In vitro, in vivo metabolism and quantification of the novel synthetic opioid N-piperidinyl etonitazene (etonitazepipne).

OBJECTIVES: N-piperidinyl etonitazene (etonitazepipne) is a newly synthesized opioid related to the 2-benzylbenzimidazole analog class. Etonitazepipne has been formally notified and placed under intensive monitoring in Europe in January 2022. Nitazenes have high affinity at µ-opioid receptor (MOR). Etonitazepipne, specifically shows a EC50 of 2.49 nM, suggesting about 50 times higher potency combined with higher efficacy compared to morphine. Antinociceptive potency l ('hot plate test' with rats) was 192-fold greater than that of morphine. METHODS: Here we report on a post-mortem case involving etonitazepipne and its quantification using a standard addition method (SAM) through liquid chromatography tandem mass spectrometry (LC-MS/MS). In addition, characterization and identification of phase I human metabolites using in vitro assay based on pooled human liver microsomes (pHLM) was performed along with the analysis of authentic urine samples by means of high-performance liquid chromatography high-resolution tandem mass spectrometry (LC-HRMS/MS). RESULTS: The concentration of etonitazepipne in post-mortem blood and urine was 8.3 and 11 ng/mL, respectively. SAM was validated by assessing the following parameters: intraday and interday repeatability, matrix effect and recovery rate in post-mortem blood. A total of 20 and 14 metabolites were identified after pHLM incubation and urine analysis, respectively. Most pronounced in vitro and in vivo transformations were O-deethylation, hydroxylation, ketone reduction, and combinations thereof. CONCLUSIONS: Considering small traces of the parent drug often found in real cases, the identification of metabolic biomarkers is crucial to identify exposure to this drug. O-deethylated, oxidated metabolites, and combination thereof are proposed as urinary biomarkers along with the parent compound.

Human metabolism of four synthetic benzimidazole opioids: isotonitazene, metonitazene, etodesnitazene, and metodesnitazene.

Following isotonitazene scheduling in 2019, the availability of alternative 2-benzylbenzimidazole opioids (nitazenes) on the global drug market increased, resulting in many fatalities worldwide. Nitazenes are potent µ-opioid receptor agonists with strong narcotic/analgesic effects, and their concentrations in biological matrices are low, making the detection of metabolite biomarkers of consumption crucial to document use in clinical and forensic settings. However, there is little to no data on the metabolism of the most recently available nitazenes, especially desnitro-analogues. The aim of the research was to assess isotonitazene, metonitazene, etodesnitazene, and metodesnitazene human metabolism and identify specific metabolite biomarkers of consumption. The four analogues were incubated with 10-donor-pooled human hepatocytes, and the incubates were analyzed by liquid chromatography-high-resolution tandem mass spectrometry and data mining with Compound Discoverer (Thermo Scientific); the analysis was supported by in silico metabolite predictions with GLORYx open-access software. Metabolites were identified in postmortem blood and/or urine samples from two metonitazene-positive and three etodesnitazene-positive cases following the same workflow, with and without glucuronide hydrolysis in urine, to confirm in vitro results. Twelve, nine, twenty-two, and ten metabolites were identified for isotonitazene, metonitazene, etodesnitazene, and metodesnitazene, respectively. The main transformations were N-deethylation at the N,N-diethylethanamine side chain, O-dealkylation, and further O-glucuronidation. In vitro and autopsy results were consistent, demonstrating the efficacy of the 10-donor-pooled human hepatocyte model to predict human metabolism. We suggest the parent and the corresponding O-dealkyl- and N-deethyl-O-dealkyl metabolites as biomarkers of exposure in urine after glucuronide hydrolysis, and the corresponding N-deethyl metabolite as additional biomarker in blood.

New Perspectives in Third Molar Auto-Transplantation: Literature Review and a Case Report of Clinical, Financial and Forensic Implications.

