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Determining the post-mortem interval (PMI) is one of forensic pathology's primary objectives and one of its most challenging tasks. Numerous studies have demonstrated the accuracy of histomorphology and immunohistochemical investigations in determining the time of death. Nevertheless, the skin, a robust and easy-to-remove tissue, has only been partially analyzed so far. By studying 20 adult male mice, we tried to determine whether post-mortem immunohistochemical detection in the skin of HMGB1 proteins and associated components (Beclin1 and RAGE) could be used for this purpose. We discovered that nuclear HMGB1 overexpression indicates that death occurred within the previous 12 h, nuclear HMGB1 negativization with high cytoplasmic HMGB1 intensity indicates that death occurred between 12 and 36 h earlier and cytoplasmic HMGB1 negativization indicates that more than 48 h have passed since death. RAGE and Beclin1 levels in the cytoplasm also decreased with time. The latter proteins' negativization might indicate that more than 24 and 36 h, respectively, have passed from the time of death. These indicators might potentially be helpful in forensic practice for determining the PMI using immunohistochemistry.

This study reports the detection of a set of 35 peptide fragments and 7 intact proteins in the vitreous humour using a top-down proteomic platform based on high-resolution HPLC-MS and MS/MS analysis. The concentrations of thymosin b4 (R = 0.932) and two peptide fragments (i.e., vimentin fragment (Fr.) 443-465 (R = 0.998) and polyubiquitin Fr. 1-73 (R = 0.968)) were observed to have very strong linear correlations with postmortem intervals. Data are available via ProteomeXchange with identifier PXD037095. These preliminary results suggest that some biochemical molecular events are linearly related to the postmortem interval and that the concentrations of these peptides and fragments can be clinically useful in establishing the time of death if measured within the first 160 h postmortem. (c) 2022 Elsevier B.V. All rights reserved.

Background and Purpose: AKB48 is a synthetic cannabinoid illegally sold for its psychoactive cannabis-like effects that have been associated with acute intoxication and whose effects are poorly known. Experimental Approach: Using a behavioural, neurochemical, and immunohistochemical approach, we investigated the pharmaco-toxicological effects, pharmacokinetics, and neuroplasticity at cannabinoid CB1 receptors in the cerebellum and cortex induced by repeated AKB48 administration in male and female mice. Key Results: The effects of AKB48 varied significantly depending on sex and treatment duration. The first injection impaired sensorimotor responses and reduced body temperature, analgesia, and breath rate to a greater extent in females than in males; the second injection induced stronger effects in males while the third injection of AKB48 induced weaker responses in both sexes, suggesting emergence of tolerance. The CB1 receptor antagonist NESS-0327 prevented the effects induced by repeated AKB48, confirming a CB1 receptor-mediated action. Blood AKB48 levels were higher in females than in males and repeated administration caused a progressive rise of AKB48 levels in both sexes, suggesting an inhibitory effect on cytochrome activity. Finally, immunohistochemical analysis revealed higher expression of CB1 receptors in the cerebellum and cortex of females, and a rapid CB1 receptor down-regulation in cerebellar and cortical areas following repeated AKB48 injections, with neuroadaptation occurring generally more rapidly in females than in males. Conclusion and Implications: We have shown for the first time that AKB48 effects significantly vary with prolonged use and that sex affects the pharmacodynamic/pharmacokinetic responses to repeated administration, suggesting a sex-tailored approach in managing AKB48-induced intoxication.

