Asbestos exposure determined 357 days after death through autopsy: a report of a multidisciplinary approach.

Asbestosis is an interstitial lung disease caused by the inhalation of asbestos fibers and poses a significant risk to individuals working in construction, shipping, mining, and related industries. In a forensic context, postmortem investigations are crucial for accurate diagnosis, for which the gold standard is the histopathological examination. This case report describes the autopsy and related investigations conducted on an 84-year-old man, nearly one year (357 days) after his death. After a post-mortem CT scan, an autoptic investigation was performed, followed by histopathological, immunohistochemical, and scanning electron microscopy examinations. The integration of the evidence from these examinations with previously available personal and clinical information conclusively confirmed the diagnosis of asbestosis. We demonstrated the efficacy and reliability of our diagnostic protocol in detecting asbestosis and asbestos fibers and excluding mesothelioma even in decomposed tissues. According to our findings autopsy remains the diagnostic gold standard in cases of suspected asbestosis within a forensic context, even 1 year after death, therefore it is always highly recommended, even in cases where the body has decomposed.

Systematic Review of Fatal Sodium Nitrite Ingestion Cases: Toxicological and Forensic Implications.

Documented cases of sodium nitrite toxicity are almost exclusively caused by accidental ingestion; however, self-poisoning with sodium nitrite represents an increasing trend in nitrate-related deaths. This systematic review summarizes the most crucial evidence regarding the fatal toxicity of sodium nitrite. It identifies gaps and differences in the diagnostic forensic approaches and the detection methods of sodium nitrite intoxication. A total of eleven research articles were selected for qualitative and quantitative data. Most of the studies (6/11) were case reports. Fifty-three cases of fatal intoxication with sodium nitrite were chosen for the review. More research is required to develop cost-effective techniques and uniform cutoffs for blood nitrite and nitrate levels in the event of deadly sodium nitrite poisoning. There is still a lack of critical information on other matrices and the impact of time since death on toxicological results in such situations. The available evidence provides useful recommendations for forensic pathologists and health practitioners engaged in instances of sodium nitrite poisoning or death. The data should also set off alarm bells in the public health system, in prosecutor's offices, and for policymakers so that they may undertake preventative measures to stop and restrict the unregulated market for these substances.

Ethical and Forensic Issues in the Medico-Legal and Psychological Assessment of Women Asylum Seekers.

Asylum-seeking migrants represent a vulnerable segment of the population, and among them, women constitute an even more vulnerable group. Most of these women and girls have been exposed to threats, coercion, and violence of many kinds, including rape, forced prostitution, harassment, sexual slavery, forced marriage and pregnancy, female genital mutilation/excision, and/or other violations of their rights (e.g., deprivation of education, prohibition to work, etc.). The perpetrators of the violence from which they flee are often their own families, partners, and even institutional figures who should be in charge of their protection (such as police officers). In the process for the acceptance/rejection of an asylum application, the forensic and psychological certification can make the difference between successful and unsuccessful applications, as it can support the credibility of the asylum seeker through an assessment of the degree of compatibility between the story told and the diagnostic and forensic evidence. This is why constant and renewed reflection on the ethical, forensic, and methodological issues surrounding medico-legal and psychological certification is essential. This article aims to propose some reflections on these issues, starting from the experience of the inward healthcare service dedicated to Migrant Victims of Maltreatment, Torture, and Female Genital Mutilation operating since 2018 at the Institute of Forensic Medicine of the University Hospital of Palermo.

A fatal suicidal sodium nitrite ingestion determined six days after death.

