Autophagy in myocardial ischemia and ischemia/reperfusion.

Myocardial infarction (MI) is a life-threatening condition that leads to loss of viable heart tissue. The best way to treat acute MI and limit the infarct size is to re-open the occluded coronary artery and restore the supply of oxygenated and nutrient-rich blood, but reperfusion can cause additional damage. Autophagy is an intracellular process that recycles damaged cytoplasmic components (molecules and organelles) by loading them into autophagosomes and degrading them in autolysosomes. Autophagy is increased in in vivo animal models of permanent ischemia and ischemia/reperfusion but by different molecular mechanisms. While autophagy is protective during permanent ischemia, it is detrimental during ischemia/reperfusion. Its modulation is being investigated as a potential target to reduce reperfusion injury. This review provides a synopsis of the current knowledge about autophagy, summarizes findings specifically in permanent ischemia and ischemia/reperfusion, and briefly discusses the potential implication of experimental findings.

[Forensic radiology : Introduction and overview]. / Forensische Radiologie : Einführung und Übersicht.

BACKGROUND: In forensic medicine, documentation of findings is essential. During an autopsy, this is usually achieved by photography. However, there are numerous injuries that remain undetected even during a classic autopsy. In recent years, the importance of forensic radiology has grown in many countries to improve the documentation of findings and to increase the quality of post-mortem examinations. METHODS: While many methods, such as conventional X­rays or computed tomography, can be transferred quite easily to the post-mortem field, there are other methods that are more difficult to adapt. For example, performing a post-mortem angiography requires a specific concept that allows the vascular system to be filled and a contrast agent to circulate. Performing post-mortem magnetic resonance imaging is also a challenge, as image contrast depends on the temperature of the body being examined. When applying forensic radiology on living persons in the field of "clinical forensic medicine", there are further elements to consider. In particular, the question arises if radiological methods are acceptable for purely forensic medical purposes without a clinical indication. CONCLUSION: This overview article is intended to explain the various methods of forensic radiology, their areas of application, and their advantages and disadvantages. It also describes important historical developments in the use of forensic radiology and its current spread in German-speaking countries as well as current and future developments. Thanks to this information and a summarizing overview table, clear indications and recommendations for the use of forensic radiology in practice can be obtained.

Acute aconitine poisoning resulting from the ingestion of medicinal liquor.

Diester diterpenoid alkaloids (DDAs) are the main active ingredients of herbaceous perennial plants Aconitum. DDAs possess cardiotoxic and neurotoxic properties. Although most deaths caused by DDA poisoning are accidental, a few instances of suicide and homicide have been reported. Presented is a case of an acute aconitine (AC) poisoning following the ingestion of approximately 50 mL of homemade medicinal liquor. We described the clinical manifestations after poisoning and detailed postmortem changes, and detected the concentrations of AC and hypaconitine (HA) by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The decedent experienced a burning sensation in the gastrointestinal tract after poisoning, followed by flushing and paralysis of the face and limbs, and severe cardiac arrhythmia. An autopsy revealed cyanosis of the lips and nail beds; conjunctival hemorrhage in both eyes; pulmonary edema; tissue hemorrhage and congestion in multiple organs; and inflammatory cell infiltration in the stomach, duodenum, pancreas, and cardiac muscle. The concentrations of AC and HA were as follows: cardiac blood, 38.4 ng/mL and 7.1 ng/mL; pericardial fluid, 7.3 ng/mL and 41 ng/mL; urine, 28.1 ng/mL and 574 ng/mL; bile, 38.5 ng/mL and 108 ng/mL; gastric contents, 0.06 mg and 0.56 mg; liver tissue, 10.7 ng/g and 109.6 ng/g; and medicinal liquor, 0.568 mg/mL and 0.664 mg/mL, respectively. The clinical manifestations, anatomy findings, and quantitative data on the concentrations of AC and HA in body fluids and tissues will aid forensic investigations of deaths caused by acute AC poisoning.

Loneliness, cerebrovascular and Alzheimer's disease pathology, and cognition.

