Endothelial CLEC-1b plays a protective role against cancer hematogenous metastasis.

Metastasis, which is the spread of cancer cells into distant organs, is a critical determinant of prognosis in patients with cancer, and blood vessels are the major route for cancer cells to spread systemically. Extravasation is a critical process for the hematogenous metastasis; however, its underlying molecular mechanisms remain poorly understood. Here, we identified that senescent ECs highly express C-type lectin domain family 1 member B (CLEC-1b), and that endothelial CLEC-1b inhibits the hematogenous metastasis of a certain type of cancer. CLEC-1b expression was enhanced in ECs isolated from aged mice, senescent cultured human ECs, and ECs of aged human. CLEC-1b overexpression in ECs prevented the disruption of endothelial integrity, and inhibited the transendothelial migration of cancer cells expressing podoplanin (PDPN), a ligand for CLEC-1b. Notably, target activation of CLEC-1b in ECs decreased the hematogenous metastasis in the lungs by cancer cells expressing PDPN in mice. Our data reveal the protective role of endothelial CLEC-1b against cancer hematogenous metastasis. Considering the high CLEC-1b expression in senescent ECs, EC senescence may play a beneficial role with respect to the cancer hematogenous metastasis.

Factors determining the resection ability of snares in cold snare polypectomy: Construction of an ex vivo model for accurately evaluating resection ability.

OBJECTIVES: Cold snare polypectomy (CSP)-dedicated snares (DSs) may have a higher resection ability than conventional snares. However, a model that can accurately and objectively evaluate and compare the resection ability of each snare has yet to be determined, and characteristics of snare parts that increase resection ability remain unknown. Therefore, we elucidated DSs' resection ability and all characteristics of the parts required for acquiring high resection ability. METHODS: An ex vivo model for evaluating resection ability was generated using human colons obtained from forensic autopsy specimens. The force required to resect a 15 mm wide human colonic mucosa (FRR) was measured using this model; if the FRR is small, the resection ability is high. Next, after measuring the stiffness of each snare part, the correlation between the stiffness and resection ability was analyzed. RESULTS: The force required to resect using SnareMaster Plus, Micro-Tech Cold Snare, Captivator Cold, Exacto Cold Snare, or Captivator II was 13.6 ± 1.0, 12.5 ± 1.2, 7.4 ± 1.2, 6.5 ± 1.0, and 28.7 ± 3.7 N, respectively. All DSs had significantly lower FRR than the conventional snare (Captivator II) and had higher resection ability (P < 0.001). A negative correlation was found between FRR and sheath or wire spindle stiffness, with correlation coefficients of 0.72 (P = 0.042) or 0.94 (P < 0.001), respectively. Moreover, 1 × 7 type wire rings had significantly higher friction coefficients than 1 × 3 type wire rings (P < 0.002). CONCLUSION: Sheath and wire spindle stiffness should be increased to increase resection ability; 1 × 7 type wire rings may be suitable for CSP-snare parts.

Higher Viral Stability and Ethanol Resistance of Avian Influenza A(H5N1) Virus on Human Skin.

Evaluating the stability of highly pathogenic avian influenza viruses on human skin and measuring the effectiveness of disinfectants are crucial for preventing contact disease transmission. We constructed an evaluation model using autopsy skin samples and evaluated factors that affect the stability and disinfectant effectiveness for various subtypes. The survival time of the avian influenza A(H5N1) virus on plastic surfaces was ≈26 hours and on skin surfaces ≈4.5 hours, >2.5-fold longer than other subtypes. The effectiveness of a relatively low ethanol concentration (32%-36% wt/wt) against the H5N1 subtype was substantially reduced compared with other subtypes. Moreover, recombinant viruses with the neuraminidase gene of H5N1 survived longer on plastic and skin surfaces than other recombinant viruses and were resistant to ethanol. Our results imply that the H5N1 subtype poses a higher contact transmission risk because of its higher stability and ethanol resistance, which might depend on the neuraminidase protein.

