Characterization of human brown adipose tissue by chemical-shift water-fat MRI.

PubMed

Hu, Houchun H; Perkins, Thomas G; Chia, Jonathan M; Gilsanz, Vicente

2013-01-01

The purpose of this study was to characterize human brown adipose tissue (BAT) with chemical-shift water-fat MRI and to determine whether trends and differences in fat-signal fractions and T2(*) relaxation times between BAT and white adipose tissue (WAT) are consistently observed postmortem and in vivo in infants, adolescents, and adults. A postmortem body and eight patients were studied. A six-echo spoiled gradient-echo chemical-shift water-fat MRI sequence was performed at 3 T to jointly quantify fat-signal fraction and T2(*) in interscapular-supraclavicular BAT and subcutaneous WAT. To confirm BAT identity, biopsy and histology served as the reference in the postmortem study and PET/CT was used in five of the eight patients who required examination for medical care. Fat-signal fractions and T2(*) times were lower in BAT than in WAT in the postmortem example and in seven of eight patients. With the exception of one case, nominal comparisons between brown and white adipose tissues were statistically significant (p < 0.05). Between subjects, a large range of fat-signal fraction values was observed in BAT but not in WAT. We have shown that fat-signal fractions and T2(*) values jointly derived from chemical-shift water-fat MRI are lower in BAT than in WAT likely because of differences in cellular structures, triglyceride content, and vascularization. The two metrics can serve as complementary biomarkers in the detection of BAT.

Experimental Investigation of Cavitation as a Possible Damage Mechanism in Blast-Induced Traumatic Brain Injury in Post-Mortem Human Subject Heads.

PubMed

Salzar, Robert S; Treichler, Derrick; Wardlaw, Andrew; Weiss, Greg; Goeller, Jacques

2017-04-15

The potential of blast-induced traumatic brain injury from the mechanism of localized cavitation of the cerebrospinal fluid (CSF) is investigated. While the mechanism and criteria for non-impact blast-induced traumatic brain injury is still unknown, this study demonstrates that local cavitation in the CSF layer of the cranial volume could contribute to these injuries. The cranial contents of three post-mortem human subject (PMHS) heads were replaced with both a normal saline solution and a ballistic gel mixture with a simulated CSF layer. Each were instrumented with multiple pressure transducers and placed inside identical shock tubes at two different research facilities. Sensor data indicates that cavitation may have occurred in the PMHS models at pressure levels below those for a 50% risk of blast lung injury. This study points to skull flexion, the result of the shock wave on the front of the skull leading to a negative pressure in the contrecoup, as a possible mechanism that contributes to the onset of cavitation. Based on observation of intracranial pressure transducer data from the PMHS model, cavitation onset is thought to occur from approximately a 140 kPa head-on incident blast.

GrinLine identification using digital imaging and Adobe Photoshop.

PubMed

Bollinger, Susan A; Brumit, Paula C; Schrader, Bruce A; Senn, David R

2009-03-01

The purpose of this study was to outline a method by which an antemortem photograph of a victim can be critically compared with a postmortem photograph in an effort to facilitate the identification process. Ten subjects, between 27 and 55 years old provided historical pictures of themselves exhibiting a broad smile showing anterior teeth to some extent (a grin). These photos were termed "antemortem" for the purpose of the study. A digital camera was used to take a current photo of each subject's grin. These photos represented the "postmortem" images. A single subject's "postmortem" photo set was randomly selected to be the "unknown victim." These combined data of the unknown and the 10 antemortem subjects were digitally stored and, using Adobe Photoshop software, the images were sized and oriented for comparative analysis. The goal was to devise a technique that could facilitate the accurate determination of which "antemortem" subject was the "unknown." The generation of antemortem digital overlays of the teeth visible in a grin and the comparison of those overlays to the images of the postmortem dentition is the foundation of the technique. The comparisons made using the GrinLine Identification Technique may assist medical examiners and coroners in making identifications or exclusions.

Cellular GABAergic neuroactive steroid (3α,5α)-3-hydroxy-pregnan-20-one (3α,5α-THP) immunostaining levels are increased in the ventral tegmental area of the human Alcohol Use Disorder patients: A postmortem study

PubMed Central

Hasirci, A. Sait; Maldonado-Devincci, Antoniette M.; Beattie, Matthew C.; O'Buckley, Todd K.; Morrow, A. Leslie

2016-01-01

Background The GABAergic neuroactive steroid (3α,5α)-3-hydroxy-pregnan-20-one (3α,5α-THP, allopregnanolone) enhances GABAergic activity and produces subjective effects similar to ethanol. The effect of chronic alcohol exposure on 3α,5α-THP concentrations has been studied in mouse, rat, and monkey limbic brain areas. Chronic ethanol exposure produced divergent brain region and cell specific changes in 3α,5α-THP concentrations in animal studies. However, 3α,5α-THP levels in similar human brain regions have never been examined in individuals diagnosed with alcohol use disorder (AUD). Therefore, we used immunohistochemistry to examine 3α,5α-THP levels in the ventral tegmental area (VTA), substantia nigra pars medialis (SNM), and amygdala of human postmortem brains of patients diagnosed with AUD compared to social drinkers. The effects of sex and liver disease on 3α,5α-THP concentrations were examined in the aforementioned brain regions. Methods Human postmortem brains of AUD patients and age-matched controls were obtained from the New South Wales Brain Tissue Resource Center. Immunohistochemistry was performed using anti-3α,5α-THP antibody on formalin fixed and paraffin embedded brain sections to detect cellular 3α,5α-THP levels. Immunoreactivity was analyzed by pixel density/mm2 for the comparison between AUD patients and controls. Results 3α,5α-THP immunoreactivity was increased by 23.2±9% in the VTA of AUD patients compared to age matched controls (p= 0.014). Moreover, a 29.6±10% increase in 3α,5α-THP immunoreactivity was observed in the SNM of male AUD patients compared to male controls (p<0.01), but not in female subjects. 3α,5α-THP immunoreactivity in the VTA and SNM regions did not differ between non-cirrhotic and cirrhotic AUD patients. A sex difference in 3α,5α-THP immunoreactivity (female 51±18% greater than male) was observed among control subjects in the SNM, but no other brain region. 3α,5α-THP immunoreactivity in the basolateral and lateral amygdala were negatively correlated with the length of the tissue fixation time as well as the age of the subjects, precluding assessment of the effect of AUD. Conclusions Cellular 3α,5α-THP levels in VTA are increased in human AUD patients, an effect that is likely independent of sex and liver disease. The differences between animal models and human studies should be factored into the interpretation of the physiological significance of elevated 3α,5α-THP levels in humans. PMID:28068457

Alterations of ubiquitin related proteins in the pathology and development of schizophrenia: Evidence from human and animal studies.

PubMed

Andrews, Jessica L; Goodfellow, Frederic J; Matosin, Natalie; Snelling, Mollie K; Newell, Kelly A; Huang, Xu-Feng; Fernandez-Enright, Francesca

2017-07-01

Gene expression analyses in post-mortem schizophrenia brains suggest that a number of ubiquitin proteasome system (UPS) genes are associated with schizophrenia; however the status of UPS proteins in the schizophrenia brain is largely unknown. Ubiquitin related proteins are inherently involved in memory, neuronal survival and morphology, which are processes implicated in neurodevelopmental disorders such as schizophrenia. We examined levels of five UPS proteins (Protein Inhibitor of Activated STAT2 [PIAS2], F-Box and Leucine rich repeat protein 21 [FBXL21], Mouse Double Minute 2 homolog [MDM2], Ubiquitin Carboxyl-Terminal Hydrolase-L1 [UCHL1] and Ubiquitin Conjugating Enzyme E2D1 [UBE2D1]) involved in these neuronal processes, within the dorsolateral prefrontal cortex of post-mortem schizophrenia subjects and matched controls (n = 30/group), in addition to across neurodevelopmental time-points (juvenile, adolescent and adult stages of life), utilizing a well-established neurodevelopmental phencyclidine (PCP) animal model of schizophrenia. We observed significant reductions in PIAS2, FBXL21 and MDM2 in schizophrenia subjects compared to controls (p-values ranging from 0.002 to 0.004). In our developmental PCP model, MDM2 protein was significantly reduced in adult PCP-treated rats compared to controls (p = 0.034). Additionally, FBXL21 (p = 0.022) and UCHL1 (p = 0.022) were significantly decreased, whilst UBE2D1 was increased (p = 0.022), in juvenile phencyclidine-treated rats compared to controls. This is the first study reporting alterations of UPS proteins in post-mortem human schizophrenia subjects and in a neurodevelopmental model of schizophrenia. The findings from this study provide strong support for a role of these UPS proteins in the pathology and development of schizophrenia. Copyright © 2017 Elsevier Ltd. All rights reserved.

UV-laser microdissection and mRNA expression analysis of individual neurons from postmortem Parkinson's disease brains.

PubMed

Gründemann, Jan; Schlaudraff, Falk; Liss, Birgit

2011-01-01

Cell specificity of gene expression analysis is essential to avoid tissue sample related artifacts, in particular when the relative number of target cells present in the compared tissues varies dramatically, e.g., when comparing dopamine neurons in midbrain tissues from control subjects with those from Parkinson's disease (PD) cases. Here, we describe a detailed protocol that combines contact-free UV-laser microdissection and quantitative PCR of reverse-transcribed RNA of individual neurons from postmortem human midbrain tissue from PD patients and unaffected controls. Among expression changes in a variety of dopamine neuron marker, maintenance, and cell-metabolism genes, we found that α-synuclein mRNA levels were significantly elevated in individual neuromelanin-positive dopamine midbrain neurons from PD brains when compared to those from matched controls.

Effect of alcohol use disorder on oxytocin peptide and receptor mRNA expression in human brain: A post-mortem case-control study.

PubMed

Lee, Mary R; Schwandt, Melanie L; Sankar, Vignesh; Suchankova, Petra; Sun, Hui; Leggio, Lorenzo

2017-11-01

Animal and human evidence supports a role for oxytocin in alcohol-seeking behaviors. There is interest, therefore, in targeting the oxytocin pathway as a new pharmacologic approach to treat alcohol use disorder. To this end, it is important to understand the effect of alcohol use disorder on endogenous oxytocin in brain regions that are relevant for the initiation and maintenance of alcohol use disorder. We examined human post-mortem brain tissue from males with alcohol use disorder (n=11) compared to nonalcohol dependent male controls (n=16). We a priori targeted five brain regions that in rodent studies, are projection areas for oxytocin neurons: nucleus accumbens, amygdala, hippocampus, ventral tegmental area and prefrontal cortex. Fold change in mRNA levels of oxytocin peptide and receptor were measured in each of the brain regions studied. Fold change for oxytocin peptide mRNA was significantly elevated in the prefrontal cortex of subjects with alcohol use disorder compared to controls (uncorrected p=0.0001; FDR-corrected p=0.001). For the entire sample of 27 subjects, there was a significant positive correlation between the fold change in oxytocin peptide mRNA in the prefrontal cortex and both daily alcohol intake (r 2 =0.38; p=0.002) and drinks per week (r 2 =0.24; p=0.02). Results are discussed in light of the previous animal and human literature on changes in the endogenous oxytocin system as an effect of chronic alcohol exposure. Copyright © 2017. Published by Elsevier Ltd.

42 CFR 35.16 - Autopsies and other post-mortem operations.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Autopsies and other post-mortem operations. 35.16 Section 35.16 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICAL CARE AND EXAMINATIONS HOSPITAL AND STATION MANAGEMENT General § 35.16 Autopsies and other post-mortem...

42 CFR 35.16 - Autopsies and other post-mortem operations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Autopsies and other post-mortem operations. 35.16 Section 35.16 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICAL CARE AND EXAMINATIONS HOSPITAL AND STATION MANAGEMENT General § 35.16 Autopsies and other post-mortem...

42 CFR 35.16 - Autopsies and other post-mortem operations.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Autopsies and other post-mortem operations. 35.16 Section 35.16 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICAL CARE AND EXAMINATIONS HOSPITAL AND STATION MANAGEMENT General § 35.16 Autopsies and other post-mortem...

42 CFR 35.16 - Autopsies and other post-mortem operations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Autopsies and other post-mortem operations. 35.16 Section 35.16 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICAL CARE AND EXAMINATIONS HOSPITAL AND STATION MANAGEMENT General § 35.16 Autopsies and other post-mortem...

42 CFR 35.16 - Autopsies and other post-mortem operations.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Autopsies and other post-mortem operations. 35.16 Section 35.16 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICAL CARE AND EXAMINATIONS HOSPITAL AND STATION MANAGEMENT General § 35.16 Autopsies and other post-mortem...

Dead in the water--are we killing the hospital autopsy with poor consent practices?

PubMed

Henry, Jaimie; Nicholas, Nick

2012-07-01

It is now a recognized fact that the practice of conducting a consent (or hospital) post-mortem examination is in decline. There have been many reasons put forth to explain this demise, but the quality of the consenting process is frequently cited as having a high impact. This article focuses on consent practices for post-mortem examinations in England and Wales, and considers if our consent techniques are adversely affecting post-mortem examination uptake. We examine the regulatory compliance of trusts with their statutory obligations by analyzing the Human Tissue Authority's compliance and inspection reports. We further analyze 21 publicly available NHS Trust policies on post-mortem examination consent procedures, and consider whether these are fit for the purpose of meeting the dual needs of clinicians and the bereaved. Despite more Human Tissue Authority inspections, there is a disproportionate rise in enforcement actions, with up to 48% of sampled Trusts exhibiting shortcomings in their legal duties. Additionally, only 52.4% of sampled trusts follow the Human Tissue Authority best-practice model, with 23.8% having no documented procedures. Despite the well founded evidence base for best-practice models, consent practices for post-mortem examinations remains poor and is likely to have a gross adverse effect on the rate of post-mortem examinations. We recommend that NHS Trusts rigorously review their protocols and introduce a team-approach between clinicians and trained bereavement staff in core-consent teams, as the Human Tissue Authority suggests, whilst at the same time placing a strong emphasis on education for junior and senior colleagues alike.

Post-mortem detection of gasoline residues in lung tissue and heart blood of fire victims.

PubMed

Pahor, Kevin; Olson, Greg; Forbes, Shari L

2013-09-01

The purpose of this study was to determine whether gasoline residues could be detected post-mortem in lung tissue and heart blood of fire victims. The lungs and heart blood were investigated to determine whether they were suitable samples for collection and could be collected without contamination during an autopsy. Three sets of test subjects (pig carcasses) were investigated under two different fire scenarios. Test subjects 1 were anaesthetized following animal ethics approval, inhaled gasoline vapours for a short period and then euthanized. The carcasses were clothed and placed in a house where additional gasoline was poured onto the carcass post-mortem in one fire, but not in the other. Test subjects 2 did not inhale gasoline, were clothed and placed in the house and had gasoline poured onto them in both fires. Test subjects 3 were clothed but had no exposure to gasoline either ante- or post-mortem. Following controlled burns and suppression with water, the carcasses were collected, and their lungs and heart blood were excised at a necropsy. The headspace from the samples was analysed using thermal desorption-gas chromatography-mass spectroscopy. Gasoline was identified in the lungs and heart blood from the subjects that were exposed to gasoline vapours prior to death (test subjects 1). All other samples were negative for gasoline residues. These results suggest that it is useful to analyse for volatile ignitable liquids in lung tissue and blood as it may help to determine whether a victim was alive and inhaling gases at the time of a fire.

Protein Markers of Neurotransmitter Synthesis and Release in Postmortem Schizophrenia Substantia Nigra.

PubMed

Schoonover, Kirsten E; McCollum, Lesley A; Roberts, Rosalinda C

2017-01-01

The substantia nigra (SN) provides the largest dopaminergic input to the brain, projects to the striatum (the primary locus of action for antipsychotic medication), and receives GABAergic and glutamatergic inputs. This study used western blot analysis to compare protein levels of tyrosine hydroxylase (TH), glutamate decarboxylase (GAD67), and vesicular glutamate transporters (vGLUT1 and vGLUT2) in postmortem human SN in schizophrenia subjects (n=13) and matched controls (n=12). As a preliminary analysis, the schizophrenia group was subdivided by (1) treatment status: off medication (n=4) or on medication (n=9); or (2) treatment response: treatment resistant (n=5) or treatment responsive (n=4). The combined schizophrenia group had higher TH and GAD67 protein levels than controls (an increase of 69.6%, P=0.01 and 19.5%, P=0.004, respectively). When subdivided by medication status, these increases were found in the on-medication subjects (TH 88.3%, P=0.008; GAD67 40.6%, P=0.003). In contrast, unmedicated schizophrenia subjects had higher vGLUT2 levels than controls (an increase of 28.7%, P=0.041), but vGLUT2 levels were similar between medicated schizophrenia subjects and controls. Treatment-resistant subjects had significantly higher TH and GAD67 levels than controls (an increase of 121.0%, P=0.0003 and 58.7%, P=0.004, respectively). These data suggest increases in dopamine and GABA transmission in the SN in schizophrenia, with a potential relation to treatment and response.

Can homemade alcohol (Raksi) be useful for preserving dead bodies? An experiment on wistar albino rats.

PubMed

Dhungel, S; Maskey, D; Jha, C B; Bhattacharya, S; Paudel, B H; Shrestha, R N

2007-01-01

Embalming is the through disinfection and art of preserving bodies after death using chemical substances. It keeps a body life like in appearance during the time it lies in a state prior to funeral. This study was undertaken to investigate the effectiveness of Raksi in sacrificed rats in arresting postmortem changes and establishing scientific fact whether Raksi can be an alternative to standard embalming constituent if it is not available. 50 albino rats were systematically randomized into control and experiment groups. Raksi and distilled water were injected for embalming purpose intraventricularly in experiment and control groups of rats respectively and kept for 48 to 96 hours for observation for postmortem changes. Observations made at 48 and 72 hours of embalming revealed that Raksi can arrest postmortem changes in the rats up to 72 hours (3rd day) successfully in the experimental group whereas moderate to severe postmortem changes were seen in the control group. The experimental group showed mild degree of putrefactive changes, liberation of gases and liquefaction of tissues only at 96 hours (4th day) of embalming. The Raksi used in this experiment contained 34% of alcohol, which was determined by an alcohol hydrometer. Experiment clearly demonstrated from its result that raksi can be utilised temporarily for embalming since it contains alcohol and has preservative, bactericidal and disinfectant properties. It is concluded from the study that this knowledge if applied to dead human subjects, may preserve dead bodies temporarily allowing delayed funeral.

Alterations in the sarcoplasmic protein fraction of beef muscle with postmortem aging and hydrodynamic pressure processing

USDA-ARS?s Scientific Manuscript database

Capillary electrophoresis (CE) and reversed-phase high performance liquid chromatography (RP-HPLC) analysis were utilized to detect differences in the sarcoplasmic protein profiles of beef strip loins subjected to aging and hydrodynamic pressure processing (HDP) treatments. At 48 h postmortem, stri...

[Using some modern mathematical models of postmortem cooling of the human body for the time of death determination].

PubMed

Vavilov, A Iu; Viter, V I

2007-01-01

Mathematical questions of data errors of modern thermometrical models of postmortem cooling of the human body are considered. The main diagnostic areas used for thermometry are analyzed to minimize these data errors. The authors propose practical recommendations to decrease data errors of determination of prescription of death coming.

Post-mortem clinical pharmacology

PubMed Central

Ferner, R E

2008-01-01

Clinical pharmacology assumes that deductions can be made about the concentrations of drugs from a knowledge of the pharmacokinetic parameters in an individual; and that the effects are related to the measured concentration. Post-mortem changes render the assumptions of clinical pharmacology largely invalid, and make the interpretation of concentrations measured in post-mortem samples difficult or impossible. Qualitative tests can show the presence of substances that were not present in life, and can fail to detect substances that led to death. Quantitative analysis is subject to error in itself, and because post-mortem concentrations vary in largely unpredictable ways with the site and time of sampling, as a result of the phenomenon of post-mortem redistribution. Consequently, compilations of ‘lethal concentrations’ are misleading. There is a lack of adequate studies of the true relationship between fatal events and the concentrations that can be measured subsequently, but without such studies, clinical pharmacologists and others should be wary of interpreting post-mortem measurements. PMID:18637886

Basolateral amygdala volume and cell numbers in major depressive disorder: a postmortem stereological study.

PubMed

Rubinow, Marisa J; Mahajan, Gouri; May, Warren; Overholser, James C; Jurjus, George J; Dieter, Lesa; Herbst, Nicole; Steffens, David C; Miguel-Hidalgo, Jose J; Rajkowska, Grazyna; Stockmeier, Craig A

2016-01-01

Functional imaging studies consistently report abnormal amygdala activity in major depressive disorder (MDD). Neuroanatomical correlates are less clear: imaging studies have produced mixed results on amygdala volume, and postmortem neuroanatomic studies have only examined cell densities in portions of the amygdala or its subregions in MDD. Here, we present a stereological analysis of the volume of, and the total number of, neurons, glia, and neurovascular (pericyte and endothelial) cells in the basolateral amygdala in MDD. Postmortem tissues from 13 subjects with MDD and 10 controls were examined. Sections (~15/subject) taken throughout the rostral-caudal extent of the basolateral amygdala (BLA) were stained for Nissl substance and utilized for stereological estimation of volume and cell numbers. Results indicate that depressed subjects had a larger lateral nucleus than controls and a greater number of total BLA neurovascular cells than controls. There were no differences in the number or density of neurons or glia between depressed and control subjects. These findings present a more detailed picture of BLA cellular anatomy in depression than has previously been available. Further studies are needed to determine whether the greater number of neurovascular cells in depressed subjects may be related to increased amygdala activity in depression.

Biochemical Fractionation and Stable Isotope Dilution Liquid Chromatography-mass Spectrometry for Targeted and Microdomain-specific Protein Quantification in Human Postmortem Brain Tissue*

PubMed Central

MacDonald, Matthew L.; Ciccimaro, Eugene; Prakash, Amol; Banerjee, Anamika; Seeholzer, Steven H.; Blair, Ian A.; Hahn, Chang-Gyu

2012-01-01

Synaptic architecture and its adaptive changes require numerous molecular events that are both highly ordered and complex. A majority of neuropsychiatric illnesses are complex trait disorders, in which multiple etiologic factors converge at the synapse via many signaling pathways. Investigating the protein composition of synaptic microdomains from human patient brain tissues will yield valuable insights into the interactions of risk genes in many disorders. These types of studies in postmortem tissues have been limited by the lack of proper study paradigms. Thus, it is necessary not only to develop strategies to quantify protein and post-translational modifications at the synapse, but also to rigorously validate them for use in postmortem human brain tissues. In this study we describe the development of a liquid chromatography-selected reaction monitoring method, using a stable isotope-labeled neuronal proteome standard prepared from the brain tissue of a stable isotope-labeled mouse, for the multiplexed quantification of target synaptic proteins in mammalian samples. Additionally, we report the use of this method to validate a biochemical approach for the preparation of synaptic microdomain enrichments from human postmortem prefrontal cortex. Our data demonstrate that a targeted mass spectrometry approach with a true neuronal proteome standard facilitates accurate and precise quantification of over 100 synaptic proteins in mammalian samples, with the potential to quantify over 1000 proteins. Using this method, we found that protein enrichments in subcellular fractions prepared from human postmortem brain tissue were strikingly similar to those prepared from fresh mouse brain tissue. These findings demonstrate that biochemical fractionation methods paired with targeted proteomic strategies can be used in human brain tissues, with important implications for the study of neuropsychiatric disease. PMID:22942359

Abnormal expression and functional characteristics of cyclic adenosine monophosphate response element binding protein in postmortem brain of suicide subjects.

PubMed

Dwivedi, Yogesh; Rao, Jagadeesh Sridhara; Rizavi, Hooriyah S; Kotowski, Jacek; Conley, Robert R; Roberts, Rosalinda C; Tamminga, Carol A; Pandey, Ghanshyam N

2003-03-01

Cyclic adenosine monophosphate response element binding protein (CREB) is a transcription factor that, on phosphorylation by protein kinases, is activated, and in response, regulates the transcription of many neuronally expressed genes. In view of the recent observations that catalytic properties and/or expression of many kinases that mediate their physiological responses through the activation of CREB are altered in the postmortem brain of subjects who commit suicide (hereafter referred to as suicide subjects), we examined the status of CREB in suicidal behavior. These studies were performed in Brodmann area (BA) 9 and hippocampus obtained from 26 suicide subjects and 20 nonpsychiatric healthy control subjects. Messenger RNA levels of CREB and neuron-specific enolase were determined in total RNA by means of quantitative reverse transcriptase-polymerase chain reaction. Protein levels and the functional characteristics of CREB were determined in nuclear fractions by means of Western blot and cyclic adenosine monophosphate response element (CRE)-DNA binding activity, respectively. In the same nuclear fraction, we determined the catalytic activity of cyclic adenosine monophosphate-stimulated protein kinase A by means of enzymatic assay. We observed a significant reduction in messenger RNA and protein levels of CREB, CRE-DNA binding activity, and basal and cyclic adenosine monophosphate-stimulated protein kinase A activity in BA 9 and hippocampus of suicide subjects, without any change in messenger RNA levels of neuron-specific enolase in BA 9. Except for protein kinase A activity, changes in CREB expression and CRE-DNA binding activity were present in all suicide subjects, irrespective of diagnosis. These changes were unrelated to postmortem intervals, age, sex, or antidepressant treatment. Given the significance of CREB in mediating various physiological functions through gene transcription, our results of decreased expression and functional characteristics of CREB in postmortem brain of suicide subjects suggest that CREB may play an important role in suicidal behavior.

Dating human skeletal remains: investigating the viability of measuring the equilibrium between 210Po and 210Pb as a means of estimating the post-mortem interval.

PubMed

Swift, B

1998-11-30

Estimating the post-mortem interval in skeletal remains is a notoriously difficult task; forensic pathologists often rely heavily upon experience in recognising morphological appearances. Previous techniques have involved measuring physical or chemical changes within the hydroxyapatite matrix, radiocarbon dating and 90Sr dating, though no individual test has been advocated. Within this paper it is proposed that measuring the equilibrium between two naturally occurring radio-isotopes, 210Po and 210Pb, and comparison with post-mortem examination samples would produce a new method of dating human skeletal remains. Possible limitations exist, notably the effect of diagenesis, time limitations and relative cost, though this technique could provide a relatively accurate means of determining the post-mortem interval. It is therefore proposed that a large study be undertaken to provide a calibration scale against which bones uncovered can be dated.

Whole-body biodistribution and brain PET imaging with [18F]AV-45, a novel amyloid imaging agent--a pilot study.

PubMed

Lin, Kun-Ju; Hsu, Wen-Chuin; Hsiao, Ing-Tsung; Wey, Shiaw-Pyng; Jin, Lee-Way; Skovronsky, Daniel; Wai, Yau-Yau; Chang, Hsiu-Ping; Lo, Chuan-Wei; Yao, Cheng Hsiang; Yen, Tzu-Chen; Kung, Mei-Ping

2010-05-01

The compound (E)-4-(2-(6-(2-(2-(2-(18)F-fluoroethoxy)ethoxy)ethoxy) pyridin-3-yl)vinyl)-N-methylbenzenamine ([(18)F]AV-45) is a novel radiopharmaceutical capable of selectively binding to beta-amyloid (A beta) plaques. This pilot study reports the safety, biodistribution, and radiation dosimetry of [(18)F]AV-45 in human subjects. In vitro autoradiography and fluorescent staining of postmortem brain tissue from patients with Alzheimer's disease (AD) and cognitively healthy subjects were performed to assess the specificity of the tracer. Biodistribution was assessed in three healthy elderly subjects (mean age: 60.0+/-5.2 years) who underwent 3-h whole-body positron emission tomography (PET)/computed tomographic (CT) scans after a bolus injection of 381.9+/-13.9 MBq of [(18)F]AV-45. Another six subjects (three AD patients and three healthy controls, mean age: 67.7+/-13.6 years) underwent brain PET studies. Source organs were delineated on PET/CT. All subjects underwent magnetic resonance imaging (MRI) for obtaining structural information. In vitro autoradiography revealed exquisitely high specific binding of [(18)F]AV-45 to postmortem AD brain sections, but not to the control sections. There were no serious adverse events throughout the study period. The peak uptake of the tracer in the brain was 5.12+/-0.41% of the injected dose. The highest absorbed organ dose was to the gallbladder wall (184.7+/-78.6 microGy/MBq, 4.8 h voiding interval). The effective dose equivalent and effective dose values for [(18)F]AV-45 were 33.8+/-3.4 microSv/MBq and 19.3+/-1.3 microSv/MBq, respectively. [(18)F]AV-45 binds specifically to A beta in vitro, and is a safe PET tracer for studying A beta distribution in human brain. The dosimetry is suitable for clinical and research application. (c) 2010 Elsevier Inc. All rights reserved.

Functional coupling between adenosine A1 receptors and G-proteins in rat and postmortem human brain membranes determined with conventional guanosine-5'-O-(3-[35S]thio)triphosphate ([35S]GTPγS) binding or [35S]GTPγS/immunoprecipitation assay.

PubMed

Odagaki, Yuji; Kinoshita, Masakazu; Ota, Toshio; Meana, J Javier; Callado, Luis F; Matsuoka, Isao; García-Sevilla, Jesús A

2018-06-01

Adenosine signaling plays a complex role in multiple physiological processes in the brain, and its dysfunction has been implicated in pathophysiology of neuropsychiatric diseases such as schizophrenia and affective disorders. In the present study, the coupling between adenosine A 1 receptor and G-protein was assessed by means of two [ 35 S]GTPγS binding assays, i.e., conventional filtration method and [ 35 S]GTPγS binding/immunoprecipitation in rat and human brain membranes. The latter method provides information about adenosine A 1 receptor-mediated Gα i-3 activation in rat as well as human brain membranes. On the other hand, adenosine-stimulated [ 35 S]GTPγS binding determined with conventional assay derives from functional activation of Gα i/o proteins (not restricted only to Gα i-3 ) coupled to adenosine A 1 receptors. The determination of adenosine concentrations in the samples used in the present study indicates the possibility that the assay mixture under our experimental conditions contains residual endogenous adenosine at nanomolar concentrations, which was also suggested by the results on the effects of adenosine receptor antagonists on basal [ 35 S]GTPγS binding level. The effects of adenosine deaminase (ADA) on basal binding also support the presence of adenosine. Nevertheless, the varied patterns of ADA discouraged us from adding ADA into assay medium routinely. The concentration-dependent increases elicited by adenosine were determined in 40 subjects without any neuropsychiatric disorders. The increases in %E max values determined by conventional assay according to aging and postmortem delay should be taken into account in future studies focusing on the effects of psychiatric disorders on adenosine A 1 receptor/G-protein interaction in postmortem human brain tissue.

Postmortem CT Angiography Compared with Autopsy: A Forensic Multicenter Study.

PubMed

Grabherr, Silke; Heinemann, Axel; Vogel, Hermann; Rutty, Guy; Morgan, Bruno; Woźniak, Krzysztof; Dedouit, Fabrice; Fischer, Florian; Lochner, Stefanie; Wittig, Holger; Guglielmi, Giuseppe; Eplinius, Franziska; Michaud, Katarzyna; Palmiere, Cristian; Chevallier, Christine; Mangin, Patrice; Grimm, Jochen M

2018-05-01

Purpose To determine if postmortem computed tomography (CT) and postmortem CT angiography help to detect more lesions than autopsy in postmortem examinations, to evaluate the strengths and weaknesses of each method, and to define their indications. Materials and Methods Postmortem CT angiography was performed on 500 human corpses and followed by conventional autopsy. Nine centers were involved. All CT images were read by an experienced team including one forensic pathologist and one radiologist, blinded to the autopsy results. All findings were recorded for each method and categorized by anatomic structure (bone, organ parenchyma, soft tissue, and vascular) and relative importance in the forensic case (essential, useful, and unimportant). Results Among 18 654 findings, autopsies helped to identify 61.3% (11 433 of 18 654), postmortem CT helped to identify 76.0% (14 179 of 18 654), and postmortem CT angiography helped to identify 89.9% (16 780 of 18 654; P < .001). Postmortem CT angiography was superior to autopsy, especially at helping to identify essential skeletal lesions (96.1% [625 of 650] vs 65.4% [425 of 650], respectively; P < .001) and vascular lesions (93.5% [938 of 1003] vs 65.3% [655 of 1003], respectively; P < .001). Among the forensically essential findings, 23.4% (1029 of 4393) were not detected at autopsy, while only 9.7% (428 of 4393) were missed at postmortem CT angiography (P < .001). The best results were obtained when postmortem CT angiography was combined with autopsy. Conclusion Postmortem CT and postmortem CT angiography and autopsy each detect important lesions not detected by the other method. More lesions were identified by combining postmortem CT angiography and autopsy, which may increase the quality of postmortem diagnosis. Online supplemental material is available for this article.

Postmortem 31P magnetic resonance spectroscopy of the skeletal muscle: α-ATP/Pi ratio as a forensic tool?

PubMed

Schmidt, Tony M; Wang, Zhiyue J; Keller, Sarah; Heinemann, Axel; Acar, Suzan; Graessner, Joachim; Schoennagel, Bjoern P; Adam, Gerhard; Fischer, Roland; Yamamura, Jin

2014-09-01

Phosphor magnetic resonance spectroscopy ((31)P MRS) is an established method for metabolic examinations of resting and exercising skeletal muscle. So far, there are few MRS investigations of human corpses. The aim of this study was to investigate the temporal postmortem pattern of phosphor metabolites in the adductor magnus muscle and to check the value of MRS as a forensic tool, especially for the determination of the time of death. Eight corpses, died of natural cause, were examined (5 males, 3 females; age: 73±7 y, weight 65.8±15.9 kg). A control group of 3 subjects (2 males, 1 female, mean age: 51±24 y, range: 24-69 y, mean body weight: 84.0±16.5 kg) was examined at a single time point as well. (31)P MRS was performed on a 1.5 T MRI (TR 700 ms, TE 0.35 ms, averages 256, flip angle 90°). A standard (31)P/(1)H heart/liver coil was employed (receiver coil diameter 12 cm). The (31)P MRS scans were repeated in intervals of 1 h over a period from 4.5 to 24 h postmortem (p.m.). The core temperature was rectally measured throughout the MRI examination. The mean core temperature decreased from 36.0°C to 25.7°C. In vivo and ex vivo spectra showed characteristic differences, especially the PCr metabolite was no longer detectable after 10 h p.m. The α-ATP/Pi ratio decreased with time from 0.445 to 0.032 over 24 h p.m. There is a characteristic postmortem time pattern of the phosphor metabolites. Especially the acquired α-ATP/Pi ratio could be described by a significant exponential time course (r(2)=0.92, p<0.001). (31)P MRS might be added to the postmortem imaging methods. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Postmortem clinical examination by experienced clinical geneticists as an alternative to conventional autopsy for assessment of fetal and perinatal deaths in countries with limited resources.

PubMed

Abdalla, Ebtesam M; El Desouky, Lubna M; Hassanein, Nargues M

2015-01-01

The aim of this study was to investigate the usefulness of postmortem external examination performed by an experienced clinical geneticist as an alternative to autopsy in countries with limited resources. We studied a consecutive cohort of couples seeking genetic counseling for fetal loss or perinatal death over a period of 3 years. The study involved 230 couples; only 57 of them submitted a fetus or dead neonate, for whom a meticulous postmortem clinical examination was performed by an experienced clinical geneticist. The diagnosis rate for the group of cases subjected to postmortem examination (57.9%) was much higher than that of the group that comprised cases for which diagnosis was made through evaluation of medical records (27.2%). Whenever fetal or neonatal autopsy is refused or is not feasible, a comprehensive fetal or perinatal postmortem external examination by an experienced clinical geneticist may be a reasonable substitute.

Inflammation and immune system activation in aging: a mathematical approach.

PubMed

Nikas, Jason B

2013-11-19

Memory and learning declines are consequences of normal aging. Since those functions are associated with the hippocampus, I analyzed the global gene expression data from post-mortem hippocampal tissue of 25 old (age ≥ 60 yrs) and 15 young (age ≤ 45 yrs) cognitively intact human subjects. By employing a rigorous, multi-method bioinformatic approach, I identified 36 genes that were the most significant in terms of differential expression; and by employing mathematical modeling, I demonstrated that 7 of the 36 genes were able to discriminate between the old and young subjects with high accuracy. Remarkably, 90% of the known genes from those 36 most significant genes are associated with either inflammation or immune system activation. This suggests that chronic inflammation and immune system over-activity may underlie the aging process of the human brain, and that potential anti-inflammatory treatments targeting those genes may slow down this process and alleviate its symptoms.

Light scatter on the surface of AcrySof intraocular lenses: part I. Analysis of lenses retrieved from pseudophakic postmortem human eyes.

PubMed

Yaguchi, Shigeo; Nishihara, Hitoshi; Kambhiranond, Waraporn; Stanley, Daniel; Apple, David J

2008-01-01

To investigate the cause of light scatter measured on the surface of AcrySof intraocular lenses (Alcon Laboratories, Inc., Fort Worth, TX) retrieved from pseudophakic postmortem human eyes. Ten intraocular lenses (Alcon AcrySofModel MA60BM) were retrieved postmortem and analyzed for light scatter before and after removal of surface-bound biofilms. Six of the 10 lenses exhibited light scatter that was clearly above baseline levels. In these 6 lenses, both peak and average pixel density were reduced by approximately 80% after surface cleaning. The current study demonstrates that a coating deposited in vivo on the lens surface is responsible for the light scatter observed when incident light is applied.

Effect of antemortem and postmortem factors on ( sup 3 H)MK-801 binding in the human brain: Transient elevation during early childhood

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kornhuber, J.; Mack-Burkhardt, F.; Konradi, C.

1989-01-01

The effect of a number of antemortem and postmortem factors on ({sup 3}H)MK-801 binding was investigated under equilibrium conditions in the frontal cortex of human brains of 38 controls. Binding values transiently increased during the early postnatal period reaching a maximum at the age of about 2 years. After age 10 years ({sup 3}H)MK-801 binding sites disappeared at 5.7% per decade. The storage time of brain tissue had a reducing effect on these binding sites. There was no effect of gender, brain weight or postmortem time interval and the binding sites were bilaterally symmetrically distributed in the frontal cortex.

Comparative performance and complementarity of four sampling methods and arthropod preference tests from human and porcine remains at the Forensic Anthropology Center in Knoxville, Tennessee.

PubMed

Schoenly, Kenneth G; Haskell, Neal H; Hall, Robert D; Gbur, J Robert

2007-09-01

Comparative performance and complementarity tests of four arthropod sampling methods (aerial netting, hand collection, pitfall traps, and sticky traps), used by forensic entomologists in death investigations, training workshops, and research trials, were conducted from simultaneously placed human and porcine subjects inside the Forensic Anthropology Center at the University of Tennessee, Knoxville, TN. A secondary aim investigated the widely held claim that pig carcasses are reliable surrogates for human corpses. Over a 35-d period in summer 1989, >72,000 invertebrates from three subjects (one human, two pigs) were sampled of which 93% were members of the forensically important (FI) fauna. Performance tests revealed that hand collections, when performed by an experienced forensic entomologist, consistently yielded the largest fraction of FI arthropods from the total invertebrate catch, followed by aerial netting, sticky traps, and pitfall traps, regardless of subject. Pitfall traps and hand collections were broadly effective at sampling both fly and beetle populations, whereas aerial netting and sticky traps mostly targeted flies. The best two-method combination, based on the highest combined catches of FI taxa, were hand collections and pitfall traps, regardless of subject. Between-subject comparisons revealed negligible preference by FI arthropods for human over pig remains. Insofar as our limited comparisons allow with only three study subjects, these results validated the concept of transferability of "best practices" from one subject to another and confirmed the claim that pig carcasses (of 23-27-kg starting mass) can substitute for human corpses in research and training programs, at least for summer-exposed and unconcealed remains in the first 5 wk postmortem.

[Value of specific 16S rDNA fragment of algae in diagnosis of drowning: an experiment with rabbits].

PubMed

Li, Peng; Xu, Qu-Yi; Chen, Ling; Liu, Chao; Zhao, Jian; Wang, Yu-Zhong; Yu, Zheng-Liang; Hu, Sun-Lin; Wang, Hui-Jun

2015-08-01

To establish a method for amplifying specific 16S rDNA fragment of algae related with drowning and test its value in drowning diagnosis. Thirty-five rabbits were randomly divided into 3 the drowning group (n=15), postmortem water immersion group (n=15, subjected to air embolism before seawater immersion), and control group(n=5, with air embolism only). Twenty samples of the liver tissues from human corpses found in water were also used, including 14 diatom-positive and 6 diatom-negative samples identified by microwave digestion-vacuum filtration-automated scanning electron microscopy (MD-VF-Auto SEM). Seven known species of algae served as the control algae (Melosira sp, Nitzschia sp, Synedra sp, Navicula sp, Microcystis sp, Cyclotella meneghiniana, and Chlorella sp). The total DNA was extracted from the tissues and algae to amplify the specific fragment of algae followed by 8% polyacrylamide gelelectrophoresis and sliver-staining. In the drowning group, algae was detected in the lungs (100%), liver (86%), and kidney (86%); algae was detected in the lungs in 2 rabbits in the postmortem group (13%) and none in the control group. The positivity rates of algae were significantly higher in the drowning group than in the postmortem group (P<0.05). Of the 20 tissue samples from human corps found in water, 15 were found positive for algae, including sample that had been identified as diatom-negative by MD-VF-Auto SEM. All the 7 control algae samples yielded positive results in PCR. The PCR-based method has a high sensitivity in algae detection for drowning diagnosis and allows simultaneous detection of multiple algae species related with drowning.

Do glutathione levels decline in aging human brain?

PubMed

Tong, Junchao; Fitzmaurice, Paul S; Moszczynska, Anna; Mattina, Katie; Ang, Lee-Cyn; Boileau, Isabelle; Furukawa, Yoshiaki; Sailasuta, Napapon; Kish, Stephen J

2016-04-01

For the past 60 years a major theory of "aging" is that age-related damage is largely caused by excessive uncompensated oxidative stress. The ubiquitous tripeptide glutathione is a major antioxidant defense mechanism against reactive free radicals and has also served as a marker of changes in oxidative stress. Some (albeit conflicting) animal data suggest a loss of glutathione in brain senescence, which might compromise the ability of the aging brain to meet the demands of oxidative stress. Our objective was to establish whether advancing age is associated with glutathione deficiency in human brain. We measured reduced glutathione (GSH) levels in multiple regions of autopsied brain of normal subjects (n=74) aged one day to 99 years. Brain GSH levels during the infancy/teenage years were generally similar to those in the oldest examined adult group (76-99 years). During adulthood (23-99 years) GSH levels remained either stable (occipital cortex) or increased (caudate nucleus, frontal and cerebellar cortices). To the extent that GSH levels represent glutathione antioxidant capacity, our postmortem data suggest that human brain aging is not associated with declining glutathione status. We suggest that aged healthy human brains can maintain antioxidant capacity related to glutathione and that an age-related increase in GSH levels in some brain regions might possibly be a compensatory response to increased oxidative stress. Since our findings, although suggestive, suffer from the generic limitations of all postmortem brain studies, we also suggest the need for "replication" investigations employing the new (1)H MRS imaging procedures in living human brain. Copyright © 2016 Elsevier Inc. All rights reserved.

The shear modulus of the human vocal fold, preliminary results from 20 larynxes.

PubMed

Goodyer, Eric; Hemmerich, Sandra; Müller, Frank; Kobler, James B; Hess, Markus

2007-01-01

Quantification of the elastic properties of the human vocal fold provides invaluable data for researchers deriving mathematical models of phonation, developing tissue engineering therapies, and as normative data for comparison between healthy and scarred tissue. This study measured the shear modulus of excised cadaver vocal folds from 20 subjects. Twenty freshly excised human larynxes were evaluated less than four days post-mortem. They were split along the saggital plane and mounted without tension. Shear modulus was obtained by two different methods. For method 1 cyclical shear stress was applied transversely to the mid-membranous portion of the vocal fold, and shear modulus derived by applying a simple shear model. For method 2 the apparatus was configured as an indentometer, and shear modulus obtained from the stress/strain data by applying an established analytical technique. Method 1 shear model for male larynxes yielded a range from 246 to 3,356 Pa, with a mean value of 1,008 and SD of 380. The range for female larynxes was 286-3,332 Pa, with a mean value of 1,237 and SD of 768. Method 2 indentometer model for male larynxes yielded a range from 552 to 2,741 Pa, with a mean value of 1,000 and SD of 460. The range for female larynxes was 509-1,989 Pa, with a mean value of 1,332 and SD of 428. We have successfully demonstrated two methodologies that are capable of directly measuring the shear modulus of the human vocal fold, without dissecting out the vocal fold cover tissue. The sample size of nine female and 11 male larynxes is too small to validate a general conclusion. The high degree of variability in this small cohort of subjects indicates that factors such as age, health status, and post-mortem delay may be significant; and that there is range of 'normality' for vocal fold tissue.

Distribution of Delta 9-Tetrahydrocannabinol and 11-Nor-9-Carboxy-Delta 9-Tetrahydrocannabinol Acid in Postmortem Biological Fluids and Tissues From Pilots Fatally Injured in Aviation Accidents

DTIC Science & Technology

2013-12-01

classified as current marijuana ( Cannabis sativa) users in the United States and 5.4 million people aged 12 and older used marijuana on a daily or almost...report from the European Union, cannabis use is common in many parts of the world.3 As a result of such widespread marijuana use and its well...knowledge regarding the postmortem distribution of cannabi - noids in humans primarily because cannabinoid testing is not routine in many postmortem

Estimation of postmortem interval based on colony development time for Anoplolepsis longipes (Hymenoptera: Formicidae).

PubMed

Goff, M L; Win, B H

1997-11-01

The postmortem interval for a set of human remains discovered inside a metal tool box was estimated using the development time required for a stratiomyid fly (Diptera: Stratiomyidae), Hermetia illucens, in combination with the time required to establish a colony of the ant Anoplolepsis longipes (Hymenoptera: Formicidae) capable of producing alate (winged) reproductives. This analysis resulted in a postmortem interval estimate of 14 + months, with a period of 14-18 months being the most probable time interval. The victim had been missing for approximately 18 months.

Relationship between sudden natural death and abdominal fat evaluated on postmortem CT scans.

PubMed

Kaichi, Y; Sakane, H; Higashibori, H; Honda, Y; Tatsugami, F; Baba, Y; Iida, M; Awai, K

2017-06-01

This study examined the association between sudden natural death and abdominal fat using postmortem computed tomography (CT) scans. Postmortem CT images at the umbilical level of 241 subjects were used to measure abdominal areas of subcutaneous- and visceral fat, the rate of visceral fat and the waist circumference. Of the study subjects, 174 died of sudden natural death (130 men and 44 women), and 67 died of different causes (46 men and 21 women). All were between 40 and 75 years of age. Logistic regression analysis was performed to identify independent abdominal parameters associated with sudden natural death. By univariate analysis, the areas of subcutaneous and visceral fat were significantly larger in sudden natural death than who died of different causes (subcutaneous fat, odds ratio [OR] = 1.004, 95% confidence interval [CI] = 1.000-1.007, p  = 0.03; visceral fat, OR = 1.008, 95% CI = 1.003-1.013, p  < 0.01). Multivariate analysis showed that the area of visceral fat was an independent factor associated with the risk of sudden natural death (OR = 1.008, 95% CI = 1.002-1.015, p  = 0.02). Postmortem CT revealed that sudden natural death was related to abdominal fat deposits.

Appearance of Sodium Dodecyl Sulfate-Stable Amyloid β-Protein (Aβ) Dimer in the Cortex During Aging

PubMed Central

Enya, Miho; Morishima-Kawashima, Maho; Yoshimura, Masahiro; Shinkai, Yasuhisa; Kusui, Kaoru; Khan, Karen; Games, Dora; Schenk, Dale; Sugihara, Shiro; Yamaguchi, Haruyasu; Ihara, Yasuo

1999-01-01

We previously noted that some aged human cortical specimens containing very low or negligible levels of amyloid β-protein (Aβ) by enzyme immunoassay (EIA) provided prominent signals at 6∼8 kd on the Western blot, probably representing sodium dodecyl sulfate (SDS)-stable Aβ dimer. Re-examination of the specificity of the EIA revealed that BAN50- and BNT77-based EIA, most commonly used for the quantitation of Aβ, capture SDS-dissociable Aβ but not SDS-stable Aβ dimer. Thus, all cortical specimens in which the levels of Aβ were below the detection limits of EIA were subjected to Western blot analysis. A fraction of such specimens contained SDS-stable dimer at 6∼8 kd, but not SDS-dissociable Aβ monomer at ∼4 kd, as judged from the blot. This Aβ dimer is unlikely to be generated after death, because (i) specimens with very short postmortem delay contained the Aβ dimer, and (ii) until 12 hours postmortem, such SDS-stable Aβ dimer is detected only faintly in PDAPP transgenic mice. The presence of Aβ dimer in the cortex may characterize the accumulation of Aβ in the human brain, which takes much longer than that in PDAPP transgenic mice. PMID:9916941

The Sun Health Research Institute Brain Donation Program: Description and Eexperience, 1987–2007

PubMed Central

Sue, Lucia I.; Walker, Douglas G.; Roher, Alex E.; Lue, LihFen; Vedders, Linda; Connor, Donald J.; Sabbagh, Marwan N.; Rogers, Joseph

2008-01-01

The Brain Donation Program at Sun Health Research Institute has been in continual operation since 1987, with over 1000 brains banked. The population studied primarily resides in the retirement communities of northwest metropolitan Phoenix, Arizona. The Institute is affiliated with Sun Health, a nonprofit community-owned and operated health care provider. Subjects are enrolled prospectively to allow standardized clinical assessments during life. Funding comes primarily from competitive grants. The Program has made short postmortem brain retrieval a priority, with a 2.75-h median postmortem interval for the entire collection. This maximizes the utility of the resource for molecular studies; frozen tissue from approximately 82% of all cases is suitable for RNA studies. Studies performed in-house have shown that, even with very short postmortem intervals, increasing delays in brain retrieval adversely affect RNA integrity and that cerebrospinal fluid pH increases with postmortem interval but does not predict tissue viability. PMID:18347928

[Post-mortem examination prior to cremation--an instrument to verify the quality of medical post-mortems and uncover non-natural deaths?].

PubMed

Germerott, Tanja; Todt, Melanie; Bode-Jänisch, Stefanie; Albrecht, Knut; Breitmeier, Dirk

2012-01-01

The external post-mortem examination, its deficient quality and possible causes have been the subject of numerous political and professional discussions. The external post-mortem examination is the basis for the decision whether further criminal investigations are required to clarify the cause of death. It is thus an essential instrument to ensure legal certainty. Before cremation, a second external post-mortem examination is performed by a public medical officer to make sure that errors of the first post-mortem are corrected. In the present study, cases were retrospectively analyzed in which a forensic autopsy had been ordered on the basis of the results of the post-mortem examination performed before cremation. The entries on the death certificate regarding the manner and cause of death were compared with the autopsy results. Between 1998 and 2007, 387 autopsies were ordered after external examination before cremation. In 55 cases (14.2%), the autopsy revealed a non-natural death, although a natural death had been attested on the death certificate. In descending order, a wrong manner of death was attested by clinicians, general practitioners and emergency physicians. With regard to the place where the first external post-mortem had been performed the lowest error rate was seen in nursing homes. Concerning the cause of death, discrepancies between the first post-mortem and autopsy were found in 59.4% of the cases. In this respect, general practitioners and clinicians were ranking first, whereas in nursing homes the cause of death was wrongly assessed in over 70% of cases. At present, the medical post-mortem does not meet the required quality standards, especially with regard to legal certainty. Determination of the cause of death on the basis of the external post-mortem examination is a challenging task even for the experienced medical examiner. As to the categorization of the manner of death it has to be stated that non-natural deaths are often not recognized or that the possibility to certify a death as unclear is not sufficiently used. As a result, it seems important to demand intensive, qualified, additional training in external post-mortem examinations for physicians.

Postmortem ventilation in cases of penetrating gunshot and stab wounds to the chest.

PubMed

Germerott, Tanja; Preiss, Ulrich S; Ross, Steffen G; Thali, Michael J; Flach, Patricia M

2013-11-01

We sought to determine the effect of postmortem ventilation in combination with a suction pump in cases showing penetrating trauma to the chest with haemo- and/or pneumothorax, for better evaluation of the lungs in postmortem computed tomography (PMCT). The study included 6 subjects (1 female, 5 male; age 32-67years) with a penetrating gunshot or stab wound to the chest and consecutive pneumo- and/or haemothorax. The pneumo- and haemothorax were evacuated by a suction pump, and postmortem ventilation was applied using a home care ventilator. PMCT images with and without postmortem ventilation were compared, as well as the autopsy results. In three cases haemo- and pneumothorax was clearly reduced. Postmortem ventilation led to distinct re-expansion of the lungs in two cases, and to re-expansion of single lung lobes in two cases with shotgun injuries. No visible effect was seen in the remaining two cases, because of extensive destruction of lung tissue and blood aspiration. In two cases the injuries sustained in the individual lung lobes were successfully located during postmortem ventilation. The bullet channel was apparent in one case; in another case, injury of the pericardium became visible by generating pneumopericardium. The present method is capable of improving evaluation of the postmortem lung in the presence of single stab or gunshot wounds and if there is no severe destruction of the respiratory system and aspiration. Forensic autopsy should still be considered as the gold standard, although in some cases the present method might be helpful, especially where no autopsy is required. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

[Three good reasons to perform a postmortem examination in all cases of juvenile sudden death].

PubMed

d'Amati, Giulia; di Gioia, Cira R T; Silenzi, Paola F; Gallo, Pietro

2009-04-01

The aim of this review is to underline the reasons why a post-mortem examination has to be performed in all cases of juvenile sudden death. Sudden death in children and young adults can be caused by potentially heritable cardiovascular disorders and fatal outcome is often the first symptom in apparently healthy subjects. In these cases, a careful autopsy, performed according to a standardized protocol, becomes the sole diagnostic tool to guide clinical and molecular genetic family screening and to adopt the proper therapeutic and preventive strategies. Thus, a post-mortem examination is a fundamental part of a multidisciplinary approach to the issue of juvenile sudden death.

Postmortem aviation forensic toxicology: an overview.

PubMed

Chaturvedi, Arvind K

2010-05-01

An overview of the subtopic aviation combustion toxicology of the field of aerospace toxicology has been published. In a continuation of the overview, the findings associated with postmortem aviation forensic toxicology are being summarized in the present overview. A literature search for the period of 1960-2007 was performed. The important findings related to postmortem toxicology were evaluated. In addition to a brief introduction, this overview is divided into the sections of analytical methods; carboxyhemoglobin and blood cyanide ion; ethanol; drugs; result interpretation; glucose and hemoglobin A(1c); and references. Specific details of the subject matter were discussed. It is anticipated that this overview will be an outline source for aviation forensic toxicology within the field of aerospace toxicology.

Effect of animal mixing as a stressor on biomarkers of autophagy and oxidative stress during pig muscle maturation.

PubMed

Rubio-González, A; Potes, Y; Illán-Rodríguez, D; Vega-Naredo, I; Sierra, V; Caballero, B; Fàbrega, E; Velarde, A; Dalmau, A; Oliván, M; Coto-Montes, A

2015-07-01

The objective of this work was to study the postmortem evolution of potential biomarkers of autophagy (Beclin 1, LC3-II/LC3-I ratio) and oxidative stress (total antioxidant activity, TAA; superoxide dismutase activity, SOD and catalase activity, CAT) in the Longissimus dorsi muscle of entire male ((Large White×Landrace)×Duroc) pigs subjected to different management treatments that may promote stress, such as mixing unfamiliar animals at the farm and/or during transport and lairage before slaughter. During the rearing period at the farm, five animals were never mixed after the initial formation of the experimental groups (unmixed group at the farm, UF), whereas 10 animals were subjected to a common routine of being mixed with unfamiliar animals (mixed group at the farm, MF). Furthermore, two different treatments were used during the transport and lairage before slaughter: 10 pigs were not mixed (unmixed group during transport and lairage, UTL), whereas five pigs were mixed with unfamiliar animals on the lorry and during lairage (mixed group during transport and lairage, MTL). These mixing treatments were then combined into three pre-slaughter treatments - namely, UF-UTL, MF-UTL and MF-MTL. The results show that MF-UTL and MF-MTL increased significantly the muscle antioxidant defense (TAA, SOD and CAT) at short postmortem times (4 and 8 h; P<0.001), followed by an earlier depletion of the antioxidant activity at 24 h postmortem (P<0.05). We also found that mixing unfamiliar animals, both at the farm and during transport and lairage, triggers postmortem muscle autophagy, which showed an earlier activation (higher expression of Beclin 1 and LC3-II/LC3-I ratio at 4 h postmortem followed by a decreasing pattern of this ratio along first 24 h postmortem) in the muscle tissues of animals from the MF-UTL and MF-MTL groups, as an adaptive strategy of the muscle cells for counteracting induced stress. From these results, we propose that monitoring the evolution of the main biomarkers of autophagy (Beclin 1, LC3-II/LC3-I ratio) and muscle antioxidant defense (TAA, SOD, CAT) in the muscle tissue within the first 24 h postmortem may help the detection of animal stress and its potential effect on the postmortem muscle metabolism.

An anatomical and functional topography of human auditory cortical areas

PubMed Central

Moerel, Michelle; De Martino, Federico; Formisano, Elia

2014-01-01

While advances in magnetic resonance imaging (MRI) throughout the last decades have enabled the detailed anatomical and functional inspection of the human brain non-invasively, to date there is no consensus regarding the precise subdivision and topography of the areas forming the human auditory cortex. Here, we propose a topography of the human auditory areas based on insights on the anatomical and functional properties of human auditory areas as revealed by studies of cyto- and myelo-architecture and fMRI investigations at ultra-high magnetic field (7 Tesla). Importantly, we illustrate that—whereas a group-based approach to analyze functional (tonotopic) maps is appropriate to highlight the main tonotopic axis—the examination of tonotopic maps at single subject level is required to detail the topography of primary and non-primary areas that may be more variable across subjects. Furthermore, we show that considering multiple maps indicative of anatomical (i.e., myelination) as well as of functional properties (e.g., broadness of frequency tuning) is helpful in identifying auditory cortical areas in individual human brains. We propose and discuss a topography of areas that is consistent with old and recent anatomical post-mortem characterizations of the human auditory cortex and that may serve as a working model for neuroscience studies of auditory functions. PMID:25120426

Microglial dystrophy in the aged and Alzheimer's disease brain is associated with ferritin immunoreactivity.

PubMed

Lopes, Kryslaine O; Sparks, D Larry; Streit, Wolfgang J

2008-08-01

Degeneration of microglial cells may be important for understanding the pathogenesis of aging-related neurodegeneration and neurodegenerative diseases. In this study, we analyzed the morphological characteristics of microglial cells in the nondemented and Alzheimer's disease (AD) human brain using ferritin immunohistochemistry. The central hypothesis was that expression of the iron storage protein ferritin increases the susceptibility of microglia to degeneration, particularly in the aged brain since senescent microglia might become less efficient in maintaining iron homeostasis and free iron can promote oxidative damage. In a primary set of 24 subjects (age range 34-97 years) examined, microglial cells immunoreactive for ferritin were found to constitute a subpopulation of the larger microglial pool labeled with an antibody for HLA-DR antigens. The majority of these ferritin-positive microglia exhibited aberrant morphological (dystrophic) changes in the aged and particularly in the AD brain. No spatial correlation was found between ferritin-positive dystrophic microglia and senile plaques in AD tissues. Analysis of a secondary set of human postmortem brain tissues with a wide range of postmortem intervals (PMI, average 10.94 +/- 5.69 h) showed that the occurrence of microglial dystrophy was independent of PMI and consequently not a product of tissue autolysis. Collectively, these results suggest that microglial involvement in iron storage and metabolism contributes to their degeneration, possibly through increased exposure of the cells to oxidative stress. We conclude that ferritin immunohistochemistry may be a useful method for detecting degenerating microglia in the human brain. (c) 2008 Wiley-Liss, Inc.

Studies on the estimation of the postmortem interval. 3. Rigor mortis (author's transl).

PubMed

Suzutani, T; Ishibashi, H; Takatori, T

1978-11-01

The authors have devised a method for classifying rigor mortis into 10 types based on its appearance and strength in various parts of a cadaver. By applying the method to the findings of 436 cadavers which were subjected to medico-legal autopsies in our laboratory during the last 10 years, it has been demonstrated that the classifying method is effective for analyzing the phenomenon of onset, persistence and disappearance of rigor mortis statistically. The investigation of the relationship between each type of rigor mortis and the postmortem interval has demonstrated that rigor mortis may be utilized as a basis for estimating the postmortem interval but the values have greater deviation than those described in current textbooks.

The black soldier fly Hermetia illucens (Diptera: Stratiomyidae) as a potential measure of human postmortem interval: observations and case histories.

PubMed

Lord, W D; Goff, M L; Adkins, T R; Haskell, N H

1994-01-01

The black soldier fly, Hermetia illucens (L.), has been shown to be a ubiquitous inhabitant of both surface and buried human remains throughout the southern, central and western United States and Hawaii. Unlike most other species of forensically important Diptera, this species frequently dominates bodies in the dry/post decay stage of decomposition. Adults of the black soldier fly appear to initiate oviposition (egg laying) 20 to 30 days postmortem. Even at warm temperatures (27.8 degrees C), subsequent completion of the life cycle can require an additional 55 days. Life history data for H. illucens, when used in combination with data for other cohabiting arthropod species and viewed in the context of local environmental conditions, can provide medicolegal investigators with valuable parameters for estimating the postmortem intervals for badly decomposed remains.

Effect of postmortem sampling technique on the clinical significance of autopsy blood cultures.

PubMed

Hove, M; Pencil, S D

1998-02-01

Our objective was to investigate the value of postmortem autopsy blood cultures performed with an iodine-subclavian technique relative to the classical method of atrial heat searing and antemortem blood cultures. The study consisted of a prospective autopsy series with each case serving as its own control relative to subsequent testing, and a retrospective survey of patients coming to autopsy who had both autopsy blood cultures and premortem blood cultures. A busy academic autopsy service (600 cases per year) at University of Texas Medical Branch Hospitals, Galveston, Texas, served as the setting for this work. The incidence of non-clinically relevant (false-positive) culture results were compared using different methods for collecting blood samples in a prospective series of 38 adult autopsy specimens. One hundred eleven adult autopsy specimens in which both postmortem and antemortem blood cultures were obtained were studied retrospectively. For both studies, positive culture results were scored as either clinically relevant or false positives based on analysis of the autopsy findings and the clinical summary. The rate of false-positive culture results obtained by an iodine-subclavian technique from blood drawn soon after death were statistically significantly lower (13%) than using the classical method of obtaining blood through the atrium after heat searing at the time of the autopsy (34%) in the same set of autopsy subjects. When autopsy results were compared with subjects' antemortem blood culture results, there was no significant difference in the rate of non-clinically relevant culture results in a paired retrospective series of antemortem blood cultures and postmortem blood cultures using the iodine-subclavian postmortem method (11.7% v 13.5%). The results indicate that autopsy blood cultures obtained using the iodine-subclavian technique have reliability equivalent to that of antemortem blood cultures.

The social life of the dead: The role of post-mortem examinations in medical student socialisation.

PubMed

Goodwin, Dawn; Machin, Laura; Taylor, Adam

2016-07-01

Dissection has held a privileged position in medical education although the professional values it inculcates have been subject to intense debate. Claims vary from it generating a dehumanising level of emotional detachment, to promotion of rational and dispassionate decision-making, even to being a positive vehicle for ethical education. Social scientists have positioned dissection as a critical experience in the emotional socialisation of medical students. However, curricular revision has provoked debate about the style and quantity of anatomy teaching thus threatening this 'rite of passage' of medical students. Consequently, some UK medical schools do not employ dissection at all. In its place, observation of post-mortem examinations - a long established, if underutilised, practice - has re-emerged in an attempt to recoup aspects of anatomical knowledge that are arguably lost when dissection is omitted. Bodies for post-mortem examinations and bodies for dissection, however, have striking differences, meaning that post-mortem examinations and dissection cannot be considered comparable opportunities to learn anatomy. In this article, we explore the distinctions between dissection and post-mortem examinations. In particular, we focus on the absence of a discourse of consent, concerns about bodily integrity, how the body's shifting ontology, between object and person, disrupts students' attempts to distance themselves, and how the observation of post-mortem examinations features in the emotional socialisation of medical students. Copyright © 2016 Elsevier Ltd. All rights reserved.

Selective localization of oxytocin receptors and vasopressin 1a receptors in the human brainstem

PubMed Central

Freeman, Sara M.; Smith, Aaron L.; Goodman, Mark M.; Bales, Karen L.

2017-01-01

Intranasal oxytocin affects a suite of human social behaviors, including trust, eye contact, and emotion recognition. However, it is unclear where oxytocin receptors (OXTR) and the structurally related vasopressin 1a receptors (AVPR1a) are expressed in the human brain. We have previously described a reliable, pharmacologically informed receptor autoradiography protocol for visualizing these receptors in postmortem primate brain tissue. We used this technique in human brainstem tissue to identify the neural targets of oxytocin and vasopressin. To determine binding selectivity of the OXTR radioligand and AVPR1a radioligand, sections were incubated in four conditions: radioligand alone, radioligand with the selective AVPR1a competitor SR49059, and radioligand with a low or high concentration of the selective OXTR competitor ALS-II-69. We found selective OXTR binding in the spinal trigeminal nucleus, a conserved region of OXTR expression in all primate species investigated to date. We found selective AVPR1a binding in the nucleus prepositus, an area implicated in eye gaze stabilization. The tissue's postmortem interval was not correlated with either the specific or nonspecific binding of either radioligand, indicating that it will not likely be a factor in similar postmortem studies. This study provides critical data for future studies of OXTR and AVPR1a in human brain tissue. PMID:26911439

Density of GFAP-immunoreactive astrocytes is decreased in left hippocampi in major depressive disorder.

PubMed

Cobb, J A; O'Neill, K; Milner, J; Mahajan, G J; Lawrence, T J; May, W L; Miguel-Hidalgo, J; Rajkowska, G; Stockmeier, C A

2016-03-01

Neuroimaging and postmortem studies of subjects with major depressive disorder (MDD) reveal smaller hippocampal volume with lengthening duration of illness. Pathology in astrocytes may contribute significantly to this reduced volume and to the involvement of the hippocampus in MDD. Postmortem hippocampal tissues were collected from 17 subjects with MDD and 17 psychiatrically-normal control subjects. Sections from the body of the hippocampus were immunostained for glial fibrillary acidic protein (GFAP), a marker of intermediate filament protein expressed in astrocytes. The density of GFAP-immunoreactive astrocytes was measured in the hippocampus using 3-dimensional cell counting. Hippocampal subfields were also assessed for GFAP-immunoreactive area fraction. In CA1, there was a significant positive correlation between age and either density or area fraction in MDD. The density of astrocytes in the hilus, but not CA1 or CA2/3, was significantly decreased only in depressed subjects not taking an antidepressant drug, but not for depressed subjects taking an antidepressant drug. The area fraction of GFAP-immunoreactivity was significantly decreased in the dentate gyrus in women but not men with depression. In CA2/3, the area fraction of GFAP-immunoreactivity was inversely correlated with the duration of depression in suicide victims. Astrocyte contributions to neuronal function in the hilus may be compromised in depressed subjects not taking antidepressant medication. Due to the cross-sectional nature of the present study of postmortem brain tissue, it remains to be determined whether antidepressant drug treatment prevented a decrease in GFAP-immunoreactive astrocyte density or restored cell density to normal levels. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Assessing cervical dislocation as a humane euthanasia method in mice.

PubMed

Carbone, Larry; Carbone, Elizabeth T; Yi, Elizabeth M; Bauer, Diana B; Lindstrom, Krista A; Parker, John M; Austin, Jamie A; Seo, Youngho; Gandhi, Anisha D; Wilkerson, James D

2012-05-01

Research investigators often choose to euthanize mice by cervical dislocation (CD) when other methods would interfere with the aims of a research project. Others choose CD to assure death in mice treated with injected or inhaled euthanasia agents. CD was first approved for mouse euthanasia in 1972 by the AVMA Panel on Euthanasia, although scientific assessment of its humaneness has been sparse. Here we compared 4 methods of spinal dislocation--3 targeting the cervical area (CD) and one the thoracic region--in regard to time to respiratory arrest in anesthetized mice. Of the 81 mice that underwent CD by 1 of the 3 methods tested, 17 (21%) continued to breathe, and euthanasia was scored as unsuccessful. Postmortem radiography revealed cervical spinal lesions in 5 of the 17 cases of unsuccessful CD euthanasia. In addition, 63 of the 64 successfully euthanized mice had radiographically visible lesions in the high cervical or atlantooccipital region. In addition, 50 of 64 (78%) mice euthanized successfully had radiographically visible thoracic or lumbar lesions or both. Intentionally creating a midthoracic dislocation in anesthetized mice failed to induce respiratory arrest and death in any of the 18 mice subjected to that procedure. We conclude that CD of mice holds the potential for unsuccessful euthanasia, that anesthesia could be valuable for CD skills training and assessment, and that postmortem radiography has minimal promise in quality-control assessments.

Assessing Cervical Dislocation as a Humane Euthanasia Method in Mice

PubMed Central

Carbone, Larry; Carbone, Elizabeth T; Yi, Elizabeth M; Bauer, Diana B; Lindstrom, Krista A; Parker, John M; Austin, Jamie A; Seo, Youngho; Gandhi, Anisha D; Wilkerson, James D

2012-01-01

Research investigators often choose to euthanize mice by cervical dislocation (CD) when other methods would interfere with the aims of a research project. Others choose CD to assure death in mice treated with injected or inhaled euthanasia agents. CD was first approved for mouse euthanasia in 1972 by the AVMA Panel on Euthanasia, although scientific assessment of its humaneness has been sparse. Here we compared 4 methods of spinal dislocation–3 targeting the cervical area (CD) and one the thoracic region–in regard to time to respiratory arrest in anesthetized mice. Of the 81 mice that underwent CD by 1 of the 3 methods tested, 17 (21%) continued to breathe, and euthanasia was scored as unsuccessful. Postmortem radiography revealed cervical spinal lesions in 5 of the 17 cases of unsuccessful CD euthanasia. In addition, 63 of the 64 successfully euthanized mice had radiographically visible lesions in the high cervical or atlantooccipital region. In addition, 50 of 64 (78%) mice euthanized successfully had radiographically visible thoracic or lumbar lesions or both. Intentionally creating a midthoracic dislocation in anesthetized mice failed to induce respiratory arrest and death in any of the 18 mice subjected to that procedure. We conclude that CD of mice holds the potential for unsuccessful euthanasia, that anesthesia could be valuable for CD skills training and assessment, and that postmortem radiography has minimal promise in quality-control assessments. PMID:22776194

Direct Comparison of the Primary Blast Response of a Physical Head Model with Post-mortem Human Subjects

DTIC Science & Technology

2014-02-27

and brain st e made from erpart. The br ace by the me is instrumen design sleev sure transduc se of the tria f the gel duri is in intima pically...filtered usin ressure signa with the hea a 10 kHz cu ty of WSU u series. The sh section sepa p to a pressu wave down re pressure a design can be...of wave generat 5m (0 ouring of the he occipital s e comparativ hod used in t tterworth filt llowing the s d of a filterin tudy (Figure o part

Histology-derived volumetric annotation of the human hippocampal subfields in postmortem MRI.

PubMed

Adler, Daniel H; Pluta, John; Kadivar, Salmon; Craige, Caryne; Gee, James C; Avants, Brian B; Yushkevich, Paul A

2014-01-01

Recently, there has been a growing effort to analyze the morphometry of hippocampal subfields using both in vivo and postmortem magnetic resonance imaging (MRI). However, given that boundaries between subregions of the hippocampal formation (HF) are conventionally defined on the basis of microscopic features that often lack discernible signature in MRI, subfield delineation in MRI literature has largely relied on heuristic geometric rules, the validity of which with respect to the underlying anatomy is largely unknown. The development and evaluation of such rules are challenged by the limited availability of data linking MRI appearance to microscopic hippocampal anatomy, particularly in three dimensions (3D). The present paper, for the first time, demonstrates the feasibility of labeling hippocampal subfields in a high resolution volumetric MRI dataset based directly on microscopic features extracted from histology. It uses a combination of computational techniques and manual post-processing to map subfield boundaries from a stack of histology images (obtained with 200μm spacing and 5μm slice thickness; stained using the Kluver-Barrera method) onto a postmortem 9.4Tesla MRI scan of the intact, whole hippocampal formation acquired with 160μm isotropic resolution. The histology reconstruction procedure consists of sequential application of a graph-theoretic slice stacking algorithm that mitigates the effects of distorted slices, followed by iterative affine and diffeomorphic co-registration to postmortem MRI scans of approximately 1cm-thick tissue sub-blocks acquired with 200μm isotropic resolution. These 1cm blocks are subsequently co-registered to the MRI of the whole HF. Reconstruction accuracy is evaluated as the average displacement error between boundaries manually delineated in both the histology and MRI following the sequential stages of reconstruction. The methods presented and evaluated in this single-subject study can potentially be applied to multiple hippocampal tissue samples in order to construct a histologically informed MRI atlas of the hippocampal formation. © 2013 Elsevier Inc. All rights reserved.

Association between polychlorinated biphenyls and Parkinson's disease neuropathology.

PubMed

Hatcher-Martin, Jaime M; Gearing, Marla; Steenland, Kyle; Levey, Allan I; Miller, Gary W; Pennell, Kurt D

2012-10-01

Polychlorinated biphenyls (PCBs) are synthetic chemicals primarily used as coolants and insulators in electrical equipment. Although banned for several decades, PCBs continue to exist in the environment because of their long half-life, continued presence in items produced before the ban, and poor disposal practices. Epidemiological and experimental studies have identified exposure to PCBs as a potential risk factor for Parkinson's disease, perhaps more so in females. The objective of this work was to examine the association between PCB levels in post-mortem human brain tissue and the diagnosis of Parkinson's disease, as well as the degree of nigral depigmentation. We also sought to determine if this association was more significant when patients were stratified by sex. Post-mortem brain samples from control patients and those diagnosed with Parkinson's disease were obtained from the Emory University Brain Bank and from the Nun Study. Concentrations of eight prevalent PCB congeners were extracted from post-mortem brain tissue and analyzed using gas chromatography-mass spectrometry. PCB congeners 153 and 180 were significantly elevated in the brains of Parkinson's disease patients. When stratified by sex, the female Parkinson's disease group demonstrated significantly elevated concentrations of total PCBs and specifically congeners 138, 153, and 180 compared to controls, whereas PCB concentrations in males were not significantly different between control and Parkinson's disease groups. In a separate population of women (Nun Study) who had no clinical signs or symptoms of PD, elevated concentrations total PCB and congeners 138, 153 and 180 were also observed in post-mortem brain tissue exhibiting moderate nigral depigmentation compared to subjects with mild or no depigmentation. These quantitative data demonstrate an association between brain PCB levels and Parkinson's disease-related pathology. Furthermore, these data support epidemiological and laboratory studies reporting a link between PCB exposure and an increased risk for Parkinson's disease, including greater susceptibility of females. Copyright © 2012 Elsevier Inc. All rights reserved.

Association between polychlorinated biphenyls and Parkinson’s disease neuropathology

PubMed Central

Hatcher-Martin, Jaime M.; Gearing, Marla; Steenland, Kyle; Levey, Allan I.; Miller, Gary W.; Pennell, Kurt D.

2012-01-01

Polychlorinated biphenyls (PCBs) are synthetic chemicals primarily used as coolants and insulators in electrical equipment. Although banned for several decades, PCBs continue to exist in the environment because of their long half-life, continued presence in items produced before the ban, and poor disposal practices. Epidemiological and experimental studies have identified exposure to PCBs as a potential risk factor for Parkinson’s disease, perhaps more so in females. The objective of this work was to examine the association between PCB levels in post-mortem human brain tissue and the diagnosis of Parkinson’s disease, as well as the degree of nigral depigmentation. We also sought to determine if this association was more significant when patients were stratified by sex. Post-mortem brain samples from control patients and those diagnosed with Parkinson’s disease were obtained from the Emory University Brain Bank and from the Nun Study. Concentrations of eight prevalent PCB congeners were extracted from post-mortem brain tissue and analyzed using gas chromatography-mass spectrometry. PCB congeners 153 and 180 were significantly elevated in the brains of Parkinson’s disease patients. When stratified by sex, the female Parkinson’s disease group demonstrated significantly elevated concentrations of total PCBs and specifically congeners 138, 153, and 180 compared to controls, whereas PCB concentrations in males were not significantly different between control and Parkinson’s disease groups. In a separate population of women (Nun Study) who had no clinical signs or symptoms of PD, elevated concentrations total PCB and congeners 138, 153 and 180 were also observed in post-mortem brain tissue exhibiting moderate nigral depigmentation compared to subjects with mild or no depigmentation. These quantitative data demonstrate an association between brain PCB levels and Parkinson’s disease-related pathology. Furthermore, these data support epidemiological and laboratory studies reporting a link between PCB exposure and an increased risk for Parkinson’s disease, including greater susceptibility of females. PMID:22906799

Storm-Related Postmortem Damage to Skeletal Remains.

PubMed

Maijanen, Heli; Wilson-Taylor, Rebecca J; Jantz, Lee Meadows

2016-05-01

In April 2011, human skeletons were exposed to heavy storms at the outdoor Anthropology Research Facility (ARF) in Knoxville, Tennessee. Of the approximate 125 skeletons at the ARF in April 2011, 30 donations exhibited postmortem damage that could be attributed to the storms. At least 20 of the affected donations exhibit postmortem damage clearly associated with hailstones due to the oval shape and similar small size of the defects observed. The irregular shape and larger size of other defects may be a product of other falling objects (e.g., tree branches) associated with the storms. Storm-related damage was observed throughout the skeleton, with the most commonly damaged skeletal elements being the scapula and ilium, but more robust elements (i.e., femora and tibiae) also displayed characteristic features of hailstone damage. Thus, hailstone damage should be considered when forensic practitioners observe unusual postmortem damage in skeletal remains recovered from the outdoor context. © 2016 American Academy of Forensic Sciences.

Best-practices approach to determination of blood alcohol concentration (BAC) at specific time points: Combination of ante-mortem alcohol pharmacokinetic modeling and post-mortem alcohol generation and transport considerations.

PubMed

Cowan, Dallas M; Maskrey, Joshua R; Fung, Ernest S; Woods, Tyler A; Stabryla, Lisa M; Scott, Paul K; Finley, Brent L

2016-07-01

Alcohol concentrations in biological matrices offer information regarding an individual's intoxication level at a given time. In forensic cases, the alcohol concentration in the blood (BAC) at the time of death is sometimes used interchangeably with the BAC measured post-mortem, without consideration for alcohol concentration changes in the body after death. However, post-mortem factors must be taken into account for accurate forensic determination of BAC prior to death to avoid incorrect conclusions. The main objective of this work was to describe best practices for relating ante-mortem and post-mortem alcohol concentrations, using a combination of modeling, empirical data and other qualitative considerations. The Widmark modeling approach is a best practices method for superimposing multiple alcohol doses ingested at various times with alcohol elimination rate adjustments based on individual body factors. We combined the selected ante-mortem model with a suggestion for an approach used to roughly estimate changes in BAC post-mortem, and then analyzed the available data on post-mortem alcohol production in human bodies and potential markers for alcohol production through decomposition and putrefaction. Hypothetical cases provide best practice approaches as an example for determining alcohol concentration in biological matrices ante-mortem, as well as potential issues encountered with quantitative post-mortem approaches. This study provides information for standardizing BAC determination in forensic toxicology, while minimizing real world case uncertainties. Copyright © 2016 Elsevier Inc. All rights reserved.

Extensive unusual lesions on a large number of immersed human victims found to be from cookiecutter sharks (Isistius spp.): an examination of the Yemenia plane crash.

PubMed

Ribéreau-Gayon, Agathe; Rando, Carolyn; Schuliar, Yves; Chapenoire, Stéphane; Crema, Enrico R; Claes, Julien; Seret, Bernard; Maleret, Vincent; Morgan, Ruth M

2017-03-01

Accurate determination of the origin and timing of trauma is key in medicolegal investigations when the cause and manner of death are unknown. However, distinction between criminal and accidental perimortem trauma and postmortem modifications can be challenging when facing unidentified trauma. Postmortem examination of the immersed victims of the Yemenia airplane crash (Comoros, 2009) demonstrated the challenges in diagnosing extensive unusual circular lesions found on the corpses. The objective of this study was to identify the origin and timing of occurrence (peri- or postmortem) of the lesions.A retrospective multidisciplinary study using autopsy reports (n = 113) and postmortem digital photos (n = 3 579) was conducted. Of the 113 victims recovered from the crash, 62 (54.9 %) presented unusual lesions (n = 560) with a median number of 7 (IQR 3 ∼ 13) and a maximum of 27 per corpse. The majority of lesions were elliptic (58 %) and had an area smaller than 10 cm 2 (82.1 %). Some lesions (6.8 %) also showed clear tooth notches on their edges. These findings identified most of the lesions as consistent with postmortem bite marks from cookiecutter sharks (Isistius spp.). It suggests that cookiecutter sharks were important agents in the degradation of the corpses and thus introduced potential cognitive bias in the research of the cause and manner of death. A novel set of evidence-based identification criteria for cookiecutter bite marks on human bodies is developed to facilitate more accurate medicolegal diagnosis of cookiecutter bites.

Postmortem sperm procurement: a legal perspective.

PubMed

Kahan, S E; Seftel, A D; Resnick, M I

1999-06-01

Postmortem sperm procurement with subsequent artificial insemination has become a technically feasible method for posthumous conception. A variety of legal questions exist involving the rights and relationships of the deceased, his family and his issue. We addressed these questions and designed a workable protocol for postmortem sperm procurement. MEDLINE, WESTLAW and LEXIS medical literature, and case law searches were conducted. United States and international case law, United States (federal and state) statutes, Uniform Law Commissions Acts, and law review commentaries and articles were reviewed. While postmortem sperm procurement is being requested throughout the United States, no standard protocol or procedural guidelines have been established by federal or state statute. Furthermore, the courts have not yet addressed this specific scenario in reported case law. Statutes and case law do address related factual scenarios and issues, including property rights in human bodies, rules governing transplantation of human organs/body parts, rights of parties in in vivo sperm bank donations and responsibilities of parents to the conceptus of artificial insemination. A workable protocol can be established by analyzing case law and statutes addressing factually similar scenarios. Urologists must focus on the express intent of the decedent and limit any postmortem sperm retrieval to the specific requests made by the decedent. Decedent requests should be documented in writing. The decedent must be competent and of majority age. In the absence of decedent expressed affirmative directive calling for sperm retrieval, no other relative or guardian may authorize this retrieval. Issues regarding the legitimacy and inheritance rights of the conceptus will most consistently be addressed when explicitly provided for in the will of the decedent.

Brain, Craniofacial, and Dental Lesions of a Free-ranging Gray Wolf (Canis lupus) Implicated in a Human Attack in Minnesota, USA.

PubMed

Schwabenlander, Marc; Stepaniuk, Kevin; Carstensen, Michelle; Armién, Aníbal G

2016-01-01

We describe significant brain, craniofacial, and dental lesions in a free-ranging wolf (Canis lupus) involved in a human attack. On postmortem examination, the wolf presented asymmetric atrophy and bone remodeling affecting the mandible, incisive, maxilla, lacrimal, palatine, frontal, and ethmoid bones. There was an asymmetrical skeletal malocclusion and dental abnormalities including rotated, malpositioned, partially erupted teeth, and an odontogenic cyst associated with an unerupted canine tooth. Brain changes were bilateral loss and atrophy of extensive cortex regions including olfactory bulb, peduncles, and tract, and the frontal lobe. We highlight the relevance of a thorough postmortem examination of wildlife to elucidate disease-based abnormal behavior as the reason for human-animal conflict.

The Spectrum of Disease in Chronic Traumatic Encephalopathy

ERIC Educational Resources Information Center

McKee, Ann C.; Stein, Thor D.; Nowinski, Christopher J.; Stern, Robert A.; Daneshvar, Daniel H.; Alvarez, Victor E.; Lee, Hyo-Soon; Hall, Garth; Wojtowicz, Sydney M.; Baugh, Christine M.; Riley, David O.; Kubilus, Caroline A.; Cormier, Kerry A.; Jacobs, Matthew A.; Martin, Brett R.; Abraham, Carmela R.; Ikezu, Tsuneya; Reichard, Robert Ross; Wolozin, Benjamin L.; Budson, Andrew E.; Goldstein, Lee E.; Kowall, Neil W.; Cantu, Robert C.

