Histologic correlates of "Choroidal abnormalities" in Neurofibromatosis type 1 (NF1).

Neurofibromatosis type 1 (NF1) is a rare autosomal dominant disorder characterized by proliferation of cells from neural crest origin. The most common manifestations are cutaneous, neurologic, skeletal and ocular. The distinction of NF1 from other syndromes with multiple café-au-lait macules may be difficult in the pediatric age group, and ocular findings, especially Lisch nodules (i.e., melanocytic hamartomas on the irides), are a useful, early diagnostic tool. In recent years, novel ocular manifestations descriptively referred to as "choroidal abnormalities", choroidal "hyperpigmented spots" and "retinal vascular abnormalities" have been recognized in NF1. Choroidal abnormalities (CA) appear as bright patchy nodules that can be best detected with near-infrared ocular coherence tomography imaging (NIR-OCT). Because of their high specificity and sensitivity for NF1, CA have been added as an ocular diagnostic criterion of NF1 as an alternative to Lisch nodules. Although CA are important ocular diagnostic criteria for NF1, the histologic correlates are controversial. We present the postmortem ocular pathology findings of an NF1 patient for whom clinical notes and ocular imaging were available. Findings in this patient included choroidal hyperpigmented spots on funduscopy and retinal vascular abnormalities, both of which have been reported to be closely associated with CA. Histologic examination of the eyes showed multiple clusters of melanocytes of varying sizes in the choroid. Pathologic review of 12 additional postmortem eyes from 6 NF1 patients showed multiple, bilateral choroidal melanocytic aggregates in all eyes. These findings suggest that the CA seen on NIR-OCT and the hyperpigmented spots seen clinically in NF1 patients are manifestations of multifocal choroidal melanocytic clusters, consistent with choroidal melanocytic hamartomas. Lisch nodules, often multiple, were present in all eyes with morphology that differed from the choroidal hamartomas. As such, although CA and Lisch nodules are melanocytic hamartomas, there are clear phenotypical differences in their morphologies.

Fatal Viral and Bacterial Septicemia in a Seventeen-Year-Old Woman with Immunodepressive Influenza A H1N1: An Autopsy Case.

Abstract: The Influenza A H1N1 subtype can present with a wide spectrum of severity, from mild symptoms of influenza to severe respiratory distress. The morbidity and mortality connected to influenza are mostly associated with secondary bacterial infections. The influenza syndrome alone can cause a massive release of cytokines with dysregulation of the immune system, and it can act in synergy with other bacteria which can enhance cytokines secretion. This article deals with a case of severe pneumonia of H1N1 in a 17-year-old woman with bacterial superinfection with Staphylococcus aureus characterized by a high level of interleukine-6 (105900 pg/mL) and the appearance of severe leukopenia with immuno-suppression, such that HIV infection and hematological diseases were included in the initial differential diagnosis. After death, the autopsy confirmed the presence of severe pneumonia, in addition to an hepatic steatosis in absence of other risk factors. This case reports the rapid and lethal course of influenza A /H1N1 in a young and healthy subject without comorbidities, in an age group in which mortality is about 0.3 deaths per 100,000. The case underlines the importance of quickly diagnosis of viral infections and the differential diagnoses with other immunosuppressive diseases, which can be fatal even in adolescent and healthy subjects.

Silhoutte of Deaths In Connection With Fatal Fall from Height Injuries.

As medicolegal consultant, we often encounter cases of fall from height related deaths which are invariably subjected to medicolegal autopsy and the numbers are gradually increasing day by day. During the study period of three years data were collected by using a pre-tested structured proforma, police inquest reports, hospital records and thorough medicolegal autopsy done at Chittagong Medical College Mortuary. This retrospective autopsy based study revealed 175 cases of fall from height casualties out of the total 2850 autopsies. We observed that the age group of 41-50 years i.e. 55 cases were mostly affected followed by 31-40 years i.e. in 40 cases. Males (144) were the main sufferers than the females (31). Maximum victims were construction workers 57 cases (32.57%) followed by 45 factory workers (25.71%). Construction sites were the main place of fall i.e. in 57 cases (32.57%) followed by working places 46 cases (26.28%). Most of the victims had head-neck injuries i.e. in 143 cases (81.71%) followed by thoracic injury 82 cases (46.85%). Multiple injuries i.e. in 92 cases (52.57%) were the main cause of death followed by head-neck injuries in 79 cases (45.14%). These casualties are definitely preventable by adopting safety measures and by educating the workers in the factories and construction sites.

