Mother, father, son and the Italian Law 40/2004. No 'delete' key.

Assisted reproductive technology (ART) has emerged in recent years as a point of significant innovation in the medical field but is also controversial from a bioethical and legal standpoint. In the Italian context, this matter is regulated by Law 40/2004, which specifically requires that informed consent should be obtained from both members of a couple before proceeding with any ART procedure. This consent is deemed irrevocable at the moment of egg fertilization. Recently, a ruling by the Italian Constitutional Court on this matter elicited controversy. The decision permitted embryo transfer even in a case of parental separation, notwithstanding the father's explicit opposition. The Court emphasized the priority of the woman's psychophysical health over the man's, highlighting the traumatic consequences of interrupting the undertaken path. As a result, both the man's right to self-determination regarding the decision to become a father and the need for informed consent at every stage of medical procedures have been downplayed. Moreover, the extensive utilization of procedures like embryo cryopreservation, with associated parental implications, particularly concerning the time frame and the actuality of informed consent, is posing challenges to the initial application framework of Law 40/2004. The objective of this Commentary is to scrutinize and discuss the issues mentioned above.

Reliability of clinical judgment for evaluation of informed consent in mental health settings and the validation of the Evaluation of Informed Consent to Treatment (EICT) scale.

Introduction: The competence assessment to give informed consent in the legal and healthcare settings is often performed merely through clinical judgment. Given the acknowledged limited reliability of clinician-based evaluation in the mental health sector, particularly for the assessment of competence to consent, our objective was to ascertain the dependability of clinical judgment when evaluating the ability of schizophrenia patients to make choices about their health. Methods: The potential convergence between clinical evaluation and scores from a new standardized assessment (the "Evaluation of Informed Consent to Treatment" - "EICT" scale) was therefore tested. The scale assesses four dimensions of competence, specifically how patients normally understand information relating to care (Understanding); how they evaluate the choice of treatment in terms of risk/benefit ratio (Evaluating); how they reason coherently in the decision-making process (Reasoning); and, finally, their ability to make a choice between treatment alternatives (Expressing a choice). Thirty-four outpatients with schizophrenia were evaluated for their competence to consent by five referring clinicians with different backgrounds (psychiatrist, forensic psychiatrist, geriatrician, anesthetist, and medico-legal doctor). Inter-raters variability was tested through correlation analyses between the scores obtained by the clinicians on a modified version of the Global Assessment of Functioning scale (GAF) designed specifically to subjectively assess functioning in each of the four competence dimensions. Two validated competence scales (Mac-CAT-T, SICIATRI-R), and a neuropsychological battery were also administered along with scales for evaluating neuropsychiatric symptoms severity and side effects of medication. Results: Clinical judgments of the individual specialists showed great inter-rater variability. Likewise, only weak/non-significant correlations were found between the EICT subscales and the respective clinicians-rated GAF scales. Conversely, solid correlations were found between the EICT and MacCAT-T subscales. As expected, healthy controls performed better in the ability to give informed consent to treatment, as measured by the three scales (i.e., EICT, MacCAT-T, and SICIATRI-R), and neuropsychological test performance. In the comparisons between patients who, according to the administered EICT, were able or not able to give informed consent to treatment, significant differences emerged for the Phonemic verbal fluency task (p = 0.038), Verbal judgments (p = 0.048), MacCAT-T subscales, and SICIATRI-R total score. Moreover, EICT exhibited excellent internal consistency (Cronbach's alphas ranging from 0.96 to 0.98 for the four subscales) while the Item Analysis, by measuring the correlation between each item of the EICT and the total score, was excellent for all items of all subscales (alphas ranging from 0.86 to 0.98). Discussion: In conclusion, our findings highlighted that the assessment of competence exclusively through clinical judgment is not fully reliable and needs the support of standardized tools. The EICT scale could therefore be useful in assessing general competence to consent both in healthcare and legal contexts, where it might be necessary to evaluate the effective competence of patients with psychiatric disorders. Finally, this scale could serve as a valuable tool for decisions regarding whether and to what extent a patient needs support.