Alcohol abuse as a potential risk factor of solitary death among people living alone: a cross-sectional study in Kyoto, Japan.

BACKGROUND: Solitary death is an emerging public health problem in developed countries. Alcohol abuse is associated with social isolation and excess mortality. However, data on the association between alcohol abuse and solitary death are limited. Our purposes were to assess whether alcohol abuse is associated with a long interval from death to discovery among people living alone. METHODS: This is a cross-sectional study using the data on subjects from the largest forensic database in Kyoto, Japan, from February 2012 to December 2015. Solitary death was defined as a phenomenon of dying alone at home and remaining undiscovered for more than 1 week. All the subjects who lived alone and aged over 18 at the time of death were included in the study. The presence of alcohol abuse was identified via an investigation during home visits. Proportional ratios were calculated using a fitted logit model to evaluate the association of alcohol abuse on solitary death after adjusting for possible confounders. RESULTS: A total of 235 subjects were included in the analysis. The mean age (standard deviation) of subjects at the time of death was 63.4 (15.1) years, and approximately 61.8% and 38.9% of subjects in the alcohol and non-alcohol abuse groups, respectively, experienced solitary death. Multivariable analyses revealed that alcohol abuse was associated with solitary death (adjusted proportion ratio: 1.50; 95% confidence interval: 1.12-2.00). CONCLUSIONS: The findings of this study could help identify individuals at higher risk of solitary death. Moreover, calling the attention of people with alcohol abuse may be beneficial to prevent solitary death.

Sudden death of a 2-year-old child due to alpha-ketoadipic aciduria.

Alpha-ketoadipic acid is one of the metabolic intermediates of lysine and tryptophan, and it is known as the biochemical hallmark of alpha-ketoadipic aciduria (α-KA). α-KA is a rare autosomal recessive disorder. Its pathophysiology is reduced alpha-ketoadipic acid dehydrogenase activity, and that makes it difficult to metabolize lysine and tryptophan. The symptoms of this disease are multiple, e.g., psychomotor retardation, epilepsy, and ataxia, and it can even be asymptomatic. We present a case of sudden death in a 2-year-old boy with alpha-ketoadipic aciduria. Postmortem computed tomography (CT) and autopsy were performed to elucidate the cause of death. No obvious lesions could be identified except for a marked fatty liver. Urinalysis showed elevated excretion of α-ketoadipic acid.

Survival of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and Influenza Virus on Human Skin: Importance of Hand Hygiene in Coronavirus Disease 2019 (COVID-19).

BACKGROUND: The stability of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on human skin remains unknown, considering the hazards of viral exposure to humans. We generated a model that allows the safe reproduction of clinical studies on the application of pathogens to human skin and elucidated the stability of SARS-CoV-2 on human skin. METHODS: We evaluated the stability of SARS-CoV-2 and influenza A virus (IAV), mixed with culture medium or upper respiratory mucus, on human skin surfaces and the dermal disinfection effectiveness of 80% (weight/weight) ethanol against SARS-CoV-2 and IAV. RESULTS: SARS-CoV-2 and IAV were inactivated more rapidly on skin surfaces than on other surfaces (stainless steel/glass/plastic); the survival time was significantly longer for SARS-CoV-2 than for IAV (9.04 hours [95% confidence interval, 7.96- 10.2 hours] vs 1.82 hours [1.65-2.00 hours]). IAV on other surfaces was inactivated faster in mucus versus medium conditions, while SARS-CoV-2 showed similar stability in the mucus and medium; the survival time was significantly longer for SARS-CoV-2 than for IAV (11.09 hours [10.22-12.00 hours] vs 1.69 hours [1.57-1.81 hours]). Moreover, both SARS-CoV-2 and IAV in the mucus/medium on human skin were completely inactivated within 15 seconds by ethanol treatment. CONCLUSIONS: The 9-hour survival of SARS-CoV-2 on human skin may increase the risk of contact transmission in comparison with IAV, thus accelerating the pandemic. Proper hand hygiene is important to prevent the spread of SARS-CoV-2 infections.

