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Intestinal Failure and Aberrant Lipid Metabolism in Patients With DGAT1 Deficiency
No full textBACKGROUND & AIMS: Congenital diarrheal disorders are rare inherited intestinal disorders characterized by intractable, sometimes life-threatening, diarrhea and nutrient malabsorption; some have been associated with mutations in diacylglycerol-acyltransferase 1 (DGAT1), which catalyzes formation of triacylglycerol from diacylglycerol and acyl-CoA. We investigated the mechanisms by which DGAT1 deficiency contributes to intestinal failure using patient-derived organoids. METHODS: We collected blood samples from 10 patients, from 6 unrelated pedigrees, who presented with early-onset severe diarrhea and/or vomiting, hypoalbuminemia, and/or (fatal) protein-losing enteropathy with intestinal failure; we performed next-generation sequencing analysis of DNA from 8 patients. Organoids were generated from duodenal biopsies from 3 patients and 3 healthy individuals (controls). Caco-2 cells and patient-derived dermal fibroblasts were transfected or transduced with vectors that express full-length or mutant forms of DGAT1 or full-length DGAT2. We performed CRISPR/Cas9-guided disruption of DGAT1 in control intestinal organoids. Cells and organoids were analyzed by immunoblot, immunofluorescence, flow cytometry, chromatography, quantitative real-time polymerase chain reaction, and for the activity of caspases 3 and 7. RESULTS: In the 10 patients, we identified 5 bi-allelic loss-of-function mutations in DGAT1. In patient-derived fibroblasts and organoids, the mutations reduced expression of DGAT1 protein and altered triacylglycerol metabolism, resulting in decreased lipid droplet formation after oleic acid addition. Expression of full-length DGAT2 in patient-derived fibroblasts restored formation of lipid droplets. Organoids derived from patients with DGAT1 mutations were more susceptible to lipid-induced cell death than control organoids. CONCLUSIONS: We identified a large cohort of patients with congenital diarrheal disorders with mutations in DGAT1 that reduced expression of its product; dermal fibroblasts and intestinal organoids derived from these patients had altered lipid metabolism and were susceptible to lipid-induced cell death. Expression of full-length wildtype DGAT1 or DGAT2 restored normal lipid metabolism in these cells. These findings indicate the importance of DGAT1 in fat metabolism and lipotoxicity in the intestinal epithelium. A fat-free diet might serve as the first line of therapy for patients with reduced DGAT1 expression. It is important to identify genetic variants associated with congenital diarrheal disorders for proper diagnosis and selection of treatment strategies
Neonatal Hyperglycemia, which threshold value, diagnostic approach and treatment?: Turkish Neonatal and Pediatric Endocrinology and Diabetes Societies consensus report
No full textHyperglycemia has become an important risk factor for mortality and morbidity in the neonatal period, especially with increased survival rates of very low birth weight babies. Hyperglycemia in the neonatal period develops as a result of various mechanisms including iatrogenic causes, inability to supress hepatic glucose production, insulin resistance or glucose intolerance, specifically in preterm babies. Initiation of parenteral or enteral feeding in the early period in preterm babies increases insulin production and sensitivity. The plasma glucose is targeted to be kept between 70 and 150 mg/dL in the newborn baby. While a blood glucose value above 150 mg/dL is defined as hyperglycemia, blood glucose values measured with an interval of 4 hours of >180-200 mg/dL and +2 glucosuria require treatment. Although glucose infusion rate is reduced in treatment, use of insulin is recommended, if two blood glucose values measured with an interval of 4 hours are >250 mg/dL and glucosuria is present in two separate urine samples. © 2018 by Turkish Pediatric Association
An answer to colon cancer treatment by mesenchymal stem cell originated from adipose tissue
No full textObjective(s): Colon cancer is risen up with its complex mechanism that directly impacts on its treatment as well as its common prevalence. Mesenchymal stem cells (MSCs) have been considered as a therapeutic candidate for conventional disease including cancer. In this research, we have focused on apoptotic effects of adipose tissue-derived MSCs in colon cancer.
Materials and Methods: MSCs were obtained from adipose tissue and characterized by Flowcytometer using suitable antibodies. MSCs, HT-29, HCT-116, RKO and healthy cell line MRC5 were cultured by different seeding procedure. After cell viability assay, changes in caspase 3 enzyme activity and the level of phosphatidylserine were measured.
Results: For cell viability assay, a 48 hr incubation period was chosen to seed all cells together. There was a 1.36-fold decrease in caspase 3 enzyme activity by co-treatment of RKO and MSCs in addition to 2.02-fold decrease in HT-29 and MSCs co-treatment, and 1.103-fold increase in HCT-116 and MSCs. The results demonstrated that HCT-116 led to the highest rate of apoptotic cell death (7.5%) compared with other cells.
