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In this article, I re-think official educational organization toward friction-zones. Thinking with a swimming event in physical education, and Deleuze's notion of pure difference and its accompanying characteristics, non-linearity, decentralization, pluralistic knowledge, virtual and actual multiplicities, nomadic waiting, and open ends, I outline conditions for official educational organization in the encounter between divergent knowledges. The aim is to bring teachers and students closer to each other and paradoxically let up-coming concepts, meanings, and ideas act instead of silence everything that is not in line with predefined educational goals. It is to create common histories of learning and knowledge productions, and hence to produce common grounds in/by motion. Ultimately, it is about inclusive processes in/by motion. And, it is also a call for us all to pay attention and resist unintentional productions of exclusion, and thus all colonizing processes that includes superior knowledge.

Since the turn of the millennium, the practice of sport has changed significantly as more and more people leave club sports in favor of self-organized sports. A common feature of this change is the need of other spatial conditions than traditional sport facilities. Simultaneously, self-organized sports have largely been overlooked within policy and programs seeking to improve today's sport facilities. The aim of this narrative review is therefore to provide a comprehensive understanding of self-organized sports and their social-spatial needs. From the databases SCOPUS, SportDiscus and ProQuest Social Sciences 66 articles are linked together for reinterpretation and development of three theoretical discussions that are accompanied by Deleuze's philosophy of immanence: The flatness, motion, and the responsivity of self-organized sports. Taking these theoretical aspects into account, it is concluded that self-organized sports need not fully defined places open for unpredictable encounters and that enable speculations of what can be created. [ABSTRACT FROM AUTHOR]

Existing databases of RCS benchmarks lack a complex, low-observable target. This paper describes the design of such a complex and low-observable measurement model. Starting point of the design is the so-called Muldicon model, developed by the NATO/STO/AVT panel. Hot spots of the original model are identified and treated with radar-absorbing materials. Simulations on the treated model demonstrate that the model is indeed low observable. The effect of the manufacturing process of 3D-printing and separable parts is assessed experimentally on a cone-sphere; the effect is found to be negligible. These results give confidence that the model, when built, satisfies the requirements of being complex and low observable; and that artefacts of the manufacturing process will not impair its signature. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the acute exercise effects of dynamic standing exercise on blood glucose and blood lactate among children and adolescents with cerebral palsy who are nonambulant. Methods: Twenty-four participants with cerebral palsy who are nonambulant performed 30 minutes of dynamic standing exercise using a motorized device enabling assisted passive movements in an upright weight-bearing position. Capillary blood samples were taken from the fingertip for measurement of blood glucose and blood lactate at rest and at the end of exercise. Results: At rest, the participants had hyperlactatemia that was unaffected after exercise, presented as median and interquartile range at rest 1.8 (1.3:2.7) mmol/L, and after exercise 2.0 (1.1:2.5) mmol/L. Children and adolescents with Gross Motor Function Classification System, level V, had higher lactate levels at rest (2.5 [1.8:2.9] vs 1.4 [1.0:2.0]; P =.030) and after exercise (2.3 [2.0:2.6] vs 1.2 [0.9:2.2]; P =.032) compared with children and adolescents with Gross Motor Function Classification System, level IV, respectively. A statistically significant larger decrease in blood lactate levels after exercise was observed in children and adolescents with higher resting blood lactate levels (ρ =.56; P =.004). There were no statistically significant changes in blood glucose. Conclusions: Forty percentage of the participants had mild hyperlactatemia at rest and participants with the highest blood lactate levels at rest had the greatest decrease in blood lactate levels after one bout of exercise. Children and adolescents who were classified with the highest level of the Gross Motor Function Classification Scale had higher blood lactate levels. More studies are needed on how to prevent chronically high resting levels of lactate with exercise in children with cerebral palsy who are nonambulant. [ABSTRACT FROM AUTHOR]

Herein, we designed alkylated lysine-dendron oxytocin amphiphiles (ALOAs) 1G-OTK and 2G-OTK, which were self-assembled into spherical nanoparticles and nanostrips, respectively, and showed superior stability compared to native oxytocin. We found similar trends in the functional activity of ALOAs and native OT for human oxytocin receptor. This work may inspire the development of peptide drugs for clinical applications. [ABSTRACT FROM AUTHOR]

Aim: Studies on frequencies of manipulated medicines in paediatric care are common, but there is little knowledge of experiences of pharmacists and registered nurses in this area. The aim of this study was to explore registered nurses' and pharmacists' reasoning in the manipulation of medicines to paediatric inpatients. Methods: Semistructured interviews with twelve registered nurses and seven pharmacists were performed at a Swedish paediatric university hospital. The interviews were transcribed verbatim and analysed using content analysis. Results: Four major categories emerged from the analysis of the interviews: medicines management, knowledge, consulting others and organisation. Medicines management involved the process of drug handling, which is prescribing, reconstitution or manipulation and administration. Knowledge concerned both the knowledge base and how healthcare personnel seek information. Consulting others involved colleagues, registered nurses and pharmacists, between registered nurses, pharmacists and physicians and between registered nurses, pharmacists and caregivers. Organisation covered documentation, time and working environment. Conclusion: Both pharmacists and registered nurses stated that manipulation of medicines to paediatric patients was often necessary but felt unsafe due to lack of supporting guidelines. Pharmacists were natural members of the ward team, contributing with specific knowledge about medicines and formulations. [ABSTRACT FROM AUTHOR]

