Fat embolism: a systematic review to facilitate the development of standardised procedures in pathology.

Fat embolism (FE) is a historically recognised but still actively researched topic in forensic pathology. Several aspects remain not fully elucidated, such as its aetiopathogenesis, its causal role in death determination, the impact of interfering factors (e.g. cardiopulmonary resuscitation or other medical procedures) and both qualitative and quantitative diagnostic methodologies in clinical and forensic contexts. These issues are further underscored by the potential involvement of FE in the causal determination of non-traumatic deaths, which often raises questions of professional liability. The present study aims to provide a comprehensive and up-to-date overview of the most recent scientific evidence relevant to forensic pathology. Our systematic research has included 58 articles from 1990 to the present on the topic of FE and fat embolism syndrome (FES). From these articles, we identified 45 case reports, from which the authors' descriptions were extracted to provide information on individual cases and the operational methods of forensic pathologists. Additionally, 21 experimental studies were identified, and their key findings have been summarised narratively. It has emerged that both traumatic and non-traumatic cases are frequently reported in the forensic context, with orthopaedic and cosmetic surgery being among the highest-risk specialities. Experimental studies have re-evaluated the role of a patent foramen ovale in the pathogenesis of FE, as well as the impact of cardiopulmonary resuscitation in causing FE severe enough to result in death. Additionally, there are new findings regarding diagnostic techniques, including radiological and immunohistological methods; however, they have not yet fully bridged the reliability gap compared to an accurate autopsy-histological evaluation. The major critical points that emerged include the lack of complete and detailed information on premortem clinical conditions, the underutilisation of grading systems and the methodological heterogeneity applied, resulting in considerable variability regarding the organs studied histologically and the diagnostic techniques used. Despite the limitations associated with the analysis of case reports and the heterogeneity of included experimental studies, we believe that this study can provide a comprehensive overview of the FE topic. It furnishes pathologists with an updated overview useful for clinical practice and guiding future research trends, as well as facilitating the development of standardised procedures.

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.

Osmotic demyelination syndrome: revisiting the diagnostic criteria through two fatal cases.

BACKGROUND: Osmotic Demyelination Syndrome (ODS) encompasses Central Pontine Myelinolysis and Extrapontine Myelinolysis, both of which are serious neurological conditions linked to the overly rapid correction of hyponatremia. Despite growing evidence, the exact etiology of ODS remains incompletely understood. The present paper describes two case studies, aiming to provide a comprehensive overview of the pathological findings and clinical outcomes associated with ODS. CASE PRESENTATION: Case #1. A 74-year-old woman was admitted to the emergency department following a head trauma caused by a loss of consciousness. Initial laboratory tests revealed severe hyponatremia (sodium level of 101 mmol/L) and hypokalemia (potassium level of 2.9 mmol/L). The patient underwent corrective therapy with saline and potassium chloride. Despite the correction of electrolyte imbalances, the patient developed a hyperintense lesion in the median portion of the pons on T2-fluid-attenuated inversion recovery (FLAIR) MRI sequence 14 days post-treatment, consistent with ODS. The patient's condition deteriorated, leading to irreversible coma and status epilepticus, culminating in death 32 days after admission. Case #2. An 81-year-old woman with a medical history of hypothyroidism, hypertension, major depression, and stage 3 chronic kidney disease presented with mild gait disturbances. Subsequent testing revealed severe hyponatremia (sodium level of 100 mmol/L). Following an initial clinical improvement due to sodium correction, the patient's condition worsened, with symptoms progressing to confusion, lethargy, and eventually, ODS. Dermatological manifestations, including blistering lesions and facial edema, appeared as the condition advanced. The patient succumbed to irreversible coma 47 days after admission. CONCLUSION: ODS traditionally carried a poor prognosis, with high mortality rates and diagnoses often made postmortem. However, recent advances in understanding the pathophysiology, along with improvements in diagnostic techniques such as MRI and intensive care treatments, have led to earlier identification, treatment, and recognition of milder forms of the syndrome. Despite these advancements, ODS remains a critical condition with significant risks, particularly following the rapid correction of severe hyponatremia.