2013-01-01

Chronic traumatic encephalopathy is a progressive tauopathy that occurs as a consequence of repetitive mild traumatic brain injury. We analysed post-mortem brains obtained from a cohort of 85 subjects with histories of repetitive mild traumatic brain injury and found evidence of chronic traumatic encephalopathy in 68 subjects: all males, ranging…

From The Cover: Microtransplantation of functional receptors and channels from the Alzheimer's brain to frog oocytes

NASA Astrophysics Data System (ADS)

Miledi, R.; Dueñas, Z.; Martinez-Torres, A.; Kawas, C. H.; Eusebi, F.

2004-02-01

About a decade ago, cell membranes from the electric organ of Torpedo and from the rat brain were transplanted to frog oocytes, which thus acquired functional Torpedo and rat neurotransmitter receptors. Nevertheless, the great potential that this method has for studying human diseases has remained virtually untapped. Here, we show that cell membranes from the postmortem brains of humans that suffered Alzheimer's disease can be microtransplanted to the plasma membrane of Xenopus oocytes. We show also that these postmortem membranes carry neurotransmitter receptors and voltage-operated channels that are still functional, even after they have been kept frozen for many years. This method provides a new and powerful approach to study directly the functional characteristics and structure of receptors, channels, and other membrane proteins of the Alzheimer's brain. This knowledge may help in understanding the basis of Alzheimer's disease and also help in developing new treatments. -aminobutyric acid receptors | sodium channels | calcium channels | postmortem brain

Aging is associated with altered inflammatory, arachidonic acid cascade and synaptic markers, influenced by epigenetic modifications, in the human frontal cortex

PubMed Central

Keleshian, Vasken L.; Modi, Hiren R.; Rapoport, Stanley I.; Rao, Jagadeesh S.

2013-01-01

Aging is a risk factor for Alzheimer’s disease (AD) and is associated with cognitive decline. However, underlying molecular mechanisms of brain aging are not clear. Recent studies suggest epigenetic influences on gene expression in AD, since DNA methylation levels influence protein and mRNA expression in postmortem AD brain. We hypothesized that some of these changes occur with normal aging. To test this hypothesis, we measured markers of the arachidonic acid (AA) cascade, neuroinflammation, pro- and anti-apoptosis factors, and gene specific epigenetic modifications in postmortem frontal cortex from nine middle-aged (41 ± 1 (SEM) years) and ten aged subjects (70 ± 3 years). The aged compared with middle-aged brain showed elevated levels of neuroinflammatory and AA cascade markers, altered pro and anti-apoptosis factors and loss of synaptophysin. Some of these changes correlated with promoter hypermethylation of BDNF, CREB, and synaptophysin and hypomethylation of BAX. These molecular alterations in aging are different from or more subtle than changes associated with AD pathology. The degree to which they are related to changes in cognition or behavior during normal aging remains to be evaluated. PMID:23336521

Conceptual modeling of postmortem evaluation findings to describe dairy cow deaths.

PubMed

McConnel, C S; Garry, F B; Hill, A E; Lombard, J E; Gould, D H

2010-01-01

Dairy cow mortality levels in the United States are excessive and increasing over time. To better define cause and effect and combat rising mortality, clearer definitions of the reasons that cows die need to be acquired through thorough necropsy-based postmortem evaluations. The current study focused on organizing information generated from postmortem evaluations into a monitoring system that is based on the fundamentals of conceptual modeling and that will potentially be translatable into on-farm relational databases. This observational study was conducted on 3 high-producing, commercial dairies in northern Colorado. Throughout the study period a thorough postmortem evaluation was performed by veterinarians on cows that died on each dairy. Postmortem data included necropsy findings, life-history features (e.g., birth date, lactation number, lactational and reproductive status), clinical history and treatments, and pertinent aspects of operational management that were subject to change and considered integral to the poor outcome. During this study, 174 postmortem evaluations were performed. Postmortem evaluation results were conceptually modeled to view each death within the context of the web of factors influencing the dairy and the cow. Categories were formulated describing mortality in terms of functional characteristics potentially amenable to easy performance evaluation, management oversight, and research. In total, 21 death categories with 7 category themes were created. Themes included specific disease processes with variable etiologies, failure of disease recognition or treatment, traumatic events, multifactorial failures linked to transition or negative energy balance issues, problems with feed management, miscellaneous events not amenable to prevention or treatment, and undetermined causes. Although postmortem evaluations provide the relevant information necessary for framing a cow's death, a restructuring of on-farm databases is needed to integrate this level of detail into useful monitoring systems. Individual operations can focus on combating mortality through the use of employee training related to postmortem evaluations, detailed forms for capturing necropsy particulars and other relevant information related to deaths, and standardized nomenclature and categorization schemes. As much as anything, the simple act of recognizing mortality as a problem might be the most fundamental step toward controlling its progression. Copyright 2010 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Differential Decomposition Among Pig, Rabbit, and Human Remains.

PubMed

Dautartas, Angela; Kenyhercz, Michael W; Vidoli, Giovanna M; Meadows Jantz, Lee; Mundorff, Amy; Steadman, Dawnie Wolfe

2018-03-30

While nonhuman animal remains are often utilized in forensic research to develop methods to estimate the postmortem interval, systematic studies that directly validate animals as proxies for human decomposition are lacking. The current project compared decomposition rates among pigs, rabbits, and humans at the University of Tennessee's Anthropology Research Facility across three seasonal trials that spanned nearly 2 years. The Total Body Score (TBS) method was applied to quantify decomposition changes and calculate the postmortem interval (PMI) in accumulated degree days (ADD). Decomposition trajectories were analyzed by comparing the estimated and actual ADD for each seasonal trial and by fuzzy cluster analysis. The cluster analysis demonstrated that the rabbits formed one group while pigs and humans, although more similar to each other than either to rabbits, still showed important differences in decomposition patterns. The decomposition trends show that neither nonhuman model captured the pattern, rate, and variability of human decomposition. © 2018 American Academy of Forensic Sciences.

A Method for Whole Brain Ex Vivo Magnetic Resonance Imaging with Minimal Susceptibility Artifacts

PubMed Central

Shatil, Anwar S.; Matsuda, Kant M.; Figley, Chase R.

2016-01-01

Magnetic resonance imaging (MRI) is a non-destructive technique that is capable of localizing pathologies and assessing other anatomical features (e.g., tissue volume, microstructure, and white matter connectivity) in postmortem, ex vivo human brains. However, when brains are removed from the skull and cerebrospinal fluid (i.e., their normal in vivo magnetic environment), air bubbles and air–tissue interfaces typically cause magnetic susceptibility artifacts that severely degrade the quality of ex vivo MRI data. In this report, we describe a relatively simple and cost-effective experimental setup for acquiring artifact-free ex vivo brain images using a clinical MRI system with standard hardware. In particular, we outline the necessary steps, from collecting an ex vivo human brain to the MRI scanner setup, and have also described changing the formalin (as might be necessary in longitudinal postmortem studies). Finally, we share some representative ex vivo MRI images that have been acquired using the proposed setup in order to demonstrate the efficacy of this approach. We hope that this protocol will provide both clinicians and researchers with a straight-forward and cost-effective solution for acquiring ex vivo MRI data from whole postmortem human brains. PMID:27965620

Lessons learned about [F-18]-AV-1451 off-target binding from an autopsy-confirmed Parkinson's case.

PubMed

Marquié, Marta; Verwer, Eline E; Meltzer, Avery C; Kim, Sally Ji Who; Agüero, Cinthya; Gonzalez, Jose; Makaretz, Sara J; Siao Tick Chong, Michael; Ramanan, Prianca; Amaral, Ana C; Normandin, Marc D; Vanderburg, Charles R; Gomperts, Stephen N; Johnson, Keith A; Frosch, Matthew P; Gómez-Isla, Teresa

2017-10-19

[F-18]-AV-1451 is a novel positron emission tomography (PET) tracer with high affinity to neurofibrillary tau pathology in Alzheimer's disease (AD). PET studies have shown increased tracer retention in patients clinically diagnosed with dementia of AD type and mild cognitive impairment in regions that are known to contain tau lesions. In vivo uptake has also consistently been observed in midbrain, basal ganglia and choroid plexus in elderly individuals regardless of their clinical diagnosis, including clinically normal whose brains are not expected to harbor tau pathology in those areas. We and others have shown that [F-18]-AV-1451 exhibits off-target binding to neuromelanin, melanin and blood products on postmortem material; and this is important for the correct interpretation of PET images. In the present study, we further investigated [F-18]-AV-1451 off-target binding in the first autopsy-confirmed Parkinson's disease (PD) subject who underwent antemortem PET imaging. The PET scan showed elevated [F-18]-AV-1451 retention predominantly in inferior temporal cortex, basal ganglia, midbrain and choroid plexus. Neuropathologic examination confirmed the PD diagnosis. Phosphor screen and high resolution autoradiography failed to show detectable [F-18]-AV-1451 binding in multiple brain regions examined with the exception of neuromelanin-containing neurons in the substantia nigra, leptomeningeal melanocytes adjacent to ventricles and midbrain, and microhemorrhages in the occipital cortex (all reflecting off-target binding), in addition to incidental age-related neurofibrillary tangles in the entorhinal cortex. Additional legacy postmortem brain samples containing basal ganglia, choroid plexus, and parenchymal hemorrhages from 20 subjects with various neuropathologic diagnoses were also included in the autoradiography experiments to better understand what [F-18]-AV-1451 in vivo positivity in those regions means. No detectable [F-18]-AV-1451 autoradiographic binding was present in the basal ganglia of the PD case or any of the other subjects. Off-target binding in postmortem choroid plexus samples was only observed in subjects harboring leptomeningeal melanocytes within the choroidal stroma. Off-target binding to parenchymal hemorrhages was noticed in postmortem material from subjects with cerebral amyloid angiopathy. The imaging-postmortem correlation analysis in this PD case reinforces the notion that [F-18]-AV-1451 has strong affinity for neurofibrillary tau pathology but also exhibits off-target binding to neuromelanin, melanin and blood components. The robust off-target in vivo retention in basal ganglia and choroid plexus, in the absence of tau deposits, meningeal melanocytes or any other identifiable binding substrate by autoradiography in the PD case reported here, also suggests that the PET signal in those regions may be influenced, at least in part, by biological or technical factors that occur in vivo and are not captured by autoradiography.

Postmortem changes in the neuroanatomical characteristics of the primate brain: the hippocampal formation

PubMed Central

Lavenex, Pierre; Lavenex, Pamela Banta; Bennett, Jeffrey L.; Amaral, David G.

2009-01-01

Comparative studies of the structural organization of the brain are fundamental to our understanding of human brain function. However, whereas brains of experimental animals are fixed by perfusion of a fixative through the vasculature, human or ape brains are fixed by immersion after varying postmortem intervals. Although differential treatments might affect the fundamental characteristics of the tissue, this question has not been evaluated empirically in primate brains. Monkey brains were either perfused, or acquired after varying postmortem intervals before immersion-fixation in 4% paraformaldehyde. We found that the fixation method affected the neuroanatomical characteristics of the monkey hippocampal formation. Soma size was smaller in Nissl-stained, immersion-fixed tissue, although overall brain volume was larger, as compared to perfusion-fixed tissue. Non-phosphorylated high-molecular-weight neurofilament immunoreactivity was lower in CA3 pyramidal neurons, dentate mossy cells and the entorhinal cortex, whereas it was higher in the mossy fiber pathway in immersion-fixed tissue. Serotonin-immunoreactive fibers were well-stained in perfused tissue but were undetectable in immersion-fixed tissue. Although regional immunoreactivity patterns for calcium-binding proteins were not affected, intracellular staining degraded with increasing postmortem intervals. Somatostatin-immunoreactive clusters of large axonal varicosities, previously reported only in humans, were observed in immersion-fixed monkey tissue. In addition, calretinin-immunoreactive multipolar neurons, previously observed only in rodents, were found in the rostral dentate gyrus in both perfused and immersion-fixed brains. In conclusion, comparative studies of the brain must evaluate the effects of fixation on the staining pattern of each marker in every structure of interest before drawing conclusions about species differences. PMID:18972553

Postmortem changes in the neuroanatomical characteristics of the primate brain: hippocampal formation.

PubMed

Lavenex, Pierre; Lavenex, Pamela Banta; Bennett, Jeffrey L; Amaral, David G

2009-01-01

Comparative studies of the structural organization of the brain are fundamental to our understanding of human brain function. However, whereas brains of experimental animals are fixed by perfusion of a fixative through the vasculature, human or ape brains are fixed by immersion after varying postmortem intervals. Although differential treatments might affect the fundamental characteristics of the tissue, this question has not been evaluated empirically in primate brains. Monkey brains were either perfused or acquired after varying postmortem intervals before immersion-fixation in 4% paraformaldehyde. We found that the fixation method affected the neuroanatomical characteristics of the monkey hippocampal formation. Soma size was smaller in Nissl-stained, immersion-fixed tissue, although overall brain volume was larger as compared to perfusion-fixed tissue. Nonphosphorylated high-molecular-weight neurofilament immunoreactivity was lower in CA3 pyramidal neurons, dentate mossy cells, and the entorhinal cortex, whereas it was higher in the mossy fiber pathway in immersion-fixed tissue. Serotonin-immunoreactive fibers were well stained in perfused tissue but were undetectable in immersion-fixed tissue. Although regional immunoreactivity patterns for calcium-binding proteins were not affected, intracellular staining degraded with increasing postmortem intervals. Somatostatin-immunoreactive clusters of large axonal varicosities, previously reported only in humans, were observed in immersion-fixed monkey tissue. In addition, calretinin-immunoreactive multipolar neurons, previously observed only in rodents, were found in the rostral dentate gyrus in both perfused and immersion-fixed brains. In conclusion, comparative studies of the brain must evaluate the effects of fixation on the staining pattern of each marker in every structure of interest before drawing conclusions about species differences.

Cardiac Implantable Electronic Device Interrogation at Forensic Autopsy: An Underestimated Resource?

PubMed

Lacour, Philipp; Buschmann, Claas; Storm, Christian; Nee, Jens; Parwani, Abdul Shokor; Huemer, Martin; Attanasio, Philipp; Boldt, Leif-Hendrik; Rauch, Geraldine; Kucher, Andreas; Pieske, Burkert; Haverkamp, Wilhelm; Blaschke, Florian

2018-06-19

Postmortem interrogations of cardiac implantable electronic devices (CIEDs), recommended at autopsy in suspected cases of sudden cardiac death, are rarely performed, and data on systematic postmortem CIED analysis in the forensic pathology are missing. The aim of the study was to determine whether nonselective postmortem CIED interrogations and data analysis are useful to the forensic pathologist to determine the cause, mechanism, and time of death and to detect potential CIED-related safety issues. From February 2012 to April 2017, all autopsy subjects in the department of forensic medicine at the University Hospital Charité who had a CIED underwent device removal and interrogation. Over the study period, 5368 autopsies were performed. One hundred fifty subjects had in total 151 CIEDs, including 109 pacemakers, 35 defibrillators, and 7 implantable loop recorders. In 40 cases (26.7%) time of death and in 51 cases (34.0%) cause of death could not be determined by forensic autopsy. Of these, CIED interrogation facilitated the determination of time of death in 70.0% of the cases and clarified the cause of death in 60.8%. Device concerns were identified in 9 cases (6.0%), including 3 hardware, 4 programming, and 2 algorithm issues. One CIED was submitted to the manufacturer for a detailed technical analysis. Our data demonstrate the necessity of systematic postmortem CIED interrogation in forensic medicine to determine the cause and timing of death more accurately. In addition, CIED analysis is an important tool to detect potential CIED-related safety issues. © 2018 American Heart Association, Inc.

[Determination of death and post-mortem examination on the high seas].

PubMed

Buschmann, Claas T; Tsokos, Michael

2009-01-01

Usually death has to be determined by a physician. Deaths on board of ocean-going vessels confront the crew with special challenges, as on the high seas--especially in the container and cargo ship business--often no physician will be available and death has to be determined by medical laymen such as the captain or the medical officer. To document the determination of death, a "Provisional Certificate of Death on the High Seas" is presented. Moreover, an algorithm "Provisional Post-Mortem Examination on the High Seas" is presented to document the results and the practical performance of the external post-mortem examination by medical laymen on a ship. With the help of concrete procedural instructions medical laymen on board of sea-going vessels are to be enabled to determine the death of a human being beyond doubt, to perform a preliminary external post-mortem examination and to store the corpse according to forensic requirements until the ship reaches a port and the body is delivered to the harbour physician.

Metabotropic glutamate receptor 5, and its trafficking molecules Norbin and Tamalin, are increased in the CA1 hippocampal region of subjects with schizophrenia.

PubMed

Matosin, Natalie; Fernandez-Enright, Francesca; Lum, Jeremy S; Andrews, Jessica L; Engel, Martin; Huang, Xu-Feng; Newell, Kelly A

2015-08-01

Metabotropic glutamate receptor 5 (mGluR5) is involved in hippocampal-dependent learning and memory, which are processes disrupted in schizophrenia. Recent evidence from human genetic and animal studies suggests that the regulation of mGluR5, including its interaction with trafficking molecules, may be altered in the disorder. However there have been no investigations of hippocampal mGluR5 or mGluR5 trafficking molecules in the postmortem schizophrenia brain to confirm this. In the present study, we investigated whether protein expression of mGluR5, as well as Norbin and Tamalin (modulators of mGluR5 signalling and trafficking), might be altered in the schizophrenia brain, using postmortem samples from the hippocampal CA1 region of schizophrenia subjects and matched controls (n=20/group). Protein levels of mGluR5 (total: 42%, p<0.001; monomer: 25%, p=0.011; dimer: 52%, p<0.001) and mGluR5 trafficking molecules (Norbin: 47%, p<0.001; Tamalin: 34%, p=0.009) were significantly higher in schizophrenia subjects compared to controls. To determine any influence of antipsychotic drug treatment, all proteins were also correlated with lifetime chlorpromazine equivalents in patients, and separately measured in the hippocampus of rats exposed to haloperidol or olanzapine treatment. mGluR5 was negatively correlated with lifetime antipsychotic drug exposure in schizophrenia patients, suggesting antipsychotic drugs could reduce mGluR5 protein in schizophrenia subjects. In contrast, mGluR5 and mGluR5 trafficking molecules were not altered in the hippocampus of antipsychotic drug treated rats. This investigation provides strong support for the hypothesis that mGluR5 is involved in the pathology of schizophrenia, and that alterations to mGluR5 trafficking might contribute to the hippocampal-dependent cognitive dysfunctions associated with this disorder. Copyright © 2015 Elsevier B.V. All rights reserved.

Postmortem redistribution of Δ9-tetrahydrocannabinol (THC), 11-hydroxy-THC (11-OH-THC), and 11-nor-9-carboxy-THC (THCCOOH)

PubMed Central

Holland, Michael G.; Schwope, David M.; Stoppacher, Robert; Gillen, Shane B.; Huestis, Marilyn A.

2012-01-01

Introduction Postmortem redistribution (PMR), a well-described phenomenon in forensic toxicology for certain drugs, can result in increased central blood concentrations relative to peripheral blood concentrations. Δ9-tetrahydrocannabinol (THC), the primary psychoactive component in cannabis or marijuana, is the illicit substance most commonly implicated in driving under the influence of drugs (DUID) cases and fatally-injured drivers. No investigation of PMR of THC in human blood has been reported to date. Methods Matched heart and iliac postmortem blood specimens were collected from 19 medical examiner cases (16 Males, 3 Females) with positive cannabinoid urine immunoassay screens. THC, its equipotent metabolite 11-hydroxy-THC (11-OH-THC) and non-psychoactive metabolite 11-nor-9-carboxy-THC (THCCOOH) were quantified by two-dimensional gas chromatography-mass spectrometry with cryofocusing, with 0.5 ng/mL limits of quantification (LOQ) for all analytes. Results 10 cases had quantifiable THC and 11-OH-THC; THCCOOH was present in all 19. Median (range) heart:iliac blood ratios were 1.5 for THC (range: 0.3–3.1); 1.6 for 11-OH-THC (range: 0.3–2.7); and 1.8 for THCCOOH (range: 0.5–3.0). Discussion Cannabinoids, in general, exhibited a mean and median central: peripheral (C: P) concentration ratio of less than 2 following death. A trend was observed for greater PMR with increasing postmortem interval between death and sampling. To our knowledge, these are the first data on THC PMR in humans, providing important scientific data to aid in the interpretation of postmortem cannabinoid concentrations in medico-legal investigations. PMID:21764230

Integrative mouse and human mRNA studies using WGCNA nominates novel candidate genes involved in the pathogenesis of major depressive disorder.

PubMed

Malki, Karim; Tosto, Maria Grazia; Jumabhoy, Irfan; Lourdusamy, Anbarasu; Sluyter, Frans; Craig, Ian; Uher, Rudolf; McGuffin, Peter; Schalkwyk, Leonard C

2013-12-01

This study aims to identify novel genes associated with major depressive disorder and pharmacological treatment response using animal and human mRNA studies. Weighted gene coexpression network analysis was used to uncover genes associated with stress factors in mice and to inform mRNA probe set selection in a post-mortem study of depression. A total of 171 genes were found to be differentially regulated in response to both early and late stress protocols in a mouse study. Ten human genes, orthologous to mouse genes differentially expressed by stress, were also found to be dysregulated in depressed cases in a human post-mortem brain study from the Stanley Foundation Brain Collection. Several novel genes associated with depression were uncovered, including NOVA1 and USP9X. Moreover, we found further evidence in support of hippocampal neurogenesis and peripheral inflammation in major depressive disorder.

Autoradiographic analysis of alpha 1-noradrenergic receptors in the human brain postmortem. Effect of suicide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gross-Isseroff, R.; Dillon, K.A.; Fieldust, S.J.

In vitro quantitative autoradiography of alpha 1-noradrenergic receptors, using tritiated prazosin as a ligand, was performed on 24 human brains postmortem. Twelve brains were obtained from suicide victims and 12 from matched controls. We found significant lower binding to alpha 1 receptors in several brain regions of the suicide group as compared with matched controls. This decrease in receptor density was evident in portions of the prefrontal cortex, as well as the temporal cortex and in the caudate nucleus. Age, sex, presence of alcohol, and time of death to autopsy did not affect prazosin binding, in our sample, as measuredmore » by autoradiography.« less

The Elusive Universal Post-Mortem Interval Formula

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vass, Arpad Alexander

The following manuscript details our initial attempt at developing universal post-mortem interval formulas describing human decomposition. These formulas are empirically derived from data collected over the last 20 years from the University of Tennessee's Anthropology Research Facility, in Knoxville, Tennessee, USA. Two formulas were developed (surface decomposition and burial decomposition) based on temperature, moisture, and the partial pressure of oxygen, as being three of the four primary drivers for human decomposition. It is hoped that worldwide application of these formulas to environments and situations not readily studied in Tennessee will result in interdisciplinary cooperation between scientists and law enforcement personnelmore » that will allow for future refinements of these models leading to increased accuracy.« less

The Effect of Body Mass on Outdoor Adult Human Decomposition.

PubMed

Roberts, Lindsey G; Spencer, Jessica R; Dabbs, Gretchen R

2017-09-01

Forensic taphonomy explores factors impacting human decomposition. This study investigated the effect of body mass on the rate and pattern of adult human decomposition. Nine males and three females aged 49-95 years ranging in mass from 73 to 159 kg who were donated to the Complex for Forensic Anthropology Research between December 2012 and September 2015 were included in this study. Kelvin accumulated degree days (KADD) were used to assess the thermal energy required for subjects to reach several total body score (TBS) thresholds: early decomposition (TBS ≥6.0), TBS ≥12.5, advanced decomposition (TBS ≥19.0), TBS ≥23.0, and skeletonization (TBS ≥27.0). Results indicate no significant correlation between body mass and KADD at any TBS threshold. Body mass accounted for up to 24.0% of variation in decomposition rate depending on stage, and minor differences in decomposition pattern were observed. Body mass likely has a minimal impact on postmortem interval estimation. © 2017 American Academy of Forensic Sciences.

Characterisation of the metabolome of ocular tissues and post-mortem changes in the rat retina.

PubMed

Tan, Shi Z; Mullard, Graham; Hollywood, Katherine A; Dunn, Warwick B; Bishop, Paul N

2016-08-01

Time-dependent post-mortem biochemical changes have been demonstrated in donor cornea and vitreous, but there have been no published studies to date that objectively measure post-mortem changes in the retinal metabolome over time. The aim of the study was firstly, to investigate post-mortem, time-dependent changes in the rat retinal metabolome and secondly, to compare the metabolite composition of healthy rat ocular tissues. To study post-mortem changes in the rat retinal metabolome, globes were enucleated and stored at 4 °C and sampled at 0, 2, 4, 8, 24 and 48 h post-mortem. To study the metabolite composition of rat ocular tissues, eyes were dissected immediately after culling to isolate the cornea, lens, vitreous and retina, prior to storing at -80 °C. Tissue extracts were subjected to Gas Chromatograph Mass Spectrometry (GC-MS) and Ultra High Performance Liquid Chromatography Mass Spectrometry (UHPLC-MS). Generally, the metabolic composition of the retina was stable for 8 h post-mortem when eyes were stored at 4 °C, but showed increasing changes thereafter. However, some more rapid changes were observed such as increases in TCA cycle metabolites after 2 h post-mortem, whereas some metabolites such as fatty acids only showed decreases in concentration from 24 h. A total of 42 metabolites were identified across the ocular tissues by GC-MS (MSI level 1) and 2782 metabolites were annotated by UHPLC-MS (MSI level 2) according to MSI reporting standards. Many of the metabolites detected were common to all of the tissues but some metabolites showed partitioning between different ocular structures with 655, 297, 93 and 13 metabolites being uniquely detected in the retina, lens, cornea and vitreous respectively. Only a small percentage (1.6%) of metabolites found in the vitreous were only detected in the retina and not other tissues. In conclusion, mass spectrometry-based techniques have been used for the first time to compare the metabolic composition of different ocular tissues. The metabolite composition of the retina stored at 4 °C post-mortem is mostly stable for at least 8 h. Copyright © 2016 Elsevier Ltd. All rights reserved.

A Comparative Genomic Study in Schizophrenic and in Bipolar Disorder Patients, Based on Microarray Expression Profiling Meta-Analysis

PubMed Central

Logotheti, Marianthi; Papadodima, Olga; Venizelos, Nikolaos; Chatziioannou, Aristotelis; Kolisis, Fragiskos

2013-01-01

Schizophrenia affecting almost 1% and bipolar disorder affecting almost 3%–5% of the global population constitute two severe mental disorders. The catecholaminergic and the serotonergic pathways have been proved to play an important role in the development of schizophrenia, bipolar disorder, and other related psychiatric disorders. The aim of the study was to perform and interpret the results of a comparative genomic profiling study in schizophrenic patients as well as in healthy controls and in patients with bipolar disorder and try to relate and integrate our results with an aberrant amino acid transport through cell membranes. In particular we have focused on genes and mechanisms involved in amino acid transport through cell membranes from whole genome expression profiling data. We performed bioinformatic analysis on raw data derived from four different published studies. In two studies postmortem samples from prefrontal cortices, derived from patients with bipolar disorder, schizophrenia, and control subjects, have been used. In another study we used samples from postmortem orbitofrontal cortex of bipolar subjects while the final study was performed based on raw data from a gene expression profiling dataset in the postmortem superior temporal cortex of schizophrenics. The data were downloaded from NCBI's GEO datasets. PMID:23554570

Towards Ultra-High Resolution Fibre Tract Mapping of the Human Brain – Registration of Polarised Light Images and Reorientation of Fibre Vectors

PubMed Central

Palm, Christoph; Axer, Markus; Gräßel, David; Dammers, Jürgen; Lindemeyer, Johannes; Zilles, Karl; Pietrzyk, Uwe; Amunts, Katrin

2009-01-01

Polarised light imaging (PLI) utilises the birefringence of the myelin sheaths in order to visualise the orientation of nerve fibres in microtome sections of adult human post-mortem brains at ultra-high spatial resolution. The preparation of post-mortem brains for PLI involves fixation, freezing and cutting into 100-μm-thick sections. Hence, geometrical distortions of histological sections are inevitable and have to be removed for 3D reconstruction and subsequent fibre tracking. We here present a processing pipeline for 3D reconstruction of these sections using PLI derived multimodal images of post-mortem brains. Blockface images of the brains were obtained during cutting; they serve as reference data for alignment and elimination of distortion artefacts. In addition to the spatial image transformation, fibre orientation vectors were reoriented using the transformation fields, which consider both affine and subsequent non-linear registration. The application of this registration and reorientation approach results in a smooth fibre vector field, which reflects brain morphology. PLI combined with 3D reconstruction and fibre tracking is a powerful tool for human brain mapping. It can also serve as an independent method for evaluating in vivo fibre tractography. PMID:20461231

Neuronal Type-Specific Gene Expression Profiling and Laser-Capture Microdissection

PubMed Central

Pietersen, Charmaine Y.; Lim, Maribel P.; Macey, Laurel; Woo, Tsung-Ung W.; Sonntag, Kai C.

2014-01-01

The human brain is an exceptionally heterogeneous structure. In order to gain insight into the neurobiological basis of neural circuit disturbances in various neurologic or psychiatric diseases, it is often important to define the molecular cascades that are associated with these disturbances in a neuronal type-specific manner. This can be achieved by the use of laser microdissection, in combination with molecular techniques such as gene expression profiling. To identify neurons in human postmortem brain tissue, one can use the inherent properties of the neuron, such as pigmentation and morphology or its structural composition through immunohistochemistry (IHC). Here, we describe the isolation of homogeneous neuronal cells and high-quality RNA from human postmortem brain material using a combination of rapid IHC, Nissl staining, or simple morphology with Laser-Capture Microdissection (LCM) or Laser Microdissection (LMD). PMID:21761317

Neuronal type-specific gene expression profiling and laser-capture microdissection.

PubMed

Pietersen, Charmaine Y; Lim, Maribel P; Macey, Laurel; Woo, Tsung-Ung W; Sonntag, Kai C

2011-01-01

The human brain is an exceptionally heterogeneous structure. In order to gain insight into the neurobiological basis of neural circuit disturbances in various neurologic or psychiatric diseases, it is often important to define the molecular cascades that are associated with these disturbances in a neuronal type-specific manner. This can be achieved by the use of laser microdissection, in combination with molecular techniques such as gene expression profiling. To identify neurons in human postmortem brain tissue, one can use the inherent properties of the neuron, such as pigmentation and morphology or its structural composition through immunohistochemistry (IHC). Here, we describe the isolation of homogeneous neuronal cells and high-quality RNA from human postmortem brain material using a combination of rapid IHC, Nissl staining, or simple morphology with Laser-Capture Microdissection (LCM) or Laser Microdissection (LMD).

Ethereal presences in holography and photography

NASA Astrophysics Data System (ADS)

Richardson, M.; Byrne, Kay

2007-02-01

This paper examines the concept of the 'Presence of Absence' in post-mortem photography and holography, drawing upon both historical and lesser-known images as reference. To create a photographic negative one needs the presence of light to expose the light sensitive surface, be it glass, a polished plate or plastic. A hologram may also be created when a coherent light source, for example from a Laser, travels through a light sensitive material and falls upon the subject to be recorded. A holograph however, retains the optical qualities of both phase and amplitude, the memory of light. Both mediums recall, as it were, 'now absent moments', and confronts us with what is 'not there' as much as 'what is'. This paper examines the exploration of absence and presence in post-mortem photography and holography and it's a richly visceral visual language. A photonic syntax can interpret death as an elegant yet horrific aesthetic, the photograph may be beautify screened and yet obscene in its content. In essence one can be a voyeur, experiencing a mere visual whisper of the true nature of the subject. Our Victorian forefathers explored postmortem photography as an object of mourning, and at the close of the nineteenth century when Jack the Ripper had the inhabitants of White Chapel in a grip of fear, photography made its mark as a documentation of violent crime. Today, within contemporary photography, death is now presented within the confines of the 'Art Gallery', as a sensual, and at times, sensationalised art form. In exploring post-mortem imagery, both in holography and conventional photography, absence presents an aspect of death as startling in its unanimated form and detailed in its finite examination of mortality.

Low μ-Opioid Receptor Status in Alcohol Dependence Identified by Combined Positron Emission Tomography and Post-Mortem Brain Analysis

PubMed Central

Hermann, Derik; Hirth, Natalie; Reimold, Matthias; Batra, Anil; Smolka, Michael N; Hoffmann, Sabine; Kiefer, Falk; Noori, Hamid R; Sommer, Wolfgang H; Reischl, Gerald; la Fougère, Christian; Mann, Karl; Spanagel, Rainer; Hansson, Anita C

2017-01-01

Blockade of the μ-opioid receptor (MOR) by naltrexone reduces relapse risk in a subpopulation of alcohol-dependent patients. Previous positron-emission-tomography (PET) studies using the MOR ligand [11C]carfentanil have found increased MOR availability in abstinent alcoholics, which may reflect either increased MOR expression or lower endogenous ligand concentration. To differentiate between both effects, we investigated two cohorts of alcoholic subjects using either post-mortem or clinical PET analysis. Post-mortem brain tissue of alcohol-dependent subjects and controls (N=43/group) was quantitatively analyzed for MOR ([3H]DAMGO)-binding sites and OPRM1 mRNA in striatal regions. [11C]carfentanil PET was performed in detoxified, medication free alcohol-dependent patients (N=38), followed by a randomized controlled study of naltrexone versus placebo and follow-up for 1 year (clinical trial number: NCT00317031). Because the functional OPRM1 variant rs1799971:A>G affects the ligand binding, allele carrier status was considered in the analyses. MOR-binding sites were reduced by 23–51% in post-mortem striatal tissue of alcoholics. In the PET study, a significant interaction of OPRM1 genotype, binding potential (BPND) for [11C]carfentanil in the ventral striatum, and relapse risk was found. Particularly in G-allele carriers, lower striatal BPND was associated with a higher relapse risk. Interestingly, this effect was more pronounced in the naltrexone treatment group. Reduced MOR is interpreted as a neuroadaptation to an alcohol-induced release of endogenous ligands in patients with severe alcoholism. Low MOR availability may explain the ineffectiveness of naltrexone treatment in this subpopulation. Finally, low MOR-binding sites are proposed as a molecular marker for a negative disease course. PMID:27510425

Differential methylation at the RELN gene promoter in temporal cortex from autistic and typically developing post-puberal subjects.

PubMed

Lintas, Carla; Sacco, Roberto; Persico, Antonio M

2016-01-01

Reelin plays a pivotal role in neurodevelopment and in post-natal synaptic plasticity and has been implicated in the pathogenesis of autism spectrum disorder (ASD). The reelin (RELN) gene expression is significantly decreased in ASD, both in the brain and peripherally. Methylation at the RELN gene promoter is largely triggered at puberty, and hypermethylation has been found in post-mortem brains of schizophrenic and bipolar patients. In this study, we assessed RELN gene methylation status in post-mortem temporocortical tissue samples (BA41/42 or 22) of six pairs of post-puberal individuals with ASD and typically developing subjects, matched for sex (male:female, M:F = 5:1), age, and post-mortem interval. ASD patients display a significantly higher number of methylated CpG islands and heavier methylation in the 5' region of the RELN gene promoter, spanning from -458 to -223 bp, whereas controls have more methylated CpG positions and greater extent of methylation at the 3' promoter region, spanning from -222 to +1 bp. The most upstream promoter region (-458 to -364 bp) is methylated only in ASD brains, while the most downstream region (-131 to +1 bp) is methylated exclusively in control brains. Within this general framework, three different methylation patterns are discernible, each correlated with different extents of reduction in reelin gene expression among ASD individuals compared to controls. The methylation pattern is different in ASD and control post-mortem brains. ASD-specific CpG positions, located in the most upstream gene promoter region, may exert a functional role potentially conferring ASD risk by blunting RELN gene expression.

S-acylation of SOD1, CCS, and a stable SOD1-CCS heterodimer in human spinal cords from ALS and non-ALS subjects.

PubMed

Antinone, Sarah E; Ghadge, Ghanashyam D; Ostrow, Lyle W; Roos, Raymond P; Green, William N

2017-01-25

Previously, we found that human Cu, Zn-superoxide dismutase (SOD1) is S-acylated (palmitoylated) in vitro and in amyotrophic lateral sclerosis (ALS) mouse models, and that S-acylation increased for ALS-causing SOD1 mutants relative to wild type. Here, we use the acyl resin-assisted capture (acyl-RAC) assay to demonstrate S-acylation of SOD1 in human post-mortem spinal cord homogenates from ALS and non-ALS subjects. Acyl-RAC further revealed that endogenous copper chaperone for SOD1 (CCS) is S-acylated in both human and mouse spinal cords, and in vitro in HEK293 cells. SOD1 and CCS formed a highly stable heterodimer in human spinal cord homogenates that was resistant to dissociation by boiling, denaturants, or reducing agents and was not observed in vitro unless both SOD1 and CCS were overexpressed. Cysteine mutations that attenuate SOD1 maturation prevented the SOD1-CCS heterodimer formation. The degree of S-acylation was highest for SOD1-CCS heterodimers, intermediate for CCS monomers, and lowest for SOD1 monomers. Given that S-acylation facilitates anchoring of soluble proteins to cell membranes, our findings suggest that S-acylation and membrane localization may play an important role in CCS-mediated SOD1 maturation. Furthermore, the highly stable S-acylated SOD1-CCS heterodimer may serve as a long-lived maturation intermediate in human spinal cord.

S-acylation of SOD1, CCS, and a stable SOD1-CCS heterodimer in human spinal cords from ALS and non-ALS subjects

PubMed Central

Antinone, Sarah E.; Ghadge, Ghanashyam D.; Ostrow, Lyle W.; Roos, Raymond P.; Green, William N.

2017-01-01

Previously, we found that human Cu, Zn-superoxide dismutase (SOD1) is S-acylated (palmitoylated) in vitro and in amyotrophic lateral sclerosis (ALS) mouse models, and that S-acylation increased for ALS-causing SOD1 mutants relative to wild type. Here, we use the acyl resin-assisted capture (acyl-RAC) assay to demonstrate S-acylation of SOD1 in human post-mortem spinal cord homogenates from ALS and non-ALS subjects. Acyl-RAC further revealed that endogenous copper chaperone for SOD1 (CCS) is S-acylated in both human and mouse spinal cords, and in vitro in HEK293 cells. SOD1 and CCS formed a highly stable heterodimer in human spinal cord homogenates that was resistant to dissociation by boiling, denaturants, or reducing agents and was not observed in vitro unless both SOD1 and CCS were overexpressed. Cysteine mutations that attenuate SOD1 maturation prevented the SOD1-CCS heterodimer formation. The degree of S-acylation was highest for SOD1-CCS heterodimers, intermediate for CCS monomers, and lowest for SOD1 monomers. Given that S-acylation facilitates anchoring of soluble proteins to cell membranes, our findings suggest that S-acylation and membrane localization may play an important role in CCS-mediated SOD1 maturation. Furthermore, the highly stable S-acylated SOD1-CCS heterodimer may serve as a long-lived maturation intermediate in human spinal cord. PMID:28120938

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dhabuwala, C.B.; Ramakrishna, C.V.; Anderson, G.F.

Beta adrenergic receptor binding was performed with /sup 125/I iodocyanopindolol on human cavernous tissue membrane fractions from normal tissue and transsexual procedures obtained postoperatively, as well as from postmortem sources. Isotherm binding studies on normal fresh tissues indicated that the receptor density was 9.1 fmoles/mg. with a KD of 23 pM. Tissue stored at room temperature for 4 to 6 hours, then at 4C in saline solution for 19 to 20 hours before freezing showed no significant changes in receptor density or affinity, and provided evidence for the stability of postmortem tissue obtained within the same time period. Beta receptormore » density of 2 cavernous preparations from transsexual procedures was not significantly different from normal control tissues, and showed that high concentrations of estrogen received by these patients had no effect on beta adrenergic receptor density. Displacement of /sup 125/iodocyanopindolol by 5 beta adrenergic agents demonstrated that 1-propranolol had the greatest affinity followed by ICI 118,551, zinterol, metoprolol and practolol. When the results of these displacement studies were subjected to Scatfit, non- linear regression line analysis, a single binding site was described. Based on the relative potency of the selective beta adrenergic agents it appears that these receptors were of the beta 2 subtype.« less

Novel Application of Postmortem CT Angiography for Evaluation of the Intracranial Vascular Anatomy in Cadaver Heads.

PubMed

van Eijk, Ruben P A; van der Zwan, Albert; Bleys, Ronald L A W; Regli, Luca; Esposito, Giuseppe

2015-12-01

Postmortem CT angiography is a common procedure used to visualize the entire human vasculature. For visualization of a specific organ's vascular anatomy, casting is the preferred method. Because of the permanent and damaging nature of casting, the organ cannot be further used as an experimental model after angiography. Therefore, there is a need for a minimally traumatic method to visualize organ-specific vascular anatomy. The purpose of this study was to develop and evaluate a contrast enhancement technique that is capable of visualizing the intracranial vascular anatomy while preserving the anatomic integrity in cadaver heads. Seven human heads were used in this study. Heads were prepared by cannulating the vertebral and internal carotid arteries. Contrast agent was injected as a mixture of tap water, polyethylene glycol 600, and an iodinated contrast agent. Postmortem imaging was executed on a 64-MDCT scanner. Primary image review and 3D reconstruction were performed on a CT workstation. Clear visualization of the major cerebral arteries and smaller intracranial branches was achieved. Adequate visualization was obtained for both the anterior and posterior intracranial circulation. The minimally traumatic angiography method preserved the vascular integrity of the cadaver heads. A novel application of postmortem CT angiography is presented here. The technique can be used for radiologic evaluation of the intracranial circulation in cadaver heads. After CT angiography, the specimen can be used for further experimental or laboratory testing and teaching purposes.

Multiscale Analysis of Independent Alzheimer's Cohorts Finds Disruption of Molecular, Genetic, and Clinical Networks by Human Herpesvirus.

PubMed

Readhead, Ben; Haure-Mirande, Jean-Vianney; Funk, Cory C; Richards, Matthew A; Shannon, Paul; Haroutunian, Vahram; Sano, Mary; Liang, Winnie S; Beckmann, Noam D; Price, Nathan D; Reiman, Eric M; Schadt, Eric E; Ehrlich, Michelle E; Gandy, Sam; Dudley, Joel T

2018-06-21

Investigators have long suspected that pathogenic microbes might contribute to the onset and progression of Alzheimer's disease (AD) although definitive evidence has not been presented. Whether such findings represent a causal contribution, or reflect opportunistic passengers of neurodegeneration, is also difficult to resolve. We constructed multiscale networks of the late-onset AD-associated virome, integrating genomic, transcriptomic, proteomic, and histopathological data across four brain regions from human post-mortem tissue. We observed increased human herpesvirus 6A (HHV-6A) and human herpesvirus 7 (HHV-7) from subjects with AD compared with controls. These results were replicated in two additional, independent and geographically dispersed cohorts. We observed regulatory relationships linking viral abundance and modulators of APP metabolism, including induction of APBB2, APPBP2, BIN1, BACE1, CLU, PICALM, and PSEN1 by HHV-6A. This study elucidates networks linking molecular, clinical, and neuropathological features with viral activity and is consistent with viral activity constituting a general feature of AD. Copyright © 2018 Elsevier Inc. All rights reserved.

Synchrotron Radiation and Energy Dispersive X-Ray Fluorescence Applications on Elemental Distribution in Human Hair and Bones

NASA Astrophysics Data System (ADS)

Carvalho, M. L.; Marques, A. F.; Brito, J.

2003-01-01

This work is an application of synchrotron microprobe X- Ray fluorescence in order to study elemental distribution along human hair samples of contemporary citizens. Furthermore, X-Ray fluorescence spectrometry is also used to analyse human bones of different historical periods: Neolithic and contemporary subjects. The elemental content in the bones allowed us to conclude about environmental contamination, dietary habits and health status influence in the corresponding citizens. All samples were collected post-mortem. Quantitative analysis was performed for Mn, Fe, Co, Ni, Cu, Zn, Br, Rb, Sr and Pb. Mn and Fe concentration were much higher in bones from pre-historic periods. On the contrary, Pb bone concentrations of contemporary subjects are much higher than in pre-historical ones, reaching 100 μg g-1, in some cases. Very low concentrations for Co, Ni, Br and Rb were found in all the analysed samples. Cu concentrations, allows to distinguish Chalcolithic bones from the Neolithic ones. The distribution of trace elements along human hair was studied for Pb and the obtained pattern was consistent with the theoretical model, based on the diffusion of this element from the root and along the hair. Therefore, the higher concentrations in hair for Pb of contemporary individuals were also observed in the bones of citizens of the same sampling sites. All samples were analysed directly without any chemical treatment.

Dynamic response due to behind helmet blunt trauma measured with a human head surrogate.

PubMed

Freitas, Christopher J; Mathis, James T; Scott, Nikki; Bigger, Rory P; Mackiewicz, James

2014-01-01

A Human Head Surrogate has been developed for use in behind helmet blunt trauma experiments. This human head surrogate fills the void between Post-Mortem Human Subject testing (with biofidelity but handling restrictions) and commercial ballistic head forms (with no biofidelity but ease of use). This unique human head surrogate is based on refreshed human craniums and surrogate materials representing human head soft tissues such as the skin, dura, and brain. A methodology for refreshing the craniums is developed and verified through material testing. A test methodology utilizing these unique human head surrogates is also developed and then demonstrated in a series of experiments in which non-perforating ballistic impact of combat helmets is performed with and without supplemental ceramic appliques for protecting against larger caliber threats. Sensors embedded in the human head surrogates allow for direct measurement of intracranial pressure, cranial strain, and head and helmet acceleration. Over seventy (70) fully instrumented experiments have been executed using this unique surrogate. Examples of the data collected are presented. Based on these series of tests, the Southwest Research Institute (SwRI) Human Head Surrogate has demonstrated great potential for providing insights in to injury mechanics resulting from non-perforating ballistic impact on combat helmets, and directly supports behind helmet blunt trauma studies.

Dynamic Response Due to Behind Helmet Blunt Trauma Measured with a Human Head Surrogate

PubMed Central

Freitas, Christopher J.; Mathis, James T.; Scott, Nikki; Bigger, Rory P.; MacKiewicz, James

2014-01-01

A Human Head Surrogate has been developed for use in behind helmet blunt trauma experiments. This human head surrogate fills the void between Post-Mortem Human Subject testing (with biofidelity but handling restrictions) and commercial ballistic head forms (with no biofidelity but ease of use). This unique human head surrogate is based on refreshed human craniums and surrogate materials representing human head soft tissues such as the skin, dura, and brain. A methodology for refreshing the craniums is developed and verified through material testing. A test methodology utilizing these unique human head surrogates is also developed and then demonstrated in a series of experiments in which non-perforating ballistic impact of combat helmets is performed with and without supplemental ceramic appliques for protecting against larger caliber threats. Sensors embedded in the human head surrogates allow for direct measurement of intracranial pressure, cranial strain, and head and helmet acceleration. Over seventy (70) fully instrumented experiments have been executed using this unique surrogate. Examples of the data collected are presented. Based on these series of tests, the Southwest Research Institute (SwRI) Human Head Surrogate has demonstrated great potential for providing insights in to injury mechanics resulting from non-perforating ballistic impact on combat helmets, and directly supports behind helmet blunt trauma studies. PMID:24688303

Production of human metabolites by gastrointestinal bacteria as a potential source of post-mortem alteration of antemortem drug/metabolite concentrations.

PubMed

Martindale, Stephanie M; Powers, Robert H; Bell, Suzanne C

2015-01-01

Previous studies have demonstrated that bacterial species are capable of transforming complex chemical substances. Several of these species, native to the human gastrointestinal tract, are active in postmortem decomposition. They have potential to cause biotransformations affecting compound-to-metabolite ratios within the human body, especially after death. Investigation of postmortem effects could supply valuable information, especially concerning compound identification and confirmation. The purpose of this research was to investigate the effects of Escherichia coli, Bacteroides fragilis, and Clostridium perfringens on diazepam and flunitrazepam in Reinforced Clostridial Medium, and to compare bacterial biotransformation products to those of human metabolism. A decrease in diazepam concentration between pre- and post-incubation was observed for samples inoculated with Escherichia coli (14.7-20.2%) as well as Bacteroides fragilis (13.9-25.7%); however there was no corresponding increase in concentration for the monitored human metabolites. Flunitrazepam demonstrated a greater concentration loss when incubated with individual bacterial species as well as mixed culture (79.2-100.0%). Samples incubated with Bacteroides fragilis, Clostridium perfringens, and mixed culture resulted in nearly complete conversion of flunitrazepam. Increased 7-aminoflunitrazepam concentrations accounted for the majority of the conversion; however discrepancies in the mass balance of the reaction suggested the possibility of a minor metabolite that was not monitored in the current analysis. These experiments served as a pilot study and proof of concept that can be adapted and applied to a realm of possibilities. Ultimately, this methodology would be ideal to study compounds that are too toxic or lethal for animal and human metabolic investigations. Copyright © 2014 John Wiley & Sons, Ltd.

Midbrain dopamine function in schizophrenia and depression: a post-mortem and positron emission tomographic imaging study.

PubMed

Howes, Oliver D; Williams, Matthew; Ibrahim, Kemal; Leung, Garret; Egerton, Alice; McGuire, Philip K; Turkheimer, Federico

2013-11-01

Elevated in vivo markers of presynaptic striatal dopamine activity have been a consistent finding in schizophrenia, and include a large effect size elevation in dopamine synthesis capacity. However, it is not known if the dopaminergic dysfunction is limited to the striatal terminals of dopamine neurons, or is also evident in the dopamine neuron cell bodies, which mostly originate in the substantia nigra. The aim of our studies was therefore to determine whether dopamine synthesis capacity is altered in the substantia nigra of people with schizophrenia, and how this relates to symptoms. In a post-mortem study, a semi-quantitative analysis of tyrosine hydroxylase staining was conducted in nigral dopaminergic cells from post-mortem tissue from patients with schizophrenia (n = 12), major depressive disorder (n = 13) and matched control subjects (n = 13). In an in vivo imaging study, nigral and striatal dopaminergic function was measured in patients with schizophrenia (n = 29) and matched healthy control subjects (n = 29) using (18)F-dihydroxyphenyl-L-alanine ((18)F-DOPA) positron emission tomography. In the post-mortem study we found that tyrosine hydroxylase staining was significantly increased in nigral dopaminergic neurons in schizophrenia compared with both control subjects (P < 0.001) and major depressive disorder (P < 0.001). There was no significant difference in tyrosine hydroxylase staining between control subjects and patients with major depressive disorder, indicating that the elevation in schizophrenia is not a non-specific indicator of psychiatric illness. In the in vivo imaging study we found that (18)F-dihydroxyphenyl-L-alanine uptake was elevated in both the substantia nigra and in the striatum of patients with schizophrenia (effect sizes = 0.85, P = 0.003 and 1.14, P < 0.0001, respectively) and, in the voxel-based analysis, was elevated in the right nigra (P < 0.05 corrected for family wise-error). Furthermore, nigral (18)F-dihydroxyphenyl-L-alanine uptake was positively related with the severity of symptoms (r = 0.39, P = 0.035) in patients. However, whereas nigral and striatal (18)F-dihydroxyphenyl-L-alanine uptake were positively related in control subjects (r = 0.63, P < 0.001), this was not the case in patients (r = 0.30, P = 0.11). These findings indicate that elevated dopamine synthesis capacity is seen in the nigral origin of dopamine neurons as well as their striatal terminals in schizophrenia, and is linked to symptom severity in patients.

Anatomically Realistic Three-Dimensional Meshes of the Pelvic Floor & Anal Canal for Finite Element Analysis

PubMed Central

Noakes, Kimberley F.; Bissett, Ian P.; Pullan, Andrew J.; Cheng, Leo K.

2014-01-01

Three anatomically realistic meshes, suitable for finite element analysis, of the pelvic floor and anal canal regions have been developed to provide a framework with which to examine the mechanics, via finite element analysis of normal function within the pelvic floor. Two cadaver-based meshes were produced using the Visible Human Project (male and female) cryosection data sets, and a third mesh was produced based on MR image data from a live subject. The Visible Man (VM) mesh included 10 different pelvic structures while the Visible Woman and MRI meshes contained 14 and 13 structures respectively. Each image set was digitized and then finite element meshes were created using an iterative fitting procedure with smoothing constraints calculated from ‘L’-curves. These weights produced accurate geometric meshes of each pelvic structure with average Root Mean Square (RMS) fitting errors of less than 1.15 mm. The Visible Human cadaveric data provided high resolution images, however, the cadaveric meshes lacked the normal dynamic form of living tissue and suffered from artifacts related to postmortem changes. The lower resolution MRI mesh was able to accurately portray structure of the living subject and paves the way for dynamic, functional modeling. PMID:18317929

Enhanced Characterization of the Smell of Death by Comprehensive Two-Dimensional Gas Chromatography-Time-of-Flight Mass Spectrometry (GCxGC-TOFMS)

PubMed Central

Dekeirsschieter, Jessica; Stefanuto, Pierre-Hugues; Brasseur, Catherine; Haubruge, Eric; Focant, Jean-François

2012-01-01

Soon after death, the decay process of mammalian soft tissues begins and leads to the release of cadaveric volatile compounds in the surrounding environment. The study of postmortem decomposition products is an emerging field of study in forensic science. However, a better knowledge of the smell of death and its volatile constituents may have many applications in forensic sciences. Domestic pigs are the most widely used human body analogues in forensic experiments, mainly due to ethical restrictions. Indeed, decomposition trials on human corpses are restricted in many countries worldwide. This article reports on the use of comprehensive two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GCxGC-TOFMS) for thanatochemistry applications. A total of 832 VOCs released by a decaying pig carcass in terrestrial ecosystem, i.e. a forest biotope, were identified by GCxGC-TOFMS. These postmortem compounds belong to many kinds of chemical class, mainly oxygen compounds (alcohols, acids, ketones, aldehydes, esters), sulfur and nitrogen compounds, aromatic compounds such as phenolic molecules and hydrocarbons. The use of GCxGC-TOFMS in study of postmortem volatile compounds instead of conventional GC-MS was successful. PMID:22723918

Postmortem diffusion MRI of the human brainstem and thalamus for deep brain stimulator electrode localization

PubMed Central

Calabrese, Evan; Hickey, Patrick; Hulette, Christine; Zhang, Jingxian; Parente, Beth; Lad, Shivanand P.; Johnson, G. Allan

2015-01-01

Deep brain stimulation (DBS) is an established surgical therapy for medically refractory tremor disorders including essential tremor (ET) and is currently under investigation for use in a variety of other neurologic and psychiatric disorders. There is growing evidence that the anti-tremor effects of DBS for ET are directly related to modulation of the dentatorubrothalamic tract (DRT), a white matter pathway that connects the cerebellum, red nucleus, and ventral intermediate nucleus of the thalamus. Emerging white matter targets for DBS, like the DRT, will require improved 3D reference maps of deep brain anatomy and structural connectivity for accurate electrode targeting. High-resolution diffusion MRI of postmortem brain specimens can provide detailed volumetric images of important deep brain nuclei and 3D reconstructions of white matter pathways with probabilistic tractography techniques. We present a high spatial and angular resolution diffusion MRI template of the postmortem human brainstem and thalamus with 3D reconstructions of the nuclei and white matter tracts involved in ET circuitry. We demonstrate accurate registration of these data to in vivo, clinical images from patients receiving DBS therapy, and correlate electrode proximity to tractography of the DRT with improvement of ET symptoms. PMID:26043869

Ex-vivo quantitative susceptibility mapping of human brain hemispheres

PubMed Central

Kotrotsou, Aikaterini; Tamhane, Ashish A.; Dawe, Robert J.; Kapasi, Alifiya; Leurgans, Sue E.; Schneider, Julie A.; Bennett, David A.; Arfanakis, Konstantinos

2017-01-01

Ex-vivo brain quantitative susceptibility mapping (QSM) allows investigation of brain characteristics at essentially the same point in time as histopathologic examination, and therefore has the potential to become an important tool for determining the role of QSM as a diagnostic and monitoring tool of age-related neuropathologies. In order to be able to translate the ex-vivo QSM findings to in-vivo, it is crucial to understand the effects of death and chemical fixation on brain magnetic susceptibility measurements collected ex-vivo. Thus, the objective of this work was twofold: a) to assess the behavior of magnetic susceptibility in both gray and white matter of human brain hemispheres as a function of time postmortem, and b) to establish the relationship between in-vivo and ex-vivo gray matter susceptibility measurements on the same hemispheres. Five brain hemispheres from community-dwelling older adults were imaged ex-vivo with QSM on a weekly basis for six weeks postmortem, and the longitudinal behavior of ex-vivo magnetic susceptibility in both gray and white matter was assessed. The relationship between in-vivo and ex-vivo gray matter susceptibility measurements was investigated using QSM data from eleven older adults imaged both antemortem and postmortem. No systematic change in ex-vivo magnetic susceptibility of gray or white matter was observed over time postmortem. Additionally, it was demonstrated that, gray matter magnetic susceptibility measured ex-vivo may be well modeled as a linear function of susceptibility measured in-vivo. In conclusion, magnetic susceptibility in gray and white matter measured ex-vivo with QSM does not systematically change in the first six weeks after death. This information is important for future cross-sectional ex-vivo QSM studies of hemispheres imaged at different postmortem intervals. Furthermore, the linear relationship between in-vivo and ex-vivo gray matter magnetic susceptibility suggests that ex-vivo QSM captures information linked to antemortem gray matter magnetic susceptibility, which is important for translation of ex-vivo QSM findings to in-vivo. PMID:29261693

Exploring the mechanical behavior of degrading swine neural tissue at low strain rates via the fractional Zener constitutive model.

PubMed

Bentil, Sarah A; Dupaix, Rebecca B

2014-02-01

The ability of the fractional Zener constitutive model to predict the behavior of postmortem swine brain tissue was examined in this work. Understanding tissue behavior attributed to degradation is invaluable in many fields such as the forensic sciences or cases where only cadaveric tissue is available. To understand how material properties change with postmortem age, the fractional Zener model was considered as it includes parameters to describe brain stiffness and also the parameter α, which quantifies the viscoelasticity of a material. The relationship between the viscoelasticity described by α and tissue degradation was examined by fitting the model to data collected in a previous study (Bentil, 2013). This previous study subjected swine neural tissue to in vitro unconfined compression tests using four postmortem age groups (<6h, 24h, 3 days, and 1 week). All samples were compressed to a strain level of 10% using two compressive rates: 1mm/min and 5mm/min. Statistical analysis was used as a tool to study the influence of the fractional Zener constants on factors such as tissue degradation and compressive rate. Application of the fractional Zener constitutive model to the experimental data showed that swine neural tissue becomes less stiff with increased postmortem age. The fractional Zener model was also able to capture the nonlinear viscoelastic features of the brain tissue at low strain rates. The results showed that the parameter α was better correlated with compressive rate than with postmortem age. © 2013 Published by Elsevier Ltd.

Role of Cardiac Myocytes Heart Fatty Acid Binding Protein Depletion (H-FABP) in Early Myocardial Infarction in Human Heart (Autopsy Study).

PubMed

Shabaiek, Amany; Ismael, Nour El-Hoda; Elsheikh, Samar; Amin, Hebat Allah

2016-03-15

Many immunohistochemical markers have been used in the postmortem detection of early myocardial infarction. In the present study we examined the role of Heart-type fatty acid binding protein (H-FABP), in the detection of early myocardial infarction. We obtained samples from 40 human autopsy hearts with/without histopathological signs of ischemia. All cases of definite and probable myocardial infarction showed a well-defined area of H-FABP depletion. All of the control cases showed strong H-FABP expression, except two markedly autolysed myocardial samples that showed affected antigenicity. Thus, we suggest H-FABP as being one of the valuable tools facing the problem of postmortem detection of early myocardial infarction/ischemia, but not in autolysis.

Identification of genes and gene pathways associated with major depressive disorder by integrative brain analysis of rat and human prefrontal cortex transcriptomes

PubMed Central

Malki, K; Pain, O; Tosto, M G; Du Rietz, E; Carboni, L; Schalkwyk, L C

2015-01-01

Despite moderate heritability estimates, progress in uncovering the molecular substrate underpinning major depressive disorder (MDD) has been slow. In this study, we used prefrontal cortex (PFC) gene expression from a genetic rat model of MDD to inform probe set prioritization in PFC in a human post-mortem study to uncover genes and gene pathways associated with MDD. Gene expression differences between Flinders sensitive (FSL) and Flinders resistant (FRL) rat lines were statistically evaluated using the RankProd, non-parametric algorithm. Top ranking probe sets in the rat study were subsequently used to prioritize orthologous selection in a human PFC in a case–control post-mortem study on MDD from the Stanley Brain Consortium. Candidate genes in the human post-mortem study were then tested against a matched control sample using the RankProd method. A total of 1767 probe sets were differentially expressed in the PFC between FSL and FRL rat lines at (q⩽0.001). A total of 898 orthologous probe sets was found on Affymetrix's HG-U95A chip used in the human study. Correcting for the number of multiple, non-independent tests, 20 probe sets were found to be significantly dysregulated between human cases and controls at q⩽0.05. These probe sets tagged the expression profile of 18 human genes (11 upregulated and seven downregulated). Using an integrative rat–human study, a number of convergent genes that may have a role in pathogenesis of MDD were uncovered. Eighty percent of these genes were functionally associated with a key stress response signalling cascade, involving NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells), AP-1 (activator protein 1) and ERK/MAPK, which has been systematically associated with MDD, neuroplasticity and neurogenesis. PMID:25734512

Influence of postmortem time on the outcome of blood cultures among cadaveric tissue donors.

PubMed

Saegeman, V; Verhaegen, J; Lismont, D; Verduyckt, B; De Rijdt, T; Ectors, N

2009-02-01

Tissue banks provide tissues of human cadaver donors for transplantation. The maximal time limit for tissue retrieval has been set at 24 h postmortem. This study aimed at evaluating the evidence for this limit from a microbiological point of view. The delay of growth in postmortem blood cultures, the identification of the species isolated and clinical/environmental factors were investigated among 100 potential tissue donors. No significant difference was found in the rate of donors with grown blood cultures within (25/65=38%) compared with after (24/65=37%) 24 h of death. Coagulase-negative staphylococci and gastro-intestinal microorganisms were isolated within and after 24 h of death. Two factors--antimicrobial therapy and "delay before body cooling"--were significantly inversely related with donors' blood culture results. From a microbiological point of view, there is no evidence for avoiding tissue retrieval among donors after 24 h of death.

A review of the changing culture and social context relating to forensic facial depiction of the dead.

PubMed

Wilkinson, Caroline

2014-12-01

The recognition of a decedent by a family member is commonplace in forensic investigation and is often employed as identity confirmation. However, it is recognised that misidentification from facial recognition is also common and faces of the dead may be extremely difficult to recognise due to decomposition or external damage, and even immediate post-mortem changes may be significant enough to confuse an observer. The depiction of faces of the dead can be a useful tool for promoting recognition leading to identification and post-mortem facial depiction is described as the interpretation of human remains in order to suggest the living appearance of an individual. This paper provides an historical context relating to the changing view of society to the presentation and publication of post-mortem facial depictions and discusses the current ethical, practical and academic challenges associated with these images. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Experimental evaluation of rigor mortis. VII. Effect of ante- and post-mortem electrocution on the evolution of rigor mortis.

PubMed

Krompecher, T; Bergerioux, C

1988-01-01

The influence of electrocution on the evolution of rigor mortis was studied on rats. Our experiments showed that: (1) Electrocution hastens the onset of rigor mortis. After an electrocution of 90 s, a complete rigor develops already 1 h post-mortem (p.m.) compared to 5 h p.m. for the controls. (2) Electrocution hastens the passing of rigor mortis. After an electrocution of 90 s, the first significant decrease occurs at 3 h p.m. (8 h p.m. in the controls). (3) These modifications in rigor mortis evolution are less pronounced in the limbs not directly touched by the electric current. (4) In case of post-mortem electrocution, the changes are slightly less pronounced, the resistance is higher and the absorbed energy is lower as compared with the ante-mortem electrocution cases. The results are completed by two practical observations on human electrocution cases.

GABAergic Mechanisms in Schizophrenia: Linking Postmortem and In Vivo Studies

PubMed Central

de Jonge, Jeroen C.; Vinkers, Christiaan H.; Hulshoff Pol, Hilleke E.; Marsman, Anouk

2017-01-01

Schizophrenia is a psychiatric disorder characterized by hallucinations, delusions, disorganized thinking, and impairments in cognitive functioning. Evidence from postmortem studies suggests that alterations in cortical γ-aminobutyric acid (GABAergic) neurons contribute to the clinical features of schizophrenia. In vivo measurement of brain GABA levels using magnetic resonance spectroscopy (MRS) offers the possibility to provide more insight into the relationship between problems in GABAergic neurotransmission and clinical symptoms of schizophrenia patients. This study reviews and links alterations in the GABA system in postmortem studies, animal models, and human studies in schizophrenia. Converging evidence implicates alterations in both presynaptic and postsynaptic components of GABAergic neurotransmission in schizophrenia, and GABA may thus play an important role in the pathophysiology of schizophrenia. MRS studies can provide direct insight into the GABAergic mechanisms underlying the development of schizophrenia as well as changes during its course. PMID:28848455

Decreased free d-aspartate levels are linked to enhanced d-aspartate oxidase activity in the dorsolateral prefrontal cortex of schizophrenia patients.

PubMed

Nuzzo, Tommaso; Sacchi, Silvia; Errico, Francesco; Keller, Simona; Palumbo, Orazio; Florio, Ermanno; Punzo, Daniela; Napolitano, Francesco; Copetti, Massimiliano; Carella, Massimo; Chiariotti, Lorenzo; Bertolino, Alessandro; Pollegioni, Loredano; Usiello, Alessandro

2017-01-01

It is long acknowledged that the N -methyl d-aspartate receptor co-agonist, d-serine, plays a crucial role in several N -methyl d-aspartate receptor-mediated physiological and pathological processes, including schizophrenia. Besides d-serine, another free d-amino acid, d-aspartate, is involved in the activation of N -methyl d-aspartate receptors acting as an agonist of this receptor subclass, and is abundantly detected in the developing human brain. Based on the hypothesis of N -methyl d-aspartate receptor hypofunction in the pathophysiology of schizophrenia and considering the ability of d-aspartate and d-serine to stimulate N -methyl d-aspartate receptor-dependent transmission, in the present work we assessed the concentration of these two d-amino acids in the post-mortem dorsolateral prefrontal cortex and hippocampus of patients with schizophrenia and healthy subjects. Moreover, in this cohort of post-mortem brain samples we investigated the spatiotemporal variations of d-aspartate and d-serine. Consistent with previous work, we found that d-aspartate content was selectively decreased by around 30% in the dorsolateral prefrontal cortex, but not in the hippocampus, of schizophrenia-affected patients, compared to healthy subjects. Interestingly, such selective reduction was associated to greater (around 25%) cortical activity of the enzyme responsible for d-aspartate catabolism, d-aspartate oxidase. Conversely, no significant changes were found in the methylation state and transcription of DDO gene in patients with schizophrenia, compared to control individuals, as well as in the expression levels of serine racemase, the major enzyme responsible for d-serine biosynthesis, which also catalyzes aspartate racemization. These results reveal the potential involvement of altered d-aspartate metabolism in the dorsolateral prefrontal cortex as a factor contributing to dysfunctional N -methyl d-aspartate receptor-mediated transmission in schizophrenia.

Differential and brain region-specific regulation of Rap-1 and Epac in depressed suicide victims.

PubMed

Dwivedi, Yogesh; Mondal, Amal C; Rizavi, Hooriyah S; Faludi, Gabor; Palkovits, Miklos; Sarosi, Andrea; Conley, Robert R; Pandey, Ghanshyam N

2006-06-01

Depression is a major public health problem. Despite many years of research, the molecular mechanisms associated with depression remain unclear. Rap-1, activated in response to many extracellular stimuli, is one of the major substrates of protein kinase A, which participates in myriad physiologic functions in the brain, including cell survival and synaptic plasticity. Rap-1 is also activated directly by cyclic adenosine monophosphate through Epac, and thus participates in mediating physiologic functions independent of protein kinase A. To examine whether the pathogenesis of depression is associated with altered activation and expression of Rap-1, as well as expression of Epac, in depressed suicide victims. Postmortem study. Tissues were obtained from the Lenhossek Human Brain Program, Semmelweis University, Budapest, Hungary, and the Brain Collection Program of the Maryland Psychiatric Research Center, Baltimore. Postmortem brains of 28 depressed suicide victims and 28 nonpsychiatric control subjects. Examination of brain tissues. Rap-1 activation as well as messenger RNA and protein levels of Rap-1 and Epac in prefrontal cortex, hippocampus, and cerebellum. Rap-1 activation was significantly reduced (P<.001) in prefrontal cortex and hippocampus in the suicide group. This was associated with significant reductions in Rap-1 messenger RNA and protein levels (P<.001). In contrast, protein level of only Epac-2 (P<.001) but not Epac-1 (P = .89) was significantly increased in prefrontal cortex and hippocampus of these subjects. These changes were present whether the 2 cohorts were analyzed together or separately. None of the measures showed any significant change in cerebellum in the suicide group. Given the importance of Rap-1 in neuroprotection and synaptic plasticity, our findings of differential regulation of Rap-1 and Epac between brain regions suggest the relevance of these molecules in the pathophysiology of depression.

Considerations for optimal use of postmortem human brains for molecular psychiatry: lessons from schizophrenia.

PubMed

Weickert, Cynthia Shannon; Rothmond, Debora A; Purves-Tyson, Tertia D

2018-01-01

Schizophrenia is a disabling disease impacting millions of people around the world, for which there is no known cure. Current antipsychotic treatments for schizophrenia mainly target psychotic symptoms, do little to ameliorate social or cognitive deficits, have side-effects that cause weight gain, and diabetes and 30% of people do not respond. Thus, better therapeutics for schizophrenia aimed at the route biologic changes are needed and discovering the underlying neurobiology is key to this quest. Postmortem brain studies provide the most direct and detailed way to determine the pathophysiology of schizophrenia. This chapter outlines steps that can be taken to ensure the best-quality molecular data from postmortem brain tissue are obtained. In this chapter, we also discuss targeted and high-throughput methods for examining gene and protein expression and some of the strengths and limitations of each method. We briefly consider why gene and protein expression changes may not always concur within brain tissue. We conclude that postmortem brain research that investigates gene and protein expression in well-characterized and matched brain cohorts provides an important foundation to be considered when interpreting data obtained from studies of living schizophrenia patients. Copyright © 2018 Elsevier B.V. All rights reserved.

Common Postmortem Computed Tomography Findings Following Atraumatic Death: Differentiation between Normal Postmortem Changes and Pathologic Lesions

PubMed Central

Gonoi, Wataru; Okuma, Hidemi; Shirota, Go; Shintani, Yukako; Abe, Hiroyuki; Takazawa, Yutaka; Fukayama, Masashi; Ohtomo, Kuni

2015-01-01

Computed tomography (CT) is widely used in postmortem investigations as an adjunct to the traditional autopsy in forensic medicine. To date, several studies have described postmortem CT findings as being caused by normal postmortem changes. However, on interpretation, postmortem CT findings that are seemingly due to normal postmortem changes initially, may not have been mere postmortem artifacts. In this pictorial essay, we describe the common postmortem CT findings in cases of atraumatic in-hospital death and describe the diagnostic pitfalls of normal postmortem changes that can mimic real pathologic lesions. PMID:26175579

A Machine Learning Approach for Using the Postmortem Skin Microbiome to Estimate the Postmortem Interval

PubMed Central

Johnson, Hunter R.; Trinidad, Donovan D.; Guzman, Stephania; Khan, Zenab; Parziale, James V.; DeBruyn, Jennifer M.

2016-01-01

Research on the human microbiome, the microbiota that live in, on, and around the human person, has revolutionized our understanding of the complex interactions between microbial life and human health and disease. The microbiome may also provide a valuable tool in forensic death investigations by helping to reveal the postmortem interval (PMI) of a decedent that is discovered after an unknown amount of time since death. Current methods of estimating PMI for cadavers discovered in uncontrolled, unstudied environments have substantial limitations, some of which may be overcome through the use of microbial indicators. In this project, we sampled the microbiomes of decomposing human cadavers, focusing on the skin microbiota found in the nasal and ear canals. We then developed several models of statistical regression to establish an algorithm for predicting the PMI of microbial samples. We found that the complete data set, rather than a curated list of indicator species, was preferred for training the regressor. We further found that genus and family, rather than species, are the most informative taxonomic levels. Finally, we developed a k-nearest- neighbor regressor, tuned with the entire data set from all nasal and ear samples, that predicts the PMI of unknown samples with an average error of ±55 accumulated degree days (ADD). This study outlines a machine learning approach for the use of necrobiome data in the prediction of the PMI and thereby provides a successful proof-of- concept that skin microbiota is a promising tool in forensic death investigations. PMID:28005908

Alteration of Cyclic-AMP Response Element Binding Protein in the Postmortem Brain of Subjects with Bipolar Disorder and Schizophrenia

PubMed Central

Ren, Xinguo; Rizavi, Hooriyah S.; Khan, Mansoor A.; Bhaumik, Runa; Dwivedi, Yogesh; Pandey, Ghanshyam N.

2013-01-01

Background Abnormalities of cyclic-AMP (cAMP) response element binding protein (CREB) function has been suggested in bipolar (BP) illness and schizophrenia (SZ), based on both indirect and direct evidence. To further elucidate the role of CREB in these disorders, we studied CREB expression and function in two brain areas implicated in these disorders, i.e., dorsolateral prefrontal cortex (DLPFC) and cingulate gyrus (CG). Methods We determined CREB protein expression using Western blot technique, CRE-DNA binding using gel shift assay, and mRNA expression using real-time RT-polymerase chain reaction (qPCR) in DLPFC and CG of the postmortem brain of BP (n = 19), SZ (n = 20), and normal control (NC, n = 20) subjects. Results We observed that CREB protein and mRNA expression and CRE-DNA binding activity were significantly decreased in the nuclear fraction of DLPFC and CG obtained from BP subjects compared with NC subjects. However, the protein and mRNA expression and CRE-DNA binding in SZ subjects was significantly decreased in CG, but not in DLPFC, compared with NC. Conclusion These studies thus indicate region-specific abnormalities of CREB expression and function in both BP and SZ. They suggest that abnormalities of CREB in CG may be associated with both BP and SZ, but its abnormality in DLPFC is specific to BP illness. PMID:24148789

Human brain diffusion tensor imaging at submillimeter isotropic resolution on a 3 Tesla clinical MRI scanner

PubMed Central

Chang, Hing-Chiu; Sundman, Mark; Petit, Laurent; Guhaniyogi, Shayan; Chu, Mei-Lan; Petty, Christopher; Song, Allen W.; Chen, Nan-kuei

2015-01-01

The advantages of high-resolution diffusion tensor imaging (DTI) have been demonstrated in a recent post-mortem human brain study (Miller et al., NeuroImage 2011;57(1):167–181), showing that white matter fiber tracts can be much more accurately detected in data at submillimeter isotropic resolution. To our knowledge, in vivo human brain DTI at submillimeter isotropic resolution has not been routinely achieved yet because of the difficulty in simultaneously achieving high resolution and high signal-to-noise ratio (SNR) in DTI scans. Here we report a 3D multi-slab interleaved EPI acquisition integrated with multiplexed sensitivity encoded (MUSE) reconstruction, to achieve high-quality, high-SNR and submillimeter isotropic resolution (0.85 × 0.85 × 0.85 mm3) in vivo human brain DTI on a 3 Tesla clinical MRI scanner. In agreement with the previously reported post-mortem human brain DTI study, our in vivo data show that the structural connectivity networks of human brains can be mapped more accurately and completely with high-resolution DTI as compared with conventional DTI (e.g., 2 × 2 × 2 mm3). PMID:26072250

Seed-competent HMW tau species accumulates in the cerebrospinal fluid of Alzheimer's disease mouse model and human patients

PubMed Central

Takeda, Shuko; Commins, Caitlin; DeVos, Sarah L.; Nobuhara, Chloe K.; Wegmann, Susanne; Roe, Allyson D.; Costantino, Isabel; Fan, Zhanyun; Nicholls, Samantha B.; Sherman, Alexis E.; Trisini Lipsanopoulos, Ana T.; Scherzer, Clemens R.; Carlson, George A.; Pitstick, Rose; Peskind, Elaine R.; Raskind, Murray A.; Li, Ge; Montine, Thomas J.; Frosch, Matthew P.; Hyman, Bradley T.

2016-01-01

Objective Cerebrospinal fluid (CSF) tau is an excellent surrogate marker for assessing neuropathological changes that occur in Alzheimer's disease (AD) patients. However, whether the elevated tau in AD CSF is just a marker of neurodegeneration or in fact a part of the disease process is uncertain. Moreover, it is unknown how CSF tau relates to the recently described soluble high-molecular-weight (HMW) species that is found in postmortem AD brain and can be taken up by neurons and seed aggregates. Methods We have examined seeding and uptake properties of brain extracellular tau from various sources including: interstitial fluid (ISF) and CSF from an AD transgenic mouse model, and postmortem ventricular and antemortem lumbar CSF from AD patients. Results We found that brain ISF and CSF tau from the AD mouse model can be taken up by cells and induce intracellular aggregates. Ventricular CSF from AD patients contained a rare HMW tau species that exerted a higher seeding activity. Notably, the HMW tau species was also detected in lumbar CSF from AD patients and its levels were significantly elevated compared with control subjects. HMW tau derived from CSF of AD patients was seed-competent in vitro. Interpretation These findings suggest that CSF from an AD brain contains potentially bioactive HMW tau species giving new insights into the role of CSF tau and biomarker development for AD. PMID:27351289

Nondrowning Asphyxia in Veterinary Forensic Pathology: Suffocation, Strangulation, and Mechanical Asphyxia.

PubMed

McEwen, B J

2016-09-01

Asphyxia in a forensic context refers to death by rapid cerebral anoxia or hypoxia due to accidental or nonaccidental injury. Death due to nondrowning asphyxia can occur with strangulation, suffocation, and mechanical asphyxia, each of which is categorized based on the mechanism of injury. Individuals dying due to various types of asphyxia may or may not have lesions, and even those lesions that are present may be due to other causes. The interpretation or opinion that death was due to asphyxia requires definitive and compelling evidence from the postmortem examination, death scene, and/or history. Beyond the postmortem examination, pathologists may be faced with questions of forensic importance that revolve around the behavioral and physiological responses in animals subjected to strangulation, suffocation, or mechanical asphyxia to determine if the animal suffered. While there is no prescriptive answer to these questions, it is apparent that, because of physiological and anatomical differences between humans and animals, for some mechanisms of asphyxia, consciousness is maintained for longer periods and the onset of death is later in animals than that described for people. Veterinary pathologists must be cognizant that direct extrapolation from the medical forensic literature to animals may be incorrect. This article reviews the terminology, classification, mechanisms, and lesions associated with asphyxial deaths in companion animals and highlights significant comparative differences of the response to various types of asphyxia in animals and people. © The Author(s) 2016.

Implementation and clinical characteristics of a posttraumatic stress disorder brain collection.

PubMed

Mighdoll, Michelle I; Deep-Soboslay, Amy; Bharadwaj, Rahul A; Cotoia, John A; Benedek, David M; Hyde, Thomas M; Kleinman, Joel E

2018-01-01

A postmortem human brain collection to study posttraumatic stress disorder (PTSD) is critical for uncovering the molecular mechanisms that contribute to this psychiatric disorder. We describe here the PTSD brain collection at the Lieber Institute for Brain Development in Baltimore, Maryland, consisting of postmortem brain donations acquired between 2012 and 2017. Thus far, 87 brains from individuals meeting DSM-5 criteria for PTSD were collected after consent was obtained from legal next-of-kin, and subsequently clinically characterized for molecular studies. PTSD brain donors had high rates of comorbid diagnoses, including depression (62.1%), substance abuse (74.7%), drug-related death (69.0%), and suicide completion (17.2%). PTSD cases were subdivided into two categories: combat-related PTSD (n = 24) and noncombat/domestic PTSD (n = 63). The major differences between the combat-related and domestic PTSD cohorts were sex, drug-related death, and the prevalence of bipolar disorder (BPD) comorbidity. The combat-related group was entirely male, with only one BPD subject (4.2%), and had significantly fewer drug-related deaths (45.8%) in contrast to the domestic group (31.8% male, 36.5% bipolar, and 77.8% drug-related deaths). Medical examiners' offices, particularly in areas with higher military populations, are an excellent source for PTSD brain donations of both combat-related and domestic PTSD. © 2017 Wiley Periodicals, Inc.

Abnormalities in the fatty acid composition of the postmortem entorhinal cortex of patients with schizophrenia, bipolar disorder, and major depressive disorder.

PubMed

Hamazaki, Kei; Hamazaki, Tomohito; Inadera, Hidekuni

2013-11-30

Previous studies of postmortem orbitofrontal cortex have shown abnormalities in levels of n-3 polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid (DHA), in individuals with schizophrenia, bipolar disorder, and major depressive disorder (MDD). We have previously measured PUFA levels in the postmortem hippocampus from patients with schizophrenia or bipolar disorder and control subjects; however, we found no significant differences between the groups except for small changes in n-6 PUFAs. Furthermore, our study of the postmortem amygdala showed no significant differences in major PUFAs in individuals with schizophrenia, bipolar disorder, or MDD in comparison with controls. In the present study, we investigated whether there were any changes in PUFAs in the entorhinal cortexes of patients with schizophrenia (n=15), bipolar disorder (n=15), or MDD (n=15) compared with unaffected controls (n=15) matched for characteristics including age and sex. In contrast to previous studies of the orbitofrontal cortex and hippocampus, we found no significant differences in major PUFAs. However, we found a 34.3% decrease in docosapentaenoic acid (DPA) (22:5n-3) in patients with MDD and an 8.7% decrease in docosatetraenoic acid (22:4n-6) in those with schizophrenia, compared with controls. Changes in PUFAs in patients with these psychiatric disorders may be specific to certain brain regions. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Evaluation of Intraosseous Fluid as an Alternative Biological Specimen in Postmortem Toxicology.

PubMed

Rodda, Luke N; Volk, Justin A; Moffat, Ellen; Williams, Chinyere M; Lynch, Kara L; Wu, Alan H B

2018-04-01

The postmortem redistribution phenomenon is an important factor in the interpretation of blood drug concentrations as a cause or factor in death. Intraosseous fluid (IOF) may serve as an alternative matrix for drug testing. Intraosseous fluid was collected from the left and right tibias and humerus of 29 decedents using the Arrow EZ-IO Intraosseous Vascular Access System. Standard autopsy specimens including blood were also collected at the same time during autopsy. Blood and IOF specimens were screened by immunoassay for opioids, fentanyl analogs, oxycodone, methadone, cocaine, methamphetamine, amphetamines, phencyclidine, tricyclic antidepressants, benzodiazepines and cannabinoids, using commercially available enzyme-linked immunosorbent assay (ELISA) kits. Correlation between cardiac/central blood ELISA and IOF ELISA results was mostly 100% for drug targets. Further blood confirmation analysis was performed by gas chromatography mass spectrometry also showed comparable correlation to IOF screen results. There was no significant difference between the IOF sites or sides of the body. This novel study supports the use of IOF as an alternative postmortem specimen for toxicological investigations as a potentially less-compromised tissue in decomposed or traumatized bodies. Preliminary data is provided for the screening of common drugs of abuse in IOF that may show to be subject to alternative rates of postmortem redistribution than to that of other biological specimens in future studies that quantitate IOF drug concentrations.

Point-of-care hemoglobin testing for postmortem diagnosis of anemia.

PubMed

Na, Joo-Young; Park, Ji Hye; Choi, Byung Ha; Kim, Hyung-Seok; Park, Jong-Tae

2018-03-01

An autopsy involves examination of a body using invasive methods such as dissection, and includes various tests using samples procured during dissection. During medicolegal autopsies, the blood carboxyhemoglobin concentration is commonly measured using the AVOXimeter® 4000 as a point-of-care test. When evaluating the body following hypovolemic shock, characteristics such as reduced livor mortis or an anemic appearance of the viscera can be identified, but these observations arequite subjective. Thus, a more objective test is required for the postmortem diagnosis of anemia. In the present study, the AVOXimeter® 4000 was used to investigate the utility of point-of-care hemoglobin testing. Hemoglobin tests were performed in 93 autopsy cases. The AVOXimeter® 4000 and the BC-2800 Auto Hematology Analyzer were used to test identical samples in 29 of these cases. The results of hemoglobin tests performed with these two devices were statistically similar (r = 0.969). The results of hemoglobin tests using postmortem blood were compared with antemortem test results from medical records from 31 cases, and these results were similar. In 13 of 17 cases of death from internal hemorrhage, hemoglobin levels were lower in the cardiac blood than in blood from the affected body cavity, likely due to compensatory changes induced by antemortem hemorrhage. It is concluded that blood hemoglobin testing may be useful as a point-of-care test for diagnosing postmortem anemia.

