One autopsy case of cyanide-gas poisoning

A fishing-boat was smoked with cyanide-gas to rid vermin. A thirty-year old male was found dead in a cabin of the boat. Autopsy revealed fluid blood, and petechial haemorrhage in conjunctivas, thymus, heart and lungs. Lung, spleen, kidney and other organs were strongly congested. Bleedings in sternocleidomastoideus and sterunohyoideus muscles were found. The bloody foam and solution were also observed in trachea. From these autopsy findings, it was considered that he failed into severe dyspnea. Furthermore, postmortem lividity was bright pink color and the left cardiac blood was also bright pink, so there was markly different between the color of right and left cardiac blood. To make clear his cause of death, during the autopsy the screening test of cyanide, Schonbein-Pagenstecher method, was tried and then it was positive. Further toxicological analysis, quantitative measurement revealed 6.25 μg/ml of cyanide from his blood. From the results of autopsy and toxicological findings, his cause of death was diagnosed as the cyanide-gas poisoning

Digital Autopsy: Popular Tools for an Unpopular Procedure

Digital autopsy is the future of postmortem examination of the human body through digital visualization. Imaging modalities such as CT scanners and MRI scanners use X rays and magnetic fields to visualize the structures within the human body. The outputs from these modalities are obtained in a DICOM (Digital Imaging and Communications of Medicine) format. They are in gray-scale consisting of information in every slice taken during the scan. This is rendered and visualized as the full body in a digital format during the digital autopsy procedure. The visualization rendering produces a three-dimensional body, further presented in colour format based on each structure of the human organ system. Digital autopsy is a technology which allows pathologists to navigate and explore deeper into the human body. It allows analysis to be done in both two-dimensional and three dimensional perspectives. Digital autopsy involves analysis of human pathology and anatomical findings for diagnostic purposes. It can also be used for education and research purposes. Another advantage of digital autopsy is the availability of information and data that can be easily and securely transferred to a different digital autopsy facility at a different location. Thus, digital autopsy provides an efficient, fast, cheaper and accurate post-mortem data enabling a forensic pathologists to play a more effective role in the criminal justice system

Accurate interpretation of genetic variants in sudden unexpected death in infancy by trio-targeted gene-sequencing panel analysis

In sudden unexpected death in infancy cases, postmortem genetic analysis with next-generation sequencing potentially can extract candidate genes associated with sudden death. However, it is difficult to accurately interpret the clinically significant genetic variants. The study aim was to conduct trio analysis of cases of sudden unexpected death in infancy and their parents to more accurately interpret the clinically significant disease-associated gene variants associated with cause of death. From the TruSight One panel targeting 4813 genes we extracted candidate genetic variants of 66 arrhythmia-, 63 inherited metabolic disease-, 81 mitochondrial disease-, and 6 salt-losing tubulopathy-related genes in 7 cases and determined if they were de novo or parental-derived variants. Thirty-four parental-derived variants and no de novo variants were found, but none appeared to be related to the cause of death. Using trio analysis and an in silico algorithm to analyze all 4813 genes, we identified OBSCN of compound heterozygous and HCCS of hemizygous variants as new candidate genetic variants related to cause of death. Genetic analysis of these deceased infants and their living parents can provide more accurate interpretation of the clinically significant genetic variants than previously possible and help confirm the cause of death

HSP70 and c-Fos expression of brain stem hypoglossal nucleus in drowning

The brain stem hypoglossal nucleus (HN) is the center of nerves innervating the upper respiratory tract and is related to control of mastication, deglutition, speech and respiration. To elucidate the relationship between asphyxia and the HN, we investigated the change of hypoglossal neurons in cases of hanging, strangulation, smothering, choking, drowning and respiratory failure. Using immunohistochemical techniques, we observed the brain stem HN with antibodies against microtubule-associated protein2(MAP2), muscarinic acetylcholine receptor (mAChR), c-fos gene product (c-Fos) and 72kD heat-shock protein (HSP70). MAP2, a cytoskeletal protein of the neuron, is a marker of neuronal damage. Muscarinic AChR was used as a marker of neuronal membrane and ACh signaling. We employed both HSP70 and c-Fos as markers of stress- or damage-related events. We measured the percentage of immunopositive neurons in total neurons of HN. Drowning produced higher expression of HSP70 and c-Fos than other causes of asphyxia, suggesting that drowning induces more severe damage in HN neurons. Furthermore, it was suspected that neuronal changes in drowning might relate to functions of the HN. These observations indicate that immunohistochemical examination of the brain stem HN could provide useful information for determining the cause of asphyxia

Generation of three induced pluripotent stem cell lines from postmortem tissue derived following sudden death of a young patient with STXBP1 mutation

We established three iPSC lines from postmortem-cultured fibroblasts derived following the sudden unexpected death of an 8-year-old girl with Lennox-Gastaut syndrome, who turned out to have the R551H-mutant STXBP1 gene. These iPSC clones showed pluripotent characteristics while retaining the genotype and demonstrated trilineage differentiation capability, indicating their utility in disease-modeling studies, i.e., STXBP1-encephalopathy. This is the first report on the establishment of iPSCs from a sudden death child, suggesting the possible use of postmortem-iPSC technologies as an epoch-making approach for precise identification of the cause of sudden death

