The Role of miRNAs as New Molecular Biomarkers for Dating the Age of Wound Production: A Systematic Review

Background:The timing of wounds production is a significant issue in forensic pathology. Although various methods have been evaluated, obtaining an accurate dating of lesions is still a challenge. The pathologist uses many parameters to value wound age, such as histological and immunohistochemical. In recent years, there have been many studies regarding the use of miRNAs in wound-age estimation; indeed, miRNAs have multiple potential uses in forensic pathology.Scope:This review aims to verify the efficacy and feasibility of miRNAs as a tool for determining the timing of lesions.Materials and Methods:The authors conducted the systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. PubMed was used as a search engine to find articles published between January, 1st 2016 and October, 1st 2021, to evaluate the current state of the art regarding wound-age estimation.Results:A total of 256 articles were collected; after screening according to PRISMA guidelines, the systematic review included 8 articles. The studies included in this review were all Original articles evaluating the use of biomarkers for wound-age determination.Discussion and Conclusion:The literature review showed that analysis of miRNA is an innovative field of study with significant potentiality in forensic pathology. There are few studies, and almost all of them are at an early stage. The challenge is to understand how to standardize the samples' selection to obtain reliable experimental data. This observation represents a necessary prerequisite to planning further clinical trials.

Forensic Impact of the Omics Science Involved in the Wound: A Systematic Review

Background: In forensic autopsies, examining the wounds is one of the most critical aspects to clarify the causal relationship between the cause of death and the wounds observed on the corpse. However, on many occasions, it is difficult to differentiate antemortem injuries from post-mortem injuries, mainly when they occur very close to the moment of death. At present, various studies try to find biomarkers and clarify the molecular mechanisms involved in a wound due to the high variability of conditions in which they occur, thus being one of the most challenging problems in forensic pathology. This review aimed to study the omics data to determine the main lines of investigation emerging in the diagnosis of vital injuries, time of appearance, estimation of the age and vitality of the wound, and its possible contributions to the forensic field.Methods: A systematic review of the human wound concerning forensic science was carried out by following PRISMA guidelines.Results: This study sheds light on the role of omics research during the process of wounding, identifying different cytokines and other inflammatory mediators, as well as cells involved in the specific stage of the wound healing process, show great use in estimating the age of a wound. On the other hand, the expression levels of skin enzymes, proteins, metal ions, and other biomarkers play an essential role in differentiating vital and post-mortem wounds. More recent studies have begun to analyze and quantify mRNA from different genes that encode proteins that participate in the inflammation phase of a wound and miRNAs related to various cellular processes.Conclusions: This study sheds light on the role of research in the molecular characterization of vital wounds, heralding a promising future for molecular characterization of wounds in the field of forensic pathology, opening up an important new area of research.Systematic Review Registration: URL: https://www.crd.york.ac.uk/prospero/#myprospero, Identifier: CRD42021286623.

The Importance of BHB Testing on the Post-Mortem Diagnosis of Ketoacidosis

Although beta-hydroxybutyrate (BHB) analysis has proved its importance in forensic pathology, its effects on cause-of-death diagnostics are unaddressed. Therefore, this study aims at evaluating the effects of BHB analysis on the number of deaths by DKA (diabetes ketoacidosis), AKA (alcoholic ketoacidosis), HHS (hyperosmolar hyperglycaemic state), hypothermia, diabetes, alcoholism, and acidosis NOS (not otherwise specified). All 2900 deaths from 2013 through 2019 in which BHB was analysed at the National Board of Forensic Medicine, and 1069 DKA, AKA, HHS, hypothermia, diabetes, alcoholism, and acidosis cases without BHB analysis were included. The prevalence of BHB-positive cases for each cause of death, and trends and proportions of different BHB concentrations, were investigated. The number of BHB analyses/year increased from 13 to 1417. AKA increased from three to 66 and acidosis from one to 20. The deaths from alcoholism, DKA, and hypothermia remained stable. It is unclear why death from alcoholism remained stable while AKA increased. The increase in unspecific acidosis deaths raises the question why a more specific diagnosis had not been used. In conclusion, BHB analysis is instrumental in detecting AKA and acidosis. The scientific basis for the diagnosis of DKA and hypothermia improved, but the number of cases did not change.

