"Hjälp, hur gör jag nu?" ­ en kvalitativ studie om pedagogers kunskap, beredskap och förhållningssätt gällande barn som far illa i hemmet

Syfte: Syftet med vår studie är att undersöka om pedagoger, med hjälp av de kunskaper de får i sin utbildning, är förberedda att hantera situationer där vissa barns hemförhållanden kan få negativa konsekvenser i den pedagogiska verksamheten. Huvudfråga: Vad har verksamma pedagoger för kunskap, beredskap, förhållningssätt och erfarenhet gällande hantering av situationer där barn far illa i hemmet? Metod och material: Vi har i vår studie använt oss av halvstrukturerade kvalitativa intervjuer. Deltagarna bestod av fem pedagoger som på något sätt har anknytning till förskoleverksamheten. Vid transkriberingen av intervjuerna, valde vi ut det material som vi ansåg vara mest relevant för våra frågeställningar. Resultat: Vi kom i vår studie fram till att de respondenter vi intervjuade, trots stora brister av denna problematik i deras utbildning, idag har bra kunskap och beredskap för att hantera situationer där barn far illa och på ett negativt sätt påverkar den pedagogiska verksamheten. Denna kunskap och beredskap har de erhållit genom flera års erfarenhet inom yrket och av kollegor som delat med sig av deras erfarenheter och kunskaper inom denna problematik. Det är alltså genom erfarenhet och utbyte av tankar, idéer och kunskaper med kollegor som pedagogerna har fått den kunskap de idag besitter. Med hjälp av respondenternas svar kunde vi av detta alltså dra en slutsats om att nyutexaminerade pedagoger inte har tillräcklig kunskap att tillgå för att hantera denna typ av problematik. Betydelse för läraryrket: Detta är en svårighet att som alla pedagoger säkerligen kommer att komma i kontakt med under sitt yrkesverksamma liv. Därför är det viktigt att redan från början få en grund att stå på. Denna grund bör därför ingå som ett obligatoriskt inslag i lärarutbildningen, för att pedagoger redan under sina första år ska vara redo att bemöta och kunna hantera denna problematik

The secondary structure of apolipoprotein A-I on 9.6-nm reconstituted high-density lipoprotein determined by EPR spectroscopy.

Apolipoprotein A-I (ApoA-I) is the major protein component of high-density lipoprotein (HDL), and is critical for maintenance of cholesterol homeostasis. During reverse cholesterol transport, HDL transitions between an array of subclasses, differing in size and composition. This process requires ApoA-I to adapt to changes in the shape of the HDL particle, transiting from an apolipoprotein to a myriad of HDL subclass-specific conformations. Changes in ApoA-I structure cause alterations in HDL-specific enzyme and receptor-binding properties, and thereby direct the HDL particle through the reverse cholesterol transport pathway. In this study, we used site-directed spin label spectroscopy to examine the conformational details of the ApoA-I central domain on HDL. The motional dynamics and accessibility to hydrophobic/hydrophilic relaxation agents of ApoA-I residues 99-163 on 9.6-nm reconstituted HDL was analyzed by EPR. In previous analyses, we examined residues 6-98 and 164-238 (of ApoA-I's 243 residues), and combining these findings with the current results, we have generated a full-length map of the backbone structure of reconstituted HDL-associated ApoA-I. Remarkably, given that the majority of ApoA-I's length is composed of amphipathic helices, we have identified nonhelical residues, specifically the presence of a β-strand (residues 149-157). The significance of these nonhelical residues is discussed, along with the other features, in the context of ApoA-I function in contrast to recent models derived by other methods

Combining H-FABP and GFAP increases the capacity to differentiate between CT-positive and CT-negative patients with mild traumatic brain injury

Mild traumatic brain injury (mTBI) patients may have trauma-induced brain lesions detectable using CT scans. However, most patients will be CT-negative. There is thus a need for an additional tool to detect patients at risk. Single blood biomarkers, such as S100B and GFAP, have been widely studied in mTBI patients, but to date, none seems to perform well enough. In many different diseases, combining several biomarkers into panels has become increasingly interesting for diagnoses and to enhance classification performance. The present study evaluated 13 proteins individually—H-FABP, MMP-1, MMP-3, MMP-9, VCAM, ICAM, SAA, CRP, GSTP, NKDA, PRDX1, DJ-1 and IL-10—for their capacity to differentiate between patients with and without a brain lesion according to CT results. The best performing proteins were then compared and combined with the S100B and GFAP proteins into a CT-scan triage panel. Patients diagnosed with mTBI, with a Glasgow Coma Scale score of 15 and one additional clinical symptom were enrolled at three different European sites. A blood sample was collected at hospital admission, and a CT scan was performed. Patients were divided into two two-centre cohorts and further dichotomised into CT-positive and CT-negative groups for statistical analysis. Single markers and panels were evaluated using Cohort 1. Four proteins—H-FABP, IL-10, S100B and GFAP—showed significantly higher levels in CT-positive patients. The best-performing biomarker was H-FABP, with a specificity of 32% (95% CI 23–40) and sensitivity reaching 100%. The best-performing two-marker panel for Cohort 1, subsequently validated in Cohort 2, was a combination of H-FABP and GFAP, enhancing specificity to 46% (95% CI 36–55). When adding IL-10 to this panel, specificity reached 52% (95% CI 43–61) with 100% sensitivity. These results showed that proteins combined into panels could be used to efficiently classify CT-positive and CT-negative mTBI patients

Improved metrics for comparing structures of macromolecular assemblies determined by 3D electron-microscopy

