Tissue and plasma free amino acid detection by LC-MS/MS method in high grade glioma patients.

PURPOSE: The changes in serum amino acid profiles are evaluated in different types of cancers and screening tests were developed for estimating the risk of cancer by rapid analysis of plasma free amino acid (PFAA) levels. There is scarce evidence about the metabolomics analysis of PFAA in malignant gliomas. The aim of the present study was to identify the most promising diagnostic amino acid biomarkers that could be objectively measured for high-grade glioma and to compare their level with the tissue counterpart. METHODS: In this prospective study, we collected serum samples from 22 patients with the pathological diagnosis of high-grade diffuse glioma according to WHO 2016 classification and 22 healthy subjects, and brain tissue from 22 controls. Plasma and tissue amino acid concentrations were analyzed applying liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. RESULTS: Serum alanine, alpha-aminobutyric acid (AABA), lysine (Lys) and cysteine concentrations were significantly higher in high-grade glioma patients despite low levels of alanine and Lys in the tumor tissue. Aspartic acid, histidine and taurine were significantly decreased in both serum and tumors of glioma patients. A positive correlation was detected between tumor volumes and serum levels of latter three amino acids. CONCLUSION: This study demonstrated potential amino acids which may have diagnostic value for high-grade glioma patients by utilizing LC-MS/MS method. Our results are preliminary to compare serum and tissue levels of amino acids in patients with malignant gliomas. The data presented here may provide feature ideas about the metabolic pathways in the pathogenesis of gliomas.

Evaluation of distal tibial epiphysis and calcaneal epiphysis according to the Vieth method in 3.0 T magnetic resonance images: a pilot study.

In forensic medicine practice, age estimation-both in living and deceased individuals-can be requested due to legal requirements. Radiologic methods, such as X-rays, for the estimation of bone age have been discussed, and ethical concerns have been raised. Given these factors, radiologic methods that reduce radiation exposure have gained importance and have become one of the research topics in forensic medicine. In this study, the MR images of the ankles of patients aged between 8 and 25 years, obtained with a 3.0 T MR scanner, were evaluated retrospectively according to the staging method defined by Vieth et al. In the study, the ankle MR images of 201 cases (83 females and 118 males) with sagittal T1-weighted turbo spin echo and T2-weighted short tau inversion recovery sequences were evaluated independently by two observers. According to the results of our study, the intra- and inter-observer agreements are at a very good level for both the distal tibial and calcaneal epiphyses. All the cases detected as stages 2, 3, and 4 in both sexes for both the distal tibial and the calcaneal epiphyses have been determined to be under the age of 18 years. According to the data obtained from our study, we consider that stage 5 for males and stage 6 for both sexes in the distal tibial epiphysis and stage 6 for males in the calcaneal epiphysis can be used to estimate the age of 15 years. As far as we know, our study is the first to evaluate ankle MR images with the method defined by Vieth et al. Further studies should be conducted to evaluate the validity of the procedure.

Evaluation of distal femoral and proximal tibial epiphyseal plate in bone age estimation with 3.0T MRI: a comparison of current methods.

OBJECTIVE: Dedouit et al, Kramer et al and Vieth et al defined different staging methods over different sequences in knee MRI for bone age determination. Our study aims to examine three different methods in which the maturation stages of the knee epiphyses are evaluated by MRI in the same population, to compare the methods and results and evaluate them for some age thresholds and to discuss their applicability in forensic age estimation. METHODS: In this study, 597 knee images obtained using a 3.0T MR scanner were evaluated retrospectively. The T 1 weighted and proton density-weighted sequences were evaluated by two observers. Knee bone development was staged on the femur and tibia, and descriptive statistics were calculated for each stage according to age and sex. Descriptive statistics were presented according to the age and sex of the cases, and intra- and interobserver agreements were evaluated by the κ and κw statistics obtained by the Fleiss approach. RESULTS: Significant changes were found in stages depending on age. The intra- and interobserver agreement levels were very good (κ > 0.80) for each method. The methods of Dedouit, Kramer and Vieth can be used as an additional criteria for forensic age estimation for 14, 15, 18 and 21 year thresholds. CONCLUSION: Knee MRI stands out as an alternative modality for age estimation and it is necessary to prefer the method intended for the investigated age range with an individual-specific approach. ADVANCES IN KNOWLEDGE: Our study stands out as the first study in which current classification methods were applied and compared in the same population for age estimation with knee MRI.

