Alpha-methyltryptamine and 5-(2-methylaminopropyl)-benzofuran (5-MAPB) fatal co-intoxication: case report and review of literature.

The scientific literature contains little reliable data regarding new psychoactive substances and designer drugs, making it difficult to assess toxic blood levels and potentially lethal threshold. Here, we report a fatal co-intoxication involving two uncommon drugs ‒ alpha-methyltryptamine (AMT) and 5-(2-methylaminopropyl)-benzofuran (5-MAPB) ‒ combined with exposure to benzodiazepines, ephedrine, and norephedrine. AMT and 5-MAPB were quantified using ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC/MS-MS), revealing concentrations of AMT 4690 ng/mL and 5-MAPB 101 ng/mL in postmortem peripheral blood. We additionally reviewed the literature to help interpret the likely roles of these molecules in the occurrence of death.

Sex estimation from coxal bones using deep learning in a population balanced by sex and age.

In the field of forensic anthropology, researchers aim to identify anonymous human remains and determine the cause and circumstances of death from skeletonized human remains. Sex determination is a fundamental step of this procedure because it influences the estimation of other traits, such as age and stature. Pelvic bones are especially dimorphic, and are thus the most useful bones for sex identification. Sex estimation methods are usually based on morphologic traits, measurements, or landmarks on the bones. However, these methods are time-consuming and can be subject to inter- or intra-observer bias. Sex determination can be done using dry bones or CT scans. Recently, artificial neural networks (ANN) have attracted attention in forensic anthropology. Here we tested a fully automated and data-driven machine learning method for sex estimation using CT-scan reconstructions of coxal bones. We studied 580 CT scans of living individuals. Sex was predicted by two networks trained on an independent sample: a disentangled variational auto-encoder (DVAE) alone, and the same DVAE associated with another classifier (Crecon). The DVAE alone exhibited an accuracy of 97.9%, and the DVAE + Crecon showed an accuracy of 99.8%. Sensibility and precision were also high for both sexes. These results are better than those reported from previous studies. These data-driven algorithms are easy to implement, since the pre-processing step is also entirely automatic. Fully automated methods save time, as it only takes a few minutes to pre-process the images and predict sex, and does not require strong experience in forensic anthropology.

Non-accidental head injury of infants: legal implications for the pediatric neurosurgeon.

BACKGROUND: Though the neurosurgeon's role in non-accidental head injury (NAHT) is the prompt recognition and care of the inflicted injuries, he/she should be aware of the possible legal implications related to this particular neurosurgical condition. MATERIAL AND METHODS: Based on published data and their own clinical and medico-legal practice, the authors review the role of the neurosurgeon in NHAT. RESULTS: Besides the contribution that can be given by the neurosurgeon to a correct differential diagnosis, he/she is likely to be involved in the interpretations of the pathological findings in the case where the judge may request for a medical opinion concerning etiology, circumstances, severity, and consequences. As a member of a multidisciplinary team, usually the neurosurgeon is only requested for information regarding the lesions he was called to recognize and treat. Nevertheless, such information may have a pivotal part in the evaluation process. Consequently, the neurosurgeon should be able to reach a correct differential diagnosis of NAHT among all the events that may share similar clinical and anatomo-pathological characteristics and be aware of the ongoing scientific controversies related to the diagnosis and pathophysiology. CONCLUSIONS: In practical terms, the pediatric neurosurgeon is called to individuate and record all the precise details of the condition to be eventually offered to the judge in case of controversy. Whereas the diagnosis of NAHT should be evoked at the initial phase in order not to leave the child unprotected, all possible alternative hypotheses should be ruled out "beyond reasonable doubt" for the court. The medical file should be maintained in the record carefully and be accessible even after a long time.

Detection of insulins in postmortem tissues: an optimized workflow based on immunopurification and LC-MS/HRMS detection.