Recent developments in 3-dimensional electron microcopy (3D-EM) techniques and a concomitant drive to look at complex molecular structures, have led to a rapid increase in the amount of volume data available for biomolecules. This creates a demand for better methods to analyse the data, including improved scores for comparison, classification and integration of data at different resolutions. To this end, we developed and evaluated a set of scoring functions that compare 3D-EM volumes. To test our scores we used a benchmark set of volume alignments derived from the Electron Microscopy Data Bank. We find that the performance of different scores vary with the map-type, resolution and the extent of overlap between volumes. Importantly, adding the overlap information to the local scoring functions can significantly improve their precision and accuracy in a range of resolutions. A combined score involving the local mutual information and overlap (LMI_OV) performs best overall, irrespective of the map category, resolution or the extent of overlap, and we recommend this score for general use. The local mutual information score itself is found to be more discriminatory than cross-correlation coefficient for intermediate-to-low resolution maps or when the map size and density distribution differ significantly. For comparing map surfaces, we implemented two filters to detect the surface points, including one based on the ‘extent of surface exposure’. We show that scores that compare surfaces are useful at low resolutions and for maps with evident surface features. All the scores discussed are implemented in TEMPy (http://tempy.ismb.lon.ac.uk/)

Structural determinants in ApoA-I amyloidogenic variants explain improved cholesterol metabolism despite low HDL levels.

Twenty Apolipoprotein A-I (ApoA-I) variants are responsible for a systemic hereditary amyloidosis in which protein fibrils can accumulate in different organs, leading to their failure. Several ApoA-I amyloidogenic mutations are also associated with hypoalphalipoproteinemia, low ApoA-I and high-density lipoprotein (HDL)-cholesterol plasma levels; however, subjects affected by ApoA-I-related amyloidosis do not show a higher risk of cardiovascular diseases (CVD). The structural features, the lipid binding properties and the functionality of four ApoA-I amyloidogenic variants were therefore inspected in order to clarify the paradox observed in the clinical phenotype of the affected subjects. Our results show that ApoA-I amyloidogenic variants are characterized by a different oligomerization pattern and that the position of the mutation in the ApoA-I sequence affects the molecular structure of the formed HDL particles. Although lipidation increases ApoA-I proteins stability, all the amyloidogenic variants analyzed show a lower affinity for lipids, both in vitro and in ex vivo mouse serum. Interestingly, the lower efficiency at forming HDL particles is compensated by a higher efficiency at catalysing cholesterol efflux from macrophages. The decreased affinity of ApoA-I amyloidogenic variants for lipids, together with the increased efficiency in the cholesterol efflux process, could explain why, despite the unfavourable lipid profile, patients affected by ApoA-I related amyloidosis do not show a higher CVD risk

Kinematic and spatiotemporal assessment of habituation to treadmill walking in Labrador retrievers

BACKGROUND: This study investigated differences in kinematic and spatiotemporal variables in Labrador retrievers during introduction to treadmill walking, with the aim to determine the time required for them to become habituated. Twenty-five healthy, treadmill-naive Labrador retrievers participated in the study. The total angular displacement of the carpus, elbow, tarsus and stifle, as well as stride time and stance duration were calculated from the 3-D tracking of skin mounted reflective markers recorded with 6 infrared light emitting video cameras at 240 Hz. The measurements were done at two walking speeds, 0.78 and 0.96 m/s, in six sessions on the treadmill during two consecutive days. RESULTS: With a 1–2 min acclimatization period following each treadmill speed change, mean values of the study variables were significantly different from the last training session mainly in the first session on the first day. However, between-stride variability was significantly larger for at least one variable even in the fourth session for the slower walking speed, and in the fifth session for the higher walking speed. CONCLUSIONS: The results show the importance of proper pre-training of dogs in locomotion studies at walk using a treadmill, and the need to consider not only variable mean values but also between-stride variability, in order to ensure that dogs are sufficiently accustomed to allow collection of reliable data

Postprandial apoE isoform and conformational changes associated with VLDL lipolysis products modulate monocyte inflammation.

ObjectivePostprandial hyperlipemia, characterized by increased circulating very low-density lipoproteins (VLDL) and circulating lipopolysaccharide (LPS), has been proposed as a mechanism of vascular injury. Our goal was to examine the interactions between postprandial lipoproteins, LPS, and apoE3 and apoE4 on monocyte activation.Methods and resultsWe showed that apoE3 complexed to phospholipid vesicles attenuates LPS-induced THP-1 monocyte cytokine expression, while apoE4 increases expression. ELISA revealed that apoE3 binds to LPS with higher affinity than apoE4. Electron paramagnetic resonance (EPR) spectroscopy of site-directed spin labels placed on specific amino acids of apoE3 showed that LPS interferes with conformational changes normally associated with lipid binding. Specifically, compared to apoE4, apoE bearing the E3-like R112→Ser mutation displays increased self association when exposed to LPS, consistent with a stronger apoE3-LPS interaction. Additionally, lipolysis of fasting VLDL from normal human donors attenuated LPS-induced TNFα secretion from monocytes to a greater extent than postprandial VLDL, an effect partially reversed by blocking apoE. This effect was reproduced using fasting VLDL lipolysis products from e3/e3 donors, but not from e4/e4 subjects, suggesting that apoE3 on fasting VLDL prevents LPS-induced inflammation more readily than apoE4.ConclusionPostprandial apoE isoform and conformational changes associated with VLDL dramatically modulate vascular inflammation