Evaluation of the Residual Disinfection Effects of Commonly Used Skin Disinfectants against Viruses: An Innovative Contact Transmission Control Method.

Lasting disinfection effects, that is, the residual disinfection effects (RDEs), of skin-coated disinfectants have rarely been considered for infection control owing to the challenges involved in the accurate evaluation of RDEs. In this study, we constructed a new skin evaluation model and determined the RDEs of existing disinfectants against viruses. Our results showed that ethanol and isopropanol had no RDE, whereas povidone-iodine, chlorhexidine gluconate, and benzalkonium chloride (BAC) exhibited RDEs, with 10% povidone-iodine and 0.2% BAC showing particularly strong RDEs. The RDE of 0.2% BAC was strong enough to reduce the median survival times of severe acute respiratory syndrome coronavirus-2, human coronavirus-OC43, and influenza virus from 670 to 5.2, 1300 to 12, and 120 to 4.2 min, respectively. Additionally, this strong RDE was maintained even 4 h after coating the skin. Clinical data also showed that the strong RDE of 0.2% BAC was maintained for more than 2 h. Thus, applying disinfectants with strong RDEs on the skin correlates with a reduction in virus survival time and appears to create a skin surface environment that is not conducive to virus survival. A prolonged reduction in virus survival decreases the contact transmission risk, thereby enabling stronger infection control.

Simple, Frequent Indicator for Personal Identification-Postmortem and Antemortem Abdominal Computed Tomography Findings of a Charred Body.

Postmortem personal identification in forensic science is performed using various methods. However, severely burnt bodies are hard to identify using odontological or skeletal features because of carbonization, and sometimes DNA profiling is impracticable because of the unavailability of the relatives. We present a case of a burn victim found after a house fire. Personal identification was attempted, but the body was heavily charred to the bones and the use of physical appearance was impracticable. There were no known relatives or personal belongings of the deceased for comparison of DNA typing. We obtained a series of abdominal computed tomography (CT) scans taken antemortem and found bilateral multiple renal cysts, left renal artery calcification, and a big right inguinal hernia, which matched the deceased's postmortem CT findings and autopsy findings. To date, studies of identification by CT have acted for a rise in precision, but they require complicated calculation or high graphical methods. Calcification of the arteries or renal cysts seen in our case are very common lesions present in many adults with abundant variation; thus, they may be helpful as simple indicators for identification.

The genome profiling method can be applied for species identification of biological materials collected at crime scenes.

BACKGROUND: Various biological materials unrelated to humans are found at crime scenes and it is often important to elucidate the origin of these materials. A genetic locus common to several species is conventionally PCR-amplified with universal primers to identify species. However, not all species can be identified using a single locus. In this study, DNA from 13 commonly handled taxa was analyzed to identify species by a genome profiling (GP) method, which involves random PCR and temperature gradient gel electrophoresis. RESULTS: In a clustering analysis, we successfully obtained a single cluster for each species. CONCLUSION: The GP method is cost-effective and does not require advanced techniques and knowledge in molecular biology. The random sampling of the whole genome using multiple primers provides substantial genomic information. Therefore, the method is effective for classifying a wide range of species, including animals, plants, and insects, and is useful for crime scene investigations.

Age estimation based on visual parameters of the skin of cadavers.

