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To the Editor, The ongoing rise of New Psychoactive Substances (NPS), i.e. psychotropic molecules devised and synthesized to replicate the effects of traditional drugs of abuse in order to circumvent banned substances schedules, has been posing a challenge of enormous magnitude to substance detection systems and law enforcement worldwide. Still, it would be remiss to ignore the role played by the unprecedented public health emergency relating to the COVID-19 pandemic in the exacerbation of the NPS crisis. The diversion of resources has in fact hindered conventional approaches to drug monitoring, surveillance, control, and public health responses. The dangerous path ahead in our struggle against NPS abuse is best exemplified by the rather recent emergence of isotonitazene, an analogue of a benzimidazole class of analgesic compounds, powerful synthetic opioid and full mu-opioid receptor agonist belonging to the 2-benzylbenzimidazole group of compounds, which comprises the structurally different clonitazene, metonitazene and etonitazene (1). Isonitazene has reportedly been detected on European markets in at least five different forms and could even supplant fentanyl derivatives (2). Currently available data on isonitazene-related abuse and fatalities seem to be emblematic of the volatile, elusive nature of NPS: deaths in which isotonitazene was involved in fact presented substantial differences from casualties arising from synthetic opioids abuse. Case reports have highlighted how flualprazolam was detected in most fatalities associated with isotonitazene whereas flualprazolam was involved in only 8% of other synthetic opioid overdose deaths (3). Rather than rising background use, such a finding seems to suggest likely co-use or co-distribution of flualprazolam and isotonitazene. The key element of polysubstance involvement is rife in synthetic opioid overdose deaths. That being said, significantly more substances were implicated in isotonitazene-related deaths than fatalities linked to other synthetic opioid overdose (4, 5). Such dynamics and mortality patterns further stress the urgency of expanding health services for those suffering from opioid addiction disorders. Fine-tuned and standardized detection mechanisms relying on specialized assays based on sensitive instrumentation are essential for the timely and accurate characterization of such novel synthetic opioids (6-8). Isotonitazene in fact cannot be detected by common fentanyl testing strips (9). Hence, the essential nature of clinical and toxicological cannot be overstated, if we are to effectively deal with the public health risks arising from new substances or classes, along with the healthcare and social costs thereof (10). As new substances appear on illicit markets and are detected, their distinctive traits can only be identified by user experience, in the early stages (11-13). Nonetheless, the pandemic scenario has brought about a profound alteration of substance abuse patterns, and opened up new avenues of supply and demand for which our surveillance/detection systems may not be fully prepared or well-suited. As the pandemic appears to recede and hopefully turn into an endemic context based on coexistence with the SARS-CoV-2 and its less harmful variants, it would be a mistake to take for granted that drug abuse/trafficking dynamics will also get back to where they were before the pandemic. Putting in place policies aimed at monitoring web-based platforms and social media can potentially constitute a valuable tool in terms of keeping in check emerging substances, given how during the COVID-19 pandemic many interactions between traffickers and buyers have moved online (14). After all, social media have been playing an increasingly relevant role as interacting platforms, which users and drug dealers can take advantage of in order to discuss drug prices, substance purity, distinctive traits of the "high" (i.e. desired drug effects) they are seeking, ways of taking the substances, dosages, and characteristics of any new NPS becoming available on such back-alley marketing channels (15). Softwares designed and specifically programmed to sift through and analyze all detectable online information in that regard may prove valuable to figure out evolving dynamics of trafficking, purchases and use. Probing social media users has proven effective tool for public health concerns, e.g. drug checking services which have been harnessed due to their harm reduction potential in places estimated to be at risk, with large crowds gathering (concerts, clubs and the like). Nonetheless, research efforts need to be directed towards the new realm of criminality, the "Dark Web", in which all sorts of illegal exchanges and interactions are known to take place. A 2020 study has highlighted the appalling risks for drug users who choose to pursue that option in order to buy drugs (16). Three dealers were selected on a specific "Dark Web" marketplace, and NPS were ordered through such a channel. All these exchanges were thoroughly documented, and an analysis was undertaken of all the substances thus bought, totaling nine samples, by NMR, HRMS, LC-UV, and two also by x-ray diffraction. It was ultimately concluded that four out of five substances bought had been labeled with NPS names that did not match the actual substance, and two out of three samples of substances sold as new (i.e. unscheduled) NPS were instead found to be already documented substances, mislabeled and peddled under false pretenses. Drug dealers were therefore either deceiving their clients or were unaware as to the actual substances which they were selling. In light of such extremely worrisome findings, it is not hard to understand the implications and the major public health risks that such new trends of trafficking and abuse may entail. It is therefore incumbent upon the scientific community and law enforcement agencies to adapt and strive to meet the new challenges brought by the new criminal ecosystems in terms of drug enforcement, first and foremost the impervious environment known as "Dark Web" relying on untraceable cryptocurrencies for illegal transactions.