Conclusion: We suggest that MSCs might remain a new treatment option for cancer by its differentiation and repair capacity
Evaluation of 2015-2016 MOTAKK HBV DNA and HCV RNA external quality assessment national program results [MOTAKK HBV DNA ve HCV RNA diş kalite kontrol ulusal programi 2015-2016 sonuçlarinin deǧerlendirilmesi]
No full textMOTAKK, as a national external quality control program has been launched to evaluate the molecular detection of viral infections including HBV DNA and HCV RNA in molecular microbiology diagnostic laboratories in Turkey. This program is prepared in compliance with ISO 17043:2010 (Conformity assessment general requirements for proficiency testing) standards, and aims to take the place of external quality control programs from abroad, contributing to standardization and accuracy of molecular diagnostic tests in our country. The aim of this study was to evaluate 2015 and 2016 results of the MOTAKK External Quality Control Program for HBV DNA and HCV RNA viral load. The calls were announced on the web page of MOTAKK (www.motakk.org). The quality control samples were sent to participating laboratories in 2015 and 2016. Main stocks were prepared from patients with chronic hepatitis B and C who had viral load detection with reference methods according to WHO reference materials for viral load studies to improve quality control sera. From these main stocks, samples with different viral loads were prepared from dilutions of plasma with HBV, HCV, HAV, HIV, Parvovirus B19 and CMV negative serologic markers. Quality control samples were sent to the participating laboratories along with the negative samples in the cold chain. The laboratories accomplished the related tests within 2-3 weeks and entered their results on the MOTAKK web page. These results were analysed according to ISO 13528 (Statistical methods for use in proficiency testing by interlaboratory comparison) and scoring reports were created by a software developed by MOTAKK and sent to participating labs. Each laboratory evaluated their own results in comparison with the other laboratory results, reassessed the tests via observing the distance from the mean result and the reference values. The number of laboratories participating in the HBV DNA and HCV RNA external quality control program was 70-73 in 2015-2016. Participants were able to comply with the program tools, registering, entering results and receiving the results reports without problem. In HBV panel, 72.6-89.1% and 84.7-90.3% of the participant laboratories were in 1 standard deviation (SD) in 2015-2016, respectively. In HCV panel, 70.8-89.1% and 84.7-90.3% of the participant laboratories were in 1 SD in 2015-2016, respectively. A national external quality control program for HBV DNA and HCV RNA in Turkey has been prepared for the first time with this project and implemented successfully. All the data provided in the MOTAKK external quality control program final report, compensate all the data provided by the quality control program final reports from abroad; additionally, the report allows comparison of used technologies and commercial products. © 2018 Ankara Microbiology Society. All rights reserved
Gastrointestinal Stromal Tumors: A Clinicopathologica and Immunohistochemical Study of 65 Cases
No full textObjective: Hie clinical behavior of gastrointestinal stromal tumors is divergent. The aim of the present study was to define the clinicopathological features that determine the patient's outcome.
Material and Method: Sixty-five gastrointestinal stromal tumors were reviewed with their histological, immunohistochemical and clinical features and compared with their clinical outcome statistically.
Results: Tumors were located in the stomach (n=39, 60%), small intestine (n=22, 33.8%) and large intestine (n=4, 6.2%). Immunohistochemically, CD 117 positivity was found in 90.8%, whereas CD34, Smooth muscle actin, Desmin and S100 positivity was found in 73.3%, 61.7%, 11.7% and 28.3% of tumors respectively. All six "CD 117-negative" cases expressed DOG-1. The mean Ki-67 proliferation index was 8.69%+/- 12.76. Liver metastasis was detected in seven cases. A significant association was detected between decreased mean survival time and increased tumor size (p<0.001), large bowel localization (p-0.047), mitosis (p<0.001), the presence of necrosis (p=0.001), metastasis (p=0.033), Ki-67 proliferation index (p-0.002) and risk category (p<0.001). CD 34 positivity was mostly seen in the stomach (p-0.001), and CD 34 positive tumors had longer overall survival (92.85.+/- 5.77 months versus 67.21 +/- 13.68 months) (p=0.046). Higher Ki-67 proliferation index (6%) was also correlated with the presence of metastases (p=0.015).
