330 results on '"De Giorgio, F."'
Search Results
102. In Vivo Bio-Activation of JWH-175 to JWH-018: Pharmacodynamic and Pharmacokinetic Studies in Mice.
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Tirri M, Arfè R, Bilel S, Corli G, Marchetti B, Fantinati A, Vincenzi F, De-Giorgio F, Camuto C, Mazzarino M, Barbieri M, Gaudio RM, Varani K, Borea PA, Botrè F, and Marti M
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- Animals, Cannabinoid Receptor Agonists pharmacology, Humans, Indoles chemistry, Male, Mice, Receptor, Cannabinoid, CB1, Cannabinoids chemistry, Cannabinoids pharmacology, Naphthalenes chemistry
- Abstract
3-(1-Naphthalenylmethyl)-1-pentyl-1H-indole (JWH-175) is a synthetic cannabinoid illegally marketed for its psychoactive cannabis-like effects. This study aimed to investigate and compare in vitro and in vivo pharmacodynamic activity of JWH-175 with that of 1-naphthalenyl (1-pentyl-1H-indol-3-yl)-methanone (JWH-018), as well as evaluate the in vitro (human liver microsomes) and in vivo (urine and plasma of CD-1 male mice) metabolic profile of JWH-175. In vitro binding studies showed that JWH-175 is a cannabinoid receptor agonist less potent than JWH-018 on mouse and human CB1 and CB2 receptors. In agreement with in vitro data, JWH-175 reduced the fESPS in brain hippocampal slices of mice less effectively than JWH-018. Similarly, in vivo behavioral studies showed that JWH-175 impaired sensorimotor responses, reduced breath rate and motor activity, and increased pain threshold to mechanical stimuli less potently than JWH-018. Metabolic studies demonstrated that JWH-175 is rapidly bioactivated to JWH-018 in mice blood, suggesting that in vivo effects of JWH-175 are also due to JWH-018 formation. The pharmaco-toxicological profile of JWH-175 was characterized for the first time, proving its in vivo bio-activation to the more potent agonist JWH-018. Thus, it highlighted the great importance of investigating the in vivo metabolism of synthetic cannabinoids for both clinical toxicology and forensic purposes.
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- 2022
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103. Epigenetic Studies for Evaluation of NPS Toxicity: Focus on Synthetic Cannabinoids and Cathinones.
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Mazdai L, Fabbri M, Tirri M, Corli G, Arfè R, Marchetti B, Bilel S, Bergamin E, Gaudio RM, Rubini M, De-Giorgio F, and Marti M
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In the recent decade, numerous new psychoactive substances (NPSs) have been added to the illicit drug market. These are synthetized to mimic the effects of classic drugs of abuse (i.e., cannabis, cocaine, etc.), with the purpose of bypassing substance legislations and increasing the pharmacotoxicological effects. To date, research into the acute pharmacological effects of new NPSs is ongoing and necessary in order to provide an appropriate contribution to public health. In fact, multiple examples of NPS-related acute intoxication and mortality have been recorded in the literature. Accordingly, several in vitro and in vivo studies have investigated the pharmacotoxicological profiles of these compounds, revealing that they can cause adverse effects involving various organ systems (i.e., cardiovascular, respiratory effects) and highlighting their potential increased consumption risks. In this sense, NPSs should be regarded as a complex issue that requires continuous monitoring. Moreover, knowledge of long-term NPS effects is lacking. Because genetic and environmental variables may impact NPS responses, epigenetics may aid in understanding the processes behind the harmful events induced by long-term NPS usage. Taken together, "pharmacoepigenomics" may provide a new field of combined study on genetic differences and epigenetic changes in drug reactions that might be predictive in forensic implications.
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- 2022
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104. Author Correction: Regarding "Fatal adrenal crisis due to Addison's disease arising in the context of autoimmune polyglandular syndrome type 1".
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De-Giorgio F, Foti F, Bergamin E, Sorice GP, and Vetrugno G
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- 2022
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105. Prevalence of Otolaryngology Diseases in an Urban Homeless Population.
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Ralli M, Marinelli A, De-Giorgio F, Crescenzi D, Vincentiis M, Greco A, Arcangeli A, and Ercoli L
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- Humans, Prevalence, Retrospective Studies, Ill-Housed Persons, Otolaryngology, Otorhinolaryngologic Diseases epidemiology
- Abstract
Objective: Otolaryngology diseases are common among people experiencing homelessness; however, they are seldom evaluated in a specialist setting, and investigations on their prevalence have rarely been conducted. The aim of this retrospective study was to evaluate the prevalence of otolaryngology conditions in an urban homeless population., Study Design: Retrospective study., Setting: Primary health care facility., Methods: The clinical records of patients referred to the medical facilities of the Primary Care Services of the Eleemosynaria Apostolica, Vatican City, between October 1, 2019, and July 31, 2021, were retrospectively reviewed; those reporting at least 1 otolaryngology disease were included in the study., Results: A total of 2516 records were retrospectively reviewed, and 484 (19.24%) were included in the study. The most common otolaryngology disease was pharyngotonsillitis (n = 118, 24.13%), followed by rhinitis with nasal obstruction (n = 107, 21.88%), hearing loss (n = 93, 19.01%), otitis (n = 81, 16.56%), abscess (n = 46, 9.40%), and sinusitis (n = 33, 6.74%). Head and neck cancer or precancerous lesions were reported in 34 subjects (7.02%). More than 1 simultaneous otolaryngology disorder was found in nearly 50% of our sample. A wide range of comorbidities was also reported., Conclusions: Our results confirm an elevated otolaryngology demand in the homeless population and encourage the development of more efficient and effective strategies for a population-tailored diagnosis and treatment of these conditions.
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- 2022
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106. Regarding "Fatal adrenal crisis due to Addison's disease arising in the context of autoimmune polyglandular syndrome type 1".
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De-Giorgio F, Foti F, Bergamin E, Sorice GP, and Vetrugno G
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- Humans, Addison Disease complications, Polyendocrinopathies, Autoimmune complications
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- 2022
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107. In vitro and in vivo pharmaco-dynamic study of the novel fentanyl derivatives: Acrylfentanyl, Ocfentanyl and Furanylfentanyl.
