Acute IL-1RA treatment suppresses the peripheral and central inflammatory response to spinal cord injury
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01.12.2021 |
Yates A.G.
Jogia T.
Gillespie E.R.
Couch Y.
Ruitenberg M.J.
Anthony D.C.
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Journal of Neuroinflammation |
10.1186/s12974-020-02050-6 |
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© 2021, The Author(s). Background: The acute phase response (APR) to CNS insults contributes to the overall magnitude and nature of the systemic inflammatory response. Aspects of this response are thought to drive secondary inflammatory pathology at the lesion site, and suppression of the APR can therefore afford some neuroprotection. In this study, we examined the APR in a mouse model of traumatic spinal cord injury (SCI), along with its relationship to neutrophil recruitment during the immediate aftermath of the insult. We specifically investigated the effect of IL-1 receptor antagonist (IL-1RA) administration on the APR and leukocyte recruitment to the injured spinal cord. Methods: Adult female C57BL/6 mice underwent either a 70kD contusive SCI, or sham surgery, and tissue was collected at 2, 6, 12, and 24 hours post-operation. For IL-1RA experiments, SCI mice received two intraperitoneal injections of human IL-1RA (100mg/kg), or saline as control, immediately following, and 5 hours after impact, and animals were sacrificed 6 hours later. Blood, spleen, liver and spinal cord were collected to study markers of central and peripheral inflammation by flow cytometry, immunohistochemistry and qPCR. Results were analysed by two-way ANOVA or student’s t-test, as appropriate. Results: SCI induced a robust APR, hallmarked by elevated hepatic expression of pro-inflammatory marker genes and a significantly increased neutrophil presence in the blood, liver and spleen of these animals, as early as 2 hours after injury. This peripheral response preceded significant neutrophil infiltration of the spinal cord, which peaked 24 hours post-SCI. Although expression of IL-1RA was also induced in the liver following SCI, its response was delayed compared to IL-1β. Exogenous administration of IL-1RA during this putative therapeutic window was able to suppress the hepatic APR, as evidenced by a reduction in CXCL1 and SAA-2 expression as well as a significant decrease in neutrophil infiltration in both the liver and the injured spinal cord itself. Conclusions: Our data indicate that peripheral administration of IL-1RA can attenuate the APR which in turn reduces immune cell infiltration at the spinal cord lesion site. We propose IL-1RA treatment as a viable therapeutic strategy to minimise the harmful effects of SCI-induced inflammation.
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Biomechanics of starting, sprinting and submaximal running in athletes with brain impairment: A systematic review
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01.12.2020 |
Fiorese B.A.
Beckman E.M.
Connick M.J.
Hunter A.B.
Tweedy S.M.
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Journal of Science and Medicine in Sport |
10.1016/j.jsams.2020.05.006 |
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© 2020 Sports Medicine Australia Objectives: Para athletes with brain impairment are affected by hypertonia, ataxia and athetosis, which adversely affect starting, sprinting and submaximal running. The aim was to identify and synthesise evidence from studies that have compared the biomechanics of runners with brain impairments (RBI) and non-disabled runners (NDR). Design: Systematic review. Methods: Five journal databases were systematically searched from inception to March 2020. Included studies compared the biomechanics of RBI (aged > 14 years) and NDR performing either block-starts, sprinting, or submaximal running. Results: Eight studies were included, analysing a total of 100 RBI (78M:22F; 18–38 years) diagnosed with either cerebral palsy (n = 44) or traumatic brain injury (n = 56). Studies analysed block-starts (n = 3), overground sprinting (n = 3) and submaximal running (n = 2), and submaximal treadmill running (n = 1). Horizontal velocity during starts, sprinting and self-selected submaximal speeds were lower in RBI. During sprinting and submaximal running, compared with NDR, RBI had shorter stride length, step length, and flight time, increased ground-contact time, increased cadence, and reduced ankle and hip range of motion. In submaximal running, RBI had decreased ankle-power generation at toe-off. Conclusions: There is limited research and small sample sizes in this area. However, preliminary evidence suggests that RBI had lower sprint speeds and biomechanical characteristics typical of submaximal running speeds in NDR, including increased ground-contact times and reduced stride length, step length, and flight times. Meaningful interpretation of biomechanical findings in RBI is impeded by impairment variability (type, severity and distribution), and methods which permit valid, reliable impairment stratification in larger samples are required.