Incident reporting is an important method to identify risks because learning from the reports is crucial in developing and implementing effective improvements. A medical malpractice claims analysis is an important tool in any case. Both incident reports and claims show cases of damage caused to patients, despite incident reporting comprising near misses, cases where no event occurred and no-harm events. We therefore compare the two worlds to assess whether they are similar or definitively different. From 1 January 2014 to 31 December 2021, the claims database of Policlinico Universitario A. Gemelli IRCCS collected 843 claims. From 1 January 2020 to 31 December 2021, the incident-reporting database collected 1919 events. In order to compare the two, we used IBNR calculation, usually adopted by the insurance industry to determine loss to a company and to evaluate the real number of adverse events that occurred. Indeed, the number of reported adverse events almost overlapped with the total number of events, which is indicative that incurred-but-not-reported events are practically irrelevant. The distribution of damage events reported as claims in the period from 1 January 2020 to 31 December 2021 and related to incidents that occurred in the months of the same period, grouped by quarter, was then compared with the distribution of damage events reported as adverse events and sentinel events in the same period, grouped by quarter. The analysis of the claims database showed that the claims trend is slightly decreasing. However, the analysis of the reports database showed that, in the period 2020–2021, the reports trend was increasing. In our study, the comparison of the two, malpractice claims and incident reporting, documented many differences and weak areas of overlap. Nevertheless, this contribution represents the first attempt to compare the two and new studies focusing on single types of adverse events are, therefore, desirable.

COVID-19 has dramatically affected working forces. We aim to report our occupational medicine service’s experience in managing suspected COVID-19 cases during the pandemic through a retrospective observational study. We compared the number of days employees were absent from work due to flu-like symptoms from March 2020 to February 2021 to the same period the previous year (2019-2020). Two hundred thirty-four patients (+47.2% compared to the previous year) who tested negative for SARS-CoV-2 reported flu-like symptoms; the number of days of absence from work was 2812 (+190.2% compared to the previous year). On average, employees with flu-like symptoms lost 12.07 working days compared to 6.12 in the previous year (p<0.0001). In conclusion, in our sample COVID-19 has increased the number of working day loss. However, our approach proved to be important, especially during the first months of the pandemic, to limit SARS-CoV-2 spread in workplaces. Clin Ter 2022; 173 (1):64-66. doi: 10.7417/CT.2022.2394

Estimating the post-mortem interval is a fundamental, albeit challenging task in forensic sciences. To this aim, forensic practitioners need to assess post-mortem changes through a plethora of different methods, most of which are inherently qualitative, thus providing broad time intervals rather than precise determinations. This challenging problem is further complicated by the influence of environmental factors, which modify the temporal dynamics of post-mortem changes, sometimes in a rather unpredictable fashion. In this context, the search for quantitative and objective descriptors of post-mortem changes is highly demanded. In this study, we used computed tomography (CT) to assess the post-mortem anatomical modifications occurring in the time interval 0–4 days after death in the brain of four corpses. Our results show that fractal analysis of CT brain slices provides a set of quantitative descriptors able to map post-mortem changes over time throughout the whole brain. Although incapable of producing a direct estimation of the PMI, these descriptors could be used in combination with other more established methods to improve the accuracy and reliability of PMI determination.

Super-concentrated electrolyte solutions are of increasing interest for safer and more stable lithium and post-lithium batteries. The combination of 7Li and 17O (at natural abundance) nuclear magnetic resonance (NMR) and electrochemical characterization is proposed here as an effective approach to investigate the Li+ solvation structures and properties of electrolytes featuring tetraethylene glycol dimethyl ether (TEGDME) and lithium-bis(trifluoromethane sulfonyl) imide (LiTFSI). Five different formulations from salt-in-solvent to solvent-in-salt with LiTFSI at different concentrations (0.1 m, 0.5 m, 2 m, 4 m, 5 m) are investigated. The NMR results, also supported by physico-chemical characterizations such as thermal gravimetric analyses, differential scanning calorimetry, specific conductivity and viscosity, give information about the association of Li+ ions with anion and solvent molecules, allowing a deeper knowledge on the relationships among structure and functional properties of super-concentrated solutions.