Determination of Etomidate in Human Postmortem Fluids and Tissues

DTIC Science & Technology

2009-02-01

8-72) Reproduction of completed page authorized CONTENTs IntroductIon...on.Agent ..Pharma- cotherapy,.3:.251-8.(1983) . 2 .. Doencke,.A ..Etomidate, a New Hypnotic Agent for Intravenous Application.,. 1. ed .. (Sprnger

Neuroanatomic connectivity of the human ascending arousal system critical to consciousness and its disorders.

PubMed

Edlow, Brian L; Takahashi, Emi; Wu, Ona; Benner, Thomas; Dai, Guangping; Bu, Lihong; Grant, Patricia Ellen; Greer, David M; Greenberg, Steven M; Kinney, Hannah C; Folkerth, Rebecca D

2012-06-01

The ascending reticular activating system (ARAS) mediates arousal, an essential component of human consciousness. Lesions of the ARAS cause coma, the most severe disorder of consciousness. Because of current methodological limitations, including of postmortem tissue analysis, the neuroanatomic connectivity of the human ARAS is poorly understood. We applied the advanced imaging technique of high angular resolution diffusion imaging (HARDI) to elucidate the structural connectivity of the ARAS in 3 adult human brains, 2 of which were imaged postmortem. High angular resolution diffusion imaging tractography identified the ARAS connectivity previously described in animals and also revealed novel human pathways connecting the brainstem to the thalamus, the hypothalamus, and the basal forebrain. Each pathway contained different distributions of fiber tracts from known neurotransmitter-specific ARAS nuclei in the brainstem. The histologically guided tractography findings reported here provide initial evidence for human-specific pathways of the ARAS. The unique composition of neurotransmitter-specific fiber tracts within each ARAS pathway suggests structural specializations that subserve the different functional characteristics of human arousal. This ARAS connectivity analysis provides proof of principle that HARDI tractography may affect the study of human consciousness and its disorders, including in neuropathologic studies of patients dying in coma and the persistent vegetative state.

Role of forensic odontologist in post mortem person identification

PubMed Central

Pramod, Jahagirdar B.; Marya, Anand; Sharma, Vidhii

2012-01-01

The natural teeth are the most durable organs in the bodies of vertebrates, and humankind's understanding of their own past and evolution relies heavily upon remnant dental evidence found as fossils. The use of features unique to the human dentition as an aid to personal identification is widely accepted within the forensic field. Comparative dental identifications play a major role in identifying the victims of violence, disaster or other mass tragedies. The comparison of ante-mortem and postmortem dental records to determine human identity has long been established. Indeed, it is still a major identification method in criminal investigations, mass disasters, grossly decomposed or traumatized bodies, and in other situations where visual identification is neither possible nor desirable. This article has comprehensively described some of the methods, and additional factors aiding in postmortem person identification. PMID:23559914

Neoplasia in Three Aye-Ayes (Daubentonia madagascariensis).

PubMed

Rodriguez Barbon, A; Cowen, R; Knott, C; Hughes, K; Allinson, K; Williams, C V; Routh, A

2018-02-01

Tumours diagnosed in three aged captive aye-ayes (Daubentonia madagascariensis), held in two different institutions, are described. A cerebral glioblastoma was diagnosed based on histological and immunohistochemical findings in one of the animals following initial presentation with bilateral mydriasis, absent pupillary reflex, head tilt and ataxia. A second animal was humanely destroyed due to impaired locomotion associated with spondylosis and a post-mortem diagnosis of cholangiocarcinoma was made based on histology with further confirmation with immunohistochemical labelling for cytokeratin 7. A third aye-aye suffering from dental disease was diagnosed with an oral squamous cell carcinoma following an excisional biopsy from a non-healing wound in the lip. Due to progression of the neoplasia the animal was humanely destroyed and post-mortem examination revealed the presence on an additional unilateral phaeochromocytoma. Copyright © 2017 Elsevier Ltd. All rights reserved.

Human Brain Modeling with Its Anatomical Structure and Realistic Material Properties for Brain Injury Prediction.

PubMed

Atsumi, Noritoshi; Nakahira, Yuko; Tanaka, Eiichi; Iwamoto, Masami

2018-05-01

Impairments of executive brain function after traumatic brain injury (TBI) due to head impacts in traffic accidents need to be obviated. Finite element (FE) analyses with a human brain model facilitate understanding of the TBI mechanisms. However, conventional brain FE models do not suitably describe the anatomical structure in the deep brain, which is a critical region for executive brain function, and the material properties of brain parenchyma. In this study, for better TBI prediction, a novel brain FE model with anatomical structure in the deep brain was developed. The developed model comprises a constitutive model of brain parenchyma considering anisotropy and strain rate dependency. Validation was performed against postmortem human subject test data associated with brain deformation during head impact. Brain injury analyses were performed using head acceleration curves obtained from reconstruction analysis of rear-end collision with a human whole-body FE model. The difference in structure was found to affect the regions of strain concentration, while the difference in material model contributed to the peak strain value. The injury prediction result by the proposed model was consistent with the characteristics in the neuroimaging data of TBI patients due to traffic accidents.

Rib Geometry Explains Variation in Dynamic Structural Response: Potential Implications for Frontal Impact Fracture Risk.

PubMed

Murach, Michelle M; Kang, Yun-Seok; Goldman, Samuel D; Schafman, Michelle A; Schlecht, Stephen H; Moorhouse, Kevin; Bolte, John H; Agnew, Amanda M

2017-09-01

The human thorax is commonly injured in motor vehicle crashes, and despite advancements in occupant safety rib fractures are highly prevalent. The objective of this study was to quantify the ability of gross and cross-sectional geometry, separately and in combination, to explain variation of human rib structural properties. One hundred and twenty-two whole mid-level ribs from 76 fresh post-mortem human subjects were tested in a dynamic frontal impact scenario. Structural properties (peak force and stiffness) were successfully predicted (p < 0.001) by rib cross-sectional geometry obtained via direct histological imaging (total area, cortical area, and section modulus) and were improved further when utilizing a combination of cross-sectional and gross geometry (robusticity, whole bone strength index). Additionally, preliminary application of a novel, adaptive thresholding technique, allowed for total area and robusticity to be measured on a subsample of standard clinical CT scans with varied success. These results can be used to understand variation in individual rib response to frontal loading as well as identify important geometric parameters, which could ultimately improve injury criteria as well as the biofidelity of anthropomorphic test devices (ATDs) and finite element (FE) models of the human thorax.

Rib Geometry Explains Variation in Dynamic Structural Response: Potential Implications for Frontal Impact Fracture Risk

PubMed Central

Murach, Michelle M.; Kang, Yun-Seok; Goldman, Samuel D.; Schafman, Michelle A.; Schlecht, Stephen H.; Moorhouse, Kevin; Bolte, John H.; Agnew, Amanda M.

2018-01-01

The human thorax is commonly injured in motor vehicle crashes, and despite advancements in occupant safety rib fractures are highly prevalent. The objective of this study was to quantify the ability of gross and cross-sectional geometry, separately and in combination, to explain variation of human rib structural properties. One hundred and twenty-two whole mid-level ribs from 76 fresh post-mortem human subjects were tested in a dynamic frontal impact scenario. Structural properties (peak force and stiffness) were successfully predicted (p<0.001) by rib cross-sectional geometry obtained via direct histological imaging (total area, cortical area, and section modulus) and were improved further when utilizing a combination of cross-sectional and gross geometry (robusticity, whole bone strength index). Additionally, preliminary application of a novel, adaptive thresholding technique, allowed for total area and robusticity to be measured on a subsample of standard clinical CT scans with varied success. These results can be used to understand variation in individual rib response to frontal loading as well as identify important geometric parameters, which could ultimately improve injury criteria as well as the biofidelity of anthropomorphic test devices (ATDs) and finite element (FE) models of the human thorax. PMID:28547660

Separating endogenous ancient DNA from modern day contamination in a Siberian Neandertal

PubMed Central

Skoglund, Pontus; Northoff, Bernd H.; Shunkov, Michael V.; Derevianko, Anatoli P.; Pääbo, Svante; Krause, Johannes; Jakobsson, Mattias

2014-01-01

One of the main impediments for obtaining DNA sequences from ancient human skeletons is the presence of contaminating modern human DNA molecules in many fossil samples and laboratory reagents. However, DNA fragments isolated from ancient specimens show a characteristic DNA damage pattern caused by miscoding lesions that differs from present day DNA sequences. Here, we develop a framework for evaluating the likelihood of a sequence originating from a model with postmortem degradation—summarized in a postmortem degradation score—which allows the identification of DNA fragments that are unlikely to originate from present day sources. We apply this approach to a contaminated Neandertal specimen from Okladnikov Cave in Siberia to isolate its endogenous DNA from modern human contaminants and show that the reconstructed mitochondrial genome sequence is more closely related to the variation of Western Neandertals than what was discernible from previous analyses. Our method opens up the potential for genomic analysis of contaminated fossil material. PMID:24469802

Analyzing reflectance spectra of human skin in legal medicine

NASA Astrophysics Data System (ADS)

Belenki, Liudmila; Sterzik, Vera; Schulz, Katharina; Bohnert, Michael

2013-01-01

Our current research in the framework of an interdisciplinary project focuses on modelling the dynamics of the hemoglobin reoxygenation process in post-mortem human skin by reflectance spectrometry. The observations of reoxygenation of hemoglobin in livores after postmortem exposure to a cold environment relate the reoxygenation to the commonly known phenomenon that the color impression of livores changes from livid to pink under low ambient temperatures. We analyze the spectra with respect to a physical model describing the optical properties of human skin, discuss the dynamics of the reoxygenation, and propose a phenomenological model for reoxygenation. For additional characterization of the reflectance spectra, the curvature of the local minimum and maximum in the investigated spectral range is considered. There is a strong correlation between the curvature of specra at a wavelength of 560 nm and the concentration of O2-Hb. The analysis is carried out via C programs, as well as MySQL database queries in Java EE, JDBC, Matlab, and Python.

Analyzing reflectance spectra of human skin in legal medicine.

PubMed

Belenki, Liudmila; Sterzik, Vera; Schulz, Katharina; Bohnert, Michael

2013-01-01

Our current research in the framework of an interdisciplinary project focuses on modelling the dynamics of the hemoglobin reoxygenation process in post-mortem human skin by reflectance spectrometry. The observations of reoxygenation of hemoglobin in livores after postmortem exposure to a cold environment relate the reoxygenation to the commonly known phenomenon that the color impression of livores changes from livid to pink under low ambient temperatures. We analyze the spectra with respect to a physical model describing the optical properties of human skin, discuss the dynamics of the reoxygenation, and propose a phenomenological model for reoxygenation. For additional characterization of the reflectance spectra, the curvature of the local minimum and maximum in the investigated spectral range is considered. There is a strong correlation between the curvature of specra at a wavelength of 560 nm and the concentration of O2-Hb. The analysis is carried out via C programs, as well as MySQL database queries in Java EE, JDBC, Matlab, and Python.

Comparison of protocols for measuring and calculating postmortem submersion intervals for human analogs in fresh water.

PubMed

Humphreys, Michael K; Panacek, Edward; Green, William; Albers, Elizabeth

2013-03-01

Protocols for determining postmortem submersion interval (PMSI) have long been problematic for forensic investigators due to the wide variety of factors affecting the rate of decomposition of submerged carrion. Likewise, it has been equally problematic for researchers to develop standardized experimental protocols to monitor underwater decomposition without artificially affecting the decomposition rate. This study compares two experimental protocols: (i) underwater in situ evaluation with photographic documentation utilizing the Heaton et al. total aquatic decomposition (TAD) score and (ii) weighing the carrion before and after submersion. Complete forensic necropsies were performed as a control. Perinatal piglets were used as human analogs. The results of this study indicate that in order to objectively measure decomposition over time, the human analog should be examined at depth using the TAD scoring system rather than utilizing a carrion weight evaluation. The acquired TAD score can be used to calculate an approximate PMSI. © 2012 American Academy of Forensic Sciences.

Postmortem diffusion MRI of the human brainstem and thalamus for deep brain stimulator electrode localization.

PubMed

Calabrese, Evan; Hickey, Patrick; Hulette, Christine; Zhang, Jingxian; Parente, Beth; Lad, Shivanand P; Johnson, G Allan

2015-08-01

Deep brain stimulation (DBS) is an established surgical therapy for medically refractory tremor disorders including essential tremor (ET) and is currently under investigation for use in a variety of other neurologic and psychiatric disorders. There is growing evidence that the anti-tremor effects of DBS for ET are directly related to modulation of the dentatorubrothalamic tract (DRT), a white matter pathway that connects the cerebellum, red nucleus, and ventral intermediate nucleus of the thalamus. Emerging white matter targets for DBS, like the DRT, will require improved three-dimensional (3D) reference maps of deep brain anatomy and structural connectivity for accurate electrode targeting. High-resolution diffusion MRI of postmortem brain specimens can provide detailed volumetric images of important deep brain nuclei and 3D reconstructions of white matter pathways with probabilistic tractography techniques. We present a high spatial and angular resolution diffusion MRI template of the postmortem human brainstem and thalamus with 3D reconstructions of the nuclei and white matter tracts involved in ET circuitry. We demonstrate registration of these data to in vivo, clinical images from patients receiving DBS therapy, and correlate electrode proximity to tractography of the DRT with improvement of ET symptoms. © 2015 Wiley Periodicals, Inc.

Effects of vacuum and modified atmosphere on textural parameters and structural proteins of cultured meagre (Argyrosomus regius) fillets.

PubMed

Sáez, María I; Martínez, Tomás F; Cárdenas, Salvador; Suárez, María D

2015-09-01

The influence of two preservation strategies (vacuum package and modified atmosphere package) on the post-mortem changes of textural parameters, pH, water holding capacity, sarcoplasmic and myofibrillar proteins, and collagen content of meagre (Argyrosomus regius) fillets was studied. Fillets were stored in a cold room in aerobic (control, C), vacuum (V) and modified atmosphere (MA) package. Samples were withdrawn at six sampling points throughout 15-day storage, and post-mortem changes were assessed. The textural parameters were significantly enhanced in V and MA compared to C. Both V and MA treatments reduced the intensity of a group of myofibrillar protein fractions (140-195 kDa) and increased insoluble collagen compared to C. Consequently, the post-mortem flesh softening in C was attributed to increased proteolysis in both intracellular and extracellular structural proteins. The preservation of the textural and biochemical characteristics of meagre fillets subjected to V and MA treatments makes these two treatments highly recommendable for the commercialization of meagre fillets. © The Author(s) 2014.

Microbial communities associated with human decomposition and their potential use as postmortem clocks.

PubMed

Finley, Sheree J; Benbow, M Eric; Javan, Gulnaz T

2015-05-01

Most forensic research that is used to better understand how to estimate the postmortem interval (PMI) entails the study of the physiochemical characteristics of decomposition and the effects that environmental factors have on the decomposition process. Forensic entomology exploits the life cycles of arthropods like Diptera (blow flies or flesh flies) and Coleoptera (beetles) deposited on the decaying carcass to determine PMI. Forensic taphonomy, from the Greek word taphos meaning burial, studies the creation of the fossils of decomposed cadavers to ascertain information as to the nature and time of death. Compared to other areas of taphonomy, there have been relatively few forensic science studies that have investigated the impact of human decomposition on the microbial changes occurring on or in a corpse or in the soil communities underneath a body. Such research may facilitate the critical determination of PMI. Therefore, the scope of this review is to provide a concise summary of the current progress in the newly emerging field of microbial diversity and the next-generation metagenomic sequencing approaches for assessing these communities in humans and in the soil beneath decomposing human.

Normalizing and scaling of data to derive human response corridors from impact tests.

PubMed

Yoganandan, Narayan; Arun, Mike W J; Pintar, Frank A

2014-06-03

It is well known that variability is inherent in any biological experiment. Human cadavers (Post-Mortem Human Subjects, PMHS) are routinely used to determine responses to impact loading for crashworthiness applications including civilian (motor vehicle) and military environments. It is important to transform measured variables from PMHS tests (accelerations, forces and deflections) to a standard or reference population, termed normalization. The transformation process should account for inter-specimen variations with some underlying assumptions used during normalization. Scaling is a process by which normalized responses are converted from one standard to another (example, mid-size adult male to large-male and small-size female adults, and to pediatric populations). These responses are used to derive corridors to assess the biofidelity of anthropomorphic test devices (crash dummies) used to predict injury in impact environments and design injury mitigating devices. This survey examines the pros and cons of different approaches for obtaining normalized and scaled responses and corridors used in biomechanical studies for over four decades. Specifically, the equal-stress equal-velocity and impulse-momentum methods along with their variations are discussed in this review. Methods ranging from subjective to quasi-static loading to different approaches are discussed for deriving temporal mean and plus minus one standard deviation human corridors of time-varying fundamental responses and cross variables (e.g., force-deflection). The survey offers some insights into the potential efficacy of these approaches with examples from recent impact tests and concludes with recommendations for future studies. The importance of considering various parameters during the experimental design of human impact tests is stressed. Published by Elsevier Ltd.

Immunohistochemical Analysis of Human Vallate Taste Buds

PubMed Central

Tizzano, Marco; Grigereit, Laura; Shultz, Nicole; Clary, Matthew S.

2015-01-01

The morphology of the vallate papillae from postmortem human samples was investigated with immunohistochemistry. Microscopically, taste buds were present along the inner wall of the papilla, and in some cases in the outer wall as well. The typical taste cell markers PLCβ2, GNAT3 (gustducin) and the T1R3 receptor stain elongated cells in human taste buds consistent with the Type II cells in rodents. In the human tissue, taste bud cells that stain with Type II cell markers, PLCβ2 and GNAT3, also stain with villin antibody. Two typical immunochemical markers for Type III taste cells in rodents, PGP9.5 and SNAP25, fail to stain any taste bud cells in the human postmortem tissue, although these antibodies do stain numerous nerve fibers throughout the specimen. Car4, another Type III cell marker, reacted with only a few taste cells in our samples. Finally, human vallate papillae have a general network of innervation similar to rodents and antibodies directed against SNAP25, PGP9.5, acetylated tubulin and P2X3 all stain free perigemmal nerve endings as well as intragemmal taste fibers. We conclude that with the exception of certain molecular features of Type III cells, human vallate papillae share the structural, morphological, and molecular features observed in rodents. PMID:26400924

Optimized lower leg injury probability curves from postmortem human subject tests under axial impacts.

PubMed

Yoganandan, Narayan; Arun, Mike W J; Pintar, Frank A; Szabo, Aniko

2014-01-01

Derive optimum injury probability curves to describe human tolerance of the lower leg using parametric survival analysis. The study reexamined lower leg postmortem human subjects (PMHS) data from a large group of specimens. Briefly, axial loading experiments were conducted by impacting the plantar surface of the foot. Both injury and noninjury tests were included in the testing process. They were identified by pre- and posttest radiographic images and detailed dissection following the impact test. Fractures included injuries to the calcaneus and distal tibia-fibula complex (including pylon), representing severities at the Abbreviated Injury Score (AIS) level 2+. For the statistical analysis, peak force was chosen as the main explanatory variable and the age was chosen as the covariable. Censoring statuses depended on experimental outcomes. Parameters from the parametric survival analysis were estimated using the maximum likelihood approach and the dfbetas statistic was used to identify overly influential samples. The best fit from the Weibull, log-normal, and log-logistic distributions was based on the Akaike information criterion. Plus and minus 95% confidence intervals were obtained for the optimum injury probability distribution. The relative sizes of the interval were determined at predetermined risk levels. Quality indices were described at each of the selected probability levels. The mean age, stature, and weight were 58.2±15.1 years, 1.74±0.08 m, and 74.9±13.8 kg, respectively. Excluding all overly influential tests resulted in the tightest confidence intervals. The Weibull distribution was the most optimum function compared to the other 2 distributions. A majority of quality indices were in the good category for this optimum distribution when results were extracted for 25-, 45- and 65-year-olds at 5, 25, and 50% risk levels age groups for lower leg fracture. For 25, 45, and 65 years, peak forces were 8.1, 6.5, and 5.1 kN at 5% risk; 9.6, 7.7, and 6.1 kN at 25% risk; and 10.4, 8.3, and 6.6 kN at 50% risk, respectively. This study derived axial loading-induced injury risk curves based on survival analysis using peak force and specimen age; adopting different censoring schemes; considering overly influential samples in the analysis; and assessing the quality of the distribution at discrete probability levels. Because procedures used in the present survival analysis are accepted by international automotive communities, current optimum human injury probability distributions can be used at all risk levels with more confidence in future crashworthiness applications for automotive and other disciplines.

DNA and RNA profiling of excavated human remains with varying postmortem intervals.

PubMed

van den Berge, M; Wiskerke, D; Gerretsen, R R R; Tabak, J; Sijen, T

2016-11-01

When postmortem intervals (PMIs) increase such as with longer burial times, human remains suffer increasingly from the taphonomic effects of decomposition processes such as autolysis and putrefaction. In this study, various DNA analysis techniques and a messenger RNA (mRNA) profiling method were applied to examine for trends in nucleic acid degradation and the postmortem interval. The DNA analysis techniques include highly sensitive DNA quantitation (with and without degradation index), standard and low template STR profiling, insertion and null alleles (INNUL) of retrotransposable elements typing and mitochondrial DNA profiling. The used mRNA profiling system targets genes with tissue specific expression for seven human organs as reported by Lindenbergh et al. (Int J Legal Med 127:891-900, 27) and has been applied to forensic evidentiary traces but not to excavated tissues. The techniques were applied to a total of 81 brain, lung, liver, skeletal muscle, heart, kidney and skin samples obtained from 19 excavated graves with burial times ranging from 4 to 42 years. Results show that brain and heart are the organs in which both DNA and RNA remain remarkably stable, notwithstanding long PMIs. The other organ tissues either show poor overall profiling results or vary for DNA and RNA profiling success, with sometimes DNA and other times RNA profiling being more successful. No straightforward relations were observed between nucleic acid profiling results and the PMI. This study shows that not only DNA but also RNA molecules can be remarkably stable and used for profiling of long-buried human remains, which corroborate forensic applications. The insight that the brain and heart tissues tend to provide the best profiling results may change sampling policies in identification cases of degrading cadavers.

Optimized magnetic resonance diffusion protocol for ex-vivo whole human brain imaging with a clinical scanner

NASA Astrophysics Data System (ADS)

Scherrer, Benoit; Afacan, Onur; Stamm, Aymeric; Singh, Jolene; Warfield, Simon K.

2015-03-01

Diffusion-weighted magnetic resonance imaging (DW-MRI) provides a novel insight into the brain to facilitate our understanding of the brain connectivity and microstructure. While in-vivo DW-MRI enables imaging of living patients and longitudinal studies of brain changes, post-mortem ex-vivo DW-MRI has numerous advantages. Ex-vivo imaging benefits from greater resolution and sensitivity due to the lack of imaging time constraints; the use of tighter fitting coils; and the lack of movement artifacts. This allows characterization of normal and abnormal tissues with unprecedented resolution and sensitivity, facilitating our ability to investigate anatomical structures that are inaccessible in-vivo. This also offers the opportunity to develop today novel imaging biomarkers that will, with tomorrow's MR technology, enable improved in-vivo assessment of the risk of disease in an individual. Post-mortem studies, however, generally rely on the fixation of specimen to inhibit tissue decay which starts as soon as tissue is deprived from its blood supply. Unfortunately, fixation of tissues substantially alters tissue diffusivity profiles. In addition, ex-vivo DW-MRI requires particular care when packaging the specimen because the presence of microscopic air bubbles gives rise to geometric and intensity image distortion. In this work, we considered the specific requirements of post-mortem imaging and designed an optimized protocol for ex-vivo whole brain DW-MRI using a human clinical 3T scanner. Human clinical 3T scanners are available to a large number of researchers and, unlike most animal scanners, have a bore diameter large enough to image a whole human brain. Our optimized protocol will facilitate widespread ex-vivo investigations of large specimen.

[Morphological characteristic of Langerhans cells from the human epidermis in case of general hypothermia].

PubMed

Stefanenko, E V; Miadelets, O D; Kukhnovets, O A; Miadelets, V O

2009-01-01

The objective of this work was to study morphological changes in the Langerhans cells of epidermis and epithelium of hair follicles from subjects who died as a result of general hypothermia. A total of 105 cadaveric skin samples from subjects of either gender aged from 19 to 83 years were available for analysis. Postmortem examination 1-2 days after death was performed at the Department of Forensic Medical Examination for the Vitebsk region. Skin samples were frozen in liquid nitrogen and studied as cryostat sections. Langerhans cells were detected using the ATPase assay as described by Wachstein and Meisel and modified by Robins and Brendon. The Langerhans cells of subjects who died from general hypothermia were shown to undergo marked morphological changes. Moreover, their number significantly decreased as a result of disintegration and transformation into fine-grain material. Surviving cells lost many of their outgrowths and exhibited enhanced ATPase activity in pericarion. The Langerhans cells from dorsal and ventral skin as well as from interfollicular epidermis and the outer sheath of hair follicles underwent virtually identical changes. A unique morphological feature of the skin in those who died from general hypothermia was formation of intraepidermal, subepidermal, and dermal blisters.

Lung ultrasound accurately detects pneumothorax in a preterm newborn lamb model.

PubMed

Blank, Douglas A; Hooper, Stuart B; Binder-Heschl, Corinna; Kluckow, Martin; Gill, Andrew W; LaRosa, Domenic A; Inocencio, Ishmael M; Moxham, Alison; Rodgers, Karyn; Zahra, Valerie A; Davis, Peter G; Polglase, Graeme R

2016-06-01

Pneumothorax is a common emergency affecting extremely preterm. In adult studies, lung ultrasound has performed better than chest x-ray in the diagnosis of pneumothorax. The purpose of this study was to determine the efficacy of lung ultrasound (LUS) examination to detect pneumothorax using a preterm animal model. This was a prospective, observational study using newborn Border-Leicester lambs at gestational age = 126 days (equivalent to gestational age = 26 weeks in humans) receiving mechanical ventilation from birth to 2 h of life. At the conclusion of the experiment, LUS was performed, the lambs were then euthanised and a post-mortem exam was immediately performed. We used previously published ultrasound techniques to identify pneumothorax. Test characteristics of LUS to detect pneumothorax were calculated, using the post-mortem exam as the 'gold standard' test. Nine lambs (18 lungs) were examined. Four lambs had a unilateral pneumothorax, all of which were identified by LUS with no false positives. This was the first study to use post-mortem findings to test the efficacy of LUS to detect pneumothorax in a newborn animal model. Lung ultrasound accurately detected pneumothorax, verified by post-mortem exam, in premature, newborn lambs. © 2016 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

TECHNICAL BRIEF: Isolation of total DNA from postmortem human eye tissues and quality comparison between iris and retina

PubMed Central

Wang, Jay Ching Chieh; Wang, Aikun; Gao, Jiangyuan; Cao, Sijia; Samad, Idris; Zhang, Dean; Ritland, Carol; Cui, Jing Z.

2012-01-01

Background Recent genomic technologies have propelled our understanding of the mechanisms underlying complex eye diseases such as age-related macular degeneration (AMD). Genotyping postmortem eye tissues for known single nucleotide polymorphisms (SNPs) associated with AMD may prove valuable, especially when combined with information obtained through other methods such as immunohistochemistry, western blot, enzyme-linked immunosorbent assay (ELISA), and proteomics. Initially intending to genotype postmortem eye tissues for AMD-related SNPs, our group became interested in isolating and comparing the quality of DNA from the iris and retina of postmortem donor eyes. Since there is no previously published protocol in the literature on this topic, we present a protocol suitable for isolating high-quality DNA from postmortem eye tissues for genomic studies. Methods DNA from 33 retinal samples and 35 iris samples was extracted using the phenol-chloroform-isoamyl method from postmortem donor eye tissues. The quantity of DNA was measured with a spectrophotometer while the quality was checked using gel electrophoresis. The DNA samples were then amplified with PCR for the complement factor H (CFH) gene. The purified amplified products were then genotyped for the SNPs in the CFH gene. Results Regarding concentration, the retina yielded 936 ng/μl of DNA, while the iris yielded 78 ng/μl of DNA. Retinal DNA was also purer than iris DNA (260/280=1.78 vs. 1.46, respectively), and produced superior PCR results. Retinal tissue yielded significantly more DNA than the iris tissue per mg of sample (21.7 ng/μl/mg vs. 7.42 ng/μl/mg). Retinal DNA can be readily amplified with PCR, while iris DNA can also be amplified by adding bovine serum albumin. Overall, retinal tissues yielded DNA of superior quality, quantity, and suitability for genotyping and genomic studies. Conclusions The protocol presented here provides a clear and reliable method for isolating total DNA from postmortem eye tissues. Retinal tissue provides DNA of excellent quantity and quality for genotyping and downstream genomic studies. However, DNA isolated from iris tissues, and treated with bovine serum albumin, may also be a valuable source of DNA for genotyping and genomic studies. PMID:23288996

Investigating the Postmortem Molecular Biology of Cartilage and its Potential Forensic Applications.

PubMed

Bolton, Shawna N; Whitehead, Michael P; Dudhia, Jayesh; Baldwin, Timothy C; Sutton, Raul

2015-07-01

This study investigated the postmortem molecular changes that articular cartilage undergoes following burial. Fresh pig trotters were interred in 30-cm-deep graves at two distinct locations exhibiting dissimilar soil environments for up to 42 days. Extracts of the metacarpophalangeal (MCP) and metatarsophalangeal (MTP) joint cartilage from trotters disinterred weekly over 6 weeks were analyzed by Western blot against the monoclonal antibody 2-B-6 to assess aggrecan degradation. In both soil conditions, aggrecan degradation by-products of decreasing molecular size and complexity were observed up to 21 days postmortem. Degradation products were undetected after this time and coincided with MCP/MTP joint exposure to the soil environment. These results show that cartilage proteoglycans undergo an ordered molecular breakdown, the analysis of which may have forensic applications. This model may prove useful for use as a human model and for forensic investigations concerning crimes against animals and the mortality of endangered species. © 2015 American Academy of Forensic Sciences.

Cryptococcosis in Acquired Immunodeficiency Syndrome Patients Clinically Confirmed and/or Diagnosed at Necropsy in a Teaching Hospital in Brazil

PubMed Central

Garcia Torres, Rafael; Etchebehere, Renata Margarida; Adad, Sheila Jorge; Micheletti, Adilha Rua; Ribeiro, Barbara de Melo; Silva, Leonardo Eurípedes Andrade; Mora, Delio Jose; Paim, Kennio Ferreira; Silva-Vergara, Mario León

2016-01-01

Cryptococcosis occurs in acquired immunodeficiency syndrome (AIDS) patients with poor compliance to antiretroviral therapy or unaware of their human immunodeficiency virus status who present severe immunosuppression at admission. Consequently, high mortality rates are observed due to disseminated fungal infection. This report presents clinical and postmortem data of AIDS patients with cryptococcosis in a teaching hospital in Brazil. Retrospectively, medical and necropsy records of AIDS patients with cryptococcosis clinically confirmed and/or postmortem verified were reviewed. Clinical data were compared with those of patients presenting a good outcome to evaluate disseminated fungal infection and the agreement between clinical and postmortem diagnosis. At admission, most of the 45 patients with cryptococcal meningitis who died, presented more altered consciousness (P = 0.0047), intracranial increased pressure (P = 0.047), and severe malnutrition (P = 0.0006) than the survivors. Of 29 (64.4%) patients with cryptococcal meningitis, 23 died before week 2 on antifungal therapy, and the other six during the next 3 months. The remaining 16 (35.6%) cases had other diagnoses and died soon after. At necropsy, 31 (68.9%) presented disseminated infection involving two or more organs, whereas 14 (31.1%) cases had meningeal or pulmonary localized infection. The agreement of 64.4% between clinical and postmortem diagnosis was similar to some studies. However, other reports have shown figures ranging from 34% to 95%. Currently, a progressive worldwide decrease of autopsies is worrying because the role of postmortem examination is pivotal to verify or identify the death causes, which contributes to improve the quality of clinical diagnosis and medical training. PMID:27458037

Muslim customs surrounding death, bereavement, postmortem examinations, and organ transplants.

PubMed Central

Gatrad, A. R.

1994-01-01

Muslims are always buried, never cremated. It is a religious requirement that the body be ritually washed and draped before burial, which should be as soon as possible after death. Those carrying out this duty should be immunised against hepatitis B and be aware of the hazards of AIDS. Muslim women never attend burials and it is rare for funeral directors to be involved. Muslim jurists from the Arab world can justify organ transplantation, but those from the Indian subcontinent are against it. They are united in the belief of the sacredness of the human body and thus deplore postmortem examinations. Images p522-a PMID:7848419

Purification and characterization of tripeptidylpeptidase-II from post-mortem human brain.

PubMed

Wilson, C; Gibson, A M; McDermott, J R

1993-07-01

A soluble tripeptidylaminopeptidase has been isolated from human post-mortem cerebral cortex by anion exchange, hydrophobic interaction and size-exclusion chromatography. From gel filtration studies the active enzyme can exist in both high molecular weight (M(r) > 10(6) and smaller forms. The enzyme hydrolyses Ala-Ala-Phe-7-amido-4-methylcoumarin with a pH optimum of around 7.5 and Km of 148 microM. It did not hydrolyse N-succinyl-Ala-Ala-Phe-7-amido-4-methylcoumarin, aminoacyl- or dipeptidyl-7-amido-methylcoumarins and was not inhibited by bestatin. The enzyme was inhibited by phenylmethylsulphonyl-fluoride, 3,4-dichloroisocoumarin, N-hydroxymercuriphenyl-sulphonic acid and N-ethylmaleimide showing that its activity is serine and cysteine dependent. The purified enzyme released tripeptides from several naturally occurring neuropeptides with quite broad specificity. Cholecystokinin octapeptide, angiotensin III and neurokinin A were the most rapidly hydrolysed. Peptides with Pro residues around the point of cleavage were not hydrolysed.

Distinct Lineage of Vesiculovirus from Big Brown Bats, United States

PubMed Central

Driscoll, Cindy; Carlos, Maria Paz; Prioleau, Algernon; Schmieder, Robert; Dwivedi, Bhakti; Wong, Jakk; Cha, Yunhee; Head, Steven; Breitbart, Mya; Delwart, Eric

2013-01-01

We identified a novel rhabdovirus, American bat vesiculovirus, from postmortem tissue samples from 120 rabies-negative big brown bats with a history of human contact. Five percent of the tested bats were infected with this virus. The extent of zoonotic exposure and possible health effects in humans from this virus are unknown. PMID:24274823

MATERNAL INFECTION AND IMMUNE INVOLVEMENT IN AUTISM

PubMed Central

Patterson, Paul H.

2011-01-01

Recent studies have highlighted a connection between infection during pregnancy and increased risk for autism in the offspring. Parallel studies of cerebral spinal fluid, blood, and postmortem brains reveal an ongoing, hyper-responsive inflammatory-like state in many young as well as adult autism subjects. There are also indications of gastrointestinal problems in at least a subset of autistic children. Work with animal models of the maternal infection risk factor indicate that aspects of brain and peripheral immune dysregulation can be begin during fetal development and be maintained through adulthood. The offspring of infected, or immune-activated dams also display cardinal behavioral features of autism, as well as neuropathology consistent with that seen in human autism. These rodent models are proving useful for the study of pathogenesis and gene-environment interaction, as well as for the exploration of potential therapeutic strategies. PMID:21482187

Postmortem brain MRI with selective tissue biopsy as an adjunct to autopsy following neonatal encephalopathy.

PubMed

Nicholl, R M; Balasubramaniam, V P; Urquhart, D S; Sellathurai, N; Rutherford, M A

2007-05-01

Following the death of a neonate it is essential that parents are given full and accurate information about the probable cause of death. Perinatal autopsy often adds new information or may even change the presumed diagnosis [Cartlidge PH, Dawson AT, Stewart JH, Vujanic GM. Value and quality of perinatal and infant postmortem examinations: cohort analysis of 400 consecutive deaths. Br Med J 1995;310(6973):155-8; Khong TY. Falling neonatal autopsy rates. Br Med J 2002;324(7340):749-50] informing decisions regarding the management of any future pregnancy. Autopsy can be considered the "gold standard" for the identification of antecedent events leading to a neonatal death. However, recent events in the UK have added to an already declining rate in neonatal autopsies [Brodlie M, Laing IA. Ten years of neonatal autopsies in tertiary referral centre: retrospective study. Br Med J 2002;324(7340):761-3]. To try and redress this balance the Chief Medical Officer has recommended that research should be commissioned into the use of non-invasive imaging to provide a similar standard of information [The Chief Medical Officer. The removal, retention and use of human organs and tissues from post mortem examination. London, England: The Stationary Office, Department of Health; 2001]. Previous publications on postmortem MRI have focused largely on investigation of the foetus and of still birth [Griffiths PD, Variend D, Evans M, Jones A, Wilkinson ID, Paley MNJ, et al. Postmortem MR imaging of the fetal and stillborn central nervous system. Am J Neuroradiol 2003;24(1):22-7; Whitby EH, Paley MN, Cohen M, GriffithsPD. Postmortem MR imaging of the fetus: an adjunct or a replacement for conventional autopsy? Semin Fetal Neonatal Med 2005;10(5):475-83]. We report our experience on the use of postmortem brain MRI combined with selective tissue biopsy, in six neonatal deaths in the setting of a large district general hospital.

Circuit- and Diagnosis-Specific DNA Methylation Changes at γ-Aminobutyric Acid-Related Genes in Postmortem Human Hippocampus in Schizophrenia and Bipolar Disorder.

PubMed

Ruzicka, W Brad; Subburaju, Sivan; Benes, Francine M

2015-06-01

Dysfunction related to γ-aminobutyric acid (GABA)-ergic neurotransmission in the pathophysiology of major psychosis has been well established by the work of multiple groups across several decades, including the widely replicated downregulation of GAD1. Prior gene expression and network analyses within the human hippocampus implicate a broader network of genes, termed the GAD1 regulatory network, in regulation of GAD1 expression. Several genes within this GAD1 regulatory network show diagnosis- and sector-specific expression changes within the circuitry of the hippocampus, influencing abnormal GAD1 expression in schizophrenia and bipolar disorder. To investigate the hypothesis that aberrant DNA methylation contributes to circuit- and diagnosis-specific abnormal expression of GAD1 regulatory network genes in psychotic illness. This epigenetic association study targeting GAD1 regulatory network genes was conducted between July 1, 2012, and June 30, 2014. Postmortem human hippocampus tissue samples were obtained from 8 patients with schizophrenia, 8 patients with bipolar disorder, and 8 healthy control participants matched for age, sex, postmortem interval, and other potential confounds from the Harvard Brain Tissue Resource Center, McLean Hospital, Belmont, Massachusetts. We extracted DNA from laser-microdissected stratum oriens tissue of cornu ammonis 2/3 (CA2/3) and CA1 postmortem human hippocampus, bisulfite modified it, and assessed it with the Infinium HumanMethylation450 BeadChip (Illumina, Inc). The subset of CpG loci associated with GAD1 regulatory network genes was analyzed in R version 3.1.0 software (R Foundation) using the minfi package. Findings were validated using bisulfite pyrosequencing. Methylation levels at 1308 GAD1 regulatory network-associated CpG loci were assessed both as individual sites to identify differentially methylated positions and by sharing information among colocalized probes to identify differentially methylated regions. A total of 146 differentially methylated positions with a false detection rate lower than 0.05 were identified across all 6 groups (2 circuit locations in each of 3 diagnostic categories), and 54 differentially methylated regions with P < .01 were identified in single-group comparisons. Methylation changes were enriched in MSX1, CCND2, and DAXX at specific loci within the hippocampus of patients with schizophrenia and bipolar disorder. This work demonstrates diagnosis- and circuit-specific DNA methylation changes at a subset of GAD1 regulatory network genes in the human hippocampus in schizophrenia and bipolar disorder. These genes participate in chromatin regulation and cell cycle control, supporting the concept that the established GABAergic dysfunction in these disorders is related to disruption of GABAergic interneuron physiology at specific circuit locations within the human hippocampus.

Circuit- and Diagnosis-Specific DNA Methylation Changes at γ-Aminobutyric Acid–Related Genes in Postmortem Human Hippocampus in Schizophrenia and Bipolar Disorder

PubMed Central

Ruzicka, W. Brad; Subburaju, Sivan; Benes, Francine M.

2017-01-01

IMPORTANCE Dysfunction related to γ-aminobutyric acid (GABA)–ergic neurotransmission in the pathophysiology of major psychosis has been well established by the work of multiple groups across several decades, including the widely replicated downregulation of GAD1. Prior gene expression and network analyses within the human hippocampus implicate a broader network of genes, termed the GAD1 regulatory network, in regulation of GAD1 expression. Several genes within this GAD1 regulatory network show diagnosis- and sector-specific expression changes within the circuitry of the hippocampus, influencing abnormal GAD1 expression in schizophrenia and bipolar disorder. OBJECTIVE To investigate the hypothesis that aberrant DNA methylation contributes to circuit- and diagnosis-specific abnormal expression of GAD1 regulatory network genes in psychotic illness. DESIGN, SETTING, AND PARTICIPANTS This epigenetic association study targeting GAD1 regulatory network genes was conducted between July 1, 2012, and June 30, 2014. Postmortem human hippocampus tissue samples were obtained from 8patients with schizophrenia, 8 patients with bipolar disorder, and 8 healthy control participants matched for age, sex, postmortem interval, and other potential confounds from the Harvard Brain Tissue Resource Center, McLean Hospital, Belmont,Massachusetts. We extracted DNA from laser-microdissected stratum oriens tissue of cornu ammonis 2/3 (CA2/3) and CA1 postmortem human hippocampus, bisulfite modified it, and assessed it with the Infinium HumanMethylation450 BeadChip (Illumina, Inc). The subset of CpG loci associated with GAD1 regulatory network genes was analyzed in R version 3.1.0 software (R Foundation) using the minfi package. Findings were validated using bisulfite pyrosequencing. MAIN OUTCOMES AND MEASURES Methylation levels at 1308 GAD1 regulatory network–associated CpG loci were assessed both as individual sites to identify differentially methylated positions and by sharing information among colocalized probes to identify differentially methylated regions. RESULTS A total of 146 differentially methylated positions with a false detection rate lower than 0.05 were identified across all 6 groups (2 circuit locations in each of 3 diagnostic categories), and 54 differentially methylated regions with P < .01 were identified in single-group comparisons. Methylation changes were enriched in MSX1, CCND2, and DAXX at specific loci within the hippocampus of patients with schizophrenia and bipolar disorder. CONCLUSIONS AND RELEVANCE This work demonstrates diagnosis- and circuit-specific DNA methylation changes at a subset of GAD1 regulatory network genes in the human hippocampus in schizophrenia and bipolar disorder. These genes participate in chromatin regulation and cell cycle control, supporting the concept that the established GABAergic dysfunction in these disorders is related to disruption of GABAergic interneuron physiology at specific circuit locations within the human hippocampus. PMID:25738424

Lower Leg Injury Reference Values and Risk Curves from Survival Analysis for Male and Female Dummies: Meta-analysis of Postmortem Human Subject Tests.

PubMed

Yoganandan, Narayan; Arun, Mike W J; Pintar, Frank A; Banerjee, Anjishnu

2015-01-01

Derive lower leg injury risk functions using survival analysis and determine injury reference values (IRV) applicable to human mid-size male and small-size female anthropometries by conducting a meta-analysis of experimental data from different studies under axial impact loading to the foot-ankle-leg complex. Specimen-specific dynamic peak force, age, total body mass, and injury data were obtained from tests conducted by applying the external load to the dorsal surface of the foot of postmortem human subject (PMHS) foot-ankle-leg preparations. Calcaneus and/or tibia injuries, alone or in combination and with/without involvement of adjacent articular complexes, were included in the injury group. Injury and noninjury tests were included. Maximum axial loads recorded by a load cell attached to the proximal end of the preparation were used. Data were analyzed by treating force as the primary variable. Age was considered as the covariate. Data were censored based on the number of tests conducted on each specimen and whether it remained intact or sustained injury; that is, right, left, and interval censoring. The best fits from different distributions were based on the Akaike information criterion; mean and plus and minus 95% confidence intervals were obtained; and normalized confidence interval sizes (quality indices) were determined at 5, 10, 25, and 50% risk levels. The normalization was based on the mean curve. Using human-equivalent age as 45 years, data were normalized and risk curves were developed for the 50th and 5th percentile human size of the dummies. Out of the available 114 tests (76 fracture and 38 no injury) from 5 groups of experiments, survival analysis was carried out using 3 groups consisting of 62 tests (35 fracture and 27 no injury). Peak forces associated with 4 specific risk levels at 25, 45, and 65 years of age are given along with probability curves (mean and plus and minus 95% confidence intervals) for PMHS and normalized data applicable to male and female dummies. Quality indices increased (less tightness-of-fit) with decreasing age and risk level for all age groups and these data are given for all chosen risk levels. These PMHS-based probability distributions at different ages using information from different groups of researchers constituting the largest body of data can be used as human tolerances to lower leg injury from axial loading. Decreasing quality indices (increasing index value) at lower probabilities suggest the need for additional tests. The anthropometry-specific mid-size male and small-size female mean human risk curves along with plus and minus 95% confidence intervals from survival analysis and associated IRV data can be used as a first step in studies aimed at advancing occupant safety in automotive and other environments.

Clinical criteria for the diagnosis of Alzheimer disease: still good after all these years.

PubMed

Ranginwala, Najeeb A; Hynan, Linda S; Weiner, Myron F; White, Charles L

2008-05-01

To examine the impact of newer neuropathological techniques on the power of National Institute of Neurological and Communicative Disorders and Stroke-AD and Related Disorders Association criteria for Alzheimer disease (AD) to detect AD at later postmortem study. We examined clinical and postmortem diagnoses of persons evaluated postmortem with thioflavin-S staining for plaques and tangles and immunohistochemical staining techniques for alpha synuclein, uhiquitin, and tau protein. Alzheimer Disease Center. Clinically evaluated persons for whom tissue diagnosis was available. Of 313 evaluees, 166 met criteria for probable AD. An additional 59 subjects had clinical diagnoses that included AD, e.g., possible AD, Lewy body variant of AD, AD and Parkinsonism, and mixed AD and vascular dementia. Of the 166 probable AD cases, 147 of 166 (88.6%) met pathologic criteria for AD. When all five AD groups were combined, 194 of 225 subjects (86.2%) met pathologic criteria for AD. There were five cases diagnosed pathologically as tangle-only dementia, which was considered a variant of AD. A pathologic diagnosis of Lewy body variant of AD was made in 56 (17.9%) of cases, including 44 of 313 (14.1%) cases diagnosed as probable or possible AD. Pure dementia with Lewy bodies was seen in 13 (4.2%). There were 9 (2.9%) cases of mixed AD and vascular dementia, and 37 (11.4%) cases of frontotemporal dementia. McKhann et al. criteria for probable and possible AD are valid for AD but do not exclude additional Lewy body pathology.

The Brain Connection: The Corpus Callosum is Larger in Left-Handers.

ERIC Educational Resources Information Center

Witelson, Sandra F.

1985-01-01

Discusses the neurobiological basis for functional specialization of the cerebral hemispheres, indicating that the size of the corpus callosum is correlated with the neurophysiological measure of hand preference. In postmortem examinations of 42 subjects there were no sex differences, but mixed-handers had significantly larger total areas of the…

Preliminary Investigation of Skull Fracture Patterns Using an Impactor Representative of Helmet Back-Face Deformation.

PubMed

Weisenbach, Charles A; Logsdon, Katie; Salzar, Robert S; Chancey, Valeta Carol; Brozoski, Fredrick

2018-03-01

Military combat helmets protect the wearer from a variety of battlefield threats, including projectiles. Helmet back-face deformation (BFD) is the result of the helmet defeating a projectile and deforming inward. Back-face deformation can result in localized blunt impacts to the head. A method was developed to investigate skull injury due to BFD behind-armor blunt trauma. A representative impactor was designed from the BFD profiles of modern combat helmets subjected to ballistic impacts. Three post-mortem human subject head specimens were each impacted using the representative impactor at three anatomical regions (frontal bone, right/left temporo-parietal regions) using a pneumatic projectile launcher. Thirty-six impacts were conducted at energy levels between 5 J and 25 J. Fractures were detected in two specimens. Two of the specimens experienced temporo-parietal fractures while the third specimen experienced no fractures. Biomechanical metrics, including impactor acceleration, were obtained for all tests. The work presented herein describes initial research utilizing a test method enabling the collection of dynamic exposure and biomechanical response data for the skull at the BFD-head interface.

Nigral dopamine type-1 receptors are reduced in Huntington's disease: A postmortem autoradiographic study using ( sup 3 H)SCH 23390 and correlation with ( sup 3 H)forskolin binding

DOE Office of Scientific and Technical Information (OSTI.GOV)

Filloux, F.; Wagster, M.V.; Folstein, S.

1990-11-01

Intrastriatal injection of excitatory amino acids, particularly quinolinic acid, has been proposed as an animal model of Huntington's disease. Such neurotoxic lesions of caudate-putamen result in marked dopamine type-1 (D1) receptor losses in the injected nuclei as well as in the ipsilateral substantia nigra pars reticulata. Postmortem human substantia nigra from Huntington's disease brains and from control brains were examined using in vitro autoradiography. A marked reduction in ({sup 3}H)SCH 23390 binding (labeling D1 receptors) in the substantia nigra of postmortem brains of Huntington's patients was identified, thus paralleling the alterations seen in the animal models. A positive, statistically significantmore » correlation was also encountered between D1 receptor binding (labeled by ({sup 3}H)SCH 23390) and ({sup 3}H)forskolin binding (which identifies adenylate cyclase, a second messenger system linked to D1 receptor activation). The results suggest that in the human--as in lower vertebrates--D1 receptors are located on striatonigral terminals and that D1 receptor loss tends to be paralleled by a reduction in adenylate cyclase. Radioactive agents selective for the D1 receptor may prove useful in future studies of Huntington's disease using positron emission tomography scanning.« less

Quantifying human decomposition in an indoor setting and implications for postmortem interval estimation.

PubMed

Ceciliason, Ann-Sofie; Andersson, M Gunnar; Lindström, Anders; Sandler, Håkan

2018-02-01

This study's objective is to obtain accuracy and precision in estimating the postmortem interval (PMI) for decomposing human remains discovered in indoor settings. Data were collected prospectively from 140 forensic cases with a known date of death, scored according to the Total Body Score (TBS) scale at the post-mortem examination. In our model setting, it is estimated that, in cases with or without the presence of blowfly larvae, approximately 45% or 66% respectively, of the variance in TBS can be derived from Accumulated Degree-Days (ADD). The precision in estimating ADD/PMI from TBS is, in our setting, moderate to low. However, dividing the cases into defined subgroups suggests the possibility to increase the precision of the model. Our findings also suggest a significant seasonal difference with concomitant influence on TBS in the complete data set, possibly initiated by the presence of insect activity mainly during summer. PMI may be underestimated in cases with presence of desiccation. Likewise, there is a need for evaluating the effect of insect activity, to avoid overestimating the PMI. Our data sample indicates that the scoring method might need to be slightly modified to better reflect indoor decomposition, especially in cases with insect infestations or/and extensive desiccation. When applying TBS in an indoor setting, the model requires distinct inclusion criteria and a defined population. Copyright © 2017 Elsevier B.V. All rights reserved.

How Well Does the Latest Anthropomorphic Test Device Mimic Human Impact Responses?

NASA Technical Reports Server (NTRS)

Newby, N.; Somers, J. T.; Caldwell, E.; Gernhardt, M.

2014-01-01

One of the goals of the NASA Occupant Protection Group is to understand the human tolerance to dynamic loading. This knowledge has to come through indirect approaches such as existing human response databases, anthropometric test devices (ATD), animal testing, post-mortem human subjects, and models. This study investigated the biofidelity of the National Highway Traffic Safety Administration's ATD named the THOR (test device for human occupant restraint). If THOR responds comparably to humans, then it could potentially be used as a human surrogate to help validate space vehicle requirements for occupant protection. The THOR responses to frontal and spinal impacts (ranging from 8 to 12 G with rise times of 40, 70, and 100 ms) were measured and compared to human volunteer responses (95 trials in frontal and 58 in spinal) previously collected by the U. S. Air Force on the same horizontal impact accelerator. The impact acceleration profiles tested are within the expected range of multi-purpose crew vehicle (MPCV) landing dynamics. A correlation score was calculated for each THOR to human comparison using CORA (CORrelation and Analysis) software. A two-parameter beta distribution model fit was obtained for each dependent variable using maximum likelihood estimation. For frontal impacts, the THOR head x-acceleration peak response correlated with the human response at 8 and 10-G 100 ms but not 10-G 70 ms. The phase lagged the human response. Head z-acceleration was not correlated. Chest x-acceleration was in phase, had a higher peak response, and was well correlated with lighter subjects (Cora = 0.8 for 46 kg vs. Cora = 0.4 for 126 kg). Head x-displacement had a leading phase. Several subjects responded with the same peak displacement but the mean of the group was lower. The shoulder x-displacement was in phase but had higher peaks than the human response. For spinal impacts, the THOR head x-acceleration was not well correlated. Head and chest z-acceleration was in phase but had a higher peak response. Chest z-acceleration was highly correlated with heavier subjects at lower G pulses (Cora = 0.86 for 125 kg at 8 G). The human response was variable in shoulder z-displacement but the THOR was in phase and was comparable to the mean peak response. Head xand z-displacement was in phase but had higher peaks. Seat pan forces were well correlated, were in phase, but had a larger peak response than most subjects. The THOR does not respond to frontal and spinal impacts exactly the same way that a human does. Some responses are well matched and others are not. Understanding the strengths and weaknesses of this ATD is an important first step in determining its usefulness in occupant protection at NASA

Single cell gene expression profiling in Alzheimer's disease.

PubMed

Ginsberg, Stephen D; Che, Shaoli; Counts, Scott E; Mufson, Elliott J

2006-07-01

Development and implementation of microarray techniques to quantify expression levels of dozens to hundreds to thousands of transcripts simultaneously within select tissue samples from normal control subjects and neurodegenerative diseased brains has enabled scientists to create molecular fingerprints of vulnerable neuronal populations in Alzheimer's disease (AD) and related disorders. A goal is to sample gene expression from homogeneous cell types within a defined region without potential contamination by expression profiles of adjacent neuronal subpopulations and nonneuronal cells. The precise resolution afforded by single cell and population cell RNA analysis in combination with microarrays and real-time quantitative polymerase chain reaction (qPCR)-based analyses allows for relative gene expression level comparisons across cell types under different experimental conditions and disease progression. The ability to analyze single cells is an important distinction from global and regional assessments of mRNA expression and can be applied to optimally prepared tissues from animal models of neurodegeneration as well as postmortem human brain tissues. Gene expression analysis in postmortem AD brain regions including the hippocampal formation and neocortex reveals selectively vulnerable cell types share putative pathogenetic alterations in common classes of transcripts, for example, markers of glutamatergic neurotransmission, synaptic-related markers, protein phosphatases and kinases, and neurotrophins/neurotrophin receptors. Expression profiles of vulnerable regions and neurons may reveal important clues toward the understanding of the molecular pathogenesis of various neurological diseases and aid in identifying rational targets toward pharmacotherapeutic interventions for progressive, late-onset neurodegenerative disorders such as mild cognitive impairment (MCI) and AD.

Brain Swelling and Loss of Gray and White Matter Differentiation in Human Postmortem Cases by Computed Tomography.

PubMed

Shirota, Go; Gonoi, Wataru; Ishida, Masanori; Okuma, Hidemi; Shintani, Yukako; Abe, Hiroyuki; Takazawa, Yutaka; Ikemura, Masako; Fukayama, Masashi; Ohtomo, Kuni

2015-01-01

The purpose of this study was to evaluate the brain by postmortem computed tomography (PMCT) versus antemortem computed tomography (AMCT) using brains from the same patients. We studied 36 nontraumatic subjects who underwent AMCT, PMCT, and pathological autopsy in our hospital between April 2009 and December 2013. PMCT was performed within 20 h after death, followed by pathological autopsy including the brain. Autopsy confirmed the absence of intracranial disorders that might be related to the cause of death or might affect measurements in our study. Width of the third ventricle, width of the central sulcus, and attenuation in gray matter (GM) and white matter (WM) from the same area of the basal ganglia, centrum semiovale, and high convexity were statistically compared between AMCT and PMCT. Both the width of the third ventricle and the central sulcus were significantly shorter in PMCT than in AMCT (P < 0.0001). GM attenuation increased after death at the level of the centrum semiovale and high convexity, but the differences were not statistically significant considering the differences in attenuation among the different computed tomography scanners. WM attenuation significantly increased after death at all levels (P<0.0001). The differences were larger than the differences in scanners. GM/WM ratio of attenuation was significantly lower by PMCT than by AMCT at all levels (P<0.0001). PMCT showed an increase in WM attenuation, loss of GM-WM differentiation, and brain swelling, evidenced by a decrease in the size of ventricles and sulci.

The influence of pre-existing rib fractures on Global Human Body Models Consortium thorax response in frontal and oblique impact.

PubMed

Zaseck, Lauren Wood; Chen, Cong; Hu, Jingwen; Reed, Matthew P; Rupp, Jonathan

2018-03-01

Many post-mortem human subjects (PMHS) considered for use in biomechanical impact tests have pre-existing rib fractures (PERFs), usually resulting from cardiopulmonary resuscitation. These specimens are typically excluded from impact studies with the assumption that the fractures will alter the thoracic response to loading. We previously used the Global Human Body Models Consortium 50th percentile whole-body finite element model (GHBMC M50-O) to demonstrate that up to three lateral or bilateral PERFs do not meaningfully influence the response of the GHBMC thorax to lateral loading. This current study used the GHBMC M50-O to explore the influence of PERFs on thorax response in frontal and oblique loading. Up to six PERFs were simulated on the anterior or lateral rib regions, and the model was subjected to frontal or oblique cylindrical impactor, frontal seatbelt, or frontal seatbelt + airbag loading. Changes in thorax force-compression responses due to PERFs were generally minor, with the greatest alterations seen in models with six PERFs on one side of the ribcage. The observed changes, however, were small relative to mid-size male corridors for the loading conditions simulated. PERFs altered rib strain patterns, but the changes did not translate to changes in global thoracic response. Within the limits of model fidelity, the results suggest that PMHS with up to six PERFs may be appropriate for use in frontal or oblique impact testing. Copyright © 2018 Elsevier Ltd. All rights reserved.

Forensic entomology

NASA Astrophysics Data System (ADS)

Amendt, Jens; Krettek, Roman; Zehner, Richard

Necrophagous insects are important in the decomposition of cadavers. The close association between insects and corpses and the use of insects in medicocriminal investigations is the subject of forensic entomology. The present paper reviews the historical background of this discipline, important postmortem processes, and discusses the scientific basis underlying attempts to determine the time interval since death. Using medical techniques, such as the measurement of body temperature or analysing livor and rigor mortis, time since death can only be accurately measured for the first two or three days after death. In contrast, by calculating the age of immature insect stages feeding on a corpse and analysing the necrophagous species present, postmortem intervals from the first day to several weeks can be estimated. These entomological methods may be hampered by difficulties associated with species identification, but modern DNA techniques are contributing to the rapid and authoritative identification of necrophagous insects. Other uses of entomological data include the toxicological examination of necrophagous larvae from a corpse to identify and estimate drugs and toxicants ingested by the person when alive and the proof of possible postmortem manipulations. Forensic entomology may even help in investigations dealing with people who are alive but in need of care, by revealing information about cases of neglect.

Vitreous humor analysis for the detection of xenobiotics in forensic toxicology: a review.

PubMed

Bévalot, Fabien; Cartiser, Nathalie; Bottinelli, Charline; Fanton, Laurent; Guitton, Jérôme

2016-01-01

Vitreous humor (VH) is a gelatinous substance contained in the posterior chamber of the eye, playing a mechanical role in the eyeball. It has been the subject of numerous studies in various forensic applications, primarily for the assessment of postmortem interval and for postmortem chemical analysis. Since most of the xenobiotics present in the bloodstream are detected in VH after crossing the selective blood-retinal barrier, VH is an alternative matrix useful for forensic toxicology. VH analysis offers particular advantages over other biological matrices: it is less prone to postmortem redistribution, is easy to collect, has relatively few interfering compounds for the analytical process, and shows sample stability over time after death. The present study is an overview of VH physiology, drug transport and elimination. Collection, storage, analytical techniques and interpretation of results from qualitative and quantitative points of view are dealt with. The distribution of xenobiotics in VH samples is thus discussed and illustrated by a table reporting the concentrations of 106 drugs from more than 300 case reports. For this purpose, a survey was conducted of publications found in the MEDLINE database from 1969 through April 30, 2015.

Lack of functional relevance of isolated cell damage in transplants of Parkinson's disease patients.

PubMed

Cooper, Oliver; Astradsson, Arnar; Hallett, Penny; Robertson, Harold; Mendez, Ivar; Isacson, Ole

2009-08-01

Postmortem analyses from clinical neural transplantation trials of several subjects with Parkinson's disease revealed surviving grafted dopaminergic neurons after more than a decade. A subset of these subjects displayed isolated dopaminergic neurons within the grafts that contained Lewy body-like structures. In this review, we discuss why this isolated cell damage is unlikely to affect the overall graft function and how we can use these observations to help us to understand age-related neurodegeneration and refine our future cell replacement therapies.

Immunohistochemical Analysis of Human Vallate Taste Buds.

PubMed

Tizzano, Marco; Grigereit, Laura; Shultz, Nicole; Clary, Matthew S; Finger, Thomas E

2015-11-01

The morphology of the vallate papillae from postmortem human samples was investigated with immunohistochemistry. Microscopically, taste buds were present along the inner wall of the papilla, and in some cases in the outer wall as well. The typical taste cell markers PLCβ2, GNAT3 (gustducin) and the T1R3 receptor stain elongated cells in human taste buds consistent with the Type II cells in rodents. In the human tissue, taste bud cells that stain with Type II cell markers, PLCβ2 and GNAT3, also stain with villin antibody. Two typical immunochemical markers for Type III taste cells in rodents, PGP9.5 and SNAP25, fail to stain any taste bud cells in the human postmortem tissue, although these antibodies do stain numerous nerve fibers throughout the specimen. Car4, another Type III cell marker, reacted with only a few taste cells in our samples. Finally, human vallate papillae have a general network of innervation similar to rodents and antibodies directed against SNAP25, PGP9.5, acetylated tubulin and P2X3 all stain free perigemmal nerve endings as well as intragemmal taste fibers. We conclude that with the exception of certain molecular features of Type III cells, human vallate papillae share the structural, morphological, and molecular features observed in rodents. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Impaired periamygdaloid-cortex prodynorphin is characteristic of opiate addiction and depression.

PubMed

Anderson, Sarah Ann R; Michaelides, Michael; Zarnegar, Parisa; Ren, Yanhua; Fagergren, Pernilla; Thanos, Panayotis K; Wang, Gene-Jack; Bannon, Michael; Neumaier, John F; Keller, Eva; Volkow, Nora D; Hurd, Yasmin L

2013-12-01

Negative affect is critical for conferring vulnerability to opiate addiction as reflected by the high comorbidity of opiate abuse with major depressive disorder (MDD). Rodent models implicate amygdala prodynorphin (Pdyn) as a mediator of negative affect; however, evidence of PDYN involvement in human negative affect is limited. Here, we found reduced PDYN mRNA expression in the postmortem human amygdala nucleus of the periamygdaloid cortex (PAC) in both heroin abusers and MDD subjects. Similar to humans, rats that chronically self-administered heroin had reduced Pdyn mRNA expression in the PAC at a time point associated with a negative affective state. Using the in vivo functional imaging technology DREAMM (DREADD-assisted metabolic mapping, where DREADD indicates designer receptors exclusively activated by designer drugs), we found that selective inhibition of Pdyn-expressing neurons in the rat PAC increased metabolic activity in the extended amygdala, which is a key substrate of the extrahypothalamic brain stress system. In parallel, PAC-specific Pdyn inhibition provoked negative affect-related physiological and behavioral changes. Altogether, our translational study supports a functional role for impaired Pdyn in the PAC in opiate abuse through activation of the stress and negative affect neurocircuitry implicated in addiction vulnerability.

Cryptococcosis in Acquired Immunodeficiency Syndrome Patients Clinically Confirmed and/or Diagnosed at Necropsy in a Teaching Hospital in Brazil.

PubMed

Torres, Rafael Garcia; Etchebehere, Renata Margarida; Adad, Sheila Jorge; Micheletti, Adilha Rua; Ribeiro, Barbara de Melo; Silva, Leonardo Eurípedes Andrade; Mora, Delio Jose; Paim, Kennio Ferreira; Silva-Vergara, Mario León

2016-10-05

Cryptococcosis occurs in acquired immunodeficiency syndrome (AIDS) patients with poor compliance to antiretroviral therapy or unaware of their human immunodeficiency virus status who present severe immunosuppression at admission. Consequently, high mortality rates are observed due to disseminated fungal infection. This report presents clinical and postmortem data of AIDS patients with cryptococcosis in a teaching hospital in Brazil. Retrospectively, medical and necropsy records of AIDS patients with cryptococcosis clinically confirmed and/or postmortem verified were reviewed. Clinical data were compared with those of patients presenting a good outcome to evaluate disseminated fungal infection and the agreement between clinical and postmortem diagnosis. At admission, most of the 45 patients with cryptococcal meningitis who died, presented more altered consciousness (P = 0.0047), intracranial increased pressure (P = 0.047), and severe malnutrition (P = 0.0006) than the survivors. Of 29 (64.4%) patients with cryptococcal meningitis, 23 died before week 2 on antifungal therapy, and the other six during the next 3 months. The remaining 16 (35.6%) cases had other diagnoses and died soon after. At necropsy, 31 (68.9%) presented disseminated infection involving two or more organs, whereas 14 (31.1%) cases had meningeal or pulmonary localized infection. The agreement of 64.4% between clinical and postmortem diagnosis was similar to some studies. However, other reports have shown figures ranging from 34% to 95%. Currently, a progressive worldwide decrease of autopsies is worrying because the role of postmortem examination is pivotal to verify or identify the death causes, which contributes to improve the quality of clinical diagnosis and medical training. © The American Society of Tropical Medicine and Hygiene.

Diagnosis of myocardial ischemia combining multiphase postmortem CT-angiography, histology, and postmortem biochemistry.

PubMed

Vanhaebost, Jessica; Ducrot, Kewin; de Froidmont, Sébastien; Scarpelli, Maria Pia; Egger, Coraline; Baumann, Pia; Schmit, Gregory; Grabherr, Silke; Palmiere, Cristian

2017-02-01

The aim of this study was to assess whether the identification of pathological myocardial enhancement at multiphase postmortem computed tomography angiography was correlated with increased levels of troponin T and I in postmortem serum from femoral blood as well as morphological findings of myocardial ischemia. We further aimed to investigate whether autopsy cases characterized by increased troponin T and I concentrations as well as morphological findings of myocardial ischemia were also characterized by pathological myocardial enhancement at multiphase postmortem computed tomography angiography. Two different approaches were used. In one, 40 forensic autopsy cases that had pathological enhancement of the myocardium (mean Hounsfield units ≥95) observed at postmortem angiography were retrospectively selected. In the second approach, 40 forensic autopsy cases that had a cause of death attributed to acute myocardial ischemia were retrospectively selected. The preliminary results seem to indicate that the identification of a pathological enhancement of the myocardium at postmortem angiography is associated with the presence of increased levels of cardiac troponins in postmortem serum and morphological findings of ischemia. Analogously, a pathological enhancement of the myocardium at postmortem angiography can be retrospectively found in the great majority of autopsy cases characterized by increased cardiac troponin levels in postmortem serum and morphological findings of myocardial ischemia. Multiphase postmortem computed tomography angiography is a useful tool in the postmortem setting for investigating ischemically damaged myocardium.

Sex-related differences in the thanatomicrobiome in postmortem heart samples using bacterial gene regions V1-2 and V4.

PubMed

Bell, Courtnee R; Wilkinson, Jeremy E; Robertson, Boakai K; Javan, Gulnaz T

2018-05-10

Recent studies have revealed distinct thanatomicrobiome (microbiome of death) signatures in human body sites after death. Thanatomicrobiome studies suggest that microbial succession after death may have the potential to reveal important postmortem biomarkers for the identification of time of death. We surveyed the postmortem microbiomes of cardiac tissues from ten corpses with varying times of death (6-58 h) using amplicon-based sequencing of the 16S rRNA gene' V1-2 and V4 hypervariable regions. The results demonstrated that amplicons had statistically significant (p <0.05) sex-dependent changes. Clostridium sp., Pseudomonas sp., Pantoea sp., and Streptococcus sp. had the highest enrichment for both V1-2 and V4 regions. Interestingly, the results also show that V4 amplicons had higher abundance of Clostridium sp. and Pseudomonas sp. in female hearts compared to males. Additionally, Streptococcus sp. was solely found in male heart samples. The distinction between sexes was further supported by Principle Coordinate Analysis, which revealed microbes in female hearts formed a distinctive cluster separate from male cadavers for both hypervariable regions. This study provides data that demonstrates that two hypervariable regions show discriminatory power for sex differences in postmortem heart samples. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Dutch guideline for clinical foetal-neonatal and paediatric post-mortem radiology, including a review of literature.

PubMed

Sonnemans, L J P; Vester, M E M; Kolsteren, E E M; Erwich, J J H M; Nikkels, P G J; Kint, P A M; van Rijn, R R; Klein, W M

2018-06-01

Clinical post-mortem radiology is a relatively new field of expertise and not common practice in most hospitals yet. With the declining numbers of autopsies and increasing demand for quality control of clinical care, post-mortem radiology can offer a solution, or at least be complementary. A working group consisting of radiologists, pathologists and other clinical medical specialists reviewed and evaluated the literature on the diagnostic value of post-mortem conventional radiography (CR), ultrasonography, computed tomography (PMCT), magnetic resonance imaging (PMMRI), and minimally invasive autopsy (MIA). Evidence tables were built and subsequently a Dutch national evidence-based guideline for post-mortem radiology was developed. We present this evaluation of the radiological modalities in a clinical post-mortem setting, including MIA, as well as the recently published Dutch guidelines for post-mortem radiology in foetuses, neonates, and children. In general, for post-mortem radiology modalities, PMMRI is the modality of choice in foetuses, neonates, and infants, whereas PMCT is advised in older children. There is a limited role for post-mortem CR and ultrasonography. In most cases, conventional autopsy will remain the diagnostic method of choice. Based on a literature review and clinical expertise, an evidence-based guideline was developed for post-mortem radiology of foetal, neonatal, and paediatric patients. What is Known: • Post-mortem investigations serve as a quality check for the provided health care and are important for reliable epidemiological registration. • Post-mortem radiology, sometimes combined with minimally invasive techniques, is considered as an adjunct or alternative to autopsy. What is New: • We present the Dutch guidelines for post-mortem radiology in foetuses, neonates and children. • Autopsy remains the reference standard, however minimal invasive autopsy with a skeletal survey, post-mortem computed tomography, or post-mortem magnetic resonance imaging can be complementary thereof.

A human neurodevelopmental model for Williams syndrome

PubMed Central

Chailangkarn, Thanathom; Trujillo, Cleber A.; Freitas, Beatriz C.; Hrvoj-Mihic, Branka; Herai, Roberto H.; Yu, Diana X.; Brown, Timothy T.; Marchetto, Maria C. N.; Bardy, Cedric; McHenry, Lauren; Stefanacci, Lisa; Järvinen, Anna; Searcy, Yvonne M.; DeWitt, Michelle; Wong, Wenny; Lai, Philip; Ard, M. Colin; Hanson, Kari L.; Romero, Sarah; Jacobs, Bob; Dale, Anders M.; Dai, Li; Korenberg, Julie R.; Gage, Fred H.; Bellugi, Ursula; Halgren, Eric; Semendeferi, Katerina; Muotri, Alysson R.

2016-01-01

Summary Williams syndrome (WS) is a genetic neurodevelopmental disorder characterized by an uncommon hypersociability and a mosaic of retained and compromised linguistic and cognitive abilities. Nearly all clinically diagnosed individuals with WS lack precisely the same set of genes, with breakpoints in chromosome band 7q11.231–5. The contribution of specific genes to the neuroanatomical and functional alterations, leading to behavioral pathologies in humans, remains largely unexplored. Here, we investigate neural progenitor cells (NPCs) and cortical neurons derived from WS and typically developing (TD) induced pluripotent stem cells (iPSCs). WS NPCs have an increased doubling time and apoptosis compared to TD NPCs. Using an atypical WS subject6, 7, we narrowed this cellular phenotype to a single gene candidate, FZD9. At the neuronal stage, WS-derived layers V/VI cortical neurons were characterized by longer total dendrites, increased numbers of spines and synapses, aberrant calcium oscillation and altered network connectivity. Morphometric alterations observed in WS neurons were validated after Golgi staining of postmortem layers V/VI cortical neurons. This human iPSC model8 fills in the current knowledge gap in WS cellular biology and could lead to further insights into the molecular mechanism underlying the disorder and the human social brain. PMID:27509850

Clinical and pathological aspects of human African trypanosomiasis (T. b. gambiense) with particular reference to reactive arsenical encephalopathy.

PubMed

Haller, L; Adams, H; Merouze, F; Dago, A

1986-01-01

Fourteen of 330 patients treated with melarsoprol (Mel B) for human African trypanosomiasis (HAT) developed a severe reactive arsenical encephalopathy (RAE). Six of these cases were fatal and postmortem examination was performed on 5 patients. Symptoms of "sleeping sickness" were compared with symptoms after treatment with arsenicals and the subsequent onset of RAE. There are 3 characteristic syndromes of RAE: convulsive status associated with acute cerebral edema, rapidly progressive coma without convulsions, and acute nonlethal mental disturbances without neurological signs. Three subjects revealed hypoxic brain damage with acute cerebral edema, and multiple hemorrhages of brain stem in those comatose. The pathology of the underlying HAT (chronic perivascular inflammation and plasma cytic infiltration of the brain) and the pathology of the RAE (characterized by acute vasculitis) are distinct. RAE occurs in the first as well as in the second stage (CNS involvement) of trypanosomiasis but the reason for this is unclear; an exclusive toxicity of the drug, or a Herxheimer reaction are possible but seem unlikely. Both clinical and laboratory findings point rather to a drug-related, delayed immune response.

Nasal osteoma in a dairy cow: a combined clinical, imaging and histopathological approach to diagnosis.

PubMed

Wuersch, K; Bischoff, M; Thoma, R; Matter, M S

2009-01-01

An 8-year-old Brown Swiss dairy cow was presented with unilateral epistaxis and mild inspiratory stridor. At that time endoscopic examination revealed a smooth-surfaced mass within the left nasal cavity. Biopsy samples were collected and a diagnosis of fibrosarcoma was made. Eighteen months later the animal developed severe respiratory distress that led to difficulties in feeding and consequently to emaciation and a dramatic drop in milk production. The cow was humanely destroyed and submitted for post-mortem examination. The head was subject to further investigation by radiography, computed tomography and magnetic resonance imaging. These techniques revealed a non-infiltrative, well-circumscribed mass of both radiodense and heterogeneously intense structures. Histopathological examination revealed a mass consisting of well-differentiated and interlacing bone trabeculae lined by osteoblasts and multinucleated osteoclasts. In contrast to the initial diagnosis, the later diagnostic approaches supported the diagnosis of osteoma.

Chromium in Postmortem Material.

PubMed

Dudek-Adamska, Danuta; Lech, Teresa; Konopka, Tomasz; Kościelniak, Paweł

2018-04-17

Recently, considerable attention has been paid to the negative effects caused by the presence and constant increase in concentration of heavy metals in the environment, as well as to the determination of their content in human biological samples. In this paper, the concentration of chromium in samples of blood and internal organs collected at autopsy from 21 female and 39 male non-occupationally exposed subjects is presented. Elemental analysis was carried out by an electrothermal atomic absorption spectrometer after microwave-assisted acid digestion. Reference ranges of chromium in the blood, brain, stomach, liver, kidneys, lungs, and heart (wet weight) in the population of Southern Poland were found to be 0.11-16.4 ng/mL, 4.7-136 ng/g, 6.1-76.4 ng/g, 11-506 ng/g, 2.9-298 ng/g, 13-798 ng/g, and 3.6-320 ng/g, respectively.

A comparative in situ decomposition study using still born piglets and leaf litter from a deciduous forest.

PubMed

Olakanye, Ayodeji O; Nelson, Andrew; Ralebitso-Senior, T Komang

2017-07-01

A cadaver and dead plant organic matter, or litter, are rich energy sources that undergo a complex decomposition process, which impact the surrounding environmental microbiota. Advances in molecular microbiology techniques, with study of the 16S RNA genes, in particular, have highlighted the application of forensic ecogenomics in addressing key knowledge gaps. To investigate subsurface microbiome shifts as a novel tool to establish "postmortem microbial clock" and augment postmortem interval (PMI) and time-since-burial estimations, an in situ study with triplicate underground burials of piglets as human taphonomic proxies and Quercus robur leaf litter was monitored for 270 days. Changes in microbial community structure and composition were related directly to changes in seasonal temperature, with microbial shifts more pronounced during the summer. For example, Methylococcaceae could be used as seasonal bacterial indicators, from winter to summer, in establishing postmortem microbial clock for this site. Furthermore, Methylophilaceae (Methylophilales order) and Anaerolineaceae would differentiate for the piglet and leaf litter soils, respectively, 180 days after internment. Copyright © 2017 Elsevier B.V. All rights reserved.

Plasma soluble CD163 is associated with postmortem brain pathology in human immunodeficiency virus infection.

PubMed

Bryant, Alex K; Moore, David J; Burdo, Tricia H; Lakritz, Jessica R; Gouaux, Ben; Soontornniyomkij, Virawudh; Achim, Cristian L; Masliah, Eliezer; Grant, Igor; Levine, Andrew J; Ellis, Ronald J

2017-04-24

Higher plasma soluble cluster of differentiation (CD)163 (sCD163), shed by monocytes and macrophages, correlates with neurocognitive impairment in HIV infection. We hypothesized that higher antemortem plasma or cerebrospinal fluid (CSF) sCD163 would be associated with greater postmortem neurodegeneration and/or microgliosis. Retrospective, postmortem observational study. We measured sCD163 levels in antemortem plasma (n = 54) and CSF (n = 32) samples from 74 HIV-seropositive participants (median 5 months before death) who donated their brains to research at autopsy. Postmortem, we quantified markers of synaptodendritic damage (microtubule-associated protein 2, synaptophysin), microgliosis [human leukocyte antigen DR (HLA-DR), ionized calcium-binding adaptor molecule 1], astrocytosis (glial fibrillary acidic protein), and impaired protein clearance (β-amyloid) in frontal cortex, hippocampus, putamen, and internal capsule. Multivariable least-squares regression was used to evaluate the association between plasma or CSF sCD163 and histological measures, correcting for multiple comparisons. Higher plasma sCD163 was associated with lower microtubule-associated protein 2 in frontal cortex [B = -0.23, 95% confidence interval (CI) -0.41 to -0.06, P = 0.04], putamen (B = 0.32, 95% CI -0.52 to -0.12, P = 0.02), and hippocampus (B = -0.23, 95% CI -0.35 to -0.10, P = 0.01), and with lower synaptophysin in hippocampus (B = -0.25, 95% CI -0.42 to -0.03, P = 0.02) but not putamen or frontal cortex (P > 0.05). Higher plasma sCD163 was associated with higher HLA-DR in putamen (B = 0.17, 95% CI 0.08 to 0.26, P = 0.008). CSF sCD163 was not associated with any histological measure (P > 0.05). Higher plasma sCD163 in life is associated with greater synaptodendritic damage and microglial activation in cortical and subcortical brain regions.

Severe malaria - a case of fatal Plasmodium knowlesi infection with post-mortem findings: a case report

PubMed Central

2010-01-01

Background Zoonotic malaria caused by Plasmodium knowlesi is an important, but newly recognized, human pathogen. For the first time, post-mortem findings from a fatal case of knowlesi malaria are reported here. Case presentation A formerly healthy 40 year-old male became symptomatic 10 days after spending time in the jungle of North Borneo. Four days later, he presented to hospital in a state of collapse and died within two hours. He was hyponatraemic and had elevated blood urea, potassium, lactate dehydrogenase and amino transferase values; he was also thrombocytopenic and eosinophilic. Dengue haemorrhagic shock was suspected and a post-mortem examination performed. Investigations for dengue virus were negative. Blood for malaria parasites indicated hyperparasitaemia and single species P. knowlesi infection was confirmed by nested-PCR. Macroscopic pathology of the brain and endocardium showed multiple petechial haemorrhages, the liver and spleen were enlarged and lungs had features consistent with ARDS. Microscopic pathology showed sequestration of pigmented parasitized red blood cells in the vessels of the cerebrum, cerebellum, heart and kidney without evidence of chronic inflammatory reaction in the brain or any other organ examined. Brain sections were negative for intracellular adhesion molecule-1. The spleen and liver had abundant pigment containing macrophages and parasitized red blood cells. The kidney had evidence of acute tubular necrosis and endothelial cells in heart sections were prominent. Conclusions The overall picture in this case was one of systemic malaria infection that fit the WHO classification for severe malaria. Post-mortem findings in this case were unexpectedly similar to those that define fatal falciparum malaria, including cerebral pathology. There were important differences including the absence of coma despite petechial haemorrhages and parasite sequestration in the brain. These results suggest that further study of knowlesi malaria will aid the interpretation of, often conflicting, information on malaria pathophysiology in humans. PMID:20064229

Statistical evaluation of time-dependent metabolite concentrations: estimation of post-mortem intervals based on in situ 1H-MRS of the brain.

PubMed

Scheurer, Eva; Ith, Michael; Dietrich, Daniel; Kreis, Roland; Hüsler, Jürg; Dirnhofer, Richard; Boesch, Chris

2005-05-01

Knowledge of the time interval from death (post-mortem interval, PMI) has an enormous legal, criminological and psychological impact. Aiming to find an objective method for the determination of PMIs in forensic medicine, 1H-MR spectroscopy (1H-MRS) was used in a sheep head model to follow changes in brain metabolite concentrations after death. Following the characterization of newly observed metabolites (Ith et al., Magn. Reson. Med. 2002; 5: 915-920), the full set of acquired spectra was analyzed statistically to provide a quantitative estimation of PMIs with their respective confidence limits. In a first step, analytical mathematical functions are proposed to describe the time courses of 10 metabolites in the decomposing brain up to 3 weeks post-mortem. Subsequently, the inverted functions are used to predict PMIs based on the measured metabolite concentrations. Individual PMIs calculated from five different metabolites are then pooled, being weighted by their inverse variances. The predicted PMIs from all individual examinations in the sheep model are compared with known true times. In addition, four human cases with forensically estimated PMIs are compared with predictions based on single in situ MRS measurements. Interpretation of the individual sheep examinations gave a good correlation up to 250 h post-mortem, demonstrating that the predicted PMIs are consistent with the data used to generate the model. Comparison of the estimated PMIs with the forensically determined PMIs in the four human cases shows an adequate correlation. Current PMI estimations based on forensic methods typically suffer from uncertainties in the order of days to weeks without mathematically defined confidence information. In turn, a single 1H-MRS measurement of brain tissue in situ results in PMIs with defined and favorable confidence intervals in the range of hours, thus offering a quantitative and objective method for the determination of PMIs. Copyright 2004 John Wiley & Sons, Ltd.

Autism BrainNet: A network of postmortem brain banks established to facilitate autism research.

