1,720,970 research outputs found

    In silico, in vitro, and in vivo human metabolism of a new semi-synthetic cannabinoid: Hexahydrocannabinol (HHC) and its stereoisomers

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    Since 2021, there was an overall increase in reports of herbal material where natural cannabinoids were found alongside synthetic cannabinoids in at least 13 European countries. It results in a growing concern that consumers of cannabis may be at risk of inadvertent exposure to synthetic cannabinoids. New regulatory challenges have emerged about the commercialisation of cannabis derivatives and about the recreational drug market. In 2022, the appearance of new semi-synthetic cannabinoids reflected these concerns. Hexahydrocannabinol (HHC) was identified in May 2022 and had been reported by 20 EU Member States by March 2023. The effects of HHC in humans have not been studied, but consumers and reports suggest they may be subjectively similar to those of cannabis. Some of the products are available in forms that may deliver high doses, raising concerns about the possible implications for public health. The purpose of this thesis was to identify the main metabolites of HHC through in silico and in vitro studies. Subsequently, a method using UHPLC-MS/MS was developed and fully validated for their detection in biological matrices. Finally, the identification and quantification of HHC stereoisomers and metabolites were carried out on real samples of oral fluid, blood, and urine from individuals who had smoked a known quantity of HHC

    Fatal coronary perforation during percutaneous coronary intervention: The medico-legal interest in establishing the correlation between in vivo imaging and post-mortem histopathology

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    A 64-year-old man diagnosed with chronic coronary syndrome (CCS) underwent elective percutaneous coronary intervention (PCI) to place a stent in a branch of the first diagonal artery. Fifteen minutes after the procedure, the patient suffered a cardiac arrest, which was subsequently determined to be caused by cardiac tamponade identified through ultrasound examination. Despite an hour of cardiopulmonary resuscitation, the patient died and a forensic investigation was requested by the public prosecutor. On review of the coronary angiography images, an extravasation of contrast was noted, which was classified as a type II perforation according to the Ellis classification. Autopsy revealed a hemorrhagic suffusion area on the anterior surface of the left ventricle with suspected epicardial discontinuity. Histopathological examination confirmed a complete rupture of the vessel wall in the distal section of the branch where the stent was placed, accompanied by adjacent hemorrhagic and fibrin-platelet material. The diagnosis of coronary perforation is typically made through imaging and histological confirmation is rarely obtained. In the present case, the correlation between in vivo imaging and post-mortem histopathology not only facilitated the precise localization of the coronary perforation but also had significant medico-legal implications in the assessment of presumed medical liability

    Post-mortem diagnosis of septic arthritis by Pasteurella multocida: a case report and literature review of fatal septic arthritis

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    The diagnosis of septic arthritis remains challenging in the clinical setting, often leading to a suspicion for medical liability. Our purpose is to describe an unusual case of a post-mortem diagnosis of P. multocida fatal septic arthritis, in a healthy 67-year-old woman presenting with pain in the right shoulder. Moreover, a literature review of cases of fatal septic arthritis is provided. The multidisciplinary approach consisted of a forensic autopsy and additional post-mortem analyses (microbiology, biochemical analyses, histopathology, and revision of radiological images) carried out during the prosecutor’s investigation for medical liability. A systematic review of the literature was performed to collect cases of fatal septic arthritis and to understand its frequency and characteristics. No clear cause of death was determined after the autopsy, that only highlighted swelling and purulent exudation in the right glenohumeral joint. The microbiological swab performed on the shoulder tested positive for P. multocida, while histopathological and biochemical data were consistent with a sepsis. These results guided the interview with the woman’s relatives, until a history of a previous contact with a stray cat emerged. The cause of death was deemed as fatal septic arthritis caused by P. multocida, occurred after cat scratches and bites and only diagnosed post-mortem. The review of the literature provided 15 articles about fatal septic arthritis, only 1 caused by P. multocida, and all with ante-mortem diagnosis. Given the nonspecific symptoms, usually including a localized pain, and the absence of a clear history, e.g. of animal contact, septic arthritis might represent an under-reported clinical and pathological diagnosis, leading to a judicial autopsy for the suspicion for medical liability. The post-mortem examination, following a multidisciplinary approach including integration of the clinical history, microbiological and histopathological analysis, could represent the only opportunity for the diagnosis of the cause of death