OBJECTIVE: To develop a deep learning-based decision tree for the primary care setting, to stratify adult patients with confirmed and unconfirmed coronavirus disease 2019 (COVID-19), and to predict the need for hospitalization or home monitoring.PATIENTS AND METHODS: We performed a retrospective cohort study on data from patients admitted to a COVID hospital in Rome, Italy, between 5 March 2020 and 5 June 2020. A confirmed case was defined as a patient with a positive nasopharyngeal RT-PCR test result, while an unconfirmed case had negative results on repeated swabs. Patients' medical history and clinical, laboratory and radiological findings were collected, and the dataset was used to train a predictive model for COVID-19 severity.RESULTS: Data of 198 patients were included in the study. Twenty-eight (14.14%) had mild disease, 62 (31.31%) had moderate disease, 64 (32.32%) had severe disease, and 44 (22.22%) had critical disease. The G(2) value assessed the contribution of each collected value to decision tree building. On this basis, SpO2 (%) with a cut point at 92 was chosen for the optimal first split. Therefore, the decision tree was built using values maximizing G(2) and LogWorth. After the tree was built, the correspondence between inputs and outcomes was validated.CONCLUSIONS: We developed a machine learning-based tool that is easy to understand and apply. It provides good discrimination in stratifying confirmed and unconfirmed COVID-19 patients with different prognoses in every context. Our tool might allow general practitioners visiting patients at home to decide whether the patient needs to be hospitalized.

Background and aim: COVID-19 is an extremely challenging disease, both from a clinical and forensic point of view, and performing autopsies of COVID-19 deceased requires adequately equipped sectorial rooms and exposes health professionals to the risk of contagion. Among one of the categories that are most affected by SARS-Cov-2 infection are the elderly residents. Despite the need for prompt diagnoses, which are essential to implement all isolation measures necessary to contain the infection spread, deceased subjects in long-term care facilities are still are often diagnosed post-mortem. In this context, our study focuses on the use of post-mortem computed tomography for the diagnosis of COVID-19 infection, in conjunction with post-mortem swabs. The aim of this study was to assess the usefulness of post-mortem whole CT-scanning in identifying COVID-19 pneumonia as a cause of death, by comparing chest CT-findings of confirmed COVID-19 fatalities to control cases. Materials and methods: The study included 24 deceased subjects: 13 subjects coming from long-term care facility and 11 subjects died at home. Whole body CT scans were performed within 48 h from death in all subjects to evaluate the presence and distribution of pulmonary abnormalities typical of COVID-19-pneumonia, including: ground-glass opacities (GGO), consolidation, and pleural effusion to confirm the post-mortem diagnosis. Results: Whole-body CT scans was feasible and allowed a complete diagnosis in all subjects. In 9 (69%) of the 13 cases from long-term care facility the cause of death was severe COVID 19 pneumonia, while GGO were present in 100% of the study population. Conclusion: In the context of rapidly escalating COVID-19 outbreaks, given that laboratory tests for the novel coronavirus is time-consuming and can be falsely negative, the post-mortem CT can be considered as a reliable and safe modality to confirm COVID-19 pneumonia. This is especially true for specific postmortem chest CT-findings th

Using postmortem CT (PMCT), changes in the volume of the lateral cerebral ventricles (LCVs) and modifications of the radiodensity of cerebrospinal fluid (CSF) have been examined to identify a possible relationship between these changes and the time of death. Subsequent periodical CT scans termed “sequential scans” for ten corpses at known time of death were obtained, and a 3D segmentation of the entire LCV was carried out to measure its volume and radiodensity over time from ~ 5.5- h up to 273-h postmortem. A linear decrease of the LCV volume for all the cases was observed in the investigated time range, together with an overall logarithmic increase of radiodensity. Although a larger sampling should be performed to improve the result reliability, our finding suggests that the postmortem variation of CSF radiodensity can be a potentially useful tool in determining postmortem interval, a finding that is worthy of further investigation.