Third molar extraction is the most common procedure in oral and maxillofacial surgery. Third molars are considered less functional than other teeth and are often extracted. Sometimes, they are also used for auto-transplantation for the benefit of oral rehabilitation. Since many biological factors are involved in this surgical approach, herein, we outline a review of the biological characteristics of medico-legal/forensic interest, in addition to presenting a successful clinical case. A scoping review of currently available research data (following the principles of PRISMA-ScR or the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) on third molar auto-transplantation was conducted by drawing upon the main databases (Scopus, PubMed, Google Scholar and LILACS) to evaluate biological and clinical characteristics possibly relatable to forensic issues. All the collected data were summarized and elaborated on for the purpose of this article. A patient underwent extraction of the right upper first molar and auto-transplantation of the unerupted ipsilateral third molar. Many biologic and clinical factors are involved in the success of this clinical procedure. Knowledge of third molar anatomy, of its development and viable surgical approaches are all essential elements; just as important are the treatment of the tooth before and after transplantation and the integrity of the periodontal ligament. Follow-up of the clinical case for 5 years made it possible to verify the stability of the procedure over time. Third molar auto-transplantation is feasible and cost-effective. However, the use of third molars as donor teeth in auto-transplantation may have medico-legal implications. The lack of official protocols and consistent evidence-based guidelines for operators still prevent such a procedure from becoming mainstream; therefore, it is viewed with suspicion by clinicians and patients, even though the biological factors herein detected point to a reasonably high degree of safety. The understanding of many specific biological and clinical factors involved in the stability of third molar auto-transplantation allows for a thorough understanding of the forensic implications relevant to clinical practice. Effective communication and information provision are therefore of utmost importance, in the interest of both patients and doctors.

Circulating miRNAs as a Tool for Early Diagnosis of Endometrial Cancer-Implications for the Fertility-Sparing Process: Clinical, Biological, and Legal Aspects.

This review article explores the possibility of developing an integrated approach to the management of the different needs of endometrial cancer (EC) patients seeking to become pregnant. Life preservation of the woman, health preservation of the baby, a precocious and-as much as possible-minimally invasive characterization of the health and fertility parameters of the patient, together with the concerns regarding the obstetric, neonatal, and adult health risks of the children conceived via assisted reproductive techniques (ART) are all essential aspects of the problem to be taken into consideration, yet the possibility to harmonize such needs through a concerted and integrated approach is still very challenging. This review aims to illustrate the main features of EC and how it affects the normal physiology of pre-menopausal women. We also focus on the prospect of a miR-based, molecular evaluation of patient health status, including both EC early diagnosis and staging and, similarly, the receptivity of the woman, discussing the possible evaluation of both aspects using a single specific panel of circulating miRs in the patient, thus allowing a relatively fast, non-invasive testing with a significantly reduced margin of error. Finally, the ethical and legal/regulatory aspects of such innovative techniques require not only a risk-benefit analysis; respect for patient autonomy and equitable health care access allocation are fundamental issues as well.

Sweat Testing for the Detection of Methylone after Controlled Administrations in Humans.

The aim of this study was to determine the excretion of methylone and its metabolites in sweat following the ingestion of increasing controlled doses of 50, 100, 150 and 200 mg of methylone to twelve healthy volunteers involved in a clinical trial. Methylone and its metabolites 4-hydroxy-3-methoxy-N-methylcathinone (HMMC) and 3,4-methylenedioxycathinone (MDC) were analyzed in sweat patches by liquid chromatography-tandem mass spectrometry. Methylone and MDC were detected in sweat at 2 h and reached their highest accumulation (Cmax) at 24 h after the administration of 50, 100, 150 and 200 mg doses. In contrast, HMMC was not detectable at any time interval after each dose. Sweat proved to be a suitable matrix for methylone and its metabolites' determination in clinical and toxicological studies, providing a concentration that reveals recent drug consumption.

Type I Dentin Dysplasia: The Literature Review and Case Report of a Family Affected by Misrecognition and Late Diagnosis.