INTRODUCTION: Loneliness has a rising public health impact, but research involving neuropathology and representative cohorts has been limited. METHODS: Inverse odds of selection weights were generalized from the autopsy sample of Rush Alzheimer's Disease Center cohorts (N = 680; 89 ± 9 years old; 25% dementia) to the US-representative Health and Retirement Study (N = 8469; 76 ± 7 years old; 5% dementia) to extend external validity. Regressions tested cross-sectional associations between loneliness and (1) Alzheimer's disease (AD) and cerebrovascular pathology; (2) five cognitive domains; and (3) relationships between pathology and cognition, adjusting for depression. RESULTS: In weighted models, greater loneliness was associated with microinfarcts, lower episodic and working memory in the absence of AD pathology, lower working memory in the absence of infarcts, a stronger association of infarcts with lower episodic memory, and a stronger association of microinfarcts with lower working and semantic memory. DISCUSSION: Loneliness may relate to AD through multiple pathways involving cerebrovascular pathology and cognitive reserve. HIGHLIGHTS: Loneliness was associated with worse cognition in five domains. Loneliness was associated with the presence of microinfarcts. Loneliness moderated cognition-neuropathology associations. Transportability methods can provide insight into selection bias.

A fatal poisoning due to consumption of crushed Abrus precatorius seeds: an autopsy case report.

Abrus precatorius is an ornamental plant that belongs to the Leguminoceae family. It contains toxalbumin, named abrin, in all of its parts. However, the seeds are more toxic when consumed in crushed form. Deaths due to abrus seed poisoning are rare. We are reporting a case of suicidal ingestion of crushed abrus precatorius seeds by a 37-year-old female. She presented to the hospital with complaints of multiple episodes of vomiting and diarrhea. She was resuscitated with fluid boluses, followed by a stomach wash and activated charcoal, and referred to our tertiary hospital, where she presented with giddiness, abdominal pain, bloody diarrhea, and epigastric tenderness. On subsequent days, she developed altered sensorium, renal failure, and electrolyte imbalance. She was managed conservatively. Blood investigation revealed elevated leucocyte count, increased urea and creatinine levels, and elevated liver enzymes. She died five days after ingesting the seeds. On autopsy examination, the brain and lungs were congested and edematous. The peritoneal cavity contained around 500mL of straw-colored fluid. Petechial hemorrhages were present over the lungs, heart, and liver surfaces. The mucosa of the gastrointestinal tract was hemorrhagic, the liver showed steatosis, and the kidneys showed congestion and obscuration of the corticomedullary junction. Histopathologically, the lungs showed mild congestion with alveolar edema, the liver showed necrosis with steatosis, and the kidney showed acute tubular necrosis. The toxicology screening was positive for abrin. This case highlights not only the rare fatality following abrus precatorius poisoning but also the toxic nature of this plant.

Retrospective analysis on the occurrence of kidney cysts in mice in a central animal facility in the years 2009-2019.

Kidney cysts in humans are mainly caused by inheritable polycystic kidney disease. Although they are a regular finding in laboratory mice, their occurrence upon dissection has not been systematically investigated, yet. Therefore, the aim of this report was to investigate on prevalence, phenotype and aetiology of spontaneously occurring kidney cysts in mice by retrospectively analysing the laboratory-receipt tables of the in-house laboratory of a central animal facility in North Rhine-Westphalia, Germany, years 2009-2019. A percentage of 0.4% of dissected mice displayed kidney cysts, with more male than female animals affected and average age equal to that of all dissected animals. Preliminary report in half of the cases was distended abdomen, and a few individuals displayed additional pathologic alterations of kidneys, most commonly dilated renal pelvis, or extrarenal comorbidities. Kidney cysts occurred independently of a renal phenotype of the transgenic strain or presence of infectious agents in health monitoring. To conclude, kidney cysts were characterized as harmless for affected mice but, as inheritability is suggested according with the literature, affected animals should be excluded from breeding.

Deadly cerebral ischemia due to carotid stenosis following a facial shot with a pellet gun: An autopsy case report.

