Indirect DNA Transfer and Forensic Implications: A Literature Review.

Progress in DNA profiling techniques has made it possible to detect even the minimum amount of DNA at a crime scene (i.e., a complete DNA profile can be produced using as little as 100 pg of DNA, equivalent to only 15-20 human cells), leading to new defense strategies. While the evidence of a DNA trace is seldom challenged in court by a defendant's legal team, concerns are often raised about how the DNA was transferred to the location of the crime. This review aims to provide an up-to-date overview of the experimental work carried out focusing on indirect DNA transfer, analyzing each selected paper, the experimental method, the sampling technique, the extraction protocol, and the main results. Scopus and Web of Science databases were used as the search engines, including 49 papers. Based on the results of this review, one of the factors that influence secondary transfer is the amount of DNA shed by different individuals. Another factor is the type and duration of contact between individuals or objects (generally, more intimate or prolonged contact results in more DNA transfer). A third factor is the nature and quality of the DNA source. However, there are exceptions and variations depending on individual characteristics and environmental conditions. Considering that secondary transfer depends on multiple factors that interact with each other in unpredictable ways, it should be considered a complex and dynamic phenomenon that can affect forensic investigation in various ways, for example, placing a subject at a crime scene who has never been there. Correct methods and protocols are required to detect and prevent secondary transfer from compromising forensic evidence, as well as the correct interpretation through Bayesian networks. In this context, the definition of well-designed experimental studies combined with the use of new forensic techniques could improve our knowledge in this challenging field, reinforcing the value of DNA evidence in criminal trials.

Migrants' human rights and health protection during the COVID-19 pandemic in the Mediterranean Sea: what we have learnt from direct inspections in two Italian hotspots.

This study aims to assess the situation of Italian hotspots for migrant reception during the COVID-19 pandemic, and specifically analyzing the situation of two hotspots located in the Sicily Region (Pozzallo harbor and Lampedusa Island), to identify critical issues. At the same time, we hypothesize solutions to guarantee the respect of human rights and suggest an operational protocol to be applied in similar situations, considering that the migration phenomenon is increasing and involving new geographical areas. Based on data obtained through the site inspections, the facilities of Pozzallo and Lampedusa exceeded their capacity to adequately contain the spread of the SARS-CoV-2 infection. Considering these findings, we suggest a practical workflow summarizing the main actions that should be applied to contain COVID-19, or other infectious disease, spreading in hotspots for migrants. The impact of the COVID-19 pandemic on migrants has received limited attention, although the migration phenomenon did not slow down during the pandemic period. Regarding the risk of spreading infectious diseases such as COVID-19, it is necessary that those countries who are most exposed to migration flows, such as Italy, plan dedicated strategies to minimize the possibility of transmission of SARS-CoV-2, using adequate protocols to monitor the possible insurgence of variants of interest (VOIs) or variants of concern (VOCs). Finally, it is important to state that these suggestions could be applied in any future pandemics.

Requests for Compensation in Cases Involving Patients' Falls in Healthcare Settings: A Retrospective Analysis.

Falls are the most frequent adverse events recorded in healthcare facilities. By employing a multifaceted strategy to ensure prevention interventions that are specific to the patient type and environmental risk management, risk factor evaluation may help to reduce falls in the hospital setting. Patient falls are one of the main causes of lawsuits against hospitals, which has led to the development of validated instruments that are beneficial in treating the patient after the incident and effective in minimizing the frequency of falls. The aim of our study is to evaluate compensation claims asserting healthcare culpability in situations where a patient fell in a hospital setting. The collected data relate to judgments issued in Italy until December 2022 regarding 30 episodes of falls that occurred between 2003 and 2018. Our research revealed that approximately 50% of Italian healthcare organizations lose the case in court when a patient falls in a hospital setting and dies or is injured. In half of these cases, the failure of the medical staff to use protective equipment against falls is what led to the court's acceptance of the compensation claim. In order to improve the quality of healthcare services, fall prevention techniques must continue to be implemented.

New Insight into Mechanisms of Cardiovascular Diseases: An Integrative Analysis Approach to Identify TheranoMiRNAs.