Background and Objectives: Type I dentin dysplasia (DD-I) is a rare genetic disorder with autosomal dominant or recessive inheritance at risk of late or long-misunderstood diagnosis because the teeth, compared to other degenerative dentin diseases, do not have coronal defects and/or alterations but only at the root level (absent, conical, pointed roots, and obliterated pulp canals). The first radiographic suspicion often occurs only in case of sudden mobility and/or abscesses of the permanent teeth. Genetic tests confirm the diagnosis. Case Presentation: This case report describes the oral and radiographic characteristics of two siblings, 12 and 10 years old, a male and a female, at an early age affected by DD-I, whose diagnosis was made for a first orthodontic visit. The father and the older child had already undergone dental and orthodontic treatments, respectively, without the disease being suspected by the dentist. Results: Genetic tests support the diagnosis of DD-I. Following the diagnosis, the patients began a process of close periodic checks every 3-4 months to monitor their situation. The male child lost upper lateral incisors, which were then replaced with a light nylon removable prosthesis. Conclusions: The ability to recognize the radiographic features characteristic of DD-I is very important to avoid prejudicial diagnostic delays and to be able to plan the long-term treatment of these patients better, especially when the pathology was primarily misrecognized in the family.

Using ncRNAs as Tools in Cancer Diagnosis and Treatment-The Way towards Personalized Medicine to Improve Patients' Health.

Although the first discovery of a non-coding RNA (ncRNA) dates back to 1958, only in recent years has the complexity of the transcriptome started to be elucidated. However, its components are still under investigation and their identification is one of the challenges that scientists are presently facing. In addition, their function is still far from being fully understood. The non-coding portion of the genome is indeed the largest, both quantitatively and qualitatively. A large fraction of these ncRNAs have a regulatory role either in coding mRNAs or in other ncRNAs, creating an intracellular network of crossed interactions (competing endogenous RNA networks, or ceRNET) that fine-tune the gene expression in both health and disease. The alteration of the equilibrium among such interactions can be enough to cause a transition from health to disease, but the opposite is equally true, leading to the possibility of intervening based on these mechanisms to cure human conditions. In this review, we summarize the present knowledge on these mechanisms, illustrating how they can be used for disease treatment, the current challenges and pitfalls, and the roles of environmental and lifestyle-related contributing factors, in addition to the ethical, legal, and social issues arising from their (improper) use.

Fertility preservation in female cancer sufferers: (only) a moral obligation?

PURPOSE: Advances in cancer diagnostics and therapeutics have thankfully led to high numbers of young cancer survivors, although some interventions may sometimes threaten fertility. The authors aimed to assess how evidence-based oncofertility counselling can be adequately fulfilled for the sake of female cancer patients, in light of its complexities and multidisciplinary nature, which require thorough counselling and consent pathways. MATERIALS AND METHODS: A search has been conducted in the databases PubMed/MEDLINE, Web of Science, Scopus, EMBASE and Google Scholar via search strings such as fertility preservation, reproductive counselling, oncofertility, cancer survivors, in order to identify relevant meaningful sources spanning the 2010-2021 period. RESULTS: Counselling needs to be implemented in compliance with international guidelines, so as to avoid medicolegal repercussions. Albeit fertility preservation is supported by most health care institutions, actual conditions at health care facilities often reflect several lingering difficulties in the oncofertility process. Oncofertility counselling should foster access to fertility preservation procedures. To best serve that purpose, it should be implemented in a manner consistent with ethical and legal standards, so that patients can make an informed decision based on comprehensive and relevant data. CONCLUSIONS: Counselling needs to be rooted in a close cooperation of oncologists, reproductive endocrinologists, mental health counsellors and clinical researchers. The provision of oncofertility services is grounded in the moral obligation to uphold individual autonomy, which is essential in a free society, unless the exercise thereof could pose a risk to the children conceived or to others.

The March 2021 Italian constitutional court ruling on surrogacy: a prelude to common European legislation for the sake of reproductive health?