[Causes of death: the uncertainty behind the numbers]. / Doodsoorzaken: de onzekerheid achter de cijfers.

When a person dies in the Netherlands it is legally required to report the cause of death. In most cases however, there is uncertainty when classifying causes of death. Additional postmortem diagnostics such as a CT scan or autopsy do not always provide absolute certainty. Data on causes of death can be used to determine what are, on a population level, relevant health problems. One must be cautious to fully rely on these data for making policy or financing healthcare and research. Firstly, incorrectly classifying the cause of death can give a distorted view of the underlying causes. Secondly, relevant health problems, such as obesity, might be overlooked in the statistics when they are not clearly a cause of death.

[Detection of some markers of the early phase of the inflammatory and reparative process in mechanical skin injuries]. / Vyyavlenie nekotorykh markerov rannei fazy vospalitel'no-reparativnogo protsessa pri mekhanicheskikh povrezhdeniyakh kozhi.

OBJECTIVE: To examine the applicability of IHC staining method: with TGF-ß1 antibodies (serial examination, statistically processed results) and with mast cell tryptase antibodies for injuries vitality determination. MATERIAL AND METHODS: 261 skin autopsy samples with mechanical injuries from 29 persons were divided to 3 groups (87 in each group): vital injuries, postmortal injuries, control non-injured samples. A routine histological examination using standard H&E stain and IHC both with TGF-ß1 and mast cells tryptase antibodies was performed. RESULTS AND CONCLUSION: The positive TGF-ß1 staining (score 2-3) was found in keratinocytes in vitally injured skin and the negative or weak one (score 0-1) was found in control postmortally injured and non-injured samples. Additionally, dermal TGF-ß1 expression was found in some vitally injured skin samples. The difference between vitally injured skin and control samples was statistically significant (p<0.05). No significant difference of dermal mast cells density in groups 1, 2, 3 was found.

Succession of medico-legal important flesh flies (Diptera: Sarcophagidae) in the temporal gradient of pig decomposition in the Brazilian Cerrado.

Flies belonging to the Sarcophagidae family play a significant role in forensic investigations by aiding in the estimation of post-mortem interval through the assessment of the developmental time of their immature stages and/or the succession patterns of species on carcasses and cadavers. In this regard, this study aimed to investigate the ecological succession of these flies on pig carcasses within Cerrado of Brazil. The progression of fly succession was examined over a 10-day period using the Threshold Indicator Taxa Analysis (TITAN) approach. Six Z + species (Oxysarcodexia thornax (Walker), Peckia (Sarcodexia) lambens (Wiedemann), Peckia (Euboettcheria) collusor (Curran & Walley), Ravinia belforti (Prado & Fonseca), Tricharaea (Sarcophagula) canuta (Wulp) and Tricharaea (Sarcophagula) occidua (Fabricius)) were identified, with change points ranging from 2.5 to 3 days during the dry season and 2.5 to 5.5 days during the rainy season. Two Z- species (Dexosarcophaga carvalhoi (Lopes) and Peckia (Sarcodexia) tridentata (Hall)) were present, with a change point of 6.5 days during the rainy season. This study provides a continuous analysis of the temporal succession of flies, enabling an investigation into species progression based on their change points and directions (Z + and Z- ), thereby offering methodological advancements to avoid the arbitrary categorization of inherently continuous data.

Clinical anatomy of pulmonary connections in young people.

