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Bruno A, Alessi M, Soresi S, et al. J Inflamm Res. 2011;4:51–59. The Editor and Publisher of Journal of Inflammation Research wish to retract the published article. Concerns were raised regarding the duplication of images in Figure 3 describing leptin receptor expression with those from an article published by the authors several years previously describing muscarinic receptor expression. Specifically: Figure 3A, Leptin receptor expression, Smokers, appears to have been duplicated with Figure 2 panel M3 COPD, for the expression of muscarinic receptors. Figure 3D, Leptin expression, Smokers, appears to have been duplicated with Figure 2 panel M1 Smokers, for the expression of muscarinic receptors. Figure 3A, Leptin receptor expression, Smokers, appears to share duplicated elements with Figure 3D, Leptin expression, Smokers. The authors did not respond to our queries and the Editor advised for the article to be retracted. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”. This retraction relates to this paper

Andreina Bruno1, Marinella Alessi2, Simona Soresi2, Anna Bonanno1, Loredana Riccobono1, Angela Marina Montalbano1, Giusy Daniela Albano1, Mark Gjomarkaj1, Mirella Profita11Institute of Biomedicine and Molecular Immunology, Italian National Research Council, Palermo, Italy; 2Dipartimento Biomedico di Biomedicina Interna e Specialistica, University Palermo, ItalyBackground: Leptin, a hormone produced mainly by adipose tissue, regulates food intake and energy expenditure. It is involved in inflammatory diseases such as chronic obstructive pulmonary disease (COPD) and its deficiency is associated with increased susceptibility to the infection. The leptin receptor is expressed in the lung and in the neutrophils.Methods: We measured the levels of leptin, tumor necrosis factor alpha (TNF-a) and soluble form of intercellular adhesion molecule-1 (sICAM-1) in sputum and plasma from 27 smoker and former smoker patients with stable COPD using ELISA methods. Further we analyzed leptin and its receptor expression in sputum cells from 16 COPD patients using immunocytochemistry.Results: In plasma of COPD patients, leptin was inversely correlated with TNF-a and positively correlated with the patient weight, whereas the levels of sICAM-1 were positively correlated with TNF-a. In sputum of COPD patients leptin levels were correlated with forced expiratory volume in 1 second/forced vitality capacity. Additionally, increased levels of sputum leptin and TNF-a were observed in COPD former smokers rather than smokers. Further the expression of leptin receptor in sputum neutrophils was significantly higher in COPD former smokers than in smokers, and the expression of leptin and its receptor was positively correlated in neutrophils of COPD former smokers.Conclusion: Our findings suggest a role of leptin in the local and systemic inflammation of COPD and, taking into account the involvement of neutrophils in this inflammatory disease, describe a novel aspect of the leptin/leptin receptor pathway in the regulation of host defense after smoking cessation.Keywords: COPD, smokers, inflammation, leptin, neutrophils

IL-17A drives inflammation and oxidative stress, affecting the progression of chronic lung diseases (asthma, chronic obstructive pulmonary disease (COPD), lung cancer, and cystic fibrosis). Oleuropein (OLP) is a polyphenolic compound present in olive oil and widely included in the Mediterranean diet. It exerts antioxidant and anti-inflammatory activities, oxidative stress resistance, and anticarcinogenic effects with a conceivable positive impact on human health. We hypothesized that OLP positively affects the mechanisms of oxidative stress, apoptosis, DNA damage, cell viability during proliferation, and cell growth in alveolar epithelial cells and tested its effect in a human alveolar epithelial cell line (A549) in the presence of IL-17A. Our results show that OLP decreases the levels of oxidative stress (Reactive Oxygen Species, Mitochondrial membrane potential) and DNA damage (H2AX phosphorylation-ser139, Olive Tail Moment data) and increases cell apoptosis in A549 cells exposed to IL-17A. Furthermore, OLP decreases the number of viable cells during proliferation, the migratory potential (Scratch test), and the single cell capacity to grow within colonies as a cancer phenotype in A549 cells exposed to IL-17A. In conclusion, we suggest that OLP might be useful to protect lung epithelial cells from oxidative stress, DNA damage, cell growth, and cell apoptosis. This effect might be exerted in lung diseases by the downregulation of IL-17A activities. Our results suggest a positive effect of the components of olive oil on human lung health.

