Shedding light on the hidden methamphetamine abuse: a nation-wide 7-year post-mortem study in Taiwan.

BACKGROUND: The number of methamphetamine-related deaths has been increasing in recent decades. However, current data primarily rely on a few large-scale national surveys, highlighting the need for diverse data sources. Post-mortem studies offer advantages that compensate for the limitations of cohort studies. In this study, we aimed to (1) examine mortality rates and years of potential life lost, (2) compare proportionate mortality with previous cohort studies, and (3) quantitatively investigate causes of death as potential risk factors associated with each manner of death. METHODS: We analyzed 740 cases from 2013 to 2019 in Taiwan. RESULTS: The mean age of cases was 38.4 years, with a notable loss of 30s years of potential life, and 79.6% were male. The crude mortality rate was 0.45 per 100,000 person-years. The proportionate mortality indicated that autopsy dataset, compared to cohort studies, provided more accurate estimations for accidental deaths, equivalent suicides, underestimated natural deaths, and overestimated homicides. Accidental deaths were evident in 67% of cases with 80% attributed to drug intoxication. Multiple substances were detected in 61% of cases, with psychiatric medications detected in 43% of cases. Higher methamphetamine concentrations and a greater proportion of multiple substances and benzodiazepines were detected in suicidal deaths. Among accidental deaths, traffic accidents (7.9%) were the second most common cause, particularly motorcycle riders. CONCLUSIONS: Using autopsy dataset as a secondary source, we identified that over half of the cases involved accidental drug intoxication. The significant proportion of cases involving multiple substances, psychiatric medications, and drug-impaired driving raises concerning.

"Breaking heart" due to hydrofluoric acid burns in a case of homicide.

Homicide attacks in which hydrofluoric acid (HF) is used are very rare, and few studies have reported the pathological changes. Hypocalcemia is thought to be the cause of sudden death from HF; nevertheless, after neutralization of the blood concentration of calcium ions, HF-induced arrhythmia may still occur, suggesting that in addition to hypocalcemia, direct toxic effects of HF may play a pivotal role in myocardial damage. Here, we report a homicidal forensic autopsy case with pathological changes of the myocardium due to HF burns. Von Kossa staining and immunohistochemical staining were also performed. The cause of death was given as HF toxicity with direct toxic effects on myocardial damage as ischemic injury may occur prior to ventricular fibrillation in the present case. The present case shows that myocardial damage should be given more attention in the clinical treatment and forensic autopsy of HF burns.

Ractopamine at legal residue dosage accelerates atherosclerosis by inducing endothelial dysfunction and promoting macrophage foam cell formation.

Ractopamine, a synthetic ß-adrenoreceptor agonist, is used as an animal feed additive to increase food conversion efficiency and accelerate lean mass accretion in farmed animals. The U.S. Food and Drug Administration claimed that ingesting products containing ractopamine residues at legal dosages might not cause short-term harm to human health. However, the effect of ractopamine on chronic inflammatory diseases and atherosclerosis is unclear. Therefore, we investigated the effects of ractopamine on atherosclerosis and its action mechanism in apolipoprotein E-null (apoe-/-) mice and human endothelial cells (ECs) and macrophages. Daily treatment with ractopamine for four weeks increased the body weight and the weight of brown adipose tissues and gastrocnemius muscles. However, it decreased the weight of white adipose tissues in apoe-/- mice. Additionally, ractopamine exacerbated hyperlipidemia and systemic inflammation, deregulated aortic cholesterol metabolism and inflammation, and accelerated atherosclerosis. In ECs, ractopamine treatment induced endothelial dysfunction and increased monocyte adhesion and transmigration across ECs. In macrophages, ractopamine dysregulated cholesterol metabolism by increasing oxidized low-density lipoprotein (oxLDL) internalization and decreasing reverse cholesterol transporters, increasing oxLDL-induced lipid accumulation. Collectively, our findings revealed that ractopamine induces EC dysfunction and deregulated cholesterol metabolism of macrophages, which ultimately accelerates atherosclerosis progression.

Tuberculosis Surveillance in Taiwan Forensic Autopsy Cases: A Retrospective Analysis of 71 Cases From 2012 to 2017.

Tuberculosis (TB) is one of the most important public health issues worldwide, and global efforts have altered the TB epidemic. This study analyzed 71 cases of TB at autopsy notified via Taiwan Medical Examiner Surveillance for Lethal Infectious Disease (Taiwan Med-X) between 2012 and 2017 and applied immunohistochemistry to formalin-fixed lung tissue. Tuberculosis was present in 0.57% (71/12,369) forensic autopsy cases in the institute. Among the study cases, 30 (42.3%) cases were newly diagnosed with TB at autopsy, whereas 41 (57.7%) cases were notified before death and have still seen the TB pathological changes. Regarding the death investigation, cause of death was TB accounted for 46.5%, and non-TB, 53.5% (including trauma, 26.8%; other diseases, 19.7%; drowning, 4.2%; and drug abuse, 2.8%, respectively). Compared with the staining signal, immunohistochemistry has better sensitivity than acid-fast staining. This study provides a reassessment of the reference value to estimate the burden of disease caused by TB and emphasizes the importance of biosafety in an autopsy room.