BACKGROUND: Previous studies have reported relationships between various visual parameters of the skin and changes due to aging. Due to an increase in the discovery of unidentified bodies, the field of forensic medicine anticipates the development of a rapid method for estimating age. The present study measured various visual parameters of the skin in human remains and investigated the correlation between these parameters and age. MATERIALS AND METHODS: Skin images were taken of four body parts (cheek, chin, brachium, and thigh) of 414 forensic cases. We interpreted eight visual parameters of the skin (smoothness, roughness, texture, dullness, brightness, erythema, color phase, and sagging) from skin photograph images, and constructed three age-prediction models, categorized by sex, postmortem interval, and age. RESULTS: Significant correlations were observed in the erythema of the cheek and chin, the roughness of the brachium, and the texture of the brachium and thigh among the visual parameters calculated in four body parts, using the three models. The root-mean-square errors, which indicate the precision of the three prediction models, were 13.06, 13.80, and 13.77. The only model that demonstrated a correlation with the visual parameters was sex (but not age or postmortem interval). CONCLUSION: Similar to living subjects, we observed a correlation with age for a number of visual parameters. The parameters that correlate with age depend on whether the site being measured was exposed to sunlight. Age estimation based on visual parameters requires measurement of visual parameters for skin both exposed and not exposed to sunlight.

5-HT2A Receptor Agonist-Induced Hyperthermia Is Induced via Vasoconstriction by Peripheral 5-HT2A Receptors and Brown Adipose Tissue Thermogenesis by Peripheral Serotonin Loss at a High Ambient Temperature.

Recreational drugs such as 3,4-methylenedioxymethamphetamine and cocaine induce hyperthermia, which is affected by ambient temperature. 2-(4-Bromo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine (25B-NBOMe), a selective agonist of 5-HT2A receptor used as a recreational drug, reportedly induces hyperthermia. This study aimed to verify whether 25B-NBOMe induces ambient temperature-dependent hyperthermia and to clarify its mechanism. Eight-week-old male Sprague-Dawley rats were administered intraperitoneal injection of 25B-NBOMe at an ambient temperature of 23°C or 29°C. 25B-NBOMe administration at 23°C did not change the core body temperature of the rats, whereas administration at 29°C induced significant hyperthermia 30-120 minutes postadministration. Tail surface temperature temporarily decreased 30 minutes postadministration, indicating heat storage by peripheral vasoconstriction despite a high ambient temperature. Because 25B-NBOMe-induced-hyperthermia was suppressed by sarpogrelate, but not by destruction of central noradrenaline or serotonin neurons, peripheral 5-HT2A receptors were considered contributors to the development of hyperthermia at a high ambient temperature, independently from central neurons. The temperature of brown adipose tissue (BAT) increased 60-120 minutes postadministration of 25B-NBOMe at 29°C, indicating thermogenesis. Previous studies have reported that peripheral serotonin contributes to the inhibition of BAT thermogenesis. Decreased plasma serotonin levels were observed at 29°C, and serotonin administration partially suppressed 25B-NBOMe-induced hyperthermia at a high ambient temperature, suggesting that decreased levels of peripheral serotonin induced BAT thermogenesis. Our findings indicate that 25B-NBOMe induces hyperthermia at a high ambient temperature via vasoconstriction regulated by 5-HT2A receptors and BAT thermogenesis mediated by decreased levels of plasma serotonin. Thus, peripheral serotonin plays a partial but important role in thermoregulation.

Detection of hepatitis B virus DNA and HBsAg from postmortem blood and bloodstains.

A large number of accidental virus infections occur in medical and non-medical workers exposed to infectious individuals and materials. We evaluated whether postmortem blood and bloodstains containing hepatitis B virus (HBV) are infectious. HBV-infected blood and bloodstains were stored for up to 60 days at room temperature and subsequently screened for hepatitis B surface antigen (HBsAg) and HBV DNA. In addition, HBV-positive postmortem blood was added to a cell line and the production of HBV virions was examined over a period of 7 days. HBsAg and HBV DNA were detected in all samples stored for 60 days at room temperature. HBV-positive postmortem blood successfully infected the cell line and progeny viruses were produced for up to 6 days. Thus, it is crucial that due care is taken when handling not only living material infected with HBV, as well as other harmful viruses, but also blood or body fluids from cadavers or medical waste.

Spectral Mining for Discriminating Blood Origins in the Presence of Substrate Interference via Attenuated Total Reflection Fourier Transform Infrared Spectroscopy: Postmortem or Antemortem Blood?

