Search

BACKGROUND: After-school programs (ASP) provide opportunities to influence children’s physical activity (PA). However, little is known about the PA levels of the youngest schoolchildren. The aim of the study was to describe the level of PA intensity and sedentary time among first graders attending ASP in Norway, and to investigate factors that are associated with PA in the ASP. METHODS: First graders from 14 ASPs were invited to participate in the study and 426 children were included. The children wore an accelerometer for five consecutive days during their stay in the ASP. Light, moderate, and vigorous PA and sedentary time were registered and analyzed. RESULTS: On average, the children accumulated 25.8 minutes of moderate and vigorous physical activity (MVPA) during their ASP-stay. However, there was considerable variation within the sample. Sex, as well as body mass, were associated with MVPA. The activity level increased substantially when the children had to be outside. CONCLUSIONS: The findings show that on average, the children were quite physically active in the ASP. However, it seems critical to devote increased attention to the least active children and to include extensive outdoor play-time in the ASP schedule.

Bicarbonate and calcium set bounds on photosynthesis and degradation processes in calcareous freshwaters. Charophytic algae use bicarbonate in photosynthesis, and direct variable proportions to assimilate organic carbon and to precipitate calcium carbonate on their surfaces. To evaluate pools of organic carbon (Corg), carbonate carbon (Ccarbonate), and phosphorus (P) in dense charophyte vegetation, we studied apical and basal tissue and carbonate surface precipitates, as well as underlying sediments in ten calcareous ponds. We also quantified the release of calcium, bicarbonate and phosphate from charophyte shoots in dark experiments. We found that the Corg:Ccarbonate quotient in charophyte stands averaged 1.19 during spring and summer. The Corg:Ccarbonate quotient in the sediments formed by dead charophytes averaged 0.97 in accordance with some respiratory CO2 release without carbonate dissolution to bicarbonate. The molar quotient of carbon to calcium was close to 2.0 in sediment and pond water. In dark incubations, shoots subjected to calcium carbonate dissolution released bicarbonate and calcium with a molar quotient of 2:1; lowered pH (7.0–8.0) increased the release. Thus, the carbonate surface crust on living charophytes was not inert, as hitherto anticipated. Phosphate dark release occurred from basal shoots only, was unrelated to pH, and may have derived from organic decomposition, rather than from carbonate dissolution. Extensive phosphorus pools were associated with the charophyte stands (200–600 mg m−2) and had about 2/3 incorporated in alga tissue and 1/3 in carbonate crust. Overall, the biogeochemistry of carbon, calcium and phosphorus are closely linked in calcareous charophyte ponds. Carbonate dissolution from charophyte crusts at night and continuously from sediment might balance extensive carbonate precipitation during daytime photosynthesis. The substantial P-pool in charophyte stands may not derive from P-deprived water, but from P-rich sediment. Charophyte photosynthesis may still contribute to nutrient-poor conditions by forming carbonate-rich sediment of high P-binding capacity.

The purpose of this research was to explore how we were becoming teacher educators as we built and engaged in relationships through collaborative teaching and research practice. By engaging with collaborative self-study as methodology-pedagogy and rhizomatics, our data pertaining to teaching-research (i.e., group and pair meetings, reflective diaries) highlight how collaborative self-study produced evolving and meaningful practices, learning, and relationships that resulted in our becoming collaborative, committed, and innovative teacher educators. This study demonstrates the potential of using collaborative self-study together with relational and non-linear frameworks such as rhizomatics to reveal different and ongoing understandings of becoming teacher educators.

After-school programs (ASPs) might influence the activities and behaviors of children. The aim of the reported study was to investigate how stationary behavior unfolds during ASP time in a sample of Norwegian first graders. A total of 42 first graders from 14 ASPs were observed during one entire ASP day. ActiGraph accelerometers were used to measure the intensity of their physical activity (PA). Children were found to be involved in stationary behavior for 54.9% of the studied ASP time—a median of 79.5 min (IQR = 62.0). However, there was considerable variation among the children in the sample. Most stationary behavior—63.5% of all stationary behavior during ASP time—was accumulated when the children were sitting indoors. The proportion of stationary behavior was significantly higher indoors than outdoors, during adult-managed time than child-managed time, and during time spent together with other children than time spent alone (p &lt, 0.05). In child-managed physical activity play outdoors, stationary behavior commonly occurred during short periods of standing still. Stationary behavior was usually rapidly broken up by longer periods of PA. Stationary periods involved activities in close relationship with other children and appeared to be important for social interaction and friendship building. The researchers suggest that ASP staff members should actively promote physical activity play that breaks up sedentary time and replaces some stationary behaviors with PA, especially among the least active children.

The simple amino acid l-alpha-alanine (ala) in polycrystalline form was among the first substances to be proposed and subsequently developed for Electron Paramagnetic Resonance (EPR)-based solid state radiation dosimetry. One disadvantage with ala is a relatively low sensitivity for doses below a few gray (Gy) which is a dose range of particular interest in medical, accident and environmental applications. A number of other compounds have been screened and some of these have shown a better sensitivity to radiation exposure than ala, in some cases up to a factor of 7-8. In particular ammonium tartrate (AT) and lithium formate (LiFo) have been taken into practical use. The present work was initially aimed to investigate the low-temperature radical products in AT, and the reactions leading to the product of dosimetric interest at room temperature. As a part of these studies, the previously characterized major room temperature radical product was re-investigated using single crystal electron magnetic resonance (EMR) techniques combined with periodic density functional theory (DFT) -type quantum chemical calculations. Surprisingly, this study showed that the molecular structure of the dominant radical at room temperature is somewhat different from that previously proposed. Furthermore, a second room temperature radical, previously not well characterized, was carefully investigated and three hyperfine coupling tensors were determined. These three tensors were sufficient to simulate all experimental observations for the second radical but not alone sufficient to permit an unambiguous molecular structure of the defect to be determined. It appears that the EPR resonance from this radical does not influence the dosimetric potential of AT.

