Finite element modeling and experimental studies on mixed mode-I/III fracture specimens

In this study, finite element modeling and experimental studies on a mode-I/III specimen similar to the compact tension specimen are presented. By using bolts, the specimen is attached to two loading apparatus that allow different levels of mode-I/III loading by changing the loading holes. Specimens having two different thicknesses are analyzed and tested. Modeling, meshing and the solution of the problem involving the whole assembly, i.e., loading devices, bolts and the specimen, with contact mechanics are performed using ANSYSTM. Then, the mode-I/III specimen is analyzed separately using a submodeling approach, in which threedimensional enriched finite elements are used in FRAC3D solver to calculate the resulting stress intensity factors along the crack front. In all of the analyses, it is clearly shown that although the loading is in the mode-I and III directions, mode-II stress intensity factors coupled with mode-III are also generated due to rotational relative deformations of crack surfaces. The results show that the mode-II stress intensity factors change sign along the crack front and their magnitudes are close to the mode-III stress intensity factors. It is also seen that magnitudes of the mode-III stress intensity factors do not vary much along the crack front. Fracture experiments also performed and, using the stress intensity factors from the analyses and crack paths and surfaces are shown

Perspective of turkish medicine students on cancer, cancer treatments, palliative care, and oncologists (ares study): A study of the palliative care working committee of the turkish oncology group (TOG)

Cancer is one of the most common causes of death all over the World (Rahib et al. in Cancer Res 74(11):2913–2921, 2014; Silbermann et al. in Ann Oncol 23(Suppl 3):iii15–iii28, 2012). It is crucial to diagnose this disease early by effective screening methods and also it is very important to acknowledge the community on various aspects of this disease such as the treatment methods and palliative care. Not only the oncologists but every medical doctor should be educated well in dealing with cancer patients. Previous studies suggested various opinions on the level of oncology education in medical schools (Pavlidis et al. in Ann Oncol 16(5):840–841, 2005). In this study, the perspectives of medical students on cancer, its treatment, palliative care, and the oncologists were analyzed in relation to their educational status. A multicenter survey analysis was performed on a total of 4224 medical school students that accepted to enter this study in Turkey. After the questions about the demographical characteristics of the students, their perspectives on the definition, diagnosis, screening, and treatment methods of cancer and their way of understanding metastatic disease as well as palliative care were analyzed. The questionnaire includes questions with answers and a scoring system of Likert type 5 (absolutely disagree = 1, completely agree = 5). In the last part of the questionnaire, there were some words to detect what the words “cancer” and “oncologist” meant for the students. The participant students were analyzed in two study groups; “group 1” (n = 1.255) were phases I and II students that had never attended an oncology lesson, and “group 2” (n = 2.969) were phases III to VI students that had attended oncology lessons in the medical school. SPSS v17 was used for the database and statistical analyses. A value of p < 0.05 was noted as statistically significant. Group 1 defined cancer as a contagious disease (p = 0.00025), they believed that early diagnosis was never possible (p = 0.042), all people with a diagnosis of cancer would certainly die (p = 0.044), and chemotherapy was not successful in a metastatic disease (p = 0.003) as compared to group 2. The rate of the students that believed gastric cancer screening was a part of the national screening policy was significantly more in group 1 than in group 2 (p = 0.00014). Group 2 had a higher anxiety level for themselves or their family members to become a cancer patient. Most of the students in both groups defined medical oncologists as warriors (57% in group 1 and 40% in group 2; p = 0.097), and cancer was reminding them of “death” (54% in group 1 and 48% in group 2; p = 0.102). This study suggested that oncology education was useful for the students’ understanding of cancer and related issues; however, the level of oncology education should be improved in medical schools in Turkey. This would be helpful for medical doctors to cope with many aspects of cancer as a major health care problem in this country. © 2018, American Association for Cancer Education

Epigenetic perturbations in the pathogenesis of mustard toxicity; hypothesis and preliminary results

Among the most readily available chemical warfare agents, sulfur mustard (SM), also known as mustard gas, has been the most widely used chemical weapon. SM causes debilitating effects that can leave an exposed individual incapacitated for days to months; therefore delayed SM toxicity is of much greater importance than its ability to cause lethality. Although not fully understood, acute toxicity of SM is related to reactive oxygen and nitrogen species, oxidative stress, DNA damage, poly(ADP-ribose) polymerase (PARP) activation and energy depletion within the affected cell. Therefore several antioxidants and PARP inhibitors show beneficial effects against acute SM toxicity. The delayed toxicity of SM however, currently has no clear mechanistic explanation. One third of the 100,000 Iranian casualties are still suffering from the detrimental effects of SM in spite of the extensive treatment. We, therefore, made an attempt whether epigenetic aberrations may contribute to pathogenesis of mustard poisoning. Preliminary evidence reveals that mechlorethamine (a nitrogen mustard derivative) exposure may not only cause oxidative stress, DNA damage, but epigenetic perturbations as well. Epigenetic refers to the study of changes that influence the phenotype without causing alteration of the genotype. It involves changes in the properties of a cell that are inherited but do not involve a change in DNA sequence. It is now known that in addition to mutations, epimutations contribute to a variety of human diseases. Under light of preliminary results, the current hypothesis will focus on epigenetic regulations to clarify mustard toxicity and the use of drugs to correct possible epigenetic defects

The insertion/deletion (I/D) polymorphism in the Angiotensin-converting enzyme gene and cancer risk: a meta-analysis

