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This paper invites readers to an encounter of novel learning in the school subject physical education, and specifically swimming training. In collaboration with Deleuze’s immanent philosophy and creative observations in a case-assemblage, I speculate about productive experiences and educational events as movements toward physical activation, higher education, and the dissolution of health inequalities. Troubling situations of a standardized model of swimming training is combined with a quantum space where multiple divergent ideas, forces, and feelings interact and produce unforeseen learnings, values, and qualities. Frictions between segmented spaces and quantum spaces orient/reorient the student’s/swimming instructor’s/my/your? learning, values, and qualities. Finally, I emphasize quantum spaces as the heart of educational movement and the importance of creating open educational systems to perhaps think physical education forward.

Development of autoimmune diseases is the result of a complex interplay between hereditary and environmental factors, with multiple genes contributing to the pathogenesis in human disease and in experimental models for disease. The T-box protein 3 is a transcriptional repressor essential during early embryonic development, in the formation of bone and additional organ systems, and in tumorigenesis. With the aim to find novel genes important for autoimmune inflammation, we have performed genetic studies of collagen-induced arthritis (CIA), a mouse experimental model for rheumatoid arthritis. We showed that a small genetic fragment on mouse chromosome 5, including Tbx3and three additional protein-coding genes, is linked to severe arthritis and high titers of anti-collagen antibodies. Gene expression studies have revealed differential expression of Tbx3in B cells, where low expression was accompanied by a higher B cell response upon B cell receptor stimulation in vitro. Furthermore, we showed that serum TBX3 levels rise concomitantly with increasing severity of CIA. From these results, we suggest that TBX3 is a novel factor important for the regulation of gene transcription in the immune system and that genetic polymorphisms, resulting in lower expression of Tbx3, are contributing to a more severe form of CIA and high titers of autoantibodies. We also propose TBX3 as a putative diagnostic biomarker for rheumatoid arthritis.

Reduced cerebral blood flow has been associated with cognitive decline and incident dementia, with oxidative stress and reduced beta-amyloid clearance as possible mechanisms for neurodegeneration. Transcranial doppler sonography is a non-invasive tool for measuring cerebrovascular hemodynamics, including mean cerebral blood flow velocity. A systematic review and meta-analysis was performed to study mean cerebral blood flow velocity in the middle cerebral artery in persons with mild cognitive impairment and dementia compared to cognitively normal elderly.

Pathological bone changes differ considerably between inflammatory arthritic diseases and most studies have focused on bone erosion. Collagen-induced arthritis (CIA) is a model for rheumatoid arthritis, which, in addition to bone erosion, demonstrates bone formation at the time of clinical manifestations. The objective of this study was to use this model to characterise the histological and molecular changes in bone remodelling, and relate these to the clinical disease development. A histological and gene expression profiling time-course study on bone remodelling in CIA was linked to onset of clinical symptoms. Global gene expression was studied with a gene chip array system. The main histopathological changes in bone structure and inflammation occurred during the first two weeks following the onset of clinical symptoms in the joint. Hereafter, the inflammation declined and remodelling of formed bone dominated. Global gene expression profiling showed simultaneous upregulation of genes related to bone changes and inflammation in week 0 to 2 after onset of clinical disease. Furthermore, we observed time-dependent expression of genes involved in early and late osteoblast differentiation and function, which mirrored the histopathological bone changes. The differentially expressed genes belong to the bone morphogenetic pathway (BMP) and, in addition, include the osteoblast markers integrin-binding sialoprotein (Ibsp), bone gamma-carboxyglutamate protein (Bglap1), and secreted phosphoprotein 1 (Spp1). Pregnancy-associated protein A (Pappa) and periostin (Postn), differentially expressed in the early disease phase, are proposed to participate in bone formation, and we suggest that they play a role in early bone formation in the CIA model. Comparison to human genome-wide association studies (GWAS) revealed differential expression of several genes associated with human arthritis. In the CIA model, bone formation in the joint starts shortly after onset of clinical symptoms, which results in bony fusion within one to two weeks. This makes it a candidate model for investigating the relationship between inflammation and bone formation in inflammatory arthritis.