Diabetes is a worldwide disease in perpetual expansion. Type 1 and sometimes type 2 diabetic patients require daily human insulin (HI) or analog administration. Easy access to insulins for insulin-treated diabetics, their relatives, and medical professionals can enable abuse for suicidal or homicidal purpose. However, demonstrating insulin overdose in postmortem blood is challenging. Tissue analyses are contributive, as insulins can accumulate before death or undergo only limited degradation. The present study describes an assay for HI and synthetic analogs (lispro, aspart, glulisine, detemir and degludec, glargine and its main metabolite (M1)) in liver, kidney, muscle, and injection site samples. It is based on a 5-step sample preparation (reduction of tissue sample size, homogenization, extraction, concentration, and immunopurification) associated with liquid chromatography coupled to high-resolution mass spectrometry (LC-MS/HRMS). Selectivity and limit of detection (LOD) for all target analogs were assessed in the above matrices. LOD was determined at 25 ng/g for HI and for analogs except detemir and degludec, where LOD was 50 ng/g in kidney and injection site samples and 80 ng/g in the liver and muscle. The method was applied to13 forensic cases in which insulin use was suspected.

False Rape Allegation and Regret: A Theoretical Model Based on Cognitive Dissonance.

The aim of this paper is to provide a model illustrating how regretful consensual intercourse may lead to false rape allegations (FRA). An intrapersonal perspective of regret based on cognitive dissonance is added to the interpersonal factors already mentioned in the literature. The intrapersonal perspective is discussed in terms of the reduction of a state of cognitive dissonance induced by the gap between social norms and the shamefully perceived behavior. First, we start with the review of the different motives that may lead to a FRA, insisting on regret caused by cognitive dissonance. We then develop the emergence of regret from a state of cognitive dissonance. Second, we describe the means used to build the model: a literature review, an extraction of the factors at play in regret-based FRA, a chronological structure of the various factors, as some are necessarily the source of others. We then build the model. Third, we illustrate how the model could encompass many possible and usual scenarios. Thirteen plausible scenarios were developed to show the relevance of the model. Finally, we comment and discuss the model for future research and prevention.

Fatal 4-MEC Intoxication: Case Report and Review of Literature.

ABSTRACT: Synthetic cathinones are one of the major pharmacological families of new psychoactive substances and 4-methylethcathinone (4-MEC) has emerged in recent years as a recreational psychostimulant. We report a case of a 35-year-old man found dead and naked at home by his friend. Although no anatomic cause of death was observed at autopsy, toxicological analysis identified 4-MEC and hydroxyzine at therapeutic level (160 ng/mL). 4-Methylethcathinone was quantified in autopsy samples by a validated method consisting in liquid-liquid extraction and gas chromatography coupled to tandem mass spectrometry: peripheral blood, 14.6 µg/mL; cardiac blood, 43.4 µg/mL; urine, 619 µg/mL; vitreous humor, right 2.9 µg/mL and left 4.4 µg/mL; bile, 43.5 µg/mL; and gastric content, 28.2 µg/mL. The cause of death was 4-MEC intoxication and the manner of death could be either accidental or suicidal. The literature concerning 4-MEC was reviewed, focusing on distribution in classical postmortem matrices and 4-MEC metabolism and postmortem redistribution and stability.

Is insulin intoxication still the perfect crime? Analysis and interpretation of postmortem insulin: review and perspectives in forensic toxicology.

Insulin is an anabolic hormone essential to glucose homeostasis. Insulin therapy, comprising human insulin (HI) or biosynthetic analogs, is critical for the management of type-1 diabetes and many of type-2 diabetes. However, medication error including non-adapted dose and confusion of insulin type, and misuse, such as massive self-administration or with criminal intent, can have lethal consequences. The aim of this paper is to review the state of knowledge of insulin analysis in biological samples and of the interpretation of insulin concentrations in the situation of insulin-related death investigations. Analytic aspects are considered, as quantification can be strongly impacted by methodology. Immunoanalysis, the historical technique, has a prominent role due to its sensitivity and ease of implementation. Recently, liquid chromatography coupled to mass spectrometry has provided indispensable selectivity in forensic contexts, distinguishing HI, analogs, and degradation products. We review the numerous antemortem (dose, associated pathology, injection-to-death interval, etc.) and postmortem parameters (in corpore degradation, in vitro degradation related to hemolysis, etc.) involved in the interpretation of insulin concentration. The interest and limitations of various alternative matrices providing a valuable complement to blood analysis are discussed. Vitreous humor is one of the most interesting, but the low diffusion of insulin in this matrix entails very low concentrations. Injection site analysis is relevant for identifying which type of insulin was administered. Muscle and renal cortex are matrices of particular interest, although additional studies are required. A table containing most case reports of fatal insulin poisoning published, with analytical data, completes this review. A logic diagram is proposed to highlight analytical issues and the main parameters to be considered for the interpretation of blood concentrations. Finally, it remains a challenge to provide reliable biological data and solid interpretation in the context of death related to insulin overdose. However, the progress of analytical tools is making the "perfect crime" ever more difficult to commit.