Analysis of miRNA Expression Profiles in Traumatic Brain Injury (TBI) and Their Correlation with Survival and Severity of Injury.

Traumatic brain injury (TBI) is the leading cause of traumatic death worldwide and is a public health problem associated with high mortality and morbidity rates, with a significant socioeconomic burden. The diagnosis of brain injury may be difficult in some cases or may leave diagnostic doubts, especially in mild trauma with insignificant pathological brain changes or in cases where instrumental tests are negative. Therefore, in recent years, an important area of research has been directed towards the study of new biomarkers, such as micro-RNAs (miRNAs), which can assist clinicians in the diagnosis, staging, and prognostic evaluation of TBI, as well as forensic pathologists in the assessment of TBI and in the estimation of additional relevant data, such as survival time. The aim of this study is to investigate the expression profiles (down- and upregulation) of a panel of miRNAs in subjects deceased with TBI in order to assess, verify, and define the role played by non-coding RNA molecules in the different pathophysiological mechanisms of brain damage. This study also aims to correlate the detected expression profiles with survival time, defined as the time elapsed between the traumatic event and death, and with the severity of the trauma. This study was conducted on 40 cases of subjects deceased with TBI (study group) and 10 cases of subjects deceased suddenly from non-traumatic causes (control group). The study group was stratified according to the survival time and the severity of the trauma. The selection of miRNAs to be examined was based on a thorough literature review. Analyses were performed on formalin-fixed, paraffin-embedded (FFPE) brain tissue samples, with a first step of total RNA extraction and a second step of quantification of the selected miRNAs of interest. This study showed higher expression levels in cases compared to controls for miR-16, miR-21, miR-130a, and miR-155. In contrast, lower expression levels were found in cases compared to controls for miR-23a-3p. There were no statistically significant differences in the expression levels between cases and controls for miR-19a. In cases with short survival, the expression levels of miR-16-5p and miR-21-5p were significantly higher. In cases with long survival, miR-21-5p was significantly lower. The expression levels of miR-130a were significantly higher in TBI cases with short and middle survival. In relation to TBI severity, miR-16-5p and miR-21-5p expression levels were significantly higher in the critical-fatal TBI subgroup. Conclusions: This study provides evidence for the potential of the investigated miRNAs as predictive biomarkers to discriminate between TBI cases and controls. These miRNAs could improve the postmortem diagnosis of TBI and also offer the possibility to define the survival time and the severity of the trauma. The analysis of miRNAs could become a key tool in forensic investigations, providing more precise and detailed information on the nature and extent of TBI and helping to define the circumstances of death.

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.

Capacity to Consent in Healthcare: A Systematic Review and Meta-Analysis Comparing Patients with Bipolar Disorders and Schizophrenia Spectrum Disorders.