Conclusion: Our study indicates that in addition to well-known risk factors such as increased tumor size, high mitotic activity and metastasis; higher Ki-67 proliferation index, the presence of necrosis, and CD34 negativity also correlate with shorter survival time
Long-Term Follow-Up of a Case with Nijmegen Breakage Syndrome
No full textThe Nijmegen Breakage Syndrome (NBS) is a rare chromosomal instability disorder clinically characterized by microcephaly, typical facial appearance, growth and mental retardation, immunodeficiency and a significant predisposition to lymphoid malignancy. The gene mutated in NBS, NBS1, has been mapped to the 8q21 chromosome. The product of this gene is a protein with a molecular weight of 95 kDa named nibrin. One of the common features of NBS is dysregulation of both cellular and humoral arms of the immune system, resulting in recurrent bacterial and viral infections, mainly of the respiratory tract. NBS is a rare syndrome. It should be considered that NBS may be associated with immunodeficienc
The Evaluation of Clinical Signs in Patients with Suspected Renovascular Hypertension
No full textOBJECTIVE: Renovascular hypertension (RVH) is the most common yet correctable cause of secondary hypertension if diagnosed early. There are many clinical signs that can suggest RVH. The aim of this study was to find which clinical or laboratory signs are more indicative in diagnosing RVH and in determining which patients should go through renal angiography.
MATERIAL and METHODS: The study included 184 patients who presented to our clinic due to hypertension and were under risk of RVH. All patients underwent three-dimensional time-of-flight Magnetic Resonance Angiography with phase-contrast. The patients were divided into two groups as with and without renal artery stenosis, supported by MRA.
RESULTS: Advanced age, low body mass index, high serum creatinine level, presence of proteinuria, and patients with diabetes mellitus and coronary artery disease were found to be significant risk factors for RVH. Only the presence of renal asymmetry and the history of coronary artery disease were found to be independent risk factors.
CONCLUSION: In conclusion, detailed patient history and the evaluation of renal size are very important for patients with hypertension. Coronary artery disease and a difference in renal size of more than 1.5 cm could be strong indicators of RVH
A Content-Based Retrieval Framework for Whole Metagenome Sequencing Samples
No full textFinding similarities and differences between metagenomic samples within large repositories has been rather a significant issue for researchers. Over the recent years, content-based retrieval has been suggested by various studies from different perspectives. In this study, a content-based retrieval framework for identifying relevant metagenomic samples is developed. The framework consists of feature extraction, selection methods and similarity measures for whole metagenome sequencing samples. Performance of the developed framework was evaluated on given samples. A ground truth was used to evaluate the system performance such that if the system retrieves patients with the same disease, -called positive samples-, they are labeled as relevant samples otherwise irrelevant. The experimental results show that relevant experiments can be detected by using different fingerprinting approaches. We observed that Latent Semantic Analysis (LSA) Method is a promising fingerprinting approach for representing metagenomic samples and finding relevance among them. Source codes and executable files are available at www.baskent.edu.tr/similar to hogul/WMS_retrieval.ra
Development of a decision support system to select materials for pressure vessels
Get PDFImprovements in technologies applied in material field and continual increase in the number of material types force to develop and use new approaches in material selection. In this paper, a multi-criteria decision support system, called MATSEL, is developed to make material selection decisions for pressure vessel components more thorough and inclusive. MATSEL consists of two separate stages. In the first elimination stage of the MATSEL, it obtains a feasible set of materials for a specified pressure vessel component. MATSEL, then, uses three different multi criteria approaches namely ELECTRE, TOPSIS and VIKOR in the second stage to rank the feasible materials. An overall total score is obtained by summing the rankings of every feasible material and MATSEL proposes the material with the lowest total score as the most suitable one for the specified component. In this study, the statistical similarities between the rankings are also calculated to analyze the differences between rankings if there are any. Instead of inputting the materials every time MATSEL is used, a material data base is formed with the usage of ASME (American Society of Mechanical Engineers) and Ashby material selection diagrams for selection of alternative materials for the specified application
Community based mental health services, in the eye of community mental health professionals
No full textObjectives: This study aims to provide views of psychiatrists, nurses, social workers and psychologists who work in community mental health centers (CMHCs) that provide services to individuals, as well as learn how to define their professional roles and responsibilities in these CMHCs.
Methods: This study is designed as a qualitative research to facilitate a comprehensive understanding of the views of research professionals. Data were collected through in-depth interviews with 11 voluntary participants from eight CMHCs in Ankara. Collected data were subjected to a qualitative analysis.
Results: The opinions of the professional staff are detailed under four headings: stigmatization, perspective of services, problems and suggestions.
Conclusion: CMHC professionals generally are evaluating community-based services in a positive manner. Recommendations include implementing regulations for development of CMHCs that are regionally based with an individual focus and integration