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Cosmetic surgery entails various ethical issues, even more so in cases involving adolescent patients. Cosmetic surgeons need to take into account how modern societies consider physical appearance an essential component of everyday life, as well as the vulnerability of youths and adolescents. For that reason, it is imperative to thoroughly assess the psychological and emotional states, in addition to the motivations, of minor patients. That goal can be achieved through the use of the DAS-59, (the Derriford Appearance Scale)1 , an effective and dependable tool devised to evaluate the psychological difficulties and distress experienced by people living with problems of appearance. Prior to undergoing cosmetic surgery procedures, adolescents should be required to go through adequate counseling, over multiple sessions and extended to their family members as well, on account of the complex issues inherent in evaluating the risk-benefit ratio and a prospective patient’s decision-making capability. A concerted effort on the part of surgeons, psychiatrists or psychologists is key in determining the real motivations behind a minor's decision to opt for cosmetic surgery in the first place. Possible psychiatric conditions may in fact prevent a minor from making a free, informed decision. From an ethical standpoint, cosmetic surgery procedures should be geared to serve the best interest of the minor patient, who may experience distress over his or her body image, from a health and psychological balance perspective and improve his or her social, affective and working life. Besides, cosmetic surgery should not be overly invasive compared to its potential benefits. Those procedures aimed at achieving "ideal beauty" are not desirable and ought to be banned. By virtue of such criteria, the authors have set out to evaluate the ethical admissibility of some aesthetic treatments. Thus, doctors should not consent to any request coming from their patients, but rather, intervene only in presence of an objective physical flaw or deformity, e.g. protruding ears, which have a potential to negatively affect social life and interactions

La cirugía estética está en constante aumento, especialmente entre los adolescentes, que son sujetos particularmente vulnerables. Es importante establecer la verdadera motivación que impulsa a la persona joven a ponerse en contacto con el cirujano estético. Por lo tanto, el médico, antes de someter al adolescente a una cirugía cosmética, debe evaluar su estado psicológico y emocional. Puede hacerlo utilizando el DAS59, una herramienta válida y confiable para evaluar la angustia psicológica. Si el adolescente muestra un trastorno psiquiátrico, este trastorno debe tratarse primero, esto permite que el paciente tome una decisión informada. Por lo tanto, la colaboración entre un cirujano estético y un psiquiatra o psicólogo es fundamental. El especialista puede evaluar las motivaciones a través de un asesoramiento cuidadoso, que se llevará a cabo en varias sesiones, también con la participación de la familia. Si el médico cree que el adolescente no está lo suficientemente maduro, debe posponer la operación. Vale la pena señalar que el adolescente va al cirujano estético no para tratar una enfermedad, sino para mejorar su apariencia, por esta razón debe recibir una información amplia y adecuada sobre los riesgos, resultados y posibles complicaciones. Desde un punto de vista ético, el Comité Nacional Italiano de Bioética considera legítimas las intervenciones estéticas que responden a un interés objetivo exclusivo de los adolescentes en términos de salud y equilibrio psicológico. Por otro lado, las intervenciones desproporcionadas, que son excesivamente invasivas o innecesariamente arriesgadas y inadecuadas en comparación con los posibles beneficios solicitados por el paciente, son inaceptables. Por lo tanto, el médico no tiene que satisfacer todas las solicitudes, sino que debe intervenir solo cuando existe una imperfección física, como orejas prominentes, que pueden impedir la vida social

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Cosmetic surgery entails various ethical issues, even more so in cases involving adolescent patients. Cosmetic surgeons need to take into account how modern societies consider physical appearance an essential component of everyday life, as well as the vulnerability of youths and adolescents. For that reason, it is imperative to thoroughly assess the psychological and emotional states, in addition to the motivations, of minor patients. That goal can be achieved through the use of the DAS-59, (the Derriford Appearance Scale)1 , an effective and dependable tool devised to evaluate the psychological difficulties and distress experienced by people living with problems of appearance. Prior to undergoing cosmetic surgery procedures, adolescents should be required to go through adequate counseling, over multiple sessions and extended to their family members as well, on account of the complex issues inherent in evaluating the risk-benefit ratio and a prospective patient's decision-making capability. A concerted effort on the part of surgeons, psychiatrists or psychologists is key in determining the real motivations behind a minor's decision to opt for cosmetic surgery in the first place. Possible psychiatric conditions may in fact prevent a minor from making a free, informed decision. From an ethical standpoint, cosmetic surgery procedures should be geared to serve the best interest of the minor patient, who may experience distress over his or her body image, from a health and psychological balance perspective and improve his or her social, affective and working life. Besides, cosmetic surgery should not be overly invasive compared to its potential benefits. Those procedures aimed at achieving ″ideal beauty″ are not desirable and ought to be banned. By virtue of such criteria, the authors have set out to evaluate the ethical admissibility of some aesthetic treatments. Thus, doctors should not consent to any request coming from their patients, but rather, intervene only in presence of an objective physical flaw or deformity, e.g. protruding ears, which have a potential to negatively affect social life and interactions.