Telehealth Intervention: A Proposal for a Telemedicine Manual to Ascertain the Civil Disability Status in Italy.

(1) This paper aims to propose a telematic method for assessing the state of disability by a social worker member of the Medico-Legal Commissions of INPS. (2) We have proceeded to delve into and compare the current methods with new strategies to enhance the experience linked to the assessment of the status of disability in terms of timing and accessibility, eliminating the need for a direct visit. (3) The proposed protocol can be applied in cases where patients cannot be physically moved, following a medical visit at home, and when the mere evaluation of documents is sufficient. In both cases, a remote session with the Commission is necessary to fill in the required information about the socio-environmental section. This protocol can be applied to different platforms such as Skype™ since it is free and widely used throughout the country. (4) It should be noted that telemedicine solutions cannot completely replace face-to-face interaction; however, in some limited cases, they can optimize the process and timing, avoiding the need to move or interact only by telephone.

Oxidative Stress in Sepsis: A Focus on Cardiac Pathology.

This study aims to analyze post-mortem human cardiac specimens, to verify and evaluate the existence or extent of oxidative stress in subjects whose cause of death has been traced to sepsis, through immunohistological oxidative/nitrosative stress markers. Indeed, in the present study, i-NOS, NOX2, and nitrotyrosine markers were higher expressed in the septic death group when compared to the control group, associated with also a significant increase in 8-OHdG, highlighting the pivotal role of oxidative stress in septic etiopathogenesis. In particular, 70% of cardiomyocyte nuclei from septic death specimens showed positivity for 8-OHdG. Furthermore, intense and massive NOX2-positive myocyte immunoreaction was noticed in the septic group, as nitrotyrosine immunostaining intense reaction was found in the cardiac cells. These results demonstrated a correlation between oxidative and nitrosative stress imbalance and the pathophysiology of cardiac dysfunction documented in cases of sepsis. Therefore, subsequent studies will focus on the expression of oxidative stress markers in other organs and tissues, as well as on the involvement of the intracellular pattern of apoptosis, to better clarify the complex pathogenesis of multi-organ failure, leading to support the rationale for including therapies targeting redox abnormalities in the management of septic patients.

miRNAs and Substances Abuse: Clinical and Forensic Pathological Implications: A Systematic Review.

Substance addiction is a chronic and relapsing brain disorder characterized by compulsive seeking and continued substance use, despite adverse consequences. The high prevalence and social burden of addiction are indisputable; however, the available intervention is insufficient. The modulation of gene expression and aberrant adaptation of neural networks are attributed to the changes in brain functions under repeated exposure to addictive substances. Considerable studies have demonstrated that miRNAs are strong modulators of post-transcriptional gene expression in substance addiction. The emerging role of microRNA (miRNA) provides new insights into many biological and pathological processes in the central nervous system: their variable expression in different regions of the brain and tissues may play a key role in regulating the pathophysiological events of addiction. This work provides an overview of the current literature on miRNAs involved in addiction, evaluating their impaired expression and regulatory role in neuroadaptation and synaptic plasticity. Clinical implications of such modulatory capacities will be estimated. Specifically, it will evaluate the potential diagnostic role of miRNAs in the various stages of drug and substance addiction. Future perspectives about miRNAs as potential novel therapeutic targets for substance addiction and abuse will also be provided.

The wounding potential of assault rifles: analysis of the dimensions of entrance and exit wounds and comparison with conventional handguns. A multicentric study.