OBJECTIVE: Aim: To study the clinical anatomy of the pulmonary ligaments of young people. PATIENTS AND METHODS: Materials and Methods: The study was carried out when performing 28 autopsies of young people aged 25 to 44 years. Methods of dissection of chest organocomplexes, macro-microscopy, morphometry and planimetry, and statistical processing were used. The shape and topography of the pulmonary ligaments was assessed, their area, the localization of lymph nodes was examined. RESULTS: Results: The pulmonary ligament is an anatomical formation, which is formed as a result of a combination of leaves of the mediastinal pleura, which, covering the surfaces of the roots of the lungs, descend towards the diaphragm and are located between the mediastinal organs and the lungs. Pulmonary connections on both sides have a few edges: the inner, outer and lower free. The pulmonary ligaments with lower free edges do not pass to the diaphragmatic surface of the pleura, but only with inner ones, which are located on the right along the esophagus, and on the left along the aorta. Pulmonary ligaments on both sides pass into the mediastinal part of the pleura, covering the pericardium. CONCLUSION: Conclusions: There are individual differences between the shape and size of the right and left pulmonary ligaments in males and females. There is no significant difference between the sizes of the right and left pulmonary ligaments, but such dimensions as: the width, the angle of inclination and the ratio of their lower free edge to the lower edge of the lungs are not found in all cases.

ADNP dysregulates methylation and mitochondrial gene expression in the cerebellum of a Helsmoortel-Van der Aa syndrome autopsy case.

BACKGROUND: Helsmoortel-Van der Aa syndrome is a neurodevelopmental disorder in which patients present with autism, intellectual disability, and frequent extra-neurological features such as feeding and gastrointestinal problems, visual impairments, and cardiac abnormalities. All patients exhibit heterozygous de novo nonsense or frameshift stop mutations in the Activity-Dependent Neuroprotective Protein (ADNP) gene, accounting for a prevalence of 0.2% of all autism cases worldwide. ADNP fulfills an essential chromatin remodeling function during brain development. In this study, we investigated the cerebellum of a died 6-year-old male patient with the c.1676dupA/p.His559Glnfs*3 ADNP mutation. RESULTS: The clinical presentation of the patient was representative of the Helsmoortel-Van der Aa syndrome. During his lifespan, he underwent two liver transplantations after which the child died because of multiple organ failure. An autopsy was performed, and various tissue samples were taken for further analysis. We performed a molecular characterization of the cerebellum, a brain region involved in motor coordination, known for its highest ADNP expression and compared it to an age-matched control subject. Importantly, epigenome-wide analysis of the ADNP cerebellum identified CpG methylation differences and expression of multiple pathways causing neurodevelopmental delay. Interestingly, transcription factor motif enrichment analysis of differentially methylated genes showed that the ADNP binding motif was the most significantly enriched. RNA sequencing of the autopsy brain further identified downregulation of the WNT signaling pathway and autophagy defects as possible causes of neurodevelopmental delay. Ultimately, label-free quantification mass spectrometry identified differentially expressed proteins involved in mitochondrial stress and sirtuin signaling pathways amongst others. Protein-protein interaction analysis further revealed a network including chromatin remodelers (ADNP, SMARCC2, HDAC2 and YY1), autophagy-related proteins (LAMP1, BECN1 and LC3) as well as a key histone deacetylating enzyme SIRT1, involved in mitochondrial energy metabolism. The protein interaction of ADNP with SIRT1 was further biochemically validated through the microtubule-end binding proteins EB1/EB3 by direct co-immunoprecipitation in mouse cerebellum, suggesting important mito-epigenetic crosstalk between chromatin remodeling and mitochondrial energy metabolism linked to autophagy stress responses. This is further supported by mitochondrial activity assays and stainings in patient-derived fibroblasts which suggest mitochondrial dysfunctions in the ADNP deficient human brain. CONCLUSION: This study forms the baseline clinical and molecular characterization of an ADNP autopsy cerebellum, providing novel insights in the disease mechanisms of the Helsmoortel-Van der Aa syndrome. By combining multi-omic and biochemical approaches, we identified a novel SIRT1-EB1/EB3-ADNP protein complex which may contribute to autophagic flux alterations and impaired mitochondrial metabolism in the Helsmoortel-Van der Aa syndrome and holds promise as a new therapeutic target.

Respiratory-related deaths and associated factors in Alicho-Weriro district, southern Ethiopia: verbal autopsy data analysis.

