The diagnostic importance of pathogenic variants and variant coexistence determined by NGS-based liquid biopsy approach in patients with lung adenocarcinoma.

BACKROUND: Identification of driver mutations and rapid detection of genetic changes in lung cancer are critical in the management of the disease. Genetic structures of tumor tissues tend to change constantly and the possibility of emergence of new pathogenic variants that will create resistance to treatment. Liquid biopsy analysis has been one of the most effective approaches used to monitor and identify individual genetic changes. METHODS: In this study, TP53, EGFR, MET, ALK, PIK3CA, MAP2K, ERBB2 and ROS genes in cf DNA samples of 324 patients with lung adenocarcinoma were screened for genetic variations by NGS method. Analysis of the data showed that there were a total of 755 variations in 324 patients. RESULTS: Pathogenic and possibly pathogenic variations were identified in 178 patients (54.9%) on TP53, 118 (36.4%) on EGFR, 55 (17.0%) on MET, 46 (14.2%) on ALK, 39 (12.0%) on MAP2K, 6 (1.9%) on ERBB2 and in 2 (0,6%) patients ROS genes. The detailed variant data of the genes included in the study were compared with the patients' stage status, metastasis status, smoking, age distribution and life span data, and the presence of possible significant relationships and candidate biomarkers for the molecular pathogenesis of the disease were investigated. CONCLUSION: As a result of data analysis, genetic changes associated with metastasis and adenocarcinoma formation were identified. It has been shown that variations identified in TP53, PIK3CA, MAP2K1 and EGFR genes can play critical roles in the pathogenesis and development of the disease.

Effects of adipokinetic hormone/red pigment-concentrating hormone family of peptides in olfactory bulbectomy model and posttraumatic stress disorder model of rats.

One of the major neuropeptide groups in insects is adipokinetic hormone/red pigment-concentrating hormone (AKH/RPCH) family of peptides. AKH had improving effects on depression and anxiety in animal models and it may be a new treatment choice in these disorders. Aim of this study was to investigate effects of Anax imperator AKH (Ani-AKH), Libellula auripennis AKH (Lia-AKH) and Phormia-Terra hypertrehalosemic hormone (Pht-HrTH) on animal behavior in olfactory bulbectomy (OBX) model and in posttraumatic stress disorder (PTSD) model of Wistar-albino rats. Lia-AKH and Pht-HrTH significantly increased time spent in escape platform's quadrant compared to sham control while Lia-AKH significantly increased time spent in escape platform's quadrant compared to OBX controls in probe trial of Morris water maze (MWM). Ani-AKH, Lia-AKH and Pht-HrTH significantly decreased immobility time compared to OBX controls in forced swimming test (FST). Pht-HrTH significantly increased %open arm time compared to OBX controls in elevated plus maze (EPM) test. Ani-AKH significantly increased %open arm entry compared to sham control while Ani-AKH and Pht-HrTH significantly increased %open arm entry compared to OBX controls in EPM. In PTSD study Ani-AKH and Lia-AKH significantly decreased immobility time compared to traumatized controls in FST. In acoustic startle reflex test, Ani-AKH, Lia-AKH and Pht-HrTH significantly decreased average startle amplitude compared to non-traumatized controls in PTSD study. Metabolomic studies showed that AKH may affect glutamatergic and dopaminergic system and neurochemistry. In conclusion, AKH peptides had wide ranging effects on behavior and improved performance in OBX and PTSD models in rats.

TP53, EGFR and PIK3CA gene variations observed as prominent biomarkers in breast and lung cancer by plasma cell-free DNA genomic testing.

Use of plasma cell-free DNA genomic testing, also know as liquid biopsy, reveals information for early detection and monitoring of solid tumors. Our study reports the analysis of 113 lung and 18 breast cancer patients using commercially available platforms. Lung and breast cancer panel hotspot regions on the genes were investigated. There was a significant increase in isolation efficiency with very fresh blood samples of at least 15 millilitres which were processed in minutes. TP53 gene variations were detected in both types of tumors. Additionally, associations were found for EGFR variations in lung tumors and PIK3CA variations in breast tumors. Mutation assessment of these three genes are recommended as useful biomarkers for predictive studies, to follow up tumor growth and for personalized treatment. Mutations observed in this study warrant further investigation for follow up studies and may justify expression studies. However, in our subsequent studies, we intensify our tumor profiling strategy with other methods. However in terms of true personalized medicine,future plans would include repeating these studies with ctDNA size analysis and methylation analysis of the non-coding region in the individual tumors.