Latent adrenal Ewing sarcoma family of tumors: A case report

Ewing sarcoma family of tumors (ESFT) is derived from the neural crest, which originates from basal embryo cells in the primitive neural tube. ESFT often arises at the bone, chest wall, and soft tissues of the thoracic region. However, ESFT that arises from the adrenal gland is much rarer and it is usually revealed by clinical symptoms. We report an autopsy case of suicidal hanging, in which adrenal ESFT was incidentally revealed. To our knowledge, this is the first case of latent ESFT arising from the adrenal gland. Autopsy can sometimes reveal latent disease. Some of these latent diseases are very rare and we would not be able to detect them without a complete autopsy. As forensic pathologists, we should attempt to perform a complete autopsy and report new discoveries for the development of medicine

Carnitine palmitoyltransferase 2 gene polymorphism is a genetic risk factor for sudden unexpected death in infancy

Rationale: Carnitine palmitoyltransferase (CPT) II is one of a pivotal enzyme in mitochondrial fatty acid oxidation, which is essential for energy production during simultaneous glucose sparing and a requirement for major energy supply, such as prolonged fasting or exercise. When infants require more energy than provided by the glycolytic system, they rely on the mitochondrial fatty acid oxidation pathway. Mutations of the CPT2 gene have been reported to cause sudden unexpected death in infancy (SUDI). A thermolabile phenotype of a CPT2 polymorphism (F352C) has been recently reported to reduce CPT II enzyme activity. The F352C variant results in energy crisis at high temperature and is suspected as a risk factor for acute encephalopathy. However, a relationship between CPT2 gene polymorphism and SUDI has not been described. Methods: Single nucleotide polymorphisms of the CPT2 gene were investigated among 54 SUDI cases and 200 healthy volunteers. Results: The frequency of the C allele was significantly higher in the SUDI group than in the control group [25.0% vs 16.0%, odds ratio (OR). = 1.75, 95% confidence interval (CI). = 1.05-2.92, p= 0.030). The frequency of the F352C homozygote was significantly higher in the SUDI group than in control group (11.1% vs 3.5%, OR. = 3.45, 95% CI. = 1.11-10.73, p= 0.036). Conclusion: The F352C CPT2 variant might be a genetic risk factor for SUDI

Targeting miR-223 in neutrophils enhances the clearance of Staphylococcus aureus in infected wounds

Abstract Argonaute 2 bound mature microRNA (Ago2‐miRNA) complexes are key regulators of the wound inflammatory response and function in the translational processing of target mRNAs. In this study, we identified four wound inflammation‐related Ago2‐miRNAs (miR‐139‐5p, miR‐142‐3p, miR‐142‐5p, and miR‐223) and show that miR‐223 is critical for infection control. miR‐223Y/− mice exhibited delayed sterile healing with prolonged neutrophil activation and interleukin‐6 expression, and markedly improved repair of Staphylococcus aureus‐infected wounds. We also showed that the expression of miR‐223 was regulated by CCAAT/enhancer binding protein alpha in human neutrophils after exposure to S. aureus peptides. Treatment with miR‐223Y/−‐derived neutrophils, or miR‐223 antisense oligodeoxynucleotides in S. aureus‐infected wild‐type wounds markedly improved the healing of these otherwise chronic, slow healing wounds. This study reveals how miR‐223 regulates the bactericidal capacity of neutrophils at wound sites and indicates that targeting miR‐223 might be of therapeutic benefit for infected wounds in the clinic

Reduced FOXO1 Expression Accelerates Skin Wound Healing and Attenuates Scarring

The forkhead box O (FOXO) family has been extensively investigated in aging and metabolism, but its role in tissue-repair processes remains largely unknown. Herein, we clarify the molecular aspect of the FOXO family in skin wound healing. We demonstrated that Foxo1 and Foxo3a were both up-regulated during murine skin wound healing. Partial knockout of Foxo1 in Foxo1 +/- mice throughout the body led to accelerated skin wound healing with enhanced keratinocyte migration, reduced granulation tissue formation, and decreased collagen density, accompanied by an attenuated inflammatory response, but we observed no wound phenotype in Foxo3a-/- mice. Fibroblast growth factor 2, adiponectin, and notch1 genes were significantly increased at wound sites in Foxo1+/- mice, along with markedly altered extracellular signal-regulated kinase 1/2 and AKT phosphorylation. Similarly, transient knockdown of Foxo1 at the wound site by local delivery of antisense oligodeoxynucleotides enhanced skin wound healing. The link between FOXO1 and scarring extends to patients, in particular keloid scars, where we see FOXO1 expression markedly increased in fibroblasts and inflammatory cells within the otherwise normal dermis. This occurs in the immediate vicinity of the keloid by comparison to the center of the mature keloid, indicating that FOXO1 is associated with the overgrowth of this fibrotic response into adjacent normal skin. Overall, our data indicate that molecular targeting of FOXO1 may improve the quality of healing and reduce pathological scarring