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Research Square Aug 2023Common neuropathologies associated with dementia include Alzheimer's disease neuropathologic change (ADNC) and limbic-predominant age-related TDP-43 encephalopathy...
BACKGROUND
Common neuropathologies associated with dementia include Alzheimer's disease neuropathologic change (ADNC) and limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC). Biofluid proteomics provides a window into the pathobiology of dementia and the information from biofluid tests may help guide clinical management.
METHODS
Participants were recruited from a longitudinal cohort of older adults at the University of Kentucky AD Research Center. A convenience sample of clinically obtained lumbar puncture cerebrospinal fluid (CSF) samples was analyzed from 29 older adults that had autopsy confirmation of the presence or absence of LATE-NC. Nine of the participants had autopsy-confirmed LATE-NC. Antemortem CSF specimens were analyzed in two separate processes: From one group, aliquots were depleted of highly abundant proteins using affinity spin columns. Tryptic digests of sample proteins were subjected to liquid chromatographic separation and mass spectrometry using an Eksigent Ekspert nanoLC 400 system in line with a Sciex 6600+ mass spectrometer. Protein identification was performed using Protein Pilot (Sciex, ver. 5) software, and relative quantification was performed using the SWATH processing microApp in PeakView and MarkerView software (Sciex), respectively. Following data analyses, additional studies were performed using western blots.
RESULTS
A total of 830 proteins were identified in the samples depleted of abundant proteins, and 730 proteins were identified in the non-depleted samples. Whereas some dementia-related proteins were detected (Aβ peptide and α-synuclein protein), others were not (TDP-43, TMEM106B, and tau proteins). When the Bonferroni correction was applied to correct for multiple comparisons, only 4 proteins showed differential expression (LATE-NC vs non-LATE-NC) in the nondepleted samples (RBP4, MIF, IGHG3 and ITM2B), whereas none showed statistically different changes in the depleted samples. Post-hoc western blots confirmed that RBP4 expression was higher in the LATE-NC cases at the group level, but there was overlap between the levels of RBP4 in LATE-NC and non-LATE-NC cases.
CONCLUSIONS
An exploratory assessment of CSF proteomes of autopsy-confirmed LATE-NC and non-LATE-NC cases from a community-based cohort failed to demonstrate a clear-cut proteomic fingerprint that distinguished the two groups. There was intriguing increase in RBP4 protein levels in CSF from LATE-NC cases. This may provide clues about pathogenetic mechanisms in LATE-NC.
PubMed: 37674727
DOI: 10.21203/rs.3.rs-3252238/v1 -
PloS One 2023In low-resource settings, it is challenging to ascertain the burden and causes of under-5 mortality as many deaths occur outside health facilities. We aimed to determine...
BACKGROUND
In low-resource settings, it is challenging to ascertain the burden and causes of under-5 mortality as many deaths occur outside health facilities. We aimed to determine the causes of childhood deaths in rural Gambia using verbal autopsies (VA).
METHODOLOGY
We used WHO VA questionnaires to conduct VAs for deaths under-5 years of age in the Basse and Fuladu West Health and Demographic Surveillance Systems (HDSS) in rural Gambia between September 01, 2019, and December 31, 2021. Using a standardized cause of death list, two physicians assigned causes of death and discordant diagnoses were resolved by consensus.
RESULTS
VAs were conducted for 89% (647/727) of deaths. Of these deaths, 49.5% (n = 319) occurred at home, 50.1% (n = 324) in females, and 32.3% (n = 209) in neonates. Acute respiratory infection including pneumonia (ARIP) (33.7%, n = 137) and diarrhoeal diseases (23.3%, n = 95) were the commonest primary causes of death in the post-neonatal period. In the neonatal period, unspecified perinatal causes of death (34.0%, n = 71) and deaths due to birth asphyxia (27.3%, n = 57) were the commonest causes of death. Severe malnutrition (28.6%, n = 185) was the commonest underlying cause of death. In the neonatal period, deaths due to birth asphyxia (p-value<0.001) and severe anaemia (p-value = 0.03) were more likely to occur at hospitals while unspecified perinatal deaths (p-value = 0.01) were more likely to occur at home. In the post-neonatal period, deaths due to ARIP (p-value = 0.04) and diarrhoeal disease (p-value = 0.001) were more likely to occur among children aged 1-11 months and 12-23 months respectively.