Double Suicide Due to the Ingestion of Levamisole-Adulterated Cocaine: Case Report and Review of the Literature

Suicide is a major public health issue and the risk of attempting and committing suicide increases with age. We present the case of an elderly couple who decided to commit suicide together by self-poisoning using levamisole-adulterated cocaine. The choice of committing a double suicide, the method selected (self-poisoning), the drug self-administered (cocaine), and the route of administration (ingestion) are events rarely encountered in the forensic pathology practice, especially not in combination. In this article, we will review the literature regarding the frequency and features of these methods of suicide. An overview of the effects and mechanism of action of levamisole is also provided, highlighting the importance of including this substance and its metabolites in the routine toxicological analyses for cocaine deaths.

Bases of Forensic Pathology Expert Testimony With Emphasis on Iowa v Tyler

Judicial scrutiny of the forensic sciences is increasing. This scrutiny targets the bases for expert opinions. Forensic pathologists must understand that when they express an opinion it must have an articulable underlying basis. Iowa v Tyler provides a cautionary tale where testimony from a forensic pathologist on the cause and manner of death based exclusively on police reports and audio and video recordings of police interviews of the suspect rather than on medical evidence were held to be inadmissible. Tyler has an odd and distinguishable set of facts, but has been widely cited as an example of problematic forensic pathology testimony.

Research progress in the estimation of postmortem interval (PMI) using non-coding RNA (ncRNA) markers

Postmortem interval (PMI) estimation has always been a crucial focus and challenging issue in forensic pathology. In recent years, specific RNA molecules and their variation have been used worldwide to estimate PMI. In this review, we summarize the methods used to detect non-coding RNAs (ncRNAs) for PMI estimation based on the literature, show the existing problems and development trends, and provide technical references for relevant studies and estimation practices.

Firsthand Experience in Graduating Three Cohorts of Forensic Pathologists Trained With Competency by Design (CBD) Curriculum

Introduction: The University of Toronto experienced graduating three cohorts of forensic pathologists trained with Competency by Design (CBD) curriculum. We achieved this as a result of multiyear development of Entrustable Professional Activities (EPAs), Required Training Experience (RTEs), and Specialty Competency Requirements (SCRs) by the Royal College of Physicians and Surgeons of Canada’s Forensic Pathology Speciality Committee, the Ontario Forensic Pathology Service, and the University of Toronto. Method: Our academic year is comprised of 13 blocks. We divided the 13-block period into 4 stages to map all the EPAs and RTEs. The first stage, Transition to Discipline, is 1 block, the second stage, Foundation of Discipline, consists of 3 blocks; the third stage, Core of Discipline, consists of 6 blocks, and the final fourth stage, Transition to Practice, consists of 3 blocks. Board-certified faculty members in Forensic Pathology with more than five years of experience supervised the trainees. We graduated 5 Canadian and 4 international trainees at the end of the third cycle of CBD-based training program. Conclusion: Using the Royal College Speciality Committee blueprint, the University of Toronto started in 2016 planning the CBD curriculum in the forensic pathology training program. By the end of June 2021, we graduated nine trainees from our CBD-based Forensic Pathology training program. We are training the fourth cohort, and they will be graduating at the end of June 2022. This article aims to share our firsthand experiencing in CBD training in forensic pathology.

MiRNAs as New Tools in Lesion Vitality Evaluation: A Systematic Review and Their Forensic Applications

Wound vitality demonstration is one of the most challenging fields in forensic pathology. In recent years, researchers focused on the application of histological and immunohistochemical staining in this sphere of study. It is based on the detection of inflammation, red cell infiltration, and tissue alterations at the histological examination, all of which are supposedly present in antemortem rather than post-mortem wounds. Nevertheless, some doubts about the reliability of those markers have arisen. Furthermore, the lack of a standardized protocol and the operator dependency of this approach make the proper interpretation of its results difficult. Moreover, a differential miRNAs expression has been demonstrated in antemortem and post-mortem wounds. Herein, a systematic review concerning the current knowledge about the use of miRNAs in lesion vitality evaluation is carried out, to encourage researchers to deepen this peculiar study area. A compendium about the potential miRNAs that may be further investigated as vitality markers is also provided. The aim is to collect all available data about this topic to direct further studies on this field and highlight the future applications of miRNAs in forensic pathology. We found 20 articles and a total of 51 miRNAs that are involved in inflammation and wound healing. Further studies are certainly needed to deepen the role of miRNAs in inflammatory processes in lesioned skin and to evaluate their reliability in distinguishing between antemortem and post-mortem lesions.