Healthcare workers are at the forefront against COVID-19, worldwide. Since Fondazione Policlinico Universitario A. Gemelli (FPG) IRCCS was enlisted as a COVID-19 hospital, the healthcare workers deployed to COVID-19 wards were separated from those with limited/no exposure, whereas the administrative staff were designated to work from home. Between 4 June and 3 July 2020, an investigation was conducted to evaluate the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin (IgG) antibodies among the employees of the FPG using point-of-care (POC) and venous blood tests. Sensitivity, specificity, and predictive values were determined with reverse-transcription polymerase chain reaction on nasal/oropharyngeal swabs as the diagnostic gold standard. The participants enrolled amounted to 4777. Seroprevalence was 3.66% using the POC test and 1.19% using the venous blood test, with a significant difference (p < 0.05). The POC test sensitivity and specificity were, respectively, 63.64% (95% confidence interval (CI): 62.20% to 65.04%) and 96.64% (95% CI: 96.05% to 97.13%), while those of the venous blood test were, respectively, 78.79% (95% CI: 77.58% to 79.94%) and 99.36% (95% CI: 99.07% to 99.55%). Among the low-risk populations, the POC test’s predictive values were 58.33% (positive) and 98.23% (negative), whereas those of the venous blood test were 92.86% (positive) and 98.53% (negative). According to our study, these serological tests cannot be a valid alternative to diagnose COVID-19 infection in progress.

Background and aim: COVID-19 is an extremely challenging disease, both from a clinical and forensic point of view, and performing autopsies of COVID-19 deceased requires adequately equipped sectorial rooms and exposes health professionals to the risk of contagion. Among one of the categories that are most affected by SARS-Cov-2 infection are the elderly residents. Despite the need for prompt diagnoses, which are essential to implement all isolation measures necessary to contain the infection spread, deceased subjects in long-term care facilities are still are often diagnosed post-mortem. In this context, our study focuses on the use of post-mortem computed tomography for the diagnosis of COVID-19 infection, in conjunction with post-mortem swabs. The aim of this study was to assess the usefulness of post-mortem whole CT-scanning in identifying COVID-19 pneumonia as a cause of death, by comparing chest CT-findings of confirmed COVID-19 fatalities to control cases. Materials and methods: The study included 24 deceased subjects: 13 subjects coming from long-term care facility and 11 subjects died at home. Whole body CT scans were performed within 48 h from death in all subjects to evaluate the presence and distribution of pulmonary abnormalities typical of COVID-19-pneumonia, including: ground-glass opacities (GGO), consolidation, and pleural effusion to confirm the post-mortem diagnosis. Results: Whole-body CT scans was feasible and allowed a complete diagnosis in all subjects. In 9 (69%) of the 13 cases from long-term care facility the cause of death was severe COVID 19 pneumonia, while GGO were present in 100% of the study population. Conclusion: In the context of rapidly escalating COVID-19 outbreaks, given that laboratory tests for the novel coronavirus is time-consuming and can be falsely negative, the post-mortem CT can be considered as a reliable and safe modality to confirm COVID-19 pneumonia. This is especially true for specific postmortem chest CT-findings th

There is still a lack of knowledge concerning the pathophysiology of death among COVID-19-deceased patients, and the question of whether a patient has died with or due to COVID-19 is still very much debated. In Italy, all deaths of patients who tested positive for SARS-CoV-2 are defined as COVID-19-related, without considering pre-existing diseases that may either contribute to or even cause death. Our study included nine subjects from two different nursing homes (Cases 1–4, Group A; Cases 5–9, Group B). The latter included patients who presumably died from CO poisoning due to a heating system malfunction. All subjects tested positive for COVID-19 both ante-and post-mortem and were examined using post-mortem computed tomography prior to autopsy. COVID-19 was determined to be a contributing cause in the deaths of four out of nine subjects (death due to COVID-19; i.e., pneumonia and sudden cardiac death). In the other five cases, for which CO poisoning was identified as the cause of death, the infection presumably had no role in exitus (death with COVID-19). In our attempt to classify our patients as dying with or due to COVID-19, we found the use of complete assessments (both histological analyses and computed tomography examination) fundamental.