Evaluation of proximal humeral epiphysis ossification in 3.0 T MR images according to the Dedouit staging method: Is it be used for age of majority?

Magnetic resonance imaging (MRI) for forensic age estimation is among the research issues since it does not lead to radiation exposure. In this study, the ossification stage of the proximal humeral epiphysis was determined retrospectively in 178 male and 109 female individuals in the 12 to 30-year age group using 3.0 T MRI. All images were evaluated with the proton density fat saturated turbo spin echo (PD TSE FS) sequence and the T2 TSE FS sequence. A five-stage scoring system was used following the method of Dedouit et al. The relevant statistics were defined as minimum, maximum, mean ± standard deviation, 95% confidence interval of mean and median and the intra- and interobserver agreement levels were very good (κ > 0.80). There were no significant age differences between males and females in any of the stages (all p-values>0.05). According to the present study, stage 5 was initially observed at age 22 years for both genders. According to our results, it is possible to determine the completion of the 18th year of life in either gender on the shoulder joint. Proximal humeral epiphysis ossification may be used as an additional method for forensic age estimation through MRI.

Applicability of 3.0 T MRI images in the estimation of full age based on shoulder joint ossification: Single-centre study.

Skeletal maturity is evaluated by many radiological methods for forensic age estimation. Direct radiography and computed tomography lead to a rise in ethical concerns due to radiation exposure. Therefore, magnetic resonance imaging (MRI) has currently been used in recent studies. In this study, the ossification stage of the shoulder joint was determined retrospectively in 178 male and 109 female individuals in the age group 12 to 30 years using 3.0 T MRI. All the images were evaluated with T1-weighted turbo spin echo (T1 TSE) sequence and T1 fast low angle shot two-dimensional sequence (T1 FL2D). The combined staging method, which was defined by Kellinghaus et al. and Schmeling et al., was used. The intra- and inter-observer agreement levels were very good (κ and κw). There were no significant age differences between males and females in all stages. In most of the stages, the ossification of the proximal humeral epiphyses occurred earlier in females than in males. Stage 4 did not occur in either of the sexes before the 18th birthday as the youngest patients in this stage was at 19 and 18 years of age in males and females, respectively. We concluded that evaluating the ossification of the proximal humeral epiphysis with MRI imaging for forensic age estimation may be beneficial. Evaluating the same anatomical structure with different MRI sequences may be useful for accurate staging diagnosis.

Evaluation of the medial clavicular epiphysis according to the Schmeling and Kellinghaus method in living individuals: A retrospective CT study.

The evaluation of the medial clavicular epiphysis via CT plays an important role in the determination of age, particularly the 19th and 22nd ages. Several authors have recommended the use of the Schmeling and Kellinghaus methods in conjunction in the evaluation of the medial clavicular epiphysis. The aim of this retrospective study was to evaluate thin section CT scan images of the medial clavicular epiphysis according to the Schmeling and Kellinghaus method, and to discuss the obtained data in the light of the literature. The thoracic CT scan images (0.6mm section thickness) of 601 patients (202 female and 399 male) aged between 10 and 35years obtained by 16-detector CT were evaluated by two examiners. The stage 2 was seen between 13 and 23years of age; stage 3 was seen between 16 and 27years of age. However, 100% of the female cases with stage 3c were ⩾18years of age, and 100% of the male cases with stage 3c were ⩾19years of age. Stage 4 was first observed at 20years of age in both sexes, and stage 5 was first observed at 25years of age in both sexes. We believe that stage 3c may be used, particularly in the determination 18-year age limit for both sexes. The outcomes of our study are consistent with those of our previous study and other studies in the literature, which is important for the confirmation of the reliability of the method.

Evaluation of the ossification of the medial clavicle according to the Kellinghaus substage system in identifying the 18-year-old age limit in the estimation of forensic age-is it necessary?