Sodium nitrite (SN) is an inorganic salt that appears as a slightly yellowish crystalline solid, odorless, and highly soluble in water at room temperature. It is highly toxic to humans at specific doses because it can oxidize hemoglobin to methemoglobin, causing severe tissue hypoxia. A 20-year-old woman was unconscious in her bedroom and died shortly after that. Two days later, following the discovery of a jar of SN and a paper in which were written instructions on how to take it (and the website from which the procedure was learned) in the same room were death occurred, the Judicial Authority ordered the execution of the autopsy on the exhumed body of the young woman. The autopsy procedure was performed ∼ 2h after exhumation. It showed greyish-purple hypostasis, labial cyanosis, stomach distension and greenish color but empty, subpleural petechiae, brownish fluid in the pleural cavities (∼300 ml), congested and edematous lungs and diffuse visceral congestion. At autopsy, foamy liquid was observed at the lung section and subsequent squeezing. In addition, the autopsy showed edema and hemorrhagic petechiae of the laryngeal, glottal, and tracheal submucosa and green-brownish foamy liquid in the tracheal lumen. The cause of death was attributed tocardiac arrest induced by anoxia resulting from acute methemoglobinemia caused by sodium nitrite poisoning, intensified by severe malnutrition. Manner of death was suicidal.

The analysis of SUDEP forensic autopsies leading to preventable events.

Introduction: The diagnosis of unexpected death by excluding non-natural causes, particularly in subjects with epilepsy, is a topic of interest and it is difficult to identify in the forensic field. Health professionals sometimes are faced with cases of sudden death, generally in young adults with a long history of epilepsy that require, for judicial purposes, an explanation in terms of cause and means to determine the death. SUDEP is an entity diagnosed by the exclusion of other causes that may have led to death, and then for forensic purposes, it requires particular attention and knowledge, and there is difficulty in identifying it. Our contribution aims to illustrate the scientific community pathological findings, medical history, and circumstantial evidence of four cases of sudden death in epileptic subjects. Method: We illustrated four cases of judicial autopsies from the Institute of Forensic Medicine of Palermo, Italy; the purpose was to exclude the criminal intervention in determining the death as non-natural. The study of victims' medical history, the toxicological investigations, and the autopsy findings analyzed both from macroscopic and microscopic aspects have made it possible to highlight some findings that can be traced back to SUDEP despite the small sample of subjects studied. Results: These presented findings of four SUDEP cases could help forensic pathologists in recognizing this entity, by highlighting its characteristics, and allowing for a pathological classification, also in relation to the use of drugs for epilepsy treatment and circumstances of death. Discussion: To obtain a definite diagnosis of SUDEP, a complex investigation process is required in a multidisciplinary approach. Considering the literature review with criticism, it could allow health professionals to select the characteristics of epileptic patients at risk of sudden death. Processing human behaviors, molecular and histopathological findings of the autopsies, but also the physiological, and pathological human body system functions thanks to Artificial Intelligence, could be the key to explaining SUDEP mechanisms and the future results to prevent it.

A fatal case of paediatric post-traumatic pyomyositis.

A 6-year-old girl was brought to the emergency department with a history of an accidental fall a few days earlier. She presented with a fever, cough and constipation. Sars-CoV-2 infection being suspected, she was transferred to a paediatric facility for Covid-positive patients. During the diagnostic process, the clinical picture suddenly deteriorated with the development of bradycardia, tachypnea and altered sensorium. Despite cardiopulmonary resuscitation attempts, the child died about 16 hours after admission to the emergency department. A judicial forensic autopsy was performed that concluded that her death was due to multiple acute pulmonary, cardiac and renal infarctions secondary to septic thromboembolism in the course of post-traumatic bacterial necrotizing pyomyositis of the right ileo-psoas muscle.

Toxicological Analysis in Tissues Following Exhumation More Than Two Years after Death (948 Days): A Forensic Perspective in a Fatal Case.

Exhumations are performed in accordance with a court order and are crucial instruments in the investigation of death allegations. When a death is thought to be the result of drug misuse, pharmaceutical overdose, or pesticide poisoning, this process may be used on human remains. However, after a protracted postmortem interval (PMI), it might be difficult to detect the cause of death by looking at an exhumed corpse. The following case report reveals problems associated with postmortem drug concentration changes following exhumation more than two years after death. A 31-year-old man was found dead in a prison cell. Onan inspection of the place, two blister packs, one with a tablet and the other empty, were taken and kept by the police officers. The evening before, the deceased would have taken cetirizine and food supplements consisting of carnitine-creatine tablets. No relevant autopsy findings have been observed. The toxicological analysis was performed by gas chromatography coupled to mass spectrometry and was negative for substances of abuse. Proteomic analysis was positive for creatine detection and negative for other drugs (clarithromycin, fenofibrate, and cetirizine). The presented case shows the methods, the findings, and the limitations of toxicological analysis in an exhumation case with a long postmortem interval (PMI).