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Biomechanics of starting, sprinting and submaximal running in athletes with brain impairment: A systematic review
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01.12.2020 |
Fiorese B.A.
Beckman E.M.
Connick M.J.
Hunter A.B.
Tweedy S.M.
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Journal of Science and Medicine in Sport |
10.1016/j.jsams.2020.05.006 |
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© 2020 Sports Medicine Australia Objectives: Para athletes with brain impairment are affected by hypertonia, ataxia and athetosis, which adversely affect starting, sprinting and submaximal running. The aim was to identify and synthesise evidence from studies that have compared the biomechanics of runners with brain impairments (RBI) and non-disabled runners (NDR). Design: Systematic review. Methods: Five journal databases were systematically searched from inception to March 2020. Included studies compared the biomechanics of RBI (aged > 14 years) and NDR performing either block-starts, sprinting, or submaximal running. Results: Eight studies were included, analysing a total of 100 RBI (78M:22F; 18–38 years) diagnosed with either cerebral palsy (n = 44) or traumatic brain injury (n = 56). Studies analysed block-starts (n = 3), overground sprinting (n = 3) and submaximal running (n = 2), and submaximal treadmill running (n = 1). Horizontal velocity during starts, sprinting and self-selected submaximal speeds were lower in RBI. During sprinting and submaximal running, compared with NDR, RBI had shorter stride length, step length, and flight time, increased ground-contact time, increased cadence, and reduced ankle and hip range of motion. In submaximal running, RBI had decreased ankle-power generation at toe-off. Conclusions: There is limited research and small sample sizes in this area. However, preliminary evidence suggests that RBI had lower sprint speeds and biomechanical characteristics typical of submaximal running speeds in NDR, including increased ground-contact times and reduced stride length, step length, and flight times. Meaningful interpretation of biomechanical findings in RBI is impeded by impairment variability (type, severity and distribution), and methods which permit valid, reliable impairment stratification in larger samples are required.
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Mitochondrial damage & lipid signaling in traumatic brain injury
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01.07.2020 |
Lamade A.M.
Anthonymuthu T.S.
Hier Z.E.
Gao Y.
Kagan V.E.
Bayır H.
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Experimental Neurology |
10.1016/j.expneurol.2020.113307 |
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© 2020 Elsevier Inc. Mitochondria are essential for neuronal function because they serve not only to sustain energy and redox homeostasis but also are harbingers of death. A dysregulated mitochondrial network can cascade until function is irreparably lost, dooming cells. TBI is most prevalent in the young and comes at significant personal and societal costs. Traumatic brain injury (TBI) triggers a biphasic and mechanistically heterogenous response and this mechanistic heterogeneity has made the development of standardized treatments challenging. The secondary phase of TBI injury evolves over hours and days after the initial insult, providing a window of opportunity for intervention. However, no FDA approved treatment for neuroprotection after TBI currently exists. With recent advances in detection techniques, there has been increasing recognition of the significance and roles of mitochondrial redox lipid signaling in both acute and chronic central nervous system (CNS) pathologies. Oxidized lipids and their downstream products result from and contribute to TBI pathogenesis. Therapies targeting the mitochondrial lipid composition and redox state show promise in experimental TBI and warrant further exploration. In this review, we provide 1) an overview for mitochondrial redox homeostasis with emphasis on glutathione metabolism, 2) the key mechanisms of TBI mitochondrial injury, 3) the pathways of mitochondria specific phospholipid cardiolipin oxidation, and 4) review the mechanisms of mitochondria quality control in TBI with consideration of the roles lipids play in this process.