PURPOSE: Surrogacy is an arrangement by which a surrogate mother bears a child for another couple or person, and is often thought of as a form of 'treatment' for couples (or even individuals) with fertility or sterility issues. Still, surrogacy entails ethical issues related to gender, fundamental human rights, exploitation and inequality. MATERIALS AND METHODS: Starting from the Italian state of affairs, the authors have set out to briefly expound upon such complexities, taking into account relevant jurisprudence on the subject, with a particular focus on inter-country surrogacy and second-parent adoption, which can themselves engender significant legal dilemmas. When residents of countries where surrogacy is banned travel abroad and hire a surrogate, that may lead to considerable legal hurdles as well. RESULTS: In Italy and elsewhere, the courts have all too often had to fill the vacuum left by the lack of targeted legislation. The Italian Constitutional Court has recently urged lawmakers to enact new legislation to uphold the minor's best interests. In fact, while some countries recognise the surrogate as the legal parent, others ascribe parenthood to the commissioning parents. That discrepancy can lead to a 'clash of laws', resulting in children ending up stateless and unable to maintain an already established family relationship. CONCLUSIONS: Just like fundamental protection of human rights and public health, the regulation of revolutionary technologies that change the very notion of reproduction, parenthood, and human identity needs to be governed by uniform standards, shared at least by nations which espouse common core values.

Neonatal Outcomes and Long-Term Follow-Up of Children Born from Frozen Embryo, a Narrative Review of Latest Research Findings.

In recent years, the growing use of ART (assisted reproductive techniques) has led to a progressive improvement of protocols; embryo freezing is certainly one of the most important innovations. This technique is selectively offered as a tailored approach to reduce the incidence of multiple pregnancies and, most importantly, to lower the risk of developing ovarian hyperstimulation syndrome when used in conjunction with an ovulation-triggering GnRH antagonist. The increase in transfer cycles with frozen embryos made it possible to study the effects of the technique in children thus conceived. Particularly noteworthy is the increase in macrosomal and LGA (large for gestational age) newborns, in addition to a decrease in SGA (small for gestational age) and LBW (low birth weight) newborns. The authors aimed to outline a broad-ranging narrative review by summarizing and elaborating on the most important evidence regarding the neonatal outcome of children born from frozen embryos and provide information on the medium and long-term follow- up of these children. However, given the relatively recent large-scale implementation of such techniques, further studies are needed to provide more conclusive evidence on outcomes and implications.

Non-Coding RNAs as Prognostic Markers for Endometrial Cancer.

Endometrial cancer (EC) has been classified over the years, for prognostic and therapeutic purposes. In recent years, classification systems have been emerging not only based on EC clinical and pathological characteristics but also on its genetic and epigenetic features. Noncoding RNAs (ncRNAs) are emerging as promising markers in several cancer types, including EC, for which their prognostic value is currently under investigation and will likely integrate the present prognostic tools based on protein coding genes. This review aims to underline the importance of the genetic and epigenetic events in the EC tumorigenesis, by expounding upon the prognostic role of ncRNAs.

Fertility Sparing Treatments in Endometrial Cancer Patients: The Potential Role of the New Molecular Classification.

Endometrial cancer is the most frequent gynecological malignancy, and, although epidemiologically it mainly affects advanced age women, it can also affect young patients who want children and who have not yet completed their procreative project. Fertility sparing treatments are the subject of many studies and research in continuous evolution, and represent a light of hope for young cancer patients who find themselves having to face an oncological path before fulfilling their desire for motherhood. The advances in molecular biology and the more precise clinical and prognostic classification of endometrial cancer based on the 2013 The Cancer Genome Atlas classification allow for the selection of patients who can be submitted to fertility sparing treatments with increasing oncological safety. It would also be possible to predict the response to hormonal treatment by investigating the state of the genes of the mismatch repair.

The highly complex issue of conscientious objection to abortion: can the recent European Court of Human Rights ruling Grimmark v. Sweden redefine the notions of care before freedom of conscience?

PURPOSE: The article aims to elaborate on two recent European Court of Human Rights (ECtHR) decisions which have rejected, on grounds of non-admissibility, the appeals by two Swedish midwives who refused to carry out abortion-related services, basing their refusal on conscientious objection, and to expound upon the legal and ethical underpinnings and core standards applied to the framing process of such a ECtHR decision. MATERIALS AND METHODS: By drawing upon relevant recommendations from international institutions, the authors have aimed to assess how the ECtHR rationale could affect the balance between CO and patient rights; searches have been conducted up until December 2020. RESULTS: In both decisions the European Court has asserted that the right to exercise conscientious objection must give way to the protection of the right to health of women seeking to have an abortion. CONCLUSIONS: ECtHR judges concluded that the failure to provide for a right to conscientious objection does not constitute, in fact, a violation of the more general right to freedom of thought, conscience and religion, if provided for by a state law to protect the right to health. The legal ethical and social ramifications of such a decision are of enormous magnitude.