BACKGROUND: Respiratory diseases disproportionately affect people living in resource-limited settings. However, obtaining information that explains respiratory-related deaths has been difficult, mainly due to a lack of medical certification of death and the fact that most deaths occur outside of health institutions. This study aimed to determine the proportion of respiratory-related deaths and identify associated factors in Alicho-Weriro district, southern Ethiopia, using the verbal autopsy method. METHODS: A community-based cross-sectional study was conducted from April to June 2022. All deceased people in the study area from January 2020 to December 2021 were included in the study. Trained physicians ascertained the cause of death from verbal autopsy data that were collected using a pre-tested and modified WHO-designed questionnaire. The binary logistic regression models were used to identify factors associated with respiratory-related deaths. RESULTS: Respiratory-related deaths accounted for 25% of the deaths from all causes, with 20.8% of male and 29.5% of female deaths. Of which, 9.7% were from tuberculosis, 8.3% were from asthma and 6.2% were from acute lower-respiratory tract infections. Moreover, being female (adjusted OR, AOR: 3.3; 95% CI: (1.75 to 6.22)), age 50-64 years (AOR: 9.3; 95% CI: (1.16 to 73.90)), age above 64 years (AOR: 8.9; 95% CI: (1.130 to 70.79)), family size of five persons or more (AOR: 1.9; 95% CI: (1.15 to 3.29)), smoking (AOR: 3.9; 95% CI: (1.86 to 8.35)), using wood and/or animal dung for household cooking (AOR: 6.6; 95% CI: (1.92 to 22.59)) and poor house ventilation (AOR: 3.1; 95% CI: (1.75 to 5.38)) were significantly associated with increased odds of dying from respiratory-related diseases. CONCLUSION: This study has determined that about a quarter of deaths from all causes were due to respiratory diseases, mainly tuberculosis, asthma and acute lower respiratory tract infections. Therefore, interventions to reduce this burden should focus on supporting early case detection and treatment, promoting healthy lifestyles, exercising women's equality at the household level and improving housing conditions.

Two cases of driver death caused by airbag rupture.

OBJECTIVE: This article reports two accidents caused by defective Takata airbags ruptured, which led to the deaths of the drivers. This is the first public report on the deaths caused by Takata airbags in China. METHODS: Determine the relationship between the driver death and airbag rupture through autopsy indings and vehicle inspection. RESULTS: Due to defects in the design of Takata's inflator, moist air was permitted to slowly enter the inflator, resulting the PSAN slowly degraded physically. The damaged propellant burned more rapidly than intended and overpressurized the inflator's steel housing, causing fragmentation and flying debris at high speed, killing or injuring vehicle occupants. CONCLUSIONS: To date, there are still tens of millions of defective Takata airbags that have not been recalled for repair, posing safety risks. This article suggests taking preventive measures to avoid the occurrence of similar accidents.

Investigation of fatal traumatic head injuries.

BACKGROUND: Traumatic head injuries (THIs) are one of the major causes of death in forensic cases. The aim of this study was to investigate the characteristics of patients with fatal THIs. METHODS: In this study, a total of 311 patients with fatal THIs, who underwent postmortem examinations and/or autopsies, were retrospectively analyzed. Cases were evaluated based on sex, age group, incident origin, cause of the incident, presence of skull fracture, type of fractured bone (if any), fracture localization and pattern, presence and type of intracranial lesion (if any), and cause of death. RESULTS: Out of the patients, 242 (77.8%) were male and 69 (22.2%) were female. Accidents accounted for 235 (75.6%) of the incidents, with in-vehicle traffic accidents causing 117 (37.6%). In 221 cases (71.1%), intracranial lesions and skull fractures were observed together. The most common fractures were base fractures (171 cases) and temporal bone fractures (153 cases). The rate of intracranial hemorrhage was lower in the adult age group (69.7%) compared to the older age group (92.6%). CONCLUSION: The results obtained in this study indicate that the cause of the incident, type of fracture, presence of skull base fracture, and multiple skull fractures increase the likelihood of fatalities. The occurrence of skull fractures reduces intracranial pressure, thereby decreasing the incidence of intracranial lesions. The development and effective enforcement of road traffic safety policies and regulations will reduce the incidence of fatalities.

