Consequences of COVID-19 restrictions on adolescent mental health and drug abuse dynamics.

The COVID-19 pandemic has hit elderly people the hardest in terms of severity and mortality. However, it is also evident that children and adolescents have been significantly impacted and experienced major disruptions in their lives. The psychological, mental, and developmental repercussions have been major and have led to a reshaping of drug abuse dynamics and substance addiction. The authors have outlined a narrative review of the major issues affecting adolescents and their mental well-being by clarifying the lingering effects and pandemic aftermath, especially on drug abuse, developmental aspects, and behavioral addiction. The unique traits of adolescent risk factors have been outlined, in order to identify areas to be prioritized for future strategies. Possible repercussions on juvenile crime linked to social estrangedness and disrupted interactions have been briefly explored as well. All such aspects are highly meaningful and relevant from a medicolegal perspective as well. The looming mental health crisis involving youngsters will have to be confronted by fine-tuning and optimizing mental health care services, building on current experiences, raising awareness, and eliminating the stigma that often comes with mental issues. Healthcare systems should look at the current scenario as an opportunity to improve care delivery to eliminate access inequalities and stigmatization of mental issues and raise awareness for the benefit and well-being of all. Similarly, law enforcement, lawmakers, and the judiciary will have to account for such factors, too, as will economic policy-makers. In that regard, a set of defining criteria has been framed in order to provide a degree of objectivity when meeting the unique challenges of the pandemic for youth mental health, in a comprehensive and tailored fashion.

Is there such a thing as an indispensable skills profile to be a good doctor? "Life skills" as essential capabilities in the medicoforensic professions.

Abstract: This writing aims to convey the essential nature and features of a cultural tool based on a set of skills and capabilities generally referred to as "life skills", which allow for the proper management (in the medical and medical-forensic professional realms) of daily situations in an effective and rewarding fashion. Such a process is based on individual tools such as communication, problem solving, stress management, self-control, the ability to make timely decisions, empathy, creativity and the opportunity to work in a multidisciplinary setting. Life skills include everything the professional should rely on in order to minimize the risks of a professional error, through the acquisition of knowledge and behavioral traits which constitute the fundamental, experience-based starting point. The chief objective of this commentary is to outline the scope of a straightforward discussion by specifically defining such skills; that in turn will make it possible to identify all the technical issues to address during the medical-diagnostic assessment, also from a medico-legal perspective, in order to frame the residual life skills and evaluate the possibilities of recovery and any disabilities, based on observation and interactions with each patient aimed at weighing their psychophysical performance.

Fresh vs. frozen embryo transfer in assisted reproductive techniques: a single center retrospective cohort study and ethical-legal implications.

OBJECTIVE: Several studies have shown higher pregnancy rates and better perinatal outcomes with frozen embryo transfers than with fresh techniques, with better results in patients with polycystic ovary syndrome (PCOS) but with a higher rate of pregnancy complications such as preeclampsia. This retrospective cohort study aims to compare the cumulative live birth rates, maternal and neonatal complications of fresh embryo transfers (ET) and frozen-embryo transfers (FET) in infertile women who underwent assisted reproduction techniques (ART) at the Azienda Ospedaliera Ospedali Riuniti (AOOR) Villa Sofia Cervello, Palermo, Italy. In addition, the authors have focused on the legislative and ethical complexities which such a procedure entails. PATIENTS AND METHODS: Out of 475 women undergoing in vitro fertilization programs from January 2017 to January 2021, 128 were enrolled; 70 patients underwent ET, and 58 patients FET. The main outcome measure was live birth rates. Secondary outcomes were clinical pregnancy, ongoing pregnancy, pregnancy loss, low birth weight (LBW), ectopic pregnancy, and obstetrical and perinatal complications. RESULTS: The cumulative live birth rates were similar between the fresh transfer (95.7%) and frozen transfer (93.1%). Biochemical pregnancy rates, clinical pregnancy, ongoing pregnancy, and pregnancy loss were similar between the groups. CONCLUSIONS: Obstetrical outcomes were not statistically different between the two groups; a higher preterm delivery rate was reported in the FET group. ET birth weights were notably lower for singletons compared to the freeze-all strategy. ET patients also had higher LBW rates, with a 2.5-fold higher rate compared to FET. No significant differences were found in cumulative live birth rates between ET and FET, which is consistent with earlier studies. FET protocols are linked to higher neonatal birth weight and lower risk of LBW than fresh ET. The ethical and legal quandaries inherent in such techniques, as technology moves on and outpaces current legislative frameworks, cannot be discounted.

