Alcohol and toxicological factors influencing fatal falls from height in the Greater Tokyo Area: a retrospective study.

Falls from height pose a significant public health concern in urban regions, including the highly urbanized Greater Tokyo Area. The Japanese population is characterized by high rates of suicide and psychoactive drug usage, underscoring the importance of investigating these attributes in falls from height. This study aimed to retrospectively analyze the alcohol and toxicological aspects influencing falls from height in the Greater Tokyo Area between 2014 and 2022 and compare the findings with existing reports on other populations. In total, 75 cases of falls from height and 159 cases of natural deaths were included. Consistent with previous findings, Fisher's exact test revealed a predominance of males (66.67%, 50/75) and young adults (57.33%, 43/75) in falls from height. Multivariate logistic regression analysis identified antidepressant usage as the most significant risk factor within the target population, while younger individuals under alcohol influence constituted another high-risk group. Notably, contradictory to other populations, female individuals involved in fatal falls in the Greater Tokyo Area exhibited a higher frequency of alcohol consumption than males (48.00%, 12/25 vs. 26.00%, 13/50), and most of them were associated with suicide (83.33%, 10/12). These findings elucidate the population characteristics that pose a high risk for fatal falls from height in Japan and can serve as a reference for other Asian populations residing in similar megacities.

Increased fatty acid synthesis and disturbed lipid metabolism in Neuro2a cells after repeated cocaine exposure: A preliminary study.

Chronic use of cocaine prompts neurodegeneration and neuroinflammation. Lipids play pivotal roles in neuronal function and pathology. Although evidence correlates cocaine use with the alteration of lipid metabolism in blood and brain, the precise mechanism remains to be elucidated. In this study, we explore the effect of cocaine on neuronal fatty acid profiles in vitro. Neuro2a cells following seven days of repeated exposure to cocaine (0, 600, 800, 1000 µM) showed apoptosis-irrelevant cell death, dysregulated autophagy, activation of atypical endoplasmic reticulum stress response, increased saturated and unsaturated fatty acid synthesis, and disrupted lipid metabolism. These preliminary findings indicated the association between lipid metabolism and cocaine-induced neurotoxicity, which should be beneficial for understanding the neurotoxicity of cocaine.

Ectopic myogenesis and fibrosis accompany adipogenesis during thymic involution induced by repeated cocaine administration.

We have shown previously that daily cocaine administration for 7-14 days in rats resulted in the acceleration of thymic involution, which is, alike to age-related thymic involution, accompanied by ectopic adipogenesis. Here we show that the thymic involution caused by repeated cocaine administration is accompanied by not only adipogenesis but also ectopic myogenesis and fibrosis. In accordance with fibrosis, we observed an increase of N-cadherin, a marker of mesenchymal cells, as well as a decrease of E-cadherin, an epithelial cell marker, in the thymus in response to cocaine administration, suggesting the occurrence of epithelial-to-mesenchymal transition (EMT). Levels of fibronectin was also increased in the thymus of cocaine group compared to control group. In addition, increases in the levels of the transcription factors for myogenic differentiation, myogenin, MYF5, and MYF6, were observed in the thymus administered cocaine for 14 days. These results indicate that the thymic involution induced by cocaine administration involves not only adipogenesis and fibrosis but also ectopic myogenesis, which is scarcely observed and rather pathological process during thymic involution.

Case report: Fatal ischemic stroke induced by unruptured traumatic intracranial vertebral artery dissection.

Intracranial vertebral artery dissection (IVAD) is rare and potentially fatal due to the risk of secondary subarachnoid hemorrhage once ruptured. Unruptured traumatic IVAD is even rarer and can result in ischemic stroke, yet mostly benign when timely diagnosed. Herein, we present an uncommon case of a patient who underwent a fatal ischemic stroke induced by unruptured traumatic IVAD. The patient was symptomatic soon after being physically assaulted but left untreated until acute deterioration for multiple brain infarctions occurred, secondary to IVAD-induced cerebellar stroke. Fifteen days later, he died, regardless of an urgently performed thrombectomy. Multiple serial histologic examinations revealed an unruptured dissection of the intracranial vertebral artery with a slit-like tear of the intimal and medial layers, considered to be the culprit lesion. The 15-day prolonged onset of stroke was rare in traumatic IVADs. Furthermore, the slit-like tear of the intimal layer in our case may support the initial intimal laceration hypothesis for VAD pathogenesis. Since limited pathohistological information is available regarding ischemic IVAD, we believe this rare case will be beneficial in understanding the pathophysiology of ischemic IVAD.