The analysis of single crystal electron magnetic resonance (EMR) data has traditionally been performed using software in programming languages that are difficult to update, are not easily available, or are obsolete. By using a modern script-language with tools for the analysis and graphical display of the data, three MatLab (R) codes were prepared to compute the g, zero-field splitting (zfs) and hyperfine coupling (hfc) tensors from roadmaps obtained by EPR or ENDOR measurements in three crystal planes. Schonlands original method was used to compute the g- and hfc-tensors by a least-squares fit to the experimental data in each plane. The modifications required for the analysis of the zfs of radical pairs with S = 1 were accounted for. A non-linear fit was employed in a second code to obtain the hfc-tensor from EPR measurements, taking the nuclear Zeeman interaction of an I = 1/2 nucleus into account. A previously developed method to calculate the g- and hfc -tensors by a simultaneous linear fit to all data was used in the third code. The validity of the methods was examined by comparison with results obtained experimentally, and by roadmaps computed by exact diagonalization. The probable errors were estimated using functions for regression analysis available in MatLab. The software will be published at https://doi.org/10.17632/ps24sw95gz.1, Input and output examples presented in this work can also be downloaded from https://old.liu.se/simarc/downloads?l=en. (C) 2021 The Author(s). Published by Elsevier Inc. Funding Agencies|Linkoping University; Ghent UniversityGhent University; University of Oslo

This chapter focuses on the role of the Danish state in stigmatizing and displacing groups from targeted common, non-profit housing estates (the so-called ghettos). It looks closer at the resistance movements, with special focus on Denmark’s largest non-profit housing estate, Gellerupparken. The chapter draws on an intersection between the literature of critical urban theory and social movement research. It highlights the increasing production of inequalities in Denmark and the concentration of precarious socio-economic groups in rental housing. The chapter explores the government’s ghetto politics, relevant policy documents, and stateled territorial stigmatization and displacement. It addresses how different actors have been trying to subvert the ghetto stigmatization through different forms of resistance such as the new social movement Almen Modstand (Common Resistance) as well as independent activists fighting against what they see as a racist politics. The ‘ghetto package’ has been met with a growing number of resistance movements and activities in Denmark.

Accidental hypothermia is associated with increased risk for arrhythmias. QRS/QTc is proposed as an ECG-marker, where decreasing values predict hypothermia-induced ventricular arrhythmias. If reliable it should also predict nonappearance of arrhythmias, observed in species like rat that regularly tolerate prolonged hypothermia. A rat model designed for studying cardiovascular function during cooling, hypothermia and subsequent rewarming was chosen due to species-dependent resistance to ventricular arrhythmias. ECG was recorded throughout the protocol. No ventricular arrhythmias occurred during experiments. QRS/QTc increased throughout the cooling period and remained above normothermic baseline until rewarmed. Different from the high incidence of hypothermia-induced ventricular arrhythmias in accidental hypothermia patients, where QRS/QTc ratio is decreased in moderate hypothermia; hypothermia and rewarming of rats is not associated with increased risk for ventricular fibrillation. This resistance to lethal hypothermia-induced arrhythmias was predicted by QRS/QTc.

Background: The current interest in models-based practice (MBP) as an innovation and framework has necessitated deeper understanding of both what MBP is and how teacher educators teach pre-service teachers about innovative approaches such as MBP. Despite several studies of individual teacher educators enacting MBP, there are few examples of how several teacher educators might go about implementing MBP in physical education teacher education (PETE) programmes. Purpose: The purpose of this study was to develop an understanding of how a collaborative approach to teaching pre-service teachers MBP can support coherence in PETE modules. The study was guided by the question: How do teacher educators teaching in one PETE module negotiate their experience of teaching about teaching as they implement MBP? Method: This collaborative self-study of teacher education practices was conducted in a Norwegian PETE department and involved five teacher educators. The particular setting for the study was one module (what might be described elsewhere as a course or unit of study) that Lasse, Berit, Anders, and Mats were to teach to first year pre-service teachers in one PETE programme (13 females and 37 males). In addition to teaching the module, the four teacher educators acted as critical friends to one another, while Tim (who was based in Canada) offered a second layer of critical friendship to group members both individually and collectively. Data generation included two primary sources: audio records of our meetings in different configurations (21 meetings and approximately 35 hours audio) and our reflective diaries (total of 10 entries and 20 pages). Data analysis involved a five-step dialogic process of ‘thinking with' Loughran’s (2006. Developing a Pedagogy of Teacher Education: Understanding Teaching and Learning About Teaching. London: Routledge) concept of developing a pedagogy of teacher education (Jackson, A. Y., and L. A. Mazzei. 2012. Thinking with Theory in Qualitative Research: Viewing Data Across Multiple Perspectives. London: Routledge). Results: This study provides insights into the affordances of taking a collaborative approach to teaching about teaching MBP and how such a collaborative approach facilitated implementation individually and collectively. Furthermore, the study highlights the ways the several collaborative processes and structures produced the development of a shared language and vision for teaching about teaching MBP. This shared vision led to coherence in how we talked and taught about MBP with each other and with pre-service teachers. These visions helped make our individual and collective practices and their articulation coherent to ourselves and to one another, and also to the pre-service teachers whom we taught. Conclusion: Our understanding is that the development of coherent PETE programmes and the modules within those programmes requires at least: (i) a professional group of teacher educators who are willing to share their understanding, challenges, and uncertainties with one another and with pre-service teachers, (ii) an inquiry-oriented stance towards researching group and departmental beliefs and practices, and (iii) a desire to better understand and share the development of new understandings with colleagues at departmental, national, and/or international levels.