The evolution of European legislation on doping: new challenges in the age of NPS.

The fight against doping in sport, formally started in 1960 with the constitution of the International Olympic Committee (IOC) and culminated in 1999 with the birth of the World Anti-Doping Agency (WADA), commissioned to chair various activities, including the publication of the annual list of prohibited substances and methods for doping. In Europe, as early as 1967, the Committee of Ministers of the Council of Europe adopted a resolution to stigmatise the intake of substances foreign to the body for the sole purpose of artificially and unfairly influencing sports performance. In 2002, the Council of Europe adopted an Additional Protocol to the 1989 Strasbourg Convention against Doping to ensure mutual recognition of doping controls and to strengthen the enforcement of the Convention. In Italy, the Law of 14 December 2000 n. 376 "Discipline of the health protection of sports activities and the fight against doping", defines doping as "the administration or intake of drugs or biologically or pharmacologically active substances and the adoption or submission to medical practices not justified by pathological conditions and suitable to modify the psychophysical or biological conditions of the organism in order to alter the athletic performance of athletes". The same law regulates the use of drugs or biologically or pharmacologically active substances and update an annual list in agreement with WADA. The article aims to analyse the legislation from a national perspective, offering as complete a view as possible of the current situation.

The armed conflict in Ukraine and the risks of inter-country surrogacy: the unsolved dilemma.

Commercial surrogacy in Ukraine has been legal since 2002, and although no official figures are released, estimates point to several thousand births occurring yearly. The country has long been regarded as one of the surrogacy capitals of the world, due to relatively affordable costs and effective targeted legislation making the surrogacy contracts enforceable. Would-be parents come from countries where surrogacy is banned or heavily restricted to start a family despite their infertility, a practice known as inter-country surrogacy. When a child is born through surrogacy, the surrogate mother forfeits her rights over the child, thus allowing the so-called "intended" or "commissioning" parents to be recognized as such on the Ukrainian birth certificate. Inter-country surrogacy has long been a highly controversial practice from an ethical and legal perspective, but the brutally destructive armed conflict erupted in the country over three months ago has laid bare all the pitfalls and deep flaws of such a system. Children born through surrogacy cannot be handed over to their intended parents, and surrogates risk legal issues and see their rights jeopardized by their choices even in a war setting, for instance if they decide to seek refuge abroad. The horrors of war thus risk victimizing the most vulnerable to an irreparable degree. An international effort is now more urgent than ever to seek a tenable balance between the desires of couples to achieve parenthood and the rights and freedom of often vulnerable women who risk exploitation and abuse and their children.

The best interest of children born through medically assisted procreation procedures as construed in 2021 Italian Constitu- tional Court rulings 32 and 33.

ABSTRACT: The authors have set out to briefly analyze the 2021 Constitutional Court rulings n.32 and 33, regarding the situation of children born in, or otherwise being raised by, same-sex couples. Such judgments address the problem by taking into account the fundamental principle of the child's best interests. This article is meant to highlight the issues that may arise if such interests were to be translated into specific law provisions or safeguards for the children's sake. Moreover, the authors aimed to focus on the valuable elements laid out in the Court rulings, while also highlighting the more critical and controversial elements therein.

Uterus transplant and controversial assisted reproductive technologies: can the right to parenthood clash with ethical precepts?

ABSTRACT: Fast-developing assisted reproductive techniques based on innova- tive technologies have given rise to incredibly consequential ethical challenges of unprecedented scope. The development of innovative assisted reproductive technologies (ARTs) has steadily risen since the late 1970s. Until just over 20 years ago, those who sought to become parents had no way to overcome their infertility or sterility issues, but can now achieve parenthood and have children with at least a partial genetic and/or biological relationship. Treatments aimed at ovarian stimulation, artificial insemination, either by using the sperm of a husband or of an unrelated donor, in vitro fertilization with embryo transfer, gamete and zygote intrafallopian transfers, and intracyto- plasmic sperm injection are among the options currently available. A major ethical quandary linked to ARTs is the one arising from unused embryos, i.e. supernumerary embryos which were not implanted. Still, aside from ethical concerns stemming from embryo rights, in such a fast-evolving field, a solid ethical foundation is absolutely necessary to provide guidance for regulations and legislation. This is especially true considering how assisted reproductive practices such as surrogacy and uterus transplant (UTx) are even more controversial, hence the need to rely on a broadly acknowledged and shared set of principles for their regulation, by virtue of their unique distinctive traits which challenge our ethical and moral compass at its very core.