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Bilel S, Azevedo Neto J, Arfè R, Tirri M, Gaudio RM, Fantinati A, Bernardi T, Boccuto F, Marchetti B, Corli G, Serpelloni G, De-Giorgio F, Malfacini D, Trapella C, Calo' G, and Marti M
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- Analgesics, Opioid, Animals, Furans, Male, Mice, Pain drug therapy, Receptors, Opioid metabolism, beta-Arrestin 2 metabolism, Fentanyl analogs & derivatives, Fentanyl pharmacology, Receptors, Opioid, mu agonists
- Abstract
Fentanyl derivatives (FENS) belongs to the class of Novel Synthetic Opioids that emerged in the illegal drug market of New Psychoactive Substances (NPS). These substances have been implicated in many cases of intoxication and death with overdose worldwide. Therefore, the aim of this study is to investigate the pharmaco-dynamic profiles of three fentanyl (FENT) analogues: Acrylfentanyl (ACRYLF), Ocfentanyl (OCF) and Furanylfentanyl (FUF). In vitro, we measured FENS opioid receptor efficacy, potency, and selectivity in calcium mobilization studies performed in cells coexpressing opioid receptors and chimeric G proteins and their capability to promote the interaction of the mu receptor with G protein and β-arrestin 2 in bioluminescence resonance energy transfer (BRET) studies. In vivo, we investigated the acute effects of the systemic administration of ACRYLF, OCF and FUF (0.01-15 mg/kg i.p.) on mechanical and thermal analgesia, motor impairment, grip strength and cardiorespiratory changes in CD-1 male mice. Opioid receptor specificity was investigated in vivo using naloxone (NLX; 6 mg/kg i.p) pre-treatment. In vitro, the three FENS were able to activate the mu opioid receptor in a concentration dependent manner with following rank order potency: FUF > FENT=OCF > ACRYLF. All compounds were able to elicit maximal effects similar to that of dermorphin, with the exception of FUF which displayed lower maximal effects thus behaving as a partial agonist. In the BRET G-protein assay, all compounds behaved as partial agonists for the β-arrestin 2 pathway in comparison with dermorphin, whereas FUF did not promote β-arrestin 2 recruitment, behaving as an antagonist. In vivo, all the compounds increased mechanical and thermal analgesia with following rank order potency ACRYLF = FENT > FUF > OCF and impaired motor and cardiorespiratory parameters. Among the substances tested, FUF showed lower potency for cardiorespiratory and motor effects. These findings reveal the risks associated with the use of FENS and the importance of studying the pharmaco-dynamic properties of these drugs to better understand possible therapeutic interventions in the case of toxicity., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2022
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108. Letter to the Editor regarding the article 'ER stress-related protein, CHOP, may serve as a biomarker of mechanical asphyxia: a primary study' by Hu and colleagues.
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Chighine A, Locci E, Ferino G, De-Giorgio F, and d'Aloja E
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- Biomarkers, Humans, Asphyxia, Heat-Shock Proteins
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- 2022
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109. Post mortem computed tomography meets radiomics: a case series on fractal analysis of post mortem changes in the brain.
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De-Giorgio F, Ciasca G, Fecondo G, Mazzini A, Di Santo R, De Spirito M, and Pascali VL
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- Humans, Reproducibility of Results, Tomography, X-Ray Computed methods, Brain diagnostic imaging, Fractals, Postmortem Changes
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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., (© 2022. The Author(s).)
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- 2022
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110. Effect of -NBOMe Compounds on Sensorimotor, Motor, and Prepulse Inhibition Responses in Mice in Comparison With the 2C Analogs and Lysergic Acid Diethylamide: From Preclinical Evidence to Forensic Implication in Driving Under the Influence of Drugs.
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Tirri M, Bilel S, Arfè R, Corli G, Marchetti B, Bernardi T, Boccuto F, Serpelloni G, Botrè F, De-Giorgio F, Golembiowska K, and Marti M
- Abstract
In the last decade, the market for new psychoactive substances has been enriched by numerous psychedelic phenethylamines, which mimic the psychoactive effect of lysergic acid diethylamide (LSD). In particular, the -NBOMe series, which are more potent than their 2C compounds analogs, are considered worthy substitutes for LSD by users. The purpose of this study was to assess the effects of 25 H -NBOMe and its halogenated derivatives (25 I -NBOMe and 25 B -NBOMe) in comparison to their 2C compounds analogs and LSD on the sensorimotor (visual, acoustic, and overall tactile), reaction time, spontaneous (total distance traveled) and stimulated (drag, accelerod test) motor activity, grip strength test, and prepulse inhibition (PPI) responses in mice. Systemic administration of -NBOMe, 2C compounds analogs, and LSD (0.001-10 mg/kg) differently impaired the sensorimotor, reaction time, motor, and PPI responses in mice. In particular, halogenated (25I and 25B)-NBOMe derivatives appear to be more effective than the entire class of 2C compounds analogs in altering visual and acoustic responses, affecting reaction time, and motor and sensory gating in PPI test. In fact, the specific rank order of compounds potency for nearly all of the experiments showed that (25I and 25B)-NBOMe were more potent than 2C compounds analogs and LSD. -NBOMe and 2C compounds analogs impaired not only the reception of incoming sensory stimuli (visual and acoustic), but their correct brain processing (PPI) in an equal and sometimes stronger way than LSD. This sensory impairment directly affected the spontaneous motor response and reaction time of mice, with no change in performance in stimulated motor activity tests. These aspects should be carefully considered to better understand the potential danger that psychedelic phenethylamines, in particular -NBOMe, may pose to public health, with particular reference to decreased performance in driving and hazardous works that require special sensorimotor skills., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tirri, Bilel, Arfè, Corli, Marchetti, Bernardi, Boccuto, Serpelloni, Botrè, De-Giorgio, Golembiowska and Marti.)
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- 2022
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111. Erratum: Generation and analysis of innovative genomically humanized knockin SOD1 , TARDBP (TDP-43), and FUS mouse models.
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Devoy A, Price G, De Giorgio F, Bunton-Stasyshyn R, Thompson D, Gasco S, Allan A, Codner GF, Nair RR, Tibbit C, McLeod R, Ali Z, Noda J, Marrero-Gagliardi A, Brito-Armas JM, Williams C, Öztürk MM, Simon M, O'Neill E, Bryce-Smith S, Harrison J, Atkins G, Corrochano S, Stewart M, Gilthorpe JD, Teboul L, Acevedo-Arozena A, Fisher EMC, and Cunningham TJ
- Abstract
[This corrects the article DOI: 10.1016/j.isci.2021.103463.]., (© 2022 The Author(s).)
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- 2022
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112. Regarding "Post-mortem CT lung findings at a medicolegal institute in SARS-CoV-2 RT-PCR positive cases with autopsy correlation".
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De-Giorgio F, Bergamin E, Cittadini F, Cina A, and Vetrugno G
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- Autopsy, Humans, Lung diagnostic imaging, Reverse Transcriptase Polymerase Chain Reaction, Tomography, X-Ray Computed, COVID-19, SARS-CoV-2
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- 2022
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113. In vitro metabolic profile of mexedrone, a mephedrone analog, studied by high- and low-resolution mass spectrometry.
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Camuto C, Guglielmelli A, De-Giorgio F, de la Torre X, Mazzarino M, Marti M, and Botrè F
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- Chromatography, High Pressure Liquid, Humans, Metabolome, Microsomes, Liver metabolism, Tandem Mass Spectrometry methods, Methamphetamine analogs & derivatives
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Mexedrone is a synthetic cathinone structurally related to mephedrone, which belongs to the class of N-alkyl cathinone derivatives, whose metabolic profile has not been fully clarified yet. This study considers the in vitro phase I metabolism of mexedrone, to pre-select the most appropriate marker(s) of intake. Mexedrone was incubated in the presence of either human liver microsomes or single recombinant CYP450 isoforms. The metabolic profile was outlined by ultra-high-performance liquid chromatography coupled to both high- and low-resolution mass spectrometry. In detail, the phase I metabolic profile of mexedrone was initially defined by a time-of-flight analyzer, while the chemical structures of the detected metabolites and the potential presence of minor metabolites were subsequently studied by tandem mass spectrometry, using a triple quadrupole analyzer. The main phase I metabolic reactions were hydroxylation and N- and O-dealkylation. The CYP450 isoforms most involved were CYP2C19, responsible for the formation of both hydroxylated and dealkylated metabolites, followed by CYP2D6 and CYP1A2, involved in the hydroxylation reactions only. Finally, a significant fraction of mexedrone unchanged was also detected. Based on this evidence, the most appropriate markers of intake are mexedrone unchanged and the hydroxylated metabolites., (© 2021 The Authors. Drug Testing and Analysis published by John Wiley & Sons Ltd.)