The appearance of a gunshot wound (GSW) is greatly influenced by the velocity of the projectile, where high-velocity projectiles (HVPs) are defined as ballistic agents reaching a muzzle velocity of > 600 m/s fired from assault rifles. The aim of the study is to present and explain the differences in the dimensions of entrance and exit wounds between the most used handguns and assault rifles and to propose a predictor of HVP, i.e., the ratio of exit and entrance wounds (EX/ENR). The surface area of entrance and exit GSWs and the EX/ENR were calculated. 66 perforating GSWs produced by NATO FMJ 7.62 × 52 mm and 5.56 × 42 mm fired from assault rifles were assigned to the HVP, while 64 lesions produced by conventional projectiles fired from revolvers and semi-automatic pistols were assigned to the low-velocity projectile (LVP) group. The dimensions of the exit wounds of the HVP group were significantly higher when compared to the LVP group (95% CI 0.9886-2.423, p < 0.05). The HVP group showed significantly higher values for the EX/ENR when compared to the LVP group (95% CI 2.617-7.173, p < 0.05). The evaluation of the EX/ENR can be considered an adequate tool to assess the type of weapon involved and to roughly estimate the associated wounding mechanisms, which can guide both the physician in the management and treatment of the patients affected by GSW, and the forensic pathologist in crime investigation.

Fourteen Deaths from Suspected Heparin Overdose in an Italian Primary-Level Hospital.

Healthcare-related homicidal cases are not novel within the medical-legal landscape, but investigations are often made difficult with the scarcity of material evidence related to the crime. For this reason, it is necessary to carefully analyze the clinical documentation and employ ancillary forensic resources such as radiology, histopathology, and toxicology. In the presented scenario, the observation of 14 deaths from abnormal bleeding in a First-Level Italian Hospital revealed the administration of massive doses of heparin by a nurse. On behalf of the Judicial Authority, a multidisciplinary medical team investigated the case through the following steps: a thorough review of the clinical documentation, exhumation of the bodies belonging to the deceased patients, performing PMCT and autopsy, and collecting tissue samples for histopathological, immunohistochemical, and toxicological investigations. All the analyzed cases have been characterized by the observation of fatal hemorrhagic episodes not explained with the clinical conditions of the patients, confirmed using autopsy observations and the histological demonstration of the vitality of the lesions. However, due to the limited availability of biological material for the toxicological analysis, the indirect evidence from hematological analyses in hospitalized patients was crucial in demonstrating heparin overdose and its link to the recorded deaths. The present scenario demonstrates the fundamental importance of a multidisciplinary approach to cases of judicial interest related to the healthcare context. Therefore, the illustrated methodologies can be interpreted as an operational framework for similar future cases.

Predictors of Defensive Practices among Italian Psychiatrists: Additional Findings from a National Survey.

Background: Defensive medicine is characterized by medical decisions made primarily as a precaution against potential malpractice claims. For psychiatrists, professional responsibility encompasses not only the appropriateness of diagnosis and treatment but also the effects of their interventions on patients and their behaviors. Objective: To investigate the socio-demographic, educational, and occupational characteristics and work-related attitudes that may serve as predictors of defensive medicine among Italian psychiatrists. This research extends the results of a previous analysis based on a national survey. Methods: A secondary analysis of the database of a national survey on attitudes and behaviors of Italian psychiatrists regarding defensive medicine and professional liability was performed for this study. Results: Among 254 surveyed psychiatrists, 153 admitted to practicing defensive medicine, while 101 had this attitude with less than half of their patients. The first group was predominantly comprised of women (p = 0.014), who were younger in age (43.34 y 9.89 vs. 48.81 y 11.66, p < 0.001) and had fewer years of professional experience (12.09 y ± 9.8 vs. 17.46 y ± 11.2, p < 0.001). There were no significant differences in prior involvement in complaints (p = 0.876) or the usual place of work (p = 0.818). The most prominent predictors for practicing defensive medicine were (1) considering guidelines and good clinical practices not only for their clinical efficacy but also or exclusively for reducing the risk of legal complaints for professional liability (OR = 3.62; 95%CI, 1.75-7.49), and (2) hospitalizing patients with violent intentions even if not warranted according to their mental state (OR = 2.28; 95%CI, 1.50-3.46, p < 0.001). Prioritizing protection from professional liability over patients' actual needs in prescribing or adjusting drug dosages and in involuntary hospitalization, as well as prescribing lower dosages than recommended for pregnant patients, were identified as additional predictors. Finally, years of professional experience exhibited a protective function against defensive practices. Conclusions: Psychiatrists advocate the need to implement a 'risk management culture' and the provision of more balanced duties in order to ensure ethical and evidence-based care to their patients. A particular source of concern stems from their professional responsibility towards not only the health of patients but also their behavior. However, these aspects conflict with a limited potential for assessment and intervention based on effective clinical tools. A reform of professional liability that considers the specificities of patients cared for by mental health services could contribute to reducing the risk of defensive medicine.