Key Points Question Does D-cycloserine potentiate the effect of concentrated exposure and response prevention in difficult-to-treat obsessive-compulsive disorder? Findings In this randomized clinical trial of 163 participants, D-cycloserine did not significantly affect treatment outcomes. Most patients responded to the concentrated exposure and response prevention treatment, and nearly 50% were recovered at 1-year follow-up. Meaning In this study, concentrated exposure and response prevention treatment was effective for patients with difficult-to-treat obsessive-compulsive disorder, but adding D-cycloserine did not potentiate the treatment., This randomized clinical trial evaluates whether D-cycloserine potentiates the effect of concentrated exposure and response prevention among patients with difficult-to-treat obsessive-compulsive disorder., Importance Evidence is lacking for viable treatment options for patients with difficult-to-treat obsessive-compulsive disorder (OCD). It has been suggested that D-cycloserine (DCS) could potentiate the effect of exposure and response prevention (ERP) treatment, but the hypothesis has not been tested among patients with difficult-to-treat OCD. Objective To evaluate whether DCS potentiates the effect of concentrated ERP among patients with difficult-to-treat OCD. Design, Setting, and Participants The study was a randomized placebo-controlled triple-masked study with a 12-month follow-up. Participants were adult outpatients with difficult-to-treat OCD. A total of 220 potential participants were referred, of whom 36 did not meet inclusion criteria and 21 declined to participate. Patients had either relapsed after (n = 100) or not responded to (n = 63) previous ERP treatment. A total of 9 specialized OCD teams within the public health care system in Norway participated, giving national coverage. An expert team of therapists from the coordinating site delivered treatment. Inclusion of patients started in January 2016 and ended in August 2017. Data analysis was conducted February to September 2019. Interventions All patients received individual, concentrated ERP treatment delivered during 4 consecutive days in a group setting (the Bergen 4-day treatment format) combined with 100 mg DCS, 250 mg DCS, or placebo. Main outcomes and Measures Change in symptoms of OCD and change in diagnostic status. Secondary outcomes measures included self-reported symptoms of OCD, anxiety, depression, and quality of life. Results The total sample of 163 patients had a mean (SD) age of 34.5 (10.9) years, and most were women (117 [71.8%]). They had experienced OCD for a mean (SD) of 16.2 (10.2) years. A total of 65 patients (39.9%) were randomized to receive 100 mg DCS, 67 (41.1%) to 250 mg of DCS, and 31 (19.0%) to placebo. Overall, 91 (56.5%) achieved remission at posttreatment, while 70 (47.9%) did so at the 12-month follow-up. There was no significant difference in remission rates among groups. There was a significant reduction in symptoms at 12 months, and within-group effect sizes ranged from 3.01 (95% CI, 2.38-3.63) for the group receiving 250 mg DCS to 3.49 (95% CI, 2.78-4.18) for the group receiving 100 mg DCS (all P

BackgroundInterventions directed at after school programs (ASPs) have the potential to support physical activity (PA) in young children. Research has indicated that interventions that emphasize competence building among the ASP staff can lead to increased PA among the children. The present study evaluates the effectiveness of theActive Play in ASPintervention—a program for ASP staff aimed at supporting physical activity among first graders in ASP.MethodsWe used a matched-pair cluster randomized design and included 456 first graders from 14 schools in Norway. From these, 7 ASPs received the intervention (N = 229), while 7 acted as controls (N = 227). Measurements were taken at baseline, immediately post intervention (7 month follow-up) and after a year (19 month follow-up). The primary outcome was moderate to vigorous physical activity (MVPA), which was estimated with predefined cut points of counts per minute (CPM) and expressed as minutes/hour. Secondary outcomes were vigorous and light intensity physical activity (VPA and LPA) and sedentary behavior. The analyses of intervention effects were based on between-group differences in outcome changes between the 3 measurement points and were conducted using a mixed-effects model for repeated measures using categorical time. In exploratory analyses, we investigated gender, baseline body mass index, and baseline CPM as potential effect modifiers.ResultsNo significant intervention effects was observed on MVPA (0.55 min/hour [99% CI -0.55:1.64]) or on the secondary outcomes, min/hour of LPA, VPA or sedentary behavior. Exploratory analyses indicated that among the 50% least physically active children at baseline, children in intervention ASPs reduced sedentary time from baseline to 19 months follow up by 1.67 min/hour (95% CI -3.12:-0.21) compared to the controls.ConclusionsAlthough the intervention did not significantly increase the mean MVPA among the children in the intervention ASPs compared to controls, it did seem to have a small effect by reducing sedentary behavior time among the least active children. An even stronger emphasis on how to identify less active children and support their activity may be needed in order to increase their PA and further reduce sedentary behavior time.Trial registrationClinicalTrials;NCT02954614, Registered 3 November 2016, −Retrospectively registered, first participant enrolled August 2016