<p>Abstract</p> <p>Background</p> <p>The insertion/deletion (I/D) polymorphism in the <it>Angiotensin-converting enzyme </it>(<it>ACE</it>) gene has been implicated in susceptibility to cancer, but a large number of studies have reported inconclusive results. The aim of this study is to assess the association between the I/D polymorphism in the <it>ACE </it>gene and cancer risk by meta-analysis.</p> <p>Methods</p> <p>A search was performed in Pubmed database, Embase database, Chinese Biomedical (CBM) database, China National Knowledge Infrastructure (CNKI) database and Weipu database, covering all studies until August 31, 2010. Statistical analysis was performed by using Revman4.2 and STATA 10.0.</p> <p>Results</p> <p>A total of 25 case-control studies comprising 3914 cancer patients and 11391 controls were identified. No significant association was found between the I/D polymorphism and over all cancer risks (OR = 0.88, 95%CI = 0.73-1.06, P = 0.17 for DD+DI vs. II). In the subgroup analysis by ethnicity, no significant association was found among Asians and Europeans for the comparison of DD+DI vs. II. In the subgroup analysis by cancer types, no significant associations were found among lung cancer, breast cancer, prostate cancer, colorectal cancer, gastric cancer for the comparison of DD+DI vs. II. Results from other comparative genetic models also indicated the lack of associations between this polymorphism and cancer risks.</p> <p>Conclusions</p> <p>This meta-analysis suggested that the <it>ACE </it>D/I polymorphism might not contribute to the risk of cancer.</p

Acute and delayed sulfur mustard toxicity; novel mechanisms and future studies

Sulfur mustard (SM), also known as mustard gas, has been the most widely used chemical weapon. The toxicity of SM as an incapacitating agent is of much greater importance than its ability to cause lethality. Acute toxicity of SM is related to reactive oxygen and nitrogen species, DNA damage, poly(ADP-ribose) polymerase activation and energy depletion within the affected cell. Therefore melatonin shows beneficial effects against acute SM toxicity in a variety of manner. It scavenges most of the oxygen- and nitrogen-based reactants, inhibits inducible nitric oxide synthase, repairs DNA damage and restores cellular energy depletion. The delayed toxicity of SM however, currently has no mechanistic explanation. We propose that epigenetic aberrations may be responsible for delayed detrimental effects of mustard poisoning. Epigenetic refers to the study of changes that influence the phenotype without causing alteration of the genotype. It involves changes in the properties of a cell that are inherited but do not involve a change in DNA sequence. It is now known that in addition to genetic mutations, epimutations can also involve in the pathogenesis of a variety of human diseases. Several actions of melatonin are now delineated by epigenetic actions including modulation of histone acetylation and DNA methylation. Future studies are warranted to clarify whether epigenetic mechanisms are involved in pathogenesis of delayed sulfur mustard toxicity and melatonin alleviates delayed toxicity of this warfare agent

Molecular, genetic and epigenetic pathways of peroxynitrite-induced cellular toxicity

Oxidative stress plays a key role in the pathogenesis of cancer and many metabolic diseases; therefore, an effective antioxidant therapy would be of great importance in these circumstances. Nevertheless, convincing randomized clinical trials revealed that antioxidant supplementations were not associated with significant reduction in incidence of cancer, chronic diseases and all-cause mortality. As oxidation of essential molecules continues, it turns to nitro-oxidative stress because of the involvement of nitric oxide in pathogenesis processes. Peroxynitrite damages via several distinctive mechanisms; first, it has direct toxic effects on all biomolecules and causes lipid peroxidation, protein oxidation and DNA damage. The second mechanism involves the induction of several transcription factors leading to cytokine-induced chronic inflammation. Finally, it causes epigenetic perturbations that exaggerate nuclear factor kappa-B mediated inflammatory gene expression. Lessons-learned from the treatment of several chronic disorders including pulmonary diseases suggest that, chronic inflammation and glucocorticoid resistance are regulated by prolonged peroxynitrite production

Prognoztic factors in non-small cell lung cancer: Review

Lung cancer is the leading cause of cancer-related mortality in both genders worldwide. Non-small cell lung cancer (NSCLC) represents about 80% of all lung cancers. Less than one-third of these patients present at an early stage, and substantial relapses are observed despite curative surgical treatment. For the most part, recurrences occur at extrathoracic sites as distant metastases. The remaining patients have advanced disease and treatment is only marginally effective in such patients. Thus, prognoztic factors continue to play a critical role in the prediction of outcome in such patients. Early investigations that mostly focused on clinical characteristics of the tumor and the patient were followed by a number of clinical laboratory tests. Recently, studies that investigate the prognoztic significance of novel factors related to cellular and molecular biology of lung cancer have increased. The aim of this study was to review the literature with regard to prognoztic factors in patients with NSCLC

Adjuvant chemotherapy for early-stage non-small cell lung cancer: Review

Lung cancer is the leading cause of death in the world. Non-small cell lung cancer (NSCLC) represents about 80% of the all lung cancers. Less than one-third of these patients present with early stage cancer and substantial relapses are observed despite curative surgical treatment. Recurrences are usually in the form of extrathoracic and distant metastases. Until recently, in the vast majority of studies involving postoperative treatments including chemotherapy and/or radiotherapy, no substantial survival advantage was demonstrated. Recent reports within the last 2 years with results favoring adjuvant chemotherapy, led to the consideration of adjuvant chemotherapy again. This review aims to summarize the role of adjuvant chemotherapy by evaluating novel adjuvant chemotherapy studies and metaanalyses for the use of this treatment modality in resected NSCLC. Copyright © 2006 by Türkiye Klinikleri