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- 2022
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114. Equal Incidence of COVID-19 among Homeless and Non-Homeless Emergency Department Patients.
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Ralli M, De-Giorgio F, Arcangeli A, and Ercoli L
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- Emergency Service, Hospital, Humans, Incidence, SARS-CoV-2, COVID-19, Ill-Housed Persons
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- 2022
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115. Ethanol enhanced MDPV- and cocaine-induced aggressive behavior in mice: Forensic implications.
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De-Giorgio F, Bergamin E, Bilel S, Tirri M, Arfè R, Marchetti B, Corli G, Serpelloni G, and Marti M
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- Aggression, Animals, Benzodioxoles, Dose-Response Relationship, Drug, Ethanol, Male, Mice, Pyrrolidines, Cocaine
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Background: Reports concerning the causal link between aggressive behavior and use and abuse of different substances (i.e., alcohol, MDPV) can be found in the literature. Nonetheless, the topic concerning the effects of acute ethanol administration on MDPV and cocaine induced aggressive behavior has yet to be thoroughly investigated. The aim of this study was to investigate such synergistic effects., Materials and Methods: A total of 360 male mice were employed in the study. Ethanol was diluted with saline solution and administered 10 min before MDPV or cocaine injection via oral gavage needles. Similarly, MDPV and cocaine were dissolved in saline solution and administered by intraperitoneal injection. Different associations of specific drug doses were then tested. To investigate the acute effects of MDPV and cocaine and their interaction with ethanol on aggression in mice, a resident-intruder test was used., Results: Ethanol alone was ineffective at dosages of 0.05 g/kg and 0.25 g/kg but increased the aggressiveness of the mice at 0.125 g/kg. Similarly, the injection of both cocaine alone and MDPV alone did not significantly increase the aggressiveness of the mice; conversely, the combination of ethanol and cocaine and ethanol and MDPV enhanced aggression at specific ethanol dosages (0.05 g/kg and 0.125 g/kg)., Conclusion: This study demonstrated that acute ethanol administration enhances MDPV- and cocaine-induced aggressive behavior in mice. This aggressive response is particularly enhanced when MDVP and cocaine are coupled with specific ethanol dosages, proving that psychostimulant drugs may act synergistically under certain conditions., (Copyright © 2021. Published by Elsevier B.V.)
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- 2021
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116. Generation and analysis of innovative genomically humanized knockin SOD1 , TARDBP (TDP-43), and FUS mouse models.
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Devoy A, Price G, De Giorgio F, Bunton-Stasyshyn R, Thompson D, Gasco S, Allan A, Codner GF, Nair RR, Tibbit C, McLeod R, Ali Z, Noda J, Marrero-Gagliardi A, Brito-Armas JM, Williams C, Öztürk MM, Simon M, O'Neill E, Bryce-Smith S, Harrison J, Atkins G, Corrochano S, Stewart M, Gilthorpe JD, Teboul L, Acevedo-Arozena A, Fisher EMC, and Cunningham TJ
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Amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) is a fatal neurodegenerative disorder, and continued innovation is needed for improved understanding and for developing therapeutics. We have created next-generation genomically humanized knockin mouse models, by replacing the mouse genomic region of Sod1 , Tardbp (TDP-43), and Fus , with their human orthologs, preserving human protein biochemistry and splicing with exons and introns intact. We establish a new standard of large knockin allele quality control, demonstrating the utility of indirect capture for enrichment of a genomic region of interest followed by Oxford Nanopore sequencing. Extensive analysis shows that homozygous humanized animals only express human protein at endogenous levels. Characterization of humanized FUS animals showed that they are phenotypically normal throughout their lifespan. These humanized strains are vital for preclinical assessment of interventions and serve as templates for the addition of coding or non-coding human ALS/FTD mutations to dissect disease pathomechanisms, in a physiological context., Competing Interests: The authors declare no competing interests., (© 2021 The Authors.)
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- 2021
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117. Estimation of the time of death by measuring the variation of lateral cerebral ventricle volume and cerebrospinal fluid radiodensity using postmortem computed tomography.
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De-Giorgio F, Ciasca G, Fecondo G, Mazzini A, De Spirito M, and Pascali VL
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- Adult, Aged, Aged, 80 and over, Female, Humans, Linear Models, Male, Middle Aged, Postmortem Changes, Time Factors, Tomography, X-Ray Computed, Cerebrospinal Fluid diagnostic imaging, Lateral Ventricles diagnostic imaging
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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., (© 2021. The Author(s).)
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- 2021
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118. Endothelial Heme Dynamics Drive Cancer Cell Metabolism by Shaping the Tumor Microenvironment.
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Petrillo S, De Giorgio F, Kopecka J, Genova T, Fiorito V, Allocco AL, Bertino F, Chiabrando D, Mussano F, Altruda F, Munaron L, Riganti C, and Tolosano E
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The crosstalk among cancer cells (CCs) and stromal cells within the tumor microenvironment (TME) has a prominent role in cancer progression. The significance of endothelial cells (ECs) in this scenario relies on multiple vascular functions. By forming new blood vessels, ECs support tumor growth. In addition to their angiogenic properties, tumor-associated ECs (TECs) establish a unique vascular niche that actively modulates cancer development by shuttling a selected pattern of factors and metabolites to the CC. The profile of secreted metabolites is strictly dependent on the metabolic status of the cell, which is markedly perturbed in TECs. Recent evidence highlights the involvement of heme metabolism in the regulation of energy metabolism in TECs. The present study shows that interfering with endothelial heme metabolism by targeting the cell membrane heme exporter Feline Leukemia Virus subgroup C Receptor 1a (FLVCR1a) in TECs, resulted in enhanced fatty acid oxidation (FAO). Moreover, FAO-derived acetyl-CoA was partly consumed through ketogenesis, resulting in ketone bodies (KBs) accumulation in FLVCR1a-deficient TECs. Finally, the results from this study also demonstrate that TECs-derived KBs can be secreted in the extracellular environment, inducing a metabolic rewiring in the CC. Taken together, these data may contribute to finding new metabolic vulnerabilities for cancer therapy.
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- 2021
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119. Dying "from" or "with" COVID-19 during the Pandemic: Medico-Legal Issues According to a Population Perspective.
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De-Giorgio F, Grassi VM, Bergamin E, Cina A, Del Nonno F, Colombo D, Nardacci R, Falasca L, Conte C, d'Aloja E, Damiani G, and Vetrugno G
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- Autopsy, Humans, Nursing Homes, SARS-CoV-2, COVID-19, Pandemics
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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.
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- 2021
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120. Worsening of the Toxic Effects of (±) Cis -4,4'-DMAR Following Its Co-Administration with (±) Trans -4,4'-DMAR: Neuro-Behavioural, Physiological, Immunohistochemical and Metabolic Studies in Mice.