Methiopropamine is a structural analog of methamphetamine that is categorized as a novel psychoactive substance. It primarily acts as a norepinephrine-dopamine reuptake inhibitor and, secondarily, as a serotonin reuptake inhibitor. In humans, methiopropamine induces stimulation and alertness and increases focus and energy. However, significant side effects are reported, such as tachycardia, anxiety, panic attacks, perspiration, headache, and difficulty in breathing. To date, little data is available regarding its pharmacodynamic effects, thereby we aimed to investigate the acute in vivo effects induced by this drug on sensorimotor responses, body temperature, pain thresholds, motor activity, and cardiovascular and respiratory systems in CD-1 male mice. We selected a range of doses that correspond to the whole range of human reported use, in order to evaluate the threshold of adverse effects presentation. This study demonstrates that methiopropamine acts as a dopaminergic and noradrenergic stimulating drug and that the highest doses (10-30 mg/kg) impair the visual placing response, facilitate the acoustic and tactile response, induce hypothermia, increase mechanical and thermal analgesia, stimulate locomotor activity, induce motor stereotypies, and strongly affected cardiovascular and respiratory parameters, increasing heart rate, breath rate, and blood pressure but reducing oxygen saturation. On the contrary, lower doses do not show any of those effects. We hypothesize that there is a range of doses that do enhance performance but do not seem hazardous to users: this gap could induce the perception of safety and increase the abuser population.

A 34-year-old man, who was previously fit and healthy, died suddenly on exercise. A post-mortem exam performed by forensic pathologists and a toxicological screening were normal; therefore, the cause of death was suspected to be sudden arrhythmic death syndrome, prompting the need for a molecular autopsy. Screening for genetic variations underlying arrhythmogenic genes by next-generation sequencing highlighted a heterozygous single-nucleotide variant in the exon n. 94 of the ryanodine receptor type 2 gene. This gene, encoding the cardiac ryanodine receptor, is one of the main genetic variants of catecholaminergic polymorphic ventricular tachycardia, estimated to affect 1 in 10,000 individuals. It manifests with syncope, seizures, or sudden death due to exercise- or emotional stress-induced bidirectional or polymorphic ventricular tachycardia, usually in children and young adults with morphologically normal hearts and normal baseline electrocardiograms. Even if this de novo missense mutation has not yet been associated with catecholaminergic polymorphic ventricular tachycardia, it is likely to be a disease-causing variant which leads to a defective protein responsible for disturbed ion flow.

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Cadaveric rigidity—also referred to as rigor mortis—is a valuable source of information for estimating the time of death, which is a fundamental and challenging task in forensic sciences. Despite its relevance, assessing the level of cadaveric rigidity still relies on qualitative and often subjective observations, and the development of a more quantitative approach is highly demanded. In this context, ultrasound shear wave elastography (US SWE) appears to be a particularly well-suited technique for grading cadaveric rigidity, as it allows non-invasive quantification of muscle stiffness in terms of Young’s modulus (E), which is a widely used parameter in tissue biomechanics. In this pilot study, we measured, for the first time in the literature, changes in the mechanical response of muscular tissues from 0 to 60 h post-mortem (hpm) using SWE, with the aim of investigating its applicability to forensic practice. For this purpose, 26 corpses were included in the study, and the muscle mechanical response was measured at random times in the 0–60 hpm range. Despite the preliminary nature of this study, our data indicate a promising role of SWE in the quantitative determination of cadaveric rigidity, which is still currently based on qualitative and semiquantitative methods. A more in-depth study is required to confirm SWE applicability in this field in order to overcome some of the inherent limitations of the present work, such as the rather low number of cases and the non-systematic approach of the measurements.

Second-generation antipsychotics (SGA) are a pharmacological class widely used in psychiatry thanks to their efficacy and good tolerability profile. One of the most used SGA is aripiprazole (ARI) because of its several formulations and safe metabolic and cardiac profile. As reported in a recent review, there are growing numbers of reports about ARI-induced gambling disorder (ARI-induced GD) which should encourage clinicians to use ARI more cautiously. Given the common genetic susceptibility of both GD and ARI's clinical response to a genetic polymorphism on the D2 receptor (DRD2/ANKK1 Taq1A; rs1800497), the hypothesis regarding the origin of this phenomenon could be found in the altered sensitization of dopamine's receptors that certain individuals carry genetically. The identification of a possible genetic susceptibility (detectable by genetic tests) could provide clinicians with an explanation for the ARI-induced GD and the possibility of using genetic screening tools for those cases of suspected predisposition; this would allow the clinician to prescribe ARI with less apprehension. The confirmation of this hypothesis through future pharmacogenetic studies may be useful for clinicians to have a correct understanding of the phenomenon.