Improvement of sleep is a central treatment goal for patients in a manic state. Blue‐blocking (BB) glasses as adjunctive treatment hasten overall recovery from mania. This method is an evolvement from dark therapy and builds on the discovery of the blue‐light‐sensitive retinal ganglion cell that signals daytime to the brain. We report effects of adjunctive BB glasses on actigraphy‐derived sleep parameters for manic inpatients as compared to placebo. Hospitalized patients with bipolar disorder in a manic state aged 18–70 years were recruited from five clinics in Norway from February 2012 to February 2015. The participants were randomly allocated to wearing BB glasses or placebo (clear glasses) as an adjunctive treatment from 18:00 to 08:00 hours for seven consecutive nights. Sleep and wake were monitored by actigraphy. From 32 eligible patients, 10 patients in each group qualified for the group analyses. The BB group's mean sleep efficiency was significantly higher at night 5 as compared to the placebo group (92.6% vs. 83.1%, p = .027). The 95% confidence interval (CI) was 89.4%–95.8% in the BB group and 75.9%–90.3% in the placebo group. There were fewer nights of interrupted sleep in the BB group: 29.6% versus 43.8% in the placebo group. The BB group received less‐intensive sleep‐promoting pharmacological treatment and showed significantly higher sleep efficiency and more consolidated sleep as compared to the placebo group. Our findings suggest sleep‐promoting effects through deactivating mechanisms. Adjunctive BB glasses seem to be useful for improving sleep for manic patients in the hospital setting. publishedVersion

BACKGROUND: Immunoglobulin E (IgE) are least abundant, tightly regulated and IgE producing B cells are rare. The cellular origin and evolution of IgE responses are poorly understood.OBJECTIVE: To investigate the cellular and clonal origin of IgE memory responses following mucosal allergen exposure by sublingual immunotherapy (SLIT).METHODS: In a randomized double-blind, placebo-controlled, time-course SLIT study, peripheral blood mononuclear cells (PBMCs) and nasal biopsies were collected from forty adults with seasonal allergic rhinitis at baseline, 4, 8, 16, 28 and 52 weeks. RNA was extracted from PBMCs, sorted B cells and nasal biopsies for VH repertoire sequencing. Moreover, monoclonal antibodies were derived from single B cell transcriptomes.RESULTS: Combining VH repertoire sequencing and single cell transcriptomics yielded direct evidence of a parallel boost of two clonally and functionally related B cell subsets of short-lived IgE+ plasmablasts and IgG+ memory B cells (termed IgGE). Mucosal grass pollen allergen exposure by SLIT resulted in highly diverse IgE and IgGE repertoires. These were extensively mutated and appeared relative stable as per heavy chain isotype, somatic hypermutations and clonal composition. Single IgGE + memory B cell and IgE+ pre-plasmablast transcriptomes encoded antibodies that were specific for major grass pollen allergens and were able to elicit basophil activation at very low allergen concentrations.CONCLUSION: For the first time, we have shown that upon mucosal allergen exposure, human IgE memory resides in allergen-specific IgG+ memory B cells. These rapidly switch isotype and expand into short-lived IgE+ plasmablasts and serve as a potential target for therapeutic intervention.

Chicken protein hydrolysates (CPHs) generated from rest raw materials through enzymatic hydrolysis using Corolase PP or Alcalase were shown to reduce inflammation and stimulate hepatic mitochondrial fatty acid oxidation in high‐fat‐fed mice. This study investigates the effect of CPH diets in atherosclerosis‐prone apolipoprotein E‐deficient (Apoe−/−) mice. Apoe−/− mice were divided into three groups of 12 animals and fed high‐fat diets with casein (control), Alcalase CPH, or Corolase PP CPH. After 12 weeks, mice were sacrificed, blood samples were collected, and aorta was dissected for subsequent én face analysis. Mice fed Corolase PP CPH but not Alcalase CPH had significantly lower % atherosclerotic plaque area in the aortic arch compared to controls (p = .015 and p = .077, respectively). Plasma and liver cholesterol and triacylglycerol remained constant, but levels of the fatty acid C20:5n‐3 were increased, accompanied by an elevated delta‐5 desaturase index in both CPHs groups. Moreover, a significant reduction of plasma MCP‐1 was detected in Corolase PP CPH compared to control. Overall, our data show that protein hydrolysates from chicken reduced atherosclerosis and attenuated systemic risk factors related to atherosclerotic disorders, not related to changes in the level of plasma cholesterol., Chicken protein hydrolysates (CPHs) generated from rest raw materials through enzymatic hydrolysis using Corolase PP or Alcalase were shown to reduce aortic atherosclerotic plaque formation compared to a casein control in Apoe‐/‐ mice fed a high‐fat diet for 12 weeks. This reduction was independent of plasma lipid levels, but may be linked to effects on fatty acid composition and systemic inflammatory processes.

Background: Development of motor competencies and learning of movements in children is dependent on varied physical activity (PA). After-school programs (ASP) might provide opportunities for young schoolchildren to participate in PA. The aim of the current study was to investigate the PA of first graders in ASP and to consider its contribution to the development of motor competencies and the learning of movements. Methods: The study was performed utilizing a mixed methods design. A total of 42 first graders were sampled from 14 ASPs in Norway. Direct observations of the children’s activities were conducted for the duration of one entire ASP day. PA intensity was measured using ActiGraph accelerometers. Qualitative data were analyzed using qualitative content analysis, while the Mann-Whitney U test and the Wilcoxon signed-rank test were used to analyze the quantitative data. Results: The median PA time among the observed children was 61.5 minutes. The median stationary time was 75.9 minutes. There was considerable variation within the sample. Girls were significantly more engaged in stationary behavior than boys. Frequent changes in activity type and intensity were typical features of the children’s ASP day. PA duration and intensity were significantly higher outdoors than indoors. Adult-managed time had longer periods of stationary behavior than child-managed time. The PA at all intensity levels contained barrier-breaking movements—especially at light intensity levels. Conclusion: Most of the first graders studied were engaged in a variety of activity types of different duration and intensity levels, favorable for the development of motor competencies and for the learning of movements. Hence, it is reasonable to highlight that light PA, in combination with moderate and vigorous PA, is also of great importance for children during the time they spend in ASP. Ultimately, there is a need for staff members who can also stimulate varied PA among the most stationary children. The study is funded by - Norwegian Fund for Postgraduate Training in Physiotherapy (http://fysiofondet.no/) - Oslo Metropolitan University (https://www.oslomet.no/en/english).