PubMed

Amaral, David G; Anderson, Matthew P; Ansorge, Olaf; Chance, Steven; Hare, Carolyn; Hof, Patrick R; Miller, Melissa; Nagakura, Ikue; Pickett, Jane; Schumann, Cynthia; Tamminga, Carol

2018-01-01

Autism spectrum disorder (ASD or autism) is a neurodevelopmental condition that affects over 1% of the population worldwide. Developing effective preventions and treatments for autism will depend on understanding the genetic perturbations and underlying neuropathology of the disorder. While evidence from magnetic resonance imaging and other noninvasive techniques points to altered development and organization of the autistic brain, these tools lack the resolution for identifying the cellular and molecular underpinnings of the disorder. Postmortem studies of high-quality human brain tissue currently represent the only viable option to pursuing these types of studies. However, the availability of high-quality ASD brain tissue has been extremely limited. Here we describe the establishment of a privately funded tissue bank, Autism BrainNet, a network of brain collection sites that work in a coordinated fashion to develop an adequate library of human postmortem brain tissues. Autism BrainNet was initiated as a collaboration between the Simons Foundation and Autism Speaks, and is currently funded by the Simons Foundation Autism Research Initiative. Autism BrainNet has collection sites (nodes) in California, Texas, New York, and Massachusetts; an affiliated, international node is located in Oxford, England. All donations to this network become part of a consolidated pool of tissue that is distributed to qualified investigators worldwide to carry out autism research. An essential component of this program is a widespread outreach program that highlights the need for postmortem brain donations to families affected by autism, led by the Autism Science Foundation. Challenges include an outreach campaign that deals with a disorder beginning in early childhood, collecting an adequate number of donations to deal with the high level of biologic heterogeneity of autism, and preparing this limited resource for optimal distribution to the greatest number of investigators. Copyright © 2018 Elsevier B.V. All rights reserved.

An evaluation of soil chemistry in human cadaver decomposition islands: Potential for estimating postmortem interval (PMI).

PubMed

Fancher, J P; Aitkenhead-Peterson, J A; Farris, T; Mix, K; Schwab, A P; Wescott, D J; Hamilton, M D

2017-10-01

Soil samples from the Forensic Anthropology Research Facility (FARF) at Texas State University, San Marcos, TX, were analyzed for multiple soil characteristics from cadaver decomposition islands to a depth of 5centimeters (cm) from 63 human decomposition sites, as well as depths up to 15cm in a subset of 11 of the cadaver decomposition islands plus control soils. Postmortem interval (PMI) of the cadaver decomposition islands ranged from 6 to 1752 days. Some soil chemistry, including nitrate-N (NO 3 -N), ammonium-N (NH 4 -N), and dissolved inorganic carbon (DIC), peaked at early PMI values and their concentrations at 0-5cm returned to near control values over time likely due to translocation down the soil profile. Other soil chemistry, including dissolved organic carbon (DOC), dissolved organic nitrogen (DON), orthophosphate-P (PO 4 -P), sodium (Na + ), and potassium (K + ), remained higher than the control soil up to a PMI of 1752days postmortem. The body mass index (BMI) of the cadaver appeared to have some effect on the cadaver decomposition island chemistry. To estimate PMI using soil chemistry, backward, stepwise multiple regression analysis was used with PMI as the dependent variable and soil chemistry, body mass index (BMI) and physical soil characteristics such as saturated hydraulic conductivity as independent variables. Measures of soil parameters derived from predator and microbial mediated decomposition of human remains shows promise in estimating PMI to within 365days for a period up to nearly five years. This persistent change in soil chemistry extends the ability to estimate PMI beyond the traditionally utilized methods of entomology and taphonomy in support of medical-legal investigations, humanitarian recovery efforts, and criminal and civil cases. Copyright © 2017 Elsevier B.V. All rights reserved.

[3H]MK-801 binding sites in post-mortem human frontal cortex.

PubMed

Kornhuber, J; Mack-Burkhardt, F; Kornhuber, M E; Riederer, P

1989-03-29

The binding of [3H]MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate) was investigated in extensively washed homogenates of post-mortem human frontal cortex. The association of [3H]MK-801 proceeded slowly (t1/2 = 553 min) and reached equilibrium only after a prolonged incubation (greater than 24 h). The dissociation of [3H]MK-801 from the binding site was also slow (t1/2 = 244 min). Glutamate, glycine and magnesium markedly increased the rate of association (t1/2 = 14.8 min) and dissociation (t1/2 = 36.5 min). At equilibrium, the binding was not altered by these substances. Specific binding was linear with protein concentration, was saturable, reversible, stereoselective, heat-labile and was nearly absent in the white matter. Scatchard analysis of the saturation curves obtained at equilibrium indicated that there was a high-affinity (Kd1 1.39 +/- 0.21 nM, Bmax1 0.483 +/- 0.084 pmol/mg protein) and a low-affinity (Kd2 116.25 +/- 50.79 nM, Bmax2 3.251 +/- 0.991 pmol/mg protein) binding site. All competition curves obtained with (+)-MK-801, (-)-MK-801, phencyclidine and ketamine had Hill coefficients of less than unity and were best explained by a two-site model. Thus, our results demonstrate the presence of binding sites for MK-801 in post-mortem human brains and provide evidence for binding site heterogeneity. Furthermore, glutamate, glycine and magnesium accelerate the association and dissociation of [3H]MK-801 to and from its binding sites. The results add support to the hypothesis that MK-801, glutamate, glycine and magnesium all bind to different sites on the NMDA receptor-ion channel complex.

Autopsy-confirmed Alzheimer's disease versus clinically diagnosed Alzheimer's disease in the Cache County Study on Memory and Aging: a comparison of quantitative MRI and neuropsychological findings.

PubMed

Fearing, Michael A; Bigler, Erin D; Norton, Maria; Tschanz, Jo Ann; Hulette, Christine; Leslie, Carol; Welsh-Bohmer, Kathleen

2007-07-01

Atrophy of specific, regional, and generalized brain structures occurs as a result of the Alzheimer's disease (AD) process. Comparing AD patients with histopathological confirmation of the disease at autopsy to those without autopsy but who were clinically diagnosed using the same antemortem criteria will provide further evidence of the utility and accuracy of neuropsychological assessments at the time of diagnosis, as well as the efficacy of quantitative magnetic resonance imaging (qMRI) in demonstrating gross neuropathological changes associated with the disease. The Cache County Study of Aging provides a unique opportunity to determine how closely AD subjects with only the clinical diagnosis match similarly diagnosed AD subjects but with postmortem confirmation of the disease. qMRI volumes of various brain structures, as well as neuropsychological outcome measures from an expanded battery, were obtained in 31 autopsy-confirmed AD subjects and 45 clinically diagnosed AD subjects. Of the various qMRI variables examined, only total temporal lobe volume was different, where those with postmortem confirmation had reduced volume. No significant differences between the two groups were found with any of the neuropsychological outcome measures. These findings confirm the similarity in neuroimaging and neuropsychological assessment findings between those with just the clinical diagnosis of AD and those with an autopsy-confirmed diagnosis in the moderate-to-severe stage of the disease at the time of diagnosis.

Postmortem computed tomography in victims of military air mishaps: radiological-pathological correlation of CT findings.

PubMed

Levy, Gad; Goldstein, Liav; Blachar, Arye; Apter, Sara; Barenboim, Erez; Bar-Dayan, Yaron; Shamis, Ari; Atar, Eli

2007-10-01

A thorough medical inquiry is included in every aviation mishap investigation. While the gold standard of this investigation is a forensic pathology examination, numerous reports stress the important role of computed tomography in the postmortem evaluation of trauma victims. To characterize the findings identified by postmortem CT and compare its performance to conventional autopsy in victims of military aviation mishaps, we analyzed seven postmortem CT examinations. Musculoskeletal injuries accounted for 57.8% of the traumatic findings identified by postmortem CT. The most frequent findings were fractures of the rib (47%), skull (9.6%) and facial bones (8.6%). Abnormally located air accounted for 24% of findings, for which CT was superior (3.5% detected by autopsy, 100% by postmortem CT, P < 0.001). The performance of autopsy in detecting injuries was superior (autopsy detected 85.8% of all injuries, postmortem CT detected 53.9%, P < 0.001), especially in the detection of superficial lesions (100% detected by autopsy, 10.5% by postmortem CT, P < 0.001) and solid organ injuries (100% by autopsy, 18.5% by postmortem CT, P < 0.001). Performance in the detection of musculoskeletal injuries was similar (91.3% for autopsy, 90.3% for postmortem CT, P = not significant). Postmortem CT and autopsy have distinct performance profiles, and although the first cannot replace the latter it is a useful complementary examination.

[Legal aspects of post-mortem radiology in the Netherlands].

PubMed

Venderink, W; Dute, J C J

2016-01-01

In the Netherlands, the application of post-mortem radiology (virtual autopsy) is on the rise. Contrary to conventional autopsy, with post-mortem radiology the body remains intact. There is uncertainty concerning the legal admissibility of post-mortem radiology, since the Dutch Corpse Disposal Act does not contain any specific regulations for this technique. Autopsy and post-mortem radiology differ significantly from a technical aspect, but these differences do not have far-reaching legal consequences from a legal perspective. Even though the body remains intact during post-mortem radiology, the bodily integrity of a deceased person is breached if it would be applied without previously obtained consent. This permission can only be obtained after the relatives are fully informed about the proposed activity. In this respect, it is not relevant which technique is used, be it post-mortem radiology or autopsy. Therefore, the other legal conditions for post-mortem radiology are essentially identical to those for autopsy.

Investigation of an alleged mechanism of finger injury in an automobile crash.

PubMed

Stacey, Stephen; Kent, Richard

2006-07-01

This investigation centers on the case of an adult male whose finger was allegedly amputated by the steering wheel of his car during a crash. The subject claimed to have been driving with his left index finger inserted through a hole in the spoke of his steering wheel and was subsequently involved in an offset frontal collision with a tree. The finger was found to be cleanly severed at the mid-shaft of the proximal phalanx after the crash. This injury was alleged to have been caused by inertial loading from the rotation of the steering wheel during the crash. To determine whether this injury mechanism was plausible, three laboratory tests representing distinct loading scenarios were carried out with postmortem human surrogates loaded dynamically by the subject's steering wheel. It was found that the inertial loads generated in this loading scenario are insufficient to amputate the finger. Additionally, artificially constraining the finger to force an amputation to occur revealed that a separation at the proximal interphalangeal joint occurs rather than a bony fracture of the proximal phalanx. Based on these biomechanical tests, it can be concluded that the subject's injury did not occur during the automobile crash in question. Furthermore, it can be shown that the injury was self-inflicted to fraudulently claim on an insurance policy.

Distribution of Non-Persistent Endocrine Disruptors in Two Different Regions of the Human Brain

PubMed Central

van der Meer, Thomas P.; Artacho-Cordón, Francisco; Swaab, Dick F.; Struik, Dicky; Makris, Konstantinos C.; Wolffenbuttel, Bruce H. R.; Frederiksen, Hanne; van Vliet-Ostaptchouk, Jana V.

2017-01-01

Non-persistent endocrine disrupting chemicals (npEDCs) can affect multiple organs and systems in the body. Whether npEDCs can accumulate in the human brain is largely unknown. The major aim of this pilot study was to examine the presence of environmental phenols and parabens in two distinct brain regions: the hypothalamus and white-matter tissue. In addition, a potential association between these npEDCs concentrations and obesity was investigated. Post-mortem brain material was obtained from 24 individuals, made up of 12 obese and 12 normal-weight subjects (defined as body mass index (BMI) > 30 and BMI < 25 kg/m2, respectively). Nine phenols and seven parabens were measured by isotope dilution TurboFlow-LC-MS/MS. In the hypothalamus, seven suspect npEDCs (bisphenol A, triclosan, triclocarban and methyl-, ethyl-, n-propyl-, and benzyl paraben) were detected, while five npEDCs (bisphenol A, benzophenone-3, triclocarban, methyl-, and n-propyl paraben) were found in the white-matter brain tissue. We observed higher levels of methylparaben (MeP) in the hypothalamic tissue of obese subjects as compared to controls (p = 0.008). Our findings indicate that some suspected npEDCs are able to cross the blood–brain barrier. Whether the presence of npEDCs can adversely affect brain function and to which extent the detected concentrations are physiologically relevant needs to be further investigated. PMID:28902174

Informed consent in research to improve the number and quality of deceased donor organs.

PubMed

Rey, Michael M; Ware, Lorraine B; Matthay, Michael A; Bernard, Gordon R; McGuire, Amy L; Caplan, Arthur L; Halpern, Scott D

2011-02-01

Improving the management of potential organ donors in the intensive care unit could meet an important public health goal by increasing the number and quality of transplantable organs. However, randomized clinical trials are needed to quantify the extent to which specific interventions might enhance organ recovery and outcomes among transplant recipients. Among several barriers to conducting such studies are the absence of guidelines for obtaining informed consent for such studies and the fact that deceased organ donors are not covered by extant federal regulations governing oversight of research with human subjects. This article explores the underexamined ethical issues that arise in the context of donor management studies and provides ethical guidelines and suggested regulatory oversight mechanisms to enable such studies to be conducted ethically. We conclude that both the respect that is traditionally accorded to the prior wishes of the dead and the possibility of postmortem harm support a role for surrogate consent of donors in such randomized controlled trials. Furthermore, although recipients will often be considered human subjects under federal regulations, several ethical arguments support waiving requirements for recipient consent in donor management randomized controlled trials. Finally, we suggest that new regulatory mechanisms, perhaps linked to existing regional and national organ donation and transplantation infrastructures, must be established to protect patients in donor management studies while limiting unnecessary barriers to the conduct of this important research.

The Effect of Decomposition on the Efficacy of Biometrics for Positive Identification.

PubMed

Sauerwein, Kelly; Saul, Tiffany B; Steadman, Dawnie Wolfe; Boehnen, Chris B

2017-11-01

Biometrics, unique measurable physiological and behavioral characteristics, are used to identify individuals in a variety of scenarios, including forensic investigations. However, data on the longevity of these indicators are incomplete. This study demonstrated that iris and fingerprint biometric data can be obtained up to four days postmortem in warmer seasons and 50 + days in the winter. It has been generally believed, but never studied, that iris recognition is only obtainable within the first 24 hours after death. However, this study showed that they remain viable for longer (2-34 days) depending upon the environmental conditions. Temperature, precipitation, insects, and scavenger activity were the primary factors affecting the retention of biometrics in decomposing human remains. While this study is an initial step in determining the utility of physiological biometrics across postmortem time, biometric research has the potential to make important contributions to human identification and the law enforcement, military, and medicolegal communities. © 2017 American Academy of Forensic Sciences.

Positive dental identification using tooth anatomy and digital superimposition.

PubMed

Johansen, Raymond J; Michael Bowers, C

2013-03-01

Dental identification of unknown human remains continues to be a relevant and reliable adjunct to forensic investigations. The advent of genomic and mitochondrial DNA procedures has not displaced the practical use of dental and related osseous structures remaining after destructive incidents that can render human remains unrecognizable, severely burned, and fragmented. The ability to conclusively identify victims of accident and homicide is based on the availability of antemortem records containing substantial and unambiguous proof of dental and related osseous characteristics. This case report documents the use of digital comparative analysis of antemortem dental models and postmortem dentition, to determine a dental identification. Images of dental models were digitally analyzed using Adobe Photoshop(TM) software. Individual tooth anatomy was compared between the antemortem and postmortem images. Digital superimposition techniques were also used for the comparison. With the absence of antemortem radiographs, this method proved useful to reach a positive identification in this case. © 2012 American Academy of Forensic Sciences.

Glucocorticoid Receptor Related Genes: Genotype And Brain Gene Expression Relationships To Suicide And Major Depressive Disorder

PubMed Central

Pantazatos, Spiro P.; Huang, Yung-yu; Rosoklija, Gorazd B.; Dwork, Andrew J.; Burke, Ainsley; Arango, Victoria; Oquendo, Maria A.; Mann, J. John

2016-01-01

Introduction We tested the relationship between genotype, gene expression and suicidal behavior and MDD in live subjects and postmortem samples for three genes, associated with the hypothalamic-pituitary-adrenal axis, suicidal behavior and major depressive disorder (MDD); FK506 binding protein 5 (FKBP5), Spindle and kinetochore-associated protein 2 (SKA2) and Glucocorticoid Receptor (NR3C1). Materials and Methods Single-nucleotide polymorphisms (SNPs) and haplotypes were tested for association with suicidal behavior and MDD in a live (N=277) and a postmortem sample (N=209). RNA-seq was used to examine gene and isoform-level brain expression postmortem (Brodmann Area 9) (N=59). Expression quantitative trait loci (eQTL) relationships were examined using a public database (UK Brain Expression Consortium). Results We identified a haplotype within the FKBP5 gene, present in 47% of the live subjects, that was associated with increased risk of suicide attempt (OR=1.58, t=6.03, p=0.014). Six SNPs on this gene, three SNPs on SKA2 and one near NR3C1 showed before-adjustment association with attempted suicide, and two SNPs of SKA2 with suicide death, but none stayed significant after adjustment for multiple testing. Only the SKA2 SNPs were related to expression in the prefrontal cortex. One NR3C1 transcript had lower expression in suicide relative to non-suicide sudden death cases (b=-0.48, SE=0.12, t=-4.02, adjusted p=0.004). Conclusion We have identified an association of FKBP5 haplotype with risk of suicide attempt and found an association between suicide and altered NR3C1 gene expression in the prefrontal cortex. Our findings further implicate hypothalamic pituitary axis dysfunction in suicidal behavior. PMID:27030168

GLUCOCORTICOID RECEPTOR-RELATED GENES: GENOTYPE AND BRAIN GENE EXPRESSION RELATIONSHIPS TO SUICIDE AND MAJOR DEPRESSIVE DISORDER.

PubMed

Yin, Honglei; Galfalvy, Hanga; Pantazatos, Spiro P; Huang, Yung-Yu; Rosoklija, Gorazd B; Dwork, Andrew J; Burke, Ainsley; Arango, Victoria; Oquendo, Maria A; Mann, J John

2016-06-01

We tested the relationship between genotype, gene expression and suicidal behavior and major depressive disorder (MDD) in live subjects and postmortem samples for three genes, associated with the hypothalamic-pituitary-adrenal axis, suicidal behavior, and MDD; FK506-binding protein 5 (FKBP5), Spindle and kinetochore-associated protein 2 (SKA2), and Glucocorticoid Receptor (NR3C1). Single-nucleotide polymorphisms (SNPs) and haplotypes were tested for association with suicidal behavior and MDD in a live (N = 277) and a postmortem sample (N = 209). RNA-seq was used to examine gene and isoform-level brain expression postmortem (Brodmann Area 9; N = 59). Expression quantitative trait loci (eQTL) relationships were examined using a public database (UK Brain Expression Consortium). We identified a haplotype within the FKBP5 gene, present in 47% of the live subjects, which was associated with increased risk of suicide attempt (OR = 1.58, t = 6.03, P = .014). Six SNPs on this gene, three SNPs on SKA2, and one near NR3C1 showed before-adjustment association with attempted suicide, and two SNPs of SKA2 with suicide death, but none stayed significant after adjustment for multiple testing. Only the SKA2 SNPs were related to expression in the prefrontal cortex (pFCTX). One NR3C1 transcript had lower expression in suicide relative to nonsuicide sudden death cases (b = -0.48, SE = 0.12, t = -4.02, adjusted P = .004). We have identified an association of FKBP5 haplotype with risk of suicide attempt and found an association between suicide and altered NR3C1 gene expression in the pFCTX. Our findings further implicate hypothalamic pituitary axis dysfunction in suicidal behavior. © 2016 Wiley Periodicals, Inc.

Functional and Structural Succession of Soil Microbial Communities below Decomposing Human Cadavers

PubMed Central

Cobaugh, Kelly L.; Schaeffer, Sean M.; DeBruyn, Jennifer M.

2015-01-01

The ecological succession of microbes during cadaver decomposition has garnered interest in both basic and applied research contexts (e.g. community assembly and dynamics; forensic indicator of time since death). Yet current understanding of microbial ecology during decomposition is almost entirely based on plant litter. We know very little about microbes recycling carcass-derived organic matter despite the unique decomposition processes. Our objective was to quantify the taxonomic and functional succession of microbial populations in soils below decomposing cadavers, testing the hypotheses that a) periods of increased activity during decomposition are associated with particular taxa; and b) human-associated taxa are introduced to soils, but do not persist outside their host. We collected soils from beneath four cadavers throughout decomposition, and analyzed soil chemistry, microbial activity and bacterial community structure. As expected, decomposition resulted in pulses of soil C and nutrients (particularly ammonia) and stimulated microbial activity. There was no change in total bacterial abundances, however we observed distinct changes in both function and community composition. During active decay (7 - 12 days postmortem), respiration and biomass production rates were high: the community was dominated by Proteobacteria (increased from 15.0 to 26.1% relative abundance) and Firmicutes (increased from 1.0 to 29.0%), with reduced Acidobacteria abundances (decreased from 30.4 to 9.8%). Once decay rates slowed (10 - 23 d postmortem), respiration was elevated, but biomass production rates dropped dramatically; this community with low growth efficiency was dominated by Firmicutes (increased to 50.9%) and other anaerobic taxa. Human-associated bacteria, including the obligately anaerobic Bacteroides, were detected at high concentrations in soil throughout decomposition, up to 198 d postmortem. Our results revealed the pattern of functional and compositional succession in soil microbial communities during decomposition of human-derived organic matter, provided insight into decomposition processes, and identified putative predictor populations for time since death estimation. PMID:26067226

Validity of Postmortem Glycated Hemoglobin to Determine Status of Diabetes Mellitus in Corneal Donors.

PubMed

Soper, Mark C; Marcovina, Santica M; Hoover, Caroline K; Calhoun, Peter M; McCoy, Kristen E; Stoeger, Christopher G; Schmidt, Gregory A; Arafah, Baha M; Price, Marianne O; Szczotka-Flynn, Loretta B; Lass, Jonathan H

2017-08-01

To examine the stability of postmortem glycated hemoglobin (HbA1c) measurement and its relationship to premortem glycemia. Postmortem blood samples were obtained from 32 donors (8 known diabetic) and shipped on ice to a central laboratory to examine the stability of HbA1c measurements during the first 9 postmortem days. Thirty-nine other suspected diabetic donors underwent comparison of premortem and postmortem HbA1c measurements. Postmortem HbA1c measurements remained stable after 9 postmortem days (all measurements within ±0.2% from baseline with a mean difference of 0.02% ± 0.10%). Of the premortem measurements obtained within 90 days before death, 79% were within ±1.0% of the postmortem measurements compared with 40% for measurements more than 90 days apart. Three of the postmortem HbA1c measurements exceeded 6.5% (considered a threshold for diabetes diagnosis), although the medical histories did not indicate any previous diabetes diagnosis. Postmortem HbA1c testing is feasible with current eye bank procedures and is reflective of glycemic control of donors during 90 days before death. HbA1c testing could potentially be a useful adjunct to review of the medical history and records for donor assessment for endothelial keratoplasty suitability and long-term graft success.

Earliest Directly-Dated Human Skull-Cups

PubMed Central

Bello, Silvia M.; Parfitt, Simon A.; Stringer, Chris B.

2011-01-01

Background The use of human braincases as drinking cups and containers has extensive historic and ethnographic documentation, but archaeological examples are extremely rare. In the Upper Palaeolithic of western Europe, cut-marked and broken human bones are widespread in the Magdalenian (∼15 to 12,000 years BP) and skull-cup preparation is an element of this tradition. Principal Findings Here we describe the post-mortem processing of human heads at the Upper Palaeolithic site of Gough's Cave (Somerset, England) and identify a range of modifications associated with the production of skull-cups. New analyses of human remains from Gough's Cave demonstrate the skilled post-mortem manipulation of human bodies. Results of the research suggest the processing of cadavers for the consumption of body tissues (bone marrow), accompanied by meticulous shaping of cranial vaults. The distribution of cut-marks and percussion features indicates that the skulls were scrupulously 'cleaned' of any soft tissues, and subsequently modified by controlled removal of the facial region and breakage of the cranial base along a sub-horizontal plane. The vaults were also ‘retouched’, possibly to make the broken edges more regular. This manipulation suggests the shaping of skulls to produce skull-cups. Conclusions Three skull-cups have been identified amongst the human bones from Gough's Cave. New ultrafiltered radiocarbon determinations provide direct dates of about 14,700 cal BP, making these the oldest directly dated skull-cups and the only examples known from the British Isles. PMID:21359211

Elevated gamma-aminobutyric acid levels in chronic schizophrenia.

PubMed

Ongür, Dost; Prescot, Andrew P; McCarthy, Julie; Cohen, Bruce M; Renshaw, Perry F

2010-10-01

Despite widely replicated abnormalities of gamma-aminobutyric acid (GABA) neurons in schizophrenia postmortem, few studies have measured tissue GABA levels in vivo. We used proton magnetic resonance spectroscopy to measure tissue GABA levels in participants with schizophrenia and healthy control subjects in the anterior cingulate cortex and parieto-occipital cortex. Twenty-one schizophrenia participants effectively treated on a stable medication regimen (mean age 39.0, 14 male) and 19 healthy control subjects (mean age 36.3, 12 male) underwent a proton magnetic resonance spectroscopy scan using GABA-selective editing at 4 Tesla after providing informed consent. Data were collected from two 16.7-mL voxels and analyzed using LCModel. We found elevations in GABA/creatine in the schizophrenia group compared with control subjects [F(1,65) = 4.149, p = .046] in both brain areas (15.5% elevation in anterior cingulate cortex, 11.9% in parieto-occipital cortex). We also found a positive correlation between GABA/creatine and glutamate/creatine, which was not accounted for by % GM or brain region. We found elevated GABA/creatinine in participants with chronically treated schizophrenia. Postmortem studies report evidence for dysfunctional GABAergic neurotransmission in schizophrenia. Elevated GABA levels, whether primary to illness or compensatory to another process, may be associated with dysfunctional GABAergic neurotransmission in chronic schizophrenia. Copyright © 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Selection of Reference Gene Expression in a Schizophrenia Brain Cohort

PubMed Central

Weickert, Cynthia Shannon; Sheedy, Donna; Rothmond, Debora A.; Dedova, Irina; Fung, Samantha; Garrick, Therese; Wong, Jenny; Harding, Antony J.; Sivagnanansundaram, Sinthuja; Hunt, Clare; Duncan, Carlotta; Sundqvist, Nina; Tsai, Shan-Yuan; Anand, Jasna; Draganic, Daren; Harper, Clive

2010-01-01

Objective To conduct postmortem human brain research into the neuropathological basis of schizophrenia, it is critical to establish cohorts that are well-characterised and well-matched. Our objective was to determine if specimen characteristics, including: diagnosis, age, postmortem interval (PMI), brain acidity (pH), and/or the agonal state of the subject at death related to RNA quality, and to determine the most appropriate reference gene mRNAs. Methods We selected a matched cohort of 74 cases (37 schizophrenia / schizoaffective disorder cases and 37 controls cases). Middle frontal gyrus tissue was pulverised, tissue pH was measured, RNA isolated for cDNA from each case, and RNA integrity number (RIN) measurements were assessed. Using RT-PCR, we measured nine housekeeper genes and calculated a geomean in each diagnostic group. Results We found that the RINs were very good (mean 7.3) and all nine housekeeper control genes were significantly correlated with RIN. Seven of nine housekeeper genes were also correlated with pH, and two clinical variables, agonal state and duration of illness did have an effect on some control mRNAs. No major impact of PMI or freezer time on housekeeper mRNAs was detected. Our results show that people with schizophrenia had significantly less PPIA, and SDHA and tended to have less GUSB and B2M mRNA suggesting that these control genes may not be good candidates for normalisation. Conclusions In our cohort, less than 10% variability in RIN values was detected and the diagnostic groups were well matched overall. Our cohort was adequately powered (0.80–0.90) to detect mRNA differences (25%) due to disease. Our study suggests that multiple factors should be considered in mRNA expression studies of human brain tissues. When schizophrenia cases are adequately matched to control cases subtle differences in gene expression can be reliably detected. PMID:20073568

Development and application of specific cytokine assays in tissue samples from a bottlenose dolphin with hyperinsulinemia

USDA-ARS?s Scientific Manuscript database

Chronic inflammation has been associated with insulin resistance and type 2 diabetes in humans. Postmortem hepatic and splenic tissue from a 46-year old geriatric male bottlenose dolphin (Tursiops truncatus) with insulin resistance (chronic hyperinsulinemia with hyperglycemia) , chronic = inflamma...

Study on the apoptosis mediated by cytochrome c and factors that affect the activation of bovine longissimus muscle during postmortem aging.

PubMed

Zhang, Jiaying; Yu, Qunli; Han, Ling; Chen, Cheng; Li, Hang; Han, Guangxing

2017-06-01

This study investigates whether bovine longissimus muscle cell apoptosis occurs during postmortem aging and whether apoptosis is dependent on the mitochondria pathway. This study also determines the apoptosis process mediated by cytochrome c after its release from mitochondria and the factors that affect the activation processes. Results indicate that apoptotic nuclei were detected at 12 h postmortem. Cytochrome c release from the mitochondria to the cytoplasm activated the caspase-9 and caspase-3 at early postmortem aging and the activation of caspase-9 occurs before the activation of caspase-3. The pH level decreased during the first 48 h postmortem, whereas the mitochondria membrane permeability increased from 6 to 12 h. Results demonstrate that an apoptosis process of bovine muscle occurred during postmortem aging. Apoptosis was dependent on the mitochondria pathway and occurred at early postmortem aging. Increased mitochondria membrane permeability and low pH are necessary conditions for the release of cytochrome c during postmortem aging.

Outdoor post-mortem bite injuries by Tapinoma nigerrimum (Hymenoptera, Formicidae) on a human corpse: Case report.

PubMed

Bonacci, Teresa; Vercillo, Vannio

2015-07-01

Ants are among the insects that colonize exposed human and animal corpses during the early stage of decomposition. In Calabria, Italy (as well as in other countries), Formicidae have been observed preying on immature stages of Diptera and other insects, as well as causing irregular scalloped areas of superficial skin loss on human corpses and animal carcasses. We present a case of injuries on a human corpse caused by ant feeding. The macroscopic appearance is described and the results of a histochemical investigation of the skin lesions caused by worker ants are reported for the first time. The investigation was carried out on the fresh corpse of a 53-year-old man discovered in a rural area of Cosenza province (Calabria, southern Italy). Numerous irregular areas of superficial skin loss caused by the ant Tapinoma nigerrimum (Nylander 1856) (Hymenoptera, Formicidae) were observed on the body surface, inflicted very early in the post-mortem period. Because the classification of lesions is of crucial importance for forensic investigations, the macroscopic appearance and distribution pattern of the lesions on the corpse are illustrated. The histochemical investigation of the damaged skin explains, for the first time, the mechanism of production of the lesions. Copyright © 2015 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

Calbindin-D28k is a more reliable marker of human Purkinje cells than standard Nissl stains: a stereological experiment.

PubMed

Whitney, Elizabeth R; Kemper, Thomas L; Rosene, Douglas L; Bauman, Margaret L; Blatt, Gene J

2008-02-15

In a study of human Purkinje cell (PC) number, a striking mismatch between the number of PCs observed with the Nissl stain and the number of PCs immunopositive for calbindin-D28k (CB) was identified in 2 of the 10 brains examined. In the remaining eight brains this mismatch was not observed. Further, in these eight brains, analysis of CB immunostained sections counterstained with the Nissl stain revealed that more than 99% Nissl stained PCs were also immunopositive for CB. In contrast, in the two discordant brains, only 10-20% of CB immunopositive PCs were also identified with the Nissl stain. Although this finding was unexpected, a historical survey of the literature revealed that Spielmeyer [Spielmeyer W. Histopathologie des nervensystems. Julius Springer: Berlin; 1922. p. 56-79] described human cases with PCs that lacked the expected Nissl staining intensity, an important historical finding and critical issue when studying postmortem human brains. The reason for this failure in Nissl staining is not entirely clear, but it may result from premortem circumstances since it is not accounted for by postmortem delay or processing variables. Regardless of the exact cause, these observations suggest that Nissl staining may not be a reliable marker for PCs and that CB is an excellent alternative marker.

Evaluation of the Nicotinic Acetylcholine Receptor-Associated Proteome at Baseline and Following Nicotine Exposure in Human and Mouse Cortex.

PubMed

McClure-Begley, Tristan D; Esterlis, Irina; Stone, Kathryn L; Lam, TuKiet T; Grady, Sharon R; Colangelo, Christopher M; Lindstrom, Jon M; Marks, Michael J; Picciotto, Marina R

2016-01-01

Nicotinic acetylcholine receptors (nAChRs) support the initiation and maintenance of smoking, but the long-term changes occurring in the protein complex as a result of smoking and the nicotine in tobacco are not known. Human studies and animal models have also demonstrated that increasing cholinergic tone increases behaviors related to depression, suggesting that the nAChR-associated proteome could be altered in individuals with mood disorders. We therefore immunopurified nAChRs and associated proteins for quantitative proteomic assessment of changes in protein-protein interactions of high-affinity nAChRs containing the β2 subunit (β2*-nAChRs) from either cortex of mice treated with saline or nicotine, or postmortem human temporal cortex tissue from tobacco-exposed and nonexposed individuals, with a further comparison of diagnosed mood disorder to control subjects. We observed significant effects of nicotine exposure on the β2*-nAChR-associated proteome in human and mouse cortex, particularly in the abundance of the nAChR subunits themselves, as well as putative interacting proteins that make up core components of neuronal excitability (Na/K ATPase subunits), presynaptic neurotransmitter release (syntaxins, SNAP25, synaptotagmin), and a member of a known nAChR protein chaperone family (14-3-3ζ). These findings identify candidate-signaling proteins that could mediate changes in cholinergic signaling via nicotine or tobacco use. Further analysis of identified proteins will determine whether these interactions are essential for primary function of nAChRs at presynaptic terminals. The identification of differences in the nAChR-associated proteome and downstream signaling in subjects with various mood disorders may also identify novel etiological mechanisms and reveal new treatment targets.

Bleeding Efficiency, Microbiological Quality and Oxidative Stability of Meat from Goats Subjected to Slaughter without Stunning in Comparison with Different Methods of Pre-Slaughter Electrical Stunning

PubMed Central

Sabow, Azad Behnan; Zulkifli, Idrus; Goh, Yong Meng; Ab Kadir, Mohd Zainal Abidin; Kaka, Ubedullah; Imlan, Jurhamid Columbres; Abubakar, Ahmed Abubakar; Adeyemi, Kazeem Dauda; Sazili, Awis Qurni

2016-01-01

The influence of pre-slaughter electrical stunning techniques and slaughter without stunning on bleeding efficiency and shelf life of chevon during a 14 d postmortem aging were assessed. Thirty two Boer crossbred bucks were randomly assigned to four slaughtering techniques viz slaughter without stunning (SWS), low frequency head-only electrical stunning (LFHO; 1 A for 3 s at a frequency of 50 Hz), low frequency head-to-back electrical stunning (LFHB; 1 A for 3 s at a frequency of 50 Hz) and high frequency head-to-back electrical stunning (HFHB; 1 A for 3 s at a frequency of 850 Hz). The SWS, LFHO and HFHB goats had higher (p<0.05) blood loss and lower residual hemoglobin in muscle compared to LFHB. The LFHB meat had higher (p<0.05) TBARS value than other treatments on d 7 and 14 d postmortem. Slaughtering methods had no effect on protein oxidation. Higher bacterial counts were observed in LFHB meat compared to those from SWS, LFHO and HFHB after 3 d postmortem. Results indicate that the low bleed-out in LFHB lowered the lipid oxidative stability and microbiological quality of chevon during aging. PMID:27035716

Bleeding Efficiency, Microbiological Quality and Oxidative Stability of Meat from Goats Subjected to Slaughter without Stunning in Comparison with Different Methods of Pre-Slaughter Electrical Stunning.

PubMed

Sabow, Azad Behnan; Zulkifli, Idrus; Goh, Yong Meng; Ab Kadir, Mohd Zainal Abidin; Kaka, Ubedullah; Imlan, Jurhamid Columbres; Abubakar, Ahmed Abubakar; Adeyemi, Kazeem Dauda; Sazili, Awis Qurni

2016-01-01

The influence of pre-slaughter electrical stunning techniques and slaughter without stunning on bleeding efficiency and shelf life of chevon during a 14 d postmortem aging were assessed. Thirty two Boer crossbred bucks were randomly assigned to four slaughtering techniques viz slaughter without stunning (SWS), low frequency head-only electrical stunning (LFHO; 1 A for 3 s at a frequency of 50 Hz), low frequency head-to-back electrical stunning (LFHB; 1 A for 3 s at a frequency of 50 Hz) and high frequency head-to-back electrical stunning (HFHB; 1 A for 3 s at a frequency of 850 Hz). The SWS, LFHO and HFHB goats had higher (p<0.05) blood loss and lower residual hemoglobin in muscle compared to LFHB. The LFHB meat had higher (p<0.05) TBARS value than other treatments on d 7 and 14 d postmortem. Slaughtering methods had no effect on protein oxidation. Higher bacterial counts were observed in LFHB meat compared to those from SWS, LFHO and HFHB after 3 d postmortem. Results indicate that the low bleed-out in LFHB lowered the lipid oxidative stability and microbiological quality of chevon during aging.

Estimation of the relative sensitivity of the comparative tuberculin skin test in tuberculous cattle herds subjected to depopulation.

PubMed

Karolemeas, Katerina; de la Rua-Domenech, Ricardo; Cooper, Roderick; Goodchild, Anthony V; Clifton-Hadley, Richard S; Conlan, Andrew J K; Mitchell, Andrew P; Hewinson, R Glyn; Donnelly, Christl A; Wood, James L N; McKinley, Trevelyan J

2012-01-01

Bovine tuberculosis (bTB) is one of the most serious economic animal health problems affecting the cattle industry in Great Britain (GB), with incidence in cattle herds increasing since the mid-1980s. The single intradermal comparative cervical tuberculin (SICCT) test is the primary screening test in the bTB surveillance and control programme in GB and Ireland. The sensitivity (ability to detect infected cattle) of this test is central to the efficacy of the current testing regime, but most previous studies that have estimated test sensitivity (relative to the number of slaughtered cattle with visible lesions [VL] and/or positive culture results) lacked post-mortem data for SICCT test-negative cattle. The slaughter of entire herds ("whole herd slaughters" or "depopulations") that are infected by bTB are occasionally conducted in GB as a last-resort control measure to resolve intractable bTB herd breakdowns. These provide additional post-mortem data for SICCT test-negative cattle, allowing a rare opportunity to calculate the animal-level sensitivity of the test relative to the total number of SICCT test-positive and negative VL animals identified post-mortem (rSe). In this study, data were analysed from 16 whole herd slaughters (748 SICCT test-positive and 1031 SICCT test-negative cattle) conducted in GB between 1988 and 2010, using a bayesian hierarchical model. The overall rSe estimate of the SICCT test at the severe interpretation was 85% (95% credible interval [CI]: 78-91%), and at standard interpretation was 81% (95% CI: 70-89%). These estimates are more robust than those previously reported in GB due to inclusion of post-mortem data from SICCT test-negative cattle.

Ethical and practical considerations concerning perimortem sperm procurement in a severe neurologically damaged patient and the apparent discrepancy in validation of proxy consent in various postmortem procedures.

PubMed

Epker, J L; de Groot, Y J; Kompanje, E J O

2012-06-01

Although sperm procurement and preservation has been become commonplace in situations in which infertility can be easily foreseen, peri- or postmortem sperm procurement for reproductive use in unexpected coma or death is not generally accepted. There are no laws and regulations for this kind of intervention in all countries and they may also differ from country to country. Intensive care specialists can be confronted with a request for peri- or postmortem sperm procurement, while not being aware of the country-specific provisions. A young male patient who suffered 17 L blood loss and half an hour of cardiopulmonary resuscitation was admitted to a university hospital for an ill-understood unstoppable abdominal bleed. After rapid deterioration of the neurological situation, due to severe post-anoxic damage, the decision was made to withdraw life-sustaining treatment. At that moment the partner of the patient asked for perimortem sperm procurement, which was denied, on the basis of the ethical reasoning that consent of the man involved was lacking. Retrospectively the decision was right according to Dutch regulations; however, with more time for elaborate ethical reasoning, the decision outcome, without the awareness of an existing prohibition, also could have been different. Guidelines and laws for peri- or postmortem sperm procurement differ from country to country, so any intensive care specialist should have knowledge from the latest legislation for this specific subject in his/her country. An overview is provided. A decision based on ethical reasoning may appear satisfying, but can unfortunately be in full contrast with the existing laws.

Prevalence of Atherosclerotic Coronary Stenosis in Asymptomatic North Indian Population: A Post-mortem Coronary Angiography Study.

PubMed

Bansal, Yogender Singh; Mandal, Shatrugan Prasad; Kumar, Senthil; Setia, Puneet

2015-09-01

A preliminary study of coronaries using post-mortem angiography was undertaken to see the prevalence of atherosclerotic coronary stenosis in non-cardiac unnatural deaths. This study was conducted in a tertiary care centre located in Chandigarh. A total of 128 medico-legal cases were studied comprising 88 males and 40 females. Post-mortem examinations of these MLC cases were conducted in the Department of Forensic Medicine, PGIMER, Chandigarh. All hearts were visually screened by post-mortem coronary angiography first and then grossly examined using serial transverse incision technique in positive screening cases to find the degree of narrowing. Of the study group, 34% males and 20% females showed evidence of narrowing on angiography. Of the males showing coronary stenosis, 83% had single vessel disease and 13% had double vessel disease, while only one individual had triple vessel disease. In cases of female, all the cases of coronary stenosis were single vessel disease. Left anterior descending coronary artery (LAD) was the most common vessel involved, followed by right coronary artery (RCA) & Left circumflex artery (LCX) and in cases of double vessel disease, LAD in combination with LCX was responsible for 75% of the cases. Remarkably 23.6% of study population in the age group of less than 40 years showed appreciable narrowing in at least one of the coronaries. In general, the prevalence of CAD is on the rise, particularly in younger population owing to the changes in their lifestyle and food habits. This preliminary study revealed evidence of narrowing of at least one coronary in 34% male and 20% female population and 23.6% subjects were less than 40 years old. Further detailed studies are needed especially in younger age group and to support the need for preventive cardiology in the early years of life.

Estimation of the Relative Sensitivity of the Comparative Tuberculin Skin Test in Tuberculous Cattle Herds Subjected to Depopulation

PubMed Central

Karolemeas, Katerina; de la Rua-Domenech, Ricardo; Cooper, Roderick; Goodchild, Anthony V.; Clifton-Hadley, Richard S.; Conlan, Andrew J. K.; Mitchell, Andrew P.; Hewinson, R. Glyn; Donnelly, Christl A.; Wood, James L. N.; McKinley, Trevelyan J.

2012-01-01

Bovine tuberculosis (bTB) is one of the most serious economic animal health problems affecting the cattle industry in Great Britain (GB), with incidence in cattle herds increasing since the mid-1980s. The single intradermal comparative cervical tuberculin (SICCT) test is the primary screening test in the bTB surveillance and control programme in GB and Ireland. The sensitivity (ability to detect infected cattle) of this test is central to the efficacy of the current testing regime, but most previous studies that have estimated test sensitivity (relative to the number of slaughtered cattle with visible lesions [VL] and/or positive culture results) lacked post-mortem data for SICCT test-negative cattle. The slaughter of entire herds (“whole herd slaughters” or “depopulations”) that are infected by bTB are occasionally conducted in GB as a last-resort control measure to resolve intractable bTB herd breakdowns. These provide additional post-mortem data for SICCT test-negative cattle, allowing a rare opportunity to calculate the animal-level sensitivity of the test relative to the total number of SICCT test-positive and negative VL animals identified post-mortem (rSe). In this study, data were analysed from 16 whole herd slaughters (748 SICCT test-positive and 1031 SICCT test-negative cattle) conducted in GB between 1988 and 2010, using a Bayesian hierarchical model. The overall rSe estimate of the SICCT test at the severe interpretation was 85% (95% credible interval [CI]: 78–91%), and at standard interpretation was 81% (95% CI: 70–89%). These estimates are more robust than those previously reported in GB due to inclusion of post-mortem data from SICCT test-negative cattle. PMID:22927952

Postmortem stability of Ebola virus.

PubMed

Prescott, Joseph; Bushmaker, Trenton; Fischer, Robert; Miazgowicz, Kerri; Judson, Seth; Munster, Vincent J

2015-05-01

The ongoing Ebola virus outbreak in West Africa has highlighted questions regarding stability of the virus and detection of RNA from corpses. We used Ebola virus-infected macaques to model humans who died of Ebola virus disease. Viable virus was isolated <7 days posteuthanasia; viral RNA was detectable for 10 weeks.

Prevalence and distribution of Baylisascaris procyonis in urban raccoons (Procyon lotor) in Winnipeg, Manitoba.

PubMed

Sexsmith, Jennifer L; Whiting, Terry L; Green, Chris; Orvis, Sheldon; Berezanski, Dean J; Thompson, Amy B

2009-08-01

The prevalence of Baylisascaris procyonis was estimated in the urban raccoon population of Winnipeg through the fecal flotation of raccoon feces collected at active latrines and through gross postmortem and fecal flotation of samples collected from nuisance raccoons. Fecal flotation of latrine-collected feces was positive in 33 of 89 samples and, of 52 latrines identified, 26 were positive on 1 or more occasions. Trapped individual raccoons subjected to postmortem examination were positive in 57 of 114 animals captured. Comparing a single fecal flotation to the gold standard of finding adult worms in the small intestine had a sensitivity of 78.9% and specificity of 92.9%. This study suggests that carriage of Baylisascaris procyonis is widespread in raccoons in the Winnipeg urban ecosystem. Raccoon latrines in Winnipeg should be treated as infectious sites and efforts should be made to limit access of pets and people at risk to those sites.

Positron emission tomography quantification of serotonin transporter in suicide attempters with major depressive disorder.

PubMed

Miller, Jeffrey M; Hesselgrave, Natalie; Ogden, R Todd; Sullivan, Gregory M; Oquendo, Maria A; Mann, J John; Parsey, Ramin V

2013-08-15

Several lines of evidence implicate abnormal serotonergic function in suicidal behavior and completed suicide, including low serotonin transporter binding in postmortem studies of completed suicide. We have also reported low in vivo serotonin transporter binding in major depressive disorder (MDD) during a major depressive episode using positron emission tomography (PET) with [(11)C]McN5652. We quantified regional brain serotonin transporter binding in vivo in depressed suicide attempters, depressed nonattempters, and healthy controls using PET and a superior radiotracer, [(11)C]DASB. Fifty-one subjects with DSM-IV current MDD, 15 of whom were past suicide attempters, and 32 healthy control subjects underwent PET scanning with [(11)C]DASB to quantify in vivo regional brain serotonin transporter binding. Metabolite-corrected arterial input functions and plasma free-fraction were acquired to improve quantification. Depressed suicide attempters had lower serotonin transporter binding in midbrain compared with depressed nonattempters (p = .031) and control subjects (p = .0093). There was no difference in serotonin transporter binding comparing all depressed subjects with healthy control subjects considering six a priori regions of interest simultaneously (p = .41). Low midbrain serotonin transporter binding appears to be related to the pathophysiology of suicidal behavior rather than of major depressive disorder. This is consistent with postmortem work showing low midbrain serotonin transporter binding capacity in depressed suicides and may partially explain discrepant in vivo findings quantifying serotonin transporter in depression. Future studies should investigate midbrain serotonin transporter binding as a predictor of suicidal behavior in MDD and determine the cause of low binding. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Abnormal GABAergic function and negative affect in schizophrenia.

PubMed

Taylor, Stephan F; Demeter, Elise; Phan, K Luan; Tso, Ivy F; Welsh, Robert C

2014-03-01

Deficits in the γ-aminobutyric acid (GABA) system have been reported in postmortem studies of schizophrenia, and therapeutic interventions in schizophrenia often involve potentiation of GABA receptors (GABAR) to augment antipsychotic therapy and treat negative affect such as anxiety. To map GABAergic mechanisms associated with processing affect, we used a benzodiazepine challenge while subjects viewed salient visual stimuli. Fourteen stable, medicated schizophrenia/schizoaffective patients and 13 healthy comparison subjects underwent functional magnetic resonance imaging using the blood oxygenation level-dependent (BOLD) technique while they viewed salient emotional images. Subjects received intravenous lorazepam (LRZ; 0.01 mg/kg) or saline in a single-blinded, cross-over design (two sessions separated by 1-3 weeks). A predicted group by drug interaction was noted in the dorsal medial prefrontal cortex (dmPFC) as well as right superior frontal gyrus and left and right occipital regions, such that psychosis patients showed an increased BOLD signal to LRZ challenge, rather than the decreased signal exhibited by the comparison group. A main effect of reduced BOLD signal in bilateral occipital areas was noted across groups. Consistent with the role of the dmPFC in processing emotion, state negative affect positively correlated with the response to the LRZ challenge in the dmPFC for the patients and comparison subjects. The altered response to LRZ challenge is consistent with altered inhibition predicted by postmortem findings of altered GABAR in schizophrenia. These results also suggest that negative affect in schizophrenia/schizoaffective disorder is associated-directly or indirectly-with GABAergic function on a continuum with normal behavior.

Perinatal postmortems: what is important to parents and how do they decide?

PubMed

Breeze, Andrew C G; Statham, Helen; Hackett, Gerald A; Jessop, Flora A; Lees, Christoph C

2012-03-01

Falling consent rates for postmortems, regardless of age of death, have been widely reported in recent years. The aim of this study was to explore parental attitudes to, and decision-making about, a perinatal postmortem after termination for fetal abnormality, late miscarriage, or stillbirth. A prospective self-completion questionnaire was given to 35 women and their partners. The participants had experienced second or third trimester pregnancy loss in a single fetal medicine and delivery unit in the United Kingdom and were making decisions about having a postmortem. They were asked to complete a questionnaire about their attitudes to, and expectations of, a perinatal postmortem. Thirty-one questionnaires were received from parents of 17 babies (49% of those asked; 16 from mothers, 15 from fathers). Parents of nine babies (53%) said they would agree to a full postmortem, of three babies to a limited postmortem, and of four babies to an external examination only; one couple were undecided. The most important issues for the parents in this study that related to their decisions about a postmortem centered on the need for information, both for future planning and about what had happened. Moderately important issues related to altruism, which is, improving medical knowledge and helping other parents experiencing similar bereavement. Among the lowest scoring issues were potential barriers, such as concerns about cultural or religious acceptability of a postmortem, funeral delays, and what would happen to the baby's body. Bereaved parents who participated in this study, where postmortem consent rates were relatively high, thought that their need for knowledge eclipsed assumed barriers when deciding whether or not to have a postmortem for their baby. © 2012, Copyright the Authors. Journal compilation © 2012, Wiley Periodicals, Inc.

Increased protein oxidation in human substantia nigra pars compacta in comparison with basal ganglia and prefrontal cortex measured with an improved dinitrophenylhydrazine assay.

PubMed

Floor, E; Wetzel, M G

1998-01-01

The dopaminergic phenotype of neurons in human substantia nigra deteriorates during normal aging, and loss of these neurons is prominent in Parkinson's disease. These degenerative processes are hypothesized to involve oxidative stress. To compare oxidative stress in the nigra and related regions, we measured carbonyl modifications of soluble proteins in postmortem samples of substantia nigra, basal ganglia, and prefrontal cortex from neurologically normal subjects, using an improved 2,4-dinitrophenylhydrazine assay. The protein carbonyl content was found to be about twofold higher in substantia nigra pars compacta than in the other regions. To further analyze this oxidative damage, the distribution of carbonyl groups on soluble proteins was determined by western immunoblot analysis. This method revealed that carbonyl content of the major proteins in each region was linearly dependent on molecular weight. This distribution raises the possibility that protein carbonyl content is controlled by a size-dependent mechanism in vivo. Our results suggest that oxidative stress is elevated in human substantia nigra pars compacta in comparison with other regions and that oxidative damage is higher within the dopaminergic neurons. Elevated oxidative damage may contribute to the degeneration of nigral dopaminergic neurons in aging and in Parkinson's disease.

A cytoarchitecture-driven myelin model reveals area-specific signatures in human primary and secondary areas using ultra-high resolution in-vivo brain MRI.

PubMed

Dinse, J; Härtwich, N; Waehnert, M D; Tardif, C L; Schäfer, A; Geyer, S; Preim, B; Turner, R; Bazin, P-L

2015-07-01

This work presents a novel approach for modelling laminar myelin patterns in the human cortex in brain MR images on the basis of known cytoarchitecture. For the first time, it is possible to estimate intracortical contrast visible in quantitative ultra-high resolution MR images in specific primary and secondary cytoarchitectonic areas. The presented technique reveals different area-specific signatures which may help to study the spatial distribution of cortical T1 values and the distribution of cortical myelin in general. It may lead to a new discussion on the concordance of cyto- and myeloarchitectonic boundaries, given the absence of such concordance atlases. The modelled myelin patterns are quantitatively compared with data from human ultra-high resolution in-vivo 7T brain MR images (9 subjects). In the validation, the results are compared to one post-mortem brain sample and its ex-vivo MRI and histological data. Details of the analysis pipeline are provided. In the context of the increasing interest in advanced methods in brain segmentation and cortical architectural studies, the presented model helps to bridge the gap between the microanatomy revealed by classical histology and the macroanatomy visible in MRI. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Regulation of Brain Glucose Metabolic Patterns by Protein Phosphorlyation and Drug Therapy

DTIC Science & Technology

2007-03-30

chlorpromazine and haloperidol revolutionized the treatment of mental illness the sedating and neuroleptic side effects produced by "typical...demonstrated in rodents chronically treated with haloperidol and clozapine. We also demonstrate significantly higher levels of lactate in the postmortem...lactate levels in the cerebellum of patients with schizophrenia (n = 35) and control subjects (n = 42) and in rats chronically treated with haloperidol

9 CFR 381.76 - Post-mortem inspection, when required; extent; traditional, Streamlined Inspection System (SIS...

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Post-mortem inspection, when required... INSPECTION REGULATIONS Post Mortem Inspection; Disposition of Carcasses and Parts § 381.76 Post-mortem...) Inspection System and the New Turkey Inspection (NTI) System; rate of inspection. (a) A post-mortem...

9 CFR 381.76 - Post-mortem inspection, when required; extent; traditional, Streamlined Inspection System (SIS...

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Post-mortem inspection, when required... INSPECTION REGULATIONS Post Mortem Inspection; Disposition of Carcasses and Parts § 381.76 Post-mortem...) Inspection System and the New Turkey Inspection (NTI) System; rate of inspection. (a) A post-mortem...

9 CFR 381.76 - Post-mortem inspection, when required; extent; traditional, Streamlined Inspection System (SIS...

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Post-mortem inspection, when required... INSPECTION REGULATIONS Post Mortem Inspection; Disposition of Carcasses and Parts § 381.76 Post-mortem...) Inspection System and the New Turkey Inspection (NTI) System; rate of inspection. (a) A post-mortem...

9 CFR 381.76 - Post-mortem inspection, when required; extent; traditional, Streamlined Inspection System (SIS...

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Post-mortem inspection, when required... INSPECTION REGULATIONS Post Mortem Inspection; Disposition of Carcasses and Parts § 381.76 Post-mortem...) Inspection System and the New Turkey Inspection (NTI) System; rate of inspection. (a) A post-mortem...

Alcohol and premature death in Estonian men: a study of forensic autopsies using novel biomarkers and proxy informants

PubMed Central

2012-01-01

Background Alcohol makes an important contribution to premature mortality in many countries in Eastern Europe, including Estonia. However, the full extent of its impact, and the mechanisms underlying it, are challenging issues to research. We describe the design and initial findings of a study aimed at investigating the association of alcohol with mortality in a large series of forensic autopsies of working-age men in Estonia. Methods 1299 male deaths aged 25-54 years were subject to forensic autopsy in 2008-2009. The routine autopsy protocol was augmented by a more systematic inspection of organs, drug testing, assay of liver enzymes and novel biomarkers of alcohol consumption (EtG, EtS and PEth), together with proxy interviews with next of kin for deaths among men who lived in or close to a major town. Results 595 augmented autopsies were performed. Of these, 66% were from external causes (26% suicide, 25% poisoning). 17% were attributed to circulatory system diseases and 7% to alcoholic liver disease. Blood alcohol concentrations (BAC) of ≥ 0.2 mg/g were found for 55% of deaths. Interviews were conducted with proxy informants for 61% of the subjects who had resided in towns. Of these, 28% were reported in the previous year to have been daily or almost daily drinkers and 10% had drunk non-beverage alcohols. Blood ethanol and the liver enzyme GGT were only associated with daily drinking. However, the novel biomarkers showed a more graded response with recent consumption. In contrast, the liver enzymes AST and ALT were largely uninformative because of post-mortem changes. The presence of extremely high PEth concentrations in some samples also suggested post-mortem formation. Conclusion We have shown the feasibility of deploying an extended research protocol within the setting of routine forensic autopsies that offer scope to deepen our understanding of the alcohol-related burden of premature mortality. The most unique feature of the study is the information on a wide range of informative alcohol biomarkers, several of which have not been used previously in this sort of post-mortem research study. We have demonstrated, for the first time, the epidemiological value and validity of these novel alcohol biomarkers in post-mortem samples. PMID:22369510

Postmortem diagnosis and toxicological validation of illicit substance use

PubMed Central

Lehrmann, E; Afanador, ZR; Deep-Soboslay, A; Gallegos, G; Darwin, WD; Lowe, RH; Barnes, AJ; Huestis, MA; Cadet, JL; Herman, MM; Hyde, TM; Kleinman, JE; Freed, WJ

2008-01-01

The present study examines the diagnostic challenges of identifying ante-mortem illicit substance use in human postmortem cases. Substance use, assessed by clinical case history reviews, structured next-of-kin interviews, by general toxicology of blood, urine, and/or brain, and by scalp hair testing, identified 33 cocaine, 29 cannabis, 10 phencyclidine and 9 opioid cases. Case history identified 42% cocaine, 76% cannabis, 10% phencyclidine, and 33% opioid cases. Next-of-kin interviews identified almost twice as many cocaine and cannabis cases as Medical Examiner (ME) case histories, and were crucial in establishing a detailed lifetime substance use history. Toxicology identified 91% cocaine, 68% cannabis, 80% phencyclidine, and 100% opioid cases, with hair testing increasing detection for all drug classes. A cocaine or cannabis use history was corroborated by general toxicology with 50% and 32% sensitivity, respectively, and with 82% and 64% sensitivity by hair testing. Hair testing corroborated a positive general toxicology for cocaine and cannabis with 91% and 100% sensitivity, respectively. Case history corroborated hair toxicology with 38% sensitivity for cocaine and 79% sensitivity for cannabis, suggesting that both case history and general toxicology underestimated cocaine use. Identifying ante-mortem substance use in human postmortem cases are key considerations in case diagnosis and for characterization of disorder-specific changes in neurobiology. The sensitivity and specificity of substance use assessments increased when ME case history was supplemented with structured next-of-kin interviews to establish a detailed lifetime substance use history, while comprehensive toxicology, and hair testing in particular, increased detection of recent illicit substance use. PMID:18201295

Development, Evaluation, and Sensitivity Analysis of Parametric Finite Element Whole-Body Human Models in Side Impacts.

PubMed

Hwang, Eunjoo; Hu, Jingwen; Chen, Cong; Klein, Katelyn F; Miller, Carl S; Reed, Matthew P; Rupp, Jonathan D; Hallman, Jason J

2016-11-01

Occupant stature and body shape may have significant effects on injury risks in motor vehicle crashes, but the current finite element (FE) human body models (HBMs) only represent occupants with a few sizes and shapes. Our recent studies have demonstrated that, by using a mesh morphing method, parametric FE HBMs can be rapidly developed for representing a diverse population. However, the biofidelity of those models across a wide range of human attributes has not been established. Therefore, the objectives of this study are 1) to evaluate the accuracy of HBMs considering subject-specific geometry information, and 2) to apply the parametric HBMs in a sensitivity analysis for identifying the specific parameters affecting body responses in side impact conditions. Four side-impact tests with two male post-mortem human subjects (PMHSs) were selected to evaluate the accuracy of the geometry and impact responses of the morphed HBMs. For each PMHS test, three HBMs were simulated to compare with the test results: the original Total Human Model for Safety (THUMS) v4.01 (O-THUMS), a parametric THUMS (P-THUMS), and a subject-specific THUMS (S-THUMS). The P-THUMS geometry was predicted from only age, sex, stature, and BMI using our statistical geometry models of skeleton and body shape, while the S-THUMS geometry was based on each PMHS's CT data. The simulation results showed a preliminary trend that the correlations between the PTHUMS- predicted impact responses and the four PMHS tests (mean-CORA: 0.84, 0.78, 0.69, 0.70) were better than those between the O-THUMS and the normalized PMHS responses (mean-CORA: 0.74, 0.72, 0.55, 0.63), while they are similar to the correlations between S-THUMS and the PMHS tests (mean-CORA: 0.85, 0.85, 0.67, 0.72). The sensitivity analysis using the PTHUMS showed that, in side impact conditions, the HBM skeleton and body shape geometries as well as the body posture were more important in modeling the occupant impact responses than the bone and soft tissue material properties and the padding stiffness with the given parameter ranges. More investigations are needed to further support these findings.

Autism spectrum disorder: neuropathology and animal models.

PubMed

Varghese, Merina; Keshav, Neha; Jacot-Descombes, Sarah; Warda, Tahia; Wicinski, Bridget; Dickstein, Dara L; Harony-Nicolas, Hala; De Rubeis, Silvia; Drapeau, Elodie; Buxbaum, Joseph D; Hof, Patrick R

2017-10-01

Autism spectrum disorder (ASD) has a major impact on the development and social integration of affected individuals and is the most heritable of psychiatric disorders. An increase in the incidence of ASD cases has prompted a surge in research efforts on the underlying neuropathologic processes. We present an overview of current findings in neuropathology studies of ASD using two investigational approaches, postmortem human brains and ASD animal models, and discuss the overlap, limitations, and significance of each. Postmortem examination of ASD brains has revealed global changes including disorganized gray and white matter, increased number of neurons, decreased volume of neuronal soma, and increased neuropil, the last reflecting changes in densities of dendritic spines, cerebral vasculature and glia. Both cortical and non-cortical areas show region-specific abnormalities in neuronal morphology and cytoarchitectural organization, with consistent findings reported from the prefrontal cortex, fusiform gyrus, frontoinsular cortex, cingulate cortex, hippocampus, amygdala, cerebellum and brainstem. The paucity of postmortem human studies linking neuropathology to the underlying etiology has been partly addressed using animal models to explore the impact of genetic and non-genetic factors clinically relevant for the ASD phenotype. Genetically modified models include those based on well-studied monogenic ASD genes (NLGN3, NLGN4, NRXN1, CNTNAP2, SHANK3, MECP2, FMR1, TSC1/2), emerging risk genes (CHD8, SCN2A, SYNGAP1, ARID1B, GRIN2B, DSCAM, TBR1), and copy number variants (15q11-q13 deletion, 15q13.3 microdeletion, 15q11-13 duplication, 16p11.2 deletion and duplication, 22q11.2 deletion). Models of idiopathic ASD include inbred rodent strains that mimic ASD behaviors as well as models developed by environmental interventions such as prenatal exposure to sodium valproate, maternal autoantibodies, and maternal immune activation. In addition to replicating some of the neuropathologic features seen in postmortem studies, a common finding in several animal models of ASD is altered density of dendritic spines, with the direction of the change depending on the specific genetic modification, age and brain region. Overall, postmortem neuropathologic studies with larger sample sizes representative of the various ASD risk genes and diverse clinical phenotypes are warranted to clarify putative etiopathogenic pathways further and to promote the emergence of clinically relevant diagnostic and therapeutic tools. In addition, as genetic alterations may render certain individuals more vulnerable to developing the pathological changes at the synapse underlying the behavioral manifestations of ASD, neuropathologic investigation using genetically modified animal models will help to improve our understanding of the disease mechanisms and enhance the development of targeted treatments.

Decreased Brain pH as a Shared Endophenotype of Psychiatric Disorders

PubMed Central

Hagihara, Hideo; Catts, Vibeke S; Katayama, Yuta; Shoji, Hirotaka; Takagi, Tsuyoshi; Huang, Freesia L; Nakao, Akito; Mori, Yasuo; Huang, Kuo-Ping; Ishii, Shunsuke; Graef, Isabella A; Nakayama, Keiichi I; Shannon Weickert, Cynthia; Miyakawa, Tsuyoshi

2018-01-01

Although the brains of patients with schizophrenia and bipolar disorder exhibit decreased brain pH relative to those of healthy controls upon postmortem examination, it remains controversial whether this finding reflects a primary feature of the diseases or is a result of confounding factors such as medication and agonal state. To date, systematic investigation of brain pH has not been undertaken using animal models that can be studied without confounds inherent in human studies. In the present study, we first reevaluated the pH of the postmortem brains of patients with schizophrenia and bipolar disorder by conducting a meta-analysis of existing data sets from 10 studies. We then measured pH, lactate levels, and related metabolite levels in brain homogenates from five neurodevelopmental mouse models of psychiatric disorders, including schizophrenia, bipolar disorder, and autism spectrum disorder. All mice were drug naive with the same agonal state, postmortem interval, and age within each strain. Our meta-analysis revealed that brain pH was significantly lower in patients with schizophrenia and bipolar disorder than in control participants, even when a few potential confounding factors (postmortem interval, age, and history of antipsychotic use) were considered. In animal experiments, we observed significantly lower pH and higher lactate levels in the brains of model mice relative to controls, as well as a significant negative correlation between pH and lactate levels. Our findings suggest that lower pH associated with increased lactate levels is not a mere artifact, but rather implicated in the underlying pathophysiology of schizophrenia and bipolar disorder. PMID:28776581

Glycoblotting method allows for rapid and efficient glycome profiling of human Alzheimer's disease brain, serum and cerebrospinal fluid towards potential biomarker discovery.

PubMed

Gizaw, Solomon T; Ohashi, Tetsu; Tanaka, Masakazu; Hinou, Hiroshi; Nishimura, Shin-Ichiro

2016-08-01

Understanding of the significance of posttranslational glycosylation in Alzheimer's disease (AD) is of growing importance for the investigation of the pathogenesis of AD as well as discovery research of the disease-specific serum biomarkers. We designed a standard protocol for the glycoblotting combined with MALDI-TOFMS to perform rapid and quantitative profiling of the glycan parts of glycoproteins (N-glycans) and glycosphingolipids (GSLs) using human AD's post-mortem samples such as brain tissues (dissected cerebral cortices such as frontal, parietal, occipital, and temporal domains), serum and cerebrospinal fluid (CSF). The structural profiles of the major N-glycans released from glycoproteins and the total expression levels of the glycans were found to be mostly similar between the brain tissues of the AD patients and those of the normal control group. In contrast, the expression levels of the serum and CSF protein N-glycans such as bisect-type and multiply branched glycoforms were increased significantly in AD patient group. In addition, the levels of some gangliosides such as GM1, GM2 and GM3 appeared to alter in the AD patient brain and serum samples when compared with the normal control groups. Alteration of the expression levels of major N- and GSL-glycans in human brain tissues, serum and CSF of AD patients can be monitored quantitatively by means of the glycoblotting-based standard protocols. The changes in the expression levels of the glycans derived from the human post-mortem samples uncovered by the standardized glycoblotting method provides potential serum biomarkers in central nervous system disorders and can contribute to the insight into the molecular mechanisms in the pathogenesis of neurodegenerative diseases and future drug discovery. Most importantly, the present preliminary trials using human post-mortem samples of AD patients suggest that large-scale serum glycomics cohort by means of various-types of human AD patients as well as the normal control sera can facilitate the discovery research of highly sensitive and reliable serum biomarkers for an early diagnosis of AD. This article is part of a Special Issue entitled "Glycans in personalised medicine" Guest Editor: Professor Gordan Lauc. Copyright © 2016 Elsevier B.V. All rights reserved.

Forensic Toxicology: An Introduction.

PubMed

Smith, Michael P; Bluth, Martin H

2016-12-01

This article presents an overview of forensic toxicology. The authors describe the three components that make up forensic toxicology: workplace drug testing, postmortem toxicology, and human performance toxicology. Also discussed are the specimens that are tested, the methods used, and how the results are interpreted in this particular discipline. Copyright © 2016 Elsevier Inc. All rights reserved.

The Anatomy of Amnesia: Neurohistological Analysis of Three New Cases

ERIC Educational Resources Information Center

Gold, Jeffrey J.; Squire, Larry R.

2006-01-01

The most useful information about the anatomy of human memory comes from cases where there has been extensive neuropsychological testing followed by detailed post-mortem neurohistological analysis. To our knowledge, only eight such cases have been reported (four with medial temporal lobe damage and four with diencephalic damage). Here we present…

Forensic use of a subtropical blowfly: the first case indicating minimum postmortem interval (mPMI) in southern Brazil and first record of Sarconesia chlorogaster from a human corpse.

PubMed

Vairo, Karine P; Corrêa, Rodrigo C; Lecheta, Melise C; Caneparo, Maria F; Mise, Kleber M; Preti, Daniel; de Carvalho, Claudio J B; Almeida, Lucia M; Moura, Mauricio O

2015-01-01

Southern Brazil is unique due to its subtropical climate. Here, we report on the first forensic entomology case and the first record of Sarconesia chlorogaster (Wiedemann) in a human corpse in this region. Flies' samples were collected from a body indoors at 20°C. Four species were found, but only Chrysomya albiceps (Wiedemann) and S. chlorogaster were used to estimate the minimum postmortem interval (mPMI). The mPMI was calculated using accumulated degree hour (ADH) and developmental time. The S. chlorogaster puparium collected was light in color, so we used an experiment to establish a more accurate estimate for time since initiation of pupation where we found full tanning after 3 h. Development of C. albiceps at 20°C to the end of the third instar is 7.4 days. The mPMI based on S. chlorogaster (developmental time until the third instar with no more than 3 h of pupae development) was 7.6 days. © 2014 American Academy of Forensic Sciences.

Expression of microRNAs in human post-mortem amyotrophic lateral sclerosis spinal cords provides insight into disease mechanisms.

PubMed

Figueroa-Romero, Claudia; Hur, Junguk; Lunn, J Simon; Paez-Colasante, Ximena; Bender, Diane E; Yung, Raymond; Sakowski, Stacey A; Feldman, Eva L

2016-03-01

Amyotrophic lateral sclerosis is a late-onset and terminal neurodegenerative disease. The majority of cases are sporadic with unknown causes and only a small number of cases are genetically linked. Recent evidence suggests that post-transcriptional regulation and epigenetic mechanisms, such as microRNAs, underlie the onset and progression of neurodegenerative disorders; therefore, altered microRNA expression may result in the dysregulation of key genes and biological pathways that contribute to the development of sporadic amyotrophic lateral sclerosis. Using systems biology analyses on postmortem human spinal cord tissue, we identified dysregulated mature microRNAs and their potential targets previously implicated in functional process and pathways associated with the pathogenesis of ALS. Furthermore, we report a global reduction of mature microRNAs, alterations in microRNA processing, and support for a role of the nucleotide binding protein, TAR DNA binding protein 43, in regulating sporadic amyotrophic lateral sclerosis-associated microRNAs, thereby offering a potential underlying mechanism for sporadic amyotrophic lateral sclerosis. Copyright © 2015 Elsevier Inc. All rights reserved.

A quantitative study of the histochemical and morphometric characteristics of the human cricopharyngeus muscle.

PubMed Central

Brownlow, H; Whitmore, I; Willan, P L

1989-01-01

Samples of human cricopharyngeus muscles obtained at postmortem were assessed for fibre type composition and fibre size. Fibre type was determined using serial cryostat sections exposed to several histochemical reactions; narrow fibre diameter and fibre area were measured from photomicrographs using a digitiser interfaced to a microcomputer. Results were compared with values from samples of vastus lateralis obtained from the same subjects. Cricopharyngeus muscle, in comparison with vastus lateralis, contained significantly more oxidative fibres but fewer glycolytic fibres and significantly more Type I fibres but fewer Type IIB. Cricopharyngeal fibres were significantly smaller than the fibres in vastus lateralis and in neither muscle were fibre sizes normally distributed. In each muscle most Type I fibres were oxidative, and the ratio of oxidative: glycolytic fibres was similar for Type IIA and IIB fibres. The fibre type proportions and fibre sizes in cricopharyngeus did not vary significantly with age or between males and females. The composition of cricopharyngeus--mostly Type I oxidative fibres and few Type II glycolytic fibres--correlated well with the functions of sustained tonicity to prevent aerophagia and occasional forceful contraction during deglutition. Images Fig. 1 PMID:2621147

Kinetic modeling of the monoamine oxidase B radioligand [¹¹C]SL25.1188 in human brain with high-resolution positron emission tomography.

PubMed

Rusjan, Pablo M; Wilson, Alan A; Miler, Laura; Fan, Ian; Mizrahi, Romina; Houle, Sylvain; Vasdev, Neil; Meyer, Jeffrey H

2014-05-01

This article describes the kinetic modeling of [(11)C]SL25.1188 ([(S)-5-methoxymethyl-3-[6-(4,4,4-trifluorobutoxy)-benzo[d]isoxazol-3-yl]-oxazolidin-2-[(11)C]one]) binding to monoamine oxidase B (MAO-B) in the human brain using high-resolution positron emission tomography (PET). Seven healthy subjects underwent two separate 90- minute PET scans after an intravenous injection of [(11)C]SL25.1188. Complementary arterial blood sampling was acquired. Radioactivity was quickly eliminated from plasma with 80% of parent compound remaining at 90 minutes. Metabolites were more polar than the parent compound. Time-activity curves showed high brain uptake, early peak and washout rate consistent with known regional MAO-B concentration. A two-tissue compartment model (2-TCM) provided better fits to the data than a 1-TCM. Measurement of total distribution volume (VT) showed very good identifiability (based on coefficient of variation (COV)) for all regions of interest (ROIs) (COV(VT)<8%), low between-subject variability (∼20%), and quick temporal convergence (within 5% of final value at 45 minutes). Logan graphical method produces very good estimation of VT. Regional VT highly correlated with previous postmortem report of MAO-B level (r(2)= ≥ 0.9). Specific binding would account from 70% to 90% of VT. Hence, VT measurement of [(11)C]SL25.1(1)88 PET is an excellent estimation of MAO-B concentration.

High Prevalence of Human Parvovirus B19 DNA in Myocardial Autopsy Samples from Subjects without Myocarditis or Dilative Cardiomyopathy▿

PubMed Central

Schenk, Thomas; Enders, Martin; Pollak, Stefan; Hahn, Ralph; Huzly, Daniela

2009-01-01

Human parvovirus B19 has been linked to a variety of cardiac diseases, as well as to erythema infectiosum, acute arthropathy, and fetal hydrops. A causal association between viral infection and cardiac disease was frequently postulated following the detection of B19 DNA by PCR in endomyocardial biopsy specimens. Since the lifelong persistence of B19 DNA in bone marrow, skin, synovia, tonsils, and liver was previously reported, the aim of our study was to investigate the possibility of asymptomatic B19 DNA persistence in heart tissue. Myocardial autopsy and postmortem blood samples were prospectively collected from 69 bodies sent to the Department of Forensic Medicine, Freiburg University Medical Center, for inquests. All study subjects were screened for B19-specific antibodies using a commercial enzyme immunoassay. Tissue samples were analyzed by real-time PCR for the presence of viral DNA. Since the presence of B19 genotype 2, known to have been circulating before 1960, would prove long-lasting persistence, the presence of the B19 genotype was retrospectively determined in seven of the study subjects by melting temperature analysis and sequencing of the PCR product. B19 DNA was found in myocardial samples from 46 of 48 seropositive and in none of 21 seronegative individuals. B19 genotype 1 was found in three patients born between 1950 and 1969. Genotype 2 was found in four patients born between 1927 and 1957. Our findings suggest lifelong persistence of B19 DNA in heart tissue. Thus, the detection of B19 DNA in myocardial biopsy specimens alone is not sufficient to postulate a relationship between B19 infection and cardiac disease. PMID:19005147

First survey of forensically important insects from human corpses in Shiraz, Iran.

PubMed

Moemenbellah-Fard, Mohammad D; Keshavarzi, Davood; Fereidooni, Mehran; Soltani, Aboozar

2018-02-01

The presence of insects on human cadavers has potential judicial value in medicolegal cases. This research emphasized the important role of insects in postmortem decomposition. It was conducted to investigate the composition and abundance of insects from human corpses during autopsies in legal medicine. It was implemented in the city of Shiraz, south Iran. Insects associated with human corpses were carefully collected and put into labelled vials. They were then identified using valid taxonomic keys. Fifteen outdoor (67%) and indoor discovered cadavers were examined. All but one was covered at the time of discovery. From these several species of entomofauna played important roles in the minimum postmortem interval (minPMI) estimate. Insects included the orders of Diptera and Coleoptera. Overall, 14 different species of arthropods were identified. Within Diptera, 2 families of Sarcophagidae and Calliphoridae were present in 73% of the cases with Calliphora vicina Robineau-Desvoidy and Chrysomya albiceps Wiedemann accounting for about half of the cases. The latter family members, Calliphoridae, were more frequently (52%) collected in autumn and winter. Only 4/15 outdoor cadavers had beetles. Four species of Coleopterans; namely Dermestes frischii Kugelann, Nitidula flavomaculata Rossi, Creophilus maxillosus Linnaeus and Saprinus chalcites Illiger; were recorded for the first time from 3 corpses in Iran. The presence and diversity of different insects on human corpses could contribute to the advancement of forensic entomology knowledge and the refined estimates of minPMI in medicolegal cases. Copyright © 2017. Published by Elsevier Ltd.

Dysbindin-1 and NRG-1 gene expression in immortalized lymphocytes from patients with schizophrenia.

PubMed

Yamamori, Hidenaga; Hashimoto, Ryota; Verrall, Louise; Yasuda, Yuka; Ohi, Kazutaka; Fukumoto, Motoyuki; Umeda-Yano, Satomi; Ito, Akira; Takeda, Masatoshi

2011-07-01

The dysbindin-1 and neuregulin-1 (NRG-1) genes are related to schizophrenia. Expression studies in postmortem brains have revealed lower expression of dysbindin-1 and higher expression of NRG-1 in brain tissue from subjects with schizophrenia. In addition to the difficulty of sampling, the use of postmortem brain tissues is not ideal because these tissues are heterogeneous with respect to biochemical parameters, lifetime history of medications and physiological status at the time of death. In contrast, medication and environmental influences that could mask the genetic basis of differences in RNA expression are removed in immortalized lymphocytes by culturing. Only a few microarray analysis studies using immortalized lymphocytes in schizophrenia have been reported, and whether immortalized lymphocytes are an appropriate alternative to neuronal tissue remains controversial. In this study, we measured the mRNA expression levels of dysbindin-1, NRG-1 and two other genes (NPY1R and GNAO1) in immortalized lymphocytes from 45 patients with schizophrenia and 45 controls using real-time quantitative reverse transcriptase-PCR. No difference was observed between patients and controls with respect to the expression of dysbindin-1, NRG-1, NPY1R or GNAO1 gene. Our findings suggest that the gene expression profile of immortalized lymphocyte from schizophrenic patients is different from that in postmortem brain tissue at least with respect to the dysbindin-1 and NRG-1 genes.

Pork Quality Traits According to Postmortem pH and Temperature in Berkshire

PubMed Central

Kim, Tae Wan; Kim, Chul Wook; Yang, Mi Ra; No, Gun Ryoung; Kim, Il-Suk

2016-01-01

This study was performed to investigate the role of pH and temperature postmortem, and to demonstrate the importance of these factors in determining meat quality. Postmortem pH45min (pH at 45 min postmortem or initial pH) via analysis of Pearson’s correlation showed high positive correlation with pH change pHc24 (pH change from pH45min to pH24h postmortem). However, postmortem pH after 24 h (pH24h or ultimate pH) had a high negative correlation with pH change, pHc24, CIE L*, and protein content. Initial temperature postmortem (T1h ) was positively associated with a change in temperature from 45 min to 24 h postmortem (Tc24) and cooking loss, but negatively correlated with water holding capacity. Temperature at 24 h postmortem (T24h) was negatively associated with Tc24. Collectively, these results indicate that higher initial pH was associated with higher pHc24, T1h, and Tc24. However, higher initial pH was associated with a reduction in carcass weight, backfat thickness, CIE a* and b*, water holding capacity, collagen and fat content, drip loss, and cooking loss as well as decreased shear force. In contrast, CIE a* and b*, drip loss, cooking loss, and shear force in higher ultimate pH was showed by a similar pattern to higher initial pH, whereas pHc24, carcass weight, backfat thickness, water holding capacity, fat content, moisture content, protein content, T1h, T24h, and Tc24 were exhibited by completely differential patterns (p<0.05). Therefore, we suggest that initial pH, ultimate pH, and temperatures postmortem are important factors in determining the meat quality of pork. PMID:27499661

Cardiac troponin T determination by a highly sensitive assay in postmortem serum and pericardial fluid.

PubMed

González-Herrera, Lucas; Valenzuela, Aurora; Ramos, Valentín; Blázquez, Antonia; Villanueva, Enrique

2016-06-01

The main objective of this study was to test, for the first time, a highly sensitive cardiac troponin T (cTnThs) assay in postmortem serum and pericardial fluid and to evaluate cardiac troponin T (cTnT) levels and their stability after death at different postmortem intervals, in an attempt to determine the viability of the cTnThs assay in the postmortem diagnosis of the cause of death. cTnT levels were determined in serum and pericardial fluid samples taken from 58 cadavers at known postmortem intervals, whose causes of death were categorized into the following groups: (1) sudden cardiac deaths, (2) multiple trauma, (3) mechanical asphyxia, and (4) other natural deaths. cTnT was determined by inmunoassay, using the Troponin T highly sensitive STAT assay (Roche(®)). Average cTnT levels measured by a highly sensitive assay in postmortem serum were markedly higher than clinical serum levels. Moreover, similar results, higher cTnT levels in postmortem pericardial fluid, were obtained when compared to levels found in pericardial fluid taken from two living patients during coronary artery bypass surgery. cTnT levels in both postmortem fluids remained stable for up to 34 h after death. No differences in cTnT levels in either postmortem fluid by sex and age were detected. Levels of cTnT found in pericardial fluid in the other natural deaths group were significantly lower than the cTnT levels found in that postmortem fluid from any of the other causes of death groups. It is therefore reasonable to conclude that determination of cTnT by a highly sensitive assay in pericardial fluid can provide forensic pathologists with a complementary test to the diagnosis of cause of death.

Quantification of endocannabinoids in postmortem brain of schizophrenic subjects.

PubMed

Muguruza, Carolina; Lehtonen, Marko; Aaltonen, Niina; Morentin, Benito; Meana, J Javier; Callado, Luis F

2013-08-01

Numerous studies have implicated the endocannabinoid system in the pathophysiology of schizophrenia. Endocannabinoids have been measured in blood and cerebrospinal fluid in schizophrenic patients but, to the date, there are no published reports dealing with measurements of endocannabinoid levels in schizophrenics' brain tissue. In the present study, postmortem brain samples from 19 subjects diagnosed with schizophrenia (DSM-IV) and 19 matched controls were studied. In specific brain regions, levels of four endocannabinoids (2-arachidonoylglycerol (2-AG), arachidonoylethanolamine (anandamide, AEA), dihomo-γ-linolenoylethanolamine (LEA), and docosahexaenoylethanolamine (DHEA)) and two cannabimimetic compounds (palmitoyl-ethanolamine (PEA) and oleoyl-ethanolamine (OEA)) were measured using quantitative liquid chromatography with triple quadrupole mass spectrometric detection. Suffering from schizophrenia significantly affects the brain levels of 2-AG (p<0.001), AEA (p<0.0001), DHEA (p<0.0001), LEA (p<0.01) and PEA (p<0.05). In schizophrenic subjects, the three studied brain regions (cerebellum: 130±18%; p=0.16; hippocampus: 168±28%, p<0.01; prefrontal cortex: 237±45%, p<0.05) showed higher 2-AG levels when compared to matched controls. Conversely, AEA levels were lower in all brain regions of schizophrenic subjects (cerebellum: 66±7%, p<0.01; hippocampus: 66±7%, p<0.01; prefrontal cortex: 75±10%, p=0.07). Statistically significant lower levels of DHEA were also found in cerebellum (60±6%, p<0.001) and hippocampus (68±7%, p<0.05) of schizophrenic subjects. PEA (71±6%, p<0.05) and LEA (72±6%, p<0.05) levels were also found to be lower in cerebellum. No significant differences were found in OEA levels. Our results evidence specific alterations in the levels of some endocannabinoids in different brain regions of schizophrenic subjects. Furthermore, these data evidence the involvement of the endocannabinoid system in the pathophysiology of schizophrenia. Copyright © 2013 Elsevier B.V. All rights reserved.

Comparing different post-mortem human samples as DNA sources for downstream genotyping and identification.