Revisiting the canonical definition of heat hematoma: A rare case of postmortem subdural heat hematoma.

Heat hematoma is generally recognized as a postmortem heat-induced artifact in extradural spaces found in burned bodies. Conversely, subdural hematoma in charred bodies is more indicative of antemortem trauma. Here, we present a rare case of a subdural heat hematoma in forensic practice. The subdural hematoma was found in a charred body that was determined to be dead before the fire without findings of antemortem head injury. Furthermore, the detailed determination and formation mechanism of this subdural heat hematoma are discussed. With this rare case, we propose a reconsideration of the canonical definition of heat hematoma. This report envisions benefitting forensic pathologists facing similar cases.

Cocaine induces vascular smooth muscle cells proliferation via DRP1-mediated mitochondrial fission and PI3K/HIF-1α signaling.

Long-term cocaine abuse is associated with cardiovascular and pulmonary vascular complications. The vascular toxicity of cocaine can lead to vascular remodeling characterized by excessive proliferation of vascular smooth muscle cells. Though hypoxia-inducible factor (HIF) signaling and mitochondrial fission have been suggested to play essential roles in the pathogenesis of hypoxia-induced vascular remodeling, pathogenetic mechanism for cocaine-related vascular remodeling remains to be elucidated. In this study, we explore the effect of cocaine on the proliferation of vascular smooth muscle cells by in vitro experiments. The findings indicated that the cocaine-induced vascular smooth muscle cell hyperproliferation is achieved by enhancing DRP1-mediated mitochondrial fission and activating PI3K/HIF-1α signaling. Current findings suggested that mitochondrial fission would play a pivotal role in cocaine-related vascular remodeling and would be helpful in understanding the vascular toxicity of cocaine.

Case Report: Molecular autopsy underlie COVID-19-associated sudden, unexplained child mortality.

Herein, we report a child with COVID-19 and seemingly no underlying disease, who died suddenly. The autopsy revealed severe anemia and thrombocytopenia, splenomegaly, hypercytokinemia, and a rare ectopic congenital coronary origin. Immunohistochemical analysis demonstrated that the patient had acute lymphoblastic leukemia of the B-cell precursor phenotype (BCP-ALL). The complex cardiac and hematological abnormalities suggested the presence of an underlying disease; therefore, we performed whole-exome sequencing (WES). WES revealed a leucine-zipper-like transcription regulator 1 (LZTR1) variant, indicating Noonan syndrome (NS). Therefore, we concluded that the patient had underlying NS along with coronary artery malformation and that COVID-19 infection may have triggered the sudden cardiac death due to increased cardiac load caused by high fever and dehydration. In addition, multiple organ failure due to hypercytokinemia probably contributed to the patient's death. This case would be of interest to pathologists and pediatricians because of the limited number of NS patients with LZTR1 variants; the complex combination of an LZTR1 variant, BCP-ALL, and COVID-19; and a rare pattern of the anomalous origin of the coronary artery. Thus, we highlight the significance of molecular autopsy and the application of WES with conventional diagnostic methods.

The proportion of false-positives in positive Seratec® prostate-specific antigen SemiQuant test results in postmortem screening for seminal fluid.

Prostate-specific antigen (PSA) tests are used in forensics to conduct rapid screening for semen in vaginal swab samples from alleged victims of sexual abuse. Although PSA membrane tests have been applied to autopsy specimens, no study has evaluated predictors of false-positive test results in relation to factors such as age, cause of death, postmortem interval, drugs, and alcohol. This study describes the results obtained with the Seratec® PSA SemiQuant Kit test in 283 deceased women, with or without a history of sexual assault. Overall, 18.4% (52/283) of the vaginal swab samples tested positive for PSA. However, 63.5% (33/52) of the PSA-positive vaginal swab samples had no sperm detected. The proportion of false-positives in positive PSA results was 94.4% in those aged over 60 years. Multivariate logistic regression for PSA-positive samples showed that the proportion of false-positives in positive PSA results increased with the age of the deceased. However, the cause of death, postmortem interval, and presence of drugs or alcohol in the blood or urine of the deceased did not affect the PSA determination. These results show that PSA membrane tests are relatively unreliable and can be misleading, especially when derived from vaginal swab samples of older women, obtained at autopsy. In forensic cases, positive PSA screening test results may have an impact on subsequent legal actions and criminal charges brought against the accused. These findings are important for both forensic pathologists and the police to ensure accurate screening of older women in cases of suspected sex crimes.