Surrogacy and "Procreative Tourism". What Does the Future Hold from the Ethical and Legal Perspectives?

Background and objectives: To explore the ethical and legal complexities arising from the controversial issue of surrogacy, particularly in terms of how they affect fundamental rights of children and parents. Surrogacy is a form of medically-assisted procreation (MAP) in which a woman "lends" her uterus to carry out a pregnancy on behalf of a third party. There are pathological conditions, such as uterine agenesis or hysterectomy outcomes, that may prevent prospective mothers from becoming pregnant or carry a pregnancy to term; such patients may consider finding a surrogate mother. Many issues relating to surrogacy remain unresolved, with significant disagreements and controversy within the scientific community and public opinion. There are several factors called into play and multiple parties and stakeholders whose objectives and interests need to somehow be reconciled. First and foremost, the authors contend, it is essential to prioritize and uphold the rights of children born through surrogacy and heterologous MAP. Materials and methods: To draw a parallel between Italy and the rest of the world, the legislation in force in twelve European countries was analyzed, eleven of which are part of the European Union (France, Germany, Italy, Spain, Greece, Netherlands, Belgium, Denmark, Lithuania, Czech Republic and Portugal) and three non-members of the same (United Kingdom, Ukraine and Russia), as well as that of twelve non-European countries considered exemplary (United States, Canada, Australia, India, China, Thailand, Israel, Nigeria and South Africa); in particular, legislative sources and legal databases were drawn upon, in order to draw a comparison with the Italian legislation currently in force and map out the evolution of the Italian case law on the basis of the judgments issued by Italian courts, including the Constitutional and Supreme Courts and the European Court of Human Rights (ECHR); search engines such as PubMed and Google Scholar were also used, by entering the keywords "surrogacy" and "surrogate motherhood", to find scientific articles concerning assisted reproduction techniques with a close focus on surrogacy. Results: SM is a prohibited and sanctioned practice in Italy; on the other hand, it is allowed in other countries of the world, which leads Italian couples, or couples from other countries where it is banned, to often contact foreign centers in order to undertake a MAP pathway which includes surrogacy; in addition, challenges may arise from the legal status of children born through surrogacy abroad: to date, in most countries, there is no specific legislation aimed at regulating their legal registration and parental status. Conclusion: With reference to the Italian context, despite the scientific and legal evolution on the subject, a legislative intervention aimed at filling the regulatory gaps in terms of heterologous MAP and surrogacy has not yet come to fruition. Considering the possibility of "fertility tourism", i.e., traveling to countries where the practice is legal, as indeed already happens in a relatively significant number of cases, the current legislation, although integrated by the legal interpretation, does not appear to be effective in avoiding the phenomenon of procreative tourism. Moreover, to overcome some contradictions currently present between law 40 and law 194, it would be appropriate to outline an organic and exhaustive framework of rules, which should take into account the multiplicity of interests at stake, in keeping with a fair and sustainable balance when regulating such practices.

Does the EU COVID Digital Certificate Strike a Reasonable Balance between Mobility Needs and Public Health?

The need to fight a highly aggressive virus such as SARS-CoV-2 has compelled governments to put in place measures, which, in the name of health protection, have constrained many freedoms we all enjoy, including freedom of movement, both nationally and within the European Union. In order to encourage and facilitate the return to free movement, the European Parliament has launched a "COVID-19 digital certificate". A spirited debate centered around the use of this certificate is still ongoing among scholars, many of whom have pointed out the uncertainties relative to COVID-19 immunity, privacy issues and the risk of discriminatory effects. The authors, while highlighting some critical aspects, argue that the COVID digital certificate in its current approved version can effectively help prevent the spread of the infection and promote free movement, while upholding the right to health as much as possible. However, they also stress the need for a thorough information campaign to illustrate the advantages and limitations of this document in order to avoid creating a false sense of security in the public opinion, who may wrongly assume that the emergency has been overcome for good.