PubMed

Calacal, Gayvelline C; Apaga, Dame Loveliness T; Salvador, Jazelyn M; Jimenez, Joseph Andrew D; Lagat, Ludivino J; Villacorta, Renato Pio F; Lim, Maria Cecilia F; Fortun, Raquel D R; Datar, Francisco A; De Ungria, Maria Corazon A

2015-11-01

The capability of DNA laboratories to perform genotyping procedures from post-mortem remains, including those that had undergone putrefaction, continues to be a challenge in the Philippines, a country characterized by very humid and warm conditions all year round. These environmental conditions accelerate the decomposition of human remains that were recovered after a disaster and those that were left abandoned after a crime. When considerable tissue decomposition of human remains has taken place, there is no other option but to extract DNA from bone and/or teeth samples. Routinely, femur shafts are obtained from recovered bodies for human identification because the calcium matrix protects the DNA contained in the osteocytes. In the Philippines, there is difficulty in collecting femur samples after natural disasters or even human-made disasters, because these events are usually characterized by a large number of fatalities. Identification of casualties is further delayed by limitation in human and material resources. Hence, it is imperative to test other types of biological samples that are easier to collect, transport, process and store. We analyzed DNA that were obtained from body fluid, bone marrow, muscle tissue, clavicle, femur, metatarsal, patella, rib and vertebral samples from five recently deceased untreated male cadavers and seven male human remains that were embalmed, buried for ∼ 1 month and then exhumed. The bodies had undergone different environmental conditions and were in various stages of putrefaction. A DNA extraction method utilizing a detergent-washing step followed by an organic procedure was used. The utility of bone marrow and vitreous fluid including bone marrow and vitreous fluid that was transferred on FTA(®) cards and subjected to autosomal STR and Y-STR DNA typing were also evaluated. DNA yield was measured and the presence or absence of PCR inhibitors in DNA extracts was assessed using Plexor(®)HY. All samples were amplified using PowerPlex(®)21 and PowerPlexY(®)23 systems and analyzed using the AB3500 Genetic Analyzer and the GeneMapper(®) ID-X v.1.2 software. PCR inhibitors were consistently detected in bone marrow, muscle tissue, rib and vertebra samples. Amplifiable DNA was obtained in a majority of the samples analyzed. DNA recovery from 0.1g biological material was adequate for successful genotyping of most of the non-bone and bone samples. Complete DNA profiles were generated from bone marrow, femur, metatarsal and patella with 0.1 ng DNA template. Using 0.5 ng DNA template resulted in increased allele recovery and improved intra- and inter-locus peak balance. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Regional distribution of neuropeptide Y mRNA in postmortem human brain.

PubMed

Brené, S; Lindefors, N; Kopp, J; Sedvall, G; Persson, H

1989-12-01

The distribution of messenger RNA encoding neuropeptide Y (NPY) was studied in 11 different postmortem human brain regions using in situ hybridization histochemistry, and RNA blot analysis. In situ hybridization data revealed that the highest numerical density of labeled cells corresponded to neurons in accumbens area, caudate nucleus, putamen, and substantia innominata. Significantly fewer NPY mRNA-containing neurons were found in frontal and parietal cortex, amygdaloid body and dentate gyrus. No NPY mRNA-containing cells were found in substantia nigra. NPY mRNA-positive neurons from all regions studied showed relatively similar labeling, as revealed by computerized image analysis. Blot analysis showed an approximately 0.8 kb NPY mRNA in all brain regions studied, except in substantia nigra and cerebellum. Densitometric scanning of the autoradiograms revealed levels of NPY mRNA in the following order: putamen greater than caudate nucleus greater than frontal cortex (Brodmann areas 4 and 6) greater than temporal cortex (Brodmann area 38) greater than parietal cortex (Brodmann areas 5 and 7) greater than frontal cortex (Brodmann area 11). Hence, although NPY mRNA is widely distributed in neurons of the human brain large regional variation exists, with the highest expression in accumbens area and parts of the basal ganglia.

Absence of significant dissent should be sufficient for deceased donor organ procurement in New Zealand.

PubMed

Douglas, Thomas M; Douglas, Nicholas M

2009-10-01

New Zealand's organ donation rates are among the lowest in the OECD. In a bid to increase organ availability, the New Zealand Human Tissue Act 2008 introduces new consent arrangements for deceased donor organ procurement. This article assesses these new arrangements and presents the case for further reform. Our assessment and arguments are based on philosophical analysis informed by empirical data on the effectiveness of alternative consent systems. We: 1) Identify widely held ethical judgments about policies and practices relevant to organ donation (e.g. those relating to coronial post-mortems), 2) Assess the implications of these judgments for the Human Tissue Act and the assumptions that underpin it, and 3) Derive policy recommendations that are consistent with the judgments. The Human Tissue Act 2008 retains a strong consent requirement for organ procurement: organs may not be transplanted unless either the deceased or the family consents. We argue that organ availability could and should be increased by shifting from a model that requires consent to one that requires the absence of significant dissent. We recommend that New Zealand adopt either 1) an organ donation system similar to the existing system for ordering coronial post-mortems, or 2) a variant of the 'opt-out' system already in place in several other countries.

Cadaver Thanatomicrobiome Signatures: The Ubiquitous Nature of Clostridium Species in Human Decomposition.

PubMed

Javan, Gulnaz T; Finley, Sheree J; Smith, Tasia; Miller, Joselyn; Wilkinson, Jeremy E

2017-01-01

Human thanatomicrobiome studies have established that an abundant number of putrefactive bacteria within internal organs of decaying bodies are obligate anaerobes, Clostridium spp. These microorganisms have been implicated as etiological agents in potentially life-threatening infections; notwithstanding, the scale and trajectory of these microbes after death have not been elucidated. We performed phylogenetic surveys of thanatomicrobiome signatures of cadavers' internal organs to compare the microbial diversity between the 16S rRNA gene V4 hypervariable region and V3-4 conjoined regions from livers and spleens of 45 cadavers undergoing forensic microbiological studies. Phylogenetic analyses of 16S rRNA gene sequences revealed that the V4 region had a significantly higher mean Chao1 richness within the total microbiome data. Permutational multivariate analysis of variance statistical tests, based on unweighted UniFrac distances, demonstrated that taxa compositions were significantly different between V4 and V3-4 hypervariable regions ( p < 0.001). Of note, we present the first study, using the largest cohort of criminal cases to date, that two hypervariable regions show discriminatory power for human postmortem microbial diversity. In conclusion, here we propose the impact of hypervariable region selection for the 16S rRNA gene in differentiating thanatomicrobiomic profiles to provide empirical data to explain a unique concept, the Postmortem Clostridium Effect.

Neuronal nuclei isolation from human postmortem brain tissue.

PubMed

Matevossian, Anouch; Akbarian, Schahram

2008-10-01

Neurons in the human brain become postmitotic largely during prenatal development, and thus maintain their nuclei throughout the full lifespan. However, little is known about changes in neuronal chromatin and nuclear organization during the course of development and aging, or in chronic neuropsychiatric disease. However, to date most chromatin and DNA based assays (other than FISH) lack single cell resolution. To this end, the considerable cellular heterogeneity of brain tissue poses a significant limitation, because typically various subpopulations of neurons are intermingled with different types of glia and other non-neuronal cells. One possible solution would be to grow cell-type specific cultures, but most CNS cells, including neurons, are ex vivo sustainable, at best, for only a few weeks and thus would provide an incomplete model for epigenetic mechanisms potentially operating across the full lifespan. Here, we provide a protocol to extract and purify nuclei from frozen (never fixed) human postmortem brain. The method involves extraction of nuclei in hypotonic lysis buffer, followed by ultracentrifugation and immunotagging with anti-NeuN antibody. Labeled neuronal nuclei are then collected separately using fluorescence-activated sorting. This method should be applicable to any brain region in a wide range of species and suitable for chromatin immunoprecipitation studies with site- and modification-specific anti-histone antibodies, and for DNA methylation and other assays.

A Comparative Taphonomic Analysis of 24 Trophy Skulls from Modern Forensic Cases.

PubMed

Yucha, Josephine M; Pokines, James T; Bartelink, Eric J

2017-09-01

Cranial remains retained from fallen enemies are commonly referred to as "trophy skulls," and many such crania were acquired as souvenirs by U.S. servicemembers during WWII and the Vietnam conflict. These remains increasingly have become the subject of forensic anthropological analysis as their possessors, typically veterans or their relatives, try to discard or repatriate them. The present research uses a qualitative analytical approach to review 24 cases of reported trophy skulls (14 previously unpublished cases and 10 from the literature) to determine which perimortem and postmortem characteristics are most useful for generating a taphonomic profile. Overall, the taphonomic signature of trophy remains includes traits relating to acquisition and preparation, ornamental display, and subsequent curation. Contextual evidence and the biological profile also are considered when determining the possible origin of human cranial remains as a trophy skull. Thorough taphonomic analysis will aid in identifying these types of remains as trophy skulls. © 2017 American Academy of Forensic Sciences.

Less-lethal hybrid ammunition wounds: a forensic assessment introducing bullet-skin-bone entity.

PubMed

de Freminville, Humbert; Prat, Nicolas; Rongieras, Frederic; Voiglio, Eric J

2010-09-01

Agencies all around the world now use less-lethal weapons with homogeneous missiles such as bean bag or rubber bullets. Contusions and sometimes significant morbidity have been reported. This study focuses on wounds caused by hybrid ammunition with the pathologists' flap-by-flap procedure. Twenty-four postmortem human subjects were used, and lesions caused on frontal, temporal, sternal, and left tibial regions by a 40-mm hybrid ammunition (33 g weight) were evaluated on various distance range. The 50% risk of fractures occurred at 79.2 m/sec on the forehead, 72.9 m/sec on the temporal, 72.5 m/sec on the sternum, and 76.7 m/sec on the tibia. Skin lesions were not predictors of bone fracture. There was no correlation between soft and bone tissue observed lesions and impact velocity (correlated to distance range). Lesions observed with hybrid ammunition were the result of bullet-skin-bone entity as the interaction of the projectile on skin and bone tissues.

Time to address the problem of post-mortem procurement of organs for transplantation occurring without proper pre-mortem consent.

PubMed

Garwood-Gowers, Austen

2013-09-01

Current cadaveric organ transplant systems allow individuals to be classified as donors after death where they registered wishes in favour of this prior to death. However, systems for registering wishes pertaining to donation fall woefully short of securing proper consent. Furthermore, even jurisdictions which technically require consent to be obtained in order to treat an individual as a donor, allow that consent to be given by next of kin after death in circumstances where there is no evidence of the individual having refused prior to death. This article explores these and related issues with current systems from the perspectives of health law norms, ethics and human rights. It concludes that proper pre-mortem consent ought to be a pre-requisite for post-mortem organ transplantation.

Metabolomics and neuroanatomical evaluation of post-mortem changes in the hippocampus.

PubMed

Gonzalez-Riano, Carolina; Tapia-González, Silvia; García, Antonia; Muñoz, Alberto; DeFelipe, Javier; Barbas, Coral

2017-08-01

Understanding the human brain is the ultimate goal in neuroscience, but this is extremely challenging in part due to the fact that brain tissue obtained from autopsy is practically the only source of normal brain tissue and also since changes at different levels of biological organization (genetic, molecular, biochemical, anatomical) occur after death due to multiple mechanisms. Here we used metabolomic and anatomical techniques to study the possible relationship between post-mortem time (PT)-induced changes that may occur at both the metabolomics and anatomical levels in the same brains. Our experiments have mainly focused on the hippocampus of the mouse. We found significant metabolomic changes at 2 h PT, whereas the integrity of neurons and glia, at the anatomical/ neurochemical level, was not significantly altered during the first 5 h PT for the majority of histological markers.

Adverse events, toxicity and post-mortem data on duloxetine: case reports and literature survey.

PubMed

Vey, Eric L; Kovelman, Inna

2010-05-01

Duloxetine, a dual acting norepinephrine serotonin reuptake inhibitor, is a relatively new pharmacologic agent utilized in the treatment of depression, as well as diabetic neuropathic pain, fibromyalgia, and female stress urinary incontinence. This expanding scope of usage will inevitably lead to its eventual appearance during routine post-mortem toxicologic assays. Currently there is a paucity of post-mortem toxicologic data concerning duloxetine. The current report provides six additional case reports of post-mortem duloxetine levels, along with a review of duloxetine's pharmacokinetics, and the toxicologic manifestations which have been reported in the literature. The post-mortem levels reported, including the highest level recorded to date, are integrated with previously published reports to generate a foundation for a nascent guide to the interpretation of post-mortem duloxetine levels that could be encountered during routine post-mortem toxicologic analyses, and establish a basis upon which the establishment of toxic and lethal thresholds for this compound can be further elucidated with greater clarity. Copyright (c) 2010 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

An Integrated Teaching Method of Gross Anatomy and Computed Tomography Radiology

ERIC Educational Resources Information Center

Murakami, Tohru; Tajika, Yuki; Ueno, Hitoshi; Awata, Sachiko; Hirasawa, Satoshi; Sugimoto, Maki; Kominato, Yoshihiko; Tsushima, Yoshito; Endo, Keigo; Yorifuji, Hiroshi

2014-01-01

It is essential for medical students to learn and comprehend human anatomy in three dimensions (3D). With this in mind, a new system was designed in order to integrate anatomical dissections with diagnostic computed tomography (CT) radiology. Cadavers were scanned by CT scanners, and students then consulted the postmortem CT images during cadaver…

A Postmortem Study of Frontal and Temporal Gyri Thickness and Cell Number in Human Obesity.

PubMed

Gómez-Apo, Erick; García-Sierra, Adrián; Silva-Pereyra, Juan; Soto-Abraham, Virgilia; Mondragón-Maya, Alejandra; Velasco-Vales, Verónica; Pescatello, Linda S

2018-01-01

This study aimed to compare cortex thickness and neuronal cell density in postmortem brain tissue from people with overweight or obesity and normal weight. The cortex thickness and neuron density of eight donors with overweight or obesity (mean = 31.6 kg/m 2 ; SD = 4.35; n = 8; 6 male) and eight donors with normal weight (mean = 21.8 kg/m 2 ; SD = 1.5; n = 8; 5 male) were compared. All participants were Mexican and lived in Mexico City. Randomly selected thickness measures of different cortex areas from the frontal and temporal lobes were analyzed based on high-resolution real-size photographs. A histological analysis of systematic-random fields was used to quantify the number of neurons in postmortem left and right of the first, second, and third gyri of frontal and temporal lobe brain samples. No statistical difference was found in cortical thickness between donors with overweight or obesity and individuals with normal weight. A smaller number of neurons was found among the donors with overweight or obesity than the donors with normal weight at different frontal and temporal areas. A lower density of neurons is associated with overweight or obesity. The morphological basis for structural brain changes in obesity requires further investigation. © 2017 The Obesity Society.

Zinc transporters protein level in postmortem brain of depressed subjects and suicide victims.

PubMed

Rafalo-Ulinska, Anna; Piotrowska, Joanna; Kryczyk, Agata; Opoka, Włodzimierz; Sowa-Kucma, Magdalena; Misztak, Paulina; Rajkowska, Grazyna; Stockmeier, Craig A; Datka, Wojciech; Nowak, Gabriel; Szewczyk, Bernadeta

2016-12-01

Major depressive disorder (MDD) is a serious psychiatric illness, associated with an increasing rate of suicide. The pathogenesis of depression may be associated with the disruption of zinc (Zn) homeostasis. In the brain, several proteins that regulate Zn homeostasis are present, including Zn transporters (ZnTs) which remove Zn from the cytosol. The present study was designed to investigate whether depression and suicide are associated with alterations in the expression of the ZnTs protein. Protein levels of ZnT1, ZnT3, ZnT4, ZnT5 and ZnT6 were measured in postmortem brain tissue from two different cohorts. Cohort A contained 10 subjects diagnosed with MDD (7 were suicide victims) and 10 psychiatrically-normal control subjects and cohort B contained 11 non-diagnosed suicide victims and 8 sudden-death control subjects. Moreover, in cohort A we measured protein level of NMDA (GluN2A subunit), AMPA (GluA1 subunit) and 5-HT1A receptors and PSD-95. Proteins were measured in the prefrontal cortex (PFC) using Western blotting. In addition, Zn concentration was measured using a voltammetric method. There was a significant increase in protein levels of ZnT1, ZnT4, ZnT5 in the PFC in MDD, relative to control subjects, while ZnT3 protein level was decreased in MDD. There was no significant difference in the Zn concentration in the PFC between control and MDD subjects. Similarly, in the PFC of suicide victims (non-diagnosed), an increase in protein levels of ZnT1, ZnT4, ZnT5 and ZnT6 was observed. Conversely, protein levels of ZnT3 were decreased in both suicide victims and subjects with MDD, in comparison with control subjects. There was also a significant decrease in the protein level of GluA1, GluN2A, PSD-95 and 5-HT1A in MDD. Our studies suggest that alterations in Zn transport proteins are associated with the pathophysiology of MDD and suicide. Copyright © 2016 Elsevier Ltd. All rights reserved.

The genome in three dimensions: a new frontier in human brain research.

PubMed

Mitchell, Amanda C; Bharadwaj, Rahul; Whittle, Catheryne; Krueger, Winfried; Mirnics, Karoly; Hurd, Yasmin; Rasmussen, Theodore; Akbarian, Schahram

2014-06-15

Less than 1.5% of the human genome encodes protein. However, vast portions of the human genome are subject to transcriptional and epigenetic regulation, and many noncoding regulatory DNA elements are thought to regulate the spatial organization of interphase chromosomes. For example, chromosomal "loopings" are pivotal for the orderly process of gene expression, by enabling distal regulatory enhancer or silencer elements to directly interact with proximal promoter and transcription start sites, potentially bypassing hundreds of kilobases of interspersed sequence on the linear genome. To date, however, epigenetic studies in the human brain are mostly limited to the exploration of DNA methylation and posttranslational modifications of the nucleosome core histones. In contrast, very little is known about the regulation of supranucleosomal structures. Here, we show that chromosome conformation capture, a widely used approach to study higher-order chromatin, is applicable to tissue collected postmortem, thereby informing about genome organization in the human brain. We introduce chromosome conformation capture protocols for brain and compare higher-order chromatin structures at the chromosome 6p22.2-22.1 schizophrenia and bipolar disorder susceptibility locus, and additional neurodevelopmental risk genes, (DPP10, MCPH1) in adult prefrontal cortex and various cell culture systems, including neurons derived from reprogrammed skin cells. We predict that the exploration of three-dimensional genome architectures and function will open up new frontiers in human brain research and psychiatric genetics and provide novel insights into the epigenetic risk architectures of regulatory noncoding DNA. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Studies on drug metabolism by fungi colonizing decomposing human cadavers. Part II: biotransformation of five model drugs by fungi isolated from post-mortem material.

PubMed

Martínez-Ramírez, Jorge A; Walther, Grit; Peters, Frank T

2015-04-01

The present study investigated the in vitro metabolic capacity of 28 fungal strains isolated from post-mortem material towards five model drugs: amitriptyline, metoprolol, mirtazapine, promethazine, and zolpidem. Each fungal strain was incubated at 25 °C for up to 120 h with each of the five models drugs. Cunninghamella elegans was used as positive control. Aliquots of the incubation mixture were centrifuged and 50 μL of the supernatants were diluted and directly analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) with product ion scanning. The remaining mixture was analyzed by full scan gas chromatography-mass spectrometry (GC-MS) after liquid-liquid extraction and acetylation. The metabolic activity was evaluated through the total number of detected metabolites (NDM) produced in each model and fungal strains and the percentage of parent drug remaining (%RPD) after up to five days of incubation. All the tested fungal strains were capable of forming mammalian phase I metabolites. Fungi from the normal fungal flora of the human body such as Candida sp., Geotrichum candidum, and Trichosporon asahii) formed up to seven metabolites at %RPD values greater than 52% but no new fungal metabolites (NFM). In contrast, some airborne fungal strains like Bjerkandera adusta, Chaetomium sp, Coriolopsis sp., Fusarium solani and Mucor plumbeus showed NDM values exceeding those of the positive control, complete metabolism of the parent drug in some models and formation of NFM. NFM (numbers in brackets) were detected in four of the five model drugs: amitriptyline (18), metoprolol (4), mirtazapine (8), and zolpidem (2). The latter NFM are potential candidates for marker substances indicating post-mortem fungal metabolism. Copyright © 2014 John Wiley & Sons, Ltd.

The Stone Cold Truth: The Effect of Concrete Encasement on the Rate and Pattern of Soft Tissue Decomposition.

PubMed

Martin, D C; Dabbs, Gretchen R; Roberts, Lindsey G; Cleary, Megan K

2016-03-01

This study provides a descriptive analysis of taphonomic changes observed in the soft tissue of ten pigs (Sus scrofa) after being encased in Quickrete (®) concrete and excavated at monthly or bimonthly intervals over the course of 2 years. The best method of subject excavation was investigated. Rate and pattern of decomposition were compared to a nonencased control subject. Results demonstrate subjects interred in concrete decomposed significantly slower than the control subject (p < 0.01), the difference being observable after 1 month. After 1 year, the encased subject was in the early stage of decomposition with purging fluids and intact organs present, versus complete skeletonization of the control subject. Concrete subjects also display a unique decomposition pattern, exhibiting a chemically burned outer layer of skin and a common separation of the dermal and epidermal layers. Results suggest using traditional methods to estimate postmortem interval on concrete subjects may result in underestimation. © 2015 American Academy of Forensic Sciences.

The radiodensity of cerebrospinal fluid and vitreous humor as indicator of the time since death.

PubMed

Koopmanschap, Desirée H J L M; Bayat, Alireza R; Kubat, Bela; de Bakker, Henri M; Prokop, Mathias W M; Klein, Willemijn M

2016-09-01

After death, a series of changes occur naturally in the human body in a fairly regular pattern. These postmortem changes are detectable on postmortem CT scans (PMCT) and may be useful in estimating the postmortem interval (PMI). The purpose of our study is to correlate the PMCT radiodensities of the cerebrospinal fluid (CSF) and vitreous humor (VH) to the PMI. Three patient groups were included: group A consisted of 5 donated cadavers, group B, 100 in-hospital deceased patients, and group C, 12 out-of-hospital forensic cadavers. Group A were scanned every hour for a maximum of 36 h postmortem, and the tympanic temperature was measured prior to each scan. Groups B and C were scanned once after death (PMI range 0.2-63.8 h). Radiodensities of the VH and CSF were measured in Hounsfield units. Correlation between density and PMI was determined using linear regression and the influence of temperature was assessed by a multivariate regression model. Results from group A were validated in groups B and C. Group A showed increasing radiodensity of the CSF and VH over time (r (2) CSF, 0.65). PMI overruled the influence of temperature (r = 0.99 and p = 0.000). Groups B and C showed more diversity, with CSF and VH radiodensities below the mean regression line of Group A. The formula of this upper limit indicated the maximum PMI and was correct for >95 % of the cadavers. The results of group A showed a significant correlation between CSF radiodensity and PMI. The radiodensities in groups B and C were higher than in group A, therefore the maximum PMI can be estimated with the upper 95 % confidence interval of the correlation line of group A.

Quantification of interstitial fluid on whole body CT: comparison with whole body autopsy.

PubMed

Lo Gullo, Roberto; Mishra, Shelly; Lira, Diego A; Padole, Atul; Otrakji, Alexi; Khawaja, Ranish Deedar Ali; Pourjabbar, Sarvenaz; Singh, Sarabjeet; Shepard, Jo-Anne O; Digumarthy, Subba R; Kalra, Mannudeep K; Stone, James R

2015-12-01

Interstitial fluid accumulation can occur in pleural, pericardial, and peritoneal spaces, and subcutaneous tissue planes. The purpose of the study was to assess if whole body CT examination in a postmortem setting could help determine the presence and severity of third space fluid accumulation in the body. Our study included 41 human cadavers (mean age 61 years, 25 males and 16 females) who had whole-body postmortem CT prior to autopsy. All bodies were maintained in the morgue in the time interval between death and autopsy. Two radiologists reviewed the whole-body CT examinations independently to grade third space fluid in the pleura, pericardium, peritoneum, and subcutaneous space using a 5-point grading system. Qualitative CT grading for third space fluid was correlated with the amount of fluid found on autopsy and the quantitative CT fluid volume, estimated using a dedicated software program (Volume, Syngo Explorer, Siemens Healthcare). Moderate and severe peripheral edema was seen in 16/41 and 7/41 cadavers respectively. It is not possible to quantify anasarca at autopsy. Correlation between imaging data for third space fluid and the quantity of fluid found during autopsy was 0.83 for pleural effusion, 0.4 for pericardial effusion and 0.9 for ascites. The degree of anasarca was significantly correlated with the severity of ascites (p < 0.0001) but not with pleural or pericardial effusion. There was strong correlation between volumetric estimation and qualitative grading for anasarca (p < 0.0001) and pleural effusion (p < 0.0001). Postmortem CT can help in accurate detection and quantification of third space fluid accumulation. The quantity of ascitic fluid on postmortem CT can predict the extent of anasarca.

Optical clearing of the dura mater using glycerol: a reversible process to aid the post-mortem investigation of infant head injury.

PubMed

Cheshire, Emma C; Malcomson, Roger D G; Joseph, Shiju; Biggs, Mike J B; Adlam, David; Rutty, Guy N

2015-09-01

In cases of suspected abusive head trauma, a thorough and systematic study of the cranium and its contents is essential, preferably using the best available methods for observing the brain and its coverings. Building upon recent developments in skull bone removal techniques in infant autopsies, we have assessed the use of two optical clearing agents (OCAs), glycerol and mannitol, on pediatric dura mater in an attempt to increase the transparency of this tissue and thereby enhance the post-mortem assessment of infant head injuries, particularly subdural hematomas. Extracorporeal testing revealed glycerol to be the more effective OCA. Therefore, in situ investigations were commenced using glycerol during 33 pediatric post-mortem examinations. An increase in the transparency of the dura was observed in 32 of the 33 cases, within 1 min of application of the OCA. In a 2 year old with cerebral palsy, only partial optical clearance of the dura was seen, most likely due to a significantly atrophic brain, prominent gelatinous leptomeninges, and abnormally thickened dura. This technique allowed for detection of minimal amounts of subdural bleeding over the convexities, before dissection of the dura, avoiding post-mortem blood spillage from artifactually disrupted bridging veins. Optical clearing of the dura aided in the evaluation of patterns of subdural hemorrhage in three cases of non-accidental head injury, three cases of peri-natal head injury and one case of overlaying, apparently resulting in minor crush injury to the head. We have demonstrated that glycerol is an effective and easy-to-use OCA to effect the readily reversible optical clearing of human infant calvarial dura at autopsy.

[Research Progress of Carrion-breeding Phorid Flies for Post-mortem Interval Estimation in Forensic Medicine].

PubMed

Li, L; Feng, D X; Wu, J

2016-10-01

It is a difficult problem of forensic medicine to accurately estimate the post-mortem interval. Entomological approach has been regarded as an effective way to estimate the post-mortem interval. The developmental biology of carrion-breeding flies has an important position at the post-mortem interval estimation. Phorid flies are tiny and occur as the main or even the only insect evidence in relatively enclosed environments. This paper reviews the research progress of carrion-breeding phorid flies for estimating post-mortem interval in forensic medicine which includes their roles, species identification and age determination of immatures. Copyright© by the Editorial Department of Journal of Forensic Medicine.

Application of contrast media in post-mortem imaging (CT and MRI).

PubMed

Grabherr, Silke; Grimm, Jochen; Baumann, Pia; Mangin, Patrice

2015-09-01

The application of contrast media in post-mortem radiology differs from clinical approaches in living patients. Post-mortem changes in the vascular system and the absence of blood flow lead to specific problems that have to be considered for the performance of post-mortem angiography. In addition, interpreting the images is challenging due to technique-related and post-mortem artefacts that have to be known and that are specific for each applied technique. Although the idea of injecting contrast media is old, classic methods are not simply transferable to modern radiological techniques in forensic medicine, as they are mostly dedicated to single-organ studies or applicable only shortly after death. With the introduction of modern imaging techniques, such as post-mortem computed tomography (PMCT) and post-mortem magnetic resonance (PMMR), to forensic death investigations, intensive research started to explore their advantages and limitations compared to conventional autopsy. PMCT has already become a routine investigation in several centres, and different techniques have been developed to better visualise the vascular system and organ parenchyma in PMCT. In contrast, the use of PMMR is still limited due to practical issues, and research is now starting in the field of PMMR angiography. This article gives an overview of the problems in post-mortem contrast media application, the various classic and modern techniques, and the issues to consider by using different media.

Postmortem analysis of sand grain crushing from pile interface using X-ray tomography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Silva, I. Matias; Combe, Gaeel; Foray, Pierre

2013-06-18

Pile foundations of offshore platforms, wind and water turbines are typically subjected to a variety of cyclic loading paths due to their complex environment. While many studies focus on global pile behaviour, the soil-pile interface is explored here by a micromechanical study of the soil layer in contact with the pile surface. This work is devoted to the analysis of frozen post-mortem silica sand samples recovered at the pile interface following installation and cyclic loading tests in a calibration chamber using x-ray tomography. An experimental procedure developed for three dimensional (3D) snow imaging was adapted for the recovery of themore » in-situ sand samples to preserve their structure during tomography scans. 3D images at a pixel size of 7 {mu}m were then obtained using a cryogenic cell. Results confirm the presence of a shear band at the pile surface as well as void ratios changes in the direction of the pile's radius.« less

Carcass composition and breast muscle microstructure in guinea fowl (Numida meleagris L.) of different origin.

PubMed

Bernacki, Zenon; Bawej, Małgorzata; Kokoszyński, Dariusz

2012-01-01

Evaluation of dressing percentage and postmortem traits in 14-week-old white and grey guinea fowl, extended with evaluation of breast muscle microstructure, was the aim of the study. Subjects were two varieties of guinea fowl kept in an environmentally controlled house. Birds received complete commercial feeds. At 14 weeks of rearing, their whole carcasses were dissected postmortem. Diameters and percentages of white (alphaW) and red muscle fibres (betaR) were determined based on histological analysis of the musculus pectoralis superficialis. Similar dressing percentage was found in both guinea fowl varieties. At 14 weeks of age, grey guinea fowl had greater body weight, and weight and proportion of leg muscles and wings compared to white guinea fowl. Females of the white variety had greater weight of breast muscles than males. Breast muscle microstructure showed significantly (P < or = 0.05) greater content and diameter of white fibres in grey guinea fowl, and of red fibres in white guinea fowl.

Death without warning? A clinical postmortem study of suicide in 43 Israeli adolescent males.

PubMed

Apter, A; Bleich, A; King, R A; Kron, S; Fluch, A; Kotler, M; Cohen, D J

1993-02-01

Forty-three consecutive Israeli male suicides, 18 to 21 years of age, that occurred during compulsory military service were studied using preinduction assessment data, service records, and extensive postmortem interviews with family and peers. At preinduction, subjects, as a group, appeared above average in intelligence, physical fitness, and measures predictive of successful adaptation to military service. Active duty performance was generally satisfactory. Ascertained post mortem, 53.5% met formal criteria for major depressive disorder; most cases, however, appeared recent and reactive. Narcissistic and/or schizoid traits were common. Substance abuse was absent and antisocial personality disorder was rare (4.7%). Furthermore, in eight patients (18.6%) no Axis I diagnosis could be made; half of these also lacked any significant Axis II pathology. These findings, at partial variance with US studies, suggest a complex relationship between suicide and mental disorder. The striking failure of intensive screening and preventive measures to prevent these suicides highlights unresolved questions of etiology and intervention.

Testing photogrammetry-based techniques for three-dimensional surface documentation in forensic pathology.

PubMed

Urbanová, Petra; Hejna, Petr; Jurda, Mikoláš

2015-05-01

Three-dimensional surface technologies particularly close range photogrammetry and optical surface scanning have recently advanced into affordable, flexible and accurate techniques. Forensic postmortem investigation as performed on a daily basis, however, has not yet fully benefited from their potentials. In the present paper, we tested two approaches to 3D external body documentation - digital camera-based photogrammetry combined with commercial Agisoft PhotoScan(®) software and stereophotogrammetry-based Vectra H1(®), a portable handheld surface scanner. In order to conduct the study three human subjects were selected, a living person, a 25-year-old female, and two forensic cases admitted for postmortem examination at the Department of Forensic Medicine, Hradec Králové, Czech Republic (both 63-year-old males), one dead to traumatic, self-inflicted, injuries (suicide by hanging), the other diagnosed with the heart failure. All three cases were photographed in 360° manner with a Nikon 7000 digital camera and simultaneously documented with the handheld scanner. In addition to having recorded the pre-autopsy phase of the forensic cases, both techniques were employed in various stages of autopsy. The sets of collected digital images (approximately 100 per case) were further processed to generate point clouds and 3D meshes. Final 3D models (a pair per individual) were counted for numbers of points and polygons, then assessed visually and compared quantitatively using ICP alignment algorithm and a cloud point comparison technique based on closest point to point distances. Both techniques were proven to be easy to handle and equally laborious. While collecting the images at autopsy took around 20min, the post-processing was much more time-demanding and required up to 10h of computation time. Moreover, for the full-body scanning the post-processing of the handheld scanner required rather time-consuming manual image alignment. In all instances the applied approaches produced high-resolution photorealistic, real sized or easy to calibrate 3D surface models. Both methods equally failed when the scanned body surface was covered with body hair or reflective moist areas. Still, it can be concluded that single camera close range photogrammetry and optical surface scanning using Vectra H1 scanner represent relatively low-cost solutions which were shown to be beneficial for postmortem body documentation in forensic pathology. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Influence of dietary canola oil and palm oil blend and refrigerated storage on fatty acids, myofibrillar proteins, chemical composition, antioxidant profile and quality attributes of semimembranosus muscle in goats.

PubMed

Adeyemi, Kazeem D; Sabow, Azad B; Shittu, Rafiat M; Karim, Roselina; Sazili, Awis Q

2015-01-01

Improving the unsaturated fatty acid content of ruminant meat is essential due to the generally saturated nature of fatty acids in ruminant meat and the negative effects this can have on human health. Nonetheless, enhancing the unsaturated fatty acid content of ruminant meat can have adverse effects on the shelf life and quality attributes of the meat. This study assessed the effects of dietary 80 % canola oil and 20 % palm oil blend (CPOB) on fatty acid composition, antioxidants, oxidative spoilage, cholesterol and physicochemical properties of semimembranosus (SM) muscle from goats. Twenty four Boer bucks were randomly assigned to diets containing on dry matter basis 0, 4 and 8 % CPOB, fed for 100 d and slaughtered. The carcasses were subjected to a 7 d postmortem refrigerated storage. All analyses were conducted on the SM muscle. Diet had no effect (P > 0.05) on the concentration of free thiol and carbonyl and the band intensity of myosin heavy chain, actin and troponin T. The muscle glycogen, pH, water holding capacity, tenderness, glutathione peroxidase (GPX) activity, total carotenoid, δ-tocopherol, cholesterol and proximate composition did not differ (P > 0.05) between diets. The SM muscle from goats fed 4 and 8 % CPOB had lower (P < 0.05) concentration of C14:0 and C16:0 and higher (P < 0.05) concentration of C18:1 trans-11, C18:1ω-9, C18:3ω-3, C20:5ω-3 and C22:5ω-3 than the SM muscle from the control goats. Dietary CPOB increased (P < 0.05) the concentration of α and γ tocopherol and meat redness (a*) on d 1 and 4 postmortem. Regardless of diet, antioxidant vitamins, and shear force decreased (P < 0.05) while drip loss, lipid and protein oxidation increased (P < 0.05) as postmortem storage progressed. Results evince that dietary CPOB can be used as a management tool to enhance the beneficial fatty acids and antioxidant contents of chevon without deleterious effects on its physicochemical properties and shelf life.

Blood creatinine level in postmortem cases.

PubMed

Nishida, Atsushi; Funaki, Hironao; Kobayashi, Masaki; Tanaka, Yuka; Akasaka, Yoshihisa; Kubo, Toshikazu; Ikegaya, Hiroshi

2015-05-01

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. Copyright © 2014 Forensic Science Society. Published by Elsevier Ireland Ltd. All rights reserved.

Migration Pathways of Thalamic Neurons and Development of Thalamocortical Connections in Humans Revealed by Diffusion MR Tractography.

PubMed

Wilkinson, Molly; Kane, Tara; Wang, Rongpin; Takahashi, Emi

2017-12-01

The thalamus plays an important role in signal relays in the brain, with thalamocortical (TC) neuronal pathways linked to various sensory/cognitive functions. In this study, we aimed to see fetal and postnatal development of the thalamus including neuronal migration to the thalamus and the emergence/maturation of the TC pathways. Pathways from/to the thalami of human postmortem fetuses and in vivo subjects ranging from newborns to adults with no neurological histories were studied using high angular resolution diffusion MR imaging (HARDI) tractography. Pathways likely linked to neuronal migration from the ventricular zone and ganglionic eminence (GE) to the thalami were both successfully detected. Between the ventricular zone and thalami, more tractography pathways were found in anterior compared with posterior regions, which was well in agreement with postnatal observations that the anterior TC segment had more tract count and volume than the posterior segment. Three different pathways likely linked to neuronal migration from the GE to the thalami were detected. No hemispheric asymmetry of the TC pathways was quantitatively observed during development. These results suggest that HARDI tractography is useful to identify multiple differential neuronal migration pathways in human brains, and regional differences in brain development in fetal ages persisted in postnatal development. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Contralateral cortico-ponto-cerebellar pathways reconstruction in humans in vivo: implications for reciprocal cerebro-cerebellar structural connectivity in motor and non-motor areas.

PubMed

Palesi, Fulvia; De Rinaldis, Andrea; Castellazzi, Gloria; Calamante, Fernando; Muhlert, Nils; Chard, Declan; Tournier, J Donald; Magenes, Giovanni; D'Angelo, Egidio; Gandini Wheeler-Kingshott, Claudia A M

2017-10-09

Cerebellar involvement in cognition, as well as in sensorimotor control, is increasingly recognized and is thought to depend on connections with the cerebral cortex. Anatomical investigations in animals and post-mortem humans have established that cerebro-cerebellar connections are contralateral to each other and include the cerebello-thalamo-cortical (CTC) and cortico-ponto-cerebellar (CPC) pathways. CTC and CPC characterization in humans in vivo is still challenging. Here advanced tractography was combined with quantitative indices to compare CPC to CTC pathways in healthy subjects. Differently to previous studies, our findings reveal that cerebellar cognitive areas are reached by the largest proportion of the reconstructed CPC, supporting the hypothesis that a CTC-CPC loop provides a substrate for cerebro-cerebellar communication during cognitive processing. Amongst the cerebral areas identified using in vivo tractography, in addition to the cerebral motor cortex, major portions of CPC streamlines leave the prefrontal and temporal cortices. These findings are useful since provide MRI-based indications of possible subtending connectivity and, if confirmed, they are going to be a milestone for instructing computational models of brain function. These results, together with further multi-modal investigations, are warranted to provide important cues on how the cerebro-cerebellar loops operate and on how pathologies involving cerebro-cerebellar connectivity are generated.

Activated forms of astrocytes with higher GLT-1 expression are associated with cognitive normal subjects with Alzheimer pathology in human brain.

PubMed

Kobayashi, Eiji; Nakano, Masako; Kubota, Kenta; Himuro, Nobuaki; Mizoguchi, Shougo; Chikenji, Takako; Otani, Miho; Mizue, Yuka; Nagaishi, Kanna; Fujimiya, Mineko

2018-01-26

Although the cognitive impairment in Alzheimer's disease (AD) is believed to be caused by amyloid-β (Aβ) plaques and neurofibrillary tangles (NFTs), several postmortem studies have reported cognitive normal subjects with AD brain pathology. As the mechanism underlying these discrepancies has not been clarified, we focused the neuroprotective role of astrocytes. After examining 47 donated brains, we classified brains into 3 groups, no AD pathology with no dementia (N-N), AD pathology with no dementia (AD-N), and AD pathology with dementia (AD-D), which represented 41%, 21%, and 38% of brains, respectively. No differences were found in the accumulation of Aβ plaques or NFTs in the entorhinal cortex (EC) between AD-N and AD-D. Number of neurons and synaptic density were increased in AD-N compared to those in AD-D. The astrocytes in AD-N possessed longer or thicker processes, while those in AD-D possessed shorter or thinner processes in layer I/II of the EC. Astrocytes in all layers of the EC in AD-N showed enhanced GLT-1 expression in comparison to those in AD-D. Therefore these activated forms of astrocytes with increased GLT-1 expression may exert beneficial roles in preserving cognitive function, even in the presence of Aβ and NFTs.

Bleedout efficiency, carcass damage, and rigor mortis development following electrical stunning or carbon dioxide stunning on a shackle line.

PubMed

Kang, I S; Sams, A R

1999-01-01

In Experiment 1, 400 male broilers were stunned using a gradient of 40 to 60% CO2 over a period of 25 s or a 1% brine solution that was electrically charged (35 mA) for 7 s. Blood loss during bleeding was measured in 30-s intervals for a total of 120 s. After conventional processing and chilling, carcass damage was subjectively evaluated. Results indicated that the birds stunned with electricity bled faster than the CO2-stunned birds until 60 s. However, the cumulative blood loss was not different after 90 s. Carcass damage evaluation indicated that birds stunned with CO2 had a significantly lower percentage of broken clavicles, and had fewer hemorrhages on the surface of the Pectoralis. However, there was no difference between the two stunning methods in the frequency of damage at the shoulder. In Experiment 2, 256 broilers were stunned using the same conditions as in Experiment 1. Measurements of pH, R-value, sarcomere length (SL), and fragmentation index (FI) were evaluated from the left breast fillets harvested at 0, 1, 2, and 6 h postmortem. Shear values (SV) were determined using the right fillets harvested at the same four postmortem times and aged on ice until 24 h. No significant difference in breast muscle pH value was observed at 0, 2, and 6 h postmortem. However, CO2-stunned fillets had significantly higher pH values than the ES fillets at 1 h postmortem. Carbon dioxide produced greater R values than electricity at 2 and 6 h. Sarcomere length, FI, and SV were not significantly different at any time tested. These data suggest that CO2 stunning reduced carcass damage but did not reduce the need for aging before deboning when compared to the electrical stunning method used.

Extravascular lung water assessed by transpulmonary single thermodilution and postmortem gravimetry in sheep

PubMed Central

Kirov, Mikhail Y; Kuzkov, Vsevolod V; Kuklin, Vladimir N; Waerhaug, Kristine; Bjertnaes, Lars J

2004-01-01

Introduction Acute lung injury is associated with accumulation of extravascular lung water (EVLW). The aim of the present study was to compare two methods for quantification of EVLW: transpulmonary single thermodilution (EVLWST) and postmortem gravimetric (EVLWG). Methods Eighteen instrumented and awake sheep were randomly assigned to one of three groups. All groups received Ringer's lactate (5 ml/kg per hour intravenously). To induce lung injury of different severities, sheep received Escherichia coli lipopolysaccharide 15 ng/kg per min intravenously for 6 hours (n = 7) or oleic acid 0.06 ml/kg intravenously over 30 min (n = 7). A third group (n = 4) was subjected to sham operation. Haemodynamic variables, including EVLWST, were measured using a PiCCOplus monitor (Pulsion Medical Systems, Munich, Germany), and the last measurement of EVLWST was compared with EVLWG. Results At the end of experiment, values for EVLWST (mean ± standard error) were 8.9 ± 0.6, 11.8 ± 1.0 and 18.2 ± 0.9 ml/kg in the sham-operated, lipopolysaccharide and oleic acid groups, respectively (P < 0.05). The corresponding values for EVLWIG were 6.2 ± 0.3, 7.1 ± 0.6 and 11.8 ± 0.7 ml/kg (P < 0.05). Ranges of EVLWIST and EVLWIG values were 7.5–21.0 and 4.9–14.5 ml/kg. Regression analysis between in vivo EVLWST and postmortem EVLWG yielded the following relation: EVLWST = 1.30 × EVLWG + 2.32 (n = 18, r = 0.85, P < 0.0001). The mean bias ± 2 standard deviations between EVLWST and EVLWG was 4.9 ± 5.1 ml/kg (P < 0.001). Conclusion In sheep, EVLW determined using transpulmonary single thermodilution correlates closely with gravimetric measurements over a wide range of changes. However, transpulmonary single thermodilution overestimates EVLW as compared with postmortem gravimetry. PMID:15566591

Antipsychotic drugs attenuate aberrant DNA methylation of DTNBP1 (dysbindin) promoter in saliva and post-mortem brain of patients with schizophrenia and Psychotic bipolar disorder.

PubMed

Abdolmaleky, Hamid M; Pajouhanfar, Sara; Faghankhani, Masoomeh; Joghataei, Mohammad Taghi; Mostafavi, Ashraf; Thiagalingam, Sam

2015-12-01

Due to the lack of genetic association between individual genes and schizophrenia (SCZ) pathogenesis, the current consensus is to consider both genetic and epigenetic alterations. Here, we report the examination of DNA methylation status of DTNBP1 promoter region, one of the most credible candidate genes affected in SCZ, assayed in saliva and post-mortem brain samples. The Illumina DNA methylation profiling and bisulfite sequencing of representative samples were used to identify methylation status of the DTNBP1 promoter region. Quantitative methylation specific PCR (qMSP) was employed to assess methylation of DTNBP1 promoter CpGs flanking a SP1 binding site in the saliva of SCZ patients, their first-degree relatives and control subjects (30, 15, and 30/group, respectively) as well as in post-mortem brains of patients with SCZ and bipolar disorder (BD) versus controls (35/group). qRT-PCR was used to assess DTNBP1 expression. We found DNA hypermethylation of DTNBP1 promoter in the saliva of SCZ patients (∼12.5%, P = 0.036), particularly in drug-naïve patients (∼20%, P = 0.011), and a trend toward hypermethylation in their first-degree relatives (P = 0.085) versus controls. Analysis of post-mortem brain samples revealed an inverse correlation between DTNBP1 methylation and expression, and normalization of this epigenetic change by classic antipsychotic drugs. Additionally, BD patients with psychotic depression exhibited higher degree of methylation versus other BD patients (∼80%, P = 0.025). DTNBP1 promoter DNA methylation may become a key element in a panel of biomarkers for diagnosis, prevention, or therapy in SCZ and at risk individuals pending confirmatory studies with larger sample sizes to attain a higher degree of significance. © 2015 Wiley Periodicals, Inc.

The absorption characteristics of the human cornea in ultraviolet-a crosslinking.

PubMed

Koppen, Carina; Gobin, Laure; Tassignon, Marie-José

2010-03-01

With respect to the safety of ultraviolet-A (UVA) crosslinking for the corneal endothelium, an absorption coefficient is used that has been calculated in riboflavin soaked porcine corneas. We aim to validate this value for clinical use by measuring the absorption coefficient for UVA 365 nm in postmortem human corneas after instilling riboflavin on the corneal surface. Corneal thickness was measured in nine pairs of human donor eyes of which one eye was subjected to manual removal of the epithelium, whereas the epithelium of the fellow eye was left intact. Both eyes were instilled with riboflavin 0.1% in dextran 20% on the intact globe. After 20 min, the corneas were rinsed, and a corneoscleral button was trephined. The transmission of the cornea for UVA 365 nm was measured by transillumination, which allows calculation of the absorption coefficient. Measurement of average corneal thickness was 658.5 +/- 51.5 microm when the epithelium was removed, and 758.3 +/- 98.8 microm without epithelial removal. The average transmittance for UVA 365 nm was 12.89 +/- 4.10% with epithelial debridement and 28.52 +/- 4.39% without (P<0.05). The resultant average absorption coefficient is 32 +/- 5 cm when the epithelium is removed and 17 +/- 2 cm when it is left intact (P<0.05). Our results show an absorption coefficient for human corneas that is much lower than the values reported in the literature. This finding may be relevant when considering endothelial safety of the clinical crosslinking treatment.

Pericardial fluid is suitable as an alternative specimen for the measurement of β-hydroxybutyrate within 96 h after death.

PubMed

Mizutani, Tatsushi; Yoshimoto, Takashi; Ishii, Akira

2018-05-21

We examined postmortem β-hydroxybutyrate (BHB) levels in the body fluids obtained from 253 forensic autopsy cases whose causes of death were determined. Postmortem changes of BHB levels according to postmortem intervals (PMI) in various body fluids (plasma, urine, vitreous humor, and pericardial fluids) were investigated to determine appropriate alternative specimens as plasma samples. Our study has indicated the following points: 1) the BHB levels in plasma specimens from three sampling sites showed no significant differences, 2) postmortem changes of BHB levels in plasma and pericardial fluids could be negligible within 96 h PMI, while urine and vitreous humor BHB levels showed postmortem changes, and 3) pericardial fluid would thus be most suitable as an alternative to plasma in postmortem BHB level. We have also proposed that BHB levels could be applicable for the diagnosis of metabolic disorders in forensic autopsy. Copyright © 2018 Elsevier B.V. All rights reserved.

The difficult task of assessing perimortem and postmortem fractures on the skeleton: a blind text on 210 fractures of known origin.

PubMed

Cappella, Annalisa; Amadasi, Alberto; Castoldi, Elisa; Mazzarelli, Debora; Gaudio, Daniel; Cattaneo, Cristina

2014-11-01

The distinction between perimortem and postmortem fractures is an important challenge for forensic anthropology. Such a crucial task is presently based on macro-morphological criteria widely accepted in the scientific community. However, several limits affect these parameters which have not yet been investigated thoroughly. This study aims at highlighting the pitfalls and errors in evaluating perimortem or postmortem fractures. Two trained forensic anthropologists were asked to classify 210 fractures of known origin in four skeletons (three victims of blunt force trauma and one natural death) as perimortem, postmortem, or dubious, twice in 6 months in order to assess intraobserver error also. Results show large errors, ranging from 14.8 to 37% for perimortem fractures and from 5.5 to 14.8% for postmortem ones; more than 80% of errors concerned trabecular bone. This supports the need for more objective and reliable criteria for a correct assessment of peri- and postmortem bone fractures. © 2014 American Academy of Forensic Sciences.

[Contents of vitreous humor of dead body with different postmortem intervals].

PubMed

Tao, Tao; Xu, Jing; Luo, Tong-Xing; Liao, Zhi-Gang; Pan, Hong-Fu

2006-11-01

To establish regression correlations between postmortem interval (PMI) and contents of human vitreous humor of dead bodies for forensic purposes. The human vitreous humor were taken from 126 dead bodies between 0.5 to 216 hours after death, and 11 chemical elements were detected by the OLYMPUS AU400 auto-biochemistry instrument. (1) The glucose, natrium and chlorine in human vitreous humor decreased, while the urea, creatinine, uric acid, potassium, calcium, magnesium, phosphorus, and micro-protein increased after death. The change of glucose, potassium and phosphorus were well correlated with the PMI (r = 0.824, 0.967, 0.880). But the uric acid and micro-protein did not have a good correlation with the PMI(r = 0.350, 0.153). (2) The stepwise regression analysis established the following equations for the PMI (Y): Y = -35. 15+6.05X, R2 = 0.957 (X = potassium); Y = -27.83+ 5.49X(1) - 1.35X(2), R2 = 0.960 (X(1) = potassium, X(2) = glucose); Y = -6.37+3.93X(1) -2.29X(2) + 5.36X(3), R2 = 0.966 (X(1) = potassium, X(2) = glucose, X(3) = phosphorus). (1) Eleven chemical components in human vitreous humor change after death, among which postassium has the best linear correlation with the PMI within 72 hours after death. (2) The accuracy of the estimation of PMI could be improved by establishing a multi-variable equation through stepwise regression.

Myositis, Ganglioneuritis, and Myocarditis with Distinct Perifascicular Muscle Atrophy in a 2-Year-Old Male Boxer

PubMed Central

Rossman, Paul M.; Thomovsky, Stephanie A.; Schafbuch, Ryan M.; Guo, Ling T.; Shelton, G. D.

2018-01-01

A 2-year-old male, intact Boxer was referred for chronic diarrhea, hyporexia, labored breathing, weakness and elevated creatine kinase, and alanine aminotransferase activities. Initial examination and diagnostics revealed a peripheral nervous system neurolocalization, atrial premature complexes, and generalized megaesophagus. Progressive worsening of the dog’s condition was noted after 36 h; the dog developed aspiration pneumonia, was febrile and oxygen dependent. The owners elected humane euthanasia. Immediately postmortem biopsies of the left cranial tibial and triceps muscles and the left peroneal nerve were obtained. Postmortem histology revealed concurrent myositis, myocarditis, endocarditis, and ganglioneuritis. Mixed mononuclear cell infiltrations and a distinct perifascicular pattern of muscle fiber atrophy was present in both muscles. This is a novel case of diffuse inflammatory myopathy with a distinct perifascicular pattern of atrophy in addition to endocarditis, myocarditis, and epicarditis. PMID:29516006

α2-Adrenoceptor Functionality in Postmortem Frontal Cortex of Depressed Suicide Victims

PubMed Central

Valdizán, Elsa M.; Díez-Alarcia, Rebeca; González-Maeso, Javier; Pilar-Cuéllar, Fuencisla; García-Sevilla, Jesús A.; Meana, J. Javier; Pazos, Angel

2013-01-01

Background Alterations in brain density and signaling associated with monoamine receptors are believed to play a role in depressive disorders. This study evaluates the functional status of α2A-adrenoceptors in postmortem frontal cortex of depressed subjects. Methods G-protein activation and inhibition of adenylyl cyclase (AC) activity induced by the α2-adrenoceptor agonist UK14304 were measured in triplicate in samples from 15 suicide victims with an antemortem diagnosis of major depression and 15 matched control subjects. Results Basal [35S] guanosine γ thio-phosphate (GTPγS) binding and cyclic adenosine monophosphate accumulation did not differ between groups. In depressed victims, an increase in [35S] GTPγS binding potency (EC50 = .58 μmol/L vs. EC50 = 3.31 μmol/L; p < .01; depressed vs. control) and a significant reduction in the maximal inhibition of AC activity (Imax = 27 ± 4% vs. Imax = 47 ± 5%; p < .01) were observed after incubation with the α2-adrenoceptor agonist UK14304. No differences were found between antidepressant-free and antidepressant-treated subjects. A significant relationship between EC50 values for [35S] GTPγS and Imax values for AC assay was found (n = 30; r = −.43; p < .05). Conclusions The dual regulation of α2A-adrenoceptor signaling pathways raises the possibility that factors affecting the G-protein cycle and/or selective access of Gαi/o–protein to AC might be relevant to receptor abnormalities in depression, providing further support for the involvement of α2A-adrenoceptors in the pathogenesis of depression. PMID:20864091

Advances in Raman spectroscopy for the diagnosis of Alzheimer's disease

NASA Astrophysics Data System (ADS)

Sudworth, Caroline D.; Archer, John K. J.; Black, Richard A.; Mann, David

2006-02-01

Within the next 50 years Alzheimer's disease is expected to affect 100 million people worldwide. The progressive decline in the mental health of the patient is caused by severe brain atrophy generated by the breakdown and aggregation of proteins, resulting in β-amyloid plaques and neurofibrillary tangles. The greatest challenge to Alzheimer's disease lies in the pursuit of an early and definitive diagnosis, in order that suitable treatment can be administered. At the present time, definitive diagnosis is restricted to post-mortem examination. Alzheimer's disease also remains without a long-term cure. This research demonstrates the potential role of Raman spectroscopy, combined with principle components analysis (PCA), as a diagnostic method. Analyses of ethically approved ex vivo post-mortem brain tissues (originating from frontal and occipital lobes) from control (3 normal elderly subjects and 3 Huntingdon's disease subjects) and Alzheimer's disease (12 subjects) brain sections, and a further set of 12 blinded samples are presented. Spectra originating from these tissues are highly reproducible, and initial results indicate a vital difference in protein content and conformation, relating to the abnormally high levels of aggregated proteins in the diseased tissues. Further examination of these spectra using PCA allows for the separation of control from diseased tissues. The validation of the PCA models using blinded samples also displays promise for the identification of Alzheimer's disease, in conjunction with secondary information regarding other brain diseases and dementias. These results provide a route for Raman spectroscopy as a possible non-invasive, non-destructive tool for the early diagnosis of Alzheimer's disease.

Are animal models predictive for human postmortem muscle protein degradation?

PubMed

Ehrenfellner, Bianca; Zissler, Angela; Steinbacher, Peter; Monticelli, Fabio C; Pittner, Stefan

2017-11-01

A most precise determination of the postmortem interval (PMI) is a crucial aspect in forensic casework. Although there are diverse approaches available to date, the high heterogeneity of cases together with the respective postmortal changes often limit the validity and sufficiency of many methods. Recently, a novel approach for time since death estimation by the analysis of postmortal changes of muscle proteins was proposed. It is however necessary to improve the reliability and accuracy, especially by analysis of possible influencing factors on protein degradation. This is ideally investigated on standardized animal models that, however, require legitimization by a comparison of human and animal tissue, and in this specific case of protein degradation profiles. Only if protein degradation events occur in comparable fashion within different species, respective findings can sufficiently be transferred from the animal model to application in humans. Therefor samples from two frequently used animal models (mouse and pig), as well as forensic cases with representative protein profiles of highly differing PMIs were analyzed. Despite physical and physiological differences between species, western blot analysis revealed similar patterns in most of the investigated proteins. Even most degradation events occurred in comparable fashion. In some other aspects, however, human and animal profiles depicted distinct differences. The results of this experimental series clearly indicate the huge importance of comparative studies, whenever animal models are considered. Although animal models could be shown to reflect the basic principles of protein degradation processes in humans, we also gained insight in the difficulties and limitations of the applicability of the developed methodology in different mammalian species regarding protein specificity and methodic functionality.

Overlapping regional distribution of CCK and TPPII mRNAs in Cynomolgus monkey brain and correlated levels in human cerebral cortex (BA 10).

PubMed

Radu, Diana; Tomkinson, Birgitta; Zachrisson, Olof; Weber, Günther; de Belleroche, Jacqueline; Hirsch, Steven; Lindefors, Nils

2006-08-09

Tripeptidyl peptidase II (TPPII) is a high molecular weight exopeptidase important in inactivating extracellular cholecystokinin (CCK). Our aims were to study the anatomical localization of TPPII and CCK mRNA in the Cynomolgus monkey brain as a basis for a possible functional anatomical connection between enzyme (TPPII) and substrate (CCK) and examine if indications of changes in substrate availability in the human brain might be reflected in changes of levels of TPPII mRNA. mRNA in situ hybridization on postmortem brain from patients having had a schizophrenia diagnosis as compared to controls and on monkey and rat brain slices. overlapping distribution patterns of mRNAs for TPPII and CCK in rat and monkey. High amounts of TPPII mRNA are seen in the neocortex, especially in the frontal region and the hippocampus. TPPII mRNA is also present in the basal ganglia and cerebellum where CCK immunoreactivity and/or CCK B receptors have been found in earlier studies, suggesting presence of CCK-ergic afferents from other brain regions. Levels of mRNAs for CCK and TPPII show a positive correlation in postmortem human cerebral cortex Brodmann area (BA) 10. TPPII mRNA might be affected following schizophrenia. overall TPPII and CCK mRNA show a similar distribution in rat and monkey brain, confirming and extending earlier studies in rodents. In addition, correlated levels of TPPII and CCK mRNA in human BA 10 corroborate a functional link between CCK and TPPII in the human brain.

A toxicology-based review of fentanyl-related deaths in New Mexico (1986-2007).

PubMed

Krinsky, Clarissa S; Lathrop, Sarah L; Crossey, Michael; Baker, Ginger; Zumwalt, Ross

2011-12-01

Since its approval in the United States, fentanyl has become increasingly popular for the medical management of pain and as a substance of abuse. Fentanyl is unique among the opioids in its widespread use with a transdermal delivery system, which contributes to its unique pharmacokinetics and abuse potential. We examined the demographics of deaths with fentanyl identified on toxicologic analysis and reviewed specific challenges in the laboratory detection of postmortem fentanyl levels. The New Mexico Office of the Medical Investigator database was searched for all cases from January 1986 through December 2007 with fentanyl reported as present or quantified. Those deaths with a cause of death identified as drug overdose were then analyzed separately. From 1986 to 2007, 154 cases were identified with fentanyl present in postmortem samples, with 96 of the cases identified as fentanyl-related drug overdoses. The number of fentanyl-related deaths has increased over the past 20 years, corresponding to both statewide increases in the medical use of fentanyl and the abuse of prescription opioids. The demographics of these fentanyl-related overdoses showed that subjects were more likely to be female, white non-Hispanic, and older than those in previously described overdose deaths. Several cases were identified with central and peripheral blood samples and antemortem and postmortem samples available for fentanyl quantification. Given the uncharacteristic demographics of fentanyl-related deaths and the complexity of the laboratory analysis of fentanyl, forensic scientists must use caution in both the detection and interpretation of fentanyl concentrations.

"Blind spots" in forensic autopsy: improved detection of retrobulbar hemorrhage and orbital lesions by postmortem computed tomography (PMCT).

PubMed

Flach, P M; Egli, T C; Bolliger, S A; Berger, N; Ampanozi, G; Thali, M J; Schweitzer, W

2014-09-01

The purpose of this study was to correlate the occurrence of retrobulbar hemorrhage (RBH) with mechanism of injury, external signs and autopsy findings to postmortem computed tomography (PMCT). Six-teen subjects presented with RBH and underwent PMCT, external inspection and conventional autopsy. External inspection was evaluated for findings of the bulbs, black eye, raccoon eyes and Battle's sign. Fractures of the viscerocranium, orbital lesions and RBH were evaluated by PMCT. Autopsy and PMCT was evaluated for orbital roof and basilar skull fracture. The leading manner of death was accident with central regulatory failure in cases of RBH (31.25%). Imaging showed a high sensitivity in detection of orbital roof and basilar skull fractures (100%), but was less specific compared to autopsy. Volume of RBH (0.1-2.4ml) correlated positively to the presence of Battle's sign (p<0.06) and the postmortem interval. Ecchymosis on external inspection correlated with RBH. There was a statistical significant correlation between bulbar lesion and RBH. Orbital roof fracture count weakly correlated with the total PMCT derived RBH volume. Maxillary hemosinus correlated to maxillary fractures, but not to RBH. RBH are a specific finding in forensically relevant head trauma. PMCT is an excellent tool in detecting and quantifying morphological trauma findings particularly in the viscerocranium, one of the most relevant "blind spots" of classic autopsy. PMCT was superior in detecting osseous lesions, scrutinizing autopsy as the gold standard. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Automated retinofugal visual pathway reconstruction with multi-shell HARDI and FOD-based analysis.

PubMed

Kammen, Alexandra; Law, Meng; Tjan, Bosco S; Toga, Arthur W; Shi, Yonggang

2016-01-15

Diffusion MRI tractography provides a non-invasive modality to examine the human retinofugal projection, which consists of the optic nerves, optic chiasm, optic tracts, the lateral geniculate nuclei (LGN) and the optic radiations. However, the pathway has several anatomic features that make it particularly challenging to study with tractography, including its location near blood vessels and bone-air interface at the base of the cerebrum, crossing fibers at the chiasm, somewhat-tortuous course around the temporal horn via Meyer's Loop, and multiple closely neighboring fiber bundles. To date, these unique complexities of the visual pathway have impeded the development of a robust and automated reconstruction method using tractography. To overcome these challenges, we develop a novel, fully automated system to reconstruct the retinofugal visual pathway from high-resolution diffusion imaging data. Using multi-shell, high angular resolution diffusion imaging (HARDI) data, we reconstruct precise fiber orientation distributions (FODs) with high order spherical harmonics (SPHARM) to resolve fiber crossings, which allows the tractography algorithm to successfully navigate the complicated anatomy surrounding the retinofugal pathway. We also develop automated algorithms for the identification of ROIs used for fiber bundle reconstruction. In particular, we develop a novel approach to extract the LGN region of interest (ROI) based on intrinsic shape analysis of a fiber bundle computed from a seed region at the optic chiasm to a target at the primary visual cortex. By combining automatically identified ROIs and FOD-based tractography, we obtain a fully automated system to compute the main components of the retinofugal pathway, including the optic tract and the optic radiation. We apply our method to the multi-shell HARDI data of 215 subjects from the Human Connectome Project (HCP). Through comparisons with post-mortem dissection measurements, we demonstrate the retinotopic organization of the optic radiation including a successful reconstruction of Meyer's loop. Then, using the reconstructed optic radiation bundle from the HCP cohort, we construct a probabilistic atlas and demonstrate its consistency with a post-mortem atlas. Finally, we generate a shape-based representation of the optic radiation for morphometry analysis. Copyright © 2015 Elsevier Inc. All rights reserved.

Oral mark in the application of an individual identification: From ashes to truth.

PubMed

Chugh, Anshul; Narwal, Anumeha

2017-01-01

Forensic odontology is the branch of dentistry which deals with the proper handling, examination, evaluation and presentation of dental findings in the interest of justice. After major disasters and perimortem assaults such as earthquakes, fires, severe head and neck trauma or gross decomposition, accurate and early identification of dead and injured becomes important. In the absence of other records in such cases, identification is based on restorations, missing teeth and prosthetic devices such as partial and complete removable/fixed prosthesis or implant retained devices. This brings out the major role of prosthodontics to investigate the identity of suspects in the criminal cases as well as the deceased human beings in traumatic injuries or in disasters. Denture identification systems are being used as means of postmortem identification of edentulous persons which has evolved from the inclusion of some form of printed label in a denture to more high-tech methods. The provision of implant retained complete lower denture, antemortem, and postmortem radiographs of edentulous persons and correlation of bite marks using special impression techniques provide another potential source of evidence for human identification. Hence, this literature review throws some light on the role played by prosthodontist in forensic odontology.

Prevalence of bovine tuberculosis in slaughter cattle in Kenya: a postmortem, microbiological and DNA molecular study.

PubMed

Gathogo, Stephen M; Kuria, Joseph K N; Ombui, Jackson N

2012-10-01

A study to determine the presence and prevalence of bovine tuberculosis in slaughter cattle in Kenya was carried out in two abattoirs from July to November 2009. Routine postmortem meat inspection was performed on a subpopulation of 929 cattle selected randomly from among 4,984. Carcases were inspected for gross tuberculous lesions which were then examined for acid-fast bacilli, (AFB), cultured for isolation of mycobacteria and the isolates characterised by DNA molecular analysis. Of the carcases examined, 176 (18.95 %, 95 % CI) had lesions suggestive of tuberculosis. AFB were observed in 63/176 of the lesioned cattle and mycobacteria were isolated from 64 of them. The isolates were identified as Mycobacterium bovis (19/64), Mycobacterium tuberculosis, (2/64) and mycobacteria other than tuberculosis (43/64). The prevalence of M. bovis by molecular analysis was 2.05 % (95 % CI). This study documents for the first time the presence of bovine tuberculosis among slaughter cattle in Kenya. There is therefore a need to formulate and implement control programmes in order to minimise transmission among animals and to humans. Isolation of M. tuberculosis from cattle underscores the risk tuberculous humans pose to animals.

Simultaneous quantification of nicotine, opioids, cocaine, and metabolites in human fetal postmortem brain by liquid chromatography tandem mass spectrometry

PubMed Central

Shakleya, Diaa M.

2011-01-01

A validated method for simultaneous LCMSMS quantification of nicotine, cocaine, 6-acetylmorphine (6AM), codeine, and metabolites in 100 mg fetal human brain was developed and validated. After homogenization and solid-phase extraction, analytes were resolved on a Hydro-RP analytical column with gradient elution. Empirically determined linearity was from 5–5,000 pg/mg for cocaine and benzoylecgonine (BE), 25–5,000 pg/mg for cotinine, ecgonine methyl ester (EME) and 6AM, 50–5000 pg/mg for trans-3-hydroxycotinine (OH-cotinine) and codeine, and 250–5,000 pg/mg for nicotine. Potential endogenous and exogenous interferences were resolved. Intra- and inter-assay analytical recoveries were ≥92%, intra- and inter-day and total assay imprecision were ≤14% RSD and extraction efficiencies were ≥67.2% with ≤83% matrix effect. Method applicability was demonstrated with a postmortem fetal brain containing 40 pg/mg cotinine, 65 pg/mg OH-cotinine, 13 pg/mg cocaine, 34 pg/mg EME, and 525 pg/mg BE. This validated method is useful for determination of nicotine, opioid, and cocaine biomarkers in brain. PMID:19229524

The use of Leptodyctium riparium (Hedw.) Warnst in the estimation of minimum postmortem interval.

PubMed

Lancia, Massimo; Conforti, Federica; Aleffi, Michele; Caccianiga, Marco; Bacci, Mauro; Rossi, Riccardo

2013-01-01

The estimation of the postmortem interval (PMI) is still one of the most challenging issues in forensic investigations, especially in cases in which advanced transformative phenomena have taken place. The dating of skeletal remains is even more difficult and sometimes only a rough determination of the PMI is possible. Recent studies suggest that plant analysis can provide a reliable estimation for skeletal remains dating, when traditional techniques are not applicable. Forensic Botany is a relatively recent discipline that includes many subdisciplines such as Palynology, Anatomy, Dendrochronology, Limnology, Systematic, Ecology, and Molecular Biology. In a recent study, Cardoso et al. (Int J Legal Med 2010;124:451) used botanical evidence for the first time to establish the PMI of human skeletal remains found in a forested area of northern Portugal from the growth rate of mosses and shrub roots. The present paper deals with a case in which the study of the growth rate of the bryophyte Leptodyctium riparium (Hedw.) Warnst, was used in estimating the PMI of some human skeletal remains that were found in a wooded area near Perugia, in Central Italy. © 2012 American Academy of Forensic Sciences.

The Impact of Oxidative Stress Factors on the Viability, Senescence, and Methylation Status of Olfactory Bulb-Derived Glial Cells Isolated from Human Cadaver Donors.

PubMed

Marycz, Krzysztof; Kornicka, Katarzyna; Grzesiak, Jakub; Tomaszewski, Krzysztof A; Szarek, Dariusz; Kopacz, Paweł

2017-01-01

The olfactory bulb (OB) is a unique structure in the central nervous system that retains the ability to create new neuronal connections. Glial cells isolated from the OB have been recently considered as a novel and promising tool to establish an effective therapy for central nervous system injuries. Due to the hindered access to autologous tissue for cell isolation, an allogeneic source of tissues obtained postmortem has been proposed. In this study, we focused on the morphological and molecular characteristics of human OB-derived glial cells isolated postmortem, at different time points after a donor's death. We evaluated the proliferative activity of the isolated cells, and investigated the ultrastructure of the mitochondria, the accumulation of intracellular reactive oxygen species, and the activity of superoxide dismutase. The data obtained clearly indicate that the duration of ischemia is crucial for the viability/senescence rate of OB-derived glial cells. The OB can be isolated during autopsy and still stand as a source of viable glial cells, but ischemia duration is a major factor limiting its potential usefulness in therapies. © 2017 S. Karger AG, Basel.

Portraying the Dead.

ERIC Educational Resources Information Center

Ruby, Jay

1989-01-01

Explores custom of post-mortem photography. Describes practice of post-mortem photography in 19th century America and traces changes in post-mortem photography in the 20th century. Discusses value of photographs in mourning process and suggests more thorough examination of the place of death-related photographs in grief management. (Author/NB)

[Post-mortem microbiology analysis].

PubMed

Fernández-Rodríguez, Amparo; Alberola, Juan; Cohen, Marta Cecilia

2013-12-01

Post-mortem microbiology is useful in both clinical and forensic autopsies, and allows a suspected infection to be confirmed. Indeed, it is routinely applied to donor studies in the clinical setting, as well as in sudden and unexpected death in the forensic field. Implementation of specific sampling techniques in autopsy can minimize the possibility of contamination, making interpretation of the results easier. Specific interpretation criteria for post-mortem cultures, the use of molecular diagnosis, and its fusion with molecular biology and histopathology have led to post-mortem microbiology playing a major role in autopsy. Multidisciplinary work involving microbiologists, pathologists, and forensic physicians will help to improve the achievements of post-mortem microbiology, prevent infectious diseases, and contribute to a healthier population. Crown Copyright © 2012. Published by Elsevier Espana. All rights reserved.

The Relationship Between the Changes in Local Stiffness of Chicken Myofibril and the Tenderness of Muscle During Postmortem Aging

NASA Astrophysics Data System (ADS)

Iwasaki, T.; Hasegawa, Y.; Yamamoto, K.; Nakamura, K.

We have investigated that the relationship between the stiffness of myofibrils and the tenderness of muscle during postmortem aging. The stiffness (elasticity) of A and I bands as well as Z-line of chicken myofibrils during postmortem aging were measured by atomic force microscope. The stiffness of all regions increased till 12 hr of postmortem, then it decreased to 96 hr. This tendency was the same as the changes of shear force value of whole muscle during postmortem aging. The elasticity of the Z-line of chicken myofibrils treated with calcium ions in the presence of protease inhibitor decreased with treating time. This indicates that the nonenzymatic structural changes of myofibrils is one of the causes of meat tenderization.

The impact of antemortem computed tomographic scanning on postmortem examination rate and frequency of missed diagnosis: A retrospective analysis of postmortem examination data.

PubMed

Liisanantti, Janne Henrik; Ala-Kokko, Tero Ilmari

2015-12-01

The present study was conducted to explore the impact of computed tomographic (CT) scanning on the diagnostic discrepancy rate. This single-center, retrospective study reviewed postmortem examination results, clinical diagnoses, and radiologic imaging data for patients admitted to the intensive care unit (ICU) in 2008 to 2013. The Goldman criteria were used to classify diagnostic discrepancies. The data of 577 patients who died during their ICU stay were retrieved. The postmortem examination rate was 42.9% (n=248). Significant diagnostic discrepancies (Goldman I and II) were recorded in 24 cases (9.7%). The postmortem examination rate decreased significantly from the first half (n=143; 51.1%) to the second half (n=105; 35.4%) of the study period (P<.0001). Among those with postmortem examinations, the use of antemortem body CT scans increased significantly from the first half (n=59; 41.3%) to the second half (n=64; 51.0%; P=.002) of the study period. The significant diagnostic discrepancy rate did not change with time (8.4% vs 11.4%, respectively; P=.424). The postmortem examination rate has decreased, whereas antemortem CT scans has increased. Copyright © 2015 Elsevier Inc. All rights reserved.

Neck injury criteria formulation and injury risk curves for the ejection environment: a pilot study.

PubMed

Parr, Jeffrey C; Miller, Michael E; Pellettiere, Joseph A; Erich, Roger A

2013-12-01

Helmet mounted displays provide increased pilot capability, but can also increase the risk of injury during ejection. The National Highway Transportation Safety Administration's (NHTSA's) neck injury criteria (Nij) metric is evaluated for understanding the impact of helmet mass on the risk of injury and modified risk curves are developed which are compatible with the needs of the aviation community. Existent human subject data collected under various accelerative and head loading conditions were applied to understand the sensitivity of the Nij construct to changes in acceleration and helmet mass, as well as its stability with respect to gender, body mass, neck circumference, and sitting height. A portion of this data was combined with data from an earlier postmortem human subject study to create pilot study modified risk curves. These curves were compared and contrasted with the NHTSA risk curves. A statistically significant difference in the peak mean Nij was observed when seat acceleration increased by 2 G, but not when helmet mass was varied from 1.6 kg to 2 kg at a constant seat acceleration of 8 G. Although NHTSA risk curves predict a 13% risk of AIS 2+ injury for the 8-G, 2-kg helmet condition mean Nij of 0.138, no AIS 2+ injuries were observed. Modified risk curves were produced which predict a 0.91% risk of AIS 2+ injury under these conditions. The Nij was shown to be sensitive to changes in acceleration and generally robust to anthropometric differences between individuals. Modified risk curves are proposed which improve risk prediction at lower Nij values.

Daily thanatomicrobiome changes in soil as an approach of postmortem interval estimation: An ecological perspective.

PubMed

Adserias-Garriga, Joe; Hernández, Marta; Quijada, Narciso M; Rodríguez Lázaro, David; Steadman, Dawnie; Garcia-Gil, Jesús

2017-09-01

Understanding human decomposition is critical for its use in postmortem interval (PMI) estimation, having a significant impact on forensic investigations. In recognition of the need to establish the scientific basis for PMI estimation, several studies on decomposition have been carried out in the last years. The aims of the present study were: (i) to identify soil microbiota communities involved in human decomposition through high-throughput sequencing (HTS) of DNA sequences from the different bacteria, (ii) to monitor quantitatively and qualitatively the decay of such signature species, and (iii) to describe succesional changes in bacterial populations from the early putrefaction state until skeletonization. Three donated individuals to the University of Tennessee FAC were studied. Soil samples around the body were taken from the placement of the donor until advanced decay/dry remains stage. Bacterial DNA extracts were obtained from the samples, HTS techniques were applied and bioinformatic data analysis was performed. The three cadavers showed similar overall successional changes. At the beginning of the decomposition process the soil microbiome consisted of diverse indigenous soil bacterial communities. As decomposition advanced, Firmicutes community abundance increased in the soil during the bloat stage. The growth curve of Firmicutes from human remains can be used to estimate time since death during Tennessee summer conditions. Copyright © 2017 Elsevier B.V. All rights reserved.

Individual Differences in the Alignment of Structural and Functional Markers of the V5/MT Complex in Primates

PubMed Central

Large, I.; Bridge, H.; Ahmed, B.; Clare, S.; Kolasinski, J.; Lam, W. W.; Miller, K. L.; Dyrby, T. B.; Parker, A. J.; Smith, J. E. T.; Daubney, G.; Sallet, J.; Bell, A. H.; Krug, K.

2016-01-01

Extrastriate visual area V5/MT in primates is defined both structurally by myeloarchitecture and functionally by distinct responses to visual motion. Myelination is directly identifiable from postmortem histology but also indirectly by image contrast with structural magnetic resonance imaging (sMRI). First, we compared the identification of V5/MT using both sMRI and histology in Rhesus macaques. A section-by-section comparison of histological slices with in vivo and postmortem sMRI for the same block of cortical tissue showed precise correspondence in localizing heavy myelination for V5/MT and neighboring MST. Thus, sMRI in macaques accurately locates histologically defined myelin within areas known to be motion selective. Second, we investigated the functionally homologous human motion complex (hMT+) using high-resolution in vivo imaging. Humans showed considerable intersubject variability in hMT+ location, when defined with myelin-weighted sMRI signals to reveal structure. When comparing sMRI markers to functional MRI in response to moving stimuli, a region of high myelin signal was generally located within the hMT+ complex. However, there were considerable differences in the alignment of structural and functional markers between individuals. Our results suggest that variation in area identification for hMT+ based on structural and functional markers reflects individual differences in human regional brain architecture. PMID:27371764

[Evaluation on stability of internal controls in human cardiac muscle by real-time RT-PCR during early postmortem interval].

PubMed

Zhang, Ping; Ma, Kai-Jun; Zhang, Heng; Wang, Hui-Jun; Shen, Yi-Wen; Chen, Long

2012-04-01

To explore the stability of internal controls in human cardiac muscle by real-time RT-PCR during early postmortem interval (PMI) in order to find the most stable marker. Ten individuals with similar environmental conditions (the average store temperature: 25 degrees C) and different PMI ranging from 4.3 to 22.3 h were selected. Total RNA was extracted from each sample and six commonly internal controls were used including beta-actin, GAPDH, B2M, U6, 18S rRNA and HSA-miR-1, and the expression was detected in cardiac muscle by real-time RT-PCR. The expression stability of internal controls was evaluated using genormPLUS software during early PMI. The internal control with the most stability was selected. The relationship between the most stable marker and its expression level affected by some other parameters such as age, gender and cause of death was also analyzed. The U6 showed the most stable expression during early PMI in cardiac muscle, and its expression level was not affected by those parameters including age, gender and cause of death (P > 0.05). U6 may be a valuable internal control for the study of relationship between PMI determination and degradation of nucleic acid in human cardiac muscle by real-time RT-PCR.

Serial Murder of Four Victims, of Both Genders and Different Ethnicities, by an Ordained Baptist Minister

PubMed Central

Reavis, James A.

2011-01-01

A case of a 61-year-old African-American male who sexually assaulted and murdered four individuals, of different ethnicities and both genders, is reported. The subject additionally engaged in sexual activity with each victim postmortem. Each murder is reviewed in detail, and the subjective state of the offender during the murders is commented upon. Psychological test data are reviewed. The subject met criteria for several Axis I disorders, including Bipolar I Disorder, Pedophilia, and Sexual Sadism, and met criteria for Axis II diagnoses of Narcissistic and Antisocial Personality disorder. He was additionally classified as a Psychopath, which, in combination with his Sexual Sadism, general psychiatric state, and exquisite sensitivity to humiliation, led to his decision to murder. PMID:22937398

Malignant Neuroendocrine Tumour (Carcinoid) of the Spleen in an African Pygmy Hedgehog (Atelerix albiventris).

PubMed

Lowden, L R; Davies, J L

2016-07-01

A malignant neuroendocrine tumour (carcinoid) of the spleen was diagnosed on post-mortem examination of a 3-year-old, male African pygmy hedgehog (Atelerix albiventris). The animal presented with a history of inappetence, weight loss, lethargy, a wide-based gait and a palpable abdominal mass. The gross pathological, histopathological, histochemical and immunohistochemical findings are described. Primary splenic carcinoids are reported rarely in the human medical literature and this is believed to be the first report in a non-human animal. Copyright © 2016 Elsevier Ltd. All rights reserved.

Experimental Injury Biomechanics of the Pediatric Thorax and Abdomen

NASA Astrophysics Data System (ADS)

Kent, Richard; Ivarsson, Johan; Maltese, Matthew R.

Motor vehicle crashes are the leading cause of death and injury for children in the United States. Pediatric anthropomorphic test devices (ATD) and computational models are important tools for the evaluation and optimization of automotive restraint systems for child occupants. The thorax interacts with the restraints within the vehicle, and any thoracic model must mimic this interaction in a biofidelic manner to ensure that restraint designs protect humans as intended. To define thoracic biofidelity for adults, Kroell et al. (1974) conducted blunt impacts to the thoraces of adult postmortem human subjects (PMHS), which have formed the basis for biofidelity standards for modern adult ATD thoraces (Mertz et al. 1989). The paucity of pediatric PMHS for impact research led to the development of pediatric model biofidelity requirements through scaling. Geometric scale factors and elastic moduli of skull and long bone have been used to scale the adult thoracic biofidelity responses to the 3-, 6-, and 10-year-old child (Irwin and Mertz 1997; Mertz et al. 2001; van Ratingen et al. 1997). There is currently a need for data that apply to the child without scaling, both for validation of scaling methods used in the past and to confirm the validity of the specifications currently used to develop models of the child.

Phencyclidine and violence: clinical and legal issues.

PubMed

Brecher, M; Wang, B W; Wong, H; Morgan, J P

1988-12-01

Phencyclidine (PCP) abuse has diminished since PCP's intrusion into American culture in the late 1970s. One of its legacies is the assumption that it provokes violent behavior in humans with predictable regularity. This assumption is so accepted that ingestion of the drug both accidentally and knowingly prior to committing a crime has been used as a defense in criminal trials. We reviewed 81 clinical reports of toxicity in humans published chiefly in North American medical journals. We searched for descriptions of violent behavior in these reports and subjected them to the following questions: (1) Was the violent behavior corroborated or only self-reported? (2) Was the presence of PCP confirmed by analysis of bodily fluids or postmortem tissue? (3) Was the presence of other drugs excluded by similar analysis of bodily fluids? We had planned to examine the reports to see whether clinicians sought evidence of previous violent behavior, but such an inquiry was rarely conducted. Of the hundreds of patients described, only three satisfied these criteria. Further, some of the papers offered evidence that reports of violence were exaggerated. These findings plus the pre-1970 prospective evaluation of thousands of patients with PCP, in which violence was never reported, led us to conclude that clinical and forensic assumptions about PCP and violence are not warranted.

Effect of postmortem aging on marination performance of broiler breast pectoralis major categorized by color lightness

USDA-ARS?s Scientific Manuscript database

The objective was to evaluate the effect of postmortem aging on marinade uptake and retention by early-deboned chicken breast fillets with different color lightness. Effects of marination on product yield and muscle shear force were also determined. Early deboned (2 h postmortem) broiler butterflies...

9 CFR 355.41 - Antemortem and postmortem inspection for mules.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Animal Food, Mule Meat By-Product § 355.41 Antemortem and postmortem inspection for mules. (a)(1) An... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Antemortem and postmortem inspection for mules. 355.41 Section 355.41 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE...

Virtopsy: postmortem imaging of laryngeal foreign bodies.

PubMed

Oesterhelweg, Lars; Bolliger, Stephan A; Thali, Michael J; Ross, Steffen

2009-05-01

Death from corpora aliena in the larynx is a well-known entity in forensic pathology. The correct diagnosis of this cause of death is difficult without an autopsy, and misdiagnoses by external examination alone are common. To determine the postmortem usefulness of modern imaging techniques in the diagnosis of foreign bodies in the larynx, multislice computed tomography, magnetic resonance imaging, and postmortem full-body computed tomography-angiography were performed. Three decedents with a suspected foreign body in the larynx underwent the 3 different imaging techniques before medicolegal autopsy. Multislice computed tomography has a high diagnostic value in the noninvasive localization of a foreign body and abnormalities in the larynx. The differentiation between neoplasm or soft foreign bodies (eg, food) is possible, but difficult, by unenhanced multislice computed tomography. By magnetic resonance imaging, the discrimination of the soft tissue structures and soft foreign bodies is much easier. In addition to the postmortem multislice computed tomography, the combination with postmortem angiography will increase the diagnostic value. Postmortem, cross-sectional imaging methods are highly valuable procedures for the noninvasive detection of corpora aliena in the larynx.