The evaluation of suicide letters in Turkey from a cognitive perspective.

BACKGROUND: Different methods are used to understand the suicidal mind. Suicide note analysis may be most direct way to do this. AIMS: To study the content of suicide letters under forensic evaluation in terms of psychological and cognitive aspects. METHODS: A total of 51 letters were referred to The Council of Forensic Medicine from different cities of Turkey and analyzed by a research group with ten members including forensic medicine specialists and psychiatrists. The Questionnaire of Content Analysis of Suicide Letters (The Q-CAS), developed by researchers, was used to analyze the cognitive and cultural themes of suicide letters. The cognitive distortions about the self, the world, and the future as well as cultural phenomena were evaluated including sociodemographic features. RESULTS: Financial problems in males and relationship problems in females were the most frequent life events related to suicide. Hopelessness, weakness, loneliness--in decreasing order--were the most predominant cognitions and emotions. The total score of females were higher than that of males (p=.002). CONCLUSIONS: These negative cognitions should be taken into consideration when therapeutic interventions are planned on individuals with suicidal thoughts.

Gender and the lateral angle of the internal acoustic canal meatus as measured on computerized tomography of the temporal bone.

INTRODUCTION: Cadaveric studies yielded promising results in sexing the temporal bones by measuring the lateral angle of the internal acoustic canal meatus. In this study, we evaluated the capability of computerized tomography of the temporal bone to reproduce these results. METHODS: Lateral angle of the internal acoustic canal meatus was measured in 92 patients (47 females and 45 males) on axial slices of high resolution computerized tomography scans of the temporal bone. The patients underwent computerized tomography as part of clinical work up for ear-related complaints. The measurement technique was modified from a cadaveric study in which a significantly higher mean lateral angle measurement was observed in females than in males. The mean values from females and males were compared statistically. RESULTS: The mean lateral angle as measured on computerized tomography of the temporal bone is greater in females (45.5+/-7.1 degrees ) than in males (41.6+/-6.7 degrees ). The difference is significant at p<0.01, as tested by one-way ANOVA. Due to significant overlap in ranges of measurements, no single cut-off value that satisfactorily differentiates between the genders could be determined. However, measurements of 35 degrees and lesser were 93.6% specific for male gender and measurements of 60 degrees and greater were 97.7% specific for female gender. CONCLUSION: Computerized tomography of the temporal bone is capable of replicating the results from the cadaveric measurements in determining the lateral angle. Due to the large range of measurements within both genders, this measurement should be regarded as supportive and not conclusive evidence for the sex of the subject.

A descriptive study of medical malpractice cases in Turkey.

BACKGROUND: Medical malpractice claims in Turkey have increased. We evaluated the problem by describing medical malpractice cases assessed by the Higher Health Council between 1993 and 1998. Our recommendations should help to improve care and decrease medical malpractice claims. METHODS: We reviewed 997 medical malpractice cases reported to the Higher Health Council between 1993 and 1998 and examined the decisions made by the Higher Health Council. We collected data on demographic characteristics, such as the type of the institution where the defendants worked, type of medical malpractice, and medical outcome. RESULTS: There were 997 medical malpractice cases reported to the Higher Health Council in the six years between 1993 and 1998. The Higher Health Council decided that 47.7% of the physicians were liable. Malpractice cases were mostly seen in state hospitals (42.4%). Fifty-nine percent of the cases resulted in death. Among actions that led to malpractice lawsuits against all health care workers, including physicians, the most common were negligence, inappropriate treatment, and diagnostic failure. CONCLUSION: We think it is necessary to revise the health system and working conditions in hospitals and to develop clinical practice guidelines. We are of the opinion that an emphasis on the use of diagnosis and therapy protocols, standards, post-graduation education, clear and informed patient consent, and improved communication with patients will drastically decrease medical malpractice claims.