Ligand binding and conformational changes that accompany signaling from G protein–coupled receptors (GPCRs) have mostly focused on the role of transmembrane helices and intracellular loop regions. However, recent studies, including several GPCRs cocrystallized with bound ligands, suggest that the extracellular surface (ECS) of GPCRs plays an important role in ligand recognition, selectivity, and binding, as well as potentially contributing to receptor activation and signaling. This study applied alanine-scanning mutagenesis to investigate the role of the complete ECS of the α1B-adrenoreceptor on norepinephrine (NE) potency, affinity, and efficacy. Half (24 of 48) of the ECS mutations significantly decreased NE potency in an inositol 1-phosphate assay. Most mutations reduced NE affinity (17) determined from [3H]prazosin displacement studies, whereas four mutations at the entrance to the NE binding pocket enhanced NE affinity. Removing the influence of NE affinity and receptor expression levels on NE potency gave a measure of NE efficacy, which was significantly decreased for 11 of 48 ECS mutants. These different effects tended to cluster to different regions of the ECS, which is consistent with different regions of the ECS playing discrete functional roles. Exposed ECS residues at the entrance to the NE binding pocket mostly affected NE affinity, whereas buried or structurally significant residues mostly affected NE efficacy. The broad potential for ECS mutations to affect GPCR function has relevance for the increasing number of nonsynonymous single nucleotide polymorphisms now being identified in GPCRs.

Background and aim: Hip fracture is a leading cause of mortality, morbidity, and disability in older people. The aim of the present study was to prospectively assess the development of physical performance in patients with hip fracture after surgery.Setting: Prospective, observational study in a Swedish university hospital.Methods: Assessment of 102 consecutive patients (65 females), with a mean age of 82 years (range 35-98) without specific inclusion or exclusion criteria. Seven physical functions were assessed using the following 4 measuring methods and 3 rating scales at baseline 7 to 10 days after surgery and follow-up after 4 months (F4): 10-m habitual walking speed (HWS), timed up and go (TUG), 30-second chair stand test (CST), handgrip strength (HGS), Berg balance scale (BBS), functional ambulation category (FAC), and general mobility.Results: The 47% dropout patients were significantly older and more often lived alone or in nursing homes and used indoor walking aids. At baseline, the mean HWS was 0.4/0.5 (females/males) m/s; TUG 53/30 s; CST 4/5 kg, and HGS 17.4/31.2 kg. The medians of BBS and FAC were 20/20 and 4/4, respectively. There were significant mean improvements at F4 for all 4 measured functions, except for HGS in males but for neither of the rating scales. There was a large heterogeneity in all assessed variables, both at baseline and regarding change at 4 months. Therefore, the mean/median results are depicted in figures, showing all individual results at baseline and F4, compared to reference values and discussed in relation to degree of improvement.Conclusion: The observed large heterogeneity at baseline as well as F4 makes it essentially meaningless to report means and median data of functional assessment of patients with hip fracture. There is a strong need for individualization in both health analysis and how the treatment program is targeted, carried through, and evaluated over time in patients with hip fracture.

OBJECTIVE: The minor G-allele of FOXO3A rs2802292 has been associated with longevity. We aimed to investigate whether a phenotype related to healthy metabolic aging could be identified in individuals carrying the longevity-associated FOXO3A rs2802292 G-allele. Research Design and Methods: rs2802292 was genotyped in a phenotypically well-characterized population of young and elderly twins (n = 190) and in the population-based Inter99 cohort (n = 5768). All participants underwent oral glucose tolerance tests, and the twin population was additionally examined with an iv glucose tolerance test and a hyperinsulinemic, euglycemic clamp. Basal and insulin-stimulated FOXO3A mRNA expression was assessed in skeletal muscle biopsies from the twin population. RESULTS: In the twin sample, carriers of the minor G-allele of rs2802292 showed reduced fasting plasma insulin [per allele effect (β) = –13% (–24; –1) (95% confidence interval), P = 0.03] and lower incremental area under the curve 0–120 min for insulin after an oral glucose load [β = –14% (–23; –5), P = 0.005]. The G-allele was associated with increased peripheral insulin action [glucose disposal rate clamp, β = 0.85 mg · kgfat-free mass–1· min–1(0.049; 1.64), P = 0.04] and lower hepatic insulin resistance index [β = –13% (–25; –1), P = 0.03]. Furthermore, carriers of the G-allele had increased basal FOXO3A mRNA expression in skeletal muscle compared with T-allele carriers [β = 16% (0; 33), P = 0.047]. In the Inter99 sample, we found an association with reduced incremental area under the curve 0–120 min for insulin after an oral glucose load [β = –3% (–5; –0.07), P = 0.04], but this association was not significant after adjustment for body mass index. CONCLUSION: Our data indicate that the minor G-allele of FOXO3A rs2802292 is associated with enhanced peripheral and hepatic insulin sensitivity in our small twin cohort, which may be mediated through increased FOXO3A mRNA expression, although no major metabolic impact of rs2802292 was found in the large Inter99 cohort.

Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating disease of the CNS, most frequently starting with a series of bouts, each followed by complete remission and then a secondary, progressive phase during which the neurological deficit increases steadily. The underlying molecular mechanisms responsible for disease progression are still unclear. Herein, we demonstrate that high mobility group box chromosomal protein 1 (HMGB1), a DNA‐binding protein with proinflammatory properties, is evident in active lesions of MS and experimental autoimmune encephalomyelitis (EAE) and that HMGB1 levels correlate with active inflammation. Furthermore, the expression of the innate HMGB1 receptors—receptor for advanced glycation end products, TLR2, and TLR4—was also highly increased in MS and rodent EAE. Additionally, in vitro activation of rodent CNS‐derived microglia and bone marrow‐derived macrophages demonstrated that microglia were equally as capable as macrophages of translocating HMGB1 following LPS/IFN‐γ stimulation. Significant expression of HMGB1 and its receptors on accumulating activated macrophages and resident microglia may thus provide a positive feedback loop that amplifies the inflammatory response during MS and EAE pathogenesis.

The objectives of this study were to determine the relationship between fear of falling and functional characteristics of patients after stroke as well as to determine what characterizes fallers who score high fall-related self-efficacy, and nonfallers who score low fall-related self-efficacy. Patients (n140) treated in a stroke unit during a 12-month period were included. On follow-up, fallers were identified and patients answered the questions in the Falls Efficacy Scale, Swedish version (FES-S). Assessments of motor capacity, functional mobility and balance were also made. In univariate analysis, low fall-related self-efficacy was significantly associated with increased age, female sex, earlier falls, visual and cognitive impairment, low mood and impaired physical function. In multivariate analysis, only earlier falls and physical function remained significant. Twenty percent of the patients scored low fall-related self-efficacy without having experienced a fall, and 11 who experienced a fall scored high fall-related self-efficacy. Impaired physical function was significantly associated with scoring low fall-related self-efficacy, for both fallers and nonfallers. Fear of falling is significantly associated with poor physical function and earlier falls. Falls Efficacy Scale, Swedish version could add useful information to a fall risk analysis. Patients scoring low fall-related self-efficacy should be offered fall prevention measures whether they have fallen or not.

Rodents typically demonstrate strain‐specific susceptibilities to induced autoimmune models such as experimental arthritis and encephalomyelitis. A common feature of the local pathology of these diseases is an extensive infiltration of activated macrophages (MΦ). Different functional activation states can be induced in MΦ during innate immune activation, and it is this differential activation that might be important in susceptibility/resistance to induction or perpetuation of autoimmunity. In this study, we present an extensive, comparative analysis of the activation phenotypes of MΦ derived from autoimmune‐susceptible and autoimmune‐resistant rat strains to describe a cellular phenotype that defines the disease phenotype. We included investigation of receptor function, intracellular signaling pathways, cytokines, and other soluble mediators released after activation of cells using a panel of stimuli embracing many activation routes. We report that activation of MΦ from the autoimmune‐susceptible strain was associated with alternative activation indicated by induction of arginase activity, a lower production of classical proinflammatory mediators, and a high production of interleukin (IL)‐23, and MΦ from the autoimmune‐resistant strains were associated with a higher production of proinflammatory mediators, a classical activation phenotype, and preferential induction of IL‐12. These MΦ phenotypes thus reflect disparate, genetic cellular programs that define autoimmune susceptibility.

Objective:To characterise patients who collect their prescribed medicines from pharmacy representatives and compare them with those using regular pharmacies.Method:Data were collected from the prescriptions delivered via pharmacy representatives and by questionnaires to the patients. Data for pharmacies were obtained from the Swedish drug statistics. The data were used to determine gender and age of the patients and the types of drugs delivered from the pharmacies and from the pharmacy representatives.Setting:Pharmacy representatives connected to 20 randomly selected pharmacies in Sweden.Key findings:Prescriptions were analysed with respect to the patients' gender, age and prescribed medicine(s). The proportion of elderly patients (≥ 75 years) was greater among users of pharmacy representatives than among pharmacy users (40% compared to 24%), but in most other respects the two patient groups were similar. Patients used pharmacy representatives because it was more convenient, and only 5% of patients using pharmacy representatives had called the pharmacy to ask how their medicine should be used. Conclusions:Patients using the pharmacy representatives may serve as reference groups in studies of the effect of pharmaceutical care interventions. Only a small number of these patients receive any advice from the pharmacists and this may have a negative effect on adherence and therapy outcome.