Estimation of postmortem interval through albumin in CSF by simple dye binding method.

PubMed

Parmar, Ankita K; Menon, Shobhana K

2015-12-01

Estimation of postmortem interval is a very important question in some medicolegal investigations. For the precise estimation of postmortem interval, there is a need of a method which can give accurate estimation. Bromocresol green (BCG) is a simple dye binding method and widely used in routine practice. Application of this method in forensic practice may bring revolutionary changes. In this study, cerebrospinal fluid was aspirated from cisternal puncture from 100 autopsies. A study was carried out on concentration of albumin with respect to postmortem interval. After death, albumin present in CSF undergoes changes, after 72 h of death, concentration of albumin has become 0.012 mM, and this decrease was linear from 2 h to 72 h. An important relationship was found between albumin concentration and postmortem interval with an error of ± 1-4h. The study concludes that CSF albumin can be a useful and significant parameter in estimation of postmortem interval. Copyright © 2015 The Chartered Society of Forensic Sciences. Published by Elsevier Ireland Ltd. All rights reserved.

[External post-mortem examination].

PubMed

Hartwig, S

2016-09-01

The external post-mortem examination in Germany is a non-delegable medical duty for determination of death, identity of the deceased, cause of death, manner of death, time of death and notifiable infectious diseases. Within the framework of rescue service missions the physician is limited to ascertaining that death has occurred. The determination of death must be reliable and is automatically followed by a complete external post-mortem examination of the body, if necessary by another physician. The certain signs of death are livor mortis, rigor mortis and putrefaction. Reliable features for the occurrence of death are injuries which are not compatible with life and brain death. The external post-mortem examination is the basis for the decision on whether further criminal investigations are necessary. The external post-mortem examination and the accompanying death certification must always be meticulously carried out.

Sarcomere length influences postmortem proteolysis of excised bovine semitendinosus muscle.

PubMed

Weaver, A D; Bowker, B C; Gerrard, D E

2008-08-01

The interaction between sarcomere length and postmortem proteolysis as related to meat tenderness is not clear. The extent of thick and thin filament overlap alters actomyosin binding and may alter substrate availability during aging-induced tenderization. The objective of this study was to determine the influence of sarcomere length on proteolytic degradation in beef. Strips from bovine semitendinosus were either stretched 40% and restrained or allowed to shorten unrestrained in an ice bath. After rigor completion, 0.6-cm cross sections were fabricated and were randomly assigned to 2, 4, 7, or 10 d of aging treatments. Myofibrils were isolated for sarcomere length determination. Samples were collected and frozen for shear force analysis, and muscle proteins were extracted for SDS-PAGE and Western blotting analyses to determine troponin T (TnT) proteolysis. Sarcomere length was greater (P < 0.01) in stretched muscle samples compared with shortened samples (2.57 vs. 1.43 microm, respectively). Correspondingly, shear force values were greater (P < 0.05) in shortened samples than stretched samples. Western blots revealed the presence of 3 major intact TnT bands that diminished with time postmortem and 4 bands (TnT degradation products) that accumulated during postmortem storage. Quantification of intact TnT showed increased (P < 0.05) proteolysis at 4 and 7 d postmortem in samples with long sarcomeres. By 10 d, only traces of the greatest molecular weight intact TnT band were evident in both shortened and stretched samples, suggesting this TnT band may be more susceptible to proteolysis than other intact TnT bands. Degradation products of TnT appeared earlier postmortem in samples with long sarcomeres. The 30-kDa TnT fragment appeared after 7 d of postmortem storage in samples with long sarcomeres but not until 10 d in muscle containing short sarcomeres. Collectively, these data show that postmortem TnT proteolysis is sarcomere length-dependent and suggest that thick and thin filament overlap may influence the postmortem aging process in beef.

Causes and manners of death among users of heroin, methadone, amphetamine, and cannabis in relation to postmortem chemical tests for illegal drugs.

PubMed

Eksborg, Staffan; Rajs, Jovan

2008-01-01

A 12-year medicolegal investigation of deceased illegal drug users (ILDU) in Stockholm, Sweden, classified on the basis of postmortem chemical tests, showed noticeable variations in causes and manners of death as well as in the distribution of suicide methods. This study offers objective information about connection between the postmortem findings of illegal drugs and the causes and manners of death of their users. However, further studies, comparing prevalence of drug use in general population and at the postmortem tests, are needed for more detailed elucidation of this connection.

MANAGEMENT OF ENDOMETRIOSIS IN TWO CAPTIVE MANDRILLS (MANDRILLUS SPHINX).

PubMed

Okeson, Danelle M; Higbie, Christine T; Mylniczenko, Natalie D; Haynes, April; Bennett, Suzanne; Klocke, Emily; Carpenter, James W

2016-06-01

Endometriosis has been reported in humans, great apes, and Old World monkeys. Although cases are noted anecdotally in Mandrillus spp., and a previously reported case was noted on postmortem examination, to the authors' knowledge, no previous reports of case management have been published in the peer-reviewed literature. This paper describes the medical and surgical management of endometriosis in two mandrills (Mandrillus sphinx).

Altered cytokine profiles of human retinal pigment epithelium: Oxidant injury and replicative senescence

PubMed Central

Cao, Sijia; Walker, Gregory B.; Wang, Xuefeng; Cui, Jing Z.

2013-01-01

Purpose Age-related macular degeneration (AMD) is a local, chronic inflammatory disease of the eye that is influenced by oxidative stress and dysregulation of the retinal pigment epithelium (RPE) associated with aging. The purpose of this study is to characterize the effects of oxidative stress and replicative senescence on the secreted cytokine profiles of RPE in vitro. Methods We used multiple, serial passages of human RPE cells from primary culture as an in vitro model of aging. Responses of early passage 5 (P5) and late passage 21 (P21) RPE cells were compared. Oxidative stress was induced in RPE cells (P5) by exposure to 75 μM hydroquinone (HQ) for 24 h. The secretome profiles of the RPE cells were measured with a multiplex suspension assay that assayed human cytokine, chemokine, and growth factors. Immunohistochemistry on younger (≤55 years old) and older (≥70 years old) human post-mortem donor eyes was used to verify selected cytokines. Results Supernatant of HQ-treated RPE cultures exhibited increased secreted levels of vascular endothelial growth factor (VEGF), interleukin (IL)-12, and IL-10 that reached statistical significance (p<0.05). Supernatant of late passage P21 RPE cultures exhibited decreased secreted levels of stromal cell-derived factor (SDF)-1α, granulocyte macrophage colony-stimulating factor (GM-CSF), IL-8, IL-15, IL-6, and an increased level of IL-1ra compared to early passage P5 RPE cultures that reached statistical significance (p<0.05). Immunohistochemical analysis demonstrated increased expression of IL-1ra in RPE cells from older post-mortem donor eyes (≥70 years old) versus younger eyes (≤55 years old). Conclusions Our data demonstrate a unique cytokine secretion profile of primary culture RPE cells at early and late passage. Our in vitro data suggest an age-specific modulation of cytokine secretion in RPE and is consistent with immunohistochemical analysis on post-mortem eyes. The secretion profile associated with RPE under conditions that mimic oxidative stress, another factor associated with the pathogenesis of AMD, emphasizes upregulation of the angiogenic growth factor, vascular endothelial growth factor. Together, these data support the role of advanced age and oxidative stress in inflammatory cytokine modulation in RPE cells. PMID:23559866

Running a postmortem service--a business case and clinical experience.

PubMed

Cohen, Marta C; Whitby, Elspeth; Fink, Michelle A; Collett, Jacquelene M; Offiah, Amaka C

2015-04-01

The purpose of the postmortem examination is to offer answers to explain the cause and manner of death. In the case of perinatal, infant and paediatric postmortem examinations, the goal is to identify unsuspected associated features, to describe pathogenic mechanisms and new conditions, and to evaluate the clinical management and diagnosis. Additionally, the postmortem examination is useful to counsel families regarding the probability of recurrence in future pregnancies and to inform family planning. Worldwide the rate of paediatric autopsy examinations has significantly declined during the last few decades. Religious objections to postmortem dissection and organ retention scandals in the United Kingdom provided some of the impetus for a search for non-invasive alternatives to the traditional autopsy; however, until recently, imaging studies remained an adjunct to, rather than a replacement for, the traditional autopsy. In 2012, Sheffield Children's Hospital National Health Service Foundation Trust set up the service provision of minimally invasive fetal, perinatal and neonatal autopsy, while a postmortem imaging service has been running in Melbourne, Australia, since 2008. Here we summarise the essentials of a business case and practical British and Australian experiences in terms of the pathological and radiologic aspects of setting up a minimally invasive clinical service in the United Kingdom and of developing a clinical postmortem imaging service as a complementary tool to the traditional autopsy in Australia.

Human iPSC-derived neurons and lymphoblastoid cells for personalized medicine research in neuropsychiatric disorders.

PubMed

Gurwitz, David

2016-09-01

The development and clinical implementation of personalized medicine crucially depends on the availability of high-quality human biosamples; animal models, although capable of modeling complex human diseases, cannot reflect the large variation in the human genome, epigenome, transcriptome, proteome, and metabolome. Although the biosamples available from public biobanks that store human tissues and cells may represent the large human diversity for most diseases, these samples are not always sufficient for developing biomarkers for patient-tailored therapies for neuropsychiatric disorders. Postmortem human tissues are available from many biobanks; nevertheless, collections of neuronal human cells from large patient cohorts representing the human diversity remain scarce. Two tools are gaining popularity for personalized medicine research on neuropsychiatric disorders: human induced pluripotent stem cell-derived neurons and human lymphoblastoid cell lines. This review examines and contrasts the advantages and limitations of each tool for personalized medicine research.

[The theory of postmortem rigidity: the history and an original concept].

PubMed

Kil'diushov, E M; Tumanov, É V; Sokolova, Z Iu

2012-01-01

The original theory of postmortem rigidity has been developed and substantiated based on the concept of postmortem muscular contracture. It is postulated that the unrestricted growth of Ca2+ concentration in myoplasm of contractile cells during the immediate postmortal period brings the actin-myosine complex to the force generation state without subsequent relaxation.

Postmortem aging and freezing and thawing storage enhance ability of early deboned chicken pectoralis major muscle to hold added salt water

USDA-ARS?s Scientific Manuscript database

The effects of postdeboning aging and frozen storage on water-holding capacity (WHC) of chicken breast pectoralis major muscle were investigated. Broiler breast muscle was removed from carcasses either early postmortem (2 h) or later postmortem (24 h). Treatments included: no postdeboning aging; 1-...

Distribution of \\0x03949-Tetrahydrocannabinol and 11-Nor-9-Carboxy-\\0x03949-Tetrahydrocannabinol acid in postmortem biological fluids and tissues from pilots fatally injured in aviation accidents.

DOT National Transportation Integrated Search

2013-12-01

Despite a long history of research on the pharmacology of 9-tetrahydrocannabinol (THC), the primary active cannabinoid in marijuana, little is known of its distribution in postmortem fluids and tissues. This study presents postmortem fluid and tiss...

[Postmortem CT examination in a case of alleged drowning--a case report].

PubMed

Woźniak, Krzysztof; Urbanik, Andrzej; Rzepecka-Woźniak, Ewa; Moskała, Artur; Kłys, Małgorzata

2009-01-01

The authors present an analysis of postmortem CT examination in a case of drowning in fresh water of a young male. Both the results of conventional forensic autopsy and radiologic examination have been compared. The analysis is illustrated by two-dimensional and three-dimensional reconstructions based on the DICOM files obtained during postmortem CT examination.

Qualification of serological infectious disease assays for the screening of samples from deceased tissue donors.

PubMed

Kitchen, A D; Newham, J A

2011-05-01

Whilst some of the assays used for serological screening of post-mortem blood samples from deceased tissue donors in some countries have been specifically validated by the manufacturer for this purpose, a significant number of those currently in use globally have not. Although specificity has previously been considered a problem in the screening of such samples, we believe that ensuring sensitivity is more important. The aim of this study was to validate a broader range of assays for the screening of post-mortem blood samples from deceased tissue donors. Six microplate immunoassays currently in use within National Health Service Blood and Transplant (NHSBT) for the screening of blood, tissue and stem cell donations were included. Representative samples from confirmed positive donors were titrated in screen negative post-mortem samples in parallel with normal pooled negative serum to determine if there was any inhibition with the post-mortem samples. There were no significant differences seen (P < 0.005) between the dilution curves obtained for the positive samples diluted in post-mortem samples and normal pooled sera. Although small numbers of samples were studied, it can be surmised that the post-mortem blood samples from deceased tissue donors, collected according to United Kingdom guidelines, are a suitable substrate for the assays evaluated. No diminution of reactivity was seen when dilution with sera from deceased donors was compared to dilution using pooled serum from live donors. In the absence of genuine low titre positive post-mortem samples, the use of samples spiked with various levels of target material provides a means of qualifying serological screening assays used by NHSBT for the screening of post-mortem blood samples from deceased tissue donors.

Meat quality and rigor mortis development in broiler chickens with gas-induced anoxia and postmortem electrical stimulation.

PubMed

Sams, A R; Dzuik, C S

1999-10-01

This study was conducted to evaluate the combined rigor-accelerating effects of postmortem electrical stimulation (ES) and argon-induced anoxia (Ar) of broiler chickens. One hundred broilers were processed in the following treatments: untreated controls, ES, Ar, or Ar with ES (Ar + ES). Breast fillets were harvested at 1 h postmortem for all treatments or at 1 and 6 h postmortem for the control carcasses. Fillets were sampled for pH and ratio of inosine to adenosine (R-value) and were then individually quick frozen (IQF) or aged on ice (AOI) until 24 h postmortem. Color was measured in the AOI fillets at 24 h postmortem. All fillets were then cooked and evaluated for Allo-Kramer shear value. The Ar treatment accelerated the normal pH decline, whereas the ES and AR + ES treatments yielded even lower pH values at 1 h postmortem. The Ar + ES treatment had a greater R-value than the ES treatment, which was greater than either the Ar or 1-h controls, which, in turn, were not different from each other. The ES treatment had the lowest L* value, and ES, Ar, and Ar + ES produced significantly higher a* values than the 1-h controls. For the IQF fillets, the ES and Ar + ES treatments were not different in shear value but were lower than Ar, which was lower than the 1-h controls. The same was true for the AOI fillets except that the ES and the Ar treatments were not different. These results indicated that although ES and Ar had rigor-accelerating and tenderizing effects, ES seemed to be more effective than Ar; there was little enhancement when Ar was added to the ES treatment and fillets were deboned at 1 h postmortem.

Rigor mortis at the myocardium investigated by post-mortem magnetic resonance imaging.

PubMed

Bonzon, Jérôme; Schön, Corinna A; Schwendener, Nicole; Zech, Wolf-Dieter; Kara, Levent; Persson, Anders; Jackowski, Christian

2015-12-01

Post-mortem cardiac MR exams present with different contraction appearances of the left ventricle in cardiac short axis images. It was hypothesized that the grade of post-mortem contraction may be related to the post-mortem interval (PMI) or cause of death and a phenomenon caused by internal rigor mortis that may give further insights in the circumstances of death. The cardiac contraction grade was investigated in 71 post-mortem cardiac MR exams (mean age at death 52 y, range 12-89 y; 48 males, 23 females). In cardiac short axis images the left ventricular lumen volume as well as the left ventricular myocardial volume were assessed by manual segmentation. The quotient of both (LVQ) represents the grade of myocardial contraction. LVQ was correlated to the PMI, sex, age, cardiac weight, body mass and height, cause of death and pericardial tamponade when present. In cardiac causes of death a separate correlation was investigated for acute myocardial infarction cases and arrhythmic deaths. LVQ values ranged from 1.99 (maximum dilatation) to 42.91 (maximum contraction) with a mean of 15.13. LVQ decreased slightly with increasing PMI, however without significant correlation. Pericardial tamponade positively correlated with higher LVQ values. Variables such as sex, age, body mass and height, cardiac weight and cause of death did not correlate with LVQ values. There was no difference in LVQ values for myocardial infarction without tamponade and arrhythmic deaths. Based on the observation in our investigated cases, the phenomenon of post-mortem myocardial contraction cannot be explained by the influence of the investigated variables, except for pericardial tamponade cases. Further research addressing post-mortem myocardial contraction has to focus on other, less obvious factors, which may influence the early post-mortem phase too. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Whole brain analysis of postmortem density changes of grey and white matter on computed tomography by statistical parametric mapping.

PubMed

Nishiyama, Yuichi; Kanayama, Hidekazu; Mori, Hiroshi; Tada, Keiji; Yamamoto, Yasushi; Katsube, Takashi; Takeshita, Haruo; Kawakami, Kazunori; Kitagaki, Hajime

2017-06-01

This study examined the usefulness of statistical parametric mapping (SPM) for investigating postmortem changes on brain computed tomography (CT). This retrospective study included 128 patients (23 - 100 years old) without cerebral abnormalities who underwent unenhanced brain CT before and after death. The antemortem CT (AMCT) scans and postmortem CT (PMCT) scans were spatially normalized using our original brain CT template, and postmortem changes of CT values (in Hounsfield units; HU) were analysed by the SPM technique. Compared with AMCT scans, 58.6 % and 98.4 % of PMCT scans showed loss of the cerebral sulci and an unclear grey matter (GM)-white matter (WM) interface, respectively. SPM analysis revealed a significant decrease in cortical GM density within 70 min after death on PMCT scans, suggesting cytotoxic brain oedema. Furthermore, there was a significant increase in the density of the WM, lenticular nucleus and thalamus more than 120 min after death. The SPM technique demonstrated typical postmortem changes on brain CT scans, and revealed that the unclear GM-WM interface on early PMCT scans is caused by a rapid decrease in cortical GM density combined with a delayed increase in WM density. SPM may be useful for assessment of whole brain postmortem changes. • The original brain CT template achieved successful normalization of brain morphology. • Postmortem changes in the brain were independent of sex. • Cortical GM density decreased rapidly after death. • WM and deep GM densities increased following cortical GM density change. • SPM could be useful for assessment of whole brain postmortem changes.

Differences in sampling techniques on total post-mortem tryptase.

PubMed

Tse, R; Garland, J; Kesha, K; Elstub, H; Cala, A D; Ahn, Y; Stables, S; Palmiere, C

2018-05-01

The measurement of mast cell tryptase is commonly used to support the diagnosis of anaphylaxis. In the post-mortem setting, the literature recommends sampling from peripheral blood sources (femoral blood) but does not specify the exact sampling technique. Sampling techniques vary between pathologists, and it is unclear whether different sampling techniques have any impact on post-mortem tryptase levels. The aim of this study is to compare the difference in femoral total post-mortem tryptase levels between two sampling techniques. A 6-month retrospective study comparing femoral total post-mortem tryptase levels between (1) aspirating femoral vessels with a needle and syringe prior to evisceration and (2) femoral vein cut down during evisceration. Twenty cases were identified, with three cases excluded from analysis. There was a statistically significant difference (paired t test, p < 0.05) between mean post-mortem tryptase by aspiration (10.87 ug/L) and by cut down (14.15 ug/L). The mean difference between the two methods was 3.28 ug/L (median, 1.4 ug/L; min, - 6.1 ug/L; max, 16.5 ug/L; 95% CI, 0.001-6.564 ug/L). Femoral total post-mortem tryptase is significantly different, albeit by a small amount, between the two sampling methods. The clinical significance of this finding and what factors may contribute to it are unclear. When requesting post-mortem tryptase, the pathologist should consider documenting the exact blood collection site and method used for collection. In addition, blood samples acquired by different techniques should not be mixed together and should be analyzed separately if possible.

Search for fungi-specific metabolites of four model drugs in postmortem blood as potential indicators of postmortem fungal metabolism.

PubMed

Martínez-Ramírez, Jorge A; Strien, Juliane; Walther, Grit; Peters, Frank T

2016-05-01

Fungi colonizing cadavers are capable of drug metabolism and may thus change the metabolite pattern or concentration of drugs in forensic postmortem samples. The purpose of this study was to check for the presence of such changes by searching fungi-specific metabolites of four model drugs (amitriptyline, metoprolol, mirtazapine, and zolpidem) in decomposed postmortem blood samples from 33 cases involving these drugs. After isolation and identification of fungal strains present in the samples, each isolate was incubated in Sabouraud medium at 25°C for up to 120h with each model drug. One part of the supernatants was directly analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), another after liquid-liquid extraction with chlorobutane and concentration. From 21 out of 33 decomposed postmortem blood samples (64%) a total of 30 different strains could be isolated, one from the class of Ascomycete and the rest belonging to 15 species from 8 different genera (number of species): Aspergillus (2), Botrytis (1), Candida (8), Fusarium (1), Mucor (1), Penicillium (1), and Rodothorula (1). In the in vitro studies, these microorganisms were found capable of N-demethylation and N-oxidation of amitriptyline and mirtazapine, O-demethylation followed by side chain oxidation of metoprolol as well as hydroxylation of all four-model drugs. In two of the postmortem blood samples, from which the fungi Aspergillus jensenii, Candida parapsilosis. and Mucor circinelloides had been isolated, a fungi-specific hydroxy zolpidem metabolite was detected. The presence of this metabolite in postmortem samples likely indicates postmortem fungal biodegradation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Postmortem examination of Australian sea snakes ( Hydrophiinae): Anatomy and common pathologic conditions.

PubMed

Gillett, Amber K; Ploeg, Richard; Flint, Mark; Mills, Paul C

2017-09-01

There is limited published information about disease in wild sea snakes and no standardized guideline for postmortem examination of sea snakes. Identifying causes of morbidity and mortality of marine vertebrate species has been pivotal to understanding disease factors implicated in stranding events and assisting with the formulation of conservation plans. Additionally, postmortem findings can provide valuable information on life history traits and the ecology of these reclusive species. Sick, moribund, or dead sea snakes are intermittently washed ashore along Australian and international beaches and provide an opportunity to examine a subset of the population and identify causes of population decline. We present an illustrated description of sea snake anatomy and describe a systematic approach to postmortem examination of sea snakes. We describe common pathologic conditions identified from clinical and postmortem examinations of stranded Australian sea snakes from southeast Queensland. Notable pathologic conditions include traumatic injury, inflammatory conditions, parasitic infections, and neoplasia.

Increased White Matter Inflammation in Aging- and Alzheimer's Disease Brain.

PubMed

Raj, Divya; Yin, Zhuoran; Breur, Marjolein; Doorduin, Janine; Holtman, Inge R; Olah, Marta; Mantingh-Otter, Ietje J; Van Dam, Debby; De Deyn, Peter P; den Dunnen, Wilfred; Eggen, Bart J L; Amor, Sandra; Boddeke, Erik

2017-01-01

Chronic neuroinflammation, which is primarily mediated by microglia, plays an essential role in aging and neurodegeneration. It is still unclear whether this microglia-induced neuroinflammation occurs globally or is confined to distinct brain regions. In this study, we investigated microglia activity in various brain regions upon healthy aging and Alzheimer's disease (AD)-related pathology in both human and mouse samples. In purified microglia isolated from aging mouse brains, we found a profound gene expression pattern related to pro-inflammatory processes, phagocytosis, and lipid homeostasis. Particularly in white matter microglia of 24-month-old mice, abundant expression of phagocytic markers including Mac-2, Axl, CD16/32, Dectin1, CD11c, and CD36 was detected. Interestingly, in white matter of human brain tissue the first signs of inflammatory activity were already detected during middle age. Thus quantification of microglial proteins, such as CD68 (commonly associated with phagocytosis) and HLA-DR (associated with antigen presentation), in postmortem human white matter brain tissue showed an age-dependent increase in immunoreactivity already in middle-aged people (53.2 ± 2.0 years). This early inflammation was also detectable by non-invasive positron emission tomography imaging using [ 11 C]-(R)-PK11195, a ligand that binds to activated microglia. Increased microglia activity was also prominently present in the white matter of human postmortem early-onset AD (EOAD) brain tissue. Interestingly, microglia activity in the white matter of late-onset AD (LOAD) CNS was similar to that of the aged clinically silent AD cases. These data indicate that microglia-induced neuroinflammation is predominant in the white matter of aging mice and humans as well as in EOAD brains. This white matter inflammation may contribute to the progression of neurodegeneration, and have prognostic value for detecting the onset and progression of aging and neurodegeneration.

Altered transition metal homeostasis in Niemann-Pick disease, Type C1

PubMed Central

Hung, Ya Hui; Faux, Noel G.; Killilea, David W.; Yanjanin, Nicole; Firnkes, Sally; Volitakis, Irene; Ganio, George; Walterfang, Mark; Hastings, Caroline; Porter, Forbes D.; Ory, Daniel S.; Bush, Ashley I.

2014-01-01

The loss of NPC1 protein function is the predominant cause of Niemann-Pick type C1 disease (NP-C1), a systemic and neurodegenerative disorder characterized by late-endosomal/lysosomal accumulation of cholesterol and other lipids. Limited evidence from post-mortem human tissues, an Npc1−/− mouse model, and cell culture studies also suggest failure of metal homeostasis in NP-C1. To investigate these findings, we performed a comprehensive transition metal analysis of cerebrospinal fluid (CSF), plasma and tissue samples from human NP-C1 patients and an Npc1−/− mouse model. NPC1 deficiency in the Npc1−/− mouse model resulted in a perturbation of transition metal homeostasis in the plasma and key organs (brain, liver, spleen, heart, lungs, and kidneys). Analysis of human patient CSF, plasma and post-mortem brain tissues also indicated disrupted metal homeostasis. There was a disparity in the direction of metal changes between the human and the Npc1−/− mouse samples, which may reflect species-specific metal metabolism. Nevertheless, common to both species is brain zinc accumulation. Furthermore, treatment with the glucosylceramide synthase inhibitor miglustat, the only drug shown in a controlled clinical trial to have some efficacy for NP-C1, did not correct the alterations in CSF and plasma transition metal and ceruloplasmin (CP) metabolism in NP-C1 patients. These findings highlight the importance of NPC1 function in metal homeostasis, and indicate that metal-targeting therapy may be of value as a treatment for NP-C. PMID:24343124

Postmortem aging can significantly enhance water-holding capacity of broiler pectoralis major muscle measured by the salt-induced swelling/centrifuge method

USDA-ARS?s Scientific Manuscript database

Water-holding capacity (WHC) is one of the most important functional properties of fresh meat and can be significantly affected by postmortem muscle changes. Two experiments were carried out to evaluate the effects of postmortem aging on WHC of broiler pectoralis (p.) major muscle indicated with % s...

Analysis of Sertraline in Postmortem Fluids and Tissues in 11 Aviation Accident Victims

DTIC Science & Technology

2012-11-01

likely undergoes significant postmortem redistribution. 17. Key Words 18. Distribution Statement Forensic Toxicology , Sertraline, Norsertraline... Toxicology .. Forensic Sci Int,.142:.75-100.(2004) . 29 .. Skopp,.G ..Postmortem.Toxicology .. Forensic Sci Med Pathol,.6:.314-25.(2010) . ... toxicological . analysis. on. specimens.from.….aircraft.accident.fatalities”.and.“in- vestigate.….general.aviation.and.air.carrier.accidents. and. search

Cardiac mesenchymal progenitors from postmortem cardiac tissues retained cellular characterization.

PubMed

Kami, D; Kitani, T; Nakata, M; Gojo, S

2014-05-01

Currently, cells for transplantation in regenerative medicine are derived from either autologous or allogeneic tissue. The former has the drawbacks that the quality of donor cells may depend on the condition of the patient, while the quantity of the cells may also be limited. To solve these problems, we investigated the potential of allogeneic cardiac mesenchymal progenitors (CMPs) derived from postmortem hearts, which may be immunologically privileged similar to bone marrow-derived mesenchymal progenitors. We examined whether viable CMPs could be isolated from C57/B6 murine cardiac tissues harvested at 24 hours postmortem. After 2- to 3-week propagation with a high dose of basic fibroblast growth factor, we performed cellular characteristics analyses, which included proliferation and differentiation property flow cytometry and microarray analyses. Postmortem CMPs had a longer lag phase after seeding than CMPs obtained from living tissues, but otherwise had similar characteristics in all the analyses. In addition, global gene expression analysis by microarray showed that cells derived from postmortem and living tissues had similar characteristics. These results indicate that allogeneic postmortem CMPs have potential for cell transplantation because they circumvent the issue of both the quality and quantity of donor cells. Copyright © 2014 Elsevier Inc. All rights reserved.

Postmortem Cholesterol Levels in Peripheral Nerve Tissue: Preliminar Considerations on Interindividual and Intraindividual Variation.

PubMed

Vacchiano, Giuseppe; Luna Maldonado, Aurelio; Matas Ros, Maria; Fiorenza, Elisa; Silvestre, Angela; Simonetti, Biagio; Pieri, Maria

2018-06-01

The study reports the evolution of the demyelinization process based on cholesterol ([CHOL]) levels quantified in median nerve samples and collected at different times-from death from both right and left wrists. The statistical data show that the phenomenon evolves differently in the right and left nerves. Such a difference can reasonably be attributed to a different multicenter evolution of the demyelinization. For data analysis, the enrolled subjects were grouped by similar postmortem intervals (PMIs), considering 3 intervals: PMI < 48 hours, 48 hours < PMI < 78 hours, and PMI > 78 hours. Data obtained from tissue dissected within 48 hours of death allowed for a PMI estimation according to the following equations: PMI = 0.000 + 0.7623 [CHOL]right (R = 0.581) for the right wrist and PMI = 0.000 + 0.8911 [CHOL]left (R = 0.794) for the left wrist.At present, this correlation cannot be considered to be definitive because of the limitation of the small size of the samples analyzed, because the differences in the sampling time and the interindividual and intraindividual variation may influence the demyelinization process.

Death of a female cocaine user due to the serotonin syndrome following moclobemide-venlafaxine overdose.

PubMed

Kłys, Małgorzata; Kowalski, Piotr; Rojek, Sebastian; Gross, Adam

2009-01-30

To our knowledge, the majority of evidence supporting the relationship between the serotonin syndrome and medications that effect 5HT is based on case reports. The justification for taking up this subject has been a fatal outcome of a 21 year-old female following an administration of toxic doses of moclobemide (MAOI) and venlafaxine (SNRI). As a result of complex toxicological investigations including antemortem and postmortem material, antemortem clinical observations and postmortem examinations, the cause of death was identified as overdose with antidepressants--moclobemide and venlafaxine--in the mechanism of the clinically fully developed severe toxic serotonin syndrome. The analysis of a hair strand collected from the victim documented the use of the above-mentioned drugs simultaneously with cocaine in the period of at least 20 months preceding death. The fact is a matter of considerable interest in view of the employed pharmacotherapy, giving rise to suspicion that the woman had not developed the serotonin syndrome during the almost 2-year antemortem period until she took toxic doses of both medications.

A comparison of two methods for surveying mortality of beached birds in British Columbia.

PubMed Central

Stephen, C; Burger, A E

1994-01-01

Systematic surveys of beached birds are often limited in their ability to classify the causes of death of the carcasses recovered. Two methods of determining the cause of death of seabirds encountered during surveys of beaches of southwestern Vancouver Island, British Columbia, are compared. Birds were either subjected to external visual examinations by volunteer beach surveyors or submitted for gross postmortem examination by a veterinarian. The reliance on external examination of birds on beaches often prevented the accurate classification of the reproductive status and cause of death of the birds collected, but was valuable for describing the species, locations, and numbers of birds affected. The use of gross postmortem examinations of carcasses allowed for a more refined classification of the cause of death, as well as providing reliable descriptions of the bodily condition and sex of the birds examined. However, almost one half of the carcasses encountered were unsuitable for necropsy because of scavenging and decomposition. It is concluded that a combination of field and necropsy observations provides a useful method with which to monitor the pattern of mortality of beached seabirds. PMID:7994705

Competing targets of microRNA-608 affect anxiety and hypertension

PubMed Central

Hanin, Geula; Shenhar-Tsarfaty, Shani; Yayon, Nadav; Hoe, Yau Yin; Bennett, Estelle R.; Sklan, Ella H.; Rao, Dabeeru. C.; Rankinen, Tuomo; Bouchard, Claude; Geifman-Shochat, Susana; Shifman, Sagiv; Greenberg, David S.; Soreq, Hermona

2014-01-01

MicroRNAs (miRNAs) can repress multiple targets, but how a single de-balanced interaction affects others remained unclear. We found that changing a single miRNA–target interaction can simultaneously affect multiple other miRNA–target interactions and modify physiological phenotype. We show that miR-608 targets acetylcholinesterase (AChE) and demonstrate weakened miR-608 interaction with the rs17228616 AChE allele having a single-nucleotide polymorphism (SNP) in the 3′-untranslated region (3′UTR). In cultured cells, this weakened interaction potentiated miR-608-mediated suppression of other targets, including CDC42 and interleukin-6 (IL6). Postmortem human cortices homozygote for the minor rs17228616 allele showed AChE elevation and CDC42/IL6 decreases compared with major allele homozygotes. Additionally, minor allele heterozygote and homozygote subjects showed reduced cortisol and elevated blood pressure, predicting risk of anxiety and hypertension. Parallel suppression of the conserved brain CDC42 activity by intracerebroventricular ML141 injection caused acute anxiety in mice. We demonstrate that SNPs in miRNA-binding regions could cause expanded downstream effects changing important biological pathways. PMID:24722204

Depression and treatment response: dynamic interplay of signaling pathways and altered neural processes

PubMed Central

Duric, Vanja

2014-01-01

Since the 1960s, when the first tricyclic and monoamine oxidase inhibitor antidepressant drugs were introduced, most of the ensuing agents were designed to target similar brain pathways that elevate serotonin and/or norepinephrine signaling. Fifty years later, the main goal of the current depression research is to develop faster-acting, more effective therapeutic agents with fewer side effects, as currently available antidepressants are plagued by delayed therapeutic onset and low response rates. Clinical and basic science research studies have made significant progress towards deciphering the pathophysiological events within the brain involved in development, maintenance, and treatment of major depressive disorder. Imaging and postmortem brain studies in depressed human subjects, in combination with animal behavioral models of depression, have identified a number of different cellular events, intracellular signaling pathways, proteins, and target genes that are modulated by stress and are potentially vital mediators of antidepressant action. In this review, we focus on several neural mechanisms, primarily within the hippocampus and prefrontal cortex, which have recently been implicated in depression and treatment response. PMID:22585060

Prevention of abnormal pulmonary mechanics in the postmortem guinea pig lung.

PubMed

Reynolds, A M; McEvoy, R D

1988-04-01

Severe postmortem bronchoconstriction has been shown previously in guinea pig lungs and linked to pulmonary blood loss during exsanguination (Lai et al., J. Appl. Physiol. 56: 308-314, 1984). To reexamine this phenomenon we measured postmortem airway function in anesthetized open-chest guinea pigs after sudden circulatory arrest. Animals were divided into 4 groups of 10 and ventilated for 15 min postmortem with different gases: 1) room air, 2) conditioned air, 3) dry 5% CO2-21% O2-74% N2, and 4) conditioned 5% CO2-21% O2-74% N2. In room air-ventilated lungs there was a 50% decrease in dynamic compliance (Cdyn) by 15 min and marked gas trapping compared with control lungs. Conditioning the room air did not attenuate these changes, but when 5% CO2 was added to the conditioned postmortem inspirate, gas trapping was eliminated and the fall in Cdyn was almost abolished. Ventilation with a dry 5% CO2 gas mixture at room temperature resulted in a 31% fall in Cdyn at 15 min but no gas trapping. We conclude that marked abnormalities of airway function occur postmortem in room air-ventilated guinea pig lungs in the absence of pulmonary blood loss. The changes are mainly due to airway hypocarbia, a known cause of bronchoconstriction, but a reduction in Cdyn can also occur if there is marked airway cooling and drying. Acute postmortem airway dysfunction can be prevented in the guinea pig by maintaining normal airway gas composition.

Germ-line and somatic EPHA2 coding variants in lens aging and cataract.

PubMed

Bennett, Thomas M; M'Hamdi, Oussama; Hejtmancik, J Fielding; Shiels, Alan

2017-01-01

Rare germ-line mutations in the coding regions of the human EPHA2 gene (EPHA2) have been associated with inherited forms of pediatric cataract, whereas, frequent, non-coding, single nucleotide variants (SNVs) have been associated with age-related cataract. Here we sought to determine if germ-line EPHA2 coding SNVs were associated with age-related cataract in a case-control DNA panel (> 50 years) and if somatic EPHA2 coding SNVs were associated with lens aging and/or cataract in a post-mortem lens DNA panel (> 48 years). Micro-fluidic PCR amplification followed by targeted amplicon (exon) next-generation (deep) sequencing of EPHA2 (17-exons) afforded high read-depth coverage (1000x) for > 82% of reads in the cataract case-control panel (161 cases, 64 controls) and > 70% of reads in the post-mortem lens panel (35 clear lens pairs, 22 cataract lens pairs). Novel and reference (known) missense SNVs in EPHA2 that were predicted in silico to be functionally damaging were found in both cases and controls from the age-related cataract panel at variant allele frequencies (VAFs) consistent with germ-line transmission (VAF > 20%). Similarly, both novel and reference missense SNVs in EPHA2 were found in the post-mortem lens panel at VAFs consistent with a somatic origin (VAF > 3%). The majority of SNVs found in the cataract case-control panel and post-mortem lens panel were transitions and many occurred at di-pyrimidine sites that are susceptible to ultraviolet (UV) radiation induced mutation. These data suggest that novel germ-line (blood) and somatic (lens) coding SNVs in EPHA2 that are predicted to be functionally deleterious occur in adults over 50 years of age. However, both types of EPHA2 coding variants were present at comparable levels in individuals with or without age-related cataract making simple genotype-phenotype correlations inconclusive.

Germ-line and somatic EPHA2 coding variants in lens aging and cataract

PubMed Central

Bennett, Thomas M.; M’Hamdi, Oussama; Hejtmancik, J. Fielding

2017-01-01

Rare germ-line mutations in the coding regions of the human EPHA2 gene (EPHA2) have been associated with inherited forms of pediatric cataract, whereas, frequent, non-coding, single nucleotide variants (SNVs) have been associated with age-related cataract. Here we sought to determine if germ-line EPHA2 coding SNVs were associated with age-related cataract in a case-control DNA panel (> 50 years) and if somatic EPHA2 coding SNVs were associated with lens aging and/or cataract in a post-mortem lens DNA panel (> 48 years). Micro-fluidic PCR amplification followed by targeted amplicon (exon) next-generation (deep) sequencing of EPHA2 (17-exons) afforded high read-depth coverage (1000x) for > 82% of reads in the cataract case-control panel (161 cases, 64 controls) and > 70% of reads in the post-mortem lens panel (35 clear lens pairs, 22 cataract lens pairs). Novel and reference (known) missense SNVs in EPHA2 that were predicted in silico to be functionally damaging were found in both cases and controls from the age-related cataract panel at variant allele frequencies (VAFs) consistent with germ-line transmission (VAF > 20%). Similarly, both novel and reference missense SNVs in EPHA2 were found in the post-mortem lens panel at VAFs consistent with a somatic origin (VAF > 3%). The majority of SNVs found in the cataract case-control panel and post-mortem lens panel were transitions and many occurred at di-pyrimidine sites that are susceptible to ultraviolet (UV) radiation induced mutation. These data suggest that novel germ-line (blood) and somatic (lens) coding SNVs in EPHA2 that are predicted to be functionally deleterious occur in adults over 50 years of age. However, both types of EPHA2 coding variants were present at comparable levels in individuals with or without age-related cataract making simple genotype-phenotype correlations inconclusive. PMID:29267365

Differential Nuclear and Mitochondrial DNA Preservation in Post-Mortem Teeth with Implications for Forensic and Ancient DNA Studies

PubMed Central

Higgins, Denice; Rohrlach, Adam B.; Kaidonis, John; Townsend, Grant; Austin, Jeremy J.

2015-01-01

Major advances in genetic analysis of skeletal remains have been made over the last decade, primarily due to improvements in post-DNA-extraction techniques. Despite this, a key challenge for DNA analysis of skeletal remains is the limited yield of DNA recovered from these poorly preserved samples. Enhanced DNA recovery by improved sampling and extraction techniques would allow further advancements. However, little is known about the post-mortem kinetics of DNA degradation and whether the rate of degradation varies between nuclear and mitochondrial DNA or across different skeletal tissues. This knowledge, along with information regarding ante-mortem DNA distribution within skeletal elements, would inform sampling protocols facilitating development of improved extraction processes. Here we present a combined genetic and histological examination of DNA content and rates of DNA degradation in the different tooth tissues of 150 human molars over short-medium post-mortem intervals. DNA was extracted from coronal dentine, root dentine, cementum and pulp of 114 teeth via a silica column method and the remaining 36 teeth were examined histologically. Real time quantification assays based on two nuclear DNA fragments (67 bp and 156 bp) and one mitochondrial DNA fragment (77 bp) showed nuclear and mitochondrial DNA degraded exponentially, but at different rates, depending on post-mortem interval and soil temperature. In contrast to previous studies, we identified differential survival of nuclear and mtDNA in different tooth tissues. Futhermore histological examination showed pulp and dentine were rapidly affected by loss of structural integrity, and pulp was completely destroyed in a relatively short time period. Conversely, cementum showed little structural change over the same time period. Finally, we confirm that targeted sampling of cementum from teeth buried for up to 16 months can provide a reliable source of nuclear DNA for STR-based genotyping using standard extraction methods, without the need for specialised equipment or large-volume demineralisation steps. PMID:25992635

Quantitative Susceptibility Mapping of Amyloid-β Aggregates in Alzheimer's Disease with 7T MR.

PubMed

Tiepolt, Solveig; Schäfer, Andreas; Rullmann, Michael; Roggenhofer, Elisabeth; Gertz, Hermann-Josef; Schroeter, Matthias L; Patt, Marianne; Bazin, Pierre-Louis; Jochimsen, Thies H; Turner, Robert; Sabri, Osama; Barthel, Henryk

2018-05-28

PET imaging is an established technique to detect cerebral amyloid-β (Aβ) plaques in vivo. Some preclinical and postmortem data report an accumulation of redox-active iron near Aβ plaques. Quantitative susceptibility mapping (QSM) at high-field MRI enables iron deposits to be depicted with high spatial resolution. Aim of this study was to examine whether iron and Aβ plaque accumulation is related and thus, whether 7T MRI might be an additive diagnostic tool to Aβ PET imaging. Postmortem human Alzheimer's disease (AD) and healthy control (HC) frontal gray matter (GM) was imaged with 7T MRI which resulted in T1 maps and QSM. Aβ plaque load was determined by histopathology. In vivo, 10 Aβ PET-positive AD patients (74.1±6.0a) and 10 Aβ PET-negative HCs (67.1±4.4a) underwent 7T MR examination and QSM maps were analyzed. Severity of cognitive deficits was determined by MMSE. Postmortem, the susceptibility of Aβ plaque-containing GM were higher than those of Aβ plaque-free GM (0.011±0.002 versus - 0.008±0.003 ppm, p <  0.001). In vivo, only the bilateral globus pallidus showed significantly higher susceptibility in AD patients compared to HCs (right: 0.277±0.018 versus - 0.009±0.009 ppm; left: 0.293±0.014 versus - 0.007±0.012 ppm, p <  0.0001). The pallidal QSM values were negatively correlated with those of the MMSE (r = - 0.69, p = 0.001). The postmortem study revealed significant susceptibility differences between the Aβ plaque-containing and Aβ plaque-free GM, whereas in vivo only the QSM values of the globus pallidus differed significantly between AD and HC group. The pallidal QSM values correlated with the severity of cognitive deficits. These findings encourage efforts to optimize the 7T-QSM methodology.

A Combined Metabonomic and Proteomic Approach Identifies Frontal Cortex Changes in a Chronic Phencyclidine Rat Model in Relation to Human Schizophrenia Brain Pathology

PubMed Central

Wesseling, Hendrik; Chan, Man K; Tsang, T M; Ernst, Agnes; Peters, Fabian; Guest, Paul C; Holmes, Elaine; Bahn, Sabine

2013-01-01

Current schizophrenia (SCZ) treatments fail to treat the broad range of manifestations associated with this devastating disorder. Thus, new translational models that reproduce the core pathological features are urgently needed to facilitate novel drug discovery efforts. Here, we report findings from the first comprehensive label-free liquid-mass spectrometry proteomic- and proton nuclear magnetic resonance-based metabonomic profiling of the rat frontal cortex after chronic phencyclidine (PCP) intervention, which induces SCZ-like symptoms. The findings were compared with results from a proteomic profiling of post-mortem prefrontal cortex from SCZ patients and with relevant findings in the literature. Through this approach, we identified proteomic alterations in glutamate-mediated Ca2+ signaling (Ca2+/calmodulin-dependent protein kinase II, PPP3CA, and VISL1), mitochondrial function (GOT2 and PKLR), and cytoskeletal remodeling (ARP3). Metabonomic profiling revealed changes in the levels of glutamate, glutamine, glycine, pyruvate, and the Ca2+ regulator taurine. Effects on similar pathways were also identified in the prefrontal cortex tissue from human SCZ subjects. The discovery of similar but not identical proteomic and metabonomic alterations in the chronic PCP rat model and human brain indicates that this model recapitulates only some of the molecular alterations of the disease. This knowledge may be helpful in understanding mechanisms underlying psychosis, which, in turn, can facilitate improved therapy and drug discovery for SCZ and other psychiatric diseases. Most importantly, these molecular findings suggest that the combined use of multiple models may be required for more effective translation to studies of human SCZ. PMID:23942359

Biomechanical and injury response to posterolateral loading from torso side airbags.

PubMed

Hallman, Jason J; Yoganandan, Narayan; Pintar, Frank A

2010-11-01

This study characterized thoracoabdominal response to posterolateral loading from a seat-mounted side airbag. Seven unembalmed post-mortem human subjects were exposed to ten airbag deployments. Subjects were positioned such that the deploying airbag first contacted the posterolateral thorax between T6 and L1 while stationary (n = 3 x 2 aspects) or while subjected to left lateral sled impact at ΔV = 6.7 m/s (n = 4). Chestband contours were analyzed to quantify deformation direction in the thoracic x-y plane (zero degrees indicating anterior and 180° indicating posterior), magnitude, rate, and viscous response. Skeletal injuries were consistent with posterolateral contact; visceral injuries consisted of renal (n = 1) or splenic (n = 3) lacerations. Deformation direction was transient during sled impact, progressing from 122 ± 5° at deformation onset to 90° following maximum deflection. Angles from stationary subjects progressed from 141 ± 9° to 120°. Peak normalized deflections, peak rates, and VCmax ranges were 0.075 - 0.171, 3.7 - 12.7 m/s, and 0.3 - 0.6 m/s with stationary airbag, respectively; ranges were 0.167 - 0.297, 7.4 - 18.3 m/s, and 0.7 - 3.0 m/s with airbag sled impact, respectively. Peak deflections were measured at angles between 99° - 135° and 98° - 125° for stationary and dynamic conditions, respectively. Because of deflection angle transience and localized injury response, both posterolateral and lateral injury metrics may be required for this boundary condition. Contrasted with flat rigid or anterolateral loading, biomechanical response to side airbag interaction may be augmented by peak normalized deflection or VCmax at 130°.

Biomechanical and Injury Response to Posterolateral Loading from Torso Side Airbags

PubMed Central

Hallman, Jason J.; Yoganandan, Narayan; Pintar, Frank A.

2013-01-01

This study characterized thoracoabdominal response to posterolateral loading from a seat-mounted side airbag. Seven unembalmed post-mortem human subjects were exposed to ten airbag deployments. Subjects were positioned such that the deploying airbag first contacted the posterolateral thorax between T6 and L1 while stationary (n = 3 × 2 aspects) or while subjected to left lateral sled impact at ΔV = 6.7 m/s (n = 4). Chestband contours were analyzed to quantify deformation direction in the thoracic x–y plane (zero degrees indicating anterior and 180° indicating posterior), magnitude, rate, and viscous response. Skeletal injuries were consistent with posterolateral contact; visceral injuries consisted of renal (n = 1) or splenic (n = 3) lacerations. Deformation direction was transient during sled impact, progressing from 122 ± 5° at deformation onset to 90° following maximum deflection. Angles from stationary subjects progressed from 141 ± 9° to 120°. Peak normalized deflections, peak rates, and VCmax ranges were 0.075 – 0.171, 3.7 – 12.7 m/s, and 0.3 – 0.6 m/s with stationary airbag, respectively; ranges were 0.167 – 0.297, 7.4 – 18.3 m/s, and 0.7 – 3.0 m/s with airbag sled impact, respectively. Peak deflections were measured at angles between 99° – 135° and 98° – 125° for stationary and dynamic conditions, respectively. Because of deflection angle transience and localized injury response, both posterolateral and lateral injury metrics may be required for this boundary condition. Contrasted with flat rigid or anterolateral loading, biomechanical response to side airbag interaction may be augmented by peak normalized deflection or VCmax at 130°. PMID:21512911

Downregulation of Brain Phosphodiesterase Type IV Measured with 11C-(R)-Rolipram Positron Emission Tomography in Major Depressive Disorder

PubMed Central

Fujita, Masahiro; Hines, Christina S.; Zoghbi, Sami S.; Mallinger, Alan G.; Dickstein, Leah P.; Liow, Jeih-San; Zhang, Yi; Pike, Victor W.; Drevets, Wayne C.; Innis, Robert B.; Zarate, Carlos A.

2012-01-01

Background Phosphodiesterase type IV (PDE4), an important component of the cyclic adenosine monophosphate (cAMP) cascade, selectively metabolizes cAMP in the brain to the inactive monophosphate. Basic studies suggest that PDE4 mediates the effects of several antidepressants. This study sought to quantify the binding of 11C-(R)-rolipram, a PDE4 inhibitor, as an indirect measure of this enzyme’s activity in the brain of individuals with major depressive disorder (MDD) compared with healthy control subjects. Methods 11C-(R)-Rolipram brain positron emission tomography scans were performed in 28 unmedicated MDD subjects and 25 age- and gender-matched healthy control subjects. Patients were moderately depressed and about one half were treatment-naive. 11C-(R)-Rolipram binding in the brain was measured using arterial 11C-(R)-rolipram levels to correct for the influence of cerebral blood flow. Results Major depressive disorder subjects showed a widespread, approximately 20% reduction in 11C-(R)-rolipram binding (p = .002), which was not caused by different volumes of gray matter. Decreased rolipram binding of similar magnitudes was observed in most brain areas. Rolipram binding did not correlate with the severity of depressive or anxiety symptoms. Conclusions This study is the first to demonstrate that brain levels of PDE4, a critical enzyme that regulates cAMP, are decreased in unmedicated individuals with MDD in vivo. These results are in line with human postmortem and rodent studies demonstrating downregulation of the cAMP cascade in MDD and support the hypothesis that agents such as PDE4 inhibitors, which increase activity within the cAMP cascade, may have antidepressant effects. PMID:22677471

An Objective Evaluation of Mass Scaling Techniques Utilizing Computational Human Body Finite Element Models.

PubMed

Davis, Matthew L; Scott Gayzik, F

2016-10-01

Biofidelity response corridors developed from post-mortem human subjects are commonly used in the design and validation of anthropomorphic test devices and computational human body models (HBMs). Typically, corridors are derived from a diverse pool of biomechanical data and later normalized to a target body habitus. The objective of this study was to use morphed computational HBMs to compare the ability of various scaling techniques to scale response data from a reference to a target anthropometry. HBMs are ideally suited for this type of study since they uphold the assumptions of equal density and modulus that are implicit in scaling method development. In total, six scaling procedures were evaluated, four from the literature (equal-stress equal-velocity, ESEV, and three variations of impulse momentum) and two which are introduced in the paper (ESEV using a ratio of effective masses, ESEV-EffMass, and a kinetic energy approach). In total, 24 simulations were performed, representing both pendulum and full body impacts for three representative HBMs. These simulations were quantitatively compared using the International Organization for Standardization (ISO) ISO-TS18571 standard. Based on these results, ESEV-EffMass achieved the highest overall similarity score (indicating that it is most proficient at scaling a reference response to a target). Additionally, ESEV was found to perform poorly for two degree-of-freedom (DOF) systems. However, the results also indicated that no single technique was clearly the most appropriate for all scenarios.

Kisspeptin Expression in the Human Infundibular Nucleus in Relation to Sex, Gender Identity, and Sexual Orientation.

PubMed

Taziaux, Melanie; Staphorsius, Annemieke S; Ghatei, Mohammad A; Bloom, Stephen R; Swaab, Dick F; Bakker, Julie

2016-06-01

Since the discovery of its central role in reproduction, our functional neuroanatomical knowledge of the hypothalamic kisspeptin system is predominantly based on animal studies. Although sex differences in kisspeptin expression have been shown in humans in adulthood, the developmental origin of this sex difference is unknown. Our objectives were to determine the following: 1) when during development the sex difference in kisspeptin expression in the infundibular nucleus would emerge and 2) whether this sex difference is related to sexual orientation or transsexuality. Postmortem hypothalamic tissues were collected by The Netherlands Brain Bank, and sections were stained for kisspeptin by immunohistochemistry. Hypothalami of 43 control subjects were categorized into three periods: infant/prepubertal (six girls, seven boys), adult (11 women, seven men), and elderly (six aged women, six aged men). Eight male-to-female (MTF) transsexuals, three HIV(+) heterosexual men, and five HIV(+) homosexual men were also analyzed. We estimated the total number of kisspeptin-immunoreactive neurons within the infundibular nucleus. Quantitative analysis confirmed that the human infundibular kisspeptin system exhibits a female-dominant sex difference. The number of kisspeptin neurons is significantly greater in the infant/prepubertal and elderly periods compared with the adult period. Finally, in MTF transsexuals, but not homosexual men, a female-typical kisspeptin expression was observed. These findings suggest that infundibular kisspeptin neurons are sensitive to circulating sex steroid hormones throughout life and that the sex reversal observed in MTF transsexuals might reflect, at least partially, an atypical brain sexual differentiation.

Ante- and postmortem diagnostic techniques for anthrax: rethinking pathogen exposure and the geographic extent of the disease in wildlife.

PubMed

Bagamian, Karoun H; Alexander, Kathleen A; Hadfield, Ted L; Blackburn, Jason K

2013-10-01

Although antemortem approaches in wildlife disease surveillance are common for most zoonoses, they have been used infrequently in anthrax surveillance. Classically, anthrax is considered a disease with extremely high mortality. This is because anthrax outbreaks are often detected ex post facto through wildlife or livestock fatalities or spillover transmission to humans. As a result, the natural prevalence of anthrax infection in animal populations is largely unknown. However, in the past 20 yr, antemortem serologic surveillance in wildlife has indicated that not all species exposed succumb to infection, and anthrax exposure may be more widespread than originally appreciated. These studies brought about a multitude of new questions, many of which can be addressed by increased antemortem serologic surveillance in wildlife populations. To fully understand anthrax transmission dynamics and geographic extent, it is important to identify exposure in wildlife hosts and associated factors and, in turn, understand how these influences may drive environmental reservoir dynamics and concurrent disease risk in livestock and humans. Here we review our current understanding of the serologic response to anthrax among wildlife hosts and serologic diagnostic assays used to augment traditional postmortem anthrax surveillance strategies. We also provide recommendations for the use of serology and sentinel species surveillance approaches in anthrax research and management.

Using body temperature, food and water consumption as biomarkers of disease progression in mice with Eμ-myc lymphoma.

PubMed

Hunter, J E; Butterworth, J; Perkins, N D; Bateson, M; Richardson, C A

2014-02-18

Non-invasive biomarkers of disease progression in mice with cancer are lacking making it challenging to implement appropriate humane end points. We investigated whether body temperature, food and water consumption could be used to predict tumour burden. Thirty-six male, wild-type C57Bl/6 mice were implanted with subcutaneous RFID temperature sensors and inoculated with Eμ-myc tumours that infiltrate lymphoid tissue. Decrease in body temperature over the course of the study positively predicted post-mortem lymph node tumour burden (R(2)=0.68, F(1,22)=44.8, P<0.001). At experimental and humane end points, all mice that had a mean decrease in body temperature of 0.7 °C or greater had lymph nodes heavier than 0.5 g (100% sensitivity), whereas a mean decrease in body temperature <0.7 °C always predicted lymph nodes lighter than 0.5 g (100% specificity). The mean decrease in food consumption in each cage also predicted mean post-mortem lymph node tumour burden at 3 weeks (R(2)=0.89, F(1,3)=23.2, P=0.017). Temperature, food and water consumption were useful biomarkers of disease progression in mice with lymphoma and could potentially be used more widely to monitor mice with other forms of cancer.

Pork loin quality is not indicative of fresh belly or fresh and cured ham quality.

PubMed

Arkfeld, E K; Wilson, K B; Overholt, M F; Harsh, B N; Lowell, J E; Hogan, E K; Klehm, B J; Bohrer, B M; Mohrhauser, D A; King, D A; Wheeler, T L; Dilger, A C; Shackelford, S D; Boler, D D

2016-12-01

The objective was to characterize the relationship between fresh loin quality with fresh belly or fresh and cured ham quality. Pigs raised in 8 barns representing 2 seasons [cold ( = 4,290) and hot ( = 3,394)] and 2 production focuses [lean ( = 3,627) and quality ( = 4,057)] were used. Carcass characteristics and other meat quality data were collected on 7,684 carcasses. All of the carcasses were evaluated for HCW, LM depth, tenth rib fat depth, leg (ham primal) weight, instrumental color on the gluteus medius and gluteus profundus of the ham face, and subjective loin quality. Instrumental loin color and ultimate pH (≥ 22 h postmortem) were collected on the ventral side of loins along with dimensions and firmness scores of fresh bellies from 50% of the carcasses. Ten percent of the boneless loins and fresh hams were evaluated for slice shear force (SSF) or cured ham characteristics. Correlation coefficients between traits were computed using the CORR procedure of SAS and considered significantly different from 0 at ≤ 0.05. Temperature decline, beginning at 31 min postmortem and concluding at 22 h postmortem, for the longissimus dorsi and semimembranosus muscles were evaluated on 10% of the carcasses. Ultimate loin pH was correlated with dimensional belly characteristics ( ≥ |0.07|; < 0.0001) fresh ham instrumental color ( ≥ |0.03|; ≤ 0.05), and semimembranosus ultimate pH ( = 0.33; < 0.0001). Further, ultimate loin pH was correlated ( ≤ 0.01) with pump retention ( = 0.087) and cooked yield ( = 0.156) of cured hams. Instrumental L*on the ventral surface of the loin was related to L* on both muscles of the ham face ( ≤ 0.0001). Even though significant relationships between the loin, belly, and ham were detected, the variability in belly and ham quality explained by variability in loin quality was poor (≤ 22.09%). Compositional differences between the loin and belly may have contributed to those poor relationships. Additionally, differences in temperature declines during chilling between the loin and ham likely contributed to the weak nature of relationships. Equilibration of longissimus dorsi temperature to ambient cooler temperature occurred at 14 h postmortem ( = 0.0005), yet the semimembranosus had not equilibrated with ambient (equilibration bay) temperature ( < 0.0001) at 22 h postmortem. Using loin quality to draw conclusions about fresh belly and fresh and cured ham quality may be misleading.

Disruption of blood-brain barrier integrity in postmortem alcoholic brain: preclinical evidence of TLR4 involvement from a binge-like drinking model.

PubMed

Rubio-Araiz, Ana; Porcu, Francesca; Pérez-Hernández, Mercedes; García-Gutiérrez, Mª Salud; Aracil-Fernández, María Auxiliadora; Gutierrez-López, María Dolores; Guerri, Consuelo; Manzanares, Jorge; O'Shea, Esther; Colado, María Isabel

2017-07-01

Inflammatory cytokines and reactive oxygen species are reported to be involved in blood-brain barrier (BBB) disruption. Because there is evidence that ethanol (EtOH) induces release of free radicals, cytokines and inflammatory mediators we examined BBB integrity and matrix metalloproteinase (MMP) activity in postmortem human alcoholic brain and investigated the role of TLR4 signaling in BBB permeability in TLR4-knockout mice under a binge-like EtOH drinking protocol. Immunohistochemical studies showed reduced immunoreactivity of the basal lamina protein, collagen-IV and of the tight junction protein, claudin-5 in dorsolateral prefrontal cortex of alcoholics. There was also increased MMP-9 activity and expression of phosphorylated ERK1/2 and p-38. Greater number of CD45+ IR cells were observed associated with an enhanced neuroinflammatory response reflected by increased GFAP and Iba-1 immunostaining. To further explore effects of high EtOH consumption on BBB integrity we studied TLR4-knockout mice exposed to the drinking in the dark paradigm. Repetitive EtOH exposure in wild-type mice decreased hippocampal expression of laminin and collagen-IV and increased IgG immunoreactivity, indicating IgG extravasation. Western blot analysis also revealed increased MyD88 and p-ERK1/2 levels. None of these changes was observed in TLR4-knockout mice. Collectively, these findings indicate that chronic EtOH increases degradation of tight junctions and extracellular matrix in postmortem human brain and induces a neuroinflammatory response associated with activation of ERK1/2 and p-38 and greater MMP-9 activity. The EtOH-induced effects on BBB impairment are not evident in the hippocampus of TLR4-knockout mice, suggesting the involvement of TLR4 signaling in the underlying mechanism leading to BBB disruption in mice. © 2016 Society for the Study of Addiction.

A conserved BDNF, glutamate- and GABA-enriched gene module related to human depression identified by coexpression meta-analysis and DNA variant genome-wide association studies.

PubMed

Chang, Lun-Ching; Jamain, Stephane; Lin, Chien-Wei; Rujescu, Dan; Tseng, George C; Sibille, Etienne

2014-01-01

Large scale gene expression (transcriptome) analysis and genome-wide association studies (GWAS) for single nucleotide polymorphisms have generated a considerable amount of gene- and disease-related information, but heterogeneity and various sources of noise have limited the discovery of disease mechanisms. As systematic dataset integration is becoming essential, we developed methods and performed meta-clustering of gene coexpression links in 11 transcriptome studies from postmortem brains of human subjects with major depressive disorder (MDD) and non-psychiatric control subjects. We next sought enrichment in the top 50 meta-analyzed coexpression modules for genes otherwise identified by GWAS for various sets of disorders. One coexpression module of 88 genes was consistently and significantly associated with GWAS for MDD, other neuropsychiatric disorders and brain functions, and for medical illnesses with elevated clinical risk of depression, but not for other diseases. In support of the superior discriminative power of this novel approach, we observed no significant enrichment for GWAS-related genes in coexpression modules extracted from single studies or in meta-modules using gene expression data from non-psychiatric control subjects. Genes in the identified module encode proteins implicated in neuronal signaling and structure, including glutamate metabotropic receptors (GRM1, GRM7), GABA receptors (GABRA2, GABRA4), and neurotrophic and development-related proteins [BDNF, reelin (RELN), Ephrin receptors (EPHA3, EPHA5)]. These results are consistent with the current understanding of molecular mechanisms of MDD and provide a set of putative interacting molecular partners, potentially reflecting components of a functional module across cells and biological pathways that are synchronously recruited in MDD, other brain disorders and MDD-related illnesses. Collectively, this study demonstrates the importance of integrating transcriptome data, gene coexpression modules and GWAS results for providing novel and complementary approaches to investigate the molecular pathology of MDD and other complex brain disorders.

Relationship between water-holding capacity and protein denaturation in broiler breast meat.

PubMed

Bowker, B; Zhuang, H

2015-07-01

The objective of this study was to determine the relationship between water-holding capacity (WHC) attributes and protein denaturation in broiler breast meat. Boneless skinless breast fillets (n = 72) were collected from a commercial processing plant at 2 h postmortem and segregated into low-WHC and high-WHC groups based on muscle pH and color (L*a*b*). At 6 and 24 h postmortem, brine uptake (%), cooking loss (%), and protein solubility (sarcoplasmic and myofibrillar) were measured and protein fractions were analyzed using SDS-PAGE. Drip loss accumulation (%) was measured after storage for 2 and 7 days postmortem. High-WHC fillets exhibited lower L*-lightness values and greater pH values at 2 and 24 h postmortem than low-WHC fillets. High-WHC fillets had greater brine uptake and less cooking loss at both 6 and 24 h postmortem compared to low-WHC fillets. Aging from 6 to 24 h postmortem increased brine uptake in high-WHC fillets, but did not affect cooking loss in either low-WHC or high-WHC fillets. Drip loss accumulation was greater in low-WHC fillets at both 2 and 7 days postmortem. Myofibrillar protein solubility decreased with postmortem time but was not different between low-WHC and high-WHC fillets. Sarcoplasmic protein solubility increased with postmortem time and was greater in high-WHC fillets. SDS-PAGE analysis indicated that low-WHC fillets exhibited more glycogen phosphorylase denaturation than high-WHC fillets as evidenced by a more extensive shift of the protein from the sarcoplasmic to the myofibrillar protein fraction. Correlation analysis revealed that overall protein solubility measurements were not related to WHC attributes but that the degree of glycogen phosphorylase denaturation was significantly correlated (|r| = 0.52 to 0.80) to measures of WHC. Data indicated that WHC differences in broiler breast fillets were not due to differences in myofibrillar protein denaturation and suggested that the denaturation of sarcoplasmic proteins onto myofibrils may influence WHC in breast meat. © 2015 Poultry Science Association Inc.

Extracting the inclination angle of nerve fibers within the human brain with 3D-PLI independent of system properties

NASA Astrophysics Data System (ADS)

Reckfort, Julia; Wiese, Hendrik; Dohmen, Melanie; Grässel, David; Pietrzyk, Uwe; Zilles, Karl; Amunts, Katrin; Axer, Markus

2013-09-01

The neuroimaging technique 3D-polarized light imaging (3D-PLI) has opened up new avenues to study the complex nerve fiber architecture of the human brain at sub-millimeter spatial resolution. This polarimetry technique is applicable to histological sections of postmortem brains utilizing the birefringence of nerve fibers caused by the regular arrangement of lipids and proteins in the myelin sheaths surrounding axons. 3D-PLI provides a three-dimensional description of the anatomical wiring scheme defined by the in-section direction angle and the out-of-section inclination angle. To date, 3D-PLI is the only available method that allows bridging the microscopic and the macroscopic description of the fiber architecture of the human brain. Here we introduce a new approach to retrieve the inclination angle of the fibers independently of the properties of the used polarimeters. This is relevant because the image resolution and the signal transmission inuence the measured birefringent signal (retardation) significantly. The image resolution was determined using the USAF- 1951 testchart applying the Rayleigh criterion. The signal transmission was measured by elliptical polarizers applying the Michelson contrast and histological slices of the optic tract of a postmortem brain. Based on these results, a modified retardation-inclination transfer function was proposed to extract the fiber inclination. The comparison of the actual and the inclination angles calculated with the theoretically proposed and the modified transfer function revealed a significant improvement in the extraction of the fiber inclinations.

Synchrotron Study of Strontium in Modern and Ancient Human Bones

NASA Astrophysics Data System (ADS)

Pingitore, N. E.; Cruz-Jimenez, G.

2001-05-01

Archaeologists use the strontium in human bone to reconstruct diet and migration in ancient populations. Because mammals discriminate against strontium relative to calcium, carnivores show lower bone Sr/Ca ratios than herbivores. Thus, in a single population, bone Sr/Ca ratios can discriminate a meat-rich from a vegetarian diet. Also, the ratio of 87-Sr to 86-Sr in soils varies with the underlying geology; incorporated into the food chain, this local signature becomes embedded in our bones. The Sr isotopic ratio in the bones of individuals or populations which migrate to a different geologic terrane will gradually change as bone remodels. In contrast, the isotopic ratio of tooth enamel is fixed at an early age and is not altered later in life. Addition of Sr to bone during post-mortem residence in moist soil or sediment compromises application of the Sr/Ca or Sr-isotope techniques. If this post-mortem Sr resides in a different atomic environment than the Sr deposited in vivo, x-ray absorption spectroscopy could allow us to distinguish pristine from contaminated, and thus unreliable, samples. Initial examination of a suite of modern and ancient human and animal bones by extended x-ray absorption fine structure (EXAFS) showed no obvious differences between the fresh and buried materials. We note, with obvious concern, that the actual location of Sr in modern bone is controversial: there is evidence both that Sr substitutes for Ca and that Sr is sorbed on the surfaces of bone crystallites. Additional material is being studied.

Neuropathology of SUDEP: Role of inflammation, blood-brain barrier impairment, and hypoxia.

PubMed

Michalak, Zuzanna; Obari, Dima; Ellis, Matthew; Thom, Maria; Sisodiya, Sanjay M

2017-02-07

To seek a neuropathologic signature of sudden unexpected death in epilepsy (SUDEP) in a postmortem cohort by use of immunohistochemistry for specific markers of inflammation, gliosis, acute neuronal injury due to hypoxia, and blood-brain barrier (BBB) disruption, enabling the generation of hypotheses about potential mechanisms of death in SUDEP. Using immunohistochemistry, we investigated the expression of 6 markers (CD163, human leukocyte antigen-antigen D related, glial fibrillary acid protein, hypoxia-inducible factor-1α [HIF-1α], immunoglobulin G, and albumin) in the hippocampus, amygdala, and medulla in 58 postmortem cases: 28 SUDEP (definite and probable), 12 epilepsy controls, and 18 nonepileptic sudden death controls. A semiquantitative measure of immunoreactivity was scored for all markers used, and quantitative image analysis was carried out for selected markers. Immunoreactivity was observed for all markers used within all studied brain regions and groups. Immunoreactivity for inflammatory reaction, BBB leakage, and HIF-1α in SUDEP cases was not different from that seen in control groups. This study represents a starting point to explore by immunohistochemistry the mechanisms underlying SUDEP in human brain tissue. Our approach highlights the potential and importance of considering immunohistochemical analysis to help identify biomarkers of SUDEP. Our results suggest that with the markers used, there is no clear immunohistochemical signature of SUDEP in human brain. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Using single nuclei for RNA-seq to capture the transcriptome of postmortem neurons

PubMed Central

Krishnaswami, Suguna Rani; Grindberg, Rashel V; Novotny, Mark; Venepally, Pratap; Lacar, Benjamin; Bhutani, Kunal; Linker, Sara B; Pham, Son; Erwin, Jennifer A; Miller, Jeremy A; Hodge, Rebecca; McCarthy, James K; Kelder, Martin; McCorrison, Jamison; Aevermann, Brian D; Fuertes, Francisco Diez; Scheuermann, Richard H; Lee, Jun; Lein, Ed S; Schork, Nicholas; McConnell, Michael J; Gage, Fred H; Lasken, Roger S

2016-01-01

A protocol is described for sequencing the transcriptome of a cell nucleus. Nuclei are isolated from specimens and sorted by FACS, cDNA libraries are constructed and RNA-seq is performed, followed by data analysis. Some steps follow published methods (Smart-seq2 for cDNA synthesis and Nextera XT barcoded library preparation) and are not described in detail here. Previous single-cell approaches for RNA-seq from tissues include cell dissociation using protease treatment at 30 °C, which is known to alter the transcriptome. We isolate nuclei at 4 °C from tissue homogenates, which cause minimal damage. Nuclear transcriptomes can be obtained from postmortem human brain tissue stored at −80 °C, making brain archives accessible for RNA-seq from individual neurons. The method also allows investigation of biological features unique to nuclei, such as enrichment of certain transcripts and precursors of some noncoding RNAs. By following this procedure, it takes about 4 d to construct cDNA libraries that are ready for sequencing. PMID:26890679

Long-term continuous corticosterone treatment decreases VEGF receptor-2 expression in frontal cortex.

PubMed

Howell, Kristy R; Kutiyanawalla, Ammar; Pillai, Anilkumar

2011-01-01

Stress and increased glucocorticoid levels are associated with many neuropsychiatric disorders including schizophrenia and depression. Recently, the role of vascular endothelial factor receptor-2 (VEGFR2/Flk1) signaling has been implicated in stress-mediated neuroplasticity. However, the mechanism of regulation of VEGF/Flk1 signaling under long-term continuous glucocorticoid exposure has not been elucidated. We examined the possible effects of long-term continuous glucocorticoid exposure on VEGF/Flk1 signaling in cultured cortical neurons in vitro, mouse frontal cortex in vivo, and in post mortem human prefrontal cortex of both control and schizophrenia subjects. We found that long-term continuous exposure to corticosterone (CORT, a natural glucocorticoid) reduced Flk1 protein levels both in vitro and in vivo. CORT treatment resulted in alterations in signaling molecules downstream to Flk1 such as PTEN, Akt and mTOR. We demonstrated that CORT-induced changes in Flk1 levels are mediated through glucocorticoid receptor (GR) and calcium. A significant reduction in Flk1-GR interaction was observed following CORT exposure. Interestingly, VEGF levels were increased in cortex, but decreased in serum following CORT treatment. Moreover, significant reductions in Flk1 and GR protein levels were found in postmortem prefrontal cortex samples from schizophrenia subjects. The alterations in VEGF/Flk1 signaling following long-term continuous CORT exposure represents a molecular mechanism of the neurobiological effects of chronic stress.

Kinematic response of the spine during simulated aircraft ejections.

PubMed

Damon, Andrew M; Lessley, David J; Salzar, Robert S; Bass, Cameron R; Shen, Francis H; Paskoff, Glenn R; Shender, Barry S

2010-05-01

Military aviators are susceptible to spinal injuries during high-speed ejection scenarios. These injuries commonly arise as a result of strains induced by extreme flexion or compression of the spinal column. This study characterizes the vertebral motion of two postmortem human surrogates (PMHS) during a simulated catapult phase of ejection on a horizontal decelerator sled. During testing, the PMHS were restrained supinely to a mock ejection seat and subjected to a horizontal deceleration profile directed along the local z-axis. Two midsized males (175.3 cm, 77.1 kg; 185.4 cm, 72.6 kg) were tested. High-rate motion capture equipment was used to measure the three-dimensional displacement of the head, vertebrae, and pelvis during the ejection event. The two PMHS showed generally similar kinematic motion. Head injury criterion (HIC) results were well below injury threshold levels for both specimens. The specimens both showed compression of the spine, with a reduction in length of 23.9 mm and 45.7 mm. Post-test autopsies revealed fractures in the C5, T1, and L1 vertebrae. This paper provides an analysis of spinal motion during an aircraft ejection.The injuries observed in the test subjects were consistent with those seen in epidemiological studies. Future studies should examine the effects of gender, muscle tensing, out-of-position (of head from neutral position) occupants, and external forces (e.g., windblast) on spinal kinematics during aircraft ejection.

Location matters: distinct DNA methylation patterns in GABAergic interneuronal populations from separate microcircuits within the human hippocampus.

PubMed

Ruzicka, W Brad; Subburaju, Sivan; Coyle, Joseph T; Benes, Francine M

2018-01-15

Recent studies describe distinct DNA methylomes among phenotypic subclasses of neurons in the human brain, but variation in DNA methylation between common neuronal phenotypes distinguished by their function within distinct neural circuits remains an unexplored concept. Studies able to resolve epigenetic profiles at the level of microcircuits are needed to illuminate chromatin dynamics in the regulation of specific neuronal populations and circuits mediating normal and abnormal behaviors. The Illumina HumanMethylation450 BeadChip was used to assess genome-wide DNA methylation in stratum oriens GABAergic interneurons sampled by laser-microdissection from two discrete microcircuits along the trisynaptic pathway in postmortem human hippocampus from eight control, eight schizophrenia, and eight bipolar disorder subjects. Data were analysed using the minfi Bioconductor package in R software version 3.3.2. We identified 11 highly significant differentially methylated regions associated with a group of genes with high construct-validity, including multiple zinc finger of the cerebellum gene family members and WNT signaling factors. Genomic locations of differentially methylated regions were highly similar between diagnostic categories, with a greater number of differentially methylated individual cytosine residues between circuit locations in bipolar disorder cases than in schizophrenia or control (42, 7, and 7 differentially methylated positions, respectively). These findings identify distinct DNA methylomes among phenotypically similar populations of GABAergic interneurons functioning within separate hippocampal subfields. These data compliment recent studies describing diverse epigenotypes among separate neuronal subclasses, extending this concept to distinct epigenotypes within similar neuronal phenotypes from separate microcircuits within the human brain. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Postmortem computed tomography and magnetic resonance imaging facilitates forensic autopsy in a fatal case of poisoning with formic acid, diphenhydramine, and ethanol.

PubMed

Berger, Florian; Steuer, Andrea E; Rentsch, Katharina; Gascho, Dominic; Stamou, Stamatios; Schärli, Sarah; Thali, Michael J; Krämer, Thomas; Flach, Patricia M

2016-09-01

A case of fatal poisoning by ingesting formic acid, diphenhydramine, and ethanol by a 25-year-old woman who committed suicide is presented. Prior to autopsy, postmortem computed tomography and postmortem magnetic resonance tomography were performed and revealed severe damage to the stomach, the left thoracic wall, and parts of the liver. Imaging detected acid-induced fluid-fluid level within the thoracic cavity (fat-equivalent fluid and necrotic pleural effusion). This case report illustrates that postmortem cross-sectional imaging may facilitate dissection of severely damaged or complex regions, and may provide additional information compared to autopsy and toxicological examinations alone.

Phosphofructokinase and mitochondria partially explain the high ultimate pH of broiler pectoralis major muscle.

PubMed

Matarneh, Sulaiman K; Yen, Con-Ning; Elgin, Jennifer M; Beline, Mariane; da Luz E Silva, Saulo; Wicks, Jordan C; England, Eric M; Dalloul, Rami A; Persia, Michael E; Omara, Islam I; Shi, Hao; Gerrard, David E

2018-05-01

During postmortem metabolism, muscle pH gradually declines to reach an ultimate pH near 5.6 across most meat species. Yet, broiler pectoralis major (P. major) muscle generates meat with high ultimate pH (pH ∼ 5.9). For better understanding of the underlying mechanism responsible for this phenomenon, we evaluated the involvement of breast muscle chilling on the extent of postmortem metabolism. Broiler breast muscles were either subjected to chilling treatment (control) or left at room temperature (RT) for 120 min. P. major muscle from the RT treatment had lower ultimate pH, greater glycogen degradation and lactate accumulation. While these findings suggest that carcass chilling can contribute to the premature termination of postmortem metabolism, chilling did not fully explain the high ultimate pH of P. major muscle. Our results also revealed that glucose-6-phosphate (G6P) was very low at 24 h, and therefore we hypothesized that G6P was limiting. To test this hypothesis, muscle samples from P. major and porcine longissimus lumborum (LL) muscle were homogenized into a reaction buffer that mimics postmortem glycolysis with or without 0.5 mg/mL isolated mitochondria. While samples containing porcine LL muscle reached the normal level of ultimate pH, P. major muscle samples reached a value similar to that observed in vivo even in the presence of excess G6P, indicating that G6P was not limiting. Mitochondria enhanced the glycolytic flux and pH decline in systems containing muscle from both species. More importantly, however, was that in vitro system containing chicken with mitochondria reached pH value similar to that of samples containing LL muscle without mitochondria. To investigate further, phosphofructokinase (PFK) activity was compared in broiler P. major and porcine LL muscle at different pH values. PFK activity was lower in P. major muscle at pH 7, 6.5, and 6.2 than LL muscle. In conclusion, carcass chilling can partially contribute to the high ultimate pH of broiler P. major muscle, while low PFK activity and mitochondria content limit the flux through glycolysis.

United States Transuranium and Uranium Registries

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kathren, R.L.; Filipy, R.E.; Dietert, S.E.

1991-06-01

This report summarizes the primary scientific activities of the United States Transuranium and Uranium Registries for the period October 1, 1989 through September 30, 1990. The Registries are parallel human tissue research programs devoted to the study of the actinide elements in humans. To date there have been 261 autopsy or surgical specimen donations, which include 11 whole bodies. The emphasis of the Registry was directed towards quality improvement and the development of a fully computerized data base that would incorporate not only the results of postmortem radiochemical analysis, but also medical and monitoring information obtained during life. Human subjectsmore » reviews were also completed. A three compartment biokinetic model for plutonium distribution is proposed. 2 tabs.« less

Association of a History of Child Abuse With Impaired Myelination in the Anterior Cingulate Cortex: Convergent Epigenetic, Transcriptional, and Morphological Evidence.

PubMed

Lutz, Pierre-Eric; Tanti, Arnaud; Gasecka, Alicja; Barnett-Burns, Sarah; Kim, John J; Zhou, Yi; Chen, Gang G; Wakid, Marina; Shaw, Meghan; Almeida, Daniel; Chay, Marc-Aurele; Yang, Jennie; Larivière, Vanessa; M'Boutchou, Marie-Noël; van Kempen, Léon C; Yerko, Volodymyr; Prud'homme, Josée; Davoli, Maria Antonietta; Vaillancourt, Kathryn; Théroux, Jean-François; Bramoullé, Alexandre; Zhang, Tie-Yuan; Meaney, Michael J; Ernst, Carl; Côté, Daniel; Mechawar, Naguib; Turecki, Gustavo

2017-12-01

Child abuse has devastating and long-lasting consequences, considerably increasing the lifetime risk of negative mental health outcomes such as depression and suicide. Yet the neurobiological processes underlying this heightened vulnerability remain poorly understood. The authors investigated the hypothesis that epigenetic, transcriptomic, and cellular adaptations may occur in the anterior cingulate cortex as a function of child abuse. Postmortem brain samples from human subjects (N=78) and from a rodent model of the impact of early-life environment (N=24) were analyzed. The human samples were from depressed individuals who died by suicide, with (N=27) or without (N=25) a history of severe child abuse, as well as from psychiatrically healthy control subjects (N=26). Genome-wide DNA methylation and gene expression were investigated using reduced representation bisulfite sequencing and RNA sequencing, respectively. Cell type-specific validation of differentially methylated loci was performed after fluorescence-activated cell sorting of oligodendrocyte and neuronal nuclei. Differential gene expression was validated using NanoString technology. Finally, oligodendrocytes and myelinated axons were analyzed using stereology and coherent anti-Stokes Raman scattering microscopy. A history of child abuse was associated with cell type-specific changes in DNA methylation of oligodendrocyte genes and a global impairment of the myelin-related transcriptional program. These effects were absent in the depressed suicide completers with no history of child abuse, and they were strongly correlated with myelin gene expression changes observed in the animal model. Furthermore, a selective and significant reduction in the thickness of myelin sheaths around small-diameter axons was observed in individuals with history of child abuse. The results suggest that child abuse, in part through epigenetic reprogramming of oligodendrocytes, may lastingly disrupt cortical myelination, a fundamental feature of cerebral connectivity.

Detection of the source of hemorrhage using postmortem computerized tomographic angiography in a case of a giant juvenile nasopharyngeal angiofibroma after surgical treatment.

PubMed

do Nascimento, Felipe Barjud Pereira; dos Santos, Glaucia Aparecida Bento; Melo, Nelson Almeida d'Ávila; Damasceno, Eduarda Bittencourt; Mauad, Thais

2015-09-01

Postmortem computerized tomographic angiography (PMCTA) has been increasingly used in forensic medicine to detect and locate the source of bleeding in cases of fatal acute hemorrhage. In this paper, we report a case of postoperative complication in a patient with a giant juvenile nasopharyngeal angiofibroma in which the source of bleeding was detected by PMCTA. A case description and evaluations of the pre- and postoperative exams, postmortem CT angiogram, and conventional autopsy results are provided. The source of bleeding was identified by postmortem CT angiography but not by conventional autopsy. The established protocol, injecting contrast medium into the femoral artery, was effective in identifying the source of bleeding. Postoperative bleeding is a rare and frequently fatal complication of juvenile nasopharyngeal angiofibroma. As a complement to conventional autopsy, postmortem angiography is a valuable tool for the detection of lethal acute hemorrhagic foci, and establishing a routine procedure for PMCTA may improve its efficiency.

Crack propagation in teeth: a comparison of perimortem and postmortem behavior of dental materials and cracks.

