Cell Therapy for Type 1 Diabetes

Acknowledgements The work described in this review was supported by a grant from the MRC. K.R.M. is supported by a fellowship from the Scottish Translational Medicines and Therapeutics Initiative through the Wellcome Trust.Peer reviewedPublisher PD

Effects of magnesium treatment in a model of internal capsule lesion in spontaneously hypertensive rats

<p><b>Background and Purpose:</b> The study aim was to assess the effects of magnesium sulfate (MgSO4) administration on white matter damage in vivo in spontaneously hypertensive rats.</p> <p><b>Methods:</b> The left internal capsule was lesioned by a local injection of endothelin-1 (ET-1; 200 pmol) in adult spontaneously hypertensive rats. MgSO4 was administered (300 mg/kg SC) 30 minutes before injection of ET-1, plus 200 mg/kg every hour thereafter for 4 hours. Infarct size was measured by T2-weighted magnetic resonance imaging (day 2) and histology (day 11), and functional recovery was assessed on days 3 and 10 by the cylinder and walking-ladder tests.</p> <p><b>Results:</b> ET-1 application induced a small, localized lesion within the internal capsule. Despite reducing blood pressure, MgSO4 did not significantly influence infarct volume (by magnetic resonance imaging: median, 2.1 mm3; interquartile range, 1.3 to 3.8, vs 1.6 mm3 and 1.2 to 2.1, for the vehicle-treated group; by histology: 0.3 mm3 and 0.2 to 0.9 vs 0.3 mm3 and 0.2 to 0.5, respectively). Significant forelimb and hindlimb motor deficits were evident in the vehicle-treated group as late as day 10. These impairments were significantly ameliorated by MgSO4 in both cylinder (left forelimb use, P<0.01 and both-forelimb use, P<0.03 vs vehicle) and walking-ladder (right hindlimb score, P<0.02 vs vehicle) tests.</p> <p><b>Conclusions:</b> ET-1–induced internal capsule ischemia in spontaneously hypertensive rats represents a good model of lacunar infarct with small lesion size, minimal adverse effects, and a measurable motor deficit. Despite inducing mild hypotension, MgSO4 did not significantly influence infarct size but reduced motor deficits, supporting its potential utility for the treatment of lacunar infarct.</p&gt

Billy Elliot The Musical: visual representations of working-class masculinity and the all-singing, all-dancing bo[d]y

According to Cynthia Weber, ‘[d]ance is commonly thought of as liberating, transformative, empowering, transgressive, and even as dangerous’. Yet ballet as a masculine activity still remains a suspect phenomenon. This paper will challenge this claim in relation to Billy Elliot the Musical and its critical reception. The transformation of the visual representation of the human body on stage (from an ephemeral existence to a timeless work of art) will be discussed and analysed vis-a-vis the text and sub-texts of Stephen Daldry’s direction and Peter Darling’s choreography. The dynamics of working-class masculinity will be contextualised within the framework of the family, the older female, the community, the self and the act of dancing itself

Blaming Bill Gates AGAIN! Misuse, overuse and misunderstanding of performance data in sport

Recently in Sport, Education and Society, Williams and Manley (2014) argued against the heavy reliance on technology in professional Rugby Union and elite sport in general. In summary, technology is presented as an elitist, ‘gold standard’ villain that management and coaches use to exert control and by which players lose autonomy, identity, motivation, social interactions and expertise. In this article we suggest that the sociological interpretations and implications offered by Williams and Manley may be somewhat limited when viewed in isolation. In doing so, we identify some core methodological issues in Williams and Manley’s study and critically consider important arguments for utilising technology; notably, to inform coach decision making and generate player empowerment. Secondly, we present a different, yet perhaps equally concerning, practice-oriented interpretation of the same results but from alternative coaching and expertise literature. Accordingly, we suggest that Williams and Manley have perhaps raised their alarm prematurely, inappropriately and on somewhat shaky foundations. We also hope to stimulate others to consider contrary positions, or at least to think about this topic in greater detail. More specifically, we encourage coaches and academics to think carefully about what technology is employed, how and why, and then the means by which these decisions are discussed with and, preferably, sold to players. Certainly, technology can significantly enhance coach decision making and practice, while also helping players to optimise their focus, empowerment and independence in knowing how to achieve their personal and collective goals

Canine NAPEPLD-associated models of human myelin disorders

Canine leukoencephalomyelopathy (LEMP) is a juvenile-onset neurodegenerative disorder of the CNS white matter currently described in Rottweiler and Leonberger dogs. Genome-wide association study (GWAS) allowed us to map LEMP in a Leonberger cohort to dog chromosome 18. Subsequent whole genome re-sequencing of a Leonberger case enabled the identification of a single private homozygous non-synonymous missense variant located in the highly conserved metallo-beta-lactamase domain of the N-acyl phosphatidylethanolamine phospholipase D (NAPEPLD) gene, encoding an enzyme of the endocannabinoid system. We then sequenced this gene in LEMP-affected Rottweilers and identified a different frameshift variant, which is predicted to replace the C-terminal metallo-beta-lactamase domain of the wild type protein. Haplotype analysis of SNP array genotypes revealed that the frameshift variant was present in diverse haplotypes in Rottweilers, and also in Great Danes, indicating an old origin of this second NAPEPLD variant. The identification of different NAPEPLD variants in dog breeds affected by leukoencephalopathies with heterogeneous pathological features, implicates the NAPEPLD enzyme as important in myelin homeostasis, and suggests a novel candidate gene for myelination disorders in people

Modulation of mitochondrial activity in HaCaT keratinocytes by the cell penetrating peptide Z-Gly-RGD(DPhe)-mitoparan.