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Mitochondrial damage & lipid signaling in traumatic brain injury
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01.07.2020 |
Lamade A.M.
Anthonymuthu T.S.
Hier Z.E.
Gao Y.
Kagan V.E.
Bayır H.
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Experimental Neurology |
10.1016/j.expneurol.2020.113307 |
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© 2020 Elsevier Inc. Mitochondria are essential for neuronal function because they serve not only to sustain energy and redox homeostasis but also are harbingers of death. A dysregulated mitochondrial network can cascade until function is irreparably lost, dooming cells. TBI is most prevalent in the young and comes at significant personal and societal costs. Traumatic brain injury (TBI) triggers a biphasic and mechanistically heterogenous response and this mechanistic heterogeneity has made the development of standardized treatments challenging. The secondary phase of TBI injury evolves over hours and days after the initial insult, providing a window of opportunity for intervention. However, no FDA approved treatment for neuroprotection after TBI currently exists. With recent advances in detection techniques, there has been increasing recognition of the significance and roles of mitochondrial redox lipid signaling in both acute and chronic central nervous system (CNS) pathologies. Oxidized lipids and their downstream products result from and contribute to TBI pathogenesis. Therapies targeting the mitochondrial lipid composition and redox state show promise in experimental TBI and warrant further exploration. In this review, we provide 1) an overview for mitochondrial redox homeostasis with emphasis on glutathione metabolism, 2) the key mechanisms of TBI mitochondrial injury, 3) the pathways of mitochondria specific phospholipid cardiolipin oxidation, and 4) review the mechanisms of mitochondria quality control in TBI with consideration of the roles lipids play in this process.
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Medical aspects of domestic violence against women and girls (review)
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01.09.2019 |
Kekelidze Z.
Kachayeva M.
Kharitonova N.
Vasianina V.
Shishkina O.
Skibina N.
Nazarova L.
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Problemy sotsial'noi gigieny, zdravookhraneniia i istorii meditsiny |
10.32687/0869-866X-2019-27-5-936-939 |
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In recent years scientists actively study the influence of domestic violence on psychological status and occurrence of mental disorders in women and girls. Psychological, physical, sexual and other types of violence are distinguished, the consequences of which are studied in many countries under the auspices of WHO. In international studies the serious consequences of domestic violence for women are investigated. It was found out that women develop stressful disorders, depression and dependence on psychoactive substances. Negative influence of domestic violence at girls is expressed in formation of behavioral disorders, violations of sexual development, suicidal trends. At analysis of consequences of domestic violence by WHO was developed the concept of "cycle of violence" and cruelty inside family when in process of long influence of psychological traumatic factors at women and girls aggressive actions occurred so that victim and aggressor changed places. The objective of the study was to analyze the current state of the problem on the basis of the literature data, to study the data on the consequences of domestic violence and cruelty against women and girls, to identify gender-specific violations.
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Effect of mesodiencephalic stimulation on adaptation to stress and academic performance of students
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01.01.2018 |
Yumashev A.
Utyuzh A.
Admakin O.
Doroshina V.
Volchkova I.
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International Journal of Learning and Change |
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© 2018 Inderscience Enterprises Ltd. Increase in academic performance of medical universities' students is one of the most significant tasks of the modern education and healthcare systems as a factor contributing to high quality of the future doctors' qualification. Increased level of anxiety and depression negatively correlate with the level of the students' academic performance. Such a method of physiotherapy as mesodiencephalic modulation takes a stabilising effect on psychoemotional state of a person. The paper contains the analysis of emotional state of the students from the Faculty of Dentistry, defines the level of anxiety and depression, and notes their correlational interconnection with the level of academic performance in their study. The authors have practically stated positive influence of the mesodiencephalic modulation sessions on psychoemotional state of the students and indirectly on the level of their educational academic performance.