Dominant-negative variant in SLC1A4 causes an autosomal dominant epilepsy syndrome.

SLC1A4 is a trimeric neutral amino acid transporter essential for shuttling L-serine from astrocytes into neurons. Individuals with biallelic variants in SLC1A4 are known to have spastic tetraplegia, thin corpus callosum, and progressive microcephaly (SPATCCM) syndrome, but individuals with heterozygous variants are not thought to have disease. We identify an 8-year-old patient with global developmental delay, spasticity, epilepsy, and microcephaly who has a de novo heterozygous three amino acid duplication in SLC1A4 (L86_M88dup). We demonstrate that L86_M88dup causes a dominant-negative N-glycosylation defect of SLC1A4, which in turn reduces the plasma membrane localization of SLC1A4 and the transport rate of SLC1A4 for L-serine.

An Overview on the Use of miRNAs as Possible Forensic Biomarkers for the Diagnosis of Traumatic Brain Injury.

Determining the cause of death is one of the main goals of forensic pathology. However, conditions can occur in which common approaches-external inspection, autopsy, histology, etc.-might not be conclusive. With the advancement of molecular biology, several investigative techniques have been developed over the years, and the application as approaches complementary to routine procedures has proved useful in these cases. In this context, microRNA (miRNA) profiling has attracted increasing interest due to these molecules' ability to regulate physiological and pathological processes. The evidence of differential miRNA expression in both animal models and human samples of traumatic brain injury (TBI) has laid the basis for comprehension of the underlying pathophysiological mechanisms, thus allowing us to identify some of them as possible TBI diagnostic biomarkers. The present narrative review aims to explore the primary miRNAs involved in the mechanisms underlying TBI, which could be considered for future evaluation as possible markers in a post mortem setting.

Thiazides Attenuate Insulin Secretion Through Inhibition of Mitochondrial Carbonic Anhydrase 5b in ß -Islet Cells in Mice.

SIGNIFICANCE STATEMENT: Thiazide diuretics (thiazides) are among the most widely prescribed drugs worldwide, but their use is associated with glucose intolerance and new-onset diabetes mellitus. The molecular mechanisms remain elusive. Our study reveals that thiazides attenuate insulin secretion through inhibition of the mitochondrial carbonic anhydrase isoform 5b (CA5b) in pancreatic ß cells. We furthermore discovered that pancreatic ß cells express only one functional carbonic anhydrase isoform, CA5b, which is critical in replenishing oxaloacetate in the mitochondrial tricarboxylic acid (TCA) cycle (anaplerosis). These findings explain the mechanism for thiazide-induced glucose intolerance and reveal a fundamental role of CA5b in TCA cycle anaplerosis and insulin secretion in ß cells. BACKGROUND: Thiazide diuretics are associated with glucose intolerance and new-onset diabetes mellitus. Previous studies demonstrated that thiazides attenuate insulin secretion, but the molecular mechanisms remain elusive. We hypothesized that thiazides attenuate insulin secretion via one of the known molecular thiazide targets in ß cells. METHODS: We performed static insulin secretion experiments with islets of wild-type, Sodium/chloride co-transporter (NCC) (SLC12A3), and sodium-driven chloride/bicarbonate exchanger (NDCBE) (SLC4A8) knock-out (KO) mice and with murine Min6 cells with individual knockdown of carbonic anhydrase (CA) isoforms to identify the molecular target of thiazides in ß cells. CA isoform 5b (CA5b) KO mice were then used to assess the role of the putative thiazide target CA5b in ß -cell function and in mediating thiazide sensitivity in vitro and in vivo . RESULTS: Thiazides inhibited glucose- and sulfonylurea-stimulated insulin secretion in islets and Min6 cells at pharmacologically relevant concentrations. Inhibition of insulin secretion by thiazides was CO 2 /HCO 3- -dependent, not additive to unselective CA inhibition with acetazolamide, and independent of extracellular potassium. By contrast, insulin secretion was unaltered in islets of mice lacking the known molecular thiazide targets NCC or NDCBE. CA expression profiling with subsequent knockdown of individual CA isoforms suggested mitochondrial CA5b as a molecular target. In support of these findings, thiazides significantly attenuated Krebs cycle anaplerosis through reduction of mitochondrial oxaloacetate synthesis. CA5b KO mice were resistant to thiazide-induced glucose intolerance, and thiazides did not alter insulin secretion in CA5b KO islets. CONCLUSIONS: Thiazides attenuate insulin secretion via inhibition of the mitochondrial CA5b isoform in ß cells of mice.

