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Nature Communications Jun 2024Our current understanding of the spread and neurodegenerative effects of tau neurofibrillary tangles (NFTs) within the medial temporal lobe (MTL) during the early stages...
Our current understanding of the spread and neurodegenerative effects of tau neurofibrillary tangles (NFTs) within the medial temporal lobe (MTL) during the early stages of Alzheimer's Disease (AD) is limited by the presence of confounding non-AD pathologies and the two-dimensional (2-D) nature of conventional histology studies. Here, we combine ex vivo MRI and serial histological imaging from 25 human MTL specimens to present a detailed, 3-D characterization of quantitative NFT burden measures in the space of a high-resolution, ex vivo atlas with cytoarchitecturally-defined subregion labels, that can be used to inform future in vivo neuroimaging studies. Average maps show a clear anterior to poster gradient in NFT distribution and a precise, spatial pattern with highest levels of NFTs found not just within the transentorhinal region but also the cornu ammonis (CA1) subfield. Additionally, we identify granular MTL regions where measures of neurodegeneration are likely to be linked to NFTs specifically, and thus potentially more sensitive as early AD biomarkers.
Topics: Humans; Alzheimer Disease; Temporal Lobe; tau Proteins; Male; Female; Aged; Magnetic Resonance Imaging; Neurofibrillary Tangles; Aged, 80 and over; Autopsy; Neuroimaging; Middle Aged; Postmortem Imaging
PubMed: 38839876
DOI: 10.1038/s41467-024-49205-0 -
Biomedical Research (Tokyo, Japan) 2024Racial and ethnic differences in the prevalence of patent foramen ovale have been suggested, but there are insufficient data to confirm the situation. Studies have also...
Racial and ethnic differences in the prevalence of patent foramen ovale have been suggested, but there are insufficient data to confirm the situation. Studies have also not investigated detailed morphological changes in the fossa ovalis by age. This study therefore aimed to clarify the characteristics of the fossa ovalis and determine the frequency of patent foramen ovale in Japanese people, using materials from forensic autopsies. A total of 359 hearts were obtained during forensic autopsies (from 223 males and 136 females, aged from 0 to 94 years). Overall, prevalence of patent foramen ovale was 12.5%, but it was significantly higher among those under 20 years old (66.7% in males, 38.5% in females). The area of the fossa ovalis linearly increased with age in both sexes. The prevalence of patent foramen ovale was lower in Japanese adults than previously found in either White or Black people. The ratio of the area of the fossa ovalis to the heart weight was nearly constant.
Topics: Humans; Male; Female; Foramen Ovale, Patent; Adult; Aged; Autopsy; Middle Aged; Adolescent; Aged, 80 and over; Prevalence; Japan; Child; Infant; Child, Preschool; Young Adult; Infant, Newborn; Asian People; East Asian People
PubMed: 38839356
DOI: 10.2220/biomedres.45.135 -
Journal of UOEH 2024A woman in her 30s who was being treated for a mental illness with several psychotropic drugs was admitted to the hospital after being found in a state of...
A woman in her 30s who was being treated for a mental illness with several psychotropic drugs was admitted to the hospital after being found in a state of unconsciousness and respiratory arrest at home. She was pronounced dead 12 hours after she was discovered. Her autopsy revealed symmetrical hemorrhagic necrosis in the putamen on both sides of her cerebrum. Although many drugs were detected in her blood, all of those other than dextromethorphan (DXM) were within or below the therapeutic range. Her blood DXM was 1.73 μg/ml at admission and 1.61 μg/ml at autopsy, which were within the toxic range or coma-to-death range. The cause of death was diagnosed as DXM poisoning. DXM can cause hallucinations and euphoria if taken in excess, but since it is available as an over-the-counter drug at general pharmacies, an increasing number of young people are overdosing on it, mistakenly believing it to be a safe drug with few side effects. We believe that further social measures against DXM are necessary in Japan, such as disseminating correct knowledge in society and regulating over-the-counter sales.