Mental health law: a comparison of compulsory hospital admission in Italy and the UK.

In Europe, the mental health law legal framework has had several changes throughout the years to achieve and develop new reforms, better mental health care, and protect the human rights of patients. The UK national data shows rising detention rates and the disproportionate use of the legal framework among people from black and minority ethnic groups. At the national level, compulsory admissions are lower in Italy; it also shows that it has increased in the last few years in both countries. The lack of ethnic national data, especially in Italy, limited the ability to understand compulsory admission, discrimination, and stigma in mental health. The present study aims to compare the legal framework of mental health law and compulsory hospital admission in Italy and the UK. A review of each country's latest amendments to mental health law and the number of compulsory hospital admissions was conducted to understand the impact of changes in mental health care.

Vox clamantis in deserto: a survey among Italian psychiatrists on defensive medicine and professional liability.

Due to recent events, professional liability for psychiatrists in Italy is currently a matter of lively debate. Specifically, overwhelming pressure on psychiatrists' duties has been brought by regulatory developments, such as the closure of forensic psychiatric hospitals, with the consequent return of offenders to community-based care, and the mental health consequences of the pandemic. According to Italian courts, psychiatrists are not only responsible for diagnostic and therapeutic appropriateness but also for the effects of their interventions on patients, and their behaviors. The aim of this study was to explore the attitude and behaviors of Italian psychiatrists regarding defensive medicine and professional liability. A total sample of 254 psychiatrists was surveyed by means of a quantitative online questionnaire. Most psychiatrists reported practicing defensive medicine (no. 153/254, 60.2%) and felt that their position of guarantee compromised their work in healthcare for patients (no. 138/253, 54.3%). Age correlated inversely with acknowledgment of defensive practices (r = -0.245, p < 0.001), with younger physicians more prone to defensive medicine (p = 0.013), particularly for patients at risk of suicide or violence. Psychiatrists in 'closed' settings (hospital wards, residential and rehabilitation centers, mental health service units in prison) reported more malpractice claims (p = 0.037) and complaints (p = 0.031), as well as a greater propensity to act defensively. In the treatment of patients with violent behavior, suicidal ideation, dual diagnoses, and criminal convictions, defensive practices were associated more with perceived legal risks (r = 0.306, p < 0.001) than actual legal involvement (p > 0.05). Anxiety, anger, and restlessness were common reactions to legal complaints, involving no. 50/254 (19.7%) respondents, with 40% reporting impaired functioning. Most psychiatrists (no. 175/253, 68.9%) were concerned about both civil and criminal laws regarding their professional responsibility, but many were not fully informed about recent legislative regulations and younger physicians resulted scarcely trained in risk management (p < 0.001). In conclusion, our findings suggest that defensive medicine is a common phenomenon among psychiatrists and their position of guarantee drives this attitude. Education on legal implications and risk management should be provided starting from the university and continuing over time, to improve the knowledge of young and senior doctors on professional liability and inform their decision-making processes. This would also reduce defensive practices and improve the quality of healthcare. Considering the concerns of younger physicians, as well as of professionals working in acute and high-intensity medical care facilities, there is also an urgent need for a revision of the medical liability to ensure the sustainability of the National Health Service.

The Practice of Teaching and Scientific Research on Cadaveric Material Remains Crucial for Medical Education.