INTRODUCTION: Facial gunshot wounds have devastating functional and aesthetic consequences for the patient. If associated with penetrating craniocerebral injuries, the prognosis is rather compromised even with appropriate medical and surgical treatment. Chop-off injuries with penetrating wounds constitute a challenging situation for the facial reconstructive surgeon in facial trauma. OBSERVATION: This case involved a 49-year-old man who sustained an accidental facial shot from a pellet gun. Radiological and clinical investigations revealed complex ballistic trauma to the maxillofacial region, with projectiles reaching the base of the skull. One of the projectiles migrated via the carotid canal towards a cerebral artery, leading to obstruction of the artery with cerebral infarction. An autopsy was performed which evaluated that the shooting distance was compatible with a long distance, causing the dispersion of lead grains with the absence of a wad inside the trauma site. CONCLUSION: In some cases of facial gunshot wounds, despite a complex and extensive lesion assessment, death may occur due to a neurological complication rather than sustaining hemodynamic shock, depending on the trajectory of the projectiles.

Revisiting Utility of Fetal Autopsy in Genomic Era.

Background: Autopsy has been a gold standard in cases of antenatal detected anomalies or fetal demise. This helped clinicians in getting insights into the future management. In current times, ultrasound and genomic testing has become extremely powerful in further refining the etiological basis; however, fetal autopsy still has its role even now. Material and Methods: We have discussed the utility of fetal autopsy in current times by diving the cases in seven groups. Results: Case based discussions to discuss the utility of fetal autopsy. Conclusions: We suggest that fetal autopsy should be the standard of care in case of any abnormal fetal outcomes alongwith fetal genomic testing. Fetal autopsy is complementary to the ultrasound assessment and genomic investigations in reaching the final diagnosis and provides invaluable information regarding recurrence risk which may not be available when couple plans next pregnancy.

Death in a bathtub of an adolescent with neurofibromatosis type 2 exhibiting meningioangiomatosis with white matter involvement.

Neurofibromatosis type 2 (NF2) is a neurocutaneous syndrome characterized by the development of multiple benign tumors, including vestibular schwannomas and meningiomas, in the nervous system. Seizures are rarely associated with NF2, and the lethality of this condition typically stems from tumor growth and related complications, leaving the incidence of sudden death largely unreported. This report discribes a 16-year-old girl with a history of NF2 and occasional seizures who died unexpectedly in a bathtub. Postmortem examination revealed multiple tumors in the cranial nerves (schwannoma), under the dura mater (meningioma), and in the upper cervical cord (neurofibroma). Typical signs of drowning, such as foam in the airways, were not present. Upon histological examination, meningioangiomatosis (MA) was observed in the cerebellum and the cerebral cortex, specifically in the frontal lobe, temporal lobe, and insula. The MA extended into the white matter, exhibiting severe perivascular fibrosis and cystic dilatation of perivascular spaces in the frontal lobe and cerebellum. Additionally, glial microhamartomas were detected both around and separate from the MA. These autopsy findings suggest that sudden unexpected death in epilepsy (SUDEP) was the cause of death rather than drowning. Moreover, while NF2-associated MA is typically asymptomatic, unlike sporadic MA, which commonly presents with seizures, the spread of MA into the white matter is unusual in an NF2 patient. Therefore, MA with the white matter involvement could have been a factor causing the seizures and the occurrence of SUDEP in this NF2 patient.

Identification of novel TTN gene variant in a patient exhibiting severe dilated cardiomyopathy co-occurring with acute fibrinoid organizing pneumonia.

OBJECTIVES: Dilated cardiomyopathy (DCM) is often hereditary, with 20% to 40% of nonischemic cases showing familial linkage, yet genetic testing is underused. This report describes an unreported pathogenic nonsense variant in the Titin (TTN) gene (NM_001267550.2:c.92603G>A) in a 24-year-old man with severe DCM and acute fibrinoid organizing pneumonia, highlighting a unique cardiopulmonary pathology. METHODS: We conducted detailed gross, histopathologic, immunophenotypic, and exome-based DNA sequencing analysis in the workup of this case. We also included the patient's clinical and radiologic findings in our study. RESULTS: With rapid clinical deterioration and complex comorbidities, including substance abuse and psychiatric conditions, which precluded transplantation, the patient's cardiac function progressively worsened. Autopsy findings included extreme cardiomegaly, biventricular hypertrophy, and acute and chronic pericarditis. Significant pulmonary pathology consistent with acute fibrinoid organizing pneumonia was also noted. Molecular testing confirmed a deleterious maternally inherited TTN variant that was absent in the sibling of the proband and the extant medical literature, highlighting its rarity and significance. CONCLUSIONS: This case contributes to the ongoing body of work on the impact of TTN variants on DCM. It suggests a potential link between genetic variants and complex cardiac injury patterns, emphasizing the need for further investigation into the interplay between cardiomyopathy and pulmonary pathology.