The evaluation of the ossification of the medial clavicular epiphysis being part of an assigned expert approach according to standard plays an important role within civil and criminal proceedings in assessing whether a person has reached her/his 19th or 22nd year of age. Evaluation of the medial clavicular epiphysis with thin-section CT is one of the methods recommended by the Study Group on Forensic Age Diagnostics of the German Association of Forensic Medicine. In this retrospective study, we evaluated the thin-section CT (section thickness of 0.6 and 1 mm) images of 254 patients (146 male, 108 female) with an age range of 13-28 years according to the Kellinghaus substage system. The mean values of female patients were observed to be about 10 months lower for stage 2a than the mean values of the male patients, about 13 months lower for stage 2b, and about 18 months lower for stage 2c. The earliest appearance for stage 3c was at 19 years in both sexes. Our data from this study were consistent with both our previous studies and the data of other studies. We think that stage 3c is important in determining whether a person has reached the age of 18 or not and, therefore, that the Kellinghaus substage system is a requirement in the assessment of forensic age.

Pathophysiological Function of ADAMTS Enzymes on Molecular Mechanism of Alzheimer's Disease.

The extracellular matrix (ECM) is an environment that has various enzymes attended in regeneration and restoration processes which is very important to sustain physiological and biological functions of central nervous system (CNS). One of the participating enzyme systems in ECM turnover is matrix metalloproteinases. A disintegrin-like and metalloproteinase with thrombospondin type 1 motifs (ADAMTS) is a unique family of ECM proteases found in mammals. Components of this family may be distinguished from the ADAM (A Disintegrin and Metalloproteinase) family based on the multiple copies of thrombospondin 1-like repeats. The considerable role of the ADAMTS in the CNS continues to develop. Evidences indicate that ADAMTS play an important role in neuroplasticity as well as nervous system pathologies such as Alzheimer's disease (AD). It is hopeful and possible that ADAMTS family members may be utilized to develop therapies for CNS pathologies, ischemic injuries, neurodegenerative and neurological diseases. To understand and provide definitive data on ADAMTS to improve structural and functional recovery in CNS injury and diseases, this review aimed to enlighten the subject extensively to reach certain information on metalloproteinases and related molecules/enzymes. It will be interesting to examine how ADAMTS expression and action would affect the initiation/progression of above-mentioned clinical situations, especially AD.

Evaluation of age estimation in forensic medicine by examination of medial clavicular ossification from thin-slice computed tomography images.

Forensic age estimation, a recent topic of research in forensic medicine, is of primary importance to criminal and civil law. Previous studies indicate that the observation of medial clavicular ossification allows for age discrimination along the completed 18th and 21st years of life. Experts recommend that the Schmeling and Kellinghaus methods be used together. In this study, we used these staging methods to retrospectively analyze 725 case studies (385 males, 340 females) of thin-slice computed tomography (CT) images, ranging from 0.6 to 1 mm in thickness, from individuals aged 10 to 35 years. Stage 1 was found at 18 years of age maximum for males, whereas it was found at 17 years of age for females. Stage 2a was found at 18 years of age maximum for both genders. Stage 3c was initially observed at 18 years for both genders. Stage 4 was initially found at 21 years for males and 20 years for females. Stage 5 was initially observed at 25 years for both genders. Of note, stage 3c was found close to 19 years of age for both genders (18.92 years for male, 18.99 years for female), and it may be employed to differentiate along the age majority cutoff. The data obtained from our study were consistent with previous studies. We believe that such a comprehensive database will greatly contribute to future studies focusing on medial clavicular ossification based on thin-slice CT. Moreover, we also recommend that if medial clavicular ossification based on CT is to be examined for forensic age estimation, both methods should be employed together.

The Role of ADAMTS1 and Versican in Human Myocardial Infarction: A Postmortem Study.

OBJECTIVE: To determine the role of a disintegrin and metalloproteinase with thrombospondin type 1 motif (ADAMTS1) and fragmented versican in the myocardial infarction (MI) process in humans and to evaluate the diagnostic efficacy of ADAMTS1 for postmortem diagnosis of MI. METHODS: Thirty autopsied individuals were allocated into 2 groups, namely, a study group of individuals who died of myocardial infarction (n = 20), and a control group who died of trauma (n = 10). We performed standard immunohistochemical staining on myocardial tissue specimens, studying anti-ADAMTS1, anti-versican, and anti-versican C terminal peptide sequence (DPEAAE) fragments. RESULTS: Strong, diffuse staining was observed throughout myocardial tissue for ADAMTS1 in the 2 groups. However, in the study group, we observed no expression for ADAMTS1 around fibrotic areas but detected slight staining in coagulative and necrotic zones. CONCLUSION: Similar localizations of ADAMTS and fragmented versican in human heart tissue indicate that versican presumably is cleaved by ADAMTS1. Hence, ADAMTS1 can be regarded as a new marker for postmortem differential diagnosis of MI.