CONCLUSION
According to VA analysis of deaths identified within two HDSS in rural Gambia, half of deaths amongst children under-5 in rural Gambia occur at home. ARIP and diarrhoea, and the underlying cause of severe malnutrition remain the predominant causes of child mortality. Improved health care and health-seeking behaviour may reduce childhood deaths in rural Gambia.
Topics: Child; Infant, Newborn; Female; Pregnancy; Humans; Infant; Autopsy; Cause of Death; Gambia; Asphyxia; Respiratory Tract Infections; Protein-Energy Malnutrition; Diarrhea
PubMed: 37410741
DOI: 10.1371/journal.pone.0277377 -
International Journal of Legal Medicine Sep 2023Post-mortem interval (PMI) is the cornerstone of the forensic field to investigate. The examination technique by seeing the changes in the body such as algor mortis,... (Review)
Review
BACKGROUND
Post-mortem interval (PMI) is the cornerstone of the forensic field to investigate. The examination technique by seeing the changes in the body such as algor mortis, rigor mortis, and livor mortis is a traditional technique in which accuracy is influenced by many factors. A biomolecular technique that uses microRNA (miRNA) biomarkers is developing because miRNA has good stability than other RNA, so it meets the requirements to be used for PMI estimation.
METHOD
Following the PRISMA guidelines, journals were taken from 5 databases: Scopus, Science Direct, PubMed, Embase, and Springer. The review was carried out by two people. Inclusion criteria in this review are original research, published in the last 10 years, discussing miRNA as a biomarker for PMI estimation, and free full access. While exclusion criteria are not original research and not using English.
RESULT
Eighteen journals were reviewed in this study. The study was conducted using test animals (rats) and human samples with tissue sources taken from the liver, skeletal muscle, blood, bone, heart, skin, saliva, semen, brain, lung, vitreous humor, spleen, and kidney. miRNA expression levels after death showed different results based on miRNA target, tissue source, and others.
DISCUSSION
The results of each study are different due to the use of different types of miRNA targets and tissue sources. miRNA has great potential to estimate PMI in forensic science, but it is necessary to control the influencing factors to obtain an accurate conclusion.
Topics: Humans; Animals; Rats; MicroRNAs; Autopsy; Postmortem Changes; Forensic Medicine; Forensic Sciences; Biomarkers
PubMed: 37253884
DOI: 10.1007/s00414-023-03015-z -
Neurology Feb 2024More than 2,900 US children aged younger than 4 years die from unknown causes each year, accounting for more than 219,000 life years lost annually. They are mostly...
BACKGROUND AND OBJECTIVES
More than 2,900 US children aged younger than 4 years die from unknown causes each year, accounting for more than 219,000 life years lost annually. They are mostly sleep-related and unwitnessed with unremarkable autopsies, limiting our understanding of death mechanisms. We sought to understand potential mechanisms of death by evaluating videos of sudden deaths in toddlers.
METHODS
In our registry of 301 sudden unexplained child deaths, a series of 7 consecutively enrolled cases with home video recordings of the child's last sleep period were independently assessed by 8 physicians for video quality, movement, and sound.
RESULTS
Four boys and 3 girls (13-27 months at death) with terminal videos shared similar demographic features to the 293 other registry cases without video recordings. Five video recordings were continuous and 2 were triggered by sound or motion. Two lacked audio. All continuous recordings included a terminal convulsive event lasting 8-50 seconds; 4 children survived for >2.5 minutes postconvulsion. Among discontinuous videos, time lapses limited review; 1 suggested a convulsive event. Six were prone with face down, and 1 had autopsy evidence of airway obstruction. Primary cardiac arrhythmias were not supported; all 7 children had normal cardiac pathology and whole-exome sequencing identified no known cardiac disease variants.