Background: Mental capacity is a fundamental aspect that enables patients to fully participate in various healthcare procedures. To assist healthcare professionals (HCPs) in assessing patients' capacity, especially in the mental health field, several standardized tools have been developed. These tools include the MacArthur Competence Assessment Tool for Treatment (MacCAT-T), the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR), and the Competence Assessment Tool for Psychiatric Advance Directives (CAT-PAD). The core dimensions explored by these tools include Understanding, Appreciation, Reasoning, and Expression of a choice. Objective: This meta-analysis aimed to investigate potential differences in decision-making capacity within the healthcare context among groups of patients with bipolar disorders (BD) and schizophrenia spectrum disorders (SSD). Methods: A systematic search was conducted on Medline/Pubmed, and Scopus. Additionally, Google Scholar was manually inspected, and a manual search of emerging reviews and reference lists of the retrieved papers was performed. Eligible studies were specifically cross-sectional, utilizing standardized assessment tools, and involving patients diagnosed with BD and SSD. Data from the studies were independently extracted and pooled using random-effect models. Hedges' g was used as a measure for outcomes. Results: Six studies were identified, with three studies using the MacCAT-CR, two studies the MacCAT-T, and one the CAT-PAD. The participants included 189 individuals with BD and 324 individuals with SSD. The meta-analysis revealed that patients with BD performed slightly better compared to patients with SSD, with the difference being statistically significant in the domain of Appreciation (ES = 0.23, 95% CI: 0.01 to 0.04, p = 0.037). There was no statistically significant difference between the two groups for Understanding (ES = 0.09, 95% CI:-0.10 to 0.27, p = 0.352), Reasoning (ES = 0.18, 95% CI: -0.12 to 0.47, p = 0.074), and Expression of a choice (ES = 0.23, 95% CI: -0.01 to 0.48, p = 0.60). In the sensitivity analysis, furthermore, when considering only studies involving patients in symptomatic remission, the difference for Appreciation also resulted in non-significant (ES = 0.21, 95% CI: -0.04 to 0.46, p = 0.102). Conclusions: These findings indicate that there are no significant differences between patients with BD and SSD during remission phases, while differences are minimal during acute phases. The usefulness of standardized assessment of capacity at any stage of the illness should be considered, both for diagnostic-therapeutic phases and for research and advance directives. Further studies are necessary to understand the reasons for the overlap in capacity between the two diagnostic categories compared in this study.

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.

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.

FOXO3 Depletion as a Marker of Compression-Induced Apoptosis in the Ligature Mark: An Immunohistochemical Study.

One of the most challenging issues in forensic pathology is lesion vitality demonstration, particularly in cases of hanging. Over the past few years, immunohistochemistry has been applied to this field with promising results. In particular, protein and transcription factors involved in the apoptotic process have been studied as vitality markers for the ligature mark. This study represents an implementation of our previous studies on ligature mark vitality demonstration. In this study, we evaluated the FOXO3 expression in post-mortem cervical skin samples through an immunohistochemical analysis. To evaluate FOXO3 expression, anti-FOXO3 antibodies (GTX100277) were used. The study group comprised 21 cases, 8 women and 13 men, whereas the control group consisted of 13 cases of subjects who died due to other causes. Decomposition and no clear circumstantial data were exclusion criteria. We found that FOXO3 is decreased in hanging cases compared with normal skin in other causes of death (p-value < 0.05). No differences were seen concerning the type of hanging material (hard or soft), type of hanging (complete or incomplete), and position of the knot. Our results suggest that FOXO3 depletion could be a valid immunohistochemical marker of ligature mark vitality.

The Expression of FOXO3a as a Forensic Diagnostic Tool in Cases of Traumatic Brain Injury: An Immunohistochemical Study.

Traumatic brain injury (TBI) is one of the most well-known causes of neurological impairment and disability in the world. The Forkhead Box class O (FOXO) 3a is a transcription factor that is involved in different molecular processes, such as cell apoptosis regulation, neuroinflammation and the response to oxidative stress. This study is the first to evaluate the post-mortem immunohistochemical (IHC) positivity of FOXO3a expression in human cases of TBI deaths. The autopsy databases of the Legal Medicine and Forensic Institutes of the "Sapienza" University of Roma and the University of Pisa were retrospectively reviewed. After analyzing autopsy reports, 15 cases of TBI deaths were selected as the study group, while the other 15 cases were chosen among non-traumatic brain deaths as the control group. Decomposed bodies and those with initial signs of putrefaction were excluded. Routine histopathological studies were performed using hematoxylin-eosin (H&E) staining. Furthermore, an IHC investigation on cerebral samples was performed. To evaluate FOXO3a expression, anti-FOXO3a antibodies (GTX100277) were utilized. Concerning the IHC analysis, all 15 samples of TBI cases showed positivity for FOXO3a in the cerebral parenchyma. All control cerebral specimens showed FOXO3a negativity. In addition, the longer the survival time, the greater the positivity to the reaction with FOXO3a was. This study shows the important role of FOXO3a in neuronal autophagy and apoptosis regulation and suggests FOXO3a as a possible potential pharmacological target.