Diaphragmatic Eventration: Autopsy Case Report.

Presented case was a 36-year-old deceased man with a sequel of poliomyelitis who was reportedly found death at home. On external examination at autopsy, deformity of the lower extremity secondary to polimyelitis, and an obliquely coursing scar tissue 5 cm in length at the same level with the costal arch on the right axillary line were seen. On internal examination at autopsy, diaphragmatic eventration caused by bilateral elevation of the diaphragm towards thoracic cavity was detected. On the left side, stomach, spleen, and small intestines, and on the right side liver were pushed into the thoracic cavity. Cause of death was reported as heart failure of the patient with bilateral diaphragmatic eventration. We aimed to discuss rarely encountered diaphragmatic eventration in autopsy practice from a perspective of forensic medicine.

Death due to coronary artery anomaly with coexistence of Chiari network.

Coronary artery anomalies rarely detected in autopsy series and angiograms can be a component of complex malformations, besides, can be also associated with sudden cardiac death. Presented case was 22-year-old male, who had suddenly fainted during a football match played on artificial turf, he was transferred into the hospital, however had died during intensive care therapy. He had been evaluated by local prosecutor, and sent to our center for autopsy. At autopsy, internal macroscopic examination revealed absence of the right coronary artery. A total of two coronary artery ostia were observed. One of them originated from the left aortic sinus, and the other one stemmed from 8 mm above the sinotubular line. Besides, Chiari network formation was seen in the right atrium. This case with coronary artery anomaly associated with formation of Chiari network was discussed from the perspective of forensic medicine in the light of the literature information.

A Case of Death Caused by 2700°C Molten Magnesite Burns.

Magnesite (MgCO3) is a mineral which is theoretically composed of 52.2% CO2, 47.8% MgO, and very scarce amounts of Fe2O3 with a degree of hardness varying between 3.4-4.5 kgf, and specific gravity of 2.9-3.1 g/cm(3). Its color varies between white, yellow or gray, and brown. Magnesite is used in agriculture, and drug industry, brick, iron-steel, paper, and sugar industries. Our case was a 30-year-old male whose dead was reportedly associated with exposure to 2700°C molten magnesite in the melting potansiyel of the plant where he was working as a metal worker. At autopsy, on external examination, except from his left forearm, all over his body was charred from severe burns. Both of his legs from ankles, and right forearm from its middle third were nearly amputated, and body muscles were partly detached because of high temperature. Widespread areas of thermal rupture were observed. On internal examination scalded appearance of internal organs was noted. Blood, and urine analysis did not reveal any substance abuse. Herein, we have aimed to discuss, and evaluate dead events because of exposure to very high temperatures from the perspective of forensic medicine, and occupational safety.

A case of cerebral hypoplasia/dysplasia detected at autopsy.

UNLABELLED: Presented case was a 2-year-old baby girl who had been treated for nearly one year with the indication of multifocal epileptiform anomaly. She was found dead in her bed in morning hours, autopsy was planned after prosecutors investigation. On internal autopsy examination, shrinkage of gyral structures in the frontal, and parietal lobes of the left hemisphere, markedly enlarged sulci, and a hypoplastic appearance were noted. Histopathological examination revealed evidence of pneumonia, brain exposed microgyral formations, disordered cortical stratification, hypercellularity, dysmorphic neuronal structures, balloon cells with diagnosis of cortical dysplasia. Pneumonia was reported as a cause of death. We aimed to discuss in the light of the literature a case with cerebral hypoplasia which is rarely seen at forensic autopsies. KEYWORDS: cerebral hypoplasia/dysplasia - autopsy - congenital malformation - sudden death.

Retroperitoneal Liposarcoma: an Autopsy Case.