MiRNAs regulate both physiological and pathological heart functions. Altered expression of miRNAs is associated with cardiovascular diseases (CVDs), making miRNAs attractive therapeutic strategies for the diagnosis and treatment of heart diseases. A recent publication defined, for the first time, the term theranoMiRNA, meaning the miRNAs that may be used both for diagnosis and treatment. The use of in silico tools may be considered fundamental for these purposes, clarifying several molecular aspects, suggesting future directions for in vivo studies. This study aims to explore different bioinformatic tools in order to clarify miRNA interactions with candidate genes, demonstrating the need to use a computational approach when establishing the most probable associations between miRNAs and target genes. This study focused on the functions of miR-133a-3p, miR-21-5p, miR-499a-5p, miR-1-3p, and miR-126-3p, providing an up-to-date overview, and suggests future lines of research in the identification of theranoMiRNAs related to CVDs. Based on the results of the present study, we elucidated the molecular mechanisms that could be linked between miRNAs and CVDs, confirming that these miRNAs play an active role in the genesis and development of heart damage. Given that CVDs are the leading cause of death in the world, the identification of theranoMiRNAs is crucial, hence the need for a definition of in vivo studies in order to obtain further evidence in this challenging field of research.

miRNA Dysregulation in Cardiovascular Diseases: Current Opinion and Future Perspectives.

MicroRNAs (miRNAs), small noncoding RNAs, are post-transcriptional gene regulators that can promote the degradation or decay of coding mRNAs, regulating protein synthesis. Many experimental studies have contributed to clarifying the functions of several miRNAs involved in regulatory processes at the cardiac level, playing a pivotal role in cardiovascular disease (CVD). This review aims to provide an up-to-date overview, with a focus on the past 5 years, of experimental studies on human samples to present a clear background of the latest advances to summarize the current knowledge and future perspectives. SCOPUS and Web of Science were searched using the following keywords: (miRNA or microRNA) AND (cardiovascular diseases); AND (myocardial infarction); AND (heart damage); AND (heart failure), including studies published from 1 January 2018 to 31 December 2022. After an accurate evaluation, 59 articles were included in the present systematic review. While it is clear that miRNAs are powerful gene regulators, all the underlying mechanisms remain unclear. The need for up-to-date data always justifies the enormous amount of scientific work to increasingly highlight their pathways. Given the importance of CVDs, miRNAs could be important both as diagnostic and therapeutic (theranostic) tools. In this context, the discovery of "TheranoMIRNAs" could be decisive in the near future. The definition of well-setout studies is necessary to provide further evidence in this challenging field.

Healthcare Liability and Thyroidectomy: When Is the Surgeon Wrong?

Thyroid surgeries can often lead to operative complications, sometimes with consequences on the patient's health. This often leads to claims for compensation but the assessments of consultants and judges are not always objective. Based on these considerations, the authors analyzed forty-seven sentences issued between 2013 and 2022 regarding claims of alleged medical malpractice. This analysis aims to examine the cases presented in the sentences and the evaluations proposed by the judges to offer ideas for objective evaluation by the legislation in force in Italy.

Impact of anabolic androgenic steroids on male sexual and reproductive function: a systematic review.