Forensic Pathological Analysis of Death Due to Pulmonary Thromboembolism: A Retrospective Study Based on 145 Cases.

ABSTRACT: Pulmonary thromboembolism (PTE) is a common cause of sudden unexpected death in forensic and clinical practice. Although the prevention of thrombosis has been paid more attention in clinical practice in recent years, the number of deaths due to PTE remains extensive. In the present study, 145 cases of fatal PTE were collected and retrospectively analyzed from 2001 to 2020 at the School of Forensic Medicine, China Medical University in Liaoning Province, northeast of China. The demographic characteristics, risk factors of PTE, origins of thrombi, and time interval from the occurrence of main risk factors to PTE were retrospectively analyzed. The 40 to 59 age group accounted for the 51.0% of the total cases. Immobilization, trauma (especially fracture of the pelvis, femur, tibia, or fibula), surgery, cesarean section, and mental disorders were the top 5 high-risk factors. Among the involved cases, 92.9% of the PTE (130/140) occurred within 60 days and peak at 8 to 15 days after the exposure of main risk factors. According to the autopsy findings, 87.6% of the thrombi blocked the bilateral pulmonary arteries at pulmonary hilus, with a maximum diameter of 1.6 cm and a maximum length of 21.9 cm, which were mainly derived from lower limb (65.5%) or pelvic veins (10.3%). Although the embolus limited the pulmonary circulation, there is no difference on the ratio of lung-to-heart weight between PTE and the disease-free accident victims. Overall, our present retrospective study provides important information for the forensic analysis on the cause of death and potential guidance on clinical prevention of PTE.

Contraction Band Necrosis with Dephosphorylated Connexin 43 in Rat Myocardium after Daily Cocaine Administration.

Contraction band necrosis (CBN) is a common abnormality found in the myocardium of cocaine abusers, but is rarely reported in experimental models of cocaine abuse. Connexin 43 (Cx43) is essential for cardiac intercellular communication and the propagation of CBN. Under stress or injury, cardiac Cx43 is dephosphorylated, which is related to cardiomyocyte dysfunction and pathogenesis, whereas adiponectin exerts beneficial effects in the myocardium. In this study, we explore the effects of cocaine on cardiac Cx43 in vivo. Rats were administered cocaine via the tail vein at 20 mg/kg/day for 14 days, and showed widespread CBN, microfocal myocarditis and myocardial fibrosis, corresponding to a dysfunction of cardiac mitochondria under increased oxidative stress. The increase in dephosphorylated cardiac Cx43 and its negative correlation with the myocardial distribution of CBN after cocaine administration were determined. In addition, apoptosis and necroptosis, as well as increased adiponectin levels, were observed in the myocardium after cocaine exposure. Accordingly, we found altered profiles of cardiac Cx43, CBN and its negative correlation with dephosphorylated cardiac Cx43, and the possible involvement of adiponectin in the myocardium after 14 days of cocaine administration. The latter might play a protective role in the cardiotoxicity of cocaine. The current findings would be beneficial for establishing novel therapeutic strategies in cocaine-induced cardiac consequences.

Two fatal cases due to inadvertent discharge of carbon dioxide fire suppressant: Intoxication or asphyxiation?

Carbon dioxide (CO2) is widely used for fire protection and is lethal when inhaled at the minimum design concentration. Two workers were performing periodic maintenance of isolated stored CO2 cylinders of a fire extinguishing system, and during the maintenance, CO2 was accidently discharged into the storage room. The workers were found unconscious beside the cylinders and were confirmed dead in the hospital soon after. Arterial blood gas analysis revealed severe acute hypercapnia accompanied by respiratory acidosis. Combined with the scene investigation and autopsy findings, the cause of their death was determined to be CO2 intoxication and possible involvement of asphyxiation. Considering the repeated occurrences of unfortunate deaths involving CO2 fire extinguishing systems, this report will be useful for forensic pathologists when dealing with similar cases.

Fatal consequence after MiraDry® treatment: Necrotizing fasciitis complicated with streptococcal toxic shock syndrome.