BACKGROUND Endogenous antibodies to signaling molecules and receptors (Abs) are associated with Alzheimer's disease (AD). OBJECTIVES To investigate the association of 33 Abs to dopaminergic, serotoninergic, muscarinic, adrenergic, vascular, and immune receptors with cognitive, neuropsychiatric, and mortality outcomes. METHODS Ninety-one patients with mild AD were followed annually for 5 years with the Mini-Mental State Examination (MMSE) and the Neuropsychiatric Inventory (NPI; composite outcomes: "psychosis" (item 1 + 2), "mood" (item 4 + 5 + 7), and "agitation" (item 3 + 8 + 9)). Abs were quantified in sera obtained at baseline by ELISA and reduced to principal components (PCs). Associations between Abs and outcomes were assessed by a mixed model (MMSE decline), zero-inflated fixed effects count models (composite NPI scores), and Cox regression (mortality). The resulting p-values were adjusted for multiple testing according to a false discovery rate of 0.05 (Benjamini-Hochberg). RESULTS The measured levels of the 33 Abs formed four PCs. PC1 (dopaminergic and serotonergic Abs) was associated with increased mortality (Hazard ratio 2.57, p < 0.001), PC2 (serotonergic, immune, and vascular Abs) with decreased agitation symptoms (β - 0.19, p < 0.001), and PC3 (cholinergic receptor Abs) with increased mood symptoms (β 0.04, p = 0.002), over time. There were no associations between Abs and MMSE decline. CONCLUSION The associations between Abs, mortality, and neuropsychiatric symptoms reported in this cohort are intriguing. They cannot, however, be generalized. Validation in independent sample sets is required.

Naturally occurring antibodies are linked to inflammation, tissue injury and apoptosis, processes also linked to heart failure. Associations between antibodies, inflammation and myocardial damage, have not been elucidated in heart failure.We investigated if 25 antibodies to receptors expressed in the cardiovascular system were associated with troponin-T, biomarkers of inflammation and clinical measures of disease severity, in patients with heart failure.Antibodies in sera from patients (n=191) with ischemic (n=155) or non-ischemic (n=36) heart failure were measured with full-receptor sandwich enzyme-linked immunosorbent assays. All patients underwent coronary angiography with determination of left ventricular ejection fraction (LVEF) and left ventricular end-diastolic pressure (LVEDP). Measured biomarkers included troponin-T, C-reactive protein, erythrocyte sedimentation rate, fibrinogen and neopterin.Stabilin-1-antibodies correlated with troponin-T (β 0.23 p=0.008), soluble endoglin-antibodies with erythrocyte sedimentation rate (β 0.19, p=0.007) and fibrinogen (β 0.28, p0.001). Platelet-derived growth factor subunit β-antibodies were associated with neopterin (β 0.17, p=0.002). All antibodies were correlated (R 0.26 to 0.91) and formed 4 principal components (PCs). Patients with high CRP and high PC2 had higher NYHA class and patients with high troponin-T and high PC1 had lower LVEDP (interactions, all p0.05).Antibodies to receptors are correlated and are associated with biomarkers of inflammation and myocardial damage, which further modifies their association with disease severity in heart failure. Their functional activity and immunological function, remain undecided.

Background: Alzheimer's disease (AD) is associated with several antibodies as well as signaling molecules and receptors. These may be detrimental in the presence of a disrupted blood-brain barrier (BBB). Objective: To investigate whether the levels of antibodies toward 33 signaling molecules involved in neurotransmitter, vascular, and immune functions were associated with AD and, within the AD group; cognitive function and mood. Methods: Antibodies in sera from patients with mild AD [(n = 91) defined as a Mini-Mental State Examination ≥ 20 or a Clinical Dementia Rating Scale≤1] and healthy controls (n = 102) were measured with enzyme-linked immunosorbent assays. Levels in AD and controls were compared by Mann-Whitney test. In the AD group, associations between antibodies and psychometric test scores were analyzed by robust regression. The false discovery threshold was set to 0.05. Results: Antibodies to serotonin receptors [5-HT2AR (effect size (r) = 0.21, p = 0.004), 5-HT2CR (r = 0.25, p = 0.0005) and 5-HT7R (r = 0.21, p = 0.003)], vascular endothelial growth factor receptor 1 [VEGFR1 (r = 0.29, p

Presenation at Frampeik, Tromsø, 11-13 October 2019. Frampeik is the annual research conference for medicine and dentistry students in Norway. More information at https://www.frampeik.no/.