Splenic rupture in dairy cattle: Report of 24 cases.

Splenic rupture in cattle is scarcely described in the literature. The aim of this work was to report the occurrence of splenic rupture in cattle in southern Brazil as well as to describe the causes of the condition. Between 2013 and 2022, 24 of the 1769 bovine necropsies performed in southern Brazil were due to splenic rupture, accounting for 1.36% of the diagnoses. Animals died due to hemoperitoneum caused by a rupture in the splenic capsule, typically associated with marked splenomegaly and a large hematoma between the capsule and the parenchyma. Clinical signs were described in a subset of cases (11 of 24 cases, 46%) and included apathy, abdominal pain, mucosal pallor, tachycardia, and respiratory distress. However, the majority (13 of 24 cases, 54%) presented as sudden death. The underlying cause of splenic rupture was established as follows: 16 cases (67%) secondary to babesiosis, 4 cases (17%) due to lymphoma, 1 case (4%) due to a thrombus, 1 case (4%) due to external trauma, 1 case due to a ruptured nodular lymphoid hyperplasia (4%), and 1 case of undetermined cause (4%). Hypovolemic shock caused by splenic rupture is an important cause of death of dairy cattle, and babesiosis and bovine leukemia virus-associated lymphoma are among the most common etiologic diagnoses (84% of cases). The description of the causes of this condition is important to clarify the pathogenesis and occurrence of splenic rupture in dairy cattle.

Genetic and pathophysiological insights from autopsied patient with primary familial brain calcification: novel MYORG variants and astrocytic implications.

Primary familial brain calcification (PFBC) is a genetic neurological disorder characterized by symmetric brain calcifications that manifest with variable neurological symptoms. This study aimed to explore the genetic basis of PFBC and elucidate the underlying pathophysiological mechanisms. Six patients from four pedigrees with brain calcification were enrolled. Whole-exome sequencing identified two novel homozygous variants, c.488G > T (p.W163L) and c.2135G > A (p.W712*), within the myogenesis regulating glycosidase (MYORG) gene. Cerebellar ataxia (n = 5) and pyramidal signs (n = 4) were predominant symptoms, with significant clinical heterogeneity noted even within the same family. An autopsy of one patient revealed extensive brainstem calcifications, sparing the cerebral cortex, and marked by calcifications predominantly in capillaries and arterioles. The pathological study suggested morphological alterations characterized by shortened foot processes within astrocytes in regions with pronounced calcification and decreased immunoreactivity of AQP4. The morphology of astrocytes in regions without calcification remains preserved. Neuronal loss and gliosis were observed in the basal ganglia, thalamus, brainstem, cerebellum, and dentate nucleus. Notably, olivary hypertrophy, a previously undescribed feature in MYORG-PFBC, was discovered. Neuroimaging showed reduced blood flow in the cerebellum, highlighting the extent of cerebellar involvement. Among perivascular cells constituting the blood-brain barrier (BBB) and neurovascular unit, MYORG is most highly expressed in astrocytes. Astrocytes are integral components of the BBB, and their dysfunction can precipitate BBB disruption, potentially leading to brain calcification and subsequent neuronal loss. This study presents two novel homozygous variants in the MYORG gene and highlights the pivotal role of astrocytes in the development of brain calcifications, providing insights into the pathophysiological mechanisms underlying PFBC associated with MYORG variants.

The need for mandatory autopsy teaching in Forensic Medicine for medical students.