(1) Background: Femicide is an increasing phenomenon consisting of the murder of a woman for gender-related reasons. Despite the enactment of new laws aimed at controlling the phenomenon by toughening the penalties and introducing aggravating circumstances, there is an increasing trend that testifies to the persistence of a flaw in the actual measures. (2) Case Presentation. We report the case of the murder of a 32-year-old woman-perpetrated by an ex-husband who refused to accept the end of the marriage-the analysis of which allowed us to frame the case as femicide. (3) Discussion. Despite global awareness of this phenomenon, the identification of risk factors to predict and prevent femicide is of utmost importance. This can be achieved by a multidisciplinary approach involving police officers, legal professionals, hospitals, governmental and nongovernmental organizations, and medico-legal departments aimed at promoting standardized methodologies. (4) Conclusions. We evaluate the contribution of forensic investigations to the identification of key elements that can help frame the murder of a woman as a femicide. Considering the devastating consequences for children who witness this kind of violence within the domestic setting, the planning of more impactful preventive actions is, thus, mandatory to minimize effects on public health.

Splenic rupture and hematoma are significant complications that can occur in patients with non-Hodgkin lymphoma (NHL). Understanding these associated complications is essential for optimal patient management and enhanced patient outcomes. Histopathological and immunohistochemical analyses are crucial in diagnosing NHL and assessing splenic involvement. In this study, a judicial autopsy had been requested by the Prosecutor's Office for a malpractice claim due to a fall in the hospital. In the Emergency Department, a 72-year-old man fell from a gurney and reported sustaining a wound to his forehead. No other symptoms were reported. A face and brain CT scan showed no abnormalities. Nine days after discharge, the patient presented with abdominal pain. An abdominal CT revealed splenic rupture and hemoperitoneum. The patient underwent open splenectomy but showed signs of hemodynamic shock and subsequently died. The evidence from the autopsy allowed us to diagnose mantle cell non-Hodgkin lymphoma with spleen involvement, previously unknown. Histopathological and immunohistochemical analyses were performed to assess the diagnosis of splenic rupture and estimate its timing. The findings strongly suggest that the splenic rupture was associated with the patient's fall and the pre-existing malignancy. This case highlights the importance of considering an underlying hematological malignancy when investigating delayed splenic rupture. An immunohistochemical study of spleen samples allowed the timing of splenic hematoma and rupture to be assessed, leading to the establishment of a causal relationship with trauma.

Frequent and excessive consumption of alcohol, be it episodic or sustained misuse, ranks among the top causes of mortality globally. This comprehensive analysis seeks to elucidate how alcohol misuse precipitates death, with a particular focus on associated cardiac anomalies. Notably, the phenomenon of "Holiday Heart Syndrome", linked to binge drinking, is recognized for inducing potentially fatal cardiac arrhythmias. Moreover, persistent alcohol consumption is implicated in the development of alcoholic cardiomyopathy, a condition that underlies heart failure and arrhythmic disturbances of the heart. Additionally, individuals undergoing withdrawal from alcohol frequently exhibit disruptions in normal heart rhythm, posing a risk of death. This review further delves into additional alcohol-related mortality factors, including the heightened likelihood of hypertension, cerebrovascular accidents (strokes), and the connection between excessive alcohol use and Takotsubo syndrome.

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., (© 2024. The Author(s).)

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.

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.

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.

Autophagy is the key process by which the cell degrades parts of itself within the lysosomes. It maintains cell survival and homeostasis by removing molecules (particularly proteins), subcellular organelles, damaged cytoplasmic macromolecules, and by recycling the degradation products. The selective removal or degradation of mitochondria is a particular type of autophagy called mitophagy. Various forms of cellular stress (oxidative stress (OS), hypoxia, pathogen infections) affect autophagy by inducing free radicals and reactive oxygen species (ROS) formation to promote the antioxidant response. Dysfunctional mechanisms of autophagy have been found in different respiratory diseases such as chronic obstructive lung disease (COPD) and asthma, involving epithelial cells. Several existing clinically approved drugs may modulate autophagy to varying extents. However, these drugs are nonspecific and not currently utilized to manipulate autophagy in airway diseases. In this review, we provide an overview of different autophagic pathways with particular attention on the dysfunctional mechanisms of autophagy in the epithelial cells during asthma and COPD. Our aim is to further deepen and disclose the research in this direction to stimulate the develop of new and selective drugs to regulate autophagy for asthma and COPD treatment.