    Use of cognitive enhancers: Methylphenidate and analogs

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    OBJECTIVE: In the last decades, several cognitive-enhancing drugs have been sold onto the drug market. Methylphenidate and analogs represent a sub-class of these new psychoactive substances (NPS). We aimed to review the use and misuse of methylphenidate and analogs, and the risk associated. Moreover, we exhaustively reviewed the scientific data on the most recent methylphenidate analogs (methylphenidate and ethylphenidate excluded). MATERIALS AND METHODS: Literature search was performed on methylphenidate and analogs, using specialized search engines accessing scientific databases. Additional reports were retrieved from international agencies, institutional websites, and drug user forums. RESULTS: Methylphenidate/Ritalin has been used for decades to treat attention deficit disorders and narcolepsy. More recently, it has been used as a cognitive enhancer and a recreational drug. Acute intoxications and fatalities involving methylphenidate were reported. Methylphenidate was scheduled as an illegal drug in many countries, but NPS circumventing the ban and mimicking the psychostimulant effects of methylphenidate started being available: ethylphenidate, 3,4-dichloromethylphenidate, 3,4-dichloroethylphenidate, 4-fluoromethylphenidate, 4-fluoroethylphenidate, methylnaphthidate, ethylnaphthidate, isopropylphenidate, propylphenidate, 4-methylmethylphenidate, and N-benzylethylphenidate have been available in the past few years. Only little data is currently available for these substances. Many intoxications involving methylphenidate analogs were reported. To date, ethylphenidate was involved in 28 fatalities, although it was reportedly directly related to the cause of death in only 7 cases; 3,4-dichloroethylphenidate was involved in 1 death. CONCLUSIONS: The rapid expansion of methylphenidate analogs onto the drug market in the past few years makes likely the occurrence of intoxications and fatalities in the next years. Careful monitoring and systematic control of methylphenidate analogs should be undertaken to reduce the uprising threat, and education efforts should be made among high-risk populations. © 2019 Verduci Editore s.r.l. All rights reserved

    Reliability in distinguishing murder from accidental event with current forensic criteria in traumatic head injury

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    Discovering a body displaying signs of multiple head trauma requires a thorough examination by the forensic pathologist, and a multidisciplinary approach is recommended. However, determining the manner of death is not always possible. We present a case in which the body of a 60-year-old man was discovered lying face down on the floor of his apartment, partially unclothed, surrounded by blood and vomit, and presenting numerous head injuries. The autopsy concluded that the cause of death was a result of post-traumatic brain injury. Nevertheless, applying current criteria made it challenging to ascertain whether the trauma stemmed from an accidental event or an assault

    Gastric ischemia as an under-reported cause of death in older people

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    Acute gastric ischemia is a rare condition due to the rich vascular supply of the stomach. Here we present a case of fatal gastric ischemia associated with bowel ischemia, only diagnosed at autopsy, which was requested for the suspicion of medical liability. A complete post-mortem examination was conducted, along with a macroscopic analysis of the superior mesenteric artery and detailed histological analyses. Past clinical data was also reviewed. The macroscopic blackish discoloration of the stomach and the bowel, coupled with the presence of neutrophils in the mucosa and submucosal non-occlusive thrombi, were consistent with gastric and bowel ischemia, despite the presence of confounding putrefactive changes. The unique aspect of this case resides in the ante-mortem peculiar vascularization of the stomach, supplied by small collateral vessels. No mechanical occlusion was identified, and the cause of the ischemia was deemed as non-occlusive, likely due to systemic hypoperfusion. The analysis of clinical data and documentation of associated comorbidities are strongly recommended, especially when a rare cause of death is suspected. With the aging population, especially among women, and the prevalence of risk factors, the forensic pathologist could increasingly encounter rare cases of gastric ischemia

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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