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.

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.

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.

6-Monoacetylmorphine-antibody distribution in tissues from heroin-related death cases: An experimental study to investigate the distributive response.

Heroin, a semisynthetic opioid drug synthesized from morphine, is the 3,6-diacetyl ester of morphine (diacetylmorphine). The post-mortem diagnosis of heroin-related death could be an issue and usually rely on a combination of investigations, including the autopsy, histological and toxicological analysis. We conducted the present study to evaluate the correlation between the heroin concentration in biological fluids (peripheral blood, bile and urine) and the post-mortem anti-6-MAM antibody expression in various tissues (brain, heart, lung, liver and kidney) using immunohistochemical staining. A quantitative analysis of the immunohistochemical reaction was carried out. 45 cases of heroin-related death investigated at the Forensic Pathology Institutes of the University of Rome, Foggia and Pisa were included. The control group was composed of 15 cases of death due to other causes, without brain lesions and negative toxicological analysis for drugs. We found a positive immunohistochemical reaction in different organs and it was related to the timing of heroin metabolization. No reaction was found in the control group. Our findings show that immunohistochemistry can be a valuable tool for the post-mortem diagnosis of acute heroin abuse. A better understanding of the timing of heroin's metabolism can be useful in the forensic field and for future therapeutic applications.

Anabolic androgenic steroids used as performance and image enhancing drugs in professional and amateur athletes: Toxicological and psychopathological findings.

OBJECTIVE: The use of anabolic androgenic steroids (AASs) as performance and image enhancing drugs (PIEDs), once restricted to professional athletes, now includes amateurs and regular gym visitors. AAS use is associated with psychopathology, yet this relationship is complex and not fully understood. We aimed to assess the presence of AASs and other misused substances in athletes' biological samples and link toxicological to psychopathological findings. METHODS: A multicentre, cross-sectional study in fitness centres in Italy recruited 122 professional and amateur athletes training in several sports (84 men; age range = 18-45 years). Athletes completed questionnaires, interviews, and toxicology testing for AASs, other PIEDs, illicit drugs, and non-prescribed psychotropics. Toxicology was conducted in blood, urine, and hair. RESULTS: Self-reported and toxicologically detected use rates of AASs and other misused substances showed slight-to-fair agreement (Fleiss' κ = 0.104-0.375). There was slight-to-moderate agreement among the three biological samples used for AAS testing (κ = 0.112-0.436). Thirty-one athletes (25.4%) tested positive for AASs. More sport hours/week, narcissistic or antisocial personality disorders, and higher nonplanning impulsiveness scores predicted AAS use (pseudo-R2  = 0.665). AAS users did not differ significantly from non-users in major psychopathology, but their Hypomania Checklist-32 score, which also predicted AAS use, was significantly higher (p < 0.001), suggesting increased odds for cyclothymic disorder or subthreshold hypomania. CONCLUSIONS: Our results have implications for studying AAS users, as they identify a cluster of variables that may be relevant in future understanding of AAS use risks (e.g., personality disorders). Possible disagreements between AAS assessment methods should be considered when implementing harm reduction interventions, such as needle and syringe distribution, health education, and counselling, as well as surveillance programmes.

Post-traumatic intracranial pseudo-aneurysms of posterior circulation: a comprehensive review of an under-diagnosed and rare entity.