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Argo, Puntarello, Malta, Buscemi, Scalzo, Triolo, Albano and Zerbo.)

Aims: The lung epithelial cells form a physical barrier to the external environment acting as the first line of defence against potentially harmful environmental stimuli. These cells interact with several other cellular components, of which macrophages are some of the most relevant. We analysed the effects of the PBDE-47 on the microRNA cargo of THP-1 macrophage like derived small Extracellular Vesicles (sEVs) and the effects on A549 lung epithelial cells., Main Methods: sEVs from M(LPS) THP-1 macrophage-like cells after PBDE-47 treatment (sEVs PBDE+LPS ) were characterized by nanoparticle tracking analysis and their microRNA cargo studied by qPCR. Confocal microscopy was applied to study sEVs cellular uptake by A549 cells. The expression of tight junctions (TJs), adhesion molecules, inflammation markers and mucus production in A549 cultured in air liquid interface (ALI) conditions were studied by Real Time PCR and confocal microscopy., Key Findings: sEVs PBDE+LPS microRNA cargo analysis showed that the PBDE-47 modulated the expression of the miR-15a-5p, miR29a-3p, miR-143-3p and miR-122-5p. Furthermore, ALI cultured A549 cells incubated with sEVs PBDE+LPS showed that zonula occludens-1 (p ≤ 0.04), claudin (p ≤ 0.02), E-cadherin (p ≤ 0.006) and Vimentin (p ≤ 0.0008) mRNAs were increased in A549 cells after sEVs PBDE+LPS treatment. Indeed, Interleukin (IL)-8 (p ≤ 0.008) and mucin (MUC5AC and MUC5B) (p ≤ 0.03 and p ≤ 0.0001) mRNA expression were up- and down-regulated, respectively., Significance: PBDE-47 treated macrophages secrete sEVs with altered microRNA cargo that affect the mRNA expression of TJs, adhesion molecules, cytokines and EMT markers damaging the normal function of the lung epithelium, potentially contributing to the development of lung diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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.

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.

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.

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.

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.

Inflammation of the human lung is mediated in response to different stimuli (e.g., physical, radioactive, infective, pro-allergenic, or toxic) such as cigarette smoke and environmental pollutants. These stimuli often promote an increase in different inflammatory activities in the airways, manifesting themselves as chronic diseases (e.g., allergic airway diseases, asthma chronic bronchitis/chronic obstructive pulmonary disease, or even lung cancer). Non-coding RNA (ncRNAs) are single-stranded RNA molecules of few nucleotides that regulate the gene expression involved in many cellular processes. ncRNA are molecules typically involved in the reduction of translation and stability of the genes of mRNAs s. They regulate many biological aspects such as cellular growth, proliferation, differentiation, regulation of cell cycle, aging, apoptosis, metabolism, and neuronal patterning, and influence a wide range of biologic processes essential for the maintenance of cellular homeostasis. The relevance of ncRNAs in the pathogenetic mechanisms of respiratory diseases has been widely established and in the last decade many papers were published. However, once their importance is established in pathogenetic mechanisms, it becomes important to further deepen the research in this direction. In this review we describe several of most recent knowledge concerning ncRNA (overall miRNAs) expression and activities in the lung.