Histological dating of subdural hematoma in infants.

BACKGROUND: After infant deaths due to non-accidental head injury (NAHI) with subdural hematoma (SDH), the magistrates ask experts to date the traumatic event. To do so, the expert only has tools based on adult series of NAHI. We aimed to develop an SDH dating system applicable to infants aged under 3 years. METHODS AND RESULTS: We studied a retrospective multicenter collection of 235 infants who died between the ages of 0 and 36 months, diagnosed with SDH by forensic pathological examination and with known posttraumatic interval (PTI). Two pathologists assessed blindly and independently 12 histomorphological criteria relating to the clot and 14 relating to the dura mater in 73 victims (31 girls, 42 boys) whose median age was 3.8 months. Histopathological changes were significantly correlated with PTI for the appearance of red blood cells (RBCs) and the presence or absence of siderophages, and regarding the dura mater, the quantity of lymphocytes, macrophages, and siderophages; presence or absence of hematoidin deposits; collagen and fibroblast formation; neomembrane thickness; and presence or absence of neovascularization. Dating systems for SDH in adults are not applicable to infants. Notably, neomembrane of organized connective tissue is formed earlier in infants than in adults. CONCLUSION: Our dating system improves the precision and reliability of forensic pathological expert examination of NAHI, particularly for age estimation of SDH in infants. However, the expert can only define a time interval. Histopathology is indispensable to detect repetitive trauma.

A case of suicide by self-injection of adrenaline.

Adrenaline (epinephrine) auto-injectors provide life-saving pre-hospital treatment for individuals experiencing anaphylaxis in a community setting. Errors in handling adrenaline auto-injectors, particularly by children and healthcare professionals, have been reported. Reports of adrenaline overdoses are limited in the medical literature. In most of these cases, accidental adrenaline administration results from medical error. Exogenous administration of catecholamine is responsible for cardiovascular and metabolic responses, which may cause supraventricular tachycardia, ventricular dysrhythmias and myocardial ischemia. The authors present a unique autopsy case involving a 34 year-old woman who intentionally self-injected adrenaline using an adrenaline auto-injector as part of a suicide plan. Catecholamines and metanephrines were measured in peripheral and cardiac blood as well as urine and vitreous humor. Based on the results of all postmortem investigations, the cause of death was determined to be cardiac dysrhythmia and cardiac arrest following adrenaline self-injection.

Modern toxic antipersonnel projectiles.

In the spring of 1944, Kurt von Gottberg, the SS police chief in Minsk, was shot and injured by 2 Soviet agents. Although he was only slightly injured, he died 6 hours later. The bullets were hollow and contained a crystalline white powder. They were 4-g bullets, semi-jacketed in cupronickel, containing 28 mg of aconitine. They were later known as akonitinnitratgeschosse. The Sipo (the Nazi security police) then ordered a trial with a 9-mm Parabellum cartridge containing Ditran, an anticholinergic drug with hallucinogenic properties causing intense mental confusion. In later years, QNB was used and given the NATO code BZ (3-quinuclidinyl-benzylate). It was proven that Saddam Hussein had this weapon (agent 15) manufactured and used it against the Kurds. Serbian forces used the same type of weapon in the Bosnian conflict, particularly in Srebrenica.The authors go on to list the Cold War toxic weapons developed by the KGB and the Warsaw pact countries for the discreet elimination of dissidents and proindependence leaders who had taken refuge in the West. These weapons include PSZh-13 launchers, the Troika electronic sequential pistol, and the ingenious 4-S110T captive piston system designed by the engineer Stechkin. Disguised as a cigarette case, it could fire a silent charge of potassium cyanide. This rogues gallery also includes the umbrella rigged to inject a pellet of ricin (or another phytalbumin of similar toxicity, such as abrin or crotin) that was used to assassinate the Bulgarian writer and journalist Georgi Markov on September 7, 1978, in London.During the autopsy, the discovery of a bullet burst into 4 or 5 parts has to make at once suspecting the use of a toxic substance. Toxicological analysis has to look for first and foremost aconitine, cyanide, suxamethonium, Ditran, BZ, or one of the toxic phytalbumins. The use of such complex weapons has to make suspect a powerful organization: army, secret service, terrorism. The existence of the Russian UDAR spray gun in the present day, however, shows that these weapons are still present. The possibility that one might be used to spray a charge of cyanide is still very real, especially as it would not be very difficult for an informed amateur to produce homemade toxic ammunition by adapting existing civil or military cartridges.