Useful Evidence by Post-Mortem CT and Stereomicroscopy in Bone Injury: A Case Series from Forensic Practice.

The investigation of bone injuries is an essential topic in forensics. We sometimes have to deal with charred or dismembered human remains that have lost soft tissue, making it difficult to diagnose the mechanisms of injury that led to death. Our contribution aims to share with the scientific community how we approached two cases of very different bone injuries and the techniques used to differentiate relevant pathology findings of bone fragments. Two cases are analyzed from the case history of the forensic medicine institute of Palermo. PMCT made it possible to differentiate heat bone lesions from traumatic lesions. The stereomicroscope was superior to PMCT in being able to better characterize and evaluate shear injuries, allowing a more accurate measurement of acute lesions. Injury to bone remains can be appropriately investigated with rapid techniques such as PMCT and stereomicroscopy. The presented methodology shows the importance of a multidisciplinary approach when dealing with bone injuries in forensics that could find further applications in other circumstances to answer forensic questions.

Focus on Liability of Residences for Elderly and Sick People: A Case Series and Medico-Legal Issues.

Residences for elderly and sick people, self-sufficient or dependent, are varied. To date, the liability profiles of these structures are not clearly delineated, and increasingly often, their operating and organization criteria are entrusted to subnational, regional, or local regulations. Among the various deficits, there is the keeping of a complete and detailed documentation/diary of the patient, the lack of which can generate medico-legal problems. In this paper, we present three cases of guests in residences for a dependent person brought to the attention of the Institute of Forensic Medicine of the University Hospital of Palermo due to criminal proceedings, where the lack of existing documentation in the structure and, in some cases, the behavior of the professionals working there, led the evaluator to deduce the organization's culpability.

Torture and Maltreatment in Prison: A Medico-Legal Perspective.

The maltreatment and torture of prisoners constitute a global problem. Methods of maltreatment are classified as the psychological and the physical, and physical methods inevitably lead to psychological sequelae. Our review offers an analysis from the medico-legal perspective of the literature on the torture and physical and sexual abuse experienced by prisoners and their psychological sequelae and aims to investigate the medico-legal issues of investigating maltreatment in prison so as to suggest methodologies and updated approaches for dealing with such cases in a forensic context. We performed a comprehensive literature search of peer-reviewed publications (articles and reviews), research reports, case studies, books, service models, protocols, and institutional documents available online using key electronic databases (Scopus, PubMed) and search engines (Google Scholar) with the following keywords: physical violence, psychological violence, torture, maltreatment, physical abuse, psychological abuse AND prison OR prisoner OR jail OR custody. In the medical literature, most of the publications on torture are based on retrospective studies of torture among survivors and often refer to asylum seekers. Forensic evaluation is crucial for assessing the determinant elements of torture and maltreatment. A multidisciplinary approach and standardized and updated methodologies are needed to support policymakers, national institutions, and public health system initiatives in this field.

Intrauterine and Neonatal Exposure to Opioids: Toxicological, Clinical, and Medico-Legal Issues.