Monitoring Perinatal Exposure to Cannabis and Synthetic Cannabinoids.

PURPOSE: Drug use during pregnancy is a critical global challenge, capable of severe impacts on neonatal development. However, the consumption of cannabis and synthetic cannabinoids is on the rise in pregnant women. Obstetric complications with increased risks of miscarriage, fetal growth restriction, and brain development impairment have been associated with perinatal cannabis exposure, but data on synthetic cannabinoid use during pregnancy are limited. METHODS: We reviewed studies that investigated the risks associated with cannabis and synthetic cannabinoid use and those that reported the concentrations of cannabinoids and synthetic cannabinoids in maternal (breast milk) and neonatal (placenta, umbilical cord, meconium, and hair) matrices during human pregnancy. A MEDLINE and EMBASE literature search to identify all relevant articles published in English from January 1998 to April 2019 was performed. RESULTS: Cannabis use during pregnancy is associated with increased risks of adverse obstetrical outcomes, although neurobehavioral effects are still unclear. Analyses of cannabinoids in meconium are well documented, but further research on other unconventional matrices is needed. Adverse effects due to perinatal synthetic cannabinoid exposure are still unknown, and analytical data are scarce. CONCLUSIONS: Awareness of the hazards of drug use during pregnancy should be improved to encourage health care providers to urge pregnant women to abstain from cannabis and, if cannabis-dependent, seek treatment. Moreover, substances used throughout pregnancy should be monitored as a deterrent to cannabis use, and potential cannabis-dependent women should be identified, so as to limit cannabis-fetal exposure during gestation, and provided appropriate treatment.

Δ9-Tetrahydrocannabinol and Cannabidiol Time Courses in the Sera of "Light Cannabis" Smokers: Discriminating Light Cannabis Use from Illegal and Medical Cannabis Use.

BACKGROUND: Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) time courses in serum and physiological and behavioral effects associated with smoking 1 or 4 "light cannabis" cigarettes were studied. Biomarkers to differentiate light cannabis versus illegal and medical cannabis use were also investigated. METHODS: Sera were obtained at different times from 6 healthy light cannabis consumers and 6 individuals who smoked 1 and 4 cigarettes, within 4 hours through a liquid-liquid method and analyzed by liquid chromatography-tandem mass spectrometry. RESULTS: In serum, minimal THC concentration was observed after a single cigarette smoke, while repeated smoking increased it by 1 order of magnitude. CBD concentrations were higher, but did not increase linearly, probably because it does not preferentially volatilize compared with THC. The highest THC and CBD concentrations were observed 0.5 hours after the start of the smoking of 1 cigarette. Serum THC ranged from 2.7 to 5.9 ng/mL, while serum CBD varied from 5.7 to 48.2 ng/mL. Similarly, the highest THC and CBD concentrations were observed 0.5 hours after the smoking of 4 cigarettes. Specifically, the ranges were THC: 11.0-21.8 ng/mL and CBD: 19.4-35.3 ng/mL. In both cases, the mean THC/CBD concentration ratio ranged from 0.2 to 0.9. There were no significant changes in blood pressure, heart rate, and body temperature, but participants who smoked 4 cigarettes experienced severe drowsiness. CONCLUSIONS: THC and CBD time courses in the sera of light cannabis smokers were similar to those previously observed in oral fluid and blood. Serum THC/CBD concentration ratio not higher than the mean value of 0.9 might be a useful biomarker to identify use of light cannabis versus that of illegal THC cannabis (where THC/CBD concentration ratios are generally greater than 10) or versus that of medical cannabis (where ratios are greater than 1). Consumers should be advised of possible drowsiness after he repeated smoking of light cannabis cigarettes.

Development and validation of fast UHPLC-MS/MS screening method for 87 NPS and 32 other drugs of abuse in hair and nails: application to real cases.

