Plasma neurofilament light chain protein is not increased in forensic psychiatric populations: a pilot study

IntroductionNeurofilament light chain protein (NfL) is a fluid biomarker of neural injury measurable in cerebrospinal fluid and blood. Patients with different neurodegenerative disorders and mild traumatic brain injury display elevated levels of NfL. However, so far, elevated levels of NfL have not been demonstrated in persons with psychiatric disorders. To our knowledge, the occurrence of NfL in the blood has not previously been studied in persons undergoing forensic psychiatric assessment or persons treated in forensic mental health services. Supposedly, these persons suffer from experiences and conditions with a higher risk of neural injury than other psychiatric patients.MethodsIn this pilot study, we investigated plasma levels of NfL in 20 persons undergoing forensic psychiatric assessment and 20 patients at a forensic psychiatric hospital. NfL values were compared with control groups of healthy individuals matched for age and sex.ResultsThe prevalence of increased NfL in both forensic groups was low and did not differ compared with the controls. However, some persons undergoing forensic psychiatric assessment showed slightly elevated values.DiscussionThe slightly elevated values were observed in the group investigated closer in time to the index crime, when elevated NfL levels could be expected to be more prevalent due to acute conditions from the time of the offense. This gives reason to look further into this group

Serum IGFBP-1 Concentration as a Predictor of Outcome after Ischemic Stroke—A Prospective Observational Study

Insulin-like growth factor-binding protein-1 (IGFBP-1) regulates insulin-like growth factor-I (IGF-I) bioactivity, and is a central player in normal growth, metabolism, and stroke recovery. However, the role of serum IGFBP-1 (s-IGFBP-1) after ischemic stroke is unclear. We determined whether s-IGFBP-1 is predictive of poststroke outcome. The study population comprised patients (n = 470) and controls (n = 471) from the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). Functional outcome was evaluated after 3 months, 2, and 7 years using the modified Rankin Scale (mRS). Survival was followed for a minimum of 7 years or until death. S-IGFBP-1 was increased after 3 months (p 2) after 7 years [fully adjusted odds ratio (OR) per log increase 2.9, 95% confidence interval (CI): 1.4-5.9]. Moreover, higher s-IGFBP-1 after 3 months was associated with a risk of poor functional outcome after 2 and 7 years (fully adjusted: OR 3.4, 95% CI: 1.4-8.5 and OR 5.7, 95% CI: 2.5-12.8, respectively) and with increased mortality risk (fully adjusted: HR 2.0, 95% CI: 1.1-3.7). Thus, high acute s-IGFBP-1 was only associated with poor functional outcome after 7 years, whereas s-IGFBP-1 after 3 months was an independent predictor of poor long-term functional outcome and poststroke mortality

Cerebrospinal fluid lipocalin 2 as a novel biomarker for the differential diagnosis of vascular dementia

The clinical diagnosis of vascular dementia (VaD) is based on imaging criteria, and specific biochemical markers are not available. Here, we investigated the potential of cerebrospinal fluid (CSF) lipocalin 2 (LCN2), a secreted glycoprotein that has been suggested as mediating neuronal damage in vascular brain injuries. The study included four independent cohorts with a total n = 472 samples. LCN2 was significantly elevated in VaD compared to controls, Alzheimer's disease (AD), other neurodegenerative dementias, and cognitively unimpaired patients with cerebrovascular disease. LCN2 discriminated VaD from AD without coexisting VaD with high accuracy. The main findings were consistent over all cohorts. Neuropathology disclosed a high percentage of macrophages linked to subacute infarcts, reactive astrocytes, and damaged blood vessels in multi-infarct dementia when compared to AD. We conclude that CSF LCN2 is a promising candidate biochemical marker in the differential diagnosis of VaD and neurodegenerative dementias

Barn i behov av särskilt stöd : en kvalitativ intervjustudie om förskollärarnas bemötande och arbetssätt med barn i behov av särskilt stöd

Vårt syfte har varit att undersöka förskollärarnas bemötande och arbetssätt för och med barn i behov av särskilt stöd. Det vi fördjupade oss i var hur förskollärarna ser på begreppet barn i behov av särskilt stöd, deras arbetssätt med barn i behov av stöd och vilket stöd de får för att kunna bemöta barn som är i behov av särskilt stöd. Vår studie är baserad på kvalitativa intervjuer. Vi har genomfört fyra intervjuer med fyra förskollärare på olika förskolor. Det resultat vi har fått fram i vår intervjustudie är att förskollärarna anser att de har barn som är i behov av särskilt stöd i sin barngrupp. Att rutiner och tydlighet är viktigt i arbetet med barn i behov av särskilt stöd och att förskollärarna har tillgång till stöd genom olika resurser. Det saker som påverkar förskollärarnas arbete har varit huruvida man har stöd från förskolechef, personaltäthet i arbetslaget, rätt kompetens, en bra sammanhållning och samarbete i arbetslaget och antal barn i barngruppen. Det framkommer även att gemensam planering av rutiner och arbetsscheman i arbetslaget är otroligt viktig för att kunna bemöta alla barn på bästa möjliga sätt. Alla förskollärare i studien tar upp vikten av att inte se barnet som ett problem, utan att det är viktigt att istället fokusera på hur de kunde arbeta med omgivande miljö för att bemöta alla barns olika behov. Vår slutsats efter att ha genomfört denna intervjustudie är att alla barn någon gång under sin tid på förskolan kommer att vara i behov av särskilt stöd men att behoven kan se olika ut hos varje enskilt barn. Under arbetets gång har vi fått mer insikt i hur man kan arbeta med barn i behov av särskilt stöd. Vi har tagit till oss och fördjupat vår kunskap om hur man kan tänka kring begreppet barn i behov av särskilt stöd och hur stödet utifrån ser ut. Vi har även fått kännedom om vikten att ta hjälp utifrån när man känner att man inte klarar situationen själva på förskolan