A non-randomized pilot trial of the use of prazosin in the prevention of transition from acute stress disorder to post-traumatic stress disorder.

BACKGROUND: Following a traumatic event, 40-80% of the patients with acute stress disorder (ASD) will develop post-traumatic stress disorder (PTSD), 67% at 6 months. Alpha1-blockers are effective in treating some symptoms of PTSD but their usefulness in acute stress situations remains unclear. We hypothesized that reducing noradrenergic hyperactivity with an alpha1-blocker during the acute phase after a traumatic event could prevent the transition to PTSD in patients with ASD. OBJECTIVE: To investigate the efficacy and safety of a 1-month course of alpha1-blocker (prazosin) to prevent the transition to PTSD in patients with ASD at 6 months. METHOD: In a monocentric open-label prospective pilot study, 15 patients with ASD were included within 3-7 days of exposure to a traumatic event. After enrolment, they received prazosin LP at home at bedtime at 2.5 mg/day for 7 days and then 5 mg/day for 21 days. Incidence of PTSD was assessed at 6 months using the Clinician Administrated PTSD Scale (CAPS). RESULTS: At 6 months, 22% of patients who completed the study (2/9) met the diagnostic criteria for PTSD. This rate was significantly lower than that observed in previous studies (67%; p = .047). The treatment was well tolerated and there were no serious adverse events. CONCLUSIONS: These preliminary findings indicating the safety of prazosin and suggesting its potential to prevent the development of PTSD in ASD require to be replicated in large-scale randomized placebo-controlled studies.Trial registration: The study was pre-registered on a public database (www.clinicalTrials.gov identifier: NCT03045016).

Alpha1-blockers are safe and well tolerated in patients with acute stress disorder.The use of alpha1-blockers 3­7 days after traumatic exposure is worthy of study.Alpha1-blockers could prevent the transition to PTSD in ASD patients at 6 months.

α-Methyltryptamine (α-MT) Metabolite Profiling in Human Hepatocyte Incubations and Postmortem Urine and Blood.

α-MT is a hallucinogenic and stimulant tryptamine that was involved in several overdose fatalities in the United States and Europe. Analytical toxicology, and particularly the identification of metabolite biomarkers in biological samples, often is the only way to prove tryptamine use in clinical and forensic caseworks. We aimed to identify optimal α-MT metabolite biomarkers of consumption in humans. We identified α-MT metabolites in 10-donor-pooled human hepatocyte incubations and postmortem urine and blood from an α-MT overdose case using in silico metabolite predictions, liquid chromatography high-resolution-tandem mass spectrometry (LC-HRMS/MS), and software-assisted data mining. Nine metabolites were identified in vitro and eight additional metabolites were found in urine; five metabolites were found in blood. Metabolic transformations were hydroxylation, O-sulfation, O-glucuronidation, N-glucuronidation, and N-acetylation, consistent with the metabolism of structural analogues. The findings in hepatocyte incubations and postmortem samples were consistent, proving the in vitro model suitability. We suggest α-MT, hydroxy-α-MT glucuronide, and two hydroxy-α-MT sulfates as biomarkers of α-MT use in non-hydrolyzed urine; we suggest α-MT, two hydroxy-α-MT sulfates and N-acetyl-α-MT as biomarkers of α-MT use in blood. Further studies on α-MT clinical and forensic caseworks with different doses and routes of administration are necessary to better explore α-MT metabolism.