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A role of inflammasomes in the pathogenesis of neurological and mental diseases
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01.01.2018 |
Pirozhkov S.
Terebilina N.
Litvitskiy P.
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Zhurnal Nevrologii i Psihiatrii imeni S.S. Korsakova |
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© 2018, Media Sphera Publishing Group. All rights reserved. Inflammasomes are macromolecular complexes that contain many copies of receptors recognizing molecular patterns of pathogenic agents (PAMP) and damage-associated structures (DAMP), and also include molecules of adapter protein ASC and procaspase- 1. Activation of inflammasomes leads to the formation of active caspase-1 that, in turn, provides the maturation of pro-IL-1β and pro-IL-18 to IL-1β and IL-18. The latter cytokines play an important role in control of neuroinlfammation in the central nervous system contributing to the pathogenesis of a series of neurological, neurodegenerative and mental disorders. The review discusses the involvement of NLRP3 inflammasome and other their types in the development of the traumatic brain injury, ischemic and hemorrhagic stroke, brain tumors, CNS infections, Alzheimer’s and Parkinson’s diseases, epilepsy, amyotrophic lateral sclerosis, depressiver, and consequences of alcohol abuse. The elucidation of molecular mechanisms and signaling pathways controlled by inflammasomes will allow the development of new therapeutic measures for diseases, in which neuroinflammation plays a leading pathogenetic role.
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Radiology of postoperative period in patients with orbital trauma
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01.01.2018 |
Pavlova O.
Serova N.
Davydov D.
Shilova M.
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Russian Electronic Journal of Radiology |
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© 2018 Russian Electronic Journal of Radiology.All right reserved. Purpose: To assess the possibilities of radiology diagnostics in patients with orbital trauma in postoperative period. Materials and methods: From 2015 to 2018 years in the clinic of Sechenov University 72 patients (100%) with traumatic injuries were examined. All patients (n = 72, 100%) were diagnosed with orbital trauma. After the admission all patients (n = 72, 100%) underwent multispiral computed tomography (MSCT) before and after the operation using Toshiba Aquilion One 640 modality, volume mode, slice thickness - 0.5 mm, bone and soft tissue reconstruction. Results: According to MSCT data in postoperative period with orbital volumes were reconstructed and symmetrical compared to the other side in 48 patients (64%). In 24 cases (33%) orbital volumes weren't reconstructed with remaining prolapse of orbital soft tissue structures in the maxillary sinus through the inferior orbital wall defect. Insufficient implantation of the inferior orbital wall prosthesis occurred in 7 patients (10%). Conclusion: MSCT is a method of choice in examining the patients with injuries of the midface. Computed tomography allows detailed determination of performed surgical treatment, to reveal the risk of postoperative complications and assess the dynamic of a patient in late periods.
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Features of diagnostics and "whole body" multispiral computed tomography in patients with severe combined trauma
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01.01.2018 |
Dushin D.
Ternovoy S.
Burenchev D.
Karaseva E.
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Russian Electronic Journal of Radiology |
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1 |
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© 2018 Russian Electronic Journal of Radiology.All right reserved. Purpose: This scientific review of the literature presents the most relevant discussions in the world community, aimed at improving the implementation of the diagnostic algorithm in patients with severe combined trauma. Materials and methods: The work deals with the main traumatic injuries of various anatomical zones, the criteria of the Advanced Trauma Life Support (ATLS) protocol and diagnostic methods aimed at detecting acute traumatic pathology. Conclusion: The authors consider unsolved issues, as well as the improvement of the multislice computed tomography (MSCT) algorithm in the "whole body" mode, to optimize diagnostic activities aimed at managing patients with severe combined trauma.
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Cognitive impairment in anxiety disorders
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01.01.2018 |
Volel B.
Petelin D.
Akhapkin R.
Malyutina A.