MiraDry® is a microwave-based cosmetic device commonly used to treat hyperhidrosis and osmidrosis by affecting apocrine and eccrine sweat glands. In most countries, its application is limited to the axillary region. A healthy woman received MiraDry® treatment in the perineal, genital, and perianal regions for body odor in a cosmetic clinic. She experienced severe adverse effects after treatment, including persistent fever, sustained pain, and bleeding in the treated area. The condition deteriorated rapidly with systemic symptoms, and she died on the sixth day. Group A Streptococcus was detected in her skin in the treated areas, and in blood obtained in the hospital and during autopsy. Combined with the clinical diagnosis and autopsy findings, the woman's death was attributed to fatal necrotizing fasciitis (Fournier's gangrene) complicated by streptococcal toxic shock syndrome. Pathogen inoculation was most likely attributable to skin disruption caused by MiraDry® treatment. The MiraDry® application on the genital and perineum is occasionally performed by cosmetic surgeons; however, this case demonstrates the possibility of a rare but fatal complication. Therefore, this case report may be noteworthy and beneficial in forensic practice, and relevant in cosmetic clinical practice.

Role of Mitochondrial Dynamics in Cocaine's Neurotoxicity.

The dynamic balance of mitochondrial fission and fusion maintains mitochondrial homeostasis and optimal function. It is indispensable for cells such as neurons, which rely on the finely tuned mitochondria to carry out their normal physiological activities. The potent psychostimulant cocaine impairs mitochondria as one way it exerts its neurotoxicity, wherein the disturbances in mitochondrial dynamics have been suggested to play an essential role. In this review, we summarize the neurotoxicity of cocaine and the role of mitochondrial dynamics in cellular physiology. Subsequently, we introduce current findings that link disturbed neuronal mitochondrial dynamics with cocaine exposure. Finally, the possible role and potential therapeutic value of mitochondrial dynamics in cocaine neurotoxicity are discussed.

Forensic evaluation of fatal-suffocating retropharyngeal haematoma secondary to cervical fractures: Report of two cases.

PURPOSE: Traumatic retropharyngeal haematoma, a condition of low incidence, often occurs secondary to cervical injuries. Owing to the adjacent anatomical location and its insidious formation, retropharyngeal haematoma is prone to cause airway obstruction, which can occasionally be fatal. Though well known in clinical practice, retropharyngeal haematomas are rarely encountered in forensic practice and are not sufficiently explored from a forensic perspective. CASE PRESENTATION: Herein, we present two cases of fatal-suffocating retropharyngeal haematoma following cervical vertebral fractures. In both cases, the time from injury to death was evident, showing unusually long periods from injury to death, specifically 4 days and 2 days, respectively. The causes of death were illustrated, and the delayed onset of fatal airway obstruction was explained. The important points regarding autopsies suspected to be fatal traumatic retropharyngeal haematomas were discussed. CONCLUSIONS: Knowledge of the possibility of late onset and understanding of the features of imaging and autopsy findings of traumatic retropharyngeal haematoma is beneficial for forensic pathologists dealing with similar cases.

Altered cardiac mitochondrial dynamics and biogenesis in rat after short-term cocaine administration.

Abuse of the potent psychostimulant cocaine is widely established to have cardiovascular consequences. The cardiotoxicity of cocaine is mainly associated with oxidative stress and mitochondrial dysfunction. Mitochondrial dynamics and biogenesis, as well as the mitochondrial unfolded protein response (UPRmt), guarantee cardiac mitochondrial homeostasis. Collectively, these mechanisms act to protect against stress, injury, and the detrimental effects of chemicals on mitochondria. In this study, we examined the effects of cocaine on cardiac mitochondrial dynamics, biogenesis, and UPRmt in vivo. Rats administered cocaine via the tail vein at a dose of 20 mg/kg/day for 7 days showed no structural changes in the myocardium, but electron microscopy revealed a significant increase in the number of cardiac mitochondria. Correspondingly, the expressions of the mitochondrial fission gene and mitochondrial biogenesis were increased after cocaine administration. Significant increase in the expression and nuclear translocation of activating transcription factor 5, the major active regulator of UPRmt, were observed after cocaine administration. Accordingly, our findings show that before any structural changes are observable in the myocardium, cocaine alters mitochondrial dynamics, elevates mitochondrial biogenesis, and induces the activation of UPRmt. These alterations might reflect cardiac mitochondrial compensation to protect against the cardiotoxicity of cocaine.

Diagnosis by forensic autopsy of cannula malposition resulting in fatal tension pneumothorax after attempted percutaneous tracheostomy: A short communication.