Geometric and harmonic study of the aging of the fourth rib.

One of the current reference methods, namely the Iscan method for estimating age at death, consists in the subjective observation of the sternal end of the fourth rib. In this study, we looked to identify the morphometric characteristics of the sternal end of the fourth rib that were most affected by aging by measuring them in an objective way. For this purpose, we collected measurements from the fourth rib tip of 414 French males and used mathematical algorithms derived from pattern recognition and signal processing to identify variables that reflect both geometric characteristics and serration patterns of the ribs. Completed analysis was carried out on the 284 ribs for which all the variables could be collected. We showed that the three least collinear variables that best explain age objectively are the postero-superior pit depth, the fine serrations of the ovoid (delineating the pit shape), and its posterior flaring. This work provides a useful basis for subsequent studies on aging and age prediction.

State-of-the-art of bone marrow analysis in forensic toxicology: a review.

Although blood is the reference medium in the field of forensic toxicology, alternative matrices are required in case of limited, unavailable or unusable blood samples. The present review investigated the suitability of bone marrow (BM) as an alternative matrix to characterize xenobiotic consumption and its influence on the occurrence of death. Basic data on BM physiology are reported in order to highlight the specificities of this matrix and their analytical and toxicokinetic consequences. A review of case reports, animal and human studies involving BM sample analysis focuses on the various parameters of interpretation of toxicological results: analytic limits, sampling location, pharmacokinetics, blood/BM concentration correlation, stability and postmortem redistribution. Tables summarizing the analytical conditions and quantification of 45 compounds from BM samples provide a useful tool for toxicologists. A specific section devoted to ethanol shows that, despite successful quantification, interpretation is highly dependent on postmortem interval. In conclusion, BM is an interesting alternative matrix, and further experimental data and validated assays are required to confirm its great potential relevance in forensic toxicology.

Interpretation of drug concentrations in an alternative matrix: the case of meprobamate in vitreous humor.

The use of vitreous humor (VH) as an alternative matrix to blood in the field of forensic toxicology has been described for numerous drugs. Interpretation of drug concentrations measured in VH, as in other matrices, requires statistical analysis of a data set obtained on a significant series. In the present study, two diagnostic tests interpreting postmortem VH concentrations of meprobamate in 117 sets of autopsy data are reported. (1) A VH meprobamate concentration threshold of 28 mg/l was statistically equivalent to that of blood meprobamate concentration threshold of 50 mg/l distinguishing overdose from therapeutic use in blood. The intrinsic qualities of the test were good, with sensitivity of 0.95 and absolute specificity of 1. (2) A novel interpretation tool is proposed, allowing blood concentration range to be evaluated, with a known probability, from VH concentration.

Toxicological detection of pholcodine in blood, urine and hair in three cases of fatal intoxication.

Pholcodine is an opioid antitussive reputed for its low toxicity and absence of addictive effect. We report three cases of pholcodine intoxication with fatal outcome. Large concentrations of pholcodine were quantified by gas chromatography coupled to mass spectrometry (GC/MS) in peripheral postmortem blood (respectively 2890 ng/mL, 979 ng/mL and 12,280 ng/mL). Segmental hair analyses by GC/MS and detected pholcodine in three 1.5-2 cm segments (38-161 ng/mg, 8.54-41.6 ng/mg, and 0.26-2.66 ng/mg, respectively). These findings underline that pholcodine can be involved in fatal poisoning and raise the question of misuse or abuse and of taking account of this drug in opioid overdose prevention policies.

Forensic autopsy-confirmed COVID-19-induced out-of-hospital cardiac arrest.