INTRODUCTION: Anabolic-androgenic steroids (AASs) are a complex cluster of synthetic derivatives of testosterone. AAS abuse is considered a major public health issue since it has increased among young/adolescent males. The use of steroids has a prevalence rate of 14% in young athletes and 30-75% in professional athletes or bodybuilders. AASs simulate the testosterone mechanism, binding the intracellular androgen receptor, and dysregulating the normal hypothalamic-pituitary-gonadal axis in the same way as exogenous testosterone. Abuse can produce several side effects on organs, such as the genital system. The physio-pathological mechanisms that cause AAS abuse-related, genital system disorders in humans are still not completely known. EVIDENCE ACQUISITION: This study focuses on the effect of AASs on the male reproductive organs in humans and animals. EVIDENCE SYNTHESIS: A systematic review was performed using SCOPUS, PubMed, Google Scholar, and Web of Sciences database up to 31 December 2021 using the keywords: "anabolic-androgenic steroids," "erectile dysfunction," "spermatogenesis" and "infertility;" (anabolic agents) "erectile dysfunction," "spermatogenesis" and "infertility." The review of the literature identified 66 articles published until 2021. Sixty-two articles were included. The use of AASs induces testicular atrophy and azoospermia known as "anabolic steroid-induced hypogonadism." Anabolic steroid induced infertility is characterized by oligo or azoospermia and abnormalities in sperm motility and morphology. Although sperm quality recovers in most cases within 4 months of stopping anabolic steroid abuse, the negative consequences on spermatogenesis can take up to 3 years to disappear. Human studies reported a positive correlation between AAS abuse in athletes and an increase in morphologically abnormal spermatozoa. Animal studies showed the destruction of Leydig cells and testicular atrophy in animals treated with cycles of AASs. CONCLUSIONS: The present review of the literature highlights how little is known about the action of AASs on the male genital system. However, although their use is prohibited in many countries, the black market for these substances is still very frequent. The scientific landscape still has a lot to invest in the research of AAS on the male genital system to make young people even more aware of the negative aspects of these substances, contributing to the reduction of these products in an inappropriate way.

Congenital Cystic Adenomatoid Malformation (CCAM) Type II: A Rare Case of Sudden Infant Death.

Congenital cystic adenomatoid malformation (CCAM) is a developmental lesion of the lungs and terminal respiratory structures, which is characterized by pseudocysts, lesions, and cystically dilated airways. CCAM is also known as congenital pulmonary airway malformation (CPAM). Various classification systems for CCAM have been described, and based on a recent classification, CCAMs are classified morphologically into five different types (Type 0, I, II, III, and IV) based on lesion sizes. The most common manifestation of CCAM in neonates and children is respiratory distress (RD). Spontaneous pneumothorax is a rare manifestation of CCAM. In this case report, we discuss a CCAM type-II case of a 38-day-old female infant with a radiological post-mortem diagnosis of a large left-side spontaneous pneumothorax. The gross examination of the lungs revealed multiple emphysematous air bubbles up to 0.5 cm in diameter, and the histological examination revealed focal pleural fibrosis, accompanied by thickened septa and atelectasis. In this scenario, the routine use of prenatal ultrasonography would be important to obtain a timely prenatal diagnosis. At the same time, improvements in surgical techniques, as well as greatly improved imaging techniques, have improved the outcome of these patients. Finally, it is important to remark on the importance of autopsy in the case of sudden infant death with a suspected CCAM.

Histological and immunohistochemical findings in a fatal case of thrombotic thrombocytopenia after ChAdOx1 nCov-19 vaccination.

This case report describes a fatal case of a young woman with superior sagittal, transverse and sigmoid sinus thrombosis after administration of the ChAdOx1 nCov-19 vaccination. Eleven days post-vaccination she was found unconscious and transferred to the Emergency Department. Blood parameters showed low platelets, and a CT scan showed an extensive left intracranial hemorrhage and the presence of an occlusive thrombus of the superior sagittal sinus. She under-went a craniectomy, but after the intervention, she remained in a comatose state. After a few days, her clinical conditions worsened, and she died. A complete autopsy was performed which showed a thrombosis of the cerebral venous district, of the upper and lower limbs. A blood sample was also performed to carry out a gene study about the predisposition to thrombosis. The organ samples were studied through light microscope both in hematoxylin-eosin and immunohistochemical examination, and showed a strong inflammatory response in all samples and at the site of thrombosis. Our study aims to provide a proper autopsy technique to study the entire cerebral venous system through a multidisciplinary approach (anatomical dissection and neurosurgery) in post-vaccine venous thrombosis.

Understanding the Relationship between Fetal Alcohol Spectrum Disorder (FASD) and Criminal Justice: A Systematic Review.

Prenatal alcohol exposure is considered one of the main causes of preventable birth disorders; however, it represents the main form of developmental delay in the world. Among the so-called secondary disabilities related to fetal alcohol spectrum disorder (FASD), there is a close connection with criminal behavior. This systematic review aims to provide up-to-date information about the relationship between FASD subjects and criminal justice analyzing different aspects. In light of the results of this review, a further goal is to provide several suggestions in order to reduce the public cost impact of FASD. A systematic review of the literature was conducted according to the PRISMA guidelines, producing 20 articles that met the inclusion criteria. Based on the results published in the selected studies, fetal alcohol syndrome (FAS) is a leading cause of preventable birth disorders and developmental disabilities in newborns. Moreover, these subjects seem to be more inclined to criminal acts compared to others. In conclusion, it should be pointed out that FASD entails high public health costs, both regarding the support measures provided to the affected individual and to their family, as well as the cost and social impact of any criminal offenses committed.