Methiopropamine is a structural analog of methamphetamine that is categorized as a novel psychoactive substance. It primarily acts as a norepinephrine-dopamine reuptake inhibitor and, secondarily, as a serotonin reuptake inhibitor. In humans, methiopropamine induces stimulation and alertness and increases focus and energy. However, significant side effects are reported, such as tachycardia, anxiety, panic attacks, perspiration, headache, and difficulty in breathing. To date, little data is available regarding its pharmacodynamic effects, thereby we aimed to investigate the acute in vivo effects induced by this drug on sensorimotor responses, body temperature, pain thresholds, motor activity, and cardiovascular and respiratory systems in CD-1 male mice. We selected a range of doses that correspond to the whole range of human reported use, in order to evaluate the threshold of adverse effects presentation. This study demonstrates that methiopropamine acts as a dopaminergic and noradrenergic stimulating drug and that the highest doses (10-30 mg/kg) impair the visual placing response, facilitate the acoustic and tactile response, induce hypothermia, increase mechanical and thermal analgesia, stimulate locomotor activity, induce motor stereotypies, and strongly affected cardiovascular and respiratory parameters, increasing heart rate, breath rate, and blood pressure but reducing oxygen saturation. On the contrary, lower doses do not show any of those effects. We hypothesize that there is a range of doses that do enhance performance but do not seem hazardous to users: this gap could induce the perception of safety and increase the abuser population.

The aim of this work was to characterise three non-toxic ammunition (NTA) from the GECO and Fiocchi brands, which are available in the Italian market. Characterisation was carried out by considering both the elemental chemical composition and morphology, using scanning electron microscopy coupled with energy-dispersive X-ray analysis (SEM-EDS). Particles were collected from both the cartridge cases and the shooters' hands after shooting tests. Six volunteers fired two shots for each ammunition. Several elements, such as aluminium, potassium, silicon, sulphur, titanium and zinc were found in gunshot residue (GSR) particles from different ammunition. We also studied the persistence of these types of GSR on the hands of the shooters in a range between 1 and 6 h after shooting. The GSR particles from the three NTA tested were found on the hands of shooters until 6 h after the shots. The characterisations undertaken in this work will be useful for specialists in forensic science and legal medicine to evaluate trace evidence from these new NTA in casework, as such formulations are in growth.

BACKGROUND: The aims of the study were to assess prevalence and gender differences of addictive behaviors (substance- and non-substance-related) in an adolescent population, and their association with psychopathological features and academic performance. MATERIAL AND METHODS: A sample of high school Italian students (n = 996; M = 240, F = 756) was examined using a self-report survey concerning sociodemographic characteristics, cigarette smoking, alcohol and substance use, perceived academic performance, activities, and behaviors (Internet use, gambling, and physical exercising). The Internet Addiction Test, the South Oaks Gambling Screen-revised Adolescent, and the Exercise Addiction Inventory-Short Form were administered to identify problematic behaviors. The Barratt Impulsiveness Scale for Adolescent, the Snaith-Hamilton Pleasure Scale, the Dissociative Experience Scale for Adolescent, and the Toronto Alexithymia Scale were used to investigate psychopathological dimensions. RESULTS: Frequent alcohol intake and lifetime substances consumption were more common among males. The occurrence of other addictive behaviors was 22.1% for problematic Internet use (M = F), 9.7% for at-risk/problematic gambling (M > F), and 6.2% for maladaptive physical exercise (M = F). We also found an association between substance-/non-substance-related addictive behaviors and psychopathological dimensions. Addictive behaviors were more frequent among students reporting poor school performance. CONCLUSION: Our study showed a relevant prevalence of addictive behaviors in a sample of Italian high school students, with specific gender differences. We underlined the cooccurrence of substance and non-substance-related addictive behaviors, and their association with worse school performance. Dissociative proneness, anhedonia, alexithymia, and impulsivity were associated with addictive behaviors in adolescents and might represent vulnerability factors for the development of psychiatric disorder