Is there anything left of the Italian law governing medically-assisted procreation?

Medically-assisted-procreation via in vitro fertilization, an integral part of of the so-called "reproductive revolution", is a valuable option for couples with sterility or fertility issues. That has however brought about three relevant results: the rift between procreation and sexual intercourse, the opportunity to use heterologous fertilization through donated gametes, and the ensuing increase in the number of "reproductive contributors" (male and/or female gamete donors, surrogate mothers). In Italy, Law n. 40 has put in place several restrictions, stricter than in most other European countries. Before being declared partly unconstitutional, Law 40 used to impose an array of bans and restrictions other than the ones still currently in force, such as the still unchanged prohibition to use human embryos for experimentation purposes and the ban on surrogacy. For same-sex couples who travel abroad to get around the Italian ban on heterologous fertilization, surrogacy, and MAP for homosexual couples. The authors have attempted to lay out a short analysis of how Italian courts have attempted to uphold the best interests of children born abroad in homosexual families, by taking into account the latest decisions on the subject.

Beginning of life ethics at the dawn of a new era of genome editing: are bioethical precepts and fast-evolving biotechnologies irreconcilable?

The amazing and almost unimaginable advances that have unfolded over the past decades in biotechnologies (heritable germline editing in particular) have brought bioethical issues to the forefront, sparking public debate and increasing attention worldwide. Such mind-blowing progress has already resulted in major improvement and enhancements for humans, and holds the potential for even more. Technology and bioengineering have begun to take over in the life sciences industry. Man's capacity to genetically engineer the biological world is nothing short of mind-boggling in its current magnitude, and may even evolve, in a not too distant future, into attempts to fuse man and machine into a cohesive bioengineered entity; a "super human being", endowed with enhanced cognitive and physical capabilities and impervious to disease, may be not too far down the road. That will not come without caveats, however. In fact, scientific advancements at such an accelerated pace have already negatively affected our cultural, ethical, and legal values and our ability to harness the opportunities and face the dangers posed by such developments. As a matter of fact, science seems to consistently outpace public morals, ethics and policymaking, which calls for a high degree of caution and common answers.

No more only one mom? European Court of Human Rights and Italian jurisprudences' ongoing evolution.

The author has delved into the most significant Italian and European court rulings related to heterologous fertilization and surrogate motherhood between 2012 and 2019, with a close focus on same-sex couples seeking to have their donor-conceived children born abroad legally registered in their country of origin. Undeniably, surrogacy has brought about a crisis in the traditional family model, made up of a mother and a father. The paper draws upon European Court of Human Rights established jurisprudence that upholds the children's best interests. Italian Court rulings are expounded upon as well, which have been instrumental in establishing the principles by which parental figures do not necessarily coincide with those who have generated the children (through biological bonds or delivery), but rather with those who wish to be recognized as parents. The cases herein examined involve homosexual couples who decided to travel abroad in order to gain access to surrogacy, from which children were born. In the case regarding two fathers, the child had no genetic tie with either one intended parent. The Italian Supreme Court's joint sessions have ruled that such children cannot be legally registered in Italy, since their foreign-issued birth certificates indicate no genetic connection between the children and their intended parents. The Author believes that the Supreme Court decision is valuable, but further legislative interventions will be necessary on account of scientific advancements; the issue of surrogacy is utterly complex and multi-faceted.

Medically-assisted procreation and the rise of off-center, new types of "parenthood": it is incumbent upon lawmakers to intervene.

Medically-assisted procreation (MAP) has given rise to a crisis in the traditional family model, made up of a mother and a father, and led to the births of babies who are genetically and biologically unrelated to their legal parents. Italian legal statutes ban such practices, which are punishable by law; yet there is currently no legislation aimed at governing and regulating the legal registration of children born through such procedures abroad. Italian jurisprudence, on the other hand, has acknowledged the right to parenthood for homosexual couples, ruling that the children thus born be considered legally bound to their social parents, by virtue of the affection-based bond, rooted in harmony and listening, that has been formed within the family setting, however unconventional it may be. The paper's author feels that an intervention from lawmakers is urgent and inescapable, in order to provide targeted legislation in such a sensitive realm.

The unethicality of doping in sports.