PubMed

Hughes, Cris E; White, Crystal A

2009-03-01

This study presents a new method for understanding postmortem heat-induced crack propagation patterns in teeth. The results demonstrate that patterns of postmortem heat-induced crack propagation differ from perimortem and antemortem trauma-induced crack propagation patterns. Dental material of the postmortem tooth undergoes dehydration leading to a shrinking and more brittle dentin material and a weaker dentin-enamel junction. Dentin intertubule tensile stresses are amplified by the presence of the pulp cavity, and initiates crack propagation from the internal dentin, through the dentin-enamel junction and lastly the enamel. In contrast, in vivo perimortem and antemortem trauma-induced crack propagation initiates cracking from the external surface of the enamel toward the dentin-enamel junction where the majority of the energy of the crack is dissipated, eliminating the crack's progress into the dentin. These unique patterns of crack propagation can be used to differentiate postmortem taphonomy-induced damage from antemortem and perimortem trauma in teeth.

Measurement of Postmortem Pupil Size: A New Method with Excellent Reliability and Its Application to Pupil Changes in the Early Postmortem Period.

PubMed

Fleischer, Luise; Sehner, Susanne; Gehl, Axel; Riemer, Martin; Raupach, Tobias; Anders, Sven

2017-05-01

Measurement of postmortem pupil width is a potential component of death time estimation. However, no standardized measurement method has been described. We analyzed a total of 71 digital images for pupil-iris ratio using the software ImageJ. Images were analyzed three times by four different examiners. In addition, serial images from 10 cases were taken between 2 and 50 h postmortem to detect spontaneous pupil changes. Intra- and inter-rater reliability of the method was excellent (ICC > 0.95). The method is observer independent and yields consistent results, and images can be digitally stored and re-evaluated. The method seems highly eligible for forensic and scientific purposes. While statistical analysis of spontaneous pupil changes revealed a significant polynomial of quartic degree for postmortem time (p = 0.001), an obvious pattern was not detected. These results do not indicate suitability of spontaneous pupil changes for forensic death time estimation, as formerly suggested. © 2016 American Academy of Forensic Sciences.

Fatal fentanyl patch misuse in a hospitalized patient with a postmortem increase in fentanyl blood concentration.

PubMed

Moore, Philip W; Palmer, Robert B; Donovan, Joseph Ward

2015-01-01

Opioid-related mortality happens, even in healthcare settings. We describe serial postmortem fentanyl blood concentrations in a hospital inpatient who fatally abused transdermal fentanyl. This is a single-patient case report. A 42-year-old man with lymphoma was started on transdermal fentanyl therapy while hospitalized for chronic abdominal pain. The patient was last seen awake 1.3 h prior to being found apneic and cyanotic. During the resuscitation attempt, a small square-shaped film was removed from the patient's oropharynx. Femoral blood was collected 0.5 and 2 h postmortem, and the measured fentanyl concentration increased from 1.6 to 14 ng/mL. Study limitations include potential laboratory or collection errors and missing data. (i) Providers must be vigilant for signs of fentanyl patch abuse. (ii) Postmortem blood concentrations are not static postmortem, likely secondary to decreasing pH, increased aqueous solubility, and tissue redistribution, and are therefore unlikely to accurately represent antemortem blood concentrations. © 2014 American Academy of Forensic Sciences.

Gastrointestinal Functionality of Aquatic Animal (Oreochromis niloticus) Carcass in Water Allows Estimating Time of Death.

PubMed

Hahor, Waraporn; Thongprajukaew, Karun; Yoonram, Krueawan; Rodjaroen, Somrak

2016-11-01

Postmortem changes have been previously studied in some terrestrial animal models, but no prior information is available on aquatic species. Gastrointestinal functionality was investigated in terms of indices, protein concentration, digestive enzyme activity, and scavenging activity, in an aquatic animal model, Nile tilapia, to assess the postmortem changes. Dead fish were floated indoors, and samples were collected within 48 h after death. Stomasomatic index decreased with postmortem time and correlated positively with protein, pepsin-specific activity, and stomach scavenging activity. Also intestosomatic index decreased significantly and correlated positively with protein, specific activity of trypsin, chymotrypsin, amylase, lipase, and intestinal scavenging activity. In their postmortem changes, the digestive enzymes exhibited earlier lipid degradation than carbohydrate or protein. The intestine changed more rapidly than the stomach. The findings suggest that the postmortem changes of gastrointestinal functionality can serve as primary data for the estimation of time of death of an aquatic animal. © 2016 American Academy of Forensic Sciences.

Postmortem Concentrations of Tramadol and O-Desmethyltramadol in 11 Aviation Accident Fatalities

DTIC Science & Technology

2010-12-01

Crump University of Central Oklahoma Edmond, OK 73034 December 2010 Final Report Postmortem Concentrations of Tramadol and O-Desmethyltramadol in...Subtitle 5. Report Date Postmortem Concentrations of Tramadol and O-Desmethyltramadol in 11 Aviation Accident Fatalities December 2010 6. Performing...This work was accomplished under the approved task AM-B-10-TOX-204. 16. Abstract Tramadol is a centrally acting analgesic used to treat moderate

Postmortem computed tomography findings in suicide victims.

PubMed

Garetier, M; Deloire, L; Dédouit, F; Dumousset, E; Saccardy, C; Ben Salem, D

2017-02-01

Suicide is the eighth cause of mortality in France and the leading cause in people aged between 25 and 34 years. The most common methods of suicide are hanging, self-poisoning with medicines and firearms. Postmortem computed tomography (CT) is a useful adjunct to autopsy to confirm suicide and exclude other causes of death. At autopsy, fractures of the hyoid bone or thyroid cartilage, or both, are found in more than 50% of suicidal hangings. Cervical vertebra fractures are rare and only seen in suicide victims jumping from a great height. Three-dimensional reconstructions from CT data are useful to visualize the ligature mark on the neck. In suicides by firearm, postmortem CT shows entry and exit wounds, parenchymal lesions along the bullet path, as well as projectiles in case of penetrating trauma. However, in the chest and abdomen it is more difficult to identify the path of the projectile. Postmortem CT also shows specific features of suicide by drowning or stabbing, but its use is limited in cases of self-poisoning. The use of postmortem CT is also limited by decomposition and change of body position. This article presents the imaging features seen on postmortem CT according to the method of suicide. Copyright © 2016 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.

Influence of porcine circovirus type 2 vaccination on the probability and severity of pneumonia detected postmortem.

PubMed

Raith, J; Kuchling, S; Schleicher, C; Schobesberger, H; Köfer, J

2015-01-31

To evaluate the influence of porcine circovirus type 2 vaccination (PCV-2) on the probability and severity of pneumonia, postmortem findings of 247,505 pigs slaughtered between 2008 and 2011 were analysed by applying a cumulative link mixed model. Three major effects could be observed: (1) PCV-2 vaccination significantly (P<0.01) reduced the odds (coefficient: -0.05) of postmortem findings of mild, moderate and severe pneumonia for vaccinated pigs. (2) Pigs from fattening farms were less likely (coefficient: -0.44; P<0.05) to exhibit signs of pneumonia at slaughter than pigs from farrow-to-finish farms. (3) When vaccinated, the odds of detecting postmortem signs showed an even more pronounced reduction (coefficient: -0.19; P<0.001) for pigs from fattening farms. Combining PCV-2 vaccination, farm type and interaction effects between these two factors, a pig vaccinated against PCV-2 from a fattening farm had only half the chance (OR 0.51) of pneumonia being detected at postmortem than a non-vaccinated pig from a farrow-to-finish farm. The study demonstrates the benefit of a vaccination programme against PCV-2 as an important tool to reduce the risk of postmortem pneumonia findings and the severity of pneumonia in pigs at slaughter. British Veterinary Association.

Influence of porcine circovirus type 2 vaccination on the probability and severity of pneumonia detected postmortem

PubMed Central

Raith, J.; Kuchling, S.; Schleicher, C.; Schobesberger, H.; Köfer, J.

2015-01-01

To evaluate the influence of porcine circovirus type 2 vaccination (PCV-2) on the probability and severity of pneumonia, postmortem findings of 247,505 pigs slaughtered between 2008 and 2011 were analysed by applying a cumulative link mixed model. Three major effects could be observed: (1) PCV-2 vaccination significantly (P<0.01) reduced the odds (coefficient: −0.05) of postmortem findings of mild, moderate and severe pneumonia for vaccinated pigs. (2) Pigs from fattening farms were less likely (coefficient: −0.44; P<0.05) to exhibit signs of pneumonia at slaughter than pigs from farrow-to-finish farms. (3) When vaccinated, the odds of detecting postmortem signs showed an even more pronounced reduction (coefficient: −0.19; P<0.001) for pigs from fattening farms. Combining PCV-2 vaccination, farm type and interaction effects between these two factors, a pig vaccinated against PCV-2 from a fattening farm had only half the chance (OR 0.51) of pneumonia being detected at postmortem than a non-vaccinated pig from a farrow-to-finish farm. The study demonstrates the benefit of a vaccination programme against PCV-2 as an important tool to reduce the risk of postmortem pneumonia findings and the severity of pneumonia in pigs at slaughter. PMID:25413158

Postmortem eyefluid analysis in dogs, cats and cattle as an estimate of antemortem serum chemistry profiles.

PubMed Central

Hanna, P E; Bellamy, J E; Donald, A

1990-01-01

This study was carried out to determine the diagnostic usefulness of postmortem eyefluid analysis in estimating antemortem concentrations of serochemical constituents. A total of 31 cattle, 18 dogs and 22 cats were selected from routine elective euthanasia submissions to a diagnostic laboratory. For all cases, a biochemical profile, including determinations for electrolytes, glucose, urea, creatinine, enzymes, cholesterol, bilirubin, protein and osmolality was performed on antemortem serum, and postmortem aqueous and vitreous humors at 0 and 24 h incubation periods. The association between serum and postmortem eyefluid chemistry values was examined using simple linear regression. A strong correlation between serum and postmortem eyefluid urea and creatinine concentrations was demonstrated in the three species examined over a 24 h postmortem interval. We concluded that an accurate estimate of antemortem serum urea or creatinine can be made from the analysis of aqueous or vitreous fluid at necropsy. An estimation of antemortem serum electrolytes (including calcium in cattle) cannot be made with a high degree of accuracy due to the amount of variability in the relationship between serum and eyefluid electrolyte values. For large molecules such as proteins, enzymes, cholesterol and bilirubin there was very poor correlation between serum and eyefluid values. PMID:2249181

Reliability of postmortem fentanyl concentrations in determining the cause of death.

PubMed

Gill, James R; Lin, Peter T; Nelson, Lewis

2013-03-01

Transdermal fentanyl, an opioid used for management of marked pain, also is abused and may cause death. We reviewed medical examiner reports of 92 decedents who had one or more fentanyl transdermal patches on their body and had fentanyl detected in their postmortem toxicology analysis. The manners of death included 40 accidents, 36 natural, 8 suicides, 5 therapeutic complications, and 3 undetermined deaths. Among the accidental fentanyl intoxication deaths, 32 of 37 involved substance abuse. The majority (95 %) of the 37 accidental deaths involving fentanyl were multi-drug intoxications. The substance abuse deaths had a mean fentanyl blood concentration (26.4 ng/ml or μg/L) that was over twice that of the natural group (11.8 ng/ml). Our analysis suggests a relationship between total patch dosage and mean postmortem fentanyl concentration up to the 100-μg/h dose. The very wide and overlapping ranges of postmortem fentanyl concentrations effectively nullify the utility of correlating the dose and expected postmortem concentration for any particular death. Based on the variable relationship between dose and blood concentration, the antemortem dose cannot be reliably predicted based on the postmortem concentration. This does not, however, render the medical examiner/coroner unable to determine the cause and manner of death because the toxicology results are only one datum point among several that are considered. Although there was a weakly positive relationship between body mass index and fentanyl concentration, further research is needed to determine whether adipose tissue represents a significant depot for postmortem release of fentanyl.

Expression of Immune Genes on Chromosome 6p21.3-22.1 in Schizophrenia

PubMed Central

Sinkus, Melissa L.; Adams, Catherine E.; Logel, Judith; Freedman, Robert; Leonard, Sherry

2013-01-01

Schizophrenia is a common mental illness with a large genetic component. Three genome-wide association studies have implicated the major histocompatibility complex gene region on chromosome 6p21.3-22.1 in schizophrenia. In addition, nicotine, which is commonly abused in schizophrenia, affects the expression of central nervous system immune genes. Messenger RNA levels for genes in the 6p21.3-22.1 region were measured in human postmortem hippocampus of 89 subjects. The effects of schizophrenia diagnosis, smoking and systemic inflammatory illness were compared. Cell-specific expression patterns for the class I major histocompatibility complex gene HLA-A were explored utilizing in situ hybridization. Expression of five genes was altered in schizophrenic subjects. Messenger RNA levels for the class I major histocompatibility complex antigen HLA-B were increased in schizophrenic nonsmokers, while levels for smokers were indistinguishable from those of controls. β2 microglobulin, HLA-A and Notch4 were all expressed in a pattern where inflammatory illness was associated with increased expression in controls but not in subjects with schizophrenia. Schizophrenia was also associated with increased expression of Butyrophilin 2A2. HLA-A was expressed in glutamatergic and GABAergic neurons in the dentate gyrus, hilus, and the stratum pyramidale of the CA1-CA4 regions of the hippocampus, but not in astrocytes. In conclusion, the expression of genes from the major histocompatibility complex region of chromosome 6 with likely roles in synaptic development is altered in schizophrenia. There were also significant interactions between schizophrenia diagnosis and both inflammatory illness and smoking. PMID:23395714

Developmental timeframes for induction of microgyria and rapid auditory processing deficits in the rat.

PubMed

Threlkeld, Steven W; McClure, Melissa M; Rosen, Glenn D; Fitch, R Holly

2006-09-13

Induction of a focal freeze lesion to the skullcap of a 1-day-old rat pup leads to the formation of microgyria similar to those identified postmortem in human dyslexics. Rats with microgyria exhibit rapid auditory processing deficits similar to those seen in language-impaired (LI) children, and infants at risk for LI and these effects are particularly marked in juvenile as compared to adult subjects. In the current study, a startle response paradigm was used to investigate gap detection in juvenile and adult rats that received bilateral freezing lesions or sham surgery on postnatal day (P) 1, 3 or 5. Microgyria were confirmed in P1 and 3 lesion rats, but not in the P5 lesion group. We found a significant reduction in brain weight and neocortical volume in P1 and 3 lesioned brains relative to shams. Juvenile (P27-39) behavioral data indicated significant rapid auditory processing deficits in all three lesion groups as compared to sham subjects, while adult (P60+) data revealed a persistent disparity only between P1-lesioned rats and shams. Combined results suggest that generalized pathology affecting neocortical development is responsible for the presence of rapid auditory processing deficits, rather than factors specific to the formation of microgyria per se. Finally, results show that the window for the induction of rapid auditory processing deficits through disruption of neurodevelopment appears to extend beyond the endpoint for cortical neuronal migration, although, the persistent deficits exhibited by P1 lesion subjects suggest a secondary neurodevelopmental window at the time of cortical neuromigration representing a peak period of vulnerability.

Evaluation of distribution of adenosine A2A receptors in normal human brain measured with [11C]TMSX PET.

PubMed

Mishina, Masahiro; Ishiwata, Kiichi; Kimura, Yuichi; Naganawa, Mika; Oda, Keiichi; Kobayashi, Shiro; Katayama, Yasuo; Ishii, Kenji

2007-09-01

Adenosine A(2A) receptor (A2AR) is thought to interact with dopamine D(2) receptor. Selective A2AR antagonists have attracted attention as the treatment of Parkinson's disease. In this study, we investigated the distribution of the A2ARs in the living human brain using positron emission tomography (PET) and [7-methyl-(11)C]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine ([(11)C]TMSX). We recruited five normal male subjects. A dynamic series of PET scans was performed for 60 min, and the arterial blood was sampled during the scan to measure radioactivity of the parent compound and labeled metabolites. Circular regions of interest of 10-mm diameter were placed in the PET images over the cerebellum, brainstem, thalamus, head of caudate nucleus, anterior and posterior putamen, frontal lobe, temporal lobe, parietal lobe, occipital lobe, and posterior cingulate gyrus for each subject. A two-tissue, three-compartment model was used to estimate K(1), k(2), k(3), and k(4) between metabolite-corrected plasma and tissue time activity of [(11)C]TMSX. The binding potential (BP) was the largest in the anterior (1.25) and posterior putamen (1.20), was next largest in the head of caudate nucleus (1.05) and thalamus (1.03), and was small in the cerebral cortex, especially frontal lobe (0.46). [(11)C]TMSX PET showed the largest BP in the striatum in which A2ARs were enriched as in postmortem and nonhuman studies reported, but that the binding of [(11)C]TMSX was relatively larger in the thalamus to compare with other mammals. To date, [(11)C]TMSX is the only promising PET ligand, which is available to clinical use for mapping the A2ARs in the living human brain.

Evaluation of biofidelity of THUMS pedestrian model under a whole-body impact conditions with a generic sedan buck.

PubMed

Wu, Taotao; Kim, Taewung; Bollapragada, Varun; Poulard, David; Chen, Huipeng; Panzer, Matthew B; Forman, Jason L; Crandall, Jeff R; Pipkorn, Bengt

2017-05-29

The goal of this study was to evaluate the biofidelity of the Total Human Model for Safety (THUMS; Ver. 4.01) pedestrian finite element models (PFEM) in a whole-body pedestrian impact condition using a well-characterized generic pedestrian buck model. The biofidelity of THUMS PFEM was evaluated with respect to data from 3 full-scale postmortem human subject (PMHS) pedestrian impact tests, in which a pedestrian buck laterally struck the subjects using a pedestrian buck at 40 km/h. The pedestrian model was scaled to match the anthropometry of the target subjects and then positioned to match the pre-impact postures of the target subjects based on the 3-dimensional motion tracking data obtained during the experiments. An objective rating method was employed to quantitatively evaluate the correlation between the responses of the models and the PMHS. Injuries in the models were predicted both probabilistically and deterministically using empirical injury risk functions and strain measures, respectively, and compared with those of the target PMHS. In general, the model exhibited biofidelic kinematic responses (in the Y-Z plane) regarding trajectories (International Organization for Standardization [ISO] ratings: Y = 0.90 ± 0.11, Z = 0.89 ± 0.09), linear resultant velocities (ISO ratings: 0.83 ± 0.07), accelerations (ISO ratings: Y = 0.58 ± 0.11, Z = 0.52 ± 0.12), and angular velocities (ISO ratings: X = 0.48 ± 0.13) but exhibited stiffer leg responses and delayed head responses compared to those of the PMHS. This indicates potential biofidelity issues with the PFEM for regions below the knee and in the neck. The model also demonstrated comparable reaction forces at the buck front-end regions to those from the PMHS tests. The PFEM generally predicted the injuries that the PMHS sustained but overestimated injuries in the ankle and leg regions. Based on the data considered, the THUMS PFEM was considered to be biofidelic for this pedestrian impact condition and vehicle. Given the capability of the model to reproduce biomechanical responses, it shows potential as a valuable tool for developing novel pedestrian safety systems.

Rasd2 Modulates Prefronto-Striatal Phenotypes in Humans and ‘Schizophrenia-Like Behaviors' in Mice

PubMed Central

Vitucci, Daniela; Di Giorgio, Annabella; Napolitano, Francesco; Pelosi, Barbara; Blasi, Giuseppe; Errico, Francesco; Attrotto, Maria Teresa; Gelao, Barbara; Fazio, Leonardo; Taurisano, Paolo; Di Maio, Anna; Marsili, Valentina; Pasqualetti, Massimo; Bertolino, Alessandro; Usiello, Alessandro

2016-01-01

Rasd2 is a thyroid hormone target gene, which encodes for a GTP-binding protein enriched in the striatum where, among other functions, it modulates dopaminergic neurotransmission. Here we report that human RASD2 mRNA is abundant in putamen, but it also occurs in the cerebral cortex, with a distinctive expression pattern that differs from that present in rodents. Consistent with its localization, we found that a genetic variation in RASD2 (rs6518956) affects postmortem prefrontal mRNA expression in healthy humans and is associated with phenotypes of relevance to schizophrenia, including prefrontal and striatal grey matter volume and physiology during working memory, as measured with magnetic resonance imaging. Interestingly, quantitative real-time PCR analysis indicated that RASD2 mRNA is slightly reduced in postmortem prefrontal cortex of patients with schizophrenia. In the attempt to uncover the neurobiological substrates associated with Rasd2 activity, we used knockout mice to analyze the in vivo influence of this G-protein on the prepulse inhibition of the startle response and psychotomimetic drug-related behavioral response. Data showed that Rasd2 mutants display deficits in basal prepulse inhibition that, in turn, exacerbate gating disruption under psychotomimetic drug challenge. Furthermore, we documented that lack of Rasd2 strikingly enhances the behavioral sensitivity to motor stimulation elicited by amphetamine and phencyclidine. Based on animal model data, along with the finding that RASD2 influences prefronto-striatal phenotypes in healthy humans, we suggest that genetic mutation or reduced levels of this G-protein might have a role in cerebral circuitry dysfunction underpinning exaggerated psychotomimetic drugs responses and development of specific biological phenotypes linked to schizophrenia. PMID:26228524

Rasd2 Modulates Prefronto-Striatal Phenotypes in Humans and 'Schizophrenia-Like Behaviors' in Mice.

PubMed

Vitucci, Daniela; Di Giorgio, Annabella; Napolitano, Francesco; Pelosi, Barbara; Blasi, Giuseppe; Errico, Francesco; Attrotto, Maria Teresa; Gelao, Barbara; Fazio, Leonardo; Taurisano, Paolo; Di Maio, Anna; Marsili, Valentina; Pasqualetti, Massimo; Bertolino, Alessandro; Usiello, Alessandro

2016-02-01

Rasd2 is a thyroid hormone target gene, which encodes for a GTP-binding protein enriched in the striatum where, among other functions, it modulates dopaminergic neurotransmission. Here we report that human RASD2 mRNA is abundant in putamen, but it also occurs in the cerebral cortex, with a distinctive expression pattern that differs from that present in rodents. Consistent with its localization, we found that a genetic variation in RASD2 (rs6518956) affects postmortem prefrontal mRNA expression in healthy humans and is associated with phenotypes of relevance to schizophrenia, including prefrontal and striatal grey matter volume and physiology during working memory, as measured with magnetic resonance imaging. Interestingly, quantitative real-time PCR analysis indicated that RASD2 mRNA is slightly reduced in postmortem prefrontal cortex of patients with schizophrenia. In the attempt to uncover the neurobiological substrates associated with Rasd2 activity, we used knockout mice to analyze the in vivo influence of this G-protein on the prepulse inhibition of the startle response and psychotomimetic drug-related behavioral response. Data showed that Rasd2 mutants display deficits in basal prepulse inhibition that, in turn, exacerbate gating disruption under psychotomimetic drug challenge. Furthermore, we documented that lack of Rasd2 strikingly enhances the behavioral sensitivity to motor stimulation elicited by amphetamine and phencyclidine. Based on animal model data, along with the finding that RASD2 influences prefronto-striatal phenotypes in healthy humans, we suggest that genetic mutation or reduced levels of this G-protein might have a role in cerebral circuitry dysfunction underpinning exaggerated psychotomimetic drugs responses and development of specific biological phenotypes linked to schizophrenia.

γ-secretase binding sites in aged and Alzheimer's disease human cerebrum: the choroid plexus as a putative origin of CSF Aβ.

PubMed

Liu, Fei; Xue, Zhi-Qin; Deng, Si-Hao; Kun, Xiong; Luo, Xue-Gang; Patrylo, Peter R; Rose, Gregory M; Cai, Huaibin; Struble, Robert G; Cai, Yan; Yan, Xiao-Xin

2013-05-01

Deposition of β -amyloid (Aβ) peptides, cleavage products of β-amyloid precursor protein (APP) by β-secretase-1 (BACE1) and γ-secretase, is a neuropathological hallmark of Alzheimer's disease (AD). γ-Secretase inhibition is a therapeutical anti-Aβ approach, although changes in the enzyme's activity in AD brain are unclear. Cerebrospinal fluid (CSF) Aβ peptides are thought to derive from brain parenchyma and thus may serve as biomarkers for assessing cerebral amyloidosis and anti-Aβ efficacy. The present study compared active γ-secretase binding sites with Aβ deposition in aged and AD human cerebrum, and explored the possibility of Aβ production and secretion by the choroid plexus (CP). The specific binding density of [(3) H]-L-685,458, a radiolabeled high-affinity γ-secretase inhibitor, in the temporal neocortex and hippocampal formation was similar for AD and control cases with similar ages and post-mortem delays. The CP in post-mortem samples exhibited exceptionally high [(3) H]-L-685,458 binding density, with the estimated maximal binding sites (Bmax) reduced in the AD relative to control groups. Surgically resected human CP exhibited APP, BACE1 and presenilin-1 immunoreactivity, and β-site APP cleavage enzymatic activity. In primary culture, human CP cells also expressed these amyloidogenic proteins and released Aβ40 and Aβ42 into the medium. Overall, our results suggest that γ-secretase activity appears unaltered in the cerebrum in AD and is not correlated with regional amyloid plaque pathology. The CP appears to be a previously unrecognised non-neuronal contributor to CSF Aβ, probably at reduced levels in AD. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

γ-Secretase binding sites in aged and Alzheimer’s disease human cerebrum: The choroid plexus as a putative origin of CSF Aβ

PubMed Central

Liu, Fei; Xue, Zhi-Qin; Deng, Si-Hao; Kun, Xiong; Luo, Xue-Gang; Patrylo, Peter R.; Rose, Gregory M.; Cai, Huaibin; Struble, Robert G.; Cai, Yan; Yan, Xiao-Xin

2013-01-01

Deposition of β-amyloid (Aβ) peptides, cleavage products of β-amyloid precursor protein (APP) by β-secretase-1 (BACE1) and γ-secretase, is a neuropathological hallmark of Alzheimer’s disease (AD). γ-Secretase inhibition is a therapeutical anti-Aβ approach, although less is clear about the change of the enzyme’s activity in AD brain. Cerebrospinal fluid (CSF) Aβ peptides are considered to derive from brain parenchyma, thus may serve as biomarkers for assessing cerebral amyloidosis and anti-Aβ efficacy. The present study compared active γ-secretase binding sites with Aβ deposition in aged and AD human cerebrum, and explored a possibility of Aβ production and secretion by the choroid plexus (CP). Specific binding density of [3H]-L-685,458, a radiolabeled high affinity γ-secretase inhibitor, in the temporal neocortex and hippocampal formation was similar for AD and control cases with comparable ages and postmortem delays. The CP in postmortem samples exhibited exceptionally high [3H]-L-685,458 binding density, with the estimated maximal binding sites (Bmax) reduced in the AD relative to control groups. Surgically resected human CP exhibited APP, BACE1 and presenilin-1 immunoreactivity, and β-site APP cleavage enzymatic activity. In primary culture, human CP cells also expressed these amyloidogenic proteins but released Aβ40 and Aβ42 into the medium. These results suggest that γ-secretase activity appears not altered in the cerebrum in AD related to aged control, nor correlated with regional amyloid plaque pathology. The choroid plexus appears to represent a novel non-neuronal source in the brain that may contribute Aβ into cerebrospinal fluid, probably at reduced levels in AD. PMID:23432732

Age-related decline in ovarian follicle stocks differ between chimpanzees (Pan troglodytes) and humans.

PubMed

Cloutier, Christina T; Coxworth, James E; Hawkes, Kristen

2015-02-01

Similarity in oldest parturitions in humans and great apes suggests that we maintain ancestral rates of ovarian aging. Consistent with that hypothesis, previous counts of primordial follicles in postmortem ovarian sections from chimpanzees (Pan troglodytes) showed follicle stock decline at the same rate that human stocks decline across the same ages. Here, we correct that finding with a chimpanzee sample more than three times larger than the previous one, which also allows comparison into older ages. Analyses show depletion rates similar until about age 35, but after 35, the human counts continue to fall with age, while the change is much less steep in chimpanzees. This difference implicates likely effects on ovarian dynamics from other physiological systems that are senescing at different rates, and, potentially, different perimenopausal experience for chimpanzees and humans.

Microsurgical and Tractographic Anatomy of the Supplementary Motor Area Complex in Humans.

PubMed

Bozkurt, Baran; Yagmurlu, Kaan; Middlebrooks, Erik H; Karadag, Ali; Ovalioglu, Talat Cem; Jagadeesan, Bharathi; Sandhu, Gauravjot; Tanriover, Necmettin; Grande, Andrew W

2016-11-01

To evaluate the microsurgical anatomy of the fiber tract connections of the supplementary motor area (SMA) and pre-SMA, and examine its potential functional role with reference to clinical trials in the literature. Ten postmortem formalin-fixed human brains (20 sides) and 1 cadaveric head were prepared following Klingler's method. The fiber dissection was performed in a stepwise fashion, from lateral to medial and also from medial to lateral, under an operating microscope, with 3D images captured at each stage. Our findings were supported by in vivo magnetic resonance imaging tractography in 2 healthy subjects. The connections of the SMA complex, composed of the pre-SMA and the SMA proper, are composed of short "U" association fibers and the superior longitudinal fasciculus I, cingulum, claustrocortical fibers, callosal fibers, corticospinal tract, frontal aslant tract, and frontostriatal tract. The claustrocortical fibers may play an important role in the integration of motor, language, and limbic functions of the SMA complex. The frontostriatal tract connects the pre-SMA to the putamen and caudate nucleus, and also forms parts of both the internal capsule and the dorsal external capsule. The SMA complex has numerous connections throughout the cerebrum. An understanding of these connections is important for presurgical planning for lesions in the frontal lobe and helps explain symptoms related to SMA injury. Copyright © 2016 Elsevier Inc. All rights reserved.

Photoreceptor disc shedding in the living human eye

PubMed Central

Kocaoglu, Omer P.; Liu, Zhuolin; Zhang, Furu; Kurokawa, Kazuhiro; Jonnal, Ravi S.; Miller, Donald T.

2016-01-01

Cone photoreceptors undergo a daily cycle of renewal and shedding of membranous discs in their outer segments (OS), the portion responsible for light capture. These physiological processes are fundamental to maintaining photoreceptor health, and their dysfunction is associated with numerous retinal diseases. While both processes have been extensively studied in animal models and postmortem eyes, little is known about them in the living eye, in particular human. In this study, we report discovery of the optical signature associated with disc shedding using a method based on adaptive optics optical coherence tomography (AO-OCT) in conjunction with post-processing methods to track and monitor individual cone cells in 4D. The optical signature of disc shedding is characterized by an abrupt transient loss in the cone outer segment tip (COST) reflection followed by its return that is axially displaced anteriorly. Using this signature, we measured the temporal and spatial properties of shedding events in three normal subjects. Average duration of the shedding event was 8.8 ± 13.4 minutes, and average length loss of the OS was 2.1 μm (7.0% of OS length). Prevalence of cone shedding was highest in the morning (14.3%) followed by the afternoon (5.7%) and evening (4.0%), with load distributed across the imaged patch. To the best of our knowledge these are the first images of photoreceptor disc shedding in the living retina. PMID:27895995

Risk Factors for Fatal Hyperglycaemia Confirmed by Forensic Postmortem Examination - A Nationwide Cohort in Sweden.

PubMed

Walz, Lotta; Jönsson, Anna K; Zilg, Brita; Östgren, Carl Johan; Druid, Henrik

2016-01-01

The aim of this study was to identify risk factors associated with confirmed fatal hyperglycaemia, which could predispose potentially preventable deaths in individuals on glucose lowering drugs. A retrospective register-based case-control study conducted on a nationwide cohort with individuals who died due to hyperglycaemia as determined by forensic postmortem examination, in Sweden August 2006 to December 2012. Vitreous glucose was used to diagnose hyperglycaemia postmortem. The forensic findings stored in the National Forensic Medicine Database were linked to nationwide registers. Cases that died due to confirmed hyperglycemia with dispensed glucose lowering drugs were identified and living controls with dispensed glucose lowering drugs were randomly selected in the Swedish prescribed drug register and matched on age and sex. Information on comorbidities, dispensed pharmaceuticals, clinical data and socioeconomic factors were obtained for cases and controls. Adjusted multiple logistic regression models were used to identify risk factors associated with fatal hyperglycaemia. During the study period 322 individuals, mostly males (79%) with the mean age of 53.9 years (SD.± 14) died due to confirmed hyperglycaemia. Risk factors for fatal hyperglycaemia included; insulin treatment (OR = 4.40; 95%CI,1.96, 9.85), poor glycaemic control (OR = 2.00 95%CI,1.23, 3.27), inadequate refill-adherence before death (OR = 3.87; 95%CI,1.99, 7.53), microvascular disease (OR = 3.26; 95% CI, 1.84, 5.79), psychiatric illness (OR = 2.30; 95% CI,1.32, 4.01), substance abuse (OR = 8.85; 95%CI,2.34, 35.0) and/or living alone (OR = 2.25; 95%CI,1.21, 4.18). Our results demonstrate the importance of clinical attention to poor glycaemic control in subjects with psychosocial problems since it may indicate serious non-adherence, which consequently could lead to fatal hyperglycaemia.

Pulmonary and cardiac pathology in sudden unexpected death in epilepsy (SUDEP).

PubMed

Nascimento, Fábio A; Tseng, Zian H; Palmiere, Cristian; Maleszewski, Joseph J; Shiomi, Takayuki; McCrillis, Aileen; Devinsky, Orrin

2017-08-01

To review studies on structural pulmonary and cardiac changes in SUDEP cases as well as studies showing pulmonary or cardiac structural changes in living epilepsy patients. We conducted electronic literature searches using the PubMed database for articles published in English, regardless of publication year, that included data on cardiac and/or pulmonary structural abnormalities in SUDEP cases or in living epilepsy patients during the postictal period. Fourteen postmortem studies reported pulmonary findings in SUDEP cases. Two focused mainly on assessing lung weights in SUDEP cases versus controls; no group difference was found. The other 12 reported descriptive autopsy findings. Among all SUDEP cases with available descriptive postmortem pulmonary examination, 72% had pulmonary changes, most often pulmonary edema/congestion, and, less frequently, intraalveolar hemorrhage. Eleven studies reported on cardiac pathology in SUDEP. Cardiac abnormalities were found in approximately one-fourth of cases. The most common findings were myocyte hypertrophy and myocardial fibrosis of various degrees. Among living epilepsy patients, postictal pulmonary pathology was the most commonly reported pulmonary abnormality and the most common postictal cardiac abnormality was transient left ventricular dysfunction - Takotsubo or neurogenic stunned myocardium. Cardiac and pulmonary pathological abnormalities are frequent among SUDEP cases, most commonly pulmonary edema/congestion and focal interstitial myocardial fibrosis. Most findings are not quantified, with subjective elements and undefined interobserver reliability, and lack of controls such as matched epilepsy patients who died from other causes. Further, studies have not systematically evaluated potential confounding factors, including postmortem interval to autopsy, paramedic resuscitation and IV fluids administration, underlying heart/lung disease, and risk factors for cardiac or pulmonary disease. Prospective studies with controls are needed to define the heart and lung changes in SUDEP and understand their potential relationship to mechanisms of death in SUDEP. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of probiotics feeding on meat quality of chicken breast during postmortem storage.

PubMed

Kim, H W; Yan, F F; Hu, J Y; Cheng, H W; Kim, Y H B

2016-06-01

This study evaluated the effects of dietary probiotic supplement and postmortem storage on meat quality of chicken breast during retail display. A total of 35 birds were randomly obtained from 3 feeding groups (control without probiotic supplement, 250 ppm Sporulin, and 500 ppm PoultryStar). The probiotic supplement had no influence on feed conversion ratio and body weight gain, as well as body weight at 29 and 44 d (P > 0.05). After slaughter, each side of the breast muscles (M. Pectoralis major) was assigned to either one d or 5 d of postmortem storage. Probiotic supplement had no influence on the rate of pH decline of chicken breast muscles during the initial 6 h postmortem (P > 0.05). No interactions between probiotic supplement and postmortem storage on meat quality were found (P > 0.05). Postmortem storage decreased drip loss from 25.30 to 18.05% (P < 0.05). Probiotics-fed chicken groups, particularly PoultryStar treatment, had a higher myofibrillar fragmentation index than the control group (P < 0.05). However, shear force values were not affected by the probiotic treatments. Decreases in color and lipid stabilities of breast muscles were found during display (P < 0.05), but were not affected by the probiotic supplement (P > 0.05). Our result suggests that probiotic supplement had no adverse impacts on proteolysis and oxidative changes during 5 d postmortem display storage. Published by Oxford University Press on behalf of Poultry Science Association 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Nitrobenzodiazepines: Postmortem brain and blood reference concentrations.

PubMed

Skov, Louise; Holm, Karen Marie Dollerup; Linnet, Kristian

2016-11-01

Reference concentrations are needed to evaluate postmortem toxicology results and usually femoral blood is the specimen of choice. However, brain tissue has been suggested as a viable alternative specimen, since postmortem blood concentrations can be difficult to interpret due to postmortem redistribution, among other factors. Here we present reference concentrations of postmortem brain and femoral blood of the nitrobenzodiazepines clonazepam, flunitrazepam, and nitrazepam that are of particular interest since they commonly are converted to their corresponding 7-aminometabolites in the postmortem situation. The drugs and metabolites were quantified in both matrices using LC-MS-MS in 69 cases. In 63 cases the compounds were judged not to have been of significance for the death (C cases), whereas they were considered to have been a contributing factor in 6 cases (B cases). No cases were observed with a nitrobenzodiazepine being the sole cause of death (A cases). The brain-blood ratios for clonazepam and nitrazepam were 5.5 and 4.7, respectively, while the brain-blood ratios for the 7-aminometabolites ranged from 0.4 to 0.5. Flunitrazepam only occurred as the 7-aminometabolite. A positive correlation between brain and blood concentrations was found with Spearman's rank correlation coefficients (r s ) ranging from 0.77 to 0.96. The measured femoral blood concentrations agree with literature values, but only few brain concentrations were available for comparison. The drug-metabolite ratios for clonazepam and nitrazepam were 10-12 times higher in brain than in blood. The pre-analytical variation in brain of 5.9% was fairly low, suggesting that brain tissue is a useful alternative to blood. The reported brain and femoral blood concentrations serve as reference values in postmortem investigations. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Effect of fast pH decline during the early postmortem period on calpain activity and cytoskeletal protein degradation of broiler M. pectoralis major.

PubMed

Huang, J C; Yang, J; Huang, F; Huang, M; Chen, K J; Xu, X L; Zhou, G H

2016-10-01

The objective of this study was to determine the effects of fast pH decline during the early postmortem period on calpain activity and the degradation of cytoskeletal proteins in broilers. Eighty broilers were randomly categorized into two groups: physical restraint (PR) and free struggle (FS). M. pectoralis major (PM) was used for determination of calpain activity, shear value, ultrastructure of myofibrils, and the degradation of desmin, titin, nebulin, and troponin-T. The pH (6.05) of FS group is significantly low than PR group (6.38) at 0.3 h postmortem. Fast pH decline during the early postmortem period led to a decrease of μ/m-calpain activities at 0.3 and 3 h postmortem (P < 0.05), but did not affect the ultimate μ/m-calpain activity. An initial fast decrease in pH increased the degradation of desmin, titin, nebulin, and increased the 30 kDa degradation fragments of troponin-T. Therefore, the fast pH decline during the early postmortem period decreased the μ/m-calpain activity and increased the degradation of cytoskeletal proteins in broiler muscle. It is possible that the fast pH decline experienced an earlier activation of calpains that resulted in earlier protein degradation and ultimately lower shear force. © 2016 Poultry Science Association Inc.

The endogenous and reactive depression subtypes revisited: integrative animal and human studies implicate multiple distinct molecular mechanisms underlying major depressive disorder.

PubMed

Malki, Karim; Keers, Robert; Tosto, Maria Grazia; Lourdusamy, Anbarasu; Carboni, Lucia; Domenici, Enrico; Uher, Rudolf; McGuffin, Peter; Schalkwyk, Leonard C

2014-05-07

Traditional diagnoses of major depressive disorder (MDD) suggested that the presence or absence of stress prior to onset results in either 'reactive' or 'endogenous' subtypes of the disorder, respectively. Several lines of research suggest that the biological underpinnings of 'reactive' or 'endogenous' subtypes may also differ, resulting in differential response to treatment. We investigated this hypothesis by comparing the gene-expression profiles of three animal models of 'reactive' and 'endogenous' depression. We then translated these findings to clinical samples using a human post-mortem mRNA study. Affymetrix mouse whole-genome oligonucleotide arrays were used to measure gene expression from hippocampal tissues of 144 mice from the Genome-based Therapeutic Drugs for Depression (GENDEP) project. The study used four inbred mouse strains and two depressogenic 'stress' protocols (maternal separation and Unpredictable Chronic Mild Stress) to model 'reactive' depression. Stress-related mRNA differences in mouse were compared with a parallel mRNA study using Flinders Sensitive and Resistant rat lines as a model of 'endogenous' depression. Convergent genes differentially expressed across the animal studies were used to inform candidate gene selection in a human mRNA post-mortem case control study from the Stanley Brain Consortium. In the mouse 'reactive' model, the expression of 350 genes changed in response to early stresses and 370 in response to late stresses. A minimal genetic overlap (less than 8.8%) was detected in response to both stress protocols, but 30% of these genes (21) were also differentially regulated in the 'endogenous' rat study. This overlap is significantly greater than expected by chance. The VAMP-2 gene, differentially expressed across the rodent studies, was also significantly altered in the human study after correcting for multiple testing. Our results suggest that 'endogenous' and 'reactive' subtypes of depression are associated with largely distinct changes in gene-expression. However, they also suggest that the molecular signature of 'reactive' depression caused by early stressors differs considerably from that of 'reactive' depression caused by late stressors. A small set of genes was consistently dysregulated across each paradigm and in post-mortem brain tissue of depressed patients suggesting a final common pathway to the disorder. These genes included the VAMP-2 gene, which has previously been associated with Axis-I disorders including MDD, bipolar depression, schizophrenia and with antidepressant treatment response. We also discuss the implications of our findings for disease classification, personalized medicine and case-control studies of MDD.

Consensus recommendations for the postmortem diagnosis of Alzheimer's disease. The National Institute on Aging, and Reagan Institute Working Group on Diagnostic Criteria for the Neuropathological Assessment of Alzheimer's Disease.

PubMed

1997-01-01

This report summarizes the consensus recommendations of a panel of neuropathologists from the United States and Europe to improve the postmortem diagnostic criteria for Alzheimer's disease. The recommendations followed from a two-day workshop sponsored by the National Institute on Aging (NIA) and the Ronald and Nancy Reagan Institute of the Alzheimer's Association to reassess the original NIA criteria for the postmortem diagnosis of Alzheimer's disease published in 1985. The consensus recommendations for improving the neuropathological criteria for the postmortem diagnosis of Alzheimer's disease are reported here, and the "position papers" by members of the Working Group that accompany this report elaborate on the research findings and concepts upon which these recommendations were based. Further, commentaries by other experts in the field also are included here to provide additional perspectives on these recommendations. Finally, it is anticipated that future meetings of the Working Group will reassess these recommendations and the implementation of postmortem diagnostic criteria for Alzheimer's disease.

When does the lung die? Kfc, cell viability, and adenine nucleotide changes in the circulation-arrested rat lung.

PubMed

Jones, D R; Becker, R M; Hoffmann, S C; Lemasters, J J; Egan, T M

1997-07-01

Lungs harvested from cadaveric circulation-arrested donors may increase the donor pool for lung transplantation. To determine the degree and time course of ischemia-reperfusion injury, we evaluated the effect of O2 ventilation on capillary permeability [capillary filtration coefficient (Kfc)], cell viability, and total adenine nucleotide (TAN) levels in in situ circulation-arrested rat lungs. Kfc increased with increasing postmortem ischemic time (r = 0.88). Lungs ventilated with O2 1 h postmortem had similar Kfc and wet-to-dry ratios as controls. Nonventilated lungs had threefold (P < 0.05) and sevenfold (P < 0.0001) increases in Kfc at 30 and 60 min postmortem compared with controls. Cell viability decreased in all groups except for 30-min postmortem O2-ventilated lungs. TAN levels decreased with increasing ischemic time, particularly in nonventilated lungs. Loss of adenine nucleotides correlated with increasing Kfc values (r = 0.76). This study indicates that lungs retrieved 1 h postmortem may have normal Kfc with preharvest O2 ventilation. The relationship between Kfc and TAN suggests that vascular permeability may be related to lung TAN levels.

Usefulness and limitations of postmortem computed tomography in forensic analysis of gunshot injuries: Three case reports.

PubMed

Usui, Akihito; Kawasumi, Yusuke; Hosokai, Yoshiyuki; Kozakai, Masataka; Saito, Haruo; Funayama, Masato

2016-01-01

Gunshot injury has always been an important field of investigation in postmortem forensic radiology. The localization and retrieval of the bullet and of potentially important fragments are vital to these cases. Using postmortem multidetector-row computed tomography (MDCT) prior to forensic autopsy, we sought to illustrate the importance of this modality in the noninvasive characterization of gunshot wounds. We obtained and analyzed MDCT images in three cases of gunshot wounds (accidental close-range shotgun shooting, suicidal contact gunshot to the head and accidental long-range buckshot shooting). We discuss the value of postmortem MDCT findings in gunshot wound cases by comparing with forensic autopsy findings in Japan, a developing country with miserably low autopsy rate. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The development of a post-mortem interval estimation for human remains found on land in the Netherlands.

PubMed

Gelderman, H T; Boer, L; Naujocks, T; IJzermans, A C M; Duijst, W L J M

2018-05-01

The decomposition process of human remains can be used to estimate the post-mortem interval (PMI), but decomposition varies due to many factors. Temperature is believed to be the most important and can be connected to decomposition by using the accumulated degree days (ADD). The aim of this research was to develop a decomposition scoring method and to develop a formula to estimate the PMI by using the developed decomposition scoring method and ADD.A decomposition scoring method and a Book of Reference (visual resource) were made. Ninety-one cases were used to develop a method to estimate the PMI. The photographs were scored using the decomposition scoring method. The temperature data was provided by the Royal Netherlands Meteorological Institute. The PMI was estimated using the total decomposition score (TDS) and using the TDS and ADD. The latter required an additional step, namely to calculate the ADD from the finding date back until the predicted day of death.The developed decomposition scoring method had a high interrater reliability. The TDS significantly estimates the PMI (R 2  = 0.67 and 0.80 for indoor and outdoor bodies, respectively). When using the ADD, the R 2 decreased to 0.66 and 0.56.The developed decomposition scoring method is a practical method to measure decomposition for human remains found on land. The PMI can be estimated using this method, but caution is advised in cases with a long PMI. The ADD does not account for all the heat present in a decomposing remain and is therefore a possible bias.

A Novel Method for Quantifying Human In Situ Whole Brain Deformation under Rotational Loading Using Sonomicrometry.

PubMed

Alshareef, Ahmed; Giudice, J Sebastian; Forman, Jason; Salzar, Robert S; Panzer, Matthew B

2018-03-01

Traumatic brain injuries (TBI) are one of the least understood injuries to the body. Finite element (FE) models of the brain have been crucial for understanding concussion and for developing injury mitigation systems; however, the experimental brain deformation data currently used to validate these models are limited. The objective of this study was to develop a methodology for the investigation of in situ three-dimensional brain deformation during pure rotational loading of the head, using sonomicrometry. Sonomicrometry uses ultrasonic pulses to measure the dynamic distances between piezoelectric crystals implanted in any sound-transmitting media. A human cadaveric head-neck specimen was acquired 14 h postmortem and was instrumented with an array of 32 small sonomicrometry crystals embedded in the head: 24 crystals were implanted in the brain, and 8 were fixed to the inner skull. A dynamic rotation was then applied to the head using a closed-loop controlled test device. Four pulses with different severity levels were applied around three orthogonal anatomical axes of rotation. A repeated test of the highest severity rotation was conducted in each axis to assess repeatability. All tests were completed within 56 h postmortem. Overall, the combined experimental and sonomicrometry methods were demonstrated to reliably and repeatedly capture three-dimensional dynamic deformation of an intact human brain. These methods provide a framework for using sonomicrometry to acquire multidimensional experimental data required for FE model development and validation, and will lend insight into the deformations sustained by the brain during impact.

Communicating with families about post-mortems: practice guidance.

PubMed

Henderson, Nicola

2006-02-01

In January 2001 the Chief Medical Officer announced the Public Inquiry (Redfern Report) into post-mortem practice at Alder Hey Hospital in Liverpool. It was expected that this inquiry report would influence post-mortem practice in general and communication with parents in particular and in May 2003 a code of practice for clinical staff was produced by the Department of Health (DH) (2003a). This article discusses the code of practice Families and Post Mortems and explores the relevance of these recommendations to neonatal and children's nurses.

Investigation of Post-mortem Tissue Effects Using Long-time Decorrelation Ultrasound

NASA Astrophysics Data System (ADS)

Csány, Gergely; Balogh, Lajos; Gyöngy, Miklós

Decorrelation ultrasound is being increasingly used to investigate long-term biological phenomena. In the current work, ultrasound image sequences of mice who did not survive anesthesia (in a separate investigation) were analyzed and post-mortem tissue effects were observed via decorrelation calculation. A method was developed to obtain a quantitative parameter characterizing the rate of decorrelation. The results show that ultrasound decorrelation imaging is an effective method of observing post-mortem tissue effects and point to further studies elucidating the mechanism behind these effects.

Expansion of Microbial Forensics

PubMed Central

Schmedes, Sarah E.; Sajantila, Antti

2016-01-01

Microbial forensics has been defined as the discipline of applying scientific methods to the analysis of evidence related to bioterrorism, biocrimes, hoaxes, or the accidental release of a biological agent or toxin for attribution purposes. Over the past 15 years, technology, particularly massively parallel sequencing, and bioinformatics advances now allow the characterization of microorganisms for a variety of human forensic applications, such as human identification, body fluid characterization, postmortem interval estimation, and biocrimes involving tracking of infectious agents. Thus, microbial forensics should be more broadly described as the discipline of applying scientific methods to the analysis of microbial evidence in criminal and civil cases for investigative purposes. PMID:26912746

Utility of Postmortem Autopsy via Whole-Body Imaging: Initial Observations Comparing MDCT and 3.0T MRI Findings with Autopsy Findings

PubMed Central

Cha, Jang Gyu; Kim, Dong Hun; Kim, Dae Ho; Paik, Sang Hyun; Park, Jai Soung; Park, Seong Jin; Lee, Hae Kyung; Hong, Hyun Sook; Choi, Duek Lin; Chung, Nak Eun; Lee, Bong Woo; Seo, Joong Seok

2010-01-01

Objective We prospectively compared whole-body multidetector computed tomography (MDCT) and 3.0T magnetic resonance (MR) images with autopsy findings. Materials and Methods Five cadavers were subjected to whole-body, 16-channel MDCT and 3.0T MR imaging within two hours before an autopsy. A radiologist classified the MDCT and 3.0T MRI findings into major and minor findings, which were compared with autopsy findings. Results Most of the imaging findings, pertaining to head and neck, heart and vascular, chest, abdomen, spine, and musculoskeletal lesions, corresponded to autopsy findings. The causes of death that were determined on the bases of MDCT and 3.0T MRI findings were consistent with the autopsy findings in four of five cases. CT was useful in diagnosing fatal hemorrhage and pneumothorax, as well as determining the shapes and characteristics of the fractures and the direction of external force. MRI was effective in evaluating and tracing the route of a metallic object, soft tissue lesions, chronicity of hemorrhage, and bone bruises. Conclusion A postmortem MDCT combined with MRI is a potentially powerful tool, providing noninvasive and objective measurements for forensic investigations. PMID:20592923

Effect of pre-rigor stretch and various constant temperatures on the rate of post-mortem pH fall, rigor mortis and some quality traits of excised porcine biceps femoris muscle strips.

PubMed

Vada-Kovács, M

1996-01-01

Porcine biceps femoris strips of 10 cm original length were stretched by 50% and fixed within 1 hr post mortem then subjected to temperatures of 4 °, 15 ° or 36 °C until they attained their ultimate pH. Unrestrained control muscle strips, which were left to shorten freely, were similarly treated. Post-mortem metabolism (pH, R-value) and shortening were recorded; thereafter ultimate meat quality traits (pH, lightness, extraction and swelling of myofibrils) were determined. The rate of pH fall at 36 °C, as well as ATP breakdown at 36 and 4 °C, were significantly reduced by pre-rigor stretch. The relationship between R-value and pH indicated cold shortening at 4 °C. Myofibrils isolated from pre-rigor stretched muscle strips kept at 36 °C showed the most severe reduction of hydration capacity, while paleness remained below extreme values. However, pre-rigor stretched myofibrils - when stored at 4 °C - proved to be superior to shortened ones in their extractability and swelling.

Quantitative Susceptibility Mapping by Inversion of a Perturbation Field Model: Correlation with Brain Iron in Normal Aging

PubMed Central

Poynton, Clare; Jenkinson, Mark; Adalsteinsson, Elfar; Sullivan, Edith V.; Pfefferbaum, Adolf; Wells, William

2015-01-01

There is increasing evidence that iron deposition occurs in specific regions of the brain in normal aging and neurodegenerative disorders such as Parkinson's, Huntington's, and Alzheimer's disease. Iron deposition changes the magnetic susceptibility of tissue, which alters the MR signal phase, and allows estimation of susceptibility differences using quantitative susceptibility mapping (QSM). We present a method for quantifying susceptibility by inversion of a perturbation model, or ‘QSIP’. The perturbation model relates phase to susceptibility using a kernel calculated in the spatial domain, in contrast to previous Fourier-based techniques. A tissue/air susceptibility atlas is used to estimate B0 inhomogeneity. QSIP estimates in young and elderly subjects are compared to postmortem iron estimates, maps of the Field-Dependent Relaxation Rate Increase (FDRI), and the L1-QSM method. Results for both groups showed excellent agreement with published postmortem data and in-vivo FDRI: statistically significant Spearman correlations ranging from Rho = 0.905 to Rho = 1.00 were obtained. QSIP also showed improvement over FDRI and L1-QSM: reduced variance in susceptibility estimates and statistically significant group differences were detected in striatal and brainstem nuclei, consistent with age-dependent iron accumulation in these regions. PMID:25248179

Posttraumatic stress symptoms following forensic dental identification: Mt. Carmel, Waco, Texas.

PubMed

McCarroll, J E; Fullerton, C S; Ursano, R J; Hermsen, J M

1996-06-01

This study was conducted to determine risk factors for posttraumatic stress in medical care professionals who perform postmortem identifications. Thirty-one dentists (29 men and two women) who had identified the dead from the fire at the Branch Davidian compound in April 1993 were compared to 47 dentists (45 men and two women) who lived in the area but had not identified any of these remains. Posttraumatic symptoms in both groups were measured by using the Impact of Event Scale and the Brief Symptom Inventory. For the remains handlers only, the subjective distress of handling remains and the social support received during the procedure were reported. Higher scores on the Impact of Event Scale intrusion subscale, the overall Impact of Event Scale, and the obsessive-compulsive subscale of the Brief Symptom Inventory were found for the remains handlers than for the comparison group. Within the remains handler group, distress was significantly related to the hours of exposure to the remains, prior experience handling remains, age, and the support received from spouses and co-workers during the identifications. Posttraumatic stress symptoms can be expected in some health professionals who perform postmortem identifications. Prior experience and social support may mitigate some of these responses.

The effect of charging rate on the graphite electrode of commercial lithium-ion cells: A post-mortem study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Somerville, L.; Bareno, J.; Trask, S.

Increased charging rates negatively affect the lifetime of lithium-ion cells by increasing cell resistance and reducing capacity. This work is a post-mortem study of 18650 cells subjected to charge rates of 0.7-, 2-, 4-, and 6-C. For cells charged at 0.7-C to 4-C, this performance degradation is primarily related to surface film thickness with no observable change in surface film chemical composition. However, at charge rates of 6-C, the chemical composition of the surface film changes significantly, suggesting that this change is the reason for the sharper increase in cell resistance compared to the lower charge rates. In addition, wemore » found that surface film formation was not uniform across the electrode. Surface film was thicker and chemically different along the central band of the electrode “jelly roll”. This result is most likely attributable to an increase in temperature that results from non-uniform electrode wetting during manufacture. As a result, this non-uniform change further resulted in active material delamination from the current collector owing to chemical changes to the binder for the cell charged at 6-C.« less

The effect of charging rate on the graphite electrode of commercial lithium-ion cells: A post-mortem study

DOE PAGES

Somerville, L.; Bareno, J.; Trask, S.; ...

2016-10-22

Increased charging rates negatively affect the lifetime of lithium-ion cells by increasing cell resistance and reducing capacity. This work is a post-mortem study of 18650 cells subjected to charge rates of 0.7-, 2-, 4-, and 6-C. For cells charged at 0.7-C to 4-C, this performance degradation is primarily related to surface film thickness with no observable change in surface film chemical composition. However, at charge rates of 6-C, the chemical composition of the surface film changes significantly, suggesting that this change is the reason for the sharper increase in cell resistance compared to the lower charge rates. In addition, wemore » found that surface film formation was not uniform across the electrode. Surface film was thicker and chemically different along the central band of the electrode “jelly roll”. This result is most likely attributable to an increase in temperature that results from non-uniform electrode wetting during manufacture. As a result, this non-uniform change further resulted in active material delamination from the current collector owing to chemical changes to the binder for the cell charged at 6-C.« less

Lung aeration on post-mortem magnetic resonance imaging is a useful marker of live birth versus stillbirth.

PubMed

Barber, Joy L; Sebire, Neil J; Chitty, Lyn S; Taylor, Andrew M; Arthurs, Owen J

2015-05-01

Aim of this study was to investigate whether lung assessment on post-mortem magnetic resonance imaging (PMMR) can reliably differentiate between live birth and stillbirth. We retrospectively assessed PMMR imaging features of a group of late foetal terminations following fetocide and stillbirths (without witnessed breathing) and early infant deaths (breathed spontaneously before death). PMMR images were reviewed for evidence of lung aeration and other features, blinded to the clinical and autopsy data. Nineteen infant deaths (mean age 3.0 ± 6.5 post-natal weeks) and 23 foetal terminations or stillbirths (mean age 32.6 ± 10.2-week gestation) were compared. Subjective appearances of lung aeration on PMMR were the best indicator of live birth, with a sensitivity of 89.5% (95% confidence interval 68.6, 97.1%) and specificity of 95.6% (79.0, 99.2%) and positive and negative predictive values of 94.4% and 91.7%, respectively. Lung aeration on PMMR appears to have high overall accuracy for confirmation of live birth versus intrauterine foetal death but now requires validating in a larger cohort of perinatal deaths.

Targeting the Cholinergic System to Develop a Novel Therapy for Huntington's Disease.

PubMed

D'Souza, Gary X; Waldvogel, Henry J

2016-12-15

In this review, we outline the role of the cholinergic system in Huntington's disease, and briefly describe the dysfunction of cholinergic transmission, cholinergic neurons, cholinergic receptors and cholinergic survival factors observed in post-mortem human brains and animal models of Huntington's disease. We postulate how the dysfunctional cholinergic system can be targeted to develop novel therapies for Huntington's disease, and discuss the beneficial effects of cholinergic therapies in pre-clinical and clinical studies.

Downregulation of the neuronal opioid gene expression concomitantly with neuronal decline in dorsolateral prefrontal cortex of human alcoholics.

PubMed

Bazov, Igor; Sarkisyan, Daniil; Kononenko, Olga; Watanabe, Hiroyuki; Karpyak, Victor M; Yakovleva, Tatiana; Bakalkin, Georgy

2018-06-20

Molecular changes in cortical areas of addicted brain may underlie cognitive impairment and loss of control over intake of addictive substances and alcohol. Prodynorphin (PDYN) gives rise to dynorphin (DYNs) opioid peptides which target kappa-opioid receptor (KOR). DYNs mediate alcohol-induced impairment of learning and memory, while KOR antagonists block excessive, compulsive-like drug and alcohol self-administration in animal models. In human brain, the DYN/KOR system may undergo adaptive changes, which along with neuronal loss, may contribute to alcohol-associated cognitive deficit. We addressed this hypothesis by comparing the expression levels and co-expression (transcriptionally coordinated) patterns of PDYN and KOR (OPRK1) genes in dorsolateral prefrontal cortex (dlPFC) between human alcoholics and controls. Postmortem brain specimens of 53 alcoholics and 55 controls were analyzed. PDYN was found to be downregulated in dlPFC of alcoholics, while OPRK1 transcription was not altered. PDYN downregulation was confined to subgroup of subjects carrying C, a high-risk allele of PDYN promoter SNP rs1997794 associated with alcoholism. Changes in PDYN expression did not depend on the decline in neuronal proportion in alcoholics, and thereby may be attributed to transcriptional adaptations in alcoholic brain. Absolute expression levels of PDYN were lower compared to those of OPRK1, suggesting that PDYN expression is a limiting factor in the DYN/KOR signaling, and that the PDYN downregulation diminishes efficacy of DYN/KOR signaling in dlPFC of human alcoholics. The overall outcome of the DYN/KOR downregulation may be disinhibition of neurotransmission, which when overactivated could contribute to formation of alcohol-related behavior.

Dysregulated post-synaptic density and endocytic zone in the amygdala of human heroin and cocaine abusers

PubMed Central

Ökvist, Anna; Fagergren, Pernilla; Whittard, John; Garcia-Osta, Ana; Drakenberg, Katarina; Horvath, Monika Cs.; Schmidt, Carl J.; Keller, Eva; Bannon, Michael J.; Hurd, Yasmin L.

2010-01-01

Background Glutamatergic transmission in the amygdala is hypothesized as an important mediator of stimulus-reward associations contributing to drug-seeking behavior and relapse. Insight is, however, lacking regarding the amygdala glutamatergic system in human drug abusers. Methods We examined glutamate receptors and scaffolding proteins associated with the post-synaptic density (PSD) of excitatory synapses in the human post-mortem amygdala. mRNA or protein levels were studied in a multi-drug (7 heroin, 8 cocaine, 7 heroin/cocaine and 7 control) or predominant heroin (29 heroin and 15 control) population of subjects. Results The amygdala of drug abusers was characterized by a striking positive correlation (r > 0.8) between AMPA GluA1 and post-synaptic protein-95 (PSD-95) mRNA levels, which was not evident in controls. Structural equation multi-group analysis of protein correlations also identified the relationship between GluA1 and PSD-95 protein levels as the distinguishing feature of abusers. In line with the GluA1—PSD-95 implications of enhanced synaptic plasticity, Homer 1b/c protein expression was significantly increased in both heroin and cocaine users as was its binding partner dynamin-3, localized to the endocytic zone. Furthermore, there was a positive relationship between Homer 1b/c and dynamin-3 in drug abusers that reflected an increase in the direct physical coupling between the proteins. A noted age-related decline of Homer 1b/c—dynamin-3 interactions, as well as GluA1 levels, was blunted in abusers. Conclusions Impairment of key components of the amygdala PSD and coupling to the endocytic zone, critical for the regulation of glutamate receptor cycling, may underlie heightened synaptic plasticity in human drug abusers. PMID:21126734

Using body temperature, food and water consumption as biomarkers of disease progression in mice with Eμ-myc lymphoma

PubMed Central

Hunter, J E; Butterworth, J; Perkins, N D; Bateson, M; Richardson, C A

2014-01-01

Background: Non-invasive biomarkers of disease progression in mice with cancer are lacking making it challenging to implement appropriate humane end points. We investigated whether body temperature, food and water consumption could be used to predict tumour burden. Methods: Thirty-six male, wild-type C57Bl/6 mice were implanted with subcutaneous RFID temperature sensors and inoculated with Eμ-myc tumours that infiltrate lymphoid tissue. Results: Decrease in body temperature over the course of the study positively predicted post-mortem lymph node tumour burden (R2=0.68, F(1,22)=44.8, P<0.001). At experimental and humane end points, all mice that had a mean decrease in body temperature of 0.7 °C or greater had lymph nodes heavier than 0.5 g (100% sensitivity), whereas a mean decrease in body temperature <0.7 °C always predicted lymph nodes lighter than 0.5 g (100% specificity). The mean decrease in food consumption in each cage also predicted mean post-mortem lymph node tumour burden at 3 weeks (R2=0.89, F(1,3)=23.2, P=0.017). Conclusion: Temperature, food and water consumption were useful biomarkers of disease progression in mice with lymphoma and could potentially be used more widely to monitor mice with other forms of cancer. PMID:24407190

Identification of exhumed remains of fire tragedy victims using conventional methods and autosomal/Y-chromosomal short tandem repeat DNA profiling.

PubMed

Calacal, Gayvelline C; Delfin, Frederick C; Tan, Michelle Music M; Roewer, Lutz; Magtanong, Danilo L; Lara, Myra C; Fortun, Raquel dR; De Ungria, Maria Corazon A

2005-09-01

In a fire tragedy in Manila in December 1998, one of the worst tragic incidents which resulted in the reported death of 23 children, identity could not be established initially resulting in the burial of still unidentified bodies. Underscoring the importance of identifying each of the human remains, the bodies were exhumed 3 months after the tragedy. We describe here our work, which was the first national case handled by local laboratories wherein conventional and molecular-based techniques were successfully applied in forensic identification. The study reports analysis of DNA obtained from skeletal remains exposed to conditions of burning, burial, and exhumation. DNA typing methods using autosomal and Y-chromosomal short tandem repeat (Y-STR) markers reinforced postmortem examinations using conventional identification techniques. The strategy resulted in the identification of 18 out of the 21 human remains analyzed, overcoming challenges encountered due to the absence of established procedures for the recovery of mass disaster remains. There was incomplete antemortem information to match the postmortem data obtained from the remains of 3 female child victims. Two victims were readily identified due to the availability of antemortem tissues. In the absence of this biologic material, parentage testing was performed using reference blood samples collected from parents and relatives. Data on patrilineal lineage based on common Y-STR haplotypes augmented autosomal DNA typing, particularly in deficiency cases.

Human cadaver multipotent stromal/stem cells isolated from arteries stored in liquid nitrogen for 5 years

PubMed Central

2014-01-01

Introduction Regenerative medicine challenges researchers to find noncontroversial, safe and abundant stem cell sources. In this context, harvesting from asystolic donors could represent an innovative and unlimited reservoir of different stem cells. In this study, cadaveric vascular tissues were established as an alternative source of human cadaver mesenchymal stromal/stem cells (hC-MSCs). We reported the successful cell isolation from postmortem arterial segments stored in a tissue-banking facility for at least 5 years. Methods After thawing, hC-MSCs were isolated with a high efficiency (12 × 106) and characterized with flow cytometry, immunofluorescence, molecular and ultrastructural approaches. Results In early passages, hC-MSCs were clonogenic, highly proliferative and expressed mesenchymal (CD44, CD73, CD90, CD105, HLA-G), stemness (Stro-1, Oct-4, Notch-1), pericyte (CD146, PDGFR-β, NG2) and neuronal (Nestin) markers; hematopoietic and vascular markers were negative. These cells had colony and spheroid-forming abilities, multipotency for their potential to differentiate in multiple mesengenic lineages and immunosuppressive activity to counteract proliferation of phytohemagglutinin-stimulated blood mononuclear cells. Conclusions The efficient procurement of stem cells from cadaveric sources, as postmortem vascular tissues, demonstrates that such cells can survive to prolonged ischemic insult, anoxia, freezing and dehydration injuries, thus paving the way for a scientific revolution where cadaver stromal/stem cells could effectively treat patients demanding cell therapies. PMID:24429026

Diagnosis of Vitality in Skin Wounds in the Ligature Marks Resulting From Suicide Hanging.

PubMed

Legaz Pérez, Isabel; Falcón, Maria; Gimenez, M; Diaz, F Martínez; Pérez-Cárceles, M D; Osuna, E; Nuno-Vieira, D; Luna, A

2017-09-01

Ascertaining the vital origin of skin wounds is one of the most challenging problems in forensic pathology. The forensic literature describes biomarkers and methods for differentiating vital and postmortem wounds, although no clear conclusions have been reached. The aim of this study was to characterize human vital wounds by analyzing the concentrations of metallic ions and the expression of P-selectin and cathepsin D in skin wounds in the ligature marks in a cohort of suicidal hangings for which vitality was previously demonstrated.A total of 71 skin wounds were analyzed within a postmortem interval of 19 to 36 hours. The concentration of Fe, Zn, Mg, and Ca and the expression of P-selectin and cathepsin D were analyzed together and separately. The majority of autopsied suicidal hangings were men (86%) with complete hanging mode (60.7%) in which there was a high frequency of subcutaneous injuries (78.3%). High concentrations of Ca and Mg compared with Fe and Zn were found. Ca and Zn concentrations decreased, and Fe concentration increased with the seriousness of the injury. A high percentage of moderately negative expression of both proteins was correlated with subcutaneous injury and low or medium concentrations of Fe.In conclusion, the joint study of metallic ions and proteins allows to characterize and to differentiate an injured vital wound of noninjured skin, especially when the damage in the tissue affects to the majority of the structures of the skin, but these results will need to be complemented with other biomarkers in time-controlled samples to further help in the differentiation of vital and postmortem wounds.

GABA receptor subunit distribution and FMRP-mGluR5 signaling abnormalities in the cerebellum of subjects with schizophrenia, mood disorders, and autism

PubMed Central

Fatemi, S. Hossein; Folsom, Timothy D.

2016-01-01

Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the brain. GABAergic receptor abnormalities have been documented in several major psychiatric disorders including schizophrenia, mood disorders, and autism. Abnormal expression of mRNA and protein for multiple GABA receptors has also been observed in multiple brain regions leading to alterations in the balance between excitatory/inhibitory signaling in the brain with potential profound consequences for normal cognition and maintenance of mood and perception. Altered expression of GABAA receptor subunits has been documented in Fragile X mental retardation 1 (FMR1) knockout mice, suggesting that loss of its protein product, fragile X mental retardation protein (FMRP), impacts GABAA subunit expression. Recent postmortem studies from our laboratory have shown reduced expression of FMRP in brains of subjects with schizophrenia, bipolar disorder, major depression, and autism. FMRP acts as a translational repressor and, under normal conditions, inhibits metabotropic glutamate receptor 5 (mGluR5)-mediated signaling. In fragile X syndrome (FXS), absence of FMRP is hypothesized to lead to unregulated mGluR5 signaling, ultimately resulting in the behavioral and intellectual impairments associated with this disorder. Our laboratory has identified changes in mGluR5 expression in autism, schizophrenia, and mood disorders. In the current review article, we discuss our postmortem data on GABA receptors, FMRP, and mGluR5 levels and compare our results with other laboratories. Finally, we discuss the interactions between these molecules and the potential for new therapeutic interventions that target these interconnected signaling systems. PMID:25432637

Interspecies nuclear transfer using fibroblasts from leopard, tiger, and lion ear piece collected postmortem as donor cells and rabbit oocytes as recipients.

PubMed

Yelisetti, Uma Mahesh; Komjeti, Suman; Katari, Venu Charan; Sisinthy, Shivaji; Brahmasani, Sambasiva Rao

2016-06-01

Skin fibroblast cells were obtained from a small piece of an ear of leopard, lion, and tiger collected postmortem and attempts were made to synchronize the skin fibroblasts at G0/G1 of cell cycle using three different approaches. Efficiency of the approaches was tested following interspecies nuclear transfer with rabbit oocytes as recipient cytoplasm. Fluorescence-activated cell sorting revealed that the proportion of G0/G1 cells increased significantly (P < 0.05) when cells subjected to serum starvation, contact inhibition, and 3 mM sodium butyrate (NaBu) treatment when compared with cycling cells. However, 3 mM NaBu treatment caused alterations in cell morphology and increase in dead cells. Thus, interspecies nuclear transfer was carried out using fibroblast cells subjected to contact inhibition for 72 h, serum starvation for 48 h, and cells treated with 1.0 mM NaBu for 48 h. The fusion rates, the proportion of fused couplets that cleaved to two-cell and developed to blastocyst, were highest in all three species when the donor cells were treated with 1.0 mM NaBu for 48 h. But, the blastocyst percentage of interspecies nuclear embryos (5-6%) was significantly lower when compared with rabbit-rabbit nuclear transfer embryos (22.9%). In conclusion, fibroblast cells of leopard, lion, and tiger were successfully synchronized and used for the development of blastocysts using rabbit oocytes as recipient cytoplasm.

Interferon gamma-inducible protein-10 (IP-10) and eotaxin as biomarkers in age-related macular degeneration.

PubMed

Mo, Fong Ming; Proia, Alan D; Johnson, Walter H; Cyr, Desiree; Lashkari, Kameran

2010-08-01

To analyze serum cytokine levels in subjects with different stages of AMD and to study the expression of salient cytokines in postmortem eyes with AMD. A suspension array system was used to analyze sera (n = 18 to 20/group) from control subjects and those with early AMD (AREDS stage 1), intermediate dry AMD (AREDS stage 3), advanced AMD with geographic atrophy (GA), or neovascular AMD (CNV). Postmortem eyes with AMD or control eyes were examined immunohistochemically for expression of IP-10 and eotaxin (n = 4 to 8/group). Serum eotaxin and IP-10 levels were significantly elevated in all stages of AMD, except for eotaxin levels in neovascular AMD (P < 0.07). The peak of serum IP-10 concentration was at intermediate dry AMD. In donor eyes, IP-10 and eotaxin expressions were increased in the RPE of eyes with early AMD, GA, and CNV. Eotaxin accumulated within the layer of basal linear/laminar deposits in all stages of AMD, while IP-10 was mainly in eyes with GA and CNV. IP-10 was abundant in the connective tissue matrix associated with CNV, and eotaxin was usually present but more focally and with less intense staining. Both IP-10 and eotaxin were expressed by neovascular endothelial cells. Both IP-10 and eotaxin were expressed in the neurosensory retina, but there was no detectable difference in staining between eyes with or without AMD. IP-10 and eotaxin may be early biomarkers in AMD. The authors hypothesize that the relative balance between levels of IP-10 and eotaxin is critical in regulating the neovascular response.

Classifying serial killers.

PubMed

Promish, D I; Lester, D

1999-11-08

We attempted to match the appearance and demeanor of 27 serial killers to the postmortem 'signatures' found on their victims' bodies. Our results suggest that a link may exist between postmortem signatures and two complementary appearance-demeanor types.

Differences between postmortem computed tomography and conventional autopsy in a stabbing murder case

PubMed Central

Zerbini, Talita; da Silva, Luiz Fernando Ferraz; Ferro, Antonio Carlos Gonçalves; Kay, Fernando Uliana; Junior, Edson Amaro; Pasqualucci, Carlos Augusto Gonçalves; do Nascimento Saldiva, Paulo Hilario

2014-01-01

OBJECTIVE: The aim of the present work is to analyze the differences and similarities between the elements of a conventional autopsy and images obtained from postmortem computed tomography in a case of a homicide stab wound. METHOD: Comparison between the findings of different methods: autopsy and postmortem computed tomography. RESULTS: In some aspects, autopsy is still superior to imaging, especially in relation to external examination and the description of lesion vitality. However, the findings of gas embolism, pneumothorax and pulmonary emphysema and the relationship between the internal path of the instrument of aggression and the entry wound are better demonstrated by postmortem computed tomography. CONCLUSIONS: Although multislice computed tomography has greater accuracy than autopsy, we believe that the conventional autopsy method is fundamental for providing evidence in criminal investigations. PMID:25518020

Effects of tea polyphenols on the post-mortem integrity of large yellow croaker (Pseudosciaena crocea) fillet proteins.

PubMed

Zhao, Jin; Lv, Weijin; Wang, Jinlin; Li, Jianrong; Liu, Xiaoxiang; Zhu, Junli

2013-12-01

Tea polyphenols (TP) are known to be important for the post-mortem deterioration of fish muscle and can enhance food quality. To shed light on the influence of TP on the status of large yellow croaker muscle proteins, control and treated fillets (0.1% TP, 0.2% TP and 0.3% TP, w/v) were analysed periodically for myofibrillar protein functional properties (Ca(2+)-ATPase activity, surface hydrophobicity, total sulfhydryl content, emulsion stability index and rheological behaviour). Degradation of the myofibrillar protein myosin could be clearly observed; several proteins were also observed to vary in abundance following post-mortem storage for 25 days. The present study offers new evidence that TP have an effective impact on muscle protein integrity post-mortem. Copyright © 2013 Elsevier Ltd. All rights reserved.

Unusual injury pattern in a case of postmortem animal depredation by a domestic German shepherd.

PubMed

Tsokos, M; Schulz, F; Püschel, K

1999-09-01

A case is presented of a 38-year-old woman with skeletization of the head, neck, and collar region and a circumscribed 26-cm x 19-cm defect on the left chest with sole removal of the heart through the opened pericardium but undamaged mediastinum and lungs. The injuries showed V-shaped puncture wounds and superficial claw-induced scratches adjacent to the wound margins that have been described as typical for postmortem animal depredation of carnivore origin and derived from postmortem animal damage by the woman's domestic German shepherd. The circumscribed destruction of the left chest with unusual opening of the pericardium is explained by the physiognomy of the muzzle of the German shepherd and differs from previous reports. Any case presented as postmortem animal mutilation should be viewed with skepticism and undergo a full autopsy.

[Current macro-diagnostic trends of forensic medicine in the Czech Republic].

PubMed

Frišhons, Jan; Kučerová, Štěpánka; Jurda, Mikoláš; Sokol, Miloš; Vojtíšek, Tomáš; Hejna, Petr

2017-01-01

Over the last few years, advanced diagnostic methods have penetrated in the realm of forensic medicine in addition to standard autopsy techniques supported by traditional X-ray examination and macro-diagnostic laboratory tests. Despite the progress of imaging methods, the conventional autopsy has remained basic and essential diagnostic tool in forensic medicine. Postmortem computed tomography and magnetic resonance imaging are far the most progressive modern radio diagnostic methods setting the current trend of virtual autopsies all over the world. Up to now, only two institutes of forensic medicine have available postmortem computed tomography for routine diagnostic purposes in the Czech Republic. Postmortem magnetic resonance is currently unattainable for routine diagnostic use and was employed only for experimental purposes. Photogrammetry is digital method focused primarily on body surface imaging. Recently, the most fruitful results have been yielded from the interdisciplinary cooperation between forensic medicine and forensic anthropology with the implementation of body scanning techniques and 3D printing. Non-invasive and mini-invasive investigative methods such as postmortem sonography and postmortem endoscopy was unsystematically tested for diagnostic performance with good outcomes despite of limitations of these methods in postmortem application. Other futuristic methods, such as the use of a drone to inspect the crime scene are still experimental tools. The authors of the article present a basic overview of the both routinely and experimentally used investigative methods and current macro-diagnostic trends of the forensic medicine in the Czech Republic.

Increased White Matter Inflammation in Aging- and Alzheimer’s Disease Brain

PubMed Central

Raj, Divya; Yin, Zhuoran; Breur, Marjolein; Doorduin, Janine; Holtman, Inge R.; Olah, Marta; Mantingh-Otter, Ietje J.; Van Dam, Debby; De Deyn, Peter P.; den Dunnen, Wilfred; Eggen, Bart J. L.; Amor, Sandra; Boddeke, Erik

2017-01-01

Chronic neuroinflammation, which is primarily mediated by microglia, plays an essential role in aging and neurodegeneration. It is still unclear whether this microglia-induced neuroinflammation occurs globally or is confined to distinct brain regions. In this study, we investigated microglia activity in various brain regions upon healthy aging and Alzheimer’s disease (AD)-related pathology in both human and mouse samples. In purified microglia isolated from aging mouse brains, we found a profound gene expression pattern related to pro-inflammatory processes, phagocytosis, and lipid homeostasis. Particularly in white matter microglia of 24-month-old mice, abundant expression of phagocytic markers including Mac-2, Axl, CD16/32, Dectin1, CD11c, and CD36 was detected. Interestingly, in white matter of human brain tissue the first signs of inflammatory activity were already detected during middle age. Thus quantification of microglial proteins, such as CD68 (commonly associated with phagocytosis) and HLA-DR (associated with antigen presentation), in postmortem human white matter brain tissue showed an age-dependent increase in immunoreactivity already in middle-aged people (53.2 ± 2.0 years). This early inflammation was also detectable by non-invasive positron emission tomography imaging using [11C]-(R)-PK11195, a ligand that binds to activated microglia. Increased microglia activity was also prominently present in the white matter of human postmortem early-onset AD (EOAD) brain tissue. Interestingly, microglia activity in the white matter of late-onset AD (LOAD) CNS was similar to that of the aged clinically silent AD cases. These data indicate that microglia-induced neuroinflammation is predominant in the white matter of aging mice and humans as well as in EOAD brains. This white matter inflammation may contribute to the progression of neurodegeneration, and have prognostic value for detecting the onset and progression of aging and neurodegeneration. PMID:28713239

Effects of postmortem aging and USDA quality grade on Warner-Bratzler shear force values of seventeen individual beef muscles.

PubMed

Gruber, S L; Tatum, J D; Scanga, J A; Chapman, P L; Smith, G C; Belk, K E

2006-12-01

Forty USDA Select and 40 upper two-thirds USDA Choice beef carcasses were used to determine the effects of postmortem aging on tenderness of 17 individual beef muscles. Biceps femoris-long head, complexus, gluteus medius, infraspinatus, longissimus dorsi, psoas major, rectus femoris, semimembranosus, semitendinosus, serratus ventralis, spinalis dorsi, supraspinatus, tensor fasciae latae, teres major, triceps brachii-long head, vastus lateralis, and vastus medialis muscles were removed from each carcass. Seven steaks (2.54-cm thick) were cut from every muscle, and each steak was assigned to one of the following postmortem aging periods: 2, 4, 6, 10, 14, 21, or 28 d postmortem. After completion of the designated aging period, steaks were removed from storage (2 degrees C, never frozen), cooked to a peak internal temperature of 71 degrees C, and evaluated using Warner-Bratzler shear force (WBSF). Analysis of WBSF revealed a 3-way interaction (P = 0.004) among individual muscle, USDA quality grade, and postmortem aging period. With the exception of the Select teres major, WBSF of all muscles (both quality grades) decreased with increasing time of postmortem storage. Nonlinear regression was used to characterize the extent (aging response) and rate of decrease in WBSF from 2 through 28 d postmortem for each muscle within each quality grade. In general, WBSF of upper two-thirds Choice muscles decreased more rapidly from 2 to 10 d postmortem than did corresponding Select muscles. Muscles that had greater aging responses generally had greater 2-d WBSF values. The upper two-thirds Choice psoas major, serratus ventralis, and vastus lateralis muscles required similar aging times to complete a majority of the aging response (< or =0.1 kg of aging response remaining) compared with analogous Select muscles. The upper two-thirds Choice complexus, gluteus medius, semitendinosus, triceps brachii-long head, and vastus medialis muscles required 4 to 6 d less time to complete a majority of the aging response than did comparable Select muscles. Aging times for Select biceps femoris-long head, infraspinatus, longissimus dorsi, rectus femoris, semimembranosus, spinalis dorsi, supraspinatus, and tensor fasciae latae muscles were > or =7 d longer than those for corresponding upper two-thirds Choice muscles. Results from this study suggest that muscle-to-muscle tenderness differences depend on quality grade and aging time and that postmortem aging should be managed with respect to individual muscle and USDA quality grade.

Technical note: validation of a model for online classification of US Select beef carcasses for longissimus tenderness using visible and near-infrared reflectance spectroscopy.

PubMed

Shackelford, S D; Wheeler, T L; Koohmaraie, M

2012-03-01

The present experiment was conducted to provide a validation of a previously developed model for online classification of US Select carcasses for LM tenderness based on visible and near-infrared (VISNIR) spectroscopy and to determine if the accuracy of VISNIR-based tenderness classification could be enhanced by making measurements after postmortem aging. Spectroscopy was conducted online, during carcass grading, at a large-scale commercial fed beef-processing facility, and the strip loin was obtained from the left side of US Select carcasses (n = 467). Slice shear force (SSF) was measured on fresh steaks at 2 and 14 d postmortem. Online VISNIR tenderness classes differed in mean SSF values at both 2 d (29.4 vs. 33.6 kg) and 14 d (18.0 vs. 21.2 kg) postmortem (P < 10(-7)). Online VISNIR tenderness classes differed in both the percentage of carcasses with LM SSF values greater than 40 kg at 2 d postmortem (5.1 vs. 21.0%; P < 10(-6)) and the percentage of carcasses with LM SSF values greater than 25 kg at 14 d postmortem (6.8 vs. 23.2%; P < 10(-5)). Whereas 15.0% of the carcasses sampled for this experiment had LM SSF values greater than 25 kg at 14 d postmortem, only 6.8% of the carcasses classified as tender by VISNIR had LM SSF values greater than 25 kg. All the carcasses sampled that had LM SSF values greater than 35 kg at 14 d postmortem were accurately classified as tough by VISNIR. Before measurement of SSF on d 14, VISNIR spectroscopy was conducted on the SSF steak. Tenderness classes based on d 14 VISNIR spectra differed both in mean SSF value at 14 d postmortem (17.7 vs. 21.6 kg; P < 10(-11)) and the percentage of carcasses with LM SSF values greater than 25 kg at 14 d postmortem (7.3 vs. 22.7%; P < 10(-5)). These data support our previous work showing that VISNIR spectroscopy can be used to classify US Select carcasses noninvasively for LM tenderness, and the results establish that this technology could also be applied to aged US Select strip loins. This technology would allow packing companies and other segments of the beef marketing chain to identify US Select carcasses or strip loins that excel in LM tenderness for use in branded beef programs.