Objective— To determine the incidence of drug‐related therapy problems (DRTPs) among patients obtaining medicines for allergy, asthma or pain.

The proportion of CD4⁻ CD8⁻ double-negative (DN) α β T cells is increased both in the thymus and in peripheral lymphoid organs of TCR α chain-transgenic mice. In this report we have characterized this T cell population to elucidate its relationship to α β and γ δ T cells. We show that the transgenic DN cells are phenotypically similar to γ δ T cells but distinct from DN NK T cells. The precursors of DN cells have neither rearranged endogenous TCRα genes nor been negatively selected by the Mls^a antigen, suggesting that they originate from a differentiation stage before the onset of TCR α chain rearrangements and CD4/CD8 gene expression. Neither in-frame VδDδJδ nor VγJγ rearrangements are over-represented in this population. However, since peripheral γ δ T cells with functional TCRβ gene rearrangements have been depleted in the transgenics, we propose that the transgenic DN population, at least partially, originates from the precursors of those cells. The present data lend support to the view that maturation signals to γ δ lineage-committed precursors can be delivered via TCR α β heterodimers.

In this report, we have assessed the lineage relationships and cytokine dependency of natural killer (NK) T cells compared with mainstream TCR-αβ T cells and NK cells. For this purpose, we studied common γ chain (γc)-deficient mice, which demonstrate a selective defect in CD3− NK cell development relative to conventional TCR-αβ T cells. NK thymocytes differentiate in γc− mice as shown by the normal percentage of TCR Vβ8+ CD4−CD8− cells and the normal quantity of thymic Vα14–Jα281 mRNA that characterize the NK T repertoire. However, γc-deficient NK thymocytes fail to coexpress the NK-associated markers NKR-P1 or Ly49, yet retain characteristic expression of the cytokine receptors interleukin (IL)-7Rα and IL-2Rβ. Despite these phenotypic abnormalities, γc− NK thymocytes could produce normal amounts of IL-4. These results define a maturational progression of NK thymocyte differentiation where intrathymic selection and IL-4–producing capacity can be clearly dissociated from the acquisition of the NK phenotype. Moreover, these data suggest a closer ontogenic relationship of NK T cells to TCR-αβ T cells than to NK cells with respect to cytokine dependency. We also failed to detect peripheral NK T cells in these mice, demonstrating that γc-dependent interactions are required for export and/or survival of NK T cells from the thymus. These results suggest a stepwise pattern of differentiation for thymically derived NK T cells: primary selection via their invariant TCR to confer the IL-4–producing phenotype, followed by acquisition of NK-associated markers and maturation/export to the periphery.

Commentary to:Influence of E3 region on conditionally replicative adenovirus mediated cytotoxicity in hepatocellular carcinoma cellsQin Lu, De-Hong Yu, Chao Fang, Fang Liu, Xun Ye, Yi Zhao, Jie Qin, Xiao-Kui Guo, Min Liang, Fang Hu, Hong-zhuan Chen

A simple and rapid method for Shiga toxin purification based on specific binding to the Galα1 → 4Galβ1 → 4Glc globotrioside trisaccharide covalently linked to polyacryl/polyvinyl (Fractogel) has been developed. A cell-free sonicate-filtrate of Shigella dysenteriaetype 1, strain 114Sd was passed over the globotrioside-Fractogel column, and bound toxin eluted with 6 M guanidine-HCl. A yield of 36 mg pure toxin/1 sonicate-filtrate was otained, i.e. a one step 1224-fold purification. The recovery of biologically active toxin was 87%. The toxin was purified to homogeneity as shown by native PAGE and SDS-PAGE.

A simple and rapid method for Shiga toxin purification based on specific binding to the Galα1 → 4Galβ1 → 4Glc globotrioside trisaccharide covalently linked to polyacryl/polyvinyl (Fractogel) has been developed. A cell‐free sonicate‐filtrate of Shigella dysenteriaetype 1, strain 114Sd was passed over the globotrioside‐Fractogel column, and bound toxin eluted with 6 M guanidine‐HCl. A yield of 36 mg pure toxin/1 sonicate‐filtrate was otained, i.e. a one step 1224‐fold purification. The recovery of biologically active toxin was 87%. The toxin was purified to homogeneity as shown by native PAGE and SDS‐PAGE.

Inactive conformations of α1B-AR and β2-AR are structurally similar but exhibit distinct pharmacological properties.