DISCUSSION
Audio-visual recordings in 7 toddlers with unexplained sudden deaths strongly implicate that deaths were related to convulsive seizures, suggesting that many unexplained sleep-related deaths may result from seizures.
Topics: Male; Female; Humans; Child, Preschool; Infant; Death, Sudden; Heart Diseases; Arrhythmias, Cardiac; Seizures, Febrile; Seizures; Cause of Death; Death, Sudden, Cardiac
PubMed: 38175965
DOI: 10.1212/WNL.0000000000208038 -
Genes Oct 2023Sudden cardiac death (SCD) is one of the leading causes of death in the world and for this reason it has attracted the attention of numerous researchers in the field of... (Review)
Review
Sudden cardiac death (SCD) is one of the leading causes of death in the world and for this reason it has attracted the attention of numerous researchers in the field of legal medicine. It is not easy to determine the cause in a SCD case and the available methods used for diagnosis cannot always give an exhaustive answer. In addition, the molecular analysis of genes does not lead to a clear conclusion, but it could be interesting to focus attention on the expression level of miRNAs, a class of non-coding RNA of about 22 nucleotides. The role of miRNAs is to regulate the gene expression through complementary binding to 3'-untraslated regions of miRNAs, leading to the inhibition of translation or to mRNA degradation. In recent years, several studies were performed with the aim of exploring the use of these molecules as biomarkers for SCD cases, and to also distinguish the causes that lead to cardiac death. In this review, we summarize experiments, evidence, and results of different studies on the implication of miRNAs in SCD cases. We discuss the different biological starting materials with their respective advantages and disadvantages, studying miRNA expression on tissue (fresh-frozen tissue and FFPE tissue), circulating cell-free miRNAs in blood of patients affected by cardiac disease at high risk of SCD, and exosomal miRNAs analyzed from serum of people who died from SCD.
Topics: Humans; Death, Sudden, Cardiac; MicroRNAs; Autopsy; Biomarkers; RNA Stability
PubMed: 37895303
DOI: 10.3390/genes14101954 -
Clinical Microbiology and Infection :... May 2024Fungal infections are common in HIV-infected individuals and significantly contribute to mortality. However, a substantial number of cases are undiagnosed before death. (Review)
Review
BACKGROUND
Fungal infections are common in HIV-infected individuals and significantly contribute to mortality. However, a substantial number of cases are undiagnosed before death.
OBJECTIVE
To determine the frequency of fungal pathogens in autopsy studies of people who died with HIV in Africa.
METHODS
We conducted a scoping review of autopsy studies conducted in Africa.
DATA SOURCES
PubMed, Scopus, Web of Science, Embase, Google Scholar, and African Journal Online.
STUDY ELIGIBILITY CRITERIA
The review encompasses studies published from inception to September 2023, and no language restrictions were imposed during the search process. We included studies that reported histopathological or microbiological evidence for the diagnosis of fungal infections and other pathogens.
DATA SYNTHESIS
Data were summarized using descriptive statistics and no meta-analysis was performed.
RESULTS
We examined 30 articles reporting studies conducted between 1991 and 2019, encompassing a total of 13 066 HIV-infected decedents across ten African countries. In five studies, the autopsy type was not specified. Among those studies with specified autopsy types, 20 involved complete diagnostic autopsies, whereas 5 were categorized as partial or minimally invasive autopsies. There were 2333 pathogens identified, with 946 (40.5%) being mycobacteria, 856 (36.7%) fungal, 231 (3.8%) viral, 208 (8.9%) parasitic, and 92 (3.9%) bacterial. Of the 856 fungal pathogens identified, 654 (28.0%) were Cryptococcus species, 167 (7.2%) Pneumocystis jirovecii, 16 (0.69%) Histoplasma species, 15 (0.64%) Aspergillus species, and 4 (0.17%) Candida species. Other major non-fungal pathogens identified were cytomegalovirus 172 (7.37%) and Toxoplasma gondii 173 (7.42%).