Traumatic aneurysms are rare and the total number of cases involving the posterior circulation (TIPC) is even smaller. Traumatic brain injury (TBI) may be responsible not only of rupture in brain aneurysm (BrA) pre-existing to trauma, but it has been identified also as a possible pathogenetic cause of TIPC formation in patients not affected by intracranial vascular lesions. A complete literature review was performed of all reported cases regarding rupture of BrA with SAH resulting from TIPC not previously identified at the first radiological screening. A representative case of a left posterior inferior cerebellar artery (PICA) pseudo-aneurysm caused by left vertebral artery's dissection is reported. We show a unique complete collection of all 34 cases. Despite their rarity, TIPCs are associated with a significant morbidity and mortality rate, as high as 40-60%. Of the 22 patients with good neurological status (64.7%), we did not notice a significant correlation with regard to the location of the aneurysm, type of treatment, or clinical onset. Early recognition of a pseudo-aneurysm and adequate treatment seem to be the most important prognostic factor for these patients. Despite their rarity, TIPCs are associated with a significant morbidity and mortality rate. A TIPC should be suspected in case of delayed deterioration in head-injured patient and should be investigated with angiography. Conservative management is worsened by poor prognosis and the goal of treatment is to exclude the aneurysm from circulation with surgical or endovascular methods as soon as possible.

Glymphatic System a Window on TBI Pathophysiology: A Systematic Review.

BACKGROUND: In recent years, the attention of the scientific world has focused on a clearance system of brain waste metabolites, called the glymphatic system, based on its similarity to the lymphatic system in peripheral tissue and the relevant role of the AQP4 glial channels and described for the first time in 2012. Consequently, numerous studies focused on its role in organ damage in cases of neuropathologies, including TBI. METHODS: To evaluate the role that the glymphatic system has in the pathogenesis of TBI, on 23 March 2022, a systematic review of the literature according to PRISMA guidelines was carried out using the SCOPUS and Medline (via PubMed) databases, resulting in 12 articles after the selection process. DISCUSSION AND CONCLUSION: The present review demonstrated that an alteration of AQP4 is associated with the accumulation of substances S100b, GFAP, and NSE, known markers of TBI in the forensic field. In addition, the alteration of the functionality of AQP4 favors edema, which, as already described, constitutes alterations of secondary brain injuries. Moreover, specific areas of the brain were demonstrated to be prone to alterations of the glymphatic pathway, suggesting their involvement in post-TBI damage. Therefore, further studies are mandatory. In this regard, a study protocol on cadavers is also proposed, based on the analyzed evidence.

Expression of MicroRNAs in Sepsis-Related Organ Dysfunction: A Systematic Review.

Sepsis is a critical condition characterized by increased levels of pro-inflammatory cytokines and proliferating cells such as neutrophils and macrophages in response to microbial pathogens. Such processes lead to an abnormal inflammatory response and multi-organ failure. MicroRNAs (miRNA) are single-stranded non-coding RNAs with the function of gene regulation. This means that miRNAs are involved in multiple intracellular pathways and thus contribute to or inhibit inflammation. As a result, their variable expression in different tissues and organs may play a key role in regulating the pathophysiological events of sepsis. Thanks to this property, miRNAs may serve as potential diagnostic and prognostic biomarkers in such life-threatening events. In this narrative review, we collect the results of recent studies on the expression of miRNAs in heart, blood, lung, liver, brain, and kidney during sepsis and the molecular processes in which they are involved. In reviewing the literature, we find at least 122 miRNAs and signaling pathways involved in sepsis-related organ dysfunction. This may help clinicians to detect, prevent, and treat sepsis-related organ failures early, although further studies are needed to deepen the knowledge of their potential contribution.

State-of-the-Art on Wound Vitality Evaluation: A Systematic Review.

The vitality demonstration refers to determining if an injury has been caused ante- or post-mortem, while wound age means to evaluate how long a subject has survived after the infliction of an injury. Histology alone is not enough to prove the vitality of a lesion. Recently, immunohistochemistry, biochemistry, and molecular biology have been introduced in the field of lesions vitality and age demonstration. The study was conducted according to the preferred reporting items for systematic review (PRISMA) protocol. The search terms were "wound", "lesion", "vitality", "evaluation", "immunohistochemistry", "proteins", "electrolytes", "mRNAs", and "miRNAs" in the title, abstract, and keywords. This evaluation left 137 scientific papers. This review aimed to collect all the knowledge on vital wound demonstration and provide a temporal distribution of the methods currently available, in order to determine the age of lesions, thus helping forensic pathologists in finding a way through the tangled jungle of wound vitality evaluation.