The practice of teaching and scientific research on cadaveric material remains crucial for medical education, especially in surgical disciplines. However, in Italy, this practice has been neglected due to legislative insufficiency and financial constraints. Although innovative methods and tools like simulators and e-learning have been adopted, direct hands-on experience with human cadavers remains irreplaceable for medical and surgical education. The absence of clear legislation governing cadaveric dissection has limited availability for teaching and research, resulting in economic burdens for universities and individuals seeking proper surgical training. To address this issue, Law No. 10/2020 and the recent implementing decree were introduced in Italy, providing detailed legislation on the donation of bodies for educational and research purposes. The law emphasizes the importance of respecting the donor's specific choices and aligns with constitutional principles promoting culture, research, and health protection. However, some critical issues related to consent procedures, duration of body availability, and preservation of anatomical parts remain. Additionally, the law's dissemination among the population needs improvement. Future optimization could include allowing donors to choose the timing of body donation and considering different timeframes for body availability. Furthermore, the implementation of consent procedures could be simplified to increase donations. The law should also address the need for appropriate reception centers and allocate resources for effective dissemination. Despite these challenges, Law No. 10/2020 represents a significant step forward in enhancing medical-surgical training, scientific research, and the overall quality of patient care in Italy.

The Dark Side of Energy Drinks: A Comprehensive Review of Their Impact on the Human Body.

In recent years, the consumption of energy drinks by young adults and athletes has risen significantly, but concerns have been raised about the potential health risks associated with excessive consumption. These concerns include cardiovascular problems, nervous system disorders, and the potential for addiction. This review aims to examine the reported effects of acute or chronic abuse of energy drinks on human health. The analysis shows a significant prevalence of adverse effects, particularly on the cardiovascular and neurovegetative systems. In particular, the analysis identified nine cases of cardiac arrest, three of which were fatal. The aetiology of these adverse effects is attributed to the inherent neurostimulant properties of these beverages, of which caffeine is the predominant component. A comparison of documented effects in humans with experimental studies in animal models showed an overlap in results. This review highlights the need for greater rigour in the assessment of sudden cardiac death, particularly in young people, as legal substances such as energy drinks may be involved. We propose stricter limits on the consumption of these beverages than for caffeine, based on the evidence found and the data in the literature. This review also calls for the establishment of regulations governing the consumption of these products in view of their potential impact on human health.

Oxidative Stress Markers in Human Brain and Placenta May Reveal the Timing of Hypoxic-Ischemic Injury: Evidence from an Immunohistochemical Study.

During pregnancy, reactive oxygen species (ROS) serve as crucial signaling molecules for fetoplacental circulatory physiology. Oxidative stress is thought to sustain the pathogenesis and progression of hypoxic-ischemic encephalopathy (HIE). A retrospective study was performed on the brains and placentas of fetuses and newborns between 36-42 weeks of gestation (Group_1: Fetal intrauterine deaths, Group_2: Intrapartum deaths, Group_3: Post-partum deaths, Control group sudden neonatal death); all groups were further divided into two subgroups (Subgroup_B [brain] and Subgroup_P [placenta]), and the study was conducted through the immunohistochemical investigations of markers of oxidative stress (NOX2, 8-OHdG, NT, iNOS), IL-6, and only on the brain samples, AQP4. The results for the brain samples suggest that NOX2, 8-OHdG, NT, iNOS, and IL-6 were statistically significantly expressed above the controls. iNOS was more expressed in the fetal intrauterine death (Group_1) and less expressed in post-partum death (Group_3), while in intrapartum death (Group_2), the immunoreactivity was very low. IL-6 showed the highest expression in the brain cortex of the fetal intrauterine death (Group_1), while intrapartum death (Group_2) and post-partum death (Group_3) showed weak immunoreactivity. Post-partum death (Group_3) placentas showed the highest immunoreactivity to NOX2, which was almost double that of the fetal intrauterine death (Group_1) and intrapartum death (Group_2) placentas. Placental tissues of fetal intrauterine death (Group_1) and intrapartum death (Group_2) showed higher expression of iNOS than post-partum death (Group_3), while the IL-6 expression was higher in the fetal intrauterine death (Group_1) than the post-partum death (Group_3). The AQP4 was discarded as a possible marker because the immunohistochemical reaction in the three groups of cases and the control group was negative. The goal of this study, from the point of view of forensic pathology, is to provide scientific evidence in cases of medical liability in the Obstetric field to support the clinical data of the timing of HIE.