Vaccine-induced immune thrombotic thrombocytopenia with atypical vein thrombosis: Implications for clinical practice.

OBJECTIVES: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a new and rare syndrome resulting from the largest vaccination campaign against SARS-CoV-2 in the history of mankind. The aim of this review is to clarify underlying mechanisms, pathology, diagnosis, and therapy, with the related clinical implications. METHODS: We performed a comprehensive literature review in order to collect the clinical and treatment data about patients suffering from VITT. PubMed, Ovid Medline, Ovid EMBASE, Scopus, and Web of Science were screened regarding patients who developed VITT. Last search was launched on June 30th 2021. RESULTS: Abdominal and/or neurological symptoms develop between 5 and 20 days after vaccine administration and do not involve the lower extremities. VITT is suspected if the platelet count is lower than 100.000/mm3 and D-dimer is higher than the age-adjusted range. Medical treatment is mainly based on intravenous immunoglobulins, corticosteroids, and anticoagulant drugs with a short plasma half-life, but the complete avoidance of low molecular weight heparin is recommended. Endovascular treatment and/or decompressive craniectomy might be an option in a minority of cases. CONCLUSION: Due to widespread vaccination concerns, the vascular specialist and phlebologist are increasingly consulted to prevent or diagnose VITT. The latter has peculiar and completely different localizations, symptoms, and treatment compared to the common pictures of venous thrombosis.

Autopsy Findings and Causality Relationship between Death and COVID-19 Vaccination: A Systematic Review.

The current challenge worldwide is the administration of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. Considering that the COVID-19 vaccination represents the best possibility to resolve this pandemic, this systematic review aims to clarify the major aspects of fatal adverse effects related to COVID-19 vaccines, with the goal of advancing our knowledge, supporting decisions, or suggesting changes in policies at local, regional, and global levels. Moreover, this review aims to provide key recommendations to improve awareness of vaccine safety. All studies published up to 2 December 2021 were searched using the following keywords: "COVID-19 Vaccine", "SARS-CoV-2 Vaccine", "COVID-19 Vaccination", "SARS-CoV-2 Vaccination", and "Autopsy" or "Post-mortem". We included 17 papers published with fatal cases with post-mortem investigations. A total of 38 cases were analyzed: 22 cases were related to ChAdOx1 nCoV-19 administration, 10 cases to BNT162b2, 4 cases to mRNA-1273, and 2 cases to Ad26.COV2.S. Based on these data, autopsy is very useful to define the main characteristics of the so-called vaccine-induced immune thrombotic thrombocytopenia (VITT) after ChAdOx1 nCoV-19 vaccination: recurrent findings were intracranial hemorrhage and diffused microthrombi located in multiple areas. Moreover, it is fundamental to provide evidence about myocarditis related to the BNT162B2 vaccine. Finally, based on the discussed data, we suggest several key recommendations to improve awareness of vaccine safety.

Morphological Alterations and Stress Protein Variations in Lung Biopsies Obtained from Autopsies of COVID-19 Subjects.

Molecular chaperones, many of which are heat shock proteins, play a role in cell stress response and regulate the immune system in various ways, such as in inflammatory/autoimmune reactions. It would be interesting to study the involvement of these molecules in the damage done to COVID-19-infected lungs. In our study, we performed a histological analysis and an immunomorphological evaluation on lung samples from subjects who succumbed to COVID-19 and subjects who died from other causes. We also assessed Hsp60 and Hsp90 distribution in lung samples to determine their location and post-translational modifications. We found histological alterations that could be considered pathognomonic for COVID-19-related lung disease. Hsp60 and Hsp90 immunopositivity was significantly higher in the COVID-19 group compared to the controls, and immunolocalization was in the plasma membrane of the endothelial cells in COVID-19 subjects. The colocalization ratios for Hsp60/3-nitrotyrosine and Hsp60/acetylate-lisine were significantly increased in the COVID-19 group compared to the control group, similar to the colocalization ratio for Hsp90/acetylate-lisine. The histological and immunohistochemical findings led us to hypothesize that Hsp60 and Hsp90 might have a role in the onset of the thromboembolic phenomena that lead to death in a limited number of subjects affected by COVID-19. Further studies on a larger number of samples obtained from autopsies would allow to confirm these data as well as discover new biomarkers useful in the battle against this disease.