Dysregulation of the tryptophan (Trp)-NAD+ pathway has been related to several pathological conditions, and the metabolites in this pathway are known to influence mitochondrial respiration and redox status. The aim of this project was to investigate if stimulation of beta-oxidation and mitochondrial proliferation by the mitochondrial-targeted compound 2-(tridec-12-yn-1-ylthio)acetic acid (1-triple TTA) would influence metabolites of the Trp-Kyn-NAD+ pathway. We wished to investigate how carnitine depletion by meldonium-treatment influenced these metabolites. After dietary treatment of male Wistar rats with 1-triple TTA for three weeks, increased hepatic mitochondrial- and peroxisomal fatty acid oxidation resulted. The plasma content of total carnitines decreased compared to control animals, whereas hepatic genes involved in CoA biosynthesis were upregulated by 1-triple TTA treatment. The plasma Trp level and individual metabolites in the kynurenine pathway were increased by 1-triple TTA, associated with decreased hepatic gene expression of indoleamine2,3-dioxygenase. 1-triple TTA treatment increased conversion of Trp to nicotinamide (Nam) as the plasma content of quinolinic acid, Nam and N1-methylnicotinamide (mNam) increased, accompanied with suppression of hepatic gene expression of α-amino-α-carboxymuconate-e-semialdehyde decarboxylase. A positive correlation between mitochondrial fatty acid oxidation and Trp-derivatives was found. Almost identical results were obtained by 1-triple TTA in the presence of meldonium, which alone exerted minor effects. Moreover, the plasma Kyn:Trp ratio (KTR) correlated negatively to mitochondrial function. Whether increased flux through the Trp-NAD+ pathway increased redox status and lowered inflammation locally and systemically should be considered.

BACKGROUND Metabolites of the kynurenine pathway (mKP) relate to important aspects of heart failure pathophysiology, such as inflammation, energy-homeostasis, apoptosis, and oxidative stress. We aimed to investigate whether mKP predict mortality in patients with heart failure. METHODS The study included 202 patients with heart failure (73.8% with coronary artery disease (CAD)), propensity score matched to 384 controls without heart disease, and 807 controls with CAD (71%). All underwent coronary angiography and ventriculography at baseline. Plasma mKP, pyridoxal 5'phosphate (PLP) and CRP were measured at baseline. Case-control differences were assessed by logistic regression and survival by Cox regression, adjusted for age, gender, smoking, diabetes, ejection fraction, PLP, eGFR and CRP. Effect measures are reported per standard deviation increments. RESULTS Higher plasma levels of kynurenine, 3- hydroxykynurenine (HK), quinolinic acid (QA), the kynurenine-tryptophan-ratio (KTR) and the ratio of HK to xanthurenic acid (HK/XA) were detected in heart failure compared to both control groups. The mortality rate per 1000 person-years was 55.5 in patients with heart failure, 14.6 in controls without heart disease and 22.2 in CAD controls. QA [HR 1.80, p = 0.013], HK [HR 1.77, p = 0.005], HK/XA [HR 1.67, p < 0.001] and KTR [HR 1.55, p = 0.009] were associated with increased mortality in patients with heart failure, while XA [HR 0.68-0.80, p = 0.013-0.037] were associated with lower mortality in all groups. HK and HK/XA had weak associations with increased mortality in CAD-controls. CONCLUSION Elevated plasma levels of mKP and metabolite ratios are associated with increased mortality, independent of CAD, in patients with heart failure.

IgE is the least abundant immunoglobulin and tightly regulated, and IgE-producing B cells are rare. The cellular origin and evolution of IgE responses are poorly understood.The cellular and clonal origin of IgE memory responses following mucosal allergen exposure by sublingual immunotherapy (SLIT) were investigated.In a randomized double-blind, placebo-controlled, time course SLIT study, PBMCs and nasal biopsy samples were collected from 40 adults with seasonal allergic rhinitis at baseline and at 4, 8, 16, 28, and 52 weeks. RNA was extracted from PBMCs, sorted B cells, and nasal biopsy samples for heavy chain variable gene repertoire sequencing. Moreover, mAbs were derived from single B-cell transcriptomes.Combining heavy chain variable gene repertoire sequencing and single-cell transcriptomics yielded direct evidence of a parallel boost of 2 clonally and functionally related B-cell subsets of short-lived IgEFor the first time, we have shown that on mucosal allergen exposure, human IgE memory resides in allergen-specific IgG

The doctoral dissertation is a key component of postgraduate education that plays an important role for knowledge production and hence the development of a discipline. Swedish human geography currently lacks an overview of dissertations. This article fills this knowledge gap by reporting findings from a unique database covering all doctoral dissertations between 1884 and 2015. The paper focuses on the demographics of the authors (age, gender), the format of the dissertation and explores productivity variations for authors of compilation dissertations. The findings show a notable increase in the number of doctoral dissertations since the late 1960s but a decreasing share of doctoral dissertations in the social sciences since the 1970s. In terms of demographics, we show that while the age of the authors remains relatively stable, the gender-balance has improved considerably. In terms of format, the monograph has rapidly given way to compilation dissertations, which now account for half the number of dissertations. More than 70% of all dissertations are now published in English. Statistical results suggest that the likelihood of completing a compilation dissertation is greater if the doctoral candidate is young and if attending Umea University. But individual author productivity for compilation dissertations is mainly influenced by unobservables.

Background Results from studies on diabetes and migraine risk are conflicting, which may be due to methodological limitations. Prospective studies with long follow-up could increase our understanding of the relationship between the two diseases. Method We performed a cohort study including the whole Norwegian population alive on 01.01.2004, using prescriptions registered in the Norwegian prescription database to identify individuals developing type 1 diabetes, type 2 diabetes and migraine during follow-up (10 years). We used Cox proportional hazards regression to estimate rate ratios with corresponding 95% confidence intervals for the effect of diabetes on migraine risk, adjusting for age, sex, and educational level. Result We identified 7,883 type 1 diabetes patients and 93,600 type 2 patients during the study period. Type 1 diabetes was significantly associated with a subsequent decreased migraine risk during follow-up in the age- and sex-adjusted analyses (0.74; 0.61–0.89). Type 2 diabetes was also associated with a significantly lower migraine risk (0.89; 0.83–0.95). Further adjustment for educational level yielded similar results for both diabetes. Conclusion Both type 1 and type 2 diabetes were significantly associated with a decreased risk of migraine. This suggests that diabetes or diabetes treatment may have a protective effect on the development of migraine.