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Nevrologiya, Neiropsikhiatriya, Psikhosomatika |
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1 |
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© 2018 Ima-Press Publishing House. All rights reserved. Anxiety disorders are an important biomedical problem due to the high prevalence and significant negative impact on the quality of life and the course of concomitant somatic and neurological diseases. Cognitive impairment (CI) is one of the most intensively studied aspects of pathological anxiety. Impairments in attention, executive functions, memory, cognitive deficit, as well as abnormal cognitions and metacognitions are identified in anxiety disorders. Moreover, the treatment of the latter with the most frequently used drugs (antidepressants, atypical antipsychotics, anticonvulsants, tranquilizers) does not lead to a significant improvement in cognitive functions, and often contributes to their worsening. In this connection, in addition to psychotherapy, cognitive function-improving agents play a large role in treating anxiety diseases associated with cognitive dysfunction. Ginkgo Biloba extract (EGb 761, Tanakan®) that positively affects cognitive functions, especially in the domains of memory, concentration and attention deserves special attention.
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The interrelation of post-trauma stress disorders with reactive and personal anxiety
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01.01.2018 |
Lopatkova I.
Serykh A.
Miroshkin D.
Shcherbakova O.
Kochetkov I.
Deberdeeva N.
Diatlova E.
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Electronic Journal of General Medicine |
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6 |
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© 2018 by the authors; licensee Modestum Ltd., UK. Objective: The relationship of situational (reactive) and personal anxiety in the sample of respondents with post-trauma stress disorder (PTSD) has been considered in the article. The study found that a significant level of situational anxiety and an average level of personal anxiety is observed in respondents with post-trauma stress disorder. Method: The survey and testing of respondents was conducted on the basis of their voluntary and anonymous participation among the staff of public authorities and law enforcement bodies. Clinical, psychopathological and statistical research methods were used in this work. While conducting a psychopathological survey, the Mississippi scale (MS), military and civilian variants, the severity questionnaire for psychopathological symptoms (AFPS), and the scale for assessing the level of reactive and personal anxiety (Charles D. Spilberger, Yu. L. Khanin) were used to determine the qualitative and quantitative parameters. The levels of reactive and personal anxiety were determined on a scale: up to 30 points-low anxiety; from 31 to 45 points-moderate anxiety; 46 points or more-high anxiety. The statistical processing of research results included the calculation of the arithmetic mean value for the quantitative (M) and qualitative (P) indices and their errors (m and p). When comparing the data obtained in groups and subgroups, the Student’s t-test was used, while the correlation analysis of interrelationships-the Spearman correlation coefficient was used. The sample comprised respondents with signs that meet the diagnostic criteria for PTSD (ICD-10 \ DSM-R). Results: The manifestation of the influence of the experienced psychological trauma on the level of anxiety is: an increased heart rate; Blanchet syndrome; a nervous condition; tension of all groups of muscles; feeling a sense of guilt; a feeling of fever followed by shivers; long confusion; insomnia; migraine; uncontrollable anger. The symptoms of anxiety persist and accumulate, at the time of a stressful situation, and after its resolution, contributing to a decrease in performance, fatigue and exhaustion. In addition, the results of the study indicate that anxiety and its level plays an important role, both in clinical findings and in the pathogenesis of PTSD. At the same time, differences were found among men and women. Men with PTSD are characterized by an increase in the level of situational anxiety as the severity of the disorder increases. Women are characterized by a moderate level of situational anxiety, regardless of the severity of the disorder. For both male and female subjects, high indices of personal anxiety are more significant than situational in the development of PTSD of different severity levels. Conclusion: Anxiety and its level, plays an important role both in clinical findings and in the pathogenesis of PTSD. At the same time, differences were found among men and women. Men with PTSD are characterized by an increase in the level of situational anxiety as the severity of the disorder increases. Women are characterized by a moderate level of situational anxiety, regardless of the severity of the disorder. High indices of personal anxiety are more significant for both male and female subjects than situational one in the development of PTSD of different severity levels. The level of personal anxiety in men increased as the severity of PTSD increased. In women, the high level of anxiety increased with increasing severity of the disorder and stabilized with severe PTSD. Most women and men with PTSD are characterized by a high level of personal anxiety. Moreover, the prevalence of women with a high level of personal anxiety in comparison with men is essential with a mild severity of the disorder. With a moderate degree of the disorder, the differences in the proportion of men and women with a high level of personal anxiety are practically insignificant, and in case of a severe degree of the disorder, their proportion levels off, reaching 100%, both among men and women.
