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.

Multidisciplinary Forensic Approach in "Complex" Bodies: Systematic Review and Procedural Proposal.

The recovery of severely altered cadavers (i.e., extensively decomposed, mummified, charred or dismembered) can be a challenge for forensic pathologists due to the difficulties in identification, PMI estimation and manner and cause of death determination. In such cases, integrating routine approaches (autopsy, histology, toxicology) to more specific forensic branches can be fundamental to improving the investigative process. In this paper a systematic review using PubMed, Scopus and Web of Science databases has been performed. The aim was to evaluate the forensic approaches implemented in the management of severely altered bodies due to decomposition, mummification, skeletonization, charring or dismemberment (to which we refer to as "complex"), and the role of each approach in the solution of a case. Then, the literature revision results were used to propose a schematic flowchart summarizing the post mortem activities that can be performed in forensic practice, adaptable in relation to each case.

Suicide, depression and thyroid dysregulation: An unusual case of unplanned complex suicide.

Complex suicides are rare events pursued by the victims by means of two or more different fatal methods and can be further classified in planned or unplanned depending on the simultaneous or sequential application of the methods, respectively. The multiplicity of the injuries detected can frequently lead to misinterpretations, thus making a multidisciplinary approach of utmost importance. Here an unusual unplanned complex suicide was described discussing the post-mortem data leading to the forensic diagnosis; moreover, a focus on the depression cause was reported. The case regarded a 48-year-old man with a recent diagnosis of depression who self-stabbed his neck and, subsequentially, fallen from height. Data obtained from autopsy, histology, radiology and toxicology were described, highlighting the main findings for achieving the differential diagnosis between suicide and homicide. Moreover, microscopic findings compatible with an unrecognized thyroiditis led to consider the thyroid dysfunction as a possible substrate of depression, suggesting it potential effect on suicidal behaviour.

State of the Art on the Role of Postmortem Computed Tomography Angiography and Magnetic Resonance Imaging in the Diagnosis of Cardiac Causes of Death: A Narrative Review.

The need of a minimally invasive approach, especially in cases of cultural or religious oppositions to the internal examination of the body, has led over the years to the introduction of postmortem CT (PMCT) methodologies within forensic investigations for the comprehension of the cause of death in selected cases (e.g., traumatic deaths, acute hemorrhages, etc.), as well as for personal identification. The impossibility to yield clear information concerning the coronary arteries due to the lack of an active circulation to adequately distribute contrast agents has been subsequently overcome by the introduction of coronary-targeted PMCT Angiography (PMCTA), which has revealed useful in the detection of stenoses related to calcifications and/or atherosclerotic plaques, as well as in the suspicion of thrombosis. In parallel, due to the best ability to study the soft tissues, cardiac postmortem MR (PMMR) methodologies have been further implemented, which proved suitable for the detection and aging of infarcted areas, and for cardiomyopathies. Hence, the purpose of the present work to shed light on the state of the art concerning the value of both coronary-targeted PMCTA and PMMR in the diagnosis of coronary artery disease and/or myocardial infarction as causes of death, further evaluating their suitability as alternatives or complementary approaches to standard autopsy and histologic investigations.

An Insight into the Role of Postmortem Immunohistochemistry in the Comprehension of the Inflammatory Pathophysiology of COVID-19 Disease and Vaccine-Related Thrombotic Adverse Events: A Narrative Review.

On 11 March 2020, the World Health Organization (WHO) declared a pandemic due to the spread of COVID-19 from Wuhan, China, causing high mortality rates all over the world. The related disease, which mainly affects the lungs, is responsible for the onset of Diffuse Alveolar Damage (DAD) and a hypercoagulability state, frequently leading to Severe Acute Respiratory Syndrome (SARS) and multiorgan failure, particularly in old and severe-critically ill patients. In order to find effective therapeutic strategies, many efforts have been made aiming to shed light on the pathophysiology of COVID-19 disease. Moreover, following the late advent of vaccination campaigns, the need for the comprehension of the pathophysiology of the fatal, although rare, thrombotic adverse events has become mandatory as well. The achievement of such purposes needs a multidisciplinary approach, depending on a correct interpretation of clinical, biochemical, biomolecular, and forensic findings. In this scenario, autopsies have helped in defining, on both gross and histologic examinations, the main changes to which the affected organs undergo and the role in assessing whether a patient is dead "from" or "with" COVID-19, not to mention whether the existence of a causal link exists between vaccination and thrombotic adverse events. In the present work, we explored the role of postmortem immunohistochemistry, and the increasingly used ancillary technique, in helping to understand the mechanism underlying the pathophysiology of both COVID-19 disease and COVID-19 vaccine-related adverse and rare effects.