Objective: N‐methyl‐d‐aspartate (NMDA) receptors are expressed at synaptic sites, where they mediate fast excitatory neurotransmission. NMDA receptors are critical to brain development and cognitive function. Natural variants to the GRIN1 gene, which encodes the obligatory GluN1 subunit of the NMDA receptor, are associated with severe neurological disorders that include epilepsy, intellectual disability, and developmental delay. Here, we investigated the pathogenicity of three missense variants to the GRIN1 gene, p. Ile148Val (GluN1‐3b[I481V]), p.Ala666Ser (GluN1‐3b[A666S]), and p.Tyr668His (GluN1‐3b[Y668H]). Methods: Wild‐type and variant‐containing NMDA receptors were expressed in HEK293 cells and primary hippocampal neurons. Patch‐clamp electrophysiology and pharmacology were used to profile the functional properties of the receptors. Receptor surface expression was evaluated using fluorescently tagged receptors and microscopy. Results: Our data demonstrate that the GluN1(I481V) variant is inhibited by the open pore blockers ketamine and memantine with reduce potency but otherwise has little effect on receptor function. By contrast, the other two variants exhibit gain‐of‐function molecular phenotypes. Glycine sensitivity was enhanced in receptors containing the GluN1(A666S) variant and the potency of pore block by memantine and ketamine was reduced, whereas that for MK‐801 was increased. The most pronounced functional deficits, however, were found in receptors containing the GluN1(Y668H) variant. GluN1(Y668H)/2A receptors showed impaired surface expression, were more sensitive to glycine and glutamate by an order of magnitude, and exhibited impaired block by extracellular magnesium ions, memantine, ketamine, and MK‐801. These variant receptors were also activated by either glutamate or glycine alone. Single‐receptor recordings revealed that this receptor variant opened to several conductance levels and activated more frequently than wild‐type GluN1/2A receptors. Significance: Our study reveals a critical functional locus of the receptor (GluN1[Y668]) that couples receptor gating to ion channel conductance, which when mutated may be associated with neurological disorder. [ABSTRACT FROM AUTHOR]

Introduction: Transcranial Doppler (TCD) sonography is a noninvasive tool for measuring cerebrovascular hemodynamics. Studies have reported alterations in cerebrovascular hemodynamics in normal aging, mild cognitive impairment (MCI), and dementia, as well as in different etiologies of dementia. This systematic review and meta-analysis was designed to investigate the relationship between cerebral blood velocity (CBv) and pulsatility index (PI) in the middle cerebral artery (MCA) in persons with MCI and dementia. Methods: A systematic literature search was conducted in Pubmed, Embase, Cochrane Library, Epistemonikos, PsychINFO, and CINAHL. The search was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. After screening of 33,439 articles, 86 were reviewed in full-text, and 35 fulfilled the inclusion criteria. Results: CBv was significantly lower and PI significantly higher in MCA in vascular dementia (VaD) and Alzheimer's disease (AD) compared to cognitively normal (CN) older persons. Also, CBv was lower in MCI compared to CN. There were no significant differences in CBv in MCA in AD compared with VaD, although PI was higher in VaD compared to AD. Conclusion: Alterations in cerebrovascular hemodynamics are seen in AD, VaD, and MCI. While PI was slightly higher in VaD compared to AD, the reduction in CBv appears to be equally pronounced across neurodegenerative and vascular etiologies of dementia. [ABSTRACT FROM AUTHOR]

These were the proportion of the active pharmaceutical ingredients (APIs) in a tablet and the aqueous solubility of the active substance in relation to the intended concentration after dispersing the tablet in water according to a frequently used paediatric medicine preparation technique. Abbreviation API active pharmaceutical ingredients Providing medicines for children with different ages, body weights and capacities poses clinical challenges. [Extracted from the article]

This article challenge research political assumptions of research interests as context specific phenomena predefined by researchers and others in case study research on sports. By adopting a Deleuzian perspective of materiality, the aim is to overturn academic power dimensions as well as anthropocentric focuses and instead explore how research interests emerge in case-assemblages. This is a radical shift that re-theorizes the production of research interests as co-produced capacities in researching bodies. The analysis is done by mapping territorializing, deterritorializing, and reterritorializing affects as well as molar and molecular affects. We use these affects to explore how our research interest evolved in a case study on a swimming event. We conclude by extending this critical exploration to the production of research interests in general and the exaggerated belief that research interests are attributes of specific human bodies (researchers) that precede studies. [ABSTRACT FROM AUTHOR]