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Delivery room infections are frequent, and many of them could be avoided through higher standards of care. The authors examine this issue by comparing it to English and French reality. Unlike England, in Italy and France the relationship established between health facility, physician and patient is outlined in a contract. In England, the judges' decisions converge toward a better and higher protection of the patient-the actor-and facilitate the probative task. In case of infections, including those occurring in the delivery room, three issues are evaluated: the hospital's negligent conduct, damages if any and causal nexus. Therefore, the hospital must demonstrate to have taken the appropriate asepsis measures according to current scientific knowledge concerning not only treatment, but also diagnosis, previous activities, surgery and post-surgery. In order to avoid a negative sentence, both physicians and hospital have to demonstrate their correct behavior and that the infection was caused by an unforeseeable event. The authors examine the most significant rulings by the Courts and the Supreme Court. They show that hospitals can avoid being accused of negligence and recklessness only if they can demonstrate to have implemented all the preventive measures provided for in the guidelines or protocols.

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The Assisted Reproductive Technology (ART) was born in order to help couples with infertility issues in having a baby. The first treatments of IVF used the spontaneous cycle of the women, with the retrieval of only one oocyte. Further studies have shown that it is possible to induce ovulation by administrating gonadotropins during the menstrual cycle, in order to obtain a higher number of oocytes. Many stimulation protocols have been introduced for controlled ovarian hyperstimulation of patients undergoing in vitro fertilization treatment. This review describe the different stimulation protocols using follicle-stimulating hormone (FSH) in combination with Gonadotropin releasing hormone (GnRH) either agonist or antagonist, oral supplementations and ovarian triggering. Using GnRH antagonist protocols have been demonstrated to improve significantly the clinical pregnancy rates for expected poor and high-responders, and in those women at high risk of developing ovarian hyperstimulation syndrome (OHSS). Two meta-analyses showed a better outcome in terms of the live birth rate when highly purified human menopausal gonadotropin (HMG) was used for ovarian stimulation compared with recombinant follicle stimulating hormone (rFSH) in the GnRH agonist long protocol. One of the most efficient stimulation protocol is the use of a combined protocol of human derived urinary FSH (uFSH) and rFSH. Combined protocol has resulted in a significant increase in the proportion of mature metaphase II oocytes and grade 1 embryos when compared to either rFSH or uFSH alone. A significantly higher delivery rate was achieved in rFSH+uFSH compared to the other protocols in poor and normal responders. Studying the combination of melatonin with myo-inositol and folic acid has also showed a higher percentage of mature oocytes in the melatonin group and a higher percentage of G1 embryos as well. However, It remains a crucial step to confirm the efficacy of such protocols for clinical application and it is still needs to comparison studies on larger scale with more focused on the differences in patients' response criteria and additional confounding variables, in order to draw more defined conclusions.

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Nandrolone is included in the class II of anabolic androgenic steroids (AAS) which is composed of 19-nor-testosterone-derivates. In general, AAS is a broad and rapidly increasing group of synthetic androgens used both clinically and illicitly. AAS in general and nandrolone decanoate (ND) in particular have been associated with several behavioral disorders. The purpose of this review is to summarize the literature concerning studies dealing with ND exposure on animal models, mostly rats that mimic human abuse systems (i.e. supraphysiological doses). We have focused in particular on researches that have investigated how ND alters the function and expression of neuronal signaling molecules that underlie behavior, anxiety, aggression, learning and memory, reproductive behaviors, locomotion and reward.

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Medically Assisted Reproduction (MAR), involving in vitro fertilisation (IVF), and research on embryos have created expectation to many people affected by infertility; at the same time it has generated a surplus of laws and ethical and social debates. Undoubtedly, MAR represents a rather new medical field and constant developments in medicine and new opportunities continue to defy the attempt to respond to those questions. In this paper, the authors reviewed the current legislation in the 28 EU member states trying to evaluate the different legislation paths adopted over the last 15 years and highlighting those EU countries with no specific legislation in place and MAR is covered by a general health Law and those countries in which there are no laws in this field but only "guidelines." The second aim of this work has been to compare MAR legislation and embryo research in EU countries, which derive from different origins ranging from an extremely prohibitive approach versus a liberal one, going through a cautious regulatory approach.

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We describe a case of unintentional intoxication due to tramadol and propofol self administration, occurred in a middle aged man, healthcare provider, deceased despite advanced medical assistance an hour later the onset of severe and increasing dyspnea. Toxicological analysis performed with gas chromatography-mass spectrometry in blood sample, evidenced a lethal tramadol concentration and therapeutic level of Propofol. Quantitative determination was also performed in other specimens such as bile, tissues (liver, spleen, kidney) and pubic hair, to assess chronic exposure. Toxicological results and autopsy findings, supported by clinical and hematochemical data, suggested a myocardial damage, associated with respiratory failure.

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