Often in criminal investigations, discrimination of types of body fluid evidence is crucially important to ascertain how a crime was committed. Compared to current methods using biochemical techniques, vibrational spectroscopic approaches can provide versatile applicability to identify various body fluid types without sample invasion. However, their applicability is limited to pure body fluid samples because important signals from body fluids incorporated in a substrate are affected strongly by interference from substrate signals. Herein, we describe a novel approach to recover body fluid signals that are embedded in strong substrate interferences using attenuated total reflection Fourier transform infrared (ATR FT-IR) spectroscopy and an innovative multivariate spectral processing. This technique supported detection of covert features of body fluid signals, and then identified origins of body fluid stains on substrates. We discriminated between ATR FT-IR spectra of postmortem blood (PB) and those of antemortem blood (AB) by creating a multivariate statistics model. From ATR FT-IR spectra of PB and AB stains on interfering substrates (polyester, cotton, and denim), blood-originated signals were extracted by a weighted linear regression approach we developed originally using principal components of both blood and substrate spectra. The blood-originated signals were finally classified by the discriminant model, demonstrating high discriminant accuracy. The present method can identify body fluid evidence independently of the substrate type, which is expected to promote the application of vibrational spectroscopic techniques in forensic body fluid analysis.

Search and removal of radioactive seeds: another application of postmortem computed tomography prior to autopsy.

We herein introduce 3 cases illustrating a new application for pre-autopsy postmortem computed tomography (PMCT). In all 3 cases, there was insufficient background information about the victims provided to the forensic pathologists' department. PMCT showed metallic particles in the prostate gland, an indication of metallic seeds containing radioactive isotopes. In 2 of 3 cases, migrated seeds were also detected by CT imaging in the lungs and the heart. Also in 2 of 3 cases, authorities reinvestigated the victim's history before autopsy was completed, which resulted in following appropriate procedure for dealing with the seeds. Although all 3 cadavers were cremated after autopsy, the International Commission on Radiological Protection (ICRP) discourages cremation for deaths soon after radioactive seeds implantation to prevent air pollution by radioactive isotopes in the ash. Our opinion from the present cases is that pre-autopsy PMCT can be recommended for use by forensic pathologists and guidelines for investigating deaths after permanent brachytherapy should include how to deal with cadavers when medical history is limited.

Isolation and unnatural death of elderly people in the aging Japanese society.

PURPOSE: Japanese society has reached an unprecedented level of aging, with elderly people accounting for 25.1% of the population in October 2013. These changes have created concerns regarding deaths among the elderly. In this study, we compared recent forensic autopsy cases with cases from about 20 years ago, with the goal of understanding the context of death among the elderly within Japanese society today. METHODS: We investigated the forensic autopsy records of 297 people aged 65 years or above. In order to examine the effect of residential circumstances, we classified these cases into two groups: people who lived alone (group A) and those who lived with their family (group B). Forty-five of these autopsy cases were conducted about 20 years ago (1989 to 1993) and 252 cases were recent (2009 to 2013). The cases were limited to people who had been found dead or in a critical situation at home. We investigated the first finder, the period of time elapsed between death and discovery, and the cause of death. RESULTS: The incidence of the first finder being a family member was more than 20% greater in group B compared with group A. The proportions of cases for which it took more than three days for someone to find the body or an abnormal situation were about 14% and 7% in groups A and B, respectively, 20 years ago, and about 48% and 19% among the recent cases. These proportions were significantly higher among the recent cases. Among recent cases, a post-mortem elapsed time of more than 3 days occurred more often in group A than group B (p=0.0002). None of the older cases had an unknown cause of death in either group. However, among the recent cases from both groups, 20-30% of cases resulted in unknown causes of death. The incidences of unknown causes of death were significantly higher among the recent cases in both groups (p=0.015) and in group B alone (p=0.037). The incidences of murder cases were significantly lower in group B among the recent cases (p=0.0022). DISCUSSION: Elderly people who live alone are not easily found or aided when in critical situations, and they may only be discovered after death. Prolongation of the postmortem interval (PMI) results in the deterioration of the corpse making determination of cause of death problematic. The results of this study suggest that there are three factors that isolate elderly people and increase the difficulty in determining their cause of death: reduced communication with family members, reduced communication with neighbors or the community, and the increasing prevalence of the nuclear family. In group B, the prolonged discovery time and the increased incidence of unknown causes of death suggest reduced communication with family members, even though the incidence of being found by a family member was higher than in group A. The murder rate was significantly lower in group B, which may suggest that cases of domestic murder were overlooked. Support for a safe life and peaceful ending for the elderly requires a system based on three factors: remote monitoring to ensure safety, the establishment of elderly groups providing mutual support, and increased visits from welfare workers. Understanding the circumstances of the elderly who die alone is beneficial to countries facing an aging society with weakened family or community structures, and who hope for better support for the elderly.