Performance enhancing drug use in sport arguably constitutes a crisis, and as such, targeted measures are needed in order to stem it. Substance abuse in professional sports and competitions has besmirched many world-class athletes' reputations and standing, in addition to jeopardizing their health. Furthermore, there are many instances of amateur athletes and school-aged competitors who have taken to using such substances as well, significantly exacerbating the overall picture. The widespread acknowledgement of the potentially life-threatening consequences of performance-enhancing drug use has prodded sports organizations and governments into cooperating on many different levels to preserve the ethical grounding and soundness of sport competitions; unlawful substance abuse is in fact liable to undermine the very core of fairness in competition. Doping, along with various forms of cheating, has been recorded throughout the history of sport: prohibition in itself is all but ineffective without reliable and systematic detection strategies and enforcement of sanctions.

The human embryo, subjectivity and legal capacity. Notes in the light of art. 1 of the Italian law on "medically assisted procreation".

AIM: This paper aims to examine the legal status of the human embryo taking into consideration Article 1 of the Italian law on medically assisted procreation, which protects the human embryo, which is recognised as an individual holding the same rights as already born children. The progressive increase in legal decisions regarding reproductive technologies requires a re-examination of the traditional legal categories of "subjectivity" and legal capacity, and a deeper understanding of the status of the human embryo as a subject, or individua. MATERIALS AND METHODS: The following sources were searched: Institutional websites, Research Centre for Social Investments reports, updated jurisprudence and Rulings of Italian Constitutional Court and European Court of Human Rights. In addition, also the following databases were searched: PubMed and Scopus, using the following keywords: medically assisted procreation (MAP) and embryo. RESULTS: The authors believe that the best orientation is the modern principle of equality (non-discrimination); according to them, the need to protect unborn life requires therefore the consideration of interests which can no longer be confined to the solely patrimonial ones held by the embryo. The paper draws attention to a series of non-patrimonial interests, for whose protection the legal expert has to adopt innovative safeguarding techniques. In this context, there emerge some rights worthy of protection whose potential holders are as yet unborn.

Magnetic Nanodrug Delivery Through the Mucus Layer of Air-Liquid Interface Cultured Primary Normal Human Tracheobronchial Epithelial Cells.

Superparamagnetic iron oxide (Fe3O4) and highly anisotropic barium hexaferrite (BaFe12O19) nanoparticles were coated with an anti-inflammatory drug and magnetically transported through mucus produced by primary human airway epithelial cells. Using wet planetary ball milling, dl-2-amino-3-phosphonopropionic acid-coated BaFe12O19 nano-particles (BaNPs) of 1-100 nm in diameter were prepared in water. BaNPs and conventional 20-30-nm Fe3O4 nanoparticles (FeNPs) were then encased in a polymer (PLGA) loaded with dexamethasone (Dex) and tagged for imaging. PLGA-Dex-coated BaNPs and FeNPs were characterized using dynamic light scattering (DLS), transmission electron microscopy (TEM), and superconducting quantum interference device (SQUID) magnetometry. Both PLGA-Dex-coated BaNPs and FeNPs were transferred to the surface of a ~100-µm thick mucus layer of air-liquid interface cultured primary normal human tracheobronchial epithelial (NHTE) cells. Within 30 min, the nanoparticles were pulled successfully through the mucus layer by a permanent neodymium magnet. The penetration time of the nanomedicine was monitored using confocal microscopy and tailored by varying the thickness of the PLGA-Dex coating around the particles.

Early prediction of treatment response to sorafenib with elastosonography in a mice xenograft model of hepatocellular carcinoma: a proof-of-concept study.

PURPOSE: Sorafenib is the reference therapy for advanced hepatocellular carcinoma (HCC). There is no method for predicting in the early period subsequent individual response. Starting from the clinical experience in humans that subcutaneous metastases may rapidly change consistency under sorafenib and that elastosonography allows assessment of tissue elasticity, we investigated the role of this ultrasound-based technique in the early prediction of tumor response to sorafenib in a HCC mice model. MATERIALS AND METHODS: HCC subcutaneous xenografting in mice was utilized. Mice were randomized to vehicle (17 mice) or treatment with sorafenib (19 mice). Strain elastosonography (Esaote, Italy) of the tumor mass was performed at different time points (day 0, + 2 and + 14 from treatment start) until the mice were sacrificed (day + 14). At the same time points, the volume was calculated with ultrasonography. RESULTS: Sorafenib-treated mice showed a smaller increase in tumor size on day + 14 in comparison to vehicle-treated mice (tumor volume increase + 175 % vs. + 382 %, p = 0.009). The median tumor elasticity increased in both groups on day + 2 (+ 5.65 % and + 3.86 %, respectively) and decreased on day + 14 (-3.86 % and -3.63 %, respectively). However, among Sorafenib-treated tumors, 13 mice with a growth percentage delta < 200 % (considered as good treatment response) showed an increase in elasticity on day + 2 (+ 8.9 %, range -12.6 - + 64) while the other 6 with a growth percentage delta > 300 % (considered as poor treatment response) showed a decrease in elasticity (-17 %, range -30.2 - + 15.3) (p = 0.044). CONCLUSION: Elastosonography appears to be a promising noninvasive new technique for the early treatment prediction of HCC tumor response to sorafenib. Specifically, an early increase in tumor elasticity (corresponding to tumors becoming softer) is associated with a good response.