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Tirri M, Frisoni P, Bilel S, Arfè R, Trapella C, Fantinati A, Corli G, Marchetti B, De-Giorgio F, Camuto C, Mazzarino M, Gaudio RM, Serpelloni G, Schifano F, Botrè F, and Marti M
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- Animals, Male, Mice, Mice, Inbred ICR, Oxazoles classification, Oxazoles urine, Psychophysiologic Disorders chemically induced, Psychotropic Drugs classification, Psychotropic Drugs urine, Stereoisomerism, Behavior, Animal drug effects, Oxazoles toxicity, Psychophysiologic Disorders metabolism, Psychophysiologic Disorders pathology, Psychotropic Drugs toxicity
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4,4'-Dimethylaminorex (4,4'-DMAR) is a new synthetic stimulant, and only a little information has been made available so far regarding its pharmaco-toxicological effects. The aim of this study was to investigate the effects of the systemic administration of both the single (±) cis (0.1-60 mg/kg) and (±) trans (30 and 60 mg/kg) stereoisomers and their co-administration (e.g., (±) cis at 1, 10 or 60 mg/kg + (±) trans at 30 mg/kg) in mice. Moreover, we investigated the effect of 4,4'-DMAR on the expression of markers of oxidative/nitrosative stress (8-OHdG, iNOS, NT and NOX2), apoptosis (Smac/DIABLO and NF-κB), and heat shock proteins (HSP27, HSP70, HSP90) in the cerebral cortex. Our study demonstrated that the (±) cis stereoisomer dose-dependently induced psychomotor agitation, sweating, salivation, hyperthermia, stimulated aggression, convulsions and death. Conversely, the (±) trans stereoisomer was ineffective whilst the stereoisomers' co-administration resulted in a worsening of the toxic (±) cis stereoisomer effects. This trend of responses was confirmed by immunohistochemical analysis on the cortex. Finally, we investigated the potentially toxic effects of stereoisomer co-administration by studying urinary excretion. The excretion study showed that the (±) trans stereoisomer reduced the metabolism of the (±) cis form and increased its amount in the urine, possibly reflecting its increased plasma levels and, therefore, the worsening of its toxicity.
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- 2021
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121. COVID-19 and Homelessness: Prevalence Differences Between Sheltered and Unsheltered Individuals.
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Ralli M, Arcangeli A, De-Giorgio F, Morrone A, and Ercoli L
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- Housing, Humans, Prevalence, SARS-CoV-2, COVID-19, Ill-Housed Persons
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- 2021
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122. Comparison of N-methyl-2-pyrrolidone (NMP) and the "date rape" drug GHB: behavioral toxicology in the mouse model.
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Arfè R, Bilel S, Tirri M, Frisoni P, Serpelloni G, Neri M, Boccuto F, Bernardi T, Foti F, De-Giorgio F, and Marti M
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- Adjuvants, Anesthesia toxicity, Animals, Dose-Response Relationship, Drug, Hypnotics and Sedatives toxicity, Locomotion physiology, Male, Mice, Mice, Inbred ICR, Models, Animal, Psychomotor Performance physiology, Rape, Reflex, Startle physiology, Respiratory Insufficiency chemically induced, Respiratory Insufficiency physiopathology, Illicit Drugs toxicity, Locomotion drug effects, Psychomotor Performance drug effects, Pyrrolidinones toxicity, Reflex, Startle drug effects, Sodium Oxybate toxicity
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N-methyl-2-pyrrolidone (NMP) and γ-hydroxybutyrate acid (GHB) are synthetic solvents detected in the recreational drug market. GHB has sedative/hypnotic properties and is used for criminal purposes to compromise reaction ability and commit drug-facilitated sexual assaults and other crimes. NMP is a strong solubilizing solvent that has been used alone or mixed with GHB in case of abuse and robberies. The aim of this experimental study is to compare the acute pharmaco-toxicological effects of NMP and GHB on neurological signs (myoclonia, convulsions), sensorimotor (visual, acoustic, and overall tactile) responses, righting reflex, thermoregulation, and motor activity (bar, drag, and accelerod test) in CD-1 male mice. Moreover, since cardiorespiratory depression is one of the main adverse effects related to GHB intake, we investigated the effect of NMP and GHB on cardiorespiratory changes (heart rate, breath rate, oxygen saturation, and pulse distension) in mice. The present study demonstrates that NMP inhibited sensorimotor and motor responses and induced cardiorespiratory depression, with a lower potency and efficacy compared to GHB. These results suggest that NMP can hardly be used alone as a substance to perpetrate sexual assault or robberies., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2021
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123. Use of post-mortem chest computed tomography in Covid-19 pneumonia.
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De-Giorgio F, Cittadini F, Cina A, Cavarretta E, Biondi-Zoccai G, Vetrugno G, Natale L, Colosimo C, and Pascali VL
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- Adult, Aged, Aged, 80 and over, Autopsy methods, Case-Control Studies, Female, Humans, Male, Middle Aged, Pleural Effusion diagnostic imaging, Retrospective Studies, Sensitivity and Specificity, Whole Body Imaging, COVID-19 diagnosis, Lung diagnostic imaging, Tomography, X-Ray Computed
- Abstract
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 that are rather characteristic of COVID-19 fatalities., Competing Interests: Declarations of interest None., (Crown Copyright © 2021. Published by Elsevier B.V. All rights reserved.)
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- 2021
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124. In Vitro and In Vivo Pharmaco-Toxicological Characterization of 1-Cyclohexyl-x-methoxybenzene Derivatives in Mice: Comparison with Tramadol and PCP.
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Bilel S, Tirri M, Arfè R, Sturaro C, Fantinati A, Cristofori V, Bernardi T, Boccuto F, Cavallo M, Cavalli A, De-Giorgio F, Calò G, and Marti M
- Subjects
- Analgesics, Opioid chemistry, Animals, Anisoles chemistry, Benzene Derivatives chemistry, Cells, Cultured, Cricetinae, Hallucinogens chemistry, In Vitro Techniques, Male, Mice, Mice, Inbred ICR, Models, Animal, Phencyclidine chemistry, Psychotropic Drugs chemistry, Tramadol chemistry, Analgesics, Opioid toxicity, Anisoles toxicity, Benzene Derivatives toxicity, Hallucinogens toxicity, Phencyclidine toxicity, Psychotropic Drugs toxicity, Receptors, Opioid metabolism, Tramadol toxicity
- Abstract
1-cyclohexyl-x-methoxybenzene is a novel psychoactive substance (NPS), first discovered in Europe in 2012 as unknown racemic mixture of its three stereoisomers: ortho, meta and para. Each of these has structural similarities with the analgesic tramadol and the dissociative anesthetic phencyclidine. In light of these structural analogies, and based on the fact that both tramadol and phencyclidine are substances that cause toxic effects in humans, the aim of this study was to investigate the in vitro and in vivo pharmacodynamic profile of these molecules, and to compare them with those caused by tramadol and phencyclidine. In vitro studies demonstrated that tramadol, ortho, meta and para were inactive at mu, kappa and delta opioid receptors. Systemic administration of the three stereoisomers impairs sensorimotor responses, modulates spontaneous motor activity, induces modest analgesia, and alters thermoregulation and cardiorespiratory responses in the mouse in some cases, with a similar profile to that of tramadol and phencyclidine. Naloxone partially prevents only the visual sensorimotor impairments caused by three stereoisomers, without preventing other effects. The present data show that 1-cyclohexyl-x-methoxybenzene derivatives cause pharmaco-toxicological effects by activating both opioid and non-opioid mechanisms and suggest that their use could potentially lead to abuse and bodily harm.
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- 2021
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125. Low-normal doses of methiopropamine induce aggressive behaviour in mice.