Inflammation of the human lung is mediated in response to different stimuli (e.g., physical, radioactive, infective, pro-allergenic or toxic) such as cigarette smoke and environmental pollutants. They often promote an increase in inflammatory activities in the airways that manifest themselves as chronic diseases (e.g., allergic airway diseases, asthma, chronic bronchitis/chronic obstructive pulmonary disease (COPD) or even lung cancer). Increased levels of oxidative stress (OS) reduce the antioxidant defenses, affect the autophagy/mitophagy processes, and the regulatory mechanisms of cell survival, promoting inflammation in the lung. In fact, OS potentiate the inflammatory activities in the lung, favoring the progression of chronic airway diseases. OS increases the production of reactive oxygen species (ROS), including superoxide anions (O 2 - ), hydroxyl radicals (OH) and hydrogen peroxide (H 2 O 2 ), by the transformation of oxygen through enzymatic and non-enzymatic reactions. In this manner, OS reduces endogenous antioxidant defenses in both nucleated and non-nucleated cells. The production of ROS in the lung can derive from both exogenous insults (cigarette smoke or environmental pollution) and endogenous sources such as cell injury and/or activated inflammatory and structural cells. In this review, we describe the most relevant knowledge concerning the functional interrelation between the mechanisms of OS and inflammation in airway diseases.

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 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.

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.

The best evidence provided in the literature worldwide suggests the importance of harmonizing the investigation in drug-related fatalities. In this study, the application of a multidisciplinary approach in eight cases of drug-related deaths is presented. Although death scene findings could be highly suggestive of drug intoxication, external examination and toxicological screening test alone are insufficient. There are several variables, and it is not always easy to give the proper interpretation of the drug detection. A complete autopsy is necessary to correctly complete organ and tissues sampling for further histological and toxicological studies and obtain body fluids. The use of peripheral blood is recommended to avoid artifacts. The collection of many specimens is warranted to get more responses. The sampling aims to provide a picture of the distribution of the substance in the body. The sample and the selection of the drugs and the matrices to investigate are case-dependent. The presented diagnostic algorithm provides the coroner with all the elements to investigate drug-related deaths and cooperate with toxicologists. Toxicological forensic diagnosis is still extremely heterogeneous in regional and national contexts. Funding for method development, research, networking, facilities, and technologies improvement is mandatory to standardize the toxicological investigation.

Biomedical research is multidisciplinary and often uses integrated approaches performing different experimental models with complementary functions. This approach is important to understand the pathogenetic mechanisms concerning the effects of environmental pollution on human health. The biological activity of the substances is investigated at least to three levels using molecular, cellular, and human tissue models. Each of these is able to give specific answers to experimental problems. A scientific approach, using biological methods (wet lab), cell cultures (cell lines or primary), isolated organs (three-dimensional cell cultures of primary epithelial cells), and animal organisms, including the human body, aimed to understand the effects of air pollution on the onset of diseases of the respiratory system. Biological methods are divided into three complementary models: in vitro, ex vivo, and in vivo. In vitro experiments do not require the use of whole organisms (in vivo study), while ex vivo experiments use isolated organs or parts of organs. The concept of complementarity and the informatic support are useful tools to organize, analyze, and interpret experimental data, with the aim of discussing scientific notions with objectivity and rationality in biology and medicine. In this scenario, the integrated and complementary use of different experimental models is important to obtain useful and global information that allows us to identify the effect of inhaled pollutants on the incidence of respiratory diseases in the exposed population. In this review, we focused our attention on the impact of air pollution in airway diseases with a rapid and descriptive analysis on the role of epithelium and on the experimental cell models useful to study the effect of toxicants on epithelial cells.