Liposarcoma is very rare mesenchymal tumor that occurs in deep soft tissue and mostly seen in limbs and retroperitoneum, accounts for 24% of extremity and 45% of retroperitoneal soft tissue sarcomas. Retroperitoneal liposarcomas are typically present with advanced disease and often carry a poor prognosis. Retroperitoneal liposarcomas grow slowly in the very expandable retroperitoneal space in the deeply hidden and clinically silent therefore diagnosis is usually made late. Liposarcomas have five histological subtypes; well-differentiated liposarcoma (WDLS), dedifferentiated liposarcoma (DDLS), pleomorphic, myxoid and round cell liposarcoma. Our case is 81-year-old male who was found dead in the village homeless shelter. This was classified as a suspicious death and transferred to our service for autopsy. The external examination revealed rectal prolapse, abdominal distension and scrotal swelling. The internal autopsy showed green membrane on the peritoneum, brown smelly contents in the abdominal space, a perforation area 1.5x1 cm in size that in the first part of the duodenum and the dimension of tumor was 48x30x6 cm in the retroperitoneal space. The pathological report was dedifferentiated liposarcoma. We present a rare case of a dedifferentiated retroperitoneal liposarcoma with duodenal ulcer perforation.

Death Due to Myocardial Bridging.

Myocardial bridging is a congenital coronary pathology described as a segment of coronary artery which courses through the myocardial wall beneath the muscle bridge. Although the myocardial bridging prognosis is benign, have been also reported sudden death in medical literature. ¬A 30-year-old married woman was found dead at her home. After local prosecutors' investigation the death was declared as suspicious and forensic autopsy was obliged. The left anterior descending coronary artery was detected embedded deeply in the myocardium 2 cm from its coronary ostial origin. There were no other pathology to explain death. We analyzed sudden death case occurred because of myocardial bridging and the pathophysiological mechanisms in the light of medico-legal literature.

Medicolegal aspects of atypical firearm injuries: a case report.

Our case was a twenty year-old man, who was injured during the military duty with G3 infantry rifle in the training area. An atypical firearm entry wound on the left side of sternum which was 4.5 cm in diameter, and was surrounded by six irregular skin burn wounds by a flash-suppressor and a 0.7 cm diameter firearm exit wound at space on the left midscapular line. Our case emphasizes that the interpretation of properties of these atypical firearm entry wounds need to be carefully assessed by physicians.

Scuba diver deaths due to air embolism: two case reports.

Barotraumas and decompression sickness are the two most well-known complications of diving. First presented case was 32 year-old male with recreational diver, who was found floating prone position on the bottom of sea in a depth of 33 m. He had been carried to the surface in a controlled ascent. Second case was a 39 year-old male experienced dive instructor in a diving school, after following an uneventful duration of dive was found unconscious with a floating supine position in a depth of 30 m and there were no signs of life when they were transported to the hospital. Extensive subcutaneous emphysema of the extremities was detected by palpation of the skin. In the autopsy diffuse gas bubbles like beads were seen in the coronary arteries and in ventricles, basilar artery and all of the cerebral arteries. The cause of death was attributed due to gas embolism and drowning.

An unusual case of penetrating intracranial injury due to scissors.

Craniocerebral penetrating non-missile injuries caused by metallic foreign bodies are uncommon events. Healthy 10 year-old boy applied to the hospital emergency service with his parents. Family members stated that the scissors have been stalled his head accidentally by his sister when they had played together. During physical examination the scissors located on left parietal region of the head was examined. There was no loss of consciousness and oriented with normal vital signs. Radiological investigation demonstrated a hyper dense foreign body (scissors) penetrating cranial cavity and ended before reaching posterior region of the left parietal lobe. To our knowledge, the presented was rare case of intracranial penetrating scissor, which was not removed until, injured, reached the hospital. Our goal was to discuss the rare case of penetrating non-missile foreign body cranial injury from medico legal aspect.

An unusual case of firearm injury: bullet lodged in the tongue.

Firearm-related injuries are a major problem worldwide, in forensic medicine practice. and unusual presentation of bullet trajectory can create surgical or medico-legal diagnostic problems. A 23-year-old man suffered two gunshot wounds, was taken to emergency department immediately after the incident. Physical examination revealed two entrance gunshot wounds on the left lumbar region under the lower margin of left scapulae and right gluteal region. An exit wound was defined on the lateral side of the right gluteal region which was located 5 cm distance of entrance wound. Radiological investigation showed a bullet in the tongue without any life threatening impairment. A thoracic CT scan and abdominal USG were normal. Following the initial examinations he was hospitalized and the bullet removed from the tongue by a simple surgical operation. An interesting case of gunshot injury where the passage route of bullet extending along from upper posterior part of the left lumbar region to the tongue without vital organ injury or serious disability has been reported.