Housing was a backbone of the Danish welfare state, but this has been profoundly challenged by the past decades of neoliberal housing politics. In this article we outline the rise of the Danish model of association-based housing on the edge of the market economy (and the state). From this, we demonstrate how homes in private cooperatives through political interventions in the context of a booming real estate market have plunged into the market economy and been transformed into private commodities in all but name, and we investigate how non-profit housing associations frontally and stealthily are attacked through neoliberal reforms. This carries the seeds for socio-spatial polarization and may eventually open the gate for commodification – and thus the dismantling of the little that is left of a socially just housing sector. Yet, while the association-based model was an accessary to the commodification of cooperative housing, it can possibly be an accomplice in sustaining non-profit housing as a housing commons.

Background: Autoantibodies with agonist function are described in cardiovascular disorders. Since vascular risk factors are associated with an increased risk for Alzheimer’s disease (AD), we investigated a potential association between antibodies to the angiotensin 2 type 1 receptor (anti-AT1R) and AD. Objective: The primary objective of this study was to investigate the association between anti-AT1R and AD. The secondary objective was to investigate the association between clinical or biomarker features of AD and anti-AT1R. Methods: Samples from patients with mild AD participating in a longitudinal study in Western Norway (n = 92, 65 [71%] females, mean age 74.8 [range 50–89]) and age- and gender-matched healthy controls (n = 102) were included. Cerebrospinal fluid (CSF) AD biomarkers were assessed in a subgroup of patients. Patients were examined annually, including Mini-Mental State Examination. ELISA was used to measure anti-AT1R in serum. Non-parametric tests were used for statistical calculations and a p < 0.05 was considered significant. Results: AD patients had significantly higher levels of anti-AT1R compared with healthy controls (10.2 U/mL versus 8.1 U/mL, p = 0.04). This difference was found only in patients without hypertension and diabetes. Anti-AT1R levels correlated with CSF total tau (p = 0.03) and phosphorylated tau (p = 0.03) levels, and inversely with blood pressure in AD (Spearman R −0.277, p = 0.008). Discussion: AD is associated with increased levels of anti-AT1R, and the antibodies correlated with CSF total, and phosphorylated tau levels. Further research is needed to understand the blood pressure response in AD without hypertension and a potential link between tau and anti-AT1R in AD.

Major Depressive Disorder (MDD) is often associated with high levels of stress and disturbances in the Hypothalamic Pituitary Adrenal (HPA) system, yielding high levels of cortisol, in addition to cognitive dysfunction. Previous studies have shown a relationship between cortisol profile and cognitive functioning in recurrent MDD in general. More specifically, the association between hypercortisolism and cognitive functioning, such as memory and Executive Functioning (EF), and also more recently cortisol suppression has been explored. However, no studies have investigated these relationships in patients diagnosed with first episode MDD. The aim of the present study was to examine the relationship between cortisol levels before and after the Dexamethasone suppression test (DST) and cognitive function in first episode MDD patients. Twenty-one patients meeting the DSM-IV criteria for a first episode of MDD diagnosis were included in the study. The control group was matched for age, gender and education level. Cortisol was measured in saliva collected with Salivette sampling devices. Saliva samples were collected 4 times during a 24 hours period over two consecutive days: at awakening, after 45 minutes, after 7 hours and at 11 pm. Dexamethasone (1.0 mg) was given orally on Day 1 at 11 pm. The neuropsychological test battery consisted of standardized tests measuring executive functioning (EF) and memory functioning. Cortisol levels did not differ significantly between patients and controls on Day 1, except for the last sample before Dexamethasone administration, where the control group showed higher levels. Both groups showed suppression after Dexamethasone. On Day 2 there was a significant difference between groups at the third sample, showing a significantly lower level in the control group, suggesting that the controls have a more effective suppression profile than the patients. There were no significant correlations between cortisol levels before or after Dexamethasone and cognitive measures. The results indicate impairment on HPA-axis functioning in first episode MDD patients, with less suppression functioning compared to healthy controls, but no relationship between cortisol profile and cognitive functioning in EF or Memory.

Patients with Alzheimer’s disease (AD) have blood-brain barrier (BBB) dysfunction. Methods to study cells of the BBB in vivo would facilitate analyses of neurovascular damage in early AD. Thus, we conducted a pilot study to investigate if brain-derived endothelial cells (BDCECs) could be identified from a cell population of circulating endothelial cells (CECs). Peripheral blood was sampled from early AD patients (n = 9), patients with vascular diseases (myocardial infarction (n = 8) and ischemic stroke (n = 8)), and healthy controls (n = 8). We enumerated CD34+/CD146+/CD45− cells (CECs) and Glucose transporter-1 (Glut1+ CECs (BDCECs)) by flow cytometry. We found that BDCECs formed a separate, aggregate cell population. Glut1 expression on BDCECs, measured by the median fluorescence intensity, was significantly decreased in patients with AD compared to both the healthy controls and patients with myocardial infarction ((p