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Foti F, Bilel S, Tirri M, Arfè R, Boccuto F, Bernardi T, Serpelloni G, De-Giorgio F, and Marti M
- Subjects
- Aggression physiology, Animals, Central Nervous System Stimulants administration & dosage, Central Nervous System Stimulants chemistry, Central Nervous System Stimulants toxicity, Dose-Response Relationship, Drug, Locomotion physiology, Male, Methamphetamine administration & dosage, Methamphetamine chemistry, Methamphetamine toxicity, Mice, Mice, Inbred ICR, Thiophenes chemistry, Aggression drug effects, Locomotion drug effects, Methamphetamine analogs & derivatives, Thiophenes administration & dosage, Thiophenes toxicity
- Abstract
Recreational use of illicit methiopropamine (MPA) is a public health concern because it produces neurochemical effects comparable with those induced by methamphetamine (METH). The present study investigated the effects of MPA on the expression of an aggressive behaviour. Eighty CD-1 male mice, after receiving intraperitoneal injection of saline, MPA (0.01-10 mg/kg), METH (0.01-10 mg/kg), or AMPH (0.01-10 mg/kg), once a week over a 5-week period, underwent the resident-intruder test and spontaneous locomotor activity measurement. Results showed that all psychostimulants induce aggressive behaviour even at low doses, with a dose-dependent increase and a time-dependent sensitisation. MPA potency was similar to METH and superior to AMPH. Therefore, MPA-induced aggressive behaviour may appear even at MPA dosages free of cardiovascular or other behavioural adverse effects and could become a non-intentional side effect that users experience after increasing and repeating MPA consumption.
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- 2021
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126. Impact of COVID-19 pandemic on the medical activities of the Directorate of Health and Hygiene, Vatican City State.
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Ralli M, Arcangeli A, Soave PM, Carbone L, Ercoli L, and De-Giorgio F
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- Female, Humans, Male, Pandemics, Pneumonia, Viral epidemiology, Pneumonia, Viral prevention & control, Pneumonia, Viral virology, SARS-CoV-2, Vatican City epidemiology, COVID-19 epidemiology, COVID-19 prevention & control, Communicable Disease Control organization & administration, Delivery of Health Care organization & administration
- Abstract
Objectives: To report the changes in volume and characteristics of medical activities in the Vatican City State during COVID-19 pandemic., Methods: Data for general / emergency procedures , specialty consultations, radiology examinations and diagnostic procedures delivered by the Directorate of Health and Hygiene of the Vatican City State were retrospectively analysed. Analysis focused on the entire year 2020 and on the lockdown period 9 March - 18 May 2020., Results: In 2020, 73.932 procedures were performed compared to 95.218 in 2019 (-22.4%). During lockdown, general / emergency activities decreased by 61.1%, specialty consultations by 85.3%, radiology examinations by 95.8%, and diagnostic procedures by 96.5%. A decrease was found for nearly all specialties; the most affected were occupational medicine and dermatology, whilst an increase was found for legal medicine, psychiatry and angiology., Conclusion: Medical activities of the Vatican City State have been severely impacted, especially during the first months of the pandemic. However, organizational efforts allowed rapid restoration to near-normal volumes., (© 2021 The Association for the Publication of the Journal of Internal Medicine.)
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- 2021
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127. Let us learn from litigation claims: actuarial tools can improve safety.
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Foti F, De-Giorgio F, and Vetrugno G
- Subjects
- Health Expenditures, Humans, Jurisprudence, Malpractice statistics & numerical data, Predictive Value of Tests, Risk Management methods, Safety standards, Liability, Legal economics, Malpractice legislation & jurisprudence, Risk Management statistics & numerical data, Safety legislation & jurisprudence
- Abstract
Competing Interests: Competing interests: None declared.
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- 2021
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128. Metabolomics improves the histopathological diagnosis of asphyxial deaths: an animal proof-of-concept model.
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Locci E, Chighine A, Noto A, Ferino G, Baldi A, Varvarousis D, Xanthos T, De-Giorgio F, Stocchero M, and d'Aloja E
- Subjects
- Animals, Asphyxia metabolism, Asphyxia pathology, Disease Models, Animal, Female, Histological Techniques, Humans, Swine, Asphyxia diagnosis, Metabolomics methods, Proton Magnetic Resonance Spectroscopy methods
- Abstract
The diagnosis of mechanical asphyxia remains one of the most difficult issues in forensic pathology. Asphyxia ultimately results in cardiac arrest (CA) and, as there are no specific markers, the differential diagnosis of primitive CA and CA secondary to asphyxiation relies on circumstantial details and on the pathologist experience, lacking objective evidence. Histological examination is currently considered the gold standard for CA post-mortem diagnosis. Here we present the comparative results of histopathology versus those previously obtained by
1 H nuclear magnetic resonance (NMR) metabolomics in a swine model, originally designed for clinical purposes, exposed to two different CA causes, namely ventricular fibrillation and asphyxia. While heart and brain microscopical analysis could identify the damage induced by CA without providing any additional information on the CA cause, metabolomics allowed the identification of clearly different profiles between the two groups and showed major differences between asphyxiated animals with good and poor outcomes. Minute-by-minute plasma sampling allowed to associate these modifications to the pre-arrest asphyxial phase showing a clear correlation to the cellular effect of mechanical asphyxia reproduced in the experiment. The results suggest that metabolomics provides additional evidence beyond that obtained by histology and immunohistochemistry in the differential diagnosis of CA.- Published
- 2021
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129. Post-mortem ocular changes and time since death: Scoping review and future perspective.
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De-Giorgio F, Grassi S, d'Aloja E, and Pascali VL
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- Autopsy, Eye, Face, Humans, Time Factors, Forensic Medicine, Postmortem Changes
- Abstract
The forensics literature on the relationship between ocular changes and the postmortem interval (PMI) has traditionally focused on time-related variations in concentrations of metabolites and elements within the eye. However, structural changes within the eye over time deserve the same attention because there is significant evidence of their importance in determining the time since death. Therefore, we reviewed publications that provided substantial evidence on this issue. In light of our inclusion and exclusion criteria, 26 papers were eligible for review. On the basis of the ocular parameters considered, we grouped the reviewed evidence into eight thematic areas: corneal opacities, corneal thickness, drug-induced pupil diameter variations, retinal changes, segmentation of retinal vessels, intraocular pressure reduction, globe temperature and crystalline alterations. The most important and common limitations of the reviewed studies were small study populations (many were monocentric studies), absence of robust statistical methodology, use of mathematical models valid only in ideal conditions and validation only for short PMIs. Although many phenomena cannot be used to reliably estimate PMI, there is rigorous evidence suggesting that promising factors, including corneal thickness, require methodological innovations for application to forensics practice but could be used in the near future to reliably estimate the time since death., (Copyright © 2021 Elsevier B.V. All rights reserved.)
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- 2021
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130. Comparative use of aqueous humour 1 H NMR metabolomics and potassium concentration for PMI estimation in an animal model.
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Locci E, Stocchero M, Gottardo R, De-Giorgio F, Demontis R, Nioi M, Chighine A, Tagliaro F, and d'Aloja E
- Subjects
- Animals, Disease Models, Animal, Electrophoresis, Capillary, Proton Magnetic Resonance Spectroscopy, Regression Analysis, Sheep, Aqueous Humor chemistry, Metabolomics, Postmortem Changes, Potassium analysis
- Abstract
Estimation of the post-mortem interval (PMI) remains a matter of concern in the forensic scenario. Traditional and novel approaches are not yet able to fully address this issue, which relies on complex biological phenomena triggered by death. For this purpose, eye compartments may be chosen for experimental studies because they are more resistant to post-mortem modifications. Vitreous humour, in particular, has been extensively investigated, with potassium concentration ([K
+ ]) being the marker that is better correlated with PMI estimation. Recently, a1 H nuclear magnetic resonance (NMR) metabolomic approach based on aqueous humour (AH) from an animal model was proposed for PMI estimation, resulting in a robust and validated regression model. Here we studied the variation in [K+ ] in the same experimental setup. [K+ ] was determined through capillary ion analysis (CIA) and a regression analysis was performed. Moreover, it was investigated whether the PMI information related to potassium could improve the metabolome predictive power in estimating the PMI. Interestingly, we found that a part of the metabolomic profile is able to explain most of the information carried by potassium, suggesting that the rise in both potassium and metabolite concentrations relies on a similar biological mechanism. In the first 24-h PMI window, the AH metabolomic profile shows greater predictive power than [K+ ] behaviour, suggesting its potential use as an additional tool for estimating the time since death.- Published
- 2021
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131. Biomarkers of Low-Level Environmental Exposure to Benzene and Oxidative DNA Damage in Primary School Children in Sardinia, Italy.