Immobilized lipodisks as model membranes in high-throughput HPLC-MS analysis

Lipodisks, also referred to as polyethylene glycol (PEG)-stabilized bilayer disks, have previously been demonstrated to hold great potential as model membranes in drug partition studies. In this study, an HPLC-MS system with stably immobilized lipodisks is presented. Functionalized lipodisks were immobilized on two different HPLC support materials either covalently by reductive amination or by streptavidin-biotin binding. An analytical HPLC column with immobilized lipodisks was evaluated by analysis of mixtures containing 15 different drug compounds. The efficiency, reproducibility, and stability of the system were found to be excellent. In situ incorporation of cyclooxygenase-1 (COX-1) in immobilized lipodisks on a column was also achieved. Specific binding of COX-1 to the immobilized lipodisks was validated by interaction studies with QCM-D. These results, taken together, open up the possibility of studying ligand interactions with membrane proteins by weak affinity chromatography.De två (2) första författarna delar förstaförfattarskapet.</p

PEG-stabilized lipid disks as carriers for amphiphilic antimicrobial peptides

Antimicrobial peptides hold potential as a possible alternative, or complement, to conventional antibiotics but new, safe and efficient means are needed for formulation and administration of the peptides. In this study we have investigated the utility of a novel type of lipid particles, the polyethylene glycol-stabilized lipid-disks, as carriers for the model peptide melittin. The structural integrity of the carrier particle when loaded with the peptide was investigated using cryo-transmission electron microscopy. Liposome leakage upon addition of the peptide-lipid-disks was monitored as a means to verify the membrane lytic effect of the formulation. The susceptibility of melittin to tryptic digestion was studied and compared in the absence and presence of lipid-disks. Finally, the antibacterial effect of the peptide-lipid-disk formulation was compared to that of free melittin after both single and repeated exposure to Escherichia coli. The results show that melittin can redistribute from the disk into a new host membrane and that formulation in the disks does not compromise melittin's membrane permeabilizing ability. Further, the peptide was found to be fully protected against degradation when bound to the disks. Time-kill experiments revealed that all the antibacterial effect of melittin administered in free form was gone after a single exposure to E. coli. In contrast, the disk formulation showed significant cell-killing effect also upon a second exposure to bacteria, indicating an extended release of peptide from the lipid-disks. These results suggest that the lipid-disks constitute a new class of promising carriers for peptide antibiotics

Evaluation of the Cerebrospinal Fluid Amyloid-beta(1-42)/Amyloid-beta(1-40) Ratio Measured by Alpha-LISA to Distinguish Alzheimer's Disease from Other Dementia Disorders

Background: The well-established core biomarkers used to identify Alzheimer's disease (AD) overlap with other dementia disorders such as dementia with Lewy bodies (DLB) and Parkinson's disease with dementia (PDD). This study aimed to evaluate whether the cerebrospinal fluid (CSF) amyloid-beta (A beta)(1-42)/A beta(1-40) ratio, measured by a novel method, could improve the differential diagnosis of AD, DLB and PDD. Method: CSF levels of A beta(1-40) and A beta(1-42) in patients with PDD, DLB, AD, Parkinson's disease and controls were analyzed using an amplified luminescent proximity homogenous immunoassay along with conventional immunoassays. Results: The CSF A beta(1-42)/A beta(1-40) ratio increased discrimination of AD from PDD and DLB compared with either of the two A beta biomarkers individually. Conclusion: The use of the A beta(1-42)/A beta(1-40) ratio could improve the differentiation of AD from PDD and DLB. (C) 2013 S. Karger AG, Base

Beneficial effects of increased lysozyme levels in Alzheimer\u27s disease modelled in Drosophila melanogaster

Genetic polymorphisms of immune genes that associate with higher risk to develop Alzheimer\u27s disease (AD) have led to an increased research interest on the involvement of the immune system in AD pathogenesis. A link between amyloid pathology and immune gene expression was suggested in a genome-wide gene expression study of transgenic amyloid mouse models. In this study, the gene expression of lysozyme, a major player in the innate immune system, was found to be increased in a comparable pattern as the amyloid pathology developed in transgenic mouse models of AD. A similar pattern was seen at protein levels of lysozyme in human AD brain and CSF, but this lysozyme pattern was not seen in a tau transgenic mouse model. Lysozyme was demonstrated to be beneficial for different Drosophila melanogaster models of AD. In flies that expressed Aβ1-42 or AβPP together with BACE1 in the eyes, the rough eye phenotype indicative of toxicity was completely rescued by coexpression of lysozyme. In Drosophila flies bearing the Aβ1-42 variant with the Arctic gene mutation, lysozyme increased the fly survival and decreased locomotor dysfunction dose dependently. An interaction between lysozyme and Aβ1-42 in the Drosophila eye was discovered. We propose that the increased levels of lysozyme, seen in mouse models of AD and in human AD cases, were triggered by Aβ1-42 and caused a beneficial effect by binding of lysozyme to toxic species of Aβ1-42, which prevented these from exerting their toxic effects. These results emphasize the possibility of lysozyme as biomarker and therapeutic target for AD