The effectiveness of the autopsy as an educational tool in forensic medicine courses has been widely acknowledged, and medical students were expected to attend regularly. Nevertheless, the use of autopsies for teaching has dramatically declined in recent years and worldwide despite their high-value benefits. This study aims to understand the importance and relevance of attending autopsies during forensic teaching sessions and identify any challenges that may impede attendance. A self-administered online questionnaire that assesses the knowledge, attitudes, and practices related to autopsies attendance was distributed to fourth-year medical students at the National Defence University of Malaysia and Universiti Sains Islam Malaysia. A total of 99 respondents were involved in this study. Our findings indicate that most respondents (over 85%) demonstrated good knowledge of forensic medicine. Pearson's statistical test revealed a significant correlation between the knowledge and students' attitudes toward autopsy. This study demonstrates the need to strategically integrate autopsy attendance into medical curricula to encourage constructive attitudes and practices among medical students. Students gain the most benefits from frequently attending autopsies. Passionate educators can conduct preparatory sessions to set expectations and address concerns, encourage students to process their experiences, and reinforce learning outcomes in the mortuary setting. Mandatory autopsy teaching should be integrated into the curriculum to ensure medical students have the necessary skills and knowledge to become competent doctors.

The last days of Daniel Webster: A detailed analysis of his cause of death.

Daniel Webster (1782-1852) was one of the most impactful United States political figures of the early and mid-nineteenth century. He served in Congress and as the Secretary of State for three Presidents. He died in October of 1852 and his autopsy appeared in the medical literature. Historians have reported that his cause of death was either related to a traumatic head injury he sustained in May of 1852 or from complications of alcoholic cirrhosis. In this manuscript, we will review Webster's medical history and autopsy to determine his cause of death.

Abdominal stab wound with an unusual presentation: A case report.

The forensic literature has described unusual wounds of entry into fatal stab wounds that are rarely found in autopsies. Stab wounds are considered fatal injuries when they occur in vital organs. Many authors have suggested that the description of the wound track helps recreate the crime scene. Still, many say that the recreation of a crime scene is a static event, whereas the actual event is dynamic. We received the dead body of a 25-year-old male for postmortem examination. During autopsy, we found a wedge-shaped stab wound in the epigastric region. Interestingly, when we dissected the skin and subcutaneous tissue without disturbing the wound, we observed two separate wedge-shaped wounds over the rectus sheath. A knife can produce an atypical appearance after plunging into the body. With a single external primary stab wound, two different wound tracks can be made internally. Thus, examining only the wound track made it impossible to comment on the circumstances of violence.

Efficacy of Minor Salivary Glands as Indicators of Depth of Resection for Superficial Hypopharyngeal Carcinoma.

Objective: This study aimed to investigate the utility of minor salivary glands in the hypopharynx as novel indicators for safe resection of superficial hypopharyngeal carcinomas with fewer complications. Study Design: Cadaveric study. Setting: Cadavers were stored in the pathology laboratory at Kansai Medical University. Methods: Twenty-three cadaveric specimens were examined for minor salivary glands in the pyriform sinus, posterior wall, and postcricoid regions of the hypopharynx. Their count, size, and depth were assessed. Resected specimens from 5 consecutive patients with superficial hypopharyngeal carcinomas were pathologically analyzed to determine the positional relationship between cancer and minor salivary glands. Results: Minor salivary glands were present in more than 70% of patients in each region during autopsy, with the postcricoid region having a larger count and size. The glands were universally present, regardless of sex, height, or body mass index. Minor salivary glands in the pyriform sinus and postcricoid region were present at a depth of 30% from the bottom of the submucosal layer, whereas those in the posterior wall were present in the shallow muscularis. During surgery, endoscopic findings revealed minor salivary glands as small white nodules in the submucosal layer. Pathological examination of the resected specimen confirmed that the white nodule was a minor salivary gland. In addition, tumor position in relation to minor salivary glands provided an adequate margin for resection. Conclusion: Minor salivary glands may serve as reliable indicators for determining adequate deep safety margins during surgery for superficial hypopharyngeal carcinoma.

A scoping review on virtual autopsy: Main concepts, qualified professionals and future prospects.