Interest on keratinized matrix analysis for clinical and forensic purposes has been recently grown due to the wide temporary detection window for psychotropic and toxic substances entrapped after repeated consumption. The aim of this study was the development and full validation of an UHPLC-MS/MS screening method to quantify 119 molecules among most abused classic drugs and new psychoactive substances in hair and in nails, to assess the polyconsumption. Twenty-five milligrams of hair or nail samples, added with the internal standard mixture, were cut and incubated with 500 µL M3® buffer reagent at controlled temperature. After cooling, 1 µL supernatant was injected in the chromatographic system equipped with an Oasis HLB column. After the 10 min chromatographic separation through a gradient mobile phase (aqueous ammonium formate, phase A; acetonitrile, phase B), the target compounds were detected in multiple reaction monitoring mode. The method was linear (r2 always better than 0.99) in a calibration range of LOQ 20000 pg compound for milligram hair and of LOQ 1000 pg compound per milligram nail. Process efficiency of analytes under investigation was always better than 65% and no significant ion suppression due to matrix effect was observed. Intra-assay and inter-assay precision and accuracy were always better than 15%. The applicability and trueness of the method were examined by analysing real samples of hair and nail from users of psychoactive drugs in recreational contexts. Both classic drugs and new psychoactive substances could be determined as result of single or repeated use and accumulation in keratin matrices. Graphical abstract.

The rise of new psychoactive substances and psychiatric implications: A wide-ranging, multifaceted challenge that needs far-reaching common legislative strategies.

The ever-growing number of novel psychoactive substances (NPS) that have been surfacing globally, as well as related changes in drug abuse trends, undoubtedly constitute a difficult and multifaceted challenge for psychiatry. The intake and abuse of such substances has been linked to a risk of psychopathological disturbances, which stem from imbalances of a range of neurotransmitter pathways and receptors. Through an analysis of relevant research articles and reviews (particularly those outlining NPS neurological and cerebral mechanisms of action and psychopathological consequences arising from NPS abuse; research papers more closely focused on chemical/pharmacological aspects have been ruled out), through a systematic analysis of Pubmed, Medline, PsycLIT and EMBASE literature, as well as data released by health care institutions and drug enforcement agencies (among which the World Health Organization, the United Nations Office on Drugs and Crime, the European Monitoring Centre for Drugs and Drug Addiction, Eurojust, the Novel Psychoactive Treatment UK Network, the Court of Justice of the European Union), the authors aimed to elaborate on the most relevant data relative to NPS-related psychiatric effects, focusing on the conceptual and definition-related complexities inherent to NPS, clinical management and motivations for NPS use; moreover, an effort has been made to highlight the possible measures in order to tackle the unremitting rise of such elusive and potentially harmful substances.

Medicolegal Issues in Power Morcellation: Cautionary Rules for Gynecologists to Avoid Unfavorable Outcomes.

Power morcellation in laparoscopic surgery enables specialists to carry out minimally invasive procedures such as hysterectomies and myomectomies by cutting specimens into smaller pieces using a rotating blade and removing pieces through a laparoscope. Unexpected uterine sarcoma treated by surgery involving tumor disruption could be associated with poor prognosis. The current study aims to shed light on power morcellation from a medicolegal perspective: the procedure has resulted in adverse outcomes and litigation, and compensation for plaintiffs, as published in various journals cited in PubMed and MEDLINE, Cochrane Library, EMBASE, and GyneWeb. Considering the claims after the US Food and Drug Administration warnings on morcellation, the current study broadens the scope of research by including search engines, legal databases, and court filings (DeJure, Lexis Nexis, Justia, superior court of New Jersey, and US district court of Minnesota) between 1995 and 2019. Legal records show that courts determine professional responsibility regarding complications, making it essential to document adherence to safety protocols and specific guidelines, when available. Sound medical practices and clearly stated institute best practices result in better patient outcomes and are important when unfavorable clinical outcomes occur; adverse legal decisions can be avoided if there are grounds to prove professional conformity with specific guidelines and the unpredictability of an event.