MDPV is a synthetic cathinone illegally marketed and consumed for its psychostimulant effects, which are similar to those produced by cocaine, amphetamines, and MDMA. Clinical reports indicate that MDPV produces euphoria, increases alertness, and at high doses causes agitation, psychosis, tachycardia and hypertension, hallucinations, delirium, hyperthermia, rhabdomyolysis, and even death. In rodents, MDPV reproduces the typical physiological effects of psychostimulant drugs, demonstrating greater potency than cocaine. Nevertheless, its role in aggressive behavior has been reported but not yet experimentally confirmed. Therefore, the aim of this study was to evaluate the effects of acute and repeated MDPV (0.01–10 mg/kg i.p.) administration on aggressive behavior in mice and to compare them with those of cocaine (0.01–10 mg/kg i.p.) administration. To this purpose, the resident–intruder test in isolated mice and the spontaneous and stimulated aggressiveness tests for group-housed mice were employed. The present study shows for the first time that MDPV enhances aggressive behavior and locomotion in mice with greater potency and efficacy than cocaine treatment. Moreover, the aggressive and locomotor responses are enhanced after repeated administration, indicating that a sensitization mechanism comes into play. These results, although from preclinical investigation, are suggestive that human MDPV intake could be a problem for public health and the criminal justice system. Thus, investigation by police officers and medical staff is needed to prevent interpersonal violence induced by the consumption of synthetic cathinones.

Introduction: The estimation of the time since death, or post-mortem interval (PMI), still remains a main conundrum in forensic science. Several approaches have been so far proposed from either a qualitative or a quantitative point of view, but they still lack reliability and robustness. Recently, metabolomics has shown to be a potential tool to investigate the time-related post-mortem metabolite modifications in animal models. Objectives: Here we propose, for the first time, the use of a 1 H NMR metabolomic approach for the estimation of PMI from aqueous humour (AH) in an ovine model. Methods: AH samples were collected at different times after death (from 118 to 1429 min). 1 H NMR experiments were performed and spectral data analysed by multivariate statistical tools. Results: A multivariate calibration model was built to estimate PMI on the basis of the metabolite content of the samples. The model was validated with an independent test set, obtaining a prediction error of 59 min for PMI < 500 min, 104 min for PMI from 500 to 1000 min, and 118 min for PMI > 1000 min. Moreover, the metabolomic approach suggested a picture of the mechanisms underlying the post-mortem biological modifications, highlighting the role played by taurine, choline, and succinate. Conclusion: The time-related modifications of the 1 H NMR AH metabolomic profile seem to be encouraging in addressing the issue of a reproducible and robust model to be employed for the estimation of the time since death.

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AKB48 is a designer drug belonging to the indazole synthetic cannabinoids class, illegally sold as herbal blend, incense, or research chemicals for their psychoactive cannabis-like effects. In the present study, we investigated the in vivo pharmacological and behavioral effects of AKB48 in male rats and measured the pharmacodynamic effects of AKB48 and simultaneously determined its plasma pharmacokinetic. AKB48 at low doses preferentially stimulated dopamine release in the nucleus accumbens shell (0.25 mg/kg) and impaired visual sensorimotor responses (0.3 mg/kg) without affecting acoustic and tactile reflexes, which are reduced only to the highest dose tested (3 mg/kg). Increasing doses (0.5 mg/kg) of AKB48 impaired place preference and induced hypolocomotion in rats. At the highest dose (3 mg/kg), AKB48 induced hypothermia, analgesia, and catalepsy; inhibited the startle/pre-pulse inhibition test; and caused cardiorespiratory changes characterized by bradycardia and mild bradipnea and SpO2 reduction. All behavioral and neurochemical effects were fully prevented by the selective CB1 receptor antagonist/inverse agonist AM251. AKB48 plasma concentrations rose linearly with increasing dose and were correlated with changes in the somatosensory, hypothermic, analgesic, and cataleptic responses in rats. For the first time, this study shows the pharmacological and behavioral effects of AKB48 in rats, correlating them to the plasma levels of the synthetic cannabinoid.