Topics: Humans; Dextromethorphan; Female; Autopsy; Adult; Fatal Outcome
PubMed: 38839290
DOI: 10.7888/juoeh.46.221 -
Neurobiology of Disease Aug 2024Multiple system atrophy (MSA) is characterized by glial cytoplasmic inclusions (GCIs) containing aggregated α-synuclein (α-syn) in oligodendrocytes. The origin of...
Multiple system atrophy (MSA) is characterized by glial cytoplasmic inclusions (GCIs) containing aggregated α-synuclein (α-syn) in oligodendrocytes. The origin of α-syn accumulation in GCIs is unclear, in particular whether abnormal α-syn aggregates result from the abnormal elevation of endogenous α-syn expression in MSA or ingested from the neuronal source. Tubulin polymerization promoting protein (TPPP) has been reported to play a crucial role in developing GCI pathology. Here, the total cell body, nucleus, and cytoplasmic area density of SNCA and TPPP transcripts in neurons and oligodendrocytes with and without various α-syn pathologies in the pontine base in autopsy cases of MSA (n = 4) and controls (n = 2) were evaluated using RNAscope with immunofluorescence. Single-nucleus RNA-sequencing data for TPPP was evaluated using control frontal cortex (n = 3). SNCA and TPPP transcripts were present in the nucleus and cytoplasm of oligodendrocytes in both controls and diseased, with higher area density in GCIs and glial nuclear inclusions in MSA. Area densities of SNCA and TPPP transcripts were lower in neurons showing cytoplasmic inclusions in MSA. Indeed, TPPP transcripts were unexpectedly found in neurons, while the anti-TPPP antibody failed to detect immunoreactivity. Single-nucleus RNA-sequencing revealed significant TPPP transcript expression predominantly in oligodendrocytes, but also in excitatory and inhibitory neurons. This study addressed the unclear origin of accumulated α-syn in GCIs, proposing that the elevation of SNCA transcripts may supply templates for misfolded α-syn. In addition, the parallel behavior of TPPP and SNCA transcripts in GCI development highlights their potential synergistic contribution to inclusion formation. In conclusion, this study advances our understanding of MSA pathogenesis, offers insights into the dynamics of SNCA and TPPP transcripts in inclusion formation, and proposes regulating their transcripts for future molecular therapy to MSA.
Topics: alpha-Synuclein; Multiple System Atrophy; Humans; Oligodendroglia; Inclusion Bodies; Aged; Female; Male; Middle Aged; Nerve Tissue Proteins; Neurons; Aged, 80 and over
PubMed: 38839023
DOI: 10.1016/j.nbd.2024.106551 -
International Journal of Cardiology Sep 2024
Topics: Humans; Female; Death, Sudden, Cardiac; Middle Aged; Aged; Age Factors; Myocardial Ischemia; Adult; Aged, 80 and over
PubMed: 38838747
DOI: 10.1016/j.ijcard.2024.132238 -
Forensic Science International May 2024In infantile abusive head injury (AHT), subdural haemorrhage (SDH) is commonly held to result from traumatic damage to bridging veins traversing from the surface of the...
In infantile abusive head injury (AHT), subdural haemorrhage (SDH) is commonly held to result from traumatic damage to bridging veins traversing from the surface of the brain to the dura and dural venous sinuses. However, there are limited published radiological or autopsy demonstrations of ruptured bridging veins and several authors also assert that bridging veins are too large to rupture due to the forces associated with AHT. There have been several studies on the size, locations and numbers of adult bridging veins and there is one small study of infant bridging veins. However, there are no microscopic studies of infant bridging veins and only a select few ultrastructural investigations of adult bridging veins. Hitherto, it has been assumed that bridging veins from infants and younger children will display the same anatomical characteristics as those in adulthood. At 19 neonatal, infant and young child post-mortem examinations, we macroscopically examined and sampled bridging veins for microscopy. We compared the histology of those samples with bridging veins from an older child and two adults. We demonstrate that adult bridging veins are usually surrounded by supportive meningeal tissue that appears to be lacking or minimally present around the bridging veins of younger children. Neonatal, infant and young children's veins had a free 'bridging' section. Neonatal and infant bridging veins had smaller diameter ranges and thinner walls (some only 5-7 µm) than those seen in older children and adults. Bridging vein walls contained both fine strands of elastic fibers and a more pronounced elastic lamina. The presence of an elastic lamina occurred more frequently in the older age groups These anatomical differences between the veins of adults and young children may help to explain apparent increased vulnerability of neonatal/infant bridging veins to the forces associated with a shaking-type traumatic event.