BACKGROUND: In the setting of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, data from autopsy in subjects who died at home during lockdown are scarce. We here report the first forensic autopsy series of coronavirus disease 2019 (COVID-19)-related out-of-hospital cardiac arrest (OHCA). METHODS: Between March and April 2020, four COVID-19-related OHCA were autopsied at the Institute of Legal Medicine of the metropolitan area of Lyon (France) according safe recommended procedures. RESULTS: Four Caucasian individuals (3 men/1 woman; age: 56.8±2.1 years, body mass index: 29.5±7.4 kg/m2), presenting symptomatic COVID-19 were autopsied. Autopsies of 3 individuals reported natural death by acute respiratory failure implicating SARS-CoV-2 with typical COVID-19 pulmonary aspect of gross findings and pulmonary microscopy findings, i.e., diffusely congestive edematous lungs with peripheral thrombi and diffuse alveolar damage (DAD) at different stages of inflammatory reaction. For one individual, autopsy concluded of violent death due to suicidal acute alcohol intoxication in a patient that could no longer endure COVID-19 lockdown. No significant lesions were found in the heart. CONCLUSIONS: We report here OHCAs of non-cardiac cause directly implicating COVID-19 at various stages of SARS-CoV-2-related DAD. Thus, autopsy remain of interest during this epidemic, both legally and medically to better understand the pathogenic processes of this emerging infectious disease.

Fatal intoxication involving 4-methylpentedrone (4-MPD) in a context of chemsex.

4-methylpentedrone (4-MPD) is a new psychoactive substance (NPS) belonging to the cathinone class. We report an original case of death mainly involving 4-MPD, along with cocaine, sildenafil, bromazepam and nevirapine. The investigation data and the autopsy findings indicated fatal intoxication in a chemsex context (drug use during sex). 4-MPD concentrations were determined in peripheral blood (1285 ng/mL), cardiac blood (1128 ng/mL), urine (>10,000 ng/mL), bile (1187 ng/mL) and vitreous humor (734 and 875 ng/mL in left and right samples, respectively) by gas chromatography (GC) coupled to tandem mass spectrometry. 4-MPD metabolites were explored by GC coupled to high resolution mass spectrometry. Due to the paucity of data concerning 4-MPD, its use and effects were gathered from online user testimonies. This case illustrates the toxicity of this infrequent pentedrone derivate and confirms the significant overdose risk associated with chemsex.

Third molar maturity index for indicating the legal adult age in southeastern France.

The estimation of age in living subjects is today a significant issue because of the increase in the situations in which it arises and its legal consequences. In line with the Study Group on Forensic Age Diagnostics of the German Association of Legal Medicine's recommendations, it is based on the concomitant use of physical examination and methods for estimating bone age and dental age. Given the variations between the populations, the use of the latter requires their validation on all the ethnic groups on which they can be used. This aim of this study was to access the interest of the Cameriere's third molar maturity index (I3M) to indicate if an individual had reached the age of 18 in a sample of individuals from southeastern France. The studied sample consisted of OPTs 339 (184 females and 155 males) subjects aged between 14 and 22 years old. A logistic regression analysis with the adult age and minor age as dichotomous dependent variable and gender and I3M as predictor variables showed that gender was not statistically significant in discriminating adults and minors. The receiver operating curve (ROC) analysis showed the best discrimination performance of the specific cut-off value of I3M<0.08 in discriminating adults from minors. The proportion of accurate classification was 0.897 and 0.916 for females and males, respectively. The specificity (Sp) and sensitivity (Se) results for females were 0.962 and 0.813, respectively. Sp and Se for males were 0.953 and 0.871, respectively. The Bayes post-test probability was 0.961 and 0.955 in females and males respectively. Obtained results showed that a cut-off value of I3M<0.08 may be an additional tool for indicating adult age in the tested population.

The prospects for application of computational anatomy in forensic anthropology for sex determination.

The purpose of this study is to assess the relevance of computational anatomy for the sex determination in forensic anthropology. A novel groupwise registration algorithm is used, based on keypoint extraction, able to register several hundred full body images in a common space. Experiments were conducted on 83 CT scanners of living individuals from the public VISCERAL database. In our experiments, we first verified that the well-known criteria for sex discrimination on the hip-bone were well preserved in mean images. In a second experiment, we have tested semi-automatic positioning of anatomical landmarks to measure the relevance of groupwise registration for future research. We applied the Probabilistic Sex Diagnosis tool on the predicted landmarks. This resulted in 62% of correct sex determinations, 37% of undetermined cases, and 1% of errors. The main limiting factors are the population sample size and the lack of precision for the initial manual positioning of the landmarks in the mean image. We also give insights on future works for robust and fully automatic sex determination.