Caspase 9 and Caspase 3 Immunohistochemical Pattern in Skeletal and Cardiac Muscles at Different Times after Death: An Experimental Study on PMI Estimation.

(1) Background: The estimation of the post mortem interval (PMI) is a challenge for forensic pathologists because data emerging from methods commonly applied are not always conclusive, since several conditions exist that may affect the reliability of these parameters. Thus, new approaches have been proposed to overcome such a limit. In recent years, several studies have been performed on proteins analyzing their expression/degradation patterns in relation to the progressing of the post mortem interval. (2) Methods: The immunoreactivity patterns of two apoptosis mediators-Caspase 9 and Caspase 3-have been tested in order to evaluate their potential role as markers of the post mortem interval. The immunohistochemical analysis was performed on samples of skeletal and cardiac muscles obtained from rats at 0, 4, 8, 12, 24 and 72 h after death. (3) Results: The observed immunoreactivity patterns of both Caspase 9 and Caspase 3 showed a significant correlation with increasing post mortem interval either in skeletal or cardiac muscles, while the comparison of the immunoreactivity patterns of the two apoptotic mediators within each tissue appeared consistent with a preliminary activation of the "initiator" Caspase 9, which, in turn, subsequently activates the "executioner" Caspase 3. (4) Conclusion: The different expressions and decrease immunohistochemically observed on both caspases with progressing PMI support the usefulness of the combined analysis for post mortem interval estimation.

Investigation of the skin lesions in lightning strike death.

Lightning strike-related deaths are unusual, and the victim bodies can present different lesions due to the different injury mechanisms associated with this event. Since the post mortem assessment can be challenging, the evaluation of the characteristics of the skin lesions becomes fundamental to reconstruct the event. Due to the paucity of literature on this topic, the authors report the case of a 59-year-old man found dead near his home after a thunderstorm. Initially considered a murder by gunshot, the autopsy revealed the typical lightning strike lesions, also known as Lichtenberg figures. The adequate interpretation of the autopsy data and the histological evidences allowed to reconstruct the death dynamic and to relate it to a lightning strike. The main lesions due to lightening are here reported and discussed in order to provide a workflow for the identification of lightening as cause of death in unwitnessed cases.

Forensic investigative issues in a fireworks production factory explosion.

Since their discovery in ancient China, fireworks rapidly spread throughout the world, where they have always been used to celebrate either popular or private events. Their use is nonetheless related to several risks, especially within production factories, since several injuries or even death can occur following an accidental ignition. In cases of major disasters related to fireworks explosions, stating the accidental or intentional nature of the event might prove challenging, thus raising the need of a multidisciplinary approach. In this regard, we here discuss the case of an accidental explosion that occurred in a fireworks production factory, accountable for five deaths and two hospitalisations.

Unusual attempted suicide or covered attempted homicide? A neck stabbing case report and review of literature.

A medico-legal consult is frequently required in a clinical context in order to assess the eventual compatibility of specific wounds with a self- or hetero-infliction. Accordingly, the case of a 52-year-old man with a single, penetrating stab wound of the neck, reported as self-inflicted, is here presented. The forensic aspects, taken into account in order to determine the self- or hetero-infliction nature of the wound, are further discussed and compared to cases described in the literature.

Post-Mortem Investigations for the Diagnosis of Sepsis: A Review of Literature.

To date, sepsis is still one of the most important causes of death due to the difficulties concerning the achievement of a correct diagnosis. As well as in a clinical context, also in a medico-legal setting the diagnosis of sepsis can reveal challenging due to the unspecificity of the signs detected during autopsies, especially when no ante-mortem clinical data, laboratory, and cultural results are available. Thus, a systematic review of literature was performed to provide an overview of the main available and updated forensic tools for the post-mortem diagnosis of sepsis. Moreover, the aim of this review was to evaluate whether a marker or a combination of markers exist, specific enough to allow a correct and definite post-mortem diagnosis. The review was conducted searching in PubMed and Scopus databases, and using variable combinations of the keywords "post mortem sepsis diagnosis", "macroscopic signs", "morphology", "histology", "immunohistochemical markers", "biochemical markers", and "forensic microbiology". The article selection was carried out following specific inclusion and exclusion criteria. A total of 44 works was identified, providing data on morphological aspects of the organs examined, histological findings, immunohistochemical and biochemical markers, and cultural assays. The review findings suggested that the post-mortem diagnosis of sepsis can be achieved by a combination of data obtained from macroscopic and microscopic analysis and microbial investigations, associated with the increased levels of at least two of three biochemical and/or immunohistochemical markers evaluated simultaneously on blood samples.