Characterization of primary and recurrent nodules in liver cirrhosis using contrast-enhanced ultrasound: which vascular criteria should be adopted?

PURPOSE: To assess the impact of different vascular patterns at contrast-enhanced ultrasound (CEUS) on the characterization of small liver nodules (10-30 mm) in cirrhosis and to determine whether primary nodules and recurrent nodules (after a previously treated hepatocellular carcinoma) display variations in enhancement pattern. MATERIALS AND METHODS: A total of 135 cirrhotic patients were evaluated. A diagnosis of hepatocellular carcinoma (HCC) was established according to AASLD Guidelines, based on imaging (computed tomography and/or magnetic resonance) or liver biopsy. All patients underwent CEUS. Different CEUS patterns were evaluated in terms of diagnostic accuracy: HYPER-HYPO: Arterial hyperenhancement followed by washout (hypoechoic appearance compared with surrounding parenchyma) in late phase; HYPER-ISO: Arterial hyperenhancement followed by isoenhancement (isoechoic appearance) in late phase; ISO-ISO: Isoenhancement in all vascular phases. RESULTS: A total of 155 consecutive primary (n = 90) or recurrent (n = 65) nodules were detected. HCC was diagnosed in 127 nodules (71 primary, 56 recurrent). A characteristic HYPER-HYPO CEUS pattern was revealed in 52/127 (40.9%) HCCs (31 primary, 21 recurrent) giving a positive predictive value (PPV) of 98% (97% primary, 100% recurrent) and an accuracy of 51% (54% primary, 46% recurrent). A HYPER-ISO pattern was noted in 46 HCCs (31 primary, 15 recurrent). Assuming this pattern to also be indicative of HCC, the PPV and accuracy were 94% (93% primary, 97% recurrent) and 77% (84% primary, 68% recurrent), respectively. An ISO-ISO pattern was present in 29 HCCs (9 primary, 20 recurrent) and 22 non-HCCs (14 primary, 8 recurrent). CONCLUSION: These data confirm that the HYPER-HYPO pattern at CEUS is definitely diagnostic for HCC in cirrhosis and that the HYPER-ISO pattern has a similar PPV, indicating that this pattern is highly suspicious for HCC. The ISO-ISO pattern was found in > 50% of recurrent nodules and indicates a high risk of HCC.

ProNGF\NGF imbalance triggers learning and memory deficits, neurodegeneration and spontaneous epileptic-like discharges in transgenic mice.

ProNGF, the precursor of mature nerve growth factor (NGF), is the most abundant form of NGF in the brain. ProNGF and mature NGF differ significantly in their receptor interaction properties and in their bioactivity. ProNGF increases markedly in the cortex of Alzheimer's disease (AD) brains and proNGF\NGF imbalance has been postulated to play a role in neurodegeneration. However, a direct proof for a causal link between increased proNGF and AD neurodegeneration is lacking. In order to evaluate the consequences of increased levels of proNGF in the postnatal brain, transgenic mice expressing a furin cleavage-resistant form of proNGF, under the control of the neuron-specific mouse Thy1.2 promoter, were derived and characterized. Different transgenic lines displayed a phenotypic gradient of neurodegenerative severity features. We focused the analysis on the two lines TgproNGF#3 and TgproNGF#72, which shared learning and memory impairments in behavioral tests, cholinergic deficit and increased Aß-peptide immunoreactivity. In addition, TgproNGF#3 mice developed Aß oligomer immunoreactivity, as well as late diffuse astrocytosis. Both TgproNGF lines also display electrophysiological alterations related to spontaneous epileptic-like events. The results provide direct evidence that alterations in the proNGF/NGF balance in the adult brain can be an upstream driver of neurodegeneration, contributing to a circular loop linking alterations of proNGF/NGF equilibrium to excitatory/inhibitory synaptic imbalance and amyloid precursor protein (APP) dysmetabolism.