The airway epithelium is a dynamic tissue that undergoes slow but constant renewal. Dysregulation of airway epithelial function related to cigarette smoke exposure plays an important role in the pathophysiology of COPD. Oct4 is a transcription factor responsible for maintaining cellular self-renewal and regeneration, and CD146 and CD105/Endoglin are adhesion molecules involved in cell proliferation, differentiation, epithelial-mesenchymal-transition and tissue remodeling. Bronchial biopsy specimens (BBs) were obtained from 7 healthy controls (HC) and 10 COPD and subjected to paraffin embedding; BBs from HC were also used for epithelial cell expansion and pHBEC/ALI (air-liquid interface) culture. pHBEC/ALI were exposed to cigarette smoke extract (CSE) for 7, 14 and 21 days. In BBs, Oct4, CD146 and CD105 were evaluated by immunohistochemistry. In pHBEC/ALI, the expression of Oct4, CD146, CD105 and acetyl-αtubulin was evaluated by Western Blot, MUC5AC and IL-8 measurements by ELISA. The Oct4 epithelial immunoreactivity was lower in COPD than in HC, whilst CD146 and CD105 expression was higher in COPD than in HC. In pHBEC/ALI, Transepithelial Electrical Resistance values, measured over 7 to 21 days of differentiation, decreased by 18% (2.5% CSE) and 29% (5% CSE) compared to untreated samples. Oct4 and acetyl-αtubulin were induced after one-week differentiation and downregulated by CSE in reconstituted epithelium; CD146, CD105, MUC5AC and IL-8 were increased by CSE. Oct4 de-regulation and CD146 and CD105 overexpression, induced by cigarette smoke exposure, might play a role in airway epithelial dysfunction by causing changes in self-renewal and mesenchymal transition mechanisms, leading to alteration of epithelium homeostasis and abnormal tissue remodeling involved in progression of COPD., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The role of PAR-1 expression and activation was described in epithelial cells from the central and distal airways of COPD patients using an ex vivo/in vitro model. PAR-1 immunoreactivity was studied in epithelial cells from surgical specimens of the central and distal airways of COPD patients and healthy control (HC). Furthermore, PAR-1 expression and activation were measured in both the human bronchial epithelial cell line (16HBE) and normal human bronchial epithelial cells (NHBEs) exposed to cigarette smoke extract (CSE) (10%) or thrombin. Finally, cell proliferation, apoptosis, and IL-8 release were detected in stimulated NHBEs. We identified higher levels of PAR-1 expression/activation in epithelial cells from the central airways of COPD patients than in HC. Active PAR-1 increased in epithelial cells from central and distal airways of COPD, with higher levels in COPD smokers (correlated with pack-years) than in COPD ex-smokers. 16HBE and NHBEs exposed to CSE or thrombin showed increased levels of active PAR-1 (localized in the cytoplasm) than baseline conditions, while NHBEs treated with thrombin or CSE showed increased levels of IL-8 proteins, with an additional effect when used in combination. Smoking habits generate the upregulation of PAR-1 expression/activation in airway epithelial cells, and promoting IL-8 release might affect the recruitment of infiltrating cells in the airways of COPD patients.

Aims: We aimed to investigate the effect of PBDEs (47, 99, 209) on cellular events involved in epigenetic modification, inflammation, and epithelial mesenchymal transition (EMT)., Materials and Methods: We studied: 1) ERK1/2 phosphorylation; 2) Enhancer of Zester Homolog 2 (EZH2); 3) Histone H3 tri-methylated in lysine 27 (H3K27me3); 4) K-RAS; 5) silencing disabled homolog 2-interacting protein gene (DAB2IP), 6) let-7a; 7) Muc5AC/Muc5B, and 8) IL-8 in a 3D in vitro model of epithelium obtained with primary Normal Human Bronchial Epithelial cells (pNHBEs) or A549 cell line, chronically exposed to PBDEs (47, 99, 209)., Key Findings: PBDEs (10 nM, 100 nM and 1 μM) increased ERK1/2 phosphorylation, and EZH2, H3K27me3, and K-RAS protein expression, while decreased DAB2IP and Let-7a transcripts in pNHBEs ALI culture. Furthermore PBDEs (47, 99) (100 nM) increased Muc5AC and Muc5B mRNA, and PBDE 47 (100 nM) IL-8 mRNA via EZH2 in pNHBEs. Finally, PBDEs (100 nM) affected EZH2, H3K27me3, K-RAS protein expression, and DAB2IP, Let-7a transcripts and cell invasion in A549 cells. Gsk343 (methyltransferase EZH2 inhibitor) (1 mM) and U0126 (inhibitor of MEK1/2) (10 μM) were used to show the specific effect of PBDEs., Significance: PBDE inhalation might promote inflammation/cancer via EZH2 methyltransferase activity and H3K27me3, k-RAS and ERk1/2 involvement, generating adverse health outcomes of the human lung., (Copyright © 2021 Elsevier Inc. All rights reserved.)