PubMed: 38838611
DOI: 10.1016/j.forsciint.2024.112080 -
PLoS Pathogens Jun 2024COVID-19 has affected more than half a billion people worldwide, with more than 6.3 million deaths, but the pathophysiological mechanisms involved in lethal cases and...
COVID-19 has affected more than half a billion people worldwide, with more than 6.3 million deaths, but the pathophysiological mechanisms involved in lethal cases and the host determinants that determine the different clinical outcomes are still unclear. In this study, we assessed lung autopsies of 47 COVID-19 patients and examined the inflammatory profiles, viral loads, and inflammasome activation. Additionally, we correlated these factors with the patient's clinical and histopathological conditions. Robust inflammasome activation was detected in the lungs of lethal cases of SARS-CoV-2. Experiments conducted on transgenic mice expressing hACE2 and infected with SARS-CoV-2 showed that Nlrp3-/- mice were protected from disease development and lethality compared to Nlrp3+/+ littermate mice, supporting the involvement of this inflammasome in disease exacerbation. An analysis of gene expression allowed for the classification of COVID-19 patients into two different clusters. Cluster 1 died with higher viral loads and exhibited a reduced inflammatory profile than Cluster 2. Illness time, mechanical ventilation time, pulmonary fibrosis, respiratory functions, histopathological status, thrombosis, viral loads, and inflammasome activation significantly differed between the two clusters. Our data demonstrated two distinct profiles in lethal cases of COVID-19, thus indicating that the balance of viral replication and inflammasome-mediated pulmonary inflammation led to different clinical outcomes. We provide important information to understand clinical variations in severe COVID-19, a process that is critical for decisions between immune-mediated or antiviral-mediated therapies for the treatment of critical cases of COVID-19.
Topics: COVID-19; Animals; Humans; SARS-CoV-2; Mice; Virus Replication; Female; Male; Viral Load; Lung; Middle Aged; Inflammasomes; Aged; NLR Family, Pyrin Domain-Containing 3 Protein; Mice, Transgenic; Pneumonia; Angiotensin-Converting Enzyme 2; Mice, Knockout; Adult
PubMed: 38838044
DOI: 10.1371/journal.ppat.1012222 -
Cureus May 2024In Japan, many cases occur wherein housemates fail to report dead bodies found in their homes. However, only individual cases are reported through press and court...
INTRODUCTION
In Japan, many cases occur wherein housemates fail to report dead bodies found in their homes. However, only individual cases are reported through press and court records, and analysis including unreported cases has not been conducted. In this study, we evaluated cases handled by our Forensic Science Department in which housemates did not immediately report a dead body found in their home. We analyzed the overall picture and forensic characteristics of such cases, stratifying whether the abandoners were estimated hikikomori.
METHODS
Of the 1,179 legal autopsy cases handled by the Department of Forensic Medicine of Tokai University from January 1, 2017, to July 1, 2023, we evaluated 45 cases in which housemates did not immediately report dead bodies. The characteristics analyzed were body age, cause of death, autopsy findings, duration from the body's discovery by the abandoner to the police report, the reason for the lack of report in the first body discovery by the abandoner, and the reason for the report. In this study, the criteria for estimating whether a hikikomori abandoned the body were (1) the police provided the information that the person was a hikikomori or (2) the person met the following four criteria: 20-64 years old, unemployed, not in school, and living with parents.