CONCLUSIONS
Invasive fungal infections occur in over one-third of people who succumb to HIV in Africa. In addition to cryptococcosis and Pneumocystis jirovecii pneumonia, integrating other priority fungal pathogen detection and management strategies into the broader framework of HIV care in Africa is recommended. This involves increasing awareness regarding the impact of fungal infections in advanced HIV disease and strengthening diagnostic and treatment capacity.
Topics: Humans; Autopsy; Africa; HIV Infections; Mycoses; Fungi; AIDS-Related Opportunistic Infections
PubMed: 38145865
DOI: 10.1016/j.cmi.2023.12.016 -
International Journal of Legal Medicine Nov 2023Forensic pathologists may use 3D prints as demonstrative aids when providing expert testimony in court of law, but the effects remain unclear despite many assumed...
Forensic pathologists may use 3D prints as demonstrative aids when providing expert testimony in court of law, but the effects remain unclear despite many assumed benefits. In this qualitative study, the effects of using a 3D print, demonstrating a blunt force skull fracture, in court were explored by thematic analysis of interviews with judges, prosecutors, defence counsels, and forensic pathologists with the aim of improving the expert testimony. Five semi-structured focus groups and eight one-to-one interviews with a total of 29 stakeholders were transcribed ad verbatim and analysed using thematic analysis. The study found that a highly accurate 3D print of a skull demonstrated autopsy findings in detail and provided a quick overview, but sense of touch was of little benefit as the 3D print had different material characteristics than the human skull. Virtual 3D models were expected to provide all the benefits of 3D prints, be less emotionally confronting, and be logistically feasible. Both 3D prints and virtual 3D models were expected to be less emotionally confronting than autopsy photos. Regardless of fidelity, an expert witness was necessary to translate technical language and explain autopsy findings, and low-fidelity models may be equally suited as demonstrative aids. The court infrequently challenged the expert witnesses' conclusions and, therefore, rarely had a need for viewing autopsy findings in detail, therefore rarely needing a 3D print.
Topics: Humans; Printing, Three-Dimensional; Expert Testimony; Skull Fractures; Focus Groups; Male; Female; Autopsy; Interviews as Topic; Qualitative Research; Forensic Pathology; Adult; Skull
PubMed: 37391670
DOI: 10.1007/s00414-023-03054-6 -
Pathologie (Heidelberg, Germany) May 2024Autopsies have long been considered the gold standard for quality assurance in medicine, yet their significance in basic research has been relatively overlooked. The... (Review)
Review
BACKGROUND
Autopsies have long been considered the gold standard for quality assurance in medicine, yet their significance in basic research has been relatively overlooked. The COVID-19 pandemic underscored the potential of autopsies in understanding pathophysiology, therapy, and disease management. In response, the German Registry for COVID-19 Autopsies (DeRegCOVID) was established in April 2020, followed by the DEFEAT PANDEMIcs consortium (2020-2021), which evolved into the National Autopsy Network (NATON).
DEREGCOVID
DeRegCOVID collected and analyzed autopsy data from COVID-19 deceased in Germany over three years, serving as the largest national multicenter autopsy study. Results identified crucial factors in severe/fatal cases, such as pulmonary vascular thromboemboli and the intricate virus-immune interplay. DeRegCOVID served as a central hub for data analysis, research inquiries, and public communication, playing a vital role in informing policy changes and responding to health authorities.
NATON
Initiated by the Network University Medicine (NUM), NATON emerged as a sustainable infrastructure for autopsy-based research. NATON aims to provide a data and method platform, fostering collaboration across pathology, neuropathology, and legal medicine. Its structure supports a swift feedback loop between research, patient care, and pandemic management.