Still without Sales Restriction? Fatal Caffeine Toxicity A case report.

Caffeine-containing drinks are popular daily beverages worldwide and highly concentrated caffeine in the form of tablets is easily obtainable in local chemists. It is common to detect caffeine in toxicological screens in autopsy cases, but we always have to take in account that caffeine itself possesses toxicity which may sometimes lead to death The case was a 44-year-old woman who was found dead in her room one day in June. Empty packages of 'Estaron Mocha 12®, accounting for 14 tablets, were found at the scene. The autopsy showed nothing remarkable suggesting external forces, apart from white granules in her stomach. Toxicological analysis revealed 127 mg/L of caffeine concentration in the deceased's blood, which was considered to be fatal. Caffeine intoxication cases have been reported from many countries. Some are caused by accidental overtake of energy drinks, and many others are caused by intentional intake of caffeine tablets. We think that some restrictions will be effective to prevent this kind of death.

A Fatal Case of Cervical Hemorrhage After Fine Needle Aspiration and Core Needle Biopsy of the Thyroid Gland.

Fine needle aspiration (FNA) and core needle biopsy (CNB) are recognized to be safe, useful, and inexpensive diagnostic tools for the evaluation of thyroid nodules. However, complications can arise during the procedure, albeit rarely and typically minor in nature. We report here an unusual fatal case of massive hematoma of the neck after FNA and CNB that may have caused airway obstruction. A 68-year-old Japanese woman underwent both procedures and was found dead at home later the same day. Although severe complications of FNA or CNB such as major bleeds or deaths are rarely reported, clinicians and forensic pathologists should be cognizant that complications can arise.

Blood creatinine level in postmortem cases.

Blood chemical analysis for the diagnosis of diseases in forensic cases should be conducted in the same way as for clinical cases. However, it is sometimes difficult to obtain serum samples in forensic cases because of postmortem changes such as hemolysis and putrefaction. This study aimed to evaluate renal function in postmortem cases by blood creatinine analysis. The blood creatinine level was measured by high performance liquid chromatography (HPLC) using whole blood samples taken from 77 postmortem cases, and the relationships between blood creatinine level, postmortem interval, and cause of death were examined. The median blood creatinine level was found to be 1.15 mg/dL, with no significant differences between blood samples taken from different parts of the body. The blood creatinine level was stable for 3 days after death and gradually increased after that period, in line with a previous study using enzymatic analysis that found the serum creatinine level was stable in the early postmortem period. The blood creatinine level was high in the cases of blunt injury, intoxication, and in deaths caused by fire. This was considered to reflect acute renal dysfunction. However, the postmortem blood creatinine level remained higher than the clinical normal value despite omitting cases with renal dysfunction from the analysis. Therefore, we next investigated the change in postmortem creatinine levels in mice and found that the blood creatinine level increased with the emergence of rigor mortis. Our findings indicate that HPLC is useful in the postmortem evaluation of renal function even in the cases where serum cannot be obtained. However, the presence of rigor mortis should be considered in the evaluation of blood creatinine values.