Re-establishment of rigor mortis: evidence for a considerably longer post-mortem time span.

PubMed

Crostack, Chiara; Sehner, Susanne; Raupach, Tobias; Anders, Sven

2017-07-01

Re-establishment of rigor mortis following mechanical loosening is used as part of the complex method for the forensic estimation of the time since death in human bodies and has formerly been reported to occur up to 8-12 h post-mortem (hpm). We recently described our observation of the phenomenon in up to 19 hpm in cases with in-hospital death. Due to the case selection (preceding illness, immobilisation), transfer of these results to forensic cases might be limited. We therefore examined 67 out-of-hospital cases of sudden death with known time points of death. Re-establishment of rigor mortis was positive in 52.2% of cases and was observed up to 20 hpm. In contrast to the current doctrine that a recurrence of rigor mortis is always of a lesser degree than its first manifestation in a given patient, muscular rigidity at re-establishment equalled or even exceeded the degree observed before dissolving in 21 joints. Furthermore, this is the first study to describe that the phenomenon appears to be independent of body or ambient temperature.

Maggot development during morgue storage and its effect on estimating the post-mortem interval.

PubMed

Huntington, Timothy E; Higley, Leon G; Baxendale, Frederick P

2007-03-01

When insect evidence is obtained during autopsy, forensic entomologists make decisions regarding the effects of low-temperature (-1 degrees C to 4 degrees C) storage of the body and associated insects when estimating the post-mortem interval (PMI). To determine the effects of storage in a morgue cooler on the temperature of maggot masses, temperatures inside and outside of body bags containing a human cadaver and porcine cadavers (seven replicates) were measured during storage. Temperatures remained significantly higher (p<0.05) inside of the body bags relative to the cooler, and remained at levels sufficient for maggot feeding and development. If the assumption that no insect development takes place during preautopsy refrigeration is made, potential error rates in PMI estimation of 8.6-12.8% occur. The potential for blow fly larvae to undergo significant development while being stored in the morgue is a possibility that forensic entomologists should consider during an investigation involving samples collected from autopsy. Case and experimental evidence also demonstrate that substantial tissue loss can occur from maggot feeding during morgue storage.

State-of-the-art of bone marrow analysis in forensic toxicology: a review.

PubMed

Cartiser, Nathalie; Bévalot, Fabien; Fanton, Laurent; Gaillard, Yvan; Guitton, Jérôme

2011-03-01

Although blood is the reference medium in the field of forensic toxicology, alternative matrices are required in case of limited, unavailable or unusable blood samples. The present review investigated the suitability of bone marrow (BM) as an alternative matrix to characterize xenobiotic consumption and its influence on the occurrence of death. Basic data on BM physiology are reported in order to highlight the specificities of this matrix and their analytical and toxicokinetic consequences. A review of case reports, animal and human studies involving BM sample analysis focuses on the various parameters of interpretation of toxicological results: analytic limits, sampling location, pharmacokinetics, blood/BM concentration correlation, stability and postmortem redistribution. Tables summarizing the analytical conditions and quantification of 45 compounds from BM samples provide a useful tool for toxicologists. A specific section devoted to ethanol shows that, despite successful quantification, interpretation is highly dependent on postmortem interval. In conclusion, BM is an interesting alternative matrix, and further experimental data and validated assays are required to confirm its great potential relevance in forensic toxicology.

Postmortem ICD interrogation in mode of death classification.

PubMed

Nikolaidou, Theodora; Johnson, Miriam J; Ghosh, Justin M; Marincowitz, Carl; Shah, Saumil; Lammiman, Michael J; Schilling, Richard J; Clark, Andrew L

2018-04-01

The definition of sudden death due to arrhythmia relies on the time interval between onset of symptoms and death. However, not all sudden deaths are due to arrhythmia. In patients with an implantable cardioverter defibrillator (ICD), postmortem device interrogation may help better distinguish the mode of death compared to a time-based definition alone. This study aims to assess the proportion of "sudden" cardiac deaths in patients with an ICD that have confirmed arrhythmia. We conducted a literature search for studies using postmortem ICD interrogation and a time-based classification of the mode of death. A modified QUADAS-2 checklist was used to assess risk of bias in individual studies. Outcome data were pooled where sufficient data were available. Our search identified 22 studies undertaken between 1982 and 2015 with 23,600 participants. The pooled results (excluding studies with high risk of bias) suggest that ventricular arrhythmias are present at the time of death in 76% of "sudden" deaths (95% confidence interval [CI] 67-85; range 42-88). Postmortem ICD interrogation identifies 24% of "sudden" deaths to be nonarrhythmic. Postmortem device interrogation should be considered in all cases of unexplained sudden cardiac death. © 2018 Wiley Periodicals, Inc.

Postmortem distribution of guaifenesin concentrations reveals a lack of potential for redistribution.

PubMed

McIntyre, Iain M; Navarrete, Aylmer; Mena, Othon

2014-12-01

Therapeutic (or non-toxic) postmortem guaifenesin blood and liver concentrations have not been previously described. Peripheral blood guaifenesin concentrations were compared to central blood and liver concentrations in eight medical examiner cases. Specimens were initially screened for alcohol and simple volatiles, drugs of abuse, alkaline, and acid/neutral drugs. Guaifenesin, when detected by the acid/neutral drug screen, was subsequently confirmed and quantified by a high performance liquid chromatography procedure. Data suggest that postmortem guaifenesin peripheral blood concentrations may be considered non-toxic to at least 5.4mg/L with liver concentrations to at least 7.0mg/kg. Overall, guaifenesin concentrations ranged from 1.9 to 40mg/L in peripheral blood, 2.2-150mg/L in central blood, and 2.6-36mg/kg in liver. The median guaifenesin central blood to peripheral blood ratio was 1.1 (N=8). Similarly, liver to peripheral blood ratios showed a median value of 0.9L/kg (N=5). Given that a liver to peripheral blood ratio less than 5L/kg is consistent with little to no propensity for postmortem redistribution, these data suggest that guaifenesin is not prone to substantial postmortem redistribution. Published by Elsevier Ireland Ltd.

14. VIEW IN THE WEST OPERATING GALLERY OF POSTMORTEM CELL ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

14. VIEW IN THE WEST OPERATING GALLERY OF POST-MORTEM CELL WORK STATION AND MANIPULATOR ARMS. - Nevada Test Site, Engine Maintenance Assembly & Disassembly Facility, Area 25, Jackass Flats, Mercury, Nye County, NV

Neurodevelopmental model of schizophrenia: update 2012

PubMed Central

Rapoport, JL; Giedd, JN; Gogtay, N

2012-01-01

The neurodevelopmental model of schizophrenia, which posits that the illness is the end state of abnormal neurodevelopmental processes that started years before the illness onset, is widely accepted, and has long been dominant for childhood-onset neuropsychiatric disorders. This selective review updates our 2005 review of recent studies that have impacted, or have the greatest potential to modify or extend, the neurodevelopmental model of schizophrenia. Longitudinal whole-population studies support a dimensional, rather than categorical, concept of psychosis. New studies suggest that placental pathology could be a key measure in future prenatal high-risk studies. Both common and rare genetic variants have proved surprisingly diagnostically nonspecific, and copy number variants (CNVs) associated with schizophrenia are often also associated with autism, epilepsy and intellectual deficiency. Large post-mortem gene expression studies and prospective developmental multi-modal brain imaging studies are providing critical data for future clinical and high-risk developmental brain studies. Whether there can be greater molecular specificity for phenotypic characterization is a subject of current intense study and debate, as is the possibility of neuronal phenotyping using human pluripotent-inducible stem cells. Biological nonspecificity, such as in timing or nature of early brain development, carries the possibility of new targets for broad preventive treatments. PMID:22488257

Attempts to revive Mycobacterium tuberculosis from 300-year-old human mummies.

PubMed

Lemma, Eshetu; Zimhony, Oren; Greenblatt, Charles L; Koltunov, Viktoria; Zylber, María Inés; Vernon, Kim; Spigelman, Mark

2008-06-01

Environmental persistence of Mycobacterium tuberculosis is subject to speculation. However, the reality that infected postmortem tissues can be a danger to pathologists and embalmers has worrisome implications. A few experimental studies have demonstrated the organism's ability to withstand exposure to embalming fluid and formalin. Recently, a failure was reported in an attempt to resuscitate an original isolate of Robert Koch to determine the lifetime of the tubercle bacillus. The present study also considers a historical approach to determine persistence under favorable environmental conditions. It asks whether acid-fast forms observed in tissues of 300-year-old Hungarian mummies can be resuscitated. Finding organisms before the advent of antibiotics and pasteurization may yield valuable genetic information. Using various media modifications, as well as guinea pig inoculation, an attempt was made to culture these tissues for M. tuberculosis. In addition, a resuscitation-promoting factor, known to increase colony counts in high G+C bacteria, was applied to the cultures. Although an occasional PCR-positive sample was detected, no colonies of M. tuberculosis were obtained. Our results may indicate that the life span of the tubercle bacillus is less than a few hundred years, even though in the short run it can survive harsh chemical treatment.

PKCδ inhibition normalizes the wound-healing capacity of diabetic human fibroblasts.

PubMed

Khamaisi, Mogher; Katagiri, Sayaka; Keenan, Hillary; Park, Kyoungmin; Maeda, Yasutaka; Li, Qian; Qi, Weier; Thomou, Thomas; Eschuk, Danielle; Tellechea, Ana; Veves, Aris; Huang, Chenyu; Orgill, Dennis Paul; Wagers, Amy; King, George L

2016-03-01

Abnormal fibroblast function underlies poor wound healing in patients with diabetes; however, the mechanisms that impair wound healing are poorly defined. Here, we evaluated fibroblasts from individuals who had type 1 diabetes (T1D) for 50 years or more (Medalists, n = 26) and from age-matched controls (n = 7). Compared with those from controls, Medalist fibroblasts demonstrated a reduced migration response to insulin, lower VEGF expression, and less phosphorylated AKT (p-AKT), but not p-ERK, activation. Medalist fibroblasts were also functionally less effective at wound closure in nude mice. Activation of the δ isoform of protein kinase C (PKCδ) was increased in postmortem fibroblasts from Medalists, fibroblasts from living T1D subjects, biopsies of active wounds of living T1D subjects, and granulation tissues from mice with streptozotocin-induced diabetes. Diabetes-induced PKCD mRNA expression was related to a 2-fold increase in the mRNA half-life. Pharmacologic inhibition and siRNA-mediated knockdown of PKCδ or expression of a dominant-negative isoform restored insulin signaling of p-AKT and VEGF expression in vitro and improved wound healing in vivo. Additionally, increasing PKCδ expression in control fibroblasts produced the same abnormalities as those seen in Medalist fibroblasts. Our results indicate that persistent PKCδ elevation in fibroblasts from diabetic patients inhibits insulin signaling and function to impair wound healing and suggest PKCδ inhibition as a potential therapy to improve wound healing in diabetic patients.

Lateral hypothalamic orexin and melanin-concentrating hormone neurons provide direct input to gonadotropin-releasing hormone neurons in the human

PubMed Central

Skrapits, Katalin; Kanti, Vivien; Savanyú, Zsófia; Maurnyi, Csilla; Szenci, Ottó; Horváth, András; Borsay, Beáta Á.; Herczeg, László; Liposits, Zsolt; Hrabovszky, Erik

2015-01-01

Hypophysiotropic projections of gonadotropin-releasing hormone (GnRH)-synthesizing neurons form the final common output way of the hypothalamus in the neuroendocrine control of reproduction. Several peptidergic neuronal systems of the medial hypothalamus innervate human GnRH cells and mediate crucially important hormonal and metabolic signals to the reproductive axis, whereas much less is known about the contribution of the lateral hypothalamic area to the afferent control of human GnRH neurons. Orexin (ORX)- and melanin-concentrating hormone (MCH)-synthesizing neurons of this region have been implicated in diverse behavioral and autonomic processes, including sleep and wakefulness, feeding and other functions. In the present immunohistochemical study, we addressed the anatomical connectivity of these neurons to human GnRH cells in post-mortem hypothalamic samples obtained from autopsies. We found that 38.9 ± 10.3% and 17.7 ± 3.3% of GnRH-immunoreactive (IR) perikarya in the infundibular nucleus of human male subjects received ORX-IR and MCH-IR contacts, respectively. On average, each 1 mm segment of GnRH dendrites received 7.3 ± 1.1 ORX-IR and 3.7 ± 0.5 MCH-IR axo-dendritic appositions. Overall, the axo-dendritic contacts dominated over the axo-somatic contacts and represented 80.5 ± 6.4% of ORX-IR and 76.7 ± 4.6% of MCH-IR inputs to GnRH cells. Based on functional evidence from studies of laboratory animals, the direct axo-somatic and axo-dendritic input from ORX and MCH neurons to the human GnRH neuronal system may convey critical metabolic and other homeostatic signals to the reproducive axis. In this study, we also report the generation and characterization of new antibodies for immunohistochemical detection of GnRH neurons in histological sections. PMID:26388735

Altered pharyngeal muscles in Parkinson disease.

PubMed

Mu, Liancai; Sobotka, Stanislaw; Chen, Jingming; Su, Hungxi; Sanders, Ira; Adler, Charles H; Shill, Holly A; Caviness, John N; Samanta, Johan E; Beach, Thomas G

2012-06-01

Dysphagia (impaired swallowing) is common in patients with Parkinson disease (PD) and is related to aspiration pneumonia, the primary cause of death in PD. Therapies that ameliorate the limb motor symptoms of PD are ineffective for dysphagia. This suggests that the pathophysiology of PD dysphagia may differ from that affecting limb muscles, but little is known about potential neuromuscular abnormalities in the swallowing muscles in PD. This study examined the fiber histochemistry of pharyngeal constrictor and cricopharyngeal sphincter muscles in postmortem specimens from 8 subjects with PD and 4 age-matched control subjects. Pharyngeal muscles in subjects with PD exhibited many atrophic fibers, fiber type grouping, and fast-to-slow myosin heavy chain transformation. These alterations indicate that the pharyngeal muscles experienced neural degeneration and regeneration over the course of PD. Notably, subjects with PD with dysphagia had a higher percentage of atrophic myofibers versus with those without dysphagia and controls. The fast-to-slow fiber-type transition is consistent with abnormalities in swallowing, slow movement of food, and increased tone in the cricopharyngeal sphincter in subjects with PD. The alterations in the pharyngeal muscles may play a pathogenic role in the development of dysphagia in subjects with PD.

Structural Associations of Symptomatic Knee Osteoarthritis

PubMed Central

Stoppiello, Laura A; Mapp, Paul I; Wilson, Deborah; Hill, Roger; Scammell, Brigitte E; Walsh, David A

2014-01-01

Objective Structural changes of osteoarthritis (OA) may occur in the absence of pain. In this study, we aimed to identify histopathologic features that are associated with symptomatic knee OA. Methods Medial tibial plateaus and synovium samples were obtained at the time of total knee replacement (TKR) surgery for OA (advanced OA group) or were obtained postmortem from subjects who had not sought medical attention for knee pain during the last year of life (non-OA control group). To identify features of OA, we compared the patients with advanced OA with the age-matched non-OA controls (n = 26 per group). To identify OA features associated with symptoms, we compared two additional groups of subjects who were matched for severity of chondropathy (n = 29 per group): patients undergoing TKR for symptomatic OA (symptomatic chondropathy group) and postmortem subjects with similar severity of chondropathy who were asymptomatic during the last year of life (asymptomatic chondropathy group). The histologic features of the samples were graded, and immunoreactivities for macrophages (CD68) and nerve growth factor (NGF) in the synovium were quantified. The cellular localization of synovial NGF was determined by double immunofluorescence analysis. Results Advanced OA cases displayed more severe changes in the synovium (synovitis, increased synovial NGF, and CD68-immunoreactive macrophages) and cartilage (loss of cartilage surface integrity, loss of proteoglycan, tidemark breaching, and alterations in chondrocyte morphology) than did the non-OA controls. Synovial NGF was localized predominantly to fibroblasts and to some macrophages. The symptomatic chondropathy group displayed greater levels of synovitis, synovial NGF, and loss of cartilage integrity, in addition to alterations in chondrocyte morphology, than did the asymptomatic chondropathy group (P < 0.05 for each comparison). Conclusion Synovitis, increased synovial NGF, alterations in chondrocyte morphology, and loss of cartilage integrity are features of knee OA that may be associated with symptoms. PMID:25049144

SU-F-SPS-03: Direct Measurement of Organ Doses Resulting From Head and Cervical Spine Trauma CT Protocols

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carranza, C; Lipnharski, I; Quails, N

Purpose: This retrospective study analyzes the exposure history of emergency department (ED) patients undergoing head and cervical spine trauma computed tomography (CT) studies. This study investigated dose levels received by trauma patients and addressed any potential concerns regarding radiation dose issues. Methods: Under proper IRB approval, a cohort of 300 trauma cases of head and cervical spine trauma CT scans received in the ED was studied. The radiological image viewing software of the hospital was used to view patient images and image data. The following parameters were extracted: the imaging history of patients, the reported dose metrics from the scannermore » including the volumetric CT Dose Index (CTDIvol) and Dose Length Product (DLP). A postmortem subject was scanned using the same scan techniques utilized in a standard clinical head and cervical spine trauma CT protocol with 120 kVp and 280 mAs. The CTDIvol was recorded for the subject and the organ doses were measured using optically stimulated luminescent (OSL) dosimeters. Typical organ doses to the brain, thyroid, lens, salivary glands, and skin, based on the cadaver studies, were then calculated and reported for the cohort. Results: The CTDIvol reported by the CT scanner was 25.5 mGy for the postmortem subject. The average CTDIvol from the patient cohort was 34.1 mGy. From these metrics, typical average organ doses in mGy were found to be: Brain (44.57), Thyroid (33.40), Lens (82.45), Salivary Glands (61.29), Skin (47.50). The imaging history of the cohort showed that on average trauma patients received 26.1 scans over a lifetime. Conclusion: The average number of scans received on average by trauma ED patients shows that radiation doses in trauma patients may be a concern. Available dose tracking software would be helpful to track doses in trauma ED patients, highlighting the importance of minimizing unnecessary scans and keeping doses ALARA.« less

Region-specific Alterations in Glucocorticoid Receptor Expression in the Postmortem Brain of Teenage Suicide Victims

PubMed Central

Pandey, Ghanshyam N.; Rizavi, Hooriyah S.; Ren, Xinguo; Dwivedi, Yogesh; Palkovits, Miklós

2013-01-01

Introduction Abnormal function of the hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the pathophysiology of depression and suicide. The purpose of this study was to test the hypothesis that the reported dysregulation of the HPA axis in suicide may be related to a disturbed feedback inhibition caused by decreased corticoid receptors in the brain. We therefore determined the protein and gene expression of glucocorticoid (GR) and mineralocorticoid receptors (MR) in the postmortem brain of teenage suicide victims and matched normal controls. Methods Protein and mRNA expression of GR (GR-α and GR-β) and MR and the mRNA expression of glucocorticoid-induced leucine zipper (GILZ), a target gene for GR were determined by immunolabeling using Western blot technique and the real-time RT-polymerase chain reaction (qPCR) technique in the prefrontal cortex (PFC), hippocampus, subiculum, and amygdala obtained from 24 teenage suicide victims and 24 teenage control subjects. Results We observed that protein and gene expression of GR-α was significantly decreased in the PFC and amygdala, but not in the hippocampus or subiculum, of teenage suicide victims compared with normal control subjects. Also, the mRNA levels of GR inducible target gene GILZ was significantly decreased in PFC and amygdaloid nuclei but not in hippocampus compared with controls. In contrast, no significant differences were observed in protein or gene expression of MR in any of the areas studied between teenage suicide victims and normal control subjects. There was no difference in the expression of GR-β in the PFC between suicide victims and normal controls. Conclusions These results suggested that the observed dysregulation of the HPA axis in suicide may be related to a decreased expression of GR-α and GR inducible genes in the PFC and amygdala of teenage suicide victims. The reason why GR receptors are not dysregulated in the hippocampus or subiculum, presumably two sites of stress action, are not clear at this time. PMID:23845513

Relationship between clinical signs and postmortem test status in cattle experimentally infected with the bovine spongiform encephalopathy agent

PubMed Central

2010-01-01

Background Various clinical protocols have been developed to aid in the clinical diagnosis of classical bovine spongiform encephalopathy (BSE), which is confirmed by postmortem examinations based on vacuolation and accumulation of disease-associated prion protein (PrPd) in the brain. The present study investigated the occurrence and progression of sixty selected clinical signs and behaviour combinations in 513 experimentally exposed cattle subsequently categorised postmortem as confirmed or unconfirmed BSE cases. Appropriate undosed or saline inoculated controls were examined similarly and the data analysed to explore the possible occurrence of BSE-specific clinical expression in animals unconfirmed by postmortem examinations. Results Based on the display of selected behavioural, sensory and locomotor changes, 20 (67%) orally dosed and 17 (77%) intracerebrally inoculated pathologically confirmed BSE cases and 21 (13%) orally dosed and 18 (6%) intracerebrally inoculated but unconfirmed cases were considered clinical BSE suspects. None of 103 controls showed significant signs and were all negative on diagnostic postmortem examinations. Signs indicative of BSE suspects, particularly over-reactivity and ataxia, were more frequently displayed in confirmed cases with vacuolar changes in the brain. The display of several BSE-associated signs over time, including repeated startle responses and nervousness, was significantly more frequent in confirmed BSE cases compared to controls, but these two signs were also significantly more frequent in orally dosed cattle unconfirmed by postmortem examinations. Conclusions The findings confirm that in experimentally infected cattle clinical abnormalities indicative of BSE are accompanied by vacuolar changes and PrPd accumulation in the brainstem. The presence of more frequently expressed signs in cases with vacuolar changes is consistent with this pathology representing a more advanced stage of disease. That BSE-like signs or sign combinations occur in inoculated animals that were not confirmed as BSE cases by postmortem examinations requires further study to investigate the potential causal relationship with prion disease. PMID:21143919

[The foreign experience with the application of the modern radiodiagnostic methods for the estimation of prescription of death coming and time of infliction of injury].

PubMed

Fetisov, V A; Kuprina, T A; Sinitsyn, V E; Dubrova, S E; Filimonov, B A

2016-01-01

We undertook the analysis of the foreign publications concerning the application of the modern radiodiagnostic methods (including MSCT- and MRI-visualization) with reference to the solution of the traditional problems facing forensic medical expertise, such as the estimation of prescription of death coming and time of infliction of injury in the dead bodies. Both advantages and disadvantages of postmortem visualization of the corpses of adult subjects are discussed taking into consideration the period of time that elapsed between the death and the onset of the study as well as the character of the injuries. It was shown that the examination of the corpses using the up-to-date methods of radiodiagnostics prior to autopsy makes it possible for morphologists, jointly with radiologists, to identify, to see in the new light, and to evaluate the number of charges in the dead body, such as the alteration of the blood cell sedimentation rate, the formation of postmortem hypostases in the internal organs, the hardening of the walls of aorta and major blood vessels, right heart dilatation, gradual smoothing of the borderline between grey and white matter of the brain. Virtual autopsy can be useful , even for the study of such long-term processes in the corpses as putrefaction, saponification, mummification, and peat tanning. Moreover, this technique may be instrumental in the elucidation of the specific features of topographic-anatomical relationships between individual 'tissues and organs, detection of the concealed lesions, and a variety of pathological changes. Postmortem visualization allows for the quantitative evaluation of the severity of these transformations and the preliminary estimation of prescription of death coming. Also, radiodiagnostic methods can be employed to reliably visualize and measure various hemorrhagic events (from the density of such ones as liquid and clotted blood) in the tissues surrounding the fractures, in body cavities, and internal organs as well as to establish the facts of inter-vital aspiration of blood, alimentary masses, liquid and solid foreign bodies penetrating into the upper sections of the respiratory and gastrointestinal tracts as the consequence f an injury. It is concluded that the postmortem visualization techniques employed to estimate prescription of death coming and time of infliction of injury as well as other complicated problems facing forensic medical expertize need the further scientifically based development.

A review of ethylphenidate in deaths in east and west Scotland.

PubMed

Parks, Claire; McKeown, Denise; Torrance, Hazel J

2015-12-01

Ethylphenidate is a psychostimulant and analogue of methylphenidate. Interestingly it is also produced as a metabolite from the co-ingestion of methylphenidate and alcohol (ethanol). In the UK, between April and June 2015, ethylphenidate and 6 other methylphenidate based novel psychoactive substances (NPS) were subjected to a temporary class drug order under the Misuse of Drugs Act 1971. Ethylphenidate is being abused by both novel and habitual drug users, more prominently in the East of Scotland. What is unknown in the literature is the contribution of ethylphenidate in deaths. A search was conducted for an 18 month period (July 2013 to December 2014) to identify cases where ethylphenidate was detected during post-mortem toxicological analysis. Nineteen cases were identified and these cases were examined with regards to case circumstances, pathology findings, toxicology results and adverse effects. The individuals ranged in age from 20 to 54 (median 37) and the majority were male (n=14) and from the East of Scotland (n=16), more specifically Edinburgh and surrounding area. Current or previous heroin abuse was a common theme in these cases (n=16) and injection was a common route of administration of "legal highs" or "burst". The concentration of ethylphenidate in the cases ranged from 0.008 mg/L to over 2 mg/L in post-mortem femoral blood (median 0.25 mg/L, average 0.39 mg/L). Other drugs commonly detected were benzodiazepines (n=15), followed by opiates (n=11, 4 of which were positive for 6-monoacetylmorphine) and then methadone (n=8). All 19 cases received a full post-mortem examination and there were 10 cases where drug toxicity was the sole or potentially contributory factor to the cause of death. Ethylphenidate was specifically mentioned in the cause of death for 5 cases, chronic intravenous (IV) drug use was named as part of the cause of death for 2 cases and in 6 cases there was evidence of complications and infections through IV drug use. As far as it is known to the authors, this is the first review of post-mortem cases involving the use of ethylphenidate in East and West Scotland. This study can be used as a guide for toxicologists and pathologists when interpreting cases which are positive for ethylphenidate. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Bony injuries in homicide cases (1994-2014). A retrospective study.

PubMed

Flieger, Alexander; Kölzer, Sarah C; Plenzig, Stefanie; Heinbuch, Sara; Kettner, Mattias; Ramsthaler, Frank; Verhoff, Marcel A

2016-09-01

Even when human skeletal remains are found in contexts indicative of body disposal after homicide, none of the bones may manifest injuries. When skeletons are incomplete, there are two possibilities, the injured bones are missing or none were injured. This leads to the question how frequently bones are injured during homicide, where the injuries tend to be placed, and whether the frequency of injury is related to the type of homicide. To answer these questions, the postmortem reports from all autopsies performed for homicide victims at the Institute of Legal Medicine at the University Hospital in Frankfurt am Main, Germany, between 1994 and 2014, were retrospectively evaluated for bony injuries discovered during autopsy. In 90 cases, a preliminary postmortem computed tomography (pmCT) examination had been performed. The cases were categorized into the following five groups by type of fatal trauma: blunt force, sharp force, gunshot injury, strangulation, or other. In total, the postmortem reports for 897 homicides (527 male, 370 female) were evaluated. The number of victims per trauma category were sharp force, 309; blunt force, 179; gunshot injury, 242; strangulation, 92; and other, 75. Bony injuries had been reported in 70.9 % of the homicides. The "gunshot" category contained the highest proportion of victims with bony injuries (92.6 %). With 80.4 %, the second-highest proportion of victims with bony injuries was in the "blunt force" category, followed by 66.3 % of victims in the "sharp force" group. In contrast, with 53.3 %, the second-lowest proportion of victims with bony injuries was in the "strangulation" category, which contained a preponderance of female victims, followed by 17.3 % of victims with bony injuries in the "other" category. Bony injuries thus occurred in the majority of homicides. Forensic osteological analysis should, therefore, always be performed on badly decomposed human remains. Where necessary, the additional use of visualization techniques, in particular, pmCT, or maceration may be considered. The absence of bony injuries does not rule out homicide; e.g., in strangulations, bony injuries are manifest in only half the victims, even when the skeleton is intact. The relevant structures are also easily lost to decomposition, scavenging, or scattering.

Venous air embolism: An under-recognised entity in blunt-force trauma and the importance of radiology.

PubMed

du Plessis, Marna; du Toit-Prinsloo, Lorraine

2017-04-01

Air embolism (AE) is considered a rare event and can be either iatrogenic or traumatic. Various post-mortem methods to detect AE exist, of which radiology is preferred. The presence of air in the heart can be demonstrated using special dissection techniques where the heart is opened under water or by needle puncture from a water-filled syringe. Three cases of blunt-force head injury are presented herein, with AE being diagnosed by conventional radiography using a Lodox Statscan® full-body digital X-ray machine in all cases. This case series demonstrates that AE due to blunt-force trauma to the head and sinuses might be under-recognised in the forensic post-mortem setting. It also highlights the importance of radiology in diagnosing AE post-mortem, especially where the results of post-mortem techniques might be unsatisfactory.

[The expressions of HSP 70 mRNA and c-fos mRNA in the skeletal muscle and cardiac muscle of rabbits by electrocuted].

PubMed

Wang, Ye; Liu, Min; Cheng, Wei-bo; He, Gui-qiong; Li, Fan; Liao, Zhi-gang

2008-08-01

To study the changes of HSP 70 mRNA and c-fos mRNA expression and to find a method to differentiate antemortem from postmortem electrocution. Fifteen New Zealand rabbits were randomly divided into three groups, the antemortem electrocution group, the postmortem electrocution group, and the control group. Each group consists of five rabbits. The levels of HSP 70 mRNA and c-fos mRNA in skeletal muscle and cardiac muscle were examined with quantitative fluorescent RT-PCR. The levels of HSP 70 mRNA and c-fos mRNA in the antemortem electrocution group increased significantly (P<0.05), compared with that of the postmortem electrocution group. The changes of HSP 70 mRNA and c-fos mRNA expression in skeletal muscle and cardiac muscle can be used as an indicator to distinguish antemortem from postmortem electrocution.

Convection Enhanced Delivery: A Comparison of infusion characteristics in ex vivo and in vivo non-human primate brain tissue.

PubMed

Miranpuri, Gurwattan; Hinchman, Angelica; Wang, Anyi; Schomberg, Dominic; Kubota, Ken; Brady, Martin; Raghavan, Raghu; Bruner, Kevin; Brodsky, Ethan; Block, Walter; Grabow, Ben; Raschke, Jim; Alexander, Andrew; Ross, Chris; Simmons, Heather; Sillay, Karl

2013-07-01

Convection enhanced delivery (CED) is emerging as a promising infusion toolto facilitate delivery of therapeutic agents into the brain via mechanically controlled pumps. Infusion protocols and catheter design have an important impact on delivery. CED is a valid alternative for systemic administration of agents in clinical trials for cell and gene therapies. Where gel and ex vivo models are not sufficient in modeling the disease, in vivo models allow researchers to better understand the underlying mechanisms of neuron degeneration, which is helpful in finding novel approaches to control the process or reverse the progression. Determining the risks, benefits, and efficacy of new gene therapies introduced via CED will pave a way to enter human clinical trial. The objective of this study is to compare volume distribution (Vd)/ volume infused (Vi) ratios and backflow measurements following CED infusions in ex vivo versus in vivo non-human primate brain tissue, based on infusion protocols developed in vitro. In ex vivo infusions, the first brain received 2 infusions using a balloon catheter at rates of 1 μL/min and 2 μL/min for 30 minutes. The second and third brains received infusions using a valve-tip (VT) catheter at 1 μL/min for 30 minutes. The fourth brain received a total of 45 μL infused at a rate of 1 μL/min for 15 minutes followed by 2 μL/min for 15 minutes. Imaging was performed (SPGR FA34) every 3 minutes. In the in vivo group, 4 subjects received a total of 8 infusions of 50 μL. Subjects 1 and 2 received infusions at 1.0 μL/min using a VT catheter in the left hemisphere and a smart-flow (SF) catheter in the right hemisphere. Subjects 3 and 4 each received 1 infusion in the left and right hemisphere at 1.0 μL/min. MRI calculations of Vd/Vi did not significantly differ from those obtained on post-mortem pathology. The mean measured Vd/Vi of in vivo (5.23 + /-1.67) compared to ex vivo (2.17 + /-1.39) demonstrated a significantly larger Vd/Vi for in vivo by 2.4 times (p = 0.0017). We detected higher ratios in the in vivo subjects than in ex vivo. This difference could be explained by the extra cellular space volume fraction. Studies evaluating backflow and morphology use in vivo tissue as a medium are recommended. Further investigation is warranted to evaluate the role blood pressure and heart rate may play in human CED clinical trials.

Expansion of Microbial Forensics.

PubMed

Schmedes, Sarah E; Sajantila, Antti; Budowle, Bruce

2016-08-01

Microbial forensics has been defined as the discipline of applying scientific methods to the analysis of evidence related to bioterrorism, biocrimes, hoaxes, or the accidental release of a biological agent or toxin for attribution purposes. Over the past 15 years, technology, particularly massively parallel sequencing, and bioinformatics advances now allow the characterization of microorganisms for a variety of human forensic applications, such as human identification, body fluid characterization, postmortem interval estimation, and biocrimes involving tracking of infectious agents. Thus, microbial forensics should be more broadly described as the discipline of applying scientific methods to the analysis of microbial evidence in criminal and civil cases for investigative purposes. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Laser balloon angioplasty: effect of tissue temperature on weld strength of human postmortem intima-media separations.

PubMed

Jenkins, R D; Sinclair, I N; Anand, R; Kalil, A G; Schoen, F J; Spears, J R

1988-01-01

Dehiscence of portions of atheromatous plaques fractured during percutaneous transluminal coronary angioplasty may contribute to both abrupt reclosure and gradual restenosis. Laser balloon angioplasty has been shown to be effective in welding human plaque-arterial wall separations in vitro by heating tissues with a Nd:YAG laser during balloon inflation. To define the potentially useful therapeutic range of tissue temperature required to achieve thermal welds, 220 1-cm diameter discs of human postmortem atheromatous aortic tissue, the intimal plaque of which had been separated from the media, were exposed to 3-25 watts of Nd:YAG laser radiation delivered over a 12-mm2 nominal spot size for 20 seconds via a 400-micron core optical fiber. As measured with a thermistor, adventitial temperature reflected the temperature at the plaque-media junction to within 10 degrees C. The degree of tissue temperature elevation was related to delivered energy, while effective tissue penetration increased to maximum depth of 3 mm at the highest power density. Strength of tissue welds was defined as the force required to shear opposing layers of welded segments. Adventitial tissue temperatures below 80 degrees C were not associated with appreciable welds, while equilibrium temperatures between 95 degrees C and 140 degrees C were consistently associated with effective mean weld strengths, which increased linearly from 25 to 110 g, respectively. Temperatures greater than 150 degrees C were associated with rapid tissue dehydration and charring. These data suggest that the therapeutic range of tissue temperature that provides effective thermal fusion of intima-media separations is broad and that the depth and degree of thermal coagulation can be controlled by manipulation of laser energy delivery.

Mechanical disruption of the blood-brain barrier following experimental concussion.

PubMed

Johnson, Victoria E; Weber, Maura T; Xiao, Rui; Cullen, D Kacy; Meaney, David F; Stewart, William; Smith, Douglas H

2018-05-01

Although concussion is now recognized as a major health issue, its non-lethal nature has limited characterization of the underlying pathophysiology. In particular, potential neuropathological changes have typically been inferred from non-invasive techniques or post-mortem examinations of severe traumatic brain injury (TBI). Here, we used a swine model of head rotational acceleration based on human concussion to examine blood-brain barrier (BBB) integrity after injury in association with diffuse axonal injury and glial responses. We then determined the potential clinical relevance of the swine concussion findings through comparisons with pathological changes in human severe TBI, where post-mortem examinations are possible. At 6-72 h post-injury in swine, we observed multifocal disruption of the BBB, demonstrated by extravasation of serum proteins, fibrinogen and immunoglobulin-G, in the absence of hemorrhage or other focal pathology. BBB disruption was observed in a stereotyped distribution consistent with biomechanical insult. Specifically, extravasated serum proteins were frequently observed at interfaces between regions of tissue with differing material properties, including the gray-white boundary, periventricular and subpial regions. In addition, there was substantial overlap of BBB disruption with regions of axonal pathology in the white matter. Acute perivascular cellular uptake of blood-borne proteins was observed to be prominent in astrocytes (GFAP-positive) and neurons (MAP-2-positive), but not microglia (IBA1-positive). Parallel examination of human severe TBI revealed similar patterns of serum extravasation and glial uptake of serum proteins, but to a much greater extent than in the swine model, attributed to the higher injury severity. These data suggest that BBB disruption represents a new and important pathological feature of concussion.

Native Mutant Huntingtin in Human Brain

PubMed Central

Sapp, Ellen; Valencia, Antonio; Li, Xueyi; Aronin, Neil; Kegel, Kimberly B.; Vonsattel, Jean-Paul; Young, Anne B.; Wexler, Nancy; DiFiglia, Marian

2012-01-01

Huntington disease (HD) is caused by polyglutamine expansion in the N terminus of huntingtin (htt). Analysis of human postmortem brain lysates by SDS-PAGE and Western blot reveals htt as full-length and fragmented. Here we used Blue Native PAGE (BNP) and Western blots to study native htt in human postmortem brain. Antisera against htt detected a single band broadly migrating at 575–850 kDa in control brain and at 650–885 kDa in heterozygous and Venezuelan homozygous HD brains. Anti-polyglutamine antisera detected full-length mutant htt in HD brain. There was little htt cleavage even if lysates were pretreated with trypsin, indicating a property of native htt to resist protease cleavage. A soluble mutant htt fragment of about 180 kDa was detected with anti-htt antibody Ab1 (htt-(1–17)) and increased when lysates were treated with denaturants (SDS, 8 m urea, DTT, or trypsin) before BNP. Wild-type htt was more resistant to denaturants. Based on migration of in vitro translated htt fragments, the 180-kDa segment terminated ≈htt 670–880 amino acids. If second dimension SDS-PAGE followed BNP, the 180-kDa mutant htt was absent, and 43–50 kDa htt fragments appeared. Brain lysates from two HD mouse models expressed native full-length htt; a mutant fragment formed if lysates were pretreated with 8 m urea + DTT. Native full-length mutant htt in embryonic HD140Q/140Q mouse primary neurons was intact during cell death and when cell lysates were exposed to denaturants before BNP. Thus, native mutant htt occurs in brain and primary neurons as a soluble full-length monomer. PMID:22375012

Brain urea increase is an early Huntington's disease pathogenic event observed in a prodromal transgenic sheep model and HD cases.

PubMed

Handley, Renee R; Reid, Suzanne J; Brauning, Rudiger; Maclean, Paul; Mears, Emily R; Fourie, Imche; Patassini, Stefano; Cooper, Garth J S; Rudiger, Skye R; McLaughlan, Clive J; Verma, Paul J; Gusella, James F; MacDonald, Marcy E; Waldvogel, Henry J; Bawden, C Simon; Faull, Richard L M; Snell, Russell G

2017-12-26

The neurodegenerative disorder Huntington's disease (HD) is typically characterized by extensive loss of striatal neurons and the midlife onset of debilitating and progressive chorea, dementia, and psychological disturbance. HD is caused by a CAG repeat expansion in the Huntingtin ( HTT ) gene, translating to an elongated glutamine tract in the huntingtin protein. The pathogenic mechanism resulting in cell dysfunction and death beyond the causative mutation is not well defined. To further delineate the early molecular events in HD, we performed RNA-sequencing (RNA-seq) on striatal tissue from a cohort of 5-y-old OVT73 -line sheep expressing a human CAG-expansion HTT cDNA transgene. Our HD OVT73 sheep are a prodromal model and exhibit minimal pathology and no detectable neuronal loss. We identified significantly increased levels of the urea transporter SLC14A1 in the OVT73 striatum, along with other important osmotic regulators. Further investigation revealed elevated levels of the metabolite urea in the OVT73 striatum and cerebellum, consistent with our recently published observation of increased urea in postmortem human brain from HD cases. Extending that finding, we demonstrate that postmortem human brain urea levels are elevated in a larger cohort of HD cases, including those with low-level neuropathology (Vonsattel grade 0/1). This elevation indicates increased protein catabolism, possibly as an alternate energy source given the generalized metabolic defect in HD. Increased urea and ammonia levels due to dysregulation of the urea cycle are known to cause neurologic impairment. Taken together, our findings indicate that aberrant urea metabolism could be the primary biochemical disruption initiating neuropathogenesis in HD.

Levels of select PCB and PBDE congeners in human post-mortem brain reveal possible environmental involvement in 15q11-q13 duplication autism spectrum disorder

PubMed Central

Mitchell, Michelle M.; Woods, Rima; Chi, Lai-Har; Schmidt, Rebecca J.; Pessah, Isaac N.; Kostyniak, Paul J.; LaSalle, Janine M.

2013-01-01

Persistent organic pollutants (POPs), including polychlorinated biphenyls (PCBs) and polybrominated diphenylethers (PBDEs) that bioaccumulate in lipid-rich tissues are of concern as developmental neurotoxicants. Epigenetic mechanisms such as DNA methylation act at the interface of genetic and environmental factors implicated in autism-spectrum disorders. The relationship between POP levels and DNA methylation patterns in individuals with and without neurodevelopmental disorders has not been previously investigated. In this study, a total of 107 human frozen post-mortem brain samples were analyzed for 8 PCBs and 7 PBDEs by GC-micro electron capture detector and GC/MS using negative chemical ionization. Human brain samples were grouped as neurotypical controls (n=43), neurodevelopmental disorders with known genetic basis (n=32, including Down, Rett, Prader-Willi, Angelman, and 15q11-q13 duplication syndromes), and autism of unknown etiology (n=32). Unexpectedly, PCB 95 was significantly higher in the genetic neurodevelopmental group, but not idiopathic autism, as compared to neurotypical controls. Interestingly, samples with detectable PCB 95 levels were almost exclusively those with maternal 15q11-q13 duplication (Dup15q) or deletion in Prader-Willi syndrome. When sorted by birth year, Dup15q samples represented five out of six of genetic neurodevelopmental samples born after the 1976 PCB ban exhibiting detectable PCB 95 levels. Dup15q was the strongest predictor of PCB 95 exposure over age, gender, or year of birth. Dup15q brain showed lower levels of repetitive DNA methylation measured by LINE-1 pyrosequencing, but methylation levels were confounded by year of birth. These results demonstrate a novel paradigm by which specific POPs may predispose to genetic copy number variation of 15q11-q13. PMID:22930557

Exploratory Metabolomic Analyses Reveal Compounds Correlated with Lutein Concentration in Frontal Cortex, Hippocampus, and Occipital Cortex of Human Infant Brain

PubMed Central

Lieblein-Boff, Jacqueline C.; Johnson, Elizabeth J.; Kennedy, Adam D.; Lai, Chron-Si; Kuchan, Matthew J.

2015-01-01

Lutein is a dietary carotenoid well known for its role as an antioxidant in the macula, and recent reports implicate a role for lutein in cognitive function. Lutein is the dominant carotenoid in both pediatric and geriatric brain tissue. In addition, cognitive function in older adults correlated with macular and postmortem brain lutein concentrations. Furthermore, lutein was found to preferentially accumulate in the infant brain in comparison to other carotenoids that are predominant in diet. While lutein is consistently related to cognitive function, the mechanisms by which lutein may influence cognition are not clear. In an effort to identify potential mechanisms through which lutein might influence neurodevelopment, an exploratory study relating metabolite signatures and lutein was completed. Post-mortem metabolomic analyses were performed on human infant brain tissues in three regions important for learning and memory: the frontal cortex, hippocampus, and occipital cortex. Metabolomic profiles were compared to lutein concentration, and correlations were identified and reported here. A total of 1276 correlations were carried out across all brain regions. Of 427 metabolites analyzed, 257 were metabolites of known identity. Unidentified metabolite correlations (510) were excluded. In addition, moderate correlations with xenobiotic relationships (2) or those driven by single outliers (3) were excluded from further study. Lutein concentrations correlated with lipid pathway metabolites, energy pathway metabolites, brain osmolytes, amino acid neurotransmitters, and the antioxidant homocarnosine. These correlations were often brain region—specific. Revealing relationships between lutein and metabolic pathways may help identify potential candidates on which to complete further analyses and may shed light on important roles of lutein in the human brain during development. PMID:26317757

Functional consequences of neurite orientation dispersion and density in humans across the adult lifespan.

PubMed

Nazeri, Arash; Chakravarty, M Mallar; Rotenberg, David J; Rajji, Tarek K; Rathi, Yogesh; Michailovich, Oleg V; Voineskos, Aristotle N

2015-01-28

As humans age, a characteristic pattern of widespread neocortical dendritic disruption coupled with compensatory effects in hippocampus and other subcortical structures is shown in postmortem investigations. It is now possible to address age-related effects on gray matter (GM) neuritic organization and density in humans using multishell diffusion-weighted MRI and the neurite-orientation dispersion and density imaging (NODDI) model. In 45 healthy individuals across the adult lifespan (21-84 years), we used a multishell diffusion imaging and the NODDI model to assess the intraneurite volume fraction and neurite orientation-dispersion index (ODI) in GM tissues. We also determined the functional correlates of variations in GM microstructure by obtaining resting-state fMRI and behavioral data. We found a significant age-related deficit in neocortical ODI (most prominently in frontoparietal regions), whereas increased ODI was observed in hippocampus and cerebellum with advancing age. Neocortical ODI outperformed cortical thickness and white matter fractional anisotropy for the prediction of chronological age in the same individuals. Higher GM ODI sampled from resting-state networks with known age-related susceptibility (default mode and visual association networks) was associated with increased functional connectivity of these networks, whereas the task-positive networks tended to show no association or even decreased connectivity. Frontal pole ODI mediated the negative relationship of age with executive function, whereas hippocampal ODI mediated the positive relationship of age with executive function. Our in vivo findings align very closely with the postmortem data and provide evidence for vulnerability and compensatory neural mechanisms of aging in GM microstructure that have functional and cognitive impact in vivo. Copyright © 2015 the authors 0270-6474/15/351753-10$15.00/0.

Pilot-Reported Beta-Blockers Identified by Forensic Toxicology Analysis of Postmortem Specimens

DOT National Transportation Integrated Search

2017-01-01

This study compared beta-blockers reported by pilots with the medications found by postmortem toxicology analysis of specimens received from fatal aviation accidents between 1999 and 2015. Several studies have compared drugs using the standard approa...

Decreased SGK1 Expression and Function Contributes to Behavioral Deficits Induced by Traumatic Stress

PubMed Central

Licznerski, Pawel; Duric, Vanja; Banasr, Mounira; Alavian, Kambiz N.; Ota, Kristie T.; Kang, Hyo Jung; Jonas, Elizabeth A.; Ursano, Robert; Krystal, John H.; Duman, Ronald S.

2015-01-01

Exposure to extreme stress can trigger the development of major depressive disorder (MDD) as well as post-traumatic stress disorder (PTSD). The molecular mechanisms underlying the structural and functional alterations within corticolimbic brain regions, including the prefrontal cortex (PFC) and amygdala of individuals subjected to traumatic stress, remain unknown. In this study, we show that serum and glucocorticoid regulated kinase 1 (SGK1) expression is down-regulated in the postmortem PFC of PTSD subjects. Furthermore, we demonstrate that inhibition of SGK1 in the rat medial PFC results in helplessness- and anhedonic-like behaviors in rodent models. These behavioral changes are accompanied by abnormal dendritic spine morphology and synaptic dysfunction. Together, the results are consistent with the possibility that altered SGK1 signaling contributes to the behavioral and morphological phenotypes associated with traumatic stress pathophysiology. PMID:26506154

Post-mortem diagnosis of chronic Chagas's disease comparative evaluation of three serological tests on pericardial fluid.

PubMed

Lopes, E R; Chapadeiro, E; Batista, S M; Cunha, J G; Rocha, A; Miziara, L; Ribeiro, J U; Patto, R J

1978-01-01

In an attempt to improve the post-mortem diagnosis of Chagas's disease the authors performed haemagglutination tests (HAT), fluorescent Trypanosoma cruzi antibody tests (FAT), and complement fixation tests (CFT) on the pericardial fluid obtained at autopsy of 50 individuals with Chagas's heart disease, and 93 patients in whom this disease was not thought to be present. The results demonstrate that all three tests are efficient for the post-mortem diagnosis of Chagas's disease but suggest that their combined use would detect more cases than would one isolated reaction only.

Association of Postmortem Blood Hemoglobin A1c Levels With Diabetic Conditions in Aviation Accident Pilot Fatalities

DTIC Science & Technology

2001-07-01

A1c ( HbA1c ) at selected time intervals during the 52-day period. Postmortem blood specimens from 34 aviation accident pilot fatalities were also...analyzed. Some of these pilots had a known history of diabetes. Results. HbA1c values in blood from volunteers did not significantly change for up to 52...days. The HbA1c concentration in postmortem blood samples from pilots ranged from 3.9-10.5%. Only one pilot with a HbA1c over 6.0% did not have a

Principles and procedures in forensic toxicology.

PubMed

Wyman, John F

2012-09-01

The principles and procedures employed in a modern forensic toxicology lab are detailed in this review. Aspects of Behavioral and Postmortem toxicology, including certification of analysts and accreditation of labs, chain of custody requirements, typical testing services provided, rationale for specimen selection, and principles of quality assurance are discussed. Interpretation of toxicology results in postmortem specimens requires the toxicologist and pathologist to be cognizant of drug-drug interactions, drug polymorphisms and pharmacogenomics, the gross signs of toxic pathology, postmortem redistribution, confirmation of systemic toxicity in suspected overdoses, the possibility of developed tolerance, and the effects of decomposition on drug concentration.

[Methodology of determination of the time of death and outlooks for the further development].

PubMed

Novikov, P I; Vlasov, A Iu; Shved, E F; Natsentov, E O; Korshunov, N V; Belykh, S A

2004-01-01

A methodological analysis of diagnosing the prescription of death coming (PDC) is described in the paper. Key philosophic fundamentals for further novel and more effective methods of PDC determination are elucidated. Main requirement applicable to postmortem diagnosis are defined. Different methods of modeling the postmortem process are demonstrated by the example of cadaver cooling, i.e. in real time, by analogue computer systems and by mathematic modeling. The traditional empiric and the adaptive approaches are comparatively analyzed in modeling the postmortem processes for the PDC diagnosis. A variety of promising trends for further related research is outlined.

External foam and the post-mortem period in freshwater drowning; results from a retrospective study in Amsterdam, the Netherlands.

PubMed

Reijnen, G; Buster, M C; Vos, P J E; Reijnders, U J L

2017-11-01

Determining the time of death of bodies recovered from water can be difficult. A feature of drowning is the presence of external foam. This study describes the presence of external foam in relation to the post-mortem period. The study utilizes a database of death reports dated between January 2011 and July 2016. For bodies recovered from fresh water, the presence or absence of external foam was noted. In this study, 112 death reports are included. Of these reports, 18 mentioned external foam, which account for 16.1% of the entire study population. In the population with a post-mortem period of less than 24 h, external foam was detected in 27.7% of cases. All 18 incidents with external foam had an estimated post-mortem period of less than 24 h. In our study, external foam was only present in freshwater drowning cases with a post-mortem period of less than 24 h. Based on this finding, the presence of external foam may be useful as an additional indicator when estimating the time of death in freshwater drowning. Copyright © 2017 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

UV–Vis and ATR–FTIR spectroscopic investigations of postmortem interval based on the changes in rabbit plasma

PubMed Central

Wang, Qi; He, Haijun; Li, Bing; Lin, Hancheng; Zhang, Yinming; Zhang, Ji

2017-01-01

Estimating PMI is of great importance in forensic investigations. Although many methods are used to estimate the PMI, a few investigations focus on the postmortem redistribution. In this study, ultraviolet–visible (UV–Vis) measurement combined with visual inspection indicated a regular diffusion of hemoglobin into plasma after death showing the redistribution of postmortem components in blood. Thereafter, attenuated total reflection–Fourier transform infrared (ATR–FTIR) spectroscopy was used to confirm the variations caused by this phenomenon. First, full-spectrum partial least-squares (PLS) and genetic algorithm combined with PLS (GA-PLS) models were constructed to predict the PMI. The performance of GA-PLS model was better than that of full-spectrum PLS model based on its root mean square error (RMSE) of cross-validation of 3.46 h (R2 = 0.95) and the RMSE of prediction of 3.46 h (R2 = 0.94). The investigation on the similarity of spectra between blood plasma and formed elements also supported the role of redistribution of components in spectral changes in postmortem plasma. These results demonstrated that ATR-FTIR spectroscopy coupled with the advanced mathematical methods could serve as a convenient and reliable tool to study the redistribution of postmortem components and estimate the PMI. PMID:28753641

Postmortem dynamic cerebral angiography for detecting aneurysm and bleeding sites in cases of subarachnoid hemorrhage.

PubMed

Inokuchi, Go; Yajima, Daisuke; Hayakawa, Mutsumi; Motomura, Ayumi; Chiba, Fumiko; Torimitsu, Suguru; Makino, Yohsuke; Iwase, Hirotaro

2014-12-01

One of the advantages of postmortem imaging is its ability to obtain diagnostic findings in a non-destructive manner when autopsy is either difficult or may destroy forensic evidence. In recent years, efforts have been made to incorporate computed tomography (CT) based postmortem angiography into forensic pathology; however, it is not currently clear how well the modality can determine sites of bleeding in cases of subarachnoid hemorrhage. Therefore, in this study, we investigated the utility of postmortem cerebral angiography using multi-detector row CT (MDCT) by injecting a contrast medium through a catheter inserted into the internal carotid and vertebral arteries of 10 subarachnoid hemorrhage cases. While postmortem MDCT angiography (PMCTA) was capable of detecting aneurysms in a non-destructive manner, it was sometimes difficult to identify the aneurysm and bleeding sites because of a large amount of contrast medium leaking into the extravascular space. To overcome this problem, we developed the novel contrast imaging method "dynamic cerebral angiography," which involves scanning the same area multiple times while injecting contrast medium to enable real-time observation of the contrasted vasculature. Using multiphase contrast images acquired by this method, we successfully captured the moment when contrast medium leaked from the hemorrhage site. This method will be useful for identifying exact bleeding sites on PMCTA.

Usability of Immunohistochemistry in Forensic Samples With Varying Decomposition.

PubMed

Lesnikova, Iana; Schreckenbach, Marc Niclas; Kristensen, Maria Pihlmann; Papanikolaou, Liv Lindegaard; Hamilton-Dutoit, Stephen

2018-05-24

Immunohistochemistry (IHC) is an important diagnostic tool in anatomic and surgical pathology but is used less frequently in forensic pathology. Degradation of tissue because of postmortem decomposition is believed to be a major limiting factor, although it is unclear what impact such degradation actually has on IHC staining validity. This study included 120 forensic autopsy samples of liver, lung, and brain tissues obtained for diagnostic purposes. The time from death to autopsy ranged between 1 and more than 14 days. Samples were prepared using the tissue microarray technique. The antibodies chosen for the study included KL1 (for staining bile duct epithelium), S100 (for staining glial cells and myelin), vimentin (for endothelial cells in cerebral blood vessels), and CD45 (for pulmonary lymphocytes). Slides were evaluated by light microscopy. Immunohistochemistry reactions were scored according to a system based on the extent and intensity of the positive stain. An overall correlation between the postmortem interval and the IHC score for all tissue samples was found. Samples from decedents with a postmortem interval of 1 to 3 days showed positive staining with all antibodies, whereas samples from decedents with a longer postmortem interval showed decreased staining rates. Our results suggest that IHC analysis can be successfully used for postmortem diagnosis in a range of autopsy samples showing lesser degrees of decomposition.

Putative presynaptic dopamine dysregulation in schizophrenia is supported by molecular evidence from post-mortem human midbrain

PubMed Central

Purves-Tyson, T D; Owens, S J; Rothmond, D A; Halliday, G M; Double, K L; Stevens, J; McCrossin, T; Shannon Weickert, C

2017-01-01

The dopamine hypothesis of schizophrenia posits that increased subcortical dopamine underpins psychosis. In vivo imaging studies indicate an increased presynaptic dopamine synthesis capacity in striatal terminals and cell bodies in the midbrain in schizophrenia; however, measures of the dopamine-synthesising enzyme, tyrosine hydroxylase (TH), have not identified consistent changes. We hypothesise that dopamine dysregulation in schizophrenia could result from changes in expression of dopamine synthesis enzymes, receptors, transporters or catabolic enzymes. Gene expression of 12 dopamine-related molecules was examined in post-mortem midbrain (28 antipsychotic-treated schizophrenia cases/29 controls) using quantitative PCR. TH and the synaptic dopamine transporter (DAT) proteins were examined in post-mortem midbrain (26 antipsychotic-treated schizophrenia cases per 27 controls) using immunoblotting. TH and aromatic acid decarboxylase (AADC) mRNA and TH protein were unchanged in the midbrain in schizophrenia compared with controls. Dopamine receptor D2 short, vesicular monoamine transporter (VMAT2) and DAT mRNAs were significantly decreased in schizophrenia, with no change in DRD3 mRNA, DRD3nf mRNA and DAT protein between diagnostic groups. However, DAT protein was significantly increased in putatively treatment-resistant cases of schizophrenia compared to putatively treatment-responsive cases. Midbrain monoamine oxidase A (MAOA) mRNA was increased, whereas MAOB and catechol-O-methyl transferase mRNAs were unchanged in schizophrenia. We conclude that, whereas some mRNA changes are consistent with increased dopamine action (decreased DAT mRNA), others suggest reduced dopamine action (increased MAOA mRNA) in the midbrain in schizophrenia. Here, we identify a molecular signature of dopamine dysregulation in the midbrain in schizophrenia that mainly includes gene expression changes of molecules involved in dopamine synthesis and in regulating the time course of dopamine action. PMID:28094812

Magnetic resonance diffusion tensor imaging for the pedunculopontine nucleus: proof of concept and histological correlation.

PubMed

Alho, A T D L; Hamani, C; Alho, E J L; da Silva, R E; Santos, G A B; Neves, R C; Carreira, L L; Araújo, C M M; Magalhães, G; Coelho, D B; Alegro, M C; Martin, M G M; Grinberg, L T; Pasqualucci, C A; Heinsen, H; Fonoff, E T; Amaro, E

2017-08-01

The pedunculopontine nucleus (PPN) has been proposed as target for deep brain stimulation (DBS) in patients with postural instability and gait disorders due to its involvement in muscle tonus adjustments and control of locomotion. However, it is a deep-seated brainstem nucleus without clear imaging or electrophysiological markers. Some studies suggested that diffusion tensor imaging (DTI) may help guiding electrode placement in the PPN by showing the surrounding fiber bundles, but none have provided a direct histological correlation. We investigated DTI fractional anisotropy (FA) maps from in vivo and in situ post-mortem magnetic resonance images (MRI) compared to histological evaluations for improving PPN targeting in humans. A post-mortem brain was scanned in a clinical 3T MR system in situ. Thereafter, the brain was processed with a special method ideally suited for cytoarchitectonic analyses. Also, nine volunteers had in vivo brain scanning using the same MRI protocol. Images from volunteers were compared to those obtained in the post-mortem study. FA values of the volunteers were obtained from PPN, inferior colliculus, cerebellar crossing fibers and medial lemniscus using histological data and atlas information. FA values in the PPN were significantly lower than in the surrounding white matter region and higher than in areas with predominantly gray matter. In Nissl-stained histologic sections, the PPN extended for more than 10 mm in the rostro-caudal axis being closely attached to the lateral parabrachial nucleus. Our DTI analyses and the spatial correlation with histological findings proposed a location for PPN that matched the position assigned to this nucleus in the literature. Coregistration of neuroimaging and cytoarchitectonic features can add value to help establishing functional architectonics of the PPN and facilitate neurosurgical targeting of this extended nucleus.

Altered Mitochondrial DNA Methylation Pattern in Alzheimer Disease-Related Pathology and in Parkinson Disease.

PubMed

Blanch, Marta; Mosquera, Jose Luis; Ansoleaga, Belén; Ferrer, Isidre; Barrachina, Marta

2016-02-01

Mitochondrial dysfunction is linked with the etiopathogenesis of Alzheimer disease and Parkinson disease. Mitochondria are intracellular organelles essential for cell viability and are characterized by the presence of the mitochondrial (mt)DNA. DNA methylation is a well-known epigenetic mechanism that regulates nuclear gene transcription. However, mtDNA methylation is not the subject of the same research attention. The present study shows the presence of mitochondrial 5-methylcytosine in CpG and non-CpG sites in the entorhinal cortex and substantia nigra of control human postmortem brains, using the 454 GS FLX Titanium pyrosequencer. Moreover, increased mitochondrial 5-methylcytosine levels are found in the D-loop region of mtDNA in the entorhinal cortex in brain samples with Alzheimer disease-related pathology (stages I to II and stages III to IV of Braak and Braak; n = 8) with respect to control cases. Interestingly, this region shows a dynamic pattern in the content of mitochondrial 5-methylcytosine in amyloid precursor protein/presenilin 1 mice along with Alzheimer disease pathology progression (3, 6, and 12 months of age). Finally, a loss of mitochondrial 5-methylcytosine levels in the D-loop region is found in the substantia nigra in Parkinson disease (n = 10) with respect to control cases. In summary, the present findings suggest mtDNA epigenetic modulation in human brain is vulnerable to neurodegenerative disease states. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

A virtual reconstruction and comparative analysis of the KNM-ER 42700 cranium.

PubMed

Bauer, Catherine C; Harvati, Katerina

2015-01-01

The taxonomic attribution of the 1.55 million year old young adult fossil calvaria KNM-ER 42700   from Ileret, Kenya, is subject to ongoing controversy. It has been attributed to H. erectus based on comparative description and linear measurements. However, 3-D geometric morphometric analysis found that this specimen fell outside the range of variation of H. erectus in its cranial shape, which was intermediate between H. erectus and modern humans. One problem is that analyses so far were conducted on the original specimen, which shows slight post-mortem distortion. Here we use a surface scan of a high resolution cast of KNM-ER 42700 to virtually reconstruct the calvaria and conduct a new 3D geometric morphometric analysis of both its original and its reconstructed shape. Our comparative sample included several specimens of H. erectus (s.l., including the subadult KNM-WT 15000), H. habilis, H. heidelbergenis (s.l.) and H. neanderthalensis, as well as early and Upper Paleolithic H. sapiens. Our principal component analysis results showed that, like the original specimen, our virtual reconstruction of KNM-ER 42700 is also intermediate in shape between fossil Homo and modern humans. Taphonomic distortion, therefore, appears to not have been a major factor affecting previous 3-D geometric morphometric analyses. The intermediate shape of KNM-ER 42700 might instead be related to the young developmental age of the specimen. Further work on reconstructing the original specimen or based on computed tomorgraphic scans is needed to confirm these results.

Dating human skeletal remains using a radiometric method: biogenic versus diagenetic 90Sr and 210Pb in vertebrae.

PubMed

Schrag, Bettina; Uldin, Tanya; Mangin, Patrice; Froidevaux, Pascal

2012-07-10

In forensic science, there is a strong interest in determining the post-mortem interval (PMI) of human skeletal remains up to 50 years after death. Currently, there are no reliable methods to resolve PMI, the determination of which relies almost exclusively on the experience of the investigating expert. Here we measured (90)Sr and (210)Pb ((210)Po) incorporated into bones through a biogenic process as indicators of the time elapsed since death. We hypothesised that the activity of radionuclides incorporated into trabecular bone will more accurately match the activity in the environment and the food chain at the time of death than the activity in cortical bone because of a higher remodelling rate. We found that determining (90)Sr can yield reliable PMI estimates as long as a calibration curve exists for (90)Sr covering the studied area and the last 50 years. We also found that adding the activity of (210)Po, a proxy for naturally occurring (210)Pb incorporated through ingestion, to the (90)Sr dating increases the reliability of the PMI value. Our results also show that trabecular bone is subject to both (90)Sr and (210)Po diagenesis. Accordingly, we used a solubility profile method to determine the biogenic radionuclide only, and we are proposing a new method of bone decontamination to be used prior to (90)Sr and (210)Pb dating. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

The measurement of intracranial pressure and brain displacement due to short-duration dynamic overpressure loading

NASA Astrophysics Data System (ADS)

Iwaskiw, A. S.; Ott, K. A.; Armiger, R. S.; Wickwire, A. C.; Alphonse, V. D.; Voo, L. M.; Carneal, C. M.; Merkle, A. C.

2018-01-01

The experimental measurement of biomechanical responses that correlate with blast-induced traumatic brain injury (bTBI) has proven challenging. These data are critical for both the development and validation of computational and physical head models, which are used to quantify the biomechanical response to blast as well as to assess fidelity of injury mitigation strategies, such as personal protective equipment. Therefore, foundational postmortem human surrogate (PMHS) experimental data capturing the biomechanical response are necessary for human model development. Prior studies have measured short-duration pressure transmission to the brain (Kinetic phase), but have failed to reproduce and measure the longer-duration inertial loading that can occur (Kinematic phase). Four fully instrumented PMHS were subjected to short-duration dynamic overpressure in front-facing and rear-facing orientations, where intracranial pressure (ICP), global head kinematics, and brain motion (as measured by high-speed X-ray) with respect to the skull were recorded. Peak ICP results generally increased with increased dose, and a mirrored pressure response was seen when comparing the polarity of frontal bone versus occipital bone ICP sensors. The head kinematics were delayed when compared to the pressure response and showed higher peak angles for front-facing tests as compared to rear-facing. Brain displacements were approximately 2-6 mm, and magnitudes did not change appreciably between front- and rear-facing tests. These data will be used to inform and validate models used to assess bTBI.

The endogenous and reactive depression subtypes revisited: integrative animal and human studies implicate multiple distinct molecular mechanisms underlying major depressive disorder

PubMed Central

2014-01-01

Background Traditional diagnoses of major depressive disorder (MDD) suggested that the presence or absence of stress prior to onset results in either ‘reactive’ or ‘endogenous’ subtypes of the disorder, respectively. Several lines of research suggest that the biological underpinnings of ‘reactive’ or ‘endogenous’ subtypes may also differ, resulting in differential response to treatment. We investigated this hypothesis by comparing the gene-expression profiles of three animal models of ‘reactive’ and ‘endogenous’ depression. We then translated these findings to clinical samples using a human post-mortem mRNA study. Methods Affymetrix mouse whole-genome oligonucleotide arrays were used to measure gene expression from hippocampal tissues of 144 mice from the Genome-based Therapeutic Drugs for Depression (GENDEP) project. The study used four inbred mouse strains and two depressogenic ‘stress’ protocols (maternal separation and Unpredictable Chronic Mild Stress) to model ‘reactive’ depression. Stress-related mRNA differences in mouse were compared with a parallel mRNA study using Flinders Sensitive and Resistant rat lines as a model of ‘endogenous’ depression. Convergent genes differentially expressed across the animal studies were used to inform candidate gene selection in a human mRNA post-mortem case control study from the Stanley Brain Consortium. Results In the mouse ‘reactive’ model, the expression of 350 genes changed in response to early stresses and 370 in response to late stresses. A minimal genetic overlap (less than 8.8%) was detected in response to both stress protocols, but 30% of these genes (21) were also differentially regulated in the ‘endogenous’ rat study. This overlap is significantly greater than expected by chance. The VAMP-2 gene, differentially expressed across the rodent studies, was also significantly altered in the human study after correcting for multiple testing. Conclusions Our results suggest that ‘endogenous’ and ‘reactive’ subtypes of depression are associated with largely distinct changes in gene-expression. However, they also suggest that the molecular signature of ‘reactive’ depression caused by early stressors differs considerably from that of ‘reactive’ depression caused by late stressors. A small set of genes was consistently dysregulated across each paradigm and in post-mortem brain tissue of depressed patients suggesting a final common pathway to the disorder. These genes included the VAMP-2 gene, which has previously been associated with Axis-I disorders including MDD, bipolar depression, schizophrenia and with antidepressant treatment response. We also discuss the implications of our findings for disease classification, personalized medicine and case-control studies of MDD. PMID:24886127

Lethal Respiratory Disease Associated with Human Rhinovirus C in Wild Chimpanzees, Uganda, 2013.

PubMed

Scully, Erik J; Basnet, Sarmi; Wrangham, Richard W; Muller, Martin N; Otali, Emily; Hyeroba, David; Grindle, Kristine A; Pappas, Tressa E; Thompson, Melissa Emery; Machanda, Zarin; Watters, Kelly E; Palmenberg, Ann C; Gern, James E; Goldberg, Tony L

2018-02-01

We describe a lethal respiratory outbreak among wild chimpanzees in Uganda in 2013 for which molecular and epidemiologic analyses implicate human rhinovirus C as the cause. Postmortem samples from an infant chimpanzee yielded near-complete genome sequences throughout the respiratory tract; other pathogens were absent. Epidemiologic modeling estimated the basic reproductive number (R 0 ) for the epidemic as 1.83, consistent with the common cold in humans. Genotyping of 41 chimpanzees and examination of 24 published chimpanzee genomes from subspecies across Africa showed universal homozygosity for the cadherin-related family member 3 CDHR3-Y 529 allele, which increases risk for rhinovirus C infection and asthma in human children. These results indicate that chimpanzees exhibit a species-wide genetic susceptibility to rhinovirus C and that this virus, heretofore considered a uniquely human pathogen, can cross primate species barriers and threatens wild apes. We advocate engineering interventions and prevention strategies for rhinovirus infections for both humans and wild apes.

Shells and Bones: A Forensic Medicine Study of the Association of Terrestrial Snail Allopeas micra with Buried Human Remains in Brazil.

PubMed

Galvão, Malthus Fonseca; Pujol-Luz, José Roberto; de Assis Pujol-Luz, Cristiane Vieira; de Rosa, Cássio Thyone Almeida; Simone, Luiz Ricardo L; Báo, Sônia Nair; Barros-Cordeiro, Karine Brenda; Pessoa, Larissa; Bissacot, Giovanna

2015-09-01

Little is known regarding the scavenger fauna associated with buried human corpses, particularly in clandestine burials. We report the presence of 20 shells of the terrestrial snail Allopeas micra, within hollow bones of human remains buried for 5 years, during the process of collecting DNA material. The fact that a large number of shells of A. micra had been found in the corpse and in the crime scene supports the assumption that there was no attempt to remove the corpse from the area where the crime occurred. Despite this, our observations cannot be used to estimate the postmortem interval because there is no precise knowledge about the development of this species. This is the first record of a terrestrial snail associated with a human corpse and its role in this forensic medicine case. © 2015 American Academy of Forensic Sciences.

COB231 targets amyloid plaques in post-mortem human brain tissue and in an Alzheimer mouse model.

PubMed

Garin, Dominique; Virgone-Carlotta, Angélique; Gözel, Bülent; Oukhatar, Fatima; Perret, Pascale; Marti-Battle, Danièle; Touret, Monique; Millet, Philippe; Dubois-Dauphin, Michel; Meyronet, David; Streichenberger, Nathalie; Laferla, Frank M; Demeunynck, Martine; Chierici, Sabine; Sallanon Moulin, Marcelle; Ghezzi, Catherine

2015-03-01

Previous works have shown the interest of naturally fluorescent proflavine derivatives to label Abeta deposits in vitro. This study aimed to further characterize the properties of the proflavine 3-acetylamino-6-[3-(propargylamino)propanoyl]aminoacridine (COB231) derivative as a probe. This compound was therefore evaluated on human post-mortem and mice brain slices and in vivo in 18-month-old triple transgenic mice APPswe, PS1M146V and tauP301L (3xTgAD) mice presenting the main characteristics of Alzheimer's disease (AD). COB231 labelled amyloid plaques on brain slices of AD patients, and 3xTgAD mice at 10 and 0.1 μM respectively. However, no labelling of the neurofibrillary tangle-rich areas was observed either at high concentration or in the brain of fronto-temporal dementia patients. The specificity of this mapping was attested in mice using Thioflavin S and IMPY as positive controls of amyloid deposits. After intravenous injection of COB231 in old 3xTgAD mice, fluorescent amyloid plaques were detected in the cortex and hippocampus, demonstrating COB231 blood–brain barrier permeability. We also controlled the cellular localization of COB231 on primary neuronal cultures and showed that COB231 accumulates into the cytoplasm and not into the nucleus. Finally, using a viability assay, we only detected a slight cytotoxic effect of COB231 (< 10%) for the highest concentration (100 μM).

Dynamics of the oral microbiota as a tool to estimate time since death.

PubMed

Adserias-Garriga, J; Quijada, N M; Hernandez, M; Rodríguez Lázaro, D; Steadman, D; Garcia-Gil, L J

2017-06-27

The oral cavity harbors one of the most diverse microbiomes in the human body. It has been shown to be the second most complex in the body after the gastrointestinal tract. Upon death, the indigenous microorganisms lead to the decomposition of the carcass. Therefore, the oral cavity and gastrointestinal tract microbiomes play a key role in human decomposition. The aim of the present study is to monitor the microbiome of decaying bodies on a daily basis and to identify signature bacterial taxa, that can improve postmortem interval estimation. Three individuals (one male and two female) donated to the University of Tennessee Forensic Anthropology Center for the W.M. Bass Donated Skeletal Collection were studied. Oral swab samples were taken daily throughout the different stages of cadaveric putrefaction. DNA was extracted and analyzed by next-generation sequencing techniques. The three cadavers showed similar overall successional changes during the decomposition process. Firmicutes and Actinobacteria are the predominant phyla in the fresh stage. The presence of Tenericutes corresponds to bloat stage. Firmicutes is the predominant phylum in advanced decay, but the Firmicutes community is a different one from the predominant Firmicutes of the fresh stage. This study depicts the thanatomicrobiome successional changes in the oral cavity, and highlights its potential use in forensic cases as a quantitative and objective approach to estimate postmortem interval, from an ecological rationale. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Examination of forensic entomology evidence using computed tomography scanning: case studies and refinement of techniques for estimating maggot mass volumes in bodies.

PubMed

Johnson, Aidan; Archer, Melanie; Leigh-Shaw, Lyndie; Pais, Mike; O'Donnell, Chris; Wallman, James

2012-09-01

A new technique has recently been developed for estimating the volume of maggot masses on deceased persons using post-mortem CT scans. This allows volume to be measured non-invasively and factored into maggot mass temperature calculations for both casework and research. Examination of admission scans also allows exploration of entomological evidence in anatomical areas not usually exposed by autopsy (e.g. nasal cavities and facial sinuses), and before autopsy disrupts the maggot distribution on a body. This paper expands on work already completed by providing the x-ray attenuation coefficient by way of Hounsfield unit (HU) values for various maggot species, maggot masses and human tissue adjacent to masses. Specifically, this study looked at the HU values for four forensically important blowfly larvae: Lucilia cuprina, L. sericata, Calliphora stygia and C. vicina. The Calliphora species had significantly lower HU values than the Lucilia species. This might be explained by histological analysis, which revealed a non-significant trend, suggesting that Calliphora maggots have a higher fat content than the Lucilia maggots. It is apparent that the variation in the x-ray attenuation coefficient usually precludes its use as a tool for delineating the maggot mass from human tissue and that morphology is the dominant method for delineating a mass. This paper also includes three case studies, which reveal different applications for interpreting entomological evidence using post-mortem CT scans.

GABRA2 Alcohol Dependence Risk Allele is Associated with Reduced Expression of Chromosome 4p12 GABAA Subunit Genes in Human Neural Cultures.

PubMed

Lieberman, Richard; Kranzler, Henry R; Joshi, Pujan; Shin, Dong-Guk; Covault, Jonathan

2015-09-01

Genetic variation in a region of chromosome 4p12 that includes the GABAA subunit gene GABRA2 has been reproducibly associated with alcohol dependence (AD). However, the molecular mechanisms underlying the association are unknown. This study examined correlates of in vitro gene expression of the AD-associated GABRA2 rs279858*C-allele in human neural cells using an induced pluripotent stem cell (iPSC) model system. We examined mRNA expression of chromosome 4p12 GABAA subunit genes (GABRG1, GABRA2, GABRA4, and GABRB1) in 36 human neural cell lines differentiated from iPSCs using quantitative polymerase chain reaction and next-generation RNA sequencing. mRNA expression in adult human brain was examined using the BrainCloud and BRAINEAC data sets. We found significantly lower levels of GABRA2 mRNA in neural cell cultures derived from rs279858*C-allele carriers. Levels of GABRA2 RNA were correlated with those of the other 3 chromosome 4p12 GABAA genes, but not other neural genes. Cluster analysis based on the relative RNA levels of the 4 chromosome 4p12 GABAA genes identified 2 distinct clusters of cell lines, a low-expression cluster associated with rs279858*C-allele carriers and a high-expression cluster enriched for the rs279858*T/T genotype. In contrast, there was no association of genotype with chromosome 4p12 GABAA gene expression in postmortem adult cortex in either the BrainCloud or BRAINEAC data sets. AD-associated variation in GABRA2 is associated with differential expression of the entire cluster of GABAA subunit genes on chromosome 4p12 in human iPSC-derived neural cell cultures. The absence of a parallel effect in postmortem human adult brain samples suggests that AD-associated genotype effects on GABAA expression, although not present in mature cortex, could have effects on regulation of the chromosome 4p12 GABAA cluster during neural development. Copyright © 2015 by the Research Society on Alcoholism.

13. VIEW OF EAST OPERATING GALLERY ALONG THE POSTMORTEM CELLS. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

13. VIEW OF EAST OPERATING GALLERY ALONG THE POST-MORTEM CELLS. A NUMBER OF MANIPULATOR ARMS COVERED WITH PLASTIC ARE ON THE LEFT WALL. - Nevada Test Site, Engine Maintenance Assembly & Disassembly Facility, Area 25, Jackass Flats, Mercury, Nye County, NV

N-ethylmaleimide-sensitive factor interacts with the serotonin transporter and modulates its trafficking: implications for pathophysiology in autism

PubMed Central

2014-01-01

Background Changes in serotonin transporter (SERT) function have been implicated in autism. SERT function is influenced by the number of transporter molecules present at the cell surface, which is regulated by various cellular mechanisms including interactions with other proteins. Thus, we searched for novel SERT-binding proteins and investigated whether the expression of one such protein was affected in subjects with autism. Methods Novel SERT-binding proteins were examined by a pull-down system. Alterations of SERT function and membrane expression upon knockdown of the novel SERT-binding protein were studied in HEK293-hSERT cells. Endogenous interaction of SERT with the protein was evaluated in mouse brains. Alterations in the mRNA expression of SERT (SLC6A4) and the SERT-binding protein in the post-mortem brains and the lymphocytes of autism patients were compared to nonclinical controls. Results N-ethylmaleimide-sensitive factor (NSF) was identified as a novel SERT-binding protein. NSF was co-localized with SERT at the plasma membrane, and NSF knockdown resulted in decreased SERT expression at the cell membranes and decreased SERT uptake function. NSF was endogenously co-localized with SERT and interacted with SERT. While SLC6A4 expression was not significantly changed, NSF expression tended to be reduced in post-mortem brains, and was significantly reduced in lymphocytes of autistic subjects, which correlated with the severity of the clinical symptoms. Conclusions These data clearly show that NSF interacts with SERT under physiological conditions and is required for SERT membrane trafficking and uptake function. A possible role for NSF in the pathophysiology of autism through modulation of SERT trafficking, is suggested. PMID:24834316

Deaths among adult patients with hypopituitarism: hypocortisolism during acute stress, and de novo malignant brain tumors contribute to an increased mortality.

PubMed

Burman, P; Mattsson, A F; Johannsson, G; Höybye, C; Holmer, H; Dahlqvist, P; Berinder, K; Engström, B E; Ekman, B; Erfurth, E M; Svensson, J; Wahlberg, J; Karlsson, F A

2013-04-01

Patients with hypopituitarism have an increased standardized mortality rate. The basis for this has not been fully clarified. To investigate in detail the cause of death in a large cohort of patients with hypopituitarism subjected to long-term follow-up. All-cause and cause-specific mortality in 1286 Swedish patients with hypopituitarism prospectively monitored in KIMS (Pfizer International Metabolic Database) 1995-2009 were compared to general population data in the Swedish National Cause of Death Registry. In addition, events reported in KIMS, medical records, and postmortem reports were reviewed. Standardized mortality ratios (SMR) were calculated, with stratification for gender, attained age, and calendar year during follow-up. An excess mortality was found, 120 deaths vs 84.3 expected, SMR 1.42 (95% confidence interval: 1.18-1.70). Infections, brain cancer, and sudden death were associated with significantly increased SMRs (6.32, 9.40, and 4.10, respectively). Fifteen patients, all ACTH-deficient, died from infections. Eight of these patients were considered to be in a state of adrenal crisis in connection with death (medical reports and post-mortem examinations). Another 8 patients died from de novo malignant brain tumors, 6 of which had had a benign pituitary lesion at baseline. Six of these 8 subjects had received prior radiation therapy. Two important causes of excess mortality were identified: first, adrenal crisis in response to acute stress and intercurrent illness; second, increased risk of a late appearance of de novo malignant brain tumors in patients who previously received radiotherapy. Both of these causes may be in part preventable by changes in the management of pituitary disease.

Freezing and calcium chloride marination effects on beef tenderness and calpastatin activity.

PubMed

Whipple, G; Koohmaraie, M

1992-10-01

Because freezing samples decreases calpastatin activity and the application of exogenous calcium activates the calpain proteolytic system, thereby improving tenderness, the objective of this study was to determine whether freezing would enhance the effects of CaCl2 marination on the tenderness of beef steaks. Longissimus steaks were obtained from 10 beef steers 6 d postmortem. One-half of the steaks were frozen at -30 degrees C for 6 wk. The remaining steaks were treated fresh; one-half were subjected to a 150 mM CaCl2 marinade for 48 h. Frozen steaks were thawed and subjected to the same treatment. Treatments consisted of 1) fresh control, 2) fresh marinated, 3) frozen control, and 4) frozen marinated. Samples were taken before and after treatment (6 and 8 d) for calpastatin activity determination and d 8 for SDS-PAGE. Warner-Bratzler shear force values were measured 8 d postmortem. Data were analyzed using a paired comparison t-test procedure. Results showed that freezing and marination significantly decreased calpastatin activity. A .35-kg improvement (P = .07) in Warner-Bratzler shear force was observed with freezing, whereas a .78-kg improvement (P less than .01) in tenderness was observed with marination. However, prior freezing enhanced the effects of marination. Therefore, the decrease in calpastatin activity seemed to allow greater proteolysis by the calpains with the application of Ca2+. The SDS-PAGE of myofibril preparations indicated that more small polypeptide fragments (28 to 32 kDa) appeared and a 95-kDa fragment was more intense in the marinated samples than in control samples, indicating that proteolysis was enhanced.(ABSTRACT TRUNCATED AT 250 WORDS)

Study of chemiluminescence measured by luminometry and its application in the estimation of postmortem interval of bone remains.

PubMed

Sarabia, Jesús; Pérez-Martínez, Cristina; Hernández Del Rincón, Juan Pedro; Luna, Aurelio

2018-05-05

A substantial challenge faced by forensic medicine is determining the postmortem interval (PMI) of skeletonized remains. Currently, the luminol method is of limited forensic usefulness, since it uses qualitative and subjective methods to estimate PMI by the naked eye assessing the degree of chemiluminescence (CL) emitted by bone remains, a technique which is not sensitive enough to distinguish between historical or forensically significant time intervals. The aim of the present study was to use a direct and accurate measurement of the CL by luminol technique in relative light units (RLU) using a luminometer to establish this method as a possible complementary and low cost tool for the determination of the PMI for distinguishing between remains of medical-legal (<20 years) and historical (≥20 years) interest in 102 femur remains with a range of PMI between 15 and 64 years. The results suggest that, under favorable conditions, the luminol technique can detect haemoglobin in the bone in a PMI range of 0-65 years, finding significant differences in the CL intensity among samples with PMI < 20 years and PMI ≥ 20 years. In addition, the intensities of CL measured at 10 s, 15 s and 20 s after reaction with luminol show a statistically significant inverse relationship with PMI in the bone studied, following a decreasing logarithmic model. The conclusion is that this quantitative, objective and contrastable technique could be very useful for determining the PMI in bone remains, since it allows a good degree of precision and eliminates the subjectivity introduced by qualitative techniques. Copyright © 2018 Elsevier B.V. All rights reserved.