Fatal parvovirus B19 infections: a report of two autopsy cases.

Parvovirus B19 (PVB19) commonly infects children and is usually asymptomatic. Lethal outcomes of PVB19 infection are unusual; nevertheless, the two cases reported here are rare examples of PVB19-induced hemophagocytic syndrome and myocarditis in infants and children. The two cases show the indisputable usefulness of immunohistochemistry and in situ hybridization in the detection of PVB19. In the death investigations, histopathological examinations provided stronger evidence than did serology or molecular biology. The cases also highlight the importance of forensic autopsy in vaccine-related death. As vaccine-related deaths are what people fear and may cause declines in vaccination rates, it is important to clarify deaths temporally or causally associated with vaccine administration.

Rhabdomyolysis observed at forensic autopsy: a series of 52 cases.

Rhabdomyolysis is characterized by skeletal muscle injury resulting in the release of intracellular proteins (such as myoglobin) and electrolytes into the blood circulation, which cause acute kidney injury, myoglobinuria and electrolyte imbalances. Clinical diagnosis of rhabdomyolysis is made on the basis of biochemical analysis; however, for forensic autopsies, biochemical data are often not available, and it is necessary to diagnose rhabdomyolysis via histopathological examinations. This study analyzed 52 cases with rhabdomyolysis and applied myoglobin immunohistochemistry to kidney, urine and blood samples. We found that blunt force injuries were the most common cause of rhabdomyolysis across all age groups, and drugs were the second most common cause. The drugs included ketamines, amphetamines, synthetic cathinones, entheogens, benzodiazepines, opioid analgesics, and anesthesia. Less than 60% of our cases had biochemical data, including myoglobin (92.5~416,978 ng/mL), creatine kinase (220~774,015 U/L), potassium (1.6~10.3 meq/L), calcium (2.7~29.2 mg/dL), and phosphorus (2.6~14.2 mg/dL). In the kidney tissue sections, we found that 95% of the rhabdomyolysis cases were positive for myoglobin immunohistochemistry and that 96% were associated with acute tubular necrosis. Our findings describe the features of fatal rhabdomyolysis in a large series and suggest that myoglobin immunohistochemistry can be used in post-mortem blood and urine cell blocks to detect myoglobin.

Dengue virus infection induces autophagy: an in vivo study.

BACKGROUND: We and others have reported that autophagy is induced by dengue viruses (DVs) in various cell lines, and that it plays a supportive role in DV replication. This study intended to clarify whether DV infection could induce autophagy in vivo. Furthermore, the effect of DV induced autophagy on viral replication and DV-related pathogenesis was investigated. RESULTS AND CONCLUSIONS: The physiopathological parameters were evaluated after DV2 was intracranially injected into 6-day-old ICR suckling mice. Autophagy-related markers were monitored by immunohistochemical/immunofluorescent staining and Western blotting. Double-membrane autophagic vesicles were investigated by transmission-electron-microscopy. DV non-structural-protein-1 (NS1) expression (indicating DV infection) was detected in the cerebrum, medulla and midbrain of the infected mice. In these infected tissues, increased LC3 puncta formation, LC3-II expression, double-membrane autophagosome-like vesicles (autophagosome), amphisome, and decreased p62 accumulation were observed, indicating that DV2 induces the autophagic progression in vivo. Amphisome formation was demonstrated by colocalization of DV2-NS1 protein or LC3 puncta and mannose-6-phosphate receptor (MPR, endosome marker) in DV2-infected brain tissues. We further manipulated DV-induced autophagy by the inducer rapamycin and the inhibitor 3-methyladenine (3MA), which accordingly promoted or suppressed the disease symptoms and virus load in the brain of the infected mice.We demonstrated that DV2 infection of the suckling mice induces autophagy, which plays a promoting role in DV replication and pathogenesis.

Resveratrol inhibits alpha-melanocyte-stimulating hormone signaling, viability, and invasiveness in melanoma cells.

Melanoma is a malignancy with high potential to invasion and treatment resistance. The α -melanocyte-stimulating hormone ( α -MSH) signal transduction involving Wnt/ ß -catenin, c-Kit, and microphthalmia-associated transcription factor (MITF), a known pathway to produce melanin, has been demonstrated as one of cancer stem cell characteristics. This study was aimed to examine the effect of resveratrol, an abundant ingredient of grape and medicinal plants, on α -MSH signaling, viability, and invasiveness in melanoma cells. By α -MSH treatment, the melanin production in B16 melanoma cells was augmented as a validation for activation of α -MSH signaling. The upregulated expression of α -MSH signaling-related molecules ß -catenin, c-Kit, and MITF was suppressed by resveratrol and/or STI571 treatment. Nuclear translocation of MITF, a hallmark of α -MSH signaling activation, was inhibited by combined treatment of resveratrol and STI571. At effective concentration, resveratrol and/or STI571 inhibited cell viability and α -MSH-activated matrix metalloproteinase- (MMP-)9 expression and invasion capacity of B16 melanoma cells. In conclusion, resveratrol enhances STI571 effect on suppressing the α -MSH signaling, viability, and invasiveness in melanoma cells. It implicates that resveratrol may have potential to modulate the cancer stem cell characteristics of melanoma.