An oxytocin derivative that may not trigger adverse side effects has been generated.

Sjögren's syndrome is an autoimmune disease with a complex etiology depending on hereditary and environmental factors. The disease is characterized by lymphocytic infiltration and inflammation in the salivary and lacrimal glands, leading to oral and ocular dryness. To understand the genetic susceptibility in Sjögren's syndrome, studies of disease phenotypes have been performed in the non-obese diabetic (NOD) mouse. By the identification of genetic regions controlling development of autoimmune exocrinopathy in the NOD mouse and by reducing one of these regions considerably, Nguyen et al. in a recent issue of Arthritis Research and Therapypropose candidate genes for development of Sjögren's syndrome.

BackgroundImmigration to Sweden from lower latitude countries has increased in recent years. Studies in the general population in other Nordic countries have demonstrated that these groups are at risk of developing vitamin D deficiency, but studies in primary health care patients are rare.ObjectivesThe aim of this study is to examine possible differences in plasma-25(OH)-vitamin D levels and intake of vitamin D between Swedish and immigrant female patients in a primary health care centre located at 60°N, where half of the inhabitants have an immigrant background. Another objective was to estimate what foods contribute with most vitamin D.DesignThirty-one female patients from the Middle East and Africa and 30 from Sweden were recruited. P-25(OH)D was measured and intake of vitamin D was estimated with a modified food frequency questionnaire (FFQ).ResultsVitamin D deficiency (plasma-25(OH)D <25 nmol/L) was common among immigrant women (61%). One immigrant woman and half of the Swedish women had optimal levels (plasma-25(OH)D >50 nmol/L). There was a positive correlation between the intake of vitamin D from food and plasma-25(OH)D. Only three women, all Swedish, reached the recommended intake of vitamin D from food. The immigrant women had lower intake compared to Swedish women (median: 3.1 vs. 5.1 µg/day). The foods that contributed with most vitamin D were fatty fish, fortified milk and margarine. Immigrant women consumed less fortified milk and margarine but more meat. Irrespective of origin, patients with plasma-25(OH)D <25 nmol/L consumed less margarine but more meat.ConclusionVitamin D deficiency was common in the immigrant patients and their intake of vitamin D was lower. This highlights the need to target information about vitamin D to immigrant women in order to decrease the risk for vitamin D deficiency. The FFQ was well adapted to its purpose to estimate intake of vitamin D.

In a cross between two mouse strains, the susceptible B10.RIII (H-2r) and resistant RIIIS/J (H-2r) strains, a locus on mouse chromosome 5 (Eae39) was previously shown to control experimental autoimmune encephalomyelitis (EAE). Recently, quantitative trait loci (QTL), linked to disease in different experimental arthritis models, were mapped to this region. The aim of the present study was to investigate whether genes within Eae39, in addition to EAE, control development of collagen-induced arthritis (CIA).

Introduction Collagen-induced arthritis (CIA) in mice is a commonly used experimental model for rheumatoid arthritis (RA). We have previously identified a significant quantitative trait locus denoted Cia40 on chromosome 11 that affects CIA in older female mice. This locus colocalizes with another locus, denoted Pregq2, known to affect reproductive success. The present study was performed to evaluate the role of the Cia40 locus in congenic B10.Q mice and to identify possible polymorphic candidate genes, which may also be relevant in the context of RA.Methods Congenic B10.Q mice carrying an NFR/N fragment surrounding the Cia40/Pregq2 loci were created by 10 generations of backcrossing (N10). The congenic mice were investigated in the CIA model, and the incidence and severity of arthritis as well as the serum levels of anti-collagen II (CII) antibodies were recorded.Results Significant effects on onset, incidence, severity, and anti-CII antibody titers were observed in female mice carrying a heterozygous congenic Cia40/Pregq2 fragment of NFR/N origin, containing one or more polymorphic genes. Congenic male mice did not show increased incidence of CIA, but males carrying a heterozygous fragment showed a significant increase in severity in comparison with wildtype B10.Q males (littermates).Conclusion The Cia40/Pregq2 locus at chromosome 11 contains one or more polymorphic genes of NFR/N origin that significantly influence both incidence and severity of CIA in heterozygous congenic mice of the B10.Q strain. The major polymorphic candidate genes for the effects on CIA are Cd79b, Abca8a, and Map2k6. The congenic fragment also contains polymorphic genes that affect reproductive behavior and reproductive success. The Sox9 gene, known to influence sex reversal, is a candidate gene for the reproductive phenotype.