CONCLUSION
DeRegCOVID has significantly contributed to understanding COVID-19 pathophysiology, leading to the establishment of NATON. The National Autopsy Registry (NAREG), as its successor, embodies a modular and adaptable approach, aiming to enhance autopsy-based research collaboration nationally and, potentially, internationally.
Topics: Humans; COVID-19; Germany; Autopsy; Registries; Pandemics; SARS-CoV-2
PubMed: 38427066
DOI: 10.1007/s00292-024-01307-8 -
Indian Journal of Pathology &... 2023Non-thrombotic pulmonary embolism, an uncommon entity, is defined as the embolization of tissues, microorganisms, air, or foreign material. One subset in this...
BACKGROUND
Non-thrombotic pulmonary embolism, an uncommon entity, is defined as the embolization of tissues, microorganisms, air, or foreign material. One subset in this non-thrombotic category is septic pulmonary embolism (SPE) that refers to embolism of microorganisms with or without a thrombotic mantle into the pulmonary vasculature. This condition is often recognized on the basis of imaging with a clinical correlation. Unfortunately, data regarding the pathological features are meager. This has prompted to review such cases at autopsy.
AIMS
To study the pathological features of SPE at autopsy.
MATERIALS AND METHODS
Ten-year (2012 to 2021) autopsy records of the hospital were retrospectively reviewed. The diagnosis was based on the identification of acute necrotizing pulmonary arteritis with peri-bronchoarterial consolidation. These cases were analyzed with reference to the demographics, clinical characteristics, and pulmonary/extrapulmonary findings at autopsy.
STATISTICAL ANALYSIS
Nil.
RESULTS
According to the inclusion criterion, 19 cases demonstrated the presence of SPE. There were 11 men and 8 women with a mean age of 32.1 years. The major source of infection included infection arising from skin and musculo-skeletal system (11 patients, 59.7%). The common clinical presentation included fever, dyspnea, chest pain, hemoptysis, and altered sensorium. The cause of death was mainly due to septicemia and/or confluent lung consolidations. A large number of bacterial colonies were seen in all; Candida species were also identified in two cases. Other lung findings included diffuse alveolar damage, fresh arterial thrombosis, infarction, arterial pseudo-aneurysms, abscess formation, and pyogenic pleuritis.
CONCLUSION
Presence of an extrapulmonary infection with persistent fever, bacteremia, and pulmonary complaints should raise suspicion for this entity, particularly in resource-poor settings, to prevent grave pulmonary complications.
Topics: Male; Humans; Female; Adult; Retrospective Studies; Sepsis; Pulmonary Embolism; Lung; Bacteremia
PubMed: 38084525
DOI: 10.4103/ijpm.ijpm_528_22 -
Cureus Jan 2024Undifferentiated cancer is a rapidly progressing cancer with poor prognosis. Sometimes, it is diagnosed at an advanced stage, and its origin is difficult to detect. A...
Undifferentiated cancer is a rapidly progressing cancer with poor prognosis. Sometimes, it is diagnosed at an advanced stage, and its origin is difficult to detect. A very unusual cancer was revealed by autopsy. The patient was an 83-year-old survivor of colon cancer, melanoma, and laryngeal cancer. He had been under watchful course observation after survival from laryngeal cancer but suddenly died due to aspiration pneumonia. The autopsy revealed undifferentiated cancer infiltrated the entire body, which was misdiagnosed with positron emission tomography (PET)/CT scan and MRI. The origin of this cancer was a mystery even with vigorous pathological evaluation. The patient was told that his previous cancers were all healed; however, undifferentiated cancer progressed rapidly to the entire body, just like "cancer diaspora". This report highlights the limit of diagnostic imaging tools for aggressive cancer, sounding the alarm for clinicians to look beyond old presumptions.
PubMed: 38389606
DOI: 10.7759/cureus.52798