OBJECTIVE: Biologically active cell penetrating peptides (CPPs) are an emerging class of therapeutic agent. The wasp venom peptide mastoparan is an established CPP that modulates mitochondrial activity and triggers caspase-dependent apoptosis in cancer cells, as does the mastoparan analogue mitoparan (mitP). Mitochondrial depolarisation and activation of the caspase cascade also underpins the action of dithranol, a topical agent for treatment of psoriasis. The effects of a potent mitP analogue on mitochondrial activity were therefore examined to assess its potential as a novel approach for targeting mitochondria for the treatment of psoriasis. RESULTS: In HaCaT keratinocytes treated with the mitP analogue Z-Gly-RGD(DPhe)-mitP for 24 h, a dose-dependent loss of mitochondrial activity was observed using the methyl-thiazolyl-tetrazolium (MTT) assay. At 10 μmol L-1, MTT activity was less than 30% that observed in untreated cells. Staining with the cationic dye JC-1 suggested that Z-Gly-RGD(DPhe)-mitP also dissipated the mitochondrial membrane potential, with a threefold increase in mitochondrial depolarisation levels. However, caspase activity appeared to be reduced by 24 h exposure to Z-Gly-RGD(DPhe)-mitP treatment. Furthermore, Z-Gly-RGD(DPhe)-mitP treatment had little effect on overall cell viability. Our findings suggest Z-Gly-RGD(DPhe)-mitP promotes the loss of mitochondrial activity but does not appear to evoke apoptosis in HaCaT keratinocytes

Enhancement of the Deuteron-Fusion Reactions in Metals and its Experimental Implications

Recent measurements of the reaction d(d,p)t in metallic environments at very low energies performed by different experimental groups point to an enhanced electron screening effect. However, the resulting screening energies differ strongly for divers host metals and different experiments. Here, we present new experimental results and investigations of interfering processes in the irradiated targets. These measurements inside metals set special challenges and pitfalls which make them and the data analysis particularly error-prone. There are multi-parameter collateral effects which are crucial for the correct interpretation of the observed experimental yields. They mainly originate from target surface contaminations due to residual gases in the vacuum as well as from inhomogeneities and instabilities in the deuteron density distribution in the targets. In order to address these problems an improved differential analysis method beyond the standard procedures has been implemented. Profound scrutiny of the other experiments demonstrates that the observed unusual changes in the reaction yields are mainly due to deuteron density dynamics simulating the alleged screening energy values. The experimental results are compared with different theoretical models of the electron screening in metals. The Debye-H\"{u}ckel model that has been previously proposed to explain the influence of the electron screening on both nuclear reactions and radioactive decays could be clearly excluded.Comment: 22 pages, 12 figures, REVTeX4, 2-column format. Submitted to Phys. Rev. C; accepte

MotivATE: A Pretreatment Web-Based Program to Improve Attendance at UK Outpatient Services Among Adults With Eating Disorders.

BACKGROUND: In the UK, eating disorders affect upward of 725,000 people per year, and early assessment and treatment are important for patient outcomes. Around a third of adult outpatients in the UK who are referred to specialist eating disorder services do not attend, which could be related to patient factors related to ambivalence, fear, and a lack of confidence about change. This lack of engagement has a negative impact on the quality of life of patients and has implications for service costs. OBJECTIVE: To describe the development of a Web-based program ("MotivATE") designed for delivery at the point of referral to an eating disorder service, with the aim of increasing service attendance. METHODS: We used intervention mapping and a person-based approach to design the MotivATE program and conducted a needs assessment to determine the current impact of service nonattendance on patients (via a review of the qualitative evidence) and services (through a service provision survey to understand current issues in UK services). Following the needs assessment, we followed the five steps of program development outlined by Bartholomew et al (1998): (1) creating a matrix of proximal program objectives; (2) selecting theory-based intervention methods and strategies; (3) designing and organizing the program; (4) specifying adoption and implementation plans; and (5) generating program evaluation plans. RESULTS: The needs assessment identified current nonattendance rates of 10%-32%. We defined the objective of MotivATE as increasing attendance rates at an eating disorder service and considered four key determinants of poor attendance: patient ambivalence about change, low patient self-efficacy, recognition of the need to change, and expectations about assessment. We chose aspects of motivational interviewing, self-determination theory, and the use of patient stories as the most appropriate ways to enable change. Think-aloud piloting with people with lived experience of an eating disorder resulted in positive feedback on the MotivATE program. Participants related well to the stories used. Nonetheless, because of feedback, we further modified the program in line with patients' stage of change and addressed issues with the language used. A consultation with service staff meant that we could make clear implementation plans. Finally, a randomized controlled trial is currently underway to evaluate the MotivATE program. CONCLUSIONS: Using intervention mapping, we have developed a novel pretreatment Web-based program that is acceptable to people with eating disorders. To our knowledge, this is the first such program. The model of development described here could be a useful template for designing further programs for other difficult-to-engage populations