Ziconotide (ω‐conotoxin MVIIA) is an approved analgesic for the treatment of chronic pain. However, the need for intrathecal administration and adverse effects have limited its widespread application. Backbone cyclization is one way to improve the pharmaceutical properties of conopeptides, but so far chemical synthesis alone has been unable to produce correctly folded and backbone cyclic analogues of MVIIA. In this study, an asparaginyl endopeptidase (AEP)‐mediated cyclization was used to generate backbone cyclic analogues of MVIIA for the first time. Cyclization using six‐ to nine‐residue linkers did not perturb the overall structure of MVIIA, and the cyclic analogues of MVIIA showed inhibition of voltage‐gated calcium channels (CaV2.2) and substantially improved stability in human serum and stimulated intestinal fluid. Our study reveals that AEP transpeptidases are capable of cyclizing structurally complex peptides that chemical synthesis cannot achieve and paves the way for further improving the therapeutic value of conotoxins. [ABSTRACT FROM AUTHOR]

Voltage-gated sodium (NaV) channels are critical regulators of neuronal excitability and are targeted by many toxins that directly interact with the pore-forming α subunit, typically via extracellular loops of the voltage-sensing domains, or residues forming part of the pore domain. Excelsatoxin A (ExTxA), a pain-causing knottin peptide from the Australian stinging tree Dendrocnide excelsa, is the first reported plant-derived NaV channel modulating peptide toxin. Here we show that TMEM233, a member of the dispanin family of transmembrane proteins expressed in sensory neurons, is essential for pharmacological activity of ExTxA at NaV channels, and that co-expression of TMEM233 modulates the gating properties of NaV1.7. These findings identify TMEM233 as a previously unknown NaV1.7-interacting protein, position TMEM233 and the dispanins as accessory proteins that are indispensable for toxin-mediated effects on NaV channel gating, and provide important insights into the function of NaV channels in sensory neurons. Voltage-gated sodium channels function as multiprotein signaling complexes. Here, authors show that the dispanin TMEM233 is essential for activity of stinging nettle toxins and that co-expression of TMEM233 modulates the gating properties of NaV1.7. [ABSTRACT FROM AUTHOR]

This is a registry-based study with the aim of describing and comparing the frequency of manipulations of solid oral and rectal medicines in 2009 and 2019 at inpatient units and an emergency department in a paediatric hospital within a Swedish university hospital. All patients aged 1 month–18 years with oral or rectal administrations were included. In total, 140,791 oral and rectal administrations were included in 2009, and 167,945 oral and rectal administrations were included in 2019. The frequency of patients receiving at least one manipulated oral medicine decreased between the study years, both in inpatient units and in the emergency department (from 19% to 17%, p = 0.0029 and from 11% to 5%, p < 0.0001, respectively). The frequency of patients receiving a manipulated rectal medicine also decreased between the study years, both in inpatient units and in the emergency department (from 22% to 10%, p < 0.0001 and from 35% to 7% 2019, p < 0.0001, respectively). The results show a decrease in the manipulation of both oral and rectal medicines to paediatric patients in 2019 compared to 2009. Even though this implies a safer practice, there is still a pronounced lack of child-friendly dosage forms and suitable strengths enabling the safe administration of medicines to sick children. [ABSTRACT FROM AUTHOR]

Background and Purpose: Over past decades, targeted therapies and immunotherapy have improved survival and reduced the morbidity of patients with BRAF-mutated melanoma. However, drug resistance and relapse hinder overall success. Therefore, there is an urgent need for novel compounds with therapeutic efficacy against BRAF-melanoma. This prompted us to investigate the antiproliferative profile of a tachykinin-peptide from the Octopus kaurna, Octpep-1 in melanoma.Experimental Approach: We evaluated the cytotoxicity of Octpep-1 by MTT assay. Mechanistic insights on viability and cellular damage caused by Octpep-1 were gained via flow cytometry and bioenergetics. Structural and pharmacological characterization was conducted by molecular modelling, molecular biology, CRISPR/Cas9 technology, high-throughput mRNA and calcium flux analysis. In vivo efficacy was validated in two independent xerograph animal models (mice and zebrafish).Key Results: Octpep-1 selectively reduced the proliferative capacity of human melanoma BRAFV600E -mutated cells with minimal effects on fibroblasts. In melanoma-treated cells, Octpep-1 increased ROS with unaltered mitochondrial membrane potential and promoted non-mitochondrial and mitochondrial respiration with inefficient ATP coupling. Molecular modelling revealed that the cytotoxicity of Octpep-1 depends upon the α-helix and polyproline conformation in the C-terminal region of the peptide. A truncated form of the C-terminal end of Octpep-1 displayed enhanced potency and efficacy against melanoma. Octpep-1 reduced the progression of tumours in xenograft melanoma mice and zebrafish.Conclusion and Implications: We unravel the intrinsic anti-tumoural properties of a tachykinin peptide. This peptide mediates the selective cytotoxicity in BRAF-mutated melanoma in vitro and prevents tumour progression in vivo, providing a foundation for a therapy against melanoma. [ABSTRACT FROM AUTHOR]