Do We Really Need Hazard Prevention at the Expense of Safeguarding Death Dignity in COVID-19?

To date, little is known regarding the transmission risks of SARS-CoV-2 infection for subjects involved in handling, transporting, and examining deceased persons with known or suspected COVID-19 positivity at the time of death. This experimental study aims to define if and/or how long SARS-CoV-2 persists with replication capacity in the tissues of individuals who died with/from COVID-19, thereby generating infectious hazards. Sixteen patients who died with/from COVID-19 who underwent autopsy between April 2020 and April 2021 were included in this study. Based on PMI, all samples were subdivided into two groups: 'short PMI' group (eight subjects who were autopsied between 12 to 72 h after death); 'long PMI' (eight subjects who were autopsied between 24 to 78 days after death). All patients tested positive for RT-PCR at nasopharyngeal swab both before death and on samples collected during post-mortem investigation. Moreover, a lung specimen was collected and frozen at -80 °C in order to perform viral culture. The result was defined based on the cytopathic effect (subjective reading) combined with the positivity of the RT-PCR test (objective reading) in the supernatant. Only in one sample (PMI 12 h), virus vitality was demonstrated. This study, supported by a literature review, suggests that the risk of cadaveric infection in cases of a person who died from/with COVID-19 is extremely low in the first hours after death, becoming null after 12 h after death, confirming the World Health Organization (WHO) assumed in March 2020 and suggesting that the corpse of a subject who died from/with COVID-19 should be generally considered not infectious.

Post-Mortem Detection of SARS-CoV-2 RNA in Long-Buried Lung Samples.

The Coronavirus Disease 19 (COVID-19) pandemic has caused an unexpected death toll worldwide. Even though several guidelines for the management of infectious corpses have been proposed, the limited number of post-mortem analyses during the pandemic has led to inaccuracies in the counting of COVID-19 deaths and contributed to a lack of important information about the pathophysiology of the SARS-CoV-2 infection. Due to the impossibility of carrying out autopsies on all corpses, the scientific community has raised the question of whether confirmatory analyses could be performed on exhumed bodies after a long period of burial to assess the presence of SARS-CoV-2 RNA. Post-mortem lung samples were collected from 16 patients who died from COVID-19 infection and were buried for a long period of time. A custom RNA extraction protocol was developed to enhance extraction of viral RNA from degraded samples and highly sensitive molecular methods, including RT-qPCR and droplet digital PCR (ddPCR), were used to detect the presence of SARS-CoV-2 RNA. The custom extraction protocol developed allowed us to extract total RNA effectively from all lung samples collected. SARS-CoV-2 viral RNA was effectively detected in all samples by both RT-qPCR and ddPCR, regardless of the length of burial. ddPCR results confirmed the persistence of the virus in this anatomical niche and revealed high viral loads in some lung samples, suggesting active infection at the time of death. To the best of our knowledge, this is the first study to demonstrate the persistence of SARS-CoV-2 viral RNA in the lung even after a long post-mortem interval (up to 78 days). The extraction protocol herein described, and the highly sensitive molecular analyses performed, could represent the standard procedures for SARS-CoV-2 detection in degraded lung specimens. Finally, the innovative results obtained encourage post-mortem confirmatory analyses even after a long post-mortem interval.

COVID-19 Vaccine and Death: Causality Algorithm According to the WHO Eligibility Diagnosis.