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Clinical and radiological manifestations and anatomical and topographical rationale for a possible combined injury of the hip joint and proximal part of the sciatic nerve (clinical and experimental study)
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01.01.2018 |
Nikolenko V.
Chekhonatskiy A.
Osadchuk M.
Ilyasova E.
Osadchuk A.
Chekhonatskiy V.
Reshetnikov A.
Levchenko K.
Bahteeva N.
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Russian Electronic Journal of Radiology |
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© 2018 Russian Electronic Journal of Radiology.All right reserved. Purpose: To study peculiarities of clinico-radiological and anatomico-topographic relationship of sciatic nerve and acetabulum. Materials and Methods: Two stages experimental research was conducted in vitro on 20 human corpses, died due to various reasons. Clinico-radiological study was carried out in vivo on 41 patients with injuries of sciatic nerve and acetabulum. Results: Research data can confidently state that topographic proximity of sciatic nerve to acetabulum especially to its posterior-upper edge determines high risk of nerve lesion at acetabulum fractures due to influence of bone fragments, formed hematoma, forming scars. Conclusion: Acetabulum fractures are potentially dangerous for possibility of simultaneous injury of sciatic nerve; in this case a patient has to be subjected to special examination with the purpose of his sciatic nerve status evaluation.
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Virtual autopsy as a screening test before traditional autopsy: The verona experience on 25 Cases
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01.01.2018 |
Cirielli V.
Cima L.
Bortolotti F.
Narayanasamy M.
Scarpelli M.
Danzi O.
Brunelli M.
Eccher A.
Vanzo F.
Ambrosetti M.
El-Dalati G.
Vanezis P.
De Leo D.
Tagliaro F.
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Journal of Pathology Informatics |
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1 |
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© 2018 Journal of Pathology Informatics. Background: Interest has grown into the use of multidetector computed tomography (CT) and magnetic resonance imaging as an adjunct or alternative to the invasive autopsy. We sought to investigate these possibilities in postmortem CT scan using an innovative virtual autopsy approach. Methods: Twenty-five postmortem cases were scanned with the Philips Brilliance CT-64 and then underwent traditional autopsy. The images were interpreted by two blinded forensic pathologists assisted by a radiologist with the INFOPSY® Digital Autopsy Software System which provides three-dimensional images in Digital Imaging and Communications in Medicine format. Diagnostic validity of virtual autopsy (accuracy rate, sensitivity, specificity, and predictive values) and concordance between the two forensic pathologists (kappa intraobserver coefficients) were determined. Results: The causes of death at traditional autopsies were hemorrhage due to traumatic injuries (n = 8), respiratory failure (5), asphyxia due to drowning (4), asphyxia due to hanging or strangulation (2), heart failure (2), nontraumatic hemorrhage (1), and severe burns (1). In two cases, the cause of death could not be ascertained. In 15/23 (65%) cases, the cause of death diagnosed after virtual autopsy matched the diagnosis reported after traditional autopsy. In 8/23 cases (35%), traditional autopsy was necessary to establish the cause of death. Digital data provided relevant information for inferring both cause and manner of death in nine traumatic cases. The validity of virtual autopsy as a diagnostic tool was higher for traumatic deaths than other causes of death (accuracy 84%, sensitivity 82%, and specificity 86%). The concordance between the two forensic pathologists was almost perfect (>0.80). Conclusions: Our experience supports the use of virtual autopsy in postmortem investigations as an alternative diagnostic practice and does suggest a potential role as a screening test among traumatic deaths.
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