Percutaneous tracheostomy is commonly performed in the emergency department or intensive care unit to secure the airways of patients. This procedure is associated with a low incidence of complications; however, some of them, such as iatrogenic pneumothorax, can be fatal. Pneumothorax after percutaneous tracheostomy is most often caused by perforation of the tracheal wall or malposition of the cannula. A woman in her 80s was referred to the emergency department owing to persistent and prolonged coughing. Having speculated that she had acute epiglottitis, and having failed to achieve oral tracheal intubation, the physician performed a percutaneous tracheostomy to secure her airway. However, progressive percutaneous emphysema developed immediately thereafter, and the patient died shortly. Postmortem computed tomography showed bilateral pneumothorax. Forensic autopsy revealed that the tracheostomy cannula had failed to reach the trachea and was erroneously inserted into the right thoracic cavity via peritracheal route. Thus, it was determined that the patient's death was attributable to tension pneumothorax caused by cannula malposition during attempted tracheostomy. To the best of our knowledge, this is the first forensic autopsy case report on fatal tension pneumothorax caused by attempted percutaneous tracheostomy.

Fatal anaphylaxis due to alpha-gal syndrome after initial cetuximab administration: The first forensic case report.

Cetuximab is mainly used for the treatment of advanced and metastatic colorectal cancer. Owing to the oligosaccharide galactose-α-1,3-galactose (α-gal) in its heavy chain, cetuximab can induce severe IgE-dependent anaphylaxis. α-Gal is also the antigen responsible for α-gal syndrome, known as mammalian meat allergy. Patients with α-gal syndrome may suffer from cetuximab-induced anaphylaxis at the first administration because of developed α-gal-specific IgE antibodies. A male patient in his 50 s with metastatic colon cancer was receiving chemotherapy involving scheduled cetuximab administration. However, he died soon after the first administration. Forensic autopsy confirmed rectal cancer, metastatic rectal cancer in the liver, and renal cancer. Laboratory blood tests revealed the presence of cetuximab- and beef-specific IgE antibodies before cetuximab administration and an extremely high level of tryptase after administration. Thus, we determined that the death was caused by cetuximab-induced anaphylaxis due to the preexisting α-gal syndrome. To the best of our knowledge, this is the first autopsy case report in forensic medicine of fatal anaphylaxis after initial cetuximab administration.

Comparative genomics analysis of two banana Fusarium wilt biocontrol endophytes Bacillus subtilis R31 and TR21 provides insights into their differences on phytobeneficial trait.

Fusarium wilt of banana is considered one of the most destructive plant diseases. Bacillus subtilis R31 and TR21, isolated from Dendrobium sp. leaves, exhibit different phytobeneficial effects on banana Fusarium wilt bio-controlling. Here, we performed genome sequencing and comparative genomics analysis of R31 and TR21 to enhance our understanding of the different phytobeneficial traits. These results revealed that the strain-specific genes of R31 involved in sporulation, quorum sensing, and antibiotic synthesis allow R31 to present a better capacity of sporulation, rhizosphere adaptation, and quorum sensing than TR21. Selective pressure analysis indicated that the glycosylase and endo-alpha-(1- > 5)-L-arabinanase genes were strong positive selected, which may contribute to the TR21 to colonize well in banana's vascular bundles. Altogether, our findings presented here should advance further agricultural application of R31 and TR21 as two promising resources of plant growth promotion and biological control via genetic engineering.

Comparative study of treatment for striae alba stage striae gravidarum: 1565-nm non-ablative fractional laser versus fractional microneedle radiofrequency.

Striae gravidarum is a common dermatologic condition for females caused by multiple factors during pregnancy. It remains a therapeutic challenge especially in the striae alba (SA) stage, generating psychological and emotional distress to those affected. This study aims to compare the efficacy and safety of 1565-nm non-ablative fractional laser (NAFL) and fractional microneedle radiofrequency (MRF) for treatment of SA striae gravidarum. Fourteen Chinese women with SA striae gravidarum were included in this study. Patient abdomens were randomly divided into NAFL and MRF treatment sides, treated three times at 6-week intervals. Treatment efficacy was evaluated by subjective (clinical assessments, patient satisfaction rating, adverse effects assessment) assessments and objective (skin melanin index measurement, histological study) assessments. Clinical assessment suggested MRF was more effective (P = 0.0143) for improving the appearance of SA striae gravidarum. Both NAFL and MRF demonstrated effective improvement (P = 0.0082 and P = 0.0158, respectively), with no significant difference according to patient satisfaction ratings and changes in melanin index (P = 0.5900). Both treatments induced limited adverse reactions, but MRF treatment caused significant pain compared with the more moderate NAFL treatment (P = 0.0003). MRF treatment increased neocollagen and elastic fibers more significantly than NAFL, based on histological assessments (P = 0.0298 and P = 0.0048, respectively). MRF treatment improved collagen regeneration in SA striae gravidarum more than NAFL but caused considerable pain during treatment. Corresponding treatment or therapeutic strategies should be applied according to clinical scenario.