Neural adhesion proteins are crucial in the development and maintenance of functional neural connectivity. Growing evidence suggests that the IgLON family of neural adhesion molecules LSAMP, NTM, NEGR1, and OPCML are important candidates in forming the susceptibility to schizophrenia (SCZ). IgLON proteins have been shown to be involved in neurite outgrowth, synaptic plasticity and neuronal connectivity, all of which have been shown to be altered in the brains of patients with the diagnosis of schizophrenia. Here we optimized custom 5′-isoform-specific TaqMan gene-expression analysis for the transcripts of human IgLON genes to study the expression of IgLONs in the dorsolateral prefrontal cortex (DLPFC) of schizophrenic patients (n = 36) and control subjects (n = 36). Uniform 5′-region and a single promoter was confirmed for the human NEGR1 gene by in silico analysis. IgLON5, a recently described family member, was also included in the study. We detected significantly elevated levels of the NEGR1 transcript (1.33-fold increase) and the NTM 1b isoform transcript (1.47-fold increase) in the DLPFC of schizophrenia patients compared to healthy controls. Consequent protein analysis performed in male subjects confirmed the increase in NEGR1 protein content both in patients with the paranoid subtype and in patients with other subtypes. In-group analysis of patients revealed that lower expression of certain IgLON transcripts, mostly LSAMP 1a and 1b, could be related with concurrent depressive endophenotype in schizophrenic patients. Additionally, our study cohort provides further evidence that cannabis use may be a relevant risk factor associated with suicidal behaviors in psychotic patients. In conclusion, we provide clinical evidence of increased expression levels of particular IgLON family members in the DLPFC of schizophrenic patients. We propose that alterations in the expression profile of IgLON neural adhesion molecules are associated with brain circuit disorganization in neuropsychiatric disorders, such as schizophrenia. In the light of previously published data, we suggest that increased level of NEGR1 in the frontal cortex may serve as molecular marker for a wider spectrum of psychiatric conditions.
BackgroundAlcohol 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.Methods1299 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.Results595 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.ConclusionWe 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.
Motor vehicle accidental injuries are a frequent cause of death among young children and adolescents. The goal of this study was to compare patterns of injury between three capitals (Budapest, Vilnius, and Tallinn). Information on 190 fatal traffic accidents (69 pedestrians, 14 bicyclists, and 107 motor vehicle occupants) between 2002 and 2006 was collected from databases of medico-legal autopsies. The role of victims in accidents, the location of injuries, cause of death, survival period, and blood alcohol levels were evaluated. One-hundred and forty-one (74%) victims had a passive role in traffic as pedestrians, passengers in cars, or public transport. In victims who died at the scene, the rate of head injury was higher than in cases who received medical treatment (odds ratio = 2.58, CI = 1.2-5.55, p = 0.0127). These results underline the importance of postmortem studies to examine the pathomechanism of fatal traffic accidental injuries and to provide information for the prevention of road traffic accidents against children and adolescents.
AimsAlcohol can induce diverse serious pathologies, yet this complexity may be obscured when alcohol-related deaths are classified according to a single underlying cause. We sought to quantify this issue and its implications for analysing mortality data.Design, Setting and ParticipantsCross-sectional study included 554 men aged 25–54 in Estonia undergoing forensic autopsy in 2008–09.MeasurementsPotentially alcohol-related pathologies were identified following macroscopic and histological examination. Alcohol biomarkers levels were determined. For a subset (26%), drinking behaviour was provided by next-of-kin. The Estonian Statistics Office provided underlying cause of death.FindingsMost deaths (75%) showed evidence of potentially alcohol-related pathologies, and 32% had pathologies in two or more organs. The liver was most commonly affected [60.5%, 95% confidence interval (CI) = 56.3–64.6] followed by the lungs (18.6%, 95% CI = 15.4–22.1), stomach (17.5%, 95% CI = 14.4–20.9), pancreas (14.1%, 95% CI = 11.3–17.3), heart (4.9%, 95% CI = 3.2–7.0) and oesophagus (1.4%, 95% CI = 0.6–2.8). Only a minority with liver pathology had a second pathology. The number of pathologies correlated with alcohol biomarkers (phosphatidylethanol, gamma-glytamyl transpeptidase in blood, ethylglucuronide, ethylsulphate in urine). Despite the high prevalence of liver pathology, few deaths had alcoholic liver disease specified as the underlying cause.ConclusionThe majority of 554 men aged 25–54 undergoing forensic autopsy in Estonia in 2008–09 showed evidence of alcohol-related pathology. However, the recording of deaths by underlying cause failed to capture the scale and nature of alcohol-induced pathologies found.
The manuscript presents the International Guidelines developed by the Working Group on Personal Injury and Damage under the patronage of the International Academy of Legal Medicine (IALM) regarding the Methods of Ascertainment of any suspected Whiplash-Associated Disorders (WAD).The document includes a detailed description of the logical and methodological steps of the ascertainment process as well as a synoptic diagram in the form of Flow Chart.
Background: Official mortality registers are of fundamental importance in research, however the comparability of data across countries and different versions of ICD (International Classification of Diseases) must be monitored. The aim of this article is to examine the impact of ICD coding rules, as there were three major updates between 2002 and 2010 affecting fatal poisoning data. Method: Data on all fatal poisonings registered by the Estonian Forensic Science Institute from 2000-2009 were coded according to ICD (effective in 2010), correspondence between forensic diagnosis and ICD categories and the impact of changes on ICD examined. Results: Priority lists to select the main substance in the case of multi-substance poisoning do not always result in the most dangerous drug. In particular, highly toxic fentanyles are rated below psychostimulants, which leads (in the case of Estonia) to significant distortion of drug-related mortality patterns. Implementation of the updates to ICD coding rules stating that aspiration may be due to other conditions results in a 16.8% increase in drug-related mortality. Tranquillizers such as benzodiazepines and barbiturates are absent from this list altogether. There are no guidelines to deal with surrogate alcohol. Conclusion: Implementation of the 2010 version of ICD must be carefully monitored by statistical authorities and researchers. The priority list for substances could be amended to give priority to fentanyles over psychostimulants and to frequently abused tranquillizers (benzodiazepines and barbiturates) over non-opioid analgesics. Certain combinations of toxic agents could have separate codes in ICD, especially if they have a coalitive effect.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.