Autoimmune Heart Disease: A Comprehensive Summary for Forensic Practice.

Autoimmune heart disease is a non-random condition characterised by immune system-mediated aggression against cardiac tissue. Cardiac changes often exhibit nonspecific features and, if unrecognised, can result in fatal outcomes even among seemingly healthy young individuals. In the absence of reliable medical history, the primary challenge lies in differentiating between the various cardiopathies. Numerous immunohistochemical and genetic studies have endeavoured to characterise distinct types of cardiopathies, facilitating their differentiation during autopsy examinations. However, the presence of a standardised protocol that forensic pathologists can employ to guide their investigations would be beneficial. Hence, this summary aims to present the spectrum of autoimmune cardiopathies, including emerging insights such as SARS-CoV-2-induced cardiopathies, and proposes the utilisation of practical tools, such as blood markers, to aid forensic pathologists in their routine practice.

Autoptic Findings in Cases of Sudden Death Due to Kawasaki Disease.

Kawasaki disease (KD) is the second-most-common childhood vasculitis, and its etiology is still unknown today. Even though the acute illness is usually self-limiting, sometimes, it can generate complications, such as coronary artery aneurysms (CAA), acute myocardial infarction (AMI), heart failure, or arrhythmias, and can rarely cause sudden or unexpected deaths. We present a review of the literature, which collects autoptic and histopathological data relating to many of the cases of these deaths. On the basis of the titles and abstracts, we selected 54 scientific publications for a total of 117 cases. Among them, as expected, the majority of the deaths were due to AMI (41.03%), arrhythmia (8.55%), acute coronary syndrome (8.55%), and CAA rupture (11.97%), involving mostly 20-year-olds or younger individuls (69.23%). This is not surprising since the CAs are the most involved arteries. Gross autoptic and histopathological findings are reported in the paper. Our work revealed that, when compared with the incidence of KD, only a few cases suffered from sudden death, underwent an autoptic examination, and were then described in the literature. We suggest that researchers should perform autopsies to gain a better understanding of the molecular pathways involved in KD so as to propose further innovative therapeutic protocols or implement more appropriate prevention schemes.

Correction: Aquaro et al. Post-Mortem Cardiac Magnetic Resonance in Explanted Heart of Patients with Sudden Death. Int. J. Environ. Res. Public Health 2022, 19, 13395.

The authors wish to make the following corrections to this paper [...].

New Insights into the Diagnosis and Age Determination of Retinal Hemorrhages from Abusive Head Trauma: A Systematic Review.

(1) Background: Head trauma represents the first cause of death in abused children, but diagnostic knowledge is still limited. The characteristic findings of abusive head trauma (AHT) are retinal hemorrhages (RH) and additional ocular findings, including optic nerve hemorrhages (ONH). However, etiological diagnosis must be cautious. (2) Methods: The Preferred Reporting Items for Systematic Review (PRISMA) standards were employed, and the research focus was the current gold standard in the diagnosis and timing of abusive RH. (3) Results: Sixteen articles were included for qualitative synthesis. The importance of an early instrumental ophthalmological assessment emerged in subjects with a high suspicion of AHT, with attention to the localization, laterality, and morphology of the findings. Sometimes it is possible to observe the fundus even in deceased subjects, but the current techniques of choice consist of Magnetic Resonance Imaging and Computed Tomography, also useful for the timing of the lesion, the autopsy, and the histological investigation, especially if performed with the use of immunohistochemical reactants against erythrocytes, leukocytes, and ischemic nerve cells. (4) Conclusions: The present review has made it possible to build an operational framework for the diagnosis and timing of cases of abusive retinal damage, but further research in the field is needed.

Analysis of Medico-Legal Complaint Data: A Retrospective Study of Three Large Italian University Hospitals.