Opioids have a rapid transplacental passage (i.e., less than 60 min); furthermore, symptoms characterize the maternal and fetal withdrawal syndrome. Opioid withdrawal significantly impacts the fetus, inducing worse outcomes and a risk of mortality. Moreover, neonatal abstinence syndrome (NAS) follows the delivery, lasts up to 10 weeks, and requires intensive management. Therefore, the prevention and adequate management of NAS are relevant public health issues. This review aims to summarize the most updated evidence in the literature regarding toxicological, clinical, and forensic issues of intrauterine exposure to opioids to provide a multidisciplinary, evidence-based approach for managing such issues. Further research is required to standardize testing and to better understand the distribution of opioid derivatives in each specimen type, as well as the clinically relevant cutoff concentrations in quantitative testing results. A multidisciplinary approach is required, with obstetricians, pediatricians, nurses, forensic doctors and toxicologists, social workers, addiction specialists, and politicians all working together to implement social welfare and social services for the baby when needed. The healthcare system should encourage multidisciplinary activity in this field and direct suspected maternal and neonatal opioid intoxication cases to local referral centers.

Juvenile sudden cardiac death due to congenital coronary ostial valve-like ridges: A case report and literature review.

Coronary artery anomalies are a heterogeneous group of congenital disorders affecting the coronary pattern with a characteristic (origin, number, number of hosts, course, etc.). They are rarely found in the population. We report the case of a 21-year-old male who died from sudden cardiac death caused by an isolated coronary ostial obstruction, secondary to a rare anomaly, the presence of a valve-like ridge consisting of a small fold in the Valsalva aortic sinus. The study provides a brief literature review on the pathophysiology, diagnosis, and clinical and medico-legal issues in coronary artery anomaly cases that may be helpful in forensic practice when dealing with sudden cardiac death in young people and highlights key points for further research and public health measures.

Implementation of A Year-Long Antimicrobial Stewardship Program in A 227-Bed Community Hospital in Southern Italy.

BACKGROUND: Healthcare-Acquired Infections (HAIs) are serious healthcare complications affecting hospital stay, in-hospital mortality, and costs. Root cause analysis has identified the inappropriate use of antibiotics as the main causative factor in the expansion of multi-drug-resistant organisms (MDRO) in our hospital. An Antimicrobial Stewardship (AMS) program was implemented to optimize antibiotic use, limit the development of resistance, improve therapeutic efficacy and clinical outcomes, and reduce costs. METHODS: The stewardship strategies were: antimicrobial oversight on "critical" antibiotics; the development of hospital guidelines on antibiotic selection with the production of a consensus document; the implementation of clinical and management control algorithms with visual impact and Business Intelligence methods; training and updating; and the monitoring of outcome measures and process indicators. RESULTS: Clinical outcomes: length of stay reduced by 0.23 days, hospital readmission/first month rates decreased by 19%, and mortality for infections reduced by 8.8%. Microbiological Outcomes: Clostridium Difficile colitis incidence reduced by 9.1%.Economic Outcomes: Reduction in antimicrobial costs by 35% on average fee/discharged patient. CONCLUSIONS: The systematic application of the AMS program in a small hospital led to multiple improvements in clinical, microbiological, and economic outcome measures. The analysis of the core indicators for our hospital AMS program showed a significant adherence to the model and hospital recommendations.

Toxicological Findings of Self-Poisoning Suicidal Deaths: A Systematic Review by Countries.

The use of illicit and non-illicit substances is widespread in suicides. The toxicological data may help in understanding the mechanism of death. This systematic review aimed to analyze autopsies related to suicides by consuming poison, focusing on the correlation between substance use and the country of origin to create an alarm bell to indicate that suicide maybe attempted and prevent it. The systematic review was conducted according to the PRISMA guidelines, with the primary objective of identifying autopsies conducted in cases of suicide by consuming poison in specific geographic areas. Significant differences in substances were observed between low-income and Western countries that confirm previous literature data. In rural areas and Asian countries, most suicides by consuming poison involve the use of pesticides, such as organophosphates and carbamates. In Western countries, illicit drugs and medically prescribed drugs are the leading cause of suicide by self-poisoning. Future research should shed light on the correlation between social, medical, and demographic characteristics and the autopsy findings in suicides by self-poisoning to highlight the risk factors and implement tailored prevention programs worldwide. Performing a complete autopsy on a suspected suicide by self-poisoning could be essential in supporting worldwide public health measures and policy makers. Therefore, complete autopsies in such cases must be vigorously promoted.