The current challenge worldwide is the administration of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines. Even if rarely, severe vascular adverse reactions temporally related to vaccine administration have induced diffidence in the population at large. In particular, researchers worldwide are focusing on the so-called "thrombosis and thrombocytopenia after COVID-19 vaccination". This study aims to establish a practical workflow to define the relationship between adverse events following immunization (AEFI) and COVID-19 vaccination, following the basic framework of the World Health Organization (WHO). Post-mortem investigation plays a pivotal role to support this causality relationship when death occurs. To demonstrate the usefulness and feasibility of the proposed workflow, we applied it to two exemplificative cases of suspected AEFI following COVID-19 vaccination. Based on the proposed model, we took into consideration any possible causality relationship between COVID-19 vaccine administration and AEFI. This led us to conclude that vaccination with ChAdOx1 nCov-19 may cause the rare development of immune thrombocytopenia mediated by platelet-activating antibodies against platelet factor 4 (PF4), which clinically mimics heparin-induced autoimmune thrombocytopenia. We suggest the adoption of the proposed methodology in order to confirm or rule out a causal relationship between vaccination and the occurrence of AEFI.

Pathological Findings in COVID-19 as a Tool to Define SARS-CoV-2 Pathogenesis. A Systematic Review.

Introduction: The World Health Organization declared the COVID-19 pandemic in March 2020. COVID-19 still represents a worldwide health emergency, which causesa severe disease that has led to the death of many patients. The pathophysiological mechanism of SARS-CoV-2 determining the tissue damage is not clear and autopsycan be auseful tool to improve the knowledge of this infection and, thus, it can help achieve a timely diagnosis and develop an appropriate therapy. This is an overview of the main post-mortem findings reporting data on the infection effects on several organs. Methods: A systematic literature search was conducted in the PubMed database searching for articles from 1 January to August 31, 2020. Thearticles were selected identifying words/concepts in the titles and/or abstracts that indicated the analysis of the morphological/pathological tissue injuries related to SARS-CoV-2 disease by several investigations. Results: A total of 63 articles were selected. The main investigated tissue was the lung showing a diffuse alveolar damage (DAD) frequently associated with pulmonary thrombotic microangiopathy. Inflammatory findings and vascular damage were observed in other organs such as heart, liver, kidney, brain, spleen, skin and adrenal gland. The immunohistochemical analysis showed tissue inflammatory cells infiltrates. The virus presence was detected by several investigations such as RT-PCR, immunohistochemistry and electron microscope, showing the effect ofSARS-CoV-2not exclusively in the lung. Discussion: The evidence emerging from this review highlighted the importance of autopsy to provide a fundamental base in the process of understanding the consequences ofSARS-CoV-2 infection. COVID-19 is strictly related to a hyper inflammatory state that seems to start with DAD and immuno-thrombotic microangiopathy. Massive activation of the immune system and microvascular damage might also be responsible for indirect damage to other organs, even if the direct effect of the virus on these tissues cannot be excluded.

Safe Management Strategies in Clinical Forensic Autopsies of Confirmed COVID-19 Cases.

To date, there is poor evidence on the transmission of infection in individuals handling the bodies of deceased persons infected with SARS-CoV-2 and in particular, during autopsies. The aim of this study was to demonstrate that when appropriate strategies are adopted autopsy is a safe procedure with a minimal infection risk for all subjects involved (pathologists, technical personnel, and others) when proper strategies are adopted. We performed 16 autopsies on cadavers of persons who had died with confirmed COVID-19 with different post-mortem intervals (PMI). To confirm the presence of SARS-CoV-2 RNA, for each autopsy, 2 swabs were sampled from lungs, while to evaluate environmental contamination, 11 swabs were taken at three different times: T0 (before autopsy), T1 (at the end of the autopsy, without removing the corpse), and T2 (after cleaning and disinfecting the autopsy room). Specifically, 2 swabs were sampled on face shields used by each pathologist, and 4 swabs were collected on the autopsy table; 4 swabs were also collected from walls and 1 from floor. Lung swabs confirmed the presence of SARS-CoV-2 RNA in all cases. Environmental swabs, collected at T0 and T2 were all negative, while swabs sampled at T1 were shown to be positive. Interestingly, no association was shown between PMI length and environmental contamination. Infection control strategies for safe management of clinical forensic autopsies of bodies with suspected or confirmed COVID-19 are also described.