Hanging disguised as bondage: accidental or suicidal death?

The concept of autoerotic asphyxiation refers to the use of devices or substances intended to enhance one's arousal by inducing cerebral hypoxia, which can involuntarily lead to death. Although in most cases death occurs accidentally, it is nonetheless true that the same devices might be used by the practitioners in order to attempt suicide. The case of a 34-year-old practitioner of autoerotic asphyxiation found dead in his apartment with bondage-like ligatures and masking is reported here. The case raised some issues concerning the accidental or suicidal nature of the act. The aspects taken into account in the management of the case are discussed, along with a compared approach to the data provided by literature.

Are there positive lessons for Italy's NHS resulting from the Covid-19 pandemic?

The authors evaluate the importance of prevention measures and health care from their own experience and briefly analyse the factors that may have contributed to the rapid spread of Covid-19 in Italy, and hope this will feed into appropriate and new and improved health policies.

A unique fatal case of Waterhouse-Friderichsen syndrome caused by Proteus mirabilis in an immunocompetent subject: Case report and literature analysis.

INTRODUCTION: The Waterhouse-Friderichsen syndrome (WFS), also known as purpura fulminans, is a potentially lethal condition described as acute hemorrhagic necrosis of the adrenal glands. It is often caused by infection. Classically, Neisseriae meningitidis represents the main microorganism related to WFS, although, infrequently, also other infectious agents are reported as a possible etiologic agent. The authors report the first case of death due to Proteus mirabilis infection, with postmortem evidence of WFS. PATIENT CONCERNS: After a facial trauma that provoked a wound on the nose, the subject, a healthy 40-years old man, was conducted to the local hospital (in Sicily, Italy) after the primary care he was discharged. Subsequently, after 2 days of general malaise, he returned to the hospital due to the worsening of the clinical condition. During the hospitalization, hypotension, and neurological impairment appeared; the laboratory analysis showed leukocytosis and the alteration of renal, hepatic and coagulative parameters. Microbiological blood analysis resulted positive for a P mirabilis infection. DIAGNOSIS: Multiorgan failure (MOF) with disseminated intravascular coagulation (DIC) due to sepsis was diagnosed. INTERVENTIONS: The practitioners administered intensive support, antibiotic therapy, antithrombin III, vitamin K, and plasma. OUTCOMES: After 3 days the subject died. The autopsy and the microscopic investigation were performed revealing, also, the adrenal diffuse micronodular hyperplasia associated with a cortico-medullary hemorrhagic apoplexy. CONCLUSION: To our knowledge, this is the first case of MOF with WFS due to P mirabilis infection. This case report suggests that P mirabilis should be added to the list of unusual bacteria causing WFS. Furthermore, it supports the theory that any bacterium which causes DIC may cause adrenal hemorrhage and should suggest to clinicians the importance to consider a potential adrenal involvement in every patient with sepsis and DIC.

Forensic microbiology applications: A systematic review.

According to the Human Microbiome Project (HMP), a healthy human body contains ten times more microbes than human cells. Microbial communities colonize different organs of the body, playing fundamental roles both in human health and disease. Despite the vast scientific knowledge of the role of microbial communities in a living body, little is known at present about microbial changes occurring after death, thus leading many authors to investigate the composition of the thanatomicrobiome and its potential applications in the forensic field. The aim of the following review is to provide a general overview of the advances of postmortem microbiology research, mainly focusing on the role of microbiological investigations carried out on internal organs and fluids. To this end, a total of 19 studies have been sistematically reviewed, each one chosen according to specific inclusion/exclusion criteria. The selected studies assess the contribution of contamination, postmortem transmigration and agonal spread to microbial isolation from dead body samples, and shed light on the role of postmortem microbiological investigations in several forensic fields, such as cause of death or PMI determination.