Volabolomic Fingerprinting for Post-Mortem Interval Estimation: A Novel Physiological Approach.

Death is a multifaceted process wherein each individual cell and tissue has a metabolic homeostasis and a time of functional cessation defined by the dying process as well as by intrinsic and extrinsic factors. Decomposition is physiologically associated with the release of different types of volatile organic compounds (VOCs), and these form volaboloma mortis. The main purpose of this study was to record the volabolomic fingerprint produced by volatile molecules during the physiological decomposition process of human tissue and muscle cells. The volatile chemical signature has important implications for an open issue in forensics and pathology, namely the estimation of the postmortem interval (PMI), which decreases in accuracy with the passage of time. Volatile metabolites emitted from human tissues and muscle cells at 0, 24, 48, and 72 h were recorded in real time with an electronic nose sensor device. The key findings were the continuous sampling of VOCs emitted from tissues and cells. These showed a common behavior as time progressed; particularly, after 48 h the distributions became dispersed, and after 72 h they became more variable. Volabolomic fingerprinting associated with time progression relevant to the study of PMIs was reconstructed. Additionally, there may be broader applications, such as in dog training procedures for detecting human remains, and perhaps even for studying scavenger and insect attractants.

An Autopsy Case of Fulminant Myocarditis with Massive Left Ventricular Calcification.

Myocardial calcification in myocarditis is rare and may be linked to poor outcomes. We herein report a case of fulminant myocarditis with massive myocardial calcification and its pathological outcomes at autopsy. A 49-year-old man experienced chest pain and was diagnosed with acute myocarditis. His cardiac function did not recover despite mechanical circulatory support in combination with V-A extracorporeal membrane oxygenation and IMPELLA CP®. He eventually developed sepsis and gastrointestinal bleeding and died on day 27. Diffuse myocardial calcification was observed on computed tomography at autopsy. The pathological autopsy depicted that calcification filled every myocardial cell in the left ventricle.

Characteristics and circumstances of rail suicides in England 2019-2021: A cluster analysis and autopsy study.

BACKGROUND: Around 4 % of all suicide deaths in Great Britain occur on the railways. This exploratory study was designed to increase understanding of the individuals that take their lives in this way, and the circumstances of their death. METHOD: Data were obtained from fatality investigation files compiled by the British Transport Police (BTP) relating to suspected suicides on the mainline railway in England from April 2019 to March 2021. Cluster analysis was carried out to identify grouped associations of characteristics and circumstances relating to rail suicide. RESULTS: A total of 436 files were analysed, representing 93 % of all suspected railway suicides during this period. Cluster analysis identified four groups of almost equal size, distinguished principally by age, living arrangements, employment status and location of death. The study is novel in the way it integrates individual characteristics and circumstances of death. The identified clusters may provide a multidimensional way of conceptualising suicide risk that could inform more targeted interventions at rail locations. LIMITATIONS: A high proportion of missing data means that the findings need to be interpreted with caution. It also restricted the multivariate analysis to those categories of information for which sufficient information was available. CONCLUSION: The characteristics and circumstances of suicide deaths on the railways are complex and multifaceted. The typology identified in this study may help to target preventative strategies prior to the incident as well as at different location types.

Significance of Contusion at the Vocal Cord and Perivocal Cord Area in Cases of Non-intubated Death.

Every finding during a neck autopsy may be essential for accurately diagnosing and explaining the mechanism of death. In this prospective study in the Department of Forensic Medicine and Toxicology of Jordan University Hospital, 17 out of 95 neck autopsies revealed contusions of the laryngeal mucosa in the vocal or perivocal area. These contusions were found to be associated with various causes of death, including mechanical asphyxia (such as throttling, ligature strangulation, hanging, smothering, choking, plastic bag asphyxia, gagging, and inhalation of blood) and other causes (such as atypical drowning, carbon monoxide poisoning, head injury due to a road traffic accident, burns, electrocution, and brain edema). This study provides insight into the mechanisms of this important lesion and may contribute to a better understanding of the cause of death.