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Pilia I, Campagna M, Marcias G, Fabbri D, Meloni F, Spatari G, Cottica D, Cocheo C, Grignani E, De-Giorgio F, Cocco P, and d'Aloja E
- Subjects
- Biomarkers, Child, DNA Damage, Environmental Exposure analysis, Environmental Monitoring, Humans, Italy, Oxidative Stress, Schools, Benzene analysis, Benzene toxicity, Occupational Exposure analysis
- Abstract
Background: The main anthropic sources of exposure to airborne benzene include vehicular traffic, cigarette smoke, and industrial emissions., Methods: To detect early genotoxic effects of environmental exposure to benzene, we monitored environmental, personal, and indoor airborne benzene in children living in an urban area and an area near a petrochemical plant. We also used urinary benzene and S-phenylmercapturic acid (S-PMA) as biomarkers of benzene exposure and urinary 8-hydroxydeoxyguanosine (8-OHdG) as a biomarker of early genotoxic effects., Results: Although always below the European Union limit of 5 μg/m
3 , airborne benzene levels were more elevated in the indoor, outdoor, and personal samples from the industrial surroundings compared to the urban area ( p = 0.026, p = 0.005, and p = 0.001, respectively). Children living in the surroundings of the petrochemical plant had urinary benzene values significantly higher than those from the urban area in both the morning and evening samples ( p = 0.01 and p = 0.02, respectively). Results of multiple regression modelling showed that age was a significant predictor of 8-OHdG excretion, independent of the sampling hour. Moreover, at the low exposure level experienced by the children participating in this study, neither personal or indoor airborne benzene level, nor personal monitoring data, affected 8-OHdG excretion., Conclusions: Our results suggest the importance of biological monitoring of low-level environmental exposure and its relation to risk of genotoxic effects among children.- Published
- 2021
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132. SARS-CoV-2 seroprevalence in the Vatican City State.
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Ralli M, Arcangeli A, Soave PM, Voglino MC, and De-Giorgio F
- Subjects
- Antibodies, Viral, Humans, Seroepidemiologic Studies, Vatican City, COVID-19, SARS-CoV-2
- Published
- 2021
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133. Communication and Resolution Programs in the COVID-19 Era: A Unique Opportunity to Enhance Patient Safety (and Save Money).
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Foti F, De-Giorgio F, and Vetrugno G
- Subjects
- Communication, Delivery of Health Care, Humans, SARS-CoV-2, COVID-19, Patient Safety
- Published
- 2021
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134. Border areas in head and neck pathologies: professional liability in the multidisciplinary approach.
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Vetrugno G, De-Giorgio F, Pascali VL, and Oliva A
- Subjects
- Humans, Liability, Legal, Malpractice
- Published
- 2021
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135. COVID-19 Seroprevalence among Healthcare Workers of a Large COVID-19 Hospital in Rome Reveals Strengths and Limits of Two Different Serological Tests.
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Vetrugno G, La Milia DI, D'Ambrosio F, Di Pumpo M, Pastorino R, Boccia S, Ricci R, De-Giorgio F, Cicconi M, Foti F, Pascucci D, Castrini F, Carini E, Cambieri A, D'Alfonso ME, Capalbo G, Fantoni M, Moscato U, Staiti D, De Simone FM, Berloco F, Damiani G, Zega M, Cattani P, Posteraro B, Sanguinetti M, and Laurenti P
- Subjects
- Antibodies, Viral, Health Personnel, Hospitals, Humans, Rome, SARS-CoV-2, Seroepidemiologic Studies, Serologic Tests, COVID-19
- Abstract
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.
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- 2021
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136. Mass vaccination campaign for residents and workers and assistance to vulnerable populations during COVID-19 pandemic: The experience of the healthcare services of the Vatican City.
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Ralli M, De-Giorgio F, Soave PM, Ercoli L, and Arcangeli A
- Abstract
Competing Interests: None Funding: none
- Published
- 2021
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137. Regarding "Death due to atypical urinothorax following percutaneous nephrolithotomy".
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Foschi N, Foti F, Vetrugno G, and De-Giorgio F
- Subjects
- Humans, Nephrolithotomy, Percutaneous adverse effects, Pleural Effusion etiology
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- 2021
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138. The Vatican City State Internal Healthcare System Response to COVID-19 Pandemic: Prevention and Control Strategies.
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Arcangeli A, Ralli M, De-Giorgio F, Soave PM, and Ercoli L
- Subjects
- Humans, SARS-CoV-2, Vatican City epidemiology, COVID-19 epidemiology, COVID-19 prevention & control, Communicable Disease Control organization & administration, Delivery of Health Care organization & administration, Pandemics prevention & control
- Published
- 2021
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139. A potential cause of asbestos-related granulomatosis due to adulterant contamination in a drug abuser.
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Lazzaro MC, Romanò S, Santoro S, Camuto C, Carbone A, Casamassima R, Abate S, and De-Giorgio F
- Subjects
- Adult, Asbestos administration & dosage, Autopsy, Central Nervous System Stimulants administration & dosage, Cocaine administration & dosage, Drug Users, Fatal Outcome, Female, Granuloma, Foreign-Body pathology, Granuloma, Respiratory Tract pathology, Humans, Asbestos adverse effects, Central Nervous System Stimulants adverse effects, Cocaine adverse effects, Cocaine-Related Disorders complications, Drug Contamination, Granuloma, Foreign-Body etiology, Granuloma, Respiratory Tract etiology, Substance Abuse, Intravenous complications
- Abstract
Drug adulterants containing contaminants have been known to cause lung disease by inhalation or intravenous intake. Talcosis due to intravenous talc injection has been widely described in the literature, whereas the hypothesis of granulomatosis due to asbestos related to adulterated cocaine injection has not yet been explored. Herein, a case of pulmonary granulomatosis due to asbestos fibres related to cocaine injection in a young woman is described. Inorganic material in the lung was first individuated by light microscopy and last was identified using the SEM-EDX method. This case is unique since the occupational and passive inhalation of asbestos was excluded with absolute certainty.
- Published
- 2021
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140. Urinary excretion profile of methiopropamine in mice following intraperitoneal administration: A liquid chromatography-tandem mass spectrometry investigation.
