Laustenconner3493

OBJECTIVE Meningioma is the most common intracranial primary brain tumor. Risk factors such as age and exposure to radiation as well as prognostic factors such as grade, location, and extent of surgical resection have been reported in the literature worldwide; however, to our knowledge, data from the Middle East is still warranted. In this study, we aim to identify the characteristics, risk factors and outcomes of meningioma patients treated at a multidisciplinary regional referral center in the Middle East. PATIENTS AND METHODS This is a retrospective chart review with a prospective follow up of outcomes. It included patients diagnosed with meningioma between January 2005 and December 2015 at the American University of Beirut Medical Center. Patient's demographics, risk factors and outcomes were first retrospectively collected. Then, we conducted phone calls to all included alive patients to update their disease status and outcomes. RESULTS One-hundred and ninety-five patients were included. 69 % had grade Irognosis in our population of Middle Eastern patients. DNA methylation is important in regulating gene expression and genomic stability while aberrant DNA methylation is associated with disease. Riboflavin (FAD) is a cofactor for methylenetetrahydrofolate reductase (MTHFR), a critical enzyme in folate recycling, which generates methyl groups for homocysteine remethylation to methionine, the pre-cursor to the universal methyl donor S-adenosylmethionine (SAM). A polymorphism (C677T) in MTHFR results in decreased MTHFR activity and increased homocysteine concentration. Previous studies demonstrated that riboflavin modulates this phenotype in homozygous adults (MTHFR 677 TT genotype), however, DNA methylation was not considered. This study examined DNA methylation, globally and at key MTHFR regulatory sites, in adults stratified by MTHFR genotype and the effect of riboflavin supplementation on DNA methylation in individuals with the 677 TT genotype. Samples were accessed from participants, screened for the MTHFR C677T polymorphism, who participated in observational (n = 80) and targeted riboflavin (1.6 mg/day) RCTs (n = 80). DNA methylation at LINE-1 and key regulatory regions of the MTHFR locus were analysed by pyrosequencing in peripheral blood leukocytes. LINE-1 (+1.6%; p = 0.011) and MTHFR south shelf (+4.7%, p  less then  0.001) were significantly hypermethylated in individuals with the MTHFR 677 TT compared to CC genotype. Riboflavin supplementation resulted in decreased global methylation, albeit only significant at one CpG. A significant reduction in DNA methylation at the MTHFR north shore (-1.2%, p  less then  0.001) was also observed in TT adults following intervention with riboflavin. This provides the first RCT evidence that DNA methylation may be modulated by riboflavin in adults with the MTHFR 677 TT genotype. V.The interaction of tumor cells with the extracellular matrix (ECM) may affect the rate of cancer progression and metastasis. One of the major components of ECM are laminins, the heterotrimeric glycoproteins consisting of α-, β-, and γ-chains (αβγ). Laminins interact with their cell surface receptors and, thus, regulate multiple cellular processes. In this work, we demonstrate that shRNA-mediated knockdown of the α5 laminin chain results in Wnt- and mTORC1-dependent partial dedifferentiation of colorectal cancer cells. check details Furthermore, we showed that this dedifferentiation involved activation of ER-stress signaling, pathway promoting the sensitivity of cells to 5-fluorouracil. V.INTRODUCTION Graduating surgery residents often feel unprepared to practice autonomously in the current era of surgical training. We implemented an integrated simulation curriculum to improve resident autonomy and increase their confidence to practice independently. In this study, we chose a laparoscopic ventral hernia repair (LVHR) as our pilot operation to test proof of concept and on which we would construct our integrated curriculum. STUDY DESIGN The curriculum included a web-based cognitive component, inanimate model simulation session with follow up at 2 weeks and 6 months, and self-confidence questionnaires. Faculty rated each resident's procedure-specific skill "in situ" by using a modified Global Operative Assessment of Laparoscopic Skills (GOALS) criteria and a task specific checklist. RESULTS Thirteen junior residents, seven senior residents, and seven faculty surgeons completed the curriculum. Four junior residents (31%) achieved proficiency at their first session, ten (77%) after the second session (p=0.031), and six (67%) at 6 months (p=>.99). Three residents regressed and did not maintain proficiency after the second assessment. Performance (GOALS) scores improved (p=0.0313) at week 2 and maintained at 6 months (p=0.5625). Faculty direction required decreased (p=0.004) and resident confidence in completing the procedure independently improved (p less then 0.004) over the 6 month curriculum. CONCLUSIONS Assessing procedure specific and global laparoscopic skills through a simulation based-curriculum is feasible and can be used to augment resident training. Our curriculum demonstrated improvement in proficiency and self-confidence while performing a LVHR. Further study is needed to examine the optimal way to integrate procedure specific simulation models into training programs. In the EU, one of the key determinants in the regulation and management of substances to ensure adequate protection of human health is the outcome of toxicity studies. These studies should therefore be performed in a way that the data generated are adequate to fulfil all regulatory requirements. However, in recent years, an increasing number of toxicity studies use dose levels that induce only slight, or even no toxicity, while the top dose lies well below the limit dose of 1000 mg/kg bw/d. The results of these studies have limited value for the hazard and subsequent risk assessment and risk management of substances. This paper shows why conducting toxicity studies with too low doses has severe consequences for among others classification and labelling, identification of endocrine disruptors, health impact assessment, and incident management. With this paper we aim to raise awareness on this issue and want to stress the importance of the use of sufficiently high dosing in toxicity studies. Given their central role in toxicity testing, it is therefore key to adapt where necessary the descriptions in OECD test guidelines and guidance documents on requirements for dose level setting, to make sure they are as explicit and unambiguous as possible.