RESULTS
Positive significant differences were found in the body's decomposition and the time from the body's discovery to the report to the police when the abandoner was suspected to be a hikikomori for more than one, four, or eight days. No significant differences were found in the cause of death. Regarding the reported characteristics, when the abandoner was an estimated hikikomori, positive and significant differences were found for recognizing the body and did not report immediately due to shock. Conversely, negative and significant differences were found for the person who reported as the abandoner.
CONCLUSION
This is the first study that reports on body abandonment by housemates and elaborates on its complications to forensic doctors. The incidence rate of abandonment is higher than expected. This study suggests that hikikomori are more likely to hide the bodies for longer, which hinders the death cause investigation.
PubMed: 38836149
DOI: 10.7759/cureus.59664 -
Journal of Neuroimmune Pharmacology :... Jun 2024Reverse transcriptase inhibitors (RTIs) are currently broadly prescribed for the treatment of HIV infection but are also thought to prevent Alzheimer's disease (AD)...
Reverse transcriptase inhibitors (RTIs) are currently broadly prescribed for the treatment of HIV infection but are also thought to prevent Alzheimer's disease (AD) progression by protecting against amyloidosis. Our study evaluates the hypothesis that reverse transcriptase inhibitors protect against Alzheimer-type brain amyloidogenesis in the context of HIV infection. We compiled a case series of participants from a prospective study of the neurological consequences of HIV infection at the HIV Neurobehavioral Research Program (HNRP) who had serial neuropsychological and neurological assessments and were on RTIs. Two participants had gross and microscopic examination and immunohistochemistry of the brain at autopsy; one was assessed clinically for Alzheimer's disease by cerebrospinal fluid (CSF) analysis of phosphorylated-Tau, Total-Tau and Aβ42. Additionally, a larger cohort of 250 autopsied individuals was evaluated for presence of amyloid plaques, Tau, and related pathologies. Three older, virally suppressed individuals with HIV who had long-term treatment with RTIs were included in analyses. Two cases demonstrated substantial cerebral amyloid deposition at autopsy. The third case met clinical criteria for AD based on a typical clinical course and CSF biomarker profile. In the larger cohort of autopsied individuals, the prevalence of cerebral amyloidosis among people with HIV (PWH) was greater for those on RTIs. Our study showed that long-term RTI therapy did not protect against Alzheimer-type brain amyloidogenesis in the context of HIV infection in these patients. Given the known toxicities of RTIs, it is premature to recommend them to individuals at risk or with Alzheimer's disease who do not have HIV infection.
Topics: Humans; HIV Infections; Alzheimer Disease; Male; Middle Aged; Female; Amyloidosis; Aged; Prospective Studies; tau Proteins; Brain; Cohort Studies; Amyloid beta-Peptides
PubMed: 38829507
DOI: 10.1007/s11481-024-10126-w -
Sultan Qaboos University Medical Journal May 2024Blood-filled cysts of the heart valves are frequently reported at postpartum autopsies of infants. They are seen as round nodules mostly in the paediatric age group in... (Review)
Review
Blood-filled cysts of the heart valves are frequently reported at postpartum autopsies of infants. They are seen as round nodules mostly in the paediatric age group in infants less than 2 months of age and disappear spontaneously within 6 months of life. We report a unique case of an 11-month-old girl who presented at a tertiary healthcare hospital in 2022 with a blood-filled cyst on the posterior leaflet of the pulmonary valve that was successfully treated. This case report highlights the characteristics and course of a paediatric patient with blood-filled cysts. Further studies are yet needed to better understand the diagnostic approaches to blood-filled cysts as well as treatment modalities to fill the gap in clinical settings.
Topics: Female; Humans; Infant; Cysts; Pulmonary Valve
PubMed: 38828236
DOI: 10.18295/squmj.5.2023.037