- Author
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Camuto C, Pellegrini S, De-Giorgio F, de la Torre X, Marti M, Mazzarino M, and Botrè F
- Subjects
- Animals, Central Nervous System Stimulants administration & dosage, Central Nervous System Stimulants urine, Chromatography, Liquid, Designer Drugs administration & dosage, Designer Drugs analysis, Illicit Drugs urine, Infusions, Parenteral, Male, Methamphetamine administration & dosage, Methamphetamine urine, Mice, Mice, Inbred ICR, Substance Abuse Detection, Tandem Mass Spectrometry, Thiophenes administration & dosage, Methamphetamine analogs & derivatives, Thiophenes urine
- Abstract
We have considered the urinary excretion profile of methiopropamine (MPA), a thiophene ring-based structural analog of methamphetamine with similar stimulant effects, with the aim of selecting the most appropriate marker(s) of intake that may be useful in forensic analysis. For this purpose, in vitro studies were preliminarily performed on human liver microsomes for tracing the phase I metabolic pathways of MPA, preselecting the best candidates as potential target analytes, and designing the optimal experimental strategy. In vivo studies were then conducted on mice, after the intraperitoneal administration of a 10-mg/kg dose. Urine samples were collected every 3 h in the first 9 h and, subsequently, from 24 to 36 h, and stored at -80°C until further analysis. The measurements were performed using a targeted procedure based on liquid/liquid extraction followed by liquid chromatography-tandem mass spectrometry analysis. Our results show that in the time interval 0-9 h after administration, MPA was extensively oxidized mainly to nor-MPA, oxo-MPA, and two hydroxylated metabolites (ie, hydroxy-aryl-methiopropamine and hydroxy-alkyl-methiopropamine). All phase I metabolites underwent phase II metabolism, with the formation of nor-hydroxy-methiopropamine only in phase II, confirmed by the results obtained after enzymatic hydrolysis with β-glucuronidase and arylsulfatase. In the time interval 24-36 h after administration, only unchanged MPA and nor-MPA were detected, suggesting that these two markers are those endowed with the highest diagnostic value. The method was validated for these two principal markers, proving to be fit for anti-doping, toxicological, and forensic analyses., (© 2020 John Wiley & Sons, Ltd.)
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- 2021
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141. Prescription Drug Misuse in "Clubbers" and Disco Goers in Ibiza.
- Author
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di Giannantonio M, Negri A, Schiavone S, Vannini C, Pettorruso M, De-Giorgio F, Verrastro V, Trabace L, Corbo M, Gottardo R, Camuto C, Mazzarino M, Barra A, De Berardis D, Lopez JI, Del Villar CM, Schifano F, and Martinotti G
- Abstract
Background: Prescription drug misuse and its related risks are considered a worldwide public health issue. Current trends show that the extent of such phenomenon may not be limited to subjects with psychiatric disorders, as it also spreads to dance party and nightclub attendees, who often consume prescription drugs in combination with alcohol and psychoactive substances. This study aims to report the sociodemographic data and the psychiatric and clinical features of a sample of clubbers reporting prescription drugs use. Methods: Patients admitted to the psychiatry ward of the Can Misses Hospital in Ibiza were recruited for the study during a span of four consecutive years (2015-2018). The inclusion criteria were age 18-75 years old and the intake of psychoactive substances or more than five alcohol units during the previous 24 h. Substance use habits, psychopathological features, and use of unprescribed pharmaceuticals were investigated. Urine samples were collected and analyzed using gas chromatography/mass spectrometry. Results: A total of 110 subjects with psychoactive substance intoxication were recruited for the study. Among these, 37 (40%) disclosed the use of prescription drugs without medical supervision. The most common compounds were benzodiazepines (66%), antiepileptic drugs (8%), antidepressants (6%), opioids (6%), antipsychotics (6%), stimulants (6%), and non-steroidal anti-inflammatory drugs (NSAIDs, 2%). Prescription drug misuse was negatively associated with the use of psychodysleptics (two-tailed Fisher's exact test p = 0.018, ρ = -0.262). Conclusions: The use of prescription drugs is also common among clubbers, usually characterized by low propensity to be prescribed benzodiazepines, antipsychotics, or antidepressants. Prescription drugs may be an alternative to classic and novel psychoactive compounds or may be used to tamper and self-medicate the effects determined by the use of substances. Party goers should be adequately informed about possible risks of co-intake of psychoactive substances and prescription drugs to prevent serious medical and psychiatric consequences., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 di Giannantonio, Negri, Schiavone, Vannini, Pettorruso, De-Giorgio, Verrastro, Trabace, Corbo, Gottardo, Camuto, Mazzarino, Barra, De Berardis, Lopez, Del Villar, Schifano and Martinotti.)
- Published
- 2020
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142. Regarding "Rapid development of an iatrogenic aortic dissection following transcatheter aortic valve implantation".
- Author
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De-Giorgio F, Vetrugno G, and D'Onofrio A
- Subjects
- Aortic Valve surgery, Fluoroscopy, Humans, Iatrogenic Disease, Aortic Dissection etiology, Transcatheter Aortic Valve Replacement adverse effects
- Published
- 2020
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143. Psychopathological Burden and Quality of Life in Substance Users During the COVID-19 Lockdown Period in Italy.
- Author
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Martinotti G, Alessi MC, Di Natale C, Sociali A, Ceci F, Lucidi L, Picutti E, Di Carlo F, Corbo M, Vellante F, Fiori F, Tourjansky G, Catalano G, Carenti ML, Incerti CC, Bartoletti L, Barlati S, Romeo VM, Verrastro V, De Giorgio F, Valchera A, Sepede G, Casella P, Pettorruso M, and di Giannantonio M
- Abstract
Background: Following the development of the COVID-19 pandemic, a rigid public health strategy of reduced social contact and shelter-in-place has been adopted by the Italian Government to reduce the spread of the virus. In this paper, we aim at evaluating the impact that the COVID-19 pandemic, and the relative containment measures, have had on a real-life sample of patients suffering from substance use disorders (SUDs) and/or behavioral addictions., Methods: An anonymous questionnaire was filled out by 153 addicted patients, both outpatients and residential inpatients, recruited across Italy and highly representative of the current Italian population suffering from addictions. Psychopathological burden (anxiety and depressive symptomatology, somatization, irritability, and post-traumatic symptoms), quality of life, and craving changes in daily habits were assessed., Results: In our sample, we found moderate rates of depression (22.9%), anxiety (30.1%), irritability (31.6%), and post-traumatic stress (5.4%) symptoms. Psychopathological burden was globally higher among residential patients. Reported levels of craving were generally low., Discussion: This study is the first attempt to collect Italian data regarding the effects of the rigid quarantine period, during the COVID-19 pandemic, on patients suffering from a SUD and/or behavioral addictions. The presence of a moderate psychopathological burden correlated to poor quality of life and low craving scores represented the main outcomes. Long-term studies, with follow-up after the end of the restrictive measures, should be considered to implement our findings., (Copyright © 2020 Martinotti, Alessi, Di Natale, Sociali, Ceci, Lucidi, Picutti, Di Carlo, Corbo, Vellante, Fiori, Tourjansky, Catalano, Carenti, Incerti, Bartoletti, Barlati, Romeo, Verrastro, De Giorgio, Valchera, Sepede, Casella, Pettorruso and di Giannantonio.)
- Published
- 2020
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144. Repeatability and reproducibility of post-mortem central corneal thickness measurements using a portable optical coherence tomography system in humans: a prospective multicenter study.