Arrhythmogenic Right Ventricular Cardiomyopathy Post-Mortem Assessment: A Systematic Review.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic disorder characterized by the progressive fibro-fatty replacement of the right ventricular myocardium, leading to myocardial atrophy. Although the structural changes usually affect the right ventricle, the pathology may also manifest with either isolated left ventricular myocardium or biventricular involvement. As ARVC shows an autosomal dominant pattern of inheritance with variable penetrance, the clinical presentation of the disease is highly heterogeneous, with different degrees of severity and patterns of myocardial involvement even in patients of the same familiar group with the same gene mutation: the pathology spectrum ranges from the absence of symptoms to sudden cardiac death (SCD) sustained by ventricular arrhythmias, which may, in some cases, be the first manifestation of an otherwise silent pathology. An evidence-based systematic review of the literature was conducted to evaluate the state of the art of the diagnostic techniques for the correct post-mortem identification of ARVC. The research was performed using the electronic databases PubMed and Scopus. A methodological approach to reach a correct post-mortem diagnosis of ARVC was described, analyzing the main post-mortem peculiar macroscopic, microscopic and radiological alterations. In addition, the importance of performing post-mortem genetic tests has been underlined, which may lead to the correct identification and characterization of the disease, especially in those ARVC forms where anatomopathological investigation does not show evident morphostructural damage. Furthermore, the usefulness of genetic testing is not exclusively limited to the correct diagnosis of the pathology, but is essential for promoting targeted screening programs to the deceased's family members. Nowadays, the post-mortem diagnosis of ARVC performed by forensic pathologist remains very challenging: therefore, the identification of a clear methodological approach may lead to both a reduction in under-diagnoses and to the improvement of knowledge on the disease.

ADVANCED DIAGNOSTIC IMAGING AND PATHOLOGIC FINDINGS OF THYROID LESIONS IN TWO SHORT-BEAKED ECHIDNAS (TACHYGLOSSUS ACULEATUS).

Two zoo-maintained short-beaked echidnas (Tachyglossus aculeatus) had long histories of intermittent anorexia and lethargy. Case 1 presented with a recurrence of these signs after transfer to another facility and died shortly after arrival. A focal area of hyperattenuation within the paratracheal tissue of the cranial mediastinum was noted antemortem on CT. Postmortem, this corresponded with severe thyroid follicular hyperplasia with lymphoplasmacytic thyroiditis. Additional findings included a systemic fungal infection without an inflammatory response, suggesting underlying factors such as torpor or immunosuppression. In Case 2, an intrathoracic mass was identified during a preshipment examination. CT confirmed a contrast-enhanced mass compressing the cranial vena cava and right atrium, and the animal was euthanized. The mass was diagnosed histologically as thyroid adenocarcinoma. These cases report thyroiditis and thyroid adenocarcinoma in echidna and describe the use of IV contrast and CT as a diagnostic aid in this species.

Visualization Analysis of Artificial Intelligence Literature in Forensic Research.

OBJECTIVES: To analyze the literature on artificial intelligence in forensic research from 2012 to 2022 in the Web of Science Core Collection Database, to explore research hotspots and developmental trends. METHODS: A total of 736 articles on artificial intelligence in forensic medicine in the Web of Science Core Collection Database from 2012 to 2022 were visualized and analyzed through the literature measuring tool CiteSpace. The authors, institution, country (region), title, journal, keywords, cited references and other information of relevant literatures were analyzed. RESULTS: A total of 736 articles published in 220 journals by 355 authors from 289 institutions in 69 countries (regions) were identified, with the number of articles published showing an increasing trend year by year. Among them, the United States had the highest number of publications and China ranked the second. Academy of Forensic Science had the highest number of publications among the institutions. Forensic Science International, Journal of Forensic Sciences, International Journal of Legal Medicine ranked high in publication and citation frequency. Through the analysis of keywords, it was found that the research hotspots of artificial intelligence in the forensic field mainly focused on the use of artificial intelligence technology for sex and age estimation, cause of death analysis, postmortem interval estimation, individual identification and so on. CONCLUSIONS: It is necessary to pay attention to international and institutional cooperation and to strengthen the cross-disciplinary research. Exploring the combination of advanced artificial intelligence technologies with forensic research will be a hotspot and direction for future research.