answers given to short and long forms were evaluated through kapa statistics. RESULTS: 100% of the answers obtained using the long form was above the average, 20% of the answers obtained using the short form was above the average and 80% was below the average. Kappa between the answers in the long and short from was found as 81%. The results obtained from the long form were determined to be seven times better than the short one (OR:7,0). The non-random alignment between responses to the long and short form was found to be 81% (Cohen Kappa: 0,814). When the score average scores obtained from the answers given according to the demographic qualities of the participants, no meaningful relation was found. CONCLUSION: The long version of the context of informed was found more effective than the short one