The beginning of post-mortem evaluation studies through minimally invasive procedures began between 1800 and 1930. It started with Dr. Howard Kelly and was later followed by Décio Parreiras and Werneck Genofre, due to the yellow fever outbreak in Brazil. However, despite its early beginnings, the intensification of the research on this field occurred around 2010, when the publications about this subject became three times more frequent than before. There are basically two classifications for this procedure. The first one is virtual non-invasive autopsy, which is based only on imaging exams; the second is the minimally invasive autopsy, in which imaging exams are associated with other techniques such as biopsy and angiography. The main objective of the present study is to evaluate the existent data published about virtual autopsy from 2010, and highlight the key concepts related to this theme. A search was conducted in PUBMED, MEDLINE, and LILACS databases using the descriptors "virtual autopsy" and "minimally invasive autopsy", the review protocol has been registered on Open Science Framework (OSF), the total number of studies included were 28, and the data was presented through the PRISMA-ScR flowchart. Although, it is well known that this theme is recent in research fields and, because of that, there is still a lot to explore.

The artificial intelligence in autopsy and crime scene analysis.

Background: In the evolving field of forensic medicine, artificial intelligence (AI) technologies may revolutionize traditional autopsy practices by enhancing the precision and efficiency of postmortem examinations. Methods: A review of the literature was carried out on the Pub-med and Scopus search engines by inserting the keywords "artificial intelligence" AND "forensic" AND ("autopsy" OR "crime scene management" OR "forensic odontology" OR "post mortem interval" OR "forensic anthropology" OR "forensic sciences"). The works that analyzed the applications of artificial intelligence in the forensic and autopsy field were analyzed. Conclusion: The results showed the application of different forms of artificial intelligence such as machine learning, deep learning, robotics, artificial neural networks. Various applications are therefore possible in the autopsy field including forensic identification, analysis of radiological data through Virtopsy, estimation of the weapon used through analysis of firearm damage with ballistics, estimation of the Post-Mortem Interval (PMI), forensic toxicology. AI's potential to aid in the precise identification of causes of death, estimation of postmortem intervals. With forensic pathologists facing the constant challenge of making accurate diagnoses under pressure, AI applications can offer much-needed support by reducing subjective judgment and the inherent human error due to fatigue. Therefore, the integration of AI into autopsies, while promising in terms of efficiency and accuracy, demands a careful balance between technological advancement and ethical responsibility to ensure trust and integrity in forensic practices.

Pulmonary Tumor Thrombotic Microangiopathy With Versican Expression in a Patient With Advanced Gastric Cancer: A Case Report of a Rare Autopsy.

Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare but fatal complication of a malignant tumor that causes rapidly progressive pulmonary hypertension (PH). We report the case of a 70-year-old Japanese man who died of respiratory failure during chemotherapy for gastric cancer and was diagnosed with PTTM at autopsy. The autopsy revealed PTTM-specific histological findings, such as tumor emboli with fibrin-rich clots and fibrocellular intimal proliferation in the vessels. The cancer cells were immunohistochemically positive for vascular endothelial growth factor and platelet-derived growth factor, whereas the thickened intima of the pulmonary arteries was positive for versican (VCAN). As VCAN is an extracellular matrix proteoglycan that is dramatically increased in vascular lesions of pulmonary arterial hypertension, this case demonstrates that VCAN is also involved in the pathophysiology of PTTM.

Ruptured pulmonary artery aneurysm with prior dissection and persistent ductus arteriosus: Autopsy case report.

Cardiac tamponade from ruptured intrathoracic organs can lead to sudden cardiac death. In rare circumstances, the pulmonary artery can be the source of hemopericardium. We describe a case of a 62-year-old woman with no significant past medical history, who presented with sudden unexpected death. A forensic autopsy revealed 500 ml of hemopericardium. Further dissection demonstrated a saccular aneurysm in the pulmonary artery trunk, along with the evidence of prior dissection, i.e., neointimal layer. Persistent ductus arteriosus (PDA) was also present. Pulmonary artery aneurysms (PAA) are rare and often associated with congenital heart disease (CHD). PDA is the most common CHD related to PAA. Secondary pulmonary hypertension makes the pulmonary artery vulnerable to medial degeneration and increases the risk of dissection and rupture. Careful inspection of the great vessels and congenital anomalies are essential in the forensic autopsies for sudden death investigation.