Neuroleptic malignant syndrome is an unpredictable iatrogenic neurologic emergency condition, mainly arising as an idiosyncratic reaction to antipsychotic agent use. It is characterized by distinctive clinical features including a change in mental status, generalized rigidity, hyperpyrexia, and dysautonomia. It can be lethal if not diagnosed and treated properly. Mortality and morbidity attributed to this syndrome have recently declined markedly due to greater awareness, earlier diagnosis, and intensive care intervention. In most cases, the syndrome occurs as a result of a rapid increase in a dose of neuroleptic, especially one of the long-acting ones. Pathophysiology behind this syndrome is attributed to a dopamine receptor blockade inside the neurons rendered by the offending drug and excessive calcium release from the sarcoplasmic reticulum of skeletal myocytes. Laboratory tests, although not diagnostic, may assist in assessing the severity of the syndrome and also the consequent complications. The syndrome has been described in all age groups and occurs more in males than in females. Genetics appears to be central regarding the etiology of the syndrome. Stopping the use of the offending agent, cold intravenous fluids, and removal of the causative agent and its possible active metabolites is the cornerstone of treatment. Periodic observation of psychotic patients recently started on antipsychotic medications, especially those being treated with depot preparations, may aid to an early diagnosis of the syndrome and lead to early treatment. publishedVersion

Head and neck squamous cell carcinoma (HNSCC) tumours are associated with high mortality despite advances in therapy. The monoclonal antibody cetuximab (Erbitux®) has been approved for the treatment of advanced HNSCC. However, only a subset of HNSC patients receiving cetuximab actually responds to treatment, underlining the need for a means to tailor treatments of individual patients. The aim of the present study was to investigate the effect of cetuximab treatment on tumour growth, on tumour partial oxygen pressure as measured by LiPc electron paramagnetic resonance oximetry and on the expression of proteins involved in tumour growth, metabolism and hypoxia. Two HNSCC cell lines, UT-SCC-2 and UT-SCC-14, were used to generate xenografts on female BALB/c (nu/nu) nude mice. Mice with xenografts were given three injections of intraperitoneal cetuximab or phosphate-buffered saline, and the tumour volume was recorded continuously. After treatment the tumour partial oxygen pressure was measured by LiPc electron paramagnetic resonance oximetry and the expression of epidermal growth factor receptor (EGFR), phosphorylated EGFR, Ki-67, MCT1, MCT4, GLUT1, CAIX and HIF-1α were investigated by immunohistochemistry. In xenografts from both cell lines (UT-SCC-2 and UT-SCC-14) cetuximab had effect on the tumour volume but the effect was more pronounced on UT-SCC-14 xenografts. A higher tumour oxygenation was measured in cetuximab-treated tumours from both cell lines compared to untreated controls. Immunocytochemical staining after cetuximab treatment shows a significantly decreased expression of EGFR, pEGFR, Ki67, CAIX and nuclear HIF-1α in UT-SCC-14 tumours compared to untreated controls. MCT1 and GLUT1 were significantly decreased in tumours from both cell lines but more pronounced in UT-SCC-14 tumours. Taken together, our results show that cetuximab treatment decreases the tumour growth and increases the tumour partial oxygen pressure of HNSCC xenografts. Furthermore we found a potential connection between the partial oxygen pressure of the tumours and the expression of proteins involved in tumour growth, metabolism and hypoxia. Funding agencies: Swedish Research Council [2009-5430]; LiU Cancer (Linkoping University); LiU Cancer (Region Ostergotland)

A radical drug treatment for bipolar affective disorder (BD) is currently unavailable. This is attributed to the fact that the precise pathophysiology of this ailment is unclear though a genetic factor is an essential element in etiology. Dissimilar to other serious psychiatric categories such as psychoses and major depression the forecast of this disease is unpredictable. There is a high suicidal risk among BD affected individuals. In this review we will consider lithium, the drug of choice in treatment of this disorder with special emphasis on pharmacology and toxicity. We have also elucidated the alternatives to lithium, since it has a wide spectrum of side-effects. Lithium is known to interact with many types of drugs used to treat different ailments in humans. This could cause either augmentation or minimization of the therapeutic action, causing secondary undesired effects of the agent. This necessitates a search for other alternatives and/or different combinations to lithium in order to decrease the range of unwanted effects for which it has received discredit. These alternatives should be potent mood stabilizers as monotherapy so as to avoid polypharmacy. If not, one should find the best combination of drugs (synergistic agents) such that the lithium dose can be minimized, thereby securing a more potent drug therapy. This study also focuses on the provision of instruction to psychiatric care givers, such as junior doctors in residency, nurses in psychiatric units, psychiatric emergency personnel and, additionally, medical and pharmacy students.

The structures of the free radicals formed by the irradiation of potassium dithionate (K2S2O6) with 60Co γ-rays and 14N7+ ions were investigated by EPR to further examine a recently proposed LET effect in this material. Two types of SO 3 − radical ions were identified in X-irradiated single crystals by measurements at X- and Q bands. One of these (S1) exhibited 33S hyperfine couplings A⊥ = 12.49, A|| = 15.60 mT, the other (S2) A⊥ = 11.29, A|| = 13.92 mT. The g-factors were nearly isotropic, g⊥ = 2.0010, g|| = 2.0003; and g⊥ = 2.0026, g|| = 2.0008, respectively. The 33S hyperfine coupling tensors and g-tensors were axially symmetric about the trigonal -axis, coinciding with the direction of the S–S bonds of the two non-equivalent S 2 O 6 2 − ions in the crystal. A model for the radiation damage was proposed in which the SO 3 − radical ions retain the orientation of the SO3 groups, aligned along the trigonal axis. The structure of a third main radical species (S3) with g⊥ = 2.0026, g|| = 2.0052 could not be unambiguously assigned, due to undetected 33S features. The relative integrated intensities of S1, S2 and S3 depended on the radiation quality and were approximately estimated as 0.18: 0.65:0.17 for 60Co γ-rays and 0.47: 0.38: 0.15 for 14N7+ ions. Additional weak lines on the low field side of the main signal were tentatively attributed to SO 2 − radical ions. An even weaker strongly anisotropic pair of lines was attributed to SO 3 − radical pairs separated by 0.93–0.95 nm along the trigonal axis.