EtG Quantification in Hair and Different Reference Cut-Offs in Relation to Various Pathologies: A Scoping Review.

Ethyl glucuronide (EtG) is a non-volatile, non-oxidative, hydrophilic, and stable ethanol phase II metabolite. EtG is produced through ethanol glucuronidation by UDP-glucuronosyltransferase (UGT), a phase II enzyme. EtG can be extracted from different biological matrices, including keratin ones, such as hair or nails. The purpose of this scoping review is to describe the relationship between EtG levels in hair and some of the most common and frequent pathological conditions and verify whether different reference cut-offs in relation to various pathologies have been identified in the scientific literature. In fact, in-depth knowledge of the influence of pathologies, such as diabetes mellitus, hepatic and renal dysfunction, on EtG production and its storage in keratin matrices would allow a more appropriate interpretation of obtained data and rule out false positives or false negatives. This scoping review is based on bibliographic research carried out on PubMed regarding the quantification of EtG in hair of subjects affected by different pathological conditions. According to the scientific literature, the main and most common pathologies that can affect the concentration of EtG in hair are liver and kidney diseases and diabetes. The EtG quantification analytical data should be interpreted carefully as they may have a great impact in both forensic and clinical contexts.

The Impact on Healthcare Workers of Italian Law n. 24/2017 "Gelli-Bianco" on Patient Safety and Medical Liability: A National Survey.

Italian "Gelli-Bianco" law (law n. 24 enacted by the Italian Government on 8 March 2017) introduced innovative changes and regulations regarding patient safety and healthcare workers' (HCWs) liability. We promoted a national survey to evaluate the effect of the law on HCWs. The questionnaire was edited and distributed using the free online tool "Google Forms" (Google LLC). The mode of administration chosen for the questionnaire was telematic self-completion. In particular, the questionnaire was sent to several portals of information, websites, in the scientific and medical sectors. Four hundred forty-five subjects participated in the survey. The differences in categorical variables for Gelli-Bianco Law reading with professional variables were analyzed in a univariate analysis using the Chi-square test and Fisher's exact test. Reading the law is significantly and positively related to knowledge and communication of adverse events and sentinel events, checklist adoption, and participation in educational activities on risk management. The law's implementation and promotion is a reliable educational tool for increasing patient safety culture and involving HCWs in risk management activities. Knowledge of the law, related education, and understanding of its application are still inadequate; therefore, educational programs regarding patient safety, risk management, and the contents of the law itself must be vigorously promoted to achieve clinical governance goals.

Discovery of novel gating checkpoints in the Orai1 calcium channel by systematic analysis of constitutively active mutants of its paralogs and orthologs.

In humans, there are three paralogs of the Orai Ca2+ channel that form the core of the store-operated calcium entry (SOCE) machinery. While the STIM-mediated gating mechanism of Orai channels is still under active investigation, several artificial and natural variants are known to cause constitutive activity of the human Orai1 channel. Surprisingly, little is known about the conservation of the gating checkpoints among the different human Orai paralogs and orthologs in other species. In our work, we show that the mutation corresponding to the activating mutation H134A in transmembrane helix 2 (TM2) of human Orai1 also activates Orai2 and Orai3, likely via a similar mechanism. However, this cross-paralog conservation does not apply to the "ANSGA" nexus mutations in TM4 of human Orai1, which is reported to mimic the STIM1-activated state of the channel. In investigating the mechanistic background of these differences, we identified two positions, H171 and F246 in human Orai1, that are not conserved among paralogs and that seem to be crucial for the channel activation triggered by the "ANSGA" mutations in Orai1. However, mutations of the same residues still allow gating of Orai1 by STIM1, suggesting that the ANSGA mutant of Orai1 may not be a surrogate for the STIM1-activated state of the Orai1 channel. Our results shed new light on these important gating checkpoints and show that the gating mechanism of Orai channels is affected by multiple factors that are not necessarily conserved among orai homologs, such as the TM4-TM3 coupling.