(1) Background: Identifying hospital-related critical, and excellent, areas represents the main goal of this paper, in both a national and local setting. Information was collected and organized for an internal company's reports, regarding civil litigation that has been affecting the hospital, to relate the obtained results with the phenomenon of medical malpractice on a national scale. This is for the development of targeted improvement strategies, and for investing available resources in a proficient way. (2) Methods: In the present study, data from claims management in Umberto I General Hospital, Agostino Gemelli University Hospital Foundation and Campus Bio-Medico University Hospital Foundation, from 2013 to 2020 were collected. A total of 2098 files were examined, and a set of 13 outcome indicators in the assessment of "quality of care" was proposed. (3) Results: From the total number, only 779 records (37.1%) were attributable to the categories indexable for the present analysis. This data highlights how, following a correct and rigorous categorization of hospital events, it is possible to analyze these medico-legal aspects using a small number of indicators. Furthermore, it is important to consider how a consistent percentage of remaining events was difficult to index, and was also of poor scientific interest. (4) Conclusions: The proposed indicators do not require standards to be compared to, but provide a useful instrument for comparative purposes. In fact, in addition to comparative assessment between different business realities distributed throughout the territory, the use of outcome indicators allows for a longitudinal analysis evaluating the performance of an individual structure over time.

Assisted Suicide and Euthanasia in Mental Disorders: Ethical Positions in the Debate between Proportionality, Dignity, and the Right to Die.

The admission of people suffering from psychiatric and neurocognitive disorders to euthanasia and physician-assisted suicide (E/PAS) in some European and non-European countries represents a controversial issue. In some countries, the initial limitation of E/PAS to cases of severe physical illness with poor prognosis in the short term has been overcome, as it was considered discriminatory; thus, E/PAS has also been made available to subjects suffering from mental disorders. This decision has raised significant ethical questions regarding the capacity and freedom of self-determination; the family, social, and economic contexts; the social consideration of the sense of dignity and the pressure on the judgment of one's personal value; the contextual therapeutic possibilities; the identification of figures involved in the validation and application; as well as the epistemological definitions of the clinical conditions in question. To these issues must be added the situation of legislative vacuum peculiar to different countries and the widespread lack of effective evaluation and control systems. Nonetheless, pessimistic indicators on global health status, availability of care and assistance, aging demographics, and socioeconomic levels suggest that there may be further pressure toward the expansion of such requests. The present paper aims to trace an international overview with the aim of providing ethical support to the debate on the matter. Precisely, the goal is the delimitation of foundations for clinical practice in the complex field of psychiatry between the recognition of the irreversibility of the disease, assessment of the state of physical and mental suffering, as well as the possibility of adopting free and informed choices.

Molecular Autopsy in Asphyxia Deaths: Diagnostic Perspectives of miRNAs in the Evaluation of Hypoxia Response.

The forensic investigation of asphyxia deaths still poses a challenge due to the need to demonstrate vital exposure to hypoxic insult according to high levels of evidence. The pulmonary effects of hypoxia are complex and the understanding of the mechanisms underlying the acute pneumotoxicity induced by hypoxia is still incomplete. Redox imbalance has been suggested as the protagonist of the main acute changes in pulmonary function in the hypoxic context. The development of knowledge in biochemistry and molecular biology has allowed research in forensic pathology to identify some markers useful in immunohistochemical diagnostics of asphyxia deaths. Several studies have highlighted the diagnostic potential of markers belonging to the HIF-1α and NF-kB pathways. The central role of some highly specific microRNAs has recently been recognized in the complex molecular mechanisms involved in the hypoxia response; thus, several research activities are currently aimed at identifying miRNAs involved in the regulation of oxygen homeostasis (hypoxamiR). The aim of the manuscript is to identify, the miRNAs involved in the early stages of the cellular response to hypoxia, in order to characterize the possible implications in the forensic field of the determination of expression profiles. At present, more than 60 miRNAs involved in the hypoxia response with different expression profiles (upregulation and downregulation) have been identified. Despite the multiple and different effects on reprogramming following the hypoxic insult, the evaluation of the diagnostic implications of hypoxamiRs in the forensic field presupposes a specific treatment of the influences on HIF-1α regulation, cell cycle progression, DNA repair, and apoptosis.