- Author
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Napoli PE, Nioi M, Gabiati L, Laurenzo M, De-Giorgio F, Scorcia V, Grassi S, d'Aloja E, and Fossarello M
- Subjects
- Aged, Cadaver, Cornea physiology, Female, Humans, Male, Middle Aged, Observer Variation, Prospective Studies, Reproducibility of Results, Tomography, Optical Coherence methods, Cornea diagnostic imaging, Corneal Pachymetry methods, Tomography, Optical Coherence instrumentation
- Abstract
To assess the repeatability and reproducibility of post-mortem central corneal thickness (CCT) measurements made by the portable iVue spectra-domain (SD) optical coherence tomography OCT (Optovue Inc, Fremont, CA) system in humans, and to prospectively establish the time-course of CCT after death. In a prospective multicenter setting, CCT measurements were obtained from 58 human eyes at the following 16 time-points after death: immediately (within 2 h), and at each hour by the next 17 h. The range of CCT values for each subject was determined and longitudinal data were used to illustrate the variation in open and close eye mode. All measurements were made by two independent and well-trained examiners for session. Main outcome measures were intraclass correlation coefficients (ICC), repeatability and reproducibility coefficients, and coefficients of variation of the average central (0-2 mm). Overall, a total of 5,568 OCT measurements were performed by examiners. The repeatability coefficient varied from 0.3 to 1.7% and the reproducibility coefficient varied from 0.3 to 1.6% throughout the entire experimental time frame. Furthermore, the values of the different ICCs were also high during the different postmortem intervals, thus demonstrating the excellent repeatability and reproducibility of the present OCT approach. When CCT measurements were analyzed longitudinally, corneal thickness showed different behavior based on the open or close eye mode. The present study demonstrates that portable OCT imaging can be reliably used for corneal pachymetric measurements in supine subjects and during the post mortem period, i.e. without visual fixation and normal physiology/architecture of examined tissues.
- Published
- 2020
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145. An evaluation of the objectivity and reproducibility of shear wave elastography in estimating the post-mortem interval: a tissue biomechanical perspective.
- Author
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De-Giorgio F, Ciasca G, D'Amico R, Trombatore P, D'Angelo A, Rinaldi P, Milano F, Locci E, De Spirito M, d'Aloja E, Colosimo C, and Pascali VL
- Subjects
- Aged, Aged, 80 and over, Biomechanical Phenomena, Female, Humans, Male, Middle Aged, Pilot Projects, Reproducibility of Results, Elasticity Imaging Techniques methods, Forensic Anthropology methods, Rigor Mortis
- Abstract
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.
- Published
- 2020
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146. Methiopropamine and its acute behavioral effects in mice: is there a gray zone in new psychoactive substances users?
- Author
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De-Giorgio F, Bilel S, Tirri M, Arfè R, Trapella C, Camuto C, Foti F, Frisoni P, Neri M, Botrè F, and Marti M
- Subjects
- Animals, Dose-Response Relationship, Drug, Male, Methamphetamine pharmacology, Mice, Mice, Inbred ICR, Models, Animal, Psychotropic Drugs pharmacology, Methamphetamine analogs & derivatives, Thiophenes pharmacology
- Abstract
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.
- Published
- 2020
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147. Reliable Postmortem Computed Tomography Scan Diagnosis of COVID-19 Pneumonia.
- Author
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Cittadini F, De-Giorgio F, Cina A, and Pascali VL
- Subjects
- COVID-19, Containment of Biohazards, Humans, SARS-CoV-2, Tomography, Betacoronavirus, Coronavirus Infections, Pandemics, Pneumonia, Viral
- Published
- 2020
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148. Club Drugs: Psychotropic Effects and Psychopathological Characteristics of a Sample of Inpatients.
- Author
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Martinotti G, Negri A, Schiavone S, Montemitro C, Vannini C, Baroni G, Pettorruso M, De Giorgio F, Giorgetti R, Verrastro V, Trabace L, Garcia A, Castro I, Iglesias Lopez J, Merino Del Villar C, Schifano F, and di Giannantonio M
- Abstract
Background: Growing evidence supports the possibility of significant psychiatric consequences related to novel and traditional psychoactive substance consumption. The problem of differential diagnosis has hampered research on specific psychopathologies with unclear outcomes. The aim of our study was to report psychiatric and clinical features of subjects admitted to a psychiatric ward in Ibiza, Spain, with a clinical diagnosis of substance abuse or intoxication., Methods: A survey was administered to a sample of inpatients hospitalized due to psychiatric symptoms related to recent use of psychoactive substances. The questionnaire investigated sociodemographic factors, familiar and personal anamnesis, substance use habits, general and psychopathological features. Urine samples were collected and analyzed in a toxicology laboratory using gas chromatography and mass spectrometry., Results: A total of 110 patients were included in the study. Most patients (70%) declared multiple substance use, and 33% of patients reported more than two substances; nevertheless, it was possible to identify 17 (15%) depressor users, 44 (40%) stimulant users and 49 (45%) psychodysleptics users. A positive association with a lifetime diagnosis of bipolar disorder was found (two-tailed Fisher's exact test: p = 0.013). Psychomotor agitation, reference, and paranoid delusions, affective symptoms, consciousness disorders, and aggressiveness represented some of the most frequent symptoms at entry evaluation., Conclusions: In this study, we described the acute psychiatric presentations related to recreational drug use in subjects on holiday in Ibiza. The use of psychoactive substances was characterized by poly-use of both traditional and novel substances, with several psychopathological consequences. Future research should focus on a better understanding of the psychopathological effects of specific substances, defining signs and symptoms to help make a differential diagnosis and prospectively examine long-term effects., (Copyright © 2020 Martinotti, Negri, Schiavone, Montemitro, Vannini, Baroni, Pettorruso, De Giorgio, Giorgetti, Verrastro, Trabace, Garcia, Castro, Iglesias Lopez, Merino Del Villar, Schifano and di Giannantonio.)
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- 2020
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149. Consent for elective surgery: audiovisual devices could be used.
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Foti F, Vetrugno G, De-Giorgio F, and Cicconi M
- Abstract
Competing Interests: Competing interests: None declared.
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- 2020
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150. Hopelessness, Dissociative Symptoms, and Suicide Risk in Major Depressive Disorder: Clinical and Biological Correlates.
- Author
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Pettorruso M, d'Andrea G, Martinotti G, Cocciolillo F, Miuli A, Di Muzio I, Collevecchio R, Verrastro V, De-Giorgio F, Janiri L, di Giannantonio M, Di Giuda D, and Camardese G
- Abstract
Background: Major depressive disorder (MDD) has different clinical presentations and is associated with neurobiological alterations. Hopelessness, anhedonia, and dissociation represent some of the most pervasive psychopathological symptoms that often lead to suicidal thoughts, attempts, and actions. To further research on the concept of depression endophenotypes, this study aimed to assess the possible relationships between hopelessness and other clinical and biological correlates (i.e., striatal dopaminergic dysfunction) in depressed patients. Methods: We recruited 51 subjects with MDD. All subjects underwent
123 I-FP-CIT SPECT to assess striatal dopamine transporter (DAT) availability and a psychometric evaluation using the psychometric scale to assess depressive, anxious, dissociative, and hopelessness symptoms aside from suicidal ideation. Result: An inverse correlation between the hopelessness score and dopamine transporter availability in all basal ganglia was bilaterally found. (Right Putamen, r = -0.445, p < 0.01; Left Putamen, r = -0.454, p < 0.01; Right Caudate, r = -0.398, p < 0.01; Left Caudate, r = -0.467, p < 0.01) Moreover, a positive correlation was also found between hopelessness and dissociative symptoms. Conclusions: These results provide important evidence on the neurobiological and clinical correlates of different psychopathological symptoms of depression with potential implications in terms of devising